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Keywords:

  • ESES;
  • CSWS;
  • Idiopathic partial epilepsies;
  • EEG;
  • Landau–Kleffner syndrome

Abstract

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONCLUSIONS
  7. REFERENCES

Summary: Purpose: Questioning the presence of any possible prognostic predictors, this study includes a long-term follow-up of clinical and EEG characteristics of 16 patients with idiopathic partial epilepsy (IPE) who subsequently developed epilepsy with electrical status epilepticus during slow sleep (ESES) spectrum disorders.

Methods: Epilepsy, cognitive and behavioral parameters, and waking and non–rapid eye movement (NREM) EEG data were evaluated and scored for initial stage (i.e., IPE stage), preESES, ESES, and ESES remission periods, individually, on a chronologic basis. Data from 25 healthy subjects who had had IPE at the appropriate ages served for comparison with the patients' data during the IPE stage.

Results: Results revealed a higher incidence in seizure frequency and variability in the ESES group and a resistance to a single antiepileptic drug (AED), as compared with controls, during the IPE stage. Mean age at onset of epilepsy was younger in the ESES group versus controls (5.5 and 7.3 years, respectively). At least one of the premonitory clinical features for development of ESES [an increase in the seizure frequency and/or addition of new types of seizures (93%), appearance of cognitive and/or behavioural changes (81.2%), or a progression in EEG abnormalities (66%)] was present in all patients. Epilepsy remitted in patients within the ESES spectrum at a similar age as in controls in 81.2%, as ESES findings in the EEG disappeared by age 13 years in 94%. Seizure prognosis proved to be the most favorable among the questioned parameters.

Conclusions: An increase in seizure frequency or development of new seizure types, a deviance in behavior or decrease in cognitive performance, or a spreading tendency of the previously focal abnormalities in control EEGs may be premonitory features of a developing ESES and necessitate close follow-ups with sleep EEGs in children with IPEs.

The term epilepsy with electrical status epilepticus during slow sleep (ESES) has been introduced as an age-limited EEG characteristic associated with a heterogeneous group of clinical conditions, the majority of which include epilepsy and/or cognitive and behavioral defects or focal neurologic symptoms in a previously healthy child or one with brain lesions (1). Spike-and-wave (SW) activity occupying ≥85% of non–rapid eye movement (NREM) sleep has been agreed on as the EEG index for ESES; however, Landau-Kleffner syndrome (LKS), a condition classified under this heading, may possess neither such abundance in SWs nor clinical epilepsy, at least in some patients. There seems to be no single feature common for all conditions within this spectrum, except the temporal behavior of the bioelectric abnormalities in the EEG and, to a certain extent, the apparent relation of the clinical features to the localization and the diffusion of those abnormalities. Thus much remains to be said about ESES and its clinical implications, because growing evidence suggests that it may not be as rare as it was previously thought, and some cases of partial epilepsies may exhibit ESES during some time throughout their evolution (2–4). Early recognition and management in such situations may provide prevention of some cognitive and behavioral deficits that may otherwise be permanent in the long run.

This study includes clinical and EEG characteristics of 16 patients with IPEs in whom ESES developed in their EEGs sometime during the course of the disease as compared with a group of 25 patients with typical IPEs.

METHODS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONCLUSIONS
  7. REFERENCES

Study group

Of a group of 77 children with at least one EEG with ESES during their follow-ups, 16 cases meeting the following criteria were selected for this study:

  • 1
    Having IPE according to the criteria proposed by the International League Against Epilepsy (ILAE) (5), including partial seizures, focal EEG abnormalities, normal background activity in the EEGs, normal premorbid psychomotor development and neurologic status, and normal cranial magnetic resonance imagings (MRI)s and laboratory data.
  • 2
    Having at least yearly clinical and EEG follow-up since the onset of epilepsy, and for ≥2 years after the onset of ESES in the EEGs.

ESES is described here as SW discharges occupying ≥85% of NREM sleep with symmetrical or mildly asymmetrical bilateral distribution (6).

Results of the study group were evaluated on the basis of three different stages during the course of the disease. Those stages were as follows.

  • 1
    Stage of IPE: Period from the first afebrile seizure to the onset of the pre-ESES stage.
  • 2
    Pre-ESES/ESES stage: ESES stage designates the time segment including the initial and the latest EEGs with ESES. A retrograde period of 6 months preceding the first EEG with ESES is called the pre-ESES stage.
  • 3
    ESES remission stage: This term is used for conditions in which two EEGs of a given patient with an ≥6-month interval are free of ESES.

Data belonging to each of those three periods were evaluated as epilepsy, cognitive/behavioral and EEG findings.

  • 1
    Epilepsy: During follow-up interviews once a month to once in 3 months, depending on the patient's characteristics, parental information including the seizure frequency, seizure types, and response to treatment were noted. The term epilepsy of remission was used for a seizure-free period of ≥1-year duration with or without antiepileptic drug (AED) treatment.
  • 2
    Cognitive and behavioral functions: No IQ tests were given to the patients during IPE stage; therefore our evaluations were based only on our observations and examinations during the interviews and information gained from the parents and the school records. During the ESES and ESES remission stages, Conner's Evaluation Scale was given to the parents and the teachers; for the patients, WISC-R and Bender Gestalt tests were given. Neurologic examinations and notes on behavioral parameters also were recorded by us during the follow-ups. Results <70 were considered to indicating low IQ in WISC-R test.
  • 3
    EEG: In total, 172 video-EEGs including at least one sleep–waking cycle were performed. All-night sleep EEGs were recorded when confirmation for remission of ESES was indicated. Apart from determining the SW index during NREM, presence or absence of epileptogenic foci, their locations and spreading characteristics, the presence of bilateral paroxysmal discharges, and all other apparently abnormal findings during waking and sleep were noted, and results were classified according to IPE, pre-ESES, ESES, and ESES remission stages.

The following terms were used to define the EEG parameters:

  • 1
    According to the localization and spreading of epileptogenic foci: Single epileptogenic focus (SEF): Unilateral SW activity with restricted localization. Bilateral synchronous epileptogenic foci (BSEF): Bilateral synchronous SW activity in analog regions. Bilateral asynchronous epileptogenic foci (BAEF): Bilateral asynchronous SW activity in analog or nonanalog regions. Multiple epileptogenic foci (MEF): SW activity with more than two independent localizations in a single hemisphere (unilateral multiple epileptogenic foci, UMEF) or both hemispheres (bilateral multiple epileptogenic foci, BMEF). Spreading focal epileptogenic discharges (SFEDs): Focal SW activity with a tendency to extend to adjacent regions and/or to the other hemisphere. Focal slowing: Focal continuous or paroxysmal activity in lower frequency than that in adjacent areas and analog regions of the other hemisphere.
  • 2
    According to the characteristics of ESES: Near-ESES: SW discharges occupying ≥50 to <85% of NREM sleep with symmetrical or mildly asymmetrical bilateral distribution. Hemi-ESES: ESES strictly limited to a single hemisphere. Asymmetric ESES: ESES predominant on one hemisphere with consistent interhemispheric voltage asymmetry (≥50%) in SW paroxysms.

Control group

A group of 25 patients fulfilling the following criteria was selected to compare the clinical and EEG variables with those of the study group during the IPE stage.

  • 1
    They were diagnosed as having IPE according to the criteria proposed by the ILAE (5).
  • 2
    They were being followed up clinically and with sleep EEG recordings with regular intervals on a once- or twice-yearly basis since the onset of the first afebrile seizure, by us.
  • 3
    They all were age 15 years or older, and they had no seizures, no EEG abnormalities, and no treatment for at least the last 2 years. This group was considered to be free of epilepsy.

Clinical data belonging of the control group were evaluated similarly. After examining 112 sleep and waking video-EEGs, at least a single EEG with maximal abnormal findings was selected for evaluation, for each individual, in the control group.

Statistics

The Mann–Whitney U and Student's t tests were used to compare the clinical and EEG results in the study group during the IPE stage with those of the controls.

RESULTS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONCLUSIONS
  7. REFERENCES

The age range of 16 patients (M/F: 10:6) in the study group was 7–17 years (mean, 11.3 ± 3.2 years), and their follow-up duration was 4–11 years (mean, 5.8 ± 2.1 years). Milestones in the clinical and EEG changes in relation to age are demonstrated in Table 1. The mean age at onset of seizures was 5.5 ± 2.7/7.3 ± 2.2 years for the patient versus control groups, a finding with statistical significance (p < 0.05). Age at the last seizure in the 13 patients in remission, however, showed a close similarity to the same measure in the control group (9.1 ± 3.1/9.1 ± 2.3 years), respectively.

Table 1. Ages at onset, remission, and durations of epilepsy and ESES
Pt. no.Age at last exam (yr)Age at seizure onset (yr)Age at last seizure (yr)Time since last seizure (yr)Age at onset of ESES (yr)Duration of ESESAge at remission of ESES (yr)Time lapse after ESES remittedr
(yr)(mo)(yr)(mo)
  1. Cont, continues; ESES, epilepsy with electrical status epilepticus during slow sleep.

 116812 4 10.5  1.5124
 2 9263  4.52  6.5  2.5
 3 7  2.5525352
 4  11.5  7.5Cont.9392
 511574  6.5674
 6  10.54 8.527  1.5  8.52
 7  9.546  3.56396
 8 93Cont.4  1.5  5.5  3.5
 911  3.5Cont.7Cont. 4 yr  
10 746156  5.5  1.5
1117  8.513 4136 13.5  3.5
1210  5.5827182
13  12.5  8.511   1.59  2.5 11.51
141612 14 2134 133
15106918191
1616513 312  1.5 13.5  2.5

IPE stage

Events in the antecedent

In the study group, previous head trauma was reported in seven (43.7%) of 16 patients; epilepsy was present in the family members of six (37.5%) patients, and four (25%) patients had febrile seizures during infancy. Five (31.2%) patients had neither of these events. Those with previous head trauma and epilepsy in the family members had a lower incidence in the control group, without statistical significance.

A. Epilepsy:Table 2 shows types of seizures and their frequencies in the study group. Only a single subject in the control group had seizures more than once in 2 months, whereas this ratio was 10 (62.5%) of 16 in patients with ESES. Except three cases with intermediate features, 16 (64%) subjects in the control group had had benign rolandic epilepsy, and six (24%) had been diagnosed as having Panayiotopoulos syndrome (7). Their seizure characteristics were readily available for syndromic classification.

Table 2. Seizure characteristics of patients during IPE stage
Pt. no.Seizure characteristics during IPE stageDur (min)Relat. to vigilance (during)Freq/ total no.Age (yr)
  1. Pts, patients; Dur, duration; Relat, relation; Freq, frequency; Sec. Gen., secondary generalization; aw, awakening; cont, continuous; IPE, idiopathic partial epilepsy.

 11 Left brachiofacial tonic contraction, drooling<2Sleep1–2/mo8
2 Confusional episode<1WakingSingle8
 21 Version of the head and eyes to right, followed by right-sided tonic–clonic seizure ± sec. gen.2–3Sleep1/1–3 mo2
2 Head dropsBriefWaking2–3 mo3
3 Episodic contraction of the legs leading to fallsBriefWaking3–4/day 6–8/day3
 31 Febrile and afebrile staring, bilateral eye-blinking, flexion of the arms, legs extended<10Sleep1/1–3 mo2
2 Tight closure of the jaws, teeth grinding, gazing to the parents, arms & legs extended, vibrating, anarthric, conscious<10On aw.2–3 mo Single5
 41 Staring, vomiting5Aw. from sleepSingle8
2 Staring, right hemitonic attack, Todd paralysis<10 Total 2/7 mo9
 5Staring, irregular breathing, arms in flexion, legs in extension, aware, anarthric. Postictal hypotonia5Aw. from sleepTotal 5/6 mo5
 6Version of the head and eyes to right, followed by right-sided tonic attack1–30Aw. from sleepTotal 3/9 mo4
 7Gazing upward, vomiting2Aw. from sleepTotal 5/2 yr4
 81 Clonic and/or tonic contraction of the mouth to leftBriefSleep or waking3–4/mo3
2 Erratic myocloniasBriefSleepQuasi-cont.3
 9Version of the head and eyes to right, Todd paralysis2–3SleepTotal 3/3 yr3
101 Staring, facial cyanosis, anarthria, vomiting; consciousness preserved<5Aw. from sleepSingle4
2 Clonic seizures (left arm/leg; left hemiclonic) ± sec. gen.1–5SleepA few/week4
111 Hypotonic, eyes deviated upward, anarthric2–3WakingSingle1,5 
2 Lapses in consciousnessBriefWakingA few/day5
3 Staring to upper right, expressing “weakness,” contraction of the mouth to right10WakingSingle8
4 Loss of postural tonus, anarthria, vomiting5WakingSingle9
12Partial tonic–versive seizures with alternating laterality<2Sleep1/wk-mo5
131 Hemifacial tonic–clonic<5Sleep or wakingMax 1/2days; min 1/2 mo8
2 Myoclonic jerksBriefSleepQuasi-cont.8
3 Lapses in consciousnessBriefAwakeSeveral/day8
14Version of the head and eyes to right, followed by right-sided clonic movements2sleepTotal 5/2 yr11 
151 Hearing sounds→asymmetric tonic posturing→sec.gen.∼1Sleep1/2 mo6
2 Lapses in consciousnessBriefWaking?6
161 Staring, weakness on the right leg2Aw. from sleepCluster: 2–3/wk with 2–3 mo interval5
2 Tonic brachiofacial1–2Aw. from sleep 12 

No prompt response to treatment was encountered in any patient during the IPE stage in the study group. In half of the patients, either no change in the seizure frequency occurred (two patients), or they increased in number (six patients). Polypharmacy for seizure control was needed in 12 (75%) patients in the study group versus 16% of the controls. This result yielded a high statistical significance (p < 0.0001). No increase in the seizure frequency was recorded throughout the clinical course in the control group.

B. Cognition and Behavior: As in the control group, no major alterations in cognitive or behavioral faculties were either reported by the parents or observed by us during the IPE stage in the study group.

C. EEG: Waking EEGs during the IPE stage in the patient group were evaluated on the basis of 15 patients. All waking EEGs of two (13.3%) patients in this group revealed normal findings. BSEF were predominant in the EEGs of six (40%) patients, SEF in four (26.6%), BAEF in one (6.6%), and BMEF in the remaining two (13.3%) patients. A finding with clinical yet not statistical significance was a twice as much incidence of SFED in patients (40%) versus controls (20%). EEGs during the NREM stage in the IPE period were available for 13 patients, and predominant findings were BSEF (46.1%), MEF (30.7%), and SEF (23%). A finding worth mentioning was the presence of continuous focal slowing during both waking and NREM, in the same region with the major interictal epileptogenic focus in four (30.7%) patients in the study group (Fig. 1), and in none of the controls. Finally, rare, bilateral, diffuse, brief, 2- to 3-Hz slow SW discharges during transition to sleep were seen in three (23%) patients and in one (4%) control subject (Table 3).

image

Figure 1. A: Right frontotemporal focal slowing and spike–wave discharges during waking, in idiopathic partial epilepsy stage. B: Same recording: Enhancement of spike–wave activity during non–rapid eye movement sleep (NREM). C: Diffuse and continuous spike–wave during NREM 6 months later (epilepsy with electrical status epilepticus during slow sleep stage).

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Table 3. EEG results during IPE stage
EEG parametersStudy group No./total patientsControl group No./total patientsp Valuea
  1. aMann–Whitney U test.

  2. EF, epileptogenic foci; SFED, spreading focal epileptogenic discharges; IPE, idiopathic partial epilepsy.

Waking (total)1525 
 Bilateral EF9/159/25>0.05
 SFED6/155/25>0.05
NREM (total)1325 
 Bilateral EF9/1311/25>0.05
 SFED5/136/25>0.05
Focal slowing (during waking and NREM)4/130/25>0.05

II. Pre-ESES/ESES Stage:

A. Epilepsy: This period was characterized by either an increase in the frequency of the original seizures or the appearance of new seizures in the vast majority (15 patients: 93.7%) of patients. In a single case, seizures stopped after the onset of ESES in the EEG. Increase in seizure frequency despite treatment took place in six (37.5%) cases, and new seizures were seen in 13 (81.2%). Four patients experienced both conditions. Seizures starting in the pre-ESES/ESES period were absences, myoclonic absences, head drops, and atonic seizures.

B. Cognitive and Behavioral Changes: Behavioral and psychological problems such as anxiety, depression, distractibility, hyperactivity, impulsivity, and easy frustration were either reported by the parents and/or detected in the psychometric testings. Such problems took place in 13 (81.2%) patients, and eight (50%) patients had predominantly cognitive and/or neurologic involvement related to speech and memory. Nocturnal enuresis was found in a single case during this period, and this symptom had a close relation with the fluctuations of ESES that lasted for 3 years in that child.

C. EEG:

Pre-ESES stage: EEG signs suggesting a change in the course of the condition were present in nine (56%) cases. Near-ESES was present in five (55.5%) cases. Focal slowing seen in the IPE stage of four cases was more prominent, and spikes on slow activity were more abundant in the pre-ESES period. Another case had multiple epileptogenic foci.

These clinical (epilepsy, cognition and behaviour, and EEG) changes in the pre-ESES and/or ESES periods are seen in Table 4. A change relating to at least one of those parameters was present in every patient; eight patients had changes relating to all three, six patients to two, and two patients, to a single parameter.

Table 4. Clinical and EEG changes in relation to the Pre-ESES/ESES stages
FeaturesNo. of pts.%
  1. ESES, epilepsy with electrical status epilepticus during slow sleep; CSWS, continuous spike–waves during slow-wave sleep.

1. Changes in seizure characteristics (no. = 16)1593.7
 Increase in seizure frequency 637.5
 Appearance of new types of seizures1381.2
2. Changes in cognition and behavior (no. = 16)1381.2
3. EEG changes: Pre-ESES stage, only (no. = 9) 666.6
 Appearance of near-CSWS 555.5
 Marked in focal slowing 444.4
 Increase in epileptogenic sites 111.1

ESES stage: Age range of the patients at the first time ESES was detected in the EEGs was 4.5–13 years (mean, 7.9 ± 2.9 years). In a total of 14 waking stages in those EEGs, SEF and BSEF were present in eight (57%) cases, and BAEF and MEF in six (43%) cases. Spreading of focal discharges to adjacent regions and/or to the other hemisphere was found in nine (64.2%) patients.

During the NREM stage, asymmetrical ESES was present in various EEGs of nine (56%) cases, and sleep spindles were clearly evident in all records in seven (43.7%) patients. A finding of considerable interest was intraindividual variability in the frequency of SW complexes. Nine patients had 1- to 2-Hz SW discharges in all of their NREMs with ESES, whereas a range in this parameter such as 1–3 Hz and 1–5 Hz was detected in five and two other patients, respectively. Both faster and slower SW complexes could be present in the same record of a given patient. They were infrequent and appeared mostly in clusters. No relation of this activity was seen with any particular drug. ESES in waking stage was seen in two patients.

III. ESES Remission Stage: Remission in ESES took place within 3 months to 3 years (mean, 14.2 ± 10.1 months) in 15 of 16 patients in the study group. Age range at the onset of remission was 5.5–13.5 years (mean, 9.1 ± 2.9 years).

A. Epilepsy: In 11 (73%) patients of 15 with remission in ESES, epileptic seizures ceased within the same 6-month segment with the remission in ESES. In nine cases of this group, seizure termination took place a few months earlier than ESES remission. Two patients had ongoing seizures in spite of the disappearance of ESES in their EEGs.

B. Cognition and behavior: In one of the patients with partial epilepsy, aphasia developed during the course of the ESES period and was diagnosed as LKS. He was still handicapped both in linguistic and behavioral faculties 1 year after the remission of ESES. Behavioral abnormalities remained resistant to all medical and behavioral treatments in another patient with CSWS syndrome until the last visit 7 months after the resolution of ESES in the EEG. Excellent recovery was attained in three patients with atypical benign childhood epilepsy after the remission of ESES in the EEG. The remaining nine patients performed better according to cognitive and/or behavioral tests and/or observations, but they had not achieved premorbid levels.

C. EEG: Major EEG findings after the resolution of ESES in 15 patients were presence of near-ESES (two patients), hemi-ESES (two patients) (Fig. 2), and bilateral SW discharges in NREM in addition to focal or multifocal activities. SW frequency might reach up to 6–8 Hz in four patients during that period (Fig. 3). NREM EEGs revealed normal findings in seven patients by 7–15 years (mean, 12.1 ± 3 years), SEF in four, and BSEF, BAEF, and hemi-ESES in single cases at the latest controls. A single case with LKS had ongoing ESES for 4 years, along with severe clinical symptoms.

image

Figure 2. Hemi–epilepsy with electrical status epilepticus during slow sleep (ESES) in non–rapid eye movement sleep, 6 months later than the last EEG with ESES.

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image

Figure 3. Clustering of 5- to 7-Hz spike–waves in non–rapid eye movement sleep during epilepsy with electrical status epilepticus during slow sleep remission stage.

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Medical treatment

During the initial IPE period, carbamazepine, valproate (VPA), phenobarbitone, vigabatrin, and phenytoin were the drugs used either alone or in combinations in 13, 10, four, one, and one patient, respectively. VPA (15 patients), ethosuximide (eight patients), and hydrocortisone (seven patients) were the major drugs used by us during our follow-up and at the time of clinical and EEG remissions. Data regarding the treatment issue are discussed in a separate report.

DISCUSSION

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONCLUSIONS
  7. REFERENCES

Starting with the introduction of the concept of continuous SW activity during NREM, in 1971 (6), growing interest in the nosology and syndrome-related characteristics of this phenomenon, its impact on neurologic and behavioral functions, and its pathophysiological aspects has been accumulated. The term ESES, used by Tassinari et al. (1), was proposed to be modified as CSWS in 1989 by the ILAE. The reason for the new proposal was that epilepsy is a clinical, not an electrographic, phenomenon, and that this activity is not always associated with epilepsy. However, although with some nuances, both terms are currently used. Leaving reserve for further nosologic considerations, the term ESES is used for only the EEG changes in this text. “ESES spectrum disorders” is used for all conditions associated with ESES in the EEG, including LKS. Although association of ESES with lesion-related epilepsies is a well-known condition (8), such cases were not included in this study because of the possibility that they might possess some varying individual characteristics in relation to the localizations and nature of the brain pathologies. Besides, the target of the study was the IPE stage; and the question was whether any signs suggesting a tendency to progress into an ESES spectrum disorder could exist early during their course. Some such changes, in fact, when compared with typical cases of IPE stage in the study, were present in the patient group. Those were a higher incidence in seizure frequency and in the variability of seizure types and resistance to a single AED (75%:16%, in the study/IPE groups). An EEG finding present in 25% of the patients but in none of the controls was a focal slowing in the EEG at the site of the predominant epileptogenic foci in both waking and NREM periods, starting from the very early stages of epilepsy. This finding was continuous rather than paroxysmal and could be easily misinterpreted as suggesting a destructive lesion rather than a functional change, especially in some epochs without any visible spikes interfering with the slow activity. Such a finding may be related to the severity and the stability of the neuronal firing, because it persisted in all the EEGs of those patients throughout the later stages of the disease and always in the same region as before. This slow activity served for the origin of bilateral discharges pertaining to the ESES stage (Fig. 1) later.

No significant relation between the bilaterality of epileptogenic foci and progression into ESES stage was found in this study. Those findings suggest that the possibility of an evolution into ESES may be considered in the IPE stage when a continuous slow-wave activity is present in the predominant epileptogenic locus in the EEG, when there are multiple seizure types, and when the seizures are resistant to conventional AEDs in patients with IPE.

Age at the onset of the first afebrile seizure in the study group was younger than the respective age in the controls (5.5 vs. 7.3 years), which was a finding with statistical significance.

Family history of epilepsy (including febrile seizures) was mentioned in ∼15% of patients with ESES (8). In our study, the patient population with epileptic members in the family was found to be ∼3 times higher in the study group (37.5%) than in the controls (12%). This difference may suggest an additional genetic tendency for evolution of ESES, in the setting of IPE, which is already known as a condition with genetic nature. No other family member with epilepsy, conversely, was diagnosed or suspected by us according to the patients' reports, to have any ESES spectrum disorder in our study group. This topic may require bigger patient populations.

Major head trauma in the history was remarkably high (43%) in the patient group. Only events with serious injury leading to necessity to be cared in emergency units but resulting in no clinical and radiologic abnormalities were included in this parameter. This surprisingly high incidence in the patient group may lead to questioning a past cranial trauma as a predisposing factor for ESES, in patients with IPE.

EEG changes starting from the IPE stage throughout evolution into the ESES stage very likely takes some time, possibly with interindividual variances. Precise duration of this process is almost always impossible to determine in a given patient, unless found at the time of routine follow-up recordings. The inclusion of an arbitrary period of 6 months as the pre-ESES stage was decided on the basis of such a necessity in this study. This stage was the time in the middle of two consecutive EEGs (because patients with IPE have sleep-waking EEGs taken at least once a year in our routine) when the latest EEG showed ESES and the previous one had findings typical for the IPE stage. Changes in seizure characteristics were the most consistent clinical stigmata during pre-ESES or at the onset of ESES stages, with an incidence of 93.5%. Increase in seizure frequency and addition of new seizures types at the time of ESES in epilepsy patients have been reported previously (9). New types of seizures developed in 13 (81.3%) patients in our study group, and six (38%) had an increase in the preexisting partial seizures. Seizures associated with ESES have been documented as absences, absence status, head drops, and falling attacks (8). Other paroxysmal phenomena less frequently seen were negative myoclonias (8,10), tonic contraction of facial muscles, myoclonic absences, epileptic spasms, and generalized convulsions (8,11). Tonic seizures were reported to be absent in those patients (8,12). ESES-associated seizures in our patient group were absences, head drops, drop attacks, rare myoclonic absences, facial myoclonias, or partial versive–tonic seizures during sleep and leading to awakening sometimes, and also an increase in the tendency for secondary generalization of the rolandic type of partial seizures.

A benign course and good response to treatment in seizures in ESES spectrum disorders have been reported previously (13). Independent of the severity of epilepsy, seizures are known to disappear by the termination of ESES (8). A benign course of epilepsy was a similar finding in our study, and the seizures disappeared almost at the same age as in the control subjects with IPE, only. The concordance rate for the remission of epilepsy and ESES in the EEG was also very high (84.6%), and in the majority of this group, seizures disappeared some months earlier. Epilepsy was active during the latest control in only two cases, and ESES was not totally abolished, but transformed to hemi-ESES in one.

Behavioral and/or cognitive involvement also was prominent (81.2%), but a less frequently complained of phenomenon than seizures, during the stages of pre-ESES and ESES in our patient group. As the feature with most serious consequences in the ESES spectrum disorders, it is reported to exist in varying degrees in nearly all cases (8,14–17). It may have a prompt onset in rare conditions, but a progressive course is the usual fashion. Very rarely, it may precede epilepsy. Mild to severe disturbances in cognitive and/or behavioral performances such as deterioration in language, temporospatial disorientation, distractibility, hyperactivity, aggressiveness, impulsivity, reduced attention span, and communication problems, rarely up to the degree of psychotic features, may be encountered (18,19). Major complaints pertaining to 10 (62.5%) patients in our study were speech problems (primarily, a decrease in the speed and fluency of the spoken language), hyperactivity, attention deficit, easy frustration, emotional outbursts, and a decline in memory and in school performance. A single patient had nocturnal enuresis by the onset of ESES, and this symptom showed a direct relation with the fluctuations of ESES in her EEGs. Severe cognitive decline was persistent in three cases. The single patient with LKS was resistant to treatment with major AEDs in various combinations and hydrocortisone. At his latest control, epilepsy and ESES in his EEG were present for 11.5 and 4 years, respectively. The remaining two patients had low IQ scores after 7 and 12 months, each, later than their last EEGs, which were free of ESES. Cognitive and neuropsychological impairments are known to contribute to ESES spectrum disorders as the most resistant feature to treatment (13). Therefore the significance of ESES in the EEG, which is always an age-limited phenomenon, is solely related to the cognitive and behavioral consequences that may lead to permanent deficits. Mental deterioration has been related to the duration of ESES in previous reports. A long-duration (>2 years) of ESES was found to be the major factor predicting a bad prognosis in cognitive and behavioral modalities (20,21). However, two of three cases with severe cognitive impairment in our study had ESES with durations of 4 months and 1 year. Conversely, two other patients with ESES with 2 and 3 years' duration had no more major cognitive or behavioral problems at the ESES remission period. This discrepancy suggests the possibility that variables other than the duration of ESES also may be responsible for the long-term cognitive consequences, at least in some cases.

EEG as a parameter signaling the development of ESES was in the third level after seizures and cognitive and behavioral changes. To our knowledge, EEG changes in the IPE stage suggesting an evolution into ESES have not been discussed before. Among nine patients with EEG recordings during the pre-ESES period, five (55.6%) showed abnormalities suggesting a progression into ESES. They all had secondary bilateralization of the previously focal epileptogenic activity. This picture was called near-ESES if the bilateral discharges covered ≥50% of NREM stage. Asymmetry in bilateral discharges of near-ESES was much more prominent than in those of ESES. The pre-ESES stage, in our opinion, may be a critical time to decide on more efficient treatment procedures to prevent possible future consequences of ESES. Similar suggestions regarding early interventions before the development of full SW index (i.e., 85%) have been proposed previously by others (4,22,23). The question whether a SW index of 85%/NREM be needed to recognize a condition as ESES may be subject to further considerations. Presently, it seems that when some clinical and/or EEG features in children with partial epilepsies predict a development toward ESES, early measures may provide more benefit than may vigorous treatment strategies after months or years of surviving ESES. Our observations on some newer patients not included in this study suggest that they are more responsive to modifications in the AED regimens during the pre-ESES period than in the ESES stage, the time when corticosteroids are frequently needed.

CONCLUSIONS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONCLUSIONS
  7. REFERENCES

The present data suggest that some premonitory clinical and EEG evidence of an evolution into ESES spectrum disorders may be useful in many patients before the fully established ESES (i.e., ≥85% of NREM) in the EEG develops. Neuropsychological abnormalities associated with <85% SW index have been reported before (8,11,16). Premonitory clinical symptoms in our patients before the ESES stage were an increase in the frequency and variability of existing seizures, addition of new seizures, and appearance of cognitive and/or behavioral changes. EEG features indicating a progression into ESES were the presence of continuous slowing in the main epileptogenic site and a tendency of the focal discharges to extend to adjacent areas, especially to the other hemisphere. The presence of one or more of these changes may serve as a predictor of a developing ESES and may provide the means for an earlier prevention of future consequences that may be irreversible, if persisting until later.

REFERENCES

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONCLUSIONS
  7. REFERENCES
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