Dravet综合征诊断与治疗的中国专家共识

<正>Dravet综合征(Dravet syndrome, DS)(OMIM:607208)为婴儿期起病的难治性癫痫综合征,由法国医生Charlotte Dravet在1978年首次报道,既往又称婴儿严重肌阵挛癫痫(Severe myoclonic epilepsy in infancy,SMEI)^[1]。DS临床特点为2～15月龄起病,开始常为热性惊厥,随后逐渐出现多种发作类型的无热发作;发作具有热敏感的特点;病程中容易出现癫痫持续状态(Status epilepticus,SE);抗癫痫发作药物(Anti-seizure medications,ASMs)疗效欠佳;     

肌阵挛-失张力癫痫研究进展

肌阵挛-失张力癫痫( myoclonic-atonic epilepsy,MAE)又称Doose综合征[1],1970年由Doose首先描述,是一种少见的婴幼儿癫痫综合征,以肌阵挛及失张力性发作为主要特征。MAE占儿童期起病各类癫痫的1％～2％,发病高峰年龄为3～4岁,其诊断主要依靠临床症状及脑电图表现,目前尚无统一诊断标准。根据国际抗癫痫联盟(ILAE)及国内外学者描述,其诊断要点为：(1)起病前发育正常;(2)无器质性疾病及其他导致癫痫发作的疾病;(3)发病年龄在7个月至6岁;(4)男女发病比例为2∶1,1岁内为1∶1.5,常有遗传易患性;(5)癫痫发作形式包括肌阵挛、失张力发作、肌阵挛-失张力发作、失神发作、强直性发作、阵挛性发作、全面性强直-阵挛发作;(6)癫痫持续状态较常见;(7)脑电图最初可能为正常或θ波背景,无局灶性放电,后可出现全面性棘慢波或多棘慢波综合;(8)除外婴儿型良性及重症肌阵挛癫痫、隐源性Lennox-Gastaut综合征等[1-3]。     

青少年肌阵挛癫痫一例

正青少年肌阵挛癫痫(Juvenile myoclonic epilepsy,JME)是一种常见的年龄相关的特发性全身性癫痫综合征,占所有癫痫的2.8%～11.9%~([1]),占儿童特发性全身性癫痫的20%。JME起病年龄在12岁～18岁之间占76%。其典型发作形式是肌阵挛发作,可合并全面性强直-阵挛发作和失神发作,脑电图(EEG)特征为发作间期广泛性棘慢波或多棘慢波发放。治疗上以口服抗癫痫药物(AEDs)为     

青少年肌阵挛性癫癎87例临床及治疗特点分析

目的分析青少年肌阵挛性癫的临床及治疗特点。方法对87例青少年肌阵挛性癫患者进行回顾性分析,包括家族史、热性惊厥史、发病规律、临床表现、脑电图、变化及治疗效果。结果10例(11.5%)患者亲属中有癫史,12例(13.8%)患者有热性惊厥。肌阵挛发作起病年龄(13.1±3.4)岁;伴发强直阵挛发作平均起病年龄(14.3±3.8)岁;伴失神发作平均起病年龄(10.0±3.3)岁。平均延误诊断时间2.2年。睡眠诱发、闪光诱发刺激脑电图检查可提高性放电检出阳性率。16例患者在抗癫治疗中出现了癫发作次数或强度的增加。给予丙戊酸钠单药治疗的45例(75%)患者癫发作可得到控制。结论临床工作中对该病认识不足,极易误诊,造成疾病治疗迁延不愈,甚至出现治疗中因抗癫药物选择不合理而引起癫发作增加;小剂量丙戊酸钠治疗有效。     

青少年肌阵挛性癲痫20例临床特点分析

目的 研究青少年肌阵挛性癫痫患者(juvenile myoclonic epilepsy,JME)的临床及脑电图特点,探讨JME诊断要点.方法 回顾性分析在宣武医院癫痫门诊就诊的20例JME患者,总结其一般特点、发作类型及脑电图特点.结果 20例患者均有肌阵挛发作,部分合并全面强直一阵挛发作或典型失神发作.16例患者的脑电图可见全导爆发出现的棘慢波或多棘慢波,其中4例合并局灶性的异常.导致漏诊的最主要因素是肌阵挛发作的病史询问欠详.结论 JME的正确诊断主要依据其临床特点,询问肌阵挛发作的病史以得到诊断的关键信息,脑电图只是辅助的诊断工具.     

青少年肌阵挛癫痫和睡眠肌阵挛的比较研究

目的比较分析青少年肌阵挛癫痫(JME)和睡眠肌阵挛(SM)的临床和脑电图(EEG)特点.方法对20例JME患者和25例SM进行分析.结果JME多见于青春期发病,有遗传性,男女无差别,常在清醒时表现为双侧单一或反复的不规则无节律的肌阵挛发作,无意识障碍,可伴全身强直阵挛性发作(GTCS),少有失神,易被剥夺睡眠和闪光诱发,EEG示快而弥漫的不规则棘慢波和多棘慢波复合;SM可见于各年龄组,在入睡不久出现肢体或手指不自主、无规律地抽动一下,双侧不同时出现,发作频率和动作幅度不等,EEG监测在肢体抖动时,亦无异常放电.结论JME是一种遗传性、与年龄相关的以肌阵挛发作为主的癫痫综合征,其预后好;SM是一种无需治疗的生理现象.     

癫痫伴肌阵挛-失张力发作的临床及脑电图特征分析

目的探讨癫痫伴肌阵挛-失张力发作(epilepsy with myoclonic-atonic seizures,EMAS)的临床及视频脑电图特点,以提高对该病的认识。方法对2017年12月-2018年12月吉林大学白求恩第一医院小儿神经科收治的6例EMAS患儿临床及脑电特征进行回顾性分析。结果 6例EMAS患儿中,男5例,女1例;发病前智力运动发育正常,影像学正常。发病年龄2岁2个月～6岁,确诊时间2个月～1年6个月。6例患儿至少有肌阵挛、肌阵挛-失张力、失张力发作、不典型失神发作中两种发作形式。其中4例在上述发作前或后出现强直-阵挛发作,1例在病程晚期有强直发作。6例患儿中5例背景活动正常; 1例背景活动偏慢。6例患儿的脑电图在清醒期及睡眠期均出现广泛性2～4 Hz棘慢波、多棘慢波不规则或节律性发放,睡眠期放电有时类似高度失律,均无局灶性发作。所有患儿影像学检查均正常。6例患儿均给予正规抗癫痫药物治疗,其中2例治疗反应良好,4例治疗无效后给予甲基强的松龙治疗,其中3例有效缓解,1例虽然没有发作仍有大量放电。结论 EMAS好发于学龄前期儿童,癫痫发作类型主要包括肌阵挛、失张力或肌阵挛-失张力发作,但不典型失神等,脑电图主要为广泛性棘慢波、多棘慢波发放,治疗以抗癫痫药物和激素治疗为主,预后相对较好。     

儿童肌阵挛癫(癎)临床和录像脑电图分析

目的:探讨儿童肌阵挛癫(癎)患儿的临床、脑电图(EEG)和治疗特点.方法:对35例肌阵挛癫(癎)患儿的临床表现、录像脑电图(V-EEG)及抗癫(癎)药物的治疗效果进行回顾性分析.结果:35例均有肌阵挛发作,以肌阵挛为唯一的发作形式9例,其它26例合并强直阵挛发作、强直发作、部分性发作等发作类型.30例患儿EEG可见全导...     

良性成人家族性肌阵挛癫痫三家系临床特点分析

对三个良性家族性肌阵挛癫痫(BAFME)家系中的31例存活患者的临床资料进行回顾性分析.31例患者年龄为16-83岁,平均45.9岁.家系一发病年龄为14～46岁,家系二为15～39岁,家系三为31～50岁.男女发病率无明显差异.所有患者均以皮质震颤、肌阵挛伴或不伴癫痫发作为主要临床表现.28例存活者行脑电图检查,21例显示异常,主要表现为多棘波或棘慢、尖慢复合波的出现.25例存活者行体感诱发电位检查,21例可见巨大电位.丙戊酸钠能有效控制患者的肌阵挛或全身强直-阵挛发作.     

肌阵挛失神发作1例并文献复习

目的:探讨肌阵挛失神发作的临床症状学、神经电生理学特点及治疗效果.方法:报告1例肌阵挛失神发作的临床表现、脑电图、肌电图特点及治疗效果,并结合文献进行回顾性分析.结果:肌阵挛失神发作临床表现为失神伴双侧节律性肌阵挛,常伴发肢体的强直,脑电图表现为双侧、广泛、节律性3 Hz的棘慢复合波,肌电图则表现为与发作期放电频率一致的肌电暴发.此类患者对药物治疗反应较差,伴有强直发作的患者可行胼胝体切开术,该手术可有效减少强直发作导致的跌倒.结论:肌阵挛失神发作病程多样,大部分患者药物治疗反应差,伴有强直发作的患者可以考虑手术治疗.     

Seizure characterization and electroencephalographic features in Glut-1 deficiency syndrome

PURPOSE: To characterize seizure types and electroencephalographic features of glucose transporter type 1 deficiency syndrome (Glut-1 DS). METHODS: Twenty children with clinical and laboratory features of Glut-1 DS were evaluated. Age at seizure diagnosis, seizure classification, and response to treatment were determined by chart review. Thirty-two continuous 24-h EEG monitoring sessions and reports of 42 routine EEG studies were assessed. RESULTS: Age at seizure diagnosis was between 4 weeks and 18 months (mean, 5 months). Seizure types were generalized tonic or clonic (14), absence (10), partial (nine), myoclonic (six), or astatic (four). During 24-h EEGs, background activity showed generalized 2.5- to 4-Hz spike-wave discharges (41%), generalized slowing or attenuation (34%), no abnormalities (34%), focal epileptiform discharges (13%), or focal slowing or attenuation (9%). No seizures were captured during 69% of the studies; the remainder had absence (19%), myoclonic (9%), or partial seizures (3%). On evaluation of routine and 24-h EEG studies, focal epileptiform discharges (24%) and slowing (11%) were more frequent in ages 0-24 months. In older children (2-8 years), generalized epileptiform discharges (37.5%) and slowing (21%) were more common. CONCLUSIONS: In all ages, a normal interictal EEG was the most common EEG finding. When abnormalities occurred, focal slowing or epileptiform discharges were more prevalent in the infant. In older children (2 years or older), a generalized 2.5- to 4-Hz spike-wave pattern emerged. Seizure types observed included, absence, myoclonic, partial, and astatic.     

Seizure semiology and neuroimaging findings in patients with midline spikes

PURPOSE: Midline epileptiform discharges are rare compared with discharges at other scalp locations. Neuroimaging results and semiologic seizure characteristics of patients with midline spikes are not adequately described. The aim of this study was to describe the neuroimaging findings and detailed seizure semiologies in patients with midline spikes. METHODS: We reviewed the EEG database of the University of Michigan Medical Center and identified 35 patients with midline spikes. Information about seizure types and neuroimaging results was obtained from a review of medical records. The seizures were classified according to the International League Against Epilepsy (ILAE) criteria and semiologic classification. RESULTS: Twenty-nine (83%) patients had a history of seizures. Complex partial seizures and simple partial seizures were the most common seizure types, experienced by 66% of patients. The age at seizure onset was within the first 10 years in 90% of patients. According to the semiologic seizure classification, automotor seizures and tonic seizures were the most common seizure types. Neuroimaging studies were abnormal in 45% of patients. When focal abnormalities were detected, they were lateralized to one of the frontal lobes in all cases. CONCLUSIONS: Our results indicate that in the majority of patients, midline spikes represent focal epileptiform activity rather than fragments of generalized discharges, and are most commonly associated with seizures of partial onset. Automotor seizures and tonic seizures are the most common semiologies. Focal radiologic abnormalities tend to be lateralized to one of the frontal lobes.     

Long-term prognosis of epilepsies and related seizure disorders in Fukuyama-type congenital muscular dystrophy

Fukuyama-type congenital muscular dystrophy is an autosomal recessive disorder prevalent in Japan that is characterized by congenital muscular dystrophy, cobblestone lissencephaly, and eye anomalies. We examined 46 patients with Fukuyama-type congenital muscular dystrophy and followed their progress for more than 3 years, with special reference to long-term prognosis of seizure disorders and the relationship between seizures and neuropathologic abnormalities. Seizures were observed in 37 patients (80%). The average age at onset was 3 years, 1 month. Initial seizures usually occurred after a febrile episode, although one third of patients had afebrile seizures from the onset. All patients had generalized tonic-clonic convulsions at febrile disorders, and these were followed by complex partial seizures or secondary generalized seizures. Later these seizures developed into Lennox-Gastaut syndrome in three patients. Electroencephalography (EEG) showed paroxysmal discharges in 22 of 37 patients with seizures (59%). The main focus was in the frontal, temporal, or central region. Lesions with marked cortical dysplasia detected by computed tomography, magnetic resonance imaging, or autopsy showed focal paroxysmal discharges on EEG.     

Factors predicting the outcome following medical treatment of mesial temporal epilepsy with hippocampal sclerosis

PurposeThere is a lack of information from South America regarding factors that predict the clinical outcomes of patients treated medically for mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). This study was conducted to determine which of these factors are the most important.MethodsThis study included 110 South American patients with MTLE-HS treated with antiepileptic drugs. The factors considered included age, gender, age of epilepsy onset, interval between the lesion and the first seizure, central nervous system infection, traumatic brain injury, perinatal asphyxia, febrile convulsion, history of status epilepticus, types of seizures, site of hippocampal sclerosis (HS), extrahippocampal pathology, and electroencephalogram (EEG) abnormalities. The patients were divided into two groups based on the response to treatment: Group I, seizure free for at least two years; and Group II, not seizure free.ResultsOn the multivariate analysis, the factors associated with a poor prognosis in terms of seizure frequency and control following treatment included the presence of an early onset of seizure, more than 10 seizures per month before treatment, and EEG abnormalities.ConclusionThe recognition of risk factors, such as early onset of seizures, more than 10 seizures per month before treatment, and EEG abnormalities, could lead to the identification of risk groups among patients with MTLE-HS and refractory epilepsy, possibly designating these individuals as candidates for early epilepsy surgery.     

Clinical Electroencephalographic Biomarker for Impending Epilepsy in Asymptomatic Tuberous Sclerosis Complex Infants

BackgroundWe assessed the clinical utility of routine electroencephalography (EEG) in the prediction of epilepsy onset in asymptomatic infants with tuberous sclerosis complex.MethodsThis multicenter prospective observational study recruited infants younger than 7 months, seizure-free and on no antiepileptic drugs at enrollment, who all underwent serial physical examinations and video EEGs throughout the study. Parental education on seizure recognition was completed at the time of initial enrollment. Once seizure onset occurred, standard of care was applied, and subjects were followed up until 24 months.ResultsForty patients were enrolled, 28 older than 12 months with completed EEG evaluation at the time of this interim analysis. Of those, 19 (67.8%) developed seizures. Epileptic spasms occurred in 10 (52.6%), focal seizures in five (26.3%), generalized tonic-clonic seizure in one (5.3%), and a combination of epileptic spasms and focal seizures in three (15.7%). Fourteen infants (73.6%) had the first emergence of epileptiform abnormalities on EEG at an average age 4.2 months, preceding seizure onset by a median of 1.9 months. Hypsarrhythmia or modified hypsarrhythmia was not found in any infant before onset of epileptic spasms. All children with epileptiform discharges subsequently developed epilepsy (100% positive predictive value), and the negative predictive value for not developing epilepsy after a normal EEG was 64%.ConclusionsSerial routine EEGs in infants with tuberous sclerosis complex is a feasible strategy to identify individuals at high risk for epilepsy. The most frequent clinical presentation was epileptic spasms followed by focal seizures, and then a combination of both seizure types.     

难治性癫痫60例临床分析

目的明确难治性癫痫的临床特点,早期诊断难治性癫痫。方法采用回顾性病例对照分析方法对60例难治性癫痫患者的临床资料进行分析。结果与对照组相比,症状性癫痫比例、5岁之前发病率、早期频繁发作几率、出现多种癫痫发作形式和并发智能障碍几率明显增高;影像学异常改变和脑电图重度改变的几率增高;需要3种及以上药物控制发作的几率增高。结论难治性癫痫多具有如下特点:症状性癫痫、发病年龄早、病初发作频繁、出现多种发作形式、伴发或继发智能障碍、影像学异常改变、脑电图重度异常、应用多种抗癫痫药物疗效差。     

Generalized onset seizures with focal evolution (GOFE) — A unique seizure type in the setting of generalized epilepsy

PurposeWe report clinical and electrographic features of generalized onset seizures with focal evolution (GOFE) and present arguments for the inclusion of this seizure type in the seizure classification.MethodsThe adult and pediatric Epilepsy Monitoring Unit databases at Vanderbilt Medical Center and Children's Hospital were screened to identify generalized onset seizures with focal evolution. We reviewed medical records for epilepsy characteristics, epilepsy risk factors, MRI abnormalities, neurologic examination, antiepileptic medications before and after diagnosis, and response to medications. We also reviewed ictal and interictal EEG tracings, as well as video-recorded semiology.ResultsTen patients were identified, 7 males and 3 females. All of the patients developed generalized epilepsy in childhood or adolescence (ages 3–15 years). Generalized onset seizures with focal evolution developed years after onset in 9 patients, with a semiology concerning for focal seizures or nonepileptic events. Ictal discharges had a generalized onset on EEG, described as either generalized spike-and-wave and/or polyspike-and-wave discharges, or generalized fast activity. This electrographic activity then evolved to focal rhythmic activity most commonly localized to one temporal or frontal region; five patients had multiple seizures evolving to focal activity in different regions of both hemispheres. The predominant interictal epileptiform activity included generalized spike-and-wave and/or polyspike-and-wave discharges in all patients. Taking into consideration all clinical and EEG data, six patients were classified with genetic (idiopathic) generalized epilepsy, and four were classified with structural/metabolic (symptomatic) generalized epilepsy. All of the patients had modifications to their medications following discharge, with three becoming seizure-free and five responding with > 50% reduction in seizure frequency.ConclusionGeneralized onset seizures may occasionally have focal evolution with semiology suggestive of focal seizures, leading to a misdiagnosis of focal onset. This unique seizure type may occur with genetic as well as structural/metabolic forms of epilepsy. The identification of this seizure type may help clinicians choose appropriate medications, avoiding narrow spectrum agents known to aggravate generalized onset seizures.     

Prognosis of epilepsy withdrawn from antiepileptic drugs

Abstract Antiepileptic drugs (AED) were discontinued in 55 epileptics who had been free from seizures treated with AED, in accordance with the following criteria and procedures. (i) A reduction in AED commences when patients have been free from seizures for at least 2 years and epileptic discharges have also disappeared in repeated electroencephalogram (EEG) recordings during that period. (ii) AED are gradually reduced if no relapse is seen in clinical seizures and epileptic discharges in EEG. (iii) As a rule at least 2 years are required as the interval from the onset of a reduction to the withdrawal of AED. Forty-three patients were followed up by a questionnaire and/or by telephone and the follow-up period from the withdrawal of AED to the survey ranged from 0.9 to 8.8 years; in 38 patients (88.4%) the period was longer than 2 years. No relapse of seizures was found in any of the 43 patients. The severity of epilepsy judged by the total number and frequency of seizures, the presence of neuropsychiatric complications, the combination of different types of seizures, and the duration of epilepsy from the seizure onset to the last seizure appeared not to be risk factors for the recurrence of seizure. Normal EEG was, however, considered to be an important prerequisite for a good prognosis.     

Clinical and electrophysiological characteristics of startle epilepsy in childhood

ObjectiveStartle epilepsy is one syndrome of reflex epilepsies. We studied its clinical and EEG characteristics.MethodsAnalysis of the clinical and EEG characteristics of startle epilepsy.ResultsOf 11 patients, five were female. Age of onset ranged from 5 months to 7.5 years. Abnormal etiologies were found in seven patients, as a result of perinatal and postnatal factors. Neuroimaging showed abnormalities, commonly focal atrophy, in nine patients. Spontaneous seizures preceded or followed the startle seizures and were present in all patients. Startle seizures experienced included tonic, myoclonic, tonic–myoclonic, tonic–atypical absence, asymmetric tonic motor seizure and tonic–clonic seizure. Diffuse electrodecremental pattern was the most common ictal EEG pattern seen. The triggering stimuli of the startle seizures were sound in seven patients, touch in three and both sound and touch in one. Interictal EEG revealed abnormalities in 10 patients including generalized, multifocal or focal discharges. Many different anti-epileptic drugs were often unsatisfactory.ConclusionStartle epilepsies were often symptomatic reflex epilepsies and there were several types of startle seizure. The ictal EEG often showed a diffuse electrodecremental pattern. This disease has a bad prognosis.SignificanceWe delineated the clinical and EEG characteristics of startle epilepsy in childhood.     

Lennox-Gastaut syndrome with late-onset and prominent reflex seizures in trisomy 21 patients

Purpose:   Lennox-Gastaut syndrome (LGS) is a severe epileptic condition characterized by multiple seizure types including tonic seizures, slow spike-and-wave discharges on electroencephalography (EEG), and cognitive impairment. LGS can occur in apparently healthy subjects or in patients with preexisting brain damage. The onset peaks between 3 and 5 years of age and the prognosis is usually poor. Herein we report 13 subjects with trisomy 21 who developed LGS.
Methods:   We retrospectively reviewed the clinical and EEG data of consecutive patients with LGS and trisomy 21 referred to five epilepsy centers over the last 30 years.
Results:   Data for 13 patients (8 male, 5 female) were collected. The mean age at onset was 9.1 years (range 5–16). The mean age at last follow-up was 23.5 years (range 11–43 years). Seizure onset was after age 8 years in eight (62%) patients and between age 5 and 8 in the other five. In none of the cases did a West syndrome precede the onset of LGS. Nine of 13 patients (69%) had unambiguous reflex seizures, mostly precipitated by sudden unexpected sensory stimulations, usually preceding or accompanying the onset of a full-blown LGS picture. Interictal and ictal EEG findings were typical for LGS. All patients were drug-resistant.
Discussion:   Patients with trisomy 21 may present a peculiar LGS, characterized by late onset and high occurrence of reflex seizures. Mechanisms underlying this particular presentation of LGS may include dendritic rarefaction and decreased interneurons, as well as functional abnormalities leading to overall decreased brain inhibition in these patients.