Epilepsy with Electrical Status Epilepticus During Slow Sleep and Secondary Bilateral Synchrony

Summary: In 3 children with "epilepsy with electrical status epilepticus during slow sleep" (ESES), we estimated interhemispheric small time differences (TDs) during spike-wave activity in EEG by coherence and phase analysis by the two-dimensional autoregressive model to differentiate their continuous diffuse spike-waves during slow-wave sleep (CSWS) between primary bilateral synchrony and secondary bilateral synchrony (SBS). Maximal TDs at onset of apparently bilateral synchronous spike-wave bursts (BSSWs) during slow-wave sleep were 12·0–26·5 ms (mean 20·3 ms) with consistent leading hemispheres in eight bursts of the 3 patients, indicating SBS as pathophysiology of their CSWS. This suggestion was supported by their clinico-EEG findings, including the effect of a single oral dose of clobazam (CLB) on EEG. Three ictal BSSWs of atypical absence seizures in 2 patients were also analyzed to obtain maximal TDs of 17·9–41·7 ms (mean 26·3 ms) at onset, with the same leading sides as in sleep, also indicating SBS. Examination of intraburst TD variations showed no consistent disappearance of TDs during the latter part of the bursts, in either sleep or the ictal EEGs of atypical absences, and a role of the corpus callosum was suggested in the generation of SBS in ESES.     

Medical Management With Diazepam for Electrical Status Epilepticus During Slow Wave Sleep in Children

ObjectiveOral diazepam, administered in varying doses, is among the few proposed treatment options for electrical status epilepticus during slow wave sleep in children. We sought to retrospectively evaluate the long-term efficacy of high-dose oral diazepam in reducing electrographic and clinical evidence of electrical status epilepticus during slow wave sleep in children. Additionally, we surveyed caregivers to assess safety and behavioral outcomes related to ongoing therapy.MethodsWe collected demographic and clinical data on children treated for electrical status epilepticus during slow wave sleep between October 2010 and March 2013. We sought to identify the number of patients who achieved at least a 50% reduction in spike wave index on electroencephalograph after receiving high-dose oral diazepam. We also administered a questionnaire to caregivers to assess for behavioral problems and side effects.ResultsWe identified 42 evaluable patients who received high-dose diazepam (range 0.23-2.02 mg/kg per day) to treat electrical status epilepticus during slow wave sleep. Twenty-six patients had spike reduction data and 18/26 (69.2%) children achieved a greater than 50% reduction in spike wave count from an average of 15.54 to 5.05 (P = 0.001). We received 28 responses to the questionnaire. Some patients experienced new onset of difficulties with problem-solving and speech and writing development. Sleep disturbances (50%) and irritability (57.1%) were the most frequent side effects reported. There did not appear to be a dose-related effect with electroencephalograph changes, behavioral effects, or side effects.ConclusionsHigh-dose oral diazepam significantly reduces the spike wave count on electroencephalograph in children with electrical status epilepticus during slow wave sleep. Although this therapy improves electroencephalograph-related findings, it can be associated with concerning neurological and behavioral side effects in some individuals, so further study is warranted.     

Syndrome of Electrical Status Epilepticus During Sleep: Epileptic Encephalopathy Related to Brain Development

BackgroundEpileptic encephalopathy with electrical status epilepticus during sleep is an age-related and self-limited disorder. The present study analyzed the etiology, demographics, and pathogenesis of patients with electrical status epilepticus during sleep to provide information on the diagnosis and therapy of this syndrome.MethodsThe etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in patients admitted in Chinese People's Liberation Army General Hospital from 2009 to 2014 were retrospectively analyzed. Patients were classified into the genetic, structural-metabolic, and unknown groups according to the etiology. Demographics and clinical characteristics of all the patients were then analyzed and compared among groups.ResultsThe etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in 75 patients mainly included benign childhood epilepsy with centrotemporal spikes, Landau-Kleffner syndrome, polymicrogyria, and migration disorders. Age at onset of epilepsy did not show a specific pattern, but age at onset of epileptic encephalopathy with electrical status epilepticus during sleep was concentrated at age 6-9 years. The mean age at onset of epilepsy in the genetic group was significantly older than that in the structural-metabolic group (P < 0.05). Age at onset of epileptic encephalopathy with electrical status epilepticus during sleep did not significantly differ between the two groups.ConclusionsElectrical status epilepticus during sleep is an epileptic encephalopathy related to brain development and presents an age-dependent occurrence.     

Efficacy of Levetiracetam in Electrical Status Epilepticus During Sleep of Children: A Multicenter Experience

BackgroundElectrical status epilepticus during sleep is characterized by epilepsy, a specific electroencephalographic pattern, and neuropsychological impairment. This study aims to evaluate the efficacy and safety of levetiracetam in treating children with electrical status epilepticus during sleep.MethodsA multicenter, retrospective, open-label study enrolled 73 children (mean age: 8 years) affected by electrical status epilepticus during sleep. The efficacy was rated according to the seizure frequency and electroencephalography response.ResultsAfter a mean treatment period of 19 months (range: 6 to 24 months), 33 (63.5%) of 52 patients became seizure-free or had experienced remarkable reduction in seizures. The electrical status epilepticus of 41 (56.2%) of 73 patients disappeared off their electroencephalography. The electroencephalography efficacy of levetiracetam treatment was noted in the monotherapy (61.9%) and add-on (53.9%) groups. The clinical (67.7%) and electroencephalography (64.3%) response rates of the idiopathic group were better than those of the symptomatic group (57.1% and 45.2%, respectively). No patient discontinued the trial because of intolerability of side effects.ConclusionsLevetiracetam is effective in individuals with electrical status epilepticus during sleep with tolerable side effects.     

Focal Status Epilepticus: Clinical Features and Significance of Different EEG Patterns

PURPOSE: Focal status epilepticus is typically diagnosed by the observation of continuous jerking motor activity, but many other manifestations have been described. EEG evidence of focal status may take several forms, and their interpretation is controversial. We detailed the clinical spectrum of focal status in patients diagnosed by both clinical deficit and EEG criteria and contrasted clinical manifestations in patients with different EEG patterns. METHODS: Patients were diagnosed with a neurologic deficit and discrete recurrent focal electrographic seizures or rapid, continuous focal epileptiform discharges on EEG. Clinical findings were determined by chart review. RESULTS: Of 41 patients with focal status, acute vascular disease was the cause in 21; 10 of 41 had exacerbations of prior epilepsy. A variety of clinical seizure types occurred, both before and after the EEG diagnosis, but the diagnosis was not expected in 28 patients before the EEG. Three had no obvious clinical seizures. Focal motor seizures and an abnormal mental status were the most common manifestations at the time of the EEG. With antiepileptic drugs, almost all had control of clinical seizures, and most improved in mental status. Patients with rapid continuous focal epileptiform discharges were nearly identical in presentation, likelihood of diagnosis, subsequent seizures, response to medication, and outcome to those with discrete seizures on EEG. CONCLUSIONS: Focal status epilepticus may be seen with a wide variety of clinical seizure types or without obvious clinical seizures. The diagnosis is often delayed or missed and should be considered after strokes or clinical seizures when patients do not stabilize or improve as expected. The diagnosis should be made equally whether patients have discrete electrographic seizures or continuous rapid focal epileptiform discharges on the EEG, and the same response to medications and outcome should be anticipated for the two groups.     

A novel de novo TET3 loss-of-function variant in a Turkish boy presenting with neurodevelopmental delay and electrical status epilepticus during slow-wave sleep

BackgroundBeck-Fahrner syndrome is caused by homozygous or heterozygous mutations in TET3 on chromosome 2p13. The general characteristics of this syndrome include behavioral abnormalities such as autistic features, attention-deficit hyperactivity disorder, learning disabilities, and epilepsy.Case presentationSix years old male patient was found to have a de novo TET3 loss-of-function variant by whole-exome sequencing (WES) analysis and was diagnosed with electrical status epilepticus during slow-wave sleep (ESES) based on clinical and electroencephalogram (EEG) characteristics. The patient had a neurodevelopmental delay from the age of 3 months and started experiencing generalized tonic–clonic seizures and regression at the age of 5 years. EEG findings were consistent with ESES, and WES analysis revealed a novel heterozygous nonsense NM_001366022.1:c.1594C > T (p.Arg532*) variant in TET3. Valproic acid and immunotherapy were administered for the first 6 months, and clobazam was administered orally in addition to oral valproic acid therapy for the next 6 months. Clinical improvement was noted regardless of EEG improvement for the first 6 months. EEG improvement was achieved with clobazam. No regression was observed following the discontinuation of immunotherapy.ConclusionDecreased TET3 enzyme activity may be one of the new genetic etiologies of ESES.     

Measuring spike strength in patients with continuous spikes and waves during sleep: Comparison of methods for prospective use as a clinical index

ObjectiveTo compare methods of estimating spike strength as a potential index in the assessment of continuous spikes and waves during sleep (CSWS).MethodsSpikes were searched and averaged automatically from pre- and postoperative EEGs of ten patients with CSWS who underwent corpus callosotomy (eight) or resective epilepsy surgery (two). From the most prominent spike, we measured peak amplitude and root mean square (RMS) over ±150 ms window around the peak. In order to compensate for spatiotemporal instability of spikes, the cumulative amplitude and RMS were computed from the highest quartile of electrodes (Ampl-Q and RMS-Q, respectively). The stability of parameters was studied by comparing two ten minute epochs during the first hour of NREM sleep, as well as by analyzing overnight variation of indices in further ten patients with CSWS. The Ampl-Q and RMS-Q were compared between pre- and postoperative recordings.ResultsAll four measures, amplitude, RMS, Ampl-Q and RMS-Q, were correlated with each other and highly dependent on NREM/REM-sleep stage and arousals. Expectedly, Ampl-Q and RMS-Q had the greatest intra-individual stability. The amplitude had up to 71% intra-individual variation making it unhelpful for clinical use. Ampl-Q and RMS-Q were comparable in assessing change following surgical treatment.ConclusionsComputing an integrated RMS over multiple electrodes during steady NREM sleep offers a stable and reliable parameter for evaluating the strength of spikes in CSWS.SignificanceAnalyzing spike strength with RMS-Q may offer a clinically useful, supplementary index for EEG monitoring of CSWS where spike index has been of limited value.     

In Nonconvulsive Status Epilepticus (NCSE), Treat to Burst-Suppression: Pro and Con

Summary:  When refractory NCSE is combined with acute brain injury, it produces synergistically compounded brain damage that is time dependent. Treating to EEG burst-suppression is the most rapid and effective method for stopping NCSE. The risks of burst-suppression are common to many intensive care interventions and can be minimized with expert management.     

Epileptic encephalopathy with continuous spikes and waves during sleep in children with shunted hydrocephalus: a study of nine cases

Purpose: We present a series of nine patients with early‐onset hydrocephalus who had seizures and continuous spikes and waves during slow sleep (CSWS) associated with neurocognitive and motor deterioration. Methods: Six boys and three girls aged 9–16 years (mean 11.3 years) were studied. [Correction added after online publication 12‐Apr‐2008: Number of girls and boys has been updated.] All patients underwent clinical examinations, electroencephalographic evaluations, neuroradiological imaging and neuropsychological assessment at first examination. Antiepileptic drugs (AEDs) were given in all cases and changed according to clinical and EEG evolution. Results: Onset of epilepsy occurred from age 8 to 60 months (mean 19.6 months and median 14 months) with focal seizures with or without secondary generalized tonic–clonic seizures. Between ages 6 and 13 years (mean 10.4 years and median 8 years), hyperkinesia, aggressiveness, and poor socialization appeared in all nine cases. Reduced attention span, deterioration of language, and temporospatial disorientation were found in three of them. Negative myoclonus was found in two patients. The EEG showed CSWS. Response to change in treatment was good in all patients. None of the patients had relapses, seven of them have remained seizure free, and two continued having sporadic focal motor seizures during 2–5 years (mean 3 years) of follow‐up. Conclusion: In children with early‐onset hydrocephalus, particularly with behavioral and language disturbances and/or motor deterioration, CSWS should be considered. Periodic EEG recordings during sleep should be done in these children. The early identification of this particular electroclinical picture is crucial to start adequate treatment to avoid progressive cognitive deterioration.     

Non-linear EEG analysis in children with epilepsy and electrical status epilepticus during slow-wave sleep (ESES)

OBJECTIVE: The objective of this work was to study the non-linear aspects of electroencephalography (EEG) in children with epilepsy and electrical status epilepticus during slow-wave sleep (ESES). METHODS: In this study, we recorded the sleep EEG in 5 subjects with ESES (4 males and one female, aged 6.5-10 years) who were also mentally retarded and affected by cerebral palsy (3 subjects) and hydrocephalus (two subjects). The signals were sampled at 128Hz and stored on hard disk. All the subsequent computational steps were performed on EEG epochs (4096 data points) selected from wakefulness and non-rapid eye movement (non-REM) (with ESES) or REM sleep. The dynamic properties of the EEG were assessed by means of the non-linear cross prediction (NLCP) test which uses 3 different 'model' time series in order to predict non-linearly the original data set (Pred, Ama and Tir). Pred is a measure of the predictability of the time series and Ama and Tir are measures of asymmetry, indicating non-linear structure. Moreover, the correlation dimension (D2) was estimated by means of the algorithm by for the epochs showing non-linear nature. RESULTS: The NLCP test provided evidence of significant non-linear dynamics in all epochs of non-REM sleep, when ESES was evident. Only during this stage, the possible presence of low-dimensional chaos could also be suspected (average D2=4.02; range 3.16-6.21). EEG without ESES could not be distinguished from linearly filtered noise. CONCLUSIONS: The results of the present study seem to indicate that subjects with ESES show a profound modification of their EEG dynamics with the occurrence, during sleep, of long periods characterized by non-linear dynamics and, probably, low-dimensional chaotic structure able to modify in a substantial way their brain functioning during sleep.     

Atypical language impairment in two siblings: relationship with electrical status epilepticus during slow wave sleep

We report the case of a young girl who presented severe learning disabilities in oral and written language related to a continuous spike-waves during slow sleep (CSWS) syndrome. A sleep EEG recording obtained in her younger brother, who presented a clinical pattern suggesting developmental dysphasia, also showed a CSWS syndrome. These two clinical cases underscore the need to look for this syndrome in the siblings of an affected child when learning difficulties appear in a child who previously had normal psychomotor development.     

Levetiracetam efficacy in epileptic syndromes with continuous spikes and waves during slow sleep: experience in 12 cases

PURPOSE: To assess the add-on efficacy of levetiracetam on the EEG, behavior, and cognition of children with continuous spikes and waves during slow sleep (CSWS). METHODS: Charts of children with behavioral and/or cognitive deterioration associated with CSWS who received levetiracetam at 50 mg/kg/day as add-on treatment were retrospectively reviewed. Awake and sleep EEG recordings and detailed neuropsychological and behavioral assessments were available at baseline and 2 months after levetiracetam initiation. In children showing clinical and/or electrophysiological improvement after 2 months, levetiracetam was continued with a new evaluation at 1 year. RESULTS: Twelve patients were included (9 cryptogenic and 3 symptomatic cases). Seven patients (58.3%) showed improvement of EEG record. Among these seven patients, neuropsychological evaluation was improved in three, and in the other four patients, not testable because of severe cognitive impairment, behavior was improved. Two patients improved in neuropsychological evaluation despite the lack of EEG improvement. Eight patients (66.6%) continued levetiracetam treatment after 2 months. After 1 year, four patients were still on levetiracetam, two because sustained effect on EEG and behavior and the two others because improvement in neuropsychological testing despite unchanged EEG. Levetiracetam was discontinued in the other four patients because of neuropsychological or behavioral deterioration associated with CSWS pattern, between 9 and 11 months after treatment initiation. CONCLUSIONS: This retrospective study suggests that levetiracetam has a positive effect on the EEG, the behavior, and the cognition of patients with epilepsy and CSWS. Additional studies are warranted in order to assess the place of this drug in these epileptic conditions.