神经病学课件：多发性硬化

MultiplesclerosisKeyWordsmultiplesclerosis(MS)多发性硬化myelin髓鞘demyelination脱髓鞘whitemattertracts脑白质束axon轴突autoimmune

自身免疫的opticnerve视神经relapsing-remitting复发-缓解的MagneticResonanceImaging(MRI)磁共振成象acutedisseminatedencephalomyelitis(ADEM)

急性播散性脑脊髓炎leukodystrophy脑白质营养不良methylprednisolone甲强龙prednisone

泼尼松Definition

MultipleSclerosis(MS)isachronicdiseasethatusuallybeginsinyoungadults.Pathologically,itischaracterizedbymultipleareasofcentralnervoussystem(CNS)whitematterdemyelination.Epidemiology

Ageatonsetfollowsaunimodaldistributionwithpeakbetweenages20-40years.MSismorecommonamongwomenthanmenEtiologyandPathogenesis

Immunology:presentstudiessupportthatMShasanautoimmunebasis,themyelinantibodyagainstmyelinandresulttothedisease.VirusesGeneticsusceptibilityOtherfactors:environmentPathology

Grossappearance

1)Externalsurfaceofthebrainisusuallynormal.2)Long-standingcases,thereisevidenceofatrophyandwideningofcerebralsulciwithenlargementofthelateralandthirdventricles.PathologyMicroscopicevaluation

Demyelination

leadingtolossofmyelinfromCNSaxons.PathologyDemyelination—AreasofdemyelinationintheCNS-

cerebralhemisphere,brainstem,whitemattertractsclosetothelateralventricles,spinalcord,etal.PathologyTcellsgetintobrainTcellsrecognizemyelinasforeignandattackitInflammatoryprocessesbetriggeredOtherimmunecellsandthereleaseofsolublefactorsaretriggeredFurtherbreakdownoftheBBBOtherdamagingeffectslossofmyelinDisruptionsintheblood–brainbarrierInflammationPathologyBreakdownofblood–brainbarrier(BBB)BBBmaybecomepermeabletoTcellssecondarytoaninfectionbyavirusorbacteria.TcellmayremaintrappedinsidetheCNSevenwheninfectionhascleared.Clinicaltype

Basedonitscourse,MSisdividedintofourclinicaltypes.Clinicaltype

Relapsing-remittingform---RRMS(85%):Initialepisodeoffewdaysorweeks,followedbyaninternalofmonthsoryears.Newepisode:newsymptomsandoriginalsymptoms.Relapsesmaybetriggeredbyinfection,pregnancy.Afteranumberofrelapseand

incompleteremissions,patientsmaybecomeincreasinglydisabled.Somecaseswouldturnintothesecondtype.Clinicaltype

Secondaryprogressiveform---SPMS:afteraninitialrelapsingremittingpattern,thediseasegraduallyprogresses.Primaryprogressiveform---PPMS:fromclinicalonset,thereisgradualprogressionofdisabilitywithoutremission.Progressiverelapsingform---PRMS:occursrarely(10%),acuterelapsesaresuperimposedonaprimaryprogressivecourse.Symptomsandsigns

AlmostanyneurologicalsymptomorsignofCNS.Central/visual/speech/throat/muscu-loskeletal/sensation/bowel/urinaryproblemscouldoccur.1)VisualsymptomsIncludediplopia,blurredvisionorlossofvisualacuityononeorbothsides,visualfielddefectsrangingfromaunilateralscotomaorfieldcontraction.Blurredvision,likelyamanifestationofacuteopticneuritis,isaverycommoninitialsymptomsofMS.2)TrigeminallemniscusandcorticobulbartractInvolvementofthedescendingrootofthefifthcranialnerve

(trigeminal).Impairpainsensationintheface.Weaknessofthefacialmusclesofthelowerhalfofonesideofthefaceiscommon.Thecornealreflexmaybediminishedorlost.3)CorticospinaltractLimbweaknessisthemostcommonsignAlmostalwayspresentinadvancedcasesasmonoparesis,hemiparesis,ortetraparesis—mostoften,asymmetricparaparesis4)Input/outputfibersofcerebellum•Dysarthria,gaitataxia,tremor,andincoordinationofthetrunkorlimbs.5)SpinothalamictractParesthesiasandsensoryimpairmentarecommon.Patientsusuallyfeeltinglingornumbnessinthelimbs,trunk,orface.TheLhermittesignisasensationof“electricity”radiatingdownthebackorarmsafterflexionoftheneck.-indicativeofspinalposteriorcolumndysfunction.Others:FatigueUrinarysymptomSexualdysfunctionPsychiatricmooddisordersymptomsCognitive,judgment,andmemorydisorders

Auxiliary

Examination

NopathognomonictestforMSexists,butMRI,CSFexamination,andevokedpotentialstudiesarehelpful.1.BrainMagneticResonanceImaging(MRI)-Themostvaluablelaboratoryaid.Positiveratecouldreachto62%-94%Acute-phaseplaquesappearasroundedareasofhigh-signalintensityonFLAIRandT2sequences.Leisionshaveapropensityfortheperiventricularandsubcorticalwhitematter,middlecerebellarpeduncle,pons,orcervical

cordperiventricularandsubcorticalwhitemattercerebellarpedunclecervical

cord2.CerebrospinalFluid(CSF):

thecharacteristicchangesinCSFgammaglobulins(IgG)arethemostusefulfindings.3.Corticalevokedresponses：Visualevokedpotentials(VEPs),Somatosensoryevokedpotentials(SEP),Brainstemauditoryevokedpotentials(BAEP).Diagnosis

Clinical,laboratory,andradiologicevidenceoflesions.Thediagnosisrequiresevidencethatatleasttwodifferentregionsofthecentralwhitematterhavebeeninvolvedatdifferenttime.---Mostcommonlyusedmethodofdiagnosis!McDonaldcriteria

(2001)-mostcommonlyusedmethodofdiagnosis.Differentialdiagnosis

ADEM(acutedisseminatedencephalomyelitis)similarinitialclinicalpresentationwithMSusuallyoccursmoreurgentlyaftervaccinationorrespiratoryinfectionsaffectschildrenmorethanadultswidespreadormultifocalMRIabnormalities

-ADEM2.Leukodystrophy:Characterizedbydegenerationofthewhitematterinthebrain.Usuallyhappensinchildrenorteenagers.Withoutarelapsing-remittingprocess.LesionsonMRIweresymmetrical.DifferentialdiagnosisOthers:TumorsofbrainorspinalcordVasculardiseasearteriovenousmalformations,etalManagement

NoknowncureexistsbynowThenaturalhistoryofMScanbefavorablyaltered.Theprimaryaimsoftherapyarereturningfunctionafteranattack,preventingnewattacks,andpreventingdisability.1.

Immunosuppressions1）Corticosteroids:

☆

Methylprednisolone:1000mg,iv./d,3~5ds,followedbyoralprednisone60-80mg/d,or1mg/kg/d,forweeks–months.2）Interferonβ:Interferonβ-1a30ug,im,1/week；Interferonβ-1b50ug,sc,qod3）Otherimmunosuppressions-equivocalbenefits

Cyclophosphamide50mg,BID,1yrazathioprine2mg/kg.d,2yrsmethotrexate7.5mg/wk,2yrscyclosporinA5~10mg/kg.d,>1yr2.

Intravenousimmunoglobulin,IVIG

NoevidencethatitismoreeffectivethanotherapprovedtherapiesforMSandexspensive.

0.4g/kg.d,5d,1/month,3-6months3.

Plasmaexchange，PEPrimarilyatthelevelofhumoralresponses;lessimportantinMSthancellularresponses50ml/kg/1-2w,10-20times/period,followedbyoralprednisoneafewday.4.Symptomatictherapy1）SpasticityBaclofen-themostcommonlyuseddrug;40-80mg/day;forlocalizedadductorspasmsInjectionsofbotulinummaybeuseful2)BladderCholinergicdrugs-urinaryretentionAnticholinergicdrugs-urinary

incontinence3)Painpainfulradiculopathy;neuralgia;painfulparesthesiaNSAIDs,gabapentin,pregabalin,tricyclicantidepressants.Narcoticmedicationsareprobablyavoided-exacerbatefatigueandcognitivedysfunction.4)FatigueSufficientrest---critical.Pharmacologictherapy:

amantadine,dilantin,modafinil.5)TremorArtane,levodopa.CourseandPrognosis

TheclinicalcourseofMSvaries.Exceptionalcases:clinicallysilentforalifetime;orrapidlyprogressiveormalignant.Overallmortality:onlyafewyearslessthangeneralpopulation.Exceptions:relentlesslyprogressive,leadingtodeath.Ifuntreated,20%areunabletowalk