Free Papers: Clinical Course and Prognosis


*Hideji Hattori, *∥Tsunekazu Yamano, †∥Kitami Hayashi, †∥Makiko Osawa, ‡∥Shinichiro Hamano, and §∥Kenichiro Kaneko *Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka ; †Department of Pediatrics, Tokyo Woman's Medical University, School of Medicine, Tokyo ; ‡Division of Neurology, Saitama Children's Medical Center, Saitama ; §Department of Pediatrics, Juntendo University Urayasu Hospital, Japan ; and ∥Research Committee on Clinical Evidence of Medical Treatment for Status Epileptics in Childhood .

Purpose: To evaluate the efficacy of intravenous lidocaine therapy in the management of status epilepticus (SE) in childhood.

Subjects and Methods: This was a multiinstitutional, retrospective study. Questionnaires were sent to 30 hospitals with pediatric departments. Patients admitted for SE and managed with lidocaine were included. We collected background information of the patients (underlying diseases, seizure type, etc.), treatment, and efficacy.

Results: Case cards (279) were collected. Patients older than 15 years and younger than 1 month were excluded. The data set analyzed included 257 cases. The mean age was 3.8 years, and 66% were younger than 3 years. Epilepsy was the diagnosis in 145 cases. The remaining 112 had nonepileptic diseases. The etiology of epilepsy was determined in 103 cases; of which 79 were from prenatal factors, eight from perinatal factors, and 16 from postnatal factors. Epilepsy type was diagnosed as localization related in 94 cases, generalized in 27 cases, and unclassified in 24 cases. Nonepileptic acute illness included 30 cases of benign infantile convulsion, 30 cases of acute encephalopathy/encephalitis, 13 cases of meningitis, and 39 other causes. Seizure type was diagnosed as generalized in 102 cases, secondarily generalized in 94 cases, and partial in 61 cases. We categorized SE into three groups: continuous (type I); cluster (type II); and frequently repeated (type III). Type III patients regained consciousness between seizures; therefore, type III did not meet the common definition of SE. The numbers of type I, type II, and type III cases were 73, 73, and 111, respectively. The mean dosage of lidocaine in initial loading therapy was 1.65 ± 1.12 mg/kg (206 cases), and the mean starting dosage of maintenance therapy was 2.11 ± 1.19 mg/kg/h (211 cases). The maximum maintenance dosage was 2.60 ± 1.69 mg/kg/h. Lidocaine was infused for a mean of 105 h. Lidocaine was selected as the first drug in 57 cases, the second in 83 cases, the third in 75 cases, and after the fourth in 42 cases. We defined effective as complete seizure control or seizure reduction by >50%, with no or mild adverse side effects. Overall, lidocaine was effective in 57% of cases. The treatment lag time and the order of medication used did not influence the efficacy of lidocaine. No difference in the efficacy rate was found between epileptic and nonepileptic disorders. Patients with benign infantile convulsions showed good responses to lidocaine, whereas SE patients with CNS infection showed poor responses. Efficacy was better in patients with types II and III SE compared with type I. Patients who showed good response to initial loading therapy of lidocaine were well controlled with maintenance therapy, whereas poor responders to initial infusion therapy showed almost no response to maintenance therapy. Therefore if the patients do not respond to the initial therapy, maintenance therapy will be unsuccessful. Adverse side effects were seen in 35 (13.6%) cases, and the risk of side effects was high with maintenance doses >4 mg/kg/h.

Conclusions: Lidocaine is useful for the management of SE in childhood. It may be used as a first- or second-line medication for benign infantile convulsions, and patients with types II and III SE are good candidates for lidocaine use. However, lidocaine may be useful in every stage of SE when SE is not controlled by other medications. Patients who do not respond to an initial loading infusion will not achieve control by maintenance infusion.


*Kimio Minagawa and *Toshihide Watanabe *Department of Pediatrics, Hokkaido Children's Hospital and Medical Center, Otaru, Hokkaido, Japan .

Purpose: Effectiveness of treatment with intravenous midazolam (MDL) for status epilepticus and clusters of seizures in children was studied.

Methods: All children who received intravenous (MDL) for status epilepticus and clusters of seizures from April 1994 to July 2002 were investigated. MDL was given as a bolus, followed by continuous infusion. After seizure control was achieved, the infusion was continued for ≥24 h. Subsequently, MDL infusion was gradually tapered.

Results: Eighty-two episodes of status epilepticus or clusters of seizures in 45 children were treated with intravenous MDL. Twenty-two children had epilepsy, and 23 had acute symptomatic seizures, including acute encephalitis/encephalopathy, purulent meningitis, hypoxic–ischemic encephalopathy, cerebral infarct, theophylline-related seizures, febrile seizures, and hyponatremia. MDL was administered as an intravenous bolus dose at 0.06–0.4 mg/kg (mean, 0.173 mg/kg), followed by continuous intravenous infusion at 0.05–0.4 mg/kg/h (mean, 0.191 mg/kg/h). The duration of treatment was 3–768 h (mean, 132.7 h). Complete arrest of seizures was achieved in 62 episodes, and >50% decrease in seizure frequency in eight clusters of seizures. In these 70 (85.4%) successfully treated cases, the effect appeared within 45 min after the initiation of therapy. No severe adverse effects were noted except stridor and mild respiratory suppression in two cases.

Conclusions: MDL is an effective and safe drug to be used as first-line or second-line therapy for status epilepticus and clusters of seizures in children.


*Shinji Fujimoto, *Kiyo Hamaguchi, *Naoki Ando, *Tatsuya Ishikawa, and *Hajime Togari *Department of Pediatrics, Neonatology and Congenital Disorders, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan .

Purpose: Mexiletine is a supplemental antiepileptic drug (AED) for refractory epilepsy, especially symptomatic localization-related epilepsy. We encountered a 14-year-old boy with eating epilepsy characterized by periodic spasms, who was treated with lidocaine and mexiletine.

Case Reports: The patient was born at term by normal delivery after an uneventful pregnancy. He had a history of acute myelocytic leukemia (M2) at age 6 years and received chemotherapy. Intracranial radiotherapy was not conducted because of the absence of metastasis to the brain. He achieved complete remission, and chemotherapy was terminated at 7 years of age. His physical and mental development was normal until age 10 years, when the patient began to have seizures induced by eating. The periodic attacks were a series of tonic spasms, which involved the axial muscles and upper and lower limbs associated with eye adversion. Tonic spasms repeated periodically at intervals of ∼10–15 s, and the episode lasted 3–30 min (median, 10 min), occurring three to five times a day. About 90% of the seizures occurred while eating. Eating-provoked seizures commonly started 5–10 min after the initiation of eating, but occasionally began just before eating. With a diagnosis of symptomatic localization-related epilepsy, we initiated treatment with several AEDs, including carbamazepine, phenytoin, zonisamide, sodium valproate, clonazepam, and clobazam. However, the frequency and duration of seizures did not change at all for 4 years. Behavior problems, including hyperactivity and lack of concentration, deteriorated with time. We tried to treat the patient with continuous intravenous infusion of lidocaine (1.25–2.0 mg/kg/h) at age 14 years. No seizures were observed during the treatment. Oral mexiletine (350 mg/day) after the lidocaine treatment has maintained good seizure control for 6 months with no significant adverse effects. The frequency and duration of the seizure decreased by 90% compared with the pretreatment state. In addition, behavior problems improved rapidly. However, the frequency and duration of seizures increased gradually, and behavior problems deteriorated after 6 months. Intravenous lidocaine infusion had no effect on seizure control at that time. Now the frequency and duration of the seizures are ∼30% compared with the pretreatment state.

Conclusions: Lidocaine combined with mexiletine achieved good seizure control for 6 months in a 14-year-old boy with eating epilepsy characterized by periodic spasms. However, tolerance to lidocaine and mexiletine developed thereafter. Tolerance of mexiletine has not previously been reported.


*Yukio Sawaishi, †Hajime Tamura, *Tamami Yano, and *Goro Takada *Department of Pediatrics, Akita University School of Medicine ; and †Department of Radiology, Tohoku University School of Medicine, Japan .

Purpose: Diffusion tensor imaging (DTI) is a method of mapping the diffusivity of free water molecules in the brain. In regions where axon tracts form an ordered structure, water diffusion has directionality (anisotropy). Application of this technique to the brain has shown that the white matter has higher anisotropy than gray matter. For each voxel, the direction of maximal diffusivity can be used to display the course of white matter fibers. We have applied diffusion tensor analysis to evaluate fiber tracts of the brain in two patients with cortical malformations and related the findings to the epileptogenic background of each condition.

Methods: Patient 1 was a 1-year-old girl with pachygyria who had been followed up since early infancy because of tonic seizures and developmental delay (DQ = 40). The patient was relieved of seizures with phenobarbital and showed interictal EEG with background abnormality of high-amplitude fast waves. Patient 2 was a 6-year-old girl with band heterotopia. The patient developed more slowly than normal and manifested a few complex partial seizures. The interictal EEG showed an irregular background of high-amplitude fast waves. Diffusion weighting was performed on Siemens Magneton Vision 1.5-T along nine axes, by using a b-value of 1,000 s/mm2. Diffusion tensors at each pixel were calculated by using multivariate linear least-square fitting and diagonalized. The eigen vector associated with the largest eigen value was assumed to represent the local fiber direction. DTI-based color maps were created from fractional anisotropy (FA) values and the three elements of eigen vector. Original software was used to visualize fiber directions, with the eigen vector with the largest eigen value superimposed on a T2-weighted image. The length of the arrow is proportional to the relative anisotropy.

Results: In patient 1 (pachygyria), the degree of diffusion anisotropy was exceptionally high in the abnormally thick cortex, and the arrows were regularly oriented toward the surface through the cortex, obscuring the discrimination between the cortex and the white matter. In patient 2 (band heterotopia), the subcortical ectopic gray matter showed increased anisotropy compared with the cortex. An excess of short association fibers entered the ectopic gray matte from the deep white matter, whereas long association fibers and the optic radiation were hardly discernible.

Conclusions: It has been reported that DTI depicts reduced anisotropy within the abnormal focal cortexes associated with epilepsy. These results are possibly caused by a defect of neurogenesis or cell loss resulting in increased extracellular space. Conversely, increased anisotropy within the abnormal cortex of pachygyria seems to be associated with preservation of premature cortical structures, because the cortex of embryonic mouse brain has increased anisotropy because of vectors running perpendicular to the surface of the brain. This speculation is consistent with the understanding that in pachygyria, migration waves are normal initially but are arrested later. In band heterotopia, the deep ectopic gray matter has been shown to have a structure different from that of the cortex, rather similar to the abnormally thick cortex of pachygyria. These immature directional structures possibly contribute to the abnormal EEG background and epileptogenicity in these migration disorders.

This preliminary study indicates the usefulness of DTI for the evaluation of cerebral fiber tracts in cortical malformations. This technique may be applied to assess localized milder cortical malformations associated with epilepsy.


*Katsuya Yamamoto, *Masatoshi Otake, and *Masaru Takayanagi *Department of Pediatrics, Sendai City Hospital, Japan .

Purpose: The hemophagocytic syndrome (HPS) is a reactive disorder characterized by generalized proliferation of benign histiocytes with marked hemophagocytosis. The clinical features of HPS include fever, hepatosplenomegaly, lymphadenopathy, skin rash, cytopenias, liver dysfunction, and coagulopathy. Abnormality in the immune regulatory system with resulting hypercytokinemia has been postulated to play an important role in the pathogenesis of HPS. We present a pediatric patient with phenytoin-induced HPS successfully treated with corticosteroid.

Case Report: The patient was an 8-year-old girl with epileptic seizures presenting as frequent diurnal head nodding and drooling. Three years before admission, she showed frequent nocturnal hemifacial twitching and was diagnosed as having benign childhood epilepsy with centrotemporal spike (BCECT). She had been treated with phenobarbital, followed by sodium valproate and zonisamide. On admission, her EEG revealed diffuse spike-and-wave bursts in addition to bilateral centrotemporal spikes during wakefulness and continuous spike-and-wave discharges during sleep. The clinical and EEG findings were diagnostic of atypical benign partial epilepsy evolved from BCECT. Intravenous and subsequent oral administration of phenytoin (PHT) completely controlled the seizures. On hospital day 4, a high fever with malaise developed. On hospital day 8, she had skin rash on her neck, hands, and feet, and the blood showed leukocytopenia. PHT was discontinued, considering the possibility of allergic reaction. She showed, however, cervical lymphadenopathy, thrombocytopenia, and mild elevation of transaminases on the following day. Bone marrow examination, performed based on a suspicion of HPS, disclosed hemophagocytosis. All laboratory markers of the activity of HPS, including serum ferritin and soluble interleukin-2 receptor, and urine β2-microgloblin levels, were elevated. The diagnosis of HPS was made, and prednisolone (PSL) was started on day 10 at a dose of 2 mg/kg/day. Rapid improvement was observed. Fever, rash, and lymphadenopathy disappeared over the next 3 days, and serum ferritin level normalized on day 17. PSL was tapered slowly and discontinued on day 23. No relapse of HPS and no recurrence of seizures thereafter were observed. The lymphocyte-stimulating test, performed on day 37, was positive against PHT, with a stimulating index of 225%.

Conclusions: Anticonvulsant-related HPS has been thought to be an extremely rare condition with, to our knowledge, only four reports of anticonvulsant-induced HPS. Conversely, HPS and the so-called anticonvulsant hypersensitivity syndrome (AHS) have a number of clinical features in common, and the similarities between HPS and AHS might create a diagnostic problem. Regarding the pathophysiologic mechanisms of AHS, recent studies have indicated that T-cell activation caused by reactive metabolites of drugs might play an etiologic role, and some viral infections might facilitate the process. Therefore it is postulated that some patients with AHS might develop HPS through hypercytokinemia produced by activated T cells. Correct diagnosis of HPS is most important because early and adequate corticosteroid therapy, sometimes combined with more potent immunosuppressive agents such as cyclosporin A, should be considered for HPS.


*Shigeki Kameyama, *Hiroshi Masuda, *Jumpei Homma, *Makoto Oishi, *Takehiko Ueno, *Matsuo Sasagawa, *Osamu Kanazawa, *Jun Tohyama, *Akiyoshi Kakita, and *Hitoshi Takahashi *Epilepsy Center, National Nishi-Niigata Central Hospital, and Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan .

Purpose: In 80% of our patients with neocortical epilepsy, magnetic resonance imaging (MRI) demonstrated neoplastic or nonneoplastic lesions. We already reported that epilepsy patients with focal cortical dysplasia (FCD) had different epileptogenicity compared with those with dysembryoplastic neuroepithelial tumors. The MRI-depicted lesions of Taylor-type FCD showed findings similar to those of tuberous sclerosis (TS). The two lesions are well known to share similar histopathologic features. Recent reports showed similarities of the two lesions in relation to TSC1 and TSC2 genes. However, we demonstrated by neurophysiologic methods that the FCD and TS lesions have different types of epileptogenicity in neocortical epilepsy patients. Subdural and/or intraoperative EEG analyses disclose the physiological differences between the lesions. This difference has important clinical significance in the choice of favorable operative strategies for epilepsy patients with FCD or TS.

Methods: Seven patients with FCD (average age at operation, 20.1 years) and four with TS (average age at operation, 15.8 years), all of whom underwent surgical resection, were compared in terms of epileptogenicity, based on the relation between the lesions and the epileptogenic areas. We analyzed the localization of the MRI-depicted lesions and the epileptogenic area identified by magnetoencephalography (MEG) and subdural and/or intraoperative electrocorticogram (ECoG). In one patient each with FCD and TS, we performed intraoperative depth recording within the lesions, besides the cortical surface recordings. The equivalent current dipoles (ECDs) analyzed from MEG data were overlaid on three-dimensional MRI, which produced magnetic source images (MSIs). Additionally, we studied the relation between the MRI lesion and hyperperfusion areas on ictal single-photon emission computed tomography (SPECT) with [99mTc]-ECD (ethyl cysteinate dimer). Postoperative follow-up periods were >12 months.

Results: In all the FCD patients, hyperperfusion areas on ictal SPECT and a cluster of ECDs of MSIs were concordant with the localization of the MRI lesions. Ictal subdural ECoG and/or intraoperative ECoG recordings demonstrated that the FCD lesion had strong epileptogenicity. Intraoperative depth recording showed repetitive spikes within the FCD lesion itself. In contrast, epileptogenic areas were identified near one of TS lesions. MSIs showed clusters of ECDs discordant with the MRI TS lesions in all patients. Intraoperative ECoG in two patients showed an interictal epileptogenic area adjacent to one of the TS lesions. Intraoperative depth recording demonstrated no spikes within the TS lesion. Therefore, TS lesions itself did not have epileptogenicity; whereas epileptic foci resided in the peri-lesional cortex. Based on the physiologic differences, we used different surgical strategies for these different categories of epilepsy patients. All patients with FCD achieved freedom from seizure after total lesionectomy. All but one patient with TS became seizure free after both lesionectomy and focus resection. The surgical strategies we devised were reliable to obtain good seizure outcomes.

Conclusions: Although the FCD and TS lesions had similar MRI findings and similar histopathologic features, electrophysiologic analyses of the two lesions showed different types of epileptogenicity in the lesions. These results helped us devise rational surgical strategies for patients with these lesions. Better understanding of the epileptogenicity in the FCD and TS lesions has led to good seizure outcome after surgery.


*Takato Morioka, *Tadao Kawamura, *Kimiko Fukui, *Tomio Sasaki, and *Department of Neurosurgery, Kyushu University, Fukuoka ; and †Department of Pediatrics, National Saisyunsou Hospital, Kumamoto, Japan .

Purpose: Surgeries, including anatomic and functional hemispherectomies for intractable epilepsy associated with Sturge–Weber syndrome, are still challenging for the surgeons. We report a patient first seen with intractable psychomotor seizures, who became seizure free after focal corticectomy.

Case Report: In a 34-year-old woman, intractable complex partial seizures developed, with onset at age 1 year. She had angiomas on her left forehead and in her frontal region. Neuroradiologic examination revealed angiomas in the left temporooccipital lobes and calcification in the left occipital lobe. Thus she was diagnosed as having Sturge–Weber syndrome. Her seizure semiology consisted of oral and limb automatisms and impaired consciousness with secondarily generalized tonic–clonic seizures. Ictal scalp EEG demonstrated that ictal discharges began in the left frontotemporal region. Hypometabolism and hypoperfusion of the left temporooccipital lobes were noted on fluorodeoxyglucose–positron emission tomography (FDG-PET) and ethyl cysteinate dimer (ECD)–single-photon emission computed tomography (SPECT), respectively. Left occipital and frontotemporoparietal craniotomies were performed, disclosing extensive leptomeningeal angiomatosis both in the temporal and occipital lobes. Prolonged subdural electrode recordings from both lobes localized the ictal-onset zone on the lateral surface of the occipital lobe. With use of cortical stimulation and visual evoked potentials, visual cortex was localized over a subregion of the interhemispheric surface of the occipital lobe, far from the ictal-onset zone. Corticectomy of the ictal-onset zone was performed, and she became seizure free. No visual field defect was produced by the resection.

Conclusions: In occipital lobe epilepsy, seizure semiology and scalp EEG often reflect seizure propagation rather than seizure origin. Long-term subdural electrode recording from both lobes is mandatory in Sturge–Weber patients with intractable complex partial seizures to obtain a good seizure outcome with surgery.


*Department of Neuropsychiatry, St. Paul Hospital and Seisen-no-Sato ; and Departments of †Neurosurgery , ‡Clinical Neuropathology , and §Neuropsychiatry, Tokyo Medical University, Tokyo, Japan .

Purpose: Most focal epilepsies are single-lobe epilepsies with the epileptogenic focus localized in one lobe. Conversely, focal epilepsies with multiple foci sometimes are encountered. We selected multiple lobe epilepsies (MLEs) with wide epileptogenic foci extending from the frontal lobe to other lobes and studied the focal lesions, EEG, neuroimaging findings, and clinical symptoms.

Methods: Seventeen surgical cases of MLEs with foci involving the frontal lobe and other lobes were selected. We investigated the epileptogenic regions, EEGs, neuroimaging findings, and the characteristics of clinical symptoms.

Results: In 17 cases of MLEs, the epileptogenic foci in the frontal lobe were found in the orbitofrontal (eight cases: left, five; right, three), opercular (four cases: left, two; right, two), frontolateral (14 cases: left, 13; right, one), left cingular (one case), right interhemispheric interval (one case), left motor cortex (one case), left frontobasal (one case), left rolandic facial (one case), and left prefrontal area (one case) regions. Foci in other lobes were in the temporal pole (six cases: left, five; right, one), temporolateral (five cases: left, four; right, one), right tempora1 (three cases), left temporobasa1 (two cases), left temporouncinate (one case), left amygdala (one case), left hippocampus (one case), left parietal (one case), and right temporomedial (one case) regions. On EEG, spikes were observed over all four lobes of the brain. Furthermore, spike–waves and slow waves showed diverse findings. Magnetic resonance imaging (MRI) findings consisted of no significant abnormality (six cases), frontotemporal basal cortical dysplasia (three cases), hippocampal atrophy (two cases: left, one; right, one), left frontal arachinoid cyst (two cases), left tempomedial ganglioma (two cases), right orbitofrontal tumor (one case), right temporal tumor (one case), multiple tuberous sclerosis (one case), right temporomedial cyst (one case), and frontotemporal vascular malformation (one case). Clinical seizures were focal motor seizures (11 cases), autonomic seizures (12 cases), psychic seizures (seven cases), and secondarily generalized tonic–clonic seizures (eight cases). No oral automatisms were observed.

Conclusions: We conducted a clinical study on MLEs with foci including the frontal lobe and other lobes. For epileptogenic foci, we found foci localized widely in the frontotemporal area. Diverse MRI findings, EEG, and clinical symptoms were observed in MLEs. Differential diagnosis between single-lobe and MLEs is important.


*†Mieko Yoshioka, *†Takako Matsumoto, ‡Yoshihisa Higuchi, and †Hiroko Ikeda *Section of Pediatric Neurology, Kobe City Pediatric and General Rehabilitation Center for the Challenged , and †Department of Pediatrics, Kobe City General Hospital, Kobe ; and ‡Utano National Hospital, Kyoto, Japan .

Purpose: Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive disorder prevalent in Japan, characterized by congenital muscular dystrophy, cobblestone lissencephaly, and eye anomalies. Neuroimaging with magnetic resonance imaging (MRI) reflects gross pathologic findings. Within the cerebral cortex, unlayered polymicrogyria is seen primarily in the frontal lobes, and cobblestone lissencephaly is largely temporooccipital. The association of epilepsies and related seizure disorders in FCMD has been reported in more than half of the patients. It could be a natural model for studying the epileptogenesis of prenatal cortical lesions. However, the long-term prognosis of seizure disorders has scarcely been studied. In addition, the relation between seizures and neuropathologic abnormalities is not clear. In this study, we examined patients with FCMD with special emphasis on these points.

Patients and Methods: Between 1971 and 2003, 53 patients were diagnosed as having FCMD, according to the clinical criteria of FCMD described by Fukuyama et al. in 1960. Among them, 42 patients (19 male and 23 female patients) were followed up for >3 years and were analyzed in this study. The follow-up period ranged from 3 to 22 years, with an average of 11 years. Cortical dysplasia was examined with computed tomography (CT) or MRI in all cases, whereas neuropathologic findings were obtained from autopsies along with neuroimaging in three cases. Classification of epilepsies and epileptic syndromes and that of epileptic seizures was performed by using patients' clinical history and EEG findings.

Results: Seizures were observed in 30 (71%) of 42 patients. Age at onset of seizures ranged from 6 months to 14 years 6 months, with an average of 3 years 1 month. Patients were divided into three groups according to the seizure status: group I (G-I): nine patients with persistent febrile convulsions from onset, group II (G-II): 12 patients with febrile seizures at onset, followed by development of afebrile seizures, and group III (G-III): nine patients with afebrile seizures from onset. The average age at onset of seizures in each group was 2 years 6 months in G-I, 1 year 6 months in G-II, and 5 years 9 months in G-III. In G-II, the duration between febrile and afebrile seizures was within 1 year in three patients and >10 years in one patient, with an average of 3 years 7 months. Five of nine patients in G-I had a seizure once, whereas most patients in G-II and G-III had intractable seizures. As for seizure types, all patients in G-I had generalized tonic–clonic seizures (GTCs) as febrile disorders. In G-II, GTCs as febrile disorders were followed by complex partial seizures (CPSs) or partial seizures evolving to secondarily generalized seizures (sGTCs). Later, these seizures developed into Lennox–Gastaut syndrome (LGS) in two patients in G-II. In G-III, patients showed CPSs or sGTCs at onset and evolved to LGS in one patient. EEGs showed paroxysmal activities during follow-up in 19 (60%) of 30 patients with seizures. The main focus was observed in the frontal, temporal, or central region. These paroxysmal discharges were focal and asymmetrical in almost all cases. Lesions with marked cortical dysplasia depicted on CT/MRI or revealed in autopsies were consistent with focal paroxysmal discharges in EEG.

Conclusions: Among FCMD patients with seizures, some had persistent febrile seizures from the onset (G-I), whereas afebrile seizures developed later (G-II) or from onset (G-III). Classic lissencephaly (type 1) usually showed symptomatic generalized epilepsies, whereas FCMD belongs to cobblestone lissencephaly (type II) and had localization-related epilepsies.


*Shigeki Sunaga, *Hiroyuki Shimizu, and †Kensuke Kawai *Department of Neurosurgery, Tokyo Metropolitan Neurological Hospital ; and †Department of Neurosurgery, the University of Tokyo Hospital, Tokyo, Japan .

Purpose: Genuine drop attacks are extremely rare in patients with temporal lobe epilepsy. We recently encountered two cases of temporal lobe epilepsy accompanied by severe drop attacks. Based on preoperative clinical evaluation and surgical results, we concluded that drop attacks in these patients have completely different mechanisms in pathogenesis.

Case Reports: Case 1: A 53-year-old woman had the first complex partial seizures at the age of 17 years. Her seizures started with uprising epigastric feeling followed by conscious impairment. At the age of 50 years, almost >30 years after her initial seizure, she suddenly began falling to a sitting position with a frequency of at least once a month. She was referred to our hospital for surgical treatment. Repetitive scalp EEG with sphenoidal leads detected active epileptic discharges in the left anterior temporal region. Magnetic resonance imaging (MRI) with fluid-attenuated inversion recovery (FLAIR) sequence demonstrated high signal intensity in an atrophied left hippocampus, compatible with the findings of hippocampal sclesoris. After left anterior temporal lobectomy, her seizures, including complex partial seizures and drop attacks, completely disappeared for a follow-up interval of >1.6 years. This clinical course indicated that her drop attacks originated in the left temporal lobe and should be categorized as one of the clinical symptoms of temporal lobe epilepsy.

Case 2: A 41-year-old woman previously had experienced status epilepticus, triggered by high fever. At age 20 years, she started having recurrent seizures characterized by epigastric discomfort, nausea, and then loss of consciousness, followed by oral automatisms. Since age 30 years, she has manifested another type of seizure with sudden, severe falls. When she was admitted to our hospital for surgical treatment, scalp EEG demonstrated active epileptic discharges in two separate areas. Bilaterally synchronized spike–wave activity was recorded in bilateral frontal regions. Spike discharges also were recorded in the right anterior temporal area, independent of the frontal discharges. Surgical treatment involved anterior one-third corpus callosotomy and right anterior temporal lobectomy. After surgery, both categories of seizures have completely remitted for a follow-up interval of >2.5 years. In this case, the mechanism of drop attacks is attributable to explosive synchronization of bifrontal epileptic discharges, and corpus callosotomy has been very effective.