JournalofNeurologyNeurosurgeryandPsychiatry199255692696Wilsonsdi - PDF document

JournalofNeurology,Neurosurgery,andPsychiatry1992;55:692-696Wilson'sdisease:theproblemofdelayeddiagnosisJMWalshe,MYeallandAbstractTodiscovertheearliestsymptomsandsignsofneurologicalWilson'sdiseaseweanalysedthecasehistoriesof136patientswhowereseenbetween1955-87:patientswithhepaticorpresymptomaticWilson'sdiseasewereexcludedfromthisseries.Thirtyonepatients(23%)gaveahistoryofanepisodeofliverdamage.Theonsetofsymptomsrangedfromnineto40yearswithamedianof16-2years.Thecorrectdiagnosiswasmadeatpresentationinonly43patients.Themeandelaybeforediagnosiswas12-8monthsfortheothers.Theearliestsymptomsweredysarthriaordifficultywiththehands,oroftenboth.Therewasoftenanassociatedchangeinpersonalityordeterioratingperformanceatschool.Thefourcommonclinicalpic-tureswereParkinsonian(61cases),"pseudosclerotic"(33cases),dystonic(21cases)andchoreic(15cases):sixcaseswereunclassified.Parkinsoniansymp-tomswereequallycommoninchildren(under17years)andadults,a"pseudo-sclerotic"picturewasmuchmorecom-moninadultsbutdystonicandchoreicsymptomswereseenmoreofteninchil-dren.Experiencesuggeststhatnotwopatientsareeverthesame,eveninasibship.(_NeurolNeurosurgPsychiatry1992;55:692-696)UniversityDepartmentofMedicineandtheDepartmentofNeurology,Addenbrooke'sHospital,Cambridge,UKJMWalsheMYeallandCorrespondenceto:DrWalshe,TheDepartmentofNeurology,TheMiddlesexHospital,LondonWIA8AA,UKReceived12August1991andinrevisedform20November1991.Accepted27November1991MorethanthirtyyearsofinvestigationandmanagementofpatientswithWilson'sdiseasehasshownthatthereisfrequentlyanunaccep-tabledelayinestablishingthecorrectdiag-nosis.Thisisgreatlytothedisadvantageofthepatientnotonlybyprolongingunnecessarilythedurationoftheillnessbutalsobyaffectingadverselytheprospectsforrecovery.Iftoomuchdamageisallowedtooccurinthebrainbeforetheinitiationof"decoppering"therapythenfullrestorationoffunctionisdifficulttoachievedespitetheremarkableimprovementswhichhavebeenobservedinCTscanappearances.Themeandelayindiagnosisforpatientspresentingwithneurologicalsymptomsinthisserieshasbeeninexcessofoneyear.TheonsetofhepaticWilson'sdisease,itsevolutionandresponsetotreatmenthasbeendescribedelsewhere.2ItmightbearguedthatWilson'sdiseaseissorarethatfailuretorecogniseitsoonafteronsetisnotsurprising.However,itisnowestablishedthattheprevelanceinthegeneralpopulationis30permillion35andapproximatelyhalfofthesewillpresentwithneurologicalsymptoms.6ThusintheUnitedKingdom,withabirthrateofbetween600000and700000,therewillbeonaverage10newpatientspresentingannuallytoalltheneuro-logicalclinicsintheBritishIsles.Littleattentionhasbeenpaidinthelit-eraturetotheveryearliestneurologicalsymp-tomsandsignsofthisdiseaseexceptforbriefmentioninScheinbergandSternlieb'smon-ograph.4Whilewearelargelyinagreementwiththeirobservationsitisourintentiontodescribeingreaterdetailthisimportantstageintheevolutionoftheillness.Inmanycasesithasbeendifficulttoidentifytheveryearliestsymptoms.Mostpatientswillhavebeenseenbyanumberofdoctors,oftenofdifferentdisciplines(generalmedical,psy-chiatricandneurological)andhavehadtheircasehistoriestakenonnumerousoccasionsbeforereferral.Thustheirrecollectionofhowtheillnessstartedwillhavefadedwiththepassageoftimeandwillalsohavebeeninfluencedbydirectquestioningdictatedbythepreconceptionoftheexaminingphysician.Also,inmanycasesthelaterdevelopmentofmoredramaticsymptomsandsignswillhavecolouredthepatient'sviewofthedisease.Webelievethattheanalysisofsomanycasehistories,alltakenbyoneofus,overaperiodinexcessof30years,hasenabledustoestablishtheonset,evolutionandvaryingclinicalpicturesofthisdisease.Thereappearstobeonlyonethingwhichallpatientshaveincommon,apartfromKayserFleischercornealpigment,namelythattheyarealldifferent.Itisthereforeunwisetorelyonseeing"thetypicalpictureofWilson'sdisease"beforemakingthediagnosis.MaterialandmethodsWeselectedforstudy136patients(F=70,M=66)presentingwithneurologicalsignsfromsome250casesofWilson'sdiseaseseenbetween1955-87,themajorityatAddenbrooke'sHospital,Cambridge;patientsseensubsequentlywerenotincluded.Onehundredandfourteencaseshavebeenomittedbecausethediagnosiswasmadebeforetheonsetofneurologicalsymptoms.Thirtyone(23%)gaveahistoryofanearlierepisodeofliverdamagethesignificanceofwhichwasnotappreciatedatthetime.TheclinicalpictureofhepaticWilson'sdisease,itsdiagnosisandmanagementofthepresymptomaticstagehavebeendescribedelsewhere.6-8EightyfivepatientscamefromtheUnitedKingdomand692 Wilson'sdisease:theproblemofdelayeddiagnosis51fromabroad;mostlytheMediterraneancountriesandtheNearEast.AllpatientsshowedtheclassicalbiochemicallesionofWilson'sdisease,thatisalowserumcopper,alowcaeruloplasminandahighserum"freecopper"togetherwithanincreasedurinaryoutputofthemetal.TheyalsoallhadKayserFleischercornealpigment,thoughnotnecessarilycompleterings,9whenfirstsee

nbyus.Allpatientswereexaminedbyoneofus(JMW)immediatelyafterreferralandthemajoritywereexaminedbybothofussepa-rately.Wereliedupontherecollectionsofthepatientsandthelettersofreferringphysiciansforinformationabouttheearlieststagesoftheillness.Aminorityofpatientsonlywereseensoonaftertheonsetofsymptoms.Wilson'sdiseasehasarecessivemodeofinheritancesothatitisprobablethatfamilieswillbeseeninwhichmorethanonesiblingisaffected.IfthediagnosisofWilson'sdiseasehasalreadybeenconfirmedinonesiblingthereshouldbenoprobleminmakingthecorrectdiagnosisifasecondsiblingdevelopssimilarsymptoms.Inourseries16familieshadmorethanoneaffectedsiblingandinonekinshipfirstcousinsdevelopedneurologicalWilson'sdisease.IneightsibshipsscreeningstudiesledtothediagnosisofpresymptomaticWilson'sdiseaseinayoungersibling.Inthreeotherfamiliesasecondsiblinghadearlysymptomsofneurologicalinvolvement.InthreefamiliesthediagnosisofWilson'sdiseaseinthepropo-situswasnotfollowedupandasecondsiblingdevelopedsymptomsatalaterdate.Inonefamilythediagnosisintheeldersiblingwasonlymadeafterasecondsiblingdevelopedsymptoms.InanotherfamilytheestablishmentofthediagnosisofWilson'sdiseaseinaneldersiblingwithneurologicalsymptomsledtothefindingthatheryoungersister,whowasbeingtreatedforchronichepatitis,alsohadthesamedis-ease.Interestingly,the43patientsinwhomthediagnosisofWilson'sdiseasewasmadeatthefirsttimeofinvestigation,ninehadaffectedsiblings,whereasintheremaining93casesonlythreesiblingshadWilson'sdisease.Thediagnosesmadewhenthepatientsfirstconsultedadoctorfallintofourgroups:1)anorganicdisorderotherthanWilson'sdisease(35);2)apsychiatricillness(32);3)agroupinwhichnodiagnosiswasmadeorelsethepatientdeclaredfit(26);4)Wilson'sdisease(43).Incorrectorganicdiagnoseswereasdiverseasflatfeet,myxoedema,myastheniagravis,encephalitis,multiplesclerosisandPar-kinson'sdisease.Patientspresentedtopaediat-ric,generalmedical,neurologicalandpsychiatricclinics.Psychiatricdiagnoseswereschizophrenia,depression,anxietystateandhysteria.Thetypeofproblemspatientssufferinthediagnosticprocessareillustratedbytwobriefcasehistories.Case1hadanexcellentacademicrecorduntil,attheageof17years,shedeveloped"anacuteanxietystate"whichwasattributedtothebreak-upofherparents'marriage.Follow-ingtreatmentwithantidepressantsshedevel-opedParkinsoniansymptomsconsideredsecondarytophenothiazines.Duringthenexttwoyearsshesufferedfromincreasingtremorofthearmsandslurringofspeech.Shewasreferredtoaconsultantneurologistwhocon-sideredhersymptomstobehysterical.Asshebecameincreasinglydisabledshetookanoverdoseofphenothiazineswhichwasfollowedbyexacerbationofhertremor.Shewasthenreferredtoapsychiatristwhoagreedwiththediagnosisofhysteria.Latershewasseenbyasecondneurologistwhocouldfindnoevidenceoforganicdisease.Sixmonthslaterathirdneurologistinvestigatedherand,atthattime,anophthalmologistsuggestedthatshemighthaveKayserFleischerringsbutthiswasignoredandagainshewassaidtohavenoorganicdisease.Finallyherspeechdefectbecamesoseverethatshewasrenderedmute.Atthatstagethepartnerinherfather'sgeneralpracticesuggestedthediagnosisofWilson'sdiseaseandshewasreferredtous.Wefoundthatshehaddense,broad,completeKayserFleischerrings,blepharospasm,saccadiceyemovements,anarthria,severeactionandrest-ingtremorofthearmsandtruncaltremor.Sheeventuallymadeanexcellentrecoveryonpenicillamine.Case2acivilengineernoticedattheageof30yearsachangeinhishandwritingandinhisspeechwhichbecamequaveringandrapid.Thiswasfollowedbytremorofbotharms.AdiagnosisofmultiplesclerosiswasmadeandhewastreatedwithACTH.Thefollowingyearhedevelopednoddingtremoroftheheadandhisworkwasseriouslyimpeded.Aconsultantneurologistcouldfindnoabnormalityinhisspeechbutconfirmedthetremoroftheheadandarms,thegaitwasnormal.AcursoryexaminationoftheeyesdidnotrevealthepresenceofKayserFleischerrings.ACTbrainscanshoweddilatationoftheventricles,moremarkedontheleft,andatrophicchangesinthecerebralandinthecerebellarcortex.Theserumcaeruloplasminwasjustbelowthelowernormallimitforthelaboratory.ThediagnosisofWilson'sdiseasewasdiscardedinfavouroffamilialtremor.Hewasseenregularlyforfollowupandduringthistimetherewasachangeinhispersonality,hetooktodrinkandtohittinghiswifewholefthim.Thisledtonoreviewofthediagnosisorhismanagement.AfterthisheattendedaneurologicalclinicintheUnitedStateswherehewasnotedtohaveheadtremor,actiontremorofthearmsandslurredspeech.Hewasalsofoundtohavebroad,densecompleteKayserFleischerrings.Heimprovedontreatmentwithpenicillaminebutdevelopedimmunecomplexnephritis.Hewasreferredtousfortreatmentatthisstage.Hestillhadmildheadandarmtremorandverydensecornealrings.Hehassubsequentlymadeanexcellentrecoveryontrientine.Theageofonsetrangedfromnineto40yearswithamedianfigureof16years,themedianagefortheonsetofhepaticsymptoms,inthosepatientswhohadshownthemwas11years(fig).Wehaves

ubdividedthepatientsintotwogroups,65juveniles(16yearsofageand693 Walshe,YeallandAgeofonset2-o15Z1015202530Medianage=16-2yearsMeandelaybeforediagnosis=12*8monthsICNSIN=136Io..354010152uAge(years)FigureThisshowstheageofonsetofneurologicalsymptomsinall136patients.Atotalof31patientshadanearlierepisodeofliverdisease.under)and71adults(17yearsandover).Theeightmajorcomplaintsofpersonalitychange,speechdefect,drooling,difficultyinswallow-ing,handtremor,otherdifficultieswiththehands,abnormalgaitandadeteriorationinthequalityofschoolwork,werelargelysimilarinbothgroupsthoughdysarthriaanddroolingwererathermorecommoninthejuveniles(table1).Deteriorationinschoolworkcouldresultfromintellectualimpairment,physicalproblemsorboth.Thecombinationofaspeechdefectanddroolingwasfoundin86%ofjuveniles(56)and72%ofadults(51);despitethis-factdifficultyinswallowingwasnotcommonintheearlystagesofthedisease.Inbothchildrenandadultsdysarthriaandtremororclumsinessofthehandswerethepre-dominantearlysymptoms.IndeedoneorbothofthesenearlyalwaysheraldedtheonsetoftheTable1Number(percentage)ofpatientswithdifferentinitialsymptomsJ'uvenilesAdultsNumberofpatients6571Personalitychange21(32)23(32)Speechdefect63(41)42(30)Drooling31(20)22(16)Dysphagia14(9)7(5)Handtremor48(31)55(39)Handclumsy32(21)20(14)Abnormalgait34(22)18(13)Fallinworkatschool40(26)disease.Thespeechdefectcouldbeofgreatlyvaryingseverity.Inasmallnumberofpatientsachangeinpersonalitywastheveryearliestabnormalityandshoweditselfasfacilelaugh-ter,inappropriateandoccasionallyaggressivebehaviour,labilemood,lackofinsightanddisinhibition.Thetremorwasofvaryingseverityandclumsinessofthehandswasusuallydescribedasdifficultyinwriting.Problemsinwalkingwerenotrecordedasafirstsymptominanypatientthoughitoftenrapidlyfollowedtremorofthehands.Despitethefactthattheneuro-logicallesionisbiochemicallyinducedandthereforeaffectsthebrainuniformly,limbsymptomsandsignswerealwaysasymmetricalintheearlystagesofthedisease.Musclecrampsandspasmswererarebutdidoccurandpresumablywereresponsibleforthespontaneousdislocationofthejawcomplainedof,asafirstsymptom,bytwopatients;athirdpatienthadsuchsevereabnormaljawmove-mentsthatsheneededdentalextractionstoprotecthercheeksfromdamagebyherteeth.Ninepatientsgaveahistoryofepilepsy,eithergrandmalorfocalfits,earlyintheillness;inonepatientasinglegrandmalseizurewastheonlycomplaintwhenhewasfirstseen,butexaminationrevealedcompleteKayserFleischerringsandsunflowercataracts.Epi-lepsywasmorecommoninjuveniles(7)thaninadults(2).AdetailedaccountofepilepsyinWilson'sdiseasehasalreadybeenpresented.'0Weobservednodifferencesinsymptomsbetweenthesexes.Thesigns,forbothjuvenilesandadults,inthefourdiagnosticcategoriesareshownintables1and2.Thesewillbedescribedtogetherasmostdifferencesseeninthepatternofsignsinthe2agegroupsareprobablyexplainedbytherelativelysmallnumbersinvolved.TheoneexceptionwasthataParkinsonianfacieswasnotedthreetimesmorefrequentlyinthejuvenilesthanintheadults.In10casesnoabnormalsignswererecordedeventhoughthepatientsmayhavecomplainedofspeechdis-turbancesortremor.Presumablythiswasbecauseoftheintermittentnatureoftheearlymovementdisorders.Signsinthelimbswerealwaysasymmetricalwithnopreferenceforeitherside.Asmightbeexpectedfromthesymptomsthecommonestsignsweredysar-Table2Number(percentage)ofjuvenilesandadultswithdifferentinitialsignsJuvenilesAdults6571Personalitydisorder14(21)13(18)Dysarthria34(52)19(27)Gaitabnormal8(12)5(7)Eyemovementabnormal4(6)4(6)Drooling18(28)11(15)Parkinsonianfacies15(23)5(7)Openmouth10(15)0(0)Bradykinesia6(9)3(4)Tongueabnormal11(17)9(13)ULtremor*17(26)23(32)ULdystonia*14(21)13(18)ULspontaneousmovements*8(12)0(0)LLtremorN2(3)6(8)LLdystoniaN12(18)0(0)LLspontaneousmovementsN1(1)1(1)Liverdisease19(29)8(11)*UL%upperlimb.NLL%lowerlimb.6543Medianage=11-5yearsMeandelaybeforediagnosis=612monthsHepaticN=3110k5694 Wilson'sdisease:theproblemofdelayeddiagnosisthria(53)andtremorofthehands(40cases).Althoughpatientswithdysarthriaoftenhadabnormaltonguemovementsthesedidnotalwaysoccurtogether.Dysarthriavariedfromslightslurringofspeechtocompleteincompre-hensibility;itcouldinvolvedisturbancesoflip,tongue,palate,vocalcordanddiaphragmaticmovements.TheincidenceofabnormalitiesofspeechwasfollowedbythatofParkinsonianexpressionandbythechangeinpersonality.Disordersofeyemovement,thoughnotcom-mon,wereseen;sixpatientswererecordedasshowingnystagmuswhiletwogaveahistoryofrelativelyshortepisodesofdiplopia.Thecom-binationofanalertexpressionoftheupperfacewitharathervacuousopen-mouthedlowerface,socharacteristicoftheestablisheddisease,wasrecordedinonly10juvenilesandinnoadults.Disordersoflowerlimbfunctionwerecommonatthisstage;thegaitwasdescribedasabnormalineightchildrenbutinnoneoftheadults.Thedistributionofsigns,nomatterwhattheinitialdiagnosis,showedfewvariationsa

mongthepatients.However,personalitychangewasnotedtwiceasofteninpatientswhowerelabelled"psychiatric"asintheothergroups,whetherjuvenileoradult.KayserFleischerringswerereportedin21childrenand13adultsinthecorrectly"diagnosedgroup"butinnoothers.Inonlyonepatient,diagnosedatthisstage,wereKayserFleischerringssoughtwithaslitlampandnotseen.Whenthispatientwasreferredtoussixmonthslatertheringsweredenseandcomplete,despitesixmonthschelationtherapy.Onepatientinthe"psy-chiatric"groupwasreportedbyanophthal-mologistashavingKayserFleischerringsbutthiswasignoredbythephysician.Evidenceofpreviousliverdiseasewasmostfrequentlyseeninthe"juvenileWilson'sdisease"group.Inthepatientsnotcorrectlydiagnosedatthefirstconsultationtherewasameandelayof13monthsbeforeitwasestablishedthattheyhadWilson'sdisease.AlthoughthesymptomsandsignsofWilson'sdiseasearepleomorphicwefoundthatitwaspossibletoplaceallbutsixofthepatientsintofourmainclinicaltypes:1)Parkinsonian;2)"pseudosclerotic";3)dys-tonic;4)choreic.TheParkinsonianpatientsshowedpaucityofexpressionandmovement.Althoughtheterm"pseudosclerosis"'°haslargelybeenabandonedwehaveuseditherebecauseitisthebestdescriptionofatypeofthediseaseinwhichtremorcloselyresemblesthatseeninmultiplesclerosisandwhichcanbesevereenoughtobedescribedas"wing-beating".Thedystonicpatientsshowedhypertonicityoftenassociatedwithabnormallimbmovementswhichcouldbegrotesque.Inthechoreicgroupabnormalmovements,whichcouldbechoreicorchoreo-athetoidwereoftenassociatedwithdystonia.AParkin-sonianpictureisthemostcommoninbothchildrenandadults(table3).The"pseudo-sclerotic"presentationoccursaboutthreetimesmorefrequentlyinadultsthaninchil-drenwhilstinvoluntarymovementsareseensixtimesmoreofteninjuvenilesthaninadults.Table3DistributionofcasesinfourclinicaltypesJ'uvenilesAdultsTotalNumberofpatients6571136Parkinsonian28(43)33(46)61(45)Pseudosclerotic7(11)26(37)33(24)Dystonic14(21)7(10)21(15)Choreic13(20)2(3)15(11)Intermediate3(5)3(4)6(4)Percentagetotalsinbrackets.Bythetimethecorrectdiagnosiswasmademanyofthejuvenileshadmovedintotheadultgroupsocomparisonhereisnolongervalid.Predictablythephysicalsignshadbecomemoreobviousandwidespreadwithdysarthriaanddroolingremainingthemostcommon.Astrikingfeatureinmanypatientswasapeculiarandcharacteristiclaughoninspiration,(onceheardneverforgotten).Thefrequencyofspeechdifficultieswerecloselyfollowedbytremor,dystoniaandspontaneousmovementsoftheupperlimbs.Bythisstagedifficultyinwalkingandbradykinesiaweremuchmorecommon.KayserFleischerringswerenotedin135patientsandsunflowercataractsinthree.Inonepatient,inwhomthediagnosiswasmaderetrospectively,theringswerenotsought.DiscussionOurfindingsin136patientswithneurologicalWilson'sdiseasedemonstratethatthisdiag-nosismustseriouslybeconsideredineveryadolescentwhocomplainsofachangeinspeechanddifficultyintheuseofthehands.AchangeinpersonalitymakesthediagnosisofWilson'sdiseasethatmuchmoreprobable.Thecorrectdiagnosisatthetimeofpresenta-tionwasmadeinonly43patientsorlessthanonethird;childrenfaredslightlybetterthanadults.Fortheotherstherewasameandelayof13monthsbeforethediagnosiswasmade,35werediagnosedashavinganorganicdis-ease,32apsychiatricdisorderandin26nodiagnosiswasmadeorthepatientsweredeclaredfit.Therewasnostrikingdifferenceinsymptomsbetweenthesefourgroupsofpatients.Wheneverthediagnosisissuspected,KayserFleischerringsshouldbesoughtbyanexperiencedophthalmologist,usingaslitlamp.Theringsorcrescentscaneasilybemissedbyaninexperiencedobserverparticularlyiftheirisisbrown.Similarlylaboratoryerrorsintheestimationofcopperandcaeruloplasmincandelaythecorrectdiagnosis;experienceinthelaboratoryisasimportantasintheclinic.Alladolescentsandyoungadultswithchangesinpersonalityanddisturbancesofmovement,particularlyinvolvingspeechanduseofthehands,shouldbeconsideredaspossibleexam-plesofWilson'sdiseaseifthesensorynervoussystemisnotinvolved.Asascreeningproce-durewerecommendthattheserumcopperandcaeruloplasminshouldbedeterminedandtheeyesexaminedforKayserFleischerringsbyslitlamp.ItisinterestingtocompareourfindingswiththecasereportsinWilson'soriginalpublica-695 Walshe,Yeallandtion."Heobserved,personally,fourpatientswhoseneurologicalsymptomsshowedaslightlyolderageofonsetthanourmedianageof16years,theyoungestwas17andtheoldest25years.Twogaveaclearhistoryofanearlierepisodeofliverdamage.InthreepatientstheonsetappearedtohavebeenParkinsonianwhilethefourthshowedrigidityand"clonictremor".Onehadanearlierandapparentlyselflimitingpsychoticepisode.DennyBrown"2dividedhispatientsintotwoclinicaltypes,thefirsthecalled"pseudo-sclerotic"andthesewerecharacterisedbydysarthriaandaflappingtremorofthe"wing-beating"type,thepatientswereallover19yearsofageandtheillnessverychronic.Thesecondgroupshowedtheprogressivelenticu-lardegenerationofWilsonandwereallbetweentheagesofsevenand15yea

rs.Thefirstsymptomwas"almostalwaysrelatedtodystonia".SomepatientsshowedaParkinson-ianfaciesandfinetremorofthefingers.Thislattergroupofpatientsresponded-verybadlytotreatmentwithdimercaprol.Inthispublica-tionDennyBrowndidnotcommentontheveryearliestsymptomsexcepttomentionthattherewasoftenatendencytoinattentivenessatschool,anobservationinkeepingwithourownfindings.ThedelayinmakingacorrectdiagnosisisanotherfeatureofWilson'sdiseasewhichhasreceivedlittleattentionintheliterature.Withincreasingawarenessofthediseaseoverthepast30yearsthediagnosisisbeingmademoreoftenthanpreviouslybutthedelayrecordedinthisseriesof13monthsisunacceptablylong.Thesourceofreferralofthepatientsmadesurprisinglylittledifferencetothisfigure,13f1months(rangesixto72months)for85patientsfromtheUnitedKingdomand12-3months(rangetwoto60months)for51patientsfromabroad.Itisimpossibletoknowhowmanypatientshavediedundiagnosed.Bydrawingattentiontotheearliestsymptoms,wehopethatthisarticlewillincreasediagnosticawarenessandreducedelayssothatpatientscanstarttheirtreatmentearlierinthecourseoftheillnessandthushaveabetterprospectofachievingfullfunctionalrecovery.Finally,wehaveincludedanextractfromaletterbyapatientdescribingthestartofherillness.Shepresentedtooneofus(JMW)latein1989andisnotincludedinthisseries."Thecoppermusthavebeenbuildingupallthetimeinmybrain,butnosymptomsstartedtoshowuntilIwassixteenyearsold.IwasinmylastyearatcollegewhenIstartedtoloseconcentrationandtakedizzyspellswhenIwasworkinginthekitchen.Imanagedtofinishmycourseandgetmyqualifications.Igotajobinthehospitalasageneralcateringassistantinthestaffdiningroom.Butthedizzyspellscameback,onlythistimetheywerealotworseasonetimeIfainted.IknewsomethingwaswrongsoItoldmymumandwementionedittothedoctor.Iwasmaderedundantafter5weeksjustbeforeChristmasonDecember22nd1988.InJanuaryInoticedIwasgettingworse,starteddribblingandalsonoticedwhenIwalked,IwasstaggeringaboutasthoughIwasdrunk.WhenIsatinachairIgraduallystartedtoleanforwardasifIwasgoingtofall.Whentryingtoridemybike,Icouldn'tkeepmybalance.Thesesymptomswentonforacoupleofmonthswithfrequentvisitstothedoctortoseewhatwaswrongwithme.IthennoticedthatmyhandsstartedshakingandIcouldn'tstopthem.Istartedtolosemytemper,swearingandthrowingthings,whichwastotallyoutofcharacterforme.IfeltIwasbeingpossessedbysomeevilforceandhadlostcontrolofmyactions.IfeltliketakinganoverdosebutIcouldn't,notaftersavingafriend'slifeaftershetookanoverdoseandslashedherwrists.Ijustcouldn'tgothroughwithit.InApril1989,Iwasadmittedtohospitalbymydoctor.Iwasputthroughallthetests,lumberpuncture,catscan,ECG,EEG,magneticbrainscan,butitwasn'tuntiltheylookedinmyeyesthattheysawthecopperringsandlookeduptheirbookstofindthename.Theprofessorcametotheroomtotellmeandmymumanddadwhatthediseasewasandhowitwastreated.Iwasstartedonthetabletsstraightaway.Thedoctorswerenotpromisingaquickrecovery-itwouldtaketime,andIwouldhavegooddaysandbaddays.IamstillgoingforcheckupstoseeaspecialistinLondoneverysooften,butIamgettingbettereveryday.IowemylifetomymumforstickingbymeandputtingupwiththeabuseIgaveher,andforpushingthedoctorstohelpmegetbetter.IneverthoughtIwouldseemy20thbirthday,itwasveryspecialtome."1WilliamsFJB,WalsheJM.Wilson'sdisease.Ananalysisofthecranialcomputerisedtomographyappearancesfoundin60patientsandthechangesfoundinresponsetotreatmentwithchelatingagents.Brain1981;104:735-52.2WalsheJM.Wilson'sdiseasepresentingwithsymptomsofhepaticdysfunction:Aclinicalanalysisofeighty-sevenpatients.QuartJMed1989;70:253-63.3BachmannH,LossnerJ,GrussB,RuchholtzU.DieEpidemiologiederWilsonehenErkranjunginderDDRunddiederzeitigeProblematikeinerpopulationgenetis-chenBearbeitung.PsychiatNeurolMedPsychol(Leipzig)1979;31:393-400.4ScheinbergIH,SternliebI.Wilson'sdisease,volXXIII.Majorproblemsininternalmedicine.Philadelphia:WBSaunders,1984.5WalsheJM.Wilson'sdisease.BMJ1984;288:1689.6WalsheJM.Wilson'sdisease.HandbookofClinicalNeurol-ogy,vol5(49).In:VinkenPJ,BruymGW,KlawansHL,eds.Extrapyramidaldisorders.Amsterdam:Elsevier,1986.7WalsheJM.DiagnosisandtreatmentofpresymptomaticWilson'sdisease.Lancet1988;ii:435-7.8SternliebI,ScheinbergIH.ThepreventionofWilson'sdiseaseinasymptomaticpatients.NEngiJMed1968;278:352-9.9CairnsJE,WalsheJM.TheKayserFleischerring.TransOphthalmSocUK1970;90:187-90.10DennyTR,BerriosGE,WalsheJM.Wilson'sdiseaseandepilepsy.Brain1988;HI:1139-55.11WestphalC.UbereinedemGildederCerebrospinalengrauenDegenerationenahnlicheErkrankungdescen-tralenNervensystemsohneanatomischenBefundnebsteinigenBemerkungenuberparadoseContraction.ArchPsychiatNervenkr1983;14:87-134.12WilsonSAK.Progressivelenticulardegeneration:afamilialnervousdiseaseassociatedwithcirrhosisoftheliver.Brain1912;34:295-509.13DennyBrownD.Hepatolenticulardegeneration(Wilson'sdisease).Twodifferentcomponents.NEnglJMed1964;270:1149-56.69