Misleading effects of clonazepam in symptomatic electrical status epilepticus during sleep syndrome

Electrical status epilepticus during sleep syndrome and its variants are age-dependent epileptic encephalopathies associated with a sleep-related electroencephalographic pattern of continuous spike-waves, combined with motor or cognitive impairment. These epileptic encephalopathies are usually not responsive to conventional antiepileptic drugs. This report describes two children in whom clonazepam had no effect on cognitive and motor disorders but controlled spike activity, preventing a proper diagnosis. Withdrawal of clonazepam was accompanied by the recurrence of continuous spike-waves in slow sleep, permitting the diagnosis of electrical status epilepticus during sleep syndrome and appropriate therapeutic decisions. These two cases of the misleading effect of clonazepam in electrical status epilepticus during sleep syndrome illustrate the puzzling situation that can occur when therapeutic options only consider the electroencephalographic features without prior syndromic diagnosis.     

Epileptic Encephalopathy with Continuous Spikes and Waves During Sleep

Epileptic encephalopathy with continuous spikes and waves during slow sleep (EECSWSS) is an age-related childhood condition characterized by epilepsy, cognitive or behavioral impairment, and electroencephalographic abnormality of continuous spike–wave discharges during slow sleep. Continuous spikes and waves during slow sleep (or electrical status epilepticus during sleep) is an electrographic pattern characterized by nearly continuous spike–wave discharges during non-REM sleep, with a frequency of 1.5–3 Hz and usually diffuse and bilateral in distribution. Most authors consider EECSWSS as wide spectrum of epileptic conditions of different origin associated with heterogeneous clinical manifestations and neuropsychological impairment of different severity in close temporal concordance with the appearance of the electroencephalographic pattern of electrical status epilepticus during sleep. The long-term prognosis of this condition is overall poor owing to the persistence of neuropsychological impairment. Therefore, early recognition and effective therapy are necessary to improve long-term prognosis.     

Epilepsy with Continuous Spike-Waves During Slow Sleep and Its Treatment

Five children with epilepsy with "continuous spike-waves during slow sleep" (CSWS) are reported. The main clinical features of CSWS include (a) onset between 5 and 7 years of age, (b) the occurrence of several types of seizure (i.e., partial motor, generalized motor, and atypical absence), and (c) the presence of language disturbances and abnormal behavior based on emotional impairment. The EEG findings were characterized by sleep tracings showing almost continuous (greater than 95%), diffuse slow spike and wave activity. After treatment with valproate (VPA) (or ethosuximide, ESM) and clonazepam (CZP), the spike and wave complex status disappeared. Symptoms and signs of the CSWS also decreased. We suggest that combined treatment is an appropriate treatment for CSWS.     

Acquired epileptic frontal syndrome as long-term outcome in two children with CSWS

Continuous spikes and waves during slow sleep (CSWS) are a well-known EEG pattern that can be associated with cognitive and behavioural deterioration. We present the long-term clinical, neuropsychological and EEG follow-up of two patients who developed CSWS during childhood. In both the CSWS onset was followed immediately by rapid cognitive and behavioural deterioration. Later the CSWS fragmented or fluctuated and the spike-wave discharges diminished and this was associated with progressive clinical improvement. At the same time bilateral frontal EEG abnormalities appeared awake and in sleep. After the initial period of rapid cognitive and linguistic improvement both patients stabilised. The latest neuropsychological assessment showed a frontal syndrome. The presence of frontal EEG abnormalities superimposed on CSWS, their persistence after CSWS resolution and, in addition, the finding of subtle frontal-type neuropsychological alterations early in recovery may indicate poor long-term outcome.     

Neuropsychological Findings in Rolandic Epilepsy and Landau-Kleffner Syndrome

Summary:  In an attempt to correlate neuropsychological deficits and various neurophysiological aspects of focal epileptic activity in benign childhood epilepsy, we have reviewed the findings of a longitudinal group study of benign childhood epilepsy with centrotemporal spikes (BCECTS) and several case studies of continuous spike-waves during slow sleep syndrome (CSWS). We first distinguish the temporary neuropsychological impairments often observed in the natural history of BCECTS from the more long-lasting and more specific neuropsychological deficits associated with CSWS, of which the Landau-Kleffner syndrome (LKS) is the most studied clinical form. A series of metabolic findings from ¹⁸FDG-PET studies in BCECTS and CSWS children have shown that specific cognitive impairment is related to increased glucose uptake in cortical areas restricted to the associative cortex coincident with the focus of spike-wave discharges. From recent functional neuroimaging data of three patients recovered from LKS, we address the issue of the pathophysiology of cognitive impairment persisting after complete recovery of epilepsy. Finally, we discuss the reliability of the study of mismatch negativity to address the issue of the early effect of interictal discharges in typical and atypical BCECTS on the auditory cortex and the development of speech processing essential to verbal learning.     

Epilepsy and sleep: with special reference to nonconvulsive status epilepticus with continuous diffuse spike-waves during slow-wave sleep

There are numerous important problems concerning relationship between epilepsy and sleep. To clarify the clinical significance and pathophysiology of the nonconvulsive status epilepticus with continuous diffuse spike-waves during slow-wave sleep (CSWS) in EEG, this study was carried out on seven cases each of epilepsies with electrical status epilepticus during slow sleep (ESES) and with peculiar type of nonconvulsive status epilepticus in childhood (PNSE) and four cases of atypical benign partial epilepsy (ABPE). Mental deterioration was most frequently observed in ESES, less in PNSE but none in ABPE. In both ESES and PNSE, mentally deteriorated cases showed suppression of CSWS at significantly later ages than those without deterioration. And spike-wave indices during slow-wave sleep, which were the highest in ESES and lower in PNSE and ABPE, also had a strong relation to mental deterioration. In these three disorders, both clinical seizures and CSWS were suppressed at or before 16 years of age, although they were intractable before adolescence. This finding indicated age dependent evolutions of the three disorders. Coherence and phase analysis of CSWS was undertaken to differentiate primary and secondary bilateral synchrony in seven cases of these three disorders, which have both features of generalized and partial epilepsies. This analysis disclosed secondary bilateral synchrony as the nature of CSWS in six cases. And this analysis method was considered to provide a clue to their pathophysiology. Thus, in these disorders, importance of early diagnosis by EEG including deep sleep and early treatment was recognized.     

A review of the relationships between Landau-Kleffner syndrome, electrical status epilepticus during sleep, and continuous spike-waves during sleep

The goal of this report is to review the relationships between Landau-Kleffner syndrome (LKS), electrical status epilepticus during sleep (ESES), and continuous spike-waves during sleep (CSWS). LKS is a clinical syndrome involving mainly acquired aphasia and sometimes seizures. Other clinical findings include cognitive impairments and global regression of behavior. The EEG may evolve from more benign conditions into ESES (or CSWS), seen in 50% of patients with LKS, or may also show focal findings. Seizures include atypical absence, generalized tonic-clonic, atonic, and partial motor attacks. Effective medications are discussed. The EEG patterns CSWS and ESES are likely equivalent terms. CSWS is used by some authors, and ESES by others. Patients with these patterns usually show mental retardation, seizures, and global regression. More benign EEG patterns, like focal discharges, may develop into these more severe generalized patterns, which are associated with atypical absences, negative myoclonus, and cognitive disturbances. Memory disorders are common, because the nearly continuous generalized discharges in sleep do not allow for the memory consolidation that also occurs during sleep. Medications and possible etiologies are discussed.     

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.     

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.     

CSWS-related autistic regression versus autistic regression without CSWS

Continuous spike-waves during slow-wave sleep (CSWS) and Landau-Kleffner syndrome (LKS) are two clinical epileptic syndromes that are associated with the electroencephalography (EEG) pattern of electrical status epilepticus during slow wave sleep (ESES). Autistic regression occurs in approximately 30% of children with autism and is associated with an epileptiform EEG in approximately 20%. The behavioral phenotypes of CSWS, LKS, and autistic regression overlap. However, the differences in age of regression, degree and type of regression, and frequency of epilepsy and EEG abnormalities suggest that these are distinct phenotypes. CSWS with autistic regression is rare, as is autistic regression associated with ESES. The pathophysiology and as such the treatment implications for children with CSWS and autistic regression are distinct from those with autistic regression without CSWS.     

Acquired epileptiform opercular syndrome: a case report and results of single photon emission computed tomography and computer-assisted electroencephalographic analysis

We report here a girl aged 5 years 3 months with cryptogenic localization-related epilepsy who showed a prolonged episode characterized by dysarthria, dysphagia, drooling and paresis of the right arm associated with almost continuous diffuse sharp-slow wave complexes during sleep. These symptoms were not directly related to seizures or to each sharp-slow wave complex revealed by examination during the video electroencephalographic (EEG) recording. The interictal single photon emission compute tomography showed a localized high perfusion area in the left posterior frontal region. The introduction of clonazepam completely controlled the clinical symptoms as well as the EEG abnormality within 2 weeks. After 4 months of remission, a similar episode recurred which was associated with aggravation of EEG. The clinical and EEG characteristics of this patient were identical to those of acquired epileptiform opercular syndrome (AEOS), a newly proposed epileptic syndrome, in which a transient operculum syndrome develops in association with continuous spike-and-wave activity during slow sleep (CSWS). Computer-assisted EEG analysis demonstrated that the epileptic EEG focus was located in the left sylvian fissure, and produced secondary bilateral synchronous sharp-slow complexes. The present study further supports the hypothesis that the electrical interference by CSWS creates bilateral opercular dysfunction through the mechanism of secondary bilateral synchrony, thus producing AEOS.     

Outcome at adulthood of the continuous spike-waves during slow sleep and Landau-Kleffner syndromes

PURPOSE: The aim of this study was to determine the clinical, social, and/or professional and cognitive outcomes in adulthood of the continuous spike-waves during slow sleep (CSWS) and Landau-Kleffner syndromes, which are two rare epileptic syndromes occurring in children. METHODS: We enrolled seven young adults, five who had a CSWS syndrome, and two, a Landau-Kleffner syndrome in childhood. We evaluated their intellectual level as well as their oral and written language and executive functions. RESULTS: This study confirmed that the epilepsy associated with these syndromes has a good prognosis. Only one patient still had active epilepsy. However, the neuropsychological disorders particular to each syndrome persisted. Only two patients had followed a normal pathway in school. Three of the five patients with a CSWS syndrome during childhood remained globally and nonselectively mentally deficient. We found no evidence of the persistence of a dysexecutive syndrome in this study group. The intellectual functions of the two patients with Landau-Kleffner syndrome were normal; however, their everyday lives were disrupted by severe, disabling language disturbances. We discuss the role of some prognostic factors such as the location of the interictal electric focus and the age at onset of CSWS. CONCLUSIONS: These two epileptic syndromes of childhood are very similar in many respects, but their clinical outcomes in adulthood are different.     

The epileptic syndromes with continuous spikes and waves during slow sleep: definition and management guidelines

The authors propose to define the epileptic syndromes with continuous spikes and waves during slow sleep (CSWS) as a cognitive or behavioral impairment acquired during childhood, associated with a strong activation of the interictal epileptiform discharges during NREM sleep--whatever focal or generalized--and not related to another factor than the presence of CSWS. The type of syndrome will be defined according to the neurological and neuropsychological deficit. These syndromes have to be classified among the localization-related epileptic syndromes. Some cases are idiopathic and others are symptomatic. Guidelines for work-up and treatment are proposed.     

Neurobehavioral consequences of continuous spike and waves during slow sleep (CSWS) in a pediatric population: A pattern of developmental hindrance

IntroductionContinuous spike and waves during slow sleep (CSWS) is a typical EEG pattern defined as diffuse, bilateral and recently also unilateral or focal localization spike–wave occurring in slow sleep or non-rapid eye movement sleep. Literature results so far point out a progressive deterioration and decline of intellectual functioning in CSWS patients, i.e. a loss of previously normally acquired skills, as well as persistent neurobehavioral disorders, beyond seizure and EEG control. The objective of this study was to shed light on the neurobehavioral impact of CSWS and to identify the potential clinical risk factors for development.MethodsWe conducted a retrospective study involving a series of 16 CSWS idiopathic patients age 3–16 years, considering the entire duration of epilepsy from the onset to the outcome, i.e. remission of CSWS pattern. All patients were longitudinally assessed taking into account clinical (sex, age at onset, lateralization and localization of epileptiform abnormalities, spike wave index, number of antiepileptic drugs) and behavioral features. Intelligent Quotient (IQ) was measured in the whole sample, whereas visuo-spatial attention, visuo-motor skills, short term memory and academic abilities (reading and writing) were tested in 6 out of 16 patients.ResultsOur results showed that the most vulnerable from an intellectual point of view were those children who had an early-onset of CSWS whereas those with later onset resulted less affected (p = 0.004). Neuropsychological outcome was better than the behavioral one and the lexical-semantic route in reading and writing resulted more severely affected compared to the phonological route.ConclusionsCognitive deterioration is one but not the only consequence of CSWS. Especially with respect to verbal skills, CSWS is responsible of a pattern of consequences in terms of developmental hindrance, including slowing of development and stagnation, whereas deterioration is rare. Behavioral and academic problems tend to persist beyond epilepsy resolution.     

Motor impairment on awakening in a patient with an EEG pattern of "unilateral, continuous spikes and waves during slow sleep".

Movement disorders are rarely described in association with the "continuous spikes and waves during slow sleep (CSWS)" EEG pattern. We report the case of a young girl affected by an epileptic encephalopathy who, from the age of seven years and four months, has twice presented a movement disorder affecting the right arm, manifesting on awakening and disappearing by early afternoon. Sleep EEG during these periods showed continuous, high-amplitude, diphasic spikes and slow waves over the left hemisphere. Association of clobazam, valproic acid and, on the second occasion, ethosuccimide led to disappearance of the above-described EEG picture and associated motor symptoms. Neurophysiological investigations excluded other possible aetiologies. In view of this, and of the close relationship between the EEG picture and clinical course, we interpret the patient's impairment as "motor neglect" secondary to the continuous electrical activity recorded during sleep over the left hemisphere and involving the associative areas. This electrical activity in sleep, may be regarded as a "functional lesion" whose clinical consequences can be correlated with the site of the abnormalities.[Published with video sequences].     

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.     

Observation of continuous spike-waves during slow sleep in children with myelomeningocele

Cases Two patients with myelomeningoceles (MMC) and shunt-treated hydrocephalus are reported. At 5 and 7 years respectively, when they began presenting mental deterioration and behavioural disorders, sleep EEG showed continuous spike-waves during slow sleep (CSWS). Discussion These are the first cases of CSWS described in patients with MMC. The mechanisms of CSWS are considered. The role of hydrocephalus and the thalamic injuries found in one of the patients is discussed in detail. The usefulness of monitoring sleep EEG in patients with hydrocephalus or thalamic lesions is stressed, considering the effects of CSWS on the cognitive competencies and the soft or subclinical course that epilepsy complicated with CSWS may follow.     

Corrigendum to “Early electro-clinical features may contribute to diagnosis of the anti-NMDA receptor encephalitis in children” [Clin. Neurophysiol. 124 (2013) 2354–2361]

Objective: To describe initial and follow-up electroencephalographic (EEG) characteristics in anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis.Methods: Consecutive polygraphic video-EEG recordings were analyzed in nine pediatric patients with anti-NMDAR encephalitis at the initial stage of the disease and during the intermediate period until motor recovery. EEG characteristics in waking and sleep stages as well as EEG correlates of abnormal movements are described.Results: In six patients, the waking EEG showed preserved background activity and either focal or unilateral hemispheric slowing. These children had more favorable outcome than the three children with diffuse slowing. Unilateral abnormal movements contra-lateral to hemispheric or focal slowing were also indicative of milder severity when compared to generalized abnormal movements and diffuse slowing. During non-rapid eye movement (NREM) sleep, a decrease in the expected slow waves and unilateral or diffuse theta–alpha band rhythms were observed in six children, not correlated with the outcome, representing a suggestive EEG pattern of anti-NMDAR encephalitis.Conclusions: In pediatric patients presenting behavioral disorders and abnormal movements, early EEG patterns may be suggestive of anti-NMDAR encephalitis. Moreover early electro-clinical presentation contributes to outcome prediction.Significance: This case series demonstrates that early EEG patterns may be suggestive of anti-NMDAR encephalitis in pediatric patients with behavioral disorders and abnormal movements.