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Purpose Polymicrogyria (PMG), although the most common brain malformation, represents a low percentage among patients operated on for epilepsy. In cases of hemispheric PMG, electrical status epilepticus during slow sleep (ESESS) may occur leading to an aggravation of the neurological condition and a risk of drug resistance. In such cases, surgical treatment can be offered. Methods From a population of 230 children who underwent hemispherotomy for epilepsy, we retrospectively reviewed the patients with unilateral PMG and drug-resistant ESESS focusing on clinical charts, electrophysiological data and post-surgical outcome. Results Eighteen patients were operated on at a mean age of 7.2 years. The average age was 2 years at seizure onset and 4.4 years at diagnosis of ESESS. All the patients preoperatively had some degree of developmental delay associated with a hemiparesis. During ESESS all of them evidenced a cognitive decline and eight experienced a worsening of the hemiparesis; ESESS was resistant to at least three antiepileptic drugs. The outcome of epilepsy, with a mean follow-up of 12.8 years showed that ESESS disappeared in all patients while 16 of 18 became seizure-free. An improvement of behavior and cognitive condition was observed in all. Conclusion Hemispherotomy can be helpful in patients with drug-resistant ESESS and hemispheric PMG while keeping in mind that more often an accurate medical treatment can be sufficient. The main benefit of surgery is to definitively stop the seizures and to withdraw the medical treatment while keeping in mind the risk of motor aggravation.

Objective We describe the evolution of the electroclinical picture of patients with different types of self-limited epilepsy of childhood (SLEC) occurring at the same or at different times with or without atypical evolutions as well as patients with SLEC associated with childhood absence epilepsy (CAE). Material and methods A multicenter, retrospective, descriptive study was conducted evaluating patients with SLEC who had focal seizures of different types of SLEC including atypical evolutions as well as SLEC associated with absence epilepsy seen at eight Argentinian centers between April 2000 and April 2019. Of 7705 patients with SLEC, aged between 2 and 14 years (mean, 7.5 years), of whom 2013 were female and 5692 male (ratio, 1:2.8), 5068 patients had SLECTS, 2260 patients had self-limited childhood occipital epilepsy Panayiotopoulos type (SLE-P), 356 had self-limited childhood occipital epilepsy Gastaut type (SLE-G), and 21 had self-limited epilepsy with affective seizures (SLEAS). Electroclinical features typical of more than one SLEC syndrome were recognized in 998 (13 %) children. Results We recognized three well-defined groups of patients. The most frequent association was SLE-P and SLECTS, the paradigmatic type, but associations of SLE-P and SLE-G, SLECTS and SLE-G, and SLEAS and SLE-P or SLECTS were also recognized. The second-most-common association was SLEC and an atypical evolution. In this group, the most frequent combination was SLECTS with its atypical evolution, opercular status epilepticus, epileptic encephalopathy with continuous spike‐and‐waves during slow sleep, or Landau-Kleffner syndrome. SLE-P and SLE-G associated with an atypical evolution were also identified. The third, less-frequent group had SLECTS, SLE-P, or SLE-G associated with CAE. These cases support the concept that the different types of SLEC are part of a self-limited childhood seizure susceptibility syndrome. Conclusion Our study demonstrated that 13 % of our patients with SLEC have with different types of SLEC occurring at the same or at different times with or without atypical evolutions - i.e. CSWSS - as well as patients with SLEC associated with CAE, supporting the concept of the self-limited childhood seizure susceptibility syndrome.

Objective It is argued that early and adequate treatment of electrical status epilepticus in sleep (ESES) is essential to preserve cognitive functions and possibly recovering lost skills. Although antiepileptic drugs (AEDs) are effective in ESES, there is not much experience in the use of sulthiame. In this study, we aimed to examine the efficiency and tolerability of sulthiame in ESES. Methods The data of 39 patients diagnosed as ESES and who received sulthiame as an additional treatment between 2016 and 2020 were reviewed retrospectively. Electroencephalographic (EEG) findings and seizure rates were compared before and after the sulthiame treatment. Results The mean age was 8.5 ± 4.1 (1.5–16 years). Nine out of 39 patients had benign childhood focal epilepsies. Structural causes were identified in 13 patients. The mean duration of sulthiame use was 32.5 ± 13.7 months. After sulthiame treatment, 25 patients (64.1%) were seizure free, and 8 (20.5%) had more than a 50% decrease in seizure frequency. The mean seizure-free time after the sulthiame treatment was 27.8 ± 17.9 months. Nineteen patients (48.7%) had complete, and nine patients (23.1%) had partial EEG improvement. Complete seizure control was significantly higher in benign focal epilepsy of childhood (p = 0.01). Significant neurocognitive and behavioral recovery, improvement in school performance was observed following sulthiame treatment (p Conclusion Sulthiame was found to be effective in seizure control and EEG improvement in ESES. We think that the use of sulthiame alone can be a good choice with high efficacy and tolerability in ESES.

In young adults, memory consolidation during sleep is supported by a time-coordinated interplay of sleep spindles and slow oscillations. However, given tremendous developmental changes in sleep spindle and slow oscillation morphology, it remains elusive whether the same mechanisms as identified in young adults are comparably functional across childhood. Here, we characterise slow and fast sleep spindles and their temporal coupling to slow oscillations in 24 pre-school children. Further, we ask whether slow and fast sleep spindles and their modulation during slow oscillations are similarly associated with behavioural indicators of declarative memory consolidation as suggested from adult literature. Employing a development-sensitive, individualised approach, we reliably identify an inherent, development-specific fast sleep spindle type, though nested in the adult-like slow sleep spindle frequency range, along with a dominant slow sleep spindle type. Further, we provide evidence for the modulation of fast sleep spindles during slow oscillations, already in pre-school children. However, the temporal coordination between fast sleep spindles and slow oscillations is weaker and less precise than expected from adult research. While we do not find evidence for a critical contribution of the pattern of fast sleep spindle modulation during slow oscillations for memory consolidation, crucially, both inherent slow and fast sleep spindles separately are differentially related to sleep-associated consolidation of items of varying quality. While a higher number of slow sleep spindles is associated with stronger maintenance of medium-quality memories, more fast sleep spindles are linked to higher gain of low-quality items. Our results provide evidence for two functionally relevant inherent sleep spindle types in pre-school children despite not fully matured sleep spindle - slow oscillation coupling.

Encephalopathy related to Status Epilepticus during slow Sleep (ESES) is an age-dependent syndrome characterized by the appearance of neuropsychological and behavioral disorders associated with extreme activation of epileptic activity during sleep. The major goal of therapy in ESES is to prevent neuropsychological deficits. Effective therapy to reduce seizures and resolve the EEG pattern of status epilepticus during sleep (SES) may be crucial to improve long-term prognosis. However, whether to improve neurodevelopmental deficits by suppressing or eliminating SES remains unknown. The purpose of this article is to review current therapeutic options in ESES, in order to provide better alternatives. Treatment options consist of antiepileptic drugs, steroids, immunoglobulins, the ketogenic diet, and surgery. Maybe therapy targeted mechanisms can be developed with deep insight into the etiology of ESES.

Objective/Background Massive changes in brain morphology and function in the first years of life reveal a postero-anterior trajectory of cortical maturation accompanied by regional modifications of NREM sleep. One of the most sensible marker of this maturation process is represented by electroencephalographic (EEG) activity within the frequency range of sleep spindles. However, direct evidence that these changes actually reflect maturational modifications of fast and slow spindles still lacks. Our study aimed at answering the following questions: 1. Do cortical changes at 11.50 Hz frequency correspond to slow spindles? 2. Do fast and slow spindles show different age trajectories and different topographical distributions? 3. Do changes in peak frequency explain age changes of slow and fast spindles? Patients/Methods We measured the antero-posterior changes of slow and fast spindles in the first 60 min of nightly sleep of 39 infants and children (0–48 mo.). Results We found that (A) changes of slow spindles from birth to childhood mostly affect frontal areas (B) variations of fast and slow spindles across age groups go in opposite direction, the latter progressively increasing across ages; (C) this process is not merely reducible to changes of spindle frequency. Conclusions As a main finding, our cross-sectional study shows that the first form of mature spindle (i.e., corresponding to the adult phasic event of NREM sleep) is marked by the emergence of slow spindles on anterior regions around the age of 12 months.

Objective The aim of this study was to describe the electroclinical spectrum in children with electrical status epilepticus in sleep (ESES)/continuous spikes and waves during slow sleep (CSWS) syndrome according to the EEG patterns. Methods Clinical data of 44 patients with ESES/CSWS syndrome who were treated and followed at least two years were analyzed. Records of EEGs of patients were reevaluated to determine two aspects of the ESES pattern: (1) the spike–wave index (SWI) on the NREM sleep EEG (Group I: typical vs. atypical ESES pattern (33/11 patients)) and (2) the area of maximum amplitude of continuous epileptic activity (Group II: anterior vs. posterior ESES pattern (33/11 patients)). Results Symptomatic etiology was more defined in patients with the typical ESES pattern (40%) than the group with the atypical ESES pattern (9%) by a factor of four. All patients were receiving at least two antiepileptic drug (AED) treatments. Eighteen patients (41%) received AEDs plus ACTH therapy. Complete disappearance of the ESES pattern on the EEG was observed in 18 patients (41%), more than 50% reduction was observed in five patients (11%), less than 50% reduction was observed in eight patients (18%), and no response was observed in five patients (11%). No significant difference was found when comparing the groups in terms of reduction of seizures and the SWI. Seizure outcome at the two-year follow-up was similar between the group with ESES treated with AEDs plus ACTH and the group with ESES treated with AEDs without ACTH therapy. Significance This study demonstrated that the rate of the SWI (typical vs. atypical ESES) and the maximum amplitude of the ESES pattern (anterior vs. posterior) have no significant correlation with seizure control and reduction of the SWI on the EEG in children with ESES syndrome.

Objective The objective of the study was to investigate electroclinical and neuropsychological features, genetic background, and evolution of children with idiopathic encephalopathy with status epilepticus during slow sleep (ESES), including Landau–Kleffner syndrome (LKS). Material and methods All children diagnosed with idiopathic ESES at the Danish Epilepsy Centre between March 2003 and December 2014 were retrospectively reviewed. Repeated 24-hour electroencephalography (24-h EEG) recordings, neuropsychological assessments, and clinical–neurological evaluation were performed throughout the follow-up in all patients. In 13 children, genetic investigations were performed. Results We collected 24 children (14 males and 10 females). Mean age at ESES diagnosis was 6 years, and mean ESES duration was 2 years and 7 months. Twenty-one children had epileptic seizures. Three children had LKS. Topography of sleep-related EEG epileptic abnormalities was diffuse in 3 subjects, hemispheric in 6, multifocal in 9, and focal in 6. During the active phase of ESES, all children presented with a heterogeneous combination of behavioral and cognitive disturbances. In 14 children, a parallel between severity of the clinical picture and spike–wave index (SWI) was observed. We could not find a strict correlation between the type and severity of neurobehavioral impairment and the side/topography of sleep-related EEG discharges during the active phase of ESES. At the last follow-up, 21 children were in remission from ESES. Complete recovery from neurobehavioral disorders was observed in 5 children. Genetic assessment, performed in 13 children, showed GRIN2A variant in two (15.4%). Significance Our patients with idiopathic ESES showed a heterogeneous pattern of epileptic seizures, neurobehavioral disorders, and sleep EEG features. Only one-fourth of children completely recovered from the neuropsychological disturbances after ESES remission. Lack of correlation between severity/type of cognitive derangement and SWI and/or topography of sleep EEG epileptic abnormalities may suggest the contribution of additional factors (including impaired sleep homeostasis due to epileptic activity) in the neurobehavioral derangement that characterize ESES.

Individual circadian preference types and sleep EEG patterns related to spindle characteristics, have both been associated with similar cognitive and mental health phenotypes. However, no previous study has examined whether sleep spindles would differ by circadian preference. Here, we explore if spindle amplitude, density, duration or intensity differ by circadian preference and whether these associations are moderated by spindle location, frequency, and time distribution across the night. The participants (N = 170, 59% girls; mean age = 16.9, SD = 0.1 years) filled in the shortened 6-item Horne-Östberg Morningness-Eveningness Questionnaire. We performed an overnight sleep EEG at the homes of the participants. In linear mixed model analyses, we found statistically significant lower spindle amplitude and intensity in the morning as compared to intermediate (P 0.06 for spindle duration and density). Spindle frequency moderated the associations (P 0.2 for fast (>13 Hz)). Growth curve analyses revealed a distinct time distribution of spindles across the night by the circadian preference: both spindle amplitude and intensity decreased more towards morning in the morning preference group than in other groups. Our results indicate that circadian preference is not only affecting the sleep timing, but also associates with sleep microstructure regarding sleep spindle phenotypes.

Summary In this study, we describe three patients who each had an electroclinical overlap of two different epileptic encephalopathies (EE), with onset in a certain age period. Patient 1 had electroclinical features compatible with continuous spikes and waves during slow sleep (CSWSS) syndrome that changed into Lennox–Gastaut syndrome (LGS) (symptomatic, cause porencephalic cyst) at the age of 8.5 years. Patient 2 had LGS which evolved into CSWSS at the age of 6 years (symptomatic, cause polymicrogyria). The third patient had cryptogenic CSWSS syndrome at age the age of 7 years which evolved into LGS at the age of 7.5 years. All three patients could be considered to have two EE: CSWSS syndrome and LGS or to have had overlapping features of these epilepctic syndromes.

Since the age of three years the patient suffered from early drug-resistant partial epilepsy with electric status during slow sleep, owing to a micropolygyric malformation of the right fronto-temporo-parietal lobes. The hemispherotomy (when five years of age) was followed by immediate and persistent disappearance of the seizures and withdrawal of the treatment. The transfer of right hemispheric functions to the left hemisphere occurred very early; the child’s development was examined in relation to the restoration of these functions and the age at surgery. The early surgical intervention and the plasticity of the brain – along with an intensive cognitive rehabilitation – seem to be important in determining the favorable global cognitive outcome. Visuo-spatial abilities and multi-modal integration of these functions with memory, attention and language have been the most critical domains and are recently in progress. The rapidity of processing complex tasks is particularly lacking. This seems to be the expression of the defective development of the Central Executive System.

We present a patient with cryptogenic focal epilepsy and another with Dravet syndrome, who experienced seizure aggravation and negative myoclonus, associated with continuous spikes and waves during slow sleep, induced by levetiracetam. For both patients levetiracetam was discontinued, and there was significant improvement of this particular electroclinical picture.

Sudden epileptic falls are frequently reported in continuous spike-waves during slow sleep (CSWS) syndrome. Inhibitory seizures are usually considered as the underlying mechanism. However, published polygraphic recordings are rare. We report the case of a 22 month-old boy suffering from a symptomatic CSWS syndrome associated with a perinatal stroke involving the right middle cerebral artery territory. He presented with psychomotor regression and daily multiple falls related to myoclonic-atonic seizures. Neurophysiological examination showed secondary generalized myoclonus systematically correlated with a bilateral spike spreading from the right central area. This confirms that positive myoclonus, in addition to negative myoclonus, may be responsible for epileptic falls in CSWS syndrome. [Published with video sequences].

We developed an EEG- and audio-based sleep sensing and enhancing system, called iSleep (interactive Sleep enhancement apparatus). The system adopts a closed-loop approach which optimizes the audio recording selection based on user's sleep status detected through our online EEG computing algorithm. The iSleep prototype comprises two major parts: 1) a sleeping mask integrated with a single channel EEG electrode and amplifier, a pair of stereo earphones and a microcontroller with wireless circuit for control and data streaming; 2) a mobile app to receive EEG signals for online sleep monitoring and audio playback control. In this study we attempt to validate our hypothesis that appropriate audio stimulation in relation to brain state can induce faster onset of sleep and improve the quality of a nap. We conduct experiments on 28 healthy subjects, each undergoing two nap sessions - one with a quiet background and one with our audio-stimulation. We compare the time-to-sleep in both sessions between two groups of subjects, e.g., fast and slow sleep onset groups. The p-value obtained from Wilcoxon Signed Rank Test is 1.22e-04 for slow onset group, which demonstrates that iSleep can significantly reduce the time-to-sleep for people with difficulty in falling sleep.

Objective – To evaluate the efficacy of levetiracetam (LEV) in continuous spikes and waves during slow sleep (CSWS). Despite first description dates back to 1971, no agreement exists about CSWS treatment. The condition is rare and controlled clinical trials are very difficult to perform, so the reports about efficacy of different drugs are anecdotal. Patients and methods – We introduced LEV in three children affected by symptomatic focal epilepsy and pharmacoresistant CSWS and evaluated clinical, neuropsychological and electroencephalographic outcome. Results – Two cases responded completely, one case showed only a mild reduction of spikes and waves during slow sleep. Conclusion – Even if our report is anecdotal, LEV expands the spectrum of antiepileptic drugs that can be used for the treatment of CSWS. LEV efficacy should be confirmed in larger series.

Hormonal therapy or ketogenic diet often permits overcoming the challenging periods of many epileptic encephalopathies (West and Lennox-Gastaut syndromes and encephalopathy with continuous spike-waves in slow sleep), but relapse affects over 20% of patients. We report here a monocenter pilot series of 42 consecutive patients in whom we combined oral steroids with the ketogenic diet for corticosteroid-resistant or -dependent epileptic encephalopathy. We retrospectively evaluated the effect on seizure frequency, interictal spike activity, neuropsychological course, and steroid treatment course. Twenty-three patients had West syndrome (WS), 13 had encephalopathy with continuous spike-waves in slow sleep (CSWS), and six others had miscellaneous epileptic encephalopathies. All patients succeeded to reach 0.8 to 1.6g/l ketone bodies in the urine following the usual KD regimen. For at least 6 months, 14/42 responded to the addition of the ketogenic diet: 4/23 with WS, 8/13 with CSWS, and 2/6 with miscellaneous epileptic encephalopathies. The addition of the KD allowed withdrawing steroids in all responders. Among them, 10/15 had been patients with steroid-dependent epileptic encephalopathy and 4/27 patients with steroid-resistant epileptic encephalopathy. Therefore, the ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies. Patients presenting with steroid-dependent CSWS seem to be the best candidates.

To investigate differences in sleep spindle properties and scalp topography between patients with rapid eye movement sleep behaviour disorder (RBD) and healthy controls, whole-night polysomnograms of 35 patients diagnosed with RBD and 35 healthy control subjects matched for age and sex were compared. Recordings included a 19-lead 10-20 electroencephalogram montage and standard electromyogram, electrooculogram, electrocardiogram and respiratory leads. Sleep spindles were automatically detected using a standard algorithm, and their characteristics (amplitude, duration, density, frequency and frequency slope) compared between groups. Topological analyses of group-discriminative features were conducted. Sleep spindles occurred at a significantly (e.g. t34 = -4.49; P = 0.00008 for C3) lower density (spindles ∙ min(-1) ) for RBD (mean ± SD: 1.61 ± 0.56 for C3) than for control (2.19 ± 0.61 for C3) participants. However, when distinguishing slow and fast spindles using thresholds individually adapted to the electroencephalogram spectrum of each participant, densities smaller (31-96%) for fast but larger (20-120%) for slow spindles were observed in RBD in all derivations. Maximal differences were in more posterior regions for slow spindles, but over the entire scalp for fast spindles. Results suggest that the density of sleep spindles is altered in patients with RBD and should therefore be investigated as a potential marker of future neurodegeneration in these patients.

Objective To determine the etiology of epilepsy with continuous spikes and waves during slow sleep (CSWS)/electrical status epilepticus during sleep (ESES) in an 8-year old boy with a history of neuroblastoma and opsoclonus-myoclonus. Material & methods A combination of clinical characterization and follow-up, video EEG and laboratory investigations. Results We report the case of an 8-year old boy with a history of neuroblastoma and opsoclonus-myoclonus, who presented with intellectual disability, pharmacotherapy-resistant epilepsy and CSWS/ESES. Although the patient's neuroblastoma had been successfully treated 8 years prior to presentation and an extensive workup did not show a tumor reoccurrence, testing for onconeuronal antibodies was positive for anti-Ma2 and anti-CV2/CRMP5 antibodies. High-dose intravenous methylprednisolone and a taper of oral methylprednisolone were given, leading to a significant clinical improvement. During the taper the patient's condition and EEG manifestations deteriorated again necessitating another cycle of steroid therapy, which lead to a stable improvement. During a 6-month follow-up no CSWS/ESES was seen on EEG and anti-Ma2 and anti-CV2/CRMP5 antibodies remained undetectable. Conclusion This case suggests that onconeuronal antibodies may be involved in the pathogenesis of CSWS/ESES.

The XYY syndrome is a sex chromosome aneuploidy occurring in one of 1,000 live male births. Only few data exist regarding the correlation between this syndrome and epilepsy. An EEG pattern suggestive of benign focal epilepsy with centro-temporal spikes has recently been described in four XYY patients. We report the first patient with XYY trisomy, rolandic spikes, and atypical evolution with continuous spikes and waves during slow sleep (CSWSS). The present report suggests that the association between an EEG pattern similar to that of BECTS and 47, XYY karyotype may not be coincidental. Moreover, we show that an atypical evolution with CSWSS may occur in this chromosomal disorder.

This paper presents the relations between the slow (< 1 Hz) oscillation (characterizing the activity of corticothalamic networks during quiescent sleep in cats and humans), sleep K-complexes, and some paroxysmal developments of sleep patterns. At the cellular level, the slow oscillation is built up by rhythmic membrane depolarizations and hyperpolarizations of cortical neurons. The EEG expression of this activity is marked by periodic K-complexes which reflect neuronal excitation. The slow oscillation triggers, groups and synchronizes other sleep rhythms, such as thalamically generated spindles as well as thalamically and cortically generated delta oscillations. We discuss the distinctness of the slow (< 1 Hz) and delta (1-4 Hz) oscillations. We also show that the slow cortical oscillation underlies the onset of spike-wave seizures during sleep by transforming the periodic K-complexes into recurrent paroxysmal spike-wave complexes.

Summary Background Epileptic syndromes with continuous spikes-waves during sleep (CSWS) represent a wide spectrum of epileptic disorders having CSWS as a common EEG-feature. Defined therapeutic strategies are still lacking. We evaluated the efficacy of lacosamide add-on therapy on the EEG, behavior, and cognition in children with CSWS. Material and methods Eight children with CSWS refractory to other conventional antiepileptic drugs were included in the study. A 24-h EEG recording was performed at 6-month-interval in all patients. The spike-wave index (SWI) was obtained in each 24-h EEG recording. Neuropsychological data were obtained before lacosamide introduction and after a minimum of 12 months of therapy. Results After a 6-month period of therapy, 75% of patients was defined as responder, 12.5% as partial responder and another 12.5% as non-responder. In particular, 24-h EEG normalized in 3 cases (37%). After a minimum of 12 months, 24-h EEG normalized in another patient while two patients showed electroclinical relapses. A total of 62.5% of patients was therefore defined as responder. Neuropsychological functions slightly improved in 25% of patients. Conclusion Although further studies are needed to validate our observations, this study suggests that lacosamide add-on therapy may be safe and effective in children affected by CSWS.

A long‐term follow‐up study was conducted in patients affected by Continuous Spikes and Waves during slow Sleep (CSWS) to evaluate the long-term outcomes. Twenty-five patients (19 males, 6 females), from 2 to 16 years of age (mean age 6 years ± 3 SD), affected by CSWS syndrome, as defined by the International League Against Epilepsy (ILAE, 1989), were enrolled and followed for 11 years (mean duration of follow‐up: 3.9 years). At the time of the appearance of CSWS, one or more neuropsychiatric disorders were present in 96% of the patients, such as behavioral problems in 54%, mental retardation in 37.5%, learning disabilities in 33%, developmental coordination disorder in 17%, language disorder in 12.5%, and pervasive developmental disorder in 8%. During the follow-up, neuropsychiatric dysfunctions remained unaltered in 52% of the patients, worsened in 24%, and improved in only 24%. Our data confirm that CSWS may be associated with a broad spectrum of neuropsychiatric disorders and may promote their worsening over time. Moreover, the findings cannot be generalized to all cases of children with CSWS because most of the children in the subgroups with no change in outcome and worse outcome had symptomatic CSWS.

Cathodal transcranial direct current stimulation (tDCS) decreases cortical excitability. The purpose of the study was to investigate whether cathodal tDCS could interrupt the continuous epileptiform activity. Five patients with focal, refractory continuous spikes and waves during slow sleep were recruited. Cathodal tDCS and sham stimulation were applied to the epileptic focus, before sleep (1 mA; 20 min). Cathodal tDCS did not reduce the spike-index in any of the patients.

Purpose To evaluate the add-on effect of levetiracetam (LEV) treatment on the EEG and clinical status of children with continuous spikes-waves during slow sleep (CSWS). Methods 20 children with CSWS refractory to other conventional antiepileptic drugs (AEDs) received LEV 45–50mg/kg/day as add-on treatment, and were prospectively followed for a minimum period of 18 months. The patient population comprised seven cryptogenic, seven symptomatic and six idiopathic cases (atypical benign partial epilepsy, aBECTs). The electrographic evaluation included 24h EEG recordings taken every six months (minimum of three per child). Electrographically children were categorised as responders, partial responders or non-responders by comparing changes in the spike index (SI) during NREM-sleep with baseline SI before initiation of LEV. The clinical efficacy of LEV was assessed by comparing seizure frequency at the end of follow up with the baseline. The follow up duration varied from 18 to 53 months. Results Electrographic response was observed in 11 patients. Eight patients demonstrated a lasing response (more than 12 months): five from symptomatic, two – cryptogenic and one – idiopathic group respectively. Three children showed a partial response (6–12 months): one from symptomatic and two from idiopathic group. Eleven out of the 20 children were seizure free at baseline and during the whole follow up. The rest, six-symptomatic and three-cryptogenic patients, had seizures prior to LEV treatment initiation. Six became seizure free after add-on therapy with LEV, and in three children a significant reduction of seizure frequency was observed. Conclusion This study suggests that add-on therapy with LEV is more effective in children with CSWS resulting from a known underlying structural brain lesion (the symptomatic group).

Continuous spikes and waves during slow wave sleep (CSWS) is rare and is considered to be an age-related epileptic syndrome occurring only in children. We report the case of a 21-year-old patient diagnosed with this syndrome. The patient had a history of seizures since the age of 3 and was admitted for continuous video/EEG monitoring to evaluate seizure exacerbation and unprovoked outbursts of anger. During 3 days of monitoring, awake EEG recordings showed focal slow wave activity in the right temporal region. CSWS were observed. After a change in his antiepileptic drug regimen, subsequent EEG recordings showed resolution of CSWS. As shown in our patient, CSWS can be observed in adults. In addition, continuous video/EEG monitoring including sleep is important in the evaluation of patients with sudden deterioration of seizure control accompanied by behavioral changes.

The authors report the case of a child with cerebral palsy and refractory epilepsy who developed nonconvulsive status epilepticus without acute medical cause treated successfully with levetiracetam. In accordance with other studies whose authors hypothesized that aggressive treatment may worsen the prognosis in elderly patients with nonconvulsive status epilepticus, the present authors successfully used a more conservative approach to the treatment of nonconvulsive status epilepticus in their patient. This case suggests that levetiracetam is a useful option for the treatment of nonconvulsive status epilepticus in childhood, in accordance with some authors who have described the anticonvulsant effects of levetiracetam in experimental status epilepticus and in status epilepticus in adults and in children with continuous spike waves during slow sleep.

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).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.

A normally developed and healthy 6-year-old girl suffered the onset of epilepsy with generalized tonic-clonic seizures and atypical absences. Initially the EEG showed epileptiform activity over the temporal and parietal regions, later there were episodes of bilateral synchronous spike-wave activity with a frequency of 1.5–2.5 Hz. After a few months, deterioration of cognitive and behavioural functions appeared and gradually increased with the development of a fullblown disintegrative psychosis that went on for several months. Sleep EEG recordings showed the characteristic abnormality described as continuous spikes and waves during slow sleep. Later there was a remarkable improvement of neuropsy chiatric functions but a second outbreak of psychosis seems to have left the girl, who is now 9 years of age, with severe mental impairment.

SUMMARY: 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 (>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. RESUME Cinq enfants presentant une epilepsie avec pointes ondes continues pendant le sommeil lent (POCS) ont eteetudies par les auteurs. Les principales caracteristiques cliniques du syndrome des POCS comprennent: (1) installation entre l'âge de 5 et 7 ans, (2) survenue de plusieurs types de crises (partielles motrices, generalisees motrices et absences atypiques), (3) presence de perturbations du langage et d'anomalies comportementales fondees sur des deficits emotionnels. Les constations EEG ont ete caracterisees par l'existence sur les traces de sommeil de pointes ondes continues diffuses (+ de 95%). Un traitement associant valproate (ou ethosuximide) et clonazepam a permis d'obtenir une disparition de l'etat de mal infraclinique. Les symptomes du syndrome des POCS ont diminue Les auteurs suggerent qu'un traitement associe est justifie dans le syndrome des POCS. RESUMEN Se presentan cinco ninos con epilepsia con “complejos puntaonda continuos durante la fase de sueno lento” (CSWS). Los hallazgos clinicos mas importantes de los CSWS incluyen: 1-comienzo entre los 5 y los 7 anos de edad, 2-aparicion de varios tipos de ataques (motores parciales, motores generalizados y ausencias atipicas) y 3- presencia de trastornos del lenguaje y comportamiento anormal basados en alteraciones emocionales. Los hallazgos en el EEG se caracterizaron por registros, durante el sueno, que mostraban actividad difusa de punta-onda casi continua (mas de 95%). Despues de un tratamiento con Valproato (o etosuximida) y Clonazepam, el status de complejos punta-onda desaparecieron. Tambien disminuyeron los sintomas y signosde los CSWS. Sugerimos que un tratamiento combinado es apropiado para control de los CSWS. ZUSAMMENFASSUNG Uber 5 Kinder mit einer Epilepsie mit kontinuierlichen spikewaves wahrend des langsamen Schlafs (CSWS) wird berichtet. Klinische Hauptmerkmale sind: 1. Beginn zwischen 5. und 7. Lebensjahr 2. Auftreten von verschiedenen Anfallen, z.B. fokale und generalisierte motorische Anfalle sowie atypische Absencen. 3. Auftreten von Sprachstorungen und Verhaltensauffalligkeiten aufgrund emotionaler Verschlechterung Das EEG zeigt in den Schlafableitungen fast kontinuierliche diffuse slow-spike-wave-Aktivitat (bei fast 95%). Nach einer Kombinationstherapie mit Valproat (Suximid) und Clonazepam verschwand der SW-Status, ebenso verringerten sich die klinischen Auffalligkeiten. Aufgrund dieser Erfahrungen halten wir diese Komedikation fur die angemessene Behandlung des CSWS.

The slow wave sleep (0.5–2.5 Hz) of 42 subjects who slept in a laboratory for more than 8 h was examined. Although the amount of slow wave sleep diminished exponentially across the first 11 h of sleep, there is evidence of an increase in amount of slow wave sleep in more extended sleep. This finding complicates the concepts of slow wave sleep as an index of sleep need due to prior wakefulness or an index of a restoration process.

Twenty-one prepubertal children of small stature, 10 boys and 11 girls, aged from 4-3 to 12-8 years, were studied. Their height was less than 3rd centile, and during the preceding year all had a growth rate less than 4-5 cm/year. Arginine and L-dopa tests were given, and the release of growth hormone (GH) during monitored sleep was investigated. On the basis of the electroencephalogram and horizontal electro-oculogram, sleep was divided into stages 1-2-3-4 and rapid-eye-movement. All the children had a GH response greater than 8 ng/ml in at least one of the two pharmacological tests, and were therefore accepted as not suffering from GH deficiency. In all 21 children during sleep there was at least one secretory peak with GH greater than 8 ng/ml. Of a total of 46 secretory peaks recorded, 22 (48%) took place during deep, slow sleep (stages 3-4), 10 (22%) during light sleep (stage 2), 10 (22%) during REM sleep, and 4 (8%) during wakening. In 4 patients (19%) no secretory peak was observed during stages 3-4, even though there were peaks at other times. The data (a) show that it is essential to monitor GH throughout the night to ascertain with certainty the presence or absence of physiological secretory peaks of GH; (b) emphasise the rare disagreement between pharmacological and physiological tests; (c) suggest the use of this physiological test for GH secretion in those cases where the insulin test may be hazardous.

Summary: Polygraphic all-night sleep recordings of 11 children with benign epilepsy of childhood with rolandic spikes (BERS) were investigated from the viewpoint of spike distribution. Spike/min ratios were calculated with regard to different sleep stages and waking, identical stages of the consecutive cycles, and stages 1–2 taking place on the descending versus the ascending slopes of sleep cycles. Maximum spike/min ratios were related to slow sleep stages, especially delta sleep, and in general to the first cycle. Stages 1–2 on the descending (DESC) slopes of consecutive cycles showed a decrease in spike density during the night, as opposed to the increasing rate of activation of the same stages on the ascending (ASC) slopes. Based on our results, we suggest that the actual drive of spiking as well as seizures in BERS is the functional overweight of sleep-inducing mechanisms. RESUMEN Desde el punto de vista de la distribucion de las puntas se han estudiado 11 ninos con epilepsia benigna con puntas rolandicas mediante registros poligraficos durante la totalidad del sueno nocturne Le relacion punta/min se calculo con respecto a los diversos estadios del sueno y de vigilia, en relacion con estadios identicos de ciclos consecutivos, y en relacion con estadios su-perficiales del sueno que tienen lugar en los momentos descen-dentes o ascentes de los ciclos del sueno. Los resultados maximos de la relacion punta/min se relacionaron con estadios de sueno lento, especialmente sueno delta, y en general con el primer ciclo. El sueno superficial durante las fases descen-dientes de ciclos consecutivos mostro una reduction en la potencia de activacion durante la noche en contraposition al incre-mento del ritmo de activacion de los mismos estadios durante las fases ascendentes del sueno. Basandose en estos resultados los autores sugieren que el motor real de produccion de puntas y de ataques en la epilepsia benigna infantil reside en el exceso de mecanismos inductores del sueno. ZUSAMMENFASSUNG Polygraphische Schlaf-Nachtableitungen bei 11 Kindern mit BERS wurden ausgewertet unter Berucksichtigung der Spike-Verteilung. Das Spike/Minute Verhaltnis wurde berechnet fur die verschiedenen Schlafstadien und Wachzeiten, fur die iden-tischen Stadien aufeinanderfolgender Schlafzyklen und fur den Leichtschlaf beim Ubergang vom Erwachen zum Wiedereinsch-lafen. Das Maximum der Spike/Minute Werte war gebunden an die langsamen Schlafstadien, besonders an den Deltaschlaf und meistens an den ersten Cyclus. Im Leichtschlaf, im abstei-genden Schenkel des nachfolgenden Cyclus, nahm das Akti-vierungspotential im Laufe der Nacht ab, wahrend es beim aufsteigenden Schenkel des gleichen Stadiums zu einer Zu-nahme der Aktivierung kam. Aufgrund der Ergebnisse nehmen die Autoren ein funktionelles Ubergewicht schlafinduzierender Mechanismen an, sowohl im Verlauf der Spike-Entladung als auch im Anfall bei BERS.

A polygraphic investigation was made of daytime sleep in healthy infants with analysis of the EEG, oculogram, muscle tone, fluctuations in skin resistance, respiration, ECG, rheoencephalogram, and rheogram of the leg. Infants with cerebral palsy of perinatal genesis were investigated by the same method. The results showed that in early infancy it is possible to distinguish the basic stages of slow sleep and the stage of fast sleep, although the electroencephalographic experssion of these stages in infants has special features of its own. The age dynamics of the polygraphic picture of sleep shows that the electroencephalographic, autonomic, and motor components of sleep, although clearly coordinated in the various stages, have at the same time considerable autonomy. This is confirmed by the results obtained by analysis of the cerebral pathology. The need for adequate assessment of this complex function in order to elucidate the physiological nature of sleep is emphasized.

All-night sleep of 5 healthy male subjects was scored on the basis of EEG (paper records), EMG and EOG into the stages of wakefulness, REM sleep and slow sleep stages 1-4 according to Rechtschaffen and Kales. Spectral analysis for 8 EEG channels was then performed and spectral parameters (total power and coherence for certain frequency bands) extracted. Stepwise linear discriminant analysis was applied to these spectral parameters to see how well the polygraphically defined sleep stages were recognized. While the results of each intrasubject analysis were satisfactory (error rates between 10 and 15%), a more detailed analysis revealed that most errors occur between nearby slow sleep stages or between S1 and REM or wakefulness. This is related to the fact that Rechtschaffen and Kales classify into discrete stages an essentially continuous process and this is, to some extent, arbitrary. This interpretation is supported by examples. Cross-classification of each subject on the basis of the remaining 4 increases the error rates drastically. A simple way of avoiding this effect, by standardizing the individual data, is shown to work nicely in this case.

SUMMARY The authors polygraphically studied the nocturnal sleep of 20 neurologically normal children with typical centrotemporal spikes. The children were divided into two groups: (A) 10 children with centrotemporal spikes and benign epilepsy; and (B) 10 children with centrotemporal spikes without epilepsy. The mean age when the average period of sleep record was performed was the same for the two groups, 8.5 years. The cyclic organization of sleep and the percentages of the different stages were normal in all 20 subjects. The number of spikes was counted in all the subjects during wakefulness and during different stages of sleep. All subjects of both groups showed an important increase in the frequency of spikes going from drowsiness until slow sleep; on the other hand, the activity remained high during REM sleep only for subjects of Group A. Other differences between the two groups concerned the appearance during sleep of generalized spike waves and independent Rolandic spikes. The authors conclude with the affirmation that the polygraphic study of nocturnal sleep in children with Rolandic spikes can be an additional parameter for differential diagnosis between children with and those without epilepsy. RESUME Les auteurs ont etudie en polygraphie le sommeil de nuit complet de 20 enfants avec pointes Rolandiques sur l'EEG, sans troubles neurologiques. Ces enfants ont ete repartis en deux groups. Groupe A: 10 enfants avec pointes Rolandiques et epilepsie benigne de l'enface; Groupe B: 10 enfants avec pointes Rolandiques sans epilepsie. L'âge moyen auquel a ete pratique le traces de sommeil est homogene pour les deux groupes (8.5 ans). Les 20 sommeils ont montre une organisation cyclique et un pourcentage en phases normaux pour l'âge. Chez tous les sujets des deux groupes les decharges focales ont ete quantifiees au cours de la veille et des differentes phases du sommeil, y compris la PMO. Chez les 20 sujets il existait une tres importante activation des decharges Rolandiques, de l'endormissement au sommeil lent; par contre l'activation persistait importante en PMO, seulement chez les sujets avec epilepsie. Les auteurs considerent que cette difference d'activation au cours de la PMO, de meme que le pourcentage different des decharges generalisees de PO au cours du sommeil (40% Groupe A, 10% Groupe B) et des paroxysmes independant (20% Groupe A, 90% Groupe B) pourraient etre un element de diagnostic differentiel entre des sujets avec pointes Rolandiques, avec ou sans epilepsie.

Multi-unit activity of 14 subcortical structures was studied during drowsiness and sleep in patients with depth electrodes implanted in the brain for therapeutic purposes. The mean firing rate of the multi-unit activity was found to decrease during “slow-wave” sleep in each cycle. The multi-unit activity was sharply increased during paradoxical sleep. In successive sleep cycles the mean firing rate somewhat increased from cycle to cycle during slow sleep. The mean firing rate was considerably increased during wakefulness after a sufficiently long sleep, as compared with the initial background values. Fluctuations of the mean firing rate were characteristic of paradoxical sleep. When studying simultaneously 2 or 3 structures, both uniform or different changes of the neuronal activity were possible. Changes of the firing rate in separate structures may develop a few seconds prior to the “clinical display” of the REM phase. All (or nearly all) the structures, whose activity during sleep is rather independent, are presumed to be able to be a source of the REM phase.

The ECoG and behavioural effects of administering 3 benzodiazepines (diazepam, nitrazepam, lorazepam) were tested in baboons restrained in a chair, with arms fastened (a situation which is considered ‘anxiogenic’). Considering our previous data with ECoG recording of focal rhythms from area somatic I, the 3 drugs were revealed as ‘anxiolytic’. Differences were noticed with respect to their hypnotic effects: no sleep was elicited under diazepam; a considerable amount of slow sleep was observed with lorazepam; nitrazepam produced a succession of short waking/sleep cycles.

The method of statistical amplitude analysis is developed and applied to the study of vigilance fluctuations in the normal rat. These are then compared with the cataleptic state produced by prochlorpemazine. With unrestrained rats, the comparison between the time-courses of the integrated electrocorticogram (ECoG) and neck-muscles electromyogram (EMG), provided precise and objective data for the measurement of vigilance phases (arousal, sedation, slow sleep and paradoxical sleep) as well as drug effects. After prochlorpemazine administration a characteristic steadystate of the ECoG and EMG appeared. Compared with the normal animal, the integrated ECoG and EMG was much less variable and this effect persisted together with the cataleptic state, which is recognized by the crossing of homolateral legs. The statistical amplitude analysis was based on comparitive histograms and repartition functions (cumulative frequency curves) plotted on probability paper. The mean (voltage) integrated amplitude values were the quantified ECoG and EMG, integrated each 20-sec period. Graphic comparison was completed by numerical statistical analysis of data (Student's t -test, Snedecor's F -test and chi-square goodness of fit). This method allows discrimination between drug-effects and normal vigilance fluctuations. When catalepsy decreased, normal cortical and electromyographic variability resumed.

1. 1. GHB given in sufficient oral dosage to humans induces a slow synchronized EEG similarto the naturally occurring EEG of “slow” sleep. 2. 2. There is an abrupt EEG transition from the awake alpha record to delta and theta slowing without associated clouding of consciousness. 3. 3. Two types of paradoxical EEG-behavioral dissociation were noted: (a) alpha rhythms were seen with unconscious subjects; (b) delta and theta slowing was briefly seen in awake responsive subjects. 4. 4. It is speculated that, in the intact human, the principal action of GHB is to exert a direct inhibitory influence on reticular centers which ordinarily function to inhibit the onset of slow sleep.