2014+EFNS／ENS眼肌型重症肌无力治疗指南

EuropeanJournalofNeurology2014,21:687–693doi:10.1111/ene.12359

EFNS/ENSGUIDELINES/CMEARTICLE

EFNS/ENSGuidelinesforthetreatmentofocularmyasthenia

E.Kertya,b*,A.Elsaisa,b*,Z.Argovc,A.EvolidandN.E.Gilhuse,f

a

DepartmentofNeurology,OsloUniversityHospital,Oslo;bFacultyofMedicine,UniversityofOslo,Oslo,Norway;cDepartmentofNeu-

rology,Hadassah-HebrewUniversityMedicalCenter,Jerusalem,Israel;dInstituteofNeurology,CatholicUniversity,Roma,Italy;

e

DepartmentofClinicalMedicine,UniversityofBergen,Bergen;andfDepartmentofNeurology,HaukelandUniversityHospital,Bergen,

Norway

Keywords:

myastheniagravis,ocularmyasthenia,treatment

Received21November2013Accepted17December2013

Backgroundandpurpose:Thesymptomsofacquiredautoimmuneocularmyasthe-niaarerestrictedtotheextrinsiceyemuscles,causingdoublevisionanddroopingeyelids.Theseguidelinesaredesignedtoprovideadviceaboutbestclinicalpracticebasedonthecurrentstateofclinicalandscienti cknowledgeandtheconsensusofanexpertpanel.

Searchstrategy:EvidencefortheseguidelineswascollectedbysearchesintheMEDLINEandCochranedatabases.Thetaskforceworkinggroupreviewedevi-dencefromoriginalarticlesandsystematicreviews.Theevidencewasclassi ed(I,II,III,IV)andconsensusrecommendationgraded(A,BorC)accordingtotheEFNSguidance.Wheretherewasalackofevidencebutclearconsensus,goodpracticepointsareprovided.

Conclusions:Thetreatmentofocularmyastheniashouldinitiallybestartedwithpyridostigmine(goodpracticepoint).Ifthisisnotsuccessfulinrelievingsymptoms,oralcorticosteroidsshouldbeused

onanalternate-dayregimen(recommendationlevelC).Ifsteroidtreatmentdoesnotresultingoodcontrolofthesymptomsorifitisnec-essarytousehighsteroiddoses,steroid-sparingtreatmentwithazathioprineshouldbestarted(recommendationlevelC).Ifocularmyastheniagravisisassociatedwiththy-moma,thymectomyisindicated.Otherwise,theroleofthymectomyinocularmyas-theniaiscontroversial.Steroidsandthymectomymaymodifythecourseofocularmyastheniaandpreventmyastheniagravisgeneralization(goodpracticepoint).

Objectives

Myastheniagravis(MG)isanautoimmunedisordera ectingthepostsynapticneuromuscularjunctionmembrane.Ocularmanifestationsattheonsetofthediseaseareevidentinalargemajorityofpatients.

Whilstthereareacceptedguidelineswithregardtothetreatmentofgeneralizedmyastheniagravis(GMG)[1],thisisnotthecaseforocularmyastheniawherethetreatmentstrategyiscontroversial.AlthoughtherearealreadyEFNSguidelinesfortreat-mentofautoimmuneneuromusculartransmissiondis-Correspondence:E.Kerty,DepartmentofNeurology,Oslo

UniversityHospital,Rikshospitalet,Postbox4950Nydalen,4Oslo,Norway(tel.:+4723071829;fax:+4723070490;e-mail:emilia.kerty@medisin.uio.no).

*Thesetwoauthorscontributedequallytothispaper.

ThisisaContinuingMedicalEducationarticle,andcanbefoundwithcorrespondingquestionsontheInternetathttp://doc.guandang.net/EFNSContinuing-Medical-Education-online.301.0.html.Certi catesforcor-rectlyansweringthequestionswillbeissuedbytheEFNS.

orders,theydonotdealspeci callywithocularmyasthenia[1].

Thegoaloftherapyshouldbetominimizepatients’symptomsandpossiblypreventthegeneralizationofthediseasewithminimalsidee ects.

Background

Myastheniagravis(MG)isanacquiredorganospeci cautoimmunedisease.Inmostpatientsantibodiesaredirectedagainstthenicotinicacetylcholinereceptors(AChRs);inafewpatientsantibodiestargetposts-ynapticAChR-associatedproteinssuchasthemuscle-speci ctyrosinekinase(MuSK)andthelow-densitylipoprotein-relatedreceptor4(Lrp4).Despitethepro-gressinantibodydetection,somepatientsstillremainantibodynegative(‘sero-negative’myasthenia).

AlmostallMGpatientswillhaveocularmanifesta-tionsatsomepointduringthecourseoftheirdisease.Althoughocularsymptomsareoftenthe rsttoappear,mostpatientsprogresstoGMGandonly

©2014TheAuthor(s)

EuropeanJournalofNeurology©2014EFNS

687

688E.Kertyetal.

15%continuetohaveisolatedocularcomplaintsfortheentirecourseofthedisease[2].Inthemajorityofpatients,diseaseprogressionwilltakeplacewithinthe rstyearafteronsetandwithin2yearsinupto80%ofcases[2–4].Ifpatientshaverestrictedoculardiseasefor2yearswithoutdevelopingGMG,theyarenotlikelytodevelopitlater[5].Whenweaknessislimitedtotheextrinsicocularmusclesandlevatorpalpebraesuperioris(LPS),thediseaseiscalledocularmyasthe-nia[6].Allagesandbothgendersmaybea ected.Ptosismaybeunilateralorbilateral,anditisusu-allyasymmetric[7];thedegreeofLPSweaknessvar-iesfromslightdropofoneeyelidtonearlycompleteparalysis.Ophthalmoparesisisalsovariableandcanmimicalmostanypatternofocularmisalignment.Nearlyallpatientswithdiplopiahaveassociatedpto-sis[8].Thepupilisnota ected.Ifocularmyastheniaissuspectedonthebasisofhistoryandclinical nd-ings,thesamediagnostictestsshouldbeperformedasforGMGinordertocon rmthediagnosis,i.e.responsetotheedrophoniumtest,theicepacktestortheresttest,antibodyassays,andneurophysiolog-icaltests.40%–70%ofocularmyastheniapatientshaveanti-AChRantibodiesontheconventionalassay[9,10];theuseofacell-basedassaywithclusteredAChRsappearstosigni cantlyincreasethesensitiv-ityofanti-AChRantibodydetection[11].Ontheotherhand,highantibodylevelsandthepresenceofthymomaareuncommoninocularmyastheniaandwhenpresentareassociatedwithanincreasedriskofsecondarygeneralization[12].OnlyafewocularmyastheniacaseshaveantibodiestoMuSK[13–15],whilsttherearenodataonthefrequencyofanti-Lrp4antibodiesinthispatientpopulation[16–18].Antibodydetectioncon rmsthediagnosisofauto-immunemyasthenia.Inpatientswithoutdetectableantibodiesthesuspicionofsero-negativeMGmustbecon rmedbythepharmacologicaland/orelectro-myographytest.

Antibodiestovoltage-gatedpotassiumchannelKv1.4arerelativelyfrequentinJapaneseGMGpatientsandindicateamoreseveredisease.Suchanti-bodieshaverecentlybeenfoundinmildorpredomi-nantlyocularmyastheniainaCaucasiancohort[19].Thediagnosticrelevanceoftheseantibodiesiscur-rentlyunclear.

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