Continuous Spike-waves During Sleep Research Articles

Long-term follow-up of cognitive functions in patients with continuous spike-waves during sleep (CSWS).

Continuous spike-waves during sleep (CSWS) are associated with several cognitive, neurological, and psychiatric disorders, which sometimes persist after CSWS disappearance. The purpose of this retrospective study was to investigate the correlation between general (clinical and instrumental) and neuropsychological findings in CSWS, to identify variables that predispose patients to a poorer long-term neuropsychological outcome. Patients with spikes and waves during sleep with a frequency ≥25/min (spikes and waves frequency index - SWFI) were enrolled. There were patients presenting abnormal EEG activity corresponding to the classic CSWS and patients with paroxysmal abnormalities during sleep <85% with SWFI ≥25/min that was defined as excessive spike-waves during sleep (ESWS). Clinical and instrumental features and neuropsychological findings during and after the spike and wave active phase period were considered. A statistical analysis was performed utilizing the Spearman correlation test and multivariate analysis. The study included 61 patients; the mean follow-up (i.e., the period between SWFI ≥25 first recording and last observation) was 7years and 4months. The SWFI correlated inversely with full and performance IQ during CSWS/ESWS. Longer-lasting SWFI ≥25 was related to worse results in verbal IQ and performance IQ after CSWS/ESWS disappearance. Other variables may influence the neuropsychological outcome, like age at SWFI ≥25 first recording, perinatal distress, pathologic neurologic examination, and antiepileptic drug resistance. This confirms that CSWS/ESWS are a complex pathology and that many variables contribute to its outcome. The SWFI value above all during CSWS/ESWS and long-lasting SWFI ≥25 after CSWS/ESWS disappearance are the most significant indexes that appear mostly to determine cognitive evolution. This finding underscores the importance of EEG recordings during sleep in children with a developmental disorder, even if seizures are not reported, as well as the importance of using therapy with an early efficacy.

Sleep-potentiated epileptiform activity in early thalamic injuries: Study in a large series (60 cases)

The study aims at a better definition of continuous spike-waves during sleep (CSWS) with an early thalamic lesion, focusing on various grades of sleep-potentiated epileptiform activity (SPEA). Their possible relationship with different clinical features was studied to try to define prognostic factors of the epileptic disorder, especially relating to behavior/cognitive outcome, in order to improve prevention and treatment strategies. Sixty patients with early thalamic injury were followed since the first registration of SPEA with serial neurological, long term EEG monitoring and neuropsychological examinations, as well as neuroimaging and a detailed clinical history. They were classified in three different groups according to the sleep spike-waves (SW) quantification: electrical status epilepticus during sleep (ESES), more than 85% of slow sleep; overactivation between 50% and 85% and simple activation between 10 and 50%). Results were then examined also with a statistical analysis. In our series of CSWS occurring in early brain injured children with unilateral thalamic involvement there is a common neuropathologic origin but with various grades of SPEA severity. Statistical analysis showed that patients evolving toward ESES presented more commonly the involvement of the mediodorsal part of thalamus nuclei and a bilateral cortico-subcortical brain injury, epilepsy was more severe with a delayed onset; moreover, in the acute stage .ESES patients presented the worst behavior/cognitive performances. As to cognitive and behavior outcome, longer SPEA duration as well as bilateral brain injury and cognitive/behavior impairment in acute phase appear linked to a poor outcome; some particular neuropathology (ischemic stroke and haemorrhagic infarction) as well as hydrocephalus shunting are associated with behavior disorders. Discrete features seem to support different underlying mechanisms in ESES patients in comparison with less severe SPEA; they represent negative prognostic factors. Longer SPEA duration as well as bilateral brain injury and cognitive/behavior impairment in acute phase seem predictive of a worse cognitive/behavior outcome.

Default mode network hypometabolism in epileptic encephalopathies with CSWS

Previous studies investigating cerebral metabolic changes associated with continuous spike-waves during sleep (CSWS) compared the metabolism of children with CSWS with that of healthy adults, precluding any assessment in brain areas showing physiologic age-related metabolic changes. Here, we investigated the metabolic and connectivity changes characterizing the acute phase of CSWS activity by comparing awake brain metabolism of children with CSWS with that of pediatric pseudo-controls. Positron emission tomography using [18F]-fluorodeoxyglucose (FDG-PET) was performed in 17 awake children with cryptogenic CSWS (5 girls, age: 5-11 years). Voxel-based analyses identified significant metabolic changes in CSWS patients compared with 18 pediatric pseudo-controls (12 girls, age: 6-11 years, non-CSWS focal cryptogenic epilepsy with normal FDG-PET). CSWS-induced changes in the contribution of brain areas displaying metabolic changes to the level of metabolic activity in other brain areas were investigated using pathophysiological interaction. Hypermetabolism in perisylvian regions bilaterally and hypometabolism in lateral and mesial prefrontal cortex, precuneus, posterior cingulate cortex and parahippocampal gyri characterized the acute phase of CSWS (p<0.05 FWE). No change in thalamic metabolism was disclosed. Altered functional connectivity was found between hyper- and hypometabolic regions in CSWS patients compared with pediatric pseudo-controls. This study demonstrates hypometabolism in key nodes of the default mode network (DMN) in awake patients with CSWS, in relation with a possible phenomenon of sustained remote inhibition from the epileptic foci. This hypometabolism might account for some of the acquired cognitive or behavioral features of CSWS epileptic encephalopathies. This study failed to find any evidence of thalamic metabolic changes, which supports the primary involvement of the cortex in CSWS genesis.

Spike wave location and density disturb sleep slow waves in patients with CSWS (continuous spike waves during sleep)

In CSWS (continuous spike waves during sleep) activation of spike waves during slow wave sleep has been causally linked to neuropsychological deficits, but the pathophysiologic mechanisms are still unknown. In healthy subjects, the overnight decrease of the slope of slow waves in NREM (non-rapid eye movement) sleep has been linked to brain recovery to regain optimal cognitive performance. Here, we investigated whether the electrophysiologic hallmark of CSWS, the spike waves during sleep, is related to an alteration in the overnight decrease of the slope, and if this alteration is linked to location and density of spike waves. In a retrospective study, the slope of slow waves (0.5-2Hz) in the first hour and last hour of sleep (19 electroencephalography [EEG] electrodes) of 14 patients with CSWS (3.1-13.5years) was calculated. The spike wave "focus" was determined as the location of highest spike amplitude and the density of spike waves as spike wave index (SWI). There was no overnight change of the slope of slow waves in the "focus." Instead, in "nonfocal" regions, the slope decreased significantly. This difference in the overnight course resulted in a steeper slope in the "focus" compared to "nonfocal" electrodes during the last hour of sleep. Spike wave density was correlated with the impairment of the overnight slope decrease: The higher the SWI, the more hampered the slope decrease. Location and density of spike waves are related to an alteration of the physiologic overnight decrease of the slow wave slope. This overnight decrease of the slope was shown to be closely related to the recovery function of sleep. Such recovery is necessary for optimal cognitive performance during wakefulness. Therefore we propose the impairment of this process by spike waves as a potential mechanism leading to neuropsychological deficits in CSWS. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Neurophysiological activity underlying altered brain metabolism in epileptic encephalopathies with CSWS

We investigated the neurophysiological correlate of altered regional cerebral glucose metabolism observed in children with epileptic encephalopathy with continuous spike-waves during sleep (CSWS) by using a multimodal approach combining time-sensitive magnetic source imaging (MSI) and positron emission tomography with [(18)F]-fluorodeoxyglucose (FDG-PET). Six patients (4 boys and 2 girls, age range: 4-8 years, 3 patients with Landau-Kleffner syndrome (LKS), 3 patients with atypical rolandic epilepsy (ARE)) were investigated by FDG-PET and MSI at the acute phase of CSWS. In all patients, the onset(s) of spike-waves discharges were associated with significant focal hypermetabolism. The propagation of epileptic discharges to other brain areas was associated with focal hypermetabolism (five patients), hypometabolism (one patient) or the absence of any significant metabolic change (one patient). Interestingly, most of the hypometabolic areas were not involved in the epileptic network per se. This study shows that focal hypermetabolism observed at the acute phase of CSWS are related to the onset or propagation sites of spike-wave discharges. Spike-wave discharges propagation can be associated to other types of metabolic changes, suggesting the occurrence of various neurophysiological mechanisms at the cellular level. Most of the hypometabolic areas are not involved in the epileptic network as such and are probably related to a mechanism of remote inhibition. These findings highlight the critical value of combining FDG-PET with time-sensitive functional neuroimaging approaches such as MSI to assess CSWS epileptic network when surgery is considered as a therapeutic approach.

Neuronal networks in children with continuous spikes and waves during slow sleep

Sir, We read with great interest the paper by Siniatchkin et al. (2010), in which they report the results of electroencephalogram (EEG) combined with functional MRI studies performed in children with epileptic encephalopathies with continuous spike-waves during sleep (CSWS). This paper undoubtedly brings novel and valuable data on the pathophysiology of epileptic encephalopathies with CSWS, pointing out the implication of subcortical structures such as the striatum and the thalamus in these disorders. This study actually supports the hypothesis that the neurological regression in CSWS is not only related to the neurophysiological impairment at the site of the epileptic focus but also to epilepsy-induced changes in distant and connected brain areas with a particular involvement of the default mode network (De Tiege et al. , 2009). Nevertheless, we would like to address some limitations regarding the methodology used in this work. The EEG-functional MRI methodology enhances the statistical model used for functional MRI data analysis thanks to various EEG features such as timing, duration, amplitude, morphology and topography of the epileptic activity. In preliminary analyses, Siniatchkin et al. (2010) found a poor correlation between functional MRI results and electrical source imaging results obtained after averaging all …

Impact of severe epilepsy on development: Recovery potential after successful early epilepsy surgery

Epilepsy surgery in young children with focal lesions offers a unique opportunity to study the impact of severe seizures on cognitive development during a period of maximal brain plasticity, if immediate control can be obtained. We studied 11 children with early refractory epilepsy (median onset, 7.5 months) due to focal lesion who were rendered seizure-free after surgery performed before the age of 6 years. The children were followed prospectively for a median of 5 years with serial neuropsychological assessments correlated with electroencephalography (EEG) and surgery-related variables. Short-term follow-up revealed rapid cognitive gains corresponding to cessation of intense and propagated epileptic activity [two with early catastrophic epilepsy; two with regression and continuous spike-waves during sleep (CSWS) or frontal seizures]; unchanged or slowed velocity of progress in six children (five with complex partial seizures and frontal or temporal cortical malformations). Longer-term follow-up showed stabilization of cognitive levels in the impaired range in most children and slow progress up to borderline level in two with initial gains. Cessation of epileptic activity after early surgery can be followed by substantial cognitive gains, but not in all children. In the short term, lack of catch-up may be explained by loss of retained function in the removed epileptogenic area; in the longer term, by decreased intellectual potential of genetic origin, irreversible epileptic damage to neural networks supporting cognitive functions, or reorganization plasticity after early focal lesions. Cognitive recovery has to be considered as a "bonus," which can be predicted in some specific circumstances.

Relationships between continuous spike-waves during sleep (CSWS) and antiepileptic drug resistance

Background and aims: The spectrum of neuropsychiatric disorders associated with continuous spike-waves during slow wave sleep (CSWS) syndromes is widely debated. Although seizures and CSWS disappear within puberty, heterogeneous neuropsychological and behavioural disorders can persist. This feature has increased the interest in etiopathogenesis and negative prognostic factors of these conditions. Delayed diagnosis and appropriate therapy, the high frequency, generalization, early onset, prolonged duration and drug resistance of EEG paroxysmal abnormalities are all unfavourable prognostic factors for neuropsychological and behavioural evolution. Pre-existing cerebral lesions, in some cases, may aggravate the prognosis. Case reports: We describe five patients with drug resistant CSWS presenting different clinical-EEG features. One of them had a typical picture of CSWS with paroxysmal abnormalities occupying more than 85% of N-REM sleep EEG recording (case 4); another had a classical Landau Kleffner Syndrome (LKS) (case 5). All cases presented CSWS resistant to several antiepileptic drugs; the localization of prevailing EEG paroxysmal abnormalities showed a good relation with neuropsychological findings, irrespective of IQ. All patients except case 1 presented IQ regression, with a significant gap between VIQ and PIQ to the detriment of the PIQ for cases 2, 3 and 4 and of VIQ for case 5 with LKS. IQ improved in cases 2 and 4 even if a gap remained to the detriment of PIQ in case 2. Cases 3 and 5 improved after CSWS disappearance even though both had a borderline FIQ at the last observation. Behavioural problems were present in all cases except the first, improving after CSWS fragmentation. Seizures occurred in all patients except case 3 representing the first symptom, but they generally disappeared before CSWS fragmentation. Cerebral lesions were present in cases 2 and 4 but did not seem to be responsible for CSWS evolution. Conclusion: It is necessary to be aware that CSWS can develop and that early diagnosis is very important to start an antiepileptic treatment. Further studies with a large sample and homogeneous EEG criteria are required to better characterize the enigma of CSWS.

Reversible acquired epileptic frontal syndrome and CSWS suppression in a child with congenital hemiparesis treated by hemispherotomy

A boy with a right congenital hemiparesis due to a left pre-natal middle cerebral artery infarct developed focal epilepsy at 33 months and then an insidious and subsequently more rapid, massive cognitive and behavioural regression with a frontal syndrome between the ages of 4 and 5 years with continuous spike-waves during sleep (CSWS) on the EEG. Both the epilepsy and the CSWS were immediately suppressed by hemispherotomy at the age of 5 years and 4 months. A behavioural-cognitive follow-up prior to hemispherotomy, an per-operative EEG and corticography and serial post-operative neuropsychological assessments were performed until the age of 11 years. The spread of the epileptic activity to the “healthy” frontal region was the cause of the reversible frontal syndrome. A later gradual long-term but incomplete cognitive recovery, with moderate mental disability was documented. This outcome is probably explained by another facet of the epilepsy, namely the structural effects of prolonged epileptic discharges in rapidly developing cerebral networks which are, at the same time undergoing the reorganization imposed by a unilateral early hemispheric lesion. Group studies on the outcome of children before and after hemispherectomy using only single IQ measures, pre- and post-operatively, may miss particular epileptic cognitive dysfunctions as they are likely to be different from case to case. Such detailed and rarely available complementary clinical and EEG data obtained in a single case at different time periods in relation to the epilepsy, including per-operative electrophysiological findings, may help to understand the different cognitive deficits and recovery profiles and the limits of full cognitive recovery.

Thursday July 6, 2006 11:30-13:30 Hall 3A Discussion Group Session Further understanding of the pathophysiological mechanisms involved in Landau-Kleffener and related syndromes

Abstract 1 P. Van Bogaert ( 1 Université Libre de Bruxelles, Hôpital Erasme, Belgium ) The pathophysiological mechanisms underlying the EEG phenomenon of continuous spike-waves during sleep (CSWS) and related cognitive and behavioral deficits remain poorly understood. It is now admitted that diffusion of the epileptiform discharges during NREM sleep is related to a mechanism of secondary bilateral synchrony from a focal cortical onset. It is probable that thalamic nuclei play an important role in this phenomenon, presumably through a development of the physiological slow-sleep oscillation into diffuse slow waves because of the lack of inhibitory constraint. This hypothesis is supported by experimental CSWS-like pattern obtained in cats following unilateral thalamic ablation. The role of the thalamus in the generation of the CSWS phenomenon was recently emphasized by reports of patients showing thalamic clastic lesions on MRI. Studies performed using PET with 18F-fluorodeoxyglucose (FDG) by our group and by others in children with CSWS and normal MRI have failed to show consistent thalamic abnormalities, but data analysis is complicated by the fact that physiological metabolic changes occur in the thalamus during brain development. Indeed, the metabolic activity of the thalamus adjusted for global metabolism increases significantly during childhood. On the other hand, numerous studies have shown that cortical metabolic abnormalities are frequently found in epileptic children with CSWS. The latter consist in either focal hypermetabolism or focal hypometabolism. The analysis of our FDG-PET data led to the following conclusions: (1) The hypermetabolic zone is the ictal onset zone; (2) Hypermetabolic areas are usually associated with distinct cortical hypometabolic areas, probably as a result of either loss of functional connectivity or inhibition mechanism; (3) Both hypermetabolic and hypometabolic areas tend to decrease or even disappear at the recovery phase of CSWS; and (4) Similar types of metabolic patterns and evolution may be seen in children with CSWS associated with polymicrogyric-like lesions.

Coexistence of Idiopathic Rolandic Epilepsy and CSWS in Two Families

To report two families combining benign childhood epilepsy with centrotemporal spikes (BCECS) and cryptogenic epilepsy with continuous spike-waves during sleep (CSWS) in first-degree relatives. Clinical, EEG, and cerebral imaging data are described. FAMILY 1: The proband was 3 years old at epilepsy onset. First seizures were convulsive, with centrotemporal spikes on EEG. At age 5 years, he had complex partial seizures, psychomotor regression, and centrotemporal CSWS. [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) showed left parietal hypermetabolism. After several antiepileptic drug (AED) trials, valproate (VPA) and ethosuximide (ESM) induced seizure remission, CSWS disappearance, and psychomotor improvement. Learning disabilities, however, persisted. Family history was remarkable for BCECS in his father. FAMILY 2: The proband was 2 years old at epilepsy onset. First seizures were convulsive, with centrotemporal CSWS on EEG. Despite several AED trials including corticosteroids, focal negative myoclonia, atypical absences, and psychomotor regression occurred, leading to severe mental retardation. FDG-PET showed bilateral parietal hypermetabolism. Vagus nerve stimulator was implanted. Her family history was remarkable for BCECS in her father and febrile convulsions in infancy in her mother. These data suggest the existence of a common genetic basis between BCECS and cryptogenic epilepsies with CSWS. The higher expression in patients with CSWS could be related to other genetic or acquired factors. These data suggest that these epileptic syndromes constitute edges of a continuum.

The spectrum of acquired cognitive disturbances in children with partial epilepsy and continuous spike-waves during sleep: A 4-year follow-up case study with prolonged reversible learning arrest and dysfluency

We report a longitudinal study (7-11 years) of a previously normal boy (MR) who presented from the age of 5 years with rare partial motor seizures and atypical 'absences'. The history revealed a stagnation in development and speech difficulties a few months before onset of his epilepsy. The first waking electroencephalogram (EEG) showed rare generalized discharges during hyperventilation. Magnetic resonance imaging revealed an arachnoid cyst in the frontotemporal region. Although his epilepsy never became severe, he experienced important learning difficulties. Subsequent EEGs became increasingly active with left focal epileptic activity and continuous spike-waves during sleep (CSWS) present from the first sleep EEG. The first neuropsychological evaluation (7 years) showed a speech dysfluency, word finding and naming problems, inattention and low intelligence quotient. Carbamazepine was changed to clobazam and later ethosuximide was added with a rapid improvement (within 1 month) in linguistic and cognitive performances as well as in behaviour. Furthermore, the patient showed considerable progress in acquisition over the next months whereas learning to read had previously been very difficult. The epileptic activity gradually disappeared and he was able to follow regular school at an age-appropriate level. This case adds a new facet to the already recognized more obvious acquired neuropsychological disturbances known to occur in some partial childhood epilepsy syndromes with CSWS (aphasia, dementia). It manifested as prolonged insidious stagnation in learning and subtle language disability. This study documents rapid specific language improvement with change in anti-epileptic drugs and a restored immediate and long-term learning capacity, suggesting a direct but 'hidden' role of epilepsy.