神經(jīng)病學(xué)課件：癲癇

Epilepsy癲癇

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

NapoléonBonaparte，1769/08/15～1821/05/055古羅馬帝國(guó)——愷撒大帝，軍事家——拿破侖，諾貝爾獎(jiǎng)金創(chuàng)立者——諾貝爾，哲學(xué)家——蘇格拉底，伊斯蘭教創(chuàng)始人——穆罕默德，英國(guó)詩(shī)人——拜倫、狄更斯，圣女——貞德，美術(shù)家——梵高，音樂家——亨德爾,俄羅斯文學(xué)家——陀斯妥耶夫斯基Definition（定義）EPILEPSY:Achronicbraindisorderofvariousetiologiescharacterizedbyrecurrentseizuresduetoexcessivedischargeofcerebralneurons.癲癇:一組反復(fù)發(fā)作的神經(jīng)元異常放電所致的中樞神經(jīng)系統(tǒng)功能失常的慢性疾病。Definition（定義）SEIZURE(EpilepticSeizure):Therecurrentattacksduetoexcessivedischargeofcerebralneurons.Motor(convulsion),sensory,psychic,autonomicsymptoms,oradisturbanceofhighbrainfunction,orlossofconsciousness,oracombinationofthem.癇性發(fā)作:中樞神經(jīng)細(xì)胞異常放電引起的反復(fù)臨床發(fā)作。根據(jù)神經(jīng)元的部位和放電擴(kuò)散的范圍，功能失?？赡鼙憩F(xiàn)為運(yùn)動(dòng)、感覺、意識(shí)、行為、自主神經(jīng)等不同障礙，或兼有之。每次發(fā)作或每種發(fā)作稱為癇性發(fā)作。CharacteristicsofSeizures:Paroxysmal,transient,recurrent,stereotyped癇性發(fā)作的特點(diǎn)：

發(fā)作性，短暫性，重復(fù)性，刻板性Incidence(發(fā)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

(病因分類)Anyfactorswhichcouldcausethestructuraldamageorfunctionaldisturbanceofbrain.

1)

Idiopathicepilepsiesandsyndromes(特發(fā)性癲癇)

2)

Symptomaticepilepsiesandsyndromes(癥狀性癲癇)

3)

Cryptogenicepilepsiesandsyndromes(隱源性癲癇)4)Situation-relatedseizures(狀態(tài)關(guān)聯(lián)性癲癇發(fā)作)ClinicalManifestations（臨床表現(xiàn)）

CharacteristicManifestations:SeizuresMotorsymptoms(convulsion)SensorysymptomsPsychicsymptomsAutonomicsymptomsDisturbancesofhighbrainfunctionLossofconsciousnessOr,acombinationofthem.癇性發(fā)作臨床表現(xiàn)運(yùn)動(dòng)癥狀(驚厥)感覺癥狀精神癥狀自主神經(jīng)癥狀大腦高級(jí)功能紊亂意識(shí)喪失或,以上癥狀的組合ClassificationofEpilepticSeizures

（癇性發(fā)作分類）Basesofclassification:ClinicalmanifestationsandEEGchanges.(theoriginating,speedandextentofspreadofthedischarges.)

GeneralizedSeizures（全面性發(fā)作）

PartialSeizures（部分性發(fā)作）

UnclassifiedEpilepticSeizures（未能分類的發(fā)作）GeneralizedSeizures

(全面性發(fā)作）Tonic-clonicSeizure

(強(qiáng)直-陣攣性發(fā)作）

TonicSeizure(強(qiáng)直性發(fā)作）

ClonicSeizure(陣攣性發(fā)作）

MyoclonicSeizure(肌陣攣性發(fā)作）

Absence(失神性發(fā)作）

AtonicSeizure(失張力性發(fā)作）ClassificationofEpilepticSeizures

GeneralizedSeizures(全面性發(fā)作）

1.Tonic-clonicSeizure(強(qiáng)直-陣攣性發(fā)作）

ClassificationofEpilepticSeizuresGeneralizedSeizures(全面性發(fā)作）

2.TonicSeizure(強(qiáng)直性發(fā)作）ClassificationofEpilepticSeizuresGeneralizedSeizures(全面性發(fā)作）

3.ClonicSeizure(陣攣性發(fā)作）

ClassificationofEpilepticSeizuresGeneralizedSeizures(全面性發(fā)作）

4.MyoclonicSeizure(肌陣攣性發(fā)作）

ClassificationofEpilepticSeizuresGeneralizedSeizures(全面性發(fā)作）

5.Absence(失神性發(fā)作）ClassificationofEpilepticSeizuresGeneralizedSeizures(全面性發(fā)作）

6.AtonicSeizure(失張力性發(fā)作）ClassificationofEpilepticSeizures

PartialSeizures:

accordingtowhetherconsciousnessisimpairedornotduringattack：

SimplePartialSeizure（SPS）

ComplexPartialSeizure（CPS）

部分性發(fā)作:

根據(jù)發(fā)作時(shí)有無神志意識(shí)的缺損分為:

單純部分性發(fā)作(SPS)

復(fù)雜部分性發(fā)作(CPS)SimplePartialSeizure

（單純部分性）Partialmotor（運(yùn)動(dòng)性）seizure，JacksonianseizurePartialsensory（感覺性）

seizurePartialautonomic（植物神經(jīng)性）seizurePartialpsychic（精神性）seizure

ComplexPartialSeizure（復(fù)雜部分性）

Aura

（先兆）

Impairmentofconsciousness（意識(shí)障礙）

Automatism（自動(dòng)癥）

orothermotorsymptoms

部分性發(fā)作

1、單純部分性

運(yùn)動(dòng)性

感覺性

植物神經(jīng)性

精神性

2、復(fù)雜部分性（先兆）+意識(shí)障礙+（自動(dòng)癥）

全面性發(fā)作強(qiáng)直-陣攣強(qiáng)直陣攣肌陣攣失神失張力放電起源意識(shí)障礙Diagnosis（診斷）1.Differentiationfromeventsmimickingepilepticseizures1)Syncope2)Psychogenicattack(pseudoseizures)2.Classificationofseizures

3.Diagnosisofepilepsiesandepilepticsyndromes1)ChildhoodAbsenceEpilepsy

2)WestSyndrome

4.Determinationofetiology

癲癇的診斷1.是否為癲癇發(fā)作鑒別:1)暈厥

2)精神心理性發(fā)作(假性發(fā)作)2.發(fā)作類型的診斷3.癲癇的診斷（癲癇綜合征的診斷）4.病因診斷癲癇的診斷

1.是否為癲癇發(fā)作

鑒別:1)暈厥FeatureSyncopeSeizurePostureuprightanyposturePallorandsweatingcommonuncommonOnsetgradualsudden/auraInjuryrarenotuncommonConvulsivejerksrarecommonIncontinencerarecommonUnconsciousnesssecondsminutesRecoveryrapidoftenslowPostictalconfusionrarecommonFrequencyinfrequentmaybefrequentPrecipitatingfactorsCrowdedplaces,lackoffood,unpleasantcircumstancesrareInterictalEEGnormalabnormalDifferencesbetweensyncopeandseizures臨床特點(diǎn)暈厥

癇性發(fā)作體位直立

任何體位蒼白和出汗常見

不常見開始逐漸的

突然/先兆受傷很少

非少見肢體抽搐很少

常見遺尿很少

常見意識(shí)障礙數(shù)秒

數(shù)分鐘恢復(fù)快

較慢發(fā)作頻率不頻繁

可以頻繁誘發(fā)因素人多、饑餓、不愉快

較少發(fā)作間期腦電圖正常

多數(shù)不正常

暈厥與癇性發(fā)作的鑒別癲癇的診斷

1.是否為癲癇發(fā)作

鑒別:2)精神心理性發(fā)作(假性發(fā)作)FeatureEpilepticseizurePseudoseizureOnsetsuddenmaybegradualRetainedconsciousnessinprolongedseizureveryrarecommonPelvicthrustingrarecommonFlailing,thrashing,asynchronouslimbmovementsrarecommonRollingmovementsrarecommonMovements“waxingandwaning”rarecommonCyanosiscommonunusualTonguebitingandotherinjurycommonlesscommonStereotypicalattacksusualuncommonDurationsecondsorminutesoftenmanyminutesGazeaversionrarecommonResistancetopassivelimbmovementoreye-openingunusualcommonPreventionofhandfallingonfaceunusualcommonInducedbysuggestionrarelyoftenPostictaldrowsinessorconfusionusualoftenabsentIctalEEGabnormalityAlmostalwaysAlwaysneverPostictalEEGabnormality(afterseizurewithimpairmentofconsciousness)usuallyrarelyDifferencesbetweenepilepticseizuresandpseudoseizure

特征癇性發(fā)作假性發(fā)作起病突然可以是逐漸的發(fā)作中的意識(shí)保留很少常見骨盆甩動(dòng)少見常見非同步動(dòng)作少見常見翻滾動(dòng)作少見常見“贏虧”征少見常見紫紺常見不多見舌咬傷或其它損傷常見不常見發(fā)作形式固定基本是不常見發(fā)作時(shí)間幾秒或幾分鐘經(jīng)常較長(zhǎng)凝視回避很少常見對(duì)外界干擾的抵抗少見常見手或臉跌落的防備少見常見接受暗示少見常見發(fā)作后頭暈或迷惑常見幾乎沒有發(fā)作期EEG異常幾乎都有幾乎沒有發(fā)作后EEG異常常見罕見

癇性發(fā)作與假性發(fā)作的鑒別Diagnosis1.DifferentiationfromEventsMimickingEpilepticSeizures2.ClassificationofSeizures3.DiagnosisofEpilepsiesandEpilepticSyndromes4.DeterminationofEtiologyGeneralizedSeizures(全面性發(fā)作）

Tonic-clonicSeizure(強(qiáng)直-陣攣性發(fā)作）

TonicSeizure(強(qiáng)直性發(fā)作）

ClonicSeizure(陣攣性發(fā)作）

MyoclonicSeizure(肌陣攣性發(fā)作）

Absence(失神性發(fā)作）

AtonicSeizure(失張力性發(fā)作）SimplePartialSeizure

（單純部分性）Partialmotor（運(yùn)動(dòng)性）seizure，JacksonianseizurePartialsensory（感覺性）

seizurePartialautonomic（植物神經(jīng)性）seizurePartialpsychic（精神性）seizureComplexPartialSeizure(復(fù)雜部分性)Diagnosis1.DifferentiationfromEventsMimickingEpilepticSeizures2.ClassificationofSeizure3.DiagnosisofEpilepsiesandEpilepticSyndromes4.DeterminationofEtiologyChildhoodAbsenceEpilepsy(兒童失神性癲癇)l

Typicalabsences,generallybeginbetweenage3-10years.l

Multipleattackstendtooccurinthesameday.l

Geneticpredisposition.l

Patientsareotherwiseneurologicallynormal.l

Morecommoninfemale.l

EEGdemonstratesregular3Hzspikeandwaveactivity,normalbackground.lUsuallyresponsetovalproate(VPA).ChildhoodAbsenceEpilepsy(兒童失神性癲癇)典型失神發(fā)作,起病年齡多在3-10歲同一天內(nèi)多次發(fā)作遺傳傾向其它神經(jīng)系統(tǒng)發(fā)育基本正常女性多見典型EEG表現(xiàn)為正常背景活動(dòng)中陣發(fā)出現(xiàn)規(guī)則3Hz棘慢復(fù)合波對(duì)丙戊酸有效Westsyndrome(嬰兒痙攣)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(嬰兒痙攣)發(fā)病年齡:3-7月,男孩稍多:60%精神運(yùn)動(dòng)發(fā)育遲滯:無眼神交流,軸性肌張力低典型發(fā)作:痙攣(孤立—成簇的)發(fā)作頻率:每日數(shù)-數(shù)十次發(fā)作間期EEG:高峰失律,發(fā)作期EEG:多種多樣痙攣的發(fā)展:幾周-幾月自然停止(6-15%)5歲時(shí)痙攣停止(72-99%)預(yù)后:持續(xù)發(fā)作(50-60%),發(fā)育遲滯(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兒童期起病(1-8歲)多種發(fā)作形式:失張力、軸性強(qiáng)直、肌陣攣、非典型失神、強(qiáng)直-陣攣精神發(fā)育遲滯多種病因EEG:背景異常,棘慢復(fù)合波(1.0-2.5Hz)多,睡眠中10Hz快節(jié)律對(duì)多種AEDs無效Diagnosis1.DifferentiationfromEventsMimickingEpilepticSeizures2.ClassificationofSeizure3.DiagnosisofEpilepsiesandEpilepticSyndromes4.DeterminationofEtiologyHowtomakeadiagnosis?CombinationofclinicalmanifestationsandEEG(electroencephalogram)Otherexaminations:CT,MRI,SPECT,PET,etc.結(jié)合臨床表現(xiàn)和腦電圖其它輔助檢查Treatment（癲癇的治療）1.Etiologicaltreatment（病因治療）2.Avoidingofprecipitations（誘發(fā)因素的預(yù)防）

3.Antiepilepticdrugstherapy（藥物治療）DecisionofinitiationofAEDs(是否用藥?)

NoAEDstreatmentcurrently:

Firstseizure、normalEEG&MRISporadicorsituation-relatedseizuresRareseizuresandsevereside-effectduringAEDstherapy暫時(shí)不用藥：第一次發(fā)作、腦電圖正常、MRI無致癇灶偶發(fā)或狀態(tài)關(guān)聯(lián)性癲癇發(fā)作發(fā)作少而治療時(shí)有不可耐受的副作用Treatment(治療)Whenshouldfurtherobservationbeneeded:Onlyfewseizures,occasionalnocturnalseizures,benignsyndromes,seizureswithapparentprecipitations,ornon-disablingbriefsimplepartialseizures

Whenshouldanantiepilepticdrugbeconsidered:

TwoormoreunprovokedseizureshaveoccurredwithinashortintervalAdditionalconsiderations:

EEGfociororganiclesionsTreatment(治療)繼續(xù)觀察

發(fā)作少,偶然夜間發(fā)作,良性綜合征,明顯誘因,不造成功能缺損的短暫的簡(jiǎn)單部分性發(fā)作考慮用藥

在短期內(nèi)有兩次無誘因的發(fā)作其它考慮

腦電圖或結(jié)構(gòu)上的局灶損害Listofantiepilepticdrugs:AEDs

Old

傳統(tǒng)藥FirstyearmarketedChinaPhenobarbital苯巴比妥1912Phenytoin苯妥英鈉1938Primidone撲癇酮1952Ethosuximide乙琥胺1960Diazepam安定1963Carbamazepine卡馬西平1974Clonazepam氯硝安定1975Valproate丙戊酸1978Piracetam吡拉西坦Zonisamide唑尼沙胺Clobazam氯巴唑

New新藥FirstyearmarketedChinaLorazepam羅拉西半1977Vigabatrine氨己烯酸1989Lamotrigine拉莫三嗪1991Gabapentin加巴噴丁1993Felbamate非氨酯1993Topiramate妥比酯1995Fosphenytoin磷苯妥英1996Tiagabine替加賓1997Levetiracetam左乙拉西坦1999Oxcarbazepine奧卡西平2000Stiripentol司替戊醇2001Pregabalin普瑞巴林2005AEDs作用機(jī)制AEDsTmax(hour)T1/2(hour)Proteinbinding(%)苯巴比妥(PB)1-375-12045-60苯妥英鈉(PHT)8-127-4270-95卡馬西平(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奧卡西平(OXC)4.5940唑尼沙胺(ZNS)2-66340AEDs的藥代動(dòng)力學(xué)AEDs治療劑量中毒劑量苯妥英5-20>20-25苯巴比妥15-25>40-50撲癇酮5-12>15卡馬西平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的治療藥物濃度監(jiān)測(cè)Treatment(治療)ChoiceofAEDs(ChooseAEDsonseizureclassification)

Idiopathic,GeneralizedSeizure:

VPA(丙戊酸),LTG(拉莫三嗪)

Symptomatic,PartialSeizure:CBZ(卡馬西平),

TPM(妥吡酯)

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

(苯妥因鈉，苯巴比妥,氯硝安定)選藥原則癥狀性部分性發(fā)作：

卡馬西平，妥吡酯特發(fā)性泛化性發(fā)作：丙戊酸，拉莫三嗪

其他藥物：氯硝安定，苯妥因鈉，苯巴比妥Treatment(治療)Principlesduringdrugtreatment:

MonotherapyshouldbeusedifpossibleStartwithlowdose

Increasethedosagegradually

Monitorsideeffects,andserumlevelswhennecessarily

BewareofinteractionswithallotherdrugsDesignthescheduleof

changing,ordiscontinuingdrugscarefully用藥注意

單藥治療小劑量開始逐漸增量監(jiān)測(cè)藥物副作用和藥物濃度注意藥物之間相互作用藥物和劑量調(diào)整要謹(jǐn)慎StatusEpilepticus(癲癇持續(xù)狀態(tài))Statusepilepticus(SE)canbedefinedasrecurrentepilepticseizureslastingmorethan30min.Apracticalclassificationincludesthefollowingseizuretypes:Tonic-clonicAbsenceMyoclonicComplexpartialFocalmotor(epilepsiapartialiscontinua,EPC)StatusEpilepticus(癲癇持續(xù)狀態(tài))定義:

癲癇連續(xù)發(fā)作之間意識(shí)尚未恢復(fù)又頻繁再發(fā),或癲癇反復(fù)發(fā)作持續(xù)超過30分鐘未自行停止.SE可以包括如下的發(fā)作類型:

強(qiáng)直-陣攣失神肌陣攣復(fù)雜部分性局灶運(yùn)動(dòng)性(EPC)ManagementofSE(持續(xù)狀態(tài)的控制)SE治療的目的:

保證生命體征穩(wěn)定盡快終止發(fā)作尋找并祛除誘因處理并發(fā)癥TCSEproducesacharacteristicpatternofchangeswhich,ultimately,causeirreversiblebraindamageandpotentiallyfatalsystemiccomplications.SE會(huì)導(dǎo)致大腦不可逆性損傷和致命性的多系統(tǒng)并發(fā)癥,因此必須立即盡快治療!一般措施保證呼吸道通暢,監(jiān)測(cè)生命體征盡早建立靜脈通道防治并發(fā)癥:腦水腫、感染、降體溫、電解質(zhì)紊亂、營(yíng)養(yǎng)等ManagementofTCSEp.r.,perrectum,animportantalternativerouteofadministrationinchildrenwhenintravenousaccessisdifficultorimpossibleStageofSE

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

paraldehyde(副醛)Established(30-60min)phenytoini.v.fosphenytoin(磷苯妥英鈉)i.v.phenobartitonei.v.chlormethiazole(氯乙噻唑)Refractory(60-90min)thiopentone(硫噴妥鈉)i.v.propofol(丙泊酚)i.v.Pentobarbitone(戊巴比妥)i.v.Drugtherapy(藥物治療)首選安定10-20mg(兒童用量:0.25-0.5mg/Kg)靜脈推注,如有效,再用安定60-100mg加入5%GNS中緩慢靜脈滴注,一般不要持續(xù)使用超過24小時(shí)在早期SE,靜推安定的有效控制率為70-80%,

但10-15%有呼吸抑制和/或低血壓的副作用Drugtherapy(藥物治療)其它(二線)藥物:苯妥英鈉、10%水合氯醛(灌腸)等常規(guī)SE治療方案:安定靜推+靜脈滴注;

苯巴比妥0.1-0.2g肌