Anti-NMDA receptor encephalitis - Wikipedia

Anti-NMDA receptor encephalitis is a type of brain inflammation caused by antibodies. Early symptoms may include fever, headache, and feeling tired. Anti-NMDAreceptorencephalitis FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch Rarediseasewhichresultsinbraininflammation MedicalconditionAnti-NMDAreceptorencephalitisOthernamesNMDAreceptorantibodyencephalitis,anti-N-methyl-D-aspartatereceptorencephalitis,anti-NMDARencephalitisAschematicdiagramoftheNMDAreceptorSpecialtyNeurologySymptomsEarly:Fever,headache,feelingtired,psychosis,agitated[1][2]Later:Seizures,decreasedbreathing,bloodpressureandheartratevariability[1]ComplicationsLongtermmentalorbehavioralproblems[2]UsualonsetOverdaystoweeks[3]RiskfactorsOvarianteratoma,unknown[1][4]DiagnosticmethodSpecificantibodiesinthecerebralspinalfluid[1]DifferentialdiagnosisViralencephalitis,acutepsychosis,neurolepticmalignantsyndrome[2]TreatmentImmunosuppresivemedication,surgery[1]MedicationCorticosteroids,intravenousimmunoglobulin(IVIG),plasmaexchange,azathioprine[2]PrognosisTypicallygood(withtreatment)[1]FrequencyRare[2]Deaths~4%riskofdeath[2] Anti-NMDAreceptorencephalitisisatypeofbraininflammationcausedbyantibodies.[4]Earlysymptomsmayincludefever,headache,andfeelingtired.[1][2]Thisisthentypicallyfollowedbypsychosiswhichpresentswithfalsebeliefs(delusions)andseeingorhearingthingsthatothersdonotseeorhear(hallucinations).[1]Peoplearealsooftenagitatedorconfused.[1]Overtimeseizures,decreasedbreathing,andbloodpressureandheartratevariabilitytypicallyoccur.[1] Abouthalfofcasesareassociatedwithtumors,mostcommonlyteratomasoftheovaries.[1][4]Anotherestablishedtriggerisherpesviralencephalitis,whilethecauseinotherscasesisunclear.[1][4][5]TheunderlyingmechanismisautoimmunewiththeprimarytargettheGluN1subunitoftheN-methylD-aspartatereceptors(NMDAR)inthebrain.[1][6]Diagnosisistypicallybasedonfindingspecificantibodiesinthecerebralspinalfluid.[1]MRIofthebrainisoftennormal.[2]Misdiagnosisiscommon.[6] Treatmentistypicallywithimmunosuppresivemedicationand,ifatumorispresent,surgerytoremoveit.[1]Withtreatmentabout80%ofpeoplehaveagoodoutcome.[1]Outcomesarebetteriftreatmentisbegunearlier.[2]Long-termmentalorbehavioralproblemsmayremain.[2]About4%ofthoseaffecteddiefromthecondition.[2]Recurrenceoccursinabout10%ofpeople.[1] Theestimatednumberofcasesofthediseaseisonein1.5millionpeopleperyear.[7][5]Theconditionisrelativelycommoncomparedtootherparaneoplasticdisorders.[2]About80%ofthoseaffectedarefemale.[2]Ittypicallyoccursinadultsyoungerthan45yearsold,butitcanoccuratanyage.[4][6]ThediseasewasfirstdescribedbyJosepDalmauin2007.[1][8] Contents 1Signsandsymptoms 2Pathophysiology 2.1Antibodies 3Diagnosis 4Management 5Prognosis 6Epidemiology 7Societyandculture 8Seealso 9References 10Externallinks Signsandsymptoms[edit] Priortothedevelopmentofasymptomcomplexthatisspecifictoanti-NMDAreceptorencephalitis,peoplemayexperienceprodromalsymptoms,includingheadaches,flu-likeillness,orsymptomssimilartoanupperrespiratoryinfection.Thesesymptomsmaybepresentforweeksormonthspriortodiseaseonset.[9]Beyondtheprodromalsymptoms,thediseaseprogressesatvaryingrates,andpatientsmaypresentwithavarietyofneurologicsymptoms.Duringtheinitialstageofthedisease,symptomsvaryslightlybetweenchildrenandadults.However,behaviorchangesareacommonfirstsymptomwithinbothgroups.Thesechangesoftenincludeagitation,paranoia,psychosis,andviolentbehaviors.Othercommonfirstmanifestationsincludeseizuresandbizarremovements,mostlyofthelipsandmouth,butalsoincludingpedalingmotionswiththelegsorhandmovementsresemblingplayingapiano.Someothersymptomstypicalduringthediseaseonsetincludeimpairedcognition,memorydeficits,andspeechproblems(includingaphasia,perseverationormutism).[10][11] Thesymptomsusuallyappearpsychiatricinnature,whichmayconfoundthedifferentialdiagnosis.Inmanycases,thisleadstotheillnessgoingundiagnosed.[12]Asthediseaseprogresses,thesymptomsbecomemedicallyurgentandoftenincludeautonomicdysfunction,hypoventilation,cerebellarataxia,lossoffeelingononesideofthebody,[13]lossofconsciousness,orcatatonia.Duringthisacutephase,mostpatientsrequiretreatmentinanintensivecareunittostabilizebreathing,heartrate,andbloodpressure.[citationneeded]Onedistinguishingcharacteristicofanti-NMDAreceptorencephalitisistheconcurrentpresenceofmanyoftheabovelistedsymptoms.Themajorityofpatientsexperienceatleastfoursymptoms,withmanyexperiencingsixorsevenoverthecourseofthedisease.[10][11] Pathophysiology[edit] TheconditionismediatedbyautoantibodiesthattargetNMDAreceptorsinthebrain.ThesecanbeproducedbycrossreactivitywithNMDAreceptorsinteratomas,whichcontainmanycelltypes,includingbraincells,andthuspresentawindowinwhichabreakdowninimmunologicaltolerancecanoccur.Otherautoimmunemechanismsaresuspectedforpatientswhodonothavetumors.Whilsttheexactpathophysiologyofthediseaseisstilldebated,empiricalevaluationoftheoriginofanti-NMDAreceptorantibodiesinserumandcerebrospinalfluidleadstotheconsiderationoftwopossiblemechanisms.[citationneeded] Thesemechanismsmaybeinformedbysomesimpleobservations.SerumNMDAreceptorantibodiesareconsistentlyfoundathigherconcentrationsthancerebrospinalfluidantibodies,onaveragetentimeshigher.[14][15]Thisstronglysuggeststheantibodyproductionissystemicratherthaninthebrainorcerebrospinalfluid.WhenconcentrationsarenormalizedfortotalIgG,intrathecalsynthesisisdetected.ThisimpliesthattherearemoreNMDAreceptorantibodiesinthecerebrospinalfluidthanwouldbepredictedgiventheexpectedquantitiesoftotalIgG.[citationneeded] Passiveaccessinvolvesthediffusionofantibodiesfromthebloodacrossapathologicallydisruptedblood-brainbarrier(BBB).[16]Thiscellularfilter,separatingthecentralnervoussystemfromthecirculatorysystem,normallypreventslargermoleculesfromenteringthebrain.Avarietyofreasonsforsuchacollapseinintegrityhavebeensuggested,withthemostlikelyanswerbeingtheeffectsofacuteinflammationofthenervoussystem.Likewise,theinvolvementofcorticotropinreleasinghormoneonmastcellsinacutestresshasbeenshowntofacilitateBBBpenetration.[17]However,itisalsopossiblethattheautonomicdysfunctionmanifestedinmanypatientsduringthelaterphasesoftheconditionaidsantibodyentry.Forexample,anincreaseinbloodpressurewouldforcelargerproteins,suchasantibodies,toextravasateintothecerebrospinalfluid. Intrathecalproduction(productionofantibodiesintheintrathecalspace)isalsoapossiblemechanism.[18]Dalmauetal.demonstratedthat53outof58patientswiththeconditionhadatleastpartiallypreservedBBBs,whilsthavingahighconcentrationofantibodiesinthecerebrospinalfluid.Furthermore,cyclophosphamideandrituximab,drugsusedtoeliminatedysfunctionalimmunecells,havebeenshowntobesuccessfulsecond-linetreatmentsinpatientswherefirst-lineimmunotherapyhasfailed.[19]Thesedestroyexcessantibody-producingcellsinthethecalsac,thusalleviatingthesymptoms. Amoresophisticatedanalysisoftheprocessesinvolvedinantibodypresenceinthecerebrospinalfluidhintsatacombinationofthesetwomechanismsintandem.[citationneeded] Antibodies[edit] OncetheantibodieshaveenteredtheCSF,theybindtotheNR1subunitoftheNMDAreceptor.Therearethreepossiblemethodsinwhichneuronaldamageoccurs. AreductioninthedensityofNMDAreceptorsonthepostsynapticknob,duetoreceptorinternalizationoncetheantibodyhasbound.Thisisdependentonantibodiescrosslinking.[20] ThedirectantagonismoftheNMDAreceptorbytheantibody,similartotheactionoftheclassicdissociativeanestheticsphencyclidineandketamine. Therecruitmentofthecomplementcascadeviatheclassicalpathway(antibody-antigeninteraction).Membraneattackcomplex(MAC)isoneoftheendproductsofthiscascade[21]andcaninsertintoneuronsasamolecularbarrel,allowingwatertoenter.Thecellsubsequentlylyses.Notably,thismechanismisunlikelyasitcausesthecelltodie,whichisinconsistentwithcurrentevidence. Diagnosis[edit] Firstandforemostishighlevelofclinicalsuspicionespeciallyinyoungadultsshowingabnormalbehavioraswellasautonomicinstability.Thepersonmayhavealterationinlevelofalertnessandseizuresaswellduringearlystageoftheillness.Clinicalexaminationmayfurtherrevealdelusionsandhallucinations.[citationneeded] Theinitialinvestigationusuallyconsistsofclinicalexamination,MRIofthebrain,anEEGandalumbarpunctureforCSFanalysis.MRIofthebrainmayshowabnormalitiesinthetemporalandfrontallobes,butdosoinlessthanhalfofcases.AFDG-PETscanofthebrainmayshowabnormalitiesincaseswhentheMRIscanisnormal.[22]EEGisabnormalinalmost90%ofcasesandtypicallyshowsgeneralorfocalslowwaveactivity.[23]CSFanalysisoftenshowinflammatorychangeswithincreasedlevelsofwhitebloodcells,totalproteinandthepresenceofoligoclonalbands.[24]NMDAreceptorantibodiescanbedetectedinserumand/orCSF.WholebodyFDG-PETisusuallyperformedasapartoftumorscreening.GynecologicalultrasoundorapelvicMRImightbeperformedtosearchforanovarianteratomainwomen. Diagnosticcriteriaforprobableanddefiniteanti-NMDAreceptorencephalitishavebeenproposedtofacilitatediagnosisatanearlystageofthediseaseandhelpinitiateearlytreatment.[25] Management[edit] Ifapersonisfoundtohaveatumor,thelong-termprognosisisgenerallybetterandthechanceofrelapseismuchlower.Thisisbecausethetumorcanberemovedsurgically,thuseradicatingthesourceofautoantibodies.Ingeneral,earlydiagnosisandaggressivetreatmentisbelievedtoimprovepatientoutcomes,butthisremainsimpossibletoknowwithoutdatafromrandomizedcontrolledtrials.[10]Giventhatthemajorityofpatientsareinitiallyseenbypsychiatrists,itiscriticalthatallphysicians(especiallypsychiatrists)consideranti-NMDAreceptorencephalitisasapossiblecauseofacutepsychosisinyoungpatientswithnopastneuropsychiatrichistory.[citationneeded] Ifatumorisdetected,itsremovalshouldoccurinconjunctionwithfirst-lineimmunotherapy.Thisinvolvessteroidstosuppresstheimmunesystem,intravenousimmunoglobulin,andplasmapheresistophysicallyremoveautoantibodies.Astudyof577patientsshowedthatoverfourweeks,abouthalfthepatientsimprovedafterreceivingfirst-lineimmunotherapy.[10] Second-lineimmunotherapyincludesrituximab,amonoclonalantibodythattargetstheCD20receptoronthesurfaceofBcells,thusdestroyingtheself-reactiveBcells.Cyclophosphamide,analkylatingagentthatcross-linksDNAandisusedtotreatbothcancerandautoimmunediseases,hassometimesprovenusefulwhenothertherapieshavefailed. Othermedications,suchasalemtuzumab,remainexperimental.[26] Prognosis[edit] Therecoveryprocessfromanti-NMDARencephalitiscantakemanymonths.Thesymptomsmayreappearinreverseorder:Thepatientmaybegintoexperiencepsychosisagain,leadingmanypeopletofalselybelievethepatientisnotrecovering.Astherecoveryprocesscontinueson,thepsychosisfades.Lastly,theperson'ssocialbehaviorandexecutivefunctionsbegintoimprove.[9] Epidemiology[edit] Theestimatednumberofcasesofthediseaseis1.5permillionpeopleperyear.[5]AccordingtotheCaliforniaEncephalitisProject,thediseasehasahigherincidencethanitsindividualviralcounterpartsinpatientsyoungerthan30.[27]Thelargestcaseseriesasof2013characterized577peoplewithanti-NMDAreceptorencephalitis.Thedatawerelimited,butprovidesthebestapproximationofdiseasedistribution.Itfoundthatwomenmakeup81%ofcases.Diseaseonsetisskewedtowardchildren,withamedianageofdiagnosisof21years.Overathirdofcaseswerechildren,whileonly5%ofcaseswerepatientsovertheageof45.Thissamereviewfoundthat394outof501patients(79%)hadagoodoutcomeby24months.[10]30people(6%)died,andtherestwereleftwithmildtoseveredeficits.Thestudymentionedthatofthe38%presentingwithtumors,94%ofthosepresentedwithovarianteratomas.Withinthatsubset,African&Asianwomenweremorelikelytohaveatumor,butthiswasnotrelevanttotheprevalenceofthediseasewithinthoseracialgroups.[10] Societyandculture[edit] Anti-NMDAreceptorencephalitisissuspectedofbeinganunderlyingcauseofhistoricalaccountsofdemonicpossession.[28][29][30][31] NewYorkPostreporterSusannahCahalanwroteabooktitledBrainonFire:MyMonthofMadnessaboutherexperiencewiththedisease.[32]Thishassubsequentlybeenturnedintoafilmofthesamename.[33] DallasCowboysdefensivelinemanAmobiOkoyespent17monthsbattlinganti-NMDAreceptorencephalitis.Inadditiontothreemonthsinamedically-inducedcoma,heexperienceda145-daymemorygapandlost78pounds.HereturnedtopracticeonOctober23,2014.[34] IntheJapanesemoviecalledThe8-YearEngagement,ayoungJapanesewomanendsupbeinginacomaduetoAnti-NMDAreceptorencephalitis. Knut,apolarbearattheBerlinZoologicalGardenthatdiedon19March2011,wasdiagnosedwithanti-NMDAreceptorencephalitisinAugust2015.Thiswasthefirstcasediscoveredinanon-humananimal.[35][36][37] InHannibalWillGrahamwasaffectedbyNMDAReceptororAntibodyEncephalitis,alsoknownasAnti-NMDAREncephalitis.[38] TheTVseriesSomething'sKillingMefeaturedanepisodecalled"IntoMadness"thatfeaturedtwocasesofthedisease.[39] Seealso[edit] Anti-glutamatereceptorantibodies References[edit] ^abcdefghijklmnopqrKayser,MS;Dalmau,J(September2016)."Anti-NMDAreceptorencephalitis,autoimmunity,andpsychosis".SchizophreniaResearch.176(1):36–40.doi:10.1016/j.schres.2014.10.007.PMC 4409922.PMID 25458857. ^abcdefghijklmKayser,MS;Dalmau,J(2011)."Anti-NMDAReceptorEncephalitisinPsychiatry".CurrentPsychiatryReviews.7(3):189–193.doi:10.2174/157340011797183184.PMC 3983958.PMID 24729779. 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^Greiner,Hansel;Leach,JamesL.;Lee,Ki-Hyeong;Krueger,DarcyA.(April2011)."Anti-NMDAreceptorencephalitispresentingwithimagingfindingsandclinicalfeaturesmimickingRasmussensyndrome".Seizure.20(3):266–270.doi:10.1016/j.seizure.2010.11.013.PMID 21146427.S2CID 5839321. ^Cahalan,Susannah.BrainonFire-MyMonthofMadness,NewYork:Simon&Schuster,2013. ^IraniSR,BeraK,WatersP,ZulianiL,MaxwellS,ZandiMS,FrieseMA,GaleaI,KullmannDM,BeesonD,LangB,BienCG,VincentA(Jun2010)."N-methyl-D-aspartateantibodyencephalitis:temporalprogressionofclinicalandparaclinicalobservationsinapredominantlynon-paraneoplasticdisorderofbothsexes".Brain.133(6):1655–67.doi:10.1093/brain/awq113.PMC 2877907.PMID 20511282. ^Suh-LailamBB,HavenTR,CoppleSS,KnappD,JaskowskiTD,TeboAE(Jun2013)."Anti-NMDA-receptorantibodyencephalitis:performanceevaluationandlaboratoryexperiencewiththeanti-NMDA-receptorIgGassay".ClinChimActa.421:1–6.doi:10.1016/j.cca.2013.02.010.PMID 23454475. ^Moscato,EmiliaH.;Jain,Ankit;Peng,Xiaoyu;Hughes,EthanG(2010)."Mechanismsunderlyingautoimmunesynapticencephalitisleadingtodisordersofmemory,behaviorandcognition:Insightsfrommolecular,cellularandsynapticstudies".EuropeanJournalofNeuroscience.32(2):298–309.doi:10.1111/j.1460-9568.2010.07349.x.PMC 2955837.PMID 20646055. ^Rabchevsky,AlexanderG.;Degos,Jean-Denis;Dreyfus,PatrickA.(1999)."PeripheralinjectionsofFreund'sadjuvantinmiceprovokeleakageofserumproteinsthroughtheblood–brainbarrierwithoutinducingreactivegliosis".BrainResearch.832(1–2):84–96.doi:10.1016/S0006-8993(99)01479-1.PMID 10375654.S2CID 27036707. ^ManishMalviya,etal.(2017);NMDARencephalitis:passivetransferfrommantomousebyarecombinantantibody.AnnClinTranslNeurol.Oct3;4(11):768-783.https://doi.org/10.1002/acn3.444 ^Florance,NicoleR.;Davis,RebeccaL.;Lam,Christopher;Szperka,Christina;Zhou,Lei;Ahmad,Saba;Campen,CynthiaJ.;Moss,Heather;Peter,Nadja;Gleichman,AmyJ.;Glaser,CarolA.;Lynch,DavidR.;Rosenfeld,MyrnaR.;Dalmau,Josep(2009)."Anti-N-methyl-D-aspartatereceptor(NMDAR)encephalitisinchildrenandadolescents".AnnalsofNeurology.66(1):11–8.doi:10.1002/ana.21756.PMC 2826225.PMID 19670433. ^Hughes,E.G.;Peng,X.;Gleichman,A.J.;Lai,M.;Zhou,L.;Tsou,R.;Parsons,T.D.;Lynch,D.R.;Dalmau,J.;Balice-Gordon,R.J.(2010)."CellularandSynapticMechanismsofAnti-NMDAReceptorEncephalitis".JournalofNeuroscience.30(17):5866–75.doi:10.1523/JNEUROSCI.0167-10.2010.PMC 2868315.PMID 20427647. ^Abbas,AbulK.;Lichtman,AndrewH.H.;Pillai,Shiv(2011).CellularandMolecularImmunology(7th ed.).ElsevierHealthSciences.ISBN 978-1-4377-3573-4. ^Bacchi,Stephen;Franke,Kyle;Wewegama,Dasith;Needham,Edward;Patel,Sandy;Menon,David(June2018)."Magneticresonanceimagingandpositronemissiontomographyinanti-NMDAreceptorencephalitis:Asystematicreview".JournalofClinicalNeuroscience.52:54–59.doi:10.1016/j.jocn.2018.03.026.PMID 29605275.S2CID 4565748. ^Gillinder,Lisa;Warren,Nicola;Hartel,Gunter;Dionisio,Sasha;O’Gorman,Cullen(February2019)."EEGfindingsinNMDAencephalitis–Asystematicreview".Seizure.65:20–24.doi:10.1016/j.seizure.2018.12.015.PMID 30597400. ^Blinder,Tetyana;Lewerenz,Jan(2019-07-25)."CerebrospinalFluidFindingsinPatientsWithAutoimmuneEncephalitis—ASystematicAnalysis".FrontiersinNeurology.10:804.doi:10.3389/fneur.2019.00804.ISSN 1664-2295.PMC 6670288.PMID 31404257. 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^"AYoungReporterChroniclesHer'BrainOnFire'",NPR,14November2012. ^Tam,Johnny;Zandi,MichaelS.(2017-06-19)."ThewitchcraftofencephalitisinSalem".JournalofNeurology.264(7):1529–1531.doi:10.1007/s00415-017-8546-4.ISSN 0340-5354.PMID 28631128.S2CID 36151332. ^Sébire,Guillaume(2010-02-23)."Insearchoflosttimefrom"DemonicPossession"toanti-N-methyl-D-aspartatereceptorencephalitis".AnnalsofNeurology.67(1):141–142.doi:10.1002/ana.21928.ISSN 0364-5134.PMID 20186949.S2CID 2366741. ^"AYoungReporterChroniclesHer'BrainOnFire'".FreshAir.WHYY;NPR.November14,2012.RetrievedSeptember20,2013. ^"Whattowatchwithyourkids:'Ant-ManandtheWasp,''LeaveNoTrace'andmore".WashingtonPost.Retrieved14July2018. ^Whitmire,Keith(2014-10-23)."Cowboys'Okoyereturnstopracticeafterbattlingrarebraindisease".www.foxsports.com.FOXSportsSouthwest.Retrieved24October2014. ^Nuwer,Rachel(27August2015)."KnutthePolarBear'sMysteriousDeathFinallySolved".Smithsonian. 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Externallinks[edit] ClassificationDICD-10:Xxx.xICD-9-CM:xxxMeSH:D060426 Cahalan,Susannah(4October2009)."Mymysteriouslostmonthofmadness".NewYorkPost.—aboutherexperiencewiththedisease vteParaneoplasticsyndromesEndocrine Hypercalcaemia SIADH Zollinger–Ellisonsyndrome Cushing'ssyndrome Hematological Multicentricreticulohistiocytosis Nonbacterialthromboticendocarditis Neurological Paraneoplasticcerebellardegeneration Encephalomyelitis Limbicencephalitis Opsoclonus Polymyositis Transversemyelitis Lambert–Eatonmyasthenicsyndrome Anti-NMDAreceptorencephalitis Musculoskeletal Dermatomyositis Hypertrophicosteopathy Mucocutaneousreactiveerythema Erythemagyratumrepens Necrolyticmigratoryerythema papulosquamous Acanthosisnigricans Ichthyosisacquisita AcrokeratosisparaneoplasticaofBazex ExtramammaryPaget'sdisease Floridcutaneouspapillomatosis Leser-Trélatsign Pityriasisrotunda Tripepalms Other Febrileneutrophilicdermatosis Pyodermagangrenosum Paraneoplasticpemphigus Retrievedfrom"https://en.wikipedia.org/w/index.php?title=Anti-NMDA_receptor_encephalitis&oldid=1083275633" Categories:EncephalitisDemonicpossessionHiddencategories:ArticleswithshortdescriptionShortdescriptionisdifferentfromWikidataAllarticleswithunsourcedstatementsArticleswithunsourcedstatementsfromNovember2015ArticleswithunsourcedstatementsfromJuly2021Wikipediamedicinearticlesreadytotranslate Navigationmenu Personaltools NotloggedinTalkContributionsCreateaccountLogin Namespaces ArticleTalk English Views ReadEditViewhistory More Search Navigation MainpageContentsCurrenteventsRandomarticleAboutWikipediaContactusDonate Contribute HelpLearntoeditCommunityportalRecentchangesUploadfile Tools WhatlinkshereRelatedchangesUploadfileSpecialpagesPermanentlinkPageinformationCitethispageWikidataitem Print/export DownloadasPDFPrintableversion Languages العربيةБългарскиDeutschEspañolFrançaisItaliano日本語ଓଡ଼ିଆPolskiРусскийไทยУкраїнська Editlinks