Epilepsy

第十二章 癫癎 (Epilepsy),Department of Neurology, The 2nd affiliated hospital, Harbin Medical University,第一节 概述第二节 部分性发作 第三节 全面性发作 第四节 常见的癫癎或癫癎综合征第五节 癫癎持续状态,Section 1 Introduction,Concept:I. 癎性发作(seizure) A seizure is a transient disturbance of cerebral function caused by an abnormal neuronal discharge.,是指纯感觉性、运动性和精神运动性发作，或指每次发作及每种发作的短暂过程，患者可同时有一种或几种癎性发作。,II. 癫癎(epilepsy) 是一组由大脑神经元异常放电所引起的短暂中枢神经系统功能失常为特征的慢性脑部疾病，具有突然发生、反复发作的特点。,A group of disorders characterized by recurrent seizures.临床上可表现为运动、感觉、意识、行为和自主神经等不同程度的障碍,Etiological & classificationEpilepsy is a group of disorders or syndromes classified into two types according to etiology:原发性(特发性) (Idiopathic epilepsy) , 继发性(症状性)(symptomatic epilepsy),原发性癫癎( Idiopathic epilepsy )no specific causes can be established more than 75% of seizure disorders.是指病因尚未清楚，暂时未能确定脑内有器质性病变者。,Idiopathic epilepsy is mainly influenced by hereditary factors（mono-genic or polygenic inheritance）. It can be a partial seizures or generalized seizures.which has a better response to drug therapy.,继发性癫癎(secondary epilepsy)It is caused by a variety of damage of brain 主要是由各种原因的脑损伤所致Hereditary factors may play a part.There is a less response to drug therapy.,表12-1 国际抗癫癎联盟(1981)癎性发作分类及临床表现要点,Etiology and influential factors,1.EtiologyHeredity: Morbidity of epilepsy in close relative of patients with idiopathic epilepsy is 2%6%, much higher than general population-0.5%1%。There are different hereditary ways in idiopathic epilepsy.,Brain injury: 发作期间出现高电压细胞膜去极化，即发作性去极化漂移(paroxysmal depolarization shift, PDS)，将近发作时，PDS后超极化不再发生，代之以高频率的动作电位群，并通过突触联系和强直后易化作用诱发外围及远处的神经元同步放电。,Etiology and influential factors2.Influential factors(1) Inherent cause: can influence only the predisposition of the epilepsy, while the penetrance of it is confined by age.,(2) Environmental influenceI. Age：多种特发性癫癎的外显率与年龄有密切关系；II. Endocrinosity：如经期性、妊娠性癫癎；III. Sleep: GTCS, West syndrome, benign childhood epilepsy with centro-temporal spikes,IV. Lack of sleep, fatigue, starvation, constipation, alcohol flash, emotional impulse and transient metabolic disturbance, etc, all will promote the attack. Over-ventilation to absence seizure, over- drinking to GTCS, and flash to myoclonic seizures can induce the attacks.,Incidence: 50-70/100,000/year.morbidity: about 5.There are about 600,000 patients with EP in our country.,Epidemiology,Newly onset patients: 650,000700,000/year. 75% of them shows good response to anticonvulsants of first choice.,About 25% of them shows refractory seizures. There are at least 1,500,000pastients with refractory seizures national wide.,Localization of epilepsia source,癫癎病理灶(lesion)是指脑内形态学异常，可间接或直接导致EEG癎性放电及临床癎性发作，是癫癎发作的基础 致痫灶(seizure focus)是指脑电图上出现的一个或数个最明显的癎性放电部位。直接导致癫癎发作的是致痫灶,-单个病理灶的致痫灶多位于病理灶的边缘-广泛性癫癎病理灶的致痫灶常包含其内， 有时在远离癫癎病理灶的同侧或对侧脑区,癫癎源综合定位技术1.电生理学定位(electrophysiological localization)：EEG；ambulant-EEG；video-EEG2. 神经影像学定位(localization by image)：头颅MRI加海马相检查；功能性MRI(f-MRI)；磁共振波谱检查法(MRS) ； 脑磁图(MEG),3. SPECT: 通过检测血流动力学可发现发作时高血流量灌注引起的放射性核素聚集。 4. PET：根据脑组织对放射性核素摄取量测定代谢率，定位代谢异常病灶。 5. 脑功能定位：双侧颈内动脉阿米妥(Wada)试验，以避免手术引起重要功能损害。,The ways of diagnosis,1. The diagnosis can be made mainly depended upon detailed, reliable history of the spells, and supported by positive findings of EEG,2. EEG is the most common used test in distinguishing seizures from other causes of consciousness. However, a normal or nonspecifically abnormal EEG never excludes the diagnosis of seizures.,Video-EEG 对诊断困难者应用是提高癫癎诊断水平的重要手段。有助于鉴别癫癎与非癎性发作、确定癎性灶及癫癎的正确诊断和分类 Neuro-image examination 确定脑结构性异常或损害，MRI较CT为更敏感。,Section 2 partial seizures,Introduction: In which the seizures is the product of a demonstrable focal lesion or EEG abnormality in some part of the cerebral cortex(or perhaps in a deep nuclear structure) Is the most common type of seizures in adults.,Partial seizures can be divided into three clinical types depending upon whether the consciousness is retained or impaired. I.单纯部分性发作(simple partial seizures), no disorder of consciousness II.复杂部分性发作(complex partial seizures), with the loss of consciousness III.继发全身性强直-阵挛发作(secondary GTCS),Etiology(1) Simple partial seizures: usually they are symptomatic epilepsy with organic lesion in brain. Among them, cerebral trauma, birth trauma, encephalitis, brain tumor, cerebrovascular disease and its sequela are the most common causes.,(2) Complex partial seizures: commonly caused by birth trauma. Other etiological factors are encephalitis, brain trauma, tumor, cerebrovascular accident, cerebral arteriosclerosis, cerebrovascular malformatiom, and anoxia of brain, etc.,Mechanisms Complex partial seizures result from abnormal discharge of temporal lobe structure. Hippocampus and nucleus amygdlae play an important role in epileptic activity.,颞叶癫癎有两种病因模式，一种是可诱发癎性发作的特定结构受损，另一种为海马硬化.,Clinical features 1. simple partial seizures（录象）可分为以下四型：Somatic motor seizures: 杰克逊癫癎(Jacksons seizure)；Todd瘫痪；部分性癫癎持续状态(epilepsia partialis continua),Somatic and special sensory seizures: special sensory seizures include：视觉性(visual)听觉性(auditory)嗅觉性(olfactory)眩晕性(vertiginous)；自主神经发作Autonomic nerve seizures；精神性发作,2. complex partial seizures:The episodes begin with psychiatric symptoms or special sensory symptoms and followed by disturbance of consciousness, automatism, and amnesia. Sometimes the conscious disturbance occurs at the very beginning of the episode, and is called psychomotor seizure (精神运动性发作).,The seizure discharge usually arise from the temporal lobe, so it is also called temporal lobe seizures (颞叶癫癎)，The seizure focus can be also located in frontal lobe or olfactory cortex.,自动症(automatism): This is motor manifestation of complex partial seizures which are characterized by coordinated involuntary motor activity, and takes the form of orobuccolingual movements in about 75% of patients and other facial or neck movement in aboutt50%. Sitting up or standing, fumbling with objects, and bilateral limb movements are less common.,自动症是在癎性发作期或发作后意识障碍和遗忘状态下发生的行为，病灶多在颞叶海马部、扣带回、杏仁核、额叶眶部或边缘回等,3. 单纯或复杂部分性发作继发为全面性强直-阵挛发作,Diagnosis and differentiationDiagnosis Determine whether an episodic disorder of nervous function is indeed a seizure.Determine the seizure pattern and determine which kind of epileptic syndrome it belongs to Search and define the cause.,Differentiation MigraineTransient ischemic attack (TIA)Pseudoseizures,Section 3 Generalized seizures,Introductionepisode accompanied by the disturbance of consciousness or the disturbance of consciousness is the first symptom. The abnormal neuron discharge arises from bilateral hemisphere.是发作时伴有意识障碍或以意识障碍为首发症状，神经元癎性放电起源于双侧大脑半球。,Etiology and mechanism大部分全面性发作与遗传关系密切，至今已知150种以上少见的基因缺陷综合征是以癫癎大发作或肌阵挛发作为临床表现的，其中常染色体显性遗传疾病有25种。导致大脑弥漫性损害的病因如缺氧性脑病、中毒等也可能导致全面性发作。,Clinical features1. 失神发作 (absence seizures)(1) 典型失神发作：Also called “petit mal”. The spells are characterized by brief loss of consciousness without loss of posture tone.,EEG shows a characteristic 3/s spike-and-wave pattern during the seizures or multi spike-and slow wave with normal background activity. There may be as many as several hundred spells daily.,(2) 不典型失神发作：Disturbance of consciousness occurs and ceases slower than petit mal.Alternation in muscular tone is obviousEEG Shows slow and irregular spike-slow or sharp- slow wave with abnormal background activity.,2. 肌阵挛发作 (myoclonic seizure) Most of them are inherited disease characterized by sudden, brief, shocklike contractions that may be localized to a few muscles or one or more extremities or that may have a more generalized distribution.,Has longer interval time and usually without disturbance of consciousness. 清晨欲觉醒或刚入睡时发作较频繁。EEG shows multi-spike-slow or spike-slow waves or sharp-slow waves,3. 阵挛性发作(Clonic seizures) Can only be found in infants and characterized be repetitive clonic jerking accompanied by loss of consciousness. EEG shows rapid activity, slow wave, and irregular spike-slow waves.,4. 强直性发作 (Tonic seizures)Commonly seen in children and juvenile at sleepingCharacterized by continuing muscle contraction that can lead to fixation of the limb and to deviation of the head and eyes to one side; the accompanying arrest of ventilatory movement leads to cyanosis. Consciousness is lost.EEG shows low potential 10c/s waves with gradually increased amplitude.,5. Tonic-clonic seisuresgeneralized tonic一clonic seizure，(GTCS), 也称大发作(grand mal)，以意识丧失和全身抽搐为特征。发作可分三期：,Tonic phase：,The initial manifestations are unconsciousness and tonic contractions of limb muscles for 1030 seconds, producing extension of the extremities and arching of the body in apparent opisthotonos.,Tonic contractions of the muscles of respiration may produce an expiration-induced vocalization (cry or moan) and cyanosis, and contraction of masticatory may cause tongue trauma. The patient falls to the ground and may be injured.,Clonic seizures,The clonic phase is followed by a clonic (alternating muscle contraction and relaxation) phase of symmetric limb jerking that persists for an additional 3060 seconds or longer.,With the time, the jerking becomes less frequent, until finally with a big jerking, all movements cease and the muscles are flaccid.,During above tow phases, the patient has an increased heart rate, blood pressure, secretion of perspiration, saliva. And with corediastasis. Arrest breath, cyanosis, and areflexia.,Post-convulsion phase,After clonic phase, the patient still shows transient tonic convulsion which result in lockjaw and urinary incontinence. Ventilatory efforts return immediately.,The mouth may forth with saliva or blood and heart rate, blood pressure, respiration, and pupils will be back to normal. The patient regain consciousness gradually(for about 510min),and. There is often postictal confusion headache,Determine if the spell is a seizure first:Particular history Investigative examination：EEG, lumbar puncture, CT, MRI,Diagnosis and differentiation,Make an right judgement of the etiologyRecognition of idiopathic and secondary seizures,Differentiation： SyncopeHypoglycemiaHarcolepsyMigraine of basic artery patternpseudoepileptic seizures,Treatment1. Therapy should be directed toward the cause of the seizure, if known.2. Establish the diagnosis and the types of epilepsy before starting drug therapy. 首次发作的患者在调查病因之前，不宜过早用药,3. 根据发作类型选择AED (见表12-3) 癫癎类型与药物治疗的关系密切4. 常用剂量和不良反应(见表12-4)： 用药应采取个体化原则；药物监测(therapeutic drug monitoring, TDM),5.坚持单药治疗原则6.联合治疗7.长期坚持,8.增减药物、停药及换药原则：增减药物增药可适当的快，减药一定 要慢；停药：应遵循缓慢和逐渐减量的原则；,换药：应在第1种药逐渐减量时逐渐增加第2种药的剂量至控制发作或出现不良反应，并应监控血药浓度。,苯妥英(phenytoin, PHT)卡马西平(carbamazapine, CBZ)苯巴比妥(Phenobarbital, PB)扑痫酮(primidone, PMD)丙戊酸钠(valproato, VPA)乙琥胺(ethosuxamide, ESX),传统抗癫癎药（AEDs）,苯妥英钠作用为稳定神经膜，阻止钠离子通路和减少高频冲击后的突触易化。卡马西平为三环类化合物，作用和苯妥英钠类似。苯巴比妥为巴比妥类，作用为阻止癎性电活动的传导。,乙琥胺为琥珀酸胺，作用为减少重复性传递和抑制皮质的兴奋性传入。丙戊酸钠为脂肪酸，作用为抑制GABA转氨酶。氯硝安定为苯二氮卓类，作用于抑制性受体。扑痫酮为苯巴比妥先驱物，作用和其相同。,新 型 抗 癫 痫 药 物,托吡酯(topiramate, TPM)亦称妥泰(topamax)。对难治性部分性发作、继发GTCS、Lennox-Gastaut综合征和婴儿痉挛症等有效。远期疗效好，无明显耐受性，大剂量也用可作单药治疗。,Lamotrigine （拉莫三嗪）,已在国内试用。能阻断钙离子进入高速放电中的神经元，从而抑制谷氨酸和天门冬酸的释放。对部分性发作、失神、GTCS，尤其是Lennox-Gastaut综合征有效。常用剂量200500mg/d。副作用有共济失调、头昏、复视、嗜睡等,Vigabatrin,能强烈地抑制GABA转氨酶，从而增加脑内抑制性递质GABA。对部分性发作、Lennox