11/12/2014

Murtagh's General Practice Series - Fourth Edition

Chapter33Neurologicaldilemmas
Thediseaseisoflongdurationtoconnect,therefore,thesymptomswhichoccurinitslaterstageswith
thosewhichmarkitscommencement,requiresacontinuanceofobservationofthesamecase,oratleast
acorrecthistoryofitssymptoms,evenforseveralyears.
JamesParkinson(17551824),Anessayontheshakingpalsy
Ingeneralpracticetherearemanyneurologicalproblemsthatpresentadiagnosticdilemma,withsome
beingtruemasqueradesforthenonneurologist.Thisappliesparticularlytovariousseizuredisorders,
spaceoccupyinglesionsinthecerebrumandthecerebellum,demyelinatingdisorders,motorneurone
disordersandperipheralneuropathies.
Themostcommonpitfallthatoccurswithneurologicaldisordersismisdiagnosis,andthemostcommon
reasonformisdiagnosisisaninadequatehistory.Failuretoappreciatetheneurologicalmeaningofpoints
elicitedduringthehistoryisanotherreasonformisdiagnosis.
Someveryimportantneurologicaldisordersarepresentedinthissection:Parkinson'sdisease,whichis
commonandcanbeeasilymisdiagnosed,especiallywhentheclassicpillrollingtremorisabsentor
mildmultiplesclerosis(MS),becauseitisdifficulttodiagnoseinitiallyandacuteidiopathicdemyelinating
polyneuropathy(GuillainBarrsyndrome),becauseitcanberapidlyfatalifmisdiagnosed.MScan
masqueradeasalmostanythingIfyoudontknowwhatitis,thinkofMS.
Anotherbrainteaserforthefamilydoctoristodiagnoseaccuratelythevarioustypesofepilepsy.The
mostcommonlymisdiagnosedseizuredisordersarecomplexpartialseizuresoratypicalgeneralised
tonicclonicseizures(seeChapter54).1Evenmoredifficultisthedifferentiationofrealseizuresfrom
pseudoornonepilepticseizures.

Diplopia
Theonsetofdiplopia(doublevision)inadultsisoftenacute,verydistressingandinvariablyeasyto
diagnose.Itcanbedividedintotwodistincttypes:uniocular(confinedtooneeye)orbinocular,which
usuallyresultsfromextraocularmuscularimbalanceorweakness.Thetypeofbinoculardiplopia
vertical,horizontalorobliqueprovidescluesinidentifyingtheaffectedmuscle.

Causesofunioculardiplopia
Earlycataract(commoninolderpatientusuallyindimlightandatnight)
Dislocatedlens
Severeastigmatism
Psychogenic/functional

Causesofbinoculardiplopia
Ocularnervepalsies(3,4or6)consider:
CVAorTIA
tumour(orbitalorintracerebral)
aneurysm
diabetesmellitus
arteritis
headinjury
ophthalmoplegicmigraine(transient)
muscletethering(e.g.blowoutorbitalfracture)
concussion
multiplesclerosis(recurrentdiplopia)

myastheniagravis
hyperthyroidism

multiplemuscle
movement

Officetests
http://127.0.0.1:9000/

1/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

Testfordoublevisionwitheacheyeoccluded.Ifdiplopiapersistsitisuniocular.If,however,doublevision
disappearswheneithereyeiscovered,thereisadefectofoneofthemusclesmovingtheeyeball.
Determinewhetherdiplopiaoccursinanyparticulardirectionofgaze.Itismostmarkedwhenmovedin
thedirectionofactionoftheweakmuscle.Askpatienttofollowyourfinger,redpinorpenlightwithboth
eyesandmoveitinanHpattern.
3rdnerveeyeturnedout:divergentsquint
6thnervefailuretoabduct:convergentsquint
SeeFigure33.1.

Figure33.1Directionofmovementoftherighteyeindicatingtheresponsibleextraocularmusclesand
cranialnerves(3=oculomotor,4=trochlear,6=abducens)
Laboratorytest
ESR(considerarteritis)
Note:
Exclude3rdand6thnervepalsiesastheymaybesecondarytolifethreateningconditions.
Referurgentlyifdiplopiaisbinocular,ofrecentonsetandpersistent.

Motorweakness
Muscleweaknessisacommonfeatureofmanydisordersrangingfromneurogenicandmyogenic
disorderstometabolicandpsychiatric.Itisveryimportantclinicallytobeabletodifferentiateuppermotor
neurone(UMN)signsfromlowermotorneurone(LMN)signs(Table33.1).
Table33.1Clinicaldifferencesbetweenalowermotorneuronelesionandanuppermotorneurone
lesion
Manifestation UMN

LMN

Weakness

Present

Present

Wasting

Absentormild

Marked

Power

Reduced

Reduced

Tone

Usuallyincreased(spasticparalysis)clonus

Absentordecreased(flaccidparalysis)

Fasciculations Absent

Maybepresent

Reflexes

Absentordiminished

http://127.0.0.1:9000/

Brisktendonreflexes
Abdominalabsent
Extensorplantarresponse

2/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

Uppermotorneuronelesions
UMNsignsoccurwhenalesionhasinterruptedaneuralpathwayatalevelabovetheanteriorhorncell.2
Examplesincludelesionsinmotorpathwaysinthecerebralcortex,internalcapsule,brainstemorspinal
cord.
Clinicalexamplesincludestroke(thrombosis,embolismorhaemorrhageinthebrain),tumoursofthe
variouspathways,anddemyelinatingdisease,suchasmultiplesclerosisandinfection,forexample,HIV.

Lowermotorneuronelesions
LMNsignsoccurwhenalesioninterruptsperipheralneuralpathwaysfromtheanteriorhorncell,thatis,
thespinalreflexarc.
Clinicalexamplesincludeperipheralneuropathy,GuillainBarrsyndrome,motorneuronedisease,
poliomyelitisandathickenedperipheralnerve(e.g.leprosy).
Note:AspinalcordlesioncausesLMNsignsatthelevelofthelesionandUMNsignsbelowthatlevel.

Neurogenicandmyogenicmuscleweakness
Itisalsoimportanttodistinguishbetweenweaknesscausedbyneurologicalconditions,especiallythose
causingLMNlesionsandmusculardisorders.ThefeaturesarecomparedinTable33.2.
Table33.2Muscleweakness:mainclinicaldifferencesbetweenneurogenicandmyogeniclesions
Myogenicweakness

Neurogenicweakness

Reflexesoftenpresentdespitesevereweakness Reflexesoftenabsentdespiteminimalweakness
Weaknessoutofproportiontowasting

Wastingoutofproportiontoweakness

Sensationnormal

Sensorychanges

Nofasciculation

Fasciculationafeature

Motorneuronedisease(MND)
MNDisaprogressiveneuromusculardisorderresultinginmuscularlimbandbulbarweaknessdueto
deathofmotorneuronesinthebrain,brainstemandspinalcord.Thesensorysystemisnotinvolved,nor
thecranialnervestotheeyemuscles.Fiveto10%ofMNDisinheritedwithanautosomaldominant
patterntherestissporadic.Thethreemainpatternsare:
1. amyotrophiclateralsclerosiscombinedLMNmuscleatrophyplusUMNhyperreflexia,leadingto
progressivespasticity
2. progressivemuscleatrophywastingbeginningintheproximalmuscleswidespreadfasciculation
3. progressivebulbarandpseudobulbarpalsyLMNlesionsofthebrainstemmotornucleiresulting
inwastedfibrillatingtongue,weaknessofchewingandswallowing,andoffacialmuscles

Symptomsandsigns
Weaknessormusclewastingfirstnoticedinhands(weakgrip)orfeet
Stumbling(spasticgait,footdrop)
Difficultywithswallowing
Difficultywithspeech,e.g.slurring,hoarseness
Fasciculation(twitching)ofskeletalmusclesandtongue
Cramps
Emotionalinstability,depression
Musclepain
http://127.0.0.1:9000/

3/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

Thediagnosisisclinical.Therearenodiagnostictests,butneurophysiologicaltestshelpdifferentiate
fromotherconditions.
MNDisincurableandprogressestodeathusuallywithin35yearsfromventilatoryfailure/aspiration
pneumonia.
NotreatmentisproventoinfluenceoutcomealthoughRiluzole,asodiumchannelblocker,appearsto
slowprogressionslightly.Baclofen10mgbdmayhelpsymptomsofcramp.Botulinumtoxinmayhelp
spasticityandpropanthelineoramitriptylinefordrooling.

Tremor
Tremorisanimportantsymptomtoevaluatecorrectly.AlistofcausesispresentedinTable33.3.A
commonpitfallinpatientspresentingwithtremorisforParkinson'sdiseasetobediagnosedasbenign
essentialtremorandforbenignessentialtremortobediagnosedasParkinson'sdisease,buttheclinical
distinctionisnotalwayseasyanditmustberememberedthatasmanyas20%willexperienceboth
concurrently.
Table33.3Causesoftremor
Physiological
Benignessential(familial)tremor
Senile
Anxiety,includinghyperventilation
Hyperthyroidism
Toxic(e.g.alcohol,liverfailure,uraemia)
Drugs(e.g.lithium,narcoticwithdrawal)
Parkinson'sdisease
Druginducedparkinsonism
Cerebellardisease
Cerebraltumour(frontallobe)
Alzheimer'sdementia
Wilson'ssyndrome
Miscellaneous(e.g.rednucleuslesion,hypoglycaemia)

Tremorscanbeclassifiedasfollows:

RestingtremorParkinsonian
ThetremorofParkinson'sdiseaseispresentatrest.Thehandtremorismostmarkedwiththearms
supportedonthelapandduringwalking.Thecharacteristicmovementispillrollingwheremovementof
thefingersatthemetacarpophalangealjointsiscombinedwithmovementsofthethumb.Theresting
tremordecreasesonfingernosetestingbutafasteractiontremormaysupervene.Thebestwayto
evokethetremoristodistractthepatient,suchasfocusingattentiononthelefthandwithaviewto
examiningtherighthandorbyturningthehead.

Actionorposturaltremor
Thisfinetremorisnotedbyexaminingthepatientwiththearmsoutstretchedandthefingersapart.The
tremormayberenderedmoreobviousifasheetofpaperisplacedoverthedorsumofthehands.The
tremorispresentthroughoutmovement,beingaccentuatedbyvoluntarycontraction.
Causesinclude:
essentialtremor(alsocalledfamilialtremororbenignessentialtremor)
seniletremor
physiological
anxiety/emotional
hyperthyroidism
alcohol
drugs,forexample,drugwithdrawal(e.g.heroin,cocaine,alcohol),amphetamines,lithium,
sympathomimetics(bronchodilators),sodiumvalproate,heavymetals(e.g.mercury),caffeine,
http://127.0.0.1:9000/

4/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

amiodarone
phaeochromocytoma

Intentiontremor(cerebellardisease)
Thiscoarseoscillatingtremorisabsentatrestbutexacerbatedbyactionandincreasesasthetargetis
approached.Itistestedbyfingernosefingertouchingorrunningtheheeldowntheoppositeshin,and
pastpointingofthenoseisafeature.Itoccursincerebellarlobediseaseandwithlesionsofcerebellar
connections.

Flapping(metabolictremor)
Aflappingorwingbeatingtremorisobservedwhenthearmsareextendedwithhyperextensionofthe
wrists.Itinvolvesslow,coarseandjerkymovementsofflexionandextensionatthewrists.
Note:Flapping(asterixis)isnotstrictlyatremor.
Causes
Wilson'ssyndrome
Hepaticencephalopathy
Uraemia
Respiratoryfailure
Lesionsoftherednucleusofthemidbrain(theclassiccauseofaflap)

Essentialtremor
Essentialtremor,whichisprobablythemostcommonmovementdisorder,hasbeenvariouslycalled
benign,familial,senileorjuveniletremor.However,itisnotalwaysbenignandthereisnofamilyhistory
inabouthalfthecases.

Features
Autosomaldominantdisorder(variablepenetrance)
Oftenbeginsinearlyadultlife,evenadolescence
Beginswithaslighttremorinonehandandspreadstotheotherwithtime
Mayinvolvehead(titubation),chinandtongueandrarelytrunkandlegs
Interfereswithwriting(notmicrographic),handlingcupsofteaandspoons,etc.
Tremormostmarkedwhenarmsheldout(posturaltremor)
Tremorexacerbatedbyanxiety
Mayaffectspeechifitinvolvesbulbarmusculature
Relievedbyalcohol
Canswingarmandgaitnormal
Triadoffeatures
Positivefamilyhistory
Tremorwithlittledisability
Normalgait

DistinguishingessentialtremorfromParkinson'sdisease
ThisisnotalwayseasyasaposturaltremorcanbepresentinParkinson'sdiseasealthoughthehand
tremorismostmarkedatrestwiththearmssupportedonthelap.Parkinsoniantremorisslowerat46
Hzwhileessentialtremorismuchfasterataround813Hz.
Amostusefulwaytodifferentiatethetwocausesistoobservethegait.Itisnormalinessentialtremor
butinParkinson'stheremaybelossofarmswingandthestepisusuallyshortened.

Managementofessentialtremor
Mostpatientsdonotneedtreatmentandallthatisrequiredisanappropriateexplanation.1Ifnecessary,
usepropranolol(firstchoice)orprimidone.3Atypicalstartingdoseofpropranololis1040mgbdmany
require120240mg/day.3Ifthetremorisonlyintrusiveattimesofincreasedemotionalstress,
http://127.0.0.1:9000/

5/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

intermittentuseofbenzodiazepines(e.g.lorazepam)30minutesbeforeexposuretothestressmaybeall
thatisrequired.Modestalcoholintake(e.g.aglassofscotch)isveryeffective.Astandarddrinkof
alcoholoftenalleviatesthetremor.Largerdosesofalcoholhavenoadditionaleffect.

Parkinson'sdisease
Parkinson'sisadiseaseoftheautomaticprocessorofthebrainwhichreliesondopaminetomaintain
movementsataselectedsizeandspeed.Lossofdopaminecausesmovementstobecomesmallerand
slower.LewybodiesintheneuronesarethepathognomicsignofParkinson'sdisease.4Geneticfactors
occurin5%ofindividuals.
OneofthemostimportantclinicalaspectsofParkinson'sdisease,whichhasaslowandinsidiousonset,
istheabilitytomakeanearlydiagnosis.Sometimesthiscanbeverydifficultespeciallywhenthetremor
isabsentormild,asoccurswiththeatheroscleroticdegenerativetypeofparkinsonism.Thelackofany
specificabnormalityonspecialinvestigationleavestheresponsibilityforadiagnosisbasedonthehistory
andexamination.AsageneralruleofthumbthediagnosisofParkinson'sdiseaseisrestrictedtothose
whorespondtolevodopatherestaretermedparkinsonism.

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

Figure33.2BasicclinicalfeaturesofParkinson'sdisease

tremor
rigidity
bradykinesia(povertyofmovement)
Nonmotorautomaticdysfunctions
cognition
behaviour
http://127.0.0.1:9000/

6/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

mood
Hemiparkinsonismcanoccurallthesignsareconfinedtoonesideandthusmustbe
differentiatedfromhemiparesis.Infact,mostcasesofParkinson'sdiseasestartunilaterally.
Alwaysconsiderdruginducedparkinsonism.Theusualdrugsarephenothiazines,butyrophenones
andreserpine.Tremorisuncommonbutrigidityandbradykinesiamaybesevere.
RefertoTable33.4(onp.297).
Table33.4Parkinson'sdisease:symptomsandsigns(achecklist)
General

Tiredness
Lethargy
Restlessness

Tremor

Presentatrest
Slowrate4to6cyclespersecond
Alternating,especiallyarms
Pillrolling(severecases)
Note:maybeabsentorunilateral

Rigidity

Cogwheeljudderingonpassiveextensionoftheforearm
Leadpipelimbsresistpassiveextensionthroughmovement

Bradykinesia/hypokinesia

Slownessofinitiatingamovement
Difficultywithfinefingertasks
Micrographia(Figure33.3)
Maskedfacies
Relativelackofblinking
Impairedconvergenceofeyes
Excessivesalivation(late)
Difficultyturningoverinbedandrisingfromachair
Slowmonotonousspeech/dysarthria

Gaitdisorder

Noarmswingononeorbothsides
Starthesitation
Slowandshuffling
Shortsteps(petitpas)
Slowturningcircle
Freezingwhenapproachinganobstacle
Festination

Disequilibrium

Poorbalance
Impairedrightingreflexes
Falls(usuallylate)

Posture

Progressiveforwardflexionoftrunk
Flexionofelbowataffectedside

Autonomicsymptoms

Constipation(common)
Posturalhypotension
Depression(early)

Psychiatric

Progressivedementiain3040%usuallyafter10years6

http://127.0.0.1:9000/

7/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

Threemajortrapsinmissingearlydiagnosis:5
age:1015%are<50yearsatonset
beliefthatitisadiseaseofmen:M=F
absenceofrestingtremor(only50%haveitatonset)

Physicalsigns
Power,reflexesandsensationareusuallynormal.
Theearliestabnormalphysicalsignstoappeararelossofdexterityofrapidalternatingmovements
andabsenceofarmswing,inadditiontoincreasedtonewithdistraction.
Positivefrontallobesigns,suchasgraspandglabellartaps(onlyallowthreeblinks),aremore
commonwithparkinsonism.
Note:ThereisnolaboratorytestforParkinson'sitisaclinicaldiagnosis.Hypothyroidismand
depression,whichalsocauseslownessofmovement,maycauseconfusionwithdiagnosis.
Note:TheSteeleRichardsonsyndrome(parkinsonism,milddementiaandverticalgazedysfunction)is
worthconsidering.

Principlesofmanagement
Provideappropriateexplanationandeducation.
ExplainthatParkinson'sdiseaseisslowlyprogressive,andisimprovedbutnotcuredbytreatment.
Itisassociatedwithincreasedmortality(RRdeathcomparedwithgeneralpopulationranges1.6to
3).Thequestionofwhethertreatmentreducesmortalityremainscontroversial.7
Refertoaspecialistforsharedcare.
SupportsystemsarenecessaryforadvancedParkinson'sdisease.
Walkingstickswithappropriateeducationintotheirusemaybenecessarytohelppreventfallsand
constantcareisrequired,sothatadmissiontoanursinghomeforendstagediseasemaybe
appropriate.

Figure33.3Micrographia,oneofthesignsofParkinson'sdisease

Pharmacologicalmanagement8,9
Avoidpostponingtreatment.Itshouldbecommencedassoonassymptomsinterferewithworking
capacityorthepatient'senjoymentoflife.Thiswillbeapparentonlyifthecorrectquestionsareaskedas
thepatientmayacceptimpairedenjoymentwithoutappreciatingthatitisduetoParkinson'sdisease.
StartlowSinemet100/25(tabbd).Thereisusuallynodifferencebetweenthelevodopapreparations.
Thedosageshouldbetailoredsothatthepatientneitherdevelopssideeffectsnorisonaninadequate
doseofmedicationwithoutsignificanttherapeuticbenefit(Table33.5).
Table33.5AntiParkinsondrugs8,9
Agent

Usualdose

Mainsideeffects

Dopaminergic(standardand
slowrelease)

levodopa+benserazide

Nauseaandvomiting

100/25250/62.5mg
tds
100/25250/50mgtds

Involuntarydyskineticmovements
Psychiatricdisturbances

levodopa+carbidopa
http://127.0.0.1:9000/

Onoffphenomena
8/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

Endofdosefailure
Constipation

Dopamineagonists
bromocriptine
carbergoline
pergolide

515mgbd
0.56mgdaily
0.051.5mgtds

Nauseaandvomiting
Dizziness,fatigue
Psychiatricdisturbances
Pleuropulmonarychanges

Anticholinergics
benzhexol
benztropine
biperiden
orphenadrine

2mgbdortds
12mgbd
12mgbd
100mgbd

Drynessofmouth
Confusioninelderly
Contraindicatedinglaucomaandprostatism
Otheranticholinergiceffects(e.g.
constipation,blurredvision)

COMTinhibitors
entacapone

200mgwitheachdose
levodopa

Diarrhoea

100mgbd

SCinjection(referto
schedule)

2.55mgoncedailyor
bd

Nauseaandvomiting
Psychiatricdisturbances
Ankleoedema
Livedoreticularis
Nausea

Others
amantadine

apomorphine

selegiline(aMAOBinhibitor)

Sleepproblems
Potentiationoflevodopa

Psychosis
Dyskinesia
Drymouth
Neuropsychiatricdisturbances
Nausea
Dizziness,fatigue
Insomnia

Theolderdrugs,suchasanticholinergicsandamantadine,haveminimalusageinmodernmanagement
aslevodopa,whichbasicallycountersbradykinesia,isthebestdrugandthebaselineoftreatment.With
theonsetofdisability(motordisturbances)levodopaincombinationwithadecarboxylaseinhibitor
(carbidopaorbenserazide)ina4:1ratioshouldbeintroduced.Levodopatherapydoesnotsignificantly
improvetremorbutimprovesrigidity,dyskinesiaandgaitdisorder.Considerbenzhexolorbenztropineif
tremoristhefeature,especiallyinyoungpatients.
Pergolidecanbeusedintreatment,especiallywiththelevodopaonoffphenomenon(fluctuations
throughouttheday).Itappearstobemosteffectivewhenusedincombination.Themajorsideeffectsof
pergolidearesimilartolevodopa.Dyskinesiaandnauseaarelessproblematicbutseverepsychiatric
disturbancesaremorecommonwithbromocriptine(adopamineagonist).Itshouldthereforebeusedwith
cautioninpatientswithahistoryofconfusionordementia.Selegilinepromisestobeaneffectivefirstline
drug.Ifthereisassociatedpain,depressionorinsomnia,thetricyclicagents(e.g.amitriptyline)canbe
effective.
Entacaponehasthepotentialtoincreaseontimeandreducemotorfluctuationsinlevodopatreated
patientswhoarebeginningtoexperienceendofdosefailure.Theinitialdoseis200mg.

Treatmentstrategy8,9
http://127.0.0.1:9000/

9/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

Mild
(minimaldisability)
Levodopapreparation(lowdose)e.g.levodopa100mg+carbidopa25mg(tabbdincrease
graduallyasnecessaryto1tab(o)tds)
Amantadine100mg(o)bdmayhelptheyoungortheelderlyforupto12months
Selegiline(canbeusedasmonotherapyandpostponeneedforlevodopa)
Moderate
(independentbutdisabled,e.g.writing,movements,gait)
Levodopapreparation
Addifnecessarypergolideorcabergolineorbromocriptine
pergolide50g(o)bd,graduallyincreasingto1.5mg(max.)bd
cabergoline0.5mg(o)daily,increasingto6mg(max.)oncedaily
Severe
(disabled,dependentonothers)
Levodopa(tomaximumtolerateddose)+pergolideorcabergoline
Addentacapone200mg(o)witheachdoseoflevodopa,e.g.Statevo
Considerantidepressants

Longtermproblems
After35yearsoflevodopatreatmentsideeffectsmayappearinaboutonehalfofpatients:5
involuntarymovementsdyskinesia(uselowerdose+pergolideorcabergoline)
endofdosefailure(reduceddurationofeffectto23hoursonly)useentacapone
onoffphenomenon(suddeninabilitytomovewithrecoveryin3090minutes)
earlymorningdystonia,suchasclawingoftoes(duetodiseasenotasideeffect)management
ofmotorproblemsissummarisedinTable33.6
Table33.6ManagementofmotorproblemsintreatedParkinson'sdisease4
Motorproblem

Management

Endofdose
failure

Dosagesclosertogether

Onoff
phenomenon

Subcutaneousapomorphineforoffphase(1haction)withdomperidone
(o)topreventvomiting
Levodopaandascorbicacidsolution

Lossofefficacy

Increaselevodopadoseashighaspossible
Dopaminergicagonist(e.g.pergolide)

Peakdose
dyskinesia

Decreaselevodopadose

Dopaminergicagonist(e.g.pergolide)

Earlymorning
dystonia

Slowreleaselevodopa

http://127.0.0.1:9000/

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

MAOBinhibitor,ifefficacylost

10/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

Dopaminergicagonists(e.g.pergolide)

Nocturnal
akinesia

Slowreleaselevodopa
Dopaminergicagonist

Advanceddisease8
Apomorphinecanbeusedforsevereakinesianotresponsivetolevodopa:
apomorphine600gto6mg(mean3.4mg)SC
Fornauseaandvomitingsideeffects:
domperidone20mg(o)tds24hourspriortoapomorphine
Bettercontrolmayalsobeachievedwith:
amantadine100mg(o)bd

Contraindicateddrugs
Phenothiazines
Butyrophenones

Surgicaltreatment
Theindicationforsurgery(pallidotomyorstereotacticthalamotomy)10isthepresenceoftremororrigidity
notrespondingtochemicaltherapy.Itisconsideredmoreappropriateforyoungerpatientswitha
unilateraltremor.8Ahighsuccessratehasbeenclaimed.Italleviatestremorandrigiditybutdoesnot
preventprogressionofbradykinesia,dysarthriaordementia.However,twosystematicreviewsfound
limitedevidencethatpallidotomyreducescontralateraltremorandrigidityduringofftimebutcarried
significantriskofmorbidityandmortality.7

Whentorefer
Ifthediagnosisisunclearatthetimeofinitialpresentation,itisappropriateeithertoreviewthepatientat
alaterdateortoreferthepatientformoreneurologicalassessment.
Oncediagnosedorhighlysuspecteditisbesttorefertoestablishthediagnosisandtoseekadviceon
initiationoftreatment.Patientsandfamiliesusuallypreferthisapproach.Intheinitialyearsbeforemotor
fluctuationsdevelop,managementcouldbeperformedbythegeneralpractitioneraccordingtoanoverall
plandevelopedinliaisonwithaneurologicalcolleague.Whenfluctuationsdevelopandendstage
diseasesmanifest(e.g.gaitdisorders),specialistsupervisionisappropriate.1

CognitiveimpairmentwithParkinson'sdisease4
ThismaybeduetomultiplefactorsincludingParkinson'sassociateddementia,Alzheimer'sdiseaseand
medication,allofwhichcaninducepsychosis,butLdopaistheleastlikely.Neuropsychiatricsymptoms,
whichcanbevariedandbizarreandusuallyworseintheevening,canoccur.Factorscontributingto
psychosisareillustratedinFigure33.4.ManagementisbasedonmonotherapywithgradualbuildupofL
dopatomaximumtolerateddose,e.g.450600mg/day.

Figure33.4Factorscontributingtopsychosis

http://127.0.0.1:9000/

11/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

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

Practicetips
Levodopaisthegoldstandardfor
therapy.
Longeractinglevodopa
preparationsmayreducetheend
ofdosefailureeffectbut
rememberthepossibleneedfora
kickstartwithshortacting
preparations(e.g.firstthinginthe
morning).
Ensurethatadistinctionismade
betweendruginducedinvoluntary
movementsandthetremorof
Parkinson'sdisease.
Keepthedoseoflevodopaaslow
aspossibletoavoidthesedrug
inducedinvoluntarymovements.
Intheelderlywithafracturedhip
alwaysconsiderParkinson's
disease(amanifestationof
disequilibrium).
Rememberthebalanceof
psychosisandParkinson'sdisease
intreatment.
Keepinmindthesundowneffect
patientsoftengopsychoticas
thesungoesdown.
Dontfailtoattendtotheneedsof
thefamily,whooftensufferin
silence.
Bromocriptineandpergolide
shouldbeusedverycautiouslyin
theelderlybecauseofpossible
acutepsychoticreactions.
Ifdrugsaretobewithdrawnthey
shouldbewithdrawnslowly.

Multiplesclerosis
Multiplesclerosis(MS)isthemostcommoncauseofprogressiveneurologicaldisabilityinthe2050year
agegroup.11ItisgenerallyacceptedthatMSisanautoimmunedisorder.Geneticandenvironmental
factorsarebelievedtoplayarole.12EarlydiagnosisisdifficultbecauseMSischaracterisedby
widespreadneurologiclesionsthatcannotbeexplainedbyasingleanatomicallesion,andthevarious
symptomsandsignsaresubjecttoirregularexacerbationsandremissions.Themostimportantissuein
diagnosisistheneedforahighindexofsuspicion.
MSisaprimarydemyelinatingdisorderwithdemyelinationoccurringinplaquesthroughoutthewhite
matterofthebrain,brainstem,spinalcordandopticnerves.Theclinicalfeaturesdependontheir
location.

Clinicalfeatures
http://127.0.0.1:9000/

12/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

(SeeFigure33.5.)

Figure33.5Basicclinicalsignsinmultiplesclerosis
Morecommoninfemales
Peakageofonsetisinthefourthdecade
Transientmotorandsensorydisturbances
UMNsigns
Symptomsdevelopoverseveraldaysbutcanbesudden
Monosymptomaticinitiallyinabout80%
Multiplesymptomsinitiallyinabout20%
Commoninitialsymptomsinclude:
visualdisturbancesofopticneuritis
blurredvisionorlossofvisioninoneeye(sometimesboth)
centralscotomawithpainoneyemovement(lookslikeunilateralpapilloedema)
diplopia(brainstemlesion)
weaknessinoneorbothlegs,paraparesisorhemiparesis
sensoryimpairmentinthelowerlimbsandtrunk
numbness,paraesthesia
bandlikesensations
clumsinessoflimb(lossofpositionsense)
feelingasthoughwalkingoncottonwool
vertigo(brainstemlesion)
Subsequentremissionsandexacerbationsthatvaryfromoneindividualtoanother
Thereisaprogressiveform,especiallyinwomenaround50years
Anxiety,depressionandothermooddisordersarerelativelycommon

Neurologicalexamination
Thefindingsdependonthesiteofthelesionorlesionsandincludeopticatrophy,weakness,hyper
reflexia,extensorplantarresponses,nystagmus(twotypescerebellarorataxic),ataxia,incoordination
http://127.0.0.1:9000/

13/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

andregionalimpairmentofsensation.
Symptomscausingdiagnosticconfusion
Bladderdisturbances,includingretentionofurineandurgency
Uselesshandduetolossofpositionsense
Facialpalsy
Trigeminalneuralgia
Psychiatricsymptoms
Inestablisheddiseasecommonsymptomsarefatigue,impotenceandbladderdisturbances.

Diagnosis
Thediagnosisisclinicalanddependsonthefollowingdeterminants:
LesionsareinvariablyUMN.
LesionsaffecttheCNSwhitematter.
>1partofCNSisinvolved,althoughnotnecessarilyattimeofpresentation.
Episodesareseparatedintime(itispossibletomakeadiagnosiswiththefirstepisode).
Otherneurologicaldisorderssuchasinfections(e.g.encephalitis),malignancies,spinalcord
compression,spinocerebellardegenerationandothersmustbeexcluded.

Investigations
Lumbarpuncture:oligoclonalIgGdetectedinCSFin90%ofcases11(onlyifnecessary)
Visualevokedpotentials:abnormalinabout90%ofcases
CTscan:rarelydemonstratesMSlesionsbutusefulinexcludingotherpathology
MRIscan:usuallyabnormal,demonstratingMSlesionsinabout90%ofcases11

Courseandprognosis
Thecourseisvariableanddifficulttopredict.Anearlyonset(<30years)isusuallybenignwhilea
lateonset(50years)isoftenmalignant.
MSfollowsaclassichistoryofrelapsesandremissionsin8085%ofpatients.13
Therateofrelapseisaboutoncein2years.
About20%haveaprogressivecoursefromtheonsetwithaprogressivespasticparaparesis
(appliesmainlytolateageonset).
TheaveragedurationofMSisabout30yearsfromdiagnosistodeath.11
Abenigncourseoccursinabout40%ofpatientswith1020%neversufferingmajordisability.
Themediantimetoneedingawalkingaidis15years.8
ThelikelihoodofdevelopingMSafterasingleepisodeofopticneuritisisabout60%.

Managementprinciples
Allpatientsshouldbereferredtoaneurologistforconfirmationofthediagnosis,whichmustbe
accurate.
Explanationaboutthedisorderanditsnaturalhistoryshouldbegiven.
Acuterelapsesrequiretreatmentifcausingsignificantdisability.
Depressionandanxiety,whicharecommon,requireearlytreatment.
Relapses
Mildrelapses

Mildsymptoms,suchasnumbnessandtingling,requireonlyconfirmation,restandreassurance.
Moderaterelapses8

Forsymptomsthatareunpleasantordisablinguseashortcourseofhighdoseprednisolone.
prednisolone75mg(o)oncedailyfor4days,then50mg(o)dailyfor4days,then25mg(o)daily
for4days
http://127.0.0.1:9000/

14/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

Severerelapsesorattacks8,14

Theseattacksincludeopticneuritis,paraplegiaorbrainstemsigns.AdmittohospitalforIVtherapy:
methylprednisolone1gin200mLsalinebyslowIVinjection(3hours)dailyfor3to5days
Observecarefullyforcardiacarrhythmias.
Drugstopreventrelapses14
Currentlyavailableimmunomodulatorsaretheinterferonsandglatiramir.
Interferonbeta1b(SCinjection)andbeta1a(IMinjection)appeartobeeffective(butexpensive)for
thosewithfrequentandsevereattacks.
Evidencebasedmedicine
Thebestevidencetodateindicatesthattheinterferonsandmethylprednisolonearelikelytobebeneficial
butglatiramir,IVimmunolobulin,cytotoxicagentsandplasmaexchangehaveunkowneffectiveness.15
OneRCTfoundamodesteffectwithglatiramironarelapserateover2yearsbutfoundnoevidenceof
aneffectondisability.
Drugstoreduceprogression8,16
Currentrecommendedtreatmentgivenundercarefulsupervision:
methotrexate7.5mg(o),on1dayeachweek+
folicacid5mg(o),3daysaftereachmethotrexatedose
Immunosuppressioncanalsobegivenwithcyclophosphamideorazathioprine.17Thechemotherapeutic
agentmitozantranehasbeenshowntoarrestprogressionofMSbutitsuseislimitedbyits
cardiotoxicty.12
Treatmentofsymptoms7
Spasticity

Physiotherapy
Baclofen1025mg(o)nocte
Forcontinuousdrugtherapy:
baclofen5mg(o)tds,increasingto25mg(o)tds
+
diazepam210mg(o)tds
Paroxysmal(e.g.neuralgias)

Carbamazepineorclonazepam
Seereferences8and16fortreatmentofothersymptoms.

Acuteidiopathicdemyelinatingpolyneuropathy
(GuillainBarrsyndrome)
GuillainBarrsyndromeisthebestknownoftheperipheralneuropathiesthathaveanacuteonset,andit
ispotentiallyfatal.Earlydiagnosisofthisseriousdiseasebythefamilydoctoriscrucialasrespiratory
paralysismayleadtodeath.Theunderlyingpathologyissegmentaldemyelinationoftheperipheral
nervesandnerveroots.

Clinicalfeatures
Paraesthesiaorpaininthelimbs
Weaknessinthelimbs(usuallysymmetrical)
Bothproximalanddistalmusclesaffected
Facialandbulbarparalysis
http://127.0.0.1:9000/

15/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

Weaknessofextraocularmuscles(rarely)
Reflexesdepressedorabsent
Variablesensorylossbutrare
Within34weeksthemotorneuropathy,whichisthemainfeature,progressestoamaximumdisability,
possiblywithcompletequadriparesisandrespiratoryparalysis.18

Investigations
CSFproteiniselevatedcellsareusuallynormal.
Motornerveconductionstudiesareabnormal.

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

Outcome
About80%ofpatientsrecoverwithoutsignificantdisability.Approximately5%relapse.18

Myastheniagravis
Myastheniagravis(MG)isanacquiredautoimmunedisorderthatusuallyaffectsmusclestrength.
Patientshavefluctuatingsymptomsandvariabledistributionofmuscleweakness.Alldegreesofseverity,
rangingfromoccasionalmildptosistofulminantquadriplegiaandrespiratoryarrest,canoccur.19See
Table33.7.Itisassociatedwiththymictumourandotherautoimmunediseases,e.g.RA,SLE.
Table33.7Clinicalclassificationofacquiredmyastheniagravis
GroupI

OcularMG

GroupIIA MildgeneralisedMG
GroupIIB ModeratetosevereMG
GroupIII Acutesevere(fulminating)MGwithrespiratorymuscleweakness
GroupIV Late(chronic)severeMG

Clinicalfeatures
Painlessfatiguewithexercise
Weaknessalsoprecipitatedbyemotionalstress,pregnancy,infection,surgery
Variabledistributionofweakness:
ocular
ptosis(60%)anddiplopia(Figure33.6)
ocularmyastheniaonlyremainsinabout10%
bulbar:weaknessofchewing,swallowing,speech(asktocountto50),whistlingandheadlolling
limbs(proximalanddistal)
generalised
respiratory:breathlessness,ventilatoryfailure

http://127.0.0.1:9000/

16/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

Figure33.6MyastheniaGravisina40yearoldwomanwitha12monthhistoryofincreasingmuscular
weaknessincludingdroopingoftheeyelids.Ptosis,especiallyontherightside,isapparent
Note:TheclassicMGimageisthethinkerthehandusedtoholdthemouthclosedandtheheadup.

Diagnostictests
Serumantiacetylcholinereceptorantibodies
Electrophysiologicaltestsifantibodytestnegative
CTscanandchestXraytodetectthymoma
Edrophoniumteststilluseful

Managementprinciples8,20
DetectpossiblepresenceofthymomawithCTorMRscanofthorax.Ifpresent,removalis
recommended.
Thymectomyisrecommendedearlyforgeneralisedmyasthenia,especiallyinallyoungerpatients
withhyperplasiaofthethymus,evenifnotconfirmedpreoperatively.
Plasmapheresisisusefulforacutecrisisorwheretemporaryimprovementisrequiredorpatients
areresistanttotreatment.
Avoiddrugsthatarerelativelycontraindicated.
Pharmacologicalagents:
anticholinesterasedrugs(e.g.pyridostigmine,neostigmineordistigmine):shouldbeusedonly
formildtomoderatesymptoms
corticosteroids:usefulforallgradesofMGshouldbeintroducedslowly

Practicetips
Thecombinationofocularand
facialweaknessshouldalertthe
familydoctortothepossibilityofa
neuromusculardisorder,especially
MGormitochondrialmyopathy.20
Lookforweaknessandfatigue.
Bewareoffacioscapulohumeral
dystrophy.
Ptosismaydeveloponlyafter
lookingupwardsforaminuteor
longer.
Smilingmayhaveacharacteristic
snarlingquality.

Ptosis
Itisworthrememberingthatthefourmajorcausesofptosisare:
http://127.0.0.1:9000/

17/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

1. 3rdcranialnervepalsyptosis,eyefacingdownandout,dilatedpupil,sluggishlightreflex
2. Horner'ssyndromeptosis,miosis(constrictedpupil),ipsilaterallossofsweating
3. Mitochondrialmyopathyprogressiveexternalophthalmoplegiaorlimbweakness,inducedby
activity
4. Myastheniagravisptosisanddiplopia

Dystonia
Definition
Dystoniasaresustainedorintermittentabnormalrepetitivemovementsorposturesresultingfrom
alterationsinmuscletone.Thedystonicspasmsmayaffectone(focal)ormore(segmental)partsofthe
bodyorthewholebody(generalised).

Keypoints
Misdiagnosisiscommonastransientsymptomsmaybemistakenforanemotionalorpsychiatric
disorder.Manycasestakeyearstodiagnose.
Dystoniasareoftenregardedasnervoustics.
Thecauseisthoughttobedisordersofthebasalgangliaofthebrain,butmainlythereisnoknown
specificcause.
Neurolepticanddopaminereceptorblockingagents(e.g.levodopa,metoclopramide)caninducea
severegeneraliseddystonia(e.g.oculogyriccrisis)whichistreatedwithbenztropine12mgIMor
IV.20

Focaldystonias
Blepharospasmisafocaldystoniaofthemusclesaroundtheeyeresultinginuncontrolledblinking,
especiallyinbrightlight.
Oromandibulardystoniaaffectsthejaw,tongueandmouth,resultinginjawgrindingmovements
andgrimacing.Properspeechandswallowingmaybedisrupted.
Meige'ssyndromeisacombinationofblepharospasmandoromandibulardystonia.
Note:Itmustbedifferentiatedfromthebuccallingualfacialmovementsoftardivedyskinesia.
Hemifacialspasminvolvesinvoluntary,irregularmusclecontractionsandspasmsaffectingone
sideoftheface.Itusuallystartswithtwitchingaroundtheeyeandthenspreadstoinvolveallthe
facialmusclesononeside.Itisusuallyduetoirritationofthefacialnerveinitsintracranialcourse
andsurgicalinterventionmayalleviatethisproblem.
Writer'scramp,typist'scramp,pianist'scramp,golfer'scramparealloccupationalfocaldystonias
ofthehandand/orforearminitiatedbyperformingtheseskilledacts.
Cervicaldystoniaorspasmodictorticollisisafocaldystoniaoftheunilateralcervicalmuscles.It
usuallybeginswithapullingsensationfollowedbytwistingorjerkingofthehead,leadingto
deviationoftheheadandnecktooneside.Inearlystagespatientscanvoluntarilyovercomethe
dystonia.
Laryngealorspasticdystoniaisafocaldystoniaofthelaryngealmusclesresultinginastrained,
hoarseorcreakingvoice.Itmayleadtoinabilitytospeakinmorethanawhisper.

Treatmentoffocaldystonias
Thecurrenttreatmentforfocalorsegmental(spreadtoanadjacentbodyregion)dystoniasislocalised
injectionofpurifiedbotulinumAtoxinintotheaffectedmusclegroups.Thedosageishighlyindividualised
andneedstoberepeatedatintervalsof3and6months.Theinjectionshavetobegivenwithgreat
caution.

Tics
MotorandvocalticsareafeatureofTourette'sdisorder.Ifsociallydisablingtreatwith:
haloperidol0.25mg(o)nocte,verygraduallyincreasingto2g(max.)daily7or
clonidine25g(o)bdfor2weeks,then5075gbd

Facialnerve(Bell's)palsy8,15
http://127.0.0.1:9000/

18/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

Facial(7thnervepalsy),whichisanacuteunilaterallowermotorneuroneparesisorparalysis,isthe
commonestcranialneuropathy.TheclassictypeisBell'spalsy,whichisusuallyidiopathicalthough
attributedtoaninflammatoryswellinginvolvingthefacialnerveinthebonyfacialcanal.IntheRamsay
Huntsyndrome,whichisduetoinfectionwithherpeszostercausingfacialnervepalsy,vesiclesmaybe
seenontheipsilateralear.
Associations:
herpessimplexvirus(postulated)
diabetesmellitus
hypertension
thyroiddisorder,e.g.hyperthyroidism

Features
abruptonset(canworsenover25days)
weaknessintheface(completeorincomplete)
precedingpaininorbehindtheear
impairedblinking
Lesscommon:
difficultyeating
lossoftasteanteriortwothirdsoftongue
hyperacusis

Management
prednisolone50mg(o)dailyindivideddosesfor4daysthentapertozeroovernext7days(start
within3daysofonset)
Note:Thisiscontroversialasevidenceisnotconvincing15(betterinseverercases).
patienteducationandreassurance
adhesivepatchortapeovereyeifcornealexposure(e.g.windyordustyconditions,duringsleep)
artificialtearsifeyeisdryandatbedtime
massageandfacialexercisesduringrecovery
Note:
Atleast7080%achievefullspontaneousrecoveryhigherifmild.
Electromyographyandnerveexcitabilityorconductionstudiesareaprognosticguideonly.
Noevidencethatnucleosideanalogue,e.g.aciclovir,isusefulbutshouldbeusedforRamsay
Huntsyndrome.
Noevidencethatsurgicalprocedurestodecompressthenervearebeneficial.15

Diagnostictriadsofneurological
dilemmas
Alltriadsshowachroniconsetunless
indicatedbyanasterisk(acuteonset).
Ifyouseethis
combinationofsigns:
Charcot'striad:
dysarthria+intention
tremor+nystagmus
visualdisturbance
(blurredortransient
loss)+weaknessin
limbsparaesthesiain
http://127.0.0.1:9000/

Consider:

=cerebellar
disease
(typicalofMS)
=multiple
sclerosis

19/21

11/12/2014

limbs
Note:herearemany
combinationsofMS
(Charcot'shashistorical
interest).
rigidity+bradykinesia
+restingtremor
tremor(posturalor
action)+headtremor+
absenceofParkinsonian
features
fatiguableand
weaknessofeyelidsand
eyemovements+limbs
+bulbarmuscles
(speechandswallowing)
weaknessoflimbs+of
face+areflexia*

(episodic)vertigo+
tinnitus+hearingloss*
dementia+myoclonus
+ataxia
drowsiness+vomiting
+headache(waking)
enophthalmos+
meiosis+ptosis
anhydrosis
blankspell+lip
smacking(orsimilar
automation)+
olfactory/gustatory
hallucination
gradualspread
(Jacksonianmarch)of
focaljerking(mouth,arm
orleg)orsensory
disturbanceor(rarely)
visualfielddisturbance
intracranialpressure
+/orfocalsigns+/or
epilepsy
dysphagia+
dysphonia/dysarthria+
spastictongue
recurrent:headache
(oftenunilateral)+
nausea(vomiting)+
visualaura*

Murtagh's General Practice Series - Fourth Edition

=Parkinson's
disease
=essential
tremor

=myasthenia
gravis

=Guillain
Barr
syndrome
(GBS)
=Meniere's
syndrome
=Creutzfeld
Jakobdisease
=
intracerebral
pressure
=Horner's
syndrome
=complex
partialseizure

=simplepartial
seizure

=cerebral
tumour
=
pseudobulbar
palsy
=migrainewith
aura(formerly
classical
migraine)

recurrent:severeretro =cluster
orbitalheadache+
headache
rhinorrhoea+
lacrimation*
instantaneous:
headachevomiting
neckstiffness
headache+visual
http://127.0.0.1:9000/

=
subarachnoid
haemorrhage
untildisproven
=benign
20/21

11/12/2014

Murtagh's General Practice Series - Fourth Edition

obscurations+
papilloedema(oftenin
obeseyoungfemale)
acuteandtransient:
amaurosisfugaxor
dysphasiaor
hemiplegia*

intracranial
hypertension

typicalfacies
(temporalisatropyand
frontalbalding)+muscle
weakness(myotonia)
+cataracts
ataxia+
ophthalmoplegia+
areflexia*

=myotonic
dystrophy

=TIA(carotid)

=MillerFisher
variantofGBS

vertigo+provokedby =BPPV
movement(especially
rollinginbed)+Hallpike
test+ve
UMNsigns+LMN
=motor
signs+fasciculations
neurone
disease

REFERENCES
1. 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.

http://127.0.0.1:9000/

21/21