11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 1/21

Chapter33NeurologicaldilemmasThediseaseisoflongdurationtoconnect,therefore,thesymptomswhichoccurinitslaterstageswiththosewhichmarkitscommencement,requiresacontinuanceofobservationofthesamecase,oratleastacorrecthistoryofitssymptoms,evenforseveralyears.

JamesParkinson(17551824),Anessayontheshakingpalsy

Ingeneralpracticetherearemanyneurologicalproblemsthatpresentadiagnosticdilemma,withsomebeingtruemasqueradesforthenonneurologist.Thisappliesparticularlytovariousseizuredisorders,spaceoccupyinglesionsinthecerebrumandthecerebellum,demyelinatingdisorders,motorneuronedisordersandperipheralneuropathies.

Themostcommonpitfallthatoccurswithneurologicaldisordersismisdiagnosis,andthemostcommonreasonformisdiagnosisisaninadequatehistory.Failuretoappreciatetheneurologicalmeaningofpointselicitedduringthehistoryisanotherreasonformisdiagnosis.

Someveryimportantneurologicaldisordersarepresentedinthissection:Parkinson'sdisease,whichiscommonandcanbeeasilymisdiagnosed,especiallywhentheclassicpillrollingtremorisabsentormildmultiplesclerosis(MS),becauseitisdifficulttodiagnoseinitiallyandacuteidiopathicdemyelinatingpolyneuropathy(GuillainBarrsyndrome),becauseitcanberapidlyfatalifmisdiagnosed.MScanmasqueradeasalmostanythingIfyoudontknowwhatitis,thinkofMS.

Anotherbrainteaserforthefamilydoctoristodiagnoseaccuratelythevarioustypesofepilepsy.Themostcommonlymisdiagnosedseizuredisordersarecomplexpartialseizuresoratypicalgeneralisedtonicclonicseizures(seeChapter54).1Evenmoredifficultisthedifferentiationofrealseizuresfrompseudoornonepilepticseizures.

DiplopiaTheonsetofdiplopia(doublevision)inadultsisoftenacute,verydistressingandinvariablyeasytodiagnose.Itcanbedividedintotwodistincttypes:uniocular(confinedtooneeye)orbinocular,whichusuallyresultsfromextraocularmuscularimbalanceorweakness.Thetypeofbinoculardiplopiavertical,horizontalorobliqueprovidescluesinidentifyingtheaffectedmuscle.

CausesofunioculardiplopiaEarlycataract(commoninolderpatientusuallyindimlightandatnight)DislocatedlensSevereastigmatismPsychogenic/functional

Causesofbinoculardiplopia

Ocularnervepalsies(3,4or6)consider:CVAorTIAtumour(orbitalorintracerebral)aneurysmdiabetesmellitusarteritisheadinjuryophthalmoplegicmigraine(transient)muscletethering(e.g.blowoutorbitalfracture)concussionmultiplesclerosis(recurrentdiplopia)

myastheniagravis multiplemuscle hyperthyroidism movement

Officetests

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 2/21

Testfordoublevisionwitheacheyeoccluded.Ifdiplopiapersistsitisuniocular.If,however,doublevisiondisappearswheneithereyeiscovered,thereisadefectofoneofthemusclesmovingtheeyeball.Determinewhetherdiplopiaoccursinanyparticulardirectionofgaze.Itismostmarkedwhenmovedinthedirectionofactionoftheweakmuscle.Askpatienttofollowyourfinger,redpinorpenlightwithbotheyesandmoveitinanHpattern.

3rdnerveeyeturnedout:divergentsquint6thnervefailuretoabduct:convergentsquint

SeeFigure33.1.

Figure33.1Directionofmovementoftherighteyeindicatingtheresponsibleextraocularmusclesandcranialnerves(3=oculomotor,4=trochlear,6=abducens)

Laboratorytest

ESR(considerarteritis)

Note:

Exclude3rdand6thnervepalsiesastheymaybesecondarytolifethreateningconditions.Referurgentlyifdiplopiaisbinocular,ofrecentonsetandpersistent.

MotorweaknessMuscleweaknessisacommonfeatureofmanydisordersrangingfromneurogenicandmyogenicdisorderstometabolicandpsychiatric.Itisveryimportantclinicallytobeabletodifferentiateuppermotorneurone(UMN)signsfromlowermotorneurone(LMN)signs(Table33.1).

Table33.1Clinicaldifferencesbetweenalowermotorneuronelesionandanuppermotorneuronelesion

Manifestation UMN LMN

Weakness Present Present

Wasting Absentormild Marked

Power Reduced Reduced

Tone Usuallyincreased(spasticparalysis)clonus Absentordecreased(flaccidparalysis)

Fasciculations Absent Maybepresent

Reflexes BrisktendonreflexesAbdominalabsentExtensorplantarresponse

Absentordiminished

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 3/21

Uppermotorneuronelesions

UMNsignsoccurwhenalesionhasinterruptedaneuralpathwayatalevelabovetheanteriorhorncell.2Examplesincludelesionsinmotorpathwaysinthecerebralcortex,internalcapsule,brainstemorspinalcord.

Clinicalexamplesincludestroke(thrombosis,embolismorhaemorrhageinthebrain),tumoursofthevariouspathways,anddemyelinatingdisease,suchasmultiplesclerosisandinfection,forexample,HIV.

Lowermotorneuronelesions

LMNsignsoccurwhenalesioninterruptsperipheralneuralpathwaysfromtheanteriorhorncell,thatis,thespinalreflexarc.

Clinicalexamplesincludeperipheralneuropathy,GuillainBarrsyndrome,motorneuronedisease,poliomyelitisandathickenedperipheralnerve(e.g.leprosy).

Note:AspinalcordlesioncausesLMNsignsatthelevelofthelesionandUMNsignsbelowthatlevel.

NeurogenicandmyogenicmuscleweaknessItisalsoimportanttodistinguishbetweenweaknesscausedbyneurologicalconditions,especiallythosecausingLMNlesionsandmusculardisorders.ThefeaturesarecomparedinTable33.2.

Table33.2Muscleweakness:mainclinicaldifferencesbetweenneurogenicandmyogeniclesions

Myogenicweakness Neurogenicweakness

Reflexesoftenpresentdespitesevereweakness Reflexesoftenabsentdespiteminimalweakness

Weaknessoutofproportiontowasting Wastingoutofproportiontoweakness

Sensationnormal Sensorychanges

Nofasciculation Fasciculationafeature

Motorneuronedisease(MND)MNDisaprogressiveneuromusculardisorderresultinginmuscularlimbandbulbarweaknessduetodeathofmotorneuronesinthebrain,brainstemandspinalcord.Thesensorysystemisnotinvolved,northecranialnervestotheeyemuscles.Fiveto10%ofMNDisinheritedwithanautosomaldominantpatterntherestissporadic.Thethreemainpatternsare:

1. amyotrophiclateralsclerosiscombinedLMNmuscleatrophyplusUMNhyperreflexia,leadingtoprogressivespasticity

2. progressivemuscleatrophywastingbeginningintheproximalmuscleswidespreadfasciculation3. progressivebulbarandpseudobulbarpalsyLMNlesionsofthebrainstemmotornucleiresulting

inwastedfibrillatingtongue,weaknessofchewingandswallowing,andoffacialmuscles

SymptomsandsignsWeaknessormusclewastingfirstnoticedinhands(weakgrip)orfeetStumbling(spasticgait,footdrop)DifficultywithswallowingDifficultywithspeech,e.g.slurring,hoarsenessFasciculation(twitching)ofskeletalmusclesandtongueCrampsEmotionalinstability,depressionMusclepain

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 4/21

Thediagnosisisclinical.Therearenodiagnostictests,butneurophysiologicaltestshelpdifferentiatefromotherconditions.

MNDisincurableandprogressestodeathusuallywithin35yearsfromventilatoryfailure/aspirationpneumonia.

NotreatmentisproventoinfluenceoutcomealthoughRiluzole,asodiumchannelblocker,appearstoslowprogressionslightly.Baclofen10mgbdmayhelpsymptomsofcramp.Botulinumtoxinmayhelpspasticityandpropanthelineoramitriptylinefordrooling.

TremorTremorisanimportantsymptomtoevaluatecorrectly.AlistofcausesispresentedinTable33.3.AcommonpitfallinpatientspresentingwithtremorisforParkinson'sdiseasetobediagnosedasbenignessentialtremorandforbenignessentialtremortobediagnosedasParkinson'sdisease,buttheclinicaldistinctionisnotalwayseasyanditmustberememberedthatasmanyas20%willexperiencebothconcurrently.

Table33.3Causesoftremor

PhysiologicalBenignessential(familial)tremorSenileAnxiety,includinghyperventilationHyperthyroidismToxic(e.g.alcohol,liverfailure,uraemia)Drugs(e.g.lithium,narcoticwithdrawal)Parkinson'sdiseaseDruginducedparkinsonismCerebellardiseaseCerebraltumour(frontallobe)Alzheimer'sdementiaWilson'ssyndromeMiscellaneous(e.g.rednucleuslesion,hypoglycaemia)

Tremorscanbeclassifiedasfollows:

RestingtremorParkinsonian

ThetremorofParkinson'sdiseaseispresentatrest.Thehandtremorismostmarkedwiththearmssupportedonthelapandduringwalking.Thecharacteristicmovementispillrollingwheremovementofthefingersatthemetacarpophalangealjointsiscombinedwithmovementsofthethumb.Therestingtremordecreasesonfingernosetestingbutafasteractiontremormaysupervene.Thebestwaytoevokethetremoristodistractthepatient,suchasfocusingattentiononthelefthandwithaviewtoexaminingtherighthandorbyturningthehead.

ActionorposturaltremorThisfinetremorisnotedbyexaminingthepatientwiththearmsoutstretchedandthefingersapart.Thetremormayberenderedmoreobviousifasheetofpaperisplacedoverthedorsumofthehands.Thetremorispresentthroughoutmovement,beingaccentuatedbyvoluntarycontraction.

Causesinclude:

essentialtremor(alsocalledfamilialtremororbenignessentialtremor)seniletremorphysiologicalanxiety/emotionalhyperthyroidismalcoholdrugs,forexample,drugwithdrawal(e.g.heroin,cocaine,alcohol),amphetamines,lithium,sympathomimetics(bronchodilators),sodiumvalproate,heavymetals(e.g.mercury),caffeine,

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 5/21

amiodaronephaeochromocytoma

Intentiontremor(cerebellardisease)

Thiscoarseoscillatingtremorisabsentatrestbutexacerbatedbyactionandincreasesasthetargetisapproached.Itistestedbyfingernosefingertouchingorrunningtheheeldowntheoppositeshin,andpastpointingofthenoseisafeature.Itoccursincerebellarlobediseaseandwithlesionsofcerebellarconnections.

Flapping(metabolictremor)Aflappingorwingbeatingtremorisobservedwhenthearmsareextendedwithhyperextensionofthewrists.Itinvolvesslow,coarseandjerkymovementsofflexionandextensionatthewrists.

Note:Flapping(asterixis)isnotstrictlyatremor.

Causes

Wilson'ssyndromeHepaticencephalopathyUraemiaRespiratoryfailureLesionsoftherednucleusofthemidbrain(theclassiccauseofaflap)

EssentialtremorEssentialtremor,whichisprobablythemostcommonmovementdisorder,hasbeenvariouslycalledbenign,familial,senileorjuveniletremor.However,itisnotalwaysbenignandthereisnofamilyhistoryinabouthalfthecases.

Features

Autosomaldominantdisorder(variablepenetrance)Oftenbeginsinearlyadultlife,evenadolescenceBeginswithaslighttremorinonehandandspreadstotheotherwithtimeMayinvolvehead(titubation),chinandtongueandrarelytrunkandlegsInterfereswithwriting(notmicrographic),handlingcupsofteaandspoons,etc.Tremormostmarkedwhenarmsheldout(posturaltremor)TremorexacerbatedbyanxietyMayaffectspeechifitinvolvesbulbarmusculatureRelievedbyalcoholCanswingarmandgaitnormal

Triadoffeatures

PositivefamilyhistoryTremorwithlittledisabilityNormalgait

DistinguishingessentialtremorfromParkinson'sdiseaseThisisnotalwayseasyasaposturaltremorcanbepresentinParkinson'sdiseasealthoughthehandtremorismostmarkedatrestwiththearmssupportedonthelap.Parkinsoniantremorisslowerat46Hzwhileessentialtremorismuchfasterataround813Hz.

Amostusefulwaytodifferentiatethetwocausesistoobservethegait.ItisnormalinessentialtremorbutinParkinson'stheremaybelossofarmswingandthestepisusuallyshortened.

Managementofessentialtremor

Mostpatientsdonotneedtreatmentandallthatisrequiredisanappropriateexplanation.1Ifnecessary,usepropranolol(firstchoice)orprimidone.3Atypicalstartingdoseofpropranololis1040mgbdmanyrequire120240mg/day.3Ifthetremorisonlyintrusiveattimesofincreasedemotionalstress,

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 6/21

intermittentuseofbenzodiazepines(e.g.lorazepam)30minutesbeforeexposuretothestressmaybeallthatisrequired.Modestalcoholintake(e.g.aglassofscotch)isveryeffective.Astandarddrinkofalcoholoftenalleviatesthetremor.Largerdosesofalcoholhavenoadditionaleffect.

Parkinson'sdiseaseParkinson'sisadiseaseoftheautomaticprocessorofthebrainwhichreliesondopaminetomaintainmovementsataselectedsizeandspeed.Lossofdopaminecausesmovementstobecomesmallerandslower.LewybodiesintheneuronesarethepathognomicsignofParkinson'sdisease.4Geneticfactorsoccurin5%ofindividuals.

OneofthemostimportantclinicalaspectsofParkinson'sdisease,whichhasaslowandinsidiousonset,istheabilitytomakeanearlydiagnosis.Sometimesthiscanbeverydifficultespeciallywhenthetremorisabsentormild,asoccurswiththeatheroscleroticdegenerativetypeofparkinsonism.Thelackofanyspecificabnormalityonspecialinvestigationleavestheresponsibilityforadiagnosisbasedonthehistoryandexamination.AsageneralruleofthumbthediagnosisofParkinson'sdiseaseisrestrictedtothosewhorespondtolevodopatherestaretermedparkinsonism.

Keyfactsandcheckpoints

Parkinson'sdiseaseisamostcommonanddisablingchronicneurologicaldisorder.TheprevalenceinAustraliais100120per100000.5Themeanageofonsetisbetween58and62years.5Theincidencerisessharplyover70yearsofage.5TheclassictriadofParkinson'sdisease(Figure33.2)is:

Figure33.2BasicclinicalfeaturesofParkinson'sdisease

tremorrigiditybradykinesia(povertyofmovement)Nonmotorautomaticdysfunctionscognitionbehaviour

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 7/21

moodHemiparkinsonismcanoccurallthesignsareconfinedtoonesideandthusmustbedifferentiatedfromhemiparesis.Infact,mostcasesofParkinson'sdiseasestartunilaterally.Alwaysconsiderdruginducedparkinsonism.Theusualdrugsarephenothiazines,butyrophenonesandreserpine.Tremorisuncommonbutrigidityandbradykinesiamaybesevere.

RefertoTable33.4(onp.297).

Table33.4Parkinson'sdisease:symptomsandsigns(achecklist)

General TirednessLethargyRestlessness

Tremor PresentatrestSlowrate4to6cyclespersecondAlternating,especiallyarmsPillrolling(severecases)

Note:maybeabsentorunilateral

Rigidity CogwheeljudderingonpassiveextensionoftheforearmLeadpipelimbsresistpassiveextensionthroughmovement

Bradykinesia/hypokinesia SlownessofinitiatingamovementDifficultywithfinefingertasksMicrographia(Figure33.3)MaskedfaciesRelativelackofblinkingImpairedconvergenceofeyesExcessivesalivation(late)DifficultyturningoverinbedandrisingfromachairSlowmonotonousspeech/dysarthria

Gaitdisorder NoarmswingononeorbothsidesStarthesitationSlowandshufflingShortsteps(petitpas)SlowturningcircleFreezingwhenapproachinganobstacleFestination

Disequilibrium PoorbalanceImpairedrightingreflexesFalls(usuallylate)

Posture ProgressiveforwardflexionoftrunkFlexionofelbowataffectedside

Autonomicsymptoms Constipation(common)PosturalhypotensionDepression(early)

Psychiatric Progressivedementiain3040%usuallyafter10years6

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 8/21

Threemajortrapsinmissingearlydiagnosis:5age:1015%are

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 9/21

Endofdosefailure Constipation

Dopamineagonists Nauseaandvomitingbromocriptine 515mgbd Dizziness,fatiguecarbergoline 0.56mgdaily Psychiatricdisturbancespergolide 0.051.5mgtds Pleuropulmonarychanges

Anticholinergics benzhexol 2mgbdortds Drynessofmouthbenztropine 12mgbd Confusioninelderlybiperiden 12mgbd Contraindicatedinglaucomaandprostatismorphenadrine 100mgbd Otheranticholinergiceffects(e.g.

constipation,blurredvision)

COMTinhibitors entacapone 200mgwitheachdose

levodopaDiarrhoea

Sleepproblems Potentiationoflevodopa

Others amantadine 100mgbd Nauseaandvomiting Psychiatricdisturbances Ankleoedema Livedoreticularisapomorphine SCinjection(referto

schedule)Nausea

Psychosis Dyskinesiaselegiline(aMAOBinhibitor) 2.55mgoncedailyor

bdDrymouth

Neuropsychiatricdisturbances Nausea Dizziness,fatigue Insomnia

Theolderdrugs,suchasanticholinergicsandamantadine,haveminimalusageinmodernmanagementaslevodopa,whichbasicallycountersbradykinesia,isthebestdrugandthebaselineoftreatment.Withtheonsetofdisability(motordisturbances)levodopaincombinationwithadecarboxylaseinhibitor(carbidopaorbenserazide)ina4:1ratioshouldbeintroduced.Levodopatherapydoesnotsignificantlyimprovetremorbutimprovesrigidity,dyskinesiaandgaitdisorder.Considerbenzhexolorbenztropineiftremoristhefeature,especiallyinyoungpatients.

Pergolidecanbeusedintreatment,especiallywiththelevodopaonoffphenomenon(fluctuationsthroughouttheday).Itappearstobemosteffectivewhenusedincombination.Themajorsideeffectsofpergolidearesimilartolevodopa.Dyskinesiaandnauseaarelessproblematicbutseverepsychiatricdisturbancesaremorecommonwithbromocriptine(adopamineagonist).Itshouldthereforebeusedwithcautioninpatientswithahistoryofconfusionordementia.Selegilinepromisestobeaneffectivefirstlinedrug.Ifthereisassociatedpain,depressionorinsomnia,thetricyclicagents(e.g.amitriptyline)canbeeffective.

Entacaponehasthepotentialtoincreaseontimeandreducemotorfluctuationsinlevodopatreatedpatientswhoarebeginningtoexperienceendofdosefailure.Theinitialdoseis200mg.

Treatmentstrategy8,9

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 10/21

Mild

(minimaldisability)

Levodopapreparation(lowdose)e.g.levodopa100mg+carbidopa25mg(tabbdincreasegraduallyasnecessaryto1tab(o)tds)Amantadine100mg(o)bdmayhelptheyoungortheelderlyforupto12monthsSelegiline(canbeusedasmonotherapyandpostponeneedforlevodopa)

Moderate

(independentbutdisabled,e.g.writing,movements,gait)

LevodopapreparationAddifnecessarypergolideorcabergolineorbromocriptinepergolide50g(o)bd,graduallyincreasingto1.5mg(max.)bdcabergoline0.5mg(o)daily,increasingto6mg(max.)oncedaily

Severe

(disabled,dependentonothers)

Levodopa(tomaximumtolerateddose)+pergolideorcabergolineAddentacapone200mg(o)witheachdoseoflevodopa,e.g.StatevoConsiderantidepressants

Longtermproblems

After35yearsoflevodopatreatmentsideeffectsmayappearinaboutonehalfofpatients:5involuntarymovementsdyskinesia(uselowerdose+pergolideorcabergoline)endofdosefailure(reduceddurationofeffectto23hoursonly)useentacaponeonoffphenomenon(suddeninabilitytomovewithrecoveryin3090minutes)earlymorningdystonia,suchasclawingoftoes(duetodiseasenotasideeffect)managementofmotorproblemsissummarisedinTable33.6

Table33.6ManagementofmotorproblemsintreatedParkinson'sdisease4

Motorproblem Management

Endofdosefailure

Dosagesclosertogether

Slowreleasepreparations MAOBinhibitor(e.g.selegiline) Dopaminergicagonist(e.g.pergolide)

Onoffphenomenon

Subcutaneousapomorphineforoffphase(1haction)withdomperidone(o)topreventvomiting

Levodopaandascorbicacidsolution

Lossofefficacy Increaselevodopadoseashighaspossible Dopaminergicagonist(e.g.pergolide)

Peakdosedyskinesia

Decreaselevodopadose

MAOBinhibitor,ifefficacylost

Dopaminergicagonist(e.g.pergolide)

Earlymorningdystonia

Slowreleaselevodopa

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 11/21

Dopaminergicagonists(e.g.pergolide)

Nocturnalakinesia

Slowreleaselevodopa

Dopaminergicagonist

Advanceddisease8

Apomorphinecanbeusedforsevereakinesianotresponsivetolevodopa:apomorphine600gto6mg(mean3.4mg)SCFornauseaandvomitingsideeffects:domperidone20mg(o)tds24hourspriortoapomorphineBettercontrolmayalsobeachievedwith:amantadine100mg(o)bd

Contraindicateddrugs

PhenothiazinesButyrophenones

Surgicaltreatment

Theindicationforsurgery(pallidotomyorstereotacticthalamotomy)10isthepresenceoftremororrigiditynotrespondingtochemicaltherapy.Itisconsideredmoreappropriateforyoungerpatientswithaunilateraltremor.8Ahighsuccessratehasbeenclaimed.Italleviatestremorandrigiditybutdoesnotpreventprogressionofbradykinesia,dysarthriaordementia.However,twosystematicreviewsfoundlimitedevidencethatpallidotomyreducescontralateraltremorandrigidityduringofftimebutcarriedsignificantriskofmorbidityandmortality.7

WhentoreferIfthediagnosisisunclearatthetimeofinitialpresentation,itisappropriateeithertoreviewthepatientatalaterdateortoreferthepatientformoreneurologicalassessment.

Oncediagnosedorhighlysuspecteditisbesttorefertoestablishthediagnosisandtoseekadviceoninitiationoftreatment.Patientsandfamiliesusuallypreferthisapproach.Intheinitialyearsbeforemotorfluctuationsdevelop,managementcouldbeperformedbythegeneralpractitioneraccordingtoanoverallplandevelopedinliaisonwithaneurologicalcolleague.Whenfluctuationsdevelopandendstagediseasesmanifest(e.g.gaitdisorders),specialistsupervisionisappropriate.1

CognitiveimpairmentwithParkinson'sdisease4

ThismaybeduetomultiplefactorsincludingParkinson'sassociateddementia,Alzheimer'sdiseaseandmedication,allofwhichcaninducepsychosis,butLdopaistheleastlikely.Neuropsychiatricsymptoms,whichcanbevariedandbizarreandusuallyworseintheevening,canoccur.FactorscontributingtopsychosisareillustratedinFigure33.4.ManagementisbasedonmonotherapywithgradualbuildupofLdopatomaximumtolerateddose,e.g.450600mg/day.

Figure33.4Factorscontributingtopsychosis

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 12/21

Managementofpsychoticproblems

Treatasaninpatient.Excludeandtreatcomorbidities,e.g.UTI.Eliminateandweanoffworstdrugs.IncreaseLdopaslowlyto150mgtdsorqid.Givequetiapineatnighttime.

PracticetipsLevodopaisthegoldstandardfortherapy.Longeractinglevodopapreparationsmayreducetheendofdosefailureeffectbutrememberthepossibleneedforakickstartwithshortactingpreparations(e.g.firstthinginthemorning).EnsurethatadistinctionismadebetweendruginducedinvoluntarymovementsandthetremorofParkinson'sdisease.Keepthedoseoflevodopaaslowaspossibletoavoidthesedruginducedinvoluntarymovements.IntheelderlywithafracturedhipalwaysconsiderParkinson'sdisease(amanifestationofdisequilibrium).RememberthebalanceofpsychosisandParkinson'sdiseaseintreatment.Keepinmindthesundowneffectpatientsoftengopsychoticasthesungoesdown.Dontfailtoattendtotheneedsofthefamily,whooftensufferinsilence.Bromocriptineandpergolideshouldbeusedverycautiouslyintheelderlybecauseofpossibleacutepsychoticreactions.Ifdrugsaretobewithdrawntheyshouldbewithdrawnslowly.

MultiplesclerosisMultiplesclerosis(MS)isthemostcommoncauseofprogressiveneurologicaldisabilityinthe2050yearagegroup.11ItisgenerallyacceptedthatMSisanautoimmunedisorder.Geneticandenvironmentalfactorsarebelievedtoplayarole.12EarlydiagnosisisdifficultbecauseMSischaracterisedbywidespreadneurologiclesionsthatcannotbeexplainedbyasingleanatomicallesion,andthevarioussymptomsandsignsaresubjecttoirregularexacerbationsandremissions.Themostimportantissueindiagnosisistheneedforahighindexofsuspicion.

MSisaprimarydemyelinatingdisorderwithdemyelinationoccurringinplaquesthroughoutthewhitematterofthebrain,brainstem,spinalcordandopticnerves.Theclinicalfeaturesdependontheirlocation.

Clinicalfeatures

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 13/21

(SeeFigure33.5.)

Figure33.5Basicclinicalsignsinmultiplesclerosis

MorecommoninfemalesPeakageofonsetisinthefourthdecadeTransientmotorandsensorydisturbancesUMNsignsSymptomsdevelopoverseveraldaysbutcanbesuddenMonosymptomaticinitiallyinabout80%Multiplesymptomsinitiallyinabout20%Commoninitialsymptomsinclude:visualdisturbancesofopticneuritisblurredvisionorlossofvisioninoneeye(sometimesboth)centralscotomawithpainoneyemovement(lookslikeunilateralpapilloedema)diplopia(brainstemlesion)weaknessinoneorbothlegs,paraparesisorhemiparesissensoryimpairmentinthelowerlimbsandtrunknumbness,paraesthesiabandlikesensationsclumsinessoflimb(lossofpositionsense)feelingasthoughwalkingoncottonwoolvertigo(brainstemlesion)

SubsequentremissionsandexacerbationsthatvaryfromoneindividualtoanotherThereisaprogressiveform,especiallyinwomenaround50yearsAnxiety,depressionandothermooddisordersarerelativelycommon

NeurologicalexaminationThefindingsdependonthesiteofthelesionorlesionsandincludeopticatrophy,weakness,hyperreflexia,extensorplantarresponses,nystagmus(twotypescerebellarorataxic),ataxia,incoordination

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 14/21

andregionalimpairmentofsensation.

Symptomscausingdiagnosticconfusion

Bladderdisturbances,includingretentionofurineandurgencyUselesshandduetolossofpositionsenseFacialpalsyTrigeminalneuralgiaPsychiatricsymptoms

Inestablisheddiseasecommonsymptomsarefatigue,impotenceandbladderdisturbances.

Diagnosis

Thediagnosisisclinicalanddependsonthefollowingdeterminants:

LesionsareinvariablyUMN.LesionsaffecttheCNSwhitematter.>1partofCNSisinvolved,althoughnotnecessarilyattimeofpresentation.Episodesareseparatedintime(itispossibletomakeadiagnosiswiththefirstepisode).

Otherneurologicaldisorderssuchasinfections(e.g.encephalitis),malignancies,spinalcordcompression,spinocerebellardegenerationandothersmustbeexcluded.

Investigations

Lumbarpuncture:oligoclonalIgGdetectedinCSFin90%ofcases11(onlyifnecessary)Visualevokedpotentials:abnormalinabout90%ofcasesCTscan:rarelydemonstratesMSlesionsbutusefulinexcludingotherpathologyMRIscan:usuallyabnormal,demonstratingMSlesionsinabout90%ofcases11

Courseandprognosis

Thecourseisvariableanddifficulttopredict.Anearlyonset(

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 15/21

Severerelapsesorattacks8,14

Theseattacksincludeopticneuritis,paraplegiaorbrainstemsigns.AdmittohospitalforIVtherapy:

methylprednisolone1gin200mLsalinebyslowIVinjection(3hours)dailyfor3to5days

Observecarefullyforcardiacarrhythmias.

Drugstopreventrelapses14

Currentlyavailableimmunomodulatorsaretheinterferonsandglatiramir.

Interferonbeta1b(SCinjection)andbeta1a(IMinjection)appeartobeeffective(butexpensive)forthosewithfrequentandsevereattacks.

Evidencebasedmedicine

Thebestevidencetodateindicatesthattheinterferonsandmethylprednisolonearelikelytobebeneficialbutglatiramir,IVimmunolobulin,cytotoxicagentsandplasmaexchangehaveunkowneffectiveness.15OneRCTfoundamodesteffectwithglatiramironarelapserateover2yearsbutfoundnoevidenceofaneffectondisability.

Drugstoreduceprogression8,16

Currentrecommendedtreatmentgivenundercarefulsupervision:

methotrexate7.5mg(o),on1dayeachweek+folicacid5mg(o),3daysaftereachmethotrexatedose

Immunosuppressioncanalsobegivenwithcyclophosphamideorazathioprine.17ThechemotherapeuticagentmitozantranehasbeenshowntoarrestprogressionofMSbutitsuseislimitedbyitscardiotoxicty.12

Treatmentofsymptoms7

Spasticity

PhysiotherapyBaclofen1025mg(o)nocteForcontinuousdrugtherapy:baclofen5mg(o)tds,increasingto25mg(o)tds+diazepam210mg(o)tds

Paroxysmal(e.g.neuralgias)

Carbamazepineorclonazepam

Seereferences8and16fortreatmentofothersymptoms.

Acuteidiopathicdemyelinatingpolyneuropathy(GuillainBarrsyndrome)GuillainBarrsyndromeisthebestknownoftheperipheralneuropathiesthathaveanacuteonset,anditispotentiallyfatal.Earlydiagnosisofthisseriousdiseasebythefamilydoctoriscrucialasrespiratoryparalysismayleadtodeath.Theunderlyingpathologyissegmentaldemyelinationoftheperipheralnervesandnerveroots.

ClinicalfeaturesParaesthesiaorpaininthelimbsWeaknessinthelimbs(usuallysymmetrical)BothproximalanddistalmusclesaffectedFacialandbulbarparalysis

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 16/21

Weaknessofextraocularmuscles(rarely)ReflexesdepressedorabsentVariablesensorylossbutrare

Within34weeksthemotorneuropathy,whichisthemainfeature,progressestoamaximumdisability,possiblywithcompletequadriparesisandrespiratoryparalysis.18

InvestigationsCSFproteiniselevatedcellsareusuallynormal.Motornerveconductionstudiesareabnormal.

Management

Admittohospital.Respiratoryfunction(vitalcapacity)shouldbemeasuredregularly(24hoursatfirst).Tracheostomyandartificialventilationmaybenecessary.Physiotherapytopreventfootandwristdropandothergeneralcareshouldbeprovided.Plasmapheresisisthemainstayoftreatment.IVimmunoglobulin(0.4g/kg/dayfor5days)isalsoeffective.17Corticosteroidsarenotgenerallyrecommended.

Outcome

About80%ofpatientsrecoverwithoutsignificantdisability.Approximately5%relapse.18

MyastheniagravisMyastheniagravis(MG)isanacquiredautoimmunedisorderthatusuallyaffectsmusclestrength.Patientshavefluctuatingsymptomsandvariabledistributionofmuscleweakness.Alldegreesofseverity,rangingfromoccasionalmildptosistofulminantquadriplegiaandrespiratoryarrest,canoccur.19SeeTable33.7.Itisassociatedwiththymictumourandotherautoimmunediseases,e.g.RA,SLE.

Table33.7Clinicalclassificationofacquiredmyastheniagravis

GroupI OcularMG

GroupIIA MildgeneralisedMG

GroupIIB ModeratetosevereMG

GroupIII Acutesevere(fulminating)MGwithrespiratorymuscleweakness

GroupIV Late(chronic)severeMG

ClinicalfeaturesPainlessfatiguewithexerciseWeaknessalsoprecipitatedbyemotionalstress,pregnancy,infection,surgeryVariabledistributionofweakness:ocularptosis(60%)anddiplopia(Figure33.6)ocularmyastheniaonlyremainsinabout10%bulbar:weaknessofchewing,swallowing,speech(asktocountto50),whistlingandheadlollinglimbs(proximalanddistal)generalisedrespiratory:breathlessness,ventilatoryfailure

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 17/21

Figure33.6MyastheniaGravisina40yearoldwomanwitha12monthhistoryofincreasingmuscularweaknessincludingdroopingoftheeyelids.Ptosis,especiallyontherightside,isapparent

Note:TheclassicMGimageisthethinkerthehandusedtoholdthemouthclosedandtheheadup.

DiagnostictestsSerumantiacetylcholinereceptorantibodiesElectrophysiologicaltestsifantibodytestnegativeCTscanandchestXraytodetectthymomaEdrophoniumteststilluseful

Managementprinciples8,20

DetectpossiblepresenceofthymomawithCTorMRscanofthorax.Ifpresent,removalisrecommended.Thymectomyisrecommendedearlyforgeneralisedmyasthenia,especiallyinallyoungerpatientswithhyperplasiaofthethymus,evenifnotconfirmedpreoperatively.Plasmapheresisisusefulforacutecrisisorwheretemporaryimprovementisrequiredorpatientsareresistanttotreatment.Avoiddrugsthatarerelativelycontraindicated.Pharmacologicalagents:anticholinesterasedrugs(e.g.pyridostigmine,neostigmineordistigmine):shouldbeusedonlyformildtomoderatesymptomscorticosteroids:usefulforallgradesofMGshouldbeintroducedslowly

Practicetips

Thecombinationofocularandfacialweaknessshouldalertthefamilydoctortothepossibilityofaneuromusculardisorder,especiallyMGormitochondrialmyopathy.20Lookforweaknessandfatigue.Bewareoffacioscapulohumeraldystrophy.Ptosismaydeveloponlyafterlookingupwardsforaminuteorlonger.Smilingmayhaveacharacteristicsnarlingquality.

PtosisItisworthrememberingthatthefourmajorcausesofptosisare:

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 18/21

1. 3rdcranialnervepalsyptosis,eyefacingdownandout,dilatedpupil,sluggishlightreflex2. Horner'ssyndromeptosis,miosis(constrictedpupil),ipsilaterallossofsweating3. Mitochondrialmyopathyprogressiveexternalophthalmoplegiaorlimbweakness,inducedby

activity4. Myastheniagravisptosisanddiplopia

DystoniaDefinitionDystoniasaresustainedorintermittentabnormalrepetitivemovementsorposturesresultingfromalterationsinmuscletone.Thedystonicspasmsmayaffectone(focal)ormore(segmental)partsofthebodyorthewholebody(generalised).

Keypoints

Misdiagnosisiscommonastransientsymptomsmaybemistakenforanemotionalorpsychiatricdisorder.Manycasestakeyearstodiagnose.Dystoniasareoftenregardedasnervoustics.Thecauseisthoughttobedisordersofthebasalgangliaofthebrain,butmainlythereisnoknownspecificcause.Neurolepticanddopaminereceptorblockingagents(e.g.levodopa,metoclopramide)caninduceaseveregeneraliseddystonia(e.g.oculogyriccrisis)whichistreatedwithbenztropine12mgIMorIV.20

FocaldystoniasBlepharospasmisafocaldystoniaofthemusclesaroundtheeyeresultinginuncontrolledblinking,especiallyinbrightlight.Oromandibulardystoniaaffectsthejaw,tongueandmouth,resultinginjawgrindingmovementsandgrimacing.Properspeechandswallowingmaybedisrupted.Meige'ssyndromeisacombinationofblepharospasmandoromandibulardystonia.

Note:Itmustbedifferentiatedfromthebuccallingualfacialmovementsoftardivedyskinesia.

Hemifacialspasminvolvesinvoluntary,irregularmusclecontractionsandspasmsaffectingonesideoftheface.Itusuallystartswithtwitchingaroundtheeyeandthenspreadstoinvolveallthefacialmusclesononeside.Itisusuallyduetoirritationofthefacialnerveinitsintracranialcourseandsurgicalinterventionmayalleviatethisproblem.Writer'scramp,typist'scramp,pianist'scramp,golfer'scramparealloccupationalfocaldystoniasofthehandand/orforearminitiatedbyperformingtheseskilledacts.Cervicaldystoniaorspasmodictorticollisisafocaldystoniaoftheunilateralcervicalmuscles.Itusuallybeginswithapullingsensationfollowedbytwistingorjerkingofthehead,leadingtodeviationoftheheadandnecktooneside.Inearlystagespatientscanvoluntarilyovercomethedystonia.Laryngealorspasticdystoniaisafocaldystoniaofthelaryngealmusclesresultinginastrained,hoarseorcreakingvoice.Itmayleadtoinabilitytospeakinmorethanawhisper.

Treatmentoffocaldystonias

Thecurrenttreatmentforfocalorsegmental(spreadtoanadjacentbodyregion)dystoniasislocalisedinjectionofpurifiedbotulinumAtoxinintotheaffectedmusclegroups.Thedosageishighlyindividualisedandneedstoberepeatedatintervalsof3and6months.Theinjectionshavetobegivenwithgreatcaution.

TicsMotorandvocalticsareafeatureofTourette'sdisorder.Ifsociallydisablingtreatwith:

haloperidol0.25mg(o)nocte,verygraduallyincreasingto2g(max.)daily7orclonidine25g(o)bdfor2weeks,then5075gbd

Facialnerve(Bell's)palsy8,15

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 19/21

Facial(7thnervepalsy),whichisanacuteunilaterallowermotorneuroneparesisorparalysis,isthecommonestcranialneuropathy.TheclassictypeisBell'spalsy,whichisusuallyidiopathicalthoughattributedtoaninflammatoryswellinginvolvingthefacialnerveinthebonyfacialcanal.IntheRamsayHuntsyndrome,whichisduetoinfectionwithherpeszostercausingfacialnervepalsy,vesiclesmaybeseenontheipsilateralear.

Associations:

herpessimplexvirus(postulated)diabetesmellitushypertensionthyroiddisorder,e.g.hyperthyroidism

Featuresabruptonset(canworsenover25days)weaknessintheface(completeorincomplete)precedingpaininorbehindtheearimpairedblinking

Lesscommon:

difficultyeatinglossoftasteanteriortwothirdsoftonguehyperacusis

Management

prednisolone50mg(o)dailyindivideddosesfor4daysthentapertozeroovernext7days(startwithin3daysofonset)

Note:Thisiscontroversialasevidenceisnotconvincing15(betterinseverercases).

patienteducationandreassuranceadhesivepatchortapeovereyeifcornealexposure(e.g.windyordustyconditions,duringsleep)artificialtearsifeyeisdryandatbedtimemassageandfacialexercisesduringrecovery

Note:

Atleast7080%achievefullspontaneousrecoveryhigherifmild.Electromyographyandnerveexcitabilityorconductionstudiesareaprognosticguideonly.Noevidencethatnucleosideanalogue,e.g.aciclovir,isusefulbutshouldbeusedforRamsayHuntsyndrome.Noevidencethatsurgicalprocedurestodecompressthenervearebeneficial.15

Diagnostictriadsofneurologicaldilemmas

Alltriadsshowachroniconsetunlessindicatedbyanasterisk(acuteonset).

Ifyouseethiscombinationofsigns:

Consider:

Charcot'striad: dysarthria+intentiontremor+nystagmus

=cerebellardisease(typicalofMS)

visualdisturbance(blurredortransientloss)+weaknessinlimbsparaesthesiain

=multiplesclerosis

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 20/21

limbsNote:herearemanycombinationsofMS(Charcot'shashistoricalinterest).

rigidity+bradykinesia+restingtremor

=Parkinson'sdisease

tremor(posturaloraction)+headtremor+absenceofParkinsonianfeatures

=essentialtremor

fatiguableandweaknessofeyelidsandeyemovements+limbs+bulbarmuscles(speechandswallowing)

=myastheniagravis

weaknessoflimbs+offace+areflexia*

=GuillainBarrsyndrome(GBS)

(episodic)vertigo+tinnitus+hearingloss*

=Meniere'ssyndrome

dementia+myoclonus+ataxia

=CreutzfeldJakobdisease

drowsiness+vomiting+headache(waking)

=intracerebralpressure

enophthalmos+meiosis+ptosisanhydrosis

=Horner'ssyndrome

blankspell+lipsmacking(orsimilarautomation)+olfactory/gustatoryhallucination

=complexpartialseizure

gradualspread(Jacksonianmarch)offocaljerking(mouth,armorleg)orsensorydisturbanceor(rarely)visualfielddisturbance

=simplepartialseizure

intracranialpressure+/orfocalsigns+/orepilepsy

=cerebraltumour

dysphagia+dysphonia/dysarthria+spastictongue

=pseudobulbarpalsy

recurrent:headache(oftenunilateral)+nausea(vomiting)+visualaura*

=migrainewithaura(formerlyclassicalmigraine)

recurrent:severeretroorbitalheadache+rhinorrhoea+lacrimation*

=clusterheadache

instantaneous:headachevomitingneckstiffness

=subarachnoidhaemorrhageuntildisproven

headache+visual =benign

11/12/2014 Murtagh's General Practice Series - Fourth Edition

http://127.0.0.1:9000/ 21/21

obscurations+papilloedema(ofteninobeseyoungfemale)

intracranialhypertension

acuteandtransient:amaurosisfugaxordysphasiaorhemiplegia*

=TIA(carotid)

typicalfacies(temporalisatropyandfrontalbalding)+muscleweakness(myotonia)+cataracts

=myotonicdystrophy

ataxia+ophthalmoplegia+areflexia*

=MillerFishervariantofGBS

vertigo+provokedbymovement(especiallyrollinginbed)+Hallpiketest+ve

=BPPV

UMNsigns+LMNsigns+fasciculations

=motorneuronedisease

REFERENCES1. IansekR.PitfallsinNeurology.Melbourne:ProceedingsofMonashUniversityMedicalSchool

UpdateCourse,1992:404.2. TalleyNJ,OConnorS.ClinicalExamination(5thedn).Sydney:ChurchillLivingstone,2005:345

6.3. MorrisJGL.Essentialtremor.In:MIMSDiseaseIndex(2ndedn).Sydney:IMSPublishing,1996:

17980.4. IansekR.Parkinson'sdiseaseanddementia.ProceedingsofMonashUniversityMedicalSchool

UpdateCourse,2005:123.5. SelbyG,HerkesG.Parkinson'sdisease.In:MIMSDiseaseIndex(2ndedn).Sydney:IMS

Publishing,1996:3958.6. FungV,HelyM,MorrisJ.Howtotreat:Parkinson'sdiseaseandParkinsoniansyndromes.

AustralianDoctor,200314November:3340.7. BartonSetal.ClinicalEvidence(Issue5).London:BMJPublishingGroup,2001:90613.8. TillerJ(Chair).TherapeuticGuidelines:Neurology(Version2).Melbourne:TherapeuticGuidelines

Ltd,2002.9. FungVS,HelyMAetal.DrugsforParkinson'sdisease.AustPrescriber,200124:925.

10. SelbyG.Stereotacticsurgery.In:KollerWCed.HandbookofParkinson'sDisease.NewYork:MarcelDekkerInc.,1987:42135.

11. McLeodJR.Multiplesclerosis.In:MIMSDiseaseIndex(2ndedn).Sydney:IMSPublishing,1996:3213.

12. BroadleyS.Multiplesclerosis:update.MedicalObserver,200416October:2730.13. MatthewsB.Multiplesclerosis.MedInt,198848:19617.14. BurnhamJAetal.TheeffectofhighdosesteroidsonMRIgadoliniumenhancementinacute

demyelinatinglesions.Neurology,199343:65561.15. BartonSetal.ClinicalEvidence(Issue5).London:BMJPublishingGroup,2001:894904.16. JacobsLetal.Advancesinspecifictherapyformultiplesclerosis.CurrOpinNeurol,19947:250

4.17. MilaneseCetal.Adoubleblindstudyonazathioprineinthetreatmentofmultiplesclerosis.J

Neurology,1993240:2958.18. PollardJ.Neuropathy,peripheral.In:MIMSDiseaseIndex(2ndedn).Sydney:IMSPublishing,

1996:346.19. McLeodJG.Peripheralneuropathy.MedInt,198848:19804.20. DarvenizaP.Myastheniagravis.In:MIMSDiseaseIndex(2ndedn).Sydney:IMSPublishing,

1996:3246.