1、癫痫 Epilepsia,Epilepsy,殷剑 北京医院神经内科,自古以来，不分贵贱、不论行业，在人类文明史上，最早的 癫痫纪录可上溯至公元前五千年的美索不达米亚。虽然历史 上有很多人对癫痫怀有极大的误解以及恐惧。有许多有创造力、影响力的人物都是癫痫病友，他们甚至被称 为天才。除了坠落之病以外， 古时候也有人将癫痫称为圣病。 我国最早在皇帝内经中。 Epilepsia最早为Hippocrates 所用。,汉穆拉比法典,亚历山大大帝 凯撒大帝， 拿破仑波拿巴,定义,WHO的定义是“癫癎是多种病因的慢性脑疾患，其特点为大脑神经元过度放电所致的暂时性中枢神经系统功能失常为特征”。功能失常可能表现为
2、运动、感觉、意识、行为、自主神经等不同障碍，或兼有之。每次发作称为癎性发作。发作具有自发性(spontaneity)、反复性(recurrence)、突发性（outbreak）及阵发性(paroxsmal)四个特点,单独一次发作不能诊断为癫癎。发作两次以上才能拟诊为癫癎。,癫痫（epilepsy）的定义：.癫痫是一种脑部疾患,其特点是持续能产生癫痫发作的脑部持久性改变,并出现相应的神经生物学、认知、心理学以及社会学等方面的后果”,并指出“同时具备至少1次癫痫发作、脑部持久性改变、伴随状态(长期发作对患者的躯体、认知、精神心理和社会功能等方面的不良影响)三个要素才可诊断癫痫”。 ，具有突然发生，
3、反复发作的特征 ILAE与IBE癫痫新定义原文: Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one ep
4、ileptic seizure. 癫痫性发作（epiletic seizure）：ILAE2005年提出的癫痫发作新定义：癫痫发作(epileptic seizure)。脑组织存在的一组神经元异常和过度放电引起的各种临床表现，如突然和短暂性意识、运动、感觉、自主神经或精神改变，但自身能够感知或被他人察觉。 1脑部神经元高度同步化的异常活动、2发作的短暂性及3特殊的临床现象足癫痫发作的3要素。患者可有一种或数种发作类型的症状。 发作（discharge）：大量神经元同时被激活造成神经元的电活动 活动性癫痫(active epilepsy)。在流行病学调查中，无论是否予抗癫痫药物(AEDs)治疗，
5、以往2.5年内至少有一次发作。也有研究将时间限定在1年以内，以保证回忆的正确性。,历史1,癫痫源于希腊语“epilepy”，意指不同特征和不同程度的反复发作现象。,历史2,随着人类癫痫学对癫痫的新认识，不断地赋于这个古老名词新的内涵，使其有新的含义。,历史3,中世纪主张用宗教、神秘力量来解释癫痫的发生，因而人们认为癫痫就足鬼神附休的结果； 18世纪初，人们给癫痫赋予的特定内涵是“脑局部积蓄的能量，不可预测地突然过度释放的现象”； 1870 年，Jacksons提出“癫痫是灰质突然的、过度的异常放电”； 1986年，人们则认为“癫痫代表着一个或几个脑部功能的发作性失调” 2001年，ILAE提出
6、的癫痫内涵是“皮质及深部核团、部分丘腑及上位脑干灰质神经元突然、发作性、短暂性异常放电所导致的脑功能紊乱的临床现象,历史4,传统癫痫定义强调2次以上发作才考虑是癫痫的观念可能延迟对部分患者的治疗。因此，2005年，ILAE提出，新的癫痫和癫痫发作的定义。 An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. ILAE提出的癫痫发作新定义认为“癫痫发作是脑部神经元
7、高度同步化异常活动所引起，由不同症状和体征组成的短暂性临床现象 脑部神经元异常放电是癫痫发作的核心，但并不是脑部神经元异常放电引起的发作都是癫痫发作，脑部神经元异常放电还可引起发作性神经痛等，ILAE认为只有大脑、丘脑皮质系统及上部脑干十神经元的异常放电才会引起癫痫发作，而且这种异常放电的特征为高度同步化。,英语中seizure来自希腊语，国内译成“发作”。医学中将其广泛用于代表突发性的严重事件，如心脏病发作、心理或生理事件的发作等，这些发作并不都是癫痫，而仅在某些方面与癫痫相似。为了强调痫性发作性质，ILAE及IBE主张将癫痫患者的发作称为癫痫发作(epileptic seizure)，以便
8、与非痫性发作区别。,历史5,2005年Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures, and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epilept
9、ic seizure. 癫痫是一种脑部疾病，其特点是脑部有持续存在的癫痫反复发作的易感性，以及由于这种疾病引起的神经生化、认知、心理和社会后果，癫痫的确定要求至少有一次癫痫发作“。脑部持续存在反复发作的易感性、至少一次癫痫发作的病史及发作伴发的神经生化、认知、心理及社会功能障碍是癫痫的三大要素。（中华医学会癫痫协会译本） “癫痫是一种具有产生多次癫痫发作的持久性倾向和具有神经生物、认知、心理及社会多种后果为特征的脑疾病。而癫痫的确定则要求至少有一次癫痫发作。”（天坛译本）,2014年ILEA临床标准公布Operational (practical) clinical definition of
10、 epilepsy,Epilepsy is a disease of the brain defined by any of the following conditions 1. At least two unprovoked (or reflex) seizures occurring 24 h apart 2.One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unpr
11、ovoked seizures, occurring over the next 10 years 3. Diagnosis of an epilepsy syndrome Epilepsy is considered to be resolved for individuals who had an age-dependent epilepsy syndrome but are now past the applicable age or those who have remained seizure-free for the last 10 years, with no seizure m
12、edicines for the last 5 years.,2014年ILEA临床标准公布Operational (practical) clinical definition of epilepsy,根据新的定义，癫痫是由以下标准定义的脑病（符合下列之一即可临床诊断）： 1. 患者出现间隔超过24小时发生的、出现至少2次的非诱发性（或反射性）痫性发作； 2.患者出现单次非诱发性（或反射性）痫性发作，评估其未来10年内，出现第二次非诱发性痫性发作几率和已知类似情况总体风险相近（发作风险至少60%）。 3. 已经诊断为癫痫综合征。 可控癫痫指1，已有10年无发作、且过去5年内患者未接受抗痫药物
13、治疗的癫痫；2，年龄相关癫痫综合征已经过了发病年龄.,癫痫综合征,ILAE提出的癫痫综合征定义为：有特殊病因，由特定的症状和体征组成的特定癫痫现象.,Disease,The ILAE and the International Bureau for Epilepsy (IBE) have recently agreed that Epilepsy is best considered to be a disease Epilepsy has traditionally been referred to as a disorder or a family of disorders, rather
14、 than a disease, to emphasize that it is comprised of many different diseases and conditions.,卒然昏倒，半身不遂，口眼斜属肝阳上亢，化风挟痰，卒中脏腑所致，为中风之中脏腑；若神志清楚，仅半身不遂或口眼斜，为中风之中经络，或中风后遗症。卒倒而口开手撒，二便失禁，是中风脱证；卒倒而牙关紧闭，两手握固，大小便闭，是中风闭证。 卒然昏倒，不省人事，伴四肢抽搐，口吐涎沫，两目上视，移时苏醒，醒后如常者多属脏气失调，肝风挟痰，阻闭清窍所致，见于痫病。 卒然昏倒，伴见四肢厥冷，而呼吸自续多为厥证。 盛夏卒倒，面赤汗
15、出，甚而昏迷痉厥者多为中暑，是暑热或暑湿秽浊之邪，闭阻气机，心神所致。,中医对癫痫的描述,癫痫发作的症状学特点-1,共性 反复性：至少一次以上 发作性：突发突止 短暂性：除非持续状态，一般3-5分钟，很少超过5分钟 刻板性：就每个个体的发作类型基本是相同的。,癫痫发作的症状学特点-2,个性，即不同个体的症状多样性 不同癫痫个体的症状差异很大，可以表现为感觉、运动、意识、精神、行为、自主神经系统等，或兼而有之，即脑有多少种功能，便可有多少种发作症状，或单独存在，或联合出现。,病因：临床上分3大类（国际抗癫痫联盟分类和名词委员会推荐的癫痫和癫痫综合征的分类(1989)）。 1、原发性癫痫idiop
16、athic epilepsy（特发性癫痫）：指除遗传因素外不具有其他潜在性病因的癫痫。 2、继发性癫痫、症状性癫痫：由明确的脑部病损和代谢障碍引起癫痫。 3 隐源性癫痫：有癫痫发作，但病因目前尚不明确的。,诱发因素,发热、过量饮水、过度换气、饮酒、缺眠、过劳和饥饿等均可诱发癫痫发作。某些药物如美解眠、丙咪嗪、戊四氮或突然撤除抗痫药物，亦可导致癫痫发作。 感觉因素：某些特定的感觉如视、听、嗅、味、前庭、躯体觉等刺激可引起不同类型的癫痫发作，称反射性癫痫。 精神因素：强烈情感活动、精神激动时可促癫痫发作。,癫癎的病因,原发性（用现有一切检查方法找不出病因者） 继发性：成人占69，儿童40,癫癎的病
17、因,210岁：产伤、发热、感染（乙脑、化脑、脑脓肿、结脑、霉菌性脑膜炎、各种脑寄生虫等）、外伤、原发性。 1120岁：原发性、外伤、先天性缺陷（大脑发育不良等）。 2140岁：外伤、脑瘤、原发性、慢性酒精中毒等。 4160岁：脑瘤、外伤、脑血管病、慢性酒精中毒等。 60岁以上： 脑血管病、脑瘤（原发、转移瘤）、外伤、变性疾患等。,癫癎的病因,外伤性癫痫0.5%5% 早期：一周以内，占5% 1/3发生于伤后1小时内 1/3发生于伤后24小时内 1/3发生于伤后2-7天内 约25%的早期癫痫患者发展为晚期癫痫,Epilepsia的流行病学（患病率）,Overall prevalence of ep
18、ilepsy the pooled prevalence rate of epilepsy was 2.89 (95% CI: 2.573.21). Prevalence by gender The prevalence of males and females was 3.83 and 3.45, respectively .the odds ratio of epilepsy for males versus females, indicating that men were 1.17 times more likely to have epilepsy than women. Preva
19、lence by location The prevalence rate in rural areas was 3.17, and was 2.34 in urban areas. the odds ratio of epilepsy in rural area versus urban areas. The meta-analysis demonstrated that people in rural areas were 1.37 times more likely to have epilepsy than those in urban areas 目前，全球约有50106例癫癫患者，
20、其中80在发展中国家，我国约9106余例患者，每年仍新增450103余例，目前活动性病例约6.50106例，其中农村地区约占2/3，治疗缺口达70 Epilepsy Research (2013) 105, 195205,Epilepsia的流行病学,Prevalence by age The prevalence rates of epilepsy among different age groups, 09, 1019, 2029, 3039, 4049, 5059, 6069 and 70 were 2.21, 3.23, 3.14, 2.83, 2.96, 2.61, 2.76 and
21、 2.22, respectively. The highest prevalence of 3.23 was found in the 1019 age group, while the lowest (2.21) was in the 09 age group Prevalence by seizure types the prevalence of seizure type (general, partial and unclassifiable) was 3.12, 0.57 and 0.23, respectively Epilepsy Research (2013) 105, 19
22、5205,流行病学,癫痫患者的死亡风险是普通人群的1.20-9.30倍(SMR:1.20-9.30)。癫痫患者的死因主要有癫痫持续状态(SE)、意外事故、自杀、癫痫猝死(SUDEP)等。,发病机制,神经元痫性放电的发生： 正常时神经元有节律性的自发放电活动，一般为1020Hz。 在癫痫病灶的周围部分，其神经元的膜电位与正常神经元有不同，在每次动作电位发生之后出现称为“阵发性去极化偏移”（PDS）的持续性去极化状态，并产生高幅高频的棘波放电。在历时数十至数百毫秒之后转入超极化状态。,神经元坏死或缺失,癫痫的发病机制,谷氨酸脱羧酶减少,谷氨酸和谷氨酰胺增加 钙离子进入细胞内增加 钾离子大量溢出,结
23、构的改变,生化学改变,动作电位超极化, 同步放电(痫性放电),病灶(Lesion),癫痫灶(Location),神经元结构紊乱 胶质细胞增生 对称性细胞体和树突减少,癫痫灶的“点燃” Igniting of seizure,阵发性去极化偏移,癫痫的发病机制,兴奋型动作电位(痫性放电),各种不同形式的痫性发作 (Seizure),痫性活动的传播 Spread of seizure,动作电位沿神经轴突的方向，在一定的范围内传导、扩散,抑制型动作电位,癫痫的发病机制,痫性发作停止 (Terminating),癫痫活动的“终止” Terminating of seizure,兴奋型动作电位(痫性放电)
24、,抑制型动作电位,癫痫性放电的传播： 部分性发作：异常放电局限于大脑皮质的某一区域；若在局部的反馈回路中长期传导，则导致部分性发作持续状态。 继发性全身性发作：当异常放电不仅扩及同侧而且扩及对侧大脑半球； 失神发作：当异常电位的起始部分在中央脑（丘脑和上部脑干）并扩及脑干网状结构上行激活系统； 全身强直-阵挛性发作：当异常电位广泛投射至两侧大脑皮质和网状脊髓束受到抑制。,国际10-20系统,其特点是： 电极有各自的名称：位于左侧的是奇数，右侧的是偶数。 按近中线的用较小的数字，较外侧的用较大的数字。 电极名称包括电极所在头部分区的第一个字母。 诸点电极的间隔均以10%和20来测量。,世界上绝大
25、多数脑电图实验室采用的是国际10-20系统(the 10-20 international System)电极放置法,正常脑电背景,脑电图,1、波；正常人以型脑电图为主，频率为813Hz 2、波；少数正常人出现型脑电图，频率为1425Hz 3、波；47Hz的电活动，称为波 4、波；4Hz以下，称为 波 5、波幅；2050 V左右，可达100 V,癫痫样放电的类型,散发性棘波：Spike: A transient, clearly distinguished from background activity, with pointed peak at conventional paper spe
26、eds and duration of 20 to under 70 ms i.e. over 1/501/14 s approximately. The main component is generally negative relative to other areas. Amplitude is variable 散发性尖波：Sharp wave: A transient, clearly distinguished from background activity, with pointed peak at conventional paper speeds and duration
27、 of 70200 ms i.e. over 1/141/5 s approximately. The main component is generally negative relative to other areas. Amplitude is variable 棘慢波或尖慢波综合波 多棘慢波 高幅失律 发作性节律波,散发尖波,棘慢波或尖慢波综合波,发作性节律波1,发作期：一侧性，常为双侧发放，弥散的或限局于颞或额颞区 发作间期：一侧或双侧广泛非同步性病灶，常在颞或额区,癫痫分类历史回顾,癫痫发作分类 1970 1981 2001,癫痫综合征分类 1989 2001,癫痫发作的临床和脑
28、电图分类,国际抗癫痫联盟分类和名词委员会推荐 1981,名词定义,Focal (synonym=partial) seizure: a seizure that has an initial semiology which indicates or is consistent with initial activation of only part of one cerebral hemisphere. 一、部分性发作(partial ,focal ,local seizures)部分性发作指的是:首发的临床和脑电图的变化表明最初的神经元的活动限于一侧半球的限局范围内 Generalised
29、(synonym = bilateral) seizure: a seizure that has an initial semiology which indicates or is consistent with more than minimal involvement of both cerebral hemispheres.全身性发作(惊厥或非惊厥性) 指:首发的临床变化表明开始即侵犯双侧半球。意识可以有障碍并可以是首发症状。运动症状为双侧性的,发作时的脑电图异常是双侧的,可能反映神经细胞发放遍及双侧半球。 Aura先兆: a subjective ictal phenomenon
30、that, in a given patient, may precede an observable seizure; if alone it constitutes a sensory seizure. 癫痫样( epileptiform seizure ) 发作，指患者的一次发作事件其临床表现甚至脑电表现均与癫痫发作高度类似、难以区别。但大脑本身仅有某种痫性发作易感性的暂时性增强改变，如许多脑外伤后的即刻或近期癫痫样发作，脑炎急性期伴发的癫痫样发作、脑梗死急性期出现的癫痫样发作等等，在急性期之后发作自行减少，逐步停止。因此，这类痫性发作不能称为癫痫。,I、部分性发作,最初的临床-EEG改
31、变表明发作从局部开始 根据有无意识障碍再分为 单纯部分性发作（累及一侧半球，无意识障碍） 复杂部分性发作（累及双侧半球，有意识障碍） 意识障碍的定义：由于知觉和/或反应能力的改变而不能对外界刺激作出正确反应,Jackson发作：。可以是严格的限局性的发作也可扩散至身体其他部位称Jackson 发作,但不扩散至全身造成全身痉挛及意识丧失。 Todd麻痹：发作停止后可使原有瘫痪暂时加重或出现暂时性局限性瘫痪。,Jacksonian seizure,癫痫综合征的举例,Epilepsy Syndromes,Epilepsy Syndrome Grouping of patients that shar
32、e similar: Seizure type(s) Age of onset Natural history/Prognosis EEG patterns Genetics Response to treatment Epilepsy is an umbrella term, under which many types of diseases and syndromes are included. Some authors distinguish between epilepsies and epileptic syndromes, depending on whether seizure
33、s are the only neurologic disorder (an epilepsy) or are one of a group of symptoms (an epileptic syndrome). Some of the epilepsies (e.g., juvenile myoclonic epilepsy) have well-defined genetics, clinical courses, and responses to medication. Others (e.g., temporal lobe epilepsy) have natural histori
34、es which are highly variable, and which reflect differences in pathology as well as in host response to that pathologic process and to the treatments administered.,C-Slide 57,Return to index,American Epilepsy Society 2010,癫痫综合征的定义,癫痫综合征：由一组类似症状和体征组成的特定的癫痫现象（根据发病年龄、发作类型、EEG及病因）,其具有独特的临床特征,病因及预后 (癫痫发作
35、和癫痫诊断方案的建议 ILAE,2001),伴有中央颞区棘波的儿童良性癫痫（Benign childhooh epilepsy with centrotemporal spikes BECTS) Rolandic Seizures,诊断标准： 1.3 and 13 years (peak 910 years) 2.发作为局限性，多位于一次口角和上肢阵挛 3.神经精神发育正常 4. 脑电图可见中央颞区双向较慢棘波 5.多在夜间发作 617岁以前发作消失,Benign childhood epilepsy with centrotemporal spikes (best known among p
36、aediatricians as Rolandic epilepsy) is defined by the ILAE as follows:,“Benign childhood epilepsy with centrotemporal spikes is a syndrome of brief, simple, partial, hemifacial motor seizures, frequently having associated somatosensory symptoms which have a tendency to evolve into generalised tonic
37、clonic seizures. Both seizure types are often related to sleep. Onset occurs between the ages of 3 and 13 years (peak 910 years) and recovery occurs before the age of 1516 years. Genetic predisposition is common, and there is a male predominance. The EEG has blunt high-voltage centrotemporal spikes,
38、 often followed by slow waves that are activated by sleep and tend to shift or spread from side to side.”,The following should be considered in future revisions of the classification of BCECTS,(a). Most of centrotemporal spikes are, in fact, Rolandic spikes; they are rarely located in the temporal e
39、lectrodes (b). The word temporal is misleading because these children do not have symptoms from the temporal lobes (c). BCECTS may occur without centrotemporal spikes and conversely centrotemporal spikes may occur in children without seizures or other clinical phenotypes of benign childhood seizure
40、susceptibility syndrome (d). Similar clinical features may appear in patients with spikes in other than centrotemporal locations (e). Children with centrotemporal spikes may manifest with symptoms typical of PS.,Centrotemporal spikes are mainly Rolandic not temporal spikes. Top, middle and bottom: T
41、he same EEG sample is shown in 3 different montages. This is from an 8-year-old boy referred for an EEG because of “recent GTCS and a 2-year history of unilateral facial spasms.?” The EEG showed frequent clusters of repetitive centrotemporal spikes on the left. Because the spikes appeared to be of h
42、igher amplitude in the temporal electrode (T3) (black arrows), the technologist rightly applied additional electrodes at C5 and C6 (Rolandic localisation). This showed that the spike is of higher amplitude in the left Rolandic region (C5) (open arrows). Another EEG 16 months later, showed a few smal
43、l spikes in the right frontal and central midline electrodes.,BECTS Management,Children with RS may not need antiepileptic medication, particularly if the seizures are infrequent, mild or nocturnal, or the onset is close to the age of natural remission of this age-limited disorder. Patients with fre
44、quent seizures and secondarily GTCS or with comorbid conditions (tics, attention-deficit hyperactivity disorder, learning disability) may need medication.63 In a recent study, AEDs significantly reduced GTCS, but did not reduce focal seizures.64 On an empirical basis, carbamazepine is the preferred
45、AED. However, some children might experience particular learning difficulties and exaggeration and new types of seizures while receiving carbamazepine. Within days after re-introduction of carbamazepine, she suffered nearly continuous, brief atonic attacks of head and arm drop and also absences (cas
46、e 17.3 in ref1) Lamotrigine may be contraindicated in RS, because of case reports with exacerbation of the condition and new types of seizures. See details in “Management of benign childhood focal seizures”,West综合症，婴儿痉挛症,1 痉挛发作 2发作期脑电图高度节律失调 3 智力发育迟滞 Clinical presentation The epileptic seizures whic
47、h can be observed in infants with West syndrome fall into three categories. Typically, the following triad of attack types appears; while the three types usually appear simultaneously, they also can occur independently of each other: Lightning attacks: Sudden, severe myoclonic convulsions of the ent
48、ire body or several parts of the body in split seconds, and the legs in particular are bent (flexor muscle convulsions here are generally more severe than extensor ones). Nodding attacks: Convulsions of the throat and neck flexor muscles, during which the chin is fitfully jerked towards the breast o
49、r the head is drawn inward. Salaam or jackknife attacks: a flexor spasm with rapid bending of the head and torso forward and simultaneous raising and bending of the arms while partially drawing the hands together in front of the chest and/or flailing. If one imagined this act in slow motion, it would appear similar to the oriental ceremonial greeting (Salaam), from which this type of attack derives its name.,West 综合症,West syndrome Therapy,West syndrome
