Effects of eslicarbazepine as add-on therapy on sleep architecture in temporal lobe epilepsy: results from “Esleep” study

RationaleStudies looking at the effect of antiseizure medications (ASMs) on the sleep microstructure of subjects with epilepsy are scarce. This study aims to evaluate the impact of eslicarbazepine (ESL) as add-on therapy on the sleep microstructure in temporal lobe epilepsy (TLE).MethodsTwelve patients affected by TLE were recruited to undergo overnight polysomnography and a subjective evaluation of nocturnal sleep utilizing the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence through the Epworth Sleepiness Scale (ESS) before and after three months of treatment with ESL as add-on therapy. Ten healthy controls (HC) matched for age, sex and BMI were recruited. Scoring and analysis of sleep macrostructure and cyclic alternating pattern (CAP) parameters were performed.ResultsTen patients completed the study. The comparison between patients in basal condition (T0) and HC showed a significant lower sleep efficiency (p = 0.049), REM percentage (p = 0.002), higher REM latency (p = 0.02), N2 (p = 0.001) and WASO (p = 0.01). Regarding CAP, patients at T0 showed higher CAP rate in N1 (p = 0.01), lower A1 (%) (p = 0.03), higher A3 (%) (p = 0.01), higher mean duration of A (p = 0.02) and A3 (p = 0.006), A3 index (p = 0.02) than HC. ESL did not induce any significant changes in nocturnal macrostructural polysomnographic variables and PSQI scores. Furthermore, the ESS score showed no modification after treatment. Lower CAP rate in N3 (p = 0.02), phase A2 index (p = 0.02) average number of CAP cycle per sequences and mean duration of CAP sequences (both p = 0.02) was evident after ESL. A trend toward significance was evident for the decrease of CAP rate in N1 (p = 0.09) and N2 (p = 0.09), and for the increase of B phase mean duration (p = 0.07).ConclusionWe found significant improvement in sleep continuity as measured by CAP after ESL. These findings suggest that ESL may positively modulate sleep fragmentation in patients with TLE, and hence enhance sleep quality. Our results suggest a favourable sleep profile with the use of ESL.     

Laryngeal motility alteration: A missing link between sleep apnea and vagus nerve stimulation for epilepsy

This study aimed to evaluate the prevalence and the relationship of sleep breathing disorders (SBDs) and laryngeal motility alterations in patients with drug‐resistant epilepsy after vagus nerve stimulator (VNS) implantation. Twenty‐three consecutive patients with medically refractory epilepsy underwent out‐of‐center sleep testing before and after VNS implantation. Eighteen eligible subjects underwent endoscopic laryngeal examination post‐VNS implantation. Statistical analysis was carried out to assess an association between laryngeal motility alterations and the onset/worsening of SBDs. After VNS implantation, 11 patients showed a new‐onset mild/moderate SBD. Half of the patients already affected by obstructive sleep apnea (OSA) showed worsening of SBD. All of the patients with a new‐onset OSA had a laryngeal pattern with left vocal cord adduction (LVCA) during VNS stimulation. The association between VNS‐induced LVCA and SBD was statistically significant. This study suggests an association between VNS and SBD, hinting to a pivotal role of laryngeal motility alterations. The relationship between SBD and VNS‐induced LVCA supports the need to routinely investigate sleep respiratory and laryngeal motility patterns before and after VNS implantation.     

Focal and generalized EEG paroxysms in childhood absence epilepsy: topographic associations and distinctive behaviors during the first cycle of non-REM sleep

Purpose: To better understand the nature of the focal spike‐wave discharges (FSWDs) and focally led generalized spike‐wave discharges (GSWDs) in typical childhood absence epilepsy (CAE) and by implication their nosologic and taxonomic significance. Methods: Twenty‐four abnormal video‐electroencephalography (EEG) studies from 13 consecutive children with CAE and good response to appropriate antiepileptic drugs (AEDs) were analyzed. We studied the association between the topography of absence onset and the ictal automatisms, and the topographic correlation between FSWDs and GSWDs and their respective behavior during hyperventilation and the different states of phasic and nonphasic non–rapid eye movement (NREM) sleep. GSWDs were considered as of “focal” onset if a lead‐in could be visibly recognized at a paper speed of 60 mm/s, and were classified by their topography. Key Findings: (1) Multifocal absences occurred in 10 children; anterior onset was noted in 81 absences (73.6%) from 12 children and posterior in 18 (16.4%) from 7 children; there was no association between topography of absence onset and ictal automatisms; (2) FSWDs occurred in 85% of children and were multifocal in 73% of them; 85% of FSWDs were anterior and 14% posterior; (3) there was good topographic association between FSWDs and the leading spike of GSWDs of “focal” onset in all children with FSWDs; (4) both FSWDs and GSWDs increased during hyperventilation; (5) FSWDs occurred mainly during noncyclical NREM sleep and during periods of reduced vigilance of cyclical NREM sleep, whereas GSWDs occurred during the periods of enhanced vigilance of NREM sleep; GSWDs occurred significantly more frequently than FSWDs at the transition from reduced to enhanced vigilance of NREM sleep. Significance: Our findings suggest that in CAE focal EEG paroxysms reflect a system of multifocal nonlocalizing electrically unstable cortical areas that under the facilitatory influence of exogenous or endogenous factors like sleep instability can foster a corticothalamic response of sufficient strength to generate 3‐Hz GSWDs that are conditionally sustainable and potentially ictal. FSWDs can be viewed as incomplete forms of the GSWDs; together they define the EEG identity of idiopathic “generalized” epileptogenesis.     

Activation of partial seizures with motor signs during cyclic alternating pattern in human sleep

Both interictal and ictal EEC phenomena are commonly activated by functional instability. The different non-REM sleep stages comprise long-lasting periods of cyclic alternating pattern (CAP) in which arousal fluctuates between ‘A phases’ of greater arousal and ‘B phases’ of less arousal, and periods in which vigilance maintains a tonic stability (non-CAP). Previous studies have revealed that phase A induces a marked enhancement of generalized EEC paroxysms, a minor though significant activation of focal lesional bursts, but no effect on rolandic functional spikes. Conversely, phase B exerts an inhibitory modulation, especially on bilateral interictal phenomena. Because of the opposite influence of phase A and phase B also on muscle tone, we assessed the amount and distribution of nocturnal partial motor seizures in 6 subjects affected by focal epilepsy. The polysomnograms included 45 motor seizures, 43 of which occurred during non-REM sleep. Nocturnal fits were significantly more frequent in stages 1 and 3 (P < 0.0001). Among the non-REM seizures, 42 appeared in CAP (P < 0.0001) and always in phase A. The transient arousal and the concomitant muscle tone activation expressed by phase A of CAP is likely to support the motor components of nocturnal seizures. Sleep analysis in terms of CAP and non-CAP provides a better understanding of the continuum from subclinical EEC paroxysms to clinical manifestations and of the relations between vigilance and seizure disorders.     

儿童良性中央-颞棘波型癫痫随访研究

目的：探讨儿童良性中央－颞棘波型癫痫的预后。方法；对１３８例儿童良笥中央－颞棘波型癫痫进行了２～１２年的随防研究。结果：抗癫痫药物均能控制临床发作，智商和社会行为不受影响，其中１１３例（８２％）终止抗癫痫药物２～１２年临床无发作，脑电图均恢复正常。结论：脑电图睡眠诱发试验可以提高本病诊断阳性率。经抗癫痫药物治疗，临床无发作，脑电图正常我年后可以停药。     

Network characteristics in benign epilepsy with centro-temporal spikes patients indicating defective connectivity during spindle sleep: A partial directed coherence study of EEG signals

Objective

To investigate the changes in EEG connectivity in children with the typical presentation of benign epilepsy with centro-temporal spikes (BECTS).

Benign epilepsy of childhood with centrotemporal spikes and unilateral developmental opercular dysplasia

The case of a 15-year-old right-handed girl with developmental delay, mild retardation, astereognosis, and tactile discrimination impairment in the left arm, is reported. During sleep, right partial simple motor seizures with sialorrhea and saliva pooling were present, sometimes followed by secondary generalization. Absences and drop attacks were also observed. Electroencephalography revealed left centrotemporal spike waves spreading to the homologous contralateral region, generalized 3-Hz spike-and-wave complexes enhanced by hyperventilation, and generalized polyspike-and-wave discharges during drowsiness. Magnetic resonance imaging showed right perisylvian (opercular) malformation. Benign epilepsy of childhood with centrotemporal spikes (BECCTS) is a focal idiopathic epilepsy presumed to be of genetic origin. Although brain damage is not expected, structural lesions including opercular macrogyria have been reported. This coexistence has been considered mainly casual and only exceptionally causal. The Foix-Chavany-Marie syndrome or operculum syndrome is the result of bilateral opercular damage. In our child the right structural and the left functional lesions appeared mutually activated, yielding a transient opercular syndrome. The concomitance of BECCTS and developmental opercular dysplasia is suggestive of a common genetic substratum.     

睡眠中失神发作的儿童失神癫痫的临床特点(附1例报告)

目的 探讨睡眠中失神发作的儿童失神癫痫(CAE)的临床特征.方法 回顾性分析1例睡眠中失神发作的CAE患儿的临床资料.结果 本例患儿以反复愣神为主要表现,同时伴有睡眠中突然睁眼、茫然无视及轻微眨眼等症状,同期视频EEG均为全导广泛性3 Hz棘慢波阵发.空腹CSF检查及头颅MRI正常.先后给予丙戊酸、拉莫三嗪及左乙拉西坦...     

儿童良性癫痫伴中央颞区棘波患者的认知损害研究

目的探讨儿童良性癫痫伴中央颞区棘波(Benign epilepsy of childhood with centrotemporal spikes,BECTS)患者的认知损害特点。方法纳入2010年9月-2019年12月于首都医科大学宣武医院神经内科就诊的BECTS患者61例(BECTS组)。选取60名年龄、性别和教育程度相匹配的健康儿童和青少年作为对照组。对BECTS组及对照组进行神经心理学任务测试以评估其注意力、记忆力、计算力、语言功能、执行能力、视空间功能、视知觉及反应能力等多项认知功能。应用SPSS 20.0统计软件,对两组的认知任务测试得分进行独立样本t检验和秩和检验,对影响认知功能损害的各项临床因素进行多元线性回归分析。结果与对照组相比,BECTS组患者的配对联结学习平均(19.56±2.91)分,词语辨析测验的平均(23.67±9.50)分,物体数量认知的平均(61.45±13.14)分,言语工作记忆的平均(6.54±1.47)分,声音知觉测验的平均(5.79±5.90)分,Taylor复杂图形测验的平均(35.10±2.33)分,选择反应时的平均(700.34±493.05)分,均显著低于对照组(P<0.05)。在BECTS组中有36例起病<8岁,与起病≥8岁组相比,前者在视觉追踪任务、空间记忆任务、简单减法任务、数字数量大小比较、汉字押韵测试、词语辨析测试和视觉感知任务等大部分神经心理测试中得分均较低(P<0.05);34例接受单药治疗,27例接受两种及以上抗癫痫药物治疗,多药治疗组在注意力、记忆力、视知觉、反应力等方面均低于单药治疗组(P<0.05)。结论 BECTS患者存在注意力、记忆力、视知觉、声音知觉及反应速度的损害。起病年龄越小其认知损害的程度越重;多药治疗患者的认知损害程度较单药治疗重。     

Neuropsychological status of children with newly diagnosed idiopathic childhood epilepsy

We characterized the neuropsychological status of children with newly diagnosed idiopathic childhood epilepsy and measured differences in IQ between children with different types of epilepsy. The Korean Education Development Institute-Wechsler Intelligence Scale for Children (KEDI-WISC) was administered to 72 patients (35 males and 37 females), of mean age 8.7 ± 2.6 years, with newly diagnosed idiopathic childhood epilepsy. Of these patients, 22 (30.6%) had generalized epilepsy, 48 (66.7%) localization-related epilepsy, and 2 (2.8%) mixed epilepsy. Children with generalized epilepsy and benign childhood epilepsy with centro-temporal spikes (BCECTS) were of similar verbal IQ and full-scale IQ, although performance IQ was significantly lower in patients with generalized epilepsy. Among children with BCECTS, those with unilateral spikes had higher full-scale and performance IQ scores than those with bilateral spikes. Follow-up studies on large numbers of patients are needed to determine the effects of epilepsy per se, and antiepileptic drugs, on intelligence.     

Benign nocturnal alternating hemiplegia of childhood: A new case with unusual findings

It has been described a neuro developmental disorder labelled “Benign nocturnal alternating hemiplegia of childhood” (BNAHC) characterized by recurrent attacks of nocturnal hemiplegia without progression to neurological or intellectual impairment. We report a female patient who at 11 months revealed a motionless left arm, unusual crying without impairment of consciousness and obvious precipitating factors. The attacks occur during sleep in the early morning with lack of ictal and interictal electroencephalographic abnormalities, progressive neurological deficit, and cognitive impairment. Unlike previous reports of BNAHC our patient come from a family with a history of both migraine, hemiplegic migraine, and sleep disorders. Our study remarks on the typical features described in previous studies and stresses the uncommon aspects that could help to identify the disorder which is likely to have been underestimated. Despite some clinical similarities between BNAHC and familiar hemiplegic migraine and alternating hemiplegia of childhood, the genetic analyses of our patient did not reveal genetic mutations found in both disorders.     

Effects of antiepileptic treatment on sleep and seizures in nocturnal frontal lobe epilepsy

ObjectiveTo study the effects of antiepileptic treatment on sleep parameters and video-polysomnography (VPSG) seizures in nocturnal frontal lobe epilepsy (NFLE).MethodsTwenty patients with a clinical and VPSG diagnosis of NFLE (baseline polysomnography [PSG]) underwent a clinical follow-up and performed a second VPSG after effective antiepileptic treatment lasting for at least 6 months. Conventional sleep measures, cyclic alternating pattern (CAP) parameters, and objective VPSG seizures were assessed in NFLE patients before and after treatment and were compared with the results of 20 age- and gender-matched control subjects.ResultsAntiepileptic treatment determined a partial reduction of objective VPSG seizures of approximately 25% compared to baseline condition. Alterations of most conventional sleep measures recovered normal values, but nonrapid eye movement (NREM) sleep instability remained pathologically enhanced (CAP rate, +26% compared to controls) and was associated with persistence of daytime sleepiness.ConclusionsResidual epileptic events and high levels of unstable NREM sleep can define a sort of objective resistance of both seizures and disturbed arousal system to the therapeutic purpose of the antiepileptic drugs in NFLE. This finding could determine the need for new therapeutic options in this particular form of epilepsy.     

High‐frequency oscillations in idiopathic partial epilepsy of childhood

Purpose: We explored high‐frequency oscillations (HFOs) in scalp sleep electroencephalography (EEG) studies of patients with idiopathic partial epilepsy (IPE) of childhood in order to obtain a better understanding of the pathologic mechanisms underlying IPE. Methods: The subjects were 45 patients, including 32 with benign childhood epilepsy with centrotemporal spikes (BCECTS) and 13 with Panayiotopoulos syndrome (PS). A total of 136 EEG records were investigated through temporal expansion and filtering of traces and time‐frequency spectral analysis. Key Findings: HFOs with frequency of 93.8–152.3 Hz (mean 126.2 ± 13.6 Hz) in the band of ripples were detected in association with spikes in 97 records (71.3%). Time from last seizure to the EEG recording was significantly shorter in those with spike‐related HFOs than in the EEG recordings with spikes without HFOs (p = 0.006). Although time from last seizure reflects age, age at the time of recording was not significantly different between EEG studies with and without HFOs. Peak‐power values of the high‐frequency spots in time‐frequency spectra were significantly negatively correlated with time from last seizure (R² = 0.122, p < 0.001) but not with age at the time of recording. Peak frequencies of the high‐frequency spectral spots were not significantly correlated with age at the time of recording or with time from last seizure. Significance: The close relationship between the generation of spike‐related HFOs and the period of active seizure occurrence indicated that HFOs may tell us more about epileptogenicity in IPE than the spikes themselves. Because there is a spectrum of pediatric epileptic disorders extending from the benign end of BCECTS to the encephalopathic end of epilepsy with continuous spike‐waves during slow‐wave sleep (CSWS), and HFOs that have already been detected in association with CSWS were more prominent than HFOs in IPE, intense spike‐related HFOs may indicate poor prognosis.     

EEG characteristics related to educational impairments in children with benign childhood epilepsy with centrotemporal spikes

PURPOSE: Learning and behavioral difficulties often occur in benign childhood epilepsy with centrotemporal spikes (BCECTS). In recent years, several electroencephalogram (EEG) characteristics have been related to the occurrence of learning and behavioral problems. METHODS: From 28 children medical, school and psychological reports were present and children were rated according to a 4-point scale for educational and behavioral impairment (Part 1). Thirty 24-h EEG recordings were reanalyzed for spike frequency, the presence of atypical EEG criteria, and the presence of a nondipole spike. EEGs were scored during wakefulness, first hour of sleep and whole night sleep (minus the first hour of sleep) separately (Part 2). RESULTS: The presence of I: an intermittent slow-wave focus during wakefulness, II: a high number of spikes in the first hour of sleep (and during whole night sleep), and III: multiple asynchronous bilateral spike-wave foci in the first hour of sleep correlates significantly with a sum score > or = 3 which indicates a complicated course with educational or behavioral impairment. It is sufficient to analyze an EEG during wakefulness and a sleep EEG for only the first hour of sleep instead of a whole night recording to demonstrate those EEG criteria. CONCLUSIONS: On basis of our reanalysis we can possibly conclude that the aforementioned EEG characteristics correlate with educational impairments, and that analysing an EEG recording during wake and the first hour of sleep is sufficient to look adequately for those EEG criteria in children with BCECTS.     

Sleep cyclic alternating pattern analysis in healthy children during the first year of life: A daytime polysomnographic study

We evaluated the cyclic alternating pattern (CAP) during the first year of life in order to obtain information on the maturation of arousal mechanisms during NREM sleep and to provide normative data for CAP parameters in this age range (5-16 months). Eleven healthy children (mean age 7.9 ± 3.3 months, seven boys) were studied while they slept in the morning. They underwent a 3-h video-EEG-polysomnographic recording at the Pediatric Sleep Unit of Sant’Andrea Hospital in Rome, Italy. Sleep was scored visually for sleep architecture and CAP analysis using standard criteria. Our results were complemented by CAP data from a previous sample of healthy infants (2-4 months), studied when they slept during the morning, in order to correlate CAP parameters with age. The total sample comprised 24 children. The sleep period was approximately 2 h, with a first REM latency of about 30 min, and a clear distinction between stages N1, N2, and N3. The arousal index was 12 ± 2.1 events/hour of sleep. The total CAP rate was 23.7 ± 7.6%, and it increased progressively with the deepness of sleep; the highest values were observed during stage N3 and the lowest values during stage N1. A1 phases were the most numerous (78.2%), followed by A2 (14%) and A3 (7.7%) phases. The A1 index was higher than the A2 and A3 indices, whereas the mean duration of B was higher than that of A. The correlation showed that the CAP rate, A1, A2, A3 indices, A2, A3 percentages, and the average duration of B increased with age, whereas the A1 percentage decreased. We provide the first data on CAP analysis in children aged 5-16 months, studied when they slept during the morning. Our results confirm the trend toward an increase in CAP rate during the first year of life. In addition, we observed a progressive increase in CAP rate with deepness of sleep, and with age, reflecting maturation of slow-wave activity. The decreased percentage of A1 subtypes may reflect the maturation of arousability.     

Electrophysiological and microstructural features of sleep in children at high risk for depression: a preliminary study

ObjectiveThis preliminary study investigated electrophysiological and microstructural features of sleep in children and adolescents 4–18 years of age who were born to depressed mothers.MethodsA total of 31 healthy subjects (15 male and 16 female) participated in the study. In this sample, 20 children born to mothers diagnosed with Major Depressive Disorder (MDD) were designated as “high-risk”; 11 children born to mothers without a personal history of depression were designated as “low-risk.” Polysomnography including three-channel electroencephalography (EEG) was recorded for one night at the Pediatric Sleep Unit of the University Hospital of Lyon, France. Clinical and demographic data were collected. Sleep architectural parameters were analyzed. Sleep microstructure was assessed with the scoring of cyclic alternating pattern (CAP) and CAP measures were calculated. Spectral analysis was performed, and mean EEG band power was computed for each sleep stage. Sleep electrophysiological features (slow waves and sleep spindles) were detected, and related parameters were analyzed. Data were compared between high- and low-risk groups using Student t tests.ResultsA reduction in low-frequency spindle activity and slow spindles spatio-temporal characteristics over frontal and central derivations, and an altered distribution of CAP phase A subtypes (reduction of A1 over A2–3 ratio) were observed in the high-risk group relative to the low-risk group.ConclusionLimited spindles generation and increased non-rapid eye movement sleep instability, observed in children born to depressed mothers, might reflect functional anomalies in cortical plasticity that could represent a pathogenic factor or an epiphenomenon for MDD.     

Spatiotemporal propagation patterns of generalized ictal spikes in childhood absence epilepsy

Objective

This work investigates the spatial distribution in time of generalized ictal spikes in the typical absences of childhood absence epilepsy (CAE).

Discriminatory Effect of Cyclic Alternating Pattern in Focal Lesional and Benign Rolandic Interictal Spikes During Sleep

Twenty epileptic patients (10 male and 10 female) were polygraphically recorded during nocturnal sleep. Ten subjects, with a wide age range, were affected by focal lesional epilepsy, and 10 were children affected by benign epilepsy with rolandic spikes (BERS). In five cases a bihemispheric expression of the focal lesional bursts emerged occasionally during the night recordings. The behavior of interictal electroencephalographic (EEG) paroxysms were analyzed with respect to the two arousal states of non-rapid-eye-movement (REM) sleep: (a) the cyclic alternating pattern (CAP), expressed by biphasic EEG periodic activities and related to long-lasting fluctuations between greater (phase A) and lesser (phase B) arousal levels; and (b) the non-CAP (NCAP), manifested by EEG stationarities that reflect a sustained relative stability of arousal. The CAP/NCAP modality affected the spiking activity and distribution of the focal lesional EEG paroxysms, which appeared enhanced during CAP and which were mostly collected in phase A. The even more powerful influence of CAP and especially phase A on the secondary bisynchronous bursts suggests a crucial integration among thalamocortical circuits, arousal modulation, and epileptic generalization mechanisms. Conversely, in the BERS recordings no significant differences emerged throughout CAP and NCAP. The intense activity of the rolandic foci induced by sleep as such could be explained on the basis of the greater dependence of these functional cortical EEG abnormalities on the degree of synchronization during sleep.     

A study on epileptic negative myoclonus in atypical benign partial epilepsy of childhood

Objective. To investigate the clinical and neurophysiological characteristics, particularly therapeutic considerations, of epileptic negative myoclonus (ENM) in atypical benign partial epilepsy (ABPE) of childhood. Methods. From 1998 to 2006, 14/242 patients with benign children epilepsy with centrotemporal spikes (BECTS) were diagnosed as having ABPE with ENM. In all 14 patients, we performed video-EEG monitoring along with tests with the patient’s arms outstretched; 6/14 patients were also simultaneously underwent surface electromyogram (EMG). ENM manifestations, electrophysiological features, and responses to antiepileptic drugs were analyzed. Results. In all cases, ENM developed after the onset of epilepsy and during antiepileptic drug therapy, and the appearance of ENM were corresponding to EEG findings of high-amplitude spikes followed by a slow wave in the contralateral motor areas with secondary generalization. This was further confirmed by time-locked silent EMG. During ENM occurrence or recurrence, habitual seizures and interictal discharges were exaggerated. In some patients, the changes in antiepileptic drug regimens in relation to ENM appearance included add-on therapy with carbamazepine, oxcarbazepine, and phenobarbital or withdrawal of valproate. ENM was controlled in most cases by administration of various combinations of valproate, clonazepam, and corticosteroids. Conclusion. The incidence of ENM or ABPE in our center was approximately 5.79%. A combination of video-EEG monitoring with the patient’s arms outstretched and EMG is essential to identify ENM. The aggravation of habitual seizures and interictal discharges indicate ENM. Some antiepileptic drugs, such as carbamazepine, oxcarbazepine, and phenobarbital, may be related to ENM occurrence during spontaneous aggravation of ABPE. Various combinations of valproate, benzodiazepines, and corticosteroids are relatively effective for treating ENM that occurs in ABPE.