Purpose:  Currently, in continuous spikes and waves during sleep (CSWS) there is a lack of systematic assessments of the clinically relevant stages and the evolution of the electroencephalographic features. The aim of this study is to describe the evolution over time of clinical and electroencephalographic features in CSWS. Methods:  We enrolled patients from our video-electroencephalography (EEG) monitoring unit with CSWS and with overnight EEG studies with at least one overnight assessment per year over a minimum period of 3 years. We studied clinical presentation and electroencephalographic features. We calculated the (1) spike-wave percentage (SWP) as the percentage of 1-s bins containing at least one spike-wave complex and (2) spike frequency (SF) as the number of spikes per 100 s. Key Findings:  Nine children (six boys) met the inclusion criteria during a 15-year period. Seven (78%) had an abnormal development prior to the epilepsy onset, and in two (22%) seizures were the only presenting symptom. Median age at epilepsy onset was 2 years (range 2 days to 4 years), at neuropsychological regression 5.1 years (4-7.7 years), and at seizure freedom 8.6 years (6.5-11.4 years). Median duration and range of clinically relevant stages were as follows: dormant stage (birth-epilepsy onset median 2 years, range 2 days-4 years), prodromal stage (epilepsy onset-neuropsychological regression 3.9 years, range 0.9-7.7 years), acute stage (neuropsychological regression-seizure freedom 2.9 years, range 2.1-6.6 years), and residual stage (after seizure freedom). Seven patients (78%) had a structural lesion on neuroimaging. At last follow-up (median 11.4 years, range 7.2-20.3 years), eight patients (89%) were receiving antiepileptic treatment, and all patients had residual neurocognitive deficits. During the acute stage, SWP was <85% in 13 (42%) of 31 assessments, and after seizure freedom, 3 of 5 patients (60%) had SWP >85%. Evolution of electroencephalographic patterns included increasing-decreasing, continuously elevated, and fluctuating patterns (33.3% each). There was good correlation between SWP and SF (Spearman correlation-coefficient = 0.942; p < 0.0001). SF, which can exceed 100%, reflected changes in electroencephalography pattern in more detail than SWP, which cannot exceed 100% and therefore has a ceiling effect. Significance:  Our series systematically studied the age of occurrence of the significant clinical events. These may assist in defining clinical stages, which can provide a useful framework for future clinical trials in patients with CSWS. The severity of the epileptiform discharges on EEG did not always correlate with seizure frequency and severity; epileptiform discharges could be prominent after seizure freedom and fluctuated along the course of the disease. The values of SWP and SF correlated well, but SWP based on 1-s bins has the potential disadvantage of a ceiling effect.

Purpose:  Epileptic spasms are seizures that occur predominantly in children and are characterized by clusters of brief axial movements. Epileptic spasms may occur in the context of a variety of syndromes. Previous research has found that epileptic spasms occur in a sleep/wake and diurnal rhythm. The purpose of this study was to identify these patterns in different age groups. Methods:  Charts of 2,021 patients with epilepsy undergoing video-electroencephalography (EEG) monitoring over a 10-year period were reviewed for presence of epileptic spasms and analyzed for their occurrence during the day (6 a.m. to 6 p.m.) or night, out of wake or sleep, and in 3-h time-blocks throughout the day. Exact epileptic spasm time, EEG localization, and the presence or absence of magnetic resonance imaging lesion were also recorded. Patients were separated into two age groups: A ages 3 and under, and over age 3. Statistical analysis of seizure occurrence in time bins was carried out using binomial calculations. p-Values <0.05 were taken as significant. Using exact seizure times, a generalized linear mixed model of the Poisson-family with a square root link function was used to calculate mean seizure times. Age, as a binary variable, and time, as a categorical variable, was treated as fixed effect predictors, and individual effects were modeled as random effects. For comparison between the two age groups, over age 3 and under age 3, seizure times were transformed into circular variables. A circular analysis of variance test was used to assess for the difference in mean seizure time, assuming a von Mises distribution of the circle. Key Findings:  We analyzed 219 clusters of epileptic spasms in 51 patients (15 girls; mean age 2.15 ± 2.22 years). Forty-two patients younger than 3 years of age had 163 seizures and nine patients older than 3 years had 56 seizures. Epileptic spasms occurred predominantly during wakefulness (p < 0.001) and during daytime (p < 0.001). Epileptic spasms occurred most frequently between 9 a.m. and noon (p < 0.05) and between 3 p.m. and 6 p.m.(p < 0.001). Patients without magnetic resonance imaging lesions had most seizures between 9 a.m. and noon (p < 0.01) and 3 p.m. and 6 p.m.(p < 0.001). Thirty-seven patients had 157 epileptic spasms (71.2%) with generalized EEG patterns and 14 patients had 62 epileptic spasms (28.8%) with focal EEG patterns. Generalized EEG seizures occurred more frequently than focal EEG seizures (p < 0.001). Following age stratification, patients younger than 3 years had most epileptic spasms between 9 a.m. and noon (p < 0.05) and 3 p.m. and -6 p.m.(p < 0.01) and patients older than 3 years had most epileptic spasms between 6 a.m. and -9 a.m.(p < 0.05) and a second peak between 3 p.m. and 6 p.m., although the difference was not statistically significant due to insufficient numbers. Using continuous time analysis, the mean seizure time in the under age 3 and the over age 3 groups was 2:24 p.m. and 11:40 a.m. Using a circular analysis of variance test, the difference between mean seizure times in these groups was found to be statistically significant (p = 0.038). Significance:  Epileptic spasms occur more frequently in the waking state and daytime. Younger patients have epileptic spasms mostly between 9 a.m. and noon and 3 p.m. and -6 p.m., and older patients have epileptic spasms mostly between 6 a.m. and 9 a.m. These findings emphasize age-related changes in epileptic spasm pathophysiology or potentially evolution of disease with age.

OBJECTIVE:To compare the prevalence and type of early developmental lesions in patients with a clinical presentation consistent with electrical status epilepticus in sleep either with or without prominent sleep-potentiated epileptiform activity (PSPEA). METHODS:We performed a case-control study and enrolled patients with 1) clinical features consistent with electrical status epilepticus in sleep, 2) ≥1 brain MRI scan, and 3) ≥1 overnight EEG recording. We quantified epileptiform activity using spike percentage, the percentage of 1-second bins in the EEG tracing containing at least 1 spike. PSPEA was present when spike percentage during non-REM sleep was ≥50% than spike percentage during wakefulness. RESULTS:One hundred patients with PSPEA (cases) and 47 patients without PSPEA (controls) met the inclusion criteria during a 14-year period. Both groups were comparable in terms of clinical and epidemiologic features. Early developmental lesions were more frequent in cases (48% vs 19.2%, p = 0.002). Thalamic lesions were more frequent in cases (14% vs 2.1%, p = 0.037). The main types of early developmental lesions found in cases were vascular lesions (14%), periventricular leukomalacia (9%), and malformation of cortical development (5%). Vascular lesions were the only type of early developmental lesions that were more frequent in cases (14% vs 0%, p = 0.005). CONCLUSIONS:Patients with PSPEA have a higher frequency of early developmental lesions and thalamic lesions than a comparable population of patients without PSPEA. Vascular lesions were the type of early developmental lesions most related to PSPEA.

We describe the short-term effects of high-dose oral diazepam on sleep-potentiated epileptiform activity in patients with electric status epilepticus during sleep. We enrolled patients treated with high-dose oral bedtime diazepam from 2001-2009. We defined spike percentage as the percentage of 1-second bins containing at least one spike, and calculated it during three randomly selected 5-minute samples of wakefulness throughout the day and during the first 5 minutes of every hour of non-rapid eye movement sleep at night. In this study, patients were considered to demonstrate sleep-potentiated epileptiform activity when their spike percentage during sleep was increased by ≥50% compared with wakefulness. Twenty-nine children (18 boys) were included (median age, 7.4 years). Twenty-four hours after receiving high-dose diazepam, epileptiform activity was significantly reduced (76.7% at baseline vs 40.8% 24 hours after high-dose diazepam; Wilcoxon signed ranks test, Z = -4.287, P < 0.0001). Seven patients (24.1%) manifested mild, reversible side effects during the first 48 hours after diazepam administration. High-dose oral diazepam effectively and safely reduced epileptiform activity in patients with electric status epilepticus during sleep.

Retrospective review was performed of children aged <3 years with epileptic spasms at our center from 2004-2010. Short-term (<6 months) and long-term (≥6 months) outcomes were assessed. We included 173 children (104 boys; median age of onset, 6.8 months) with epileptic spasms of known (62%) and unknown (38%) etiology. Treatments included adrenocorticotropic hormone (n = 103), vigabatrin (n = 82), phenobarbital (n = 34), and other agents (n = 121). Short-term treatment with adrenocorticotropic hormone and vigabatrin provided better epileptic spasm control in groups with known and unknown etiology than other agents. At follow-up (6-27 months), 54% of children manifested seizures, and 83% manifested developmental delay. Known etiology was a predictor of poor developmental outcome (P = 0.006), whereas bilateral/diffuse brain lesions predicted both poor development and seizures (P = 0.001 and 0.005, respectively). Initial presentations of epileptic spasms with hypotonia or developmental delay most strongly predicted both seizures and neurodevelopmental outcomes (P < 0.001). In a child presenting with epileptic spasms with developmental delay or hypotonia, no specific treatment may offer superior benefit.

We prospectively analyzed EEGs from participants in the ongoing NIH Rare Diseases Clinical Research Network Angelman Syndrome Natural History Study. Of the one-hundred-sixty enrolled patients (2006-2010), 115 had complete data (58 boys, median age 3.6 years). Distinct EEG findings were intermittent rhythmic delta waves (83.5%), interictal epileptiform discharges (74.2%), intermittent rhythmic theta waves (43.5%), and posterior rhythm slowing (43.5%). Centro-occipital and centro-temporal delta waves decreased with age (p=0.01, p=0.03). There were no specific correlations between EEG patterns and genotypes. A classification tree allowed the prediction of deletions class-1 (5.9 Mb) in patients with intermittent theta waves in <50% of EEG and interictal epileptiform abnormalities; UPD, UBE3A mutation or imprinting defects in patients with intermittent theta in <50% of EEG without interictal epileptiform abnormalities; deletions class-2 (5.0 Mb) in patients with >50% theta and normal posterior rhythm; atypical deletions in patients with >50% theta but abnormal posterior rhythm. EEG patterns are important biomarkers in Angelman syndrome and may suggest the underlying genetic etiology.

Serotonin reuptake inhibitors may induce periodic limb movements of sleep in adults. We undertook a retrospective review of polysomnography data of 1,023 children acquired at our institution over 1 year to assess whether children receiving serotonin reuptake inhibitors have a higher risk of periodic limb movements of sleep than children that are not treated with these medications. Periodic limb movements of sleep were found in 13 (31.7%) of 41 children receiving serotonin reuptake inhibitors and in 77 (7.8%) of 982 children not receiving serotonin reuptake inhibitors (odds ratio 5.45). Furthermore, the median periodic limb movement index in patients receiving serotonin reuptake inhibitors was significantly higher than patients not receiving serotonin reuptake inhibitors (11.2 and 6.5 respectively; P < 0.05). Children receiving serotonin reuptake inhibitors are at risk of periodic limb movements of sleep. Appropriate clinical judgment and medical management may result in better control of periodic limb movements of sleep and improved quality of life in these patients.

This study examined diurnal patterns of seizures and their occurrence during wakefulness and sleep in children with lesional focal epilepsy. We reviewed 332 consecutive children with lesional focal epilepsy and video-electroencephalogram monitoring during a 3-year period. Data were analyzed in relationship to clock time, wakefulness/sleep, and seizure localization. The distribution of lesions in 66 children (259 seizures) included mesial temporal, 29%; neocortical temporal, 18%; frontal, 29%; parietal, 13.5%; and occipital, 12%. Seizures in patients with frontal lesions occurred mostly during sleep (72%). Seizures in mesial temporal (64%), neocortical temporal (71%), and occipital (66%) lesional epilepsy occurred mostly during wakefulness. Temporal lobe seizures occurred more frequently during wakefulness (66%), compared with extratemporal seizures (32%)(odds ratio, 2.67; 95% confidence interval, 1.61-4.42). Temporal lobe seizures peaked between 9:00 am and noon and 3:00-6:00 pm, whereas extratemporal seizures peaked between 6:00-9:00 am. Sleep, not clock time, provides a more robust stimulus for seizure onset, especially for frontal lobe seizures. Temporal lobe seizures are more frequent during wakefulness than are extratemporal seizures. Circadian patterns of seizures may provide additional diagnostic and treatment options, such as differential medication dosing and sleep-schedule adjustments.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive genetic disorder, characterized by multiple congenital anomalies, and intellectual disability. It is caused by a genetically inherited deficiency of the enzyme 7-dehydrocholesterol-delta-7-reductase, which results in increased serum levels of 7-dehydrocholesterol (7-DHC), and decreased levels of cholesterol. This study assesses the prevalence of sleep problems in patients with SLOS. The study group comprised 18 subjects with SLOS, ages 2-31 years (median 10.7 ± 8.5 years). Parents completed several questionnaires (Intake Demographic Form; Pediatric Sleep Questionnaire; Pediatric Daytime Sleepiness Scale). The SLOS subjects had symptoms of sleep-disordered breathing (50% snoring; 66.7% mouth breathing), problems with sleep onset [difficulty falling asleep (61.1%) sleep onset time >30 min (62%)], sleep maintenance [wake up screaming (61.1%), waking up more than twice (44.4%), having trouble falling back to sleep (66.7%), waking up early in the morning (61.1%), and restless sleep (50%)]. The subjects with SLOS needed parents in the room to fall asleep (50%), watch TV or listen to music to fall asleep (44.4%), and described bed sharing (33.3%), indicating sleep-anxiety and sleep-associations. Symptoms of excessive-daytime-sleepiness were frequently reported [un-refreshed in the morning (38.9%), daytime sleepiness (44.4%), and daytime naps (55.6%)]. Parents frequently observed difficulty of organizing tasks (66.7%), and easy distractibility (88.9%). Sleep problems such as sleep-disordered breathing, sleep-related anxiety and sleep associations, disturbed sleep patterns at night, and excessive daytime sleepiness are frequent in children with SLOS.

We describe our experience with intraoperative electroencephalography in moyamoya surgery, a method to monitor for ischemic changes during the procedure and to minimize the risk of intraoperative and perioperative stroke. Case records and intraoperative electroencephalography recordings of all patients (n=220) treated with surgical revascularization for moyamoya (pial synangiosis) performed for 14 years (1994-2008) were reviewed. Electroencephalographic slowing occurred in 100 cases (45.5%), and was persistent in nine cases (9%). Slowing coincided with specific operative manipulations, most commonly while suturing the donor vessel to the pia, and during closure of the craniotomy. Slowing generally occurred bilaterally, independently of the side of intervention. The presence, length, and severity of slowing were not predictive of perioperative ischemic events. We present additional data on intraoperative electroencephalography with a modified montage to accommodate the craniotomy. Although not predictive of perioperative ischemic events in this series, electroencephalographic changes were correlated with specific operative interventions, and revealed global responses to unilateral manipulation. These findings suggest that prospective analyses of this technique may elucidate additional methods of predicting (and possibly preventing) perioperative ischemic events.