神经病学课件：癫痫

Epilepsy癫痫

GaiusJuliusCaesar,BC102/07/12～44/03/15VincentVanGogh,1853/03/30～1890/07/29

NapoléonBonaparte，1769/08/15～1821/05/055古罗马帝国——恺撒大帝，军事家——拿破仑，诺贝尔奖金创立者——诺贝尔，哲学家——苏格拉底，伊斯兰教创始人——穆罕默德，英国诗人——拜伦、狄更斯，圣女——贞德，美术家——梵高，音乐家——亨德尔,俄罗斯文学家——陀斯妥耶夫斯基Definition（定义）EPILEPSY:Achronicbraindisorderofvariousetiologiescharacterizedbyrecurrentseizuresduetoexcessivedischargeofcerebralneurons.癫痫:一组反复发作的神经元异常放电所致的中枢神经系统功能失常的慢性疾病。Definition（定义）SEIZURE(EpilepticSeizure):Therecurrentattacksduetoexcessivedischargeofcerebralneurons.Motor(convulsion),sensory,psychic,autonomicsymptoms,oradisturbanceofhighbrainfunction,orlossofconsciousness,oracombinationofthem.痫性发作:中枢神经细胞异常放电引起的反复临床发作。根据神经元的部位和放电扩散的范围，功能失常可能表现为运动、感觉、意识、行为、自主神经等不同障碍，或兼有之。每次发作或每种发作称为痫性发作。CharacteristicsofSeizures:Paroxysmal,transient,recurrent,stereotyped痫性发作的特点：

发作性，短暂性，重复性，刻板性Incidence(发病率)

andPrevalence(患病率)

INCIDENCE:50~122per100,000(~1/1000)populationperyear.(~1,000,000newpatientsperyearinChina)PREVALENCE:Theactiveepilepsyis5-8per1000population(5~8‰).(6-8millionpatientsinChina)OCCASIONALSEIZURE:3-5%ofthegeneralpopulation.

Etiology

(病因分类)Anyfactorswhichcouldcausethestructuraldamageorfunctionaldisturbanceofbrain.

1)

Idiopathicepilepsiesandsyndromes(特发性癲痫)

2)

Symptomaticepilepsiesandsyndromes(症状性癲痫)

3)

Cryptogenicepilepsiesandsyndromes(隐源性癲痫)4)Situation-relatedseizures(状态关联性癲痫发作)ClinicalManifestations（临床表现）

CharacteristicManifestations:SeizuresMotorsymptoms(convulsion)SensorysymptomsPsychicsymptomsAutonomicsymptomsDisturbancesofhighbrainfunctionLossofconsciousnessOr,acombinationofthem.痫性发作临床表现运动症状(惊厥)感觉症状精神症状自主神经症状大脑高级功能紊乱意识丧失或,以上症状的组合ClassificationofEpilepticSeizures

（痫性发作分类）Basesofclassification:ClinicalmanifestationsandEEGchanges.(theoriginating,speedandextentofspreadofthedischarges.)

GeneralizedSeizures（全面性发作）

PartialSeizures（部分性发作）

UnclassifiedEpilepticSeizures（未能分类的发作）GeneralizedSeizures

(全面性发作）Tonic-clonicSeizure

(强直-阵挛性发作）

TonicSeizure(强直性发作）

ClonicSeizure(阵挛性发作）

MyoclonicSeizure(肌阵挛性发作）

Absence(失神性发作）

AtonicSeizure(失张力性发作）ClassificationofEpilepticSeizures

GeneralizedSeizures(全面性发作）

1.Tonic-clonicSeizure(强直-阵挛性发作）

ClassificationofEpilepticSeizuresGeneralizedSeizures(全面性发作）

2.TonicSeizure(强直性发作）ClassificationofEpilepticSeizuresGeneralizedSeizures(全面性发作）

3.ClonicSeizure(阵挛性发作）

ClassificationofEpilepticSeizuresGeneralizedSeizures(全面性发作）

4.MyoclonicSeizure(肌阵挛性发作）

ClassificationofEpilepticSeizuresGeneralizedSeizures(全面性发作）

5.Absence(失神性发作）ClassificationofEpilepticSeizuresGeneralizedSeizures(全面性发作）

6.AtonicSeizure(失张力性发作）ClassificationofEpilepticSeizures

PartialSeizures:

accordingtowhetherconsciousnessisimpairedornotduringattack：

SimplePartialSeizure（SPS）

ComplexPartialSeizure（CPS）

部分性发作:

根据发作时有无神志意识的缺损分为:

单纯部分性发作(SPS)

复杂部分性发作(CPS)SimplePartialSeizure

（单纯部分性）Partialmotor（运动性）seizure，JacksonianseizurePartialsensory（感觉性）

seizurePartialautonomic（植物神经性）seizurePartialpsychic（精神性）seizure

ComplexPartialSeizure（复杂部分性）

Aura

（先兆）

Impairmentofconsciousness（意识障碍）

Automatism（自动症）

orothermotorsymptoms

部分性发作

1、单纯部分性

运动性

感觉性

植物神经性

精神性

2、复杂部分性（先兆）+意识障碍+（自动症）

全面性发作强直-阵挛强直阵挛肌阵挛失神失张力放电起源意识障碍Diagnosis（诊断）1.Differentiationfromeventsmimickingepilepticseizures1)Syncope2)Psychogenicattack(pseudoseizures)2.Classificationofseizures

3.Diagnosisofepilepsiesandepilepticsyndromes1)ChildhoodAbsenceEpilepsy

2)WestSyndrome

4.Determinationofetiology

癲痫的诊断1.是否为癲痫发作鉴别:1)晕厥

2)精神心理性发作(假性发作)2.发作类型的诊断3.癲痫的诊断（癫痫综合征的诊断）4.病因诊断癲痫的诊断

1.是否为癲痫发作

鉴别:1)晕厥FeatureSyncopeSeizurePostureuprightanyposturePallorandsweatingcommonuncommonOnsetgradualsudden/auraInjuryrarenotuncommonConvulsivejerksrarecommonIncontinencerarecommonUnconsciousnesssecondsminutesRecoveryrapidoftenslowPostictalconfusionrarecommonFrequencyinfrequentmaybefrequentPrecipitatingfactorsCrowdedplaces,lackoffood,unpleasantcircumstancesrareInterictalEEGnormalabnormalDifferencesbetweensyncopeandseizures临床特点晕厥

痫性发作体位直立

任何体位苍白和出汗常见

不常见开始逐渐的

突然/先兆受伤很少

非少见肢体抽搐很少

常见遗尿很少

常见意识障碍数秒

数分钟恢复快

较慢发作频率不频繁

可以频繁诱发因素人多、饥饿、不愉快

较少发作间期脑电图正常

多数不正常

晕厥与痫性发作的鉴别癲痫的诊断

1.是否为癲痫发作

鉴别:2)精神心理性发作(假性发作)FeatureEpilepticseizurePseudoseizureOnsetsuddenmaybegradualRetainedconsciousnessinprolongedseizureveryrarecommonPelvicthrustingrarecommonFlailing,thrashing,asynchronouslimbmovementsrarecommonRollingmovementsrarecommonMovements“waxingandwaning”rarecommonCyanosiscommonunusualTonguebitingandotherinjurycommonlesscommonStereotypicalattacksusualuncommonDurationsecondsorminutesoftenmanyminutesGazeaversionrarecommonResistancetopassivelimbmovementoreye-openingunusualcommonPreventionofhandfallingonfaceunusualcommonInducedbysuggestionrarelyoftenPostictaldrowsinessorconfusionusualoftenabsentIctalEEGabnormalityAlmostalwaysAlwaysneverPostictalEEGabnormality(afterseizurewithimpairmentofconsciousness)usuallyrarelyDifferencesbetweenepilepticseizuresandpseudoseizure

特征痫性发作假性发作起病突然可以是逐渐的发作中的意识保留很少常见骨盆甩动少见常见非同步动作少见常见翻滚动作少见常见“赢亏”征少见常见紫绀常见不多见舌咬伤或其它损伤常见不常见发作形式固定基本是不常见发作时间几秒或几分钟经常较长凝视回避很少常见对外界干扰的抵抗少见常见手或脸跌落的防备少见常见接受暗示少见常见发作后头晕或迷惑常见几乎没有发作期EEG异常几乎都有几乎没有发作后EEG异常常见罕见

痫性发作与假性发作的鉴别Diagnosis1.DifferentiationfromEventsMimickingEpilepticSeizures2.ClassificationofSeizures3.DiagnosisofEpilepsiesandEpilepticSyndromes4.DeterminationofEtiologyGeneralizedSeizures(全面性发作）

Tonic-clonicSeizure(强直-阵挛性发作）

TonicSeizure(强直性发作）

ClonicSeizure(阵挛性发作）

MyoclonicSeizure(肌阵挛性发作）

Absence(失神性发作）

AtonicSeizure(失张力性发作）SimplePartialSeizure

（单纯部分性）Partialmotor（运动性）seizure，JacksonianseizurePartialsensory（感觉性）

seizurePartialautonomic（植物神经性）seizurePartialpsychic（精神性）seizureComplexPartialSeizure(复杂部分性)Diagnosis1.DifferentiationfromEventsMimickingEpilepticSeizures2.ClassificationofSeizure3.DiagnosisofEpilepsiesandEpilepticSyndromes4.DeterminationofEtiologyChildhoodAbsenceEpilepsy(儿童失神性癫痫)l

Typicalabsences,generallybeginbetweenage3-10years.l

Multipleattackstendtooccurinthesameday.l

Geneticpredisposition.l

Patientsareotherwiseneurologicallynormal.l

Morecommoninfemale.l

EEGdemonstratesregular3Hzspikeandwaveactivity,normalbackground.lUsuallyresponsetovalproate(VPA).ChildhoodAbsenceEpilepsy(儿童失神性癫痫)典型失神发作,起病年龄多在3-10岁同一天内多次发作遗传倾向其它神经系统发育基本正常女性多见典型EEG表现为正常背景活动中阵发出现规则3Hz棘慢复合波对丙戊酸有效Westsyndrome(婴儿痉挛)Ageofonset:mainly3-7Monthsofage.Boy:60%Psychomotordeterioration:lossofvisualcontact,axialhypotoniaSeizure:isolatedspasm⇒typicalspasmsinclustersFrequencyofseizures:several-tenseries/dayInter-ictalEEG:hypsarythmia(高峰失律);IctalEEG:variableEvolutionofspasms

spontaneousremissioninafewweeksormonths(6-15%),

spasmsfreeat5Y(72-99%)Prognosis:seizure(50-60%),Mentalretardation(71-81%).Westsyndrome(婴儿痉挛)发病年龄:3-7月,男孩稍多:60%精神运动发育迟滞:无眼神交流,轴性肌张力低典型发作:痉挛(孤立—成簇的)发作频率:每日数-数十次发作间期EEG:高峰失律,发作期EEG:多种多样痉挛的发展:几周-几月自然停止(6-15%)5岁时痉挛停止(72-99%)预后:持续发作(50-60%),发育迟滞(71-8%)Lennox-GastautSyndromel

Usuallyonsetinchildhood(1-8yearsofage).lMultipleseizuretypes,includingatonic,axialtonic,myoclonic,atypicalabsence,tonic-clonic.l

Mentalretardation.l

Multiplecauses.l

EEG:abnormalbackgroundandabundantslowspikeandwaveactivity(1.0-2.5Hz);10Hzrapidrhythmsduringsleep.l

Usuallyresistanttoantiepilepticdrugs(AEDs).Lennox-GastautSyndrome儿童期起病(1-8岁)多种发作形式:失张力、轴性强直、肌阵挛、非典型失神、强直-阵挛精神发育迟滞多种病因EEG:背景异常,棘慢复合波(1.0-2.5Hz)多,睡眠中10Hz快节律对多种AEDs无效Diagnosis1.DifferentiationfromEventsMimickingEpilepticSeizures2.ClassificationofSeizure3.DiagnosisofEpilepsiesandEpilepticSyndromes4.DeterminationofEtiologyHowtomakeadiagnosis?CombinationofclinicalmanifestationsandEEG(electroencephalogram)Otherexaminations:CT,MRI,SPECT,PET,etc.结合临床表现和脑电图其它辅助检查Treatment（癲痫的治疗）1.Etiologicaltreatment（病因治疗）2.Avoidingofprecipitations（诱发因素的预防）

3.Antiepilepticdrugstherapy（药物治疗）DecisionofinitiationofAEDs(是否用药?)

NoAEDstreatmentcurrently:

Firstseizure、normalEEG&MRISporadicorsituation-relatedseizuresRareseizuresandsevereside-effectduringAEDstherapy暂时不用药：第一次发作、脑电图正常、MRI无致痫灶偶发或状态关联性癲痫发作发作少而治疗时有不可耐受的副作用Treatment(治疗)Whenshouldfurtherobservationbeneeded:Onlyfewseizures,occasionalnocturnalseizures,benignsyndromes,seizureswithapparentprecipitations,ornon-disablingbriefsimplepartialseizures

Whenshouldanantiepilepticdrugbeconsidered:

TwoormoreunprovokedseizureshaveoccurredwithinashortintervalAdditionalconsiderations:

EEGfociororganiclesionsTreatment(治疗)继续观察

发作少,偶然夜间发作,良性综合征,明显诱因,不造成功能缺损的短暂的简单部分性发作考虑用药

在短期内有两次无诱因的发作其它考虑

脑电图或结构上的局灶损害Listofantiepilepticdrugs:AEDs

Old

传统药FirstyearmarketedChinaPhenobarbital苯巴比妥1912Phenytoin苯妥英钠1938Primidone扑痫酮1952Ethosuximide乙琥胺1960Diazepam安定1963Carbamazepine卡马西平1974Clonazepam氯硝安定1975Valproate丙戊酸1978Piracetam吡拉西坦Zonisamide唑尼沙胺Clobazam氯巴唑

New新药FirstyearmarketedChinaLorazepam罗拉西半1977Vigabatrine氨己烯酸1989Lamotrigine拉莫三嗪1991Gabapentin加巴喷丁1993Felbamate非氨酯1993Topiramate妥比酯1995Fosphenytoin磷苯妥英1996Tiagabine替加宾1997Levetiracetam左乙拉西坦1999Oxcarbazepine奥卡西平2000Stiripentol司替戊醇2001Pregabalin普瑞巴林2005AEDs作用机制AEDsTmax(hour)T1/2(hour)Proteinbinding(%)苯巴比妥(PB)1-375-12045-60苯妥英钠(PHT)8-127-4270-95卡马西平(CBZ)4-85-2675丙戊酸(VPA)1-84-1285-95拉莫三嗪(LTG)1-33055妥比酯(TPM)218-2315坐乙拉西坦(LEV)0.6-1.36-8<10奥卡西平(OXC)4.5940唑尼沙胺(ZNS)2-66340AEDs的药代动力学AEDs治疗剂量中毒剂量苯妥英5-20>20-25苯巴比妥15-25>40-50扑痫酮5-12>15卡马西平6-10>15乙琥胺40-100>150丙戊酸50-100氯硝安定0.02-0.07>0.08唑尼沙胺15-40>40氯巴唑0.05-0.3AEDs的治疗药物浓度监测Treatment(治疗)ChoiceofAEDs(ChooseAEDsonseizureclassification)

Idiopathic,GeneralizedSeizure:

VPA(丙戊酸),LTG(拉莫三嗪)

Symptomatic,PartialSeizure:CBZ(卡马西平),

TPM(妥吡酯)

OtherAEDS:phenytoin(PHT),phenobarbitone(PB),clonazepam(CNZ)

(苯妥因钠，苯巴比妥,氯硝安定)选药原则症状性部分性发作：

卡马西平，妥吡酯特发性泛化性发作：丙戊酸，拉莫三嗪

其他药物：氯硝安定，苯妥因钠，苯巴比妥Treatment(治疗)Principlesduringdrugtreatment:

MonotherapyshouldbeusedifpossibleStartwithlowdose

Increasethedosagegradually

Monitorsideeffects,andserumlevelswhennecessarily

BewareofinteractionswithallotherdrugsDesignthescheduleof

changing,ordiscontinuingdrugscarefully用药注意

单药治疗小剂量开始逐渐增量监测药物副作用和药物浓度注意药物之间相互作用药物和剂量调整要谨慎StatusEpilepticus(癫痫持续状态)Statusepilepticus(SE)canbedefinedasrecurrentepilepticseizureslastingmorethan30min.Apracticalclassificationincludesthefollowingseizuretypes:Tonic-clonicAbsenceMyoclonicComplexpartialFocalmotor(epilepsiapartialiscontinua,EPC)StatusEpilepticus(癫痫持续状态)定义:

癫痫连续发作之间意识尚未恢复又频繁再发,或癫痫反复发作持续超过30分钟未自行停止.SE可以包括如下的发作类型:

强直-阵挛失神肌阵挛复杂部分性局灶运动性(EPC)ManagementofSE(持续状态的控制)SE治疗的目的:

保证生命体征稳定尽快终止发作寻找并祛除诱因处理并发症TCSEproducesacharacteristicpatternofchangeswhich,ultimately,causeirreversiblebraindamageandpotentiallyfatalsystemiccomplications.SE会导致大脑不可逆性损伤和致命性的多系统并发症,因此必须立即尽快治疗!一般措施保证呼吸道通畅,监测生命体征尽早建立静脉通道防治并发症:脑水肿、感染、降体温、电解质紊乱、营养等ManagementofTCSEp.r.,perrectum,animportantalternativerouteofadministrationinchildrenwhenintravenousaccessisdifficultorimpossibleStageofSE

TreatmentFirstchoiceAlternativesEarly(0-30min)lorazepami.v./p.rrectaldiazepami.v./p.r

paraldehyde(副醛)Established(30-60min)phenytoini.v.fosphenytoin(磷苯妥英钠)i.v.phenobartitonei.v.chlormethiazole(氯乙噻唑)Refractory(60-90min)thiopentone(硫喷妥钠)i.v.propofol(丙泊酚)i.v.Pentobarbitone(戊巴比妥)i.v.Drugtherapy(药物治疗)首选安定10-20mg(儿童用量:0.25-0.5mg/Kg)静脉推注,如有效,再用安定60-100mg加入5%GNS中缓慢静脉滴注,一般不要持续使用超过24小时在早期SE,静推安定的有效控制率为70-80%,

但10-15%有呼吸抑制和/或低血压的副作用Drugtherapy(药物治疗)其它(二线)药物:苯妥英钠、10%水合氯醛(灌肠)等常规SE治疗方案:安定静推+静脉滴注;

苯巴比妥0.1-0.2g肌