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Abstract

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Stephan Ruegg 1 , P. Hunziker 2 , S. Marsch 2 and C. Schindler 3 ( 1 Neurology, University Hospital Basel, Basel, Switzerland ; 2 Intensive Care Medicine, University Hospital Basel, Basel, Switzerland and 3 Social and Preventive Medicine, University of Basel, Basel, Switzerland )

Rationale: To investigate whether non-medical, environmental factors influence the frequency of admissions of patients with status epilepticus (SE) to the intensive care unit (ICU).

Methods: Cohort Study during July 2003-June 2006 of all patients admitted to a single university hospital ICU for the treatment of SE. Retrospective analysis using Poisson-regression and likelihood ratio tests for the determination of associations between environmental factors (daytime, weekday, season, moon cycle, and weather conditions) and the incidence of SE.

Results: Data from 184 patients (mean age 57 years (18–89)) showed a significant (p < .001) diurnal pattern with a peak of admissions between 4 to 5 p.m. and a minimum in the early morning. A significant weekly pattern was also observed (p = .045) with admissions peaking on Wednesdays/Thursdays and being lowest at weekends. There was no seasonal pattern. Admissions varied significantly across moon cycle (p = 0.003), peaking at day 3 after new moon, with a weaker peak 7 days after full moon, and a minimum 3 days before new moon. While sunshine, precipitation, and wind force did not significantly influence the admissions, high relative humidity (p < 0.01), high temperature (p < 0.05) and dark days (p = 0.02) were significantly protective factors. Bright days (p = 0.04), and daily sunshine duration (p = 0.03) increased the incidence of SE.

Conclusions: Admissions of patients with SE on ICU are significantly associated with several environmental protective and precipitating factors, like diurnal, weekly and moon cycle, and weather variables. Contrary to common belief, SE did neither peak at full moon nor at new moon, but some days after new moon. The reasons for the associations observed remain to be further elucidated.

Abstract

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John C. Nguyen 1 , K. Liow 1,2 , E. Ablah 1 , T. Sadler 2 , D. Wolfe 1 and K. Tran 1 ( 1 University of Kansas School of Medicine, Wichita, KS and 2 Via Christi Comprehensive Epilepsy Center and Neurophysiology Laboratory, Wichita, KS )

Rationale: Complementary and alternative medicine (CAM) is recognized to be commonly used by patients, yet there have been few studies regarding the scope of CAM and patients with epilepsy. This study assessed usage and perceptions of CAM by epilepsy patients in the US Midwest.

Methods: A survey of 25 items was administered to adult patients with epilepsy, with data collected from 228 patients. The survey collected information including demographics, specific CAM usage, adverse effects from CAM therapy, and perceptions on the effectiveness of CAM.

Results: Thirty-nine percent (39%) reported using CAM; 25% reported using CAM specifically for their epilepsy. Out of a list of 30 CAM therapies, prayer/spirituality was the most commonly used (46%), followed by “mega” vitamins (25%), chiropractic care (24%), and stress management (16%).

Conclusions: CAM use is common amongst US Midwest epilepsy patients. Prayer/spirituality is the most prevalent type of CAM therapy, whereas herbs/botanicals usage is uncommon as CAM therapy for epilepsy patients in the US Midwest.

Abstract

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Satish C. Rao 1 , G. Dove 2 , G. D. Cascino 1 and R. C. Petersen 1 ( 1 Neurology, Mayo Clinic, Rochester, MN and 2 Noran Neurological Clinic, Minneapolis, MN )

Rationale: The prevalence of seizure disorders increases in older-aged patients and approaches 4% in individuals over 80 years of age. Patients with neurodegenerative diseases associated with a significant cognitive impairment are at increased risk of unprovoked seizure activity. The rationale for the present study is to characterize seizure-type(s), diagnosis of dementia, MRI and EEG findings, and response to antiepileptic drug (AED) medication in these individuals.

Methods: A retrospective study was performed identifying patients in the Mayo Alzheimer Disease Patient Registry who were classified as having dementia and recurrent seizure activity. Sixty-three individuals were subsequently identified. Twenty-four of the 63 patients were excluded because of insufficient information concerning the seizure activity or response to AED therapy. The remaining 39 patients were included in the present series and subsequently analyzed.

Results: The mean age was 76.9 years (range, 52 to 100 years). There were 21 females and 18 males. The neurodegenerative diseases associated with dementia included mild cognitive impairment (n = 10), Alzheimer's disease (n = 9), vascular dementia (n = 6), and Lewy body disease (n = 5). Twenty-five patients (64%) had recurrent complex partial seizures and 15 patients (52%) had generalized tonic-clonic seizures. An MRI head was performed in 35 patients (90%). Fourteen patients (36%) had MRI-identified structural lesions that included remote stroke (n = 12) or prior intracerebral hemorrhage (n = 2). An EEG was obtained in 29 patients (74%). Fifteen patients (38%) had EEG-identified epileptiform discharges. The EEG in these individuals most commonly revealed unilateral or bitemporal spike or sharp wave discharges. Thirty-one patients (79%) became seizure-free or had a greater than 95% reduction of seizure frequency and less than three seizures per year with AED therapy. One patient (2.6%) had a 50% to 79% reduction of seizure frequency, and three individuals (7.7%) had less than a 50% reduction of seizure frequency with AED medication. Twenty-eight patients (72%) received one AED medication and 11 patients (28%) were on polypharmacy (two or more AED medications). Twelve patients (31%) had dose-related adverse effects. The most common medication related symptom was drowsiness in eight patients (21%). The remaining 27 patients (69%) had no drug-induced adverse effects.

Conclusions: The present study indicated that most individuals with the comorbidity of recurrent seizures and dementia have complex partial seizures that may be adequately controlled on AED medication. Characteristically, the patients responded to the first AED therapy with minimal adverse effects. The long-term effect of seizure activity on the neurodegenerative disorder is unknown.

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Janet Mifsud 1 , T. Camilleri 1 and R. Galea 2 ( 1 Clinical Pharmacology, University of Malta, Msida, Malta and 2 Obstetrics and Gynaecology, University of Malta, Msida, Malta )

Rationale: Pregnancy in woman with epilepsy can give rise to several serious medical problems and always belongs to the group of high obstetric risks. The aim of the retrospective study was the evaluation of the efficiency of antiepileptic treatment during pregnancy, including risk factor, effects on pregnancy and delivery in pregnant women with epilepsy in Malta, a small island state with a population of 400,000, for the period, 1996–2005, compared with the general pregnant population receiving the same obstetric care.

Methods: The medical and obstetric data records of mothers with epilepsy (PWE) who gave birth between January 1996 and December 2005 in Malta was reviewed from the 120 Monthly Birth Registers for the period 1996–2005 together with Malta Congenital Anomalies Register for the same period. Data obtained was statistically analysed and compared to that of the whole population. The study methodology used was adapted to the methodology used in similar investigations carried out by Richmond et al (2004) in Quebec.

Results: The data obtained was analysed using BPMP® statistical package, with student t-tests at the 5% significant level. In total, 58 birth outcomes in 46 PEW were documented i.e 0.1% of total births during that time. The epilepsy was idiopathic in 42 cases. In 5 cases, the PEW were not taking any AEDs. All PEW were on folic acid 5 mg daily. CBZ (n = 29) and PHT (n = 21) were the two most widely prescribed AEDs in this group: 60% were on monotherapy, while 22% on two drugs, 9% on 3 drugs and 9% were on no treatment. Birth weight (3.29 + 1.25 kg; p > 0.05), AGPAR scores (8.2 vs 8.25; p > 0.05) and incidence of congenital anomalies fitted in with the general population, but there was a higher incidence of obstetric intervention in PWE (normal vaginal delivery 50% vs 74.8%); P < 0.05).

Conclusions: The study population was too small to draw more statistically significant conclusions. Further studies to assess the level of risk of adverse outcomes over a longer follow up period are necessary. Setting up local prospective ongoing studies amongst PWE in a pregnancy registry in a small population can contribute to the pooling of data to larger international data centres. It is only with the emergence of solid evidence of the difference in the teratogenicity of AEDs, which may change current practice in the management of epilepsy in women of childbearing potential. The systematic monitoring of pregnancy outcomes after exposure will yield important information for the medical community.

Abstract

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Christopher Butson 1 , A. Alexopoulos 2 , D. Nair 2 and I. Najm 2 ( 1 Biomedical Engineering, Cleveland Clinic, Cleveland, OH and 2 Epilepsy Neurology, Cleveland Clinic, Cleveland, OH )

Rationale: Resective surgery is one of the few treatment options available for patients with pharmacoresistant epilepsy. The goal of these surgeries is to eliminate seizures with minimal loss of brain function. Prior to surgery, subdural electrode grids are implanted to map epileptic and functional areas. This method has been successfully used for many years, but little is known about the interactions between the applied electric field and the response of cortical neurons. However, important clinical decisions rely on implied correlations between the electrode location, the estimated spread of stimulation, and the cortical tissue planned for resection. In turn, there is a need to improve understanding of the neural response to cortical stimulation.

Methods: We addressed this question with an interactive system that was developed to predict the volume of tissue activated (VTA) based on patient-specific models of the electrode, electric field and neural response to cortical stimulation. The system uses the finite element method (FEM) to create a discretized brain volume with cortical surfaces constructed from MRI, electrode positions determined from CT, and electrical conductivity tensors determined from diffusion tensor MRI (DTI). VTAs were determined from simulations where the electric field from the stimulating electrodes was imposed on populations of pyramidal cell model neurons placed within layers 5/6 of cortex. VTA estimates were defined based on the position and orientation of cortical electrode(s) and the stimulation waveform within a realistic, patient-specific brain volume.

Results: In a retrospective study of a 20 year old patient we found that the position of the electrode and amplitude of stimulation both had important modulatory effects on the VTA, which was dependent on the proximity of the electrodes to the cortical surface and the thickness of the cerebrospinal fluid layer beneath the electrodes. Both of these factors were correlated with the impedance of the electrode, which may be useful for parameterizing models in multi-patient studies. Further, the inclusion of realistic cell models and DTI-based conductivities each had a strong effect on the VTA as indicated by its complex, non-spherical shape. Model validation is currently underway in a prospective study with clinically measured responses during stimulation of sensory and motor cortex.

Conclusions: Our long-term goal is to use these methods to improve the accuracy and efficacy of cortical mapping with subdural grid electrodes, and to enhance understanding of the interaction between cortical stimulation and physiological responses for epilepsy patients.

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Gina M. Jetter 1 , L. M. Moreno 1 , S. J. Rogers 1 and J. E. Cavazos 1 ( 1 Medicine (Neurology), Pharmacology, South Texas Comprehensive Epilepsy Center, UTHSCSA, San Antonio, TX )

Rationale: HMG-CoA reductase inhibitors, or statins, are the most commonly prescribed lipid lowering agents in the United States. Statin therapy has been shown to reduce cardiac mortality, a frequent co-morbidity in geriatric epilepsy. Cytochrome P450 (CYP450) in the liver, specifically isoenzyme 3A4, metabolizes simvastatin, atorvastain and lovastatin. Some anti-epileptic drugs (AEDs) induce the metabolism of CYP3A4, leading to an increased statin metabolism, lowering statin serum concentrations and half-life. It is not known whether this drug interaction leads to higher cholesterol, cardiovascular events, or higher statin dose utilization. The objective of our study was to examine drug utilization and cholesterol levels in epilepsy patients who were chronically taking AEDs and statins. We examined whether differences in statin drug utilization exist between patients taking EIAEDs and those taking Non-enzyme inducing AEDs (NEIAEDs).

Methods: This study is a retrospective analysis of men and women veteran patients who attend an out-patient seizure clinic at the Audie L Murphy VA in San Antonio, TX. The subjects were taking AEDs for epilepsy and simvastatin for hyperlipidemia, the first line cholesterol lowering agent at the VA. The patients must have been on at least one AED and simvastatin for 6 months prior to cholesterol levels being drawn. Medications dosing and type were reviewed and cholesterol levels were analyzed. Comparisons in simvastatin dose and cholesterol levels were made between patients taking EIAEDs and NEIAEDs and were analyzed using the standard t test with unequal variance.

Results: The retrospective analysis consisted of 105 patients, 102 men and 3 women who were taking simvastatin (10 mg–80 mg daily). Sixty-four patients were on EIAEDs and 41 were on only NEIAEDs. The average daily dose of simvastin was significantly higher (p < 0.05) in the EIAED group at 46.1 (±3.14) mg compared to 34.9 (±3.13) mg in the NEIAED group (Table 1). Further analysis examined the difference in cholesterol levels and LDL in the two groups. The differences between total cholesterol and LDL levels between the 2 groups are seen in Table 2. The difference is not significant.

Conclusions: The present retrospective study in a routine clinical care scenario demonstrates a significant difference in simvastatin doses between patients taking on EIAEDs and NEIAEDs, suggesting that patients on EIAEDs require larger doses of simvastatin for optimal cholesterol levels. Although the differences in total cholesterol levels and LDL between patients taking simvastatin and either EIAEDs or NEIAEDs was not significant, there was a trend for worse cholesterol lowering effect among patients taking EIAEDs despite taking on average a higher dose of simvastatin as compared to those taking NEIAEDs. The data suggests that the drug interaction between simvastatin and EIAEDs might be of clinical significance. Further studies are needed to assess whether this relatively silent drug-drug interaction increases the risk for cardiovascular morbidity and mortality.

Mean Dose of Simvastatin

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*EIAED include phenytoin, phenobarbital, carbamazepine, oxcarbazepine, felbamate.

Average Cholesterol Levels in Patients on EIAEDs vs NEIAEDs

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Abstract

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Kaiwen Lin 1 and S. R. Benbadis 1,2 ( 1 University of South Florida, Tampa, FL and 2 Tampa General Hospital, Tampa, FL )

Rationale: The over-interpretation of EEGs is common and is an important contributor to the misdiagnosis of epilepsy. We reviewed our experience in order to clarify which EEG patterns are commonly over-read as epileptiform.

Methods: We identified patients who were seen at our epilepsy clinic and were ultimately diagnosed with conditions other than epilepsy. We selected those who had previously had an EEG read as showing epileptiform discharges, and whose EEG was available for our own re-review.

Results: A total of 37 patients met the above criteria. Eventual diagnoses were psychogenic nonepileptic seizures in 10, syncope in 7, other miscellaneous diagnoses in 5 (TIA, dementia, presyncope, migraine, hypnic jerks), and 15 unexplained nonspecific symptoms. None of the EEGs had epileptiform discharges. The descriptions of the abnormalities included “temporal sharp waves” in 30, “frontal sharp waves” in 2, and “generalized spike-wave complexes” in 2. Three had no reports available to identify the alleged abnormality.

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The benign patterns mistaken for temporal (30) and frontal (2) sharp waves were simple fluctuations of background activity with anterior or midtemporal phase reversals [see figure]. Some meet criteria for wicket spikes. The 2 benign patterns mistaken for generalized spike-wave complexes were non-specific intermittent rhythmic slowing (“FIRDA”) related to hyperventilation.

Conclusions: By far the most common pattern over-read as epileptiform are non-specific fluctuations of background in the temporal regions (or wicket spikes) misread as temporal sharp waves.

Typical sample of the EEG pattern that is by far the most common one to be mis-interpreted as epileptiform. This can be described as benign fluctuations of background in the temporal regions, or as wicket spikes.

Abstract

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Jose Maria Fernandes 1 , F. Sales 2 and J. P. Silva Cunha 1 ( 1 IEETA/DETI, University of Aveiro, Aveiro, Portugal and 2 UMES/Dept Neurology, HUC, Coimbra, Portugal )

Rationale: Assessment on MTLE lesion epileptogenicity is crucial in early diagnostic stages of surgery candidates. EEG and source analysis (SA) techniques provide a good non-invasive option. Their drawback is that SA methods are demanding from the user as it implies (a) spikes selection, (b) spike type separation (clustering) and (c) careful judgment in SA results interpretation to exclude clinically unreasonable solutions.

We evaluated EPIGAUSS - a new epileptologist-friendly software for spikes SA - in the assessment of the EEG focus location over a population of 7 patients with MTLE.

Methods: For each patient the user just has to provide a spikes selection group (from visual or automated detectors) that fits the clinical conventions. All spikes (average 203 detections per patient) are then processed automatically by EPIGAUSS. The system starts by fitting spikes with a single moving dipole algorithm using a standard headmodel in a 1 seconds interval centred in the spike selection. For each patient, dipole solutions are time aligned using two criteria based on dipole solution features: (a) best goodness of fit (GOF) and (b) maximum magnitude (MAG) latencies. For both latencies, dipoles are spatially clustered using an automatic cluster analysis algorithm. The dipoles and clusters are then co-registered onto the standard model as dipole densities and both the dipole and clusters maximum density were compared with both EEG focus information and the MTLE information extracted from anatomical MRI analysis to assess their clinical lateralization value. A 75% of overall cluster density threshold was used.

Results: The dipole density at GOF provided a correct identification of the side of the lesion in all but one case where no laterality could be established. The identified dipole clusters were also in the side of the MTLE lesions (5 in the depth). Both the dipole density maximum and the dipole clusters associated at MAG latency were at the surface in temporal and frontal areas in the side of EEG focus in all patients. Clusters involving non adjacent brain areas were discarded from the analysis.

Conclusions: By combining the dipole density and clusters information on individual spikes at both GOF and MAG latencies correct information on the laterality of the lesion and EEG focus was obtained. The method produces results in an automated way, with no user involvement in the tedious spike type separation task of other methods. This protocol is a pragmatic non-invasive alternative to more complex approaches based on SA. Furthermore, by keeping the spike time relation, it may provide further information on the source stability and spread of the epileptogenic activity. Finally, given the visualization scheme used (colour coding over MRI), result interpretation is very straightforward and similar to other brain imaging techniques (fMRI, etc.).

Patient data and EPIGAUSS lateralization

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Fr - Frontal; Tp - Temporal; Ms - Mesial; R - Right; L - Left; GOF - at goodness of fit latency; MAG - at maximum dipole magnitude latency

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Abstract

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Sean Lanigar 1 and L. Selwa 1 ( 1 Neurology, University of Michigan Medical Center, Ann Arbor, MI )

Rationale: Assessment of heart rate variability (HRV) via spectral analysis can used to measure the autonomic cardiac function. One can separately measure the sympathetic and parasympathetic components of the spectrum. Reduced HRV has been shown to predict increased mortality and risk of sudden death, including patients with epilepsy. Previous studies have typically looked at 5 minute Epochs over a 24 hour period or an isolated 1 hour period. In this study we wanted to ascertain whether the data collected from one 5 minute epoch of EEG data during a standardized time could be used to differentiate the autonomic cardiac function between patients with epileptiform abnormalities on EEG and those who do not.

Methods: We retrospectively reviewed the baseline portion of 39 patient monitored in our adult epilepsy monitoring unit along with the heart rate data which is recorded with the EEG. We chose to review a five minute portion of the ECG during the baseline without activating procedures. The R-R intervals were then analyzed and the heart rate variability was determined via time domain measures and frequency domain analysis.

Results: Of the 39 patients analyzed, 20 patients had no epileptiform abnormalities on their EEG monitoring and 19 patients had epileptiform abnormalities or captured seizures on their EEG recording. Of the patients with epileptiform abnormalities on their EEG, 6 of those patients were presurgical evaluations who have medically refractory epilepsy. When the group of patients with no epileptiform abnormalities on their EEG monitoring is compared to the group of patients with epileptiform abnormalities, we see the only statistically significant differences between the groups low frequency (LF) components (p = 0.05). When we compare those patient who are assumed to have more refractory epilepsy (i.e. those patients in the presurgical group), to the patients with no epileptiform abnormalities on their EEG monitoring, we continue to see statistically significant differences in LF components (p = 0.03). We also see statistical significant differences in R-R variability (SDNN) (p = 0.05).

Conclusions: Using spectral analysis of heart rate variability, we were able to confirm that there are some components of heart rate variability (LF) which are statistically different in patients without epileptiform abnormalities on EEG and those with epileptiform abnormalities in a short 5 minute epoch. Furthermore, in patients who are assumed to have refractory epilepsy, there continues to be differences from those patients with no epileptiform abnormalities in LF, but we also start to differences in SDNN. We think that this study helps to demonstrate that measurable differences can be seen even in short term recordings. Typically a routine EEG is recorded over 30 minutes. Normally there is at least 5 minutes during that recording when no activating procedures are done. This might offers us a new way of measuring HRV in a larger population without specialized equipment and ultimately help in better ascertaining which epilepsy patient are at increased risk for sudden death.

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Michael Y. Xu 1,2 , E. Ergene 1,2 , R. N. Kawasaki 3 , N. A. Machens 1 and E. M. Spangler 1 ( 1 Neurology, OSF St. Francis Medical Center, Peoria, IL ; 2 Neurology, University of Illinois College of Medicine at Peoria, Peoria, IL and 3 Cardiology, Midwest Heart Specialists, Fox River Grove, IL )

Rationale: Long QT syndrome (LQTS) is a disorder resulting in ventricular tachyarrhythmia and sudden death. The mortality rates is estimated to 77% without treatment and 7% under treatment. It is less recognized that LQTS may initial present as syncope with convulsions and be interpreted as epilepsy. We report a LQTS case with sudden onset of ventricular tachyarrhythmia: Torsade de Pointes (TdP), presenting as epileptic seizure during inpatient video-EEG monitoring.

Methods: Case report: An 18-year-old woman had a one-year history of episodic spells. The spells were characterized by sudden onset loss of consciousness with arms stiffening, fingers curling, foaming from the mouth, and body arching back. Afterward she felt generalized weakness without significant confusion. The spells occurred 2–3 times per-month. An MRI of the brain was normal and an EEG reportedly abnormal due to “a 2 second burst of high amplitude, sharp and slow wave discharges in the range of 3 Hertz.” She was treated with zonisamide 400mg daily and levetiracetam 1500mg bid, still had 2–3 spells per month prior the visit at our institution. She was healthy previously. There is no family history of seizures. A paternal aunt had sudden death at age 21-year-old with unknown etiology.

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Results: A 4 days inpatient continuous video EEG was performed. On day number 4, she developed a typical spell. The spell occurred upon awaking from sleep. The EKG suddenly converted to a polymorphic ventricular tachycardia consistent with TdP. It lasted 2 minutes and 10 seconds, then became more idioventicular before reverted back to sinus rhythm. The Video recording showed that 9 seconds after developed TdP she developed her typical spell identical as described before. EEG demonstrated normal waking EEG acutely changed to high amplitude 1.5 to 3 Hz delta activities 22 seconds after she developed TdP. It lasted 1 minute 37 seconds, then turned to diffuse background suppression and 1.5 to 2 Hz delta slowing. The EEG was back to alpha rhythm 15 seconds after the EKG reverted back to sinus rhythm. The rest of the 4 days of EEG was normal.

Cardiology was consulted. An EKG demonstrated normal sinus rhythm with prolonged QT (corrected QT interval 0.50 seconds). A beta blocker was started and a cardioverter-defibrillator and atrial pacing were implanted subsequently. Antiepileptic medications were discontinued. Follow up for 4 months, no further events were noted clinically, nor via device interrogation.

Conclusions: Our case demonstrated how LQTS related syncope can cause convulsion and be interpreted as epilepsy with delays in both diagnosis and treatment. Our case also showed that acute cerebral hypoxia can cause high amplitude rhythmic or semi-rhythmic delta activities in EEG which may mimic a generalized spike wave discharges. Since there is very high mortality without treatment and specific and effective therapy is available, LQTS should be considered in differential diagnosis whenever there are atypical epileptic seizure features or if there is no response to antiepileptic medications.

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Andrea O. Rossetti 1 , G. Logroscino 2 , T. A. Milligan 3 , C. Michaelides 4 , S. Replansky 3 and E. B. Bromfield 3 ( 1 Neurology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland ; 2 Harvard School of Public Health, Boston, MA ; 3 Neurology, Brigham and Women's Hospital, Boston, MA and 4 Neurology, Massachusetts General Hospital, Boston, MA )

Rationale: Status epilepticus (SE) treatment may be administered with different levels of intensity, from small benzodiazepine doses to coma induction (CI). For different SE subgroups, it is still unclear how the risk of an aggressive therapeutic approach balances with outcome improvement. We recently developed a clinical prognostic score (Neurology 2006;66:1736–8) to provide clinicians with a practical tool to orient therapeutic management. It relies on the assessment of age (0 or 2 points, cutoff at 65), previous history of seizures (1 point if negative), seizure type (0–2 points) and extent of consciousness impairment (1 point if stuporous or comatose), assessed before treatment institution; a score of 3–6 is defined as unfavorable (see Table 1). The aim of this observational study was to validate the score in a heterogeneous cohort, and to analyze its potential impact on the choice of the SE treatment strategy, particularly CI.

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[ Table 1. SP = simple partial; CP = complex partial; GC = generalized convulsive; NCSEC = non-convulsive status epilepticus in coma ]

Methods: Demographical, historical and clinical variables of consecutive adult patients with SE were prospectively collected in 3 tertiary referral hospitals in the USA (BWH and MGH) and Europe (CHUV) over different time spans. The score was calculated after treatment institution but before outcome assessment (at discharge). Chi square, Fisher's exact and ANOVA tests were used to compare the variables of interest among the centers. The score's prediction for survival was assessed with the negative predictive value (NPV). A propensity score for CI was calculated using all potential variables, and effect of coma induction on survival estimated using propensity-based matching.

Results: The cohort consisted of 135 patients (BWH 61, CHUV 60, MGH 14). As compared to mortality, which occurred in 23% (see Table 2), the score had a sensitivity of 94% (95% CI: 79–98%), specificity of 58% (95% CI: 48–67%), NPV of 97% (95% CI: 89–99%), and an accuracy of 77%. Among surviving patients, likelihood of return to baseline clinical conditions was considerably higher for subjects with a favorable score (P = 0.001). CI was more frequent at BWH (P = 0.003), but age, previous history of seizures, SE etiology, SE seizure type, extent of consciousness impairment before treatment, time to treatment, score severity, and mortality were statistically similar among the centers. In patients with an unfavorable score, CI was related to a somewhat lower survival as compared to treatment without coma (48% vs. 66%), whereas in subjects with a favorable score, both strategies were associated with high survival (100% vs. 96%). Propensity-based estimation of CI effect on survival was non-significant (95%CI: −0.335 to 0.111).

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[ Table 2.  ]

Conclusions: The SE clinical prognostic score reliably identifies patients who will survive, and is a simple tool to use in practice. It also discriminates subjects with a good functional outcome. Our observations also suggest that aggressive treatment (i.e., coma induction) is not routinely warranted in patients with a favorable SE score, who will almost certainly survive their SE episode. A randomized trial using this score is nevertheless needed to confirm this hypothesis.

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Matthew T. Hoerth 1 , J. I. Sirven 1 , J. F. Drazkowski 1 and K. H. Noe 1 ( 1 Neurology, Mayo Clinic Arizona, Scottsdale, AZ )

Rationale: Status epilepticus (SE) is one of the most common neurologic emergencies occurring in about 200,000 patients yearly. One third of SE cases are refractory to treatment with first and second line drugs and are associated with a high mortality rate. Refractory SE is often correlated with encephalitis, metabolic encephalopathy, and anoxic injury. Rarely no cause for SE is ever found. Patients can be artificially supported for many week while multiple treatment modalities are attempted. We present four cases of a newly described syndrome of de novo refractory SE without an identified etiology with pathological correlation.

Methods: The Mayo Clinic Arizona EEG database was reviewed from 2002 to 2006 for SE tracings, as all patients with known SE had EEG to confirm the diagnosis and were subsequently monitored. Patients with refractory SE requiring medication induced coma lasting more than 1 week were extracted from the database. Demographic variables included length of SE, video EEG, lab results, therapeutic trials, history of previous epilepsy, pathology, and final outcome.

Results: Four cases of patients in refractory SE were found. All patients were female and ages ranged from 20 to 41 years old (mean 28.75). These patients had a preceding flu-like illness associated with behavioral changes one to two week prior to presentation. All past medical histories were negative for any risk factors for SE. Three of the patients began their seizure activity with generalized tonic-clonic seizures, while the other patient had fluctuating responsiveness. The duration of SE ranged from 10 to 56 days (mean 35). Video EEG demonstrated continuous nonfocal seizures or burst suppression. All of the patients were treated with multiple antiepileptic drugs (mean 8), including propofol, topiramate, levetiracetam, and inhalational anesthetics. Two patients had vagal nerve stimulators placed and one had a corpus callosotomy. No patient improved clinically. Magnetic resonance imaging did not reveal any abnormalities. Extensive infectious disease evaluation with cerebrospinal fluid (CSF) analysis yielded nucleated cells from 1 to 27 cells/mcL, and was completely negative for testable bacterial, viral, and fungal organisms. CSF glucose was normal in all patients and CSF protein ranged from 31 to 89 mg/dL. Furthermore, serum studies did not point to any specific etiology either. Two patients were treated empirically for an autoimmune etiology without benefit. All patients died from SE. Postmortem examination of the brain revealed no specific etiology, with only nonspecific changes expected from prolonged SE.

Conclusions: These four cases represent a rarely encountered refractory SE, which we termed as malignant SE syndrome. This syndrome effects young female patients and presents insidiously as a flu-like illness progressing in one to two week to refractory SE. Empiric treatment for any and all suspected causes and multiple treatments for the SE were completely ineffective with each case having a fatal result. The etiology of SE in these patients has yet to be determined.

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Barbara Schauble 3 , A. Schreiner 1 and K. Rettig 2 ( 1 Medical and Scientific Affairs, Janssen Cilag EMEA, Neuss, Germany ; 2 G.E.M., Meerbusch, Germany and 3 Medical and Scientific Affairs, Janssen-Cilag, Neuss, Germany )

Rationale: To describe long-term outcomes of topiramate treatment in epilepsy in both gender irrespective of seizure type or epilepsy syndrome (TOP-GER-11).

Methods: Male and female subjects with a diagnosis of epilepsy (ILAE, 1989) who had completed one of two recent trials with topiramate (TOP-GER-5 and TOP-GER-12) were eligible for this 12-month prospective, open-label, non-interventional trial. Patients were evaluated during their previous trial and after 3, 6, 9, and 12 months during this trial while on topiramate treatment with respect to seizure frequency, adverse events (AEs), and body mass index (BMI). A post-hoc gender-based analysis was added.

Results: The ITT population encompassed 102 patients (51% male, mean age 43 ± 17 years, range 16–78 years) were followed for a median of 19 months (maximum 22.5 months). Mean duration of epilepsy in men vs. women was 54 months (SD ± 96) vs 68 months (SD ± 138.2). AEDs used within the last 3 years prior to study inclusion showed a higher rate of CBZ use (33% vs 28%) for men and a higher use of VPA (14% vs 30%) in women in the preceding study. A higher preponderance for generalized epileptic syndromes was noted in women compared to men (66% vs 48%). Women were more likely to be switched due to side effects (50% vs 35%) or lack of efficacy (48% vs 25%). Initial TPM monotherapy was more frequent in men (52% vs 36%) than women. 58% of women (vs 38% of men) used concomitant medication. At endpoint, median dose of TPM was 100mg/day for both genders, which corresponded well to the doses used in the previous trial. 73% of patients were seizure free for at least 12 months with no gender differences. There was practically no change between response rates comparing results at final visit of the previous trials and final visit in the current trial. Mean BMI decreased from 26.05 kg/m2 (male subjects, SD ± 3.6) to 25.73 kg/m2 (end initial trial) and 25.56 kg/m2 (long-term trial endpoint) (p < 0.02). In women, BMI decreased from 26.86 kg/m2 (SD ± 5.8) to 25.94 and 25.50 kg/m2 respectively (p < 0.0001). 5% of patients discontinued the long-term study prematurely due to an AE, 3% due to lack of efficacy. AEs with at least possible causal relationship reported in 5% and similarly distributed between genders were paresthesias (12%), nausea (6%), somnolence (5%), decreased appetite (5%) and memory-/concentration- disturbances (6%).

Conclusions: Long term monotherapy with topiramate resulted in sustained seizure reduction in both men and women. In addition topiramate doses remained generally unchanged and topiramate was well tolerated in both gender.

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Julie Hanna 1,2 and P. Penovich 1,2 ( 1 Minnesota Epilepsy Group, PA, St. Paul, MN and 2 Neurology, University of Minnesota, Minneapolis, MN )

Rationale: The elderly population has the highest incidence and prevalence of epilepsy. These are increasing as the population ages. Special considerations surrounding epilepsy in the elderly, including epidemiological factors, socioeconomic impact, and management, exist. While more attention is being given to these issues, it is not clear how individuals who develop epilepsy later in life (>65 years) differ from other elderly patients who developed epilepsy prior to old age.

Methods: Chart reviews were performed on 49 patients with epilepsy aged 65 years and older who are followed in an epilepsy clinic. Data were collected concerning age at onset of epilepsy; seizure type; co-morbid medical, psychiatric, and neurologic diagnoses; treatment and control of epilepsy; and level of functioning in the community in terms of independence and social interaction. Data were analyzed for all the patients as a group, and then for the subgroups of individuals with onset of epilepsy at age 65 or older (late-onset epilepsy, or LOE; n = 13, mean age = 77.3 years) versus those with epilepsy onset prior to age 65 (early-onset epilepsy, or EOE; n = 36, mean age = 73.3 years).

Results: LOE patients were more likely to be on only one anti-epileptic medication (61.5%), compared to 30.6% of EOE patients (p = .051) and were also more likely to be on ≤2 anti-epileptic medications (100%), compared to EOE patients (55.6%, p = .051). The LOE group was also slightly likely to have better control of their seizures: 61.5% LOE was seizure-free compared to 52.8% EOE (p = .60); 92% LOE had two or fewer seizures per year, compared to 72% EOE (p = .14); 19.4% of the EOE group had at least one seizure per month, while none of the LOE group experienced this (p = .089). In terms of co-morbid conditions, LOE was more likely to have cerebrovascular disease (53.8%), diagnosis of dementia or memory loss (38.5%), or cerebral neoplasm (15.4%) than EOE. In EOE group, prevalence of cerebrovascular disease was 13.9% (p = .003), dementia or memory loss was 5.6% (p = .003), and cerebral neoplasm was 2.3% (p = .11). Patients in the LOE group (74.4%) were more likely to be living at home as opposed to assisted living or long-term care facilities compared to patients with EOE (58.3%, p = .091), and were also more likely to be driving (53.8% versus 21.9%, p = .018. LOE patients were slightly more likely to be depressed (46.2%) than the EOE group (33.3%, p = .42). Fewer of those in the LOE group were working (7.7%) than those in the EOE group (19.4%, p = .34). Outcomes in terms of social and physical activity were very similar for the two groups.

Conclusions: Patients who develop epilepsy at older ages experience better seizure control, are on significantly fewer AEDs and are more likely to be driving. Trends suggest differences between the groups in independence of living, prevalence of depression and employment. This information given to new onset patients may be helpful in planning, prognosis and therapy discussions.

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David C. Wheeler 1 , J. O. Elliott 2 and L. A. Waller 1 ( 1 Biostatistics, Emory University, Atlanta, GA and 2 Neurology, the Ohio State University, Columbus, OH )

Rationale: Previous research has suggested that the incidence rate for the disease of epilepsy is positively associated with various measures of social and economic disadvantage. The Centers for Disease Control and Prevention (CDC) defined epilepsy as an emerging public health issue in its 2003 report “Living Well with Epilepsy” and emphasized the importance of epilepsy studies in minorities and people of low socioeconomic status. In response, we have utilized a hierarchical Bayesian model in a study to analyze health disparities in epilepsy rates among multiple ethnicities in the city of Philadelphia, Pennsylvania. The goals of the project were to highlight any overall significant disparities in epilepsy rates between the populations of Caucasians, African Americans, and Hispanics in the study area during the years 2002–2004 and to visualize the spatial pattern of epilepsy rates by ethnicity to indicate where certain ethnic populations were most adversely effected by epilepsy within the study area.

Methods: We implemented a hierarchical Poisson Bayesian model to estimate epilepsy rates in small-area units to account for the instability of crude rate estimates. The hierarchical Bayesian model jointly estimated the smoothed relative risk of epilepsy for the three ethnicities of interest using a multivariate conditional autoregressive prior for the area-specific log relative risks. The Bayesian model estimates smoothed rates of epilepsy by borrowing strength for areas with small populations from the neighboring areas to produce more reliable rates. It also includes an age covariate to account for potential differences in population age structure among the areas. Outputs of the model include posterior estimates of overall epilepsy risk by ethnicity, local risk by ethnicity, and the overall correlation between the rates of different ethnicities.

Results: The spatial patterns of epilepsy rates vary by ethnicity and are not explained entirely by the distribution of ethnic populations. Results of the Bayesian model indicate that Hispanics have the highest epilepsy rate overall, followed by African Americans, and then Caucasians. There are significant increases in relative risk for both African Americans and Hispanics when compared with Caucasians, as indicated by the posterior mean estimates of 2.09 with a 95% credible interval of (1.67, 2.62) for African Americans and 2.97 with a 95% credible interval of (2.37, 3.71) for Hispanics. The spatial distribution of epilepsy is more correlated between African Americans and Hispanics than it is for either of these groups with Caucasians.

Conclusions: Our experience in analyzing epilepsy data demonstrates that using a Bayesian analysis in combination with geographic information system (GIS) technology can reveal spatial patterns in patient data and highlight areas of disparity in disease risk among subgroups of the population, in this case different ethnic groups. These patterns can be examined in various ways to improve outreach efforts and patient education programs, as well as for identifying community resources where such programs could be based.

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John O. Elliott 1 and L. Long 1 ( 1 Neurology, Ohio State University, Columbus, OH )

Rationale: Health literacy is defined as the degree to which individuals can obtain, process and understand basic health information and services needed to make appropriate health decisions. Based on the 2003 US National Assessment of Adult Literacy (NAAL) 63 million people (22%) have a literacy level rated as “basic” and 30 million people (14%) are “below basic”. Minorities and the elderly have the highest rates of basic or below basic health literacy. The Institute of Medicine recommends that health related information be written at < 6th grade level. One previous study found 9th grade reading levels for printed educational materials for epilepsy. Since web based health information is being accessed by > 50 million people, a reading level assessment of the National Epilepsy Foundation of America website would be useful.

Methods: Two online programs were used to assess the reading level of the National Epilepsy Foundation (EF) website (http://www.epilepsyfoundation.org) using established readability formulas. The Flesch-Kincaid (FK) reading grade level and the SMOG were utilized primarily. The Forecast score (a new tool for assessing websites that contain content not in sentence form such as images, links and lists) and the Flesch Reading Ease (FRE) were also conducted. Text from “Understanding Epilepsy” and “Living with Epilepsy” was analyzed; text written for health professionals was excluded.

Results: One hundred and seventy-six web links were evaluated; 133 under “Understanding Epilepsy” and 43 under “Living with Epilepsy”. The mean (sd) grade level of all the links was 11.2 (2.5), 12.6 (1.9) and 11.3 (0.8) for the FK, SMOG and Forcast. The grade level range was 5.6–25.7, 7.5–20.3 and 8.6–13.4 for the FK, SMOG and Forcast. The Forcast score was highly correlated with the FK (r = .54, p = .000) and the SMOG (r = .63, p = .000) demonstrating potential validity for web-based material. One-way ANOVA comparing “Understanding Epilepsy” and “Living with Epilepsy” found no significant differences for the FK, SMOG and the FRE level; for the Forcast tool, there was a significant difference (F = 8.68, p = .004). FRE scores ranged from 5.4 to 78.0, with a mean (sd) score of 46.9 (13.1) which is considered college level. Only 4 EF web pages had a FK reading level < 6.8 (equivalent to a 6th grade rating). For the other assesments, zero web pages had < 6th grade reading level. Similar results have been found in previous reviews of cancer websites and printed pediatric educational brochures for parents.

Conclusions: The National Epilepsy Foundation website contains a significant amount of health content that may not be appropriate for patients with marginal health literacy. With up to 36% of US adults having poor health literacy, major editorial changes are needed to bring the information to the recommended reading level, especially since content from the EF website is used for patients and printed for patients in the clinic setting.

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Hal M. Corwin 1 ( 1 Medicine, University of Louisville School of Medicine, Louisville, KY )

Rationale: This case series reports the efficacy of a new parameter programming strategy for vagus nerve stimulation (VNS). The benefits of 60 second ON-time plus 1.1 minute-OFF time (duty cycle of 51%) when combined with a reduction in output current were studied in three consecutive adult patients with medically intractable epilepsy of differing etiologies.

Methods: Seizure frequencies of 3 patients with refractory epilepsy that had not adequately responded to VNS for 27–83 months were studied. Patient 1, a male aged 25 years, had tuberous sclerosis and developmental regression. Patient 2, a female aged 50 years, had idiopathic partial seizures and remote history of temporal lobectomy. Patient 3, a female aged 53 years, had mental retardation/developmental delay and Lennox-Gastaut Syndrome. Patients 1 and 3 had epilepsy for their entire lives and patient 2 for her entire adult life. The nursing staff (patients 1 and 3) or the family (patient 2) kept a diary of seizures, seizure clusters (defined as 2 or more seizures without return to baseline consciousness), for a baseline of 14 to 20 week. During baseline, the VNS duty cycle was 30 seconds ON and 1.1–1.8 minutes-OFF. Each patient's VNS generator was reprogrammed to 60 seconds ON-time and 1.1 minutes OFF-time with simultaneous 0.25–0.50 mA reduction in output current, and seizure diaries were kept for 14 to 34 week follow up. Concomitant antiepileptic drugs (AEDs) remained unchanged except for patient 3 who required an additional AED during a hospitalization.

Results: Seizure frequency was reduced for all 3 patients. Patient 1 experienced a 44% seizure reduction, and seizure-free days increased from 2% to 15%. Seizures decreased by 89% for patient 2, and seizure-free week increased from 79% to 93%. Seizure reduction was 83% for patient 3, seizure clusters were reduced by 70%, and seizure-free week increased from 0% to 44%. No adverse side effects were noted by the patients or caregivers.

Conclusions: The benefits of implementing a 60-second ON-time plus 1.1 minute-OFF time combined with a reduction in output current were apparent. All patients experienced a robust reduction in seizure frequency and increases in seizure-free days or week. The number of seizure clusters was greatly reduced in the patient afflicted with this pattern. Reducing the output current had the dual advantage of reducing the potential for side effects that might occur with the longer ON-time of 60 seconds while simultaneously lowering usage of the VNS battery. This new programming paradigm may be useful for some epilepsy patients whose seizures remain refractory at more traditional VNS settings.

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Parul Aneja 1,2 , H. Kettani 1,2 , E. Passaro 4 and P. Mullin 1,3 ( 1 Saint Vincent Catholic Medical Centers, New York, NY ; 2 New York Medical College, Valhalla, NY ; 3 NYU Medical Center, New York, NY and 4 Bayfront Medical Center Neurosciences Institute, St Petersburg, FL )

Rationale: It has recently been reported that epileptic auras were equally common (70%) among patients with idiopathic generalized epilepsy (IGE) as they were among those with localization related epilepsy. The auras reported were non specific and included “feeling light-headed”, “a strong head rush”, “feeling shaky and spacey” and similar subjective sensations. Limbic auras such as olfactory hallucinations, gustatory hallucinations and déjà vu were not observed and are usually interpreted as manifestations of localization related epilepsy. We report five patients with IGE whose seizures are preceded by classic limbic auras and were therefore, on the basis of clinical semiology and outpatient EEG misdiagnosed as localization related epilepsy.

Methods: Patients were identified from a larger group with intractable seizures and poor response to the antiepileptic drug (AED) regimen who were referred to a comprehensive Epilepsy Center. Four of the five patients had been diagnosed with and treated for localization related epilepsy based on the clinical presentation and outpatient EEG. One patient had been diagnosed with attention deficit hyperactivity disorder. All patients subsequently underwent a comprehensive history and physical and an epilepsy protocol MRI. Four of the five patients underwent video-telemetry monitoring.

Results: Four patients had generalized convulsive seizures and one patient had absence seizures. All five patients had auras lasting from 10 seconds to a minute preceding their seizures. The auras were an olfactory hallucination (two patients), olfactory and gustatory hallucination (one patient) and a feeling of déjà vu (two patients). All patients had onset of seizures in adolescence. Four patients were diagnosed with localization related seizures and had several years (average 27.7 years) of poor response to the chosen anti epileptic drugs including phenytoin (three patients), carbamazepine (three patients) and oxcarbazepine (one patient). All patients had a normal neurological exam and a normal epilepsy protocol MRI. Three patients had focal abnormalities on interictal EEG. Video-telemetry monitoring was performed in four patients. All five patients were determined to have a syndrome of IGE and had a complete resolution of their seizures when treated with a broad spectrum AED.

Conclusions: Patients with IGE may have seizures preceded by limbic auras. Clinical semiology and interictal EEG were misleading in our patients and led to a delay in appropriate therapy for several years. Video-telemetry should be performed earlier in patients with a poor response to AEDs in order to ensure appropriate characterization of seizure disorder and anti convulsant therapy.

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Dietrich Blumer 1 , S. Rice 2 and B. Adamolekun 3 ( 1 Psychiatry, University of Tennessee, Memphis, TN ; 2 Family Practice Clinic - St. Francis, University of Tennessee, Memphis, TN and 3 Neurology, University of Tennessee, Memphis, TN )

Rationale: Over the past 20 years, in the course of our efforts to treat a large number of patients with nonepileptic seizure disorder (NESD), we used electroconvulsive treatment (ECT) only in a few cases with episodes of suicidality or psychotic features requiring hospitalization. Three of four patients were treated successfully for the episodes with a few ECTs; the most severely ill patient had to be maintained with monthly ECTs for 13 years through the present. Severity of abuse, always present in the early history, coincided with severity of the NESD. All patients with severe NESD have been female, as expected in a disorder that formerly was identified as “hysteria” (1).

Our recent study of patients with both epileptic and nonepileptic seizures (2) showed that excessive treatment for epilepsy worsens the NESD, while decreasing the antiepileptic treatment and allowing the risk of some epileptic seizures results in remarkable improvement of the patients' NESD. Consequently, we began to use ECT for patients with disabling NESD (with very frequent seizures, persistent pain, depression and anergia) in the absence of any concomitant epileptic seizures.

Methods: The subjects were selected from the most severely ill and intractable patients with NESD referred to us. They received usually an initial series of six ECTs (with bifrontal stimulation) during the first 2 week, followed by maintenance treatment as needed.

Results: Our current series of systematic use of ECT for the patients with severe intractable NESD includes 12 patients seen over the past 18 months. One patient refused further treatments after two ECTs because she had become more disturbed, and a second patient, who had improved, refused further treatments after eight ECTs because of headaches subsequent to the treatments. A third patient was relieved of her major seizures but became hesitant to continue after nine ECTs because of ill effects ascribed to the treatments. The other nine patients improved remarkably after a series of about six ECTs, but required maintenance treatments after 1 to 5 months. The therapeutic effect included a marked relief of the seizure frequency and significant improvement of pain, depressive mood and anergia; their progress at this point of follow-up can be rated from excellent to satisfactory.

Conclusions: The remarkable therapeutic effect of epileptic seizures on NESD, as observed in patients with both ES and NES, is replicated by the treatment with ECT of patients with severe NESD. The polarity between the epileptic and the nonepileptic disorders in the paroxysmal disorder sphere appears akin to the well-known polarities between mania and depression in the affective sphere and between paranoia and catatonia in the schizophrenic sphere (3).

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Miguel E. Fiol 1 , D. Hammerschmidt 1 and C. Gilbertson 1 ( 1 Neurology, Univ of Minnesota, Minneapolis, MN )

Rationale: Immune-mediated mechanisms has been postulated for some primary epilepsies, especially in Rasmussen's encephalitis. Inflammatory reactions have been reported (McNamara, 1999) in surgical specimens from some patients who had temporal lobectomies for refractory epilepsy.Mantegazzaa et al (2002) reported the presence of anti-GluR3 antibodies against peptides A and B in patients with Rasmussen's(RE) (n = 11), an other epilepsies (n = 85) and concluded they were specific for epilepsy not RE.

We had the opportunity of evaluating two women with adult onset progressive focal seizures and neurlogical deficit where no etiology was found and where a primary immune-mediated focal encephalitis was postulated and treated with steroids and ultimately IVIG.

Methods: A 35 years old white woman presented with the first left simple partial sensory-motor seizure that progressed to a generalized tonic-clonic. Extensive medical,infectious, immunological and neurological work up was negative except for an MRI where an incidental, small, temporal encephalocele. 5 FDG PET scan was normal.EEG studies showed severe, persistent focal right temporo-parietal slow wave and spike abnormalities.Her past medical history was unremarkable except for idiopathic primary ovarian failure. Her seizures persited in spite of multiple anti-convulsants and she developed a mild motor deficit in her left foot.

A 33 years old healthy woman developed episodes of speech arrest and progressive dysphasia associated with severe progressive EEG changes and MRI evidence of varying cortical abnormalities with T2 non-enhancing hyperintenisities in the left parietal and frontal areas without diffusion changes. Cerebral angiogram was normal.Her extensive work-up was also negative for all infectious, immunological and other possible etiologies. Multiple anti-convulsants with therapeutic levels failed to control her seizures. She failed a steroids course,and her speech deteriorated.

Results: Case 1: After failing IV steroid course, IVIG was administered in dose of 0.5 gm/kg/day on 4 consecutive days and repeated in 2 week. There was progressive resolution of focal seizures and deficit. The treatment was associated with transient neutropenia and thrombocytopenia thought due to complement activation. Her EEG studies improoved, and her anti-convulsants were reduced.

Case 2: IVIG course has been started (0.5 gm/kg) after failure of IV steroid therapy and persistent medically refractory seizures and speech deterioration.

Conclusions: Two cases of women with insidious, progressive focal encehalitis picture where treated with IVIG. One responded gratifyingly to the administration of IVIG. With the exception of primary ovarian failure, neither woman had any suggestion of prior auto-immunity. The possible role of immune process in some focal epilepsy is reviewed.

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Martina Vendrame 1 , Z. Haneef 1 and M. P. Jacobson 1 ( 1 Neurology, Temple University, Phialdelphia, PA )

Rationale: Complex partial status epilepticus (CPSE) is a major diagnostic and therapeutic challenge for the modern neurologist. Clinical features of this disorder may be very subtle and hard to recognize causing misdiagnoses and improper treatment. The diagnosis is mainly dependent on EEG. When EEG is equivocal, clinical and electrographic response to medications can be helpful.

Methods: In this study, we retrospectively reviewed the incidence, management, efficacy of medical treatment and outcome of CPSE and ARCPS in our institution over the last 3 months.

Results: Fifteen subjects were identified. Most were admitted because of seizures (65%). For 20%, the reason of admission was documented as “change in mental state” and included descriptions of transient unresponsiveness, staring, aphasia and “inappropriate behavior”. Fifty-seven percent of patients had prior epilepsy or seizures. In most subjects CPSE was recognized at admission (79%). Others developed CPSE later, ranging from within 2 days (7%) to 2 week (14%) from admission. Brain Imaging revealed the presence of acute stroke (22%), anoxic brain Injury (22%), Intracranial hemorrage (14%), tumor (14%), mesiotemporal sclerosis (7%), foreign body (7%) or no pathology (14%). All subjects were placed on long term monitoring (LTM), on the floors (43%) or in the ICU (57%). In most cases (10 out of 15 patients) CPSE was managed with phenytoin, phenobarbital and levetiracetam. Other AEDs included valproate and carbamazepine. In 3 cases adjunctive therapy with topiramate was necessary for resolution of the status. For 1 subject add on therapy with zonisamide was preferred. Complete electrographic resolution of seizures was achieved within an average of 5 days from onset. Sixty-two percent of patients were discharged home and 2 patients expired, both of multi-organ failure, not of brain pathology. This cluster of 15 subjects resulted in a doubling of long term EEG monitoring usage in comparison to previous quarters.

Conclusions: Many patients with CPSE and ARCPS present with vague symptoms generally labelled as “change in mental state”. A higher index of suspicion is needed to identify these cases earlier. LTM was necessary for establishing a diagnosis and was helpful in diagnosis of unclear cases. Most individuals responded to one or two AEDs. CPSE and ARCPS comprise a diverse group with multiple etiologies for brain pathology. Some subjects respond rapidly to therapy but better therapeutic strategies for those with refractory seizures are needed. Additional prospective studies will help in determining the best therapeutic strategy.

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Lucretia Long 1 and J. Elliot 1 ( 1 Neurology, The Ohio State University, Columbus, OH )

Rationale: Prior studies suggest that up to a third of patients with uncontrolled seizures continue to drive despite medical restrictions. Motor vehicle morbidity and mortality has occurred secondary to accidents caused by patients with intractable epilepsy (PWE). Many studies have identified variables that correlate with driving and epilepsy: Age, employment status, and fewer AEDs predict the likelihood of driving with uncontrolled seizures. Although this is helpful, there are no studies assessing perceived risk associated with driving in this population. In addition, there are limited data exploring perceptions of transportation resources for PWE. The purpose of this study is to assess health behavior concepts related to driving in PWE. This study also explores perceived availability of transportation resources.

Methods: This is an exploratory, cross-sectional study design. Persons with epilepsy were invited to complete a three page, 46-item questionnaire emphasizing demographics and health behavior concepts. Participants were identified through mailing list, EFA WEB sites and an outpatient clinic. To maintain confidentiality, identification data were not collected.

Results: Ninety-four patients completed the survey. There were no significant differences between gender, age and income for 6 health behavior scales: concern, attitudes, severity/susceptibility, barriers, social support and self-efficacy. Non-Caucasians reported higher levels of general health concern than Caucasians (F = 6.20, p = .015). Eighteen percent of patients were not completely honest with their doctor when disclosing seizure control due to the desire to drive. Persons not honest about seizure frequency had a higher level of perceived barriers for changing driving behavior (F = 4.29, p = .042). Fifty-three percent were unaware of state driving laws. Although 98% were aware that having a seizure while driving could cause injury or death, only 20% reported being counseled about the risk. Forty-two percent felt that drivers were best qualified to judge their ability to drive. While 67% agreed that family members would support changes related to driving, 43% did not want to ask family/friends to assist with transportation. Forty-one percent felt that changing driving behavior was not possible because family/friends were unavailable. Thirteen percent believed that since “things just happen”, one should not be concerned with accident prevention. Forty-four percent believed that changing driving patterns was not possible due to a lack of transportation resources.

Conclusions: While current interventions focus on disclosure and injury associated with driving and uncontrolled seizures, this study supports the need to also address perceived barriers when counseling PWE. To minimize at risk behavior, counseling interventions and outreach programs should also focus on increasing awareness of current resources and enhancing transportation options for PWE.

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Ahmad Alwan 1 , M. Al-Kaylani 1 , B. Malow 1 , Y. Song 1 and B. Abou-Khalil 1 ( 1 Neurology, Vanderbilt Medical University, Nashville, TN )

Rationale: Sleep is known to activate interictal epileptiform discharges and widen their field. Secondarily generalized tonic-clonic seizures (SGTCS) are more common in sleep, but it is not known if sleep has an effect on the field of ictal discharges at onset or if it influences the clinical manifestations of SGTCS.

Methods: We investigated the difference between waking and sleep onset SGTCS in patients that had seizures recorded in the epilepsy monitoring unit (EMU) both in waking and in sleep. Patients were identified by reviewing all reports from the Epilepsy Monitoring Unit database over 3 years. One SGTCS in waking and one in sleep were chosen for analysis based on technical factors. We recorded the clinical semiology of the partial phase and the duration of each of the partial, tonic, and clonic phases; the latency from the first EEG sign to the first clinical sign; focality of onset; degree of artifact masking onset. Statistical analysis was done using the Wilcoxon Singed Rank test to analyze the durations of each seizure phase, Mcnemar's test to evaluate the extent of masking artifact, and Bowker's test to analysis the degree of EEG onset focality. The study was approved by the Vanderbilt IRB.

Results: There were 16 patients. The mean age was 36 (range 7–58). The localization was temporal in 6 patients, frontal in 4, general in 3, frontotemporal in 1, multifocal in 1, and unclear in 1. The mean total seizure duration was 1.62 minutes in sleep and 1.38 minutes in waking. The mean partial phase duration was 0.72 minutes in sleep and 0.5 minutes in waking. The partial phase was almost nonexistent in the patients with frontal lobe epilepsy. The mean tonic-clonic duration was 0.89 minutes in sleep and 0.87 minutes in waking. The latency from first EEG changes to first clinical changes was 0.35 minutes in sleep and 0.15 minutes in waking (p = 0.2). Artifact was present at seizure onset in waking and sleep in 7 patients, absent in both in 6, present in waking but absent in sleep in 2, and present during sleep but absent in waking in one patient. The ictal EEG pattern at onset was similar in waking and sleep, except in two patients. One of these had an ictal EEG onset with generalized irregular slow activity followed by generalized rhythmic activity in waking, but generalized rhythmic activity in sleep. Another patient had an ictal EEG onset with generalized attenuation followed by focal rhythmic activity in waking but focal irregular slow activity followed by focal rhythmic activity in sleep.

Conclusions: No significant differences were found between sleep onset and waking onset seizures, in the seizure semiology of the partial phase or in the duration of the seizure and its partial and tonic-clonic phases. The latency from first EEG change to first clinical change tended to be longer in sleep (p = 0.2).

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Thaddeus Walczak 1 , J. Beattie 1 , T. Tran 1 and J. White 1 ( 1 MINCEP Epilepsy Care, Minneapolis, MN )

Rationale: Frequency, clinical features, and mechanisms of seizure related asystole are poorly understood. This information may promote understanding and prevention of sudden death in epilepsy (SUDEP).

Methods: Case series of seizure related asystole encountered during video-monitoring in an adult inpatient epilepsy unit over a 2 year period.

Results: Seizure related asystole occurred in 5/504 patients (1%). Age range was 28–60 years, epilepsy duration 1–23 years. 12 lead EKG was normal in 2 and showed sinus bradycardia in 3. Echocardiography and interictal cardiac telemetry (range 3–12 days) were normal in all cases. Only one patient had a risk factor for cardiac disease. Twelve seizures were recorded, 6 with asystole, 3 with significant bradycardia (nadir 20–36 beats per minute), 3 without significant arrhythmia. 6/9 seizures with bradyarrythmia were complex partial, 4/9 started in right hemisphere, and seizure onset area was always hemispheric or parasaggital. Seizure duration at onset of asystole ranged from 34–206 sec. Mean duration of asystole was 24 seconds (range 4–70 sec). One tonic-clonic seizure was followed by severe bilateral EEG suppression, a 70 sec central apnea, and severe oxygen desaturation; in this seizure, a 43 sec asystole started 65 sec after seizure termination. This “near SUDEP” was the only case of postictal asystole. Cardiac pacemakers were implanted in all cases. Seizures persisted but collapses decreased in all.

Conclusions: Gross cardiac pathology does not appear to play an important role in seizure related asystole. Our observations suggest two different mechanisms for this condition. In one group more than 30 seconds of medial hemispheric seizure activity induces ictal asystole and secondary generalization is not necessary. This is consistent with a report of asystole induced by stimulation of the cingulate gyrus (Epileptic Disord 2007;9:77–81). Less frequently, severe cerebral suppression following a tonic-clonic seizure results in prolonged postictal central apnea followed by asystole. This is consistent the animal model of SUDEP and a previously described “near SUDEP” case (Epilepsia 2000;41:1494–7).

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Keiko Hino 1 , T. Hori 1 , T. Imaoka 1 , K. Arai 1 , M. Watanabe 1 , Y. Watanabe 1 , M. Kato 2 , Y. Motonaga 1 and K. Honda 1 ( 1 National centre of neurology and psychiatry, Kodaira, Japan and 2 Musashino-Kokubunnji Clinic, Kokubunji, Japan )

Rationale: Convulsive seizures and an unconsciousness state frequently manifest as withdrawal syndrome, when alcohol- and substance-dependent patients cease drinking or taking drug abruptly. However some patients have seizures or unconscious state with causes unrelated to alcohol or drug withdrawal. We investigated the causes of seizures and unconsciousness state in 23 inpatients in the alcohol dependence treatment ward of a psychiatric hospital from January 2005 to May 2007.

Methods: 23 patients (20 males; 3 females) were included in the study. The clinical records of these patients were reviewed retrospectively for information of alcohol and drug history as well as diagnosis of withdrawal seizure or other clinical states according to DSM-IV and ICD-10. Blood and urine tests, electroencephalograms (EEG), as well as radiological imaging such as CT, MRI, SPECT were conducted in all cases.

Results: Clinical symptoms: Generalized tonic clonic seizure (GTC) was observed in 18 of 23 patients (78.2%). Of 18 patients, 2 developed status epilepticus, 2 had complex partial seizure (CPS), and 1 had secondary GTC. One of 23 patients (4.3% of all cases) had myoclonus. An unconsciousness state was observed in 2 patients (8.6%). Other symptoms suspected to be related to epilepsy were observed in 2 patients (8.6%).

Clinical diagnosis: Withdrawal seizure was diagnosed in 14of 23 cases (56.5%), however withdrawal seizure appeared one week after cessation of drinking in 1 case. Epilepsy was diagnosed in 5 of 23 cases (21.7%), and pseudo seizure in the remaining 4 cases (17.4%).

Complications (including multiple responses): Somatic disorders comprised alcoholic liver injury in 3 cases, as well as alcoholic liver cirrhosis, hepatitis C, diabetes mellitus, and malignant rheumatoid arthritis in 1 case each. Neuropsychiatric disorders consisted of epilepsy in 5 cases (in which 3 cases was post-traumatic epilepsy), as well as sequela of herpes encephalitis, frontotemporal dementia, mental retardation, schizophrenia, factitious disorder and personality disorder in 1 case each.

Conclusions: 1. Post-ictal twilight state should be considered as a differential diagnosis of pathological and complex drunkenness state in alcohol-dependent patients.

2. While the majority of withdrawal seizures are GTCs, CPSs were also observed in 2 patients.

3. Pseudo seizures were observed only in patients with psychiatric complications (frontotemporal dementia, mental retardation, schizophrenia, and factitious disorder).

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Julie Roth 1,2 , D. T. Sundstrom 1 , S. Kempe-Mehl 2 and K. B. Krishnamurthy 1,2 ( 1 Neurology, Beth Israel Deaconess Medical Center, Boston, MA and 2 Harvard Medical School, Boston, MA )

Rationale: Approximately half of all women with epilepsy (WWE) are in their childbearing years, and many take anticonvulsants. Both anticonvulsants as well as seizures themselves have been linked with poorer pregnancy outcomes. Clinicians therefore must carefully balance the goals of a seizure-free pregnancy and a healthy maternal-fetal outcome. Miscarriage is three to five times more common in women with epilepsy compared with the general population. Though much is known about the risks associated with “older” anticonvulsants including carbamazepine, phenobarbital, phenytoin and valproic acid, many studies of WWE and pregnancy risk predate the introduction of the “newer” anticonvulsants, including gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, and zonisamide. As many of these “newer” medications are now commonly used as monotherapy, we sought to determine if a difference exists between “older” and “newer” anticonvulsants with regard to current rates of live birth, miscarriage and fetal demise.

Methods: The clinical database of the Women's Health in Epilepsy program was reviewed to extract all subjects who (1) had a confirmed diagnosis of epilepsy, (2) took anticonvulsants for the treatment of epilepsy, (3) had a pregnancy while in the program between 1995 and 2007. We excluded pregnancies lost to follow-up. Medical records were reviewed to identify the anticonvulsants used during the first trimester, and the ultimate outcome of the pregnancy. The gestational age at completion of the pregnancy (by delivery, miscarriage, stillbirth or fetal demise, or elective abortion) was obtained.

Results: One hundred and fourteen pregnancies were identified. Of those, 90 resulted in live births, 18 ended in miscarriage, stillbirth, or fetal demise, and 6 were electively terminated. In WWE receiving monotherapy, 37/42 (88.1%) of those taking a newer anticonvulsant delivered a live infant while 5/42 (11.9%) led to miscarriage. In WWE receiving monotherapy with an older anticonvulsant, 35/46 (76.1%) delivered a live infant while 11/46 (23.9%) resulted in miscarriage.

Conclusions: WWE receiving older anticonvulsants in monotherapy during the first trimester of pregnancy were twice as likely to have a miscarriage as WWE receiving newer anticonvulsants. There was no difference in the seizure frequency or in other identifiable characteristics of the two groups as shown in table 1, suggesting that use of the older anticonvulsants may be a risk factor for miscarriage or fetal demise. Published data regarding miscarriage rate in WWE primarily focused on “older” anticonvulsants. Though our sample sizes were too small to provide statistical significance, they suggest a potential explanation for the observation that miscarriage rates are higher in WWE. Further research is needed on this topic to provide WWE with up to date information and counseling.

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Ivana Patakova 1 and S. E. Petranek 1 ( 1 Neurology, Faculty Hospital Bulovka, Prague, Czech Republic )

Rationale: In Czech Republic, member state of EU, was in accordance with EU legislation accepted the law No.277/2004 about the health ability to drive motor vehicles.

Methods: According this every driver has to perform clinical history, physical examination, orientation exam of hearing ability, visual resolution, color perception, visual field, equilibrium, neurological examination before the driving license tests and professional drivers, drivers of lories and busses every 2 years up to 50 years of age and every year after this age. All other drivers have to pass this at the age of 60 years, 65, 68 and every 2 years after that. There are as well conditions of ability to drive as private driver with epilepsy, or as professional drivers 10 years after complete cure of this illness.

Results: At once, since 1.6.2006, the change by law 411/2005 was made, in which complete neurological examination, psychological exam and EEG is necessary before the driving licenses for lories and busses, as well as for professionals. The same they have to have at the age of 50 years and every 5 years afterwards.

According to our EEG laboratory, out of 127 drivers, 12% examined drivers had focal or diffuse “hypo functional” pathology in EEG (slow waves) and another 3% more of epileptiform graphoelements (typical pages of EEG are presented). In 8% of all 24hours EEG video monitoring was necessary to perform. All of them have no case history of neurological disease until now, their neurological exams were normal.

The sense of this regulation is discussed due to common incidence of pathology in EEG in adult population

Conclusions: What to do with them - that is a question. According us they are not ill and they can drive.

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Jonathan Bird 1 , D. Kwok 1 and S. Khairullah 1 ( 1 The Burden Centre of Neuropsychiatry, Neuropsychology and Epileptology, Frenchay Hospital, Bristol, United Kingdom )

Rationale: Retrospective chart review of all adult patients with pharmacoresistant epilepsy and learning disabilities treated with adjunctive VNS Therapy during 18 months at the Burden Centre of the Frenchay Hospital (UK).

Methods: From a total of 46 patients (26 M, 20 F), 41 had enough data for analysis after 18 months of follow-up. Mean age at implantation: 36.6 ± 10.47; median: 38 years (range, 16–59). Mean number of seizures/month at baseline: 34.6 ± 38.66 (median, 17.5; range, 2–165; N = 46). Most patients had multiple seizure types, mainly generalized tonic-clonic and complex partial.

Results: After 6 months of adjunctive VNS Therapy, mean and median seizure reductions were 28.5% (7.3; 49.8) and 42.3%, respectively (N = 34); after 12 months, 39.2% (25.9; 52.4) and 41.9% (N = 30); after 18 months, 44% (30.7; 57.7) and 58.8% (N = 41). The number of seizures was significantly reduced from baseline at 6, 12, and 18 months (p = 0.0014, 0.0007 and 0.0003, respectively). Mean number of seizures/month after 18 months was 20.9 ± 39.04 (median, 7; range, 0–203; N = 41). One patient (2.4% (0.0; 7.4)) was seizure free after 18 months of treatment. Seizure reduction > = 50% occurred in 47.1% (29.4; 64.7), 46.7% (27.7; 65.6) and 58.5% (42.8; 74.3) of the patients after 6, 12 and 18 months, respectively. Adverse events were usually mild and tended to decrease over time. VNS Therapy was explanted in two patients (4.3%) due to infection.

Conclusions: These results confirm the efficacy and safety of VNS Therapy for patients with pharmacoresistant epilepsy and learning disabilities.

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A. Owega 1 , K. Rettig 2 , A. Schreiner 3 and B. Schauble 4 ( 1 Abt. für Psychiatrie, Neurologie und Psychotherapie, Klinik Links am Rhein, Köln, Germany ; 2 G.E.M., Neuss, Germany; 3 Medícal and Scientific Affairs, Janssen Cilag EMEA, Neuss, Germany and 4 Medical and Scientific Affairs, Janssen Cilag, Neuss, Germany )

Rationale: To describe differences in effectiveness and safety profile in patients treated with the most commonly prescribed AEDs in Germany transitioning to topiramate monotherapy (Topamax®, TPM).

Methods: Multicenter, open label, observational study (TOPMAT-EPY-0001) examining patients >6 yrs diagnosed with epilepsy and prior insufficient treatment (lack of effectiveness and/or tolerability) with PHT, OXC, CBZ or VPA monotherapy and planned transition to TPM monotherapy. Patients were followed for 16 week after initiation of TPM.

Results: The ITT analysis included 407 patients (53% female, no significant difference between groups) treated with VPA, CBZ, OXC or PHT. Mean age (±SD) over all groups was 45.8 ± 16.8 yrs. Between-group comparisons were performed by the Chi2- or the Kruskal-Wallis-H-test.

Patients on VPA or PHT were younger at diagnosis than patients on CBZ or OCX (p < 0.005), but epilepsy duration was longer in the PHT treated group (p < 0.001).

Overall, 75% of patients transitioned to TPM due to lack of efficacy (no differences between groups) and 61% due to insufficient tolerability (Chi2-test: p = 0.067).

TPM median dose at endpoint was 100mg/day.

Overall, seizure frequency decreased from 2.35 ± 5.4 per 4 week during the 12-weeks retrospective baseline to 1.14 ± 4.05 during the prospective observational period (Wilcoxon-test: p < 0.001).

All patients showed a significant seizure reduction while transitioning. 64.2% of all patients had an at least 50% seizure reduction and 41.8% were seizure free during the entire documentation period.

51 AEs had at least a possible relationship to TPM treatment. Treatment-related AEs (>3% out of 58 AEs) were: tiredness, nausea, weight loss, dizziness, lack of concentration, restlessness, ataxia, exanthem, and development of seizures.

Most common reasons (>3%) for discontinuation of TPM (15.8% overall) were AE (3.1%) or “unknown” (8.9%). 87% of physicians rated the effectiveness of TPM “very good” or “good” regardless of previous AED and 91% considered the patient-s situation as very much or much improved. The number of seizure related physician visits or loss of workdays decreased (p < 0.001). 82% of patients continued on TPM treatment.

Conclusions: Transitioning from PHT, VPA, CBZ or OXC to TPM was associated with a substantial seizure reduction and good tolerability regardless of the AED previously used. In addition, there was a significant reduction in seizure related physician visits and loss of workdays.

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Abdullah Al-Asmi 1 , N. Al-Belushi 1 , A. Al-Khalili 1 , Z. Al-Shabibi 1 and S. A. Rizvi 1 ( 1 Sultan Qaboos University, Muscat, Oman )

Rationale: Road Traffic Accident (RTA) is one of the leading non-medical causes of death in Oman. Epileptic patients who are driving are at higher risk of having RTA compare to general population. There are laws governing driving in epileptic patients to protect the patients and the general public. These laws are not uniform across the countries. Most of these laws depend on the duration of seizure free interval as well as treating physician opinion. However, driving is quite important in our daily life especially in places where the public transport is not well developed. Therefore, patients' compliance to the law may be questioned. To our knowledge there are no specific laws in Oman addressing this issue.

The aim of this study was to assess the attitude of Omani epileptic patients towards driving and the laws governing epilepsy and driving. Their attitude were compared with non-epileptic Omani population.

Methods: Epileptic group in the driving age attended our Neurology Clinic over the last one year who were deemed mentally competent and physically able to drive were interviewed by phone using a standard questionnaire. The questionnaire was also administered to a control group chosen from visitor of our institute to match the epileptic group by age and gender. At the beginning of the interview a verbal consent to carry the interview was taken from all the subjects who are eligible for the study. The ethic committee of our institute approved the study.

Results: 72 patients were interviewed of which 67% were male. Matched age and gender healthy subjects were also interviewed. Most our epileptic patients sampled have their attacks at least once a year during which the attack was associated with alteration of consciousness. 50% of the patients do not drive compare to only 5% in the control group. Of those 36% did not drive due to their illness. None of the sampled group was aware of any rules governing driving and epilepsy locally or internationally. However, 30% in the control group thought epileptic patients should not allowed to drive compare to 13% in the epileptic group. To our surprise, only 30% of the sampled patients were counselled regarding the risk of driving. The control group thought that the physicians should report to the licensing authority regarding their patients' compare to epileptic group (85 vs. 60%).

Conclusions: General public and epileptic patients sampled are not aware of the rules governing epilepsy and driving either locally or internationally. We found that 50% of the sampled patients who are at high risk do drive. In addition, the majority of the patients were not counselled by their treating physicians about the risk of driving in epilepsy. Our study calls for urgent formulation of a law governing this issue in collaboration with health professional managing epileptic patients. Physicians dealing with such patients must be aware of such laws and mandate to counsel their patients and documents these in their medical records.

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Charles B. Hall 1,2 , R. B. Lipton 1,2 and S. R. Haut 2,3 ( 1 Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY ; 2 Neurology, Albert Einstein College of Medicine, Bronx, NY and 3 Neurology, Montefiore Medical Center, Bronx, NY )

Rationale: Accurate seizure prediction in persons with epilepsy would create opportunities for both precautionary measures and pre-emptive treatment. Herein, we develop models to predict seizures in one sample and assess its value in predicting future seizures in the same individuals and in a similar small, independent sample. We also test the hypothesis that prediction models improve as follow-up time increases.

Methods: We conducted a 2-phase analysis of prospective daily seizure diary data. In Phase 1, using the first 60 days of study, we fit multilevel logit-normal binary response models using previously identified predictors (stress, anxiety, hours of sleep). In Phase 2, we examined how the results from that model predicted the occurrence of seizures over the next 30 days of the study in the same individuals and in a small independent sample. To assess the contribution of a longer observation period, multi-level logit-normal binary response models for the first 11 months of follow-up were predicted and tested for predictions in month 12.

Results: In Phase 1, 16 subjects contributed 585 days of observation, including 92 days with seizures, over the first 60 calendar days of diary data collection. Seizure occurrence was modeled as the outcome. In Phase 2, 15 of the 16 subjects who had contributed data to Phase 1 and 4 additional subjects contributed data to days 61 to 90 of diary data collection. During Phase 2, seizures occurred on 59 out of 519 days. For days 61 to 90, a predicted probability of seizure was computed using the Phase 1 model, including the individual level predicted values of the random intercept for any subject who contributed data to both Phase 1 and 2. For the 4 newly enrolled subjects we used only population average effects. For 80% specificity of seizure prediction, the model achieved 63% sensitivity. ROC curves were computed; the area under the curve was 0.75. Similar models were applied to the first 11 calendar months of the study in 43 subjects contributing 6276 days, including 641 with seizures. Using those 11 months of data to model seizures in the 12th month (29 Ss, none newly enrolled, with seizures in 56 out of 816 days) resulted in improved estimation of variance components for sleep and self-prediction, an increase in sensitivity to 71%, and an increase in area under the ROC curve to 0.84.

Conclusions: Development of individual-level models for prediction of future seizures based on diary data may be possible. As follow-up time increases, model predictions improve. The possibility of clinically relevant prediction should be examined in a study with electronic data capture, more specific and more frequent sampling, and with subject training and feedback based on model results.

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Teneille E. Gofton 1 , M. E. Jenkins 1 , S. Wiebe 2 and J. G. Burneo 1 ( 1 Clinical Neurosciences, University of Western Ontario, London, ON, Canada and 2 Division of Neurology, University of Calgary, Calgary, AB, Canada )

Rationale: Epilepsy research is a rapidly evolving area. There is an emerging need to prepare neurology residents in an evidence-based approach in order to equip them for future practice and in order to apply new research in a clinical setting. Given the need for evidence-based problem solving, a curriculum has been developed to train neurology residents in such a manner. The objective of this research is to illustrate an evidence-based epilepsy curriculum.

Methods: As part of the evidence-based curriculum established in 2001, neurology residents and epileptologists identify clinical cases that will serve as a basis for development of a clinical question for further discussion. The most current literature is identified for review in a learner-directed setting. Clinical epidemiology, biostatistics and critical appraisal skills are enhanced through analysis of the most relevant literature. In this cooperative setting, attending neurologists and epileptologists serve as group facilitators and resource assistance for the participants. A total of 14 evidence-based epilepsy clinical assessment tools (out of 130) have been produced.

Results: Epilepsy topics are incorporated into monthly evidence-based tutorials for neurology residents and varied topics are addressed over the five-year duration of the residency program. The completed critical appraisal of the relevant literature is summarized in a Clinical Appraisal Tool (CAT), which is then available for future reference in an electronic and portable format.

Conclusions: Using an evidence-based approach, neurology residents are equipped with the skills required for managing clinical dilemmas and furthering patient care.

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Fabio Sebastiano 1 , A. Sparano 1 , V. Esposito 1 , A. Mascia 1 , G. Cantore 1 , P. Romanelli 1 , P. Quarato 1 and G. Di Gennaro 1 ( 1 Epilepsy Surgery Unit, IRCCS “NEUROMED”, Pozzilli (IS), Italy, Pozzilli, Italy )

Rationale: To evaluate a novel method for localization of depth electrodes in presurgical assessment of patients with drug-resistant epilepsy.

Methods: We studied 12 consecutive patients with drug resistant epilepsy in whom depth electrodes were implanted for presurgical evaluation. Electrodes were detected on post-implantation brain CT scans through a semiautomated procedure based on a MATLAB routine (Fig. 1). Then, post-implantation CT scans were fused with pre-implantation MRI to localize the electrodes in relation to the cortical structures (Fig. 2).

Results: In each patient, all electrodes could be correctly localized and visualized in a stereotactic space, thus allowing optimal surgery planning.

Conclusions: While our findings need confirmation on larger samples including patients with drug resistant epilepsy, this procedure allowed to localize depth electrodes and to establish the spatial relationship of each electrode to the brain structure, either normal or damaged.

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James W. McAuley 1,2 , L. McFadden 1 and J. Elliott 2 ( 1 College of Pharmacy, The Ohio State University, Columbus, OH and 2 Department of Neurology, The Ohio State University, Columbus, OH )

Rationale: Comprehensive treatment of epilepsy involves many facets including self-management behaviors. The most common self-management strategy is adherence to an Antiepileptic Drug (AED) regimen. Non-drug related behaviors include management of information, concern for personal safety, management of the seizures themselves, and lifestyle issues. The purpose of this study was to determine the impact of clinical factors on self-management behaviors.

Methods: Adult epilepsy patients were recruited for this cross-sectional, descriptive study. A convenience sample of patients filled out two surveys aimed at assessing various self-management behaviors. The Morisky medication-taking behavior is a four question, non-Epilepsy specific adherence measure. Based on responses to the Morisky questions, patients are grouped into low, medium or high medication-taking behavior. DiIorio's 38-item Epilepsy Self-Management Scale (ESMS) assesses frequency of use of epilepsy self-management practices. Responses are divided into 5 subscales that address patient management of medication, information, safety, seizure and lifestyle. Additionally, clinical and demographic data was collected.

Results: Fifty patients (male = 27, female = 23) with a mean age of 40 participated in the study; 46 were Caucasian and 4 non-Caucasian. Sixteen (32%) reported having AED adverse events at the current clinic visit and 35 (70%) were determined to have AED resistance (failed more than 2 AEDs). Twenty-six (51%) patients indicated yes to the question “Do you ever forget to take your medications?”. Based on one-way ANOVA of the ESMS subscales, women had higher scores on information (F = 4.55, p = 0.038) and safety management (F = 4.68, p = 0.036). Persons with lower levels of education reported higher scores on the safety subscale (F = 2.94, p = 0.043). A lower health status rating was found for those reporting adverse events from AEDs (F = 4.49, p = 0.039). No significant differences were found on the ESMS subscales, based on number of AEDs taken or 3-month seizure frequency. The ESMS medication management subscale and the Morisky scale were highly correlated (r = 0.583, p = 0.000). Total number of medications was highly correlated with the ESMS medication management subscale (r = 0.40, p = 0.004), while 3-month seizure frequency (r =−0.42, p = 0.003) and ethnicity (r =−0.35, p = 0.01) were negatively correlated with the Morisky Scale. Regression modeling of the ESMS medication management scale found total number of medications, treatment for depression and poor medication compliance (when a patient feels better) were predictors (r2= 0.386, F = 5.42, p = 0.001). For the Morisky Score, ethnicity and 3-month seizure frequency were predictors (r2= 0.327, F = 5.34, p = 0.001).

Conclusions: Epilepsy self-management skills are critical to patients. Scores on a domain specific assessment and a general assessment of medication compliance, while highly correlated, are predicted by different clinical factors. Since depression is a common co-morbidity, the ESMS scale may be more useful; however it may be strengthened by including questions from a general assessment, like the Morisky scale.

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Alison Pack 1 , A. R. Davis 1 , J. Kritzer 1 , A. Yoon 1 and A. Camus 1 ( 1 Columbia University, New York, NY )

Rationale: Antiepileptic drugs (AEDs) may impact reproductive health. Certain AEDs are teratogens and some induce the hepatic p450 system increasing metabolism of contraceptive steroids and decreasing effectiveness. Published data reveal confusion regarding these effects among neurologists and obstetrician gynecologists. Whether women with epilepsy understand the effects of prescribed AED on fetal development and hormonal contraception remains unknown. Our objective was to explore knowledge regarding the reproductive health effects of AED therapy among reproductive-age women with epilepsy.

Methods: We conducted a cross-sectional questionnaire study in women aged 18–44 with epilepsy. Participants were recruited from the Columbia Comprehensive Epilepsy Center. We collected information about demographic characteristics, reproductive history, and current pharmacotherapy. We assessed knowledge about teratogenicity by asking “Do you know if (AED)affects the development of a baby during pregnancy?” and coded responses as bad effect, good effect, no effect, unknown effect, or doesn't know. To assess knowledge of interactions with hormonal contraception we asked “Do you know if (AED) changes how well birth control pills work?”and coded responses as bad effect (decreases effectiveness), no effect, or doesn't know.

Results: Participants'(n = 148) mean age was 32 years (SD ± 8); 32% spoke Spanish and described themselves as Hispanic. Participants reported a wide range of educational attainment and income. Among the 148 women, 56.9% reported currently receiving AED monotherapy. Among all AEDs prescribed (monotherapy or in combination), 31.7% were prescribed lamotrigine, 16.3% levetiracetam, 10.9% carbamazepine, and 5.4% valproate. Ten other AEDs each accounted for less than 10% of total prescribed.

For FDA Category D AEDs, 40% of subjects were unaware of potential teratogenic effects, 44% indicated a negative effect, 6% no effect, and 6% a good effect on fetal development. For Category C AEDs, 45% did not know, 29% indicated a negative effect, 16% no effect, 6% unknown effect, and 2% a good effect. AEDs potentially increasing hormonal contraceptive metabolism were prescribed 66 times. This interaction was correctly cited in 32% of women taking them. Participants did not know in 65% and 3% said no interaction. AEDs with no effect on contraceptive metabolism were prescribed 138 times; 26% incorrectly cited an interaction, 47% did not know, and 25% correctly said no interaction.

Conclusions: Reproductive aged women with epilepsy at an academic epilepsy center were most commonly prescribed lamotrigine and levetiracetam. Valproate accounted for less than 10% of prescribed AEDs. Many women prescribed Category C (45%) or Category D (40%) AEDs were unaware of potential teratogenic effects. Among those prescribed an AED increasing hormonal contraceptive metabolism, the majority (65%) were unaware of a decrease in hormonal contraceptive efficacy. Additional educational efforts should be promoted to increase knowledge of potential teratogenesis and interaction with hormonal forms of contraception.

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Meriem K. Bensalem Owen 1 and T. A. Fakhoury 1 ( 1 Neurology, University of kentucky, Lexington, KY )

Rationale: Stimulus-induced rhythmic, periodic or ictal discharges (SIRPIDs) is an electrographic pattern that was first reported by Hirsch et al. in 2004 in critically ill patients. We review five patients who exhibited this pattern and their outcome.

Methods: We prospectively identified five patients with SIRPIDs who underwent continuous video-EEG monitoring. The pattern was recognized by one of two electroencephalographers and reviewed by both. We evaluated the patients' history, examination, laboratory work-up, imaging studies and outcome.

Results: All five patients (ages 44–72 years; 4 women and 1 man) had multiple medical problems and decreased mental status at the time of continuous video-EEG monitoring. Three patients had a history of seizures or epilepsy. One of the three had progressive dementia of unclear etiology. One of the two patients without history of seizures suffered an anoxic brain injury following resuscitation for cardiopulmonary arrest. Continuous video-EEG monitoring was performed for 2 to 4 days. In all five patients, SIRPIDs were noted at onset of spontaneous stimulation induced by motor activity, eye movements, as well as sensory stimulation often due to nursing care. The electrographic pattern persisted throughout the period of stimulation, ending only after stimulation or movements ceased. Antiepileptic drugs did not appear to affect this electrographic pattern. Four of the five patients' condition improved. Three were back to their baseline upon discharge, but had to be readmitted approximately a month later with several acute medical problems. The fourth patient, with progressive dementia, was sent back to her nursing home and was seen in follow up one month approximately after her discharge. She never recovered to her baseline status. The patient who suffered anoxic brain injury expired eight days after monitoring was discontinued.

Conclusions: Three of our 5 patients with SIRPIDs recovered back to baseline. The electrographic pattern did not respond to antiepileptic medications. This electrographic pattern therefore does not appear to be ictal in origin and its presence may imply a favorable prognosis. Overall prognosis however appears to depend on the initial insult.

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Young Joo No 1 , E. Choi 1 , J. Kang 1 and S. Lee 1 ( 1 Neurology, Asan Medical Center, University of Ulsan, Seoul, South Korea )

Rationale: Several studies on quality of life (QOL) in epilepsy verified that people with epilepsy had high levels of depression and anxiety, and emphasized on the importance of depression and anxiety in QOL of people with epilepsy. Stress, which has been reported to increase the occurrence of seizures and to affect on depression, is another potential factor to affect QOL. However there are only few reports concerning its relative contribution on QOL. In our study, we aimed to determine (1) the influence of stress upon epilepsy variables, (2) the contribution of stress factor upon patient's quality of life compared to depression, anxiety, and clinical variables of epilepsy.

Methods: We included 129 adult patients with epilepsy who were interviewed at the outpatient clinic for epilepsy. All subjects completed a stress questionnaire, the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Quality Of Life In Epilepsy-31 (QOLIE-31). The stress questionnaire consisted of 36 items concerning personal, social and economical aspects. Responses are indicated on a 4-point scale with the end points being ‘not at all stressful’(1) and ‘very stressful’(4). An overall stress score is obtained by summming the ratings on the 36 items (range: 36∼141 points). The demographic, social (education level, marriage, employment, socioeconomic status, religion) and clinical seizure information (seizure onset age, frequency, number of antiepileptic drugs) were obtained by medical records. Univariate linear regression was used for statistical analysis and all univariate variables significant at P = 0.2 were entered into a hierarchical regression analysis.

Results: Mean stress score was 57.2 (range: 37∼121). Moderate and severe levels of depression (scores of ≥16) were reported in 37.9% of patients, and similar levels of anxiety were reported by 28.7%. There was a significant negative correlation between the stress and overall score of QOL (r =−0.604, P < 0.001). Depression and anxiety were also negatively correlated with QOL (r =−0.714, P < 0.001 and r =−0.491, P < 0.001, respectively). Persons with higher scores on the stress questionnaire had higher depression and anxiety scores (r = 0.51, P < 0.001; r = 0.18, P = 0.04). In order of importance, stress appeared to contribute most significantly to the overall QOL than depression and anxiety: it contributed 32% to the patients' QOL; depression and anxiety contributed 17%; clinical variables contributed only 4%. No correlation was noted between the frequency of seizures and the results of the stress and psychiatric questionnaires. None of the epilepsy variables (age of onset, seizure frequency, duration of illness) affected the QOL.

Conclusions: The large contribution of stress on quality of life suggest the need to identify the stressors found in persons with epilepsy in everyday clinical practice, specifically the stressors experienced by each person.

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Daniel Costello 1 , R. Kilbride 1 , C. Michaelides 1 , S. Cash 1 , K. Chiappa 1 , D. Hoch 1 and A. J. Cole 1 ( 1 Department of Neurology, Epilepsy service, Boston, MA )

Rationale: Status Epilepticus (SE) is a relatively common and frequently devastating neurological emergency. In the vast majority of cases, a plausible explanation for SE is evident. In a small fraction of cases, the underlying aetiology is not apparent despite extensive evaluation. Among these cases of cryptogenic SE, perhaps the most difficult to understand are patients who present de novo with refractory SE. Typically, the working diagnosis is that of ‘viral encephalitis’ on the basis of CSF and imaging findings in conjunction with the absence of an alternative explanation. However, in the final analysis, a specific pathogen may not be isolated and the CSF and imaging abnormalities may reflect the seizure activity itself. We report our experience with previously-normal patients with new onset refractory SE of unclear cause.

Methods: We describe 6 adults with de novo refractory SE. The designation of ‘de novo’ mandated that all patients were neurologically normal prior to the incident illness, and in particular did not have a history of seizures. After extensive investigations, an underlying cause for the SE was not found, resulting in the aetiologic designation of ‘cryptogenic’.

Results: All patients needed prolonged ICU care with continuous EEG monitoring, and were treated with infusion therapies due to refractory SE. Both the short-term, in-hospital and long-term morbidities were high. The average age was 27.1 years (range 21–36 years). Five cases were female. Five cases experienced a non-specific mild febrile illness within two week of the SE. Of the 5 cases that survived, the average length of hospital stay was 41 days. The other case died on day 9, due to fulminant cardiac failure. Post mortem histopathological evaluation of this case was non-diagnostic. One patient had right frontal biopsy and two cases had therapeutic cortical resections. Neuropathological examination revealed non-specific changes with lymphocytic infiltration and microglial activation. All cases showed a modest CSF pleocytosis with normal protein level. MR imaging revealed either normal findings or typical peri-ictal cortical abnormalities, in a regional distribution. One case had high levels of anti-thyroglobulin antibody, raising the possibility of Hashimoto's encephalopathy, but did not respond to successive treatment with intravenous steroids, intravenous immunoglobulin therapy, or plasmapheresis. In each case, all of the abnormalities evident during the initial and subsequent evaluation could be attributed to the ictal activity itself.

Conclusions: We describe our clinical experience with this rare form of SE and postulate an autoimmune basis for the illness. These cases have unifying features, namely young age, normal pre-morbid neurologic health, female preponderance, prodromal mild non-specific febrile illness, and a poor clinical outcome. We postulate that these cases may represent a form of parainfectious encephalitis with acute symptomatic status epilepticus as a major manifestation. Early recognition and introduction of immunosuppressive therapies may be warranted in this form of status epilepticus to avert a poor clinical outcome.

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Lana J. Boursoulian 1 and B. S. Shihabuddin 1,2 ( 1 Neurology, University of Arkansas for Medical Sciences, Little Rock, AR and 2 Arkansas Children's Hospital, Little Rock, AR )

Rationale: Rationale: Neurosyphilis is rather uncommonly encountered in the US except in immuno-compromised patients. Although seizures are relatively common in neurosyphilis, CPSE is rare. We report on complex partial status epilepticus (CPSE) as the initial manifestation of neurosyphilis in an immuno-competent patient.

Methods: A 51 year old imuno-competent man presented with a three day history of brief episodic confusion that progressed to a state of continuous confusion, slurred speech and intermittent agitation one day before admission. On examination he was confused with no localizing or lateralizing neurological findings. Head MRI showed leptomeningeal enhancement over the right cerebral hemisphere. Non convulsive seizures were suspected and video/EEG monitoring showed bihemispheric delta slow waves with right hemispheric periodic epileptiform discharges (PLEDs) maximal in the mid-posterior temporal region, with frequent ictal discharges of right mid-posterior temporal onset (Fig. 1). CSF analysis revealed 33 WBC/μL, protein 110 mg/dL, glucose 76 mg/dL and positive VDRL (1:4 titer). Serum serology was positive for FTA-ABS.

Results: CPSE was aborted by intravenous phenytoin, valproic acid and levetiracetam four days after admission. Neurosyphilis was treated with intravenous penicillin G, 4 million units every 4 hours for 14 days. After penicillin treatment and seizure control, repeat head MRI showed extensive increased signal in the right temporal lobe (Fig. 2). The patient had some cognitive improvement following treatment but he remained with a major cognitive impairment on discharge.

Conclusions: Neurosyphilis should be considered, even in immuno-competent patients with new onset complex partial seizures, especially those that progress to CPSE. Head MRI of these patients might show cerebral signal abnormalities, but it is unclear if these changes are related to the syphilitic infection or are caused by the CPSE.

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[ Figure 1. EEG sample showing right hemispheric periodic epileptiform discharges (PLEDS) followed by the onset of a right mid-posterior temporal ictal discharge. ]

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[ Figure 2. Head MRI (FLAIR image) demonstrating extensive right temporal increased signal abnormality 14 days after CPSE was controlled and 3 days after penicillin G therapy was completed. ]

Abstract

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Mark Spitz 1 , C. A. Anderson 1,3 , H. S. Wortzel 2,3 , E. H. Maa 1 and L. S. Strom 1 ( 1 Neurology, University of Colorado at Denver and the Health Sciences Center, Denver, CO ; 2 Psychiatry, University of Colorado at Denver and the Health Sciences Center, Denver, CO and 3 MIRECC, Denver Veteran Affairs Medical Center, Denver, CO )

Rationale: Disrobing has long been recognized as behavior associated with seizures in some patients with partial onset epilepsy. Little is known about the clinical aspects and medical-legal consequences of this syndrome.

Methods: We retrospectively reviewed the clinical presentation, localization, and forensic consequences in a series of patients with ictal, postictal, and coincidental disrobing. The setting is the University of Colorado Comprehensive Epilepsy Center, a tertiary referral center in the Rocky Mountain region. Patients were identified through clinical queries and consent, gathered from the 4 epileptologists in the group.

Results: We collected 12 patients with disrobing associated with epileptic seizures. Eight appeared to have them ictally or in the immediate post-ictal period. With 2/8 it occurred with most of their seizures. With the other 6/8 it was more sporadic. Of the entire series, 6 were actually monitored in our Epilepsy Monitoring Unit, and 1 was observed to disrobe repeatedly. All of these 6 patients had temporal lobe onset seizures (4 right sided, 2 left sided). Two of the remaining 6 patients had mild-moderate developmental delay and likely frontal onset seizures. Unfortunately, they were not monitored. Four of the patients reported episodes where disrobing was coincidental with the seizure. For example, they were showering at the time of the seizure, and wandered into public areas (1 was recurrent, 3 were sporadic). Finally, 2 patients had significant legal complications as a result of disrobing in public, and a third patient lost her job.

Conclusions: Disrobing can occur as either an ictal automatism or during the postictal period. Some patients have seizures when already unclothed and then wander into public areas. Most of our patients with ictal disrobing had a mesial temporal focus, but this likely represents a selection bias. This behavior has a dramatic effect on patient's quality of life and has the potential for unintended and significant legal consequences.

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Danielle McDermott 1 , E. H. Maa 2 , M. J. Doherty 3 and M. C. Spitz 2 ( 1 University of Colorado at Denver and the Health Sciences Center, Denver, CO ; 2 Neurology, University of Colorado at Denver and the Health Sciences Center, Denver, CO and 3 Swedish Epilepsy Center, Seattle Neuroscience Institute, Seattle, WA )

Rationale: The University of Colorado's Comprehensive Epilepsy Center is a tertiary referral center in the Rocky Mountain region, where we have reported on an association of new onset seizures in visitors from lower elevations. Researchers from Swedish Epilepsy Center in Seattle have noted an interesting and related trend. Doherty et al. recently reported an OR = 2.8 of a seizure happening if an atmospheric pressure change of 5.5 mBar occurs the same day. Through a joint collaboration, we repeated their methodology in our Epilepsy Monitoring Unit, at an elevation of 5280 feet.

Methods: We retrospectively reviewed patients seen in our Epilepsy Monitoring Unit during the same time period of the original study, April 2005-April 2006. Each seizure was categorized into three groups: epileptic, non-epileptic, and other. Atmospheric pressure data was gathered from the National Oceanic and Atmospheric Administration weather station at Denver International Airport. Daily maximum, minimum, and pressure range was correlated to daily number of events per patient.

Results: 151 patients were monitored, 570 epileptic seizures, 278 non-epileptic seizures, and 139 other events occurred. Preliminary results reveal epileptic seizures, and “other” events were increasingly likely to occur with only drop in atmospheric pressure as opposed to a change in absolute pressure difference. As would be expected, and similarly to the Seattle data, non-epileptic events were not effected by pressure changes at all.

Conclusions: Our preliminary findings seem to corroborate an association between atmospheric pressure and seizure frequency. While absolute pressure changes were associated with increasing seizure frequency at sea level, we found only pressure drops associated with increasing frequency in our EMU at 5280 ft of elevation. The observation that “other” events were also effected by pressure drops suggests that these events may contain a large number of epileptic events that were not characterized by visual inspection of extracranial electoencephalography.

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Mercedes P. Jacobson 1 , Z. Haneef 1 and M. Vendrame 1 ( 1 Temple University Hospital, Philadelphia, PA )

Rationale: Mirtazapine (Remeron) is a noradrenergic and specific serotonergic antidepressant (NaSSA) used in the treatment of depression. It is thought to have a very low likelihood of inducing seizures with reports of incidence ranging from 0.0008% to 0.04% among users. A single post-marketing survey indicating possibility of seizures with Mirtazapine is not well-known.

Methods: We describe 2 patients who presented with complex partial seizures following recent exposure to Mirtazapine. Patient 1 is a 61-year-old man who developed acute transient confusion and impaired language capacity followed by witnessed automatisms. This event, including post-ictal confusion was observed by healthcare professionals. He was being treated for depression with Mirtazapine which was increased 3 days prior to presentation. Patient 2 is a 40-year-old man who reported visual imagery of rain falling on his right hemi-field while driving his car, progressing to tonic-clonic activity observed by a passenger in the car, leading to a crash. He had a history of a single seizure in his childhood. He was recently started on Mirtazapine. In both patients, acute EEG showed transient abnormalities with subsequent resolution.

Results: The temporal proximity of exposure to escalating doses of Mirtazapine and seizures in our patients who had no other identifiable risk factors for seizures implies a causative role for the drug.

Conclusions: Depression co-exists in a significant percentage of epileptics and Mirtazapine is a favored drug due to its low epileptogenicity. Our experience with Mirtazapine and seizures urges caution when using this drug in a patient at risk for seizures. Physician sensitization to this possibility would help delineate the seizure potenital of this medication.

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Yasir S. Shareef 1 , J. F. Drazkowski 1 , K. H. Noe 1 , R. Zimmerman 1 and J. I. Sirven 1 ( 1 Neurophysiology- Epilepsy, Mayo Clinic, Phoenix, AZ )

Rationale: Approximately 40,000 drivers have fatal crashes every year. Risk of fatal crashes is 2–4 times higher in epileptics than patients with other diseases. California, Delaware, Nevada, New Jersey, Oregon and Pennsylvania require physicians to report patients who have seizures to the department of motor vehicles. Arizona is not a reporting state. Failure to document instructions regarding legal driving restrictions may leave physicians vulnerable to legal liability. As a systems-based practice project, we evaluated the quality of documentation that patients were counseled about driving restrictions and safety precautions following emergency room visits for episodes of altered level of consciousness and seizures.

Methods: A retrospective chart review was conducted of patients with all diagnostic codes of epilepsy, transient altered consciousness, syncope and collapse, other convulsions, and altered mental status at the Mayo Clinic Arizona emergency department, during 2006. Presence or absence of documented counseling regarding driving and safety precautions was noted.

Results: 340 patients with episodes that would require driving counseling were found. There were 140 males and 200 females. The age ranged between 2–100 years. Ninety seven patients had a seizure or convulsion diagnosis, and 243 had syncope or alteration in level of consciousness. The overall number of patients with documented counseling about driving laws and safety precautions was surprisingly low at 17 (5.00%). Age range of patients that were counseled is between 23–87 years. Twelve of 17 that were counseled regarding driving had diagnostic code of other convulsions. Three had episodes of alteration in consciousness. One patient had a focal epileptic event and one had new onset grand mal seizure

Conclusions: Counseling regarding driving laws and safety precautions for common diagnoses of seizures and episodes of alteration of consciousness are not being adequately documented by ER physicians. This finding has potential legal implications for practicing physicians. In an effort to improve the medical record, we suggest a system based practice modification in our emergency department by adding a checklist to include counseling regarding driving and safety precautions.

Counseling Data

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Gabrielle Rudolf 1 , C. Depienne 2 , S. Chassagnon 1 , C. Sabourdy 1 , M. P. Valenti 1 , E. Flori 1 , E. Leguern 2 and E. Hirsch 1 ( 1 Neurology, CHRU Strasbourg, Strasbourg, France and 2 Genetique, Groupe Hospitalier Pitie Salpetriere, Paris, France )

Rationale: More than 170 documented mutations in the sodium channel alpha subunit gene SCN1A are associated with a clinical spectrum of epilepsies with heterogeneous phenotypes (Generalized or Focal epilepsies), with GEFS+ on the mildest end of the spectrum, “post vaccinal” encephalopathy and severe myoclonic epilepsy of infancy or Dravet syndrome (SMEI) on the severest end. We reported a new mutation not described until now in an adult patient with mental retardation and seizures onset in adultdhood.

Methods: Personal and familial medical history, video-EEG monitoring in awake and sleep, neuro-psychological, neuro-radiological, genetic and metabolic investigations were performed in our patient. SCN1A was analyzed by denaturing high performance liquid chromatography for sequence variations. DNA changes were characterized by automated DNA sequence analysis.

Results: Patient mother's presented adult onset pharmaco-sensible idiopathic generalized epilepsy. Our patient, a girl presented generalized “cryptogenic” epilepsy (possibly genetic or possibly symptomatic). Birth was normal, but mental retardation (IQ = 45, language acquired at 5 years, normal motor development apart cerebellar signs) with unkown etiology was noticed. Seizures begin at 20 years of age with unclear syndromic diagnosis (a febrile tonic, astatic seizures, generalized status). Epilepsy was pharmaco-resistant from the onset but lamotrigine induced a marked improvement. High resolution cerebral MRI and FDG-PET scan were normal. All genetic investigations (Ring 20 chromosome, Fragile X, Inv (dup) 15, Glut1 deficiency, Huntingtin…), skin and muscle biopsy were normal. However, etiology of this generalized epileptic encephalopathy was still considered as “possibly” genetic. For all above, we search for a mutation of GEFS+ genes. We identify a new de novo mutation in the SCN1A gene (c.5083delG/p.Val1695LysfsX1714X) not found in a control population of 100 subjects.

Conclusions: Finding a mutation in SCN1A in an adult onset “cryptogenic” generalized epilepsy provide supporting evidence for an expand phenotype of epilepsies associated with SCN1A mutation. It seems important to investigate molecular diagnosis for determining the etiology of unclassified generalized epileptic “cryptogenic” encephalopathy because it avoid investigations looking for alternate etiologies and allows better choice of therapy (lamotrigine sodium channel blocker in this case).

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Sanjay P. Singh 1 and M. F. Khan 1 ( 1 Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE )

Rationale: Ictal thirst has not yet been described as an ictal manifestation. There have been rare reports of periictal water drinking as an automatism but here we describe two cases of ictal thirst where patient asks for water specifically or chooses water everytime over other objects available and drinks it as if she is thirsty.

Methods: The epilepsy-monitoring database (2002–2007) of the University of Nebraska Medical Center was searched for patients with a definite history of ictal thirst. All available data of the patients, particularly their original video and EEG data, were reviewed.

Results: Out of over 200 monitored patients 2 were found to have thirst as an ictal manifestation. The first patient had 4 seizures during the monitoring, she asked for water during each one of these and drank water as if she was thirsty during ictal EEG discharge. The ictal EEG seizure onset was from the right temporal lobe. The MRI showed right mesial temporal sclerosis, as seen in figure 1 & 2. She is seizure free on 3 antiepileptic medications.

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Nine seizures were recorded in the second patient. She drank water in each one of them as if she was thirsty during ictal EEG seizure discharge. In 5 seizures she had other objects available to choose from but she always picked up the water jug and drank water. The ictal EEG seizure onset was from the right temporal lobe in every seizure. The MRI Brain showed a right medial temporal cystic lesion. The patient underwent a surgical resection of the lesion and has been seizure free for 25 months.

Conclusions: Ictal thirst is an uncommon feature of temporal lobe seizures. It is not an automatism as the patient either asked specifically for water and drank it as if she was thirsty or chose a jug of water from myriad other objects available and then drank a significant amount of it as if quenching her thirst.

It is likely that the thirst center lies outside the medial temporal area but the connections of the medial temporal area render it capable of influencing such behavior. A recent study of functional neuroimaging of thirst showed maximum thirst sensation evoked 13 highly significant activations and 9 deactivations in cingulate and parahippocampal gyri, insula, thalamus, amygdala, and mesencephalon. This does explain how thirst can be a manifestation of medial temporal lobe epilepsy.

Recognition of such seizure manifestation is important in identifying seizures and aids in the correct localiztion of seizure focus.

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Gail Fromes 1 , J. Edwards 3 , L. Hudson 1 , O. Sagher 2 and D. Minecan 1 ( 1 Neurology, Univerisity of Michigan, Ann Arbor, MI ; 2 Neurosurgery, University of Michigan, Ann Arbor, MI and 3 Neurology, Medical University of South Carolina, Charleston, SC )

Rationale: Only a few studies are available reporting long term efficacy of vagus nerve stimulation (VNS). We present data on efficacy of VNS in adult patients treated for 5 years.

Methods: 58 adult patients underwent VNS implant for medically intractable epilepsy at the University of Michigan between January, 1999, and May, 2002. Patients with consistent follow up for 5 years post implant were included in the retrospective analysis. 15 patients were excluded for inadequate follow up due to VNS turned off (1), VNS explanted due to discomfort (2), VNS explanted due to infection (2), lost to follow up (8), and death (2). One patient was re-implanted post infection but did not have 5 years of treatment at the time of this data collection. All patients had anticonvulsant therapy during treatment with VNS and all patients had medication adjustments to some degree during the 5 years. 16 patients had VNS generator replacements during the 5 years due to concerns about end of battery life.

Results: The 43 patients ranged in age from 15 to 57 at implant. 14 (32%) were female. 30 had focal epilepsy (FE), 2 had primary generalized epilepsy (PGE), and 11 had symptomatic generalized epilepsy (SGE). After 6 months of VNS, 22 patients (16 FE, 6 SGE) were nonresponders, 8 (5FE, 1SGE, 2PGE) had 25% seizure reduction, 10 (6FE, 4SGE) had 50%, and 3 (FE) had 75%. At one year of VNS, 15 patients (11 FE, 5 SGE) were nonresponders, 7 (4FE, 2 SGE, 1PGE) had 25% seizure reduction, 14 (9 FE, 4 SGE, 1 PGE) had 50%, 5 (FE) had 75% and 1 (FE) had 100%. At 5 years of VNS, 13 patients (8FE, 4 SGE, 1 PGE) were nonresponders, 3 (1 FE, 2 SGE) had 25% seizure reduction, 16 (12 FE, 4 SGE) had 50%, 8 (7FE, 1 SGE) had 75%, and 3 (2 FE, 1 PGE) had 100%. Of the 22 nonresponders at 6 months, 6 patients (5 FE, 1 SGE) demonstrated efficacy at one year, 5 (3 FE, 2 SGE) at 2 years, and 2 (FE) at 3 years of treatment. Among early responders, (efficacy at 6 months of VNS), 8 patients(5 FE, 2 SGE, 1 PGE) improved further during the 5 years. 9 (6 FE, 3 SGE) early responders maintained the same efficacy over the 5 years. There were 9 patients (6 FE, 3 SGE) who were nonresponders for the entire 5 years. 4 patients (2 FE, 1 SGE, 1 PGE) had some efficacy in the first years that declined during the 5 year interval.

Conclusions: These data show that a majority of patients achieved efficacy from VNS during 5 years of treatment. Many nonresponders at 6 months improved at one year and two years of treatment, and only a couple of patients improved after that. Many early responders (efficacy at 6 months) maintained the same rate of efficacy, or had improved efficacy over the 5 years. Only a couple of patients achieved complete seizure control. A few patients were nonresponders or demonstrated declining efficacy over 5 years. These data show that patients should have at least 2 years of VNS before determining the effectiveness of treatment.

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Michal Bajacek 1 , J. Hovorka 1,2 , T. Nezadal 1 , I. Nemcova 1 and E. Herman 1 ( 1 Neurology, Epileptology and Neuropsychiatry Department, Na Františku Hospital, Prague 1, Czech Republic and 2 Neurosurgery Department, 1st Medical School, Charles University, Prague, Czech Republic )

Rationale: There is no universally accepted definition of pseudo intractable epilepsy. Pseudo intractability means, that resistance to treatment is in fact caused by clinical errors. Its main causes are errors in diagnosis, errors in drug choice or management, or poor medication compliance (Komarek V, Hovorka J,In:Brázdil M, Hadač J, Marusič P a kol. Farmakorezistentní epilepsie. Praha:Triton, ISBN 80-7254-562-0, 2004:171–172).

Methods: This was a retrospective study. The study group consists of 100 patients (54 of them are women) with epilepsy, who were advised to our epileptology and neuropsychiatry department witt initial diagnosis of intractable epilepsy. All of them were considered possible candidates for epilepsy surgery. None of this group of patients finally underwent the epilepsy surgery. All of these patients are now seizure free for minimum of two years. We have studied reasons of previous intractability, and impact on psychosocial functioning.

Results: In 35 patients we observed a failure to correctly classify the seizure type and epileptic syndrome classification(patients with idiopathic generalized epilepsy were treated as a focal seizures with a wrong choice of drug). In 45 patients inadequate medication was observed (inadequate dose in 23 out of them). Eleven patients had poor compliance in a dosing schedule. In 9 patients, triggering factors such as alcohol and drugs abuse have been observed.

Conclusions: Our results show the main causes of pseudo-intractability in treatment and management of epilepsy. It is essential to consider errors in diagnosis, inadequate medications and compliance in every case of intractable epilepsy to prevent pseudo-intractability with poor impact on psychosocial functioning. Our study suport hight incidence of pseudo-intractability in population of patients with epilepsy.

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Farzad Moien Afshari 1 , W. Fitzpatrick 1 , A. Kirk 1 and J. Tellez-Zenteno 1 ( 1 Medicine, Division of Neurology, University of Saskatchewan, Saskatoon, SK, Canada )

Rationale: An 83-year-old R-handed male presented with a two-day history of episodic jerking and “spasms” in the left arm, each lasting approximately 1 min, followed by weakness. He also described episodes of flashing colored lights in his left visual field, not always accompanied by arm jerking. The patient was also mildly confused with short-term memory impairment. His past medical history was significant for type-2 diabetes mellitus, dyslipidemia, hypertension, ischemic heart disease, cardiac pacemaker, and he was treated with prednisone for giant cell arteritis. There was no past history of seizures or migraine.

Methods: On physical examination, the patient was disoriented to date. He had a visual deficit in the inferior fields of both eyes, but was unable to clearly describe the demarcation of the visual defect. He also had a mild left upper extremity weakness (4/5) with brisk biceps and brachioradialis reflexes and an extensor plantar reflex on the left. Several brief episodes of focal motor (clonic) seizure activity involving the left upper limb were observed.

Results: Blood Glucose was 639 mg/dl and serum osmolarity 316 mosmol/l. Ketoacidosis was absent. Mg+ and Ca2+ were normal. There were mild abnormalities of Na+ and K+, which normalized with treatment in a few hours, however, clinical seizures continued for 24 hours. Two electrographic seizures from the left occipital region maximum at O1 with spread to P3 and T5 associated with visual symptoms were recorded. The ictal rhythm in both seizures was characterized by fast activity in the frequency of beta followed by post-ictal theta and then delta. CT head was normal. MRI was not obtained because of the pacemaker. The patient was treated with hydration and insulin and all the neurological symptoms including the seizures disappeared after 24 hours. In a subsequent follow up, four months later, the EEG was normal and the patient remained asymptomatic.

Conclusions: This patient had clinical and electrographic seizures from the occipital region associated with hyperglycemia. He also suffered from other transient neurological symptoms associated with hyperglycemia that eventually disappeared with the correction of the metabolic problem. This is a unique complication of hyperglycemia with only few anecdotal reports over the years. Historically the presence of focal seizures, most frequently focal motor seizures, has been described during non-ketotic hyperglycemia, however, the description of occipital seizures is exceptional. It has been demonstrated that increased extracellular glucose, in a concentration dependent manner, increases neuronal excitability via decreasing the conduction of KATP channels. Also decreased GABA levels during hyperglycemia can predispose to seizures. More potential aspects of pathophysiology and EEG findings will be presented at the congress.

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This figure demonstrates the presence of fast activity over the left occipital region with a frequency between 15 to 16 HZ. The EEG changes were present when the patient was describing flashing lights in both eyes. No changes were identified over the right occipital region.

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Mercè Falip 1 , M. Carreño 2 , V. Villanueva 3 , A. Donaire 2 , I. Maestro 2 , M. Codina 4 and M. Aiguabella 1 ( 1 Neurology, Hospital Universitari Bellvitge, Hospitalet de LLobregat, Spain ; 2 Epilepsy Unit, Hospital Clinic i Provincial, Barcelona, Spain ; 3 Epilepsy Unit, Hospital Universitari La Fe, Valencia, Spain and 4 Epilepsy Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain )

Rationale: Nearly 80% of patients with mesial temporal lobe epilepsy (MTE) associated with hippocampal sclerosis (HS) are medically resistant and need presurgical evaluation and if possible surgical treatment.

Objective: To identify electroclinical and neuroimaging features related to seizure control after medical o surgical treatment in patients with MTE associated with HS.

Methods: Patients with clinical, MRI and EEG features of mesial temporal lobe epilepsy associated with HS who were referred for presurgical evaluation at the Hospital Clínic or were followed up in the outpatient clinic of 3 other tertiary centers without surgical programme were included in the study. Patients with clinical and laboratory features that place the diagnosis of MTLE in doubt were excluded.

Parametric and non parametric test for univariate analysis were used and regression analysis when correlating continuous variables.

Results: Two hundred and two patients(84 men/ 118 women) were included, mean age 44 (16–80), mean age at epilepsy onset 16 (0–77). Referred initial precipitating injury (IPI) 119 (67%) being the most frequent a febrile seizure 56 (32%), mean age at IPI 5.19 (0–65). Aura was referred by 130 (67%) but aura persisted upon the time just in 98 (79%) of these patients. Seizure freedom (no complex partial seizures in a year) was reported by 39 (19.3%). From the medically resistant patients 86(64%) were considered good surgical candidates and 60 underwent epilepsy surgery (76%) being seizure free, after a minimum follow up of one year,42 (70%).

Factors related to poor medical control were: younger age at epilepsy onset (p:0.007), longer time of disease duration (p = 0.002), greater number of tonic-clonic seizures (GTCG) (p = 0.001),losing aura over the time (p = 0.017) and remote history of encephalitis (0 = 0.036).

Younger patients (p = 0.002) with earlier age at epilepsy onset (p = 0.002) whom suffered lower number of GTCG (p = 0.042) and with unilateral HS on MRI (p = 0.037) were considered good candidates for epilepsy surgery.

The best surgery outcome were seen in patients with remote history of febrile seizures (p = 0.0008) and longer latent period (p = 0.001).

Conclusions: Less than 20% of patients with MTLE associated to HS will reach control with medical treatment, approximately 2/3 of the medically resistant patients are good surgical candidates. Older age at epilepsy onset, presence of aura and low number of GTCG are associated with response to medical treatment; history of febrile seizures and longer latent period are associated to good surgery outcome.

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Ruth Ottman 1 , C. Barker-Cummings 1,3 , W. A. Hauser 1 , V. Vasoli 4 , C. Leibson 4 and J. R. Buchhalter 2 ( 1 Sergievsky Center, Columbia University, New York, NY ; 2 Phoenix Children's Hospital, Phoenix, AZ ; 3 Social & Scientific Systems, Inc., Durham, NC and 4 Mayo Clinic, Rochester, MN )

Rationale: Most clinical epilepsy research is carried out in referral settings, where the distribution of clinical features is biased towards more severe cases. We studied a large population-based series of incident cases, to define the range of clinical epilepsy features in the general population.

Methods: All individuals born in 1920 or later who had incidence of unprovoked seizures while residing in Rochester, Minnesota between 1935 and 1994 were identified in the Rochester Epidemiology Project. Medical records were abstracted on these cases to obtain detailed information on seizure types, syndromes, seizure frequency, EEG and neuroimaging findings, and antecedent etiologic factors.

Results: 916 incident cases were identified, of whom 885 (97%) gave permission for review of their medical records. Among these 885 subjects, 699 (79%) had epilepsy (i.e., ≥2 unprovoked seizures) and the remaining 21% had a single unprovoked seizure. Antecedent etiologic factors were identified in 34% of cases overall, and this proportion increased over time, from 28% in incidence cases from 1935–1954, to 32% in those from 1955–1974, and 38% in those from 1975–1994. The increase in the proportion of symptomatic cases was largely attributed to stroke, which comprised 4% of symptomatic cases prior to 1975 and 24% of those from 1975–1994. Overall, 78% of cases with epilepsy were classifiable with respect to broad epilepsy syndrome (primary generalized versus focal). The proportion of epilepsy cases who were classifiable increased from 64% of those diagnosed in 1935–1954 to 82% of those diagnosed in 1975–1994. The most frequent reason for lack of classifiability was absence of epileptiform EEG abnormalities (73% of unclassifiable cases). Among classifiable epilepsy cases, 33% had primary generalized epilepsy, 66% focal, and 1% both. Only 21% of all classifiable epilepsy cases were diagnosed with an idiopathic generalized epilepsy syndrome (IGE). Among the more recent cases (diagnosis 1975–1994, 82% classifiable), the proportion with IGEs was only 13%. The proportion of epilepsy cases who were seizure-free increased from 26% in the first year since diagnosis to 50%, 58%, 65% and 70% in the 2nd, 3rd, 4th, and 5th years respectively.

Conclusions: These results provide a very different picture of epilepsy prognosis than is observed in clinical series derived from referral sources. A majority of incident epilepsy cases become seizure-free within 5 years of diagnosis. Although idiopathic generalized epilepsy syndromes are often referred to as “common epilepsies” they comprise fewer than 25% of all incident cases. Increased survival from stroke has led to a concomitant increase in the number of symptomatic epilepsy cases in the population.

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Frederick Andermann 1 , J. Jacobs 1 and F. Dubeau 1 ( 1 Montreal Neurological Institute, Montreal, QC, Canada )

Rationale: Propagation of ictal epileptic discharges can influence the clinical appearance of seizures and must be recognized to characterize seizures correctly. Fast propagation from the occipital to the temporal lobe has been very well described, but until now the reverse spread has not been emphasized. The objective of this study is to describe two patients who experienced ictal propagation from temporal to occipital regions during surface EEG.

Methods: Out of telemetry studies recorded at the Montreal Neurological Hospital over a ten-year period two patients were found to have ictal propagation from temporal to occipital lobe. We retrospectively reviewed all ictal EEGs of these patients and their seizure semiology.

Results: Habitual seizures of patient one presented with altered consciousness, automatisms of the right arm followed by postictal fatigue and headache. Additionally he described an inconsistent aura of anxiety with tachycardia and visual flashes. Telemetry studies suggested a right temporal lobe generator. On one occasion propagation from temporal to occipital was documented on surface EEG during ictal SPECT. The seizure initially involved the temporal lobe followed by rapid spread of the seizure to the ipsilateral occipital lobe. At this time a definite ictal amaurosis was documented lasting a minute before seizure stopped. SPECT revealed widespread tracer enhancement in the right temporal and occipital lobe. Brain MRI studies were normal. Intracranial EEG investigation of both temporal lobes with additional electrodes in the temporo-occipital junction, revealed right temporal onset and rapid propagation contralaterally. The patient underwent a right selective amygdalo-hippocampectomy, but continued to have seizures. The second patient, with a right hemiatrophic hemisphere and porencephalic cyst, presented with seizures that started with an auditory aura, bad smell and a warm sensation in the left arm followed by impaired consciousness. Telemetry suggested a widespread centro-temporal seizure onset. During one noctural event propagation from the temporal to the occipital lobe could be observed on surface EEG. The ictal discharge remained confined to the right occipital lobe for six minutes before seizure stopped. During this period the patient was unresponsive but did not show typical occipital symptoms. Subsequent intracranial electrode investigation showed habitual temporal onset with propagation to the Heschl's gyrus. After a right mesolimbic and neocortical temporal resection including part of the Heschl's gyrus patient was free of seizures only temporarily.

Conclusions: The two patients showed that propagation from temporal to occipital lobe structures might be observed on rare occasions. Both had clinical and EEG findings suggesting neocortical temporal generators. This rare ictal temporo-occipital propagation pattern must be considered in patients, who have seizures with both temporal and occipital features. The propagation may have predictive value for their surgical outcome.

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Benjamin E. Atkinson 1 , M. Atkinson 1 , A. Shah 1 and C. Watson 1 ( 1 Neurology, Wayne State University, Detroit, MI )

Rationale: Posterior Reversible Encephalopathy Syndrome (PRES) is a syndrome characterized by increased signal intensity on T2-weighted and FLAIR MRI images, predominantly in the posterior quadrants of the cerebral hemispheres. It is most often associated with hypertensive crisis, eclampsia, chronic renal failure, and immunosuppression. Information pertaining to status epilepticus (SE) and PRES is lacking in the medical literature. A review of the literature demonstrates that it is not uncommon for patients to develop seizures in association with PRES, but only one article mentions SE in this population. Thus, the incidence of the co-existence of SE and PRES is unknown.

Methods: We report two patients who developed PRES and nonconvulsive SE (NCSE) within a single week at our institution. A thorough review of these patients' charts (paper and electronic), electroencephalograms (EEG) (continuous and routine), and all neuroimaging was undertaken.

Results: Case 1: 41-year old African American female with a history of sickle cell disease, renal failure and seizure disorder presented to the hospital with intractable nausea and vomiting and uncontrolled hypertension (275/132 mmHg). Within 24 hours of admission, the patient became obtunded and unresponsive to external stimuli. EEG revealed high amplitude spike and slow wave activity in the right posterior temporal region, which was followed by rhythmic, medium to high amplitude, 3–4 Hz spike and slow waves in the right hemisphere with spread to the left hemisphere. This continued for 18 days despite medical treatment with midazolam, propofol, phenytoin, valproate and levetiracetam. MRI confirmed PRES and demonstrated improvement in T2 signal abnormality 20 days after the initial scan.

Case 2: 62-year old African American female with a history of myocardial infarction, congestive heart failure and peripheral vascular disease presented to the hospital with headache and arm pain. The patient had uncontrolled hypertension on presentation with readings as high as 262/135 mmHg. Intubation was required for respiratory failure and declining mental status. EEG demonstrated continuous spike and wave and polyspike and wave discharges that were seen diffusely over both hemispheres. Electrographic seizures were seen between periods of burst suppression until the patient expired 7 days after onset. MRI revealed multiple areas of increased signal intensity on T2-weighted images within the periventricular, subcortical and deep white matter.

Conclusions: Two consecutive cases of PRES associated with NCSE are presented. One patient returned to prior functional status while the second expired from medical complications. The constellation of PRES and NCSE has not been described in the literature and this leads to important questions such as the incidence of NCSE in patients with PRES, the character and quality of seizures, and the type of management required when these two conditions are found together. Further research needs to answer these questions.

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Anthony L. Ritaccio 1 , T. Lynch 1 , M. Gruenthal 1 , L. Ciraulo 1 and D. Collins 1 ( 1 Neurology, Albany Medical College, Albany, NY )

Rationale: Infrequently, in the evaluation of candidacy for temporal lobe epilepsy surgery, bilateral independent ictal onsets are confirmed on scalp EEG. Mechanisms of independent bilateral expression are poorly understood. Although mesial sclerosis is the hallmark lesion, cryptogenic cases are represented in abundance. Multiple video EEG recording sessions are often required for confirmation (Koukou et al 2007). As many as 25% of surgical failures have been attributed to the elaboration of contralateral “discordant “ seizures in post-operative assessment (Hennessy et al 2000). We reviewed our experience to compare with other centers' series.

Methods: We queried our epilepsy monitoring database between 8/03 and 12/06 to identify cases of confirmed independent temporal lobe ictal onsets based on scalp EEG criteria. Retrospective chart review of verified cases was undertaken to identify risk factors, lesional basis (if any), therapeutic history and circumstance of detection.

Results: 8 cases of bilateral independent temporal lobe onsets were found. 6/8 were cryptogenic/ non-lesional. 1/8 was associated with severe antecedent head trauma and massive bitemporal encephalomalacia on MRI. 1/8 was a patient with presumed genetically based partial seizures and mental retardation that is shared with an identical twin and older brother. 3/8 required a second monitoring experience to establish bilateral ictal behavior, including one case revealed after surgical failure for presumed unitemporal epilepsy. In one unique case, 7 consecutive seizures clustered left temporal, followed by exactly alternating right and left seizures for 14 more ictal events. All patients were refractory to multiple anticonvulsant regimens as well as vagal nerve stimulation. 2/8 are undergoing presurgical assessment for potential resection of the site of most frequent onset.

Conclusions: Multiple risk factors and pathologic substrates of bilateral independent foci were identified. All cases share a history of resistance to non-resective strategies. Sequential emergence in several cases implies unique facilitory and inhibitory cyclic behaviors. Functional relationships have been documented between symmetric temporal lobe ictal zones, most commonly mutually suppressive (Chkhenkeli et al 2007). Suppressive reciprocal relationships may account for sampling error as well as the “cluster effect” (Haut et al 1997), necessitating the recording of a large number of seizures to confirm bilaterality. Not assuming simultaneity in genesis, the mechanisms and chronology of unitemporal to bitemporal expression is not understood. The surgical strategy of unitemporal resection has a variable outcome, including fatigue of the discordant side as well as reports of increased autonomy and refractoriness of the remaining contralateral ictal zone. Due to elusive diagnosis coupled with therapeutic resistance, bilateral temporal lobe epilepsy may be considered the maximal negative expression of temporal-based epilepsies and is likely more common than currently appreciated.

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Daniel O. Claassen 1 , P. J. Walting 1 , K. M. Tan 1 , P. J. Pittock 1 and E. L. So 1 ( 1 Neurology, Mayo Clinic, Rochester, MN )

Rationale: Musicogenic epilepsy is a subtype of reflex epilepsies. It is an unusual and oftentimes debilitating phenomenon. This case highlights the problematic treatment of the condition, and offers a novel environmental therapeutic approach.

Methods: Case report

Results: A 62-year-old ambidextrous woman presented with a sixteen-year history of unprovoked spells. These spells were described as a sudden feeling of intense fear accompanied by an ominous sense of a woman present beside her. EEG performed elsewhere revealed bitemporal sharp activity. The following failed to control her spells: phenytoin, carbamazepine, gabapentin, and felbamate.

One year prior to presentation, she had an abrupt change in her spells. Specifically, her spells were provoked by slow, melancholic music. They were characterized by sadness and unresponsive staring lasting minutes. The spells had occurred while singing hymns at church. When walking in the mall, she had experienced the spells while listening to ambient music in the mall. Levetiracetam was initiated for these spells, but it was discontinued due to lack of efficacy.

Background EEG recorded at our Epilepsy Monitoring Unit showed right temporal spike discharges. She listened to melancholic music for 15 minutes every hour for a total of seven hours. Three of the seven trials triggered spells characterized by fear, tachycardia, crying, then confused behavior, lip smacking, and postictal nose-wiping with the right hand. Some spells were accompanied by the ominous sense of a woman beside her. As the confused behavior and lip smacking developed, rhythmic right frontotemporal sharp theta and alpha frequency discharges developed with rapid spread to the left temporal region. She was also found to have Hashimoto's thyroiditis (TSH 8.9 mIU/L; normal of 0.3 to 5.0) and the possibility of an immune-mediated epilepsy associated with elevated TPO antibodies (868 IU/mL; normal of <40.0) was entertained though cerebrospinal fluid was normal and no benefit occurred after a course of either IV methylprednisolone or IV immunoglobulin (administered during prolonged EEG monitoring).

The patient noticed that music with an upbeat, fast-tempo rhythm did not trigger seizures, and they also aborted the onset or progression of seizures triggered by melancholic music. Therefore, when she was exposed to melancholic music, such as when walking in the mall, she would turn on her portable audio player and listen to up-tempo music sung by Elvis Presley.

Conclusions: Music and emotion are closely linked. Emotions precipitating seizures is a well-described phenomenon. In our patient, it seems that the slow tempo as well as the timbre and pathos expressed in the music triggered the patient's seizures. There have been rare reports of intrusive musical hallucinations in the elderly that were attenuated paradoxically and successfully by listening to music. In our patient, musicogenic seizures were successfully prevented or terminated by counter treatment with music of a different tempo.

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James Jordan 1 , S. Aminai 1 , S. Farhadi 1 , K. Tufenkjian 1 and M. Werz 1 ( 1 Neurological Institute, University Hospitals Case Medical Center, Cleveland, OH )

Rationale: A major effort of the past decade has been to better understand non-convulsive status epilepticus (NCSE). Convulsive status epilepticus (CSE) is known to be life-threatening, with a potential for worsened outcome depending on etiology, age, and time to treatment. In this study, we have retrospectively identified all cases of NCSE at a tertiary hospital in the year 2006, categorizing NCSE and outcome.

Methods: This study is a retrospective case series. In it, NCSE is defined as 1) a change in mental status without concurrent convulsions, and 2) electrographic seizures on the electroencephalogram (EEG). Outcome is determined by level of care needed on admission vs. discharge, with four possible endpoint scores (ES's) given, from 0 to 3: 0 = return to baseline; 1 = temporary increase in level of care from baseline (i.e., from home to rehabilitation); 2 = permanent increase in care (i.e., from home to nursing home); or 3 = death. The study is stratified by two known complicating factors in NCSE: age (younger or equal to 65 years old vs. older than 65) and level of consciousness at the time of EEG (altered metal status vs. comatose). Other variables documented include medications (time started, dosages, and serum concentrations), etiology of NCSE, and complications/comorbidities.

Results: Fifty-five cases were identified. To date, 22 of the 28 patients qualified, and of these, ten patients were treated within the first hour (“Early Treatment Group”, or ETG), while the remaining twelve were treated after one hour (“Late Treatment Group”, or LTG). Overall, those in the ETG had a mean ES of 1.2, while in the LTG, it was 1.5, showing a 20% improvement in outcome for those treated earlier. If stratified based on age, the ETG's mean ES was 1.0 for younger patients, and 1.67 for seniors. The LTG showed a mean ES of 1.17 for younger patients, and 1.83 for older patients. When stratified based on level of consciousness, the ETG had a mean ES of 0.57 if not in coma vs. a striking 2.67 if comatose. The LTG showed similar results, with a mean ES of 1.0 in the non-comatose vs. a mean ES of 2.2 in those with coma.

Conclusions: The preliminary data of this study suggest that earlier treatment for NCSE, if started within the first hour of onset, might improve outcome. Stratification based on age and level of consciousness improves outcome for the young and the non-comatose, and worsens it for seniors and especially those in a coma. This latter group's outcome is likely complicated by a more severe underlying etiology. To that end, our own analysis of etiology - as well as aggressiveness of AED dosing, and subtypes of NCSE – will be presented. This study encourages a continuing refinement in our ability to diagnose - quickly – who has NCSE and who has a “mimicker” (a post-ictal state, toxic-metabolic encephalopathy, etc.).

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Ritu Bagla 1 , M. R. Sperling 1 and M. Nei 1 ( 1 Neurology, Thomas Jefferson Medical College, Philadelphia, PA )

Rationale: Seizures are a common presenting symptom in patients with oligodendrogliomas, and are often refractory despite multiple antiepileptic drugs (AEDs). Temozolomide chemotherapy can improve seizure (sz) control in patients with oligodendrogliomas. The efficacy of chemotherapy, epilepsy surgery, specific AEDs, and radiation therapy on sz frequency in these patients with medically refractory epilepsy is unknown.

Methods: All patients (n = 9) with oligodendrogliomas who presented to our epilepsy center between 1988 and 2006 were included in this retrospective analysis. Response to epilepsy surgery, temozolomide, and antiepileptic medications were noted and graded according to sz frequency, averaged over the prior >3 months, at the time of last evaluation after each type of treatment: 1) sz-free, 2) ≥ 80% reduction, 3) ≥ 50% and <80% reduction, or 4) < 50% sz reduction, compared with sz frequency at initial presentation to our center.

Results: All 9 patients (mean age 35.7 years, range 10–50 years, 4 men and 5 women) had initial incomplete surgical resections with pathology revealing WHO grade II oligodendrogliomas (2 frontal, 3 fronto-temporal, 2 parietal, 2 parieto-occipital). The mean baseline sz frequency was 11.2 per month (range 3–30 per month), and mean duration of follow-up was 84 months (range 4–84 months). 1 patient received 6 week of radiation therapy after initial resection taking valproic acid has been sz-free on topiramate monotherapy for 35 months. 8 patients had epilepsy refractory to ≥2 AEDs (mean 6.0, range 2–14). 6 patients underwent epilepsy surgery, at which time 2 had progressed to WHO grade III. After epilepsy surgery, 1 patient was sz-free (for 41 months), and 1 patient had ≥ 80% reduction in sz frequency after being sz-free for 34 months. 4 patients received temozolomide chemotherapy, 2 of which had evidence of tumor progression on MRI prior to treatment. All of these patients had ≥ 80% sz reduction after temozolomide treatment. Of these, 2 patients had not responded to prior epilepsy surgery. 1 of these patients remains sz-free for 24 months with a prior baseline frequency of daily szs. After treatment with temozolomide, all 4 patients had evidence of tumor stability (mean follow-up of 40.0 months, range 13 months-8 years).

Conclusions: Szs can be difficult to control in patients with oligodendrogliomas. These data suggest that chemotherapy can be particularly effective in controlling medically refractory seizures, as well as in stabilizing the tumor on MRI in patients with oligodendrogliomas. Additional studies in larger populations of patients are needed to fully evaluate the roles of chemotherapy, epilepsy surgery, specific AEDs, and radiation therapy for sz control in these patients. The optimal duration of temozolomide therapy for epilepsy is unknown.

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Markus Reuber 1 and L. Plug 1 ( 1 Academic Neurology Unit, University of Sheffield, Sheffield, United Kingdom )

Rationale: The distinction of epilepsy and psychogenic non-epileptic seizures (PNES) is a great clinical challenge. Misdiagnosis rates range between 10 and 30%, depending on the clinical setting. Factual items such as tongue-biting, incontinence or sleep seizures, have been shown not to differentiate between epilepsy and PNES. In view of this we and others have explored the “diagnostic” potential of conversational features which may otherwise be considered redundant or even irritating, such as an apparent difficulty or inability to describe individual seizure episodes, hesitations, restarts or who initiates a particular subject. Systematic analysis of such features in doctor-patient consultations in different in-patient, outpatient or research settings has revealed that the two patient groups are characterized by very different communication profiles (table 1) (1, 2). Attention to these profiles can improve physicians' diagnostic accuracy. However, the interactional, topical and linguistic features which make up the profile cannot be observed if physicians adopt a fact-oriented interviewing style dominated by interruptions and lists of closed questions. Here, we explore how these differentiating features may be elicited in routine clinical encounters.

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[ Table 1.  ]

Methods: We used Conversation Analysis (CA) to analyse clinical encounters with 15 patients with video-EEG proven epilepsy or PNES. The encounters lasted less than 30 min and followed a simple schedule (table 2). The physician did not mention seizures at the outset and made few inquiries. He listened to the patient without interrupting. He was encouraged to tolerate silence, or to use mmm, right or repetitions of something the patient has said to encourage elaboration. He was strongly discouraged from introducing information to which the patient has not already referred. We assessed to what extent the communicative differences between patients with epilepsy and PNES are observed in these encounters by asking a linguist unaware of the video-EEG result to predict each patient's diagnosis on the basis of his/her communication profile.

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[ Table 2.  ]

Results: The previously described differentiating features can be clearly observed in our brief clinical encounters. They allowed the linguist to accurately predict the patient's diagnosis in all 15 cases.

Conclusions: We describe an open interviewing style, which allows patients to develop their own communicative agenda. Previous studies have shown that this style is associated with higher patient satisfaction rates and compliance with treatment recommendations. This study shows that it also allows physicians to elicit interactional, topical and linguistic features, which can help them to differentiate more accurately between epileptic seizures and PNES.

References:

(1)Schöndienst, M., Konversationsanalytische Zugänge zu Gesprächen über Anfälle. In: Jacobi, R.-.M.E., Claussen N. and Wolf, P. (eds.): Die Wahrheit der Begegnung. Festschrift für Dieter Janz zum 80. Geburtstag. Königshausen & Neumann: Würzburg, 2001: 73–84.

(2)Schwabe, M., Howell, S. J., Reuber M. Differential diagnosis of seizure disorders: a conversation analytic approach. Soc Sci Med, in press, DOI: 10.1016/j.socscimed.2007.03.045.

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Francesca Bisulli 1 , L. Licchetta 1 , I. Naldi 1 , F. Pittau 1 , F. Provini 1 , P. Montagna 1 , L. Vignatelli 1 and P. Tinuper 1 ( 1 Department of Neurological Sciences, University of Bologna, Bologna, Italy )

Rationale: Purpose: This study analyses the clinical and prognostic features of 56 patients (pts) with nocturnal frontal lobe epilepsy (NFLE) after a long follow-up.

Methods: Methods: We selected 56 patients (31 males, 25 females) with NFLE according to the following criteria: a history of nocturnal seizures with symptoms suggesting frontal lobe involvement, video-polysomnographic recording of at least one major episode (hypermotor or tonic seizures) or two stereotyped paroxysmal arousals, a follow-up period longer than 5 years, last visit within the last 24 months. All patients underwent a full clinical, neuroradiological and neurophysiological examination. On the basis of seizure frequency at the last visit our population was divided into 2 groups: pts with Negative Evolution (NE- seizure frequency varying from daily to pluri-yearly: 31 pts, 55.4%) and pts with Positive Evolution (PE- seizure-free for at least 1 year or with sporadic seizure: 25 pts, 44.6%).

Only 7 pts had positive neuroimaging findings.

Results: Results: At disease onset, seizure frequency was daily in most pts in both NE (35.5%) and PE (44%) groups. At the last visit, most NE pts (64.5%) presented monthly/weekly seizures and only 16% still had daily seizures. Among NE pts the mean age at onset of epilepsy was slightly lower than in PE pts (PE 17.8 years vs NE 11.8 years; p = 0.046); a family history of febrile convulsions (FC) was found only in the PE group (16%). No significant differences were observed between the two groups in seizure type, personal history of FC, status epilepticus, family history of epilepsy and parasomnias, secondary generalization, seizures also in wakefulness, interictal epileptiform abnormalities.

Conclusions: Conclusions: These preliminary data show only two significant differences between NE and PE pts regarding earlier age at onset in the NE group, that seems to be a negative prognostic factor, and a positive family history for FC reported only in the PE group.

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L. R. Osorio 1 , J. H. Villeda 1 and M. V. Alonso 1 ( 1 Neurochemistry, National Institute of Neurology and Neurosurgery, Mexico D.F., Mexico ; 2 Neurodegenerative Diseases, National Institute of Neurology and Neurosurgery, D.F, Mexico and 3 Surgery of Epilpsy, National Institute of neurology and Neurosurgery, Mexico D.F., Mexico )

Rationale: Cerebral hemiatrophy or Dyke-Davinoff-Masson syndrome is characterized by seizures, facial asymmetry, contralateral hemiplegia or hemiparesis, and mental retardation. Although radiological findings of this syndrome are well known, studies about aminoacids and cellular damage have not been considered in this cerebral hemiatrophy syndrome.

Methods: Surgical specimen from a patient with chronic pharmaco-resistant temporal lobe epilepsy was examined. The epileptic region was localized to the right temporal lobe, and an extensive surgical removal of the temporal lobe plus amygdala (A) and hippocampus (HP) was performed. The surgical specimens were obtained and immediately frozen in liquid nitrogen and stored at −75C for biochemical studies. The surgical specimens for histopathological evaluation were immersed and fixed in freshly prepared 1% paraformaldehyde.

Results: In this study, the levels of neurotransmitters were highest in the hippocampus compared to the temporal neocortex (T1, T2 and T3). In amygdala, only GABA was found whereas other aminoacids were absent. Positive immunoreactivities with nestin and vimentin were observed in all brain regions studied.

Conclusions: This patient's syndrome should be considered as a post-infectious event which caused hemiparesis and, later recurrent seizures. Higher expression of nestin has been observed in proliferative endothelial cells. The expression in astrocytes may mainly reflect an early response of these cells to injury. Nestin may play a role in protecting the brain from injury. It has been proposed that re-expression of embryonic genes by mature glial cells is associated with morphological plasticity.

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Line S. Roste 1 , T. Henriksen 2,3 , L. Gjerstad 1,3 , H. Husby 4 and E. Tauboll 1,3 ( 1 Dep of Neurology, Centre for Clinical Neuroscience, Rikshospitalet, Oslo, Norway ; 2 Dep of Obstetrics and Gynecology, Rikshospitalet Medical Centre, Oslo, Norway ; 3 University of Oslo, Oslo, Norway and 4 Dep of Obstetrics and Gynecology, Asker and Baerum hospital, Baerum, Norway )

Rationale: In recent years, neurologists have become increasingly aware of the importance of gender specific issues throughout life when treating women with epilepsy. In clinical practice however, general practitioners and gynaecologists are more likely to be consulted about menstrual disturbances, contraception, fertility, pregnancy, breast feeding, menopause and osteoporosis prophylaxis. Women with epilepsy experience a variety of advices in these issues or no advice at all, and national guidelines in the treatment of women with epilepsy were in demand.

Methods: Near 30 consultants in neurology and gynaecology from university and municipal hospitals in Norway participated in writing the guidelines. The clinicians were divided in 6 groups; 1) Puberty, menstrual disturbances and gender-specific side effect of antiepileptic drugs, 2) Contraception, 3) Pregnancy, 4) Breast feeding, 5) Sexuality, and 6) Menopause and bone health. Every group consisted of both neurologists and gynaecologists. The work was headed by a steering committee with a coordinator (LSR).

Results: Completed document based on consensus and advices on the treatment of women with epilepsy were given with 3 classes of evidence. The national societies for general practitioners, gynaecologists and neurologists all affirmed the document.

Conclusions: A consensus among neurologists and gynaecologists in Norway over the current treatment of women with epilepsy has been made. A nationwide distribution is made possible by publication through the Norwegian Medical Association (http://www.legeforeningen.no/asset/33810/1/338101.pdf).

An English summary of the guidelines is given in: Røste LS, Taubøll E. Expert Rev Neurotherapeutics 2007; 7, 289–300

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Tiago Mestre 1 , C. Bentes 2 , T. Paiva 2 , A. Lomba 2 and I. Henriques 2 ( 1 Neuroscience, H. Santa Maria, Lisbon, Portugal and 2 EEG/Sleep laboratory, Lisbon Medical School, Lisboa, Portugal )

Rationale: Sleep and epilepsy have multiple influences. Sleep complaints are more frequent in epilepsy patients. Epilepsy-related mood disturbances, anti-epileptic drugs (AEDs) effects and sleep-related seizures are possible contributing factors. The aim of this project is to evaluate sleepiness and sleep quality in epileptic patients.

Methods: In an outpatient epilepsy tertiary centre, a self-filled questionnaire was distributed comprehending general demographic data, the Brief Symptom Inventory (BSI), the Epsworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI) and the Medical Outcome Study (MOS) sleep questionnaires. A clinical report concerning seizure type, seizure frequency and circadian ocurrency, disease duration and number of AED in use was filled by the physician. For comparing demographics and questionnaire scores between populations the Student t-test was used and for the identification of a possible effect of epilepsy-related variables in the obtained test scores an analysis of variance was conducted.

Results: In the studied population (n = 95, F:M - 56:38, mean age 40.5 ± 15.3 years) 30.5% patients had partial seizures, 41.1% patients had generalised seizures. The mean disease duration of 21.1 ± 15.8 years. 43.2% patients were on monotherapy and 23.2% on bitherapy. 42.1% of patients were seizure-free in the month before and 26.3% had less than 1 seizure per week. The mean ESS score (8.0 ± 5.0 vs 6.8 ± 4.3) and the mean PSQI score (5.6 ± 3.3 vs 5.1 ± 3.5) were not significantly different between epileptic patients and controls (n = 86). On MOS questionnaire, the item of sleep disturbance (32.1 ± 23.9 vs 21.4 ± 22.1, p = 0.004) was the only found to be significantly higher in the epileptic population. Epileptic patients had higher scores on the mean Positive Symptom Distress Index on BSI scale (1.79 ± 0.5 vs 1.54 ± 0.4, p = 0.002). Seizure type and frequency, its circadian ocurrency, disease duration and the number of AED did not had an affect on ESS, PSQI, MOS and ISP Distress index scores.

Conclusions: Globally, epileptic patients were comparable to non-epileptic controls in terms of sleepness and sleep quality as evidenced by ESS, PSQI and MOS tests, with expection of the item sleep disturbance in the latter. The good overall disease control may be a contributive factor for the results. The studied epilepsy-related factors did not show an influence on sleepiness nor on sleep quality. The higher ISP distress index may related to epilepsy chronic course.

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Kyoung Heo 1 , B. Ye 1 , S. Jang 1 , Y. Cho 1 and B. Lee 1 ( 1 Neurology, Yonsei University College of Medicine, Seoul, South Korea )

Rationale: It is a common assumption that auras provide a clue of focal seizure onset and the seizure onset zone is closely related to the lesion in a patient with an isolated lesion. We investigated the value of aura in localization and lateralization of epileptogenic focus in patients with lobar epilepsy defined by an isolated lesion.

Methods: We selected the patient with a single lesion on MRI, who had visited the outpatient epilepsy clinic of Severance Hospital. The lesion should be confined to unilateral and single lobe (the patients with bilateral asymmetric hippocampal sclerosis were included), and the scalp EEG finding not be discordant with location and side of the lesion. The auras were classified into thirteen categories: epigastric, autonomic, emotional, cephalic sensation, vestibular, psychic, visual, somatosensory, dysphasic, olfactory, whole body sensation, auditory, and other. The lobar locations of the lesion were classified into mesial temporal, lateral temporal, frontal, parietal, and occipital lobes.

Results: The study comprised 284 patients. One hundred and eighty three patients (64.4%) experienced 282 auras with an average of 1.54 auras per patient. Mesial temporal lobe cases were most common (138 cases, 48.6%) and followed by frontal (67 cases, 23.6%), lateral temporal (56 cases, 19.7%), parietal (18 cases, 6.3%), and occipital (5 cases, 1.8%) lobe cases. Epigastric (p = 0.007), autonomic (0.015), and psychic (p = 0.006) auras were significantly more frequent in mesial temporal lobe epilepsy. However, there was no significant difference between the mesial and lateral temporal lobe epilepsy. The patients with frontal lobe epilepsy more frequently reported that they do not experience any aura, compared to the patients with other lobar epilepsies (65.7% vs. 26.7%). Somatosensory auras were more frequent in parietal lobe epilepsy (16.7%), and visual auras common in both parietal (22.2%) and occipital (40.0%) lobe epilepsy. Vestibular and visual (p = 0.002), epigastric and autonomic (p = 0.007), and olfactory and autonomic (p = 0.043) auras occurred more coincidentally. Dysphasia was more frequently found in left-sided epilepsy (n = 0 vs. n = 16), but vestibular and olfactory auras were more common in right-sided epilepsy (9 vs. 2; 6 vs. 1).

Conclusions: Our results suggest that the type of aura can provide useful localizing information, and are generally consistent with previous studies which investigated auras in surgical cases.

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Sophie Macrodimitris 1 , N. Jette 2,1 and M. Suddes 1 ( 1 Clinical Neurosciences, Calgary Health Region, Calgary, AB, Canada and 2 University of Calgary, Calgary, AB, Canada )

Rationale: The quality and safety of hospital care is becoming increasingly important as health care costs rise and clinical error is scrutinized. Admission to a seizure monitoring unit (SMU) is unique in that (a) it is often elective rather than acute; (b) medication is reduced to generate symptoms rather than increased to stop symptoms; and (c) a variety of disciplines are consulted which are not standard for other inpatient admissions. Thus, typical hospital quality and safety guidelines often do not apply to SMUs. We describe a newly implemented SMU quality and safety improvement program geared towards establishing such guidelines.

Methods: (a) Development of SMU Quality Improvement (QI) Team: With the guidance of the Neurosciences Department QI Consultant, a multidisciplinary team was developed with representatives from the various individuals involved in the SMU: EEG technologists; nursing staff; epileptologists; a psychologist; and a patient. (b) Informal Survey of Canadian Epilepsy Centres with SMUs: A survey was conducted of 12 Epilepsy Centers in Canada, exploring how they monitor the quality and safety of the SMU. (c) Program Evaluation Initiatives: Based on the program evaluation literature, we developed a Logic Model and initiated a project to identify key quality and safety indicators to track prospectively. These were based on QI principles of safety, timeliness, efficiency, effectiveness/clinical outcomes, and utilization. Finally, we identified priority projects and developed sub-teams to initiate PDSA (Plan, Develop, Study, Act) cycles, following the methods recommended for QI initiatives.

Results: (a) SMU QI Team: The multidisciplinary team is led by the psychologist and the QI consultant, with representatives from every aspect of the SMU, including a patient. (b) Informal survey: Eight of 12 Canadian SMUs responded to the survey. Number of beds ranged from 1–8 (mean = 3). Half were open 7 days/week and the other half were open Monday-Friday. Number of admissions/month ranged from 4–40 (mean = 12). Although each program had an SMU management team, none had a team devoted to monitoring quality and safety. One-third of programs evaluated staff satisfaction and one-quarter used informal means to evaluate patient satisfaction. No program had a formal evaluative process for patient satisfaction. (c) Program Evaluation Initiatives chosen for implementation: Developing objectives to guide SMU QI initiatives; quality indicators and baseline information; formal patient and staff satisfaction surveys; patient and staff education; enhancing staff consistency; tracking seizure induction procedures; and improving the safety of seizure management.

Conclusions: This project demonstrates that developing a multidisciplinary quality and safety team for SMUs is feasible and necessary. By having a SMU QI Team in place, we hope that patient and staff satisfaction can be improved, patient and staff education will be enhanced, and ultimately complications, length of stay and wait times may be reduced.

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Anna Rosati 2,6 , A. Tomassini 1 , B. Pollo 3 , C. Ambrosi 4 , S. Filipponi 5 , C. Boninsegna 5 , A. Schwarz 1 and N. Rizzuto 6 ( 1 Neurosurgery, S. Maurizio Hospital, Bolzano, Italy ; 2 Neurology, Spedali Civili, University of Brescia, Brescia, Italy ; 3 Neuropathology, Istituto Neurologico Besta, Milano, Italy ; 4 Neuroradiology, Spedali Civili, Brescia, Italy ; 5 Neurology, S. Chiara Hospital, Trento, Italy and 6 Neurology, Policlinico Borgo Roma, University of Verona, Verona, Italy )

Rationale: Epilepsy incidence in gliomas ranges between 30–80%. Low-grade gliomas are more epileptogenic than less benign brain tumours and for this reason epilepsy has been considered a positive prognostic factor. Seizures may represent the symptom carrying out the diagnosis and seem to be more frequent in frontal and parietal lobe gliomas. Epileptogenesis in glioma is multifactorial and it may explain drug resistance that usually occur in more than 30% of patients. Although it is known that the AED are not antiepileptogenic, prophylaxis in gliomas still remains an open question.

Methods: Between February 1th 2004 and April 1th 2006 all patients with glioma, who underwent surgical treatment at the Neurosurgery Division of Bolzano were prospectively unrolled on the study (last evaluation in April 1th 2007). At the enrolment time on the study (surgery time) patients were included in a list of progressive numbers. Epileptic patients enrolled with pair number and with impair number were respectively treated with PHT and LVT. However, patients with different therapy were not shifted on PHT or LVT, if seizure-free. Clinical, histological, and MRI features were analyzed.

Results: 64 patients (35 male and 29 female) were enrolled on the study. Age at the diagnosis ranged from 30 to 78 yrs (mean: 57 ± 12 yrs). Duration of disease ranged from 50 days to 8.8 yrs (median: 18 mo). Onset seizure type was focal (17), secondarily generalized (10), and epileptic status (2). Epilepsy diagnosis was made in 27 (42%) cases. Ictal semeiology was motor (8), sensitive (3), focal complex (11) and convulsive (5). Histological diagnosis was astrocytoma (3), mixed glioma (3), oligodendroglioma (10), malignant astrocytoma (4), and glioblastoma multiforme (GBM) (44). Surgical resection was total in 34, subtotal in 21 and partial in 9 cases. Adjunctive therapy was chemiotherapy (38) and/or radiotherapy (41). Glioma recurred in 46 pts and epilepsy first appeared in three of them. At the last follow-up 13/27 (48%) patients were seizure-free. Antiepileptic drugs included: PHT (10), LVT (6), CBZ (6), OXC (2), CBZ + PB (2), PB (1). All patients without AED never developed seizures during the follow-up (12 pts) or until death (23 pts). Epilepsy correlated with low-grade glioma (p = 0.02), and MRI cystic component (p = 0.04). Amongst highest grade gliomas, epilepsy was more frequent in GBM deriving from a low-grade tumour (p = 0.02).

Conclusions: 1) Seizures in glioma represent a quite exclusive onset symptom, that rarely occurs at the glioma recurrence and never during a “radiologically” stable disease. 2) Radiological and histological features indicating a low malignancy and/or a slow growing are associated to a highest epilepsy incidence. 3) A poor seizure control is associated with: motor and sensitive focal seizures; abnormal neurological examination; radiotherapy; high-grade glioma diagnosis. 4) LVT is more effective compared to old AES. 5) The absence of AED prophylactic role is prospectically confirmed.

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Houman Khosravani 1 , N. Mehrotra 1 , M. Rigby 1 , W. J. Hader 1 , R. Pinnegar 1 , N. Pillay 1 , S. Wiebe 1 and P. Federico 1,2 ( 1 Clinical Neurosciences, University of Calgary, Calgary, AB, Canada and 2 Radiology and Diagnostic Imaging, University of Calgary, Calgary, AB, Canada )

Rationale: High frequency oscillations (HFOs) > 200 Hz are believed to be associated with epileptic processes. The spatial distribution and evolution over time of HFOs leading up to seizure onset is unknown. Also, recording of HFOs through conventional intracranial electrodes is not well established. We therefore wished to determine: whether HFOs could be recorded using commercially available depth macroelectrodes, and to study the spatial distribution and temporal progression of HFOs during the pre-ictal-to-ictal transition.

Methods: Intracranial EEG recordings from seven patients (19 seizures) with temporal lobe epilepsy were obtained using commercial depth or subdural electrodes. EEG recordings were analyzed for frequency content in five spectral bands spanning DC-500 Hz in two ways: 5 s before and after seizure onset (spatial analysis), and for 30 s leading up to seizure onset (temporal analysis).

Results: Three main observations were made: HFOs (100–500 Hz) can be recorded using commercial depth and subdural grid electrodes. HFOs, but not < 100 Hz oscillations, were localized with maximal power to channels of ictal onset (100–200, 400–500 Hz p < 0.05; 300–400 Hz p < 0.001). Temporal analysis showed increased HFO power for ≈ 8 s prior to electrographic onset, with the greatest difference observed in the 100–200 Hz band when the ictal onset channel was compared with a distant contact (p < 0.05).

Conclusions: These results suggest that HFOs can be recorded by depth macroelectrodes. Also, HFOs are localized to the region of primary ictal onset, and can exhibit increased power during the transition to seizure. Thus, HFOs likely represent important precursors to seizure initiation.

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Jean Tsai 1 and S. Herman 1 ( 1 Neurology, University of Pennsylvania, Philadelphia, PA )

Rationale: Understanding the electrophysiological milieu in which seizures develop is crucial to effective treatment and prevention. During sleep, epileptic seizures are primarily seen in slow wave sleep, in which delta frequency activity (reflecting neuronal synchrony) predominates. During wakefulness, increases in theta power correlate with drowsiness, decreased vigilance, and neuronal synchronization. We explored the hypothesis that epileptic seizures during wakefulness occur during periods of increased synchronization, as reflected by increases in theta power in the EEG.

Methods: Continuous scalp EEG recordings were collected from patients with temporal lobe epilepsy who were admitted to the Epilepsy Monitoring Unit for presurgical evaluation or seizure classification. Segments of EEG containing artifact were manually rejected. Theta and delta power were calculated using Standard Fourier Transformation for channels C3 and C4.

Results: Theta power increased during afternoon and evening hours. A preliminary analysis of seizure occurrence relative to theta power was performed in 3 patients. In two patients, there was an increase in theta power prior to a seizure. Postictally, theta power remained elevated for minutes to hours. Representative examples will be presented.

Conclusions: Circadian variability in theta power can be demonstrated in the waking EEGs of patients in the Epilepsy Monitoring Unit. Theta power, reflecting level of vigilance and arousal, is increased prior to some epileptic seizures. Increases in theta power may reflect increasing neuronal synchrony, and may in part account for timing of epileptic seizures. Further analysis of larger numbers of patients and seizures will be needed to confirm this hypothesis.

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Maria Teresa G. Santana 1 , J. L. Neto 1 , V. P. Rosa 1 , K. Lin 1 , A. C. Sakamoto 1 and E. M. Yacubian 1 ( 1 Neurology and Neurosurgery, Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, Brazil )

Rationale: Epidemiological studies indicate that the overall incidence of epilepsy is slightly higher in the male than in females. Partial epilepsies are more common among men, while generalized epilepsies prevail in women. Sexual dimorphism related to phenomenology of seizures has been described in temporal lobe epilepsy related to mesial temporal sclerosis (TLE-MTS). Probably differences between sexes are expressed early in life, when differential rates of cerebral maturation occur. According to Taylor's hypothesis, there would be biological basis for the higher vulnerability of the male brain and of the left hemisphere. Cerebral maturation would be more rapid in girls, so that boys would be at a greater risk for a longer time. A potential seizure-producing insult would affect the less functionally active side, the left hemisphere. Some findings such as isolated auras, emotional and sexual auras and lateralized ictal pattern would be more frequent in women. On the other hand, men would experience secondary generalization more often.

Objective: To study epilepsy characteristics, seizure phenomenology and differences of ictal behavior between sexes.

Methods: Data from 150 patients submitted to pre-surgical evaluation due to refractory unilateral TLE-MTS was retrospectively analyzed. All patients had prolonged scalp-sphenoidal video-EEG recording and a 1.5 T MRI.

Results: Results: There were 86 women and 64 men. Seventy-four (49.3%) suffered initial precipitant injury (IPI), being 35 female and 34 male. Age at IPI was undermined in 5. While 25 (71.5%) women had IPI in the first 2 years of life, they were equally distributed throughout the first 5 years in men. Auras (pushing the button > 50% of their seizures) were recorded in video-EEG in 33 females (38.3%) and 18 males (28.1%). As to types, 39 (45.3%) women presented ≥2 types of auras in contrast with the figures in 17 men (26.5%). Ictal fear was described by 17 patients (14 females). Sexual aura occurred in only one woman with right MTS. Thirty-four subjects (22.7%) presented >50% of secondary generalization being 21.8% of the men and 23.2% of the women.

Our data confirmed Taylor's hypothesis showing a slight decline in male distribution throughout the initial five years of life while the majority of females had IPI in the first two years. The earlier the IPI, the more the left hemisphere was affected. Regarding ictal behavior, women presented a greater number of auras and types of auras; among them, ictal fear was more prominent. Finally, secondary generalization was equally seen in both sexes.

Conclusions: There are differences between genders in epilepsy characteristics and seizure expressiveness in TLE-MTS probably related to anatomical and functional development of the brain.

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Olga Selioutski 1 and L. Liu 1 ( 1 Strong Epilepsy center, Strong Memorial Hospital, Rochester, NY )

Rationale: The diagnosis of paroxysmal events in the elderly presents particular difficulties because of co-morbid diseases complicating the analysis. In addition, common diagnostic modalities used routinely may be non-specific and confusing. We sought to assess the utility of outpatient EEGs in diagnosing paroxysmal events in the elderly.

Methods: A retrospective analysis of consecutive patients above the age 60 admitted for Long Term Monitoring (LTM) between January 2005 and May 2007 was performed. Pre-surgical evaluations and patients with status epilepticus were excluded. LTM data was compared to outpatient EEG records obtained prior to LTM admission.

Results: Adequate information, including prior outpatient EEG report, was available on 25 elderly patients. Based on the LTM data, epilepsy was diagnosed in 7 (28%), psychogenic non-epileptic attacks (PNEA) in 4 (16%), and in 14 (56%) there was no evidence for active epilepsy to explain the current spells. Of the 7 patients with epilepsy, 4 (57%) had prior abnormal outpatient EEGs: 3 with unequivocal interictal epileptiform discharges (IED) and 1 with sharply contoured waves (SCW). Of the 4 patients with PNEA, 1 had SCW on outpatient EEG. In the last group, three had unequivocal epileptiform discharges. All 3 patients had preexisting epilepsy, but the current paroxysmal events were not seizures. Two of the remaining 11 had SCW on the outpatient report.

Overall, 40% of patients had either IED or SCW on the prior outpatient EEGs, including patients with preexisting epilepsy, PNEA, and other non-epileptic events.

The positive predictive value (PPV) of IED for the diagnosis of epilepsy was 100% with a sensitivity of 60%. However, the PPV of IED for the diagnosis of seizures as etiology of current paroxysmal events was only 50% with a sensitivity of 43%. SCW had no predictive value in diagnosing paroxysmal events in the elderly.

Conclusions: Although the presence of IEDs on outpatient EEGs has a high PPV and sensitivity in diagnosing epilepsy, these IEDs have a limited role in diagnosing paroxysmal events in the elderly. Outpatient EEGs without unequivocal IEDs, including those with SCW, have no predictive value in diagnosing paroxysmal events in the elderly. IED and sharply contoured activity are relatively frequent in elderly with and without diagnosis of epilepsy, including PNEA, and should be interpreted with caution. When equivocal, LTM should be considered to make a definitive diagnosis.

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David M. Ficker 1 , M. D. Privitera 1 and C. Hughes 1 ( 1 Department of Neurology, University of Cincinnati Academic Health Center, Cincinnati, OH )

Rationale: Few studies have compared health outcomes in patients with recent onset epilepsy to the general population. We compare SF-36 scores in a cohort of subjects with newly diagnosed epilepsy to population norms and between subjects seizure and those not seizure free.

Methods: We prospectively measured the QOLIE-89, Profile of Mood States (POMS) and Adverse Events Profile in patients within three months of a new diagnosis of epilepsy. Serial measures were performed every four months. The Short Form 36 (SF-36) is a generic measure of quality of life and can be used to compare to other disease states and population norms. The SF-36 contains 8 scales: Physical Function, Role Limitations - Physical, Role Limitations - Emotional, Vitality/Energy, Mental Health, Social Function, Pain and General Health. The SF-36 subscales can be calculated from the QOLIE-89.

We compared the SF-36 scores for subjects who completed follow up to published norms (Ware 1993) using one sample t-tests. We compared both global norms (population norm) and age and gender matched norms (adjusted norm). We also compared SF-36 scores between subjects who were seizure free to those who were not seizure free at last follow up using two sample t-tests.

Results: We enrolled 53 subjects with newly diagnosed epilepsy (22 males, 32 females). Follow-up data was available on 40 patients (mean duration of follow-up 1.3 years). At last follow-up, 65% were seizure free and 35% were not seizure free.

The following differences were found:

For subjects who were seizure free: The means for the following subscales of the SF-36 were significantly different greater (P < 0.05) than those of the general population as well as those of age/gender matched norms: Social Function. The remaining subscales were not significantly different.

For subjects who were not seizure free: The means for the following subscales of the SF-36 were significantly different lower (P < 0.05) than those of the general population as well as those of age/gender matched norms: Vitality/Energy. The remaining subscales were not significantly different.

Comparing subjects who were seizure free and not seizure free: The means for the following subscales of the SF-36 were significantly different higher in the seizure free group (P < 0.05) than those who were not seizure free: Vitality/Energy, Mental Health, and Social Function. The remaining subscales were not significantly different.

Conclusions: Significant differences were found in some subscales of the SF-36 between norms and patients with newly diagnosed epilepsy. In addition, significant differences were found between seizure free subjects and those not seizure free.

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Andreas Schreiner 1 , K. Rettig 2 and B. Schauble 3 ( 1 Janssen Cilag EMEA, Neuss, Germany ; 2 G.E.M, Meerbusch, Germany and 3 Janssen Cilag Neuss, Medical and Scientific Affairs, Neuss, Germany )

Rationale: To explore effectiveness and tolerability outcomes of hospitalized patients with epileptic seizures treated with topiramate (TPM)

Methods: Prospective, open label, single arm, observational study including hospitalized patients > = 12 yrs with epilepsy. Patients were evaluated during their hospitalization (visits V1-V3) and during an optional follow up visit (phone or office visit about 12 week after V3). Seizure frequency during a 4 week retrospective baseline and prospective hospital course and optional follow up visit, adverse events (AEs) and the evaluation of therapy by physician and patients were documented.

Results: 154 patients (53% male; mean age 61 yrs ± 19) were selected. 84% were treatment naïve, 16% had at least one AED before baseline. 5% of patients discontinued therapy during their hospitalization due to AEs (3%) or transition to a different AED (3%; multiple answers possible). 81% with data from V4 continued on TPM, 11% were switched to another AED, in 6% anticonvulsant therapy was discontinued. 57% of patients were > = 60. Mean age in treatment naïve patients was higher than in pretreated patients (63 yrs vs 50 yrs, p < 0.002). Therapy naïve patients were older at first diagnosis and epilepsy duration was shorter (p < 0.0001). 66% were diagnosed with partial, 22% with primary generalized epilepsy. Reasons for hospitalization were acute epileptic seizures (73%), diagnostic workup (29%), treatment initiation of TPM (8%). Reasons to initiate TPM as AED were comorbidities (66%), concomitant medication (42%) or advanced age (39%) of the patient. Initial median dose of TPM was 25 mg/day and at V3 (median 6 days) 50 mg/day (range, 25 mg–150 mg). In patients with V4 (median 103 days) median maximum daily dose was 75 mg/day. Seizure frequency decreased from 11 ± 70/4 week during the retrospective baseline to 3 ± 11 (p < 0.001) at endpoint (V3). 82% were seizure free during the hospitalisation. Taking only patients with the optional follow up visit (V4, N = 86 with seizure documentation) into account, seizure frequency decreased from 15 ± 92 to 1 ± 7 at endpoint (p < 0.0001). A total of 63 TEAE were reported and 58 were considered as treatment related; 25 occurred during hospital stay (V1-V3) and 33 after V3. AE occurring in > = 3% of the patients with optional visit V4 were headaches (3%), aggressiveness (3%), weight reduction (4%), paresthesias (7%), dizziness (12%). One SAE occurred with possible relationship to TPM. 92% (V3) and 88% (V4) of physicians rated effectiveness of TPM as “very good” or “good”. 92% of patients who received TPM as their first AED rated the tolerability as “very good” or “good” (V3) which corresponds well to the rating of 92% of physicians.

Conclusions: This explorative study suggests that in hospitalized patients TPM is well tolerated given the low discontinuation rate due to adverse events. Even doses below the recommended initial target dose are associated with a significant seizure reduction. A high percentage of patients continued on treatment after the follow up period, however, follow up data is limited to 58% of the initial population.

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Bassel F. Shneker 1 and J. O. Elliott 1 ( 1 Neurology, the Ohio State University, Columbus, OH )

Rationale: Pseudoseizures (PS) are a common type of non-epileptic spell encountered by physicians in different specialties. PS is diagnosed only by documenting the lack of ictal electroencephalogram (EEG) activity during a spell, preferably by a continuous Video-EEG study (V-EEG). Studies have shown that an early diagnosis of PS results in a better prognosis. However, most patients do not get diagnosed early. This may be related to lack of access to V-EEG, inability of physicians to recognize the problem to prompt a referral for V-EEG, and the attitude of many physicians that patients with PS are “fakers”. The purpose of this study was to gain an understanding of attitudes and beliefs among non-neurologist physicians (family medicine [FM], internal medicine [IM], and emergency medicine [EM]) who are likely to encounter persons with PS.

Methods: The Ohio State University Central Physician Database was reviewed. Physicians in the central Ohio region who listed FM, IM or EM as their specialty, and had a published E-mail address were selected. A sixteen question, online survey was developed for a secure website. The survey was designed to learn about referral patterns and comfort level in diagnosis of PS, beliefs about etiology of PS as well as opinions about diagnosis, treatment and prognosis.

Results: One-hundred and eighty-three physicians were identified and sent email invitations to participate in the survey. 72 surveys were completed (39%). Of responders 39% were female and 47% were in residency training. 50% (36) were IM, 33% (24) FM and 17% (12) EM. 85% felt that the term PS is appropriate to describe this condition. 54% believe that they can definitely diagnose PS upon witnessing a spell. 47% believe that inducing the spell at bedside confirms PS but only 26% try to induce one. 58% believe that V-EEG is not needed to establish a PS diagnosis and most patients should be referred to neurologists (83%). 94% stated that prolactin level has no value in diagnosing PS. 74% believe that PS are involuntary events, best treated by counseling and psychotherapy (92%), and occur more commonly in women (74%). 53% restrict driving privileges of patients with PS. Only 17% felt that patients with PS get significant improvement of their condition and 75% indicated that patients do not accept the diagnosis. Attitudes of the three groups of physicians were similar in most aspects. IM physicians reported they could differentiate PS from epileptic seizures more than the other two groups (p = 0.037) once they witnessed an event. On a scale from 1–10, EM physicians had the highest confidence level in dealing with PS patients (6.2 vs 4.3 for FM vs 4.2 for IM, p = .025).

Conclusions: This survey showed that there are many misperceptions around the diagnosis, treatment and prognosis of PS. This includes the need for V-EEG to establish the diagnosis, the fact that most patients with PS are not malingerers, and that even experts in the field can misinterpret a witnessed event. Since patients with PS are likely to be seen first by non-neurologists, it is important to educate referring physicians about this condition.

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Mihiri Wijesuriya 2,1 , N. Jette 2,1 , S. Macrodimitris 1 , M. Suddes 1 , J. Martini 1 , S. Sadiq 1 and N. Niaz 1 ( 1 Neurosciences, Calgary Health Region, Calgary, AB, Canada and 2 University of Calgary, Calgary, AB, Canada )

Rationale: Inpatient video-EEG monitoring is an integral part of the clinical management of many individuals with epilepsy and non-epileptic events (NEE). Research on seizure monitoring units (SMU) usually focuses on their diagnostic utility. However, studies addressing the quality and safety aspects of SMUs are scarce. Our objective was to provide a baseline assessment of (a) the quality and safety of procedures on the SMU and (b) whether admissions goals were met.

Methods: All hospital records for patients admitted to the SMU between February 2005 and May 2006 were identified. A random sample of 129 admissions (64% of all admissions) were reviewed. Descriptive variables included gender, age, developmental delay, place of residence, reason for admission, and admission urgency. Quality indicators included length-of-stay (LOS) and wait time by admission urgency. Safety indicators included level of antiepileptic drug (AED) reduction, complications, and interventions used to stop seizures. Whether the admission question was answered and whether management changes occurred as a result of the admission was also studied.

Results: Fifty-one percent of patients were male and 11.6% were developmentally delayed. Mean age was 36.7 years (SD = 11.8). Forty-one percent of patients were from out-of-town and 12% were from out-of-province. The primary reason for admission was seizure characterization (n = 60; 46.5%) followed by surgical workup (n = 53; 41.1%), suspected NEE (n = 27; 20.9%) and quantification of spells (n = 8; 6.2%). Regarding quality indicators, mean LOS was 8.2 days (SD = 4.3). Mean admission wait time was 98.2 days (SD = 108.2 days, range = 1–573). Twenty-eight percent of admissions were urgent and the wait time for urgent admissions (mean = 62.9 days) was less than that for elective admissions [mean = 113.8 days; t(116) = 2.59, p = .01]. Regarding safety issues, all AEDs were discontinued in 49.6% and reduced but not stopped in 9.3%. In 20.9%, one or more AED was stopped but at least one drug was not discontinued. Complications occurred in 10.1% of admissions. This included 4 episodes of status epilepticus, 4 injuries (3 from seizures, 1 from a seizure-related fall), 4 IV infections, 2 hemorrhages related to intracranial monitoring, 1 CNS infection, and 3 other minor complications. Lorazepam (IV and sublingual) was the most common intervention used to stop acute prolonged or repetitive seizures (used in 24% of patients). Finally, the admission goal was met in 69.8% of patients, was partially met in 24% of patients, and was not met in only 6.2% of patients. Thirty-six percent of admissions resulted in management (AED) changes.

Conclusions: The results of this study provide baseline data on key quality and safety indicators that can now be used to guide ongoing prospective quality and safety improvement initiatives in our SMU. In addition, admission goals were met in the majority of those admitted into the SMU, which provides further evidence of the utility of SMU admissions.

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Salah Baz 1 and W. T. Blume 1 ( 1 Clinical Neurosciences, University of Western Ontario / LHSC, London, ON, Canada )

Rationale: Although unilateral and asymmetrical features of motor seizures (e.g.cephalic version and “Figure 4” sign) correctly indicate laterality of secondarily generalized seizure origin in many cases, their reliability apparently diminishes during seizure progression as semiology then may reflect ictal propagation rather than origin (Chauvel etal, 1995; Williamson,1992; Kotagal etal 2000). Unstudied has been the sequential tonic postures of head and multiple limb joints as primary and secondarily generalized (PG and SG) motor seizures evolve, nor their ability to distinguish between these two generalized seizure types

Methods: We scrutinized generalized motor seizures, one each occurring among 15 in-patients evaluated for intractable epilepsy. Sequential tonic positions of head and multiple limb joints lasting at least 3 seconds divided each seizure into phases. These were analysed by authors independently without patient identity nor EEG data. Mutual review resolved interpretation discrepancies. Ictal and interictal EEGs defined PG and SG in this study

Results: Three ictal phases occurred in 7 patients, 4 in 5, and 5 in 3. Seizures involved most joints in most phases, e.g. cephalic version (12 patients), shoulders (11), elbows (11), hips (11), and knees (9). The proportion of patients in whom a majority of joints exhibited bilaterally symmetrical features (principally flexion or extension) became greater in later phases (3 and 4) than in early (1 and 2) phases (Table and Figure). Among 56 involved joints (15 patients) for which flexion or extension positions of elbows, hips or knees were visibly involved for 2 or more phases, flexion progressed to extension in 36 joints, extension to flexion in 2 while flexion and extension were each sustained in 5 and 8 joints respectively. Flexion/extension alternated in 5 joints. Bilaterally symmetrical involvement of most homologous joints occurred during phase 1 in all 5 patients with PG and in only 3 of 10 with SG (P value (Fisher's) = 0.031), whereas no such distinction appeared in phases 2–4. Cephalic version with neck extension occurred contralateral to focal origin in 6/6 patients in phase 1 and 4/4 in phase 2.Ipsiversion with neck flexion appeared in one patient. However, early version occurred in 3/5 patients with PG.Flexor and extensor symmetry (unilateral simultaneous flexion or extension of elbow and hips/knees, Foerster,1936)) (postures 1,2 of Figure) did not occur more often than by chance

Conclusions: Although asymmetrical postures of bilaterally homologous joints distinguished PG from SG in phase one, increasing symmetry of later phases blurred the distinction of these two entities. As ictal tonic postures depend largely upon activation of the reticulospinal tract (RST), the more common progression from flexion to extension likely reflects increasing excitation of RST as the generalized seizure progresses (Burnham, 1987). Lack of more common flexor or extensor symmetry implies a limited role of direct supplementary motor or premoter efferents to the spinal cord in producing tonic ictal phenomena

Symmetry of Tonic Postures and Phase (Majority of observed features)

  • image

[ P value (chi square) = 0.0167 (phase 1,2 Vs 3,4) Significant ]

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[ Posture Variations, approximately sequential. ]

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Viviane Sziklas 1 , R. Sutton 1 and M. Jones-Gotman 1 ( 1 Montreal Neurological Institute, McGill University, Montreal, QC, Canada )

Rationale: Practice effects are a concern in cognitive assessments of patients with epilepsy, who frequently must undergo repeated testing to evaluate changes related to the disease or to inteventions. However, practice effects occurring between two similar tests administered during a same testing session have received little attention. We explored effects occurring between two naming tests (the Boston and Auditory Naming tests), and between two tasks that used the same unfamiliar faces but assessed different functions (learning vs. discrimination). We also modified the Victoria Stroop test by exchanging the condition of naming the ink color of non-color words for a condition in which color-name words that are written in colored ink must be read, and we compared performance on the modified (MNI) version to the original. We predicted between-test practice effects for the two naming tests and for the two face tasks, and we expected reduced within-test practice effects in the modified Stroop compared to the original.

Methods: 41 healthy volunteers were assigned at random into one of two groups such that the groups were matched on gender, age and years of education. The two groups performed the two naming and two face tests in an opposite order from one another. One group was given the Victoria Stroop, and the other group the MNI Stroop.

Results: Prior experience with one naming test did not influence performance on the other. However, prior experience with the face discrimination test led to significantly better scores on the first trial of the face learning test, and prior experience with the face learning test resulted in significantly faster performance of the face discrimination test. Finally, significantly more subjects made errors on the interference condition of the MNI Stroop than on the original Victoria Stroop.

Conclusions: Practice effects were not observed on the naming tasks. This finding supports the notion that the Boston Naming Test and the Auditory Naming Test assess different functions and is consistent with reports that performance on the two tests is disrupted differentially by anterior vs. posterior resections from the left temporal lobe. Prior experience with each face task did improve performance on the other. It is not surprising that the learning task should facilitate the discrimination task, but it is interesting that the reverse was also true; the finding demonstrates that experience with specific stimuli can influence a learning task even when the stimuli are seen in a different context. Finally, the Stroop results confirm that naming the ink color of non-color words in the Victoria Stroop does provide practice that reduces the desired effect in the final interference condition; thus the revised task should provide a more sensitive measure of susceptibility to interference. Taken together, these findings show that within-session practice effects can occur with some stimuli, and interpretation of clinical results from patients should be made with this knowledge in mind.

Supported by Canadian Institutes of Health Research

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Lee Lineberry 1 , B. B. Wannamaker 2 , A. W. Selassie 1 , P. L. Ferguson 1 , G. M. Smith 3 and P. B. Pritchard 2 ( 1 Biostatistics, Bioinformatics, and Epidemiology, Medical University of South Carolina, Charleston, SC ; 2 Clinical Neuroscience, Medical University of South Carolina, Charleston, SC and 3 Pediatric Neurology, Medical University of South Carolina, Charleston, SC )

Rationale: To determine the utility of death certificates as a means of finding deceased patients with epilepsy (PWE) whose death might be attributed to sudden unexpected death (SUDEP). We examined characteristics of death certificates for persons with definite, probable and possible SUDEP and their medical records and compared that information to that of PWE that died of other causes.

Methods: Names, social security numbers, dates of birth and dates of death (if known) for 2,762 PWE were submitted to the state bureau of vital statistics. These PWE were seen in a single epilepsy practice and were followed for one to 30 years. There were 110 deaths known to the clinicians. However, 411 deaths were recorded as of December 31, 2005 for this cohort, and death certificates were obtained for 390. Logistic regression was performed to evaluate 24 items of information found in the death certificates for persons who died of definite/probable or possible SUDEP. Standardized mortality ratios (SMR) were calculated for all cause mortality, suicide, homicide, accidental, and natural causes.

Results: Of all deaths, 18.2% were seizure related, and 12.5% were due to definite/ probable or possible SUDEP. Death certificates of 88.2% of the definite/probable and 78.1% of the possible SUDEP cases mentioned either seizure or epilepsy. 70.6% of definite/probable, 57.1% of possible, and 28.8% of non-SUDEP cases died at home. Death certificate predictors of definite/probable SUDEP were place of death, age, and mention of seizure/epilepsy. Predictors of possible SUDEP were time of death, race, autopsy, and mention of seizure/epilepsy. Persons in the epilepsy cohort experienced 21% more mortality over what would be expected in the South Carolina population. All age groups experienced increased mortality except for persons over 75 years. The overall SMR for males was significant at 1.39, but females did not show increased mortality. The SMR for drowning was 9.94 (95% CI: 4.54–18.87), and SMRs were significantly elevated for ages 15–54 years.

Conclusions: Death certificates can provide useful information in identifying definite/probable or possible SUDEP if multiple variables are searched. Persons with epilepsy experience more mortality than the general population, especially among males and persons younger than 75. Accidental drowning is a significant problem in this population. Contrary to previous studies, in this long-term follow-up cohort, the incidence of suicide was not elevated over what would be expected. In light of the records indicating only 27% of the deaths, a better system of periodic surveillance of epilepsy clinic populations should be undertaken to ensure that all deaths are captured. (Source of funding: Epilepsy Services Research, Inc.)

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Jeff Gelblum 1 ( 1 Department of Neurology, Mt. Sinai Medical Center, Miami, FL )

Rationale: An estimated 1% of the population suffers from epileptic seizures. Despite newer drugs, many patients continue to be treated with older first-generation anti-epileptic drugs (AED's). Therapeutic ranges of AED's are believed to confer good protection against breakthrough seizure, although the historic basis for these laboratory values is often anecdotal and not supported by rigorous clinical studies.

Here, we evaluate anticonvulsant dosing among epileptic patients presenting to a large hospital Emergency Department to determine what role serum anticonvulsant levels play in medication dosing, and subsequent selection, if any, of an adjunctive agent.

Methods: Over a two year period (2003–2005), the hospital database was used to identify randomly, Emergency Department (ED) records of adult patients presenting with breakthrough seizure and pre-existing diagnosis of epilepsy. Patients ranged in age from 18 to 91 years (median,49 years).

ED charts were reviewed to capture those breakthrough patients and who had a prior existing AED regimen. 100 records were obtained, which also contained first generation serum levels.

Results: Among charts reviewed, there were 82 occurrences of pre-existing prescriptions for first generation AED's, with accompanying serum levels of the respective medication. The other 18 patients presented with no prior epilepsy diagnosis.

Of the documented epileptic group, 50 patients' serum levels (61%) were within laboratory therapeutic range; and 27 patients' serum levels (33%) were in the sub-therapeutic range. The serum levels of 5 patients (6%) reflected a supra-therapeutic level.

Within the laboratory therapeutic range group, 33 patient regimens (66%) were adjusted upward thereby increasing the already “therapeutic” dose of the first-generation compound. Within the sub-therapeutic group, 26 patients (96%) received an increased dose of the existing regimen, as would be expected. Only one patient was switched to a completely alternative AED in the ED setting.

Conclusions: This study suggests that upon breakthrough presentation to an ED, the dose of the existing first-generation AED regimen is typically raised despite a “therapeutic” level. Indeed, the contemporary paradigm of first generation AED dosing is equivalent to that which is commonly utilized with the newer second generation compounds which do not have defined therapeutic ranges. In other words, upon breakthrough seizure, the patient's existing dose of medication is customarily increased despite serum level, barring the presence of clear-cut supra-therapeutic levels.

This retrospective study of breakthrough seizure patients demonstrates that the continued usage of older first generation AED's remains common; and that acquisition of serum anticonvulsant levels remains customary. Once obtained, however, a therapeutic serum level does not significantly impact the treating physician's tendency to increase the existing monotherapy regimen, nor predispose to the prescribing of an adjunctive agent as may confer additional seizure protection.

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Linda Kopec 1 , S. Masho 2 , E. J. Waterhouse 1 , L. D. Morton 1 , S. F. Byers 1 , R. J. DeLorenzo 1 and A. R. Towne 1 ( 1 Neurology, Virginia Commonwealth University, Richmond, VA and 2 Epidemiology and Community Health, Virginia Commonwealth University, Richmond, VA )

Rationale: Status epilepticus (SE) is a serious medical condition associated with significant morbidity and mortality. Few studies have addressed this condition in the elderly. The present study examines characteristics of SE in this growing population. To achieve these objectives we will utilize a validated population based database. The population in the United States will see a dramatic increase in the elderly population over the next 50 years. Previously, it was felt that the largest percentage of patients with seizures were in the younger age groups. More recent data suggest that the elderly population contain a growing percentage of patients with seizures. SE is a particularly deadly form of seizure with a mortality exceeding 25%, in some series. However the characteristics of this deadly condition are little known the elderly population. The ability to recognize and appropriately treat this condition will hopefully reduce the mortality and morbidity associated with SE.

Methods: This is a descriptive longitudinal cross-sectional prospective population based study. We utilized a large population-based, prospectively collected database of SE cases presenting in the Richmond Metropolitan Area from July 1, 1989, to June 30, 2006. SE cases were identified during the course of this study at the Virginia Commonwealth University Health System. The characteristics of elderly patients presenting with SE including age, race, sex, duration of seizures, mortality, response to treatment, and seizure presentation were analyzed.

Results: A total of 2,220 patients were included for this analysis. One thousand four hundred and seventy-five patients (66.4%) were included in the young group which included ages from 30 days up to but not including age 60. The elderly group was comprised of 745 patients (33.6%) and included ages from age 60 and above. There were 1,035 females comprising 46.6% of the total population and 1,185 males at 53.4%. The most frequent type of status epilepticus was the group partial seizures with secondary generalization. African American patients accounted for the largest percentage of patients at 57.2%, white patients accounted for 35.8% and other races, predominantly Hispanic, accounted for 7%. The etiology of SE, in our patients, was categorized into seven broad sub-groups. The most common etiologies were in the non CNS and CNS acute categories. Low anticonvulsant levels and remote symptomatic etiologies were also seen frequently. Certain etiologies had significantly higher mortalities when compared to other etiologies. An especially high mortality was observed in the hypoxia group. Mortality in the elderly group (26.5%) was significantly higher than in the young group (OR = 3.54 CI 2.53,4.95). Analysis of the age groups demonstrated that the odds ratio for mortality increased significantly from 0.41 to 7.79.

Conclusions: SE is a serious medical condition, consisting of prolonged seizure activity, associated with a significant mortality. Elderly patients with SE represent a distinct population with unique characteristics.

Funding: Supported by NIH P50 NS25630.

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Revital Gandelman-Marton 1 , S. Kipervasser 2 , V. Chistik 2 , H. Peretz 3 , Y. Vered 4 and M. Y. Neufeld 2 ( 1 Neurology Department, Assaf Harofeh Medical Center, Zerifin, Israel ; 2 EEG and Epilepsy Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel ; 3 Clinical Biochemistry Laboratory, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel and 4 Central Laboratory, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel )

Rationale: The use of lamotrigine (LTG) in women of childbearing age is preferred by many physicians because of published data regarding fetal safety. However, LTG clearance increases during pregnancy with a consequent fall in plasma levels and the risk of seizure aggravation.

Our aim was to assess seizure occurrence during pregnancy in women with epilepsy and LTG monotherapy.

Methods: Clinical and Laboratory data were retrospectively reviewed in pregnant women with epilepsy and LTG monotherapy, who were followed at a tertiary epilepsy center. At least one value of LTG serum level was present for seven patients in the first trimester and in all women in the following trimesters. LTG ratio was calculated by multiplying LTG serum level (mg/L) by 100, and dividing the result by the prescribed LTG dose (mg).

Results: There were 11 patients, age 27 ± 5 (19–37 years). Epilepsy duration was 8.6 ± 6.9 years. Five patients had localization-related epilepsy (LRE) and six- generalized epilepsy. At least 3 month seizure freedom was documented in nine patients prior to pregnancy. Despite LTG serum level guided dose adjustments, seizures occurred only in patients with LRE (p = 0.002). LTG ratio decline, as compared to pre-pregnancy values, was most prominent in the first trimester (p = 0.011), similar in both patients with and without seizures. A significant post-pregnancy LTG ratio increase was observed in all the patients (p < 0.0001). Age, epilepsy duration, three month seizure freedom and LTG levels prior to pregnancy did not affect seizure occurrence.

Conclusions: Seizure occurrence during pregnancy in patients with epilepsy and LTG monotherapy is significantly affected by the type of epilepsy syndrome.

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Lisa M. Bateman 1 and M. Seyal 1 ( 1 Neurology, University of California, Davis, Sacramento, CA )

Rationale: Hypoxemia with partial seizures has been reported in small series of patients.

Methods: We systematically studied 30 consecutive patients with localization-related epilepsy admitted for inpatient video-EEG telemetry. Respiratory parameters, including pulse oximetry data, were recorded synchronized with EEG, video and the electrocardiogram. Anticonvulsant medications were reduced during the hospitalization.

Results: Twenty-one of 30 patients had oxygen desaturations below 90% during one or more seizures. Oxygen desaturations with partial seizures alone or with partial seizures before onset of secondary generalization were studied. 134 seizures were recorded, 39 of which had associated oxygen desaturations. The mean desaturation nadir was 79.4% (range <50% to 89%). The mean lag from seizure onset to desaturation below 90% was 70.1 seconds. The mean duration of desaturation was 85.6 seconds. There was no statistical difference in the duration of seizures with desaturations (mean 98 seconds) compared with seizures with no desaturation (mean 93 seconds). Temporal lobe localization was most common (left 9 seizures; right 17 seizures). Nine patients had no desaturations with any of 52 seizures. The mean duration of seizures was 66 seconds (range 13–366 seconds). Temporal lobe localization was most common (left 7 seizures; right 21 seizures). There was no significant difference in mean age, 35.6 years (16–62 years) compared with 41.2 years (18–62), or body mass index, 24.6 (SD 5.4) compared with 22.3 (SD 2.9), between the two groups.

Conclusions: Hypoxemia commonly occurs in association with partial seizures and may be pronounced. Seizure-related hypoxemia may be a factor in sudden unexplained death in epilepsy.

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Hidemoto Kubota 1,3 and Y. Awaya 2,3 ( 1 National Epilepsy Center, Shizuoka Institution of Epilepsy and Neurological Disorders, Shizuoka, Japan ; 2 Paediatrics, International Catholic Hospital, Department of Pediatrics, Tokyo, Japan and 3 Japanese Epilepsy Association, Tokyo, Japan )

Rationale: We initiated this study in order to assess clinical factors influencing health-related quality of life (HRQL) in Japanese patients with epilepsy, and the results are anticipated to highlight the importance of HRQL in treatment and management of epilepsy.

Methods: In the present study, the HRQL scores of 599 patients belonging to the Japanese Epilepsy Association (16 years old or more) were evaluated using a self-administered QOL questionnaire, entitled quality of life in epilepsy (QOLIE-31). To explore factors influencing on HRQL in patients with epilepsy, a stratified analysis employing various factors such as the patient's demographic characteristics (age and gender), social status (occupation), the frequency and severity of seizures, the ictal and post-ictal symptoms, co-morbidities, and medications.

Results: The mean patient age was 37.2 (SD 11.6) years; 49.9% were female. The mean duration of epilepsy was 28.8 (SD 12.1) years.

Mean scores in domains of the QOLIE-31 ranged from 46.4 to 60.9; hence in Japanese patients with epilepsy HRQL scores of the 7 remaining domains (“Seizure worry: SW”, “Overall quality of life: OQ”, “Emotional well-being: WE”, Cognitive functioning: CF”,” Medical effects: ME”, “Social functioning: SF”, and “Overall score: OS”), the exception being “Energy/fatigue: EF”, were lower than those reported by Vickrey et al in the US. Cronbach α coefficients ranged 0.747 to 0.891; hence the QOLIE-31 was demonstrated to be highly reliable in Japanese patients.

The frequency, management status, and severity of seizures were assumed to be independent variables. As for three the seizure designations of “remarkable”, “unremarkable”, and “during sleep”, significant changes in the HRQL score were noted in the first 2. Regarding the seizures which occurred during sleep, there were no the HRQL scores of any domains which tended to be significant among the categories.

Furthermore, from a clinical perspective, employment status, disturbance of intelligence, the efficacy of surgery, and number of anti-epilepsy drugs, duration of unconsciousness, frequency of injuries and fall during seizures, status of post-ictal confusion and the recovery time after seizure, factors other than frequency, control status, and the severity of seizures have been suggested as factors influencing QOLs in Japanese patients with epilepsy (ANOVA: p < 0.01–0.000).

Conclusions: In exploring the factors influencing the HRQL of Japanese patients with epilepsy in this study, we found that their QOLs were only improved in the absence of remarkable seizures for two years or more, whereas we can expect that the lower frequency of unremarkable seizures were, the higher QOLs were. The seizures which occur during sleep might have no influence on QOL.

Thus, the present study revealed decreased QOLs in Japanese patients with epilepsy to be attributable to various factors. To improve their QOLs, it is, therefore, necessary that patients with epilepsy receive comprehensive care.

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Alan Towne 1 , K. O'Hara 1 , A. Perseghin 1 and E. Burakgazi-Dalkilic 1 ( 1 Neurology, Virginia Commonwealth University, Richmond, VA )

Rationale: There is a bimodal distribution in the incidence of new onset seizures with one peak occurring in the very young and the second peak occurring in the elderly. The treatment of epilepsy in the elderly may be complicated by pharmacokinetic and pharmacodynamic changes occurring during the aging process. Three Veterans Cooperative trials evaluating antiepileptic drug (AED) therapy in the elderly demonstrated that the ability to tolerate the AED is a more determining factor for long term success than the ability to suppress seizure activity. In general, elderly patients appear more sensitive to medication side effects. This may stem from co-morbid conditions, concurrent medications, pharmacokinetic changes, and/or pharmacodynamic changes. Therefore, it is important to study the efficacy and tolerability of AEDs in the elderly. Valproic acid has been available for the treatment of partial and generalized seizures since 1978. Depakote and Depakote-ER are among the dosage forms of divalproex sodium. Depakote is administered twice a day. Depakote-ER is a controlled release drug delivery system designed to release drug over a 22 hour period which allows for once a day dosing. This study will address the efficacy and tolerability of Depakote-ER in elderly patients with epilepsy.

Methods: This is a single center, open-label, study conducted in patients age 60 and older with a confirmed diagnosis of epilepsy. Fourteen patients with newly diagnosed partial seizures, patients with uncontrolled partial seizures requiring medication adjustment, or patients with partial seizures who would benefit from once a day dosing were enrolled. All the patients were initially on Depakote and were switched to the Depakote-ER formulation. In the conversion from Depakote to Depakote-ER the dosage was increased from 10 to 20%. Each patient underwent a complete laboratory analysis and completed a Seizure Severity Questionnaire (SSQ), Beck's Depression Inventory (BDI), QOLIE-31-P, seizure count diary and the Adverse Events Profile (AEP).

Results: The primary objective of this study was to assess the effectiveness, (i.e. the efficacy and tolerability), of Depakote-ER in elderly patients with epilepsy. Effectiveness, as measured by survival in the study, was 100%. There was no significant change in the Seizure Severity Questionnaire (SSQ) score and no significant change from baseline of seizure frequency as determined by seizure counts, except in one patient who failed to increase the dose when converting to Depakote-ER. All of the patients preferred the once a day dosing and compliance was improved. Reported side effects were less with the ER formulation. There was no significant change in laboratory parameters in this series.

Conclusions: Conversion from Depakote to Depakote-ER is well tolerated in patients 60 and older. Once a day dosing was preferred by the patients and seizure frequency was unchanged when the conversion guidelines were followed.

Investigator initiated study supported by funding from Abbott.

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Tanvir U. Syed 1 , A. M. Arozullah 2 , G. P. Suciu 3 , J. B. Toub 1 , H. Kim 1 , M. L. Dougherty 1 , T. Wehner 1 , A. S. Stojic 1 , I. M. Syed 4 and A. V. Alexopoulos 1 ( 1 Neurology, Cleveland Clinic, Cleveland, OH ; 2 Sections of General Internal Medicine and Health Promotion Research of the Department of Medicine, Univ of Illinois, Chicago, IL ; 3 Department of Public Health, Nova Southeastern Univ, Fort Lauderdale, FL and 4 Florida International University, Sweetwater, FL )

Rationale: Diagnostic delay in distinguishing psychogenic nonepileptic seizures (PNES) from epileptic seizures may result in unnecessary therapeutic interventions and health care costs. Effective PNES screening tools can potentially mitigate diagnostic delay. Previous studies demonstrated that ictal eye closure during video-EEG monitoring can serve as a reliable indicator of PNES. The present study assessed whether observer or self-report of eye closure could be used to predict PNES, prior to video-EEG monitoring.

Methods: Adult epilepsy monitoring unit subjects were prospectively enrolled into the study. Self-report of eye closure was assessed using a written questionnaire, and observer report was obtained by interview. Blinded physicians determined the incidence of video-captured eye closure during PNES and epileptic seizures. Random effects models evaluated whether video-captured eye closure predicted an episode as PNES, while accounting for episode clustering by subject. The utility of observer and self-report of eye closure in predicting a diagnosis of PNES was tested using logistic regression and 2 × 2 tables.

Results: Of 132 consecutively enrolled subjects 112 met study criteria during EMU stay for either PNES (n = 43, 38.4%) or epilepsy (n = 84, 75.0%). Affirmative self and observer reports of eye closure were neither sensitive nor specific for the diagnosis of PNES. Of note, the odds ratio for PNES episode classification by video-captured eye closure decreased from 9.2 (95% CI, 5.5–15.2) for subjects with four or more episodes to 0.8 (95% CI, 0.3–2.5) for those with three or fewer.

Conclusions: Neither observer nor self report of eye closure, prior to VEEG monitoring, predicts PNES. Video-captured eye closure accurately predicts PNES only when four or more episodes are recorded.

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Olga Finlayson 1 , S. Mirsattari 1 , P. Derry 1 , J. Burneo 1 , D. Diosy 1 , W. T. Blume 1 , R. McLachlan 1 and B. Young 1 ( 1 Department of Clinical Neurological Sciences, University of Western Onario, London, ON, Canada )

Rationale: The economic burden of non-epileptic seizures (NES) on the health care system is poorly understood. We hypothesize that delay in the diagnosis of NES results in significant unnecessary costs.

Methods: Retrospective study of 50 NES patients admitted to the Epilepsy Monitoring Unit (EMU) at London Health Sciences Centre over 4 years. All the patients underwent video-EEG telemetry.

Results: Thirty-eight patients (76%) were females and 12 patients (24%) were males (mean age = 35.3, range 16–67). Eighteen patients (36%) were on disability and 7 patients (14%) were unemployed. Times from the onset of NES to the diagnosis were as following: <1 year 13 patients (26%), 1–3 years-13 patients (26%), 3–5 years-4 patients (8%), 5–10 years-6 patients (12%), >10 years-13 patients (26%), undetermined-1 patient (2%). Forty-three patients (86%) were taking antiepileptic drugs (AEDs) but 21/43 patients (42%) had neither epileptiform discharges nor history of epilepsy. From those, 8 patients (16%) were taking 1 AED, 9 patients (18%) - 2 AEDs, 1 patient (2%) - 3 AEDs, and 3 patients - >3 AEDs. The patients were extensively investigated before the diagnosis of NES was made; in particular, 22 patients (44%) had 1 MRI study, 10 patients (20%) had 2 MRIs, 6 patients (12%) had 3 MRIs and 3 patients (6%) had > 3 MRIs.

Conclusions: Delay in the diagnosis of NES was common, which led to extensive investigations, unnecessary administration of AEDs, prolongation of the illness, and higher rates of disability and unemployment. Therefore, early diagnosis of NES would avoid unnecessary costs.

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Zachary D. Repanshek 1 , Z. Haneef 1 , M. Vendrame 1 , M. P. Jacobson 1 and A. S. Azizi 1 ( 1 Department of Neurology, Temple University, Philadelphia, PA )

Rationale: In patients with frequent uncontrolled seizures, acute MRI findings can become a diagnostic quandary: are changes in the MRI the cause of epileptic seizures or the sequelae to the seizures? Transient MRI abnormalities in patients with Epilepsia Partialis Continua (EPC) have been reported in the literature.

Methods: Here we report on 3 patients with multiple seizures over several days that developed acute changes in brain MRI. We analyzed Diffusion Weighted (DW) and Fluid Attenuated Inversion Recovery (FLAIR) MRI sequences in these patients during the acute phase and followed the clinical course and MRIs of these patients.

Results: In all the patients, both FLAIR and DW MRI showed signal changes. The mesial temporal lobe was involved unilaterally in the first two patients, and the left posterior parietal lobe was involved in the third. Seizures were controlled with classic antiepileptics (phenytoin or valproate) with add-on therapy (topiramate or levetiracetam) in two cases. Seizure control was achieved within 3 days. At follow-up, all patients were free of seizures. Repeat MRIs done at one month and one week showed complete resolution of the FLAIR and DW changes.

Conclusions: Transient changes in brain MRI can occur secondary to prolonged or multiple seizures. Understanding this concept can prevent further unnecessary work-up for diagnosis of etiology of seizures. Previous studies reporting transient FLAIR and T2 abnormalities in status epilepticus attribute these to focal cerebral edema. While increased DW signal suggests cytotoxic edema, its complete resolution more strongly indicates a reversible process such as vasogenic edema. These cases add to the existing literature reporting transient MRI abnormalities in patients with EPC. A good outcome in terms of full resolution of brain lesions and full clinical recovery can be expected.

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Angela Rackley 1 , J. Szaflarski 1 , D. Schwieterman 1 , M. Privitera 1 , D. Ficker 1 , M. Szaflarski 2 and S. Yates 3 ( 1 Department of Neurology, University of Cincinnati Academic Health Center, Cincinnati, OH ; 2 Institute for the Study of Health, University of Cincinnati Academic Health Center, Cincinnati, OH and 3 UCB Inc, Medical Affairs, Smyrna, GA )

Rationale: There is a dearth of information regarding differences in seizure outcome after treatment in an epilepsy center vs. general neurology practice. We showed recently that a number of people who transitioned care from general neurology practices to an epilepsy center saw improvement in seizure control (Zakaria et al, Neurology 2007;68:Suppl 1:A72). The aim of this study was to examine whether similar improvements in seizure control are seen in patients residing in a residential care facility vs. other patients and whether the results of the previous study can be confirmed on a larger sample of epilepsy patients.

Methods: A retrospective chart review was performed on 100 patients followed at an epilepsy center; 50 institutionalized patients versus 50 patients matched for age, gender, and duration of epilepsy. T-tests were conducted to evaluate for differences in the two groups, including treatment outcomes.

Results: Mean age at the time of chart review was 42.6 ± 13.3 years; mean age at the onset of epilepsy was 16.1 ± 17 years. There were no significant differences between the groups of patients with regard to seizure control. The mean number of seizures per month at the time of first presentation to the epilepsy center was 34 ± 107 (institutionalized patients 28, other 40; p = 0.57). At the time of the last visit, the seizure frequencies were 8 ±32 (5 vs. 11; p = 0.33). The difference in initial vs. current seizure control was significant at p = 0.003 with approximately 76% decrease in seizure frequency after management at an epilepsy center. During the first month of treatment at an epilepsy center, only 9 patients did not have any seizures vs. 44 patients in the month prior to the last visit (p < 0.001).

Conclusions: Overall, treatment at an epilepsy center results in significant improvement in seizure control. No differences in seizure control between institutionalized and other patients were seen.

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Bassam Addas 1 , W. Hader 1 , S. Wiebe 1 and S. Campbell 1 ( 1 Clinical Neurosciences, Foothills Medical Center, Calgary, AB, Canada )

Rationale: Resective surgery for temporal lobe epilepsy carries a failure rate ranging from 20–40%. The cause of failure is complex and multifactorial, and some patients are amenable to reoperation. To assess factors that play a role in failed surgery, the decision to offer a repeat surgery, and the success rate of reoperation, we undertook a systematic review of the literature. Our aim was to assess not only the results of the published evidence, but also its methodology, shortcomings, and areas that require addressing in order to understand this problem better.

Methods: We systematically and exhaustively searched the literature from 1990 to 2007, using a broad array of MESH terms and text words to explore the Medline database, including “failed surgery”, “re-operation”, “second surgery”, and “repeat surgery”, and combined these with our broad target entity “epilepsy” or “seizure”. Because this yielded only nine articles, we then searched ISI-web of science for articles citing these references. We also searched manually the references of the key articles, book chapters, and asked experts. A total of nine papers were found, of which eight dealt with outcomes. For each paper we abstracted data on demographics, clinical features, surgery, etiology, and surgical results.

Results: Eight articles included 186 patients, ranging from 5 to 44 (median 22) per article. The proportion of patients undergoing reoperation ranged from 4% to 15%. The minimum interval between 1st and 2nd surgery was 3.5 years, but varied widely. The most common etiology was mesial temporal sclerosis (median 52%). Only two papers (25%) gave information on the initial surgery. Only one paper (12.5%) provided data on all relevant figures (number initially operated, number failed, number eligible for reoperation, and number reoperated). No paper gave information on the use of intracranial EEG for reoperation. Six (75%) studies attributed surgical failure to the presence of residual MTS, and one to dual pathology. Seizure freedom was obtained in nearly 50% of reoperated patients, with minimal permanent neurological complications, especially in patients with residual MTS.

Conclusions: There is a profound deficiency of sound evidence to inform clinical decision making regarding re-operation after failed surgery. Reports are few, involve few patients and do not contain the standardized information. With this limited information, the best results were obtained with residual MTS. Arguably; residual MTS will become infrequent with better localization and surgical techniques, including intraoperative neuronavigation and intraoperative MRI. However, much remains to be done to understand the determinants of failure, reoperation and outcome following the latter. At the very least, it is important to examine all the failed cases, and decrease the current selection bias in reports (only 4–15% are included). This gives a false sense of security with regards to outcomes of reoperation.

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Dipak P. Pandya 1 and N. Matalkah 1 ( 1 Neurology, St. Joseph's Regional Medical Center, Paterson, NJ )

Rationale: Cerebral hyper perfusion syndrome (CHS) can occur after carotid endarterectomy (CEA) or carotid stenting. The initial clinical features include traditional triad of ipsilateral headache, transient focal motor seizures and cerebrovascular events. Most seizures may present up to three week after CEA. The classic semiology of seizures is focal motor seizures; although secondary generalized seizures may manifest. Status epilepticus is very rare and nonconvulsive status epilepticus has not been reported in literature. We report a case of refractory nonconvulsive status epilepticus as an initial manifestation after CEA.

Methods: Hospital patients database were reviewed from 1980 to 2006. Patient's diagnosis, complications after CEA, EEG recordings, hospitalization course and imaging findings were reviewed. One patient was identified who presented with nonconvulsive status epilepticus as a presenting manifestation of CHS.

Results: Seventy four year old man with medical history of HTN and CAD who had right CEA 9 days before presenting to the ER with unilateral headache, impairment of consciousness and a generalized seizure. He was found to have right hemiparesis and was intubated. Initial MRI showed asymmetric diffusion hyperintensity within the cortex with subcortical white matter of the right frontal, parietal and temporal lobes. These changes were marked without any effect on ADC maps. There was prominent vasogenic edema over corresponding areas, as well as a small subarachnoid hemorrhage near the vasogenic edema. Considering the recent CEA and comatose patient, continuous video EEG monitoring was performed for several days. EEG showed hemispheric asymmetry and right hemisphere pseudo periodic to periodic, rhythmic, evolving waxing and waning electrographic discharges, which are epileptogenic. No clinical activities were noted during electrographic discharges. His nonconvulsive status epilepticus was initially refractory to antiepileptic medications. He was treated with dilantin, depakote, keppra, topomax, and maximum doses of propofol. His electrographic discharges were controlled with an addition of midazolam drip. After seizure control, his neurodeficits were improved and eventually had a nonfocal examination. He was transferred to rehabilitation.

Conclusions: Seizures are frequent complaints of CHS, however refractory nonconvulsive status epilepticus has not been reported in literature. Appropriate management remains a cornerstone in CHS. The etiologies for seizures after CHS remain speculative. Damage to cerebral endothelium may attenuate or abolish the myogenic autoregulation. Release of nitric oxide, oxygen derived free radicals may damage the endothelium. The relative infrequency of CHS appears to be the main reason why this entity is poorly understood.

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Jerzy P. Szaflarski 1 , A. Rackley 1 , C. Lindsell 2 , D. Schwieterman 1 , M. Privitera 1 , D. Ficker 1 , M. Szaflarski 3 and S. Yates 4 ( 1 Department of Neurology, University of Cincinnati Academic Health Center, Cincinnati, OH ; 2 Department of Emergency Medicine, University of Cincinnati Academic Health Center, Cincinnati, OH ; 3 Institute for the Study of Health, University of Cincinnati Academic Health Center, Cincinnati, OH and 4 UCB Inc. Medical Affairs, Smyrna, GA )

Rationale: Receiving epilepsy care in a specialized epilepsy center leads to improved seizure control (Zakaria et al, Neurology 2007;68:Suppl 1:A72). It is not known what factors contribute to such improvements. The goal of this study was to evaluate whether the use of second vs. first generation AEDs contributes to improved seizure control in populations of institutionalized and non-institutionalized patients and how these factors are modified by physician's training/experience (epileptologist vs. general neurologist).

Methods: A retrospective chart review was performed on 100 patients followed at an epilepsy center; 50 institutionalized patients vs. 50 patients matched for age, gender, and duration of epilepsy. The change in seizure frequency was the main outcome and whether or not the prior and current providers attempted to use new medications were the primary predictors. Paired t-tests were used to compare seizure frequency before and after the patients were seen at an epilepsy center; generalized linear models were used to assess the effect of provider prescription practice on seizure frequency. Patients with more than 100 seizures per month were excluded to prevent bias from these outliers (N = 6).

Results: There were no differences in how the AEDs were used by general neurologists vs. epileptologists in the institutionalized vs. non-institutionalized patients (all p > 0.112). There was an overall decrease in seizure frequency (p < 0.001; delta =−10.1, 95CI 5.5 to 14.8) when the patients were treated by epilepsy specialist vs. general neurologist. The modeling suggest that if the general neurologist had tried a second generation AED prior to referring to the epileptologist, the change in seizure frequency was about −14 (p < 0.001), while if they had not tried the second generation AED, the change was significantly lower at about −4 (p = 0.046). This reflects the fact that the patients who were treated only with first generation AEDs prior to referral had on average much lower seizure frequency than other patients. Whether the current provider (epilepsy specialist) tried new medication or not, it did not affect the seizure frequency (p = 0.814). When tested, there was no interaction between old and new provider attempts to use second generation AED (p = 0.824).

Conclusions: These findings indicate that improved seizure frequency in patients referred for further management in epilepsy centers is dependent on physician training and not on medication factors. In other words, there is better seizure control in patients cared for by an epilepsy specialist independently of what AED they use.

This study was supported by UCB Pharma Young Investigator Research Project to AYR.

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Christopher T. Anderson 1 , K. D. Graber 1 and R. S. Fisher 1 ( 1 Comprehensive Epilepsy Center, Stanford University, Stanford, CA )

Rationale: Rasmussen encephalitis (RE) is typically a childhood disease with intractable epilepsy and progressive hemiparesis, often treated with neurosurgery. Etiology is unknown, however, auto-antibodies against the ionotropic, glutamate receptor Glu-R3 and other epitopes, have been implicated. RE associated with anti-voltage-gated-potassium-channel antibodies (anti-VGKC-Abs) has not been described in Medline-indexed literature (search terms: Rasmussen, encephalitis, potassium). Like other diseases mediated by anti-VGKC-Abs, we hypothesized that this type of RE may be responsive to immunotherapy alone. We monitored response to various types of immunotherapy in a patient with RE and anti-VGKC-Abs.

Methods: A 26 year-old developed hemiclonic seizures and intermittent epilepsia partialis continua (EPC) with right hemibody, clonic jerking. Seizures intermittently impaired cognition and vision. She developed a progressive dystonic hemiparesis. EEG revealed left-sided, periodic sharp waves near the vertex, left temporal spikes and PLEDs, and left-sided slowing. MRI revealed left-sided atrophy. SPECT showed decreased blood volume in the left frontal, temporal, and parietal lobes. Normal and negative serum studies included the CBC, metabolic panel, coagulation panel, ESR and C-reactive protein, ACE level, RPR, antibodies to DNA, SCL-70, Ro and La, serum IgA, IgG, IgM, anti-cardiolipin and anti-phospholipid antibodies, TSH, anti-thyroglobulin and anti-TPO antibodies, immunofixation electrophoresis, and paraneoplastic antibodies (Mayo Medical Laboratories). Negative CSF tests included cell counts, glucose, protein, and cytology. Abnormal results included a rheumatoid factor level of 23 IU/ml (normal < 20) and a high titer of anti-VGKC-Abs (Kv1.1–1.4) at 170 pmol/L (negative < 100, sampled prior to IVIg). In an unblinded fashion, we monitored clinical response to corticosteroids, IVIg, and plasmapheresis.

Results: Trials of five anti-seizure medications were largely ineffective. High-dose corticosteroids and three courses of IVIg had no clear benefit, although disease progression was slow at baseline. Ultimately, two 5-day treatments of plasmapheresis reduced the amount and severity of hemiclonic jerking, seizure-propagation, and were associated with reductions hemidystonia and hemiparesis. The patient is now also participating in a treatment protocol using rituximab.

Conclusions: The etiology of adult-onset, anti-VGKC-Ab-asssociated RE may be different than typical RE. Early response to plasmapheresis is encouraging. Anti-VGKC-Abs may be associated with limbic encephalitis, peripheral nerve hyperexcitability, and encephalopathy. Among six patients with epilepsy having elevated VGKC-Ab levels (reported by Majoie et al. 2006), none had refractory focal seizures. Anti-VGKC-Ab-mediated diseases are often reversible with immunotherapy while RE is usually not. Although further study is required, patients with adult-onset RE should be screened for anti-VGKC-Abs, as this could be a variant that is responsive to non-surgical therapy.

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Jeffrey SooHoo 1 , P. Alore 2 and M. Macken 1 ( 1 Loyola University Chicago, Stritch School of Medicine, Maywood, IL and 2 Resurrection Medical Center, Chicago, IL )

Rationale: Levetiracetam is a newer anticonvulsant with a pharmacolocical profile (non-protein bound, significant renal excretion, lack of enzyme induction) which facilitates is use in a wide range of complex clinical settings. The recent availability of an IV formulation potentially extends this spectrum to those patients who cannot take oral medications, including its use in patients who present with seizures while undergoing bone marrow or solid organ transplantation.

Methods: A list of all patients recieving IV levetiracetam was obtained from a pharmacy database and a retrospective chart review was undertaken.

Data extracted included age, sex, epilepsy syndrome, seizure type, clinical setting (intubated, neutropenic) doses used, use as loading or maintenance therapy, whether used as monotherapy or adjunctive treatment, serum concentrations where available, tolerability, efficacy and side effect profile.

Results: A total of 12 patients recieved intravenous levetiracetam in the transplant setting in the period under study. All patients were undertaking complex multi-drug chemotheraputic regimes where the addition of a more commonly employed enzyme-inducing anticonvulsant like phenytoin would have sigificantly complicated or compromised the clinical protocol.

IV levetiracetam was well tolerated and clinically efficacious in this population and was not associated with acute toxicity.

Conclusions: Seizures in the transplant patient present a difficult theraputic challenge. Patients are frequently takiing multiple medications and if they develop seizures, may do so in the setting of severe morbidity which compromises the ability to take oral medications.

The availability of another intravenous anticonvulsant agent with low protein binding, significant renal excretion and lack of enzyme induction is a welcome extension of the limited theraputic options available in this difficult clinical setting.

Supported by an educational grant from UCB Pharma.

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Anju Bhardwaj 1 , R. Parikh 1 , C. Chandran 1 and D. Pandya 1 ( 1 Neurology, St. Joseph's Regional Medical Center, Paterson, NJ )

Rationale: Epoetin-alfa is a colony-stimulating factor used to treat anemia of chronic kidney disease and end stage renal disease (ESRD). Epoetin has several neuroprotective effects in ischemic, traumatic, convulsive and neurodegenerative brain diseases. However, its administration may cause hypertension, convulsions, hypertensive encephalopathy and influenza-like syndrome. Hyperkalemia is a rare but possible side effect of epoetin. We report a patient who developed polycythemia, hypertension, seizures and persistent hyperkalemia secondary to epoetin use.

Methods: This is retrospective evaluation of a patient was admitted with multiple seizures and persistent hyperkalemia who received epoetin-alfa.

Results: Our patient is a 43 years old South-Asian female with past medical history of hypertension, ESRD on hemodialysis presenting with generalized tonic-clonic seizure after being treated with epoetin for few week. Laboratory evaluation on admission revealed Hemoglobin 18.1, Hematocrit 57.1, Potassium 6.6, S.Creatinine 9.9 and LDH 307. Her neuroimagings were unremarkable. She had one unremarkable interictal EEG. Her potassium remained persistently elevated even after consecutive dialysis. Her potassium level decreased over 7–10 days once epoetin was discontinued. She did not have any seizures after discontinuation of epoetin.

Conclusions: Epoetin has been effective in reversal of anemia in patients with ESRD. It is well tolerated and has several neuroprotective effects and it has few rare side effects. Along with recently reported increased incidence of cardiovascular events, when the hemoglobin exceeds 12, neurological and hyperkalemic effects also need to be monitored. To our knowledge, this is the only case report described in literature.

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Jill Saenz 1 , R. A. Elgavish 1 , L. A. Paige 1 , L. W. Ver Hoef 1 , R. C. Martin 1 and R. C. Knowlton 1 ( 1 Neurology, University of Alabama at Birmingham, Birmingham, AL )

Rationale: Misdiagnosis of epilepsy is common and is difficult to undo. Non-epileptic seizures (NES) and epilepsy are treated differently and more than 75% of patients with NES are inappropriately treated with anticonvulsant medications. Treating NES as epilepsy can cause significant harm to the patient and outcome is better if it is recognized early. The mean time from onset of NES to diagnosis is about 7 years. Video EEG (VEEG) is the currently accepted gold standard, is a highly specific test for epilepsy, and can definitively differentiate between NES and epilepsy. However, VEEG is a poor screening test. A good screening test is quick, safe, inexpensive, easy to use, widely available, acceptable to the patient, and has high sensitivity. Many potential tests have been reported in the literature but none meet enough of these criteria. The objective of this study was to generate a formula based on common observations of patients with NES, and evaluate this formula as a screening test for differentiating patients with NES from those with epilepsy.

Methods: All adult patients completing scalp VEEG monitoring at the UAB Epilepsy Center during a six month period and diagnosed with epilepsy (78), NES (78), or both (7), were included. Minors, prisoners, and mentally retarded patients were excluded. A retrospective chart review recorded each subject's final diagnosis, age, gender, age at onset, results of MRI and routine EEG, seizure frequency, number of: drug allergies, CNS medications, AEDs tried in the past, psychogenic diagnoses. Best-subsets multiple logistic regression was performed to generate a formula based on the variables most predictive of the diagnosis. The results were cross-validated and sensitivity and specificity were calculated. VEEG was used as the gold standard.

Results: The variables found to be predictive of the diagnosis were age, age at onset, reported (unverified) EEG results, and the total number of drug allergies and psychogenic diagnoses. Variables not predictive were the gender, seizure frequency, MRI result, and the number of CNS meds and AEDs tried. When the formula was generated from patients monitored during the first 3 months, and then validated with a different group of patients seen the following 3 months, the sensitivity for diagnosing epilepsy was 100% and the specificity for epilepsy was 83%. When this order was reversed, the sensitivity was 97% and specificity was 92%. When the formula was generated from all 163 patients, and then validated with the same group of patients, the sensitivity was 98% and the specificity was 84%.

Conclusions: With the high sensitivity reported above, this formula can meet all the criteria for a good screening test. If this test is further validated, patients identified as having NES can be referred for psychological evaluation - before incurring the cost in time and money, the inconvenience of VEEG monitoring, and the exposure to unnecessary drugs - and can still be monitored at a later time. This formula can serve as an additional tool for general practitioners and neurologists in evaluating this challenging patient population.

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Nicole A. Seminario 1 , L. M. Bateman 1 and M. Seyal 1 ( 1 Neurology, UC Davis Medical Center, Sacramento, CA )

Rationale: Status epilepticus is a major cause of morbidity and mortality in epilepsy and intravenous anticonvulsant administration plays an important role in its management. Of the new anticonvulsant medications, only levetiracetam has become available in an intravenous form. At this time it is unclear whether intravenous levetiracetam has efficacy in the treatment of status epilepticus.

Methods: This is a retrospective case series evaluating the patients who received intravenous levetiracetam as one of the agents used to treat status epilepticus.

Results: Three patients were identified. Patient 1 was a 59 year old woman with multiple myeloma taking levetiracetam 500 mg daily for recent onset partial seizures. She presented with a posterior cerebral artery infarct, a subdural hematoma and epilepsia partialis continua. She was sequentially given four mg of intravenous lorazepam, 1000 mg of intravenous phenytoin, and 1000 mg intravenous and 1000 mg of oral levetiracetam. Her seizures finally abated with the addition of 1000 mg of sodium valproate. Patient 2 was a 67 year old man with post-traumatic epilepsy on valproic acid 750 mg twice daily and levetiracetam 500 mg twice daily who presented with nonconvulsive status epilepticus. He was given six mg of intravenous lorazepam, a total of 1850 mg of sodium valproate, and 3000 mg of intravenous levetiracetam. His seizures did not abate until he received intravenous phenytoin 1500 mg. Patient 3 was a 34 year old pregnant woman at 37 week gestation with Juvenile Myoclonic Epilepsy. She was taking lamotrigine 350 mg twice daily with stable serum levels. She presented with status myoclonus. She was given intravenous levetiracetam 1000 mg and her seizures abated within minutes of the infusion.

Conclusions: Intravenous levetiracetam stopped status epilepticus in one of three cases in this series. Its role in the routine management status epilepticus remains uncertain. (Source of funding is UCB Pharma, Young Investigator Research Program.)

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Carol Ulloa 1 and G. Montouris 1 ( 1 Boston University, Boston, MA )

Rationale: Serum concentrations of first generation AEDs are known to fall during pregnancy. This is particularly true for phenobarbital and phenytoin during the first trimester and carbamazepine in the third trimester. This is related to protein binding.

Little is known about changes in serum concentrations involving second generation AEDs. Many of these are renally excreted (topamax, oxcarbazepine, levetiracitam). As a result, renal clearance and GRF increase during pregnancy.

Oral contraceptives are known to decrease lamotrigine levels because of glucuronidation. The same appears to occur during pregnancy.

Therefore, close monitoring of both renally excreted second generation AEDs and lamotrigine is required to sustain seizure control during pregnancy.

Elevation in post-partum serum concentrations are seen in first generation AEDs, approximately 10 to 14 days post-partum. In contrast, as renal clearance and glucuronidation revert to the pre-gestational state, the risk of toxicity from renally excreted second generation AEDs and lamotrigine may occur immediately post-partum.

Methods: Twenty women with epilepsy, yielding twenty-three pregnancies, were followed over the last three years at Boston Medical Center.

Serum levels yielding seizure freedom were established pre-gestationally and served as the individual's therapeutic level. Serum concentrations were monitored throughout pregnancy and when below this established therapeutic level, dose adjustments were made to achieve seizure control.

Serum concentrations were checked on the day of delivery and one day post-partum when possible.

Results: Frequent dose adjustments were required to maintain each individual's therapeutic level and prevent seizures.

Only patients with refractory epilepsy had breakthrough seizures during pregnancy. All those who were seizure free pre-gestationally remained seizure free during pregnancy.

Levels one day post-partum were markedly higher than the individual's established therapeutic level, as well as the previously obtained level during pregnancy. This required immediate dose adjustments to avoid toxicity.

Conclusions: It is highly recommended that serum concentrations of both first and second generation AEDs be monitored throughout pregnancy and appropriate dose adjustments be made.

It is also imperative that immediate post-partum levels of second generation AEDs be monitored to prevent toxicity. Dose adjustments may need to be made day of delivery and/or one day post-partum.

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Trichia Ramsay 1 , J. Bainbridge 2 , T. Fredricks 3 , J. Slater 4 , R. Nemire 5,6 and R. E. Ramsay 6 ( 1 Epilepsy International, Miami, FL ; 2 Neurology, University of Colorado, Denver, CO ; 3 St Johns Medical Clinic, Springfield, MO ; 4 Neurology, University of Texas, Houston, TX ; 5 Pharmacy, Nova University, Ft Lauderdale, FL and 6 Neurology, University of Miami, Miami, FL )

Rationale: Limited number of randomized controlled clinical trials in geriatric epilepsy have been undertaken. Results of VA cooperative study #428 found a better outcome with one of the newer AEDs (lamotrigine) compared to carbamazepine which has been considered the AED of choice in focal new onset seizures (NOSz). Levetiracetam (LEV) has favorable characteristics (good tolerability, linear pharmacology and no drug interactions). NOSz occur frequently in the geriatric population and new treatment options are desirable.

Methods: Patients 60+ yo with NOSz previously untreated or inadequately untreated were recruited and randomized to levetiracetam or carbamazepine. Study drug was over encapsulated and all patients received similar appearing active medication. Exclusions included patients with unstable medical or psychiatric disease & prior exposure to study drug. Initial doses were LEV 250 mg/day and CBZ 100 mg/day and were increased weekly by the same dose to target dose of LEV 1000 mg/day or CBZ 400 mg/day. Dose reduction was allowed to reduce side effects. Dose increase was allowed for recurrent seizures. Patients were discontinued for intolerable side effect or uncontrolled seizures with maximal tolerated AED dose. Primary outcome will be patients continuing at one year.

Results: Thirty seven patients have been consented and enrolled from four centers to date. Demographics are age (20 pts 60–69, 17 pts 70+), race: White-19, Black-5, Hispanic-10, asian-1; gender male28, female-9. Maintenance dose was achieved between 2–4 week. Reason for patients discontinuing the study were generalized rash (1), excessive tired (1), underwent renal transplant (1), withdrew consent (2), lost to followup (1) and died before receiving study medication (1). All patients reported central nervous system, gastro-intestiona and genital-urinary symptoms before study medication was started. Six additional patients reported treatment emergent symptoms of sleepiness, GI upset, tired, agitation, and joint pain that were either transient or responded to dosage reduction. To date, no patient has dropped for lack of seizure control. Six months followup will be available on all enrolled patients and the 6 months outcome will be presented

Conclusions: Treatment emergent side effect rate was low (20%) likely related to high rate of neurologic, GI and GU symptoms at baseline. To date no patient has dropped for lack of seizure control. Outcome for all patients at 6 months of treatment will be presented.

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Daniela Minecan 1 , N. Kaplish 1 , G. Fromes 1 and O. Sagher 1 ( 1 Neurology, University of Michigan, Ann Arbor, MI )

Rationale: Evaluation of the long-term outcome after epilepsy surgery is important. It should take into consideration not only the seizure outcome, but also other parameters such as the social/employment status, neuropsychometric outcome, psychiatric complications if applicable.

Methods: 81 adult patients(age 18 years and older)who underwent epilepsy surgery between 2002 and 2005 were included. The seizure outcome was at least 2 years for each of the selected patients. There were a total of 43 female patients. Sixty-two patients had temporal resections(either standard temporal lobectomies or selective amygdalo-hippocampectomies). The remaining 19 patients had extratemporal resections(11 frontal).

Results: Mean follow-up was at least two years. Of the 81 patients, 54(66%) were seizure free at the long-term follow-up(up to four years). Fourteen patients were significantly improved, with only rare and/or non-disabling seizures. Only five patients remained either unchanged in respect to seizure outcome or got worse. Most patients were maintained on their antiepileptic medications for at least two years after the epilepsy surgery.

Conclusions: Long-term seizure-free rate following resective epilepsy surgery at our center is similar to that reported in other studies. Most patients (>60%) were able to become employed or maintain it after surgery. Even longer term follow up as well as stratification according to the site of resections will be important to be determined, in addition to analyzing other factors that influence quality of life.

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John DellaBadia 1 and A. Stevens 1 ( 1 Neurology, LSUHSC-Shreveport, Shreveport, LA )

Rationale: To report clinical features and associated psychiatric diagnosis in men with pseudoseizures confirmed by video-EEG monitoring.

Methods: Retrospective record review of 680 admissions to the adult epilepsy monitoring unit from 3/97 to 5/07 identified 176 patients with the diagnosis of pseudoseizures or psychogenic seizures.

Results: 28.4% (50/176) of the identified patients with pseudoseizures were men. 76% (36) of the men were Caucasian men (CM) while 28% (14) were African American men (AAM). Mean age at admission was 38.9 years old, range (16–74) with a mean age of onset of pseudoseizures of 29.6 years old. The average duration of pseudoseizures was 8.1 years. However, AAM were younger at onset (21 years old) and had a longer duration of pseudoseizures (15.7 years), compared to CM who were older at diagnosis (33.4 years) and had a shorter duration of seizures (5.2 years). 78% (39/50) of all men were on antiepileptic drugs (AEDs) with 51.3% (20/39) of them on polypharmacy. More AAM were on AEDs, 92.9% (13/14) compared to CM, 72.2% (26/36). All men had a high seizure burden with seizures ranging from daily to at least once per week in 76% (38/50). Additionally, 76% (38/50) of men had predominately motor manifestations. However, 92.9% (13/14) of AAM had motor manifestations compared to 69.4% (25/36) of the CM. 70% (35/50) of the men had spells within the first 24 hours of admission. An average of 5.1 pseudoseizures were recorded over an average of 4.8 days in the monitoring unit. CM averaged 5.75 pseudoseizures per admission compared to 3.36 for AAM. This was due to 6 CM having 10 or more pseudoseizures, while none of the AAM had 10 or more. There were no injuries during the episodes. However, one man was restrained who was propelling himself out of bed head first. There was a single instance of incontinence during a spell. Only 8% (4/50) of men had focal epileptiform changes on their EEG. 30% (15/50) of men had a prior psychiatric diagnosis. However, 40% (21) of men were on psychotrophic medications at the time of admission. The most common psychiatric diagnosis was depression in 80% (12/15). In AAM the only diagnosis previously given was depression in 28.6% (4/15). In CM 22.2% (8/36) were diagnosed with depression, but additionally 25% (9/36) had other psychiatric diagnoses. A history of life trauma was more common in men 46% (23/50), while a history of sexual abuse was rarely reported, 2% (1/50). A family history of seizures was reported in 18% (9/50) of the patients. A slightly higher rate was reported in AAM, 28.6% (4/14), compared to CM, 13.9% (5/36).

Conclusions: Although more commonly seen in women, pseudoseizures are also common in men. Pseudoseizures were more commonly of earlier age of onset with a longer duration and frequent motor features in AAM compared to CM.

AAM were also more commonly treated with AEDs. Prior known psychiatric pathology occurs in the majority of men, predominately depression. Depression was the only psychiatric diagnosis in AAM. Life trauma was common in men and sexual abuse was rare.

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Jill E. Stow 1 , T. Dunning 1 , A. M. McIntosh 1,2 and M. R. Newton 2 ( 1 School of Nursing, The University of Melbourne, Melbourne, VIC, Australia and 2 Epilepsy Research Center, Austin Health, Melbourne, VIC, Australia )

Rationale: There is evidence that people with chronic epilepsy lack knowledge in key areas, and desire more information about epilepsy. Little, however, is known about peoples' knowledge and information needs at diagnosis. There are no studies on the extent to which self-management practices are adopted following new diagnosis. We aimed to; 1) Measure the general knowledge that people have about epilepsy at time of diagnosis, and on retest six months later; 2) Measure the extent to which self-management behaviours are adopted at six-months.

Methods: A descriptive, exploratory study was used to collect data from people with a new diagnosis of epilepsy (PNDE) at a First Seizure clinic. Fifty PNDE aged 16–86 were recruited immediately following diagnosis. They completed the 55-item Epilepsy Knowledge Profile - General (EKP-G) questionnaire (Jarvie, S., et al., Seizure 1993; 2: 179–185) which contained 34 medical and 21 social questions. A second questionnaire containing the EKP-G and the 38-item Epilepsy Self-Management scale (DiIorio, C. & Henry, M., J Neurosci Nurs 1995:27(6): 338–343) was mailed six-months later. The EKP-G was scored using a true/false/unsure format (unsure responses scored as incorrect), the ESMS on a scale of one (never) to five (always).

Results: Thirty-seven (74%) PNDE returned the six-month questionnaire. The majority were females (70%), median age of 33 (range 18–86). They were well educated, 54% having completed higher education. Almost half were fully employed. Most (92%) had two or more seizures prior to diagnosis, 54% primarily generalised and 30% secondarily. Seventy percent were prescribed anti-epileptic medications (AEMs). At diagnosis EKP-G scores varied widely (median 31, range 48), by six-months the median EKP-G score had improved to 34 (p < 0.023), with a reduction in the range to 33. Participants consistently scored more highly on medical than social knowledge items. At diagnosis about 2/3 of participants didn't understand that AEMs need to be taken regularly to be effective, and that they should be continued, even if seizures stop (33%). ESMS scores were divided into quartile ranges 98–129 (n = 9), 130–135 (n = 8), 136–144 (n = 8) and 146–152 (n = 8), the highest quartile reflecting self-management strategies practised ‘most of the time’. ESM items with the highest mean score include; two items on medication adherence (4.84, SD.62) and the use of power tools with automatic shutoff (4.84, SD 1.06). Items with the lowest mean include; participation in a support group (1.33, SD 1.02) and seizure first aid practice with family and friends (1.54, SD1.02). There was no association (Pearson r = .126) between knowledge and self-management scores at six-months

Conclusions: A well-educated, mainly female, group of PNDE were found to have knowledge deficits after diagnosis at a FSC. Six-months later their knowledge levels had improved, but this was not associated with higher self-management scores. These findings will guide the development of an educational intervention to improve information giving at time of diagnosis.

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Yue-Loong Hsin 1,3 , M. Chuang 1 and T. Harnod 1,2 ( 1 Neurology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan ; 2 Neurosurgery, Buddhist Tzu Chi General Hospital, Hualien, Taiwan and 3 Institute of Medical Sciences, Buddhist Tzu Chi University, Hualien, Taiwan )

Rationale: To study the effect of multiple subpial transection (MST) on cortical excitability in patients with intractable infantile spasms and hypsarrhythmia.

Methods: Three patients received MSTs. Presurgical MRI, PET, and long-term video-EEG were used to identify and localize coexisting partial seizures. Epileptogenic gyri were transected with reference to intraoperative electrocorticography (ECoG). Surgical outcome and related neurophysiological changes were assessed using postoperative long-term scalp EEG, seizure/spasm numbers, and PET scans.

Results: Intraoperative ECoG disclosed the immediate effect of MSTs with disruption of synchronous cortical EEG activities on the targeted cortices. Clinically, the reduction of seizure/spasm frequency and developmental improvement were obtained and maintained continuously. The hypsarrhythmic EEG revealed less randomization and better organization. The glucose metabolism in the surgical regions increased.

Conclusions: The good outcome suggests the validity of MST in the treatment of uncontrolled infantile spasms and sustains the rule of focal cortical excitation in spasm seizures.

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Yoko Matsumoto 1 , K. Haginoya 1 , K. Iinuma 2 and S. Tsuchiya 1 ( 1 Pediatrics, Tohoku University, Aobaku Sendai, Japan and 2 Pediatrics, Ishinomaki Red-Cross Hospital, Ishinomaki, Japan )

Rationale: In Europe and the United States, a natural adrenocorticotropic hormone (ACTH) is available for a treatment of West syndrome (WS). In Japan, however, a natural ACTH was eliminated from the market in 1970 and a synthetic ACTH was replaced. Since the synthetic ACTH was reported to have more adverse effects than the natural ACTH, the dosage for the synthetic ACTH was usually lower than that of the natural ACTH. Recent studies showed a short-term effectiveness of lower dosages of the synthetic ACTH in reducing adverse effects. However long-term effects of the low-dose synthetic ACTH has not been precisely studied. The purpose of this study is to examine a long-term effect of the low-dose ACTH therapy for patients with WS who were treated at a single institution.

Methods: Medical record of 118 patients diagnosed as having WS at Tohoku University between 1978 and 2004, were analyzed. Patients who achieved cessation of spasm before the ACTH therapy and second trial of the ACTH therapy were excluded. Remain 55 patients received 4 week regimen of synthetic ACTH. Initial and long term outcome were measured by complete cessation of seizures and disappearance of hypsarrhythmia on EEG.

Results: Immediately after the ACTH therapy, 49 (89%) patients showed cessation of seizure. There was no severe adverse effect related to ACTH therapy. The onset age (<4 months old vs. ≥ 4 months old), the treatment lag (< 3 months vs. ≥ 3 months), the dosage of ACTH (0.02 mg/kg vs. 0.015 mg/kg), the etiology (cryptogenic vs. symptomatic) and the length of days needed to achieve the successful short-term outcome had no significant effects on the long-term outcome. The overall probability of the long-term effect was approximately 0.38 after 2000 days (5.5 years). Among patients who achieved the successful short-term outcome, about 45% of them remained seizure free for more than 5.5 years.

Conclusions: Low dose synthetic ACTH therapy benefited for seizure control as natural ACTH therapy for the initial outcome. This study indicated that 38% of patients had not experienced any seizure for at least 5.5 years after low dose synthetic ACTH therapy. Onset age, treatment lag, dosage of the ACTH, etiology and the length of days needed to achieve the successful short-term outcome had no significant effect on long-term outcome.

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Hitoshi Yamamoto 1 and M. Fukuda 1 ( 1 Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan )

Rationale: Urinary and cerebrospinal fluid (CSF) levels of 8-hydroxy-deoxyguanosine (8-OHdG) were measured to estimate the relevancy of oxidative stress to the disease in children with status epilepticus (SE). Currently, 8-OHdG is used as a sensitive marker for oxidative DNA damage. However, few studies have previously analyzed urinary or CSF 8-OHdG levels in children with an organic brain damage.

Methods: Urinary 8-OHdG levels were measured in 23 children with SE and in 51 healthy children. CSF 8-OHdG levels were studied in 13 children with SE and in 19 controls. The relationship between urinary and CSF levels of 8-OHdG was determined in 5 children where both urinary and CSF samples were available. The measurement of urinary 8-OHdG was conducted with an ELISA kit and CSF 8-OHdG was conducted with a HPLC analyzer.

Results: The levels of urinary and CSF 8-OHdG in control children were 18.1 ± 6.4 ng/mg cre and 4.14 ± 2.06 pg/ml respectively. The levels of urinary 8-OHdG in SE were 63.1 ± 99.6 ng/mg cre and there was no significant difference. The levels of CSF 8-OHdG in SE were 9.25 ± 3.08 pg/ml, which was significantly higher than in controls (P < 0.05). A positive correlation between the levels of urinary and CSF 8-OHdG in SE was noted (P < 0.05).

Conclusions: The production of free radicals by excessive stimulation of the excitatory amino acid receptors are considered to be a cause of seizures. Oxidative stress may accelerate brain tissue damage at the early stage of certain pathological processes associated with SE. Measurement of CSF 8-OHdG was useful for estimating oxidative brain damage. CSF 8-OHdG reflects active oxidative stress induced brain damage in children more closely than urinary 8-OHdG. Urinary 8-OHdG appears to be an useful marker of disease activity in childhood nervous disorders in which oxidative stress plays an important pathogenic role.

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Sally R. Monahan 1 , D. Daniels 2 , A. Hankins 1 , L. Heaton 1 , P. Clark 1 , S. Weingartner 1 , D. Schawe 1 , A. Modi 1 , J. Koumoutsos 1 , S. Fordyce 1 , Z. Daniels 1 , D. Morita 1 , K. Holland 1 , T. DeGrauw 1 and T. Glauser 1 ( 1 Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH and 2 Neurology, The Children's Hospital of Denver, Denver, CO )

Rationale: Optimizing direct care for current and future children with new onset seizures (NOS) or epilepsy requires a clinical “laboratory” where integration of clinical care, extensive education and clinical research can be tested and refined. The purpose of this effort was to develop and refine a clinic model for children with NOS or epilepsy to provide rapid multidisciplinary care and extensive education (to improve current outcomes) while conducting clinical research (to improve future outcomes).

Methods: Various workflows were constructed and assessed with the goal of minimizing wait times for both initial/follow-up visits and in-clinic wait times, while maximizing opportunities for patient education and enrollment in research studies. Children (2 to 18 years) with suspected NOS or suspected new onset epilepsy and no serious chronic medical issues are eligible for the clinic. All patients have EEGs prior to the initial clinic visit. An epileptologist performs the initial assessment using standardized data collection while an experienced pediatric epilepsy nurse practitioner conducts follow-up visits. An epileptologist follows-up each patient at least on a yearly basis. Epilepsy nurses use both verbal and written methods to provide specialized education within the clinic setting with frequent follow-up telephone contact. Social workers are rapidly available to address needs as they arise. Research protocols were specifically built upon routine clinical practice. Research assistants attend clinic to enroll and conduct research protocols in the context of clinic flow.

Results: During the past 4 years of active assessment and refinement, multiple changes to clinic structure and flow have been tried and revised. The clinic averages approximately 247 NOS first visits per year with 1425 follow-up visits. Currently, new patient evaluations are conducted within 7–10 days of referral. The overall long term seizure-free rate in this patient population for children with partial onset seizure is approximately 65% (Neurology, in press). The average time from arrival in clinic to leaving (for the last 55 follow-up patients) was 83 ± 26 minutes, with the average patient time with the nurse practitioner (for the last 59 follow-up patient visits) being 22 ± 18 minutes. Studies integrated into the clinic include recruitment for the Childhood Absence Epilepsy project (NIH NS045911, n = 43), Blood Genomics of Antiepileptic Drug Efficacy in Children (NIH NS044956, n = 300), Pharmacogenetics of Antiepileptic Drug Metabolism and Neurotoxicity in Children with Epilepsy (Epilepsy Foundation, n = 501), as well as both longitudinal and cross sectional studies examining adherence to antiepileptic drug (AED) therapy, and psychosocial outcomes of both children with epilepsy and their parents, side effects of AED therapy, and overall health outcomes (e.g., seizures, quality of life).

Conclusions: It is possible to design and refine an epilepsy clinic model that optimizes clinical care, patient education and clinical research. This design may be generalizable to other medical centers.

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Piotr Zwolinski 1 and M. Roszkowski 1 ( 1 Neurology & Neurosurgery, Warsaw Memorial Child Hospital, Warsaw, Poland)

Rationale: To evaluate long term seizure reduction and on-demand magnet use in patients < 18 years with pharmacoresistant epilepsy treated with adjunctive vagus nerve stimulation (VNS) Therapy.

Methods: N = 57 (32 M, 25 F; 59.6% < = 12 years). Mean age 11.4 ± 3.85 years; mean duration of epilepsy 9.3 ± 4.14 years; 64.9% were mentally retarded; 38.6% had neurological deficits; prior epilepsy surgery: 12.3%. Simple partial seizures: 38.6%; complex partial: 96.5%; secondarily generalized: 56.1%; myoclonic: 8.8%. Seizure reduction was evaluated after 6, 12, 24, 36 and 48 months of VNS Therapy in 56, 56, 54, 35 and 18 patients, respectively. Magnet effect (cessation of seizures, partial effect or no effect) was evaluated within the first week after implantation (‘early magnet effect’ - EME) and after 6, 12, 24, 36 and 48 months (‘stable magnet effect’ - SME).

Results: Mean seizure reduction: 48.2%, 52.4%, 57.1%, 53.4% and 53.1%; seizure reductions > = 50%: 46.4%, 50.0%, 55.6%, 51.4% and 50.0% of the patients after 6, 12, 24, 36 and 48 months, respectively. Seizure-freedom: 1.8%, 8.9%, 9.3%, 11.4% and 16.7% after 6, 12, 24, 36 and 48 months, respectively. EME: cessation of seizures, 16.1%; partial effect, 73.2%; no effect: 10.7%. SME: cessation of seizures, 8.9%, 8.9%, 9.3%, 8.6% and 5.6%; partial effect, 69.6%, 69.6%, 68.5%, 57.1% and 55.6%; no effect, 21.4%, 21.4%, 22.2%, 34.3% and 38.9% after 6, 12, 24, 36 and 48 months, respectively.

Conclusions: Adjunctive VNS Therapy is effective for children and adolescents of all ages with pharmacoresistant epilepsy.

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M. Roszkowski 1 and P. Zwolinski 1 ( 1 Neurosurgery, Warsaw Memorial Child Hospital, Warsaw, Poland)

Rationale: To describe the efficacy, safety and magnet use in children up to 6 years with pharmacoresistant epilepsy treated with VNS Therapy at the Memorial Child Hospital in Warsaw, Poland.

Methods: Seven children (3M, 4F); mean age: 4.7 ± 1.38 years (range, 3–6). Mean epilepsy duration: 3.9 ± 1.35 years (range, 2–6). Etiology: birth trauma, N = 2; West syndrome, N = 1; ceroid lipofuscinosis, N = 1; cerebral involvement of leukemia, N = 1; unknown, N = 2. Mental retardation, N = 4; neurological deficits, N = 5. MRI was abnormal in 5 children. Simple partial seizures, N = 1, complex partial, N = 6; secondarily generalized, N = 5. Magnet effect (cessation of seizures, partial effect or no effect) was evaluated within the first week after implantation (‘early magnet effect’ - EME) and after 6, 12 and 24 months (‘stable magnet effect’ - SME).

Results: Mean and median seizure reduction: 46.2% and 40% after 6 months (N = 7); 46.2% and 40% after 12 months (N = 7); 52.2% and 45% after 24 months (N = 6), respectively. Three patients (42.8%) had > = 50% seizure reduction; one patient (14.3%) remained seizure-free for 18 months. Three patients had <50% seizure reduction and 1 patient had no change in seizure frequency. The surgical procedure and treatment were well tolerated. EME: partial effect in 6 children. SME: partial effect in 7, 7 and 6 children after 6, 12 and 24 months, respectively.

Conclusions: VNS Therapy is effective and well tolerated even in young children up to 6 years of age. Magnet stimulation provided children treated with VNS Therapy with additional means for controlling their seizures.

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Robert Flamini 1 , G. Kirk 1 , J. Ganote 1 , N. Meers 1 , S. Palasis 1 , R. Cheng 1 and R. Hudgins 1 ( 1 Neurology/Epilepsy, Children's Healthcare of Altanta at Scottish Rite, Atlanta, GA)

Rationale: To analyze the results of our experience in the utilization of SISCOM (Substraction Ictal SPECT coregistered on MRI) in intractable pediatric epilepsy.

Methods: 62 patients underwent Ictal SPECT as part of their presurgical evaluation between 2004 and 2006. The study utilized Neurolyte® with 20 mCi dosing calibrated twice per day and usually administered within 30 seconds of electrical seizure onset. A follow up interictal SPECT study was completed, subtracted and superimposed on volumetric 1.5TMRI utilizing the Analyze software (SISCOM). Hyperperfusion and Hypoperfusion coregistrations were obtained. The data was analyzed in conjunction with standard digital Video-EEG, state of the art anatomic MRI and neuropsychological data for selection of surgical candidates. EEG and SISCOM data were considered localizing when one side/one region or one side/2 contiguous regions were active. Lateralization of EEG was defined as abnormal activity limited to one side, even if multifocal. All others were considered not lateralizing or localizing.

Results: Patients range in age from 2 to 21 years. MRI were abnormal in 52% of patients (9% non-focal), and normal in 48% (intractable non-lesional epilepsy).

Interictal EEG was non-lateralizing or localizing in 74% of patients, lateralizing and localizing in 26%. Ictal EEG was non-lateralizing or localizing in 71%, localizing in 26% of the patients.

SPECT studies were abnormal in 89% of the interictal studies and 97% of the ictal studies. When the data was coregistered, SISCOM hyperperfusion studies were abnormal in 60% of patients, and SISCOM hypoperfusion were abnormal in 23% of cases.

SISCOM data offered unifocal hyperperfusion in 78% of patients and multifocal lateralized hyperperfusion in 19% of patients. It was bilateral in only one patient. Hypoperfusion SISCOM offered localization in only 23% of patients.

Overall the concordance between SISCOM and EEG lateralization/localization was significant at a p = 0.0232. There was a higher statistical significant correlation between hyperperfusion SISCOM images and MRI with focal abnormalities (p = 0.0022)

Overall, 55% of patients underwent epilepsy surgery. When intracranial recordings were done, SISCOM data helped plan the localization of subdural electrodes. Surgical outcome based on localization of SISCOM and resection showed Engel I in 12%, Engel II in 54%, and Engel III in 27% of patients.

Conclusions: In selected pediatric patients, SISCOM is a very helpful test in localization of the epileptogenic zone. Hyperperfusion SISCOM localizes more frequently than other techniques. Statistically significant correlation occurred between ictal EEG, hyperpefusion SISCOM, and focal MRI abnormalities. For non lesional epilepsy, the test helps in patient surgical selection and electrode coverage for intracranial recordings. Patient outcome was favorable. For the patients with bi-frontal non-lesional epilepsy however, the test appears to lack enough power for lateralization/localization. These patients will be further evaluated with Dense Array EEG in the future for further comparison.

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Celina von Stuelpnagel 1,5 , H. Plischke 2 , R. Gruber 3 , P. Zill 4 , C. Bäumel 5 , H. Holthausen 5 and G. Kluger 5 ( 1 Clinic for Pediatrics, Hospital of Munich-Harlaching, Munich, Germany ; 2 Generation Research Programm, Human Research Center of the Ludwig-Maximilians-University, Prof.-Max-Lange-Platz 11, Bad Tölz, Germany ; 3 Laboratory for Rheumatology, Hospital of the University, Medical Policlinic - Innenstadt; Pettenkoferstr. 8a, Munich, Germany ; 4 Clinic and Policlinic for Psychiatry and Psychotherapy, LMU Munich, Nussbaumstrasse 7, Munich, Germany and 5 Clinic for Neuropediatrics and Neurological Rehabilitation, Center for Epilepsy in Children and Adolescents, Krankenhausstr. 20, Vogtareuth, Germany )

Rationale: Investigation of a possible association between pharmacoresistance to antiepileptic drugs and MDR1- polymorphisms C3435T, C1236T and G2677T/A in children with epilepsy?

Methods: 231 patients were recruited (130 male (56.3%), mean age 11.5 y.):

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    160 patients (69.3%) with drug-resistant epilepsy (> 3AED, not seizure free and/or after epilepsy-surgery);
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    71 patients (30.7%) in the control group (seizure free > 6 month).

Genomic DNA was extracted from 4 ml EDTA-blood and the MDR 1-polymorphisms for C3435T, C1236T and G2677T/A were determined by PCR and snapshot technique

Results: 1.In our study the MDR1-polymorphisms C3435T, G2677T/A and C1236T were not associated with a drug-resistant epilepsy in children (s. table 1) (in accordance with the Hardy-Weinberg-Equilibrium

2.With regard to possible haplotype-combinations the following were observed without an association for pharmacoresistance in decreasing frequency: CGC/TTT, CGT/TTT, TTT/TTT, CGC/CGC and CGC/CGT.

3.Only the AED CBZ showed a significant difference regarding the side-effect tiredness. It occurred more often in the TT-group of the C3435T-polymorphism (P = 0.035; Odds Ratio = 12.25; CI: 1.27–118.43). After applying Bonferroni correction the results were no longer statistically significant.

4.Regarding the development of tolerance for AED in the C3435T-polymorphism there was not a statistically significant difference in the TT-group and the CC-group.

Conclusions: In concordance with the results of Kim (1), Tan (4) and Sills (3) we could not confirm Siddiqui's (2) observed association between the CC-genotype of the MDR1 and the development of a drug-resistant epilepsy. Our study did also fail to confirm an association between the haplotypes CGC, CGT and TTT and the occurrence of therapy-resistant epilepsy as reported by Zimprich et al. (5).

We noticed a possible correlation between the occurrence of tiredness as side-effect and the TT-genotype of the C3435T-polymorphism. After applying Bonferroni correction the results were no longer statistically significant. In this respect this polymorphism could be a candidate in further studies investigating the pharmacokinetic interference in combination with other drugtransporterproteins.

References:

(1)Kim YO, Kim MK, Woo YJ, et al. Single nucleotide polymorphisms in the multidrug resistance 1 gene in Korean epileptics. Seizure. 2006;15:67–72.

(2)Siddiqui A, Kerb R, Weale ME, et al. Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1. N Engl J Med. 2003;348:1442–8.

(3)Sills GJ, Mohanraj R, Butler E, et al. Lack of association between the C3435T polymorphism in the human multidrug resistance (MDR1) gene and response to antiepileptic drug treatment. Epilepsia. 2005;46:643–7.

(4)Tan NC, Heron SE, Scheffer IE, et al. Failure to confirm association of a polymorphism in ABCB1 with multidrug-resistant epilepsy. Neurology. 2004;63:1090–2

(5)Zimprich F, Sunder-Plassmann R, Stogmann E, et al. Association of an ABCB1 gene haplotype with pharmacoresistance in temporal lobe epilepsy. Neurology. 2004;63:1087–9

MDR1-polymorphisms

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significance was calculated by chi2-test

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Marisa Spann 1 , L. Dix-Cooper 2 , R. Berman 3 , M. Westerveld 1 , M. Negishi 4 , J. Motelow 2 , R. T. Constable 4 , E. J. Novotny 1,5 and H. Blumenfeld 1,6 ( 1 Neurosurgery, Yale University School of Medicine, New Haven, CT ; 2 Neurology, Yale University School of Medicine, New Haven, CT ; 3 Neuroscience, Yale University School of Medicine, New Haven, CT ; 4 Diagnostic Radiology, Yale University School of Medicine, New Haven, CT ; 5 Neurology & Pediatrics, Yale University School of Medicine, New Haven, CT and 6 Neurology & Neuroscience, Yale University School of Medicine, New Haven, CT )

Rationale: Typical Childhood Absence Epilepsy (CAE) is characterized by absence seizures with 3–4 Hz spike-wave discharge on EEG. The seizures behaviorally manifest as blank staring and unresponsiveness (lasting 5–10 seconds). In the CAE child's daily living environment seizure episodes can be mistakenly identified as daydreaming, as these periods can be brief and mimic attention deficit hyperactivity disorder symptoms. Previous studies have tried to better understand “inattention” in CAE both during and between seizures (interictal). However, to our knowledge none have studied CAE patients while not on antiepileptic (AEDs) medication. The present study investigates dimensions of attention in a sample of typical CAE patients compared with normal controls.

Methods: Typical CAE patients (diagnosed by an epileptologist) were recruited from EEG centers and area neurologists. Normal controls were recruited via advertisements. All participants were administered a brief cognitive/behavioral battery including the Continuous Performance Test (CPT). After screening and training, a subset participated in simultaneous fMRI (3T) and EEG recording (standard 10–20 system), while performing the CPT. Patients remained off antiepileptic medications for 48 hours prior to the study session. The sample included 14 CAE and 10 controls, with a combined mean age of 12 years. The majority of CAE patients were female (60%) and controls were male (80%). Both groups were primarily right-hand dominant (92%).

Results: One-way ANOVA indicates a significant mean difference in the interictal omission (non-response to target; inattentive pattern) error rate (p < .02); the CAE group having higher error rates. While there was no significant difference in mean reaction time (RT), the standard deviation of the reaction time was different in the two groups (p < .04), with the CAE group having more variability in RT compared to controls. There was also a significant difference in d' or detectability scores, with the CAE group performing more poorly than controls (p < .01).

Conclusions: CAE patients make a greater number of errors on sustained attention testing when compared to controls. They fail to respond to targets at a higher rate. Further analysis of these errors suggests variability in their response speed to visual stimuli, as well as their discriminative power or ability to distinguish between target and non-targets. These findings indicate that attention problems are not just ictal, and that CAE patients experience considerable attention problems interictally. These problems occur even while off medications, suggesting that they may be related to underlying impairment of attentional networks associated with CAE.

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Angelina K. Mwesige 1 , A. Kekitiinwa 1 and J. Byarugaba 1 ( 1 Peadiatrics & Child Health, Makerere University, Kampala, Uganda )

Rationale: Childhood epilepsy is a major health problem both in the developed and developing countries and, contributes as one of the most prevalent forms of chronic and disabling childhood disorders. Fear, misunderstanding and the resulting social stigma and discrimination surrounding epilepsy often force people with this disorder “into the shadows”.

HIV/AIDS is a major public health problem in Uganda. The overall national HIV Sero-prevalence is 6.4% in adults and 0.7% in children. An estimated 84,000 children in the age group of 0–15 years were living with the disease by the end of 2003. It is not clear whether the clinical presentation of paediatric epilepsy in Ugandan children is affected by this illness.

Methods: The objective of this study was to describe the clinical features, EEG abnormalities, and seizure classification types in epileptic children with HIV/AIDS. Study was hospital based and used a case-control design. Caretakers of epileptic children aged 18 months to 12 years attending the Mulago National Referral Hopsital's Paediatric Neurology and/or HIV/AIDS clinics and fulfilled the selection criteria were interviewed using a pre-tested coded questionnaire. Data on the clinical features, EEG pattern, seizure classification types, were noted.

Results: A total of 173 children were enrolled in the study, of these 33 cases (HIV+) were matched according to age and residence with 58 controls (HIV-). There was no significant difference in the clinical epileptic history between the two groups. Clinical features significantly associated in the cases included: weight change (p = 0.005), degree of pallor (p = 0.006), skin manifestations (p = 0.000), nail changes (p = 0.023) and lymph node enlargement (p = 0.000). The predominant EEG pattern in the cases was of bilaterally synchronous spikes with sharp slow wave complexes 9(27.3%) compared to a normal EEG pattern in the controls 15(25.9%). Generalized seizures of the tonic-clonic type were the major seizure classification type in both cases and controls.

Conclusions: Results suggest that HIV/AIDS does not seem to significantly affect the clinical presentation, EEG features or seizure classification types of paediatric epilepsy in Ugandan children. A prospective cohort looking at larger numbers of children with epilepsy and HIV/AIDS is recommended.

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Kenou Van Rijckevorsel 1,2 , S. Andries 2 , M. Coutellier 3 , N. Deconinck 4 , S. Ghariani 2,1 , C. Godfraind 3 , C. Raftopoulos 1 , F. Scaravilli 5 and M. Vikkula 5 ( 1 Reference Centre for Refractory Epilepsy, Université Catholique de Louvain, Brussels, Belgium ; 2 Centre Neurologique William Lennox, Université Catholique de Louvain, Ottignies-LLN, Belgium ; 3 Anatomopathology-Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium ; 4 Infantile Neurology, HUDERF, Brussels, Belgium and 5 de Duve Institute, Université Catholique de Louvain, Brussels, Belgium )

Rationale: CSWS belongs to epileptic encephalopathies responsible for a progressive and severe decrease in cognitive function and marked behavioural problems. Most of time cause remains unknown and this syndrome is resistant to antiepileptics. We describe the case of a girl with progressive behavioural problems, seizures and CSWS.

Methods: S., a girl born in 1996 has no abnormal family story and no specific problems until September 2003. Then, she developed learning difficulties and behaviour disturbances. Later, she was regularly described as “absent” and developed aggressivity, impulsivity, echolalia, stereotyped language. First EEG, recorded in July 2004, showed spike-and-wave (SW) discharges during wakefulness and CSWS. Broad spectrum antiepileptic drugs, corticosteroids had no impact on clinical outcome. After a detailed presurgical evaluation (no metabolic or degenerative diseases, normal MRI, PETscan with bitemporal hypermetabolism and bifrontal hypometabolism), multiple subpial transections were done on left temporo-parietal areas considered as the driver hemisphere in this diffuse encaphalopathy. Electrocorticography showed continuous slow high amplitude SW on retrorolandic area and only few spikes on prerolandic area (figure 1). Biopsies were taken from temporal and parietal lobes. Surgery had no impact on no impact on electrocorticography and evolution. After biopsy results, she received galantamine.

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In May 2007, language is reduced to a few words, she has severe apraxias, unable to dress or to eat alone. She is still able to walk, but witout specific aim. Galantamine (12 mg a day) seems to reduce the speed of deterioration but focal seizures persisted and MRI shows a progressive and diffuse brain atrophy. EEG shows diffuse SW more numerous and visible on unoperated hemisphere and delta background rhythm.

Results: Brain biopsy showed massive destruction of neurons (figure 2) and Collins body inclusions. The diagnosis of neuroserpin disease was made. Usually, neuroserpin inclusions are known to produce a dementia familial encephalopathy. Genetic analysis shows sporadic punctual mutation on locus 3q26. This case is the youngest known case of neuroserpinopathy and the only proven sporadic case described.

Conclusions: Neuroserpin disease should be evoked in front of progressive mental and behavioural deterioration with seizures or CSWS, even in children without familial history of dementia.

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Maurizio Viri 1 , A. Erba 1 , M. Lodi 1 , R. Chifari 1 , V. Dell'Oglio 1 , C. Ghiroldi 1 , L. Bonvini 1 and A. Romeo 1 ( 1 Epilepsy Center, Fatebenefratelli Hospital, Milano, Italy )

Rationale: Angelman Syndrome(AS) is a neurogenetic disorder characterized by mental delay, dismorphyc face, limited or absent language,ataxia, movement disorder and epilepsy.

Epilepsy is a clinical hallmark in 90% of patients with polymorphic seizures (focal, absence, myoclonic and myoclonic- atonic seizures) with age onset at two years of life.

Epileptic myclonic state(SE) or epilepsic state can be present in AS with variable lasting from some hours to days. Epileptic states are often underestimated for their blurred presentation such as behaviour changes, like to fall in a state of apathy, a worsening of motor abilities with localized myoclonias.

|Here we aimed to study, in our AS case series, the frequency of epileptic state and its clinical presentation.

Methods: From June 1988 to December 2006, we collected 61 patients (twenty nine male, thirty two female, with a mean age at last observation of 11 years, range 5 months to 29 years) who received a diagnosis AS after a comprehensive clinical, neuroradiological and laboratory investigations.

Laboratory investigation included detailed genetic test. Long lasting Video/EEG analysis was performed in all case.

Among all case of AS we selected a subgroup of 19 patients with epileptic state, recorded by VIDEO /EEG study.

Results: The 31% (19/61) of patients with Angelman Syndrome showed epileptic states characterized by clinical blurred outlines such as behaviour changes, like to fall in a state of apathy, a worsening of motor abilities with localized myoclonias.

The electroclinical picture in all patients with SE showed continuous epileptic activity of widespread spike-waves and poly-spike waves with a predominance on frontal regions.

Genetic investigation showed a deletion of chromosome 15q11 q13 in sixteen patients, a mutation of UBE3A gene in two, and was negative in one patient.

Conclusions: In conclusion, we have described a relative high frequency (31%) of epileptic state in the context of Angelman Syndrome characterized by slight clinical presentation such as behaviour changes, like to fall in a state of apathy, a worsening of motor abilities with localized myoclonias.

Epileptologists should be aware of these peculiar SE as, in most instances, it could be underestimated.

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Luis E. Bello-Espinosa 1 ( 1 Neurology, Mayo Clinic, Rochester, MN )

Rationale: Purpose: To describe the EEG features and semiology of pediatric epilepsy with photosensitivity

Methods: The EEG records of four hundred twenty four patients between the ages of 0 to 18 years of age who had positive photosensitivity while undergoing EEG were identified between January 1996 and July 2006. Clinical history and neuroimaging records were reviewed and correlated with the identified photoparoxysmal EEG patterns. Clinical reports were reviewed to identify clinical epileptic syndromes associated with photosensitivity and its long term outcome. A minimum of one year follow up was required for the study.

Results: Four types of photosensitive EEG patterns were identified: photoparoxysmal, photoconvulsive, photomyoclonic, and pattern sensitive. All photosensitive EEG responses identified were associated with generalized seizure types and generalized epileptic syndromes. No particular photosensitivity EEG pattern was identified to be indicative of a specific primary or a symptomatic epileptic syndrome. The presence of photosensitivity did not correlate with clinical outcome.

Conclusions: Photosensitive EEG patterns tend to be specific of generalized seizure types and generalized epileptic syndromes. The predominance of generalized epileptic syndromes suggests a probable common genetic component. Cohorts of patients with specific photosensitive EEG patterns can help to delineate the molecular basis of photosensitivity.

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Lionel Carmant 1,2 , S. K. Weiss 2 , S. Whiting 2 , E. Wirrell 2 , E. Donner 2 , J. M. Dooley 2 , G. M. Ronen 2 and K. Farrell 2 ( 1 Pediatrics, Ste-Justine Hospital, Montreal, QC, Canada and 2 Infantile Spasms Study Group, Canadian Pediatric Epilepsy Network, Montreal, QC, Canada)

Rationale: To assess based on etiology the response of infantile spasms and hypsarrhythmia to vigabatrin as first line therapy with an early switch to ACTH in refractory children. This study is part of a larger randomized double blind clinical trial looking at the long-term developmental and epilepsy outcome of infantile spasms with an add-on calcium channel blocker.

Methods: We recruited 69 children with new onset infantile spasms over a 2-year period. Children were randomized to conventional treatment with flunarizine or placebo. Conventional treatment consisted of 150 mg/kg vigabatrin and 200 mg vitamin B6. After 2 week, responders defined as no spasm and no hypsarrhythmia on a 6-hour video-EEG remained on the same treatment for 6 months. For non-responders ACTH 150 IU/m2 was added with a slow taper over a 12-week course. Additional EEGs were performed at 4 and 24 week. Children who failed ACTH after 2 week were put on high-dose topiramate.

Results: 45 out of 69 children had a favorable outcome on vigabatrin at 2 week, for a 65% success rate. 5/5 with tuberous sclerosis, 4/4 children with cortical dysplasia, 2/2 with periventricular leukomalacia, 2/2 with meningoencephalitis, 2/3 with trisomy 21, 2/4 with metabolic disorders, 1/1 with schizencephaly, and 1/1 with shaken baby syndrome responded. For the cryptogenic spasms, 21/28 showed a complete response (75%) at 2 week, 2 had persistent hypsarrhythmia at 2 week, two had recurrences of spasms on vigabatrin and 5 showed no response. In total, 5 patients had a recurrence of spasms on vigabatrin. More importantly, certain etiologies were more likely to be refractory including 3/3 with neonatal strokes, 5/7 with diffuse atrophy, 4/6 with severe HIE, and 1/1 with NF1. Of the 29 who received ACTH, 23 responded within 2 week for a 80% response rate to refractory spasms. This included 3 out of the 5 with severe HIE that failed vigabatrin. The other 4 who failed ACTH included a child with trisomy 21, one with recurrent spasms due to meningoencephalitis, one child with recurrent cryptogenic spasms, and one with atrophy who developed hemispasms on ACTH that responded to topiramate. No responder at the end of the 12-week regimen recurred after. At 6 months, only 4 of 63 patients (6%) had persistent spasms and 12 (19%) had partial epilepsy. In addition to 4 deaths due to the underlying etiology, two patients are excluded from the 6-month analysis because they did not want to continue the add-on treatment as they were seizure free. Adverse events were reported in 12/69 children with vigabatrin. No child required to stop treatment. While 19 out of 29 ACTH patient had adverse events with 3 children having to stop ACTH with no recurrence of spasms.

Conclusions: In our population in light of this new prospective data, vigabatrin remains the first choice medication for infantile spasms with the possible exception of children with severe neonatal vascular insults. A two-week delay does not appear to reduce the efficacy of ACTH.

Supported by grants from CIHR and CURE

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Emily T. Klatte 1 , J. M. Paolicchi 2,1 , S. L. Hart 1 , S. Standridge 2 , D. Terry 2,1 and M. Karn 2 ( 1 Neurology, Ohio State University Medical Center, Columbus, OH and 2 Neurology, Columbus Children's Hospital, Columbus, OH )

Rationale: Children with BRE traditionally have a good prognosis with seizure resolution by adolescence. Newer data have shown that children with BRE have cognitive and behavioral problems [1]. This study examines the effects of levetiracetam (LEV) on the neuropsychiatric manifestations and overall quality of life in children with BRE. A secondary outcome measure is seizure frequency.

Methods: Children from 3–13 yrs. with BRE and ≥3 lifetime seizures are being recruited from our epilepsy program, starting 12/05. Informed consent and assent were obtained at enrollment. Subjects were followed for 12 months which included: initial screening visit, 6 week telephone follow-up, routine clinic visits at 3, 6, 9, and 12 months. LEV (20 mg/kg/day) was started at the initial visit and maintained. The dose was increased 10 mg/kg/day if a breakthrough seizure occurred more than one month since prior dosage change. The WISC-IV or WPPSI-III (<7 yrs) was administered at the initial and 12 month clinic visits. The QOLCE parental survey was administered at initial visit, 6 and 12 mos. Scores were calculated using a weighted combination of subscale scores. Seizure diary was reviewed at each visit.

Results: Currently, 7 subjects have enrolled, 2 have completed, and 0 have withdrawn. Five (71%) are male. Mean age at enrollment is 8.9 yrs (range 4–12). 3 patients (43%) had comorbidities: allergies, headache, and irritable bowel syndrome. 5 subjects (71%) had below average performance on WISC-IV or WPPSI-III subscales (some > 1): working memory (3, 43%), verbal comprehension (3, 43%), processing speed (2, 29%), perceptual reasoning (1, 14%), and full scale IQ (1, 14%). Of the two subjects who have completed the study, 1 improved in 3 parameters and FSIQ scores. The other was unable to complete the WISC-IV (behavior and attention problems). All subjects' parents rated the initial QOLCE “very good,” as did the 2 completed subjects. 4 patients had additional seizures during the first 6 week through 3 months of the study (average 3, range 2–4). LEV was increased once in 1 subject, and twice in 3 subjects resulting in seizure control. No adverse effects have been reported.

Conclusions: Although ongoing, our data suggests that BRE is “benign”: 100% of subjects noted their quality of life as “very good.” Our data also reinforces that this may represent a surface perception. The majority (71%) demonstrated neuropsychiatric deficits predominantly in working memory, verbal comprehension, and processing speed. LEV treatment was well tolerated. Additional study with larger patient numbers may further refine these findings.

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    Klatte E, Paolicchi J, Hart S, Terry D. Cognition and Behavior in a Demographic Survey of BRE. Abstract, AES 2006. Publication pending.

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Dale C. Hesdorffer 1,2 , S. Shinnar 3 , J. M. Pellock 4 , D. R. Nordli 5 , C. O'Dell 3 , D. V. Lewis 6 , L. M. Frank 7 and A. Marmarou 8 ( 1 G. H. Sergievsky Center, Columbia University, New York, NY ; 2 Epidemiology, Columbia University, New York, NY ; 3 Pediatric Neurology, Albert Einstein College of Medicine, Bronx, NY ; 4 Pediatric Neurology, Virginia Commonwealth University, Richmond, VA ; 5 Pediatric Neurology, Northwestern University, Chicago, IL ; 6 Pediatric Neurology, Duke University Medical Center, Durham, NC ; 7 Pediatric Neurology, Eastern Virginia Medical School, Norfolk, VA ; 8 Neurosurgery, Virginia Commonwealth University, Richmond, VA and 9 FEBSTAT, Study Team, Bronx, NY )

Rationale: Studies of phenomenology of first febrile seizure (FS) suggest that agreement is poor for the presence of focality (1). No prior study has examined agreement for duration of seizure in minutes and none has modeled the distribution of duration.

Methods: We analyzed a subset from a prospective study of children with first FS ascertained as part of the Columbia University Febrile Seizure study. This subset forms the control group for the FEBSTAT study. At identification, parents were questioned about the FS phenomenology and emergency department records were reviewed. Consensus, using these sources, was performed by three epileptologists as part of the FEBSTAT study. Agreement for FS semiology was assessed by the kappa statistic and by the intraclass correlation coefficient (ICC) for FS duration. The distribution of seizure duration was further modeled.

Results: Among 142 children with first FS, seizures lasted a median of 4.0 minutes (IQR = 2–8). Seizures were complex in 35.0%. Among the complex FS, 20.1% were focal, 10.6% were repeated, 15.1% were 15 minutes or longer and 7.8% met criteria for status epilepticus. Agreement on features of the febrile seizure was excellent (Table) for the comparison of each epileptologist to the final consensus. The ICC was 0.86 for seizure duration in minutes, indicating excellent agreement across reviewers. The distribution of FS duration was best fit by the sum of two exponentials [F(t) = 0.78e−t/3.0 + 0.22 e−t/21.3]. This suggests that are two distinct patient populations: one accounting for 78% of FS with mean seizure duration of 3 minutes and the other accounting for 22% of FS with mean seizure duration of 21.3 minutes.

Conclusions: Agreement was excellent for focality and duration and was better than when the same epileptologists rated focality and duration in febrile status epilepticus (2). The distribution of duration of FS is remarkably similar to that reported in children with first unprovoked seizures (3). This suggests that more than one-fifth of children with febrile and afebrile seizures have a predisposition to prolonged seizures.

Supported by grants NS 43209 from NINDS and by HD 36867 from NICHD.

References:

1. Berg AT, Steinschneider M, Kang H, Shinnar S. Classification of complex features of febrile seizures: Inter-rater agreement. Epilepsia 1992; 33:661–666.

2. Shinnar S, Hesdorffer DC, Nordli DR, Pellock JM, O'Dell C, Lewis DV, Frank LM, Moshe SL, Marmarou A, and FEBSTAT Study Team. Phenomenology of Prolonged Febrile Seizures: Preliminary Results of the FEBSTAT Study. Epilepsia 2006;47(Suppl 4);15.

3. Shinnar S, Berg AT, Moshe SL, Shinnar R. How long do new-onset seizures in children last? Ann Neurol 2001;49:659–664.

Reliability of phenomenology consensus in first febrile seizure (N = 142)

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Kay Taylor 1 and R. G. Davis 1 ( 1 Pediatric Neurology-PA, Orlando, FL )

Rationale: Lamotrigine is indicated in the treatment of generalized and complex partial seizures in the pediatric and adult population. Lamotrigine has been reported in the past to cause exacerbation of myoclonic epilepsy. Review of the literature did not report exacerbation of any other seizure types. However we report four pediatric patients with both clinical and electrographic exacerbation of non-myoclonic generalized and complex partial seizure activity with Lamotrigine.

Methods: The patients were ages 6 months to 10 years old. Two patients were diagnosed with complex partial seizure activity (right central sharps and multifocal spike waves) and the other two with generalized spike and wave activity (high amplitude spike/polyspike wave and polyspike wave of non-absence type) (Figure 1). Three of the patients were started on Lamotrigine as monotherapy, the 4th was on Keppra, Trileptal, Zonegran, Valium and Klonopin before the Lamotrigine was introduced. As their Lamotrigine dose was titrated upward, they all experienced an increase in clinical seizure activity as well as a corresponding increase in electrographic changes. (Figure 2). The titrating doses ranged from 3.5 mg/kg to 7 mg/kg. The increase in seizures occurred as soon as 2 months after the Lamotrigine was started. Three of the patients were weaned off the Lamotrigine and started on another AED. The seizure activity and electrographic changes decreased. The fourth patient improved after the Lamotrigine dose was titrated down by 3 mg/kg.

Results: The exacerbation of non-myoclonic epilepsy with Lamotrigine has had limited reporting. Two studies, one in Italy, Neurology, July 2004, reported a paradoxical reaction to Lamotrigine in a patient with idiopathic rolandic epilepsy, and an UK study, Seizure, April 1997, reported a 24% increase in seizures of patients with learning disabilities and epilepsy on Lamotrigine.

Conclusions: What is also unclear is if the exacerbation of seizures is more likely with Lamotrigine monotherapy versus adjunctive therapy. Further studies to correlate this occurrence would be indicated.

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Sajun Chung 1 ( 1 Pediatric neurology, Kyunghee University Hospital, Seoul 130–702, South Korea )

Rationale: To investigate the differences of clinical characteristics between patients with ADEM associated with seizures or without seizures at the time of the first presentation.

Methods: Medical records and MRI of 31 ADEM patients (male 18, female 13) were reviewed retrospectively. The patients were classified into 2 groups: 16 (51.6%) with seizure as a Group 1(G-1), and 15 (48.4%) without seizures as a Group 2 (G-2).

Mean age was 6.2 years (range: 1.6 to 15) and mean follow up period was 3.8 years (range: 1 to 6).

The following parameters were studied: the antecedent events, the neurological manifestations, the CSF findings, the EEG findings, the lesion sites of involvement in MRI, and the outcome.

Results: 1. There was “no defined prodrome” in 8 (50.0%)out of 16 and 6 (40.4%)out of 15, the URI symptoms in 2 (12.5%) and 4 (26.7%), the nonspecific febrile illness in 3 (18.8%) and 2 (13.3%), the gastrointestinal disturbance in 3 (18.8%) and 2 (13.3%) as the antecedent events in the G-1 and G-2, one (6.7%) in the G-2 (6.7%) showed vaccination history. There were no significant differences in the antecedent events between two groups.

2. There were the hemiparesis in 10 (62.5%) and 4 (26.7%), the altered consciousness in 6 (37.5%) and 6 (40.0%), the ataxia in 5 (31.3%) and 4 (26.7%), the visual disturbance 3 (18.8%) and 1 (6.7%) and the facial nerve palsy 2 (12.5%) and 1(6.7%) as the presenting symptoms in the G-1 and G-2. There were significant differences in frequency of the hemiparesis and the visual disturbance between the two groups (P < 0.05).

3. There were the CSF pleocytosis in 5 out of 16 (31.3%) and 3 out of 15 (20.0%), and the elevated protein in 2 (12.5%) and 3 (20.0%) in the G-1 and G-2. There was no significance between the two groups.

4. The EEG abnormalities were observed in 7 out of 16 (43.8%) and 2 out of 15 (13.3%) in the G-1 and G-2. There was a significant difference in the EEG abnormalities (P < 0.05).

5. There were the involvements of the multi- or unifocal lesions only in the cerebral white matter (WM) in 10 of 16 (62.5%) and 13(86.7%) in the G-1 and G-2, and the involvements of the gray matter (GM) with or without WM in 6 (37.5%) and 2 (13.3%) in the G-1 and G-2. In the G-1, there was more involvement of the GM than the G-2 (P < 0.05).

6. Out of 31 patients, 11 (68.6%) and 14 (86.7%) in the G-1 and G-2 made a complete recovery. There were the intractable seizures in 3 (18.8%) in the G-1, and the motor disturbance in 3 (18.6%) and 1 (6.7%) in the G-1 and G-2. There was higher rate of the complete recovery in the G-2 than G-1 (P < 0.05).

Conclusions: In ADEM with seizures, the hemiparesis and the visual disturbance as the presenting symptoms, the EEG abnormalities, the involvement of the GM, and the motor disturbance in outcome were more common than ADEM without seizures. Conclusively, the seizures may help to determine the prognosis of the ADEM patients.

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Yu-tze Ng 1 and M. M. Troester 1 ( 1 Division of Child Neurology, Barrow Neurological Institute, Phoenix, AZ )

Rationale: Klonopin® wafers (clonazepam orally disintegrating tablets) are a benzodiazepine with anticonvulsive and anxiolytic effects. Its precise mechanism is unknown although it is believed to enhance the activity of gamma aminobutyric acid (GABA). Our institution has been prescribing clonazepam wafers for the acute treatment of prolonged (more than 5 minutes) seizures for several years. Depending on the size of the patient, they were prescribed: 0.25 mg, 0.5 mg, 1.0 mg or 2.0 mg wafers. We proceeded to obtain evidence for the efficacy of this practice.

Methods: Hospital Institutional Review Board (IRB) approval was obtained for an anonymous patient survey. All children (less than 21 years of age) who had been prescribed clonazepam wafers over a six year period at our institution were mailed a detailed questionnaire (in English and Spanish). After five week, data from the returned questionnaires was collected and analyzed.

Results: Three hundred and eighty-one questionnaires were mailed. There were 79 replies. Thirty-one were excluded as the surveys reported the patient had never been prescribed clonazepam, were prescribed clonazepam for reason other than seizure, had yet to use it for prolonged seizures or their answers were ambiguous. Data was collected from the remaining 48 patients. Their average age was 9.5 (range = 2–23) years. There were 26 males. Only four patients did not have a history of developmental impairment and/or cerebral palsy. Efficacy was defined as clonazepam stopping the seizures within 10 minutes, >50% of the time. Thirty-six of the 48 (75%) patients met this criterion. From these 36 patients, 16 (44%) had their seizures stopped within one minute, 12 (33%) between 1–5 minutes and eight (22%) between 1–10 minutes. Overall the results were comparable to Diastat® (rectal diazepam) amongst the patients who had been treated with both.

Conclusions: Clonazepam wafers are an effective acute therapy for prolonged seizures. We believe that in cases of inefficacy, many of these patients were probably prescribed an insufficient dose. The relative ease of administration of this treatment may make it a viable, less expensive option than Diastat®. Further, prospective, randomized studies are planned.

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Ulrich Brandl 1 , G. Kurlemann 2 , B. Neubauer 3 , K. Rettig 6 , A. Schreiner 4 and B. Schäuble 5 ( 1 University Hospital, Division of Neuropediatrics, Jena, Germany ; 2 Division of Neuropediatrics, University Hospital, Muenster, Germany ; 3 Division of Neuropediatrics, University Hospital, Giessen, Germany ; 4 Medical and Scientific Affairs, Janssen Cilag EMEA, Neuss, Germany ; 5 Medical and Scientific Affairs, Janssen Cilag, Neuss, Germany and 6 G.E.M., Neuss, Germany )

Rationale: To explore seizure outcomes and cognitive function in children with epilepsy treated with topiramate

Methods: Open label, non-interventional multicenter trial(TOPMAT-EPP-401) in children age 6–16 with epilepsy and treatment with flexible dose TPM for 12 week. Kaufman-ABC, digit symbol test (HAWIK-3), verbal learning memory test (VLMT), tolerability, sick days, and CGI were recorded. Seizure frequency was compared to a 12 week retrospective baseline. The two sided asymptotic Mann-Whitney-U-Test was applied to test for between group differences and the two sided asymptotic Wilcoxon test to test for pre-post changes within samples (no corrections for multiple testing).

Results: 54 patients (52% male; median age 11 yrs (range, 6–17) were documented. Mean duration of epilepsy was 32 months (SD ± 40 months). 78% completed the study. Main reasons for discontinuation: AE(9%), insufficient efficacy (11%). 48% had a primary generalized, 43% with partial epilepsy. 72% used TPM in add-on therapy at beginning. 60% patients were on TPM monotherapy during the last 6 week in the study. At study end, maximum dose TPM was 3.5 mg/kg/day (age 6–12) and 2.49 mg/kg/day (>12). Seizure frequency (± SD) improved from 46.10 ± 112.82 to 28.78 ± 87.22 (p = 0.003). 56% had > = 50% seizure reduction and 35% became seizure free. K-ABC, VLMT and digit symbol test was tested at baseline and endpoint. Following groups were defined: AED naïve patients with initial monotherapy who remained on monotherapy (group 1: n = 14), patients converting from add-on to monotherapy (group 3: n = 18), patient with a baseline AED remaining on add-on therapy (group 4: n = 21). A single patient had initial TPM monotherapy and a second AED was added during the study (group 2: n = 1). In pairwise comparisons between group 1, 3 and 4, there were no significant differences between groups as well as in the pre-post comparisons within groups on the Kaufman-ABC. VLMT test results showed neither significant within- group pre-post changes nor significant between group differences in the pre-post changes (p > 0.05) beside of one spurious result in the perseveration error score in group 4. The digit symbol test did not reveal differences between the groups at first and last visit; however when comparing pre-post differences, group 1 scored significantly better than group 4, group 4 worsened (p < 0.05). Number of sick days decreased from 2.49 ± 6.79 to 0.28 ± 0.98 during the last 12 week of the study (p < 0.05). 33 AEs were at least possibly related to TPM. AE > = 5% were paresthesias (7% of patients), fatigue (7%), decreased appetite (6%), speech and language disorder (7%), and mental state problems NOS (6%). One patient was hospitalized due to vomiting with causal relationship to TPM.

Conclusions: The findings suggest that topiramate is associated with a reduction in seizure frequency in children and adolescents with epilepsy. A high number of seizure free patients was achieved, number of sick days decreased significantly. In addition, there was no significant change in cognitive function as measured by VLMT and digit symbol test at the described doses.

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Michelle E. Hartley-McAndrew 1 and A. Weinstock 1 ( 1 Department of Neurology, Women and Children's Hospital of Buffalo, Buffalo, NY )

Rationale: An increased prevalence of epilepsy and abnormal EEG's in autistic children has been described. Epileptiform EEG abnormalities are present in 10.3–72.4% of patients and interictal EEG abnormalities in 6.1–31%. The relationship between epilepsy, epileptiform discharges without clinical seizures and cognitive language and behavioral symptoms is poorly understood. It is hypothesized that epileptiform activity is associated with adverse cognitive manifestations in children with ASD. Since difficulties with socialization, and maladaptive behaviors are often found in autistic children, we inquire whether the presence of these behaviors indicates an underlying cerebral irritability or abnormal structural network that gives rise to epileptiform discharges.

Methods: The EEG database at the Women and Children's Hospital of Buffalo was reviewed, and out of 22,715 EEGs performed between 1999–2006, 123 were children with ASD. EEG abnormalities were found in 39 (31%). A control group of age and gender matched patients with normal EEGs was also obtained. Inclusion criteria: primary ASD, age above 4 years. Exclusion criteria: any concomitant disorder which would account for the autistic features. Packets mailed to families included 1) the Vineland Adaptive Behavior Scale II, 2) the Aberrant Behavior Checklist. On follow up telephone interview, the Childhood Autism Rating Scale (CARS) was administered to confirm diagnosis of ASD. Of 21 packets received, 11 had normal EEGs and 10 were abnormal.

Results: There were no statistically significant differences in behavior when comparing normal to abnormal EEG findings. However, children with ASD and seizures had statistically significant lower scores in Daily living (p = 0.009) and Socialization (p = 0.007) than children without seizures. ASD children with seizures also had higher levels of hyperactivity and irritability compared to ASD children without seizures. Differences in irritability scores nearly reached statistical significance (p = 0.058). In the statistical analysis, there was no significant difference in the degree of autism between the groups.

Conclusions: Lack of statistically significant differences in behaviors when comparing normal to abnormal EEG findings may be due to the small sample size and possible parental bias. The presence of the significant findings of lower daily living, socialization scores, higher hyperactivity, irritability scores in patients with ASD and seizures could possibly be due to the impairment of quality of life and cognitive impairment that seizures have induced in the ASD population. Perhaps the increased level of neuronal irritability which causes the manifestation of the seizures is the same as that which causes the behaviors.

This may lead to the conclusion that seizures (and not the EEG abnormalities that are found) are interconnected to the neurological disorder which causes certain behaviors. Clinically this may aid physicians in when to use EEG as a screening tool in children with ASD.

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Rebecca Schultz 1,2 and A. Wilfong 1,2 ( 1 Baylor College of Medicine, Houston, TX and 2 Texas Children's Hospital, Houston, TX )

Rationale: Patients with myoclonic astatic epilepsy (MAE) typically have medically refractory epilepsy. This chart review study investigates the efficacy of vagus nerve stimulation (VNS) in the treatment of MAE.

Methods: We retrospectively reviewed the medical records of children with MAE who received VNS for at least 12 months. The following clinical features were assessed: age of onset of epilepsy, seizure type and frequency, number of previous antiepileptic medications (AEDs), age at VNS implant, number of AEDs at implant, and response to treatment.

Results: Four children (3 boys, 1 girl) were followed for 12 months after VNS implantation. The median age at onset of epilepsy was 26 months (range 9–72 months). The median age at implantation of VNS was 5.3 years (range 4.2–8.4 years). The median number of previous AEDs was 5.5 (range 5–8). Current antiepileptic medications included Valproate (3/4), Felbamate (1/4), Zonisamide (1/4), Levetiracetam (1/4), Clonazepam (1/4). Three children were on 2 AEDs and 1 child was on 3 AEDs at the time of VNS implant. Seizure types and frequency per month at baseline were as follows: atypical absence - 3 patients had too many to count (TMTC), and 1 was controlled on Valproate; atonic- 1 patient with 8, 1 with 60, 1 with TMTC, and 1 controlled on Levetiracetam; myoclonic- 1 patient with 0, and 3 with TMTC; and GTCs - 1 with 1, 1 with 90, 1 with 4, and 1 with 0. After 3 months of VNS therapy, 2 patients had no change in seizure frequency or type; data was missing for 1 patient. The patient who had only myoclonic seizures had a ≥90% reduction in seizures. After 12 months of VNS therapy there was a ≥90% reduction in atypical absence and myoclonic seizures in three patients, a 100% reduction in atonic seizures in three patients, a ≥90% reduction in GTCs in 2 patients and 100% reduction in GTCs in one patient. All four patients reduced their AED dosages during this study period; no new AEDs were added. All patients tolerated VNS without adverse effects.

Conclusions: Three patients with MAE with refractory seizures had a total cessation of atonic seizures and a ≥90% reduction in atypical absence and myoclonic seizures 12 months after VNS implantation. Furthermore, VNS was effective in reducing GTCs by at least 90%. These results suggest that VNS therapy is effective in this refractory syndrome. Further study of VNS in the treatment of MAE is warranted.

(Funded by Department of Pediatrics, Section of Child Neurology, Baylor College of Medicine, Houston, TX)

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Kathy N. Speechley 1,5 , S. D. Levin 1 , S. Wiebe 2 , M. L. Smith 3 , C. S. Camfield 4 and G. Zou 5 ( 1 Paediatrics, University of Western Ontario, London, ON, Canada ; 2 Department of Clinical Neuroscience, The University of Calgary, Calgary, AB, Canada ; 3 Psychology, The University of Toronto, Toronto, ON, Canada ; 4 Child Neurology, IWK Health Centre, Halifax, NS, Canada and 5 Epidemiology and Biostatistics, The University of Western Ontario, London, ON, Canada )

Rationale: Understanding why some children experience compromised health-related quality of life (HRQL) over the course of epilepsy while others do not is essential to establishing appropriately timed and directed interventions to optimize HRQL. The Health-related Quality of Life in Childhood Epilepsy Study (HERQULES) was designed to: i) describe the course of HRQL during the first 2 years after diagnosis with epilepsy in children aged 4–12 years and ii) prospectively assess child and family determinants of HRQL, guided by a conceptual model of family adaptation. This presentation will describe the design and methodology of this national, prospective cohort study and provide some preliminary baseline results.

Methods: Pediatric neurologists across Canada (n = 52) initially approached parents of eligible children newly diagnosed with epilepsy and continue to provide clinical information at each data point. Parents of 446 children (97% of those eligible) agreed to participate by completing 4 mailed questionnaires: Time 1 (T1) shortly after child's diagnosis, and 6 (T2), 12 (T3) and 24 months (T4) later to provide information regarding family socio-demographic characteristics, life stressors, family adaptation, parent's mental health status and coping responses, parent's perception of their child's epilepsy care and the child's HRQL. Study accrual is complete and 376 T1 questionnaires have been returned to date; follow-up is ongoing with 285 questionnaires returned for T2, 210 for T3 and 123 for T4. HRQL was assessed using the Quality of Life in Children with Epilepsy Questionnaire (QOLCE) and the Child Health Questionnaire (CHQ). Both assess several separate domains of HRQL with scores ranging from 0 (low functioning) to100 (high functioning).

Results: Response rate for parents at T1 is 82%. The preliminary sample of 341 children aged 4–12 years (mean = 7.3 years; SD = 2.4) of which 53% are boys, is clinically diverse with 42% experiencing generalized and 58% partial seizures. Overall severity of epilepsy as rated by the neurologists ranges from not at all severe (20%) to very/quite/extremely severe (5%). QOLCE scores on its 16 subscales ranged from a mean of 45.95 (SD = 9.63) for Energy/Fatigue to 80.37 (SD-24.49) for Social Integration. The mean CHQ summary scores were 48.26 (SD = 11.16) for Physical Health and 44.62 (SD = 10.79) for Psychosocial Health.

Conclusions: HERQULES has successfully collected comprehensive data for a large, clinically diverse sample of children with newly diagnosed epilepsy. The study achieved a high initial response rate for both the pediatric neurologists and parents of eligible children from across Canada and is maintaining a high retention rate. The comprehensive information collected during the 2 years following onset of epilepsy on clinical, child and family characteristics will enable us to determine the relative importance of individual risk and protective factors and assess possible interactions among factors.

(Funded by Canadian Institutes of Health Research Grant (MOP-117493) to Speechley et al.)

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Axel Rohr 1 , J. Jacobs 3,2 , F. Moeller 2 , R. Boor 2 , E. Kobayashi 3 , J. Gotman 3 and M. Siniatchkin 2 ( 1 Department of Neuroradiology, University of Schleswig-Holstein, Kiel, Germany ; 2 Department of Neruopediatrics, University of Schleswig-Holstein, Kiel, Germany and 3 EEG-Department, Montreal Neurological Institute, Montreal, QC, Canada )

Rationale: Ninety percent of patients with TSC have epilepsy and seizures commonly start in early childhood. Seizures are often medically refractory and closely linked with mental retardation and behavioural abnormalities. Identification of epileptogenic areas can be difficult, as multiple tubers and extensive networks are involved ictally and interictally. Simultaneous recording of EEG and functional MRI (fMRI) is a non-invasive tool to evaluate such epileptogenic networks. In this study, EEG-fMRI is used for the first time to delineate the irritative zone in children with TSC.

Methods: Five children with focal epilepsy were evaluated; all were diagnosed with TSC based on clinical criteria and genetic testing. Scanning consisted of 20 minutes EEG-fMRI at 3T under sedative induced sleep. EEG was recorded from 30 scalp sites using an MRI compatible cap. EEG was filtered and spikes were identified according to spatial distribution and morphology. Each spike type was analyzed as a seperate event of a single general linear model, constituting a separate EEG-fMRI study. Spike timings were used for an event-related analysis. Tubers, subependymal nodules and subependymal giant-cell astrocytomas were marked by a neuroradiologist on MRI, based on T1, T2 and FLAIR images. Positive and negative BOLD (Blood Oxygenation Level-Dependent)responses were analyzed relative to the lesions and EEG focus.

Results: One patient was scanned twice and 4 patients showed more than one spike type, which resulted in 13 studies. A BOLD response was observed 12/13 studies (93.3%) and in all more than one tuber was involved. Ten studies showed activations as well as deactivations and two studies showed only deactivations. Lesional activations were seen in 6/13 studies (46.2%). In 4 studies activation extended to perilesional areas and one study showed exclusively perilesional activation. Eight studies showed lesional deactivations (61.5%), with 4 extending to perilesional areas. Deactivations limited to perilesional areas were seen in 6 studies (64.1%). In all patients at least one tuber in the lobe of interictal spike generation, and presumed seizure onset (according to telemetry), showed a BOLD response. In all studies the observed changes were multifocal and sometimes tubers distant from the spike field were involved.

Conclusions: In all children with TSC BOLD responses involving several tubers were observed during interictal spike generation. Although BOLD responses were limited to parts of the lesion in all tubers, extension beyond tuber boundaries and even exclusive involvement of perilesional areas was noted. All together these findings suggest a large epileptogenic network in patients with TSC. This network extends the one described in PET and SPECT studies, which often suggest only one or a few tubers to show intrinsic epileptogenicity. Nevertheless it confirms results from MEG and neurocognitive studies finding widespread brain changes in patients with TSC. This has to be kept in mind when planning surgical intervention in these patients.

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Hideo Yamanouchi 1 , G. Imataka 1 , M. Negishi 1 , R. Kuribayashi 1 , Y. Watabe 1 and O. Arisaka 1 ( 1 Pediatrics, Dokkyo Medical University, Tochigi, Japan )

Rationale: Tau protein, one of the microtubule-associated proteins, plays an important role in assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Tau protein in CSF as a marker for neuronal/axonal damage and degenerations has already been studied in several neurological disorders such as Alzheimer's disease, stroke, Creutzfeldt-Jacob disease, amyotrophic lateral sclerosis, and multiple sclerosis. However, little has been known about tau protein changes in epileptic conditions. In this study, we measure the tau protein in CSF to determine whether it could be useful to monitor the neuronal damage in convulsive status epilepticus in childhood.

Methods: Two clinical categories exhibiting febrile convulsive status epilepticus were highlighted in this study. One was “febrile convulsion status (FC status)”, and the other was “acute infantile encephalopathy predominantly affecting the frontal lobes (AIEF)”. The former is defined in here as febrile convulsion lasting for over 30 minutes, having the recovery of consciousness within 24 hours and no subsequent neurological sequelae. The latter category is recently described acute encephalopathy syndrome, characterized by the neurological manifestations suggesting frontal lobe dysfunctions and the radiological features showing selective involvement of the cerebral cortex predominantly distributed in the frontal lobes (Yamanouchi H and Mizuguchi M. Epilepsy Res 2006). Lumber CSF samples were colleted from 15 patients with FC status and 7 patients with AIEF. Tau level was measured using and ELISA kit, Fino Scholar hTAU (Innogenetics, Ghent, Belgium). For statistical analysis, Mann-Whitney test was used to investigate differences between groups.

Results: In FC status, the median and mean values of tau protein were 178 and178 pg/ml in CSF samples taken within 24 hrs (n = 11), 233 and 314 pg/ml between 24–48 hrs (n = 3) after the status. The tau protein levels between these two groups are statistically significant (p < 0.05). The values of the CSF sample taken between 48–72 hrs (n = 1) in one patient with FC status were 470 and 470 pg/ml. In contrast, the median and mean values of tau protein in CSF of patients with AIEF were markedly elevated; 736 and 1,628 pg/ml within 24 hrs (n = 3), 1,160 and 2,865 pg/ml between 24–48 hrs (n = 3) after the status. In the extremely severe case of AIEF, tau protein in CSF at the 6 day after the status was elevated up to 56,100 pg/ml. Tau levels in CSF taken within 24 hrs from patients with AIEF was higher than those from patients with FC status (p < 0.01).

Conclusions: According to this preliminary study, it could be suggested as following: 1) Tau protein level in CSF increase with the course of time after the febrile convulsive status epilepticus, 2) Tau protein level in CSF of patients with AIEF is markedly elevated even at the early period after the onset. (Supported by grants from NCNP, Ministry of Health, Labor and Welfare, Japan)

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Zachary S. Daniels 1 , T. Nick 2 , C. Liu 2 , A. Cassedy 2 and T. Glauser 1 ( 1 Neurology, Cincinnati Children's Hospital, Cincinnati, OH and 2 Center for Epidemiology and Biostatistics, Cincinnati Children's Hospital, Cincinnati, OH )

Rationale: Obesity is a nationwide epidemic affecting all ages. No pediatric studies have identified how frequently obesity occurs in children and adolescents with new onset epilepsy prior to treatment administration. The recognition of obesity prior to initiation of AED therapy can have significant impact on drug selection due to the positive and negative weight effects of some commonly used AEDs. This study aimed to determine the frequency of obesity in a cohort of children and adolescents with newly diagnosed untreated epilepsy.

Methods: A consecutive cohort of 251 patients (2–18 years of age) with newly diagnosed untreated epilepsy was identified from the New Onset Seizure clinic at Cincinnati Children's Hospital. Weight, height, and concomitant medications were recorded at the time of each patient's first visit. Body Mass Index Z-scores and percentiles adjusted for age were used as a measure for obesity. Anthropometric status was determined using a SAS program based on standard CDC growth charts (2000). Epilepsy patients' body mass index z-scores (BMIZ) were compared to CDC data using a 1-sample t-test. A secondary analysis examined the prevalence estimates of overweight and obesity in the general pediatric population from the NHANES III data set (a multistage probability sample of U.S. civilians) and compared this sample to the cohort of epilepsy patients. The SURVEYREG procedure in SAS was used to account for the complex sampling design of NHANES. To determine the relationship between BMI Z-scores and potential covariates, a series of analysis of variance (ANOVA) and analysis of covariance (ANCOVA) were conducted. Covariates not reaching a P-value of 0.50 were excluded from a subsequent multivariable analysis. Potential covariates included in the ANCOVA were age, etiology (cryptogenic, idiopathic, and symptomatic), seizure type (general, partial, unclear), concomitant medications (stimulants, non-stimulants, none), and insurance status (Private, Medicaid).

Results: There was a statistically significant difference in means BMI Z-scores between the epilepsy and CDC cohorts (P < 0.0001). Thirty nine% of children had BMI percentile for age > 85th% and 20% were > 95th%. The mean Z-score of the NHANES III cohort was not statistically different than the mean Z-score of the epilepsy cohort (P = 0.45). In unadjusted analyses, concomitant medications and etiology were significantly associated with BMI Z-score (all P < 0.05). Adjusted, ANCOVA revealed three significant predictors which included age, etiology, and concomitant medications (all P < 0.05).

Conclusions: Obesity is a common pre-existing comorbidity in children with newly diagnosed untreated epilepsy. Patients with idiopathic/cryptogenic epilepsy or those not on stimulant medications are more likely to have higher BMI Z-scores than those patients with symptomatic epilepsy, or patients taking stimulant medication. Clinicians should calculate BMI scores and percentiles adjusting for age for every epilepsy patient prior to starting AED therapy, and incorporate it into their clinical decisions when selecting medication. (Source of funding: NIH NS044956)

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Matthew Frank 1 , G. L. Holmes 2 , A. Vuong 3 , S. Kerls 3 , A. Hammer 3 and J. A. Messenheimer 3 ( 1 Children's Hospital of the King's Daughters, Norfolk, VA ; 2 Dartmouth Hitchcock Medical Center, Lebanon, NH and 3 GSK, Research Triangle Park, NC )

Rationale: While previous studies have documented the efficacy of lamotrigine as monotherapy in typical childhood absence seizures, the studies did not examine whether pre-treatment characteristics of the children were predictive of response rate. The objective of this analysis was to compare characteristics of responders and non-responders to lamotrigine in children with newly diagnosed typical absence epilepsy.

Methods: Children ranging in age between 3–13 years meeting enrollment criteria (n = 54) as demonstrated by generalized spike-wave discharges (2.5–4.5 Hz) lasting > 3 seconds on a 1-hour electroencephalogram (EEG), underwent a 24-hour ambulatory EEG and then entered an Escalation Phase (≤20-weeks) during which the lamotrigine dose was titrated until seizures were controlled or maximum dose was reached. For this study, a patient was considered a responder if they had no absence seizures for two consecutive week as confirmed by hyperventilation for clinical signs and 1-hour EEG. Patients responding to treatment then underwent a repeat 24-hour EEG.

Results: Of the 54 patients evaluated, 30 (56%) were responders (seizure-free) while 24 (44%) did not achieve seizure freedom. There were no differences in mean age (responders 7.2 ± 2.6 years; non-responders 7.5 ± 2.9 years), baseline weekly seizure count (responders 6.0 ± 2.1 seizures; non-responders 6.1 ± 2.3 seizures), baseline seizure number on the pre-treatment 24-hour EEG (responders 57.8 ± 49.3 seizures; non-responders 63.7 ± 51.4 seizures), and baseline total seizure duration on the pre-treatment 24-hour EEG (responders 532.5 ± 436 seconds; non-responders 662.8 ± 467.8 seconds). There were no significant differences in responder rate between the young children (3–7 years, n = 24; 50% response rate) and older children (8–13 years, n = 25; 62% response rate).

Conclusions: Lamotrigine was effective in suppressing absence seizures in newly diagnosed patients. Age of seizure onset, frequency and duration of absence seizures as measured on the pre-treatment 24-hour EEG was similar in the responders and non-responders. In this large cohort of drug naïve patients with typical childhood absence seizures, the response rate to lamotrigine was not influenced by age of onset, seizure frequency or seizure duration.

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Ashutosh Raina 1 , G. Acsadi 1 and M. Koul 2 ( 1 Pediatric Neurology, Children's Hospital of Michigan, Detroit, MI and 2 Transgenomic Laboratories, Omaha, NE )

Rationale: Mutations in the alpha 1 subunit of the voltage gated sodium channel (SCN1) have been identified in generalized epilepsy with febrile seizure (plus additional symptoms-GEFS+) and severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome). SMEI is characterized initially by normal development and febrile seizures followed by multiple seizure types and slowing of psychomotor development. The EEG is usually normal in the first year of life, but later generalized spikes, spike-wave or polyspike discharges are observed. These seizures are often refractory to anticonvulsants.

Methods: We report a four-year old girl who, at six months of age, developed her first febrile convulsion with focal onset lasting 15–20 minutes. Subsequently, at 15 months, afebrile tonic-clonic and myoclonic seizures appeared. Etiologies including metabolic disorders and various types of progressive myoclonic epilepsy were excluded. The EEG showed frequent bilateral spike and wave, as well as polyspike and wave activity. Lamotrigine therapy resulted in an ataxic gait and no significant relief from seizures. Valproic acid treatment resulted in reasonable seizure control. As she grew older, she exhibited difficulty in social situations, lack of eye contact, and speech delay. Genetic testing for SCN1A revealed a novel heterozygous stop codon mutation (R701X) in exon 12.

Results: N/A

Conclusions: The majority of patients with Dravet syndrome have de novo mutations in SCN1A gene on chromosome 2q24, which may lead to either a loss of function or dominant gain of function of this subunit. A genotype-phenotype correlation has been implicated for differences in clinical variants of both GEFS+ and SMEI syndromes. This case further illustrates the clinical and genetic heterogeneity of the SCN1A mutation and the importance of early recognition of this condition for choosing the most appropriate therapy.

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Ilknur Erol 1 , F. Alehan 1 , T. Cemil 2 , N. Bayraktar 3 , E. Ögüs 4 and K. Tokel 5 ( 1 Department of Pediatrics, Pediatric Neurology Division, Baskent University Faculty of Medicine, 6. Cadde 72/3 Bahcelievler 06490, Turkey ; 2 Department of Pediatrics, Baskent University Faculty of Medicine, Adana, Turkey ; 3 Department of Biochemistry, Baskent University Faculty of Medicine, Ankara, Turkey ; 4 Department of Biostatistics, Baskent University Faculty of Medicine, Ankara, Turkey and 5 Department of Pediatrics, Pediatric Cardiology Division, Baskent University Faculty of Medicine, Ankara, Turkey )

Rationale: Sudden unexpected death in epilepsy (SUDEP) is an important cause of mortality in patients with epilepsy. Myocardial ischemia has been proposed as a possible cause of SUDEP, however, there is paucity of research performed in pediatric patients. We aimed to evaluate the presence of myocardial injury during convulsive seizures by determining serum concentrations of cardiac troponin I (cTnI) and CK-MB mass and plasma levels of Brain-Type Natriuretic Peptide (BNP).

Methods: Thirty-one children (20 boys, age range: 0,9–16 years; median: 4 ± 5,34 years) who were admitted to Baskent University Hospital with febrile or afebrile tonic-clonic seizures and 50 healthy children with similar age distribution were enrolled. Serum cTnI, CK-MB mass and BNP concentrations were analyzed 12 hours after the seizure and repeated 7 days thereafter in the patient group. cTnI, CK-MB mass and BNP concentrations were obtained once in the control group.

Results: Serum concentrations of cTnI 12 h (median : 0,02 ± 0.019 ng/mL) and 7 days after the seizure (median: 0,03 ± 0.034 ng/mL) were not significantly different. Serum concentration of CK-MB mass at the 12 th h (median: 2,90 ± 3.00 μg/L) was significantly higher than that of the 7 th day (median :1,90 ± 1.83 μg/L) (p < 0.05). Similarly, plasma concentration of BNP was significantly higher 12 h postictal (median: 16,90 ± 68,31 pg/mL) compared to 7 days postictal (median: 5,00 ± 8,89 pg/mL) (p < 0.001).

cTnI levels 12 h postictal and those in controls (median : 0.030 ± 0.038 ng/mL) were not signifantly different. Comparison of CK-MB mass and BNP levels at the 12 th h after the seizure and those in the control group (CK-MB; median: 1,80 ± 1,517 μg/L), (BNP; median : 5,00 ± 3,58 pg/mL) revealed increased CK-MB mass and BNP levels in children with seizures (p < 0.05 and p < 0.001, respectively).

Conclusions: Normal cTnI levels show that there is no evidence of overt myocardial necrosis in patients with convulsive seizures. However, markedly elevated BNP concentrations together with elevated CK-MB mass levels suggest subtle cardiac dysfunction associated with convulsions. Further large-scale studies are warranted for the explanation of post-seizure elevation of both BNP and CK-MB mass levels.

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Stewart Macleod 1 , M. Beirne 1 , B. Accomb 1 and R. E. Appleton 1 ( 1 Roald Dahl EEG dept., Royal Liverpool Children's Hospital, Liverpool, United Kingdom )

Rationale: Hypsarrhythmia is the characteristic EEG pattern associated with infantile spasms (West syndrome). It most commonly occurs between 4 and 12 months of age, but may rarely persist beyond, or even appear after the age of 12 months. This study describes those children with hypsarrhythmia after the age of 12 months.

Methods: Patients older than 12 months of age with a hypsarrhythmic EEG were identified from the EEG database of this institution. Patient's records from the previous 10 years were reviewed for clinical information including underlying aetiology, age of hypsarrythmia, seizure type(s), response to antiepileptic therapy and neuro-developmental outcome.

Results: Forty patients (21 male) were identified. In 28 (70%), hypsarrhythmia was identified before, and persisted after the age of 12 months. The mean age at identification of hypsarrhythmia onset was 0.54 months. Twenty two of the 28 patients had pre-existing and severe neurological impairment including perinatal hypoxic ischaemic encephalopathy, Rett syndrome (CDKL5 mutation) and Aicardi syndrome. No cause was identified in six patients.

In the remaining 12 patients, hypsarrhythmia was identified after the age of 12 months (mean, 47.7 and range, 15–96 months). Three patients continue to demonstrate hypsarrhythmia. All 12 patients had severe underlying neurological impairments.

Two of the 40 patients had not experienced infantile or epileptic spasms.

Conclusions: Rarely, hypsarrhythmia can occur after the age of 12 months. This study appeared to identify three groups; (1) patients with symptomatic West syndrome who continue to have a hypsarrhythmic EEG beyond 12 months of age; (2) patients with severe neurological impairment, but not necessarily infantile spasms, who develop hypsarrhythmia after the age of 12 months and (3) a smaller group with cryptogenic/presumed symptomatic West syndrome who have a hypsarrhythmic EEG and persisting spasms well beyond the first year of life.

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Tiziana Granata 1 , F. Ragona 1 , I. De Giorgi 1 , E. Freri 1 , S. Binelli 4 , E. Gennaro 3 , F. Zara 2 , M. Morbi 1 and S. Franceschetti 4 ( 1 Child Neurology, Fondazione Istituto Neurologico C.Besta, Milan, Italy ; 2 Muscular and Neurodegenerative Disease Unit, Institute Gaslini, University of Genova, Genova, Italy ; 3 Laboratory of Genetics, Ospedali Galliera, Genova, Italy and 4 Clinical Neurophysiology, Fondazione Istituto Nazionale Neurologico Besta, Milano, Italy )

Rationale: SMEI,or Dravet syndrome,is an epileptic encephalopathy, frequently resulting from a de novo mutation of the SCN1A gene. The seizures onset is in the first year of life, but diagnosis is often delay at the age of 2–3 years when the electroclinical picture is enriched by cognitive deterioration, myoclonus and ataxia.

Aims of our study were a)to identify the early electroclinical manifestations of SMEI that can prompt an early diagnosis, genetic investigation and targeted treatment b)to evaluate the cognitive outcome in relation with the epileptic phenotype.

Methods: The case series includes 22 patients (present age, 11 months-27 years) that met the diagnostic criteria of SMEI, according to the ILAE classification. The patients have been followed at our Institute for a mean period of 6 years (range 2 months-18 years). The follow-up included clinical and EEG examinations, as well as standardized cognitive evaluation. Alpha-subunit type A of voltage-gated sodium channel (SCN1A) mutational screening was performed by DHPLC and multiplex ligation probe amplification (MLPA)

Results: A positive family history for epilepsy and/or febrile convulsions was reported in 55% of cases. All the infants were normal before the onset of epilepsy. The mean age at the first seizure was 5.4 months (range 3–11 months). In 9 cases, the first symptom was an isolated focal, hemigeneralized or generalized clonic seizures, that occurred during a febrile illness in 4. In the 12 remaining patients the onset was marked by epileptic status, in the course of hyperthermia in 9. The first EEG was normal in all cases. During the second year of life, the disease course was characterized by recurrence of polymorphic, difficult to treat, seizures, that, in most cases were triggered by fever, bathing with hot water, and intermittent lights. At this age epileptic activity and/or EEG photosensitivity also appeared. From the second year of life a slowing or arrest of psychomotor development was evident in 20 patients, followed in 15 cases by the appearance of behaviour disorders. Cognitive skills and behaviour disorders usually worsened in the periods of higher seizure frequency. During the follow-up the neurologic examination revealed deficits in 14 patients, characterized by ataxia, pyramidal symptoms, and myoclonus.

The genetic analysis detected mutations of SCN1A gene in 16 cases, including a truncate mutation in 11 cases and a missense mutation in 5. In 3 patients genetic analysis is still ongoing.

Conclusions: A tentative diagnosis of SMEI may be proposed by the end of the first year of life in an infant presenting with febrile status, or recurrent focal seizures and normal EEG, particularly in presence of a positive family history. A definite diagnosis can be established during the second year based on the peculiar seizure-favouring factors, EEG photosensitivity and psychomotor slowing. The temporal correlation between the high frequency of seizures and the onset of neurologic and cognitive impairment support the role of epileptic activity in the final outcome.

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Hyun-sug Lee 1 , J. H. Seo 1 , J. S. Lee 1 , Y. M. Lee 1 and H. D. Kim 1 ( 1 Pediatrics, Pediatric Epilepsy Clinic, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, South Korea )

Rationale: To reavel the therapeutic outcomes in intractable Lennox-Gastaut syndrome (LGS) after application of advanced medical and surgical treatment modalities

Methods: Sixty-one intractable LGS patients refractory to 2 or more adequately chosen anti-epileptic drugs (AEDs) were reviewed to evaluate the anti-epileptic efficacy on various modes of medical and surgical treatments including further AED trial, steroid, ketogenic diet (KD), corpus callosotomy, respective surgery and VNS application

Results: All patients had single (atonic, generalized tonic, atypical absence, myoclonic, generalized tonic-clonic) or mixed types (n = 21, 34.4%) of generalized seizures. Three patients were accompanied by complex partial seizures. Cryptogenic group was 24 (39.3%). In symptomatic group (n = 37), variable etiologies were included such as malformation of cortical development (n = 17), destructive (n = 15), metabolic (n = 3), chromosomal anomaly (n = 1) and tuberous sclerosis (n = 1), respectively. Patients were treated by multiple modalities [further AED trial, steroid 5, ketogenic diet 37, surgery 31 (VNS 9, corpus callosotomy 14, resective surgery 16)]. In 61 cases of further AED trials, 8 (13.1%) patiens became seizure free, and 23 (37.7%) cases showed seizure reduction over 50%. In 37 cases on KD, 14 (42.4%) cases became seizure free, and 6 (18.2%) cases showed seizure reduction over 50%. In 14 cases of corpus callosotomy, 3 cases (21.4%) became seizure free. In 16 cases of resective surgery, 12 (75%) cases became seizure free. In 9 cases of VNS, 2 cases showed more than 50% of seizure reduction. In 5 cases of steroids, 2 cases became seizure free. In intractable LGS, overall seizure free outcome was 35 (57.4%) and seizure reduction over 50% was 53 (86.9%).

Conclusions: By the applications of advanced modalities of medical and surgical treatment actively, 57.4% of intractable LGS could achieve the seizure free outcome.

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Amy L. McGregor 1,2 , D. Clarke 1,2 , F. Perkins 1,2 and J. Wheless 1,2 ( 1 Pediatric Neurology, University of Tennessee Health Science Center, Memphis, TN and 2 LeBonheur Comprehensive Epilepsy Program, Memphis, TN )

Rationale: Typically, cerebral folate deficiency causes developmental delay and movement disorders. Approximately one-third of patients with cerebral folate deficiency develop epilepsy. The goal of this study was to review the clinical characteristics of epilepsy patients with cerebral folate deficiency.

Methods: The charts of patients with cerebral folate deficiency who were seen at our tertiary epilepsy center in the past two years were reviewed.

Results: Four patients with cerebral folate deficiency have been evaluated at our epilepsy center.

One patient presented with a well-controlled symptomatic partial seizure disorder of right hemisphere origin, encephalopathy characterized by pervasive developmental disorder, mild left upper extremity weakness, and scoliosis. In addition to cerebral folate deficiency, she was also found to have Rett syndrome by DNA testing.

Another patient presented with intractable partial seizures with secondary generalization, encephalopathy, and spastic quadriplegia. After being diagnosed with cerebral folate deficiency and treated with leucovorin, her seizure frequency improved.

One patient who was known to have cerebral folate deficiency was transferred from an outside hospital for epilepsia partialis continua. He was treated with IVIG for suspected Rasmussen's encephalitis. When this failed, he underwent hemispherectomy. The pathologic findings were consistent with Rasmussen's encephalitis.

One patient with cerebral folate deficiency presented with intractable generalized tonic-clonic seizures. She has failed treatment with vagus nerve stimulation, more than 15 medications, anterior corpus callosotomy, bilateral frontal-parietal multiple subpial transection, and the ketogenic diet. She had some improvement on leucovorin but continued to have seizures. She was found to have antibodies to the folate receptor and has responded to treatment with prednisone.

Conclusions: The clinical manifestations of cerebral folate deficiency are variable. As this condition is treatable with leucovorin, patients with intractable seizures of unknown etiology should undergo lumbar puncture to assay neurotransmitters.

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Bo Lyun Lee 1 , J. Lee 1 , D. Seo 2 , S. Hong 2 and M. Lee 1 ( 1 Pediatrics, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, South Korea and 2 Neurology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, South Korea )

Rationale: Paroxysmal nonepileptic events (PNEs) are frequently encountered in pediatric neurologic fields. But the diagnosis is often confusing. And there is little information about their clinical characteristics. We report out experience with PNEs in pediatric patients who were evaluated with long-term video-EEG monitoring (VEM).

Methods: During a 4 year 6-month period, 204 pediatric patients were admitted to the epilepsy monitoring unit and 25 patients (12.3%) were diagnosed as PNEs on the basis of a history and typical events recorded during VEM. A retrospective analysis was done on their medical records and videotapes of the events.

Results: Mean age of symptom onset was 8.5 years (4 months∼15 years of age) and the patients were divided into two age groups: 1) the infant, toddler, and preschool age group (4 months∼6 years) that consisted of 9 patients (36%). The most common findings were normal infant behaviors, hypnic jerks, and normal sleep movements. One patient had the history of hypocalcemic seizure and developmental delay and another perinatal distress associated with preterm delivery, and the others did not have any neurologic problems. 2) The school age and adolescent group (7∼15 years) comprised 16 patients. The most frequent diagnoses were pseudo-seizure associated with somatoform disorders (8 patients, 50%) and vasogenic syncope (3 patients). One patient had the history of early onset absence epilepsy and two had concomitant epilepsy.

Conclusions: In our study, the pseudo-seizure associated with somatoform disorder were the most common PNEs which were seen in ≥ 9 years of age and its frequency were increasing with age, becoming the most common type of PNEs in adolescents. The physiologic or organic disorders predominated in infant and toddler age group. The concomitant epilepsy and neurologic problems were relatively low in their incidence.

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Carol S. Camfield 1,2 , P. R. Camfield 1 and G. Breau 2 ( 1 Pediatrics, IWK Heath Centre & Dalhousie University, Halifax, NS, Canada and 2 Clinical Psychology, Dalhousie University, Halifax, NS, Canada )

Rationale: Childhood epilepsy has a significant impact on the family's QOL. The Impact of Epilepsy Scale (IPES) is a brief (11 questions), validated, global instrument that specifically measures this issue. No QOL scale for children with epilepsy is known to be responsive or sensitive to changes in epilepsy severity over time. We assessed the responsiveness of the IPES in a cohort of children with epilepsy over 3 years and hypothesized that the impact of childhood epilepsy on the child and family would change in the same direction as seizure frequency/severity.

Methods: The original assessment of the psychometric validity of the IPES included 97 families with children at various stages of epilepsy control. Of these 63 (65%) participated in the present longitudinal study. The children (25 boys) had a variety of epilepsy syndromes. Families completed the IPES at baseline (T1) and again 3 years later (T2). The child's epilepsy frequency/severity was compared at T1 and T2 with a standardized physician-completed questionnaire that yielded 3 simple categories of seizure severity: none, low and high, depending on frequency and seizure type. Changes in IPES scores were then compared with seizure frequency/severity using standard statistical techniques including MANCOVA.

Results: Mean age at T1 was 10 years (range 2–17) and mean interval between T1 and T2 was 33 months (20–44). At T1 and T2, 66% had no behavioral diagnosis, 79% were of normal intelligence and 94% had no co-morbid neurological diagnosis. Between T1 and T2, seizure severity improved in 49%, was unchanged in 33% and deteriorated in 18%. 51% of patients had been seizure-free for a year at T2.

When all patients were considered, the total IPES scores worsened over time; however, there was a statistically significant close relationship with changes in seizure severity (MANCOVA) - those with improved seizure severity had improved IPES, those with deteriorating seizure severity had worse IPES and those with no change in seizure severity had no change in IPES (p < 0.001). All 11 items in the IPES contributed to its responsiveness over time to epilepsy severity (MANCOVA). On univariate analysis with Bonferroni adjustment 4 items were particularly statistically significant (p < 0.0045) (overall health, number of activities, academic success and loss of original hopes for child).

Conclusions: The IPES is responsive over time to changes in the severity of childhood epilepsy and is a valid instrument to study the effects of longitudinal treatment. Because of its brevity (2–3 minutes to complete) and statistical robustness, it could be considered for use in clinical settings for individual patients to highlight areas of concern.

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Anne de Saint-Martin 1 , V. Laugel 1 , C. Sabourdy 2 , M. P. Valenti 2 , E. Flori 3 , M. C. Burger 1 , C. Marescaux 2 , E. Hirsch 2 and M. Fischbach 1 ( 1 Pediatric Department, Hopitaux Universitaires, Strasbourg, France ; 2 Neurology Department, Hopitaux Universitaires, Strasbourg, France and 3 Genetic Department, Hopitaux Universitaires, Strasbourg, France )

Rationale: Glucose transporter 1 (GLUT-1) deficiency is known to be responsible for infantile-onset and refractory epilepsy, developmental delay, acquired microcephaly and complex motor abnormalities. Accurate diagnosis of this treatable neurometabolic disorder is essential to initiate a ketogenic diet which can greatly improve this condition. We present two novel cases of genetically proven GLUT-1 haploinsufficiency which broaden the clinical spectrum of the disease.

Methods: Those patients were followed both by the pediatric and neurology units of Strasbourg University Hospital. This longitudinal following included : clinical visits, video recordings, repeated wake and sleep video EEG, cognitive, radiological, biological and genetic explorations

Results: Patient 1 is a 18 years old female adult presenting with focal temporal epilepsy diagnosed at 1 year, moderate developmental delay and progressive microcephaly. In her early teens, she experienced recurrent episodes of faintness associated with palor and sweating, mainly triggered by fasting or exercise. She also presented paroxysmal ataxia and dystonic movements markedly worsened by exercise, fasting or coffee intake. Her glucose level in CSF was 0.36 g/L (as compared to 1.1 g/L in blood) and the mutation analysis of the GLUT-1 gene revealed a new mutation, absent in her parents. Her motor and cognitive abilities have been strikingly improved by the ketogenic diet.

Patient 2 is a 10 years old male child presenting with prolonged episodes of paroxysmal ataxia and weakness related to exercise at the age of 2 years, associated with mild developmental delay with hyperactivity and deficit attention. His EEG showed frequent generalized SW, activated by sleep. His head circumference is still normal at 10 years of age. Glucose level in CSF was only very mildly decreased (0.43 g/l as compared to 0.87 g/l in blood) but the sequencing of the GLUT-1 gene confirmed a new mutation, absent in his parents. His attention and cognitive deficiency, paroxysmal ataxia, and EEG abnormalities have been largely responsive to the ketogenic diet.

Conclusions: These two cases underline that suggestive clinical symptoms of GLUT-1 deficiency may appear years after the first signs of the disease and that acquired microcephaly notably may not be a constant feature. Even the characteristic hypoglycorrhachia may sometimes be difficult to demonstrate with certainty. The most prominent symptom of the disease seems to be the intolerance to exercise and fasting, with paroxysmal neurological symptoms, in those two patients.

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Lorie Hamiwka 1 , N. Singh 1 , J. Niosi 1 and E. Wirrell 1 ( 1 Alberta Children's Hospital, Calgary, AB, Canada )

Rationale: In children presenting with a presumed first seizure, to determine: (1)quality of life, (2) self-esteem and (3) parental protection.

Methods: Children were seen in a tertiary care First Seizure Clinic. Inclusion criteria were age 1–17 yrs with an unprovoked event suggestive of seizure. Children were classified as having an epileptic or non-epileptic event. Depending on the age the child, children and the primary caregiver completed all or some of the following questionaires: Child Health Questionnaire (CHQ-PF28, CHQ-CF87), Piers Harris II self- concept scale (PH II) and the Parental Protection Scale (PPS).

Results: One hundred and twenty seven children and families were seen in the clinic. Eighty-eight completed the Child Health questionnaires (seizure 67; non-epileptic 21). Compared to normative data, parents reported significantly lower scores for family activity (p < 0.03), parental impact time (p < 0.03), parental impact emotional (p < 0.01) and behavior (p < 0.02). When the seizure group was compared to the non-seizure group, total quality of life scores were significantly lower (p < 0.01) with and they also showed limitation on parental personal time and increased distress and worry (p < 0.02). Children with a true seizure also experienced significantly lower self-esteem (p < 0.01), poorer family cohesion (p < 0.04) and experience greater emotional and behavioral difficulties that impacted daily activities (p < 0.09) than those with non-seizures. When scores for those with a history of probable seizures were compared to those with only a single seizure the scores were even lower. No differences were seen in self-concept or parental protection when compared to normative data.

Conclusions: Our study is the first to show impact on quality of life in children presenting with a presumed first seizure. Parents report a limitation and interruption of family activity and the time available for personal needs, and experience a great deal of emotional worry and concern. This finding is present irrespective of whether the child had a true seizure. Interesting, children with true seizures showed significantly lower quality of life scores than those with non-epileptic events with the lowest scores in those who unknowingly had established epilepsy.

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Kazuhiro Haginoya 1,2 , N. Nakasato 3 , M. Uematsu 2 , Y. Matsumoto 2 , T. Kobayashi 2 , T. Kitamura 4 , N. Fukuyo 2 and S. Tsuchiya 2 ( 1 Pediatric Neurology, Takuto Rehabilitation Center for Children, Sendai, Japan ; 2 Pediatrics, Tohoku University School of Medicine, Sendai, Japan ; 3 Neurosurgery, Konan Hospital, Sendai, Japan and 4 Pediatrics, Sendai Municipal Hospital, Sendai, Japan )

Rationale: Malignant rolandic-sylvian epilepsy (MRSE) in children (Otsubo et al. in 2001) has been defined as a form of epilepsy characterized by sensorimotor seizures, medical refractoriness, normal MRI, frontocentrotemporal EEG spikes, rolandic-sylvian spike sources on MEG, and cognitive problems. We present clinical and neuroimaging analysis of 5 patients that fit the definitions of MRSE in order to see if its clinical and neurophysiological features are similar enough to represent an identifiable syndrome.

Methods: Five patients ranging from 7 to 14 year-old were included in this study. Patients' seizures were videotaped with EEG monitoring. FDG-PET, iomazenil-SPECT, ictal ECD-SPECT, MEG, MRI, IQ test were applied to characterize patients' epilepsy.

Results: MEG demonstrated that spike sources clustered on the bilateral postrolandic region in pts 1–3, and lt. postrolandic in pt 4 and rt. postrolandic in pt 5. IQ score was abnormal ranging from 35 to 75. Patients were divided into two subgroups. Group 1 (pts 1–2) had frequent seizures appeared every 10 minutes that were characterized by blinking, facial twitching, and head dropping lasting 1–3 seconds. Ictal EEG showed bilaterally synchronous spike-waves bursts. CSWS pattern was observed. Ictal SPECT showed hyperperfusion in the bilateral thalamus, basal ganglia and brain stem. Dysarthria, disturbed writing, dyscalculia and dysphagia were recognized during frequent seizure-period. Multiple antiepileptic drugs were ineffective. However, ethosuximide (ESM) had finally substantial effect in controlling seizures and improving EEG findings as well as cognitive problems. Group 2 (pts 3–5) had hemi-facial seizure (pt 3), lt. arm sensory seizure (pt 4) and versive/postural tonic seizures (pt 5) that appeared daily or weekly and lasted 15–25 seconds. Multiple antiepileptic drugs proved ineffective. Ictal EEG showed localized fast waves or spikes bursts originated from central region. CSWS was not observed. Ictal SPECT showed localized hyperpefusion in the rolandic region. Patient 3 revealed SCN1A missense mutation.

Conclusions: Although this is a preliminary analysis with very limited number of patients, MRSE in children may be divided into two subgroup; Group 1 characterized by CSWS, frequent rolandic seizure, synchronous ictal spike-waves bursts, subcortical propagation of ictal phenomena and effectiveness of ESM, Group 2 characterized by non-CSWS, versive/posutural tonic seizure or hemiconvulsion, local seizure onset associated with ictal hyperpefusion in the rolandic region. Interestingly, in contrast to benign rolandic epilepsy where spike sources on MEG has anterior/superior direction, all in MRSE showed posterior/inferior direction, that was useful in differentiating these two epilepsy syndrome. CSWS was associated with group 1. Ictal SPECT suggests participation of subcortical structures in the appearance of very frequent seizures and may explain why ESM was effective in patients of Group 1. SCN1A mutation should be also considered in patients with MRSE if patients are fever-sensitive.

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Agustin Legido 1 , I. Valencia 1 , J. P. de Chadarevian 2 and C. D. Katsetos 1,2 ( 1 Section of Neurology, Department of Pediatrics, St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, PA and 2 Department of Pathology and Laboratory Medicine, St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelhia, PA )

Rationale: Recent studies have suggested that the inflammatory response encountered in cerebral lesions commonly associated with intractable seizures, such as cortical dysplasias or glioneuronal tumors, may play a role in epileptogenesis. The present study aims to further expand this knowledge by deciphering morphological correlates of microglial activation in a variety of brain specimens of children with refractory epilepsy.

Methods: Formalin-fixed/paraffin-embedded brain surgical resection specimens from 12 patients with refractory epilepsy were used in this study (ages 10 ± 7 years). They were representative of epileptogenic lesions from patients with tuberous sclerosis (TS) (n = 2), focal cortical dysplasia (FCD, types Ia-IIb; n = 4), low grade neuroepithelial tumors (ganglioglioma, n = 4 and grade II diffuse astrocytomas, n = 2) and corresponding age-matched control autopsy brain samples from patients without history of seizures (n = 5). The distribution of CD68 and HLA-DR immunoreactivity was evaluated by immunohistochemistry using monoclonal antibodies. The labeling index (LI) was expressed as the number of immunolabeled CD68 or HLA-DR inflammatory cells of the monocyte-macrophage lineage counted in 10, non-overlapping high power/40x fields. The LI was compared among all groups (ANOVA, SPSS).

Results: All epileptogenic lesions were characterized by the presence of CD68+/HLA-DR+ cells of the monocyte-macrophage lineage. Tissue samples from tubers exhibited the highest LI of CD-68+/HLA-DR+ cells, followed by FCD and intratumoral/peritumoral portions of neoplasms (Table 1). Morphologically, CD68+/HLA-DR+ cells in tubers and in FCD exhibited three distribution patterns: 1) Neuropil: Variously prominent aggregates of rod-shaped and/or ameboid microglia with thick/stout cell processes; 2) Perisomatic: Spindle/rod-shaped microglia encroaching upon the cell bodies of large (cytomegalic), dysmorphic and/or balloon neurons especially in heterotopic/heterotaxic foci; and 3) Perivascular: Varying accumulations of mononuclear inflammatory cells with a monocyte/macrophage morphology in the Virchow-Robin spaces. In peritumoral areas, CD68+/HLA-DR+ cells lacked perisomatic distribution.

Conclusions: Among lesions causing refractory epilepsy, an unusually robust increase in CD68+/HLA-DR+ cells, morphologically consistent with activated microglia, is encountered in epileptogenic tubers of TS. A similar trend is detected in FCD cases. The marked variation of values in the latter -leading to a high SD- is attributed to the heterogeneity and architectural complexity of these dysplastic lesions spanning the entire spectrum of FCD types (Ia-IIb). The morphological features of microglial activation in brain areas infiltrated by tumor are distinct from those encountered in tubers and FCD. It is unclear whether this inflammatory response is functionally related to epilepsy, either as a cause of epileptogenesis or as a consequence of activation following seizure activity. Future studies are warranted to clarify this dilemma.

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[ Table 1. Labeling index per group (Mean ± SD) ]

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Joo Hee Seo 1 , K. Choi 1 , Y. Lee 1 , J. Lee 1 and H. Kim 1 ( 1 Pediatrics, Yonsei university health system, Seoul, South Korea )

Rationale: Dravet syndrome (DS) is an epileptic encephalopathy characterized in the first year of life by prolonged febrile or afebrile seizure and resultant progressive developmental delay & cognitive dysfunction. Mutations in SCN1A, encountered with the DS, but there are significant proportion of DS without mutations of SCN1A. We compared the characteristics of DS with SCN1A mutation with those without mutation.

Methods: We reviewed the medical records of 32 DS patients between 2005 and 2007 at Severance Children's Hospital. We analyzed the clinical characteristics, EEG findings, MRI findings, and developmental test in two groups.

Results: Among 32 DS patients, 22 (69%) patients have mutations of SCN1A, 10 (31%) have no mutations. There are no significant differences between SCN1A gene (+) group and SCN1A gene (−) group in clinical characteristics including family history of febrile seizure, seizure classification, seizure onset age, sex, response to antiepileptic drug and ketogenic diet, seizure frequency, and developmental state. EEG findings showed no difference between two groups. Among 10 SCN1A gene (-) patients, 4 (40.0%) have abnormal MRI findings (1 calcification, 1 hippocampal sclerosis, 1 harmatomatous lesion), compared to 2 (9.1%) out of 22 SCN1A gene (+) patients (1 cortex lesion, 1 hippocampal sclerosis) (p = 0.017).

Conclusions: We concluded that there are similar clinical manifestation in DS patients, irrespective of mutation of SCN1A except MRI findings. MRI abnormal finding were significantly more frequent in patients without SCN1A mutation.

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Tomonori Ono 1 , K. Toda 1 , H. Baba 1 and K. Ono 2 ( 1 Neurosurgery, National Nagasaki Medical Center, Omura, Japan and 2 Yokoo Hospital, Isahaya, Japan )

Rationale: Even in cases of clinically diagnosed symptomatic generalized epilepsies (SGEs), asymmetry in blood perfusion or glucose metabolism is sometimes seen on functional neuroimaging such as single photon emission computed tomography (SPECT) and Positron Emission Tomography (PET). This suggests potential differences in epileptogenicity between hemispheres. The present study examined correlations between quantitatively assessed electroencephalogram (EEG) and SPECT findings to test the above hypothesis.

Methods: Subjects comprised 11 children (5 boys, 6 girls; median age, 5.9 years; range, 1–14 years) diagnosed with SGE by long-term video-EEG monitoring as a part of presurgical evaluation for pharmacoresistant epilepsy. Underlying pathology was categorized as Lennox-Gastaut syndrome (n = 3), infantile spasms (n = 4) or other SGEs (n = 4). One or more types of generalized seizure, such as spasms, atypical absence or tonic, atonic or myoclonic seizures were observed daily in all patients. Bilaterally synchronous spike and waves and multifocal spikes on EEG, and symmetrical features on MRI, including bilateral frontal polymicrogyria in 1 patient and lissencephaly in 1 patient, were observed in all. All EEG spikes of 16 selected electrodes were extracted from an arbitrarily selected 10- to 60-min period from artifact-free sleep records. Detected spikes from each channel were averaged for measurement of amplitude. Interictal SPECT data were analyzed using a 3-dimensional stereotactic region-of-interest template technique, and radioisotope (RI) counts of 14 cortical regions were semi-quantitatively assessed. Spike amplitudes of 8 unilateral electrodes and RI counts of 7 unilateral regions in each hemisphere were respectively averaged as hemispheric values. Laterality indices (LIs) of both parameters by region or hemisphere were calculated as (L-R)/(L+R), where L and R represent values of the measurement in question. Finally, correlations were statistically tested using regression analysis.

Results: LIs of hemispheric and regional spike amplitudes ranged from −0.36 to 0.22, and from −0.77 to 0.3, respectively. Conversely, LIs of RI counts ranged from −0.005 to −0.001, and from −0.1 to −0.03, respectively, indicating that distributions of RI counts were less asymmetrical than spike amplitudes. However, LIs of spike amplitudes and RI counts displayed positive correlations to both hemispheric and regional evaluations (p = 0.006; R2 = 0.59, p < 0.001; R2 = 0.28, respectively).

Conclusions: Particularly in localization-related epilepsies, hypo- or hyperperfusion in the epileptogenic focus is usually seen on interictal or ictal SPECT, respectively. However, in SGEs, RI counts on interictal SPECT are increased in the more susceptible hemisphere as postulated by EEG spike amplitudes. These results suggest that ictal-like perfusion images are often observed in SGEs due to frequent epileptiform discharges on EEGs.

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Ching-Shiang Chi 1 , H. F. Lee 2 , C. R. Tsai 2 and C. H. Chen 2 ( 1 Tung's General Hospital, Taichung, Taiwan and 2 Dept. of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan )

Rationale: Knowledge of mitochondria and the relationship of mitochondrial dysfunction to human diseases have evolved over the past century. The clinical manifestations of mitochondrial diseases are variable because mitochondria exist in multiple organs. Among them, central nervous system (CNS) is frequently affected because it needs more ATPs to carry out cellular work. Here we report the epileptic seizures in mitochondrial diseases in infants and children in Taiwan.

Methods: From 1983 to 2007, we collected 59 cases, 35 male and 24 female, aged from 3 months to 18 years. The diagnosis of mitochondrial diseases was made by (1) electron microscopy of muscle biopsy showing abnormal mitochondrial configurations, and (2) positive mitochondrial genetic analysis, or (3) ragged-red fiber by histiochemistry stains of muscle biopsy. We retrospectively analyzed the epileptic seizures in patients with mitochondrial diseases.

Results: 28 out of 59 cases (47.5%) were specific mitochondrial syndromes (SMS) and 31 cases (52.5%) belonged to non syndromic mitochondrial disease (NSMD). 21 cases (35.6%) had no seizures, 12 were SMS and 9 were NSMD. 16 out of 28 cases (57.1%) in the group of SMS had seizures: 7 generalized seizures in terms of myoclonic and generalized tonic and/or clonic seizures, 5 focal seizures, 2 unclassified seizures, and 2 mixed seizure types. 21 out of 31 cases (71.0%) in NSMD had seizures: 10 generalized seizures, 6 focal seizures, 2 unclassified seizures, and 4 mixed seizure types. 53 of 59 cases had done EEG., 7 normal EEG, 18 epileptiform discharges in terms of focal spikes, sharp waves or hypsarrhythmia, and 28 nonspecific findings, i.e. background slow or intermittent polymorphic slow waves. 32 out of 38 cases (84.2%) with seizures had developmental delay (DD) or psychomotor retardation (PMR).

Conclusions: The epileptic seizures in mitochondrial diseases in infants and children were not uncommon (64.4%). Most of them were NSMD. All of them were refractory, most cases were associated with DD and PMR. Neurologists should be considered mitochondrial disorders in patients with refractory seizures and DD or PMR.

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Heung Dong Kim 1 , Y. Lee 1 , J. Seo 1 , H. Lee 1 and J. Lee 1 ( 1 Pediatrics, Yonsei University Health System, Seoul, South Korea )

Rationale: To reveal the clinical characteristics of infantile spasms (IS) caused by mitochondrial respiratory chain complex (MRC) defects.

Methods: We retrospectively reviewed clinical, neuroradiological and electrophysiological features of 23 IS patients with MRC defects, confirmed by biochemical assay of MRC activities in muscle biopsy. We also analyzed the treatment outcome.

Results: 1) Among 23 patients with IS caused by MRC defect, 10 (43.5%) patients were male and 13 (56.5%) were female. Their median age at seizure onset was 6 months (6.0 ± 3.3 month, 10 days–15 months).

2) Twenty (87.0%) out of 23 patients showed decreased enzyme activities in MRC I, 1 (4.3%) in MRC II, and 2 (8.7%) in MRC IV.

3) Twenty-two (95.7%) out of 23 patients showed abnormal MRI findings. Seventeen patients showed diffuse atrophy of which 1 associated to cerebellar atrophy, 3 to white matter hyperintensity; 5 patients showed signal changes in deep nuclei such as basal ganglia and thalamus; 2 patients had cortical dysplasia.

4) Lactate peak in MR spectroscopy occurred in 10 (45.5%) out of 22 cases.

5) Eight (34.8%) patients showed more than 50% reduction in the frequency of clustering spasms, whereas 13 (56.5%) had no responses to antiepileptic drugs.

6) Seven (43.8%) out of 16 patients who started on ketogenic diet showed more than 50% reduction in seizure frequency, moreover 6 (37.5%) patients had seizure free outcome.

7) Seventeen (73.9%) of the patients receiving the mitochondrial cocktail therapy with coenzyme Q10 and multi-vitamin showed clinical improvement as measured by the caretaker's global assessment form.

Conclusions: MRC defects is one of the important causes of IS and active application of KD and mitochondrial cocktail therapy is effective in significant proportion.

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Ingrid Scheffer 1,2 , J. Rodda 3 , J. McMahon 1 , S. Berkovic 1 and H. K. Graham 3 ( 1 Medicine, Austin Health, University of Melbourne, Melbourne, VIC, Australia ; 2 Paediatrics, Royal Children's Hospital, University of Melbourne, Melbourne, VIC, Australia and 3 Hugh Williamson Gait Laboratory, Royal Children's Hospital, Melbourne, VIC, Australia )

Rationale: Dravet syndrome is an increasingly recognised severe infantile-onset epilepsy syndrome associated with SCN1A mutations in 70% cases. Seizures are most severe in the first decade but gait often deteriorates in the second decade of life. Adults with Dravet syndrome may not be able to independently ambulate over long distances. The nature of the gait deterioration has not been well characterised.

Methods: 13 patients with Dravet syndrome underwent a standardized physical examination by a physiotherapist with experience in neuromuscular disorders, completion of a functional mobility scale, two dimensional videography and radiographs of the pelvis and feet.

Results: Patients were studied between 4y 9m and 22y 11m (median 11.5y). A characteristic gait pattern was observed which was present to some degree in all subjects but with much more severe expression in those who were skeletally mature, post-pubertal growth spurt. Analysis in the sagittal plane showed the evolution of a crouch gait pattern with age. In the coronal plane, severe malalignment was observed consisting of three components: inset hips, (medial femoral torsion), lateral tibial torsion and external foot progression because of pes abductovalgus. Hip radiographs showed very mild and subtle abnormalities only, there was no frank subluxation. However standing foot radiographs consistently showed mid-foot breaching and increased talo-calcaneal angles outside the normal range. Ataxia was not observed.

Conclusions: Children with Dravet syndrome show minor gait abnormalities in early childhood with a high level of independence and physical functioning. However with time and puberty, bone remodelling results in a consistent biomechanical malalignment associated with torsion of the long bones. This results in a progressive crouch gait and deterioration in physical functioning and independence. Early identification of changes may enable strategies to prevent progression. The sodium channel mutation is likely to underpin the neurobiological mechanism causing the characteristic musculoskeletal changes.

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Dorothea Kasteleijn-Trenite 1,2 , M. Piccioli 1 , P. Parisi 1 , M. P. Villa 1 , P. Tisei 1 and C. Buttinelli 1 ( 1 Neurological Sciences, Sapienza Roma University, Roma, Italy and 2 Medical Genetics, University Utrecht, Utrecht, Netherlands )

Rationale: The comorbidity between migraine and epilepsy has been known since one century ago, yet is not understood in full. Migraine and epilepsy share some risk factors, positive and negative symptoms, and preventive drug therapy. Headache, in relation to visual stimuli as a pure autonomic epileptic manifestation, is underestimated.

Methods: To examine the link between migraine and epilepsy we prospectively evaluated selected families, in which both headache and photosensitivity were reported to the (child) neurologists of the university hospital in Rome between 2005–2006. The proband and all first degree family members were invited for EEG investigation. Those who gave consent were investigated with standardized photic stimulation and striped pattern stimulation. Four families, of whom two were multi-generational, have been selected and investigated.

Results: Twelve of the total 25 family members have a history of headache; five of them had epilepsy. A PPR was found in the EEG of 8 of the 25 members often in relation with headache complaints. In addition, a visually induced autonomic seizure was registered with headache as the only complaint. In our cases, the clinical overlap between migraine and epilepsy is complete and headache might even represent the sole autonomic manifestation of an epileptic condition.

Conclusions: We advocate performing an EEG with standardised Intermittent Photic Stimulation (IPS) in all headache patients having family members with epilepsy. This has consequences for treatment.

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Cristina Go 1 , H. Otsubo 1 , A. Ochi 1 , E. J. Donner 1 , S. Weiss 1 , I. Elliot 1 and O. C. Snead 1 ( 1 Neurology, The Hospital for Sick Children, Toronto, ON, Canada )

Rationale: To understand effects of withdrawing Valproic acid (VPA) on the epileptogenic network in patients with intractable epilepsy.

In presurgical evaluation of patients with intractable epilepsy, EEG seizure onsets and initial clinical signs are of great significance in the localization of the epileptogenic zone.

In patients for possible epilepsy surgery, it is common practice to taper off some of their maintenance antiepileptic drugs (AEDs) during scalp video-EEG (VEEG) and intracranial VEEG to obtain optimal number of clinical seizures for presurgical evaluations and resective surgery. Valproic acid (VPA) is one of the effective AEDs and is used for both localization-related and generalized epilepsies. However, VPA can disturb hemostasis through its effects on platelet counts and functions to significantly increase the risk of bleeding. Therefore at The Hospital for Sick Children, we tapered off VPA at least 10 to 14 days before a planned surgery with invasive VEEG monitoring. We analyzed the difference of seizures on VEEG between on and off VPA to understand the mechanisms of VPA over the epileptogenic network.

Methods: We included patients with intractable epilepsy, who completed presurgical evaluations and underwent resective surgeries. The patients were taking one or more anticonvulsants including VPA before the surgery. VPA was tapered over one to two week period and was completely off at least four days before the repeat scalp VEEG study and at least 10 days before invasive VEEG.

We performed two scalp VEEG on and off VPA and invasive VEEG off VPA, using subdural grid with or without depth electrodes. We analyzed ictal EEG onset, latency between EEG onset and clinical onset, propagation of EEG for secondary generalization in seizures with similar clinical semiology.

Results: We identified two patients with the inclusion criteria. The pathology consisted of tuberous sclerosis and cortical dysplasia one each. Both patients received one or two other anticonvulsants in addition to VPA. The number of seizures obtained during off and on VPA was not significantly different. There was a decreased latency from ictal EEG onset to clinical onset, more than 50% shorter on scalp VEEG off VPA compared to those on VPA. When seizures became secondarily generalized, the duration between initial clinical seizures and secondary generalization became, on the average, 50% shorter off VPA compared those on VPA. In the tuberous sclerosis case with two types of partial seizures with or without secondary generalization on VPA, they merged into a single type of partial seizures with secondary generalization off VPA.

Conclusions: The withdrawal of VPA accelerated the propagation from ictal EEG onset to ictal symptomatogenic period. Furthermore, the clinical seizures quickly became secondarily generalized. Vice versa, VPA inhibited and controlled spreading of ictogenic network or inactivated part of the epileptogenic network.

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Laura P. Masters 1 and A. Weinstock 1 ( 1 Child Neurology, SUNY at Buffalo, Buffalo, NY )

Rationale: ASE is a rare entity in childhood, with most cases occurring in children with idiopathic generalized epilepsy or epileptic encephalopathy. New onset presentation of ASE (de novo ASE) has been reported in middle-aged or elderly patients without prior history of seizures. We report two such cases in developmentally normal children with no prior history of seizures.

Methods: A search of our EEG database was performed to explore the frequency of this condition. A retrospective chart and serial EEG review of an 8-year-old girl, and a 12-year-old boy presenting with several hours of altered mental status and EEG evidence of ASE was performed.

Results: Out of a database of 23,976 EEG's, 2 cases of de novo ASE were identified in children and 4 in adults. Both children were admitted to the PICU, and had a negative work up with CT, MRI, and LP. EEG upon presentation revealed continuous generalized epileptiform discharges consistent with ASE. After resolution of status epilepticus with intravenous benzodiazepines and fosphenytoin, both children were transitioned to sodium valproate with excellent long-term response. At 2-month and 15-month follow-up both children remained seizure free on valproate. Both children continued to perform normally in school without apparent sequelae.

Conclusions: Although rare, ASE may present de novo in children and should be considered in the differential diagnosis of childhood acute mental status change. Urgent EEG will confirm this diagnosis and allow appropriate therapy.

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Annapurna Poduri 1 , A. M. Bergin 1 , B. Bourgeois 1 , F. Duffy 1 , J. Madsen 2 , P. M. Black 2 and J. Riviello 1 ( 1 Neurology, Children's Hospital Boston, Boston, MA and 2 Neurosurgery, Children's Hospital Boston, Boston, MA )

Rationale: To determine whether the outcome of epilepsy surgery, measured by post-operative Engel score (4-point scale, with lower score meaning better outcome), can be predicted by patient age, duration of epilepsy, gender, presence of a lesion on MRI, cognitive status, or history of prior epilepsy surgery.

Methods: Patients who underwent invasive subdural EEG monitoring and/or focal resection for epilepsy were identified in a database that comprehensively included patients who underwent epilepsy surgery at Children's Hospital Boston from 1993 to 2003. Pre-operative data and Engel scores were obtained by retrospective chart review; Engel score was assigned if not reported. We performed univariate and multivariable linear regression analyses of the above pre-operative factors, adjusting for year of surgery to account for changes in practice over time. The outcome of interest was the Engel score at the time of the last clinical encounter, and it was treated as a continuous variable. Based on the results of this regression, we attempted to assess whether MRI lesion type predicted outcome.

Results: Of 224 patients in the database, outcome data were available for 196, with mean follow-up time of 25 months. By univariate analyses, presence of an MRI lesion and normal cognition were associated with lower Engel score, or better clinical outcome (p < .05). Linear regression revealed that, when adjusted for year of surgery, the presence of an MRI lesion was associated with Engel score 0.45 lower than no lesion (p < .05); normal cognition with Engel score 0.51 lower than mental retardation (p < .005); and history of prior epilepsy surgery with Engel score 0.56 lower than no prior surgery (p < .05). There was insufficient power to stratify outcome by type of MRI lesion. Age, gender, and duration of epilepsy did not significantly influence outcome in these analyses.

Conclusions: In patients considered candidates for epilepsy surgery, the presence of an MRI lesion, normal intelligence, and history of prior epilepsy surgery each predicts favorable post-operative seizure outcome.

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Cheryl P. Shore 1 , J. M. Buelow 1 , J. K. Austin 1 and D. W. Dunn 2 ( 1 School of Nursing, Indiana University, Indianapolis, IN and 2 School of Medicine, Indiana University, Indianapolis, IN )

Rationale: Studies exploring length of time to a diagnosis of epilepsy and the existence of previously unrecognized seizures are few. One study noted that 33% of children referred to a first seizure clinic already qualified for a diagnosis of epilepsy. We examined associations between the existence of prior unrecognized seizures and seizure type in a sample of children participating in a larger study of first recognized seizures.

Methods: The sample consisted of 126 children of normal intelligence who enrolled in the larger study. Data describing the seizure condition were collected from notes of parent interviews and medical records obtained with parent permission. Author DWD evaluated information pertaining to history of the seizure disorder from both parent and physician sources and categorized each as having or not having prior unrecognized seizures. Author DWD also evaluated seizure type(s). Main seizure type was utilized in this analysis. Data were also collected regarding child IQ and family demographics by trained nurse interviewers. Descriptive statistics and chi square analysis were calculated using SPSS 14.0.

Results: Occurrence of prior unrecognized seizures was significantly associated with seizure type χ2(5, N= 120) = 11.71, p= .04. Generalized tonic/clonic seizures and complex partial seizures with secondary generalization were more common in the group with no prior unrecognized seizures. The opposite was true for absence seizures in our sample; those children who experienced the onset of recognized absence seizures as their main seizure type were more likely to have prior unrecognized seizures. Those children with elementary partial, complex partial without generalization, and elementary partial with secondary generalization were equally represented in both groups. Demographics did not significantly differ by group, but our sample was homogeneous with the majority being Caucasian, married and insured.

Conclusions: Findings from this study are congruent with those from our previous work of delay to diagnosis in a sample of children with epilepsy and learning problems. Children with absence seizures are most likely to have prior unrecognized seizures, and those with generalized tonic/clonic seizures appear least likely to have had previous seizures. However, prior unrecognized seizures cannot be ruled out for any seizure type. Further study is indicated with a more diverse sample. (Source of funding: NINDS R01 NS 22416).

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Anita Datta 1 , T. Snyder 1 , S. N. Ahmed 1 , D. Gross 1 , L. Jurasek 1 , D. Quigley 1 , M. Wheatley 1 and B. Sinclair 1 ( 1 Pediatric Neurology, University of Alberta, Edmonton, AB, Canada )

Rationale: The detrimental effect of frequent early seizures on intelligence quotient (IQ) of children is a significant clinical issue. The decision to pursue surgical treatment must balance the potential benefit of seizure control with the potential impact and probability of cognitive decline. Patients who may benefit from epilepsy surgery might be deterred from surgical evaluation due to concerns of postoperative IQ decline.

Methods: We analyzed the pre and postoperative neuropsychological outcomes of children who underwent epilepsy surgery to determine if epilepsy surgery impacts cognition.

The Wechsler Intelligence Scales were administered pre-operatively and least 1 year post-operatively in all children. A chart review was done and demographic data, seizure type, seizure frequency, anti-epileptic medications, duration of seizures, neuroimaging, type of surgery and pathology was recorded. Neuropsychological data was compared pre and post-operatively and included full scale, verbal and performance intelligence quotients (FSIQ, VIQ, PIQ) and the child behavioral checklist (CBC).

Results: 59 patients with epilepsy surgery who had pre and post-operative neuropsychological evaluations were included in the study. Age of onset of seizures ranged from 1 month to 16 years. The mean duration of seizures prior to surgery was 5.9 years. Types of surgery included temporal lobe resection (n = 20), extratemporal and multilobar resection (n = 38) and corpus callosotomy (n = 1). No significant change in FSIQ, VIQ, PIQ or CBC was demonstrated on a group level. Lateralization, type of surgery, age at surgery, sex, and presurgical IQ did not affect outcome.

Conclusions: Epilepsy surgery in children and adolescents offers a good prognosis for seizure control and does not have a significant impact on IQ.

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Lindsay Manor 2,1 , G. Ronen 2 , L. m. Lach 3 , P. Rosenbaum 2 , D. Streiner 4 and C. Canadian 1 Pediatric Epilpesy Network (CPEN) 2 ( 1 Schulich School of Medicine, The University of Western Ontario, London, ON, Canada ; 2 Pediatrics, McMaster University, Hamilton, ON, Canada ; 3 School of Social Work, McGill University, Montreal, QC, Canada and 4 Psychiatry, University of Toronto, Toronto, ON, Canada)

Rationale: Earlier age at onset is associated with higher levels of psychosocial problems, lower IQ and memory impairment. Developmental stage at disease onset influences how children experience epilepsy, stress, and their psychosocial adjustment. Longer duration is associated with depression and anxiety. However, little is known about the relationship between health-related quality of life (HRQL) and age of onset, epilepsy duration, or proportion of life with epilepsy.

Methods: This is a cross-sectional study of 394 children with active epilepsy (mean age 11 years) and their parents. Respondents completed the self-report and proxy Childhood Epilepsy specific HRQL Measure, ‘CEHRQL’ (Epilepsia 2003;44:598–612). Statistical analysis was done with SPSS v. 12.

Results: Earlier age of onset, longer duration and higher proportion of life with epilepsy each correlated with poorer HRQL. However, these three variables correlated strongly with each other (p < 0.01), therefore, the following results focus only on epilepsy duration. The relationship between duration and HRQL differed between self-report and proxy report, overall children and adolescents rated their HRQL better than the parents did. Epilepsy duration correlated closely with the subscales of Interpersonal/Social, Intrapersonal/Emotional and Quest for Normality but not with the subscales of Worries/Concerns and Epilepsy-Secrecy.

Conclusions: Epilepsy duration may represent a marker for unspecified determinants of HRQL. Longitudinal follow-up, particularly of self-reported HRQL measures, may help us understand the life course trajectories of children with epilepsy.

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Kohilavani Velayudam 1 , P. Kotagal 1 , I. Tuxhorn 1 , E. Wyllie 1 , A. Gupta 1 , D. Lachhwani 1 , D. Abend-Skully 1 , A. Warbel 2 and W. Bingaman 2 ( 1 Pediatric Epilepsy, Cleveland Clinic Foundation, Cleveland, OH and 2 Neurosurgery, Cleveland Clinic Epilepsy Center, Cleveland, OH )

Rationale: Hemispherectomy is an effective treatment for intractable epilepsy arising from one hemisphere. However, not all patients become seizure free post operatively. A number of factors including incomplete hemispheric disconnection or diffuse bilateral epileptogenesis may contribute to failed surgery. Our objective was to analyze the significance of scalp VEEG findings prior to anatomic hemispherectomy (AH) in children who had failed functional hemispherectomy (FH) for intractable epilepsy

Methods: We identified 18 patients who underwent anatomic hemispherectomy (AH) from a subset of 145 patients (12.4%) who had functional hemispherectomy (FH) during 1997–2006. We reviewed their scalp video-EEG (VEEG) data, analyzing clinical seizure semiology, interictal and ictal EEG as well as clinical data, MRI and PET. In 10 patients we had both pre and post FH data sets. In 8 patients only post FH data was available as FH was performed elsewhere

Results: Out of 18 children 9 were male and 9/18 underwent a right hemispherectomy. Age at initial presentation ranged from birth to 72 months (median 2.5 months). The age at FH ranged from 3 months to 17 years (median 18 months) and from 5 months to 20 years (median 63 months) for AH. The etiologies were divided into two groups: 13/18 had developmental lesions (malformations of cortical development, hemimegalencephaly) and 5/18 had acquired lesions (Rasmussen's encephalitis and stroke). Post AH follow up ranged from 1 month to 24 months (median 6 months).

VEEG of 10 patients with malformations of cortical development (5 hemimegalencephaly) showed unilateral interictal and ictal findings confirming that the residual seizures were still arising from the operated hemisphere and 7/10 (70%) became seizure free post AH. The remaining three had a worthwhile seizure reduction.

Two cases with Rasmussen Syndrome had contralateral seizure onset, yet became seizure free after AH. A third patient with Rasmussen Syndrome had no interictal or ictal changes on EEG but semiology was lateralizing. After AH, seizure control improved considerably but did not become seizure free.

5 patients showed varying degrees of bihemispheric interictal and ictal findings, predominantly on the lesion side which guided the decision for AH. Of 3 children with malformations, 2 became seizure free and one improved. However, 2 patients with stroke failed AH.

Conclusions: Detailed VEEG analysis after failing FH can help to confirm residual epileptogenicity in the operated hemisphere and support patient selection for reoperation. Repeat AH offered a good prognosis for seizure control in patients with persistent ipsilateral seizure onset and in some patients with bilateral EEG findings. Contralateral ictal EEG onset in patients with Rasmussen Syndrome may not be a contraindication for AH. Stroke patients with bilateral interictal and ictal EEG findings appeared to do less well after AH

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Mazin Hussein 1 , M. Takeoka 1 , A. Torres 1 and A. Poduri 1 ( 1 Children's Hospital Boston, Boston, MA )

Rationale: We report 3 cases of reflex seizures induced by diaper-changing, tooth-brushing, and reading. Diaper-changing has not been previously reported as a trigger for reflex seizures.

Methods: History, physical examination, neuroimaging, and EEG data were reviewed for each patient.

Results: Patient 1 was a 5-year-old boy with a history of refractory infantile spasms that were eventually controlled with ACTH. MRI and an extensive genetic and metabolic evaluation were normal. After initial control of spasms, he had had occasional clusters of spasms that were refractory to treatment with valproic acid, levetiracetam, and clonazepam. He presented with a 5-month history of clusters of extensor spasms occurring only when his parents fastened his diapers closed. Video-EEG established them to be seizures, with a hallmark diffuse slow wave or a slow wave followed by an electrodecrement and beta activity at the onset of each spasm. After the use of absorbent undergarments that could be pulled up without applying pressure to his anterior hip regions, the clusters of spasms stopped completely.

Patient 2 was a 3-year-old girl with intractable epilepsy due to a congenital brain malformation consisting of a large left parietal cortical dysplasia as well as a small region of periventricular heterotopia of the right lateral ventricle. Her seizures consisted of drop seizures as well as episodes of unresponsiveness and cyanosis, all of which were refractory to multiple medications, IVIG, the ketogenic diet, and two resections of the left parietal lesion. Her baseline EEG showed voltage attenuation in the left hemisphere and very frequent spikes in the right frontopolar, frontal, temporal, and centro-parietal regions. At three years of age, she developed head drop seizures induced exclusively by tooth-brushing.

Patient 3 was a 13-year-old boy who presented with three episodes of confusion, drooling, staring, and pupillary dilatation, each lasting five minutes. All three episodes occurred at school while he was reading. He also had a history of spontaneous seizures. MRI showed a slightly enlarged left temporal horn. Baseline EEG showed left temporal spikes that were activated by sleep. Silent reading was used as an activation procedure and was associated with an increase in epileptiform activity on EEG. Thus, while the seizures have not been established by video-EEG, there was a suggestion that the patient has reading-induced epilepsy.

Conclusions: We present three cases of reflex seizures in patients with epilepsy. A careful history may suggest specific activation procedures during EEG that may lend support to the diagnosis of reflex epilepsy. The diagnosis of reflex seizures can be made most definitively by video-EEG.

While reading and tooth-brushing have been reported as stimuli for reflex epilepsy, epileptic spasms induced by diaper-changing and treated by the cessation of the use of diapers have not been previously reported. We highlight this case in part to point out the excellent response to simple avoidance of the stimulus.

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Zhao Liu 1,2 , E. Andrade 1,2 and P. R. Carney 1,2 ( 1 Pediatrics, University of Florida, Gainesville, FL and 2 McKnight Brain Institute, University of Florida Health Science Center, Gainesville, FL )

Rationale: Case description of a 3 year-old female with intractable complex partial seizures, progressive hemiparesis and pathology suggestive of a Rasmussen's syndrome variant to illustrate the possible autoimmune basis of intractable focal seizure disorders

Methods: Case report

Results: A 3 year-old white female with normal birth history had first seizure at 3 week-old with acute onset of recurrent “right” hand twitching every 30 min for 2 days. Initial MRI showed high signal T2 lesion in right central head region involving high convexity of motor area. Initial EEG showed sharp transient in right central head region. A repeat EEG one month later was normal. Patient was seizure-free for 2 years.

Patient was seen again at 18 month-old for mild left hemiparesis. MRI showed “Old cortical infarct” involving primary motor cortex on the right, with associated atrophy and wallerian degeneration. Patient had recurrent complex partial seizures since 27 month-old. Seizures were characterized as left hand twitching and sometimes involved left upper and lower extremities. Patient had video-EEG monitor at 3 year-old due to Increasing seizures and progressive left hemiparesis. Video-EEG showed frequent ictal and interictal high amplitude spike and wave discharges localized in right central head region. Repeated MRI at 3 year-old demonstrated evidence of high signal lesion in right motor cortex with atrophy and Wallerian degeneration and delayed myelination in the subcortical U fibers and periventricular white matter. Epilepsy surgery with right cortical resection was performed 3 month ago and the pathology showed findings consistent with chronic meningoencephalitis, characterized by diffuse leptomeningeal (not just superficial), and variable but widespread intraparenchymal, CD3-immunoreactive (and CD20-immunonegative) T-lymphocytes, as well as Kp1-immunoreactive monocyte/macrophages. The intraparenchymal lymphocytes are perivascular and/or vasocentric and often associated with microglial activation, which is most striking in subpial cortex, but also forms frank microglial nodules (CD45-immunoperoxidase). Cortex is also irregularly astrogliotic. In some more discrete gliotic microfoci, in both gray and white matter, there is more overt, albeit incomplete, asociated organized (old) parenchymal loss (necrosis). The most prominent such foci showed signs of ongoing inflammatory process. These finding is suggestive of Rasmussen's encephalitis. Toxoplasma and CMV are negative.

Patient was seizure-free following epilepsy surgery. In addition, her left hemiparesis and speech delay were much improved after the surgery.

Conclusions: This is an unusual case with focal pathological changes suggestive of Rasmussen' syndrome presenting with progressive complex partial seizures and progressive hemiparesis. Focal resection surgery in involved motor area has not only controlled seizures, but also improved her motor function.

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Julie E. Koumoutsos 1 , A. C. Modi 1 , D. A. Morita 2 , S. Monahan 2 and T. A. Glauser 2 ( 1 Pediatrics-Behavioral Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH and 2 Pediatrics-Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH )

Rationale: Adherence to medical regimens for pediatric conditions averages approximately 50% and, except for complete non-adherence, is difficult to detect objectively. No studies have examined the impact of non-adherence on seizure frequency and subsequent antiepileptic drug (AED) adjustments in children with new onset epilepsy. The purpose of the current study was to document the frequency of seizures and subsequent AED dosage increases occurring when patients are non-adherent to their prescribed treatment regimen.

Methods: Participants included 25 children with new-onset epilepsy (Mean age = 6.88 years; 76% males, 72% Caucasian, 72% partial epilepsy/28% generalized). Each participant was given a MicroElectronic Monitoring System (MEMS) TrackCap to assess adherence to their AED (68% carbamazepine, 32% valproic acid). Treating healthcare providers were blinded to the electronic adherence data and assessed the need for drug dosage changes based on detailed clinical history. AED dosage increases, number of seizures prior to the increase, and adherence prior to the dosage increase were recorded.

Results: Results indicated that 56% of the 25 participants had an increase in their AED after reaching the maintenance dose. Patients with partial epilepsy had more dosage increases than those with generalized epilepsy (χ2 (1) = 6.9, p < .01). Of the 25 participants, 71% of those with a dosage increase had imperfect adherence (adherence < 100%). Adherence in the week prior to the AED dosage increase was 82.6% and the mean number of seizures in the week prior was 0.38. In the week prior to the AED dosage increase, 1-week adherence was inversely related to the number of seizures that occurred that week (r =−0.56, p < .05).

Conclusions: This data suggest that in children with new onset epilepsy imperfect adherence is associated with recurrent seizures and subsequent “avoidable” AED dosage increases. Objectively identifying poor adherence to AED regimen is important to help clinicians better decide when a behavioral intervention to improve adherence rather than an AED dosage increase is warranted.

Funded by the Center for the Promotion of Adherence and Self-Management, Department of Pediatrics, Cincinnati Children's Hospital Medical Center

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Jeffrey Buchhalter 1 and K. T. Johnson 2 ( 1 Phonenix Children's Hospital, Phoenix, AZ and 2 Mayo Clinic, Rochester, MN )

Rationale: Knowledge of the risk of submersion and drowning in children with epilepsy would be useful in order provide anticipatory guidance to the families/care providers of these individuals. Therefore, we sought to answer the following questions based upon an evidence-based review of the literature: 1) What is the risk of submersion or drowning in children with epilepsy? 2) Does the risk vary with the age of the child? 3) Does the risk vary with seizure type? 4) Does the risk vary with seizure frequency? 5) Does the risk vary with specific Anti-Epileptic Drugs (AEDs)? 6) Does the risk vary with AED levels? 7) Does the risk vary with developmental status? 8) Does the risk vary with different immersion locations (e.g. bathtub, swimming pool, open water)?

Methods: MEDLINE and bibliography search including English language articles, 1966–2005, that reported two or more cases of submersion/drowning in people with epilepsy that included children.

Results: Twenty-nine articles met inclusion criteria of which 5 were evidence level V and 24 were evidence level IV. Epilepsy confers a 4–7.5% risk of drowning/submersion to a child with the condition. Children with epilepsy who drown/submerge are more likely to be over five years old than those without epilepsy. Children with epilepsy are at the greatest risk of drowning in the bath. Swimming pools present the second greatest risk of drowning to the child with epilepsy. In both locations, the risk is greatest if the child is over five years old. Some data suggest, but do not establish that therapeutic AED levels are helpful, although not always protective. Generalized tonic-clonic and complex partial seizures seem to pose the greatest risk.

Conclusions: No data exists meeting our criteria stronger than Evidence Level IV. Suggestions are made for appropriate next steps for research addressing these questions. Caution is warranted for the child with epilepsy in the bath, and swimming pool, especially if over five years old. The data suggests close supervision is protective, especially in the bath. Therapeutic AED levels should be maintained. Further research is warranted.

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Avani C. Modi 1 , J. E. Koumoutsos 1 , D. A. Morita 2 , S. Monahan 2 and T. A. Glauser 2 ( 1 Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH and 2 Pediatrics-Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH )

Rationale: Adherence to antiepileptic drug (AED) therapy can play an important role in the effectiveness of pharmacologic treatment of epilepsy. The purpose of the current study was to use an objective measure of adherence, MEMS TrackCaps to: 1) document patterns of adherence for the first month of therapy for children with new-onset epilepsy; 2) examine differences in adherence by demographic and epilepsy variables; and 3) determine whether treatment adherence improves for a short time preceding a clinic visit (e.g., “white coat compliance”) in this pediatric population.

Methods: Participants included 35 children with new-onset epilepsy (Mean age = 7.2 years, 34% female, 66% Caucasian) and their caregivers. Sixty-six percent of children were diagnosed with partial epilepsy and 34% with generalized epilepsy. Adherence to treatment was electronically monitored with MEMS TrackCap, starting with the first AED dose. Adherence was calculated across a one-month period and for the 1-, 3-, and 5 days prior to and 3 days after the clinic appointment.

Results: Mean adherence for the first month of treatment in children with new-onset epilepsy was 78.4% (S.D. = 28.2%). One-month adherence was higher in children of married parents (t (33) =−2.1; p < .05) and those with higher socio-economic status (r = 0.44; p < .01), but did not correlate with gender, age, epilepsy type or prescribed medication. Adherence across the entire one-month period was not different than adherence for the 1-, 3-, or 5 days prior to, or 3 days after the clinic visit.

Conclusions: Poor adherence seen for children with new-onset epilepsy during the first month of AED therapy is concerning. Several demographic variables influence adherence to treatment, while the proximity to a clinic visit does not. Further studies are needed to: 1) document whether this trend continues longitudinally, 2) identify predictors of non-adherence and 3) determine the clinical impact of poor adherence in order to develop and implement effective adherence interventions.

Funded by the Center for the Promotion of Adherence and Self-Management, Department of Pediatrics, Cincinnati Children's Hospital Medical Center

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Yaman Z. Eksioglu 1,2 , F. H. Duffy 1,2 and J. J. Riviello 1,2 ( 1 Neurology/Epilepsy and Clinical Neurophysiology, Children's Hospital Boston, Boston, MA and 2 Neurology, Harvard Medical School, Boston, MA )

Rationale: Electrical Status Epilepticus of Sleep (ESES) is an electrographic pattern characterized by continuous, diffuse, 1.5 to 3 Hertz spike and slow wave complexes during slow wave sleep. ESES is associated with either focal or generalized epilepsy, neuropsychological impairment, such as cognitive regression, acquired aphasia (Landau-Kleffner syndrome), visual agnosia, epileptic dysgraphia, progressive prosopagnosia, or motor impairments with ataxia or dyspraxia. The diagnostic criteria for ESES have been debated: especially the abundance of spike activity required for the diagnosis, what “continuous” means, must it involve slow wave sleep, whether it is an epiphenomenon or if focal ESES even exists? We postulate that the region involved determines the clinical impairments seen with focal ESES and suggest the term electrical epilepsia partialis continua of sleep (EEPCS) when the epileptiform activity is predominantly focal within the ESES.

Methods: We describe five children with focal ESES with motor, cognitive, speech, and visual problems related to the cortical region involved. Neurocognitive regression was prominent in all.

Results: An 8-year-old girl had a left MCA territory stroke, right hemiparesis, right visual field cut, and focal and diffuse left hemisphere ESES with cognitive/behavioral difficulties that responded to high dose diazepam, levetiracetam, and zonisamide, but ultimately required hemispherectomy.

A 12-year-old boy with a left MCA territory stroke had a right hemiparesis, complex partial seizures, cognitive/attention difficulties, and predominantly focal ESES (left frontal/parietal) that failed multiple treatments but then responded to levetiracetam.

An 18-year-old girl with left frontal-central encephalomalacia, complex partial epilepsy, cognitive, memory/ attention difficulties associated with initially ESES that evolved into focal ESES (left frontal, central and midline central) after treatment, responded to corticosteroids and vagus nerve stimulation.

An 11-year-old girl with periventricular leukomalacia, spastic quadriparesis, generalized epilepsy, and cognitive/behavioral difficulties, initially with generalized ESES which, upon treatment, evolved into focal ESES (bilateral left > right frontal then left > right occipital), had a response to sodium valproate and levetiracetam.

An 8-year-old boy with a history of intraventricular hemorrhage, periventricular leukomalacia, spastic quadriparesis, generalized epilepsy, and focal ESES (left > right occipital) had cognitive and visual difficulties that responded to treatment with high dose diazepam.

Conclusions: Focal-ESES or EEPCS is characterized by focal paroxysmal activity during slow wave sleep and is usually associated with neurological or neuropsychological symptoms related to the cortical region involved. Overall regression occurs when the activity generalizes. Both the EEPCS and clinical impairments may improve with suppression or elimination of the epileptiform activity by spike-suppressors, even with underlying structural disorders.

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Maria A. Montenegro 1 , C. I. Akman 1 , S. Jacob 1 , K. Eck 1 and F. Gilliam 1 ( 1 Columbia University, New York, NY )

Rationale: Clinical observations may have limited value to estimate the seizure frequency in patients with epilepsy. The objective of this study was to evaluate the accuracy of parental report regarding seizure identification in children with epilepsy.

Methods: This was a prospective study conducted at the Columbia Comprehensive Epilepsy Center. Inclusion criteria were age > 1 month-old and < 18 years-old and diagnosis of epilepsy. Family or caregivers were instructed to pay close attention to the child during video-EEG monitoring in order to identify all seizures. Every time a clinical seizure was identified the parent activated the alarm button. The accuracy of parental reporting was evaluated based on the video-EEG monitoring findings.

Results: From a group of 139 consecutive patients evaluated, 78 (31 girls, 47 boys) presented at least one event during video-EEG monitoring. Ages ranged from 8 months to 18 years-old (mean = 8.3±5.6). A total of 1274 events were recorded. Based on parental report, 472 seizures were correctly identified, 623 seizures were missed, and 149 non-epileptic spells were identified as seizures (sensitivity = 43.1%, positive predictive value = 76%). All seizures were correctly identified by only 18/78 (23%) of the families. In 31/78 (40%) patients, seizures were only partially identified, and 10/78 (12.5%) patients did not identify any seizures. In 19 /78 (24.5%) patients, all events identified as seizures were non epileptic spells. Chronological age, age of seizure onset, type of epileptic syndrome, seizure type (focal versus generalized) and presence of developmental delay were not predictors of accurate seizure identification.

Conclusions: Parents and children correctly identify only a minority of clinical seizures based on results from video-EEG monitoring. This finding has important implications for epidemiological and outcomes research in pediatric epilepsy. More accurate methods for seizure detection are necessary to improve both clinical care and research.

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Ingrid E. Tuxhorn 1 and H. Freitag 2 ( 1 Dept of Neurology, Cleveland Clinic, Cleveland, OH and 2 Bethel Epilepsy Center, Bielefeld, Germany )

Rationale: Sturge-Weber Syndrome (SWS) is a rare cause of catastrophic focal epilepsy associated with progressive neurologic and cognitive decline that is ameanable to early surgical treatment. This study aims to characterize longitudinal patterns of development in individual SWS cases that were treated surgically.

Methods: Pre and postoperative clinical parameters describing the severity and extent of the epileptogenic leptangiomatous disease by MRI and EEG, postsurgical seizure control and cognitive developmental profiles of 15 consecutive patients with SWS who had a surgical procedure to treat refractory epilepsy were studied.

Results: All 15 patients had a high seizure and disease burden with daily frequent seizures (3>20/day), status epilepticus (2). The localization was hemispheric in 7, multilobar in 6, bilateral in 2. Nine of 15 (60%) remitted immediately postoperatively and remained seizure free at 2 years (Engel 1A), two became seizure free after 2nd surgery and the remaining 4 (2 bilateral) cases had a significant seizure reduction (Engel 3b). Presurgical and post surgical DQs were below 2SD in all cases and varied considerably. Pre-post developmental quotients reflected: no surgery related loss of DQ, stable but delayed longitudinal DQ curves in 11 patients. Bilaterality, poor seizure outcome and additional comorbidities (deafness) were associated with DQ stagnation in 2 cases and loss od DQ in 1 patient. None of the trajectories documented a dramatic restart or catch up of development after successful surgery. There were no patients with a normal general cognitive ability.

Conclusions: Longitudinal development after epilepsy surgery in children with SWS progresses at a stable velocity but is significantly delayed. There is no evidence for catch up. Early restart of development following surgery may lead to an improved longterm developmental outcome.

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David W. Dunn 1 , T. DeGrauw 2 , C. Johnson 3 , S. Perkins 3 and J. Austin 4 ( 1 Psychiatry and Neurology, Indiana Univeristy School of Medicine, Indianapolis, IN ; 2 Neurology, Cincinnati Chldren's Hospital Medical Center, Cincinnati, OH ; 3 Biostatistics, Indiana University School of Medicine, Indianapolis, IN and 4 Environments for Health, Indiana University School of Nursing, Indianapolis, IN )

Rationale: Decisions about treatment after a first recognized seizure are usually based on the expectation of recurrence. Prior studies have found that children with very early onset seizures, symptomatic seizures, abnormal neurological examinations, and/or intellectual disability are at higher risk for developing recurrent seizures. Children without these risk factors may still develop persistent seizures but there are few data to help predict recurrence. The purpose of this study was to determine risk factors for persistent seizures in a generally healthy group of child with first recognized seizures.

Methods: The 282 children, ages 6–14 years, were part of a study of first recognized seizures. None of the children had mental retardation. Seizure history was obtained at baseline, 18 and 36 months. Seizures were considered persistent if they occurred between every available assessment. Variables assessed were age of seizure onset, IQ, psychotropic drug use, prior unrecognized seizures (n = 102), seizure type and epilepsy syndrome, antiepileptic drug (AED) use, and results of neurological examination, EEG, and MRI.

Results: Persistent seizures occurred in 42/282 (15%) children. There was no association between persistent seizures and age at seizure onset, neurological examination, presence of epileptiform activity or slowing on EEG, IQ, seizure type, epilepsy syndrome, or psychotropic drug use. Children with prior unrecognized seizures were significantly more likely to have persistent seizures (p = 0.002). Persistent seizures occurred in 23.5% of the children with prior unrecognized seizures and 10.0% of those with true first seizures. Children with a normal MRI were less likely to have persistent seizures (p = 0.049). At baseline, AED use was not associated with subsequent persistent seizures, though at follow up, AED use was associated with recurrent seizures.

Conclusions: Prospective studies of adults (Hauser et al., 1998) and children (Shinnar et al., 2000) after first seizure have shown that having a second seizure substantially increases the likelihood of multiple recurrent seizures. Out study extends this find by showing that the presence of a prior unrecognized seizure at baseline assessment significantly increases the risk for persistent seizures. The presence at baseline of prior unrecognized seizures suggests the need for initiation of AEDs.

Funding supported by: NIH/NINDS #22416

References:

1. Hauser AW, Rich SS, Lee JR, et al. Risk of recurrent seizures after two unprovoked seizures. N Eng J Med 1998; 338:429–434.

2. Shinnar S, Berg AT, O'Dell C, et al. Predictors of multiple seizures in a cohort of children prospectively followed from the time of their first unprovoked seizure. Ann Neurol 2000; 48: 140–147.

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Diego A. Morita 1 , A. C. Modi 2 , J. E. Koumoutsos 2 , S. Valentine 2 , S. R. Monahan 1 and T. A. Glauser 1 ( 1 Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH and 2 Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH )

Rationale: The goal of antiepileptic drug (AED) therapy is seizure freedom with no AED intolerable side effects, such that patients experience optimal quality of life (QOL). The purpose of the current study was to: 1) compare QOL in children with new-onset epilepsy to both a normative healthy population, as well as another sample of children with epilepsy and; 2) assess the impact of AED side effects on QOL.

Methods: Participants included 37 children with new-onset epilepsy (Mean age = 7.2 years, 38% female, 57% Caucasian) and their caregivers. Sixty-five percent of children were diagnosed with partial epilepsy and 35% with generalized epilepsy, with 54% on carbamazepine and 46% on valproic acid. Parents completed a generic (Pediatric Quality of Life Inventory: PedsQL) and epilepsy-specific (American Quality of Life in Childhood Epilepsy Questionnaire: USQOLCE) quality of life questionnaire, and the Cincinnati Antiepileptic Drug Side Effect Scale (CASE) one month after initiating AED therapy.

Results: Relative to healthy controls, patients with new-onset epilepsy had poorer Emotional (z =−2.3; p < .05), Social (z =−4.7; p < .0001), and School functioning (z =−5.3, p < .0001) but similar Physical functioning. Relative to an outpatient validation sample of children with epilepsy (Sabaz et al., Epilepsy Behav. 2003 Dec;4(6):680–91), our sample had better Energy/Fatigue (z = 5.4, p < .0001), Self-Esteem (z = 2.0, p < .05), Social Activities (z = 2.6, p < .01), and Overall Quality of Life (z = 3.2, p < .001). The relations between QOL and AED side effects were in the expected direction, with more severe AED side effects being associated with poorer QOL. Specifically, side effects were related to Physical (r =−.56; p < .0001), School (r =−.44, p < .01), Psychosocial (r =−.35, p < .05), and Total functioning (r =−.50, p < .01) on the PedsQL, and Depression (r =−.51, p < .01) and General Health (r =−.45, p < .01) on the USQOLCE.

Conclusions: Children with new-onset epilepsy have impaired QOL on several domains of functioning compared to healthy children; however, their QOL is similar or better than children with epilepsy in Sabaz's validation sample. More severe AED side effects were inversely related to QOL. In order to maximize QOL, healthcare professionals should focus on reducing seizures and minimizing AED side effects.

Funded by the Center for the Promotion of Adherence and Self-Management, Department of Pediatrics, Cincinnati Children's Hospital Medical Center

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Fawad Mian 1 and A. Rodriguez 1 ( 1 Neurology, New York University, New York, NY )

Rationale: Sleep disorders in children are common. Several studies have found an increase frequency of sleep problems in children with epilepsy when compared with normal controls. There have been no studies comparing the prevalence of sleep disorders of children with epilepsy and controls with no epilepsy who present to a Sleep Disorders Center for evaluation.

Methods: We reviewed retrospectively all the children who presented at the New York Sleep Institute from December 2005 to December 2006. We included all the children ages 1 to 20 years-old. We noted the different sleep complaints, Polysomnographic data and final diagnoses and compared children with epilepsy with children referred from the community who did not have epilepsy. We compared the results using chi square and t-student using the JMP program for statistical analysis.

Results: Twenty-three children met our inclusion criteria. Twelve children had epilepsy. The average age was 10.3 years in the epilepsy group and 9.7 years in the non-epilepsy group. The two groups had similar prevalence of symptoms of excessive daytime sleepiness, snoring, insomnia, non-restorative sleep, parasomnia and restless sleep.

The Polysomnography results in children with epilepsy showed a sleep efficiency of 90.3% and a sleep latency of 16.1 minutes. Stage 1 sleep represented 3.1%, stage 2 sleep 37.0%, slow wave sleep 49.8% and REM sleep 10.1%. There were no statistical significant differences with the control group.

Among children with Epilepsy, there were 5 patients with Obstructive Sleep Apnea (OSA), 5 patients with Restless Legs Syndrome, 3 patients with Parasomnias, 1 patient with Delayed Sleep Phase Syndrome and 2 patients with Excessive daytime sleepiness. There were 9 patients with more than one diagnosis.

Conclusions: The prevalence of sleep disorders in children with epilepsy is similar to the children with no epilepsy who present for evaluation at a Sleep disorders Center.

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Dave F. Clarke 1,2 , A. McGregor 1,2 , F. Perkins 1,2 , F. Boop 3,2 and J. Wheless 1,2 ( 1 Pediatric Neurology, University of Tennessee, Memphis, TN ; 2 Comprehensive Epilepsy Program, Le Bonheur Children's Medical Center, Memphis, TN and 3 Pediatric Neurosurgery, University of Tennessee, Memphis, TN )

Rationale: Children with tumors are at risk for intractable epilepsy. The ictal onset zone may involve the tumor or may encompass a wider field involving the surrounding tissue. When there is concern the epileptogenic zone is not isolated to the tumor, or abuts eloquent cortex, invasive monitoring may therefore be required. We proposed that depth and inter-hemispheric electrodes would better define the ictal onset zone. The depth and inter-hemispheric electrodes may also act as a neuro-anatomical border, hence assisting the neurosurgeon during surgical resection.

Methods: Children with tumors and intractable epilepsy, from June 2006-present were retrospectively reviewed. 13 cases were identified, two of whom were repeat surgeries after tumor resection did not terminate the seizures. Of the 11 children without prior surgical resection, 3 children had both depth and inter-hemispheric subdural strip electrodes placed. In two children depth electrode(s) traversed the grid between specific grid electrodes placed over the surface of the lesion and in one case the depth was just adjacent to the grid. The depth electrodes were embedded within the tumor allowing for tumor tissue sampling for epileptogenicity. Two children had tumors approximating the midline and inter-hemispheric electrodes were placed in both cases

Results: In 3 cases (100%), seizure onset, involved the depth electrode and when placed inter- hemispheric electrodes, and in two cases the subdural grid became involved over 15 seconds after seizure onset. Grid involvement in all cases encompassed an area larger than the epileptogenic zone; involving eloquent cortex defined by fMRI,and cortical motor and sensory mapping in two children. Inter-hemispheric strips and depths also complimented stereotactic guided (Stealth) MRI in defining the neuro-anatomical borders of the lesions during surgical resection. All lesions were successfully resected (a low grade oligodendroglioma, a high grade oligodendroglioma, and a harmatomatous lesion). All have remained seizure free.

Conclusions: If a subdural grid was used in isolation for the cases described, the region of ictal onset would not have been captured. Additional coverage with depths and or inter-hemispheric strips was instrumental in better defining the epileptogenic zone. It also allowed for avoidance of critical cortical functional areas. The authors suggest a surface grid may be insufficient in identifying the region of ictal onset in children with intractable epilepsy who have cortical lesions. Unless contraindicated, depth electrodes and, for parasagittal lesions, inter-hemispheric electrodes, should be used when invasive monitoring is required.

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Agathe Laurent 2,3 , E. Panagiotakaki 1 , S. de Schonen 1,2 and A. Arzimanoglou 1,3 ( 1 Epilepsy Unit, University Hospital Robert Debré AP-HP, Paris, France ; 2 LPP, CNRS, University of Paris 5, Paris, France and 3 CTRS-IDEE (Institute for Children and Adolescents with Eplepsy), Hospices Civils de Lyon, Lyon, France )

Rationale: Socio-perceptive competencies integrate and attribute meaning to non verbal cues delivered by human environment. In adults, cerebral functional imaging studies have shown that the temporal cortex is involved in this type of information processing (face identity, gaze direction, emotional expression, voice identity, phrastic and emotional prosody). These data suggest that temporal cortex damage is likely to be associated with abnormal socio-perceptive development.

Methods: To uncover the relationships between temporal cortex and visuo-and auditivo- social competencies during abnormal and normal development and to study possible differences between visual and auditory post-lesional plasticity we prospectively studied 39 children with unilateral temporal lobe epilepsy (TLE) and 9 age-matched control groups (72 healthy children), using tasks that allow evaluation of visuo- and auditory-perceptual processing of cues delivered by faces and voices. We analyzed deficits taking into account the localization of ictal and interictal EEG activity, the age at onset and the duration of the epilepsy and the data provided by cerebral neuroimaging (MRI). We also investigated correlations between socio-perceptual deficits and rest metabolism at FDG-PET (see abstract on SPeDeTEC II study by Chassoux et al.)

Results: Socio-perceptual deficits have been evidenced in 62% of the 39 children with TLE. We didn't find any relationship between the side of the epilepsy and the type of the eventual deficit. We showed that developmental deficits can be dissociated: one socio-perceptual modality impaired and not the other (visual versus auditory and vice versa) and can even be specific to a cue (for example, impairment in face identity with preserved emotional expression). Moreover, those deficits can be observed without any deficit in visual or auditory episodic memory, low level visual processing or speech perception.

Conclusions: The lack of deficit lateralization (despite an early functional asymmetry during normal development) suggests a poor rescuing by the contralateral hemisphere. It also shows a close developmental dependency between the two hemispheres. Persistence of those deficits despite many years of “good” stimulation by the environment suggests poor neuro-fonctional plasticity for those competencies.

Research programme funded by: CNRS, LFCE, FFRE, Fondation Wyeth, ARETNE.

Acknowledgements: Philippe Kahane and Lorella Minoti (Grenoble); Edouard Hirsch and Maria-Paola Valenti (Strasbourg); Marie Bourgeois and Christian Sainte-Rose (Paris, Necker); Philippe Ryvlin, and Karine Ostrowsky (Lyon); Francine Chassoux (Paris, Sainte Anne); Dominique Parrain (Rouen); The multicentric network for epilepsy surgery in children.

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Tatiana Falcone 1 , I. Tuxhorn 1 and D. Janigro 1 ( 1 Neurological Institute, Cleveland Clinic, Cleveland, OH )

Rationale: Childhood psychosis is frequently misdiagnosed leading to a delay in adequate treatment. The goal of our study was to look for markers in routine laboratory screening in a group of children with a first psychotic episode and coexisting epilepsy

Methods: We retrospectively reviewed the records of all psychotic patients admitted to a child and adolescent psychiatric inpatient unit at the Cleveland Clinic over the past 3 years. Out of 1500 cases reviewed, 102 patients below the age of 18 years were identified with first onset psychosis, among them 11 had reported epilepsy.

All the patients were evaluated by the same psychiatrist, using a structured interviewed to diagnosed psychosis and schizophrenia according to the DSM IV, the epilepsy diagnosis was done by EEG and previous past medical history, 4 of the patients were also admitted to the PEMU for further monitoring. Laboratory exams obtained were CBC, CMP, U tox, cooper, lead, ceruloplasmin, Imaging studies (brain MRI or Head CT scan), and also a Brief Psychiatric Rating Scale to quantify the severity of the psychosis

Results: 10% of our psychotic group had been diagnosed with epilepsy.

Most of our patients were male, half of them Caucasian. The most frequent psychotic symptom was hallucinations seen in all patients. 8/11 reported delusions, 5 demonstrated disorganized behavior. 9 /11 had history of violence more frequently against people, half of them against themselves, none of this patients had history of substance abuse (urine toxicology was negative). 4/11 reported a history of physical abuse. 2/11 reported history of sexual abuse. The most frequent comorbidity seen in 6/11 was ADHD. 9/11 were at school, 2/in vocational school. All 11 patietns with psychosis and epilepsy had a monocytosis in their CBC. 3/11 had abnormal EEGs consisting of nonspecific slowing and epileptiform abnormalities in 1 patient.

Conclusions: The incidence of epilepsy in an inpatient cohort of children with new onset psychosis was approximately 10%. Peripheral monocytosis was frequently seen in these patients. We postulate that inflammatory mechanisms may play a role in the CNS manifestations of psychosis and epilepsy.

During the past several years, there has been increasing interest in the role of the blood brain barrier (BBB) in epilepsy, a growing body of evidence has shown that inflammatory mechanisms may participate in the pathological changes observed in epileptic brain as well as in the patients with psychosis. Clinical data also correlate inflammation, immunological responses and psychosis.Further research is needed

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Lucia Fusco 1 , N. Specchio 1 , D. Claps 1 , M. R. Cilio 1 , M. Valeriani 1 and F. Vigevano 1 ( 1 Neuroscience, Bambino Gesù Children's Hospital, Rome, Italy )

Rationale: To describe the clinical entity characterized by severe epilepsy and severe behavioral and cognitive dysfunctions following an acute febrile seizure disorder resembling encephalitis in previously normal children, probably due to an immune-mediated cerebral disorder.

Methods: We selected, both prospectively and retrospectively, patients with intractable seizures and CNS signs of an ongoing immune-mediated encephalopathy.

Results: We studied 8 patients with a mean age of 11.7 + 7 yrs. At the age of 6.7 + 6.2 yrs (9 m–17.6yrs, median 5 yrs) they presented with fever and stupor associated with frequent partial seizures which developed in epileptic status in seven cases and subsequent seizures in one. EEG at onset showed a diffuse slow activity associated with epileptiform abnormalities involving in all cases the temporal lobe, with extension in the frontal area in one, in parietal and occipital in one and in the central regions in two cases. Viral or bacterial infections have been excluded. Oligoclonal bands were present in four out of six tested patients. Brain MRs were normal at onset and during follow-up in three cases. In the other four MRs showed at the onset T2 and FLAIR bilateral hyperintensity over peri-insular regions in three and over frontal and mesial temporal regions in one. The mean follow-up period was 4.2 + 2.2 yrs. All patients developed without latency severe partial epilepsy with relapsing remitting course in six. A spectrum from attention deficits to dementia has been observed in association with intermittent and severe behavioral disorder. Treatment with corticosteroids and/or IVIG determined a reduction of seizure number and improvement in competences.

Conclusions: In these patients severe partial epilepsy with a wide spectrum of behavioral and cognitive disorder is associated to signs of an immune-mediated cerebral ongoing process. The immune-mediated process is suggested by inflammatory CSF changes, reinforced by MR changes and sustained by the efficacy of immune-modulating therapy. The striking improvement in some patients after corticosteroids or IVIG, confirm that the recognition of this entity is highly crucial in the outcome.

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Aimee F. Luat 1,2 , H. T. Chugani 1,2 , E. Asano 1,2 , C. Juhasz 1,2 and S. Sood 1,3 ( 1 Pediatrics, Children's Hospital of Michigan/Wayne State University, Detroit, MI ; 2 Neurology, Children's Hospital of Michigan/ Wayne State University, Detroit, MI and 3 Neurosurgery, Children's Hospital of Michigan/Wayne State University, Detroit, MI )

Rationale: Rationale: Malformations of cortical development (MCD) is an important cause of refractory epilepsy in children. Epilepsy surgery in MCD is challenging because the epileptogenic zone often extends beyond the MRI defined morphological abnormalities and, in some situations, MRI can be normal. In MRI-negative cases, positron emission tomography (PET) can be helpful in identifying MCD. We analyzed the clinical, neuroimaging features, pathologic findings and surgical outcome in 32 children with MCD and intractable epilepsy who underwent epilepsy surgery (2001–2007) in Children's Hospital of Michigan, Detroit. Patients with tuberous sclerosis were not included.

Methods: Methods: Thirty-two children (age at surgery: 3 mo to 20 yrs; 19 boys) underwent presurgical evaluation including MRI, video-EEG and glucose metabolism PET. 18 patients also underwent PET scanning using [11C]-flumazenil (FMZ) and/or alpha[11C]methyl-l-tryptophan (AMT).

Results: Results: Mean age at seizure onset was 2.1 yrs (range: in-utero to 8 yrs). All patients had focal seizures with or without secondary generalization. 3 had associated myoclonic and atonic seizures. 12 patients also had epileptic spasms; 2/12 had asymmetric spasms. In 7 patients (21%), MRI was normal whereas glucose PET scan showed functional abnormalities concordant with the presumed epileptic lobe defined by video-EEG and confirmed by electrocorticography (ECOG). Moreover, in 10 of the 25 MRI-positive cases, glucose PET abnormalities extended beyond the MRI defined lesion. In 6 of these 10 cases, these PET abnormalities were proven to be epileptogenic by ECOG. In 4 patients, FMZ PET or AMT PET provided additional localizing information in identifying the epileptogenic zone. 7 patients underwent one-stage hemispherectomy. After extraoperative ECOG monitoring 2 patients underwent hemispherectomy, 1 subtotal hemispherectomy and the remaining 22 patients lobar/multilobar cortical resection. Thirteen had cortical dysplasia (4 with balloon cells), 6 had polymicrogyria, 3 had hemimegalencephaly, 3 had microdysgenesis, 2 had periventricular heterotopia, 2 had subcortical heterotopia, and one each had lissencephaly/subcortical band heterotopia spectrum, schizencephaly and unilateral perisylvian polymicrogyria. Two patients had associated corpus callosum dysgenesis. Mean follow-up period was 2.3 yrs. Twenty-five patients (78%) achieved Engel class I or II, whereas 6 had Engel class III or IV. However, these 6 surgical failures included 3 who had ‘palliative surgery’ (resection of the major focus with known bilateral epileptogenic foci), and 3 who had incomplete resection of the epileptogenic zone due to proximity to ‘eloquent’ cortex. One patient who underwent hemispherectomy died 2 days post-surgery due to DIC associated with sepsis.

Conclusions: Conclusion: The outcome of epilepsy surgery in carefully selected patients with MCD can be favorable, even in MRI negative cases where PET is particularly helpful. Even in MRI-positive cases, PET scanning provides additional information in delineating the epileptogenic zone to improve surgical outcome.

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Silvia d. Vincentiis 1 , C. A. Silva 2 , M. V. Febronio 3 and K. D. Valente 1 ( 1 Department of Psychiatry, Institute of Psychiatry-Clinics Hospital-University of Sao Paulo Medical School, São Paulo, Brazil ; 2 Pediatric Rheumatology Unit, Children's Hospital of the University of Sao Paulo Medical School, Sao Paulo, Brazil and 3 Rheumatology Division, University of Sao Paulo Medical School, Sao Paulo, Brazil )

Rationale: Women with epilepsy are more likely to have menstrual disorders than women in the general population. Epilepsy itself and antiepileptic drug (AED) use may be causal or contributory factors. There is scarce data on adolescents with epilepsy (AWE). This study was designed to evaluate whether AWE are more likely to have menstrual irregularities and to assess its association with epilepsy syndrome categories and antiepileptic drugs (AEDs).

Methods: Subjects included adolescents aged 10 to 20 years not receiving hormones. Adolescents without epilepsy or any other chronic disorder (35 controls) and AWE (n = 35) receiving AED for 6 months or more were followed during six menstrual cycles for this study.

Results: The mean age of menarche was 11.8 years, similar to that found among healthy Brazilian adolescents (p = 0.082). Fourteen patients (40,0%) had irregular menstrual cycles. Twenty-four patients (68,5%) referred dysmenorrhea. Irregular menstrual cycles (p = 0.05), with longer duration - more than 7 days (p = 0.0003) and longer intervals (p = 0.0244) were more common in adolescents with epilepsy when compared to controls. In the group of AWE, duration of epilepsy (p = 0.06) and presence of generalized seizures were correlated with irregular menstrual cycles with longer intervals. Previous use of VPA and higher seizure frequency were associated with an earlier age of menarche.

Conclusions: Menstrual disorders are significant because they are associated with anovulatory cycles that may increase risks for reproductive dysfunction. Although seizure control remains a major goal in patients with epilepsy, clinicians should also be aware of these potential complications of epilepsy and its consequences for adolescents in childbearing age.

Grant FAPESP 05/03527–3

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Freedom F. Perkins 1,2 , D. F. Clarke 1,2 , V. Brewer 1,2 , A. L. McGregor 1,2 , M. McManis 1,2 and J. W. Wheless 1,2 ( 1 Pediatrics and Neurology, University of Tennessee, Memphis, TN and 2 Le Bonheur Comprehensive Epilepsy Program, Le Bonheur Children's Hospital, Memphis, TN )

Rationale: Autism Spectrum Disorders (ASD) affect one out of 152 children in the U.S. ASD has a distinct neuropsychological profile including pervasive delay in language and social development and presumed genetic heterogeneity. Approximately 25% of children with ASD have interictal epileptiform discharges (EDs) on their EEG with a higher prevalence of seizures. In an ongoing attempt to determine the incidence of epilepsy in ASD patients with abnormal EEGs, we comprehensively evaluated eight ASD children with interictal EDs using DSM IV criteria.

Methods: Eight children (seven males, one female; age: 3–10 years) received a complete neurological evaluation. All underwent an EEG using the International 10–20 Electrode Placement System. Three underwent video EEG monitoring. The EEG was evaluated for localization, laterality, and morphology. Seven of the eight underwent high resolution chromosomal testing, Fragile X testing, complete blood counts and comprehensive metabolic testing (electrolytes, blood urea nitrogen, bicarbonate, liver function studies, serum amino acids and urine organic acids). All children underwent magnetic resonance imaging (MRI) of the brain using an epilepsy protocol with oblique, thin-cut, coronal fluid attenuation inversion recovery (FLAIR) sequences. Six children underwent detailed neuropsychological evaluations which were adapted to each child but included the Gilliam Autism Rating Scale (GARS), Child Behavior Checklist, and/or Vineland Adaptive Behavior Scales.

Results: All eight children had interictal EDs. Five children had para-sagittal EDs (two left hemisphere, two right hemisphere, and one bilateral). Two had left temporo-parietal EDs. One child had rare, right mid-temporal discharges with a predominance of left para-sagittal EDs. One child had generalized EDs. Two out of eight had a history of seizures consistent with partial events. One child with seizures had a normal MRI and left para-sagittal and rare, right mid-temporal EDs; while the other had mild diffuse atrophy with marked atrophy of the left temporal and parietal lobes and EDs in the same region. The remainder of the children had normal MRIs. Genetic and metabolic testing were normal in all children. All of the children demonstrated low adaptive skills, poor emotional and social reciprocity and/or a high probability of autism on neuropsychological testing.

Conclusions: In this ongoing study, two of eight children (25%) with ASD and interictal EDs had epilepsy. Both children had partial seizures consistent with the interictal EEG pattern. Although our case number is small, the preliminary data implies that the epilepsy rate among ASD children with interictal EDs is relatively low. Furthermore, one of those children appears to have both ASD and epilepsy as a result of focal brain injury (which represents a distinct subset of ASD patients). Thus far, neuropsychological data imply low adaptive, verbal and social skills in ASD patients and interictal EDs regardless of the presence of seizures. Continued investigation is warranted.

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Carmen Silvia M. Miziara 1 , M. G. Manreza 1 , L. Mansur 1 and M. V. Estanislau 1 ( 1 Neurology, Sao Paulo University Medical School, Sao Paulo, Brazil )

Table 1.  Qualitative and quantitative tests used on oral praxis evaluation
Tongue movements – tests
T1. Protrude the tongue
T2. Put the tongue tip on the right lip angle
T3. Put the tongue tip on the left lip angle
T4. Put the tongue tip, internally, on the right cheek
T5. Put the tongue tip, internally, on the left cheek
T6. Put the tongue tip on the papillae with the open mouth
T7. Turn down the tongue internally with the open mouth
T8. Put the tongue tip on the upper lip
T9. Put the tongue tip on the lower lip
T10. Move the tongue in and out quickly (5″)
T11. Lateralize the tongue tip to the left angle of the lip and to the right angle quickly (5″)
T12. Move the tongue tip up and down touching the lips quickly (5″)
T13. Elevate and keep the tongue tip on the papillae (3″)
T14. Click the tongue tip against the papillae
T15. Click the tongue tip against the papillae quickly (5″)
T16. Suck the tongue against the palate
T17. Suck the tongue against the palate and click quickly (5″)
T18. Vibrate the tongue tip
T19. Elevate the dorsal face of the tongue several times emitting the sound “KA”
Lips movements
T20. Protrude the lips
T21. Protrude the lips forming a closed “beak”
T22. Retract the lips as a closed smile
T23. Retract the lips as an open smile
T24. Retract the lips inside the oral cavity
T25. Make a closed “beak” and divert to right without move the jaw
T26. Make a closed “beak” and divert to left without move the jaw
T27. Alternate the closed “beak” to left and right quickly (5″)
T28. Vibrate the lips
T29. Click the lips as kissing
T30. Click the retracted lips as kissing
T31. Bite the lower lip
T32. Bite the upper lip
T33. Blow out
T34. Whistle
T35. Suck the own finger
Cheek movements
T36. Fill the cheek up with air
T37. Fill the right cheek up with air
T38. Fill the left cheek up with air
T39. Pass the air from right to left
Jaw movements
T40. Open and close the mouth
T41. Move the jaw right
T42. Move the jaw left
T43. Move the jaw forward
Palate movements
T44. Provoked move of the palate (a,ã)

Rationale: The benign focal epilepsy of childhood with centrotemporal spike (BECTS) is very frequent (25%). The seizures are focal, no frequent, and the rolandic area is involved. The cognitive functions are preserved and the neurological exam is normal, except for oral praxis. Children acquire fully developmental praxis during growth. So it is important the assessment of this cognitive function in different ages. The aim of this study is compare oral praxis of children of same age with and without rolandic epilepsy.

Methods: Seventy four right-handed children, with age ranging from 4 to 15 years entered the study. Patients fulfilled all clinical and electrographic BECTS criteria according to ILAE. The inclusion criteria were: two or more seizures, electroencephalogram with Rolandic discharge and normal brain magnetic resonance imaging (MRI). A control group with 239 right-handed children, with no familial/personal history of epilepsy was created for comparison. Control group was not submitted to a previous phonoaudiologic therapy, and was age, gender and school-matched. Both groups were evaluated on the same praxis tests. To evaluate oral praxis, a 44 tests protocol was created. Six of the tests were quantitative (T10; T11; T12; T15; T17 and T27) and the other tests were qualitative, as showed in Table 1. The motion list consisted on isolated or sequenced ones, approaching tongue, lips, cheeks, jaw and palate. All patients had routine waking and sleep EEG. Results received statistical treatment (ANOVA test, chi-square test and Kruskal-Wallis test). A 95% significance index was considered (p < 0.05), as previously reported for biological trial.

Results: There was no significant difference between both groups related to age (p = 0.171). Children with BECTS showed quantitative measurements of oral praxis lower than children of the control group (p < .0001). The same feature occurred related to some qualitative measurements: children with BECTS showed a worst performance than children without epilepsy (p < .0001) in the tests: T5; T7; T16; T25; T26; T28; T33 and T43. The others tests did not show any significant difference between the two groups.

Conclusions: There are few studies correlating oral praxis and rolandic epilepsy in childhood. Our study showed that there is some degree (quantitative or qualitative) of oral dyspraxia in those children, regardless age, when they are compared to non-epileptic children. Children with rolandic epilepsy showed a very poor result in quantitative (which have a movement sequence more difficulty than single movements) and in some qualitative tests. These tests require a more elaborated action planning, controlled by frontal lobe. We agree that the presence of those dyspraxia in epileptic group is consequence of motor planning interference, due to epileptic discharge in this area.

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Olgica Laban-Grant 1 , M. Lancman 1 and C. Zaroff 1 ( 1 Northeast Regional Epilepsy Group, White Plains, NY )

Rationale: A small percentage of patients with absence epilepsy do not respond to conventional medical therapy. Recently it was reported that newer antiepileptic medications might be a useful alternative. We present patients from our practice that failed to respond to some of the newer antiepileptic medications.

Methods: Case series.

Results: Nine patients (3 boys and 6 girls) were found not to respond to conventional therapy with ethosuxsimide and valproate. Patients were consequently placed on 3 to 8 different antiepileptic medications (levatiracetam-six patients, topiramate and lamotrigine four, zonisamide and klonopin three, phenytoin and phenobarbital two and oxcarbazepine, clobazam, primidone, gabapentin carbamazepine - one). Onset of seizures was between the ages of 2 and 8 years old. Three patients had at least one generalized tonic clonic seizure in their lifetime but absence was the predominant seizure type. One patient had occasional non-epileptic seizures characterized by unresponsiveness. EEG findings in all patients showed 3 Hz generalized spike and wave with normal background. One patient had bilateral centro-temporal spikes during sleep on initial VEEG that were not present on the following VEEG monitoring. Three patients had a family history of seizures. Three patients had history of febrile seizures. Family reported behavioral problems (agitation, irritability) in three patients. Three patients had language delays. Atypical clinical features were reported in three patients (neck hyperextension, “yawning” vocalization and facial hypotonia). No clear predisposing factors were identified in patients with medically refractory absence. Quality of life was significantly affected in all patients.

Conclusions: Childhood absence epilepsy is usually considered a benign syndrome since seizures usually respond well to monotherapy. We report cases that remained refractory to a number of antiepileptic medications from the initiation of the treatment. No clear predisposing factors were identified.

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Goretti L. Maia 1 , E. Garzon 1 , M. Spinosa 1 , M. Rahal 1 , C. Marx 1 , H. Carrete Jr 1 ., M. Gomes 1 , A. Martins 1 and A. Sakamoto 1 ( 1 Neurology, UNIPETE (Unidade de Pesquisa e Tratamento das Epilepsias) - UNIFESP-EPM, São Paulo, Brazil )

Rationale: West syndrome (WS) usually consists of a triad formed by the association of epileptic spasms, neuropsychomotor delay and hypsarrhythmia, even though one of these features may be absent. Developmental delay and regression may either precede or follow the beginning of the epileptic spasms. This type of seizure may rarely continue throughout childhood. Most patients (50–70%), however, develop other seizure types and 18–50% evolves to Lennox-Gastaut Syndrome (LGS). WS is classified in terms of etiology as symptomatic or cryptogenic. The symptomatic group comprises 80% of WS cases. Few studies have compared the electrographic evolution in WS according to this classification. The aim of this study was to compare the clinical and electrographic outcome between these two groups.

Methods: Retrospective study of patients diagnosed with WS being followed-up between 2002 and 2007 at the Child Epilepsy Ambulatory of the Neurology were evaluated giving emphasis to clinical and electrographic evolution.All patient had video-EEG or prolonged EEG for diagnosis and evolution during treatment for WS. The patients had ACTH, Vigabatrin, Valproic Acid, Topiramate or Nitrazepan for treatment of WS. The EEG were done once a week until WS be controlled. The long term follow-up was done with clinical history, prolonged EEG or video-EEG.

Results: Our sample consisted of 10 patients with mean follow-up time of 38.3 moths (14 to 49), 8 male. The mean age at admission was 11.4 months. All patients presented with some degree of neuropsychomotor delay. In Group I, cryptogenic cases (3 patients) two had language delay, one had motor delay and one showed global impairment of neuropsychomotor delay. Out of seven patients with symptomatic WS (Group II), one showed only language delay, the remaining patients had motor deficits and global neuropsychomotor delay. Regarding the EEG evolution, the group I showed focal, multifocal and generalized epileptiform discharges (1 patient each) and the group II showed focal (4 patients) and multifocal (1 patient) epileptiform abnormalities. One of the 2 remaining cases showed non epileptform abnormalities and one normal EEG.

Only 1 patient evolved to LGS (group I), 2 patients are seizure free (1 group I and 1 Group II), 6 patients evolved to focal epilepsy (group II) and 1 has both, focal and generalized seizures types (group I).

Conclusions: LGS was not the most frequent evolution from WS in our study. The majority of these cases evolved with focal epilepsy and 2 patients are seizure free.

Although the types of epileptic syndrome developed after WS obviously depend of etiology, it is known that the early diagnosis and treatment of WS, probably can modify the evolution. We believe that the high incidence of LGS described at the literature is dependent of etiologic bases and the time spend for WS control.

Maybe the precocious treatment and diagnosis of WS and weekly EEG performed during the treatment of WS had contributed to this evolution.

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Joan I. Schall 1 , J. Trabulsi 1,3 , V. A. Stallings 1 and C. A. Bergqvist 1,2 ( 1 Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA ; 2 Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA and 3 Wyeth Nutrition, Wyeth Pharmaceuticals, Collegeville, PA )

Rationale: Children with intractable epilepsy (IE) are at risk for medication side effects and continued seizure activity. Suboptimal growth and nutritional status are common.

Cerebral palsy (CP) is a common comorbid diagnosis among children with IE and is known to be associated with low REE. A better understanding of the energy requirements in children with IE with and without CP may help minimize nutritional related side effects and optimize their care. The purpose of this study was to evaluate the resting energy expenditure (REE) of children with IE compared to age-matched controls and determine factors that contribute to differences in REE.

Methods: A cross sectional study of REE and growth status was performed in prepubertal children with IE compared to healthy children matched for age, gender and fat free mass (FFM). Children with IE were subdivided into those with and without cerebral palsy (CP). REE (kcal/day) was measured by indirect calorimetry and expressed as percent predicted using Schofield equations. Energy intake from 3 day weighed food records was assessed for children with IE only and expressed as percent estimated energy requirement (%EER) for low active children. Statistical analysis included descriptive analysis, students T-test, Wilcoxon rank sum, and multiple regression analyses.

Results: 25 Children with IE (15 males, 5.4 ± 2.2 years) was compared to 75 healthy children (43 males, 6.3 ± 1.7 years). Children with IE were younger, had significantly poorer weight and BMI status, lower FFM and FM and lower REE compared to healthy children (−7% predicted, p < 0.05). Their energy intake was suboptimal with 65% below EER for low active children. Children with IE and CP had particularly poor growth status, lower weight, height, body mass index (BMI) z-score, FFM and fat mass (FM) and REE compared to healthy children (−13% predicted, p < 0.005). There was a trend (p < 0.1) towards lower energy intake compared to children with IE without CP.

REE adjusted for FFM, FM and gender was significantly lower in children with IE and CP (−110 kcal/day, p = 0.02), and tended to be lower in children with IE without CP as well (−42 kcal/day). FFM, gender and CP were significantly associated with REE and explained 60% of the variance. In children with IE, CP, FFM and energy intake significantly predicted the REE and explained 56% of the variance.

Conclusions: CP largely explained the suboptimal growth status and lower REE of children with IE compared to healthy controls. In children with IE lower REE was associated with reduced energy intake. These results suggest that the growth faltering in children with IE is not due to excessive energy expenditure and would likely respond to increased caloric intake. Future nutritional and behavioral interventional studies are needed to determine the impacts of increased caloric intake on growth and other health outcomes in children with IE.

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Shelly K. Weiss 1 , S. Whiting 2 , E. Wirrell 3 , E. Donner 1 , J. Dooley 4 , G. Ronen 5 , K. Farrell 6 , S. Litwin 1 and L. Carmant 7 ( 1 Neurology, Hospital for Sick Children, Toronto, ON, Canada ; 2 Neurology, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada ; 3 Neurology, Alberta Children's Hospital, Calgary, AB, Canada ; 4 Neurology, IWK Health Center, Halifax, NS, Canada ; 5 Neurology, McMaster University Medical Center, Hamilton, ON, Canada ; 6 Neurology, B.C. Children's Hospital, Vancouver, BC, Canada and 7 Neurology, Sainte-Justine Hospital, Montreal, QC, Canada )

Rationale: To evaluate clinical factors that predict normalization of EEG at 6 months in a prospective study of subjects with new onset infantile spasms that were treated initially with vigabatrin and vitamin B6. This study is part of a larger randomized double blind multicenter clinical trial designed to evaluate the effect of flunarizine on long-term cognitive outcome in infantile spasms. Enrollment is complete, however the study has not been unblinded.

Methods: 69 children in 7 Canadian tertiary care epilepsy centers with new onset infantile spasms were recruited over a 2-year period. All children received vigabatrin and vitamin B6 initially. Subjects were randomized to conventional treatment with flunarizine or placebo for 6 months. At 2 week those with persistent spasms and/or hypsarrythmia on video-EEG were treated with high dose ACTH. Children who failed ACTH at 1 month were converted to topiramate. In addition to video-EEG at 2 week, all subjects had routine sleep/wake EEG at baseline, 6, 12, 24 and 30 months. Subjects had detailed neuropsychological evaluation at baseline, 6, 24 and 30 months. Subjects had thorough evaluation for symptomatic etiologies including brain MRI.

Results: The factors analyzed for this study were age at diagnosis of spasms, presence of asymmetric spasms or focal seizures, time to treatment, developmental level (as reported by study neurologist enrolling child), and etiology. A Fischer exact test was used to compare each risk factor. Factors associated with normal EEG at 6 months included: age of onset between 4 and 12 months (p = 0.03), absence of developmental delay at baseline (p = 0.03), idiopathic or cryptogenic etiology (p = 0.01). Factors found to have no significance were time to onset of treatment (> or < 60 days) and whether subject had asymmetrical spasms and/or focal seizures.

Conclusions: The risk factors associated with a normal EEG at 6 months of age included: typical age range at onset of spasms; normal development prior to treatment; and absence of a demonstrated etiology. These data may be helpful in providing families of children with infantile spasms treated with a similar protocol (vigabatrin followed by ACTH for non-responders) with a more precise prognosis.

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Joan Conry 1 , A. Yaun 1 , P. L. Pearl 1 , N. Elling 1 and M. Sullivan 1 ( 1 Department of Neurology, Children's National Medical Center, Washington, DC )

Rationale: The VNS was approved by the FDA in 1997 for treatment of complex partial seizures (CPS) in persons 12 years and older. Unfortunately, effect on specific seizure types other than CPS, and efficacy in special needs children has not been systematically assessed. This study analyzes the response of drop seizures (rather than total number of seizures), and includes changes of medications as an outcome confounder.

Methods: VNS was implanted in 21 children (13 male) age 4–19 years with medically refractory severe drop seizures between 1998 and 2006. Follow-up ranges from 6 months-8 years 9 months. Seizure frequency and medications pre-implant and at latest follow-up are reported.

Results: 17 of 21 patients had a dramatic decrease in drop seizures: 10 had zero drops at latest follow-up; 7 had 90% decrease. 4 had no change in drop seizures. 10 had at least 75% reduction in other seizure types. Only 3 patients were on the same medications at latest follow-up as pre-implant. 2 had a corpus callosotomy after implant of VNS.

Conclusions: A dramatic reduction in drop seizures was seen in 75% of children in this series. VNS is effective in reducing drop seizures in children with severe medically refractory seizures. The benefit seen in these children reflects the effects of VNS therapy, medications, and in some cases corpus callosotomy.

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Maria L. Manreza 1 , C. M. Miziara 1 , V. G. Serrano 1 , E. Brandao 1 , H. Rovere 1 , S. C. Silva 1 and V. de Paula 1 ( 1 Neurology, Sao Paulo University Medical School, Sao Paulo, Brazil )

Rationale: Specific types of epilepsy are more common in adolescence, as idiopathic generalized syndromes or symptomatic localization-related syndromes. Besides, incidence of epilepsy varies as a function of age. Recently, it has been described a focal benign syndrome, probably idiopathic, in adolescents (Capovilla G, Gambardella A, Romeo A et al. Benign Partial Epilepsies of Adolescence: A Report of 37 New Cases. Epilepsia 2001; 42(12):1549–52). Thus the aim of this study is to describe the pattern of epilepsy that is observed in adolescent patients in an outpatient neurology unit.

Methods: In a prospective design, epileptic patients, aged between 11 and 20 years, were referred to Neurology Dept - Sao Paulo University Medical School - from January 2006 to December 2006. The crises and epileptic syndromes were classified according to the International League Against Epilepsy (ILAE) for epilepsy criteria. All patients were submitted to electroencephalogram (EEG), performed during drowsiness, sleep and wakefulness.

Results: 61 patients (38 boys and 23 girls) entered the study. Seizures started at the mean age of 10.86 years (range, 1–18 y). The average time of crises onset was 5.32 years (range, 1–16 y). In the male group, seizures started at the mean age of 11.3 years (range, 1–18 y) and, in the female group, at 10.13 years (range, 1–15 y). According to etiology we observed that the idiopathic epileptic syndrome was predominant (over 50%)in both groups; the symptomatic epileptic syndrome was present in 23.7% of the male group and 21.7% of the female group; and the probably symptomatic epilepsy syndrome was observed in 23.70% and 21.74% in male and female group, respectively. Our study showed that 32 (52.4%) patients have met idiopathic epilepsy syndrome criteria. Amongst with these patients 17 (53.35%) have generalized activity and 15 (46.8%) have focal activity. Patients with generalized idiopathic epilepsy had the onset of seizures at 12.35 years of mean age. Otherwise, patients with focal epilepsy had the onset of seizures at 11.9 years of mean age. Twenty five patients (41%) had symptomatic or probably symptomatic epileptic syndrome, one patient had had non epileptic seizure (pseudo-seizure), and another one had acute symptomatic seizure. Twenty-three of them have focal activity.

Conclusions: Despite the fact that idiopathic generalized epilepsy is the most frequent form of epilepsy in adolescence, other type of benign epilepsy localized-related has also been detected by few authors in this age group. In our study, idiopathic generalized epilepsy was the most common form of epileptic syndrome in adolescence. Otherwise, based in our results we believe that benign epilepsy localized-related are more common than we suspected before. In our cohort 11 patients (18%) presented a focal activity, confirmed by EEG, with normal neurological examination and normal MRI. We suppose that these results indicate a presence of a benign focal syndrome that started during adolescence. It is necessary to perform additional studies to confirm that diagnosis.

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Saulat Bilal 1 , P. Maertens 1 and J. Sosnowski 2 ( 1 Neurology, University of South Alabama, Mobile, AL and 2 Pathology, University of South Alabama, Mobile, AL )

Rationale: Early infantile epileptic encephalopathy with suppression bursts (EIEE) or Ohtahara syndrome is a rare cause of intractable cryptogenic epilepsy. Dystrophin deficiency is rare in cases of congenital myopathy and has not previously been associated with cryptogenic EIEE.

Methods: We report a full term girl who presented with severe hypotonia at birth and seizures at day 2 of life. Seizures were characterized by tonic spasms lasting 5 to 10 seconds and frequently accompanies by transient respiratory failure. Spasms occurred in clusters and appeared induced by photic stimulation or other stimuli. Dyspphagia remained a problem even after seizures improved with polypharmacy. Dysplasia survey was negative. Neuroimaging studies were normal. Extensive metabolic studies were negative. Interictal EEG showed a typical suppression-burst pattern and ictal EEG was characterized by a lateralized alpha-like activity followed by irregular polysharp slow waves. A muscle biopsy was performed.

Results: Histopathological changes within muscle biopsy specimen confirmed a congenital myopathy with diffuse dystrophin deficiency as demonstrated by immuno-chemical staining. Merosine immuno-chemical staining was not decreased.

Conclusions: We postulate that a neonatal diminished expression of dystrophin can lead to enhanced seizure susceptibility and contribute to epileptogenesis. Dystrophin deficiency should be investigated in patients with Ohtahara syndrome without structural brain pathology.

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Vrajesh Udani 1 , S. Udani 1 , P. Gadgil 1 and D. Licht 2 ( 1 Department of Pediatrics & Neurology, PD Hinduja National Hospital, Mumbai, India and 2 Children's Hospital of Philadephia, Philadelphia, PA )

Rationale: This is a clinical observational study on 8 children who had new-onset refractory status epilepticus (NORSE), a recently described entity. This report highlights the emergence of generalised dyskinesia during the course of the illness and the good response to ACTH in many of the patients with a good eventual outcome.

Methods: Retrospective chart review identified 7 patients from a tertiary care center in Mumbai, India while one active patient was included from a Philadelphia hospital. Our inclusion criteria were 1) Normal patients prior to onset of status epilepticus (SE)

2) Refractory SE defined as no / transient response to first line AEDs with clinical and / or EEG evidence of ongoing seizures

3) Lack of a known etiology despite exhaustive investigations

Results: 8 patients (5 boys, 3 girls) were included with a mean age of 4.9 yrs. They were all previously in good health. 6 patients had a transient febrile illness at onset. Between 3–6 classes of AEDs were used to control SE with all patients being on continuous midazolam infusions and 3/8 patients receiving propofol and / or pentobarbital / pentothal infusions. IVIG / methylprednisone was used in 6 patients wile the ketogenic diet was tried in 4. 5 patients required prolonged ventilation. 7 patients developed moderate to severe persistent dyskinesias (despite discontinuation of phenytoin) which started usually as the SE abated and continued for week to months.

Exhaustive investigations did not yield a definite etiology in any patient. MR imaging was normal at onset and subsequently showed varying degrees of cerebral atrophy.

In 4 patients ACTH was followed by seizure cessation within 2–14 days (mean 6.2 days). The US patient relapsed during ACTH taper after a few week only to respond again after an ACTH dose increase. In 2 patients SE responded without ACTH though dyskinesias persisted for 2 and 10 months. Dyskinesias responded within 2 and 4 week respectively.

At 1–4 years follow-up 4 patients are normal, 1 patient has moderate-severe language delay and the US patient has continuing seizures despite ACTH.

Of the 2 patients not given ACTH one is vegetative 5 years later while one has autism and mild MR.

Conclusions: A series of 8 cryptogenic NORSE patients is described most of whom developed a significant dyskinetic syndrome which has not been described in other series. We postulate a possible role for ACTH in treatment of NORSE and the subsequent dyskinesia.

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Al de Weerd 1 ( 1 SEIN Zwolle, Zwolle, Netherlands )

Rationale: Epileptic seizures occur at different times of the 24-hour day, possibly under the influence of cerebral (circadian) rhythms. Up to now, human studies in this respect are limited to the dichotomy: sleep/wake or at best mention the time of the day or sleepstage in which the seizures were seen. More detailed studies were done in animals, but gave different results. Modern methods of assessing the phase of the human circadian rhythm were not used up to now. The aims of our study are two-fold: 1) to describe the time of the 24 hr. day on which seizures occur and 2) to provide ideas and if possible guidelines, how to investigate the influence of the biological clock on seizures.

Methods: Consecutive patients were included (children 2–15 yrs. or adults) with focal seizures (clinical and EEG event for at least 5 seconds) during longterm EEG and video recording. The latter method provided the exact time of the epileptic events and the (sleep) stage the seizure occurred in. As methods to evaluate the biological clock we assessed: 1) simple clocktime, 2) questionnaires and actigraphy, 3) continuous core body temperature measurement, 4) melatonin curves, 5)manipulation of the biological clock.

Results: In total 870 seizures were assessed. Nearly half occurred when the patient was awake; the others preferentially during NREM I-II sleep. The period 2–8 pm was over represented in the prevalence of seizures. This holds for adults and children and all types of seizures with the exception of frontal seizures in adults which were seen mostly at the end of the sleep period. For the second aim of the study we had the following considerations. The results from simple methods for assessment of the influence of the biological clock (real clock time, questionnaires, actigraphy, melatonin curves and temperature measurement)are often interrelated. To delineate the real contribution of the biological clock, it is necessary to rule out factors which may be circadian as well (light/dark, meals,etc.). Constant routine procedures do so, but introduce sleepdeprivation and give again a potential bias, in particular in patients with epilepsy. The most plausible way to reach our aims is to manipulate the biological clock by changes in behaviour and using light and melatonin as tools for changing the phase of the circadian rhythm (forced desynchrony).

Conclusions: Correlation of simple clocktime and the moment a seizure occurs gives some insight in (circadian) rhythms in epilepsy. These measurements may be biased through other interfering circumstances. In order to have more precise information, new methods for the assessment of the biological clock are necessary. Melatonin curves, continuous core body temperature measurement in combination with forced desynchrony of the biological clock, are the methods of choice.

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Abuhuziefa Abubakr 1 and I. Iwuchukwu 1 ( 1 New Jersey Neuroscience Institute, JFK hospital, Seton hall university for Graduate medical education, Edison, NJ )

Rationale: Asymmetric tonic posture of upper limbs (figure 4) has been shown to be an accurate lateralizing sign in focal epilepsy of the temporal lobe. However, involvement of lower limbs in lateralization of TLE is rarely reported. Therefore we evaluated the lateralization of figure 4 of the lower limbs in TLE.

Methods: We retrospectively reviewed records of 91 consecutive patients with TLE admitted to EMU at JFK hospital. Video EEG data were analyzed for the presence of figure 4 of the lower limbs observed during secondary generalized tonic clonic seizures.

Results: There were 38 males (age range 17–71 yrs) and 53 females (age range 18–81 yrs). Thirty-one patients had right temporal lobe focus and sixty had left focus. Thirty-seven out of ninety-one patients were excluded due to lack of secondary generalized tonic clonic seizure. In fourteen patients we failed to record the seizure on camera and fourteen patients had electrographic events only. Therefore 26 patients with a total of 142 secondary generalized seizures were evaluated and 88 were assessable. Fifty-seven of eighty-eight seizures (66.8%) showed figure 4 with asymmetric tonic extension of lower limbs and all were contralateral to the epileptogenic hemisphere. This occurred equally in both sides (8 patients with left TLE and 8 with right TLE) constituting 61.3% of the patients. However, four seizures (4.6%) showed tonic flexion of the lower limbs (two patients with left and one with right focus) and 27 seizures (28.6%) showed tonic extension of the lower limbs (4 patients has left and 3 patients has right temporal lobe focus).

Conclusions: Lower limb asymmetric tonic posturing (figure 4) is frequently present during secondary GTC seizures. It has an excellent lateralizing value in TLE, which is always contralateral to the epileptogenic hemisphere.

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Batool F. Kirmani 1 and K. C. Ess 1 ( 1 Neurology, Vanderbilt University, Nasville, TN )

Rationale: Tuberous sclerosis complex (TSC) is a genetic disorder characterized by the widespread development of benign tumors in multiple organs. It is caused by mutations or deletions of either the TSC1 or TSC2 genes. While affecting multiple organs, the most common neurological manifestations of TSC are epilepsy, mental retardation, and autism. Epilepsy in particular is seen in up to 80–90% of patients and is often intractable, with a poor response to antiseizure medications. The rationale of this study is to define the natural history of TSC and frequency of status epilepticus in pediatric patients with TSC treated with levetiracetam. Status Epilepticus is defined as a seizure of greater than thirty minutes duration.

Methods: In this retrospective evaluation, we acquired patient data from two sites specializing in the care of children with TSC: Vanderbilt Children's Hospital (Nashville, Tennessee) and St. Louis Children's Hospital (St. Louis, Missouri). A patient database containing fields for the neurological and developmental manifestations of TSC was acquired and analyzed using SPSS software. We enrolled 53 patients with TSC. The age range is from 11 months to 31 years. This group was then retrospectively analyzed for presence of status epilepticus and treatment with levetiracetam.

Results: 17 (32%) of the patients were currently on levetiracetam, 11 (20%) failed levetiracetam secondary to lack of efficacy and behavior problems and 25 (48%) were never tried on levetiracetum. Suprisingly the incidence of status epilepticus was low in our patient population seen in only 8 patients (15%). 6 of these 8 patients had no further incidences of status epilepticus after the initiation of levetiracetum. The episodes of status epilepticus range from a single to four episodes. Mean follow up after initiation of levetiracetum was 17 months with a range of 9–28 months. The remaining 2 were never tried on levetiracetam.

Conclusions: The use of levetiracetam as adjunctive antiepileptic therapy may reduce the incidence of status epilepticus in patients with tuberous sclerosis complex.

This research was supported by Young Investigator Research Program (YIRP) of UCB Pharma.

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Piotr Mirowski 1 , D. Madhavan 2 , Y. LeCun 1 and R. Kuzniecky 2 ( 1 Courant Institute of Mathematical Sciences, New York University, New York, NY and 2 Comprehensive Epilepsy Center, New York University, New York, NY )

Rationale: Seizure onsets often appear widespread on intracranial EEG, leading to uncertainty in their localization. We propose a new dynamical model combined with Time-Delay Neural Networks (TDNN) that generates EEG time series prior and after simulated surgical resection. This is done for the purpose of predicting changes to seizure propagation upon alterations of certain channel parameters.

Methods: Ictal EEG recordings of 4 patients were obtained from the NYU Epilepsy Center database, and converted into numerical EEG data sampled at 400 Hz. A dynamical model was constructed that generates EEG time-series from a time-series of hidden internal sources. Inference consists in finding the most likely sequence of sources given observed EEG and a trained dynamical model (a Time-Delay Neural Network). Learning consists of iteratively adjusting the parameters of the TDNN and inferring the most likely sequence of sources. Once the TDNN is trained, the dynamical model was applied to another EEG time series of the same patient with inference of the corresponding sources. The model can be used to predict in closed-loop a short-time horizon (1–3 sec) continuation of EEG. Simulation of surgical resections on the EEG time-series was performed by (1) setting some channels to zero, (2) inferring the time-series of sources, (3) predicting the continuation of the time-series of sources, (4) generating corresponding EEG. This method was used to compare (A) deactivating channels in the seizure onset zone vs. (B) deactivating remaining channels. Linear univariate and bivariate measures were used to assess influence of (A) and (B) on seizure propagation.

Results: Numerical data from a partial seizure as recorded on a 32-channel EEG grid in a bipolar montage was used as target for the dynamical model. After training, 1-second EEG predictions were started at different times. The performance of the predictive dynamical model was assessed on unseen cross-validation data from another seizure (same patient). Similar signal-to-noise ratios were obtained for 1-step (14 dB), 20-step (0.2 sec, 5.2 dB) and 100-step (1 sec, 3 dB) iterated predictions on both in-sample and out-of-sample data (see figure). This demonstrates that the generative model is able to learn a hidden dynamical model of the propagation of epileptic seizures, and generalize it to other seizures from the same patient. However, when trying to deactivate certain channels by setting them to zero, the inferred hidden states did not properly reconstruct EEG data. Further research to address that problem involves using more realistic generative models and more hidden states.

Conclusions: We have developed a dynamical generative model able to learn patterns in intracranial EEG at ictal onset, and are currently enhancing it so that it can predict dynamic changes in response to alteration of specific EEG channels. This system could potentially aid the epileptologist in the analysis and planning of surgery, and delineate diffuse epileptic networks in brain.

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Richard C. Burgess 1 ( 1 Epilepsy Center, Cleveland Clinic, Cleveland, OH )

Rationale: The Cleveland Clinic has a 25 year history as a tertiary referral center for patients with epilepsy. Rigorously kept records of seizure/epilepsy classification and neurophysiologic results are saved electronically. With the advent of a hospital-wide electronic medical record, picture archiving and communication system, digital video recordings, and other scattered electronic repositories, data about our patients is entered electronically in many areas, but is not available in an integrated fashion when needed to generate reports to referring doctors or to carry out sophisticated research queries.

We sought to put all of this information at the neurologist's fingertips for clinical and research purposes, by developing a system that provides access via standard web browser.

Methods: The database contains both text and graphics (see figure 1). Data is imported from other servers, as well as maintained by pointers.

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[ Fig 1. Database structure ]

For access we employed the Faces framework deployed on a J2EE application server. Because of its deployment in a very busy clinical center, careful attention was paid to real-time performance issues, e.g. by employing asynchronous Javascript and XML to handle page display simultaneous with data retrieval.

In addition to the carefully classified neurophysiologic and epilepsy information, a range of graphical and tabular information has been organized for incorporation into the database. This includes pictorial information, formerly available ad hoc from a variety of sources, such as: grid placement maps, depth placement maps, stimulation maps, ictal & interictal discharge maps, MRI & PET segments, ictal SPECT, results of volume reconstructions, coregistrations showing grids, intra-operative photos, video clips, evoked potentials, pathology slides, etc.

Results: The application is a complex mix of Java files, JSP files, JSP fragments, Javascript files, configuration files, etc.—over 2000 files and approximately 14 megabytes.

In addition to ongoing data input the database has been back-filled with data on more than 65,000 patients from our previous codified textual database. Data output is provided in standardized formats that are familiar to users, easy to work with, and aesthetically pleasing, like HTML and PDF.

It is possible to create and view the inpatient evaluation reports in their entirety (see figure 2). New classes of reports (such as for patient management conferences) can be derived from the fundamental information by abstracting and using a built-in templating engine.

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[ Fig 2. Sample report ]

Conclusions: Learning from experience in previous large database development projects, we focused our efforts during this software design on a) obtaining rapid results, quickly visible to and useable by the users, and b) employing modern web-based tools to speed development and performance. This philosophy has yielded a clinical workflow aid for communication with many disparate sources and for manipulation of data in order to flexibly present results. It has also been designed to include powerful data aggregating tools for research purposes.

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Sanjib Sinha 1 , S. A. Patil 2 , V. Jayalekshmy 2 and P. Satishchandra 1 ( 1 Neurology, NIMHANS, Bangalore, India and 2 Neuomicrobiology, NIMHANS, Bangalore, India )

Rationale: The role of cytokines in people living with epilepsy (PWE) is increasingly being recognized. The mechanisms by which seizures induce the synthesis of cytokines are still unknown but could be due to glutamate release from the neurons during seizures activating the cytokine transcription from the glia. In this study, we analyzed the serum cytokine in PWE and correlated it with their phenotype and other parameters.

Methods: One hundred PWE (M:F = 61:39; age at onset and presentation: 22.4± 17.05 and 25.9 ± 16.5 years respectively; duration of epilepsy: 42.6± 70.0 months) were prospectively recruited after obtaining the consent. The serum samples was collected in all (within 24 hours of last seizure) and in 16 patients, second sample was also collected, when they were seizure-free for >2 week. The serum cytokine levels [a) Pro-inflammatory: TNFα, IFNγ IL-1β, IL-2; b) anti-inflammatory: IL-4, IL-6] was assessed by ELISA in patients and healthy controls.

Results: The type of seizures (n = 100) was major (45), partial (41) and status epilepticus (SE = 14), while the epilepsy syndromes were idiopathic generalized (53) and localization related (47). The serum cytokines (n = 100) were: a) Pro-inflammatory: TNF-α (36), IFN-γ (20), IL-1b (11), IL-2 (22), and b) anti-inflammatory: IL-4 (22) and IL-6 (42) compared to the controls. There was significant correlation between anti-inflammatory and pro-inflammatory cytokines (p = 0.002). Correlations were noted between male gender and IL-1b (p = 0.04), positive family history and IL-1b (p = 0.001), no alcohol use and TNFα (p = 0.05), >1 year history of epilepsy and IL-1b (p = 0.02), SE and IL-6 (p = 0.04). There were no correlations with type or duration of epilepsy, imaging abnormality, and mono or polytherapy. Serial analysis during the seizure-free period revealed decrease in cytokine levels: TNFα (25% to 12.5%), IFNγ (12.5% to 0%), IL-1b (25% to 0) and IL-2 (6.2% to 6.2%), IL-4 (18.8% to 0%) and IL-6 (18.8% to 6.2%).

Conclusions: Elevated serum cytokines levels were detected during the immediate post-ictal phase in PWE, which reduced when they were seizure free. Though it might suggest a cytokine-mediated inflammation, its exact pathogenesis remains unclear.

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Ji Soo Choi 1 , G. L. Krauss 1 and P. W. Kaplan 1 ( 1 Johns Hopkins School of Medicine, Baltimore, MD )

Rationale: EEG features which distinguish non-convulsive status epilepticus (NCSE) and encephalopathy are controversial. Readers may use a number of EEG domains—discharge-complex morphology, frequency, rhythmicity/evolution and focality to conclude whether a particular record shows NCSE. The prioritization of these features, however, has not been formalized. We classified EEGs previously interpreted as showing NCSE into NCSE “probability grades”. We then determined the association between NCSE “probability grades”, EEG features, and patients' clinical outcomes: history of seizures alone, acute cortical injury with a history of seizures, or acute injury only.

Methods: We identified 49 EEG records with NCSE patterns on EEG summaries. Two electroencephalographers independently read and graded the EEGs, followed by a conference to reconcile any differences. Each record was assigned a NCSE probability grade on a scale of 1–4: 1 = borderline; 2 = possible; 3 = probable; and 4 = highly probable. The spectrum of features used to determine probability grades (low to high) were: waveform morphology (slow, broad sharp/triphasic, sharp/spike), rhythmicity (non-rhythmic, quasi-rhythmic, rhythmic), frequency (<2 cps, 2–2.5 cps, > 2.5 cps) and focaility (diffuse, asymmetric, focal).

The readers independently determined final diagnosis for patients while blinded to EEG results. Based on AED response, clinical history and imaging, patients were classified as having: 1) seizures alone, 2) seizures and acute cerebral injuries and 3) acute cerebral injuries only. We then compared NCSE EEG “probability grades” and patients' final clinical diagnosis.

Results: High probability NCSE EEG grades were characterized by focal, frequent (>2.5 cps), and very sharp or very rhythmic waves; diffuse patterns were >2.5 cps, sharp and rhythmic. Lower probability grades were < 2.5 cps, slow wave morphology, and quasi-rhythmic or non-rhythmic. Nearly all (10 of 11) patients with “highly probable” NCSE on EEG had clinical NCSE (see table). Lower probability grades, however, had a variable association with seizures and acute injuries. An overall association between EEG probability grades and clinical NCSE and acute injuries was present only when patients with triphasic EEG patterns were excluded (Chi-square = 12.7, p = .0475). Most patients with triphasic waves (7/10) had acute injuries, e.g. ischemic injury.

Conclusions: Patients with highly probable NCSE grades on EEG were strongly associated with clinical NCSE whereas patients with lower probability grades had a variable association with seizures and acute injuries. Triphasic waves were not a reliable marker of NCSE. Our study shows that a specific constellation of EEG features may distinguish patients with seizures from patients with encephalopathies only.

Correlation between Clinical Diagnosis and NCSE Probability Grades

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Samrina Hanif 1 , G. Mathews 1 , A. Lagrange 1 and B. Abou-Khalil 1 ( 1 Neurology/Epilepsy, Vanderbilt, Nashville, TN )

Rationale: The international seizure classification depends primarily on the mode of seizure onset. Partial onset seizures may become secondarily generalized, whereas generalized onset seizures remain generalized throughout their course. We report the clinical and electrographic features of six patients with generalized epilepsy who had recorded seizures with a generalized onset and subsequent evolution into a focal discharge.

Methods: Patients were included if they had strong evidence for generalized epilepsy based on interictal EEG, no focal MRI or exam abnormalities, no consistent focal interictal EEG abnormalities, and recorded seizures that clearly had a generalized EEG onset with subsequent focal evolution. We reviewed these patients' medical records, video-EEG studies, imaging data, and response to treatment. IRB approval was obtained for this retrospective review.

Results: Patients were aged 2.5 to 22 at the time of their study. Five were female, one male. All patients were referred for intractable seizures and were admitted for confirmation of the diagnosis and classification of seizure type. Four were thought to have complex partial seizures by history and five of the patients were treated with antiepileptic medications which were not effective against absence or myoclonic seizures. After admission all patients had strictly generalized interictal epileptiform activity. The ictal electrographic onset was with generalized spike-and-slow-wave activity in all seizures. In 4 patients the discharge started with regular three Hz spike-and-wave typical of absence. In two patients the seizures began with irregular and brief spike-and-wave activity. The ictal discharge evolved into bitemporal rhythmic delta activity in one patient, left posterior quadrant polyspike-and-slow-wave activity in two patients, and rhythmic alpha activity in the left posterior temporal area in one patient. The video recorded clinical seizures that began as generalized absence (4 patients) or generalized myoclonic (2 patients). The most common subsequent clinical pattern was prolonged behavioral arrest with mild automatisms and altered responsiveness followed by postictal confusion (5 patients). In one patient mild generalized clonic activity occurred with later focal clonic activity. The seizures tended to be prolonged (only one lasted less than 6 minutes). Of note is that one patient also had isolated typical generalized absence and another isolated typical generalized myoclonic seizures recorded. After treatment with appropriate AEDs, three patients are seizure-free, one had marked improvement, and two had a moderate decrease in seizure frequency.

Conclusions: Some generalized-onset seizures can acquire clinical and electrographic focal features and be mistaken for complex partial seizures. However, these seizures can require antiepileptic medications with efficacy to control generalized seizures.

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Top: generalized onset seizure with focal evolution Bottom: generalized absence seizure without evolution in the same patient

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Andreas Schulze-Bonhage 1 , T. Bast 3 , F. Deimling 1 , A. Ebner 4 , C. E. Elger 5 , S. Fauser 1 , R. Keimer 7 , T. Mayer 8 , B. Oehl 1 , M. Ostertag 2 and M. Trippel 2 ( 1 Epileptology, University Hospital, Freiburg, Germany ; 2 Stereotactic Neurosurgery, University Hospital, Freiburg, Germany ; 3 Pediatric Neurology, University Hospital, Heidelberg, Germany ; 4 Mara, Bethel Epilepsy Centre, Bielefeld, Germany ; 5 Epileptology, University Hospital, Bonn, Germany ; 6 Epilepsy Centre, Kork, Germany ; 7 Olgahospital, Stuttgart, Germany and 8 Epilepsy Centre, Kleinwachau, Germany )

Rationale: The analysis of semiological elements can contribute to the classification of epileptic seizures, and to the generation of hypotheses about the localization of the epileptogenic zone in patients with focal epilepsy. We analyzed semiological characteristics of gelastic epilepsy in a homogeneous group of 23 patients with hypothalamic hamartomas.

Methods: 230 video-eeg-documented seizures from 23 patients were included in the analysis. All suffered from drug-resistant focal gelastic epilepsy due to hypothalamic hamartomas and underwent presurgical monitoring. Mean age of patients was 24.2 ± 11.9 years, 8 patients were female. Auras and motor-elements of seizures were documented and analyzed descriptively on a patient basis.

Results: The most common aura type was epigastric (occurring in 17.4% of patients), less common were cephalic and visual auras (present in 8.7% of patients). Motor phenomena included tonic, clonic, dystonic and hypermotor movements as well as automatisms. 52.2% of patients had bilateral tonic, 47.8% unilateral tonic phenomena. Clonic phenomena were noted bilaterally in 26.1% and unilateral in 30.1% of patients. Dystonia and eyelid myoclonia were less common (17.4% each). Hypermotor movements occurred in 21.3% of patients, manual automatisms in 43.5% and oral automatisms in 30.4% of patients.

Conclusions: Semiologic characteristics included typical elements of temporal and frontal lobe seizures. Particularly frequent were bilateral tonic and clonic elements. Gelastic seizures are thus difficult to differentiate from seizures of temporal or frontal origin not only regarding EEG findings but also when taking into account characteristic semiological elements except for periods of laughter.

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Friedhelm C. Schmitt 1 , D. Meinken-Jäggi 1 and H. J. Meencke 1 ( 1 Epileptologie, Epilepsie-Zentrum Berlin-Brandenburg am Evangelischen Krankenhaus Königin Elisabeth Herzberge, Berlin, Germany )

Rationale: Epilepsy surgery is a well established measure in pharmacoresistent focal epilepsy. There is a rate of seizure free patients after 1 year of 66% (Wiebe et al, N Engl J Med. 2001 Aug 2;345(5):311–8.). But there are very little data about long term seizure outcome exceeding two years (Schmidt et al, Epilepsy Res. 2004 Jul-Aug;60(2–3):187–201). We have analysed seizure outcome 10 years after epilepsy surgery in 50 patients with pharmacoresistent temporal lobe epilepsy (TLE).

Methods: We analysed the records of all consecutivly operated patients with TLE, operated on before May 1997 with a minimum follow up (FU) of 10 years. FU visits were 3 month, 6 month and than every following year post op. The outcome was defined by the Engel-outcome classification and has been prospectively documented in the patient records.

Results: The age range of 50 patients was between 9.8 and 58.2 years. 66% had a left sided, 34% a right sided TLE. The surgical approach was a modified very restricted temporal pole resection and amygdalo-hippocampectomy in mesio-temporal epilepsies and an extended lateral neocortical resection in temporo-lateral epilepsies. After 10 years FU (in 16 patients) there are still 69% patients in class I and additional 19% patients in class II. There is a slight but not significant difference between mesio-temporal and temporo-lateral epilepsies and between left and right sided operated patients. Also, in some patients, there was a shift between the classes during the 10 year period.

Conclusions: We report about an excellent seizure outcome 10 years after surgical intervention in TLE. This outcome is due to careful patient selection which considers the morphology, the occurrence of bilateral interictal discharges and the spread of seizure pattern to the contralateral side.

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Jose Tellez-Zenteno 1 and L. Hernandez 1 ( 1 Division of Neurology, University of Saskatchewan, Saskatoon SK, SK, Canada )

Rationale: Callosotomy has been used over the years to treat seizures in patients with epilepsy and is most effective for atonic seizures (“drop attacks”), tonic-clonic seizures, and tonic seizures. It is believed that the efficacy of this procedure is high in patients with drop attacks (more than 80%) and could be useful for other types of seizures. The objective of this study is to provide evidence-based estimates of the seizure outcome after callosotomy for different type of seizures

Methods: An expert in library resources and electronic databases searched electronic sources such as Medline, Index Medicus, and the Cochrane database. We also searched bibliographies of pertinent reviews and original articles, book chapters and expert consultation. Two reviewers independently applied the following inclusion criteria: studies published since 1980, with more than 10 patients undergoing callosotomy, reporting seizure outcome. We considered outcomes in children and adults. We used seizure freedom as defined by authors. Two investigators independently extracted data, resolving disagreements through discussion

Results: Of 795 available articles, 100 potentially eligible were reviewed in full text. Fifty three studies fulfilled eligibility criteria. Overall the median proportion of patients with developmental delay before callosotomy was 94% (95% CI 93–95). The proportion of patients with partial callosotomy was 83% (95% CI 83–84) and complete callosotomy was 10% (95% CI 9–11). Globally the proportion of seizure free patients after callosotomy was 11% (95% CI 9–13). The corresponding proportion of seizure free status for drop attacks was 38% (95% CI 35–41), grand mal seizures was 20% (95% CI 16–24), tonic seizures 17% (95% CI 11–22), absence seizures 24% (95% CI 17–30), myoclonic jerks 15% (95% CI 9–21) and for complex or simple partial seizures was 17% (95% CI 12–22). We explored other outcomes such as year of study and seizure outcome after partial and complete callosotomy.

Conclusions: After callosotomy, 11% of patients become seizure of all types of seizures and 38% from drop attacks. This metanalysis reports low rates of seizure free status in general and for the different type of seizures. As was expected, the benefit of callosotomy was higher in patients with drop attacks, although the rate of seizure free is lower compared with the general belief that more than 80% of patients could be seizure after this procedure. Sources of heterogeneity are explored. Sources of heterogeneity and non-seizure outcomes were analysed.

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Asma M. Moheet 1 , A. Rajarathinam 2,3 and J. Bautista 1 ( 1 Neurology, The Cleveland Clinic Foundation, Cleveland, OH ; 2 Neurology, NMC Hospital, Dubai, United Arab Emirates and 3 Neurology, Madurai Medical College and Government Rajaji Hospital, Madurai, India )

Rationale: There are two types of premonitory symptoms reported by patients with epilepsy: auras and prodromes. Auras are traditionally considered specific for focal epilepsy, and usually occur seconds to minutes prior to a seizure. Prodromes occur over longer intervals prior to seizures and may serve as early warning signs of seizures to allow a patient to prevent injury. Our objective was to determine the frequency of auras and prodromes in an outpatient epilepsy clinic population, and to compare the characteristics of auras and prodromes in both focal and generalized epilepsy patients.

Methods: Clinical records of all patients attending an adult epilepsy outpatient clinic over a six month time period were reviewed. Patients with a diagnosis of epilepsy based on International League Against Epilepsy criteria were included. Patients with only single seizures or febrile seizures were excluded. Detailed medical histories were obtained with characteristics of seizure semiology, including auras and prodromes, using standardized interviews. Prodromes were defined as symptoms minutes to days before a seizure. Auras were defined as symptoms up to one minute before a seizure.

Results: A total of 1891 consecutive epilepsy outpatients were studied. Eight hundred ten patients (43% of total) were classified as having focal epilepsy, and 1081 patients (57% of total) were classified as having generalized epilepsy. Overall, 22.1% reported auras, and 54.8% reported prodromes. The majority of prodromes were described as headache or irritability. Four hundred ten patients (50.6%) with focal epilepsy and 626 patients (57.9%) with generalized epilepsy reported prodromes. One hundred forty seven patients (18.1%) with focal epilepsy and 270 patients (25.0%) with generalized epilepsy reported auras. The most common auras were characterized by nausea, and urinary or fecal urgency. Both nausea and déjà vu auras were seen with relatively equal frequency in both generalized and focal epilepsy patients. Auras were more frequent in idiopathic generalized epilepsy compared to symptomatic generalized epilepsy.

Conclusions: These results suggest a substantial proportion of patients with both focal and generalized epilepsy have premonitory symptoms before their seizures. Interestingly, 25% of patients with generalized epilepsy in this study reported auras up to one minute before seizure occurrence. Prior studies suggest as many as 70% of idiopathic generalized epilepsy patients will report an aura. Clinicians should not let a reported aura exclude the diagnosis of generalized epilepsy if other features of the history and evaluation suggest generalized epilepsy. Patient-reported auras are not specific to focal epilepsy.

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P. Satischandra 1 , S. Sinha 1 , T. C. Yasha 2 , S. K. Shankar 2 and S. Ganesh 3 ( 1 Dept of Neurology, NIMHANS, Bangalore, India ; 2 Neuropathology, NIMHANS, Bangaloare, India and 3 Department of Molecular Genetics, IIT, Kanpur, India )

Rationale: Lafora disease (LD) is an autosomal recessive, fatal form of progressive myoclonus epilepsy characterized by the presence of intracellular polyglucosan inclusions in the brain, liver and skin. Though reported sparsely from all over the world, there are geographic isolates such as south India where higher frequency has been reported. The aim was to describe the clinical, pathological, electrophysiological and genetic aspects of Lafora disease from south India, emphasizing the specific phenotypic characteristics from this region.

Methods: The case records of the histopathological proven cases (n = 47) of Lafora disease have been reviewed and the phenotypic characteristics were analyzed.

Results: Forty seven cases of LD were seen between 1982 to 2007 at NIMHANS, Bangalore, India. The age ranged from 8 to 20 years with a mean of 13.3 ± 2.2 years. The duration of illness ranged from 2 months to 9 years (3 ± 2.2 y). All patients had myoclonus with GTCS. Cognitive decline was seen in 42 (87.3%). 10% had visual loss. Optic atrophy was seen in 10 (21.2%). Scalp EEG was abnormal in all. However photosensitivity, a hallmark of this disorder from the western countries was seen in only 8.5% of cases. It is interesting to note that EEG and SSEP gave clue in the asymptomatic sibs of the patient's, years before clinically manifested. Positive family history was noted in 15 (32%). Three families had more than 3 members affected. Axillary skin biopsy confirmed the diagnosis in 44 cases and remaining was positive in liver and brain. Genetic evaluation done in 15 cases, six were EPM2A positive and six were EPM2B. Latter had longer duration of illness compared to the former.

Conclusions: Geographic isolate 47 cases of Lafora disease, one of the largest series in the world literature have been reported from south India. This is probably due to high rate of consanguinity in this region. Genotype - phenotypic variation of this disorder will be highlighted.

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Arnoldo Soto 1 , F. Duran 2 , J. Rincón 2 , A. Marques 2 , I. Marques 2 , H. Scholtz 3 , J. Rey 4 , G. Contreras 5 , V. Sainz 5 , E. Pernía 5 , A. Faoro 5 and L. M. Rangel 5 ( 1 Unidad de Neurología, Hospital Domingo Luciani, Caracas, Venezuela ; 2 Servicio de Neurocirugía, Hospital Domingo Luciani, Caracas, Venezuela ; 3 Servicio de Neurocirugía, Centro Médico Docente La Trinidad, Caracas, Venezuela ; 4 Servicio de Neurocirugía, Clínica Atias, Caracas, Venezuela and 5 Servicio de Neurología, Hospital Universitario de Caracas, Caracas, Venezuela )

Rationale: To analyze efficacy and quality of life (QoL) data in patients with pharmacoresistant epilepsy treated with adjunctive Vagus Nerve Stimulation (VNS) Therapy at the Hospital Domingo Luciani in Caracas, Venezuela.

Methods: 23 patients (13 M/10 F) were prospectively evaluated between 2000 and 2005. Mean age: 23.3 ± 9.52 years (median, 24; range, 7–42 years). Mild mental retardation was observed in 7 patients, moderate in 7 and severe in 1; 8 patients had a normal mental development. Nine patients had partial seizures and 14 had multiple types of seizures. Seizures were counted at baseline and after 6 months (N = 23), 12 months (N = 12) and 24 months (N = 10) of treatment with VNS Therapy. QoL data from 18 patients were collected at baseline and after 6 months of VNS Therapy using the FEGEA Scale.

Results: There was a mean seizure reduction of 77.9% (95% CI: [58.5; 97.2]), 95.9% (95% CI: [93.6; 98.2]), and 95.8% (95% CI: [93.1; 98.4]) after 6, 12 and 24 months of treatment with adjunctive VNS Therapy, respectively. Median seizure reduction was 95.0% (95% CI: [86.7; 96.7], p < 0.0001), 97.1% (95% CI: [93.3; 98.7], p = 0.0005), and 96.4% (95% CI: [93.3; 98.7], p = 0.0020) after 6, 12 and 24 months of VNS Therapy, respectively. Significant improvements in QoL were observed in all evaluated domains of the FEGEA Scale after 6 months of treatment.

Conclusions: Our experience in Venezuela shows that adjunctive VNS Therapy remains an excellent option for the treatment of patients with pharmacoresistant epilepsy. VNS Therapy is also associated with improvements in quality of life.

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Marco Fedi 1 , L. Bach 2 , S. F. Berkovic 1 , J. O. Willoughby 3 , I. Scheffer 1 and D. C. Reutens 4,1 ( 1 Neurology, Austin Helath, Heidelberg, VIC, Australia ; 2 Department of Endocrinology, Alfred Hospital, Monash University, Melbourne, VIC, Australia ; 3 Department of Neuroscience, Finders University, Adelaide, SA, Australia and 4 Southern Clinical School, Monash University, Clayton, VIC, Australia )

Rationale: Mutations of the neuronal nicotinic acetylcholine receptors (nAChRs) subunits have been linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). The hypothalamo-pituitary system is densely innervated by cholinergic fibers and activation of the nAChRs modulates the release of anterior pituitary hormones. Here we studied the effect of central cholinergic activation on the release of anterior pituitary hormones in individuals affected by ADNFLE.

Methods: Thirteen subjects affected by the α4-Ser248Phe mutation (4 male, mean age 43.2 ± 16.8) and 41 healthy volunteers (24 male, mean age 36.2 ± 12.2) were studied. Serum levels of GH, LH, FSH, PRL, TSH, thyroxine and cortisol were measured at baseline, at 30 and 60 minutes after infusion of physostigmine. Anthropometric measurements in controls, subjects with ADNFLE and in additional family members without the mutation were also obtained.

Results: Cholinergic activation increased the serum levels of GH, PRL and reduced the levels of FSH in controls but not in subjects with the α4-Ser248Phe mutation. Subjects with the mutation were shorter and had a greater body mass index than unaffected members of the pedigree.

Conclusions: This study demonstrates that the α4-Ser248Phe mutation selectively affects cholinergic-mediated GH and PRL secretion. It is possible that the neuroendocrine deficit partially contributes to the clinical phenotype of ADNFLE. In addition, these findings suggest a role of the nACh receptor in human growth regulation.

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Kjell Heuser 1 , E. Tauboll 1 , M. Cvancarova 2 and L. Gjerstad 1 ( 1 Neurology, Rikshospitalet, Oslo, Norway and 2 Biostatistics, Rikshospitalet, Oslo, Norway )

Rationale: Hippocampal sclerosis (HS) is a common feature in Temporal Lobe Epilepsy (TLE). The majority of studies accomplished in the past decade indicate that TLE with HS can be considered as an epileptic condition different from other focal TLEs. However, the question whether TLE with HS is a unique biological entity is not yet answered. The aim of this study was to compare phenotypic characteristics of TLE patients with and without HS.

Methods: 218 patients were diagnosed with TLE using the ILAE criteria. Only patients of Caucasian race and age over 18 year's were included. The patients completed a standardized evaluation form, and a case record form was completed by a doctor or nurse. Epidemiological data and clinical features were compared.

Results: 56 (25.7%) patients were diagnosed with HS versus 162 patients (74.3%) without HS. Age at epilepsy onset was lower in patients with HS (p = 0.002), with 50% onset before age of 6 years in HS patients, in contrast to 23.4% in non-HS patients. Incidence of simple partial seizures (p = 0.002) and complex partial seizures (p = 0.002) was significantly higher in the HS-group. However there was no difference in generalized tonic-clonic seizures. Incidence of ictal psychiatric symptoms (p = 0.015) as well as autonomic symptoms (p < 0.001) were higher in TLE patients with HS. There was neither any significant difference in frequency and appearance of ictal motor symptoms, nor in ictal somatosensory or special-sensory symptoms. Interictal standard EEG showed no difference between the two groups. There was a higher appearance of childhood febrile seizures in patients with HS (p = 0.043). In contrast, patients without HS appeared to have more family members with febrile seizures in childhood (p = 0.019).

Conclusions: Our study identified significant differences in patients with HS regarding epidemiological, clinical and diagnostic aspects supporting that TLE with HS is a unique biological entity. A proper classification of subgroups in TLE and a clear definition of “key features” in TLE with HS are important in diagnostic-, treatment- and prognostic terms, and deliver crucial information to future phenotype-genotype studies.

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Mark Quigg 1 , M. L. Johnson 3 , C. L. Hucek 1 , K. C. Barner 2 , O. C. Prokhorenko 2 , D. P. Redmond 2 , M. E. Landau 2 and W. W. Campbell 2 ( 1 Neurology, University of Virginia, Charlottesville, VA ; 2 Neurology, Uniformed Services University of Health Sciences, Washington, DC and 3 Pharmacology, University of Virginia, Charlottesville, VA )

Rationale: Although clinical features help distinguish epileptic seizures (ES) from nonepileptic pseudoseizures (PS), continuous video-EEG (CV-EEG) is necessary for diagnosis. Artifacts, rare events, or availability may leave diagnosis ambivalent or infeasible. Regularity of convulsive motor activity may add additional diagnostic utility.

Methods: Patients between ages 16–60 y were admitted for CV-EEG diagnosis of convulsions. Spells selected for analysis consisted of generalized gross motor activities. Movements were recorded with the use of a wrist-mounted accelerometer. The temporal profile of regularity of movements were characterized with approximate entropy (ApEn) and peak-to-peak amplitude of repeated patterns (PPARP).

Results: 19 PS and 15 ES were evaluated. ES were significantly more irregular than PS (mean ApEn ES = 1.78, PS = 1.38, p = 0.0027; mean log PPARP ES = 1.72, PS = 2.80, p = 0.005 Mann-Whitney U test). Threshold values for the minimum ApEn during an event = 1.4 distinguished ES from PS with Se = 86% and Sp = 74%; mean log PPARP threshold = 1.6; Se = 73%, Sp = 84%.

Conclusions: Two measures of regularity of movements obtained with limb accelerometry distinguished convulsions arising from ES from PS with reasonable accuracy in this pilot study. Accelerometry may be developed into a useful adjunct in the diagnosis of convulsions.

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Ricardo S. Centeno 1 , F. A. Vaz-Guimarães Filho 1 , K. Lin 1 , M. H. Noffs 1 , H. Carrete Jr 1 ., A. C. Sakamoto 1 and E. M. Yacubian 1 ( 1 Department of Neurology and Neurosurgery, Federal University of São Paulo, São Paulo, Brazil )

Rationale: Patients with mesial temporal lobe epilepsy (MTLE) may present ictal onset contralateral to the unilateral hippocampal sclerosis (HS) during prolonged monitoring with scalp-sphenoidal electrodes, which has been attributed to the so-called “burned-out hippocampus.” However, depth electrode monitoring has confirmed false lateralization of the non-invasive evaluation. It has been suggested that in this situation the hippocampus is so badly damaged that recruitment of enough neocortical neurons to produce visible scalp discharges is not accomplished until propagation of the seizure to the contralateral temporal lobe. Up to now quantitative assessment to determine how damaged/sclerotic the hippocampus is to be called “burned-out” is lacking. The objective of this study was to evaluate the degree of HS in these patients using quantitative MRI.

Methods: Pre-surgical patients diagnosed with MTLE who presented false lateralization during video-EEG monitoring were re-submitted to it using semi-invasive foramen ovale electrodes. Hippocampal volume and degree of asymmetry between the atrophic and contralateral hippocampi were measured in 1.5 T MRI using the same protocol for all patients according to previously published protocols (Lin K, et al. Epilepsia. 2007 Apr 13; [Epub ahead of print]). We identified four patients harboring the so-called “burned-out hippocampus.” Surgical outcome was graded according to Engel's classification. Furthermore, a comparative analysis was performed between the group of four patients (BO group), another group with 24 matched controls (patients with MTLE not “burned-out” - MTLE group) and a healthy control group with 30 volunteers, members of the medical staff.

Results: The mean volume of the atrophic hippocampus in BO group was 1111.77 mm3 (SD 206.56) while contralateral hippocampus measured 2327.26 mm3 (SD 305.63), with degree of asymmetry of 70.52% (SD 17.05%). With a mean post-surgery follow-up period of 20 months (5–43 months) two patients were Engel I and one, Engel III. The fourth patient is still awaiting surgical treatment. The mean volume of the atrophic hippocampus of the MTLE group was 1081.82 mm3 (SD 388.21) and of the contralateral 1891.35 mm3 (SD 206.82) with asymmetry index of 58.12% (SD 29.15%). Statistical analysis did not demonstrate any difference in the volume of the atrophic hippocampus and degree of asymmetry between BO and MTLE groups (p > 0.05). Larger contralateral hippocampi were observed in BO group when compared to MTLE group. Their values reached marginally statistical significance (p = 0.06). In the healthy control group, the mean hippocampal volume was 2078.21 mm3 (SD 268.05).

Conclusions: Quantitative assessment by MRI did not demonstrate volumetric evidences of the so-called “burned-out hippocampus.” Pathophysiologic mechanisms involved in its pathogenesis need further elucidation.

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Ronald L. Thibert 1 , K. D. Conant 1 , E. K. Braun 2 , P. L. Bruno 1 , M. P. Nespeca 3 , R. R. Said 4 and E. A. Thiele 1 ( 1 Pediatric Epilepsy Program, Massachusetts General Hospital, Boston, MA ; 2 Angelman Syndrome Foundation, Aurora, IL ; 3 Pediatric Neurology, University of California, San Diego, San Diego, CA and 4 Pediatric Neurology, Comprehensive Epilepsy Program, University of Texas Southwestern Medical Center, Dallas, TX )

Rationale: Angelman Syndrome (AS) is a neurodevelopmental genetic disorder consisting of multiple genetic subtypes characterized by global developmental delays, severe speech impairment, ataxia, and frequent laughter. Over 80% of affected individuals have epilepsy, often consisting of multiple seizure types and refractory to multiple medications. Although several studies have examined epilepsy in AS, all have been limited to a cohort of less than 100 people.

Methods: An electronic survey was conducted through the Angelman Syndrome Foundation containing detailed questions relating to both the natural history of epilepsy in AS as well as various treatments of epilepsy in AS. Respondents were asked to describe their AS family member's seizures as free text as well as choose answers from a list of choices

Results: There were 461 respondents of patients with AS, with an average patient age of 13.9 years (5.3 years at diagnosis), 56% of whom were male. Of the 461 patients, 396 (86%) had epilepsy, with 60% of those with epilepsy having multiple seizure types (average of 1.9 seizure types per respondent), and an average age of epilepsy onset of 3.8 years. Of those with epilepsy, 48% had generalized tonic-clonic seizures, 41% had atypical absence seizures, 40% had atonic seizures, 32% had apparent complex partial seizures, 12% had myoclonic seizures, 9% had tonic seizures, 6% had apparent partial or focal motor seizures, 2% had infantile spasms, and 1% had other seizure types or syndromes including Lennox-Gastaut Syndrome and gelastic seizures.

A total of 59% of those with epilepsy had only generalized seizures, while only 11% had only apparent partial onset seizures (complex partial or focal motor), and 30% had mixed (both generalized and partial onset) seizures.

While 31% of those with epilepsy were seizure free at the time of this survey, at least 28% of subjects over the age of 15 actually had a worsening of their epilepsy after puberty.

Conclusions: Similar to previous studies, epilepsy was present in over 80% of individuals with AS, with a large percentage having multiple seizure types, most commonly generalized tonic-clonic seizures, atypical absence seizures, and atonic seizures. Epilepsy in AS is considered to be a generalized epilepsy, but 11% of those with seizures had only apparent partial onset seizures, while another 30% had both partial and generalized seizures. Those with deletions had a higher incidence of epilepsy as compared to those with UPD, imprinting defects, and UBE3A mutations, and likely also had more frequent seizures and more seizure types. Those with unknown mutations had epilepsy rates and seizure types similar to those with deletions. While epilepsy in AS is thought to improve with age, a significant percentage of those patients over age 15 actually had worsening of their epilepsy after puberty.

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Matthew M. Troester 1 , Y. Ng 1 , R. Haine 2 , S. Chung 3 , K. Chapman 1 , C. Drees 3 and J. Kerrigan 1 ( 1 Pediatric Neurology, Barrow Neurological Institute, Phoenix, AZ ; 2 Child and Adolescent Services Research Center, Rady Childrens Hospital - San Diego, San Diego, CA and 3 Adult Epilepsy, Barrow Neurological Institute, Phoenix, AZ )

Rationale: Hypothalamic hamartomas (HH) are an uncommon malformation of the ventral hypothalamus associated with treatment-resistant epilepsy. Since February 2003, our institution has evaluated and treated a substantial number of HH patients. We sought to determine the spectrum of EEG and ictal video EEG (VEEG) abnormalities in this patient population.

Methods: Institutional Review Board approval and patient informed consent was obtained for prospective database entry to include medical history and prior diagnostic studies. We correlated prior EEG and VEEG findings with clinical features.

Results: One hundred and forty-three charts were reviewed. Ten patients were excluded: for lacking a history of epileptic seizures (n = 4) or due to a lack of clinical data (n = 6). Data was collected and analyzed on the remaining one hundred and thirty-three patients. Mean age at time of data analysis was 15.8 years (range 1 to 59 years). There were 79 males (59%). At evaluation, 77% of patients had gelastic seizures, 58% of patients had complex partial seizures (CPS), and 21% had generalized tonic-clonic seizures. All other seizure types were seen in less than 10% of patients.

Available data for routine EEG consisted of 102 EEGs on 73 patients. Sixty-eight percent of these EEGs were abnormal. Generalized background slowing was seen in 47% of these abnormal records, and focal slowing in 41%. Epileptiform features were seen in 79% of these abnormal EEGs (26% generalized, 43% focal and 30% multifocal). Most epileptiform abnormalities were noted in the temporal (37%) and frontal lobes (32%).

Seventy of the 133 (53%) patients underwent VEEG for a mean of 55.2 hours (range <1 hour to 192 hours). A total of 82 VEEG sessions were available for review. Ten VEEG sessions failed to capture an event. Events were reviewed in the other 72 VEEG sessions on 61 patients. The majority of events were of either a gelastic (61.4%) or CPS phenotype (16.8%). There were 591 gelastic events. No ictal change was noted in 439 (74%). An ictal change was noted in 152 gelastic events (26%). Similar percentages of gelastic events were generalized (54%) or focal (44%) and a minority were multifocal (2%). Localization data was available on 69 of these 152 gelastic events and 54 (78%) localized to the frontotemporal head regions. There were 162 CPS events. No ictal change was noted in 69 events (43%). In the 93 events where an ictal change was noted, 67 events were focal (72%), 25 events were generalized (27%) and 1 event (1%) was multifocal. Localization data was available on 69 of these 93 CPS events and 65 events (94%) localized to the frontotemporal head regions.

Conclusions: There is a diversity of EEG features in the HH patient population. A significant percentage of seizure events fail to demonstrate any appreciable change in background EEG with standard visual analysis. The lack of EEG change with many clinical seizures, and the wide spectrum of abnormalities in the ictal EEG (when they do occur), suggest that scalp EEG and VEEG have limited utility in the pre-surgical evaluation of these patients.

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Morten I. Lossius 1 , E. Tauboll 2 , P. Mowinckel 3 and L. Gjerstad 4 ( 1 2 National Centre for Epilepsy, Division for Clinical Neuroscience, Rikshospitalet Medical Center, Oslo, Norway ; 2 Department of Neurology, Division for Clinical Neuroscience, Rikshospitalet Medical center, Norway, Oslo, Norway ; 3 Department of Neurology, Division for Clinical Neuroscience, Rikshospitalet Medical Center, Norway, Oslo, Norway and 4 Department of Paediatrics, Division Woman and Child, Ullevål University Hospital, Norway, oslo, Norway )

Rationale: Antiepileptic drugs (AEDs) may induce reproductive endocrine function in men and women. We wanted to investigate if these effects of AEDs on reproductive endocrine functions were reversible.

Methods: We used a prospective, randomized and double blinded design. 160 patients which had been seizure free on AEDs for more than two years were included and randomized to withdrawal or not and 150 (80 females, 53%) patients went through the intervention. Complete serum samples from before and 4 months after completed withdrawal/no withdrawal were obtained from 130 patients (63 females, 48%). Of these, 84 were treated with carbamazepine, 28 with valproate, 9 with phenytoin, 4 with phenobarbital, and 5 with lamotrigine.

Results: We found reversible endocrine changes in sex steroid hormone levels in both sexes after withdrawal of AEDs. For carbamazepine we found significant increases in serum testosterone concentrations and free androgen index (FAI) in both men (n = 19) and women (n = 19). Mean differences in change in FAI between the withdrawal group and non-withdrawal group were in men 17.49 (CI 10.16–24.81, p = < 0.001), and in women 1.61 (CI 0.62–2.61, p = < 0.001). For valproate, there was a reduction in testosterone concentration and FAI, an increase in FSH and a reduction in BMI after withdrawal in both males and females. However, only the reduction in BMI was statistically significant, probably due to the low number of patients in each group

Conclusions: Our findings support that antiepileptic drugs may have potentially negative effects of on reproductive endocrine functions in men and women, but also that some of these changes are reversible, even after years on treatment.

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Isabella Taylor 1 , S. F. Berkovic 1 and I. E. Scheffer 1 ( 1 Epilepsy Research Centre, Austin Health, Heidelberg West, Victoria, Melbourne, VIC, Australia )

Rationale: Photosensitive epilepsy where seizures are triggered by environmental flicker occurs in both idiopathic focal and idiopathic generalized epilepsies (IGE). Photosensitivity occurs in 20–30% IGE and is mandatory in the idiopathic focal epilepsy syndrome of idiopathic photosensitive occipital epilepsy (IPOE). We have previously shown that there is overlap between IPOE and Juvenile Myoclonic Epilepsy (JME).The aim of this study was to analyze phenotypic patterns in families with photosensitive epilepsy.

Methods: 29 families where at least 2 relatives had idiopathic epilepsy and electroclinical photosensitivity were studied. Affected family members underwent detailed electro-clinical assessment. A 21-channel EEG recording including intermittent photic stimulation and hyperventilation was performed. An additional Oz electrode was used in some cases. Seizure types were classified according to the international classification and the phenotypic patterns in each family were analysed.

Results: In the 29 families, there were 110 affected members who underwent detailed characterization; 84 were photosensitive (62 female, 22 male) and 26 had epilepsy without definite photosensitivity (13 female, 13 male). Three main categories of idiopathic photosensitive phenotypes were observed in individual subjects: pure IGE, mixed IPOE/ IGE, and IPOE. Within each category, subjects with seizures only with photosensitive stimuli were noted. Comparison of phenotypes between family members with photosensitive epilepsy and those with non-photosensitive epilepsy showed a significant female bias (p = 0.02) and earlier age of seizure onset (p = 0.03)for those with seizures associated with photosensitivity. Photosensitive epilepsy was associated with absence seizures, myoclonic seizures and simple visual hallucinations rather than generalized tonic-clonic seizures. For families, phenotypic heterogeneity was typical with a spectrum of phenotypes showing electroclinical overlap between IPOE and a range of IGE subsyndromes such as Childhood Absence Epilepsy.

Conclusions: Analysis of photosensitive epilepsy phenotypes shows considerable overlap between the idiopathic focal and IGE. They manifest as a continuum from IGE to mixed IPOE /IGE and IPOE. Within each of these categories, subjects with purely photosensitive seizures may be seen. Photosensitivity is an endophenotype that is likely to be useful in dissecting the polygenic aetiology of the IGE.

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Jorge Asconape 1 and J. C. McGee 1 ( 1 Neurology, Loyola University Chicago, Maywood, IL )

Rationale: Humans have individual differences in the timing of their daily activities falling between two extremes: morning types (larks) and evening types (owls). The normal work schedules, determined by light/dark cycles, tend to favor morning types and could lead to chronic sleep deprivation in evening types. Mostly anecdotal information indicates that patients with idiopathic generalized epilepsy (IGE) show a tendency for being “owls”. This particular circadian sleep pattern is often not recognized by treating physicians and can have important implications in the diagnosis and management of these patients.

Methods: We administered the English version of the Horne-Östberg self-assessment questionnaire to 23 patients with idiopathic generalized epilepsy and 20 patients with (LRE) to determine their morningness and eveningness chronotypes. This validated test assigns a score that ranges from 16, indicating extreme eveningness, to 86, indicating extreme morningness. Results were analyzed by using a one-way ANOVA.

Results: The mean test score was 41.3 (r: 28–64) for the IGE group, and 54.6 (r: 32–73) for the LRE group (F = 15.36; p = 0.0003), indicating that IGE patients have a strong tendency towards an evening chronotype. Table 1 shows the distribution of patients among the different categories based on their scores. Table 2 shows the results of the self-assessment of patients as to their chronotypes based on 4 categories.

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[ Table 1 ]

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[ Table 2 ]

The mean age of the IGE population was 23.6 years, and for the LRE group was 30.2 years (F = 3.1; NS). In the IGE group, 11 had juvenile myoclonic epilepsy, 5 juvenile absence, 6 IGE with generalized tonic-clonic seizures (GTC) only (2 of which were IGE with GTC on awakening), and 1 IGE with versive seizures.

Conclusions: This study demonstrates that the evening chronotype strongly predominates in patients with IGE. The finding of night habits in patients with GTC may suggest a diagnosis of IGE. More important, a strong evening chronotype has been associated with delayed sleep phase syndrome and chronic sleep deprivation, a well-known seizure-precipitating factor in IGE, so its recognition may be important for clinical management.

Reference:

1.Horne JA, Östberg O. A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms. Int J Chronobiol 1976;4:97–110.

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Rebecca E. Fasano 1 and D. Bergen 1 ( 1 Neurological Sciences, Rush University Medical Center, Chicago, IL )

Rationale: In the 1970s and 80s, standard treatment for childhood acute lymphocytic leukemia included both intrathecal methotrexate and whole-brain irradiation. During acute treatment, seizures were not uncommon. The development of intractable epilepsy years after treatment, however, has not been described in the literature.

Methods: We reviewed the records of five patients who were treated for acute lymphocytic leukemia as children who later developed intractable epilepsy. Charts were reviewed to determine the age at diagnosis and treatment of leukemia, type of leukemia, intravenous and intrathecal chemotherapeutic agents received, dose of cranial irradiation received, age at seizure onset, results of electroencephalogram (EEG), brain CT or MRI, seizure type(s) and frequency, anti-epileptic medications used, neuropsychological testing results, other medical and developmental history, and current level of functioning.

Results: All of the patients were diagnosed with leukemia before age 7; none of the patients had central nervous system disease. They were treated with both whole-brain irradiation and intrathecal chemotherapy; all received intrathecal methotrexate, and two patients received intrathecal cytosine arabinoside as well. All of the patients developed epilepsy one to twelve years after leukemia treatment ceased. The patients have many different seizure types, and have been tried on multiple antiepileptic drugs. In four out of the five patients, EEGs showed temporal epileptiform discharges. Three patients had areas of high T2 signal in the white matter on brain MRI. All five patients have moderate to severe cognitive impairment.

Conclusions: Successful treatment for childhood leukemia may be followed by signs of cerebral injury including intractable epilepsy. We propose that neurotoxicity resulting from exposure to intrathecal methotrexate and cranial irradiation may have contributed to the intractable epilepsy seen in our five patients. Methotrexate causes neurotoxicity by several mechanisms, including homocysteine-induced vascular endothelial injury and buildup of sulfur-containing amino acids. Cranial irradiation damages neurons in the hippocampus, where neurogenesis continues throughout life. The damage caused by these anti-leukemic treatments likely played a role in the development of intractable epilepsy in our patients.

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Anbesaw W. Selassie 1 , P. L. Feguson 1 and B. B. Wannamaker 1 ( 1 Biostatistics, Bioinformatics, Epidemiology, Medical University of South Carolina, Charleston, SC )

Rationale: Reliable, population-based estimation of incidence and prevalence of epilepsy in a large population remains a major challenge making most studies restricted to smaller geographic locus or not representative to the referent population. This study provides methodological techniques to provide reliable estimates of incidence and prevalence in a large population by utilizing validation procedures and multiple data sources in South Carolina.

Methods: Persons with epilepsy and seizure disorders were identified from four data sources: Hospital Discharge, Emergency Department, Physician Office, and Behavioral Risk Factor Surveillance System (BRFSS). Persons were identified with broader case ascertainment ICD-9-CM diagnosis codes of 345.x (epilepsy and status epilepticus), 780.31 (febrile seizures), 780.39 (seizure unspecified), 780.2 (syncope), and 293.0 (delirium). Detailed clinical information was abstracted from representative sample of 3,983 persons (5.4%) with these conditions. Sensitivity and predictive value positive (PVP) measures were conducted for each data source by diagnosis codes. Case identification through BRFSS relied on self-report using random -digit dialing telephone survey of 21,480 individuals. Model-based approach was also used to determine prevalence of epilepsy using routinely available surveillance variables in a log-linear model.

Results: BRFSS-based prevalence estimate in SC indicate a rate of 2.0% (95% CI: 1.8–2.3) for ever having epilepsy and 1.1% (95% CI: 0.9–1.2) for active epilepsy. The prevalence rate of active epilepsy derived from healthcare encounters ranges from 0.8% to 0.9% per annum—a statistically comparable rate within the confidence limit of the BRFSS estimate of active epilepsy. Model-based prevalence rate provided a conservative estimate of 0.8% using information from the case-level data on 70,000 individuals in a loglinear model. The estimated annual in Incidence rate of epilepsy for the general population of SC is 3 per 10,000 (0.03%) indicating 1,200 new onset of epilepsy every year. Among all patients with seizure, ICD-9-CM code of 345.x yielded 31% and 96% while 780.39 yielded 93% and 20% for sensitivity and PVP respectively.

Conclusions: Robust and reliable estimation of incidence and prevalence of epilepsy in a large population can be achieved when multi-focal data sources are utilized and validation techniques are incorporated.

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Patricia L. Bruno 1 , K. D. Conant 1 , R. L. Thibert 1 , E. K. Braun 2 , R. R. Said 4 , M. P. Nespeca 3 and E. A. Thiele 1 ( 1 Pediatric Epilepsy Program, Massachusetts General Hospital, Boston, MA ; 2 Angelman Syndrome Foundation, Aurora, IL ; 3 Division of Pediatric Neurology, University of California, San Diego, San Diego, CA and 4 Pediatric Neurology, Comprehensive Epilepsy Program, University of Texas Southwestern Medical Center at Dallas, Dallas, TX )

Rationale: Angelman Syndrome (AS) is a genetic disorder which occurs in approximately 1 in 10,000 to 20,000 births. Characteristics of AS include an ataxic gait, jerky limb movements, microcephaly with global developmental delays, severe expressive and receptive language impairment, and happy disposition. Epilepsy occurs in more than 80% of those with AS and is often intractable. We sought to examine a large cohort of patients with the goal of finding the most effective treatments for epilepsy in AS.

Methods: An in-depth questionnaire was electronically conducted through the Angelman Syndrome Foundation. The survey included detailed questions pertaining to the different types of treatments used for epilepsy in AS patients.

Results: The survey yielded a respondent total of of 461; 56% were male, 44% were female. The current average age of the AS patients was 13.9 years (1.3–45 years) with an average age at diagnosis of AS of 5.3 years. A total of 396 (86%) had epilepsy with an average age of onset at 3.8 years.

Treatment of epilepsy among this population consisted of the use of anticonvulsant drugs (ACD) by all AS patients. Fifteen percent responded to the first medication used,

whereas 78% were refractory to the first two medications and 64% had tried multiple medications (average of 3.2 medications). Of those who were refractory, 26% became seizure free with further treatment. At the time of data collection 40% were being treated with monotherapy (average current treatment of 1.2 medications).

The most common of greater than 20 different medications tried were: valproate 62%, clonazepam 34%, phenobarbital 30%, topiramate 30%, lamotrigine 24%, carbamazepine 24%. For those who tried multiple medications the most effective were valproate, nitrazepam, levetiracetam, lamotrigine, clorazepate, topiramate, and clonazepam. The medications perceived by the respondents to have the most negative side effects were ACTH, carbamazepine, phenobarbital, oxcarbazepine.

Seventeen percent of respondents had also used non-pharmacologic treatments for epilepsy. These included dietary therapy with the classic ketogenic diet in 31/396 (8%) and the low glycemic index treatment in 7/396 (2%). Of those that tried the ketogenic diet, 36% felt it was the most effective treatment. The vagal nerve stimulator was used by 16/396 (4%) of the AS patients, and it proved the most effective treatment for 3 of the 16. Two of the 396 (<1%) AS patients had undergone corpus callosotomies.

Conclusions: Epilepsy occurs in over 80% of individuals with AS. In our population, the majority of AS patients were treated with more than 3 medications prior to achieving seizure control. Several of the new ACDs with broad spectrum efficacy were successful at providing seizure control and were well tolerated. Seizure freedom was achieved by 66% of AS patients with either ACD monotherapy or polytherapy. Dietary therapy and the vagus nerve stimulator also appeared to significantly reduce seizures in individuals with AS.

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Tejaswini Narayanan 1 ( 1 SV National Institute of Technology, Surat, Surat, India )

Rationale: Manual Epileptic Seizure Prediction from raw Electroencephalogram (EEG) data is a cumbersome activity in Clinical Neuroscience. Computational tools like ‘Support Vector Machines’ (SVMs) and ‘Artificial Neural Networks’ can be exploited to automate this process, by modeling Epileptic Seizure Prediction as a classification problem. The application of an SVM in Epileptic Seizure Prediction is discussed. An SVM is a supervised learning algorithm which addresses the general problem of learning to discriminate between ‘positive’ and ‘negative’ members (which constitute the “Training Set”) of a given class of n-dimensional vectors. The “Training Set” is fed as input to the SVM to ‘train’ the SVM i.e. to enable it to define a separating hyperplane, which separates the positive and negative samples, which in this case are the EEG recordings that denote normalcy and seizure activity, respectively. Signal analysis aims to extract appropriate information from a signal. The notion of time-scale signal analysis using the Discrete Wavelet Transform (DWT) is recognized as a potential tool for analyzing EEG signals. The DWT representation of a signal is obtained by passing the original signal through two complementary filters that emerge as two signals (digital filtering techniques). The signal passed through the low-pass filter includes the high-scale, low-frequency components (called ‘approximation’) and that passed through the high-pass filter includes low-scale, high-frequency components (called ‘detail’).

Methods: For this study, the EEG readings were taken from http://www.epileptologie-bonn.de/front_content.php?idcat=193&lang=3&changelang=3. The sampling rate of the data is 173.61 Hz. The time series have the spectral bandwidth of 0.5 Hz to 85 Hz of the acquisition system. Firstly, a low-pass filter of 40 Hz has to be applied on the data. Wavelet transform using Daubechies 4th order Mother wavelet function “db4” is employed for decomposing the EEG signal, since it gives sufficient resolution and is proved to be efficient for seizure detection. A new set of wavelet features viz. Mean, Mean of absolute values, Average Power, Standard Deviation and Cross Correlation are extracted. These five parameters constitute one input vector for the SVM. The following algorithm will enable the use of SVM for Epileptic Seizure Prediction:

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    Standard EEG recordings (with and without Seizure activity) are taken.
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    For each frame of EEG (corresponding to 1 second recording of EEG signals), the wavelet features aforementioned, are extracted.
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    Once all frames are processed, readings that are normal and those with seizure activity are labeled +1 and −1 respectively.
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    The SVM is ‘trained’ with the training set and made to find the decision boundary.

The SVM is now ready for Epileptic Seizure Prediction of any new EEG recording.

Results: Sets of manually pre-classified EEG signals were fed as test-inputs into the SVM; it was found that the SVM was 90.1–94.7% accurate in Predicting Seizure activity.

Conclusions: Thus, employing an SVM is an efficient solution for automated Epileptic Seizure Prediction.

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Rebecca O'Dwyer 1 , A. Stojic 1 , A. Alexopoulos 1 , D. Nair 1 , W. Bingaman 2 and I. Najm 1 ( 1 Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH and 2 Dept. of Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland, OH )

Rationale: Cortical dysplasia (CD) are frequent pathological substrates in patients with pharmacoresistant epilepsy. Previous studies showed that CD are intrinsically epileptogenic and therefore a “total” resection of the “lesion” is recommended. In cases where the CD overlap with potentially eloquent regions, it remains unclear if a subtotal, tailored resection based on careful extraoperative invasive mapping would lead to a favorable seizure outcome. We report on three patients with good surgical outcomes in whom subtotal removal of the dysplastic lesion was performed on the basis of direct cortical recordings using subdural grids.

Methods: We retrospectively reviewed the Cleveland Clinic Epilepsy Center's database for patients with pathologically confirmed CD who underwent invasive EEG evaluation for intractable epilepsy and whose EEG findings were only partially concordant to neuroimaging.

Results: Three patients (36 ± 13 years) were identified with focal epilepsy arising from right perisylvian epilepsy, right frontal lobe epilepsy and left hemispheric epilepsy. These patients had extensive MRI abnormalities and one patient had bilateral perisylvian lesions. Invasive EEG recordings utilizing depth electrodes and subdural grids identified focal epileptic activity that was localized within the MRI lesion in one patient, partially within and adjacent to the lesion in another, and in a different cortical lobe (same hemisphere) in the other. A tailored resection with respect to EEG findings was thought to be more beneficial than a generous lesionectomy. All had an excellent surgical outcome, classified as Engel class I (follow up between 1.5 years and 4 years).

Conclusions: Our preliminary results suggest that subtotal tailored resection, guided by invasive EEG data can result in a good surgical outcome and preservation of eloquent function in patients with extensive dysplastic lesions. These results challenge the long held belief that complete resection of the “lesion” is required for surgical success and argue for a staged approach in those patients with extensive neocortical dysplastic lesions and/or those with lesions in potentially eloquent cortex.

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Lisa A. Stephenson 1 , S. Ginal 1 , M. Dougherty 1 and N. Foldvary 1 ( 1 Neurology, Cleveland Clinic Foundation, Cleveland, OH )

Rationale: Recent evidence suggests that obstructive sleep apnea (OSA) affects up to one-third of patients with epilepsy, strikingly higher than the general population and potentially increasing the risk of medical intractability (Malow et al., 2003; Manni et al., 2003). Several studies have shown that treatment of OSA can improve seizure control. In one study, treatment of OSA with CPAP normalized the apnea-hypopnea index (AHI) and markedly reduced spike rate in a small number of patients (Oliveria et al., 2000). We report two cases of refractory focal epilepsy and co-morbid OSA in whom video polysomnography with EEG (VPSG) was performed prior to and after initiation of therapeutic CPAP aiming to assess the impact of CPAP on the frequency of interictal discharges.

Methods: Case 1 underwent routine VPSG at baseline and after one month of stable CPAP therapy. Case 2 had been diagnosed with OSA and treated at an outside facility and underwent two consecutive nights of VPSG (with and without therapeutic CPAP) during a presurgical VEEG evaluation. Spikes were quantified for the night recording and spike rate (spikes per min) was calculated by sleep stage. Night 1 was without CPAP; Night 2 was with CPAP.

Results: Results

VariableCase 1Case 2
Night 1Night 2Night 1Night 2
Overall count73824368752
Spike Rate 
WASO11.780.300.110.02
Stage 19.764.813.881.11
Stage 27.952.6927.551.92
SWS 0000 
REM--0.690.13
Total Sleep Time (min)290314410301
Sleep Efficiency63.387.370.095.2
Sleep Latency (min)3.015.04.51.0
WASO (min)13317.511219
Stage 1 (%)4.32.51.80.9
Stage 2 (%)86.985.252.163.3
SWS (%)0023.722.8
REM (%)8.812.322.413.0
Arousals46576340
Awakenings313244
Arousal Index9.54.58.09.2
Stage Shifts92688149
AHI overall17.90.014.90.0
AHI REM35.30.040.40.0
AHI Supine17.10.025.20.0

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Elizabeth Waterhouse 1 , L. Kopec 1 , V. Ramakrishnan 2 , A. Towne 1 and R. DeLorenzo 1 ( 1 Neurology, VCU School of Medicine, Richmond, VA and 2 Department of Biostatistics, VCU School of Medicine, Richmond, VA )

Rationale: Although the epidemiology of convulsive status epilepticus (CSE) has been well described, few studies have addressed risk factors for NCSE. It has been hypothesized that NCSE patients with a history of epilepsy have a better prognosis than those with acute medical problems as an etiology. The purpose of this study was (1) to describe the clinical characteristics associated with NCSE, as compared with CSE, and (2) to assess whether NCSE in the setting of epilepsy has a lower mortality compared with other etiologies of NCSE.

Methods: Prospectively identified cases of CSE and NCSE in the Richmond, Virginia metropolitan area SE database were reviewed. NCSE included simple partial SE and complex partial SE without associated tonic-clonic or clonic activity, absence SE, subtle SE, and electrographic SE in patients with coma. CSE included primary and secondarily generalized convulsive SE, myoclonic SE, and localization-related seizures with clonic or tonic-clonic manifestations. Mortality was assessed at 30 days. Chi Square analysis was used to evaluate associations between single variables. The Kruskall-Wallis test was used to compare SE durations. Multivariate regression analyses were performed to identify independent risk factors.

Results: Of 809 cases of SE, 10% were NCSE, and 90% were CSE. There were no significant differences in age, race, or seizure history between the two groups. Among NCSE cases, those with a history of seizures had significantly lower mortality than those without a history of seizures (p = 0.0013, OR 0.1, CI 0.025–0.410), and females had lower mortality than males (p = 0.0271, OR 2.7, CI 0.085–0.863). Among CSE cases, those with a history of seizures also had a significantly higher survival rate. In-hospital onset of SE occurred in 61% of NCSE and 30% of CSE (p < 0.0001). Multivariate analysis identified SE onset location as the only independent risk factor for NCSE (p = 0.0002, OR 2.8, CI 1.6–4.9). Etiologies of hypoxia/anoxia and CNS acute occurred in a higher proportion of NCSE compared with CSE (p < 0.0001) but did not independently predict SE type or mortality in NCSE. Median SE duration was 210 minutes for NCSE and 95 minutes for CSE (p < 0.0001). Mortality was 41.7% for NCSE, and 23.0% for CSE (OR 2.4, CI 1.5–3.8). With multivariate regression analysis of NCSE and CSE groups, and mortality as outcome, increasing age, etiology, in-hospital onset and longer SE duration significantly predicted mortality, while neither SE type (NCSE vs. CSE), nor seizure history were independent risk factors for mortality.

Conclusions: In-hospital SE onset occurs significantly more frequently with NCSE than CSE. Among cases of NCSE, female gender and history of seizures are independently associated with a lower risk of mortality. Compared with CSE, NCSE has a different distribution of etiologies, and a longer duration. A history of seizures was associated with increased survival following NCSE and CSE. The odds ratio for mortality is 2.4 times higher for NCSE than CSE, but SE type does not independently predict mortality.

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Kerry D. Conant 1 , R. L. Thibert 1 , E. K. Braun 2 and E. A. Thiele 1 ( 1 Pediatric Epilepsy Program, Massachusetts General Hospital, Boston, MA and 2 Angelman Syndrome Foundation, Aurora, IL )

Rationale: Eighty to ninety percent of individuals with Angelman Syndrome have epilepsy, and sleep disturbances have been described clinically in 20–80%. Although epilepsy is thought to exacerbate sleep problems, the effect of a seizure disorder on sleep has rarely been studied in this population. The relationship of seizure type, frequency and severity to sleep disorders, and the medications used to treat them, have never been studied in a cohort greater than 109.

Methods: An online survey was conducted through the Angelman Syndrome Foundation to characterize the presentation and treatment of epilepsy in Angelman Syndrome. The Behavioral Evaluation of Disorders of Sleep questionnaire (BEDS, Schreck 1997/1998) was additionally offered to respondents to assess the prevalence of sleep disorders. The relationship of a sleep disorder to genetic subtype, epilepsy and seizure severity was evaluated, as well as the use of medications to treat both seizure and sleep disorders.

Results: 386 respondents completed the BEDS questionnaire in addition to the epilepsy survey. Eighty-four percent of BEDS respondents indicated that their child or family member had epilepsy, and sleep disturbances were described by 44%. Of those indicating a sleep disorder, 79% had epilepsy, and 69% of those describing both epilepsy and sleep problems had multiple seizure types. Complex partial, absence, generalized tonic-clonic and atonic seizures were associated with disorders of sleep, and the frequency of seizures was directly related.

Previous research findings were confirmed by comparison of the relative frequency of sleep disorders within each genetic subtype. Angelman Syndrome resulting from a maternal deletion generally presents a more severe phenotype, including a higher incidence of sleep disorders. Conversely, sleep disorders were less common in the more mildly affected phenotype of uniparental disomy.

The two most commonly described problems affecting sleep patterns were apnea (has trouble breathing, or stops breathing), and expressive sleep disturbances (wakes up screaming, or walks in sleep). Across all factors of sleep disturbance, average scores were higher for those with epilepsy than without.

Conclusions: Although the causal relationship remains unclear, sleep disturbances in Angelman Syndrome appear to show an association with the presence and severity of epilepsy, as well as multiple seizure types. The clinical presentation of Angelman Syndrome resulting from a maternal deletion includes a higher incidence of sleep disorders than other genetic subtypes. Medications used to treat these disorders are also examined.

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Harold H. Morris 1 , K. Merner 2 and J. Tavee 2 ( 1 Neurology, U of Vermont College of Medicine and Fletcher Allen Health Care, Burlington, VT and 2 Neurology, The Cleveland Clinic, Cleveland, OH )

Rationale: Sudden unexpected death in epilepsy (SUDEP) is a relatively commen cause of death in patients with epilepsy. In patients with refractory epilepsy it is even more common. Cardiac arrhythmia, suffocation, and apnea have all been suggested as causes of SUDEP. We recorded a near SUDEP in our EMU in a patient with severe postictal laryngospasm.

Methods: The patient, a 42 year old right handed man, was admitted to the EMU at the Cleveland Clinic for a presurgical evaluation for medically refractory epilepsy. He had viral encephalitis at age 2 years and his first seizure was at age 6 years. He had an indescribable aura followed by impaired awareness with or without automatisms. Sometimes he had secondary generalization. Seizures lasted several minutes and were followed by confusion. Seizure frequency was up to 4 per month. He had failed to achieve seizure control despite trials of 5 major anticonvulsants. On admission he was taking lamotrigine 600 mg daily. General medical and neurological exams were normal except for post traumatic (during a seizure) right eye blindness.

As part of a presurgical evaluation, he was admitted to the EMU at the Cleveland Clinic for continuous EEG/video monitoring. Lamotrigine was discontinued after admission.

Results: MRI scan revealed an atrophic left hippocampus and atrophic left temporal lobe and a cyst in the left temporal region.

Interictal EEG revealed frequent sharp waves at the left sphenoidal electrode and somewhat less frequent sharp waves at TP9, T7, and T9. Ictal EEG revealed paroxysmal fast activity over the left hemisphere with maximal amplitude in the temporal leads.

During 48 hours of recording, the patient had one aura, 3 partial and 2 partial seizures with secondary generalization. Seizure number 6 occurred during morning rounds and with 2 of the authors present (HM and JT). It began with tonic stiffening of the body followed by extension of the right arm, flexion of the left arm, version to the right and secondary generalization; seizure duration was approximately 3 minutes. Following termination of the seizure, the patient developed loud inspiratory stridor and marked cyanosis; oxygen saturation ranged from 50 to 60%. Attempts improve ventilation by positioning the patient, administering oxygen and use of the emergency Ambu bag did not improve his oxygen saturation. The patient did maintain normal blood pressures. An emergency team was called and the patient was promptly intubated in the epilepsy monitoring unit and transferred to the intensive care unit. The anesthesiologist consultant noted frothy secretions from his airways and a pulmonologist stated the cause for the respiratory emergency was laryngospasm probably triggered by aspiration. He recovered and was discharged home after several days.

Conclusions: This well documented case indicates that severe hypoxia resulting from postictal laryngospasm, triggered by aspiration, is one of multiple mechanisms of SUDEP.

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Jakob Christensen 1,2 , M. G. Pedersen 3 , C. B. Pedersen 3 , P. Sidenius 1 , J. Olsen 4 and M. Vestergaard 5 ( 1 Department of Neurology, Aarhus University Hospital, Aarhus, Denmark ; 2 Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark ; 3 National Center for Register-based Research, University of Aarhus, Aarhus, Denmark ; 4 Department of Epidemiology, School of Public Health, UCLA, Los Angeles, CA and 5 Department of General Practice and Department of Epidemiology, Institute of Public Health, University of Aarhus, Aarhus, Denmark )

Rationale: To estimate the occurrence of epilepsy following traumatic brain injury in Denmark between 1977 and 2002.

Methods: We used the Danish Civil Registration System to identify all persons born in Denmark between 1977 and 2002 and the Danish National Hospital Register to identify persons registered with traumatic brain injury and epilepsy. Traumatic brain injury was divided according to clinical severity into 1) brain concussion, 2) cranial fractures, and 3) structural brain injury.

Results: Among 1,605,216 persons born in Denmark between 1977 and 2002, we identified 73,326 persons with brain concussion, 5,099 persons with scull fracture and 3,850 persons with structural brain injury. We identified 17,470 persons registered with epilepsy in the follow-up period of 19,527,337 person-years. A total of 1,031 persons developed epilepsy after traumatic brain injury; 837 after brain concussion, 78 after cranial fractures and 116 after structural brain injury. There was an increased relative risk (RR) of epilepsy following concussion (RR = 2.22, 95% Confidence Interval (95% CI): 2.07–2.38); cranial fractures (RR = 2.17, 95% CI: 1.73–2.71), and structural brain injury (RR = 7.40, 95% CI: 6.16–8.89). For patients with concussions the development of epilepsy was significantly associated with gender, familial history of epilepsy, age at concussion, time since brain injury and number of concussions, but no association could be identified with duration of admission with concussion. There was a significant association between the development of epilepsy and duration of admission with scull fracture, but no other significant associations between scull fractures and epilepsy could be identified. For patients with structural brain injury there was a significant association between age at injury, duration of admission, and time since injury, but the association was not influenced by number of structural brain injuries, gender and familial history of epilepsy.

Conclusions: Even mild traumatic brain injury (concussion) is associated with an increased risk of epilepsy. The study identifies several factors that are associated with the development of epilepsy after traumatic brain injury.

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Jacqueline A. French 1 , N. R. Temkin 2 , A. E. Hammer 3 and K. E. VanLandingham 3 ( 1 Neurology, Hospital University of Pennsyvania, Philadelphia, PA ; 2 Department of Neurosurgery, University of Washington, Seattle, WA and 3 Neurosciences MDC, GlaxoSmithKline, Research Triangle Park, NC )

Rationale: Few placebo-controlled trials have been performed that assess efficacy of new AEDs for primary generalized epilepsy. In part, this is because some seizure types, such as generalized tonic-clonic seizures are infrequent, leading to long trials with slow enrollment. A new methodology, time to nth seizure, might reduce the study duration, by eliminating the need for a baseline, and reducing treatment period for non-responders. Lamotrigine (LTG) as adjunctive therapy in primary generalized tonic-clonic (PGTC) seizures has been proven effective in a standard baseline/escalation/maintenance trial assessing reduction from baseline seizure frequency. A post-hoc analysis was conducted to assess whether time to nth seizure would have been a successful trial design.

Methods: This analysis utilized data from an international, multicenter, randomized, double-blind, placebo-controlled trial with LTG. LTG-naive patients (>2 years, weighing >13 kg) with PGTC seizures, EEG at screen showing generalized spike and wave (GSW) activity or no GSW, and receiving a stable regimen of 1 or 2 AED(s) were enrolled in an 8-week baseline phase. Patients having >3 PGTC seizures were randomized (1:1) to receive either LTG or placebo (PBO). The treatment period consisted of Escalation (12 week for 2 to 12 years and 7 week for >13 years) and Maintenance (12 week) phases with dosing based on background AEDs. Patients were categorized as taking an AED regimen with enzyme inducers (induced), enzyme inhibitors (inhibited) or no effect (neutral). The primary endpoint was percent change from baseline in average monthly PGTC seizures during the entire treatment period. Tns from the start of escalation for n = 3, 6, 9 and 12 seizures (T3, T6, T9 and T12) were estimated using Kaplan-Meier analysis with the treatments compared by log-rank test.

Results: Of the 117 patients randomized, 58 received LTG and 59 received PBO. There was nearly an even distribution of patients on 1 or 2 concomitant AEDs. The median frequency of PTGC seizures per month during baseline was 2.43 in the LTG group and 2.85 in the PBO group. Tn analysis showed superiority of LTG over PBO for T3, T6, T9 and T12 (p = 0.007, 0.003, 0.003 and 0.022, respectively). This compares to the median percent decrease from baseline in seizure frequency for PGTC seizures for the entire treatment period of 66.5% for LTG and 34.2% for PBO (p = 0.006). The Kaplan-Meier plot for T3 is presented in the figure. Of the 117 patients, 74 (63%) had a 3rd PGTC seizure, 60 (51%) had a 6th PGTC seizure, 42 (36%) had a 9th PGTC seizure and 34 (29%) had a 12th PGTC seizure.

Conclusions: Time to nth seizure analysis in PGTC seizures demonstrated superiority of LTG over PBO. As PGTC seizure frequency was low, nearly two thirds of patients had fewer than 9 seizures during the trial, and therefore low N's were optimal. Time to nth seizure appears to be a viable study design for trials of low-frequency events.

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Basim Uthman 1 , C. Bazil 2 , A. Schultze-Bonhage 3 , E. Whalen 4 , T. Leon 4 , B. Emir 4 and R. Benabou 4 ( 1 Malcolm Randall VA Medical Center, Gainesville, FL ; 2 College of Physicians and Surgeons, Columbia University, New York, NY ; 3 Epilepsy Centre, University Hospital, Frieburg, Germany and 4 Global Pharmaceuticals, Pfizer, Inc., New York, NY )

Rationale: The long-term safety and tolerability of a new antiepileptic drug (AED) in the market should be adequately assessed in large patient populations long enough to continuously evaluate the current safety profile and/or detect any potential new adverse reactions. The purpose of this study was to evaluate the safety and tolerability of long-term pregabalin as add-on treatment for patients with treatment refractory partial-onset seizures.

Methods: Data were combined from 6 long-term studies involving 2061 patients receiving open-label (OL) pregabalin administered BID or TID as add-on therapy for partial-onset epilepsy. Male or female patients ≥ 12 years old, with a diagnosis of epilepsy with partial-onset seizures with or without secondary generalization and who were highly refractory to existing treatment with a pre-screening frequency of ≥3 seizures/month while receiving between 1 and 3 standard AEDs were eligible for inclusion. All spontaneous reported or observed adverse events were recorded.

Results: A total of 576 patients completed one of the 6 OL studies. Overall, at the completion date, 79.1% of patients had been exposed to pregabalin for ≥6 months, 61.2% for ≥1 year, 33.5% for ≥2 years, and 14.2% for ≥3 years for a total exposure to pregabalin of 3877 person-years. The percentages of patients completing at least 52 week was similar for all six of the OL studies. Out of 2061 patients who received OL pregabalin, 1891 (91.7%) experienced at least 1 AE and 1590 (77.1%) experienced a treatment-related AE. A total of 262 patients (12.5%) withdrew due to AEs and for 217 patients (10.5%), the AEs leading to withdrawal were considered related to treatment. The most common AEs by frequency were dizziness (30.0%), accidental injury (25.3%), somnolence (22.8%), weight gain (20.8%), infection (20.2%) headache (18.2%), asthenia (17.6%), pain (14.6%), ataxia (12.1%), amblyopia (11.0%) and diplopia (10.0%). Those were mild to moderate in intensity. The most common AEs causing patients to discontinue from the studies were somnolence (2.0%), dizziness (1.6%), weight gain (1.4%), and asthenia (1.3%). The most common AEs were observed within the first few months of OL pregabalin treatment and tended to be transient in nature. The most frequent serious adverse events reported were accidental injury (68 patients, 3.3%), pneumonia (21 patients, 1.02%), overdose (14 patients, 0.68%), depression (12 patients, 0.58%) and psychosis (10 patients, 0.48%). A total of 28 patients died, none of which were considered related to pregabalin.

Conclusions: Add on treatment with pregabalin has proven to provide sustained efficacy in patients with refractory partial onset seizures and was well tolerated during long-term treatment. No new safety concerns were identified with long-term treatment.

Study funded by Pfizer, Inc

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Andro Zangaladze 1 , A. Asadi-Pooya 1 , K. Bujarski 1 , A. Ashkenazi 2 and M. Sperling 1 ( 1 Jefferson Comprehensive Epilpsy Center, Department of Neurology, Thomas Jefferson University, Philadlphia, PA and 2 Jefferson Headache Center, Department of Neurology, Thomas Jefferson University, Philadelphia, PA )

Rationale: The associations between epilepsy and migraine are complex and only rare cases have been reported. Here, we describe a patient with FHM linked to a mutation in the CACNA1A gene, ataxia and epilepsy.

Methods: This is a case report of the patient who was seen at Jefferson Comprehensive Epilesy Center and Jefferson Headache Center for her headaches. Genetic test for CACNA1A gene mutation for performed by ATENA laboratories.

Results: The patient was a 37 year-old woman. At the age of four years, she had a head trauma and later she developed seizures. Seizures spontaneously resolved at age seven. She came off the AEDs and did well until age 12, when she started to experience episodes of right or left hemibody weakness and paresis which lasted 15 to 45 minutes and were followed by a severe throbbing headache contralateral to the weakness. About once per year, when the above-mentioned symptoms did not resolve in a few hours, the headache was followed by a prolonged period of aphasia, confusion, visual field deficit and in few occasions well documented generalized tonic-clonic seizures. She did not have sporadic seizures unrelated to FHM attacks as an adult. Between attacks physical examination showed ataxia and positive cerebellar signs, left sided clumsiness without sensory impairment and cognitive impairment. A brain MRI showed mild cerebellar atrophy. EEG showed right mid-temporal seizure and partial SE at the time of last admission. Interictal EEG showed focal polymorphic delta activity in the right hemisphere with absence of posterior dominant rhythm on that side. A genetic study showed a missense mutation with C/T substitution at the nucleotide position 653, codon position 218, on chromosome 19p, which resulted in change in one amino acid from serine to leucine. This DNA sequence variant in the CACNA1A gene has previously been reported in association with FHM type 1.

Conclusions: Epilepsy, cerebellar signs and FHM linked to CACNA1A gene is a poorly described syndrome and has not been reported elsewhere except in only two patients within the family in one study. Our patient besides sporadic seizures during her childhood had repeated episodes of status epilepticus complicating the prolonged FHM attacks since her adolescence, which makes this case the only case with triad of epilepsy, cerebellar signs and FHM with recurrent attacks of prolonged impaired consensuses and status epilepticus linked to mutation in CACNA1A gene.

We propose a syndrome consisting of a triad of cerebellar ataxia, FHM, and epilepsy, which is related to the mutations in CACNA1A gene. We also suggest that patients with the triad of seizures, ataxia, and alternating transient hemiplegia with headaches, should be genetically tested for FHM even if the etiology for any of these manifestations in isolation seems to be obvious. Aggressive treatment of FHM attacks in these patients could prevent status epilepticus.

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Deborah Shulman 1 , B. Corbett 1 , J. Drazkowski 1 , J. Sirven 1 and K. Noe 1 ( 1 Neurology, Mayo Clinic Arizona, Phoenix, AZ )

Rationale: Anecdotal evidence suggests even clinically experienced caregivers can become anxious when treating acute seizures. In a study of hospice nurses and physicians, seizures were identified as a major source of anxiety for staff. (McCluggage HL Int J Palliative Nurs. 2006 12:254). Emotional discomfort with care of seizures is not only a potential cause of job related stress for nurses, but may also adversely effect patient's attitudes toward their condition. Attitudes of hospital nurses caring for seizure patients have not been previously assessed. We hypothesized that nurses with little experience in seizure care would have higher anxiety, and sought causes for this anxiety.

Methods: We distributed a voluntary, anonymous 22 question survey to nurses at Mayo Clinic Arizona working in the epilepsy monitoring (EMU) and intensive care units (ICU). The majority of questions were scored on a 5 point Likert-type scale. Results were statistically analyzed with t-test or ANOVA.

Results: 25 surveys were returned, 13 from EMU and 12 from ICU staff. ICU nurses had significantly greater total years of clinical experience, but less exposure to patients with seizure (mean 11–30 versus 51–100 prior seizure patients seen by EMU staff). There was no significant difference in prior exposure to status epilepticus. ICU staff were significantly more likely to report anxiety when caring for a patient with a seizure (70% vs 33% in EMU reporting moderate anxiety, p = 0.03). Both agreed with statements that seizures are “dangerous” and “painful”, while ICU nurses associated convulsive seizures with a high risk of death (>11–25%). ICU nurses were less confident in their ability to recognize seizure activity, provide appropriate nursing care for seizure, or to answer patient questions pertaining to seizure. ICU staff were also less likely to agree that nursing care increases patient safety and comfort after seizure. Both groups agreed that medications were effective in treating seizures, but EMU staff were more likely to agree that medications increase patient comfort. ICU staff rated both their clinical skills and emotional comfort for treating seizure significantly lower compared to stroke, cardiac arrest, or acute respiratory distress.

Conclusions: Caring for a patient with a convulsive seizure provokes anxiety even in experienced nurses. Seizures were identified as a greater source of emotional stress for nursing staff than other medical emergencies. Potential sources of anxiety identified were lack of confidence in knowledge about seizures, lack of faith in the effectiveness of nursing intervention to improve patient comfort and safety, and a misperception that seizures are associated with high patient mortality. Education about epilepsy addressing these areas has the potential to improve the experience of both patients and hospital staff.

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Christine Restivo-Pritzl 1,2 , J. Burgos 1,2 , G. Morris 1,2 and C. M. Inglese 1,2 ( 1 Regional Epilepsy Center, Milwaukee, WI and 2 Aurora St. Luke's Medical Center, Milwaukee, WI )

Rationale: The use of intracranial EEG monitoring is a valuable tool in the localization of epileptogenic foci prior to cortical resection. Although considered standard of care, little evidence has been compiled regarding the localized reaction of brain tissue to the presence of subdurally placed electrodes, and an extensive literature search revealed only one such published investigation. Insertion of the electrodes is thought to cause mechanical injury to the highly vascular cerebral surface and subdural space, thus triggering an acute inflammatory reaction in response to those injuries as well as the presence of the biomaterial. Conceivably, this reaction may eventually lead to gliosis or localized infection, thus exerting a negative effect upon surgical outcome.

Methods: The perioperative records of 24 patients were reviewed, along with the results of pathological examination of resected cortex for the presence of inflammation.

Results: Four of twenty-four patients were determined to have evidence of inflammation via pathological evaluation of the resected cortex. The average age of those four was 23, compared to 31.5 for those without inflammation. The mean time of implant for individuals with evidence of inflammation was 3.5 days, and for those without inflammation was 5.4 days. One patient who experienced cortical inflammation went on to develop subsequent localized infection, and five of the 20 without inflammation did so. Finally, both groups experienced varying effects upon seizure outcome after surgery - of the 20 in the non-inflammation group, 5 are seizure free, 11 have experienced a reduction in seizure frequency, and 4 have had no change. Among those who had evidence of inflammation, 1 is seizure free, and 3 report a decrease in the frequency of their seizures.

Conclusions: This review of 24 patients demonstrates similar surgical outcomes and infection rates. The time that electrodes were left in place appears to not be a predictive factor in the development of inflammation, and the only obvious difference between groups was the mean age of patients. Data collection is ongoing, but from this small sample, it appears that the presence of inflammation in response to indwelling subdural electrodes is not predictive of resective outcome.

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Patricia O. Shafer 1,2 , J. A. Cramer 3,2 , S. C. Schachter 1,2 and J. Gordon 2 ( 1 Neurology Department, Beth Israel Deaconess Medical Center, Boston, MA ; 2 Epilepsy Therapy Development Project, Boston, MA and 3 Department of Psychiatry, Yale University School of Medicine, West Haven, CT )

Rationale: To evaluate user concerns, experiences and needs of people with epilepsy using a web-based survey tool on http://www.epilepsy.com.

Methods: Epilepsy.com began surveying users of the website with insta-polls in November 2005. The Insta-polls present one question with multiple choice answers developed by the ETDP team. New polls were mounted monthly at first, then biweekly as user interest increased. Clicking on a response instantly submitted an answer and allowed immediate viewing of overall survey results. The source of individual responses was not tracked. Responses were archived for later review. Surveys were rotated on a predetermined schedule. The number of responses increased over time, with total responses varying for each question.

Results: A broad range of topics were presented in 44 polls as of May 2007, with the focus on experiences and self-management concerns. Typical viewership can be described by responses. Age at first seizure (n = 590): less than 5 years for 28%, 6–12 years for 18%, 20–30 for 22%. Epilepsy diagnosis (n = 642): within 6 months after first seizure 50% and delayed 2 years or more for 26%. Balance between seizures and side effects (n = 1000): persistent seizures and side effects 47%, no seizures and no side effects 17%. Injuries from seizures (n = 117): cuts and bruises 55% and head injuries 21%. Seizure triggers (n = 307): lack of sleep 25% and missed medication 14%. Stress associated with seizures (n = 450) always or frequently for 61%. Diet was perceived as playing role in seizures for 51%. Plans for preventing injuries (n = 385): 25% had no plan and 30% had never talked to anyone about a plan. Seizure calendar or diary (n = 219) used by 52% with 30% interested in web-based diary. Plans for seizure emergencies (n = 224): 23% had none and 28% didn't know how to create one.

Conclusions: This approach to gathering information directly from people with epilepsy and their loved ones by the internet obtained data more easily than via cross-sectional studies by phone or mail surveys. This approach also provided immediate feedback to the user of their views in relation to other users. Questions can be repeated after a period of time to ascertain changes. For individual users, the immediate feedback can reinforce critical messages and highlight learning needs. For the editorial team and health care professionals, understanding the experiences of people with epilepsy and their families enhances tailoring of information and making sure that critical needs are addressed. A number of these polls highlighted the need for people to have education and resources in developing self-management plans. As with any survey, respondents are those who choose to participate and this type of survey allowed only single questions. Expansion of instapoll technology will allow more formal and extensive asssessments of experiences and needs and to help reach and tailor information and resources appropriately.

Supported by Epilepsy Therapy Development Project, a not-for-profit foundation.

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Margaret Hamilton 1 , R. S. McLachlan 2,1 and J. G. Burneo 2,1 ( 1 Epilepsy Unit, London Health Sciences Centre, London, ON, Canada and 2 Epilepsy Programme, University of Western Ontario, London, ON, Canada )

Rationale: Cigarette smoking is common in patients with intractable epilepsy. As a preliminary assessment of epilepsy and smoking, we evaluated the impact of breaks for smoking on the investigation of epilepsy patients admitted to our epilepsy monitoring unit.

Methods: Absences from the epilepsy unit at the London Health Sciences Center were monitored for 40 consecutive days by nursing personnel. During these absences, events that occurred were registered as well. This is possible using portable EEG recorders (XLTEK) that patients carry with them all the time. A disadvantage is that video recording is not available if the patient has a seizure outside the unit. Information was entered in a datasheet. Diagnosis, duration of hospital stay and frequency and amount of cigarette smoking were recorded. Descriptive statistics were performed using MS Excel 2003.

Results: 113 smoking trips were recorded. Mean duration of stay was 7.8 days (range: 4–11 days). The number of smoking trips was found not to be associated with the amount of cigarette smoking reported by the patients. Only 3 events were missed on video. None of the events had electrographic correlation, raising a suspicion of non-epileptic events (pseudoseizures).

Conclusions: Despite the low number of events missed, precious information may be lost during smoking trips by patients admitted to the epilepsy unit. Ways to avoid such trips should be implemented in epilepsy monitoring units allowing smoking breaks for patients.

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Lisa C. Ortiz 1 , C. Bordson 1 and M. Plueger 1 ( 1 Epilepsy Monitoring Unti, Barrow Neurological Institute, Phoenix, AZ and 2 St. Joseph's Hospital, Phoenix, AZ )

Rationale: Accurate classification of symptoms is essential for patients experiencing intractable seizures. To improve the assessment and treatment of unremitting seizures, a tertiary care hospital in the Southwest established an Epilepsy Monitoring Unit (EMU) in the early 1980's. In 2006, the EMU tripled in size from 5 to 15 beds, accompanied by an increase in number of nursing staff. To address these changes, a pilot project was designed to determine nurses' baseline knowledge of seizure symptoms and to serve as the basis for education planning.

Methods: 20 Staff nurses on a neuroscience unit were given a 2-part test to determine their experience, confidence and knowledge in identifying seizure types. In Part A, nurses were asked to classify 23 listed characteristics as either non-epileptic or epileptic seizures. In part B, nurses were asked to watch 6 seizure videos and identify the seizure type as a simple partial, complex partial, generalized or non-epileptic seizure.

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Results: Descriptive data indicated that mean nursing experience was 9.74 years (range = 0.0–35.00) with 4.61 years (range = 0.42–16.00) experience in neuroscience nursing. The average number of shifts worked in the EMU was 2.91 per week. Seizure type was correctly classified in 65.05% of the videos, while the 23 characteristics were identified correctly 78.48% of the time. The results were further divided by years of neuroscience nursing experience: 0–1 years, 1–5 years, 6–10 years, and 10+ years. The nurses with 0–1 years experience scored 78.26% on Part A and 53.33% on Part B. Nurses with 1–5 years experience scored 71.98% on Part A and 68.52% on Part B. The next category of nurses with 6–10 years experience scored 88.04% on Part A and 79.16% on Part B. Finally, the nurses with 10+ years of nursing experience scored 89.13% on Part A and 50.00% on Part B. When measuring the confidence level of nurses in identifying seizure types, nurses with 0–1 years experience scored 1.66 on a range of 0–10. Nurses with 1–5 years experience scored 5.18 while those with 6–10 years experience scored 3.06. Finally, nurses with 10+ years scored 7.50 on a range of 0–10.

Conclusions: Although the number of years experience is related to nurses' abilities to accurately classify seizure types by characteristics, as listed in Part A, there is no relationship between years of experience and the ability to identify a seizure type by watching the videos. When measuring the confidence level of nurses in identifying seizure types, nurses with 10+ years of experience were more confident, those with less than 1 year experience were less confident, and those with 1–5 years and 6–10 years were neither confident nor unconfident. Although all nurses scored greater than 71% on Part A, even the most experienced nurses were only able to correctly identify the seizure types 50% of the time on Part B. As a result of the findings and because accurate seizure classification is essential to the delivery of quality patient care, an educational plan will be developed. EMU nurses of all experience levels will receive further education and be reassessed at a later date.

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Latasha Dees 1,2 , D. F. Clarke 2,3 , D. Hollar 4 , A. McGregor 2,3 , F. Perkins 2,3 and J. Wheless 2,3 ( 1 Nursing, University of Tennessee Health Science Center, Memphis, TN ; 2 LeBonheur Comprehensive Epilepsy Program, Memphis, TN ; 3 Pediatric Neurology, University of Tennessee Health Science Center, Memphis, TN and 4 Office of Education and Development, University of North Carolina School of Medicine, Chapel Hill, NC )

Rationale: The purpose of this study is to examine parents' viewpoints of how well education, treatment, and communication are carried out during the long term pediatric epilepsy diagnostic and treatment experience.

Methods: The study is being conducted in a seven-bed, dedicated pediatric epilepsy monitoring unit. Data is being collected using a self administered 5-point Likert-style scaled survey developed by EMU staff. The surveys are being given to parents of n = 150 patients who had preplanned admissions to the EMU upon discharge. Data is being analyzed using SPSS, Version 15.0 and consisted of internal comparisons (independent samples t-test and oneway Analysis of Variance). The independent variables are prior EMU stay, number of days in the EMU, and whether or not the patient had a seizure during their stay. The dependent variables are education, treatment, and communication.

Results: Preliminary results show that most parents were satisfied with overall quality of care, education, and communication provided by the physicians and nursing staff. There were complaints about the size of the patients rooms. Also, parents requested more play activities to ease the fear and anxiety experienced by the patient.

Conclusions: Results thus far, highlight the importance of provider-patient communication skills, provider teamwork skills, and health literacy, as outlined in recent Institute of Medicine (IOM) reports, for addressing patient and family concerns during visits to the pediatric epilepsy monitoring unit.

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Christianne N. Krassman 1 , J. Congram 1 , E. Philip 1 , M. Rigby 1 , S. Macrodimitris 1 and M. Suddes 1 ( 1 Clinical Neurosciences, Calgary Health Region- Foothills Medical Centre, Calgary, AB, Canada )

Rationale: Little literature documenting (a) staff and patient experience of a seizure monitoring unit (SMU), and (b) quality improvement activity related to the SMU clinical processes is available. By evaluating staff perspectives and satisfaction regarding the SMU, we hope to identify areas of improvement which will guide ongoing quality improvement activity. Available literature on staff satisfaction in health care shows a link between staff satisfaction and quality of patient care; whereby staff satisfaction can influence patient's perceptions of the quality of care, and therefore a positive correlation between staff and patient satisfaction exists.

Methods: A staff satisfaction survey was developed by the SMU Quality Improvement (QI) team. Multi-professional staff members were asked to select one response for each of the questions. A five point Likert scale was used for all quantitative survey items. There were also two open-ended questions intended to elicit qualitative data.

Results: The response rates for staff are as follows: Staff MD 60%, RN 37%, EEG Tech 54%. A total of 27 responses were received with an overall response rate of 33%. The survey consisted of 34 items which measured staff satisfaction across a range of dimensions. 73% of staff who responded rated the SMU as above average or better when comparing the unit to other work areas. Survey items rating teamwork and safety were rated most positively overall, with items relating to consistency of staffing and availability of equipment being rated least positively. Chi square analysis was conducted on all survey questions to establish any significant differences in the perception of staff across different disciplines. Preliminary findings show no significant differences between the professional roles for most items. EEG techs were, however, more satisfied with the opportunity to work closely with patients than other staff (p = 0.003) and nursing staff were less satisfied than EEG techs in their ability to troubleshoot equipment problems (p = 0.015). Qualitative responses to survey questions on positive aspects of staff's experience on the SMU alongside opportunities for improvement suggest that: staff valued the unique clinical opportunities of the environment, appreciated the opportunity to work closely as a multi-professional team, and also that staff felt communication between disciplines was good. Areas for improvement included providing more continuity of nursing staff, access to equipment, improving the research profile for staff other than physicians and further developing team educational strategies.

Conclusions: With this survey, designed to generate information regarding staff satisfaction in working in the SMU, we have gained information that will be used to guide SMU Quality Improvement initiatives. We believe that a quality management approach that emphasises the importance of capturing both patient experience and staff satisfaction will help drive improvements in patient care in both a meaningful and measurable way.

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Ikuko Laccheo 1 , E. Ablah 1 , R. Heinrichs 1 , T. Sadler 2 , L. Baade 1 and K. Liow 1,2 ( 1 University of Kansas, School of Medicine, Wichita, KS and 2 Via Christi Comprehensive Epilepsy Center, Wichita, KS )

Rationale: As the population ages, it is critical that physicians are capable of managing all chronic illness, including epilepsy, the third most common neurological condition of the elderly. Optimal treatment of epilepsy should include understanding health related quality of life (HRQOL), a state of complete physical, mental, and social well-being, in addition to seizure control; however, limited information is available to guide HRQOL issues among elderly. The goal of this study is to assess HRQOL in the elderly population with epilepsy, using both a seizure-specific and a generic instrument.

Methods: The Quality of Life in Epilepsy Inventory (QOLIE-31) and The Short Form 36 (SF-36) were mailed to 56 patients age 60 and older with established diagnosis of epilepsy at Via Christi St Francis Comprehensive Epilepsy Center.

Results: Of the 56 surveys, 23 responded, a 41% response rate (mean age = 60, age range = 60–82). Our sample's overall QOLIE-31 scores (average = 62.74) were not different from that of adult epilepsy populations (average = 62.87) for which the QOLIE-31 scores were standardized [Figure 1]. Our study suggests overall QOLIE-31 score correlates with total SF-36 score (QOLIE-31 score was similar to SF-36 score). However, our SF- 36 scores were significantly lower than that of general adult population without epilepsy, t (22) =−2.228, p = 0.036. All eight of the subscale average scores were lower than the norms, and five were significantly low: physical function, t(22) =−3.641, p = 0.001; role-physical, t(22) =−3.517, p = 0.002; general health, t(22) =−2.541, p = 0.019; social functioning, t(22) =−2.861, p = 0.009; and role-emotional, t(22) =−2.909, p = 0.008 [Table 1]. Our participants reported significantly greater limitations due to their poor emotional and physical problems than that of general adult population. QOLIE-31 epilepsy-specific items indicate that though seizure worry tends to be less of a concern than general epilepsy population, 74% of our participants are worried about the long-term side effects of their anti-epileptic drug (AEDs); 61% reported physical side effects of AEDs, and 65% reported mental side effects of AEDs.

Conclusions: We conclude that seniors with epilepsy do not necessarily have poor HRQOL compared to the general populations with epilepsy. However, when compared to general adult populations, seniors with epilepsy report a significantly lower HRQOL across all domains. Though seizures are generally easily controlled in elderly, it is possible that AED side effects and depression may be affecting their HRQOL. Multiple factors that may uniquely affect HRQOL among elderly populations with epilepsy include: aging variables (dementia, stroke, etc.), comorbid conditions (depression), and epilepsy variables (independence issues, AED side effects, unpredictability of seizure etc.). However, to our knowledge, there is no one instrument that addresses all of these aspects. The development of HRQOL instruments specifically for an elderly population with epilepsy may be useful and needed.

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[ Table 1 ]

SF-36 norm: based on 2474 general population in the US

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Nancy G. Thornton 1,2 , M. Blackman 1,2 , E. Sherman 1,2 , L. Hamiwka 1,2 and E. Wirrell 1,2 ( 1 Neurosciences, Alberta Children's Hospital, Calgary, AB, Canada and 2 Calgary Health Region, Calgary, AB, Canada )

Rationale: To (1) assess family function and determine the effects of epilepsy variables on family function in cognitively normal children with epilepsy (CWE), and (2) to compare the effect of family function on CBCL Total Competence, Internalizing and Externalizing Behavior in CWE and their non-epileptic siblings (SIBS).

Methods: This was a cross-sectional, cohort survey of CWE, aged 6–17 years, with an estimated developmental quotient >70 identified through the Neurology database at the Alberta Children's Hospital. Parents were asked to complete the Family Assessment Measure III (FAM III) and a Child Behavior Checklist (CBCL) for their child with epilepsy and for his/her nearest-aged sibling without seizures. Epilepsy variables including syndrome, etiology, seizure frequency, age at onset, total AEDs used and family history of epilepsy were assessed by chart review. Family function was divided into three categories: Strong (overall FAM III rating T score <40), Average (T score >40–<60) and Weak (T score >60).

Results: 82/101 (81%) families approached for study participated. Overall, families were functioning well (mean overall rating scores on the FAM III of 49.6 - no significant difference from normative mean). Only 11% of families had T scores >60 indicating poorer family function. Families scored significantly better than the normative mean on the Involvement subscale (p < 0.03) and significantly worse than the mean on Role Performance subscale (p < 0.04) - a scale which measures agreement regarding role definitions and ability to adapt to new roles. No significant correlations were found between any epilepsy variable and overall rating score on the FAM III. However, very significant correlations were noted for both CWE and SIBS between the overall FAM III rating score and CBCL Total Competence (CWE – p < 0.004), SIBS – p < 0.03), Internalizing (CWE – p < 0.001, SIBS – p < 0.001) and Externalizing Behaviors (CWE – p < 0.001, SIBS – p < 0.002).

While CWE scored significantly lower than SIBS on Total Competence (p < 0.002), and significantly higher on Internalizing Behaviors (p < 0.001), this difference was very dependent on family function category. The proportion of CWE and SIBS in the borderline/clinical range on Total Competence and Internalizing and Externalizing Behavior was not significantly different in families functioning in the Strong or Weak categories. However, in families functioning in the Average category, significantly more CWE than SIBS were functioning in the borderline/clinical range for Internalizing (p < 0.004) and Externalizing Behavior (p < 0.05).

Conclusions: Families of cognitively normal CWE function well overall. While they score significantly higher on the Involvement subscale, they do poorly in Role Performance. Stronger family function protects against behavior and competence problems in CWE. Specific strategies aimed at improving Role Performance may strengthen family function and reduce the risk of behavioral co-morbidities.

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Malachy Bishop 1 ( 1 Malachy Bishop, University of Kentucky, Lexington, KY )

Rationale: For decades, persons with epilepsy have been characterized by higher levels of unemployment and underemployment than are seen among the general population. This has been found to be the case in the US and around the world. In the last two decades there has been significant activity internationally in the development of legislation aimed at equalizing employment opportunities for persons with disabilities. There has, in the same period, been concurrent growth in research aimed at understanding employer attitudes toward persons with epilepsy, and the employment situation of persons with epilepsy internationally. For the most part, research in these areas has been limited to single countries or regions within countries. There has been, as yet, a comprehensive international review of the employment situation for persons with epilepsy. Such a project will require the understanding of a number of basic issues. This presentation describes one such issue: the current state of employment discrimination legislation internationally for persons with disabilities, and in particular, the nature of the impact and application of these for people with epilepsy. The purpose of this project was to identify the prevalence, common features, and relevance to persons with epilepsy of legislation related to employment and epilepsy internationally.

Methods: A comprehensive review of employment and anti-discrimination law internationally was undertaken, exploring the form of anti-discrimination and employment legislation for persons with disabilities. The methodology included ensuring that nations on each continent were included, as were representative forms and structures of legislation. The scope and definitions, bodies or agencies responsible for enforcement, and related information were reviewed. In addition, the epilepsy literature was reviewed to identify the perspective of the impact of relevant legislation for persons with epilepsy.

Results: Since 1990, employment and anti-discrimination laws directed at enhancing equal opportunities for persons with disabilities have been developed in numerous countries, and multi-national groups have developed policies or guidelines relevant to this issue. We present an overview of the forms, scope, and definitions of legislation internationally, as well as important differences and similarities, and discuss the implications for persons with epilepsy.

Conclusions: This project represents one foundation for an international understanding of the employment situation for persons with epilepsy. A comprehensive understanding and knowledge base will require several additional pieces and the cooperation and knowledge of international partners. However, this project contributes to the process by significantly enhancing understanding of the legislative component of employment for persons with epilepsy internationally.

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Sandra Cushner Weinstein 1 , N. Watt-Marin 1 , K. Dassoulas 1 , P. Pearl 1,2 , W. Gaillard 1,2 and S. L. Weinstein 1,2 ( 1 Neurology, Children's National Medical Center, Washington, DC and 2 Neurology, George Washington University School of Medicine and Health Sciences, Washington, DC )

Rationale: Epilepsy can be a challenge for families as they learn to manage their child's seizures and cope with condition-related stressors. Educational programs about epilepsy, currently available, have been found to be beneficial for parents. Yet, few studies have investigated the impact of epilepsy on parents or offered interventions to promote adaptive coping. Using prior work on experimental manipulation of self-concept and self-presentation, two interventions were designed. Strategic self-presentation was used to bolster parent's confidence and image as one who successfully copes, while the intervention of emotional disclosure was utilized to promote a reduction in psychological distress. This study compares the two interventions of strategic self-presentation (SSP) and emotional disclosure (ED) with education as the control, and evaluates their impact on parental adaptive coping.

Methods: Sixty-seven parents of children with epilepsy, ages 7 to 18 years, were recruited from Children's Hospital clinics and the epilepsy camp, Great Rock. The parents were randomly assigned to one of three groups including (SSP), (ED), and the control. In the SSP and the ED groups, parents were asked sixteen similar questions in a structured videotaped interview phrased to elicit different responses. In the SSP group parents were asked to share “what worked” with their child or effective coping strategies. In the ED group, parents were asked to discuss problems related to their child's epilepsy. The control group watched a standard educational video about epilepsy and answered questions. Parents completed the Coping Health Inventory for Parents (CHIP), at baseline (n = 67), post-intervention (n = 57), and the 3 month follow-up (n = 51). Parents also completed the Family Inventory for Resource Management (FIRM) as a confounding variable. A univariate analysis of Variance (ANOVA) was used to determine homogeneity across the three groups for demographic variables and baseline measures. A paired sample t-test was used to measure change from pre and post test interventions on the CHIP. A MANOVA was used to assess interactions of gender, severity, and perception of family resources, with the CHIP.

Results: The Strategic Self Presentation group showed significant improvement (p < .05), in one domain of the CHIP, “understanding the medical situation through communication with other parents and medical staff”. The Emotional Disclosure group showed significant worsening (p < .05), in one domain of the CHIP, following the interview. There was no significant change in the control group. Effects of gender, severity and family resources were found within all groups. Three months later, without interventions or boosters, the two groups returned to their baseline.

Conclusions: Strategic self-presentation appears to demonstrate some immediate beneficial effect for parents of children with epilepsy; however, further studies with larger numbers are needed to investigate the short and long-term benefit for clinical use. Additionally, the frequency of intervention and feasibility of use in healthcare settings must be determined.

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Sharon Mason 1 and R. Doss 1 ( 1 Minnesota Epilepsy Group, P.A., St. Paul, MN )

Rationale: Treatment of the Non-epileptic seizure patient (NES) post diagnosis is a challenge for the epilepsy treatment team. In our program, NES patients are typically recommended for follow-up with both a neurologist and psychologist post inpatient diagnosis and discharge. The purpose of this study was to determine the rate of return to follow-up clinic appointments in this population.

Methods: The sample consisted of 57 patients discharged from the adult inpatient epilepsy unit with the diagnosis of NES over a 2 year period. A psychogenic etiology for their seizure events was determined after ruling out physiological causes, and conducting a thorough psychological assessment. Follow-up record review identified those patients who returned to the clinic at least one time for an appointment with the neurologist and/or psychologist.

Results: Of the 57 patients reviewed 27 (47%) returned to the clinic to meet with the neurologist. Of that group 12 (20%) also met with the psychologist. There was a cancellation rate of 12% and 4% of the patients failed their scheduled appointment. The remaining 21 patients (37%) were lost to follow up. Results will be considered in relation to demographic variables and personality characteristics.

Conclusions: These findings indicate that a significant number (52%) of NES patients do not return to meet with the Epilepsy Center neurologist or psychologist following discharge, despite specific recommendations to do so. Our program believes that outpatient follow up of these patients is crucial for resolution of psychogenic seizures and improved well-being. The discharge conference may be a critical opportunity to emphasize the importance of such follow through. Further research is needed to determine the reasons for lack of compliance with discharge recommendations.

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Suzanne R. Hawley 1 , K. Liow 1 , A. M. Paschal 1 , E. Ablah 1 , T. St.Romain 1 and C. A. Molgaard 1 ( 1 University of Kansas School of Medicine-Wichita, Wichita, KS )

Rationale: Epilepsy is a chronic neurological illness that affects 2.7 million Americans, but remains poorly understood. Care providers may not recognize their patients' need for epilepsy information, contributing to treatment barriers such as stigmatization and poor patient-provider communication.

Methods: The current study piloted a survey of epilepsy-related attitudes and perceptions of 33 Midwestern neurologists. The survey included questions about perceived barriers to and motivators for treatment, thoughts on misperceptions of epilepsy in the community and in the patient population, and potential interventions to address misperceptions.

Results: Respondents perceived misinformation and lack of knowledge in patients and the general public that could be contributing to the barriers which exist to treat patients adequately. Respondents suggested potential methods for addressing misperceptions effectively, including treatment motivators and educational formats.

Conclusions: The general public is often thought to have misperceptions about epilepsy. This study found that many respondents believe their epilepsy patients also have a lack of understanding about the condition. This indicates a communication gap between epilepsy patients and their care providers, and a significant need for education on multiple levels.

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Menascu Shay 1,2 and E. Donner 2,1 ( 1 Pediatric neurology unit, Tel-Hasomer, Tel-aviv, Israel and 2 Pediatric neurology, hospital for sick children, Toronto, ON, Canada )

Rationale: Linear nevus sebaceous syndrome (LSNS) reported to occurs in as many as 1 in 1000 live births and currently it is hypothesized that this disorder is the result of genetic mosaicism involving a lethal autosomal dominant gene.LSNS encountered a broad spectrum of abnormalities which may affects every organ system including the central nervous system,which then seizures and mental retardation are it main manifestation but many other system where also reported to be involved in this syndrome including the cardiovascular, skeletal, ophthalmological, urogenital and more.Allude LSNS occurs in relative high frequency and may affects different organ systems many physicians are not aware of it concurrent,which may delay diagnosis and treatment

Methods: We present 2 complex cases of LSNS with their evolution and review the current literature in this field

Results: This syndrome is reported to occur in as many as 1 in 1000 live births without gender predominance. In 1975, Solomon and Esterly extensively reviewed LNSS associations grouping them into one category and defining them all as epidermal naevus syndrome (ENS).As progress was made in our understanding of dermatogenesis,6 subsets of ENS have been identified, distinguished by their genetic and clinical presentations.ENS is clinically expressed by epidermal mosaicism and in up to 18% of patients the mesoderm is also involved, which results in the associated findings of different clinical syndromes.Cutaneous findings are found in up to 30% of patients with epidermal nevus syndrome including large hypopigmented patches, hemangiomas,acanthosis nigricans-like lesions,café-au-lait spots and multiple nevi.Skeletal abnormalities are reported in up to 68% of patients with epidermal nevus syndrome and include localized alterations of the cranium consistent with fibrous dysplasia, and primary or secondary bony defects.Ocular abnormalities are reported to occur in up to 68% of patients with ENS with strabismus as the principal finding and epilepsy occurs in up to 25%. Multiple epileptic syndromes have been reported in association with ENS and LSNN including infantile spasms or West syndrome, as presented in our cases, sometimes evolving into Lennox-Gastaut syndrome. Ohtahara syndrome has been reported as well, progressing to Lennox-Gastaut syndrome

Conclusions: LSNS is relatively common neurocutaneous disorder with multi-system involvement.Children with this condition may present to various sub-specialty physicians, which may delay diagnosis, as in our second case when the correct diagnosis was made only at 3 years of age. We suggest that all children with suspected diagnosis of LNSS should undergo a multisystem evaluation, including EEG, brain MRI,hepatic and renal function testing and ophthalmology assessment

Linear naevus sebaceous on a scalp

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Pic.2: Brain MRI shows a small rigth subepindemal gray matter hetrotopia of the frontal horns(big harrows) and bilateral frontal lobs polymicrogyria(small harrows)

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Cecilia E. Aragon 1 , T. Hess 2 and J. G. Burneo 3,2 ( 1 Schulich School of Dentistry, University of Western Ontario, London, ON, Canada ; 2 Schulich School of Medicine, University of Western Ontario, London, ON, Canada and 3 Epilepsy Programme, University of Western Ontario, London, ON, Canada )

Rationale: Access to dental care and delivery of quality dental health services are important for people living with epilepsy. Controversy exists about the relation of societal knowledge and attitudes regarding epilepsy. We conducted a survey to examine knowledge and attitudes among dentists, and how would it influence access to dental care.

Methods: A standardized questionnaire that evaluated knowledge regarding epilepsy as well as attitudes towards and willingness to provide dental care to persons with epilepsy was administered to all dentists in the city of London, Ontario, Canada.

Results: 196 out of 288 dentists completed the survey (68% response rate), 27% were females, and 76% were general dentists. Most of them have never known anybody with epilepsy (92%) or seen anyone having a seizure (72%). Knowledge was weakest for the approximate prevalence of epilepsy in the population, hereditary epilepsy and several other etiologies, recognition of nonconvulsive seizures as a type of epilepsy, and knowledge of antiepileptic drug-induced teratogenicity. Attitudes were found to be variable and not uniformly favorable. 3 and 14%, respectively, showed negative bias against persons with epilepsy having children and equal opportunity for occupational employment. 2 and 6%, respectively, showed attitudes against letting their children associate with somebody with epilepsy, and letting somebody of their close family marry a person with epilepsy. A significant group of respondents (21%) would put something in the mouth of a patient having a seizure while in the dental office to prevent choking; or would hold the patient tight. Of major importance is that 7% of dentists would refuse to provide services to patients with epilepsy, and the reasons were family and other patients' concerns (as they may become reluctant to see the practitioner again).

Conclusions: Attitudes were of concern, particularly knowing that the surveyed population belongs to the health professions' group. The results affect directly on the access to dental care of persons living with epilepsy. Results also indicate a lack of knowledge among an important percentage of dentists in London, which perhaps could be improved on with an educational intervention.

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Luis C. Mayor 1 , J. G. Burneo 2 and J. G. Ochoa 3 ( 1 Neurology epilepsy programme, Fundacion Santa Fe de Bogota, Bogota, Colombia ; 2 Epilepsy Programme, University of Western Ontario, London, ON, Canada and 3 Epilepsy programme, University of florida, Jacksonville, FL )

Rationale: Formal training in electroencephalography (EEG) is scarce in some Latin Americans countries. To overcome the distance barrier a web-based course in EEG was developed. In 2005, a web-based program for the teaching of EEG was started by the E-Health, Center for Education (Internet-based) and simulation from the Division of Education of the Fundación Santa Fe de Bogotá, in Colombia. We describe the preliminary results of the use of this novel strategy.

Methods: The course was accessed by physicians invited by the center in an initial pilot period of training. For subsequent users a registration and a fee were obtained. The course is given in Spanish language and can be found at the URL: http://www.e-health.edu.co/cursos_elearning/electroencefalografia.php. It consists of 12 modules, including EEG technology, normal EEG, activation procedures, variants and artifacts, abnormal EEG, EEG in coma, the epilepsies, the EEG report, video-EEG, magnetoencephalography, and a final module of clinical cases, vignettes, glossary of terminology, and questions and answers. After each module the participant had to complete a post-test to assess early retention. At the end of the course, a survey (using a rating scale) was given to all participants in order to evaluate structure, content, and delivery of information.

Results: 382 physicians from four different countries (Colombia, Ecuador, Peru, and Venezuela) accessed the course between August of 2005 and December of 2006. 85% of participants gave a maximum score to the structure of the course, 75% to the content, and 92% to the delivery of the information.

Conclusions: The high number of participants indicates the need to implement similar approaches in the teaching of EEG in areas of the world with no access to training programs. Online education is an effective and feasible method to deliver EEG training to a widely disperse professional community. The positive feedback indicated that this technique has great acceptance. Further evaluation is needed.

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Nikesh I. Ardeshna 1 , L. Schultz 2 and M. V. Spanaki 1 ( 1 Neurology, Henry Ford Hospital, Detroit, MI and 2 Biostatistics, Henry Ford Hospital, Detroit, MI )

Rationale: Epilepsy is a common neurological disorder with no racial predominance. However, little is known whether understanding and perceptions of epilepsy differ among various cultures. To the best of our knowledge only one study in the US identified a high rate of misperceptions in the Spanish population (Sirven, J. Epilepsy & Behavior, 2005). The purpose of our study was to determine and compare the awareness of epilepsy in an Indian and a Caucasian community regarding symptoms, causes, treatment, psychosocial implications, and stigma.

Methods: A 10-item multiple choice survey (IRB approved) was distributed to 170 households in an apartment complex, and a similar one to members of a Gujarati (Indian community) seniors club. The questions in the later group were written in Gujarati and clarified by an interpreter. Respondents were asked to choose which one statement out of five best described their opinion. Demographic items included age and ethnic background. Knowledge based items included symptoms of epilepsy, prevalence, treatment, and first aid. Social issues were addressed by questions pertaining to employment, driving and stigma. Descriptive statistics were applied and comparison between groups was done.

Results: Demographics: Forty five residents (81% of which were Caucasians) of the apartment complex (24%), and 87 members of the Indian community (89%) responded. Knowledge: Forty-four percent of Indians felt that shaking of the body constitutes a seizure as opposed to 75% of Caucasians who listed any of shaking, confusion, memory lapses and sensory symptoms to be part of a seizure (p < 0.001). The majority of respondents in both groups listed trauma/prior accident as the cause of epilepsy. Regarding treatment, 42% of the Indian community chose medication, as opposed to 76% of Caucasians. Behavior and psychiatric therapy was selected by 36% of Indians and only 7% of Caucasians. Surgery as a treatment option was chosen by less than 15% in both groups. When providing immediate assistance to a seizing patient, 26% of Indians indicated they would lay the person on the floor, compared with 54% of Caucasians (p = 0.003). Social issues: In both groups, the major concern for an individual upon learning that a friend had seizures was their lack of knowledge as to how better help them [90% Caucasian, 55% Indians, (p < 0.001)]. A statistically significant difference was also identified concerning a patient's working ability. Fifty six percent of Caucasians believe that epilepsy patients can work full time with limitations, as opposed to 35% of the Indian group (p = 0.025).

Conclusions: Our survey showed that knowledge about epilepsy significantly differs between the Indian and Caucasian communities in particular with respect to seizure manifestations, first aid and treatment. Physicians need to be aware of these differences when caring for their increasingly diverse patient populations. Our findings demonstrate the need to better educate epilepsy patients by tailoring education efforts to their ethnic background.

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Gayle M. Moriner 1 , D. Zhao 1 , M. Toole 1 , E. O. Richter 1 and L. Hyer 1 ( 1 Georgia Neurosurgical Institute, Macon, GA )

Rationale: The World Health Organization has identified inadequate access to high level treatment of epilepsy as a major problem. Many of the barriers to care are economic, but they are seldom compared to the economic benefits of optimal care. We examined the projected economic impact of establishing a new center in an underserved region.

Methods: Statistics from the Epilepsy Foundation of America (EFA) regarding the cost of epilepsy nationally, the CDC on prevalence of epilepsy in Georgia, and the US Census data on the population of central Georgia were applied to the 7 county region defined by a central Georgia hospital as its primary service area. From these figures an estimate of the economic impact of epilepsy on the central Georgia area was calculated. Further data from published series regarding the effect of optimal quaternary services on seizure control were then applied to these figures for an estimate of savings.

Results: Based on CDC estimates of a1% prevalence in Georgia, and US Census data of the estimated 2005 population, the primary service area of the hospital should contain roughly 7,481 epileptic patients. The estimate of $4,629/year/patient, lead to an estimated total cost of 34.6 million dollars per year for the region in epilepsy care. Conservative estimates predict at least a 40% reduction in direct costs with optimal care, leading to an annual savings of nearly 14 million dollars.

Conclusions: This analysis demonstrates that the economic impact on direct costs of optimal treatment of epilepsy patients is substantial, at least 14 million dollars per year in the defined 7 county region. Indirect costs will need to be addressed in future models, as will issues of who benefits from such savings compared to who bears the increased cost of the treatment.

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Tammy L. Still 1 , J. Loney 2 , M. Blackman 1 , N. Thornton 1 , L. Hamiwka 1,2 and E. Wirrell 1,2 ( 1 Neurosciences, Alberta Children's Hospital, Calgary, AB, Canada and 2 University of Calgary, Calgary, AB, Canada )

Rationale: In children presenting with a presumed first seizure, to determine: (1)medical information provided to children and families, (2) level of satisfaction with the information provided and (3) what children and families know about seizures before their visit to the First Seizure Clinic.

Methods: Children were identified through the First Seizure Clinic at the Alberta Children's Hospital. Included were children ages 3 to 17 years with an unprovoked first afebrile seizure. Prior to the visit with the physician, the parent completed the Nursing Parent First Seizure Questionnaire. This questionnaire included an inquiry regarding sources of information both suggested and sought by families as well as satisfaction with these sources. A true/false section was included to assess basic understanding of seizures and epilepsy with questions focusing on stigma and safety.

Results: Thirty-one families participated in the study. All families were referred from the Emergency Department. Family responses regarding information sources included: oral information 16 (64%), no information 9 (36%), combination of handouts/pamphlets and spoken information 1 (4%) and no response 1 (4%). Of the 17 families who received information, 11 (64%) were satisfied.

18 (72%) families stated they were not directed to further information sources. 21 (84%) of all parents sought further information including: combination of sources 12 (57%), internet 5 (24%), other medical resources 3 (14%) and 1 (5%) did not respond. Of these, 16 (76%) were satisfied with the information they found, and 5 (24%) were not satisfied.

In 12 families (48%) the diagnosis of seizure was discussed with them. Seven (28%) families received seizure recognition information. 11 parents (44%) were provided information about first-aid.

With regards to seizure knowledge, parents had a mean score of 69% on safety questions and 91% on stigma questions.

Conclusions: A significant portion of parents received no information regarding their child's seizure. The majority of families were not directed to further information sources however most did seek additional resources. We did not assess reliability or validity of these resources. Although family knowledge with regard to seizures was generally good, it is concerning that families had significantly greater knowledge regarding stigma compared to safety. This points to the importance of providing comprehensive and accurate seizure information. We must work with our front line colleagues to implement this practice.

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Jacki Gordon 1 , P. O. Shafer 2 , S. C. Schachter 3 , K. Macher 1 and J. A. Cramer 4 ( 1 Epilepsy Therapy Development Project, Reston, VA ; 2 Beth Israel Deaconess Medical Center, Boston, MA ; 3 Harvard Medical School-Beth Israel Deaconess Medical Center, Boston, MA and 4 Department of Psychiatry, Yale University School of Medicine, New Haven, CT )

Rationale: The importance of the Internet to patient education and physician/nurse professional development is growing rapidly. Access to medical information must be immediate, relevant, credible, and easy to use. Users demand focused and well-indexed content developed according to the defined needs of the target audiences. The Epilepsy Therapy Development Project (EDTP), established websites to provide comprehensive content to epilepsy patients, families, caregivers, and healthcare professionals.

Methods: ETDP websites were examined to determine viewer patterns, trends over time, and changes in level of content accessed. Data from March 2007 served as a sample of viewer habits. Web pages concerning related content were pooled where appropriate. The sites reviewed included: http://www.epilepsy.com (PT, patient/caregiver, debut 10/03), http://professionals.epilepsy.com (PR, professionals 12/04), and http://www.my.epilepsy.com (ME, community information exchange, 9/05).

Results: In March 2007, 1,147,664 combined page views (PT 831,145 ME 253,092 PR 63,428) represented a 7% increase over the previous month, continuing a trend toward steady growth monthly for all sites. There were 205,850 unique visitors (PT 138,385 ME 21,537, PR 45,928). Visitors came from across the US (70.5%) and around the world. The vast majority were new visitors (PT 92% ME 93% PR 95%), with some returning weekly. Community users were overwhelmingly interested in basic information, especially seizure medications (167,384 views) and epilepsy 101 (133,634 views). Specific topics had much smaller numbers. Of the audience-specific topics, people stories (27,061), family (14,320), children (13,036) were visited most frequently. Professionals most often entered the site directly, viewing more specific epilepsy topics; areas on diagnosis, co-morbid disorders, epilepsy syndromes, and hormonal aspects attracted 49%, while the resource library of tools, tables, and articles were used by 21%. Most frequent downloads were information on specific AEDs (41%–61%), followed by first aid and treatment tools (15%). Clinical trials information attracted 8167 views.

Conclusions: Use of the epilepsy.com family of websites is growing steadily. Community viewers tend to enter looking for basic information, articles about AEDs, and for support from others in the epilepsy community with information exchanges, chat rooms, and blogs. Healthcare professionals enter for both general information and to research specific questions, such as coexisting disorders and causes of epilepsy. A growing trend of using the website to access resource tools for clinical practice and using forms of experiential learning is noted, deriving from PR website features new in the past year. More research is needed to determine user satisfaction, and whether viewers exit when they have satisfied an information need or because they have not met their specific need. Work is in progress to better inform users about what is available.

(Funding Support: Epilepsy Therapy Development Project,a not-for-profit foundation)

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Elaine Hunter 1 , M. K. Campbell 1,2 , G. Zou 1 and K. N. Speechley 2,1 ( 1 Epidemiology & Biostatistics, University of Western Ontario, London, ON, Canada and 2 Paediatrics, University of Western Ontario, London, ON, Canada )

Rationale: To assess the role of family-centered care for health-related quality of life of children with epilepsy, a valid and reliable measure of family-centered care in pediatric epilepsy is required. We hypothesized that a measure initially developed for parents of children with neuro-developmental disabilities, the Measure of Processes of Care (MPOC-20), might be useful and thus adapted it for parents of children with epilepsy. The objectives of this study are to evaluate the measurement properties of the MPOC-20 and determine its feasibility for assessing parents' perceptions of the extent to which their child's epilepsy care is family-centered.

Methods: The evaluation of the measurement properties of the MPOC-20 is a sub-study of a Canada-wide study, Health-Related Quality of Life in Children with Epilepsy Study (HERQULES). An objective of HERQULES is to prospectively investigate several potential determinants of children's health related quality of life including parents' perception of epilepsy care. A mailed survey containing a slightly modified version of the MPOC-20 was completed by parents of children (4 to 12 years old) diagnosed with epilepsy by one of 52 pediatric neurologists about one month (n1 = 276), six months (n2 = 209) and 12 months (n3 = 125) post-diagnosis. Parents' responses were used to analyze face and construct validity, response variability, completeness and internal consistency. The MPOC-20 was re-administered to 23 parents to assess test-retest reliability.

Results: Face Validity- The vast majority of parents did not report any difficulty completing the MPOC-20, ranging from 93% (1 month) to 99% (12 months). Construct validity- MPOC-20 scores were moderately correlated with scores on the measure Patient Perception of Patient Centeredness for each subgroup (Pearson correlations 0.48 to 0.67, α= 0.05), but not with a measure of emotional stress. Internal Consistency- High Chronbach's alphas were observed for all three subgroups (0.93 to 0.97, α= 0.05). Test-retest reliability- MPOC-20 was highly stable (intraclass correlation coefficients 0.78 to 0.96, α= 0.05) Response variability- Entire range of responses was used for each MPOC-20 item in all subgroups. Missing Values-amount of missing data fell within the acceptable range for each domain of the MPOC-20, ranging from 10.8 to 24.9%.

Conclusions: The MPOC-20 demonstrated acceptable measurement properties when administered to parents of children with epilepsy population during the first year after diagnosis. It may be a useful measure to assess family-centered care in the management of childhood epilepsy.

(Funded by Canadian Institutes of Health Research Grant MOP-117493)

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Aylin Y. Reid 1 , N. Jetté 1 , H. Quan 2 , M. D. Hill 1,2 and S. Wiebe 1,2 ( 1 Clinical Neurosciences, University of Calgary, Calgary, AB, Canada and 2 Community Health Sciences and Centre for Health and Policy Studies, University of Calgary, Calgary, AB, Canada )

Rationale: Epilepsy is the most commonly reported neurological condition in primary health care in most of the world, affecting people of all ages, gender and socioeconomic status. As the prevalence of epilepsy is expected to rise with the aging population it is important to develop surveillance programs to monitor and project future demands epilepsy will place on society and the healthcare system. Comprehensive prospective cohorts are extremely costly and time-consuming. Passive surveillance using administrative data is a cost-effective way to follow individuals who have chronic conditions such as epilepsy. However, administrative databases must first be validated. Inpatient facilities across Canada use the ICD-10 system to code diagnoses, comorbidities and procedures in their administrative databases. The purpose of this study was to assess the validity of ICD-10 data from an inpatient administrative database.

Methods: All inpatient visits at a Canadian tertiary care center during the fiscal year 2004 with an ICD-10 code in the primary diagnostic position corresponding to epilepsy, transient ischemic attack (TIA), syncope, or classical migraine were identified. This enriched population which includes patients with diagnoses other than epilepsy was specifically chosen because these conditions can resemble seizure. A random sample of these charts (n = 132) were reviewed by an epileptologist and neurology resident and independently given an ICD-10 code. Sensitivity, specificity, positive and negative predictive values were calculated for ICD-10 epilepsy codes, as was the level of agreement between the trained health records technologists who had originally coded the charts and the epileptologist. The agreement between the epileptologist and the neurology resident was also calculated. The ICD-10 code given by the epileptologist to the particular hospital visit was considered the “gold standard”.

Results: Epilepsy coding in the primary diagnostic position using the ICD-10 system was very good, with a sensitivity of 96% (95% CI 87.9–99.0) and specificity of 99% (95% CI 92.9–99.8). The positive predictive value of an ICD-10 epilepsy code was 0.98 (0.90–1.00 and the negative predictive value was 0.97 (95% CI 0.91–0.99). Agreement between the epileptologist and trained coder was excellent with a Kappa value of 0.95 (95% CI 0.90–1.00). Agreement between the epileptologist and the neurology resident (inter-rater reliability) was also excellent at 1.00 (1.00–1.00).

Conclusions: Epilepsy cases coded in the primary diagnostic position can be accurately identified using inpatient administrative databases utilizing the ICD-10 coding system. Ongoing research targeted at validating secondary diagnostic positions coding, emergency visits and outpatient visits are necessary for the development of a future comprehensive population-based epilepsy surveillance program.

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Nathalie Jette 1,2 , A. Reid 1 , H. Quan 2,3 , M. D. Hill 1,2 and S. Wiebe 1,2 ( 1 Clinical Neurosciences, University of Calgary, Calgary, AB, Canada ; 2 Community Health Sciences, University of Calgary, Calgary, AB, Canada and 3 Centre for Health and Policy Studies, University of Calgary, Calgary, AB, Canada )

Rationale: Epilepsy affects people of all ages, gender and socioeconomic status and accounts for one percent of the global burden of disease. The prevalence of epilepsy is expected to rise with aging populations. It is thus necessary to develop surveillance programs to monitor and project the future social and clinical demands of epilepsy. The purpose of this study was to assess the validity of clinical administrative ICD-9 data to define epilepsy cases and to compare coding variations between hospital settings (adult vs. children, teaching vs. community).

Methods: All emergency and inpatient visits in calendar year 2000 coded in the primary diagnostic position with the ICD-9 epilepsy, transient ischemic attack, syncope or classical migraine codes were identified for patients of all ages. A randomly selected sample of charts coded for each of the above conditions (n = 424) were then blindly reviewed by an epileptologist and a neurology resident and independently coded with an ICD-9 code.

Results: Epilepsy coding was equally good regardless of hospital setting (community or teaching site, adult or pediatric site) with high sensitivity (Sn) and specificity (Sp). Sn and Sp were highest for inpatient admissions with Sn 98% and Sp 99%. Agreement in coding between the epileptologist and the professional coders or between the epileptologist and the neurology resident was excellent with a Kappa value of 0.97 and 0.98 respectively.

Conclusions: Epilepsy cases can be accurately identified using emergency and inpatient administrative data. Validation of outpatient databases will be required to develop a comprehensive population-based epilepsy surveillance program.

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Ki-Young Jung 1 , K. Park 1 , Y. Cho 2 , S. Yi 2 , M. Kim 3 , S. Lee 4 , I. Lee 5 , K. Kim 6 and H. Hwang 7 ( 1 Neurology, Korea University College of Medicine, Seoul, South Korea ; 2 Neurology, Dongsan Medical Center, Keimyung University College of Medicine, Daegu, South Korea ; 3 Neurology, Chonnam National University Hospital, Chonnam National University Medical School, Kwangjoo, South Korea ; 4 Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea ; 5 Neurology, KunKuk University Hospital, Kunkuk University College of Medicine, Seoul, South Korea ; 6 Pediatrics, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea and 7 Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea )

Rationale: There is no report on the subject of the difference of knowledge of and attitude to epilepsy between people with epilepsy (PWE) and healthy people (HP).

Methods: People with epilepsy and healthy people whose age was more than 18 years old were enrolled from the outpatient clinic and from health promotion center from seven university hospitals, respectively. We surveyed familiarity, knowledge and attitude towards epilepsy using structured questionnaire which consisted of 16 items.

Results: Nine hundred and thirty subjects (PWE 217, HP 713) were included in present study. Age and sex was not different between both groups. The familiarity with seizure and epilepsy (two items) was not different in both groups. The knowledge about seizure and epilepsy (7 items) was comparable except question about inheritance of epilepsy between two groups. However, the attitude towards PWE was significantly different in 6 out of 7 items. HP had more negative attitude towards PWE, most strong negativity concerning the matters related to their offspring (e.g. making friendship, marriage).

Conclusions: Our study demonstrated that healthy people in our country still have some misconception about epilepsy and have negative attitude towards PWE. It is required public health education and social campaign to lessen negative attitude to PWE.

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Thea Dupras 1 , S. Macrodimitris 1 , M. Suddes 1 , V. Gibbons 1 and N. Jette 2,1 ( 1 Clinical Neurosciences, Calgary Health Region, Calgary, AB, Canada and 2 University of Calgary, Calgary, AB, Canada )

Rationale: The paucity of literature on patient experience of the Seizure Monitoring Unit (SMU) indicates that this is a poorly understood aspect of epilepsy care. The objectives of this study were to: (1) explore patient-perceived quality of SMU care and (2) determine whether a standardized hospital satisfaction questionnaire could be used to compare patient-perceived quality of care on the SMU with other neuroscience units.

Methods: (1) The SMU Quality Improvement (QI) team developed a qualitative interview for SMU patients. Eligibility criteria included length of stay (LOS) ≥ 5 days and no developmental delay. 74.5% (n = 222) of patients admitted to the SMU were eligible. Nine were randomly selected. Interviews were transcribed verbatim and analyzed using qualitative methods. (2) The Hospital-Consumer Assessment of Healthcare Providers and Systems (H-CAHPS) is a 27-item survey endorsed for use in acute care hospitals by the Agency for Healthcare Research and Quality (AHRQ). Issues addressed include staff responsiveness, nurse and physician communication, patient-centered care, and discharge information. H-CAHPS was administered via telephone to a random sample of SMU and general neurosciences unit (GNU) patients admitted for ≥ 24 hrs in 2006.

Results: (1) Qualitative interviews - Four men and five women (M = 34.5 yrs, SD = 9.0) participated in the qualitative interviews. Mean LOS was 9.1 days (SD = 5.2). Qualitative analysis revealed the following themes: Admission procedures/information, staff responsiveness/communication, discharge procedures/information, impact on seizure management, physical set-up of SMU, issues related to being on the SMU, and patient and family involvement. Issues discussed in the interviews that were not covered by H-CAHPS included challenges with wait times and unknown admission date; change in seizure management; education about seizures; and family involvement. (2) H-CAHPS - Forty percent (n = 39) of patients discharged from the SMU and 10% (n = 81) of patients discharged from the GNU completed H-CAHPS. GNU participants were older (M = 51.1, yrs SD = 16.7) than SMU participants (M = 37.8 yrs, SD = 13.0). LOS was slightly longer for SMU participants (M = 8.2 days, SD = 4.5) than GNU participants (M = 7.6 days, SD = 5.8). Only 44% of SMU and 63% of GNU patients perceived that physicians always explained things in a way they could understand. Nurses received higher ratings (68% for both GNU and SMU). 75% of SMU patients believed that staff always responded to the call button compared to 63% of GNU patients. SMU patients were less satisfied with the quality of discharge information than GNU patients.

Conclusions: This study demonstrated that H-CAHPS is a useful tool for assessing patient feedback and highlighted areas for improvement. It can be used to compare patient perceptions of the quality of services provided on the SMU with a GNU. Patient interviews revealed that there are unique aspects of the SMU admission that are not evaluated by H-CAHPS but should be incorporated into a SMU patient survey. Future initiatives will focus on developing a SMU-specific survey based on H-CAHPS.

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Tricia Ting 1 , O. Ajayi 1 and A. Krumholz 1 ( 1 UMMS, Baltimore, MD )

Rationale: Acute repetitive seizures (ARS) frequently result in emergency department (ED) visits and carry a significant risk for status epilepticus (Haut, 1999). Of particular concern are patients repeatedly admitted for urgent management of ARS. Greater attention has, thus, been directed to identifying potentially preventable seizure precipitants. Health care studies have shown medication non-compliance to be the most common cause of seizures requiring hospitalization (Tan, 2005; Irving, 1999).

Similarly, an earlier study of ARS at the University of Maryland Medical Center (UMMC), found one of the most common precipitants in adult patients with ARS to be poor medication compliance.

Given the substantial impact of non-compliance in repeated ED visits for ARS, this study aimed to determine the patterns of discharge care, including counseling and outpatient follow-up, in order to define parameters for best practices.

Methods: Patients who presented to the UMMC Emergency Department (Baltimore, MD) with ARS between 07/01/05 through 2/1/06 were identified. Initial search criteria included all patients at least 18 years of age with discharge diagnosis code(s) for seizure(s). Patients who presented with status epilepticus or alcohol withdrawal seizures were excluded from this analysis. Records from ED admission(s) in the prior 12 months as well as the current ED admission were reviewed for documentation of patient counseling, recommendation for rescue benzodiazepine use, and follow-up care.

Results: 16 of 37 (43%) patients with ARS had multiple ED admissions within a 12-month period. Of those with multiple admissions with ARS, 13 of 16 (81%) had been counseled about the importance of medication compliance at previous admissions. None of the patients with multiple ED admissions had received a prescription for a rescue benzodiazepine. Similarly, only 2 of 21 (10%) of patients with a single ED visit for ARS in 12 months had been prescribed a rescue benzodiazepine upon discharge. Follow up at the University outpatient clinics could only be confirmed in 9 of 37 (24%) patients. 6 of 16 (38%) patients with multiple admissions had documented outpatient follow-up. ED records did not indicate whether primary care physicians or treating neurologists outside the University system were contacted to discuss AED management or follow-up care.

Conclusions: The majority of patients with multiple admissions with ARS had received counseling regarding the need for medication compliance prior to their current admission, raising the question of whether counseling in the acute setting is adequate or truly effective for improving compliance and preventing recurrent admissions. In contrast, only a minority of patients, either with a history of multiple admissions or only a single admission in the past 12 months, was given a prescription for a rescue benzodiazepine medication. Additionally, contact with treating physicians and subsequent follow-up care as documented may not be adequate to ensure the optimal management of patients with ARS, including the prevention of future seizure exacerbations.

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Sandra Magalhaes 1,2 and K. N. Speechley 1,2 ( 1 Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada and 2 Paediatrics, University of Western Ontario, London, ON, Canada )

Rationale: Delivery of Family Centered Care (FCC) has been shown to improve outcomes in various populations of children with chronic illnesses and their families, but has not been reported on for childhood epilepsy. The onset of epilepsy presents families with worries and responsibilities related to this child's health, in addition to their usual daily family activities. The onset of childhood epilepsy has the potential to affect Family Functioning (FF). This study aims to describe the relationship between FCC and FF and to assess FF over the year post-diagnosis.

Methods: Data from the Canada-wide prospective cohort study, Health Related Quality of Life in Children with Epilepsy (HERQULES) were used to examine the relationship between FCC and FF. All children between age 4 and 12 newly diagnosed by one of 52 neurologists, were recruited. Parents were surveyed following diagnosis, at 6, 12 and 24 months later. Perceptions of FCC and FF were obtained using the 20-item Measure of Processes of Care (MPOC) and the Family APGAR, respectively. Linear regressions describe the relationship between MPOC domains and FF, adjusting for family and child characteristics. Repeated measures ANOVA examined FF over time.

Results: The sample is 197 mothers of children diagnosed with epilepsy one year earlier: 78% were married; about 60% had a gross annual family income of less than $80k; and 55% of families had at least one parent who completed university. Of the children, 51% were male and had a mean age of 7.5 (sd = 2.4) at diagnosis. 56% has partial seizures, and 55% were prescribed one AED. APGAR scores did not significantly differ over time (p = 0.76). Mothers' scores were highest on the MPOC Respectful and Supportive care domain (mean = 5.38;sd = 1.43) and lowest on Providing General Information (mean = 4.06;sd = 1.96). The other domain scores: Coordinated and Comprehensive care (mean = 5.23;sd = 1.52); Enabling and Partnership (mean = 5.13;sd = 1.61); and Providing Specific Information (mean = 4.30;sd = 1.80). While simple bivariate correlations showed no significant relation between FF and MPOC domains, preliminary regression model construction revealed several variables that may be modifying the relationship. Comprehensive regression model building will describe the true relationship and will be presented separately for each MPOC domain.

Conclusions: Overall mothers report their children's care as fairly family centered, perceiving that they are treated with respect as equals and experts in their child's care, but that their general informational needs are not being met fully. FF did not change over time, suggesting it may be a stable family trait over the first year; this is limited in that the effect of diagnosis cannot be quantified because FF was not measured prior to diagnosis. Interestingly, there may be certain groups in this sample for which the effect FCC has on FF may be different, these will be explored and presented in detail.

(Sources of funding: Social Sciences and Humanities Research Council student scholarship to Sandra Magalhaes and Canadian Institutes of Health Research Grant MOP-117493 to Speechey et al).

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Timothy Welty 1,2 and S. L. Willis 3 ( 1 Pharmacy Practice, McWhorter School of Pharmacy, Birmingham, AL ; 2 Department of Neurology, University of Alabama Birmingham, Birmingham, AL and 3 CVS Pharmacy, Birmingham, AL )

Rationale: All states place some restrictions on driving for individuals with epilepsy. Many patients are unable to drive and depend on alternate forms of transportation. These individuals have limited access to services, including pharmacy. Difficulty in getting prescription refills due to limited transportation might result in poor medication compliance. A survey was developed to determine if limited transportation impacts compliance with medications due to inability to get prescription refills.

Methods: A 22 item survey was created in Zoomerang. From February 5-April 13, 2007, an invitation to participate in the survey was placed on the front page of Epilepsy.com, with a link to the survey site. Patients or caregivers who were ≥19 years old were eligible to participate. Data for patients and caregivers were collected and analyzed separately.

Results: A total of 126 completed surveys, 86 from patients, 24 from caregivers, and 16 from individuals <19 years old were received. Ages ranged from 19 to >71 years old. 77% of respondents were women. 36% of participants said they did not drive and depend on other forms of transportation. 74% indicated they have insurance coverage for medications. Of these, 56% had coverage for mail order pharmacies and only 53% with mail order coverage used it. Only 23% indicated they had seizures due to inability to get prescription refills on time. However, 41% said they had trouble getting their prescription refills due to transportation problems and 39% indicated they would miss fewer doses of medication if transportation to the pharmacy was not a problem. When cross tabulated with use of mail order pharmacies, there was no difference between those who use mail order and those who do not. Problems with transportation and getting to the pharmacy were common with individuals living in both urban and rural communities.

Conclusions: Preliminary evidence from this survey indicates patients with epilepsy have problems with medication compliance due to transportation limitations. Limited transportation appears to affect medical care in addition to other aspects of lifestyle. Further study into this problem is warranted with a goal of finding effective solutions.

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Charles E. Begley 1 , A. Hauser 2 , D. Hesdorffer 3 , F. Barnwell 4 , M. Newmark 5 , S. Dubinsky 6 , D. Lairson 7 , R. Basu 8 and T. Reynolds 9 ( 1 University of Texas School of Public Health, Houston, TX ; 2 Columbia University, New York City, NY ; 3 Columbia University, New York City, NY ; 4 Baylor College of Medicine, Houston, TX ; 5 Kelsey-Seybold, Houston, TX ; 6 Kelsey-Seybold, Houston, TX ; 7 University of Texas School of Public Health, Houston, TX ; 8 University of Texas School of Public Health, Houston, TX and 9 University of Texas School of Public Health, Houston, TX )

Rationale: Research in other chronic conditions indicates that there are disparities in health care use in the United States by socioeconomic status. Little is known about the role of socioeconomic factors in health care use among people with epilepsy. The purpose of this study is to examine the variation in health care use among low-income Medicaid and uninsured people with epilepsy receiving treatment in publicly subsidized settings compared to middle- and upper-income individuals with insurance treated in a private health care setting.

Methods: Approximatley 600 patients with epilepsy were recruited at three sites serving predominantly low-income populations in Houston, Texas and New York City and one site serving primarily middle- and upper-income patients in Houston, Texas. Patients were interviewed four times over a 12-month period. The interview questions covered demographics and coverage, seizures and health care use, drug side effects, co-morbidities, and health outcomes. Socioeconomic status was assessed in terms of income, education, and insurance coverage. We examined baseline differences in ER use, hospital admissions, physician visits, and medications with pooled data from participating patients. The role of socioeconomic factors in explaining variation in use was examined using regression models controlling for other important demographic and need characteristics of patients. Additional analyses explored the relative influence on health care use of specific socioeconomic factors.

Results: We have analyzed data from approximately 200 cases ranging in age from 13 to 78 years, with a mean of 41 years. Most patients (59%) are female; 65% are White, 31% are African American, 24% are Hispanic, and 4% indicated other backgrounds. The mean number of persons living with the respondents is three; 14% live alone. Most had completed high school (75%), 51% attended college, and 8% attended graduate or professional school. The mean number of years with epilepsy was 16 and 70% had one or more seizures in the last 12 months. About 60% were on monotherapy and 40% on polytherapy. We expect to find considerable variation by site in all four measures of health care use. Hospital admissions and emergency room visits are expected to be higher among patients treated at the three public sites. Physician visits and use of antiepileptic drugs with low drug-drug interactions is expected to be higher for middle- and upper-income groups. Controlling for all other factors, Medicaid patients are expected to have the highest use of all services followed by privately insured and uninsured. Socioeconomic factors are expected to explain a small but significant percentage of the variation in use.

Conclusions: There are disparities in health care use associated with the socioeconomic status of indviduals with epilepsy. With documentation of the nature and magnitude of these disparities we can move to the next step of determining the patient factors, health care practice issues, and environmental factors that cause the disparities.

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James L. Moore 1 , J. O. Elliott 1 and B. Lu 2 ( 1 Neurology, The Ohio State University, Columbus, OH and 2 College of Public Health, The Ohio State University, Columbus, OH )

Rationale: Several US states have added questions to ascertain epilepsy prevalence to the Centers for Disease Control's (CDC) yearly Behavioral Risk Factor Surveillance System (BRFSS). There is a critical need for population-based research in epilepsy. In persons with epilepsy one previous study using the BRFSS data have found a lifetime prevalence of 2.1%. Surveyed persons with epilepsy reported lower educational attainment, lower household income and significantly worse health status. In 2006 the state of Ohio added 4 questions to the BRFSS related to epilepsy. We sought to make comparisons to previously published studies in other states

Methods: The BRFSS dataset and codebooks were obtained from the Ohio Department of Health. The dataset was analyzed with SAS using 4 questions to assess epilepsy prevalence, current treatment, seizure frequency and quality of life. Population adjustments were made based on guidelines provided by the CDC

Results: In Ohio, 97 of 5,506 respondents reported having epilepsy yielding an unadjusted prevalence rate of 1.76% based on the question “Have you ever been told by a doctor that you have a seizure disorder or epilepsy?” Once population adjustments were made lifetime epilepsy prevalence, was 1.4764%, with 95% CI [0.8957%, 2.0571%]. Adjusted active epilepsy prevalence was 0.7425%, with 95% CI [0.3356%, 1.1494%] based on the question: “Are you currently taking any medication to control your seizure disorder or epilepsy?”−58 (60%) reported yes and 39 (40%) reported no. For the question “How many seizures of any type have you had in the last three months?” 19 (20%) reported one/more than one, 75 (77%) reported none. For seizure frequency during the past three months among active epilepsy patients, it is 31.1474%, with 95% CI [5.8929%, 56.4019%]. When asked “During the past month, to what extent has epilepsy or its treatment interfered with your normal activities like working, school, socializing with family or friends?” 69 (71%) person reported “not at all”, 7 (7%) “slightly”, 5 (5%) “moderate”, 8 (8%) “quite a bit” and 6 (6%) “extremely”.

Conclusions: For the state of Ohio adjusted epilepsy prevalence estimates support previous established epidemiology. The prevalence rate is somewhat lower than recently published estimates for Georgia and Tennessee from the BRFSS. We will look forward to other states adding questions to their BRFSS so that a more complete picture of the epidemiology of epilepsy will emerge for the entire nation.

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Judith Finegold 1 and D. Heaney 1 ( 1 Department of Clinical and Experimental Epilepsy, Institute of Neurology, UCL, London, United Kingdom )

Rationale: Many authoritative guidelines on the treatment of epilepsy - such as the NICE clinical guidelines in the UK - include information about how best to advise or treat women of child-bearing age about the issues relating to pregnancy, epilepsy and anti-epileptic drugs (AEDs). It is likely however, that many women with epilepsy (WWE) do not have contact with specialist epilepsy services. This study aimed to determine how the care of WWE attending a general obstetric service compares to NICE guidelines.

Methods: An electronic obstetric booking register was introduced to a central London hospital in July 2005. Cases with epilepsy were flagged prospectively. Consecutive bookings and notified cases were reviewed after 22 months. Demographic and clinical data were collected, including contact with neurology services in preceding 5 years. Case-notes of WWE were reviewed with respect to documentation of advice given regarding folic acid, teratogenicity, breast-feeding and mother-baby safety. These data were compared with NICE recommendations. Peri-natal details, including infant APGAR scores were recorded. WWE were contacted to obtain missing data.

Results: Analysis of 7079 bookings was completed. 53 cases of WWE (prevalence 7/1000) were identified. 12 (23%) cases contained no record of date of last seizure. 32 (60%) of women had been seizure free for >12 months. Neurology follow-up had not occurred or was not described in 28 (53%) cases. 19 (36%) were on AEDs during pregnancy. 3 (6%) had stopped medication within 1 year before pregnancy. Of those taking AEDs, 6 changed doses - 4 due to changes in serum AED levels (rather than clinical events). In 10 cases (50% on those AEDs) there was no documentation of discussion about teratogenicity. In only 7 cases (13%) was use of 5 mg-folic acid documented. One maternal death occurred at 30 week. The remainder of WWE delivered after 36 week. 32% underwent caesarean section (which is higher than departmental average).

Conclusions: Over half of WWE booked into the obstetric service were not under neurology care despite some experiencing ongoing seizures or being on AEDs. Women who had seen a neurologist were more likely to have taken high-dose folic acid, have had dose-adjustments to AEDs before or during pregnancy, and have received advice about teratogenicity. Obstetric and foetal outcome were not significantly different to the control population, although Caesarian section rate was higher. The care of WWE attending a general obstetric service does not meet national guidelines, but this may be because guidelines are aimed at epilepsy specialists rather than those concerned with general obstetric care.

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Deepa Kapoor 1 , G. Joubert 2 , A. Thind 1 and K. Speechley 1,2 ( 1 Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada and 2 Paediatrics, University of Western Ontario, London, ON, Canada )

Rationale: Emergency department (ED) utilization is higher in Canada than the U.S. and continues to rise, despite the availability of alternative and fully insured health care. Furthermore, studies show that one third of ED visits are non-urgent. The unpredictability and stress associated with seizures leads to high ED use by patients with seizures relative to other patient groups. This study hypothesizes a substantial proportion of these patients could be classified as “potentially deferrable,” defined as those cases that would have been more appropriately cared for in a non-ED setting. The objective of this study is to describe and determine the total number of patients who presented to an ED in the City of London, Ontario with a seizure event in the year 2005, and to estimate the proportion of these patients who may be classified as “potentially deferrable.”

Methods: A retrospective chart review of all patients identified with a seizure event who reported to London Health Sciences Centre, including University Hospital and Victoria Hospital, and St. Josephs Urgent Health Care Centre in the year 2005 was conducted. The Medical Records Department identified all patients whose primary reason for a visit was due to epilepsy, status epilepticus, febrile convulsions, or convulsions not elsewhere classified using the ICD-10 coding system. Criteria were developed a priori to classify whether seizure events presenting as a medical emergency were considered such by qualified health professionals or were potentially deferrable. The following seizure events were classified as non-deferrable: first time seizure, status epilepticus, febrile seizure, alcohol or drug withdrawal, increase in seizure frequency or duration, or change in type or post-ictal state, seizure with a secondary injury, patient was admitted or transferred from another hospital. All other seizure presentations were considered as potentially deferrable.

Results: A total of 832 patients presented to an ED with a seizure event in 2005, for a total of 1198 visits. Patients' mean age was 30 years (range 0–95), 65% were female, and 35% were under 18 years of age. The reason for visit (ICD-10 code) in 11.8% of patients was epilepsy, 6.0% status epilepticus, 10.3% febrile seizures, and 71.2% unspecified convulsions. Of the patients, 28% presented with a first time seizure, 9% reported an increase in seizure frequency or duration, or change in type or post-ictal state, while 10% reported a secondary injury. A total of 15% of patients were admitted to hospital. Using the criteria, 426 (36%) visits were classified as potentially deferrable. For visits among patients under 18 years of age, 21% were classified as potentially deferrable.

Conclusions: A substantial proportion of patient visits to EDs in London, Ontario for seizure events are potentially deferrable. This presents an opportunity for educational intervention to increase efficiency of ED use by patients and families dealing with seizures, and to decrease health care costs associated with potentially deferrable visits.

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Katy S. Smith 1 , B. Waldron 2 , C. Picton 2 , C. Hayes 3 , C. Dunkley 6 , J. Williams 5 , J. Lanfear 4 and W. Whitehouse 1 ( 1 School of Human Development, University of Nottingham, Nottingham, United Kingdom ; 2 Paediatric Neurology, NUH, Nottingham, United Kingdom ; 3 Dept. Neurology, NUH, Nottingham, United Kingdom ; 4 The Centre for Community Neurological Studies, Leeds Metropolitan University, Leeds, United Kingdom ; 5 Dept. Community Paediatrics, NUH, Nottingham, United Kingdom and 6 Dept. Paediatrics, Kings Mill Hospital, Mansfield, United Kingdom )

Rationale: Specialist teenage epilepsy clinics play an important role in catering for the specific needs of adolescents with epilepsy. This study aimed to ascertain the opinions and expectations of young people with epilepsies, attending hospital, as out-patients.

Methods: Two questionnaires were administered to all young people who attended the Young Person's Seizure Clinic (YPSC) in Nottingham, where feasible. The Young Person's Impact of Epilepsy Scale(1), evaluated the impact of epilepsy on different life areas. The ‘Teenage Views on Outpatient Clinics and Seizure Knowledge’ was an in-house questionnaire which enquired about positive and negative experiences of previous clinics, patient's preferences regarding clinic format, their expectations and information needs. It evaluated knowledge levels relating to understanding of epilepsy and its treatment, and the young people's opinion of their medical care.

Also the YPSC was independently evaluated according to the National Institute of Clinical Excellence (NICE) guidelines for care of young people with epilepsy and young women of childbearing potential with epilepsy(2).

Results: 74 young people aged 12–18 years completed the Impact questionnaire. 26 (35%) felt epilepsy and its' treatment had a significant impact on their lives. The areas of highest impact were shown to be on education, future plans and ambitions, the way young people felt about themselves, and hobbies and interests. Impact scores were higher with increasing age, seizure frequency, and female gender.

82 young people completed the Teenage views questionnaire. 27 specified information and advice as an important resource of epilepsy clinics. 26 (32%) had no perceived understanding of epilepsy and 45 (55%) did not know their epilepsy type. They expressed a range of views on how the clinic should be organised.

The clinic performed well in all 8 areas of the NICE guidelines catering for the physical, psychological and social aspects of young people's health and providing an appropriate setting for them to obtain important information relevant to their age. Minor improvements were proposed in 5 out of the 8 areas.

Conclusions: Young people with epilepsies have expectations regarding their medical care. The YPSC provided an ideal setting for their out-patient care, combining adult and paediatric services to provide for their specific needs.

References:

1)Lanfear JH & Baker GA (1995) Young Persons Impact Scale. Cited in young people with epilepsy: perception, attitudes and impact. Epilepsia. Vol. 40, Supplement 2, p 295.

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Daphne Quigley 1 , L. Jurasek 2 , B. Sinclair 2 , S. Ahmed 1 and D. Gross 1 ( 1 University of Alberta, Edmonton, AB, Canada and 2 Stollery Children's Hospital, Edmonton, AB, Canada )

Rationale: Transition from pediatric to adult health care services can be difficult for adolescents and their families. Barriers to transition have been identified in the literature with little pertaining to epilepsy. The University of Alberta Comprehensive Epilepsy Program encompasses both pediatric and adult services within the same facility and has been conducting a nurse-led formalized transition program for one year. Throughout this time, evaluations have been collected to help identify specific learning needs for this unique population. Through these evaluations, an educational/resource binder was developed to provide written information on topics of concern and to help facilitate independence with maintaining individual health information.

Methods: All adolescents referred from the pediatric to adult epilepsy clinic were included in this study. Prior to the first appointment with the adult neurologist, adolescents and families were seen in the transition clinic visit and provided a questionnaire regarding potential topics of interest, and assessing current level of independence regarding their health management. Based upon information gathered it was evident that additional resources were needed to assist the adolescent facilitate independence and provide individualized epilepsy information. Literature supports the use of a variety of teaching styles; therefore a resource binder was developed for adolescents and their families incorporating a health information record, and educational material and community resources.

Results: A resource binder was developed to supplement the adolescent with epilepsy transition process. The binder consists of a section specific to an individual's epilepsy health information as well as a section dedicated to epilepsy information and community resources. Each adolescent is provided with a binder to bring to their adult neurologists appointments to help ensure continuity of care.

Conclusions: The use of an education/resource binder for adolescents with epilepsy and their families seen in the transition clinic will help reinforce verbal information provided by the pediatric and adult nurses and enhance awareness of available community resources. The binder will assist with maintenance of personal health information related to epilepsy and encourage the adolescent to take control and manage their own health care.

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Francesco M. Noe' 1 , R. J. Bland 2 , V. Vaghi 1 , C. Balducci 1 , M. Carli 1 , M. J. During 3 and A. Vezzani 1 ( 1 Neuroscience, “Mario Negri” Institute for Pharmacological Research, Milano, Italy ; 2 Neurologix, Inc, Fort Lee, NJ and 3 Human Cancer Genetics Program, The Ohio State University, Columbus, OH )

Rationale: Long-lasting neuropeptide Y (NPY) overexpression in rat hippocampus is induced by local application of adeno-associated viral vector (rAAV) with chimeric 1/2 serotype (rAAV1/2-NPY) under control of the neuron-specific enolase (NSE) promoter.

rAAV1/2-NSE-NPY injected rats showed reduced seizures and delayed kindling. We optimized rAAV vector acting either at the capsid or promoter level to increase the efficiency of cell transduction and enhance NPY-mediated anticonvulsant activity without interfering with physiological functions.

Methods: Cassettes carrying the human NPY gene under the control of cytomegalovirus enhancer/chicken-beta-actin (CBA) promoter flanked by AAV2 ITRs were cross-packaged into capsids of AAV type 1 or 1/2 (a mixture of AAV1 and AAV2 capsid proteins at a 1:1 ratio). The new vectors were compared with the rAAV1/2-NSE-NPY vector. Rats were injected with rAAV-NPY vectors (3 μl 5.2 × 1012) into the septal and temporal aspects of the hippocampus bilaterally or with the corresponding rAAV-Empty-cassette vectors or saline (controls). Four week after rAAV delivery, behavioral testing of learning and memory (two platforms discrimination water maze task and passive avoidance test) and anxiety (exploration of a white-black open-field) were carried out. After one week, the same rats were intrahippocampally injected with 40 ng of kainic acid and the onset, number of seizures and time spent in seizures were evaluated by EEG analysis. Neuroprotection and inflammation were evaluated by immunohistochemistry.

Results: No differences were observed in the behavioral tests between experimental groups and their controls except for rats injected with chimeric rAAV1/2-CBA-NPY vector. These rats showed a significant delay in learning compared to their respective controls in the two platforms discrimination test. rAAV1/2-NSE-NPY or rAAV1/2-CBA-NPY rats showed on average a reduction of 40–50% in number of seizures and of 65% in the time spent in seizures compared to controls. rAAV1-CBA-NPY rats showed a larger reduction (by 80%) in the number and time spent in EEG seizures. In all vector-injected rats, anticonvulsant activity was associated with increased NPY immunostaining in hilar interneurons and mossy fibers, however rAAV1/2-CBA-NPY rats showed additional upregulation of NPY in CA1 pyramidal neurons. Additional NPY staining in the inner and outer molecular layers of the dentate gyrus and in stratum oriens CA3 was observed in rAAV1-CBA-NPY rats. Neuronal injury in the CA3 area and hilus was reduced in all experimental groups overexpressing NPY. Vector injection per se did not induce cell toxicity or inflammation.

Conclusions: Long-lasting NPY overexpression mediated by rAAV1-CBA-NPY vector in the hippocampus provides stronger anticonvulsant activity than rAAV1/2 vectors, neuroprotection and it does not alter behavioral outcomes related to physiological functions.

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Beth A. Malow 1 , B. Vaughn 2 , N. Foldvary-Schaefer 3 , R. Chervin 4 , L. Selwa 4 and K. Weatherwax 4 ( 1 Neurology, Vanderbilt University, Nashville, TN ; 2 Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC ; 3 Neurology, Cleveland Clinic Foundation, Cleveland, OH and 4 Neurology, University of Michigan, Ann Arbor, MI )

Rationale: Treatment of obstructive sleep apnea (OSA) in patients with epilepsy appears to improve seizure control and daytime sleepiness, although studies have been small and non-controlled. The goal of this pilot study was to refine design issues prior to embarking on a Phase III Trial of treating OSA in patients with epilepsy.

Methods: Adults with refractory epilepsy (2 or more seizures per month) were enrolled into the trial if they met study criteria, including a history suggestive of OSA. After polysomnography (PSG) confirmed OSA, subjects were randomized to treatment with either therapeutic or sham continuous positive airway pressure (CPAP). Subjects were maintained on stable doses of antiepileptic medications and CPAP adherence was monitored with electronic cards.

Results: Of 43 subjects undergoing PSG, 36 met criteria for OSA, defined by an apnea-hypopnea index (AHI) of 5 or more events per hour (81% true positive rate). The first night of PSG appeared sufficient for diagnosing OSA, with only one subject having OSA on night 2 (AHI 5.8) but not on night 1 (AHI 3). 22 subjects were randomized to therapeutic CPAP (with 19 completers) and 13 subjects to sham CPAP (all completed the trial). Adherence was similar in the therapeutic and sham groups (71.8% of nights, 4.4 hours per night) and significantly higher in adults ages 45 or older (5.4 hours, p = 0.01 by independent two-tailed t-test). Subjects, coordinators, and PIs were not able to distinguish therapeutic from sham CPAP (kappa values < 0.40). A 50% or greater reduction in seizures was observed in 32% of the subjects in the therapeutic group as compared to 15% of those in the sham group.

Conclusions: Treatment of obstructive sleep apnea in epilepsy appears promising in reducing seizure frequency, and a Phase III randomized multicenter clinical trial employing therapeutic and sham CPAP appears feasible.

This trial was supported by NINDS R01 NS42698 and the General Clinical Research Centers at University of Michigan (M01-RR00042), University of North Carolina-Chapel Hill (M01-RR00146) and Vanderbilt University (M01-RR00095)

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Jim Berg 1 and G. Yellen 1 ( 1 Neurobiology, Harvard Medical School, Boston, MA )

Rationale: The high fat, low carbohydrate ketogenic diet is a remarkably effective treatment for epilepsy, though its mechanism is far from understood. One of the primary metabolic consequences of for patients on the ketogenic diet is a rise in concentration of ketone bodies in the blood and CSF. Previously, we have shown that in vitro application of ketone bodies leads to a dampening of neuronal excitability in mouse brain slices. This effect is due to the opening of ATP-sensitive potassium (KATP) channels as it is eliminated via pharmacological block or in a genetic knock-out of Kir 6.2, the pore forming region of the KATP channel.

To confirm that the ketone body effect is not due to the involvement of mitochondrial KATP (mitoKATP) channels, we sought independent evidence that these channels do indeed persist in the Kir 6.2 knock-out mice. Specifically, we investigated one of the phenomena associated with mitoKATP, ROS production in response to the application of diazoxide, a classical KATP channel opener.

Methods: We utilized acute brain slices from P13–16 BL6 (wild-type) or Kir6.2 knock-out mice. Whole-cell patch clamp recordings were made from GABAergic neurons of the Substantia Nigra pars reticula in acute slices bathed in ACSF (12 mM Glucose and bubbled with 95%O2 and 5%CO2). The recording pipette contained 20 μM of the a novel cell-impermeant reactive oxygen species (ROS) sensitive dye, reduced dichlorofluorescein - cysteic acid (H2DCF-CA). Images were acquired every 30 s to reduce photobleaching and the concentration of ROS in the cell was represented by the accumulation of the fluorescent, oxidized form of the dye. Following 10 minutes of baseline ROS detection, either diazoxide (200 μM) or the physiological ketone body R-β-hydroxybutyrate (2 mM) were added and the ROS signal was recorded for an additional 40 minutes.

Results: We found that a phenomenon attributable to mitoKATP, an ROS burst due to the KATP channel opener diazoxide, is present in neurons both in wild-type and the Kir6.2 channel knock-out. Furthermore, using both H2DCF-CA and the genetically encoded ROS sensor HyPer, we found that ketone body metabolism itself produces an acute increase in reactive oxygen species.

Conclusions: The persistence of mitoKATP channels in the Kir6.2 knock-out mouse strengthens the evidence that the ketogenic diet may dampen neuronal excitability via the opening of surface membrane KATP channels. Additionally, an ROS increase due to ketone body metabolism, in combination with the known neuronal activity-dependent ROS production, may have important implications in the anti-epileptic effect of the ketogenic diet.

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S. Ebus 1 , P. Ossenblok 1 , D. Lambrechts 1 , J. Arends 1 , R. Krijn 1 , M. Majoie 1 and P. Boon 1 ( 1 Epilepsy centre Kempenhaeghe, Heeze, Netherlands )

Rationale: We examined whether interictal EEG changes predict ketogenic diet outcome. Background-slowing might predict side-effects/bad outcome. Decreased spike frequency might predict successful treatment, to be used as an argument to continue the diet. The results of the first 7 patients studied are presented.

Methods: Each patient underwent three 24-hour EEGs: 1st EEG at baseline, 2nd EEG after 6 week of ketogenic diet; 3rd EEG at 1 year treatment or at drop-out because of ineffectiveness/side-effects. Interictal spike counts were obtained from EEG during 4 hours of wakefulness and 4 hours of sleep. Detection was performed using Persyst Spike Detector Reveal version 2004.04.14 and visual artefact-rejection of clustered artefacts.

For background analysis, 20 five-second epochs from each EEG were randomly selected during wakefulness (eyes-open). Epochs containing eye-movements, artefacts or paroxysms were excluded. Spectral analysis was performed and power distributions of 20 epochs of each EEG were obtained. Mean absolute powers of 4 leads (F4-C4, C4-O2, F3-C3, C3-O1) were computed for 0.5 Hz bins from 0.5–25 Hz. These bins were analyzed by t-tests for independent samples.

Results: Spike counts were performed in all 21 EEGs. In only two patients marked changes in spike counts in the 2nd EEG compared to baseline were noted. The 2nd EEG of patient 1 (non-responder) showed a mean spike count of 1376 spikes/hour during wakefulness (compared to 4 spikes/hour during baseline) and 765 spikes/hour in sleep (362 spikes/hour baseline). The 3rd EEG recorded after 1 year also showed this severe worsening. Patient 6 (responder) had marked improvement of especially his first follow-up wake EEG with mean 36 spikes/hour in wake (633 spikes/hour baseline) and 295 spikes/hour in sleep (493/hour baseline). His 3rd EEG did not show the same improvement. This patient showed clinical improvement within few week of treatment, having still daily seizures but less frequent and severe. All other 2nd and 3rd EEGs of the other patients only showed minor changes and these were not predictable of outcome.

For spectral analysis 15 EEGs were included. Patient 6 had no spike-free epochs in EEG1 and patient 1 had background slowing related to frequent epileptic paroxysms.

The power distributions obtained for three subsequent EEGs indicated stable background activity in 4 out of 5 patients. In patient 7 the maximum of the power distribution increased in the 0.5–8.0 Hz range. Statistical testing of differences in power per 0.5 Hz bin only showed significant t-values in a few bins in this range, because of high standard deviations of the means. This patient was a responder and had no side effects of the diet.

Conclusions: The EEGs of 7 patients treated with ketogenic diet show that EEG-background is generally not worsened. In patients with marked changes in interictal spike counts at 6 week ketogenic diet, the EEG may predict outcome in terms of seizure frequency or seizure severity. Because of the small group, it is too early to advise to use EEGs to decide about continuing treatment.

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Peter F. Morrison 1 , P. L. Pyzik 1 and E. H. Kossoff 1 ( 1 Neurology, Johns Hopkins Hospital, Baltimore, MD )

Rationale: The ketogenic diet (KD) is a high fat, adequate protein and low carbohydrate diet typically used for intractable epilepsy. The vast majority of patients also receive concomitant anticonvulsant medications. Little is known, however, about which medications work well in conjunction with the KD. The aim of this study was to determine if synergy exists between the KD and commonly used anticonvulsant medications.

Methods: A retrospective study was performed of 217 patients started on the ketogenic diet from 2000–2007 at our institution. Patients who discontinued the diet prior to three months (n = 20), or for whom no follow up data were available (n = 9) were excluded from analysis. Efficacy data at 3 and 6 months for patients on the KD and the identified 6 most commonly used concomitant anticonvulsants (levetiracetam, lamotrigine, phenobarbital, topiramate, valproate, and zonisamide) were analyzed and compared.

Results: A total of 188 patients (99 male) were included in the analysis. In the subgroup of patients in whom no medication changes were made over the first 3 months of the KD (n = 124), those taking zonisamide were more likely have a >50% seizure reduction (90% vs 70%, p = 0.040) and those receiving phenobarbital were less likely (47% vs. 77%, p = 0.014). In those with Lennox Gastaut syndrome or mixed seizure types specifically (n = 58), those receiving either zonisamide (100% vs. 57%, p = 0.005) or valproate (78% vs. 53%, p = 0.050) were more likely to have a >50% response whereas patients receiving phenobarbital were again less likely (29% vs 71%, p = 0.036).

Conclusions: In this cohort, children receiving zonisamide overall and valproate (for Lennox Gastaut or multiple seizure types specifically) were more likely to respond to the ketogenic diet. Those receiving the ketogenic diet and phenobarbital together did less well.

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Akiko Uehara 1 , A. Sofue 1 , T. Fukasawa 1 , M. Morita 1 , S. Hasegawa 1 , K. Watanabe 1 and J. Natsume 2 ( 1 Nagoya Memorial Hospital, Nagoya, Japan and 2 Nagoya University Graduate School of Medicine, Nagoya, Japan )

Rationale: DEND syndrome, first described in 2004, is characterized by heterozygous activating mutation in KCNJ11 gene encoding the Kir6.2 subunit of the ATP-dependent potassium(KATP) channel. KATP channels are octameric complex with 2 kind of subunits: 4 sulfonylurea receptor 1 or 2 (SUR1 or 2) embracing 4 inwardly rectifying potassium channel (Kir). Kir6.2/SUR1 distributes to pancreatic beta cells, and plays a key role in glucose-stimulated insulin secretion. Kir6.2/SUR2 functions in brain, involving with seizure susceptibility and neurodevelopment. Thus, KCNJ11/Kir6.2 mutation is a channelopathy involving with multiple organ systems ranging from diabetes, epilepsy, and to developmental delay.

Methods: Sulfonylurea, a widely-used type-2 diabetes medicine, binds to KATP channel and improves its function, and enhances insulin secretion. Neonatal diabetes due to KATP mutation has been successfully transferred from insulin to oral sulfonylurea. Non-selective sulfonylurea (i.e. glibenclamide) refers to a subclass of sulfonylurea which binds to all type of KATP channels. It is speculated that in DEND syndrome patients, oral sulfonylureas not only controls diabetes, but may also treat neurological problems, especially when sulfonylureas are started early in life. In reality, however, all 4 cases of previously reported DEND syndrome failed to switch to sulfonylurea.

Results: A four-month-old, in-vitro-fertilized boy presented with developmental delay and spasms in cluster. Interictal electroencephalogram (EEG) showed hypsarrhythmia compatible with West syndrome. Cranial magnetic resonance imaging (MRI) revealed no structural abnormalities. His blood glucose level was 280 mg/dl, glycated hemoglobin level (HbA1c) was 9.8%. Subsequently he was diagnosed with permanent neonatal diabetes mellitus. Genetic studies of the patient and his parents revealed de novo mutation (R50P) on the patient's KCNJ11 gene.

Vitamin B6, clonazepam and valproate were ineffective for spasms. Synthetic adrenocorticotropic hormone(ACTH) was started under close monitoring of blood glucose levels. After 10-day course of 0.013 mg/kg intramuscular ACTH, cessation of spasms and resolution of hypsarrhythmia were obtained. He remains to be seizure-free.

Following genetic diagnosis, his diabetic regimen was successfully switched from intensive insulin therapy to high-dose oral sulfonylurea (glibenclamide, 0.87 mg/kg/day), resulting in good glycemic control to date. At 15 months, his functional age is 6–7 months for mental and motor aspects. He also has poor eye contact, requiring watchful observation for the emergence of pervasive developmental disorder.

Conclusions: We describe the first case of DEND syndrome who was successfully transferred from multiple-daily insulin injections to oral sulfonylurea. This disease entity shows how the molecular understanding of some monogenic/channelopathic form of epilepsy may lead to an unexpected change of the treatment.

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Christie Snively 1 , P. R. Carney 1 , Z. Liu 1 , E. O. Andrade 1 , D. Ringdahl 1 , L. E. Little 2 and P. R. Borum 2 ( 1 Pediatric Neurology, Shands at the University of Florida, Gainesville, FL and 2 Food Science and Human Nutrition, University of Florida, Gainesville, FL )

Rationale: Ketogenic therapy (KT) has been used in the treatment of intractable epilepsy for several decades. KT is often administered with calorie restriction but whether it is needed for efficacy remains a question. Growth restriction is accepted by some centers as an anticipated and often inevitable part of KT. Our retrospective analysis of patients on KT for at least 1 year indicates a significant decrease in height z-score over time on diet (0–6 months on diet =−0.7 ± 1.4, >60 months on diet =−2.9 ± 1.6, p = < 0.001). However, when patients were stratified according to time on diet, those patients who were on the diet > 60 months did not show a significant change in the height z-score over time on KT. This may be indicative that other factors besides KT may be contributing to their growth issues such as epilepsy, calorie restriction, and/or medications. We have developed evidence-based guidelines for treatment and monitoring of patients on KT and have implemented them in a prospective study conducted in the General Clinic Research Center (GCRC) at Shands/UF.

Methods: We conducted a prospective analysis of height z-score in 20 patients admitted to the University of Florida KT Program for seizures. The demographics of the population were: 11 females, 9 males; 14 Caucasian, 3 African-American, 2 Hispanic, 1 Biracial; mean age of 10.1 ± 5.3 years. The patients were on the following AEDs: Keppra (n = 9), Klonopin (n = 8), Lamictal (n = 5), Phenobarbital (n = 5), Topomax (n = 4), Primidone (n = 1), Valproic Acid (n = 1), Tegretol (n = 1), Trileptal (n = 1), Ativan (n = 1), Neurontin (n = 1). There were 4 patients on no AEDs and 12 patients on 2 or more AEDs. Seizure types were: Generalized (n = 13), Myoclonic (n = 8), Complex partial (n = 7), Absence (n = 4), Simple partial (n = 1), and Tonic (n = 1) and 9 patients had 2 or more seizure types.

Results: A prospective analysis of height z-score in 20 patients stratified according to non-ambulatory versus ambulatory shows a significant difference (non-ambulatory =−2.3 ± 1.2, ambulatory = 0.1 ± 0.5, p = < 0.001). The mean age was 6.4 yrs ± 3.4 (n = 5) for ambulatory patients and 11.3 yrs ± 5.3 (n = 15) for non-ambulatory patients. A regression analysis of calories/kg body weight versus height z-score resulted in a significant positive correlation (p = 0.003, R2 = 0.12, R = 0.35), indicating that optimal calories during therapy could help alleviate potential issues with growth.

Conclusions: Children treated with the KT for seizures show significant changes in height over time which may be alleviated through optimization of caloric needs. A prospective, controlled, randomized trial should be designed to determine ketogenic therapy's direct role in growth with and without calorie restriction.

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Christina A. Bergqvist 1 , J. I. Schall 2 , V. A. Stallings 2 , S. Sayed 3 and A. Grimberg 2 ( 1 Neurology and Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA ; 2 Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA and 3 Clinical Translational Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA )

Rationale: The ketogenic diet(KD) is an effective dietary treatment of intractable epilepsy (IE). It is a high fat, low carbohydrate and protein diet. Growth failure with the KD has been reported and several studies have shown deceleration in height Z-scores. Insulin-like growth factor 1 (IGF-I) is the principal mediator of prepubertal growth in humans, but has not previously been investigated in children treated with the KD. The purpose of this study was to evaluate the response of IGF-I over 15 months in children with IE treated with the KD, and to elucidate the relationship of IGF-I and growth status during KD initiation.

Methods: Children with IE were eligible. The KD was initiated using either a gradual (GRAD-KD) or a fasting protocol (FAST-KD). Measurements were obtained at baseline, 3, 6, 9, 12, and 15 months of KD therapy. Serum IGF-I was analyzed using standard Human IGF-1 Immmunoassay by Quantikine. IGF-I is presented as a Z-score adjusted for age and gender. Height (HAZ), weight (WAZ), and BMI (BMIZ) were measured and Z-scores calculated. Statistical analyses included descriptive, multiple regression and longitudinal mixed effects (LME) analyses.

Results: 22 children (82% males, age 5.5 ± 2.5 yr, 41% with GRAD-KD initiation)had IGF-I status assessed. Before the initiation of the KD, IGF-1Z was normal (0.2 ± 1.7), and growth status was suboptimal (HAZ −0.4 ± 1.1; WAZ −0.6 ± 1.6; BMIZ −0.4 ± 1.9). After three months of KD therapy, IGF-IZ declined precipitously to −2.3 ± 1.5 and remained low through 15 months (−3.1 ± 0.9). All measures of growth status declined by approximately −0.1 Z score after 3 months. By multiple regression, significant positive predictors of IGF-IZ at 3 months were IGF-IZ at baseline, age and GRAD-KD. LME models showed that IGF-IZ was significantly positively associated (p = 0.008) with HAZ which declined significantly (−0.51, p = 0.001) over 15 months of KD therapy. Boys tended to have higher IGF-IZ than girls (p = 0.058). WAZ did not significantly change from 3 to 15 months.

Conclusions: Prior to treatment with the KD, children with IE had relatively normal IGF-I status despite having suboptimal growth status. IGF-IZ declined sharply in the first 3 months of KD therapy. Sustained low levels of IGF-IZ were associated with progressive decline in HAZ over 15 months. GRAD-KD initiation was associated with less severe decline in IGF-IZ levels in these children.

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Heidi Pfeifer 1 and E. A. Thiele 1 ( 1 Massachusetts General Hospital, Boston, MA )

Rationale: The ketogenic diet (KD) has been used as an effective treatment for intractable epilepsy since 1921. More recently its effectiveness was reported in the successful treatment of infants, demonstrating similar seizure reduction rates historically reported in older cohorts. There have been no reports in literature regarding the continuation of breastfeeding concurrent with the KD treatment.

Methods: We conducted a retrospective review of charts of the patients that were initiated on the KD at the Massachusetts General Hospital for Children between 2002 and 2007. Two patients were identified that breastfed during their KD treatment.

Results: Two patients continued breastfeeding during ketogenic diet initiation and maintenance. Both achieved >90% seizure reduction within the first month of treatment. Patient one was a ten and a half month old male at age of diet initiation after treatment with ACTH and Vigabatrin for infantile spasms and partial seizures. The etiology of his seizures was cortical dysplasia. He continued to nurse twice a day (q AM & PM) for the first three months for a duration of 5–15 min per breast at each feeding and then once a day for the next nine months for the same duration. Each nursing session was followed by a bottle of ketogenic formula at a 4:1 ratio. His ketogenic meals during the day were started at a 2.5:1 ratio and then increased gradually to 3.25:1 ratio. Patient two was an 8-month-old male with a history of trisomy 21 with infantile spasms that proved intractable to ACTH, Topiramate, and Vigabatrin. His seizures were occurring 30–100 times per day. Prior to diet initiation he was receiving a majority of his nutrition through breast milk, nursing every 2–4 hours for an average duration of 20–30 minutes. Upon diet initiation, the mother expressed breast milk to add to his formula. Approximately 15 ml was added per feeding to provide a 3:1 ratio. The seizure frequency reduced to 3–5 per day. The mother discontinued adding breast milk to his formula after 6–8 week increasing the diet ratio to 4.7:1 without further reduction or increase in his seizure frequency.

Conclusions: Historically it has been thought that mothers cannot continue breastfeeding during the treatment of the KD. It is our experience that mothers are able to provide the benefits of nursing and breast milk while successfully using the KD for treatment of their children's seizures.

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Joji Uchiyama 1 , M. Fujii 2 , H. Imoto 2 , N. Tanaka 2 , Y. Kurata 1 , K. Nakano 3 , S. Nomura 2 , H. Fujisawa 2 , T. Saito 1 and M. Suzuki 2 ( 1 Applied Medical Engineering Science, Yamaguchi University, Ube, Japan ; 2 Neurosurgery, Yamaguchi University, Ube, Japan and 3 Institute of Industrial Sience, The University of tokyo, Meguro, Japan )

Rationale: The cooling of brain tissue has been recognized to effectively suppress epileptiform discharges (EDs) and local brain cooling using a thermoelectric device has recently gained much attention since it has a potential to be a viable alternative for a surgical resection of epileptogenic foci. We have therefore developed an implantable focal cooling system including Peltier chips in order to automatically suppress epileptic seizures immediately after detecting EDs. However, when considering implantable systems, several problems such as the electric power supply or the arrangement of the whole system in the body have to be resolved. To resolve these problems, we developed a new cooling device with a heat pipe attached to the Pertier chip and also examined the performance of this device for the treatment of experimental neocortical seizures.

Methods: We made a cooling device composed of a heat pipe and a Pertier chip with a heat sink. The heat pipe was a flat-type and the size was 100 × 5.3 mm in length and width and 2.0 mm thick. The size of the Pertier chip included a heat sink was 7.0 × 7.0 mm in length and width and 2.0 mm thick. One side of the heat pipe was exposed for the cortical cooling, while the Pertier chip was fixed to the other side of the heat pipe. The heat pipe between both sides was covered by heat insulation material. Experiments were performed on adult male Sprague-Dawley rats under halothane anesthesia. After performing a craniotomy (10 × 9 mm), one side of the heat pipe was placed on the surface of the cortex. A thermocouple and a needle electrode for recording electrocorticograms (ECoGs) were also placed just beneath the cooling site. Kainic acid (KA) was injected into the cooled cortex to provoke EDs. After confirming the appearance of EDs, the cortex was cooled by applying the current to the Pertier chip. We analyzed the changes in the temperatures and ECoGs during cooling.

Results: After the KA injection, EDs appeared within 20 min and thereafter did not disappear spontaneously. Obvious amplitude reductions of EDs by local brain cooling were observed in all rats (n = 5). The temperature of the cortical surface was maintained at 35.5 ± 0.4 °C before cooling and then decreased to below 25 °C within 15 seconds. We estimated the sequential changes of EDs by calculating the root-mean-squares (RMSs) of the ECoGs. The RMSs were significantly suppressed from 40 seconds and the slower components (0.5–8 Hz) of ECoGs also significantly decreased from 30 seconds after the start of cooling. After the temperature reached 25°C, the mean amplitude stayed low throughout the subsequent period.

Conclusions: We developed a new focal cooling device with a heat pipe and a Pertier chip and confirmed its ability to successfully suppress EDs in an experimental seizure model. A cooling device with a heat pipe may therefore be the first step in developing a new type of implantable cooling system for the control of seizures in the future.

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Maria G. Dahlin 1 , G. Spulber 1,3 , L. Hagenäs 2 and P. Åmark 1 ( 1 Dept Neuropediatrics, Astrid Lindgren Childrens Hospital, Stockholm, Sweden ; 2 Pediatric Endocrine Unit, Astrid Lindgren Childrens Hospital, Stockholm, Sweden and 3 Dept Neurobiology, Karolinska Institute, Stockholm, Sweden )

Rationale: The ketogenic diet (KD) is a high-fat, low-protein, very low-carbohydrate diet used in the treatment of severe epilepsy in children. We observed that some children showed a decrease in their height velocity rate during diet. We examined the influence of the KD on linear growth and IGF-I levels in children with pharmacotherapy-resistant epilepsy.

Methods: A prospective study was designed to evaluate growth, serum IGF-I levels, blood beta-hydroxybutyric acid (b-OHB), and seizure frequency before and during one year on the KD in 22 children. Their median age was 5.5 years and all had symptomatic epilepsy. Growth was assessed by measurements of height, height velocity, and body mass index (BMI). Standard deviation scores (SDS) were calculated for all measured parameters as well as for serum IGF-I in order to eliminate the influence of age and sex-related differences among patients.

Results: Height, height velocity, BMI, and IGF-I decreased significantly during the KD. Height velocity decreased from −0.6 ± 2.2 SD during the year before diet to −4.2 ± 1.9 SD during diet. Serum IGF-I decreased from −1.1 ± 1.0 SD before diet to −3.4 ± 0.9 SD during diet. Height velocity correlated positively with IGF-I both before and during the KD. Furthermore, the slope of the regression line decreased significantly during the diet. Height velocity correlated negatively with b-OHB during the KD. Fourteen of the 22 children were seizure responders. No correlation was found between seizure response and growth alterations.

Conclusions: A profound influence of the KD on growth and IGF-I levels was found. Height velocity was most affected in those with pronounced ketosis. Thus, in clinical practice, the level of ketosis should be related to gains in seizure response and growth. Our data indicate that the growth disturbances and the alteration of the dependence of growth on IGF-I are independent of seizure reduction.

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Erika L. Hedderick 1 , E. H. Kossoff 1 , Z. Turner 1 and J. M. Freeman 1 ( 1 Neurology, Johns Hopkins Hospital, Baltimore, MD )

Rationale: ACTH is the standard first-line therapy for new-onset infantile spasms, but it has significant side effects. We hypothesized the ketogenic diet (KD) would have similar efficacy for this condition, but better tolerability.

Methods: We conducted a retrospective, case-cohort study of all infants started on either KD (n = 13) or ACTH (n = 20) for new-onset infantile spasms at our institution since 1996. Infants started on KD were fasted 24–48 hours, calories gradually increased, and outcomes evaluated after 1 month. After that point, the KD was typically continued only if the child was spasm-free. ACTH was given intramuscularly initially at 150 units/m2/day followed by weekly tapering doses over one month.

Results: ACTH was more likely than KD to result in a spasm-free outcome (18/20 (90%) vs. 8/13 (62%), p = 0.06) and normal EEG (53% vs. 10%, p = 0.04) at 1 month. Outcomes for both ACTH and KD were similar at 3–6 months. When effective, ACTH had a slightly shorter median time to spasm freedom (4.0 vs. 6.5 days, p = 0.18). Side effects (23% vs. 80%, p = 0.002) and relapse rate after initial success (12.5% vs. 33%, p = 0.23) were lower with the KD. In the 5 children in whom the KD was unsuccessful, 4 became spasm-free subsequently with ACTH or topiramate; both of the two children who did not initially respond to ACTH became spasm-free with topiramate.

Conclusions: ACTH was more likely than KD to result in spasm-freedom and EEG normalization after one month. However, the KD was effective in nearly two-thirds of cases within 2 week, and had fewer side effects and relapses than ACTH. Further prospective study of the KD for this novel indication is warranted.

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Shannon Nelson 1 , J. Fabe 1 , B. F. Meaney 1 and R. RamachandranNair 1 ( 1 Ketogenic Diet Program, McMaster Children's Hospital, Hamilton, ON, Canada )

Rationale: The ketogenic diet (KD), although effective in treating intractable epilepsy, poses demands on the family system. Research has identified siblings' negative feelings towards epilepsy. No study to date describes siblings' perceptions & feelings about KD.

Hypothesis: The KD may significantly impact the sibling.

Objective: To qualitatively analyze siblings' perceptions and feelings about the KD, and to identify main themes for use in future prospective study.

Methods: Inclusion Criteria: Healthy siblings of children requiring KD for intractable epilepsy at McMaster Children's Hospital from August 2004–May 2007.

A data abstraction form was used to collect patient demographics, epilepsy syndrome, type of diet and seizure frequency. Age of siblings and general health status were also recorded. Siblings were interviewed by a Child Life Specialist prior, during and/or after initiation of the KD. Siblings own words were captured and analyzed for main themes.

Results: 13 siblings (aged 2.5–13 yrs; mean 7 yr 4 mo) of 9 patients (aged 9 mo–15 years, mean 5 yr 6 mo) with intractable epilepsy were interviewed. 10 were older siblings. 7 patients had started the KD and 2 awaited initiation. 71% of the patients on the KD had >50% seizure control.

Main themes identified for the siblings were:

1) Impact of the KD on daily life (“My brother gets all the attention,” age 4.5; “I have to eat in a different room. It's not fair,” age 6.5; “This diet will make him mad,” age 6.5; “We hardly get to do family things because of all the work it takes to get him ready. The diet is just going to add more work that I am going to have to do. We probably won't get to go anywhere now,” age 11; “What will he do at Christmas? He will be so mad if he can't eat all the food & the pie,” aged 6.5).

2) Expectations of the diet (“I don't think he will be able to stick to it,” age 4.5; “It will make her big sick go away,” age 3.5; “… no more medication, no more seizures, no more falling and goose eggs … her back to normal and not so tired,” age 8).

3) Misconceptions of the KD (“The food is weird and will make him in a bad mood and won't he get fat?” age 6.5; “It won't work because my brother loves bread,” age 10; “He has to eat something that my mom puts in her coffee? You aren't suppose to eat that,” age 11).

4) Feelings about the diet (“What if it doesn't work? Then what?” age 12; “Mom told my friends about his food. I was embarrassed because they thought the food looked weird,” age 6.5; “I am worried that kids at school may give her food that she is not supposed to have,” age 8; “Now I am mad that I am going to have so much more work to do. I will have to help my mom prepare the food,” age 11).

Conclusions: Siblings have strong feelings about the KD, the majority of which appear to be negative (worry, skepticism, feelings of inequality). Misconceptions about the KD appear to be common. Anticipatory cognitive therapy could be beneficial in helping siblings cope with the changes necessary for the KD. These data will be utilized for a future prospective study

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Adam Kirton 1 , A. Winter 1 , E. Wirrell 2 and O. C. Snead 1 ( 1 Pediatrics, Neurology, Hospital for Sick Children, Toronto, ON, Canada and 2 Pediatrics, Neurology, Alberta Children's Hospital, Calgary, AB, Canada )

Rationale: Evidence supporting seizure-related behaviours in dog companions of epileptic humans is emerging. Potential benefits include assistance abilities, anticipation of seizures, and enhanced quality of life (QOL). Seizure response dog (SRD) behaviours follow clinical seizure onset and may include trained assistance skills. SRD organizations are increasing but their methods and outcomes are unstudied.

Methods: All graduates of a large North American SRD training program (Lions Club Foundation) were approached for enrollment (2001–2006). A standardized survey was developed and applied by the same investigator via in-person and telephone interview. Data was captured on patient medical history, animals, training methods, SRD behaviours and effectiveness, spontaneous alerting ability, and effects on seizure frequency and QOL. Likert-scaled scoring of qualitative variables was performed and changes in QOL recorded. Program methods were evaluated including patient satisfaction and accuracy of epilepsy diagnosis.

Results: Twenty-two of 27 potential patients (81%) participated (median age 34 (12–66) years, 73% female). Most had childhood onset (87%), long-standing (22 years), intractable (36 seizures/month) and refractory (4.8 meds failed) epilepsy. Patients tended to be unmarried (81%), rural (73%), and unemployed (59%) with high school education or less (73%). All had neurologist-confirmed epilepsy diagnoses with symptomatic partial being most common (64%). SRD were large, pure bred animals living with their companions for a median of 4 years. While event-related animal anxiety was described, no adverse events or harm were reported. SRD behaviours (beginning after seizure onset) were consistent and reliable, including activation of emergency response systems in 27%. Spontaneous development of alerting behaviour (prior to clinical seizure onset) was described in 67%, usually within week of pairing after >20 seizures were witnessed. Anticipation behaviours were reliable and occurred a mean of 31 (range 0.5–180) minutes prior to seizure onset with this interval increasing over time in 42%. Alerting abilities were reported to directly influence patient management of their own epilepsy in 89%. After obtaining their SRD, decreased duration or frequency of seizures was commonly reported (45%), particularly by those with alerting dogs (86%). All patients reported improvement in QOL since obtaining their SRD (major 82%, moderate 18%). QOL benefits were distributed evenly across mood, anxiety, interpersonal relationships, and self-confidence issues. Most (73%) described direct social benefits with SRD facilitating new interpersonal relationships. Patients were very satisfied with the SRD program (89%) and all strongly recommended SRDs for others with epilepsy.

Conclusions: SRD programs can select genuine epilepsy patients, instill valuable assistance skills, and generate meaningful improvements in QOL. Untrained alerting abilities commonly develop and may confer additional benefit. The consistency and magnitude of effect, coupled with possible effects on seizure frequency, support the need for additional seizure dog research.

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Emmanuel Raffo 1,2 , J. François 1 , A. Ferrandon 1 , E. Koning 1 and A. Nehlig 1 ( 1 INSERM U666, Strasbourg, France and 2 Médecine infantile I, Hôpital d'Enfants, CHU de Nancy, Vandoeuvre-Lès-nancy, France )

Rationale: Several studies measured the threshold to pentylenetetrazol (PTZ)-induced seizures in rats fed a Ketogenic Diet (KD) or subjected to calorie restriction. These studies were only based on the observation of clinical seizure symptoms and particularly the first overt myoclonia. Our purpose was to control whether the efficacy of the KD and/or calorie restriction was similar on the different electroclinical patterns of seizures induced by PTZ.

Methods: Forty 50-day-old rats were divided in four weight-matched groups and fed controlled diets: Normocaloric Carbohydrate (NC), Hypocaloric Carbohydrate (HC), Normocaloric Ketogenic (NK) and Hypocaloric Ketogenic (HK). After 21 days of the selected diet, blood glucose and beta-hydroxybutyrate levels were determined and seizures were induced by continuous infusion of PTZ in the tail vein of freely-moving animals. The clinical and EEG course of the seizures were studied. Thresholds were determined for each seizure pattern and compared between the different groups.

Results: The electroclinical course of PTZ-induced seizures was similar in all groups. The HK group exhibited higher thresholds than NC, HC and NK ones for most clinical features: absence (p = 0.003), first overt myoclonia (p = 0.028), clonic seizure (p = 0.006) as well as for EEG features: first spike (p = 0.036), first spike-and-wave discharge (p = 0.014), subcontinuous spike-and-wave discharges (p = 0.005). The NK, HC and NC groups were not statistically significantly different from each other. Blood glucose and beta-hydroxybutyrate levels were not correlated with electroclinical seizure thresholds. Furthermore, despite the interruption of PTZ infusion when the clonic seizure began, a tonic seizure occurred in some animals, with no significant difference regarding the diet.

Conclusions: This approach permitted a precise electroclinical study of the course of PTZ- induced seizures. In this model, in addition to the usually studied first overt myoclonia, we clearly demonstrated in young adult rats the efficiency of a calorie restricted KD in elevating the thresholds to most electroclinical seizure patterns. We also confirmed the lack of efficiency of the KD to reduce seizure severity once the seizure has started.

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Takayuki Oku 1 , M. Fujii 1 , N. Tanaka 1 , H. Imoto 1 , J. Uchiyama 2 , F. Oka 1 , I. Kunitsugu 3 , K. Nakano 4 , S. Nomura 1 , H. Fujisawa 1 , T. Saito 1 and M. Suzuki 1 ( 1 Neurosurgery, University of Yamaguchi, Ube, Japan ; 2 Applied Medical Engineering Science, University of Yamaguchi, Ube, Japan ; 3 Public Health, University of Yamaguchi, Ube, Japan and 4 Industrial Science, University of Tokyo, Tokyo, Japan )

Rationale: Cooling of the brain tissue has been shown to effectively suppress epileptiform discharges (EDs). However, the influence of such cooling on the normal function and histology has not yet been thoroughly investigated. This study reports the neurophysiopathological consequences of focal cooling applied to terminate EDs.

Methods: Experiments were performed on adult male Sprague-Dawley rats (250–350 g) under halothane anesthesia. A thermoelectric (Peltier) chip (6×6×2 mm) was used as a cooling device and was placed on the surface of the sensorimotor cortex after a craniotomy (10 × 10 mm). A thermocouple was then placed between the Peltier chip and the brain surface. Focal cooling of the cortex was performed at the temperatures of 20°C, 15°C, 10°C, 5°C, 0°C and −5°C for 1 hr (5 rats in each group), which are all temperatures shown to suppress EDs. Then the cranial window was repaired. Motor function was evaluated by the beam walking score (BWS) every day for 7 days. The rats were next either deeply anesthetized and sacrificed 7 days after the operation for a histological examination of the neural tissue following staining of the tissue sections with hematoxylin-eosin, the Klüver-Barrera and the TUNEL.

Results: The BWS decreased on the day after cooling only in the −5°C group (p ≤ 0.05), while the BWS did not change in the other temperature groups. Histologically, necrosis of the neurons and proliferation of the astrocytes were only observed in the −5°C group.

Conclusions: Focal cooling of the cortex for 1 hour above a temperature of 0°C was thus found to be effective for the termination of EDs without any irreversible damage.

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Jennifer Fabe 1 , S. Nelson 1 and R. RamachandranNair 1 ( 1 Ketogenic Diet Program, McMaster Children's Hospital, Hamilton, ON, Canada )

Rationale: The Ketogenic Diet (KD) though effective, imposes a significant lifestyle change for the child and family. Literature reports of significant drop out rates of >40%. Reasons include poor parental and/or patient coping, poor compliance, lack of support, side effects and lack of efficacy.

Hypothesis: Multidisciplinary Psychosocial Support (MPS) to the family reduces the chance of drop out rate in KD program.

Objective: To determine whether MPS reduces the 1 year drop out rate in children treated with KD for intractable epilepsy

Methods: Inclusion Criteria: We studied the children (<18 years) initiated on the KD at McMaster Children's Hospital for intractable epilepsy.

Group A- Children initiated on the KD from Jan 2001–Jan 2003.

Group B- Children initiated on the KD from Jan 2004–Jan 2006.

Intervention: A registered dietitian (RD), child life specialist (CLS) and social worker (SW) formed the core MPS team since Jan 2004. Prior to this, there was no dedicated CLS or SW.

MPS included:

  • 1
    RD created menus and provided ongoing education & support to parents;
  • 2
    CLS assessed, educated, & supported patients & siblings to increase coping & adjustment;
  • 3
    SW assessed and supported parents to increase coping and empowerment;
  • 4
    KD parent support group every 8 week.

Children were followed up for 1 year or till they dropped out (which ever was earlier)

Outcome measure: 1 year drop out rate in group A & B

Results: Group A: 15 patients (ages: 0.7–18.4 years; mean 8.3 years). 74% (11) had >50% seizure control (27% seizure free, 4). One year drop out was 60% (9) due to poor seizure control (13%, 2) and, lack of psychosocial support (PS) in 47% (7).

Group B: 26 patients (ages 0.8–17.9 years; mean 7.8 yrs). 62% (16) had > 50% seizure control (27% seizure free, 7). By one year 42% (11) dropped out due to poor seizure control (19%, 5) and lack of PS (23%, 6). Drop out due to lack of PS was higher in Group A (p = 0.059, X2).

Reasons other than lack of efficacy and side effects were presumed to be ‘psychosocial’

Psychosocial reasons for drop out included: 1) Patient's/sibling's difficulties with coping in social/family activities 2) Inability of parent to support patient due to their difficulty to cope 3) Lack of patient understanding of purpose of KD 4) Patient feeling diet is too restricting/regimented 5) Negative impact of KD on family system and family quality of life.

Conclusions: We presume from the results that MPS to families is effective in reducing 1-year drop out rate (due to psychosocial reasons) of the KD therapy by 24%. This difference is clinically significant, but achieved only near statistical significance due to small sample size. The MPS allows for children and their families to have a better opportunity to benefit from the KD, which may translate into overall improved quality of life. We strongly suggest that a family centered approach that includes a CLS and SW be utilized when selecting and supporting KD families.

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Krishna Dalal 1 , M. Tripathi 1 , V. Bajpai 1 , D. Saraswat 1 and A. Singh 1 ( 1 Biophysics, All India Institute of Medical Sceinces, New Delhi, India )

Rationale: Surgery of foci and poly antiepileptic drugs (AED) have been proved to be failure in controlling the frequency and duration of the seizures of intractable epilepsy. Keeping this in view, this study deploys reflexology, together with AED to focus on the study of physical body and mind of the intractable epileptic patients.

Methods: Patients were recruited over a period of 2 years from the intractable epilepsy clinic. These were patients who would not benefit from resective epilepsy surgery or lesionectomy. A sample size of 45 - Reflexology arm (22) and AED Polytherapy arm(23)) suffering from epilepsy for a period of >2 years with >2 seizures/month while on at least 2 AED with good compliance was recruited in the this trial. After randomization, control arm patients continued treatment from neurologist while the study arm patients received reflexology in addition to pharmacotherapy. In study arm, stimulations on the reflex areas of vagus nerve which had been mapped on the hands, were applied to abort seizure during aura and to reduce the duration of ictal phase. Homeostasis in the internal organ system functions was maintained by stimulating the corresponding reflex areas mapped on the feet. Mechanical stimulations in the form of finger pressure had been applied on each reflex area. The method of applying reflexology technique had been taught to every caregiver and patient. Compliance for therapy was monitored by verbal questioning the patients as well as their caregivers and supervision of therapy sessions as applied by either both of them or the caregivers alone. A record on seizure frequency, duration of ictal phase and the number of times that seizures could be aborted during aura, was maintained. Reduction in seizure frequency up to 25% was considered as no response, 26%–50% as moderate response, 51%–75% as good response and >75% as excellent response. The primary outcome of this trial was the seizure frequency and the secondary outcome was the quality of life in epilepsy for which QOLIE-31 has been used as the instrument.

Results: The results are based on the observations during a monitoring period of 6 months to 2 years. It has been observed that 9 patients (40.9%) had excellent response, 4 (18%) had good response, 8 (36.4%) had moderate response while 1 (4.55%) had no response compared with pre-reflexology study. There is no prominent change in the seizure frequency of control group samples. The best part of this study is that by stimulating the reflex areas of the vagus nerve, one is able to abort the seizures during aura and to reduce the ictal phase of the seizure. The measurement of quality of life is yet to be calculated in order to conclude the study.

Conclusions: This intermediate clinical trial concludes that reflexology can be useful as an adjunct to the pharmacological treatment for managing patients suffering from intractable epilepsy and it certainly merits wider attention as an effective mode of medical therapy for controlling the seizure frequency with an easily available, echo-friendly and simple method.

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Annamaria Vezzani 1 , S. Balosso 1 , M. Maroso 1 , T. Ravizza 1 , M. Sanchez-Alavez 2 and T. Bartfai 2 ( 1 Neuroscience, Mario Negri Institute for Pharmacological Research, Milano, Italy and 2 Molecular and Integrative Neurosciences, The Harold L. Dorris Neurological Research Institute, The Scripps Research Institute, La Jolla, CA )

Rationale: Interleukin (IL)-1beta and its signal-transducing receptor (IL-1R1) are chronically overexpressed in glia and neurons in epileptic tissue from rodents and from patients with drug resistant epilepsies. IL-1beta contributes to the generation and maintenance of seizures in experimental models by increasing NMDA receptor-mediated neuronal excitability. We investigated the intracellular pathway that could be involved in the proconvulsant effects of IL-1beta in the mouse hippocampus.

Methods: Seizures induced by intrahippocampal (ih) injection of kainic acid (KA) were monitored and quantified for 3 h by EEG analysis in freely-moving adult male C57BL6 mice. IL-1-induced sphingomyelinase-dependent ceramide and activation of Src-kinase signaling were investigated pharmacologically by using systemic or ih administration of selective compounds that act along this pathway. Protein levels were measured in hippocampal homogenates by western blot (WB) analysis, 1 h after KA administration in additional groups.

Results: C2-ceramide (40–80 μg/kg, ih), a cell permeable analog of ceramide mimicked the proconvulsant effects of 1 ng IL-1beta by increasing 2- and 3-fold respectively the number and total duration of KA-seizures. 3-O-methylsphingomyelin (3 μg/0.5 μl, ih), a selective inhibitor of sphingomyelinase, and ifenprodil (1 mg/kg, intraperitoneally), a NR2B-selective NMDA antagonist, did not affect seizures when given alone but prevented the proconvulsant effect of IL-1beta when coadministered with this cytokine.

IL-1beta or KA similarly increased by 20% and 50% the phosphorylated form of NR2B (NR2B-P) and Src kinase (Src-P) respectively compared to vehicle-treated mice. In IL-1beta+KA-treated mice, NR2B-P and Src-P were increased by 50% and 110% respectively compared to vehicle-treated mice.

Conclusions: A sphingomyelinase-dependent pathway activated by IL-1beta during seizures leads to the production of ceramide which in turn induces Src-dependent phosphorylation of NR2B subunit of NMDA receptor. This pathway is involved in the proconvulsant actions of IL-1beta and may be targeted to attain fast anti-inflammatory effects and seizure inhibition.

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Alexander Rotenberg 1,2 , E. Bae 1,2 , D. Depositario-Cabacar 1 , M. Takeoka 1 , J. M. Tormos 2,4 , S. Schachter 3 and A. Pascual-Leone 2,3 ( 1 Neurology, Children's Hospital, Boston, MA ; 2 Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Boston, MA ; 3 Neorology, Beth Israel Deaconess Medical Center, Boston, MA and 4 Institut Guttmann, Hospital de Rehabilitació, Barcelona, Spain )

Rationale: Repetitive transcranial magnetic stimulation (rTMS) is a technique for noninvasive focal brain stimulation where small intracranial electrical currents are generated by a powerful fluctuating extracranial magnetic field. rTMS can disrupt ongoing neuronal activity, or induce lasting changes in cortical excitability, and is emerging as a novel anticonvulsive therapy. Largely, rTMS is applied interictally to reduce seizure frequency - this is generally well-tolerated, although seizure induction by rTMS is a possible side-effect. Less often, rTMS has been used ictally to terminate ongoing seizures, as in instances of epilepsia partialis continua (EPC). Whether ictal rTMS is effective and safe has not been extensively studied. In particular, the question of whether rTMS can exacerbate ongoing seizures is among the safety concerns. Accordingly, we report our recent experience with rTMS in treatment of EPC, and summarize available published reports as an early step towards evaluating the safety and efficacy of rTMS in the treatment of ongoing focal seizures.

Methods: Seven patients (six adult and one pediatric) with EPC due to mixed etiologies were treated with rTMS applied over the seizure focus as determined by seizure semiology and/or surface EEG. rTMS was delivered at or above motor threshold in high frequency (20- to 100-Hz) bursts or as prolonged low frequency (1-Hz) trains. Two patients were treated with prolonged daily 1-Hz rTMS for 9 and for 10 days, respectively. Clinical seizures were monitored in all by patient and caregiver report, and EEG was recorded in three of seven. To complement our data, we also performed a literature search to identify additional EPC cases treated with rTMS.

Results: Ongoing seizures were suppressed after treatment in three of seven patients. Notably, in a patient with EPC due to a vascular malformation, continuous right hand movements of approximately 20-years duration were initially disrupted by high frequency (100-Hz) rTMS bursts, and a durable (>4 months) EPC suppression was achieved with daily 1-Hz rTMS. Seizures in one of the remaining four patients, a child with Rasmussen's encephalitis, were suppressed only for the duration of the rTMS train, but resumed after treatment. Our literature search identified six additional reports of EPC treated with low frequency (0.5- to 1-Hz) or high frequency (6- to 20-Hz) rTMS trains. Clinical seizures were suppressed in three of six reported cases. Seizures were not exacerbated by rTMS either in our experience, or in the published reports. Side-effects were generally mild and well-tolerated - among these were transient head and limb pain, and limb stiffening during high-frequency rTMS trains.

Conclusions: rTMS may be safe and effective in suppressing ongoing seizures associated with EPC. Encouragingly, we did not identify any instance of seizure exacerbation by either high- or low-frequency rTMS. We conclude that careful and controlled evaluation of the safety and efficacy of rTMS in the treatment of EPC is warranted.

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Linda C. Laux 1 , R. Blackford 1 , D. R. Nordli Jr 1 ., P. Morrison 2 , P. Pyzik 2 , Z. Turner 2 and E. H. Kossoff 2 ( 1 Pediatric Epilepsy, Children's Memorial Hospital. Northwestern University Feinberg School of Medicine, Chicago, IL and 2 Pediatric Epilepsy, Johns Hopkins University, Baltimore, MD )

Rationale: Parents often expect immediate seizure improvement after starting the ketogenic diet (KD) for their children. However, they are often counseled by physicians that the ketogenic diet may in fact take several months to be effective. The purpose of this study was to determine the typical time to first note seizure reduction as well as the time after which it was unlikely to be helpful in those children started on the KD.

Methods: Records of all children started on the KD at Johns Hopkins Hospital (JHH), Baltimore (n = 83) and Children's Memorial Hospital (CMH), Chicago (n = 35) from 11/03–12/06 were evaluated retrospectively. There were more children with partial seizure disorders treated with the KD at JHH, but no other significant differences in baseline patient demographics between the two centers. At Johns Hopkins Hospital the KD was started after 1–2 days of fasting with a predominantly 4:1 ratio (grams of fat: carbohydrate and protein), whereas no fast after 1/05, and a majority receiving a 3:1 ratio occurred at Children's Memorial Hospital. Seizure calendars were examined to determine the first day in which seizures were reduced.

Results: Of the 118 children started on the KD, 99 (84%) had documented seizure reduction. The overall median time to first improvement was 5 days (range, 1–90 days). Seventy-five percent of children improved within 14 days and 92% within 30 days. In those children who were fasted at KD onset, the time to improvement was quicker (median 5 vs. 14 days, p = 0.004) with a higher percentage improving within 5 days (60% vs. 31%, p = 0.006). No difference was identified between fasting and non-fasting in outcomes after 3 months, however. There was no difference in times to improvement between KD ratios or baseline seizure types.

Conclusions: The KD works quickly when effective, typically within the first 1–2 week. Starting the KD after a fasting period may lead to a more rapid, but equivalent long-term seizure reduction, as has been published previously. In children in whom seizures are not improved after 2 months, the KD can probably be discontinued.

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David J. Mogul 1 , Y. Li 1 and A. Fine 2 ( 1 Biomedical Engineering, Illinois Institute of Technology, Chicago, IL and 2 Biomedical Engineering, University of Illinois, Chicago, IL )

Rationale: Intractable epilepsy that remains resistant to drug treatment is a significant public health problem with very few alternative therapeutic options besides surgery. Our laboratory has been exploring protocols by which electrical stimulation applied to a seizure focus could modulate an epileptic seizure and, ideally, terminate it. We have previously reported (Epilepsia, 2007) that control stimulation using a proportional feedback algorithm with variable feedback gain can be used to suppress although not revert epileptic seizures in the in vivo rat brain. We have more recently begun to investigate the use of feedback stimulation utilizing a phase resetting protocol to stop the progression of a seizure following induction in the in vivo rat hippocampus.

Methods: The phase-resetting algorithm uses precisely timed current-neutral pulses whose timing is based upon real-time analysis of electrical activity measured proximal to the seizure focus. Recording and stimulation occurs using separate electrodes implanted in the CA3 region of rat hippocampus. Seizure induction occurs via focal injection of kainic acid proximal to the electrodes. A major element of the hypothesis for applying such phase resetting protocols is that neuronal activity at or near a focus during a seizure sees a significant elevation in synchronous behavior. Precisely timed current stimuli may provide an effective means at disrupting the highly coherent neural activation. Dominant neural frequencies of the intracranial EEG are first determined using Fourier analysis.

Results: The effectiveness of several stimulation parameters on reverting seizure activity are currently being examined. These parameters include: phase relationship (Φ) during stimulation application, number of stimulus pulses, pulse duration and profile, and dominant vs. harmonic frequencies. Changes in phase coherence, Teager energy, and EEG amplitude variance are being used to assess the effects of different stimulation parameters on seizure disruption.

Conclusions: The use of a control feedback protocol provides a means to adjust stimulation based upon the real-time behavior of the epileptic focus so that different seizure etiologies and system nonstationarities can be adequately addressed. Furthermore, such stimulation would only be applied acutely on demand. If successful, this technique could provide an alternative therapy for seizure control in cases of intractable epilepsy.

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Krista Gilby 1 , R. Keeley 1 , A. Palmer 1 and D. C. McIntyre 1 ( 1 Institute of Neuroscience, Carleton University, Ottawa, ON, Canada )

Rationale: Rats selectively bred to be seizure-prone (SP), versus seizure-resistant (SR), naturally show significantly reduced plasma levels of non-esterified fatty acids (NEFA) despite maintenance on the same diet. This relative deficiency persists throughout pregnancy and while breastfeeding in female SP rats. Aberrant lipid handling has also been well documented in patients with epilepsy and its comorbid conditions, particularly those associated with a developmental delay.

Methods: In this study, we compared the rates of visuomotor development between post-natal day (PND) 6–20 in naive SP versus SR rat pups. We also supplemented pregnant SP and SR mothers with a high dose of salmon oil (omega-3 fatty acids) beginning 1 week prior to conception and continuing until PND23 (weaning) in order to examine its effects on visuomotor development in SP and SR offspring.

Results: The findings of this study demonstrated significantly delayed acquisition of several motor tasks including righting reflex, negative geotaxis, cliff avoidance and wire hanging in SP compared to SR rats. Surprisingly, fatty acid supplementation in pregnant females did not correct this delay and instead further delayed the development of SP offspring. It even delayed some aspects of development in SR rats.

Conclusions: Documentation of a natural developmental delay in SP pups lends further clinical validity to the use of our strains as an animal model for the study of epilepsy and its associated disorders. The findings of this study also powerfully demonstrate the role of maternal diet in pre- and post-natal pup development and caution against heavy ingestion of omega-3 fatty acids by mothers during that time regardless of genetic backdrop. (funded by CIHR grant to DCM)

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Elizabeth G. Neal 1,3 , H. Chaffe 1,3 , N. Edwards 1 , M. Lawson 1 , R. Schwartz 2 and J. H. Cross 1,3 ( 1 Neuroscience, Institute of Child Health & Great Ormond St Hospital, London, United Kingdom ; 2 Paediatrics, Central Middlesex Hospital, London, United Kingdom and 3 National Centre For Young People with Epilepsy, Lingfield, United Kingdom )

Rationale: The ketogenic diet has been used for many years in the treatment of drug resistant epilepsy in children but to date there has been no randomised controlled trial examining efficacy of the diet against no treatment, or comparing classical and medium chain triglyceride (MCT) dietary protocols.

Methods: 145 children were randomised to receive either the classical or MCT ketogenic diet, either immediately or after a 3-month delay (control group). Early discontinuations were recorded. Seizure frequency was assessed after 3 months, compared to that of controls. The efficacy of the two diets was compared.

Results: 3-month seizure data is available for 94 diet children (45 classical, 49 MCT) and 49 controls. The mean percentage of baseline seizures was significantly lower in the 94 diet children (68%) than in the controls (137%, p < 0.001), but there was no difference between the classical or MCT diets (67% and 69% respectively, p = 0.93). 39 of the 94 diet children had greater than 50% seizure reduction (41%), compared to 4 controls (8%) (p < 0.001). 7 of the diet group had greater than 90% seizure reduction (8%), compared to no controls (p < 0.1). There were no significant differences in efficacy between the two diet types. When response was reviewed by epilepsy syndrome numbers were small; the reduced mean percentage of baseline seizures was particularly striking for Lennox Gastaut syndrome (50%), myoclonic absence (55%), myoclonic astatic (58%), and unspecified myoclonic epilepsy (59%).

20 children never started the diet, 25 discontinued before 3 months, and 6 did not provide data. Of the 25 that discontinued, 5 reported increased seizures (4 classical, 1 MCT diet) and 20 reported dietary intolerance (6 classical, 14 MCT diet, p < 0.01; parental unhappiness 6, vomiting 1, diarrhoea 3, constipation 1, extreme drowsiness 1, problems with texture 1, food refusal 7).

Conclusions: Results from the first randomised controlled trial of the ketogenic diet strongly support its use in childhood epilepsy. Classical and MCT dietary protocols are comparable in efficacy after 3 months.

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Adam L. Hartman 1,2 , M. Lyle 2 , K. Wayns 2 , M. Rogawski 2,3 and M. Gasior 2,4 ( 1 John M. Freeman Pediatric Epilepsy Center, Department of Neurology, Johns Hopkins Hospital, Baltimore, MD ; 2 Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD ; 3 Department of Neurology, University of California, Davis, Sacramento, CA and 4 Cephalon, Inc., West Chester, PA )

Rationale: Prolonged, low-frequency (6 Hz) electrical stimulation in mice induces complex partial seizures characterized by a stunned or immobilized posture and rearing, forelimb clonus, and twitching. This seizure model is interesting because it has a distinct profile of pharmacological sensitivity and may identify agents with a broader spectrum of clinical activity than conventional antiepileptic drug screening tests. Since the ketogenic diet has been used clinically in drug-resistant epilepsies, we sought to determine whether it is active in the 6 Hz model.

Methods: Starting at 3 week of age (i.e., after weaning), male NIH Swiss mice were fed a normal or ketogenic diet (Bioserv F3666, Frenchtown, NJ) ad libitum and were evaluated in the 6 Hz test (stimulus duration 3 sec; pulse width 0.2 msec). Blood glucose and β-hydroxybutyrate levels were measured on the day of seizure testing.

Results: The mean CS50 (current intensity producing seizures in 50% of mice tested) values in the 6 Hz test were 50.6 (95% C.L., 46.3–55.3) mA and 15 (95% C.L., 14.0–16.1) mA in mice fed for 12 days with the ketogenic diet and the normal diet, respectively (P < 0.001). The mean CS50 value also was elevated markedly in separate experiments in which the ketogenic diet and normal diet were fed for 16 days, but not for 2, 5 and 21 days. The mean CS50 values of the 5 groups fed the normal diet did not differ significantly, indicating the CS50 value does not vary with age (from 3 to 6 week) or weight (ranging from 12 to 24 g) during the rapid growth phase studied here. β-Hydroxybutyrate levels were significantly higher and glucose levels were significantly lower in mice fed the ketogenic diet than in those fed the normal diet. Blood glucose and β-hydroxybutyrate levels did not correlate with the CS50 values.

Conclusions: The ketogenic diet strongly elevates the seizure threshold in the 6 Hz test in a time-specific manner, requiring more than 5 days of dietary treatment for seizure protection to be evident. The efficacy of the diet waned at 3 week, despite persistently elevated β-hydroxybutyrate and low blood glucose. Therefore, protection from seizures in this model appears to be unrelated to the level of ketosis. Seizure thresholds in mice fed the normal diet were insensitive to body weight and age, demonstrating that the 6 Hz model is appropriate to assess anticonvulsant regimens, including dietary therapies, where animal weight or age may be a confounding factor. The 6 Hz model may be useful in mechanistic studies of the ketogenic diet and also for experiments to determine why the ketogenic diet loses efficacy in some patients.

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Lee Stewart 1 , M. A. Cortez 2,1 and O. C. Snead 2,1 ( 1 Mental Health and Neurosciences Program, Hospital for Sick Children, Toronto, ON, Canada and 2 Division of Neurology, Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada )

Rationale: Early postnatal administration of the cholesterol biosynthesis inhibitor AY-9944 (7.5 mg/Kg) to sucking rodents, leads to a life long disorder with chronic seizure activity characterized by 5–6 Hz slow spike and wave discharges, characteristic of chronic atypical absence seizures (CAAS) (Stewart et al, Epilepsy and Behavior 2006: 9: pp 564–572; Cortez MA, Snead OC III: Pharmacological models of generalized absence seizures in rodents. In: Chapter 10: Models of Seizures and Epilepsy (Pitkanen A, Schwartzkroin PA, Moshe SL, eds). Elsevier, San Diego, California 2006: pp 111–126). The AY- induced CAAS are also associated with behavioral changes that are characteristic of hyperactivity and stereotypy (Stewart et al, Epilepsy and Behavior 2006: 9: pp 564–572), and cognitive impairment (Chan et al, Eur J Pharmacology 2006: 541(1–2): pp 64–76).

Methods: AY-treated male C3H mice (N = 16) were weaned into environmentally enriched (EE) or non- enriched standard cages (NEE) for thirty days. The behavior of EE-AY mice (N = 10) was compared to that of NEE-AY mice (N = 6) using standard testing for open-field locomotion and olfactory recognition memory.

Results: The EE-AY mice exhibited less behavioral hyperactivity during a 15-min open-field session as indicated by a decrease in total movements (576.87 ± 10.04 vs. 630 ± 13.83), as well as in episodes of rotational stereotypy (8.25 ± 1.05 vs. 18.85 ± 2.92), and jumping (3.81 ± 0.84 vs. 16.75 ± 8.45) (all P < .05, ANOVA). EE-AY mice also exhibited improved discrimination between a previously encountered odor stimulus (soiled bedding of gender- and strain-matched juvenile mice) and two subsequent unfamiliar odor stimuli at 1 hr and 24 hrs later as compared to non-enriched AY mice (both P < .05; ANOVA).

Conclusions: Environmental enrichment appears to reverse the behavioral impairment induced by AY-9944 treatment during postnatal development. Further studies are required to determine the effect of environmental enrichment in seizure severity and in the GABAB receptor modulation in the chronic model of atypical absence seizures.

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Heather Milligan 1 , T. A. Simeone 1 , P. G. Sullivan 2 and J. M. Rho 1 ( 1 Neurology Research, Barrow Neurological Institute, Phoenix, AZ and 2 University of Kentucky, Lexington, KY )

Rationale: The ketogenic diet (KD) is an effective treatment for medically refractory epilepsy, but the anticonvulsant mechanisms remain largely unknown. Here, we focused on examining the effects of the KD on neuronal and mitochondrial damage following acute and chronic seizures.

Methods: Kainic-acid (KA) was used to induce acute seizures, whereas chronic seizures were examined in Kcna1-null mice (a potassium channel deletion which causes mice to have recurrent, spontaneous limbic-like seizures). Adult wild-type and Kcna1-null mice maintained on the ketogenic diet (6:1 ratio of fats to carbohydrates and protein) were compared to littermates fed a standard rodent chow diet. KD-induced effects on behavioral seizures (Racine scale), EEG seizure detection, and hippocampal neuronal injury (Fluoro-Jade B) were determined. Also, hippocampal and cortical mitochondria were isolated and oxidative damage assessed by immunoblot analysis of lipid peroxidation, protein oxidation and protein nitration.

Results: Even though the diet did not influence the cumulative behavioral seizure scores, the KD protected mice against neuronal damage in the CA1 hippocampal region and mitochondrial oxidative damage 72 h after KA-induced acute seizures. In the chronic seizure model, the life-span of Kcna1-null mice increased from 51 ± 9 days when fed a standard diet to 66 ± 14 days while given a KD (mean ± standard deviation; P < 0.0001) indicating possible neuroprotective effects. Compared to standard diet fed null mice, KD-treated null mice had fewer, although not significant, limbic seizures per day (5.3 ± 1.5 and 12.0 ± 6.3, respectively; mean ± standard deviation; P < 0.138) and lower overall behavioral seizure scores. In addition, KD fed Kcna1-null mice had reduced mitochondrial oxidative damage compared to standard diet fed null mice.

Conclusions: These data support a mitochondrial site of action for the KD, either by enhancing mitochondrial capacity to withstand the high-energy demand caused by seizures or assisting in the reduction of mitochondrial oxidative damage.

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Kenneth A. Jenrow 1 , T. N. Nagaraja 2 , R. A. Knight 3 , L. L. McCormick 1 , J. D. Fenstermacher 2 and K. V. Elisevich 1 ( 1 Neurosurgery, Henry Ford Hospital, Detroit, MI ; 2 Anesthesiology, Henry Ford Hospital, Detroit, MI and 3 Neurology, Henry Ford Hospital, Detroit, MI )

Rationale: Epileptogenesis precipitated by status epilepticus (SE) is believed to evolve during a latent period which intervenes between SE and the emergence of spontaneous seizures. We have previously reported the evolution of pathological angiogenesis within specific limbic structures during this period, and the subsequent leakage of plasma born materials across the abnormal blood-brain barrier (BBB). Such BBB leakage has recently been shown to contribute directly to epileptogenesis. Here we report that SE-induced vascular pathogenesis is initiated by the expression of hypoxia inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF), and that these cytokines/growth factors participate in the spatiotemporal evolution of these pathologies following SE.

Methods: SE was induced in male wistar rats (250 g–350 g) by systemic kainic acid injection (10 mg/kg, i.v.), and terminated four hours after onset by injection of pentobarbital (20 mg/kg, i.p.) (KASE). The control group received vehicle injections and did not develop SE. Rats in separate cohorts were sacrificed 1, 3, 7, 14, 21, 35, 42, 49, 56, 63 days post-KASE. Bromodeoxyuridine (BrdU) injections (50 mg/kg, i.p.) were administered daily for seven consecutive days to separate cohorts beginning 1, 7, 14, 21, 28, 35, 42, or 49 days post-SE and animals in these cohorts were sacrificed 14 days after completing the BrdU injection series. Prior to sacrifice, vascular permeability was assayed serially at 7, 14, 21, 24 and 56 days post-SE, using gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging (MRI). HIf-1α and VEGF expression were assayed using single and double label immunohistochemistry (IHC). Endothelial proliferation and vascular density were assayed by single and double-label IHC for BrdU and von Willebrand factor.

Results: Pathological angiogenesis was widespread but restricted to limbic and paralimbic structures, including hippocampus, amygdala, and piriform cortex. HIF-1α and VEGF expression in these regions was apparent by 1 and 3 days post-KASE, respectively, and remained chronically upregulated thereafter. Endothelial proliferation was dramatically increased (p < 0.01) during the first 14 days (day 1 and day 7 cohorts) post-SE and fell precipitously thereafter. Pathological neovascularization evolved between 21 and 35 days post-KASE and paralleled increases in BBB permeability within these regions.

Conclusions: The evolution of pathological angiogenesis within limbic structures following KASE is initiated by hypoxia via the upregulation of HIF-1α and VEGF. These cytokines/growth factors stimulate endothelial proliferation and neovascularization within successive and relatively discrete time intervals. The resulting abnormal neovascular complexes appear to be the primary source of vascular leakage and persist within the chronically epileptic brain. Vascular pathogenesis may therefore present novel targets for antiepileptogenic/antiepileptic therapy.

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David Lyczkowski 1 , H. H. Pfeifer 1 and E. A. Thiele 1 ( 1 Pediatric Epilepsy Program, Massachusetts General Hospital, Boston MA, MA )

Rationale: To determine if the Low Glycemic Index Treatment (LGIT) is an effective epilepsy treatment for individuals with Tuberous Sclerosis Complex

Methods: We performed a retrospective chart review of patients initiating the LGIT at the Massachusetts General Hospital for Children between January of 2002 and 2007. Further analysis was limited to individuals starting LGIT who carried a diagnosis of Tuberous Sclerosis Complex (TSC). Information obtained included demographics, seizure type and frequency per parental or self report, current and previous medications and treatments for epilepsy as well as TSC genotype

Results: From January 2002–2007, ninety eight patients were educated regarding the use of the LGIT as a dietary therapy for treatment of their intractable epilepsy. Seven of these patients carried the diagnosis of TSC. Ages of the TSC patients ranged from 1.6 to 21 years. Followup on LGIT of the TSC population ranged from 2 to 29 months. The TSC group included 5 males and 2 females. Prior to diet initiation the TSC patients had previously been on a range of 2–11 anticonvulsant medications, with an average of 7.5. Two patients transitioned from the ketogenic diet(KD) to LGIT and were able to maintain the seizure control achieved while on the KD, which included complete seizure control in one patient and a < 50% seizure reduction in the other. The second patient continued on LGIT due to perceived benefit by family, as diet provided control of drop seizures; the patient continued to have intermittent nocturnal generalized tonic clonic seizures while on dietary therapy. Of the 5 TSC patients without a history of previous dietary therapy, on LGIT one experienced a >90% reduction in seizure frequency, three had a 50–90% seizure reduction, and one had < 50% reduction in seizure frequency

Conclusions: Conclusions: The low glycemic index treatment may be an effective treatment option for individuals with TSC and refractory epilepsy.

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Jennifer Hopp 1 , A. Sanchez 1 , H. Matausch 1 , K. Callison 1 , J. Zhu 1 and A. Krumholz 1 ( 1 Neurology, University of Maryland Medical School, Baltimore, MD )

Rationale: Depression and anxiety are common symptoms reported by patients with epilepsy and have a negative impact on health related quality of life (HRQOL). Despite this recognition, psychiatric disease remains under-recognized and in patients with epilepsy. Many hypotheses have been proposed to explain the relationship between emotional dysfunction and epilepsy, though this remains poorly understood. Although increased prevalence of depression and anxiety has been widely established in women in the general population, gender differences have not been extensively examined in patients with epilepsy.

This study was designed to identify gender differences in the prevalence of depression and anxiety in people with epilepsy and to examine the impact of these variables on health related quality of life.

Methods: 119 consecutive patients in the University of Maryland Epilepsy Outpatient Center and Inpatient Epilepsy Monitoring Unit (EMU) completed Beck Depression Inventory-II (BDI-II®), Beck Anxiety Inventory (BAI®), and Quality of Life in Epilepsy (QOLIE-31) measures between December, 2005 and May, 2007.

Patients who completed these questionnaires in the Epilepsy Monitoring Unit (EMU) did so on the day of admission before their medications were changed and prior to any seizure activity.

Scores were calculated for each inventory and means were compared using standard t-test calculations. Regression analysis was used for assessment of the relationship between gender, anxiety, depression and HRQOL.

Results: Mean depression (BDI-II) scores were 11.76 for men and 13.96 for women with epilepsy. This difference was not statistically significant (p = 0.27, CI −1.72 to 6.11). There was also no statistically significant difference in mean anxiety (BAI) scores between men (9.88) and women (11.47), (p = 0.44, CI −2.44 to 5.64), though both comparisons revealed a trend towards greater depression and anxiety in women. Overall HRQOL T scores were calculated for each group and were lower in women (59.37) than men (63.60), though not significant (p = 0.26, CI −11.69 to 3.22). There was also no significant difference in HRQOL scores between men and women with the same reported levels of depression or anxiety. However, both the BDI and BAI were strongly predictive of HRQOL (p < 0.001) in all patients.

Conclusions: Although it was predicted that women with epilepsy would have significantly higher rates of depression and anxiety, this hypothesis was not strongly supported by this study. These data showed trends towards higher reported symptoms of depression and anxiety and worsened HRQOL in women, though did not reach statistical significance. This may be partially explained by relatively low number and heterogeneous patient population in the study, though may suggest alternate hypotheses for this disparity. The predictive value of the BDI and BAI of HRQOL was strongly supported in this analysis, confirming the role of depression and anxiety in quality of life in this patient population.

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Dolores Castro 1 and L. Galiano 2 ( 1 Neurology, Hospital Severo Ochoa, Leganés, Spain and 2 Neurology, CE “Moratalaz” Area 1, Madrid, Spain )

Rationale: to review concomitant illnesses and pharmacological management in elderly epileptic patients

Methods: 257 elderly epileptic outpatients from two Public Health Departments in Madrid. We analyzed the presence of concomitant illnesses as well the medication they were already receiving. We compared the results between patients diagnosed under the age of 60 (n = 139) and those diagnosed over the age of 60 (n = 118)

Results: 77.4% of the elderly epileptic patients had other concomitant illnesses, the most frequent being hypertension (39%), hypercholesterolemia (24.1%) and heart pathology (20.2%). We found that 15.2% of the patients experienced one or more types of psychiatric symptoms and 3.89% cognitive impairment. The association of neurological disorder was 33.1% and in the majority of the patients this was due to cerebrovascular disease. On average, our patients were taking two types of medication (2.30 SD 2.3) in addition to their prescribed antiepileptic drugs. The most frequent additional medication included antihypertensive agents (40.1%), antiplatelet agents (28%) and statins (25.3%), 9.3% were taking antidepressants, 7% benzodiazepines and 8.9% oral anticoagulants.

Conclusions: In our group of elderly epileptic patients diagnosed over the age of 60, the incidence of concomitant illnesses was more common and this group was substantially affected by metabolic syndrome: hypertension and hyperchollesteronemia.

Because elderly persons with epilepsy frequently take many types of medication

concomitantly, the likelihood of drug interaction is quite high, especially with older AEDs. Such interaction frequently affects AED concentrations, and AED induced alterations in the kinetics of coadministered drugs are even more common.

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Michael Westerveld 1 , E. Fertig 2,1 , M. Spann 1 , L. Hahn 1 and S. McDaniel 1 ( 1 Neurosurgery, Yale University School of Medicine, New Haven, CT and 2 Neurology, Yale University School of Medicin, New Haven, CT )

Rationale: Differentiating epileptic and non-epileptic seizure patients is a complex diagnostic issue, and accurate diagnosis has implications for medical and mental health treatment. Neuropsychological evaluation, including objective assessment of personality and psychopathology, may help to identify patients with NES. The present study investigates the psychological profiles commonly associated with NES and ES using the Personality Assessment Inventory.

Methods: Patients were classified into two groups based on review by an epileptologist of the events captured by VEEG (ES = 132, NES = 31). All patients were administered the PAI as part of a comprehensive neuropsychological test battery. Nine patients were excluded due to invalid PAI profiles.

Results: Most clinical scales were in the normal range; however, NES scores were significantly higher in several domains. Oneway ANOVA indicated significant differences between groups on the Somatic Complaints scale and its subscales, Conversion and Somatization (p < .001) with the NES group having higher scores. This pattern was also found on the Depression scale and its subscales, Physiological and Affective (p < .001). Stepwise logistic regression revealed the Conversion and Somatization subscales had the strongest significant relationship with diagnosis (p < .01).

Conclusions: While patients with epilepsy may report higher levels of health concerns, anxiety, and depression than the general population, NES patients report significantly more symptoms in these areas. Elevated health concerns and somatization were the greatest predictors distinguishing the groups. Additional validation against other diagnostic groups is needed to determine the specificity of this PAI profile for NES.

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Kristin A. Kirlin 1 , S. B. Asmussen 1 , S. D. Gale 1 and S. S. Chung 2 ( 1 Clinical Neuropsychology, Barrow Neurological Institute, Phoenix, AZ and 2 Department of Neurology, Barrow Neurological Institute, Phoenix, AZ )

Rationale: The prevalence of depression in patients with seizures is estimated to be 3–9% in those with well-controlled epilepsy, 20–55% in individuals with refractory epilepsy, and 20–40% in those with psychogenic nonepileptic seizures (PNES) who are referred to epilepsy centers. Depressive symptomatology has a significant negative impact on patients with seizures. Suicide is approximately 5–10 times more common among individuals with epilepsy than the general population and studies suggest that depression is more closely related than seizure frequency to poor quality of life among individuals with epilepsy. Depression is a multidimensional condition encompassing affective, physiological, and cognitive symptoms and although depression's high comorbidity with both epileptic seizures (ES) and PNES has been established, few studies have addressed whether the types of depressive symptoms experienced differ by seizure type.

Methods: The present research retrospectively examined the self-reported depressive symptomatology of patients (n = 60 ES and 56 PNES) who underwent video-EEG monitoring and completed neuropsychological testing including self-report objective measures of psychopathology [Beck Depression Inventory-Second Edition (BDI-II); Personality Assessment Inventory (PAI)]. Differences in self-reported depressive symptoms were compared between the ES vs. PNES groups, as well as among several subgroups with ES (i.e., temporal vs. extra-temporal, right MTS vs. left MTS, and partial vs. generalized onset).

Results: The PNES group endorsed a significantly higher level of physiological symptoms of depression as measured by the PAI DEP-P subscale than the ES group (PNES mean T = 60.8, SD = 11.6; ES mean T = 55.6, SD = 12.7; [t(114) =−2.33, p < .05]). No statistically significant differences were observed between the PNES and ES patients on the BDI-II total score, PAI DEP clinical scale, or the other 2 PAI DEP subscales. Comparison of the ES subgroups' self-reported depressive symptoms did not yield statistically significant differences on any of the measures.

Conclusions: Although the BDI-II total score did not evidence a significant difference between the ES and PNES groups, depression measures that parse out different types of depressive symptoms, such as the PAI subscales, distinguished between these two groups. Relative to normative data, the self-reported level of depressive symptoms was at the upper end of normal limits for both patient groups on measures that utilize a total score; and when the different dimensions of depressive symptoms were considered, the PNES group endorsed a mildly elevated rate of physiological symptoms. No evidence was found for differences in depressive symptoms among patients with different types of ES in the present study, possible due to limited sample sizes in these subgroups. These findings highlight the importance of multidimensional assessment of depressive symptoms.

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Raza Naqvi 1 , R. S. McLachlan 1,2 , S. Matijevic 2 and J. G. Burneo 1,2 ( 1 University of Western Ontario, London, ON, Canada and 2 London Health Sciences Centre, London, ON, Canada )

Rationale: Fatigue may account for a significant portion of the effect on patient quality of life in those with epilepsy. However the causes of fatigue in patients with epilepsy have not yet been clearly delineated.

Methods: A preliminary study assessed fatigue in 56 adult outpatients with normal intelligence at the London Health Sciences Centre Epilepsy Clinic. Patients completed the Fatigue Severity Scale (FSS) and Center for Epidemiological Studies Depression Scale (CES-D). Serum was taken for CBC, electrolytes, TSH and drug levels. Further clinical information was extracted from patient charts. Univariate (ANOVA) analysis was performed between fatigue severity scale scores (≥4 out of 7 = severe fatigue) and a number of clinical variables. Multivariate analysis was also used to assess significant correlations between variables.

Results: Severe fatigue was found in 28 patients (50%). Analysis showed a significant correlation between fatigue and depression (r = 0.58, p < 0.01). Fatigue was more likely to occur in generalized epilepsy (r = 0.31, p < 0.05). There was no significant correlation between fatigue and either TSH levels or number of antiepileptic medications. There was a trend towards increased fatigue in females.

Conclusions: Symptoms of fatigue should be assessed in all patients with epilepsy. Patients reporting fatigue should be investigated for depressive symptoms.

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Jae-Moon Kim 1 , Y. Lee 1 , S. Park 2 and J. Lee 2 ( 1 Neurology, Chungnam National University Hospital, Daejeon, South Korea and 2 Neurology, Bundang Hospital, Seoul National University Hospital, Sungnam, South Korea )

Rationale: Restless legs syndrome (RLS) is a sensory-motor disorder characterized by discomfort of and urge to move the legs, primarily during rest or inactivity, partial or total relief with movement, with presence or worsening exclusively in the evening. RLS is associated with thyroid diseases, iron deficieny, renal diseases, Parkinson disease, and opioid use. There were several reports of antiepileptic drugs (AEDs) induced RLS. We performed this study to detect the relationship between AEDs and RLS.

Methods: Questionnaire for RLS were used in 114 consecutive epiletpic patients taking antiepileptic drugs(AEDs) more than one year and 100 consecutive tension type headache with no medications. Medical records including associated illnesses and concomitant medications, and symptom onset vs. start of AEDs were analyzed.

Results: Twenty-three (20.2%) out of 114 epileptic patients and 6 patient with tension type headache had RLS symptoms.(P < 0.05) RLS was developed after taking AEDs in 12 patients (10.5%, 2 patients with co-medication of antidepressant), before AEDs in 8 patients (7.0%), and uncertain in 3 patients (2.6%, 1 patient with chronic renal failure). There were no significant relationship between each AEDs and presence of RLS. Monotherapy vs. polytherapy or duration of AEDs were not related with the presence of RLS.

Conclusions: AEDs may cause RLS in epileptic patients but the mechanism of AEDs and occurrence of RLS was not closely related. To clarify these uncertain relationships, well-designed, large scale study is needed.

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Andres M. Kanner 1 , J. J. Barry 1 , F. G. Gilliam 1 , B. Hermann 1 and K. J. Meador 1 ( 1 Neurological Sciences, Rush University Medical Center, Chicago, IL )

Rationale: Symptoms of depression and anxiety have been associated with a negative impact on health related quality of life measures (HRQOL) of patients with epilepsy (PWE), including a perception of worse adverse events to antiepileptic drugs (AED). Whether a major depressive episode (MDE) with or without a comorbid anxiety disorder (AD) or whether a subsyndromic type of depression impact differently these variables is yet to be established. The purpose of this study is to answer these two questions.

Methods: 193 consecutive outpatients (130 women, mean age 39 ± 11.7 years) were recruited from five epilepsy centers. The mood module of the Structured Clinical Interview for DSM-IV (SCID-I) was used to identify current and past mood disorders. Other current Axis I DSM-IV diagnoses were identified with the MINI International Neuropsychiatric Interview (MINI). Health-related quality of life was measured with the Quality of Life in Epilepsy -89 (QOLIE-89). Patients also completed the Beck Depression Inventory-II (BDI-II). The severity of adverse events to AEDs was identified with the self-rating scale Adverse Event Profile (AEP). Subsyndromic depression (SSD) was defined as the presence of BDI-II total scores >12 in the absence of any current MDE identified with the MINI or SCID. Finally, seizure frequency was coded as seizure-freedom for at least the last six months (yes/no).

Diagnostic groups: (1) no current psychiatric symptoms. (2) Current SSD. (3) Current MDE only. (4) Current AD(s) only. (5) Current mixed MDE+AD. (6) Dysthymia.

Statistical analyses: QOLIE and AEP scores were compared among the six groups. Logistic regression models were developed to identify the predictors of poor HRQOL and toxicity to AEDs (high AEP scores).

Results: Among the 193 patients, 103 (53.4%) were asymptomatic, 22 (11.4%) had SSD, 10 (5.2%)MDE, 30 (15.5%) AD, 24 (12.4%) MDE+AD and 4 (2.1%) dysthymia. This latter group was eliminated from further analyses. As shown in the table, there was a significant difference in QOLIE-89 (F = 49.1, p < 0.0001) and AEP (F = 36.4, p < 0.0001) scores among the six groups.

Significant differences for QOLIE-89 scores were accounted by differences between: No symptoms vs all groups (p < 0.0001), SSD vs MDE+AD (p < 0.0001) and AD vs AD+MDE (p < 0.0001). For AEP scores, significant differences between the same groups were identified (p < 0.0001, p = 0.006 and p = 0.001, respectively).

Logistic regression models identified psychiatric disorders (P < 0.0001), high AEP score (P < 0.0001) and persistent seizures (p = 0.002) as predictors of poor QOLIE. Psychiatric disorders (p < 0.0001) and persistent seizures (p = 0.003) were independent predictors of worse adverse events.

Conclusions: These findings demonstrate a differential negative association between SSD, MDE and AD on HRQOL and on adverse events to AEDs, with comorbid MDE+AD yielding the worse association. The data also suggest the need to define carefully the type of psychiatric disorders in drug studies and in HRQOL research.

QOLIE-89 and AEP scores by diagnostic group

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Abstract

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Alex Taylor 1 , C. Hoffman 1 , G. Woo 1 , P. Garcia 1 and D. Cahn-Weiner 1 ( 1 UCSF, San Francisco, CA )

Rationale: Research examining patients with psychogenic nonepileptic seizures (PNES) has identified several personality features associated with this patient population. Before the results of these studies can be put into practice, however, the validity of these findings must be established. One identified threat to validity is selection/volunteer bias. Previous research has suggested that personality characteristics are significant correlates of willingness to participate in research. Some studies have suggested low participation rates for PNES patients, but this methodological issue has not been examined systematically before. The purpose of the present study is to document the frequency with which PNES patients decline participation in research examining emotional and personality facto