哈尔滨医科大学神经病学中枢神经系统脱髓鞘疾病

哈尔滨医科大学神经病学中枢神经系统脱髓鞘疾病第1页/共66页掌握MS概念、病因、发病机制、临床表现、辅助检查、治疗、诊断标准及鉴别诊断。熟悉视神经脊髓炎概念、临床表现、辅助检查、诊断及治疗。了解MS病理、预后；急性播散性脑脊髓炎概念、临床表现、诊断及治疗。Keypoints-DemyelinatingDiseasesofCNS第2页/共66页

Chapter1

Intraduction1.Concept:Agroupofdiseasecharacterizedbydemyelinatingofthe

brainandspinalcord.

PATHOLOGY:Demyelination

第3页/共66页髓鞘构成

CNSPNS第4页/共66页第5页/共66页第6页/共66页2.PathologicFindings

①

DestructionofthemyelinsheathsofCNS;oftenprimarilyinwhitematter,eitherinmultiplesmalldisseminatedfociorinlargerfoci;第7页/共66页②Infiltrationofinflammatorycellsinaperivenousdistribution;③Arelativeintegrityoftheaxiscylindersinthelesionsandalackofwallerian,thesecondarydegenerationoffibertracts.第8页/共66页临床常见脱髓鞘疾病急性播散性脑脊髓炎(acutedisseminatedencephalomyelitis,ADEM)多发性硬化症(multiplesclerosis,MS)亚型视神经脊髓炎(Devicdiseases)急性出血性白质脑病(acutehemorrhageleukoencephalitis,AHLE)第9页/共66页

多发性硬化症(MS)

第10页/共66页多发性硬化

MultipleSclerosis,MS

1.Concept:

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

demyelinationwithintheCNS.Theepisodesofdemyelinationareseparatedintimeandplace,andclassicallythediseaserunsarelapsing-remittingcourse.(brainandspinalcord)第12页/共66页是一种常见以中枢神经系统炎性脱髓鞘为特征的自身免疫性疾病病灶部位及时间上的多发性多数均以反复多次发作与缓解的病程具有免疫易感性、年轻人多见第13页/共66页2.EtiologyAndPathogenesis1)病毒感染及自身免疫反应：Sincetheexactcauseisuncertain.Immunologicalmechanismsundoubtedlyplayarole,althoughthecausationisprobablymultifactorial.麻疹病毒,人类噬T淋巴细胞病毒(HTLV-I),分子模拟,细胞免疫及体液免疫。2)遗传因素(inheritedfactor)3)环境因素(environment)第14页/共66页第15页/共66页第16页/共66页3.EpidemiologyIncidenceofMSassociatedwithlatitude.Onmovingfromahigh-prevalenceareatoalow-prevalenceareapriortopuberty,theriskofdevelopingMSishigherthaninthelow-prevalencearea;Howeverthemoveismadefollowingpuberty,theriskofthehigh-prevalenceisretained.第17页/共66页Hereditymaybeanimportantfactor.MSassociatedwiththeHLA-DRlocusonthesixthchromosome,HLA-DR2expressstronglyandthen-DR3,

B7andA3.第18页/共66页第19页/共66页4.

PathologicFindings

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

Acutestage:hyperemia,ondema,demyelination,

infiltriationofinflammatorycellsdistributedinperivenous.Recoverystage:Astrocyteproliferition,formingofastrocyticscab.

第20页/共66页

急性期:充血、水肿、炎性脱髓鞘、血管周围Lc浸润。

恢复期:星状细胞增生、胶质斑痕形成。

肉眼观：CNS内脱髓鞘斑块第21页/共66页5.ClinicalManifestations1)

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

Earlysymptomsandsigns:

①Weaknessornumbness;(1/2patientshaveparesthesiaononeormorelimbs)

②

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

Thevisuallossinoneorbotheyes;

(1/2patientshavevisualdisorders,relapsing-remitting)

③Nystagmusandpalsyofeyemuscles;(internuclearophthalmoplegia,PPRF

oneandahalfsyndrome)第24页/共66页“一个半综合征”垂直眼震第25页/共66页第26页/共66页④Sensationdisorder:Romberg’ssign,

(>1/2)Lhermitte’ssign;⑤Ataxia(1/2),Charcot’ssyndrom(laterstage);⑥ImpairmentofPNS;⑦Attacksyndrom;⑧Otherclinicalfeature.第27页/共66页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页/共66页2)Evokedpotentials:50%-90%abnormal.

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

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

96%withadefinitediagnosisofMS

70%withadiagnosisofprobableMS

30-50%withadiagnosisofpossibleMSMRICriteriafordiagnosingMS

Atleast3Lesionsandtwoofthefollowing:1

LesionsabuttingtheLateralVentricles

2Lesionswithdiametersgreaterthan5mm3LesionspresentinthePosteriorFossaSource

(OffenbacherH,FazekasF,SchmidtRetal.

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

Diagnosticcriteria1.ClinicaldefiniteMS(CDMS):

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

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

第36页/共66页3.ClinicalprobableMS(CPMS):

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

Twoattacks;CSFOB/IgG;TwoattacksinvolvingdifferentpartofCNS,intermissionatlestonemonth;eachattackmustcontinuefor24hs.第37页/共66页多发硬化的诊断标准诊断发作次数临床病灶数亚临床证据CSFOB/IgG临床确诊（CDMS）2221及1实验室支持确诊(LSDMS）211121或1及1+++临床可能(CPMS)2111211+实验室支持可能(LSPMS）2两次发作均累及CNS不同部位，间隔至少一个月，每次持续24小时。+第38页/共66页DifferentialDiagnosis1.急性播散性脑脊髓炎

2.脑动脉炎、脑干炎、脊髓血管畸形3.颈椎病脊髓型

4.热带痉挛性截瘫

5.大脑淋巴瘤第39页/共66页

Treatment目前尚无一种特效疗法，治疗的主要目的是：1.急性活动期抑制其炎症性脱髓鞘过程，遏止病情的进展。

2.尽量预防能促发的外因，减少复发次数，延长缓解间歇期。

3.预防并发症。4.对症及支持疗法。

第40页/共66页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页/共66页2.ProgressiveMS：

①Methotrexate,MTX;

②Cyclosphoamide;③CyclosporineA;④Plasmatransplantation.

第42页/共66页3.

Symptomatictreatment:

①Spasticity:baclofen,dantrolene,diazepamandtizanidinecanbehelpful.

②Bladderdysfunction:anticholinergicdrugsurinarycathetermayberequired.第43页/共66页预后分型1.良性型2.复发-缓解3.缓慢进展型4.慢性进展型第44页/共66页Examples患者，女，32岁。主诉：行走不稳1年，左耳鸣、视物双影半年。走路不稳，踩棉花感左耳鸣复视快速细小水平眼震向右凝视时明显右侧指鼻试验、轮替试验、跟膝胫试验均欠佳

Romberg征(+)，左Hoffmann征(+)四肢腱反射增高，以双下肢腱反射增高，右侧踝阵挛阳性头颅MRI未见异常第45页/共66页该患如何定位及定性？第46页/共66页

视神经和脊髓受累较多见，病灶中的软化、坏死较多见.视神经脊髓炎又称Devic病,为多发性硬化的一个亚型.中国,日本等东方人1.Introduction2.EtiologyAndPathogenesis视神经脊髓炎

(Neuromyelitisoptica,NMO)第47页/共66页3.Patholgy主要侵犯视神经、视交叉、和脊髓胸颈段第48页/共66页Acutestage:infiltrationofinflammatorycells.Astrocyteproliferition第49页/共66页ClinicalManifestations-NMO1.年轻居多，21-41岁。2.特征：急性横贯性脊髓炎和双侧同时或相继出现的ON。70%可在数日内有截瘫。3.急性起病可在数小时或数日内单或双眼失明，眼眶痛。4.脊髓症状可横贯、不对称、或呈播散性；特征为快速进展的双下肢瘫，感觉脱失平面、括约肌障碍等，1/3病人有Lhermitte征、根痛。第50页/共66页一、辅助检查1.CSF细胞数增加，73%单相、82%复发。2.复发病人脊髓MRI88%出现纵向融合超过数个节段，钆强化和肿胀常见。二、鉴别诊断1.单纯球后神经炎2.MS表现为NMO临床模式。3.亚急性视神经病三、治疗大剂量甲强冲击疗法第51页/共66页

颈髓脱髓鞘视神经炎第52页/共66页急性播散性脑脊髓炎

(acutedisseminatedencephalomylitis,ADEM)1.Introduction:ADEMisakindofacuteinflammatorydisseminateddiseaseinvolvedthewhitermatterofbrainandspinalcord.

(感染出疹或疫苗接种)爆发型：急性出血性白质脑炎(acutenecrotizinghemorrhagicencephalomyelitis,AHL)第53页/共66页2.EtiologyAndPathogenesis病毒感染，脑组织+FAC可诱发EAE，认为ADEM是急性MS或其变异型。第54页/共66页3.Pathology

脑和脊髓多数脱髓鞘病灶,小静脉周围炎性