Continuous Spike-waves During Slow-wave Sleep Research Articles

HP27: Continuous spike-waves during slow-wave sleep (CSWS): An electroclinical evaluation according to the EEG patterns

To determine a possible association between clinical manifestations and EEG characteristics of CSWS patients. Introduction: CSWS is a rare condition that occurs only in children and adolescents, characterized by a distinctive electroencephalogram (EEG) and heterogeneous clinical manifestations. Aims: To determine a possible association between clinical manifestations and EEG characteristics of CSWS patients. Methods: We reviewed data of 12 pediatric patients who received a sleep EEG showing near-continuous spike-wave (SW) discharge (>50%) on a poorly organized sleep pattern. We defined the CSWS pattern as anterior if the maximum amplitude and/or the start of the SW were frontal, fronto-central or fronto-temporal and as posterior if the maximum amplitude and/or the start of the SW were temporal, temporo-occipital or occipital on the EEG. Results: The study included 12 patients (58% male) with a mean age of 4,6 years. Seven children had an anterior pattern with motor seizures in 3 cases and loss of contact in 4 cases. Five children had a posterior pattern with sensory motor seizures, loss of contact, aphasia in 1 case each and motor seizure in 2 cases. All the children presented cognitive abnormalities. Conclusion: The association between the EEG pattern of CSWS and clinical manifestations is controversial but remains a hypothesis to be awakened.

Encephalopathy with continuous spike-waves during slow-wave sleep: evolution and prognosis.

Encephalopathy with continuous spike-waves during slow-wave sleep (CSWS) evolves over time, and three stages can be recognized: before the onset of CSWS, during CSWS, and after the CSWS period. Clinical seizures tend to remit spontaneously around puberty. This pattern is independent of the etiological lesion. The CSWS also disappears in all cases. Focal abnormalities instead, may persist for some time after the disappearance of CSWS. The disappearance of the clinical seizures and CSWS may be simultaneous or seizures may disappear before or after disappearance of the CSWS pattern on the EEG. Electroclinical parameters in the pre-CSWS period that have been proposed to predict a poor outcome are early-onset seizures, appearance of new seizures, and a significant increase in seizure frequency. From the electrical point of view, an increase in the frequency of the interictal EEG paroxysms while awake and during sleep and bilateral spike-and-wave paroxysms may also be predictive of a poor evolution in CSWS. When CSWS disappears, neurocognitive and behavioral status improve, but in most patients, residual moderate to severe neurocognitive impairments remain. In non-lesional epilepsy, cognitive recovery after cessation of the CSWS depends on the severity and duration of the initial regression. The duration of the CSWS seems to be the most important predictor of cognitive outcome. Early recognition and effective therapy to reduce the seizures and resolve the CSWS may be crucial to improve long-term prognosis. Cognitive recovery is observed in patients who respond well to AED treatment and outcome depends on the etiology.

Continuous spike‐waves during slow‐wave sleep in a mouse model of focal cortical dysplasia

To examine if mice with focal cortical dysplasia (FCD) develop spontaneous epileptic seizures and, if so, determine the key electroencephalography (EEG) features. Unilateral single freeze lesions to the S1 region (SFLS1R) were made in postnatal day 0-1 pups to induce a neocortical microgyrus in the right cortical hemisphere. Continuous 24-h recordings with intracranial EEG electrodes and behavioral tests were performed in adult SFLS1R and sham-control mice to assess neurologic status. A high percentage of adult SFLS1R animals (89%, 40/45) exhibited at least one or more spontaneous nonconvulsive seizure events over the course of 24 h. Of these animals, 60% (27/45) presented with a chronic seizure state that was persistent throughout the recording session, consisting of bursts of rhythmic high-amplitude spike-wave activities and primarily occurring during periods of slow-wave sleep. In comparison, none of the control, age-matched, mice (0/12) developed seizures. The epileptic discharge pattern closely resembled a pattern of continuous spike-waves during slow-wave sleep (CSWS) of the human syndrome described as an electrical status epilepticus during slow-wave sleep (ESES). Key findings in the SFLS1R model indicated that the observed CSWS (1) were more prevalent in female (18/23) versus male (9/22, p < 0.05), (2) were strongest in the right S1 region although generalized to other brain regions, (3) were associated with significant cognitive and behavioral deficits, (4) were temporarily alleviated by ethosuximide treatment or optogenetic activation of cortical γ-aminobutyric acid (GABA)ergic neurons, and (5) theta and alpha band rhythms may play a key role in the generalization of spike-wave activities. This is the first report of an in vivo animal FCD model that induces chronic spontaneous electrographic brain seizures. Further characterization of the abnormal oscillations in this mouse model may lead to a better understanding of the mechanisms of CSWS/ESES.

Neuropsychological approaches to epileptic encephalopathies

The International League Against Epilepsy (ILAE) Commission report on classification and terminology indicates that "diagnosing an individual as having an encephalopathic course requires demonstration of a failure to develop as expected relative to the same-aged peers or to regress in abilities." In this chapter, basing our discussion on the theoretical framework of neuroconstructivism, on the latest results deriving from functional neuroimaging and on the concept of system epilepsy, we use continuous spike-waves during slow-wave sleep (CSWS) as an example of how non-rapid eye movement (NREM) sleep spikes interfere with the organization and consolidation of neuropsychological networks in the sensitive phase of development, affecting also interconnected systems. Indeed, recent discoveries show that the normal overnight downscaling of slow wave activity (SWA) from the first to the last hours of sleep is absent in electrical status epilepticus during sleep (ESES) patients, thus impairing the neural process and possibly the local plastic changes associated with learning and other cognitive functions. Moreover, specific patterns of spike-induced activation (especially in perisylvian and/or prefrontal areas) and deactivation of default mode network (DMN) have been shown in patients with CSWS. Consequently, to date, we may conceive that the possible mechanisms underlying neuropsychological disorders in encephalopathic epilepsy (EE) may be double, since NREM sleep interictal epileptic discharges (IEDs) induce both a pathologic activation in epileptogenic areas and a pathologic deactivation of DMN beyond the epileptogenic zone. The growing body of literature on the effects of ESES in CSWS provides us with increasing knowledge on the complexity of brain development and a better understanding of plasticity, enlightening the pathogenesis of damage on developing neuropsychological functions. Finally, the need for an individually tailored interpretation of the neuropsychological testing results, expected to integrate neurophysiology and functional neuroimaging data, is suggested.

S17-2. High-frequency electroencephalographic activity in childhood epilepsy

High-frequency (HF) activity in electroencephalogram (EEG) is closely related to both epileptogenicity/ictogenicity and physiological cognitive function. HF activity beyond the beta band includes the gamma, ripple, and fast ripple bands. We have investigated HF activity in children with epileptic encephalopathy. In the pathophysiology of epileptic encephalopathy, cognitive impairment is suggested to be linked to scalp epileptic gamma rhythms that may represent the slower part of cortical HF oscillations in West syndrome. In epilepsy with continuous spike-waves during slow wave sleep (CSWS), the disturbance of higher brain functions may be related to spike-associated scalp ripple oscillations. HF oscillations have also been detected from the ictal cortical EEG of a rat model of channelopathy with SCN1A mutation. The technique to explore HF activity, however, is demanding and requires further development. A statistical comparison of HF activity through a time–frequency analysis between epileptic discharges and the background allows an objective identification of changes in HF power. Although the obtained statistical spectrum is noisy in the uncontrolled form, it can be rendered noiseless and easy to interpret with a control technique that employs the false discovery rate (FDR).

Neuropsychological impairment in early-onset hydrocephalus and epilepsy with continuous spike-waves during slow-wave sleep: A case report and literature review

Epilepsy with continuous spike-waves during slow-wave sleep (CSWS) is often characterized by a severe cognitive and behavioral impairment. Symptomatic cases also include patients with an early-onset hydrocephalus, but in literature detailed neuropsychological data on these subjects are not available. We describe the results of serial cognitive assessments in a girl with shunted early-onset hydrocephalus, followed by partial epilepsy complicated with CSWS at 4 years 10 months, in which a dramatic cognitive and behavioral deterioration occurred few months after CSWS onset. Adrenocorticotropic hormone treatment improved both clinical and electroencephalogram picture, but an impairment of visual perception, visual-motor coordination and executive functions persisted after CSWS disappearance. We hypothesize, in this case, an involvement of right occipital-parietal lobe and prefrontal lobe.

Effects of intravenous diazepam on high-frequency oscillations in EEGs with CSWS

High-frequency oscillations (HFOs) associated with continuous spike-waves during slow-wave sleep (CSWS) are speculated to be linked to the disturbance of higher brain function. We intended to investigate the generative mechanisms of HFOs in CSWS by clarifying the effects of intravenous injection (IV) of diazepam (DZP), an agonist for the gamma-aminobutyric acid A (GABAA) receptor in the GABAergic interneuron system, in patients who had previously been treated with IV DZP. The subjects were three patients with epilepsy with CSWS. For each patient, EEG data before and after IV DZP were separated into consecutive 5-min sections. Time–frequency power spectral analysis was performed on the spikes of each section, and peak-power and frequency of detected high-frequency spectral spots were compared before and after IV DZP. Spectral spots with peak-frequencies at 85.9–121.1Hz in the ripple band were revealed in all three patients. Although the amplitudes of the spikes largely returned to the baseline levels 20–25min after IV DZP, the recovery of the peak-power levels of HFOs lagged behind that of the spike amplitudes, and the power levels of HFOs were lower than the baseline data within 25min after the injection of DZP. No consistent changes were found regarding the spectral frequencies of HFOs. The dissociation of the effect of IV DZP in terms of recovery when comparing spike-amplitudes and the power of HFOs may correspond to an already suggested difference in the pathophysiological mechanisms that generate the spikes and HFOs.

Long‐term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike‐waves during slow‐wave sleep

To present the long-term follow-up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike-waves during slow wave sleep (CSWS). Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered. After a mean duration of follow-up of 15.6 years (range, 8-23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long-term outcome correlated best with duration of CSWS. Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.

A patient with 22q13 deletion syndrome accompanied by epilepsy with continuous spike-waves during slow wave sleep (CSWS) and cerebral infarction

We describe a patient with 22q13 deletion syndrome accompanied by epilepsy with continuous spike-waves during slow wave sleep (CSWS). This patient showed central hypotonia, mental retardation, disappearance of language, multiple facial anomalies, and intractable epilepsy. Overnight EEG showed CSWS (spike & wave index = 99.2%) at seven years of age. Chromosomal analysis using G-banding revealed a deletion at the end of chromosome 22, indicative of 22q13 syndrome. In addition, subsequent magnetic resonance imaging (MRI) demonstrated cerebral infarction in the left posterior temporal area, which was probably caused by recurrent status epilepticus. Unlike previous case reports, a striking feature in this patient was the development of motor deterioration after 15 years of age. The severe EEG abnormalities and frequent status epilepticus might induce this deterioration and brain infarction.

High-frequency oscillations in idiopathic partial epilepsy of childhood

We explored high-frequency oscillations (HFOs) in scalp sleep electroencephalography (EEG) studies of patients with idiopathic partial epilepsy (IPE) of childhood in order to obtain a better understanding of the pathologic mechanisms underlying IPE. The subjects were 45 patients, including 32 with benign childhood epilepsy with centrotemporal spikes (BCECTS) and 13 with Panayiotopoulos syndrome (PS). A total of 136 EEG records were investigated through temporal expansion and filtering of traces and time-frequency spectral analysis. HFOs with frequency of 93.8-152.3 Hz (mean 126.2 ± 13.6 Hz) in the band of ripples were detected in association with spikes in 97 records (71.3%). Time from last seizure to the EEG recording was significantly shorter in those with spike-related HFOs than in the EEG recordings with spikes without HFOs (p = 0.006). Although time from last seizure reflects age, age at the time of recording was not significantly different between EEG studies with and without HFOs. Peak-power values of the high-frequency spots in time-frequency spectra were significantly negatively correlated with time from last seizure (R(2) = 0.122, p < 0.001) but not with age at the time of recording. Peak frequencies of the high-frequency spectral spots were not significantly correlated with age at the time of recording or with time from last seizure. The close relationship between the generation of spike-related HFOs and the period of active seizure occurrence indicated that HFOs may tell us more about epileptogenicity in IPE than the spikes themselves. Because there is a spectrum of pediatric epileptic disorders extending from the benign end of BCECTS to the encephalopathic end of epilepsy with continuous spike-waves during slow-wave sleep (CSWS), and HFOs that have already been detected in association with CSWS were more prominent than HFOs in IPE, intense spike-related HFOs may indicate poor prognosis.

Impaired slow wave sleep downscaling in encephalopathy with status epilepticus during sleep (ESES)

Objective “Encephalopathy related to electrical status epilepticus during slow wave sleep” (ESES) is characterised by the electroencephalographic pattern of continuous spike waves during slow wave sleep (CSWS) and variable neuropsychological impairments. The synaptic homeostasis hypothesis predicts that the strength of synapses is decreased during sleep. The slope of slow waves during NREM sleep best reflects this “downscaling”. Methods In a retrospective case control study, we analysed the time course of the slope of EEG slow waves of nine patients with ESES. The patients showed continuous spike waves (>85%) associated with regression or stagnation of cognitive functions. The data of the patient group were compared to nine healthy age and gender matched controls. Results In control subjects we found the expected decrease of the slope of slow waves from the first to the last hour of sleep (17.2% decrease, p < 0.001). In contrast, patients showed no significant change in slope across the night. Conclusions This finding may reflect a disruption of the downscaling process during sleep, which may contribute to the developmental regression in these children. Significance Thus, our findings contribute to the understanding of the pathomechanisms leading to the regression observed in children with ESES and support the view that the goal of the treatment in children with ESES should not only be to reduce seizures, but also to resolve the continuous spike wave activity.

Scalp‐recorded high‐frequency oscillations in childhood sleep‐induced electrical status epilepticus

Because high-frequency oscillations (HFOs) may affect normal brain functions, we examined them using electroencephalography (EEG) in epilepsy with continuous spike-waves during slow-wave sleep (CSWS), a condition that can cause neuropsychological regression. In 10 children between 6 and 9 years of age with epilepsy with CSWS or related disorders, we investigated HFOs in scalp EEG spikes during slow-wave sleep through temporal expansion of the EEG traces with a low-cut frequency filter at 70 Hz as well as through time-frequency power spectral analysis. HFOs (ripples) concurrent with spikes were detected in the temporally expanded traces, and the frequency of the high-frequency peak with the greatest power in each patient's spectra ranged from 97.7 to 140.6 Hz. This is the first report on the detection of HFOs from scalp EEG recordings in epileptic patients. We speculate that epileptic HFOs may interfere with higher brain functions in epilepsy with CSWS.

Landau‐Kleffner syndrome: 50 years after

Landau‐Kleffner syndrome: 50 years after

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.

Corticosteroids as treatment of epileptic syndromes with continuous spike‐waves during slow‐wave sleep

To assess the efficacy and tolerability of steroids in epileptic syndromes with continuous spike-waves during slow-wave sleep (CSWS), charts of 44 children (25 boys) who received corticosteroids for cognitive and/or behavioral deterioration associated with CSWS were retrospectively reviewed. Awake and sleep electroencephalography (EEG) records, clinical and neuropsychological assessments were available before, during, and after corticosteroid therapy. Evaluation focused on effects on EEG, behavior, and cognition. All but two patients received hydrocortisone (initial dose of 5 mg/kg/day). The treatment was slowly tapered with a total duration of 21 months. There were 18 symptomatic and 26 cryptogenic cases. Mean age was 7 years and mean intelligence quotient/developmental quotient (IQ/DQ) was 65. Mean CSWS duration before corticosteroid treatment was 1.7 years. Twenty patients had tried more than two antiepileptic drugs (AEDs) before steroids. Positive response to steroids was found during the first 3 months of treatment in 34 of 44 patients (77.2%), with normalization of the EEG in 21 patients. Relapse occurred in 14 of them. Hence, 20 patients (45.4%) were long-term responders after a single but prolonged trial of steroids, including all four cases of Landau-Kleffner syndrome. Positive response to steroids was highly significantly associated with higher IQ/DQ. Shorter CSWS duration, but not age, etiology, or previous AED trials, was associated with positive response to steroids. Early discontinuation of the treatment for side effects was encountered in seven patients. We conclude that corticosteroids are safe and efficient for treatment of epilepsy with CSWS. Poor responders are patients with very low IQ and long duration of CSWS.

Age-related electrical status epilepticus during sleep and epileptic negative myoclonus in DRPLA

Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) (MIM 125370)1 is a rare autosomal dominant neurodegenerative disorder found mostly in Japanese people and caused by an expansion of the CAG repeat in the DRPLA gene on chromosome 12p.2 Childhood-onset patients generally have a phenotype of progressive myoclonus epilepsy (PME) with a large expansion of the CAG repeat.2 In the present study, we report a patient with DRPLA who showed epilepsy with electrical status epilepticus during slow sleep (ESES) or the extraordinary EEG abnormality of continuous spike-waves during slow wave sleep (CSWS) and epileptic negative myoclonus in childhood. Epilepsy with CSWS generally occurs in cryptogenic patients or symptomatic ones with nonprogressive brain pathology and is an age-related and self-limited disorder.3 Remarkably, his CSWS on EEG remitted spontaneously with age, as it does in other patients without progressive disorder, although the underlying degeneration of the brain continued relentlessly. This patient, who was born after an uneventful pregnancy, had a father with ataxia and dementia and a diagnosis of DRPLA in later life. The patient's early …

Treatment of epilepsy with electrical status epilepticus during slow sleep and its related disorders

To elucidate an effective therapeutic strategy for ‘ESES syndrome’, epilepsy with electrical status epilepticus during slow sleep (ESES) and its related epileptic disorders, we studied the effect of treatment on the EEG pattern of continuous spike-waves during slow wave sleep (CSWS) in 15 afflicted patients. Basically performed in the following order, the employed therapies included (1) high-dose valproate (VPA) therapy (serum level >100 μg/ml); (2) a combination therapy of VPA and ethosuximide (ESM); (3) short cycles of high-dose diazepam (oral or intrarectal DZP, 0.5–1 mg/kg per day for 6–7 days); and (4) intramuscular synthetic ACTH-Z therapy (0.01–0.04 mg/kg per day for 11–43 days). Regarding the initial EEG effect, a remission of CSWS was achieved by high-dose VPA therapy in 7 of 15 trials (47%), by the combination therapy of VPA and ESM in 3/7 trials (43%), by short cycles of high-dose DZP in 2/4 trials (50%), and by ACTH-Z therapy in 2/5 trials (40%). A permanent remission of ESES syndrome was achieved by high-dose VPA therapy and/or combination therapy of VPA and ESM in 10 patients (67%). The effects of short cycles of high-dose DZP and ACTH-Z therapy were at best temporary. Our strategy for the treatment of ESES syndrome is therefore considered valid.

Selected Papers: Childhood Epilepsies

Abstract *Miki Inutsuka, †Yoko Ohtsuka, †Kousuke Nakano, †Junri Hattori, *Katsuhiro Kobayashi, and †Eiji Oka Department of Child Neurology, *Okayama University Medical School ; and †Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan . Purpose: To elucidate the effect of treatment of epilepsy with electrical status epilepticus during slow sleep (ESES) and factors related to the response to treatment. Methods: We studied 26 patients with ESES who were admitted to Okayama University Hospital (age range, 2y0m to 9y7m). Patients were treated with one or more of the following therapies: (a) high-dose valproate (VPA) therapy (plasma level, >100 μg/ml), (b) a combination therapy of VPA and ethosuximide (ESM), (c) a short cycle of high-dose diazepam (DZP; 0.54–1 mg/kg/day, orally or intrarectally for 6–14 days), and (d) synthetic adrenocorticotropic hormone (ACTH) therapy (Cortrosyn-Z; 0.01–0.036 mg/kg/day, intramuscularly, for 11–43 days). Basically, we started treatment with high-dose VPA therapy. When this failed or yielded adverse side effects, we tried the combination therapy of VPA and ESM. When both were unsuccessful, we tried a short cycle of high-dose DZP or synthetic ACTH therapy. All patients were followed up for ≥2 years. We also investigated response patterns to treatments and mental outcome in each patient. Results: Treatment effects: Regarding the initial effects, treatment was defined as effective when continuous spike–waves during slow-wave sleep (CSWSs) were suppressed (≥1 month with markedly decreased or no diffuse spike-waves during slow-wave sleep). In terms of initial effect, high-dose VPA was effective in 12 (50%) of 24 trials; combination therapy with VPA and ESM in six (43%) of 14 trials; a short cycle of high-dose DZP, in six (75%) of eight trials; and synthetic ACTH, in three (43%) of seven trials. However, CSWSs recurred within 1 year of treatment in two patients treated with high-dose VPA, in four treated with a short cycle of high-dose DZP, and in all three treated with synthetic ACTH. Response patterns and mental outcomes: Subjects were divided into two groups: 15 patients with favorable EEG response to the initial treatment maintained throughout the clinical course (group A), and 11 patients with no favorable EEG response to the initial treatment, or deterioration after an initial favorable response (group B). All patients except one in group A were treated with high-dose VPA or the combination therapy of VPA and ESM or both. All patients except two in group B were treated with a short cycle of high-dose DZP or synthetic ACTH after the failure of high-dose VPA or both or the combination therapy of VPA and ESM or both. Comparing these two groups, ages at onset of ESES were significantly lower in group B (p = 0.0009). Organic brain lesions such as brain malformations were seen more often in group B. Mental deterioration after the onset of ESES was observed significantly more often in group B (p = 0.037). Regarding mental outcome, patients with normal mentality or slight mental retardation predominated in group A, whereas those with severe mental retardation were found only in group B. Conclusions: Remission of ESES was achieved in approximately half of the patients treated with high-dose VPA therapy or combination therapy with VPA and ESM or both. Even when these treatments were ineffective, a short cycle of high-dose DZP or synthetic ACTH therapy was effective in most cases. However, the effects of the latter two treatments were only temporary. Group B was characterized by early-onset patients associated with organic brain lesions. These patients responded poorly to treatment and consequently had mental deterioration and poor mental outcomes. Thus response to ESES treatment may be related to the underlying organic brain lesion(s). To prevent poor mental outcome, we believe that it is critical to achieve remission as early as possible by using intensive treatment.

Language and Behavioral Disturbances Associated with Epileptiform EEGs

ABSTRACT.The appearance of language or behavioral regression in previously normal children is a devastating experience for both the family and the patients. In some cases, evaluation with prolonged sleep electroencephalograms (EEGs) reveals a dramatic activation of epileptiform activities. These may be continuous and diffusely appearing spike-wave discharges in slow-wave sleep, also known as “electrical status epilepticus in sleep” (ESES), or they may be more focal but very frequent temporal, centrotemporal, or multifocal spikes. The typical syndromes are the encephalopathy associated with ESES or continuous spike waves during slow-wave sleep (CSWS) and Landau-Kleffner syndrome (LKS). A significant minority of children with pre-existing impairments in sociability, communication, and behavior, typical of autistic spectrum disorders, may manifest epileptiform abnormalities, which perhaps further exacerbate the language or neuropsychiatric dysfunction. Patients with autistic regression with epileptiform EEGs (AREE) may have clinical and electrographic similarities with CSWS or LKS children. In this review, we will summarize the existing knowledge about these syndromes and the existing therapeutic strategies. Awareness about these syndromes is of paramount importance in order to implement early detection and treatment, which may ameliorate the outcome.

Distribution of epileptiform discharges during nREM sleep in the CSWSS syndrome: relationship with sigma and delta activities

Purpose: The EEG pattern of epilepsy with continuous spike-waves during slow wave sleep (CSWSS) is characterized by an almost continuous activation of spike-and-slow-wave complexes during nREM sleep with a marked reduction of EEG abnormalities during REM sleep and the awake state. Experimental studies indicate that normal sleep oscillations that during nREM sleep lead to the appearance of spindles and delta waves on scalp EEG might develop into paroxysmal synchronization. Spectral analysis enables the quantitative description of the dynamics of delta (Delta Activity, DA, 0.5–4.5 Hz) and sigma activity (SA, 12–16 Hz) and can be used to assess the relationship between SA, DA and epileptiform discharges (EDs) during sleep. Methods: We analyzed the EDs distribution during sleep in five children affected by CSWSS. We used a model of the evolution of power of DA and SA to which the time series of EDs could be fitted. Results: We found a high and positive correlation between EDs and SA. DA resulted negatively correlated with EDs. Conclusion: Our data suggest that neural mechanisms involved in the generation of sleep spindles facilitate EDs production in the CSWSS syndrome. Such a mechanism seems to be an age related phenomenon shared by other epileptic syndromes of childhood.