Short-term response of sleep-potentiated spiking to high-dose diazepam in electric status epilepticus during sleep

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.     

Efficacy of Levetiracetam in Electrical Status Epilepticus During Sleep of Children: A Multicenter Experience

BackgroundElectrical status epilepticus during sleep is characterized by epilepsy, a specific electroencephalographic pattern, and neuropsychological impairment. This study aims to evaluate the efficacy and safety of levetiracetam in treating children with electrical status epilepticus during sleep.MethodsA multicenter, retrospective, open-label study enrolled 73 children (mean age: 8 years) affected by electrical status epilepticus during sleep. The efficacy was rated according to the seizure frequency and electroencephalography response.ResultsAfter a mean treatment period of 19 months (range: 6 to 24 months), 33 (63.5%) of 52 patients became seizure-free or had experienced remarkable reduction in seizures. The electrical status epilepticus of 41 (56.2%) of 73 patients disappeared off their electroencephalography. The electroencephalography efficacy of levetiracetam treatment was noted in the monotherapy (61.9%) and add-on (53.9%) groups. The clinical (67.7%) and electroencephalography (64.3%) response rates of the idiopathic group were better than those of the symptomatic group (57.1% and 45.2%, respectively). No patient discontinued the trial because of intolerability of side effects.ConclusionsLevetiracetam is effective in individuals with electrical status epilepticus during sleep with tolerable side effects.     

Functional brain connectivity in electrical status epilepticus in sleep

Aims. Electrical status epilepticus in sleep (ESES) is an age‐related, self‐limited epileptic encephalopathy. The syndrome is characterized by cognitive and behavioral abnormalities and a specific EEG pattern of continuous spikes and waves during slow‐wave sleep. While spikes and sharp waves are known to result in transient cognitive impairment during learning and memory tasks performed during the waking state, the effect of epileptiform discharges during sleep on cognition and behavior is unclear. There is increasing evidence that abnormalities of coherence, a measure of the consistency of the phase difference between two EEG signals when compared over time, is an important feature of brain oscillations and plays a role in cognition and behavior. The objective of this study was to determine whether coherence of EEG activity is altered during slow‐wave sleep in children with ESES when compared to typically developing children. Methods. We examined coherence during epochs of ESES versus epochs when ESES was not present. In addition, we compared coherence during slow‐wave sleep between typically developing children and children with ESES. Results. ESES was associated with remarkably high coherences at all bandwidths and most electrode pairs. While the high coherence was largely attributed to the spikes and spike‐and‐wave discharge, activity between spikes and spike‐and‐wave discharge also demonstrated high coherence. Conclusions. This study indicates that EEG coherence during ESES is relatively high. Whether these increases in coherence correlate with the cognitive and behavioral abnormalities seen in children with this EEG pattern remains to be determined.     

Syndrome of Electrical Status Epilepticus During Sleep: Epileptic Encephalopathy Related to Brain Development

BackgroundEpileptic encephalopathy with electrical status epilepticus during sleep is an age-related and self-limited disorder. The present study analyzed the etiology, demographics, and pathogenesis of patients with electrical status epilepticus during sleep to provide information on the diagnosis and therapy of this syndrome.MethodsThe etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in patients admitted in Chinese People's Liberation Army General Hospital from 2009 to 2014 were retrospectively analyzed. Patients were classified into the genetic, structural-metabolic, and unknown groups according to the etiology. Demographics and clinical characteristics of all the patients were then analyzed and compared among groups.ResultsThe etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in 75 patients mainly included benign childhood epilepsy with centrotemporal spikes, Landau-Kleffner syndrome, polymicrogyria, and migration disorders. Age at onset of epilepsy did not show a specific pattern, but age at onset of epileptic encephalopathy with electrical status epilepticus during sleep was concentrated at age 6-9 years. The mean age at onset of epilepsy in the genetic group was significantly older than that in the structural-metabolic group (P < 0.05). Age at onset of epileptic encephalopathy with electrical status epilepticus during sleep did not significantly differ between the two groups.ConclusionsElectrical status epilepticus during sleep is an epileptic encephalopathy related to brain development and presents an age-dependent occurrence.     

Epileptic Encephalopathy with Continuous Spikes and Waves During Sleep

Epileptic encephalopathy with continuous spikes and waves during slow sleep (EECSWSS) is an age-related childhood condition characterized by epilepsy, cognitive or behavioral impairment, and electroencephalographic abnormality of continuous spike–wave discharges during slow sleep. Continuous spikes and waves during slow sleep (or electrical status epilepticus during sleep) is an electrographic pattern characterized by nearly continuous spike–wave discharges during non-REM sleep, with a frequency of 1.5–3 Hz and usually diffuse and bilateral in distribution. Most authors consider EECSWSS as wide spectrum of epileptic conditions of different origin associated with heterogeneous clinical manifestations and neuropsychological impairment of different severity in close temporal concordance with the appearance of the electroencephalographic pattern of electrical status epilepticus during sleep. The long-term prognosis of this condition is overall poor owing to the persistence of neuropsychological impairment. Therefore, early recognition and effective therapy are necessary to improve long-term prognosis.     

Complex partial status epilepticus in children with epilepsy

Purpose: Complex partial status epilepticus (CPSE) is often under-diagnosed, especially in children. The aim of this study was to clarify the characteristics and pathophysiology of CPSE in children with epilepsy. Subjects and methods: We retrospectively reviewed the medical records and EEGs of 17 children with epilepsy who were diagnosed as having CPSE by ictal or postictal EEGs to investigate clinical and EEG features. Results: The ages at diagnosis of CPSE ranged from 3 months to 17 years. At the time of diagnosis of CPSE, 13 patients had symptomatic localization-related epilepsy, two had epilepsy with continuous spike-waves during slow wave sleep, and each patient had cryptogenic localization-related epilepsy and idiopathic localization-related epilepsy. Only subtle symptoms including autonomic ones associated with disturbance of consciousness were the main clinical features in 12 of 44 CPSE episodes. Another 22 episodes showed minor focal motor elements, and the other 10 had major convulsive phase during or immediately before CPSE. Ictal EEGs of CPSE were divided into three types according to the degree of high-voltage slow waves (HVS) and spike components. Ictal EEGs could show spike-dominant or spike and HVS mixed patterns even if patients showed only subtle symptoms. The epileptogenic areas estimated by the ictal or postictal EEGs showed variability with only two cases of temporal origin. Conclusion: The close observation of clinical symptoms such as various subtle symptoms and/or mild convulsive elements and ictal EEGs are absolutely needed for the diagnosis of CPSE in children.     

Acetazolamide for electrical status epilepticus in slow‐wave sleep

Electrical status epilepticus in slow‐wave sleep (ESES) is characterized by nearly continuous spike–wave discharges during non–rapid eye movement (REM) sleep. ESES is present in Landau‐Kleffner syndrome (LKS) and continuous spike and wave in slow‐wave sleep (CSWS). Sulthiame has demonstrated reduction in spike–wave index (SWI) in ESES, but is not available in the United States. Acetazolamide (AZM) is readily available and has similar pharmacologic properties. Our aims were to assess the effect of AZM on SWI and clinical response in children with LKS and CSWS. Children with LKS or CSWS treated with AZM at our institution were identified retrospectively. Pre‐ and posttherapy electroencephalography (EEG) studies were evaluated for SWI. Parental and teacher report of clinical improvement was recorded. Six children met criteria for inclusion. Three children (50%) demonstrated complete resolution or SWI <5% after AZM. All children had improvement in clinical seizures and subjective improvement in communication skills and school performance. Five of six children had subjective improvement in hyperactivity and attention. AZM is a potentially effective therapy for children with LKS and CSWS. This study lends to the knowledge of potential therapies that can be used for these disorders, which can be challenging for families and providers.     

Benign childhood epilepsy with Centro-Temporal spikes (BCECTSs), electrical status epilepticus in sleep (ESES), and academic decline — How aggressive should we be?

Since many of the children with BCECTSs display electrical status epilepticus during sleep and many present with different comorbidities, mainly ADHD and behavioral disturbances, clinicians are often confronted with the dilemma of how aggressive they should be with their efforts of normalizing the EEG. We conducted a retrospective study by screening medical records of all consecutive patients with BCECTSs, spike–wave index (SWI) > 30%, and ADHD/ADD that were evaluated in our pediatric epilepsy service and were followed up for at least two years. Patients with neurocognitive deterioration detected by formal testing were excluded. A total of 17 patients with mean age of 6.9 years at BCECTS diagnosis were identified. The patients' mean SWI was 60% and that dense electrical activity lasted 1.5 years on average (range: 1–4.5 years). Six children were formally diagnosed with learning disabilities in addition to ADD/ADHD. All of them were treated with an average of three antiepileptic medications, mainly for the purpose of normalizing the EEG, but none of them was treated with steroids or high-dose diazepam. The mean duration of follow-up was 5.5 years. A cognitive or behavioral deterioration was not detected in any of them. Our data suggest that when treating a child with BCECTSs, high SWI, and school difficulties, the most critical parameter that determines the necessity of using second-line antiepileptic agents such as steroids or high-dose diazepam is a formal psychological evaluation that proves cognitive (I.Q.) decline. Otherwise, these agents may be avoided.     

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

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

Therapeutic Plasma Exchange for Malignant Refractory Status Epilepticus: A Case Report

BackgroundRefractory status epilepticus is a prolongation of status epilepticus despite anticonvulsant therapy with two or three medications in proper doses; it is defined as malignant status epilepticus if it takes weeks or months. Intravenous immunoglobulin, high-dose steroids, magnesium infusion, pyridoxine, hypothermia, ketogenic diet, electroconvulsive therapy, and surgical therapy are the other treatment options for status epilepticus.PatientOur 5-year-old male patient was hospitalized at our pediatric intensive care unit because of status epilepticus secondary to meningoencephalitis. No response could be obtained with many medical and nonmedical therapies in our patient, who developed malignant status epilepticus with unknown etiology. Therapeutic plasma exchange was applied as convulsions continued.ResultOurs is the first child for whom therapeutic plasma exchange was successfully applied because of malignant refractory status epilepticus secondary to meningoencephalitis.ConclusionTherapeutic plasma exchange may be a treatment option for children with refractory status epilepticus following presumed meningoencephalitis.     

EEG features in Encephalopathy related to Status Epilepticus during slow Sleep

Encephalopathy related to Status Epilepticus during slow Sleep (ESES) is a peculiar electro‐clinical condition, with variable etiologies, characterized by an age‐dependent phenomenon of extreme activation of epileptic activity during sleep, i.e. “status epilepticus during sleep”, that is strictly associated with the appearance of cognitive and behavioral disturbances. Even though the peculiar EEG picture is fundamental for the diagnosis of ESES, clear‐cut and shared diagnostic criteria for defining the EEG boundaries of this syndrome are still lacking. The diagnosis of ESES can be further complicated by the variability of the EEG findings, that during the course of the disease can change from diffuse to more or less focal and viceversa, depending both on the spontaneous clinical evolution of this condition and/or on the effects of medications. Given the complexity and the heterogeneity of EEG parameters during the ESES course, it is important to correlate the EEG findings with the concomitant cognitive and behavioral status, possibly taking into account not only the spike‐wave index, but also other parameters, such as for instance the topography of the epileptic abnormalities, their patterns of spread, and their fluctuations over time. Moreover, the epileptiform activity not only during sleep, but also during wakefulness, the presence of focal slowing, the organization of the EEG background and a derangement of the sleep architecture may play a role in determining the clinical picture.     

抗癫癎药物对儿童临床下癎性电持续状态及认知功能的影响

目的：探讨抗癫?药物（AED）对临床发作已控制,但脑电图（EEG）上仍存在癫?性电持续状态ESES患者的认知功能的影响。方法：收集2013年3月～2015年11月本院门诊、住院治疗的儿童癫?患者,用日本光电9000型长程录像脑电图（V‐EEG）监测到的16例临床下ESES患者,临床无发作均超过半年,随访观察,调整治疗方案前后均再进行神经心理学评估和V‐EEG监测。结果：16例应用卡马西平（CBZ）、奥卡西平（OXC）临床发作均已得到控制,V‐EEG提示仍存在ESES现象,神经心理学评估均存在不同程度的认知功能障碍,治疗方案调整为丙戊酸钠／丙戊酸镁、左乙拉西坦／托吡酯,3个月后复查V‐EEG提示ESES消失,脑功能状态得到改善（P＜0．05）。结论：AED的治疗目的,不仅要控制临床发作,也要控制临床下?样放电,特别是ESES现象。     

Misleading effects of clonazepam in symptomatic electrical status epilepticus during sleep syndrome

Electrical status epilepticus during sleep syndrome and its variants are age-dependent epileptic encephalopathies associated with a sleep-related electroencephalographic pattern of continuous spike-waves, combined with motor or cognitive impairment. These epileptic encephalopathies are usually not responsive to conventional antiepileptic drugs. This report describes two children in whom clonazepam had no effect on cognitive and motor disorders but controlled spike activity, preventing a proper diagnosis. Withdrawal of clonazepam was accompanied by the recurrence of continuous spike-waves in slow sleep, permitting the diagnosis of electrical status epilepticus during sleep syndrome and appropriate therapeutic decisions. These two cases of the misleading effect of clonazepam in electrical status epilepticus during sleep syndrome illustrate the puzzling situation that can occur when therapeutic options only consider the electroencephalographic features without prior syndromic diagnosis.     

A novel de novo TET3 loss-of-function variant in a Turkish boy presenting with neurodevelopmental delay and electrical status epilepticus during slow-wave sleep

BackgroundBeck-Fahrner syndrome is caused by homozygous or heterozygous mutations in TET3 on chromosome 2p13. The general characteristics of this syndrome include behavioral abnormalities such as autistic features, attention-deficit hyperactivity disorder, learning disabilities, and epilepsy.Case presentationSix years old male patient was found to have a de novo TET3 loss-of-function variant by whole-exome sequencing (WES) analysis and was diagnosed with electrical status epilepticus during slow-wave sleep (ESES) based on clinical and electroencephalogram (EEG) characteristics. The patient had a neurodevelopmental delay from the age of 3 months and started experiencing generalized tonic–clonic seizures and regression at the age of 5 years. EEG findings were consistent with ESES, and WES analysis revealed a novel heterozygous nonsense NM_001366022.1:c.1594C > T (p.Arg532*) variant in TET3. Valproic acid and immunotherapy were administered for the first 6 months, and clobazam was administered orally in addition to oral valproic acid therapy for the next 6 months. Clinical improvement was noted regardless of EEG improvement for the first 6 months. EEG improvement was achieved with clobazam. No regression was observed following the discontinuation of immunotherapy.ConclusionDecreased TET3 enzyme activity may be one of the new genetic etiologies of ESES.     

The Use of Susceptibility-Weighted Imaging for Epileptic Focus Localization in Acute-Stage Pediatric Encephalopathy: A Case Report

BackgroundSusceptibility-weighted imaging is a novel high-spatial-resolution three-dimensional gradient-echo magnetic resonance imaging technique with phase postprocessing that accentuates the paramagnetic properties of blood products. The use of susceptibility-weighted imaging for epileptic focus localization in the acute stage of encephalopathy in a child has not been documented.PatientsWe report three pediatric patients with status epilepticus in the setting of fever, in whom susceptibility-weighted imaging showed transient prominence of the focal venous vasculature.ResultsConventional cranial T1- and T2-weighted images and diffusion-weighted images showed no abnormalities. The prominence of the focal venous vasculature in these patients, as demonstrated by susceptibility-weighted imaging, was consistent with the epileptic focuses suggested by both clinical symptoms and electroencephalograph findings and resolved completely without neurological sequelae in all patients.ConclusionsSusceptibility-weighted imaging may facilitate assessing epileptic focus localization in the acute stage of encephalopathy in children.     

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

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

First-line therapy for theophylline-associated seizures

Theophylline-associated seizures (TAS) are considered a neurologic emergency, as they can sometimes be intractable and difficult to stop with standard treatments such as intravenous administration of diazepam. As a consequence, a proportion of patients who experience status epilepticus while receiving theophylline will require endotracheal intubation. The optimal first-line therapy for TAS has not yet been fully investigated. We compared 54 cases of TAS with 779 cases of non-TAS, that had presented at a single institution between 1991 and 2002. Among the 54 cases of TAS, 36 experienced generalized tonic–clonic seizures, with the remainder experiencing partial seizures. TAS occurred mainly in children under 3 years of age, and serum theophylline levels were within the therapeutic range in 78% of the cases. The duration of TAS tended to be longer than for non-TAS, and intravenous administration of diazepam was less effective in controlling TAS (45%), compared with non-TAS (68%). Many cases required repeated injections of diazepam, and 15 cases (27%) eventually required endotracheal intubation. Reports concerning the therapy for TAS were also reviewed. Theophylline is known to antagonize the effects of benzodiazepines, and this may explain why drugs such as diazepam are relatively ineffective in treating TAS. In TAS, the prompt use of barbiturates is recommended when diazepam is not effective, to avoid potential brain injury secondary to status epilepticus.     

Treatment with flunitrazepam of continuous spikes and waves during slow wave sleep (CSWS) in children.

We describe our treatment of two boys with continuous spikes and waves during slow wave sleep (CSWS). One of the boys was suffering from non-convulsive status epilepticus and the other from conscious disturbance with automatism. Their ictal EEG readings showed continuous diffuse spike and wave complexes, which were considered to show electrical status. The boys were diagnosed as having CSWS, and were later diagnosed with Landau-Kleffner syndrome (LKS). EEG readings returned to normal on intravenous injection of flunitazepam (FZP) at a dose of 0.02 mg/kg, suggesting that FZP is an effective treatment for CSWS.     

Intravenous Lacosamide in Pediatric Status Epilepticus: An Open-Label Efficacy and Safety Study

IntroductionLacosamide is an antiepilepsy drug approved by the Food and Drug Administration for patients aged 17 years and older for partial-onset seizures as monotherapy or adjunctive therapy. We reviewed the use of intravenous lacosamide in children aged less than 17 years with status epilepticus.MethodsChildren who received at least one dose of intravenous lacosamide for status epilepticus at our tertiary care children's hospital from December 2011 to March 2014 were studied. Status epilepticus was defined as continuous seizure activity for longer than 20 minutes or two or more recurrent seizures without regaining baseline level of awareness. Efficacy was defined as seizure freedom or more than 50% reduction of seizures within 24 hours of administering lacosamide.ResultsNine children with a mean age of 5.7 years (range: three months to 16 years) were included. The mean initial or loading dose was 8.7 mg/kg, with seven of nine patients receiving a dose of 10 mg/kg. The average total amount of intravenous lacosamide administered within the initial 24 hours was 13.8 mg/kg. Lacosamide was found to be efficacious in seven of nine (77.8%) patients. Four patients (44.4%) became seizure free. Two patients continued to have status epilepticus within 24 hours of lacosamide administration. Bradycardia was observed in one patient.ConclusionIn children with status epilepticus, intravenous lacosamide was efficacious in 78% of the patients and 44% become seizure free. In addition, no significant adverse reactions were observed. An appropriate safe, effective initial, or loading dose may be 10 mg/kg.