哈爾濱醫(yī)科大學(xué)神經(jīng)病學(xué)中樞神經(jīng)系統(tǒng)脫髓鞘疾病

哈爾濱醫(yī)科大學(xué)神經(jīng)病學(xué)中樞神經(jīng)系統(tǒng)脫髓鞘疾病第1頁/共66頁掌握MS概念、病因、發(fā)病機(jī)制、臨床表現(xiàn)、輔助檢查、治療、診斷標(biāo)準(zhǔn)及鑒別診斷。熟悉視神經(jīng)脊髓炎概念、臨床表現(xiàn)、輔助檢查、診斷及治療。了解MS病理、預(yù)后；急性播散性腦脊髓炎概念、臨床表現(xiàn)、診斷及治療。Keypoints-DemyelinatingDiseasesofCNS第2頁/共66頁

Chapter1

Intraduction1.Concept:Agroupofdiseasecharacterizedbydemyelinatingofthe

brainandspinalcord.

PATHOLOGY:Demyelination

第3頁/共66頁髓鞘構(gòu)成

CNSPNS第4頁/共66頁第5頁/共66頁第6頁/共66頁2.PathologicFindings

①

DestructionofthemyelinsheathsofCNS;oftenprimarilyinwhitematter,eitherinmultiplesmalldisseminatedfociorinlargerfoci;第7頁/共66頁②Infiltrationofinflammatorycellsinaperivenousdistribution;③Arelativeintegrityoftheaxiscylindersinthelesionsandalackofwallerian,thesecondarydegenerationoffibertracts.第8頁/共66頁臨床常見脫髓鞘疾病急性播散性腦脊髓炎(acutedisseminatedencephalomyelitis,ADEM)多發(fā)性硬化癥(multiplesclerosis,MS)亞型視神經(jīng)脊髓炎(Devicdiseases)急性出血性白質(zhì)腦病(acutehemorrhageleukoencephalitis,AHLE)第9頁/共66頁

多發(fā)性硬化癥(MS)

第10頁/共66頁多發(fā)性硬化

MultipleSclerosis,MS

1.Concept:

MsisakindofautoimmunediseasescharacterizedbydemyelinationofCNS.Duetoitshighincidence,chronicityandtendencytoattackyoungadults,ithasbecomeoneofthemostimportantCNSdiseases.第11頁/共66頁Therearemultipleareasof

demyelinationwithintheCNS.Theepisodesofdemyelinationareseparatedintimeandplace,andclassicallythediseaserunsarelapsing-remittingcourse.(brainandspinalcord)第12頁/共66頁是一種常見以中樞神經(jīng)系統(tǒng)炎性脫髓鞘為特征的自身免疫性疾病病灶部位及時(shí)間上的多發(fā)性多數(shù)均以反復(fù)多次發(fā)作與緩解的病程具有免疫易感性、年輕人多見第13頁/共66頁2.EtiologyAndPathogenesis1)病毒感染及自身免疫反應(yīng)：Sincetheexactcauseisuncertain.Immunologicalmechanismsundoubtedlyplayarole,althoughthecausationisprobablymultifactorial.麻疹病毒,人類噬T淋巴細(xì)胞病毒(HTLV-I),分子模擬,細(xì)胞免疫及體液免疫。2)遺傳因素(inheritedfactor)3)環(huán)境因素(environment)第14頁/共66頁第15頁/共66頁第16頁/共66頁3.EpidemiologyIncidenceofMSassociatedwithlatitude.Onmovingfromahigh-prevalenceareatoalow-prevalenceareapriortopuberty,theriskofdevelopingMSishigherthaninthelow-prevalencearea;Howeverthemoveismadefollowingpuberty,theriskofthehigh-prevalenceisretained.第17頁/共66頁Hereditymaybeanimportantfactor.MSassociatedwiththeHLA-DRlocusonthesixthchromosome,HLA-DR2expressstronglyandthen-DR3,

B7andA3.第18頁/共66頁第19頁/共66頁4.

PathologicFindings

Characteristic:Multipledemyelinatedplaques.Position:Whitematteraroundthelateralventriclesandspinalcord,opticnerve,brainstemandcerebellar.

Acutestage:hyperemia,ondema,demyelination,

infiltriationofinflammatorycellsdistributedinperivenous.Recoverystage:Astrocyteproliferition,formingofastrocyticscab.

第20頁/共66頁

急性期:充血、水腫、炎性脫髓鞘、血管周圍Lc浸潤(rùn)。

恢復(fù)期:星狀細(xì)胞增生、膠質(zhì)斑痕形成。

肉眼觀：CNS內(nèi)脫髓鞘斑塊第21頁/共66頁5.ClinicalManifestations1)

Prodrome:Thesymptomsevolvedmoreslowly,overseveralweeksormonths.2)Acuteorsubacuteonset(Relapsing-remitting).第22頁/共66頁3)

Earlysymptomsandsigns:

①Weaknessornumbness;(1/2patientshaveparesthesiaononeormorelimbs)

②

Thevisuallossinoneorbotheyes;③Nystagmus;第23頁/共66頁4)Commonsymptomsandsigns:①paralysisandparaplegia;②

Thevisuallossinoneorbotheyes;

(1/2patientshavevisualdisorders,relapsing-remitting)

③Nystagmusandpalsyofeyemuscles;(internuclearophthalmoplegia,PPRF

oneandahalfsyndrome)第24頁/共66頁“一個(gè)半綜合征”垂直眼震第25頁/共66頁第26頁/共66頁④Sensationdisorder:Romberg’ssign,

(>1/2)Lhermitte’ssign;⑤Ataxia(1/2),Charcot’ssyndrom(laterstage);⑥ImpairmentofPNS;⑦Attacksyndrom;⑧Otherclinicalfeature.第27頁/共66頁6.LaboratoryandassistantTests1)CSFTest

①NumberofMNC<15106/L;②IgG-Index>0.7(70%);oligoclonalbands(OB)(95%);

③MBP,PLP,MAG,MOGAbsandAb-secretingcells;

④CSF-Alb/serum-Alb>1.7(probabilityofMS)第28頁/共66頁2)Evokedpotentials:50%-90%abnormal.

①visualevokedpotentials(VEP);②brainstemauditoryevokedpotentials(BAEP);③somatosensoryevokedpotentials(SEP).3)MRI:

①preiventricularplaques;②regularplaquesinbrainstem,cerebellumandspinalcord;③atrophysymptom.第29頁/共66頁第30頁/共66頁第31頁/共66頁第32頁/共66頁第33頁/共66頁第34頁/共66頁-AbnormalMRIscansarefoundin

96%withadefinitediagnosisofMS

70%withadiagnosisofprobableMS

30-50%withadiagnosisofpossibleMSMRICriteriafordiagnosingMS

Atleast3Lesionsandtwoofthefollowing:1

LesionsabuttingtheLateralVentricles

2Lesionswithdiametersgreaterthan5mm3LesionspresentinthePosteriorFossaSource

(OffenbacherH,FazekasF,SchmidtRetal.

AssessmentOfMRICriteriaForADiagnosisOfMS*Neurology1993;43:905-909)第35頁/共66頁

Diagnosticcriteria1.ClinicaldefiniteMS(CDMS):

①twotimesofattackandtwolesions;②twoattacks,onelesionandonesubclinicalevidence;2.LaboratorysupporteddefiniteMS(LSDMS):

①Twoattacks,onesubclinicalevidenceandCSFOB/IgG;②Oneattack,twolesionsandCSFOB/IgG;③Oneattack,onelesion,onesubclinicalevidenceandCSFOB/IgG;

第36頁/共66頁3.ClinicalprobableMS(CPMS):

①twoattacks,onelesion;②oneattack,twolesions;③oneattack,onelesionandothersubclinicalevidence;4.LaboratorysupportedprobableMS(LSPMS)

Twoattacks;CSFOB/IgG;TwoattacksinvolvingdifferentpartofCNS,intermissionatlestonemonth;eachattackmustcontinuefor24hs.第37頁/共66頁多發(fā)硬化的診斷標(biāo)準(zhǔn)診斷發(fā)作次數(shù)臨床病灶數(shù)亞臨床證據(jù)CSFOB/IgG臨床確診（CDMS）2221及1實(shí)驗(yàn)室支持確診(LSDMS）211121或1及1+++臨床可能(CPMS)2111211+實(shí)驗(yàn)室支持可能(LSPMS）2兩次發(fā)作均累及CNS不同部位，間隔至少一個(gè)月，每次持續(xù)24小時(shí)。+第38頁/共66頁DifferentialDiagnosis1.急性播散性腦脊髓炎

2.腦動(dòng)脈炎、腦干炎、脊髓血管畸形3.頸椎病脊髓型

4.熱帶痙攣性截癱

5.大腦淋巴瘤第39頁/共66頁

Treatment目前尚無一種特效療法，治療的主要目的是：1.急性活動(dòng)期抑制其炎癥性脫髓鞘過程，遏止病情的進(jìn)展。

2.盡量預(yù)防能促發(fā)的外因，減少?gòu)?fù)發(fā)次數(shù)，延長(zhǎng)緩解間歇期。

3.預(yù)防并發(fā)癥。4.對(duì)癥及支持療法。

第40頁/共66頁1.Relapsing-RemittingMS：

①

Anti-inflammatorytreatment:

methylprenisolone(highdosefor3d),prednison,dexamethasone;

②

Suppressionormodulationoftheimmunesystem:IFN-1

and1b

;

Azathioprine；

Immuneglublin(Ig):0.4g/kg.dIVIg3-5d

第41頁/共66頁2.ProgressiveMS：

①M(fèi)ethotrexate,MTX;

②Cyclosphoamide;③CyclosporineA;④Plasmatransplantation.

第42頁/共66頁3.

Symptomatictreatment:

①Spasticity:baclofen,dantrolene,diazepamandtizanidinecanbehelpful.

②Bladderdysfunction:anticholinergicdrugsurinarycathetermayberequired.第43頁/共66頁預(yù)后分型1.良性型2.復(fù)發(fā)-緩解3.緩慢進(jìn)展型4.慢性進(jìn)展型第44頁/共66頁Examples患者，女，32歲。主訴：行走不穩(wěn)1年，左耳鳴、視物雙影半年。走路不穩(wěn)，踩棉花感左耳鳴復(fù)視快速細(xì)小水平眼震向右凝視時(shí)明顯右側(cè)指鼻試驗(yàn)、輪替試驗(yàn)、跟膝脛試驗(yàn)均欠佳

Romberg征(+)，左Hoffmann征(+)四肢腱反射增高，以雙下肢腱反射增高，右側(cè)踝陣攣陽性頭顱MRI未見異常第45頁/共66頁該患如何定位及定性？第46頁/共66頁

視神經(jīng)和脊髓受累較多見，病灶中的軟化、壞死較多見.視神經(jīng)脊髓炎又稱Devic病,為多發(fā)性硬化的一個(gè)亞型.中國(guó),日本等東方人1.Introduction2.EtiologyAndPathogenesis視神經(jīng)脊髓炎

(Neuromyelitisoptica,NMO)第47頁/共66頁3.Patholgy主要侵犯視神經(jīng)、視交叉、和脊髓胸頸段第48頁/共66頁Acutestage:infiltrationofinflammatorycells.Astrocyteproliferition第49頁/共66頁ClinicalManifestations-NMO1.年輕居多，21-41歲。2.特征：急性橫貫性脊髓炎和雙側(cè)同時(shí)或相繼出現(xiàn)的ON。70%可在數(shù)日內(nèi)有截癱。3.急性起病可在數(shù)小時(shí)或數(shù)日內(nèi)單或雙眼失明，眼眶痛。4.脊髓癥狀可橫貫、不對(duì)稱、或呈播散性；特征為快速進(jìn)展的雙下肢癱，感覺脫失平面、括約肌障礙等，1/3病人有Lhermitte征、根痛。第50頁/共66頁一、輔助檢查1.CSF細(xì)胞數(shù)增加，73%單相、82%復(fù)發(fā)。2.復(fù)發(fā)病人脊髓MRI88%出現(xiàn)縱向融合超過數(shù)個(gè)節(jié)段，釓強(qiáng)化和腫脹常見。二、鑒別診斷1.單純球后神經(jīng)炎2.MS表現(xiàn)為NMO臨床模式。3.亞急性視神經(jīng)病三、治療大劑量甲強(qiáng)沖擊療法第51頁/共66頁

頸髓脫髓鞘視神經(jīng)炎第52頁/共66頁急性播散性腦脊髓炎

(acutedisseminatedencephalomylitis,ADEM)1.Introduction:ADEMisakindofacuteinflammatorydisseminateddiseaseinvolvedthewhitermatterofbrainandspinalcord.

(感染出疹或疫苗接種)爆發(fā)型：急性出血性白質(zhì)腦炎(acutenecrotizinghemorrhagicencephalomyelitis,AHL)第53頁/共66頁2.EtiologyAndPathogenesis病毒感染，腦組織+FAC可誘發(fā)EAE，認(rèn)為ADEM是急性MS或其變異型。第54頁/共66頁3.Pathology

腦和脊髓多數(shù)脫髓鞘病灶,小靜脈周圍炎性