Movement Disorders - Overview-1

8/7/2019 Movement Disorders - Overview-1

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SUMAIYA SALIM, M.D.


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Classification

y Hypokinesias - typified byslownessand/orpaucityofmovement, eg. parkinsonism.

y Hyperkinesias - abnormalinvoluntarymovements,eg. chorea, dystonia, myoclonus, stereotypes, tics,tremors.


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Hypokinesias

y Bradykinesia - slownessofmovement andimpairedinitiation/paucityofmovement (akinesia).

y Rigidity- cogwheeling- increasedresistance topassive movement.

y Posturalinstability- propulsion, retropulsion.


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Hyperkinesias- Chorea

y Chorea - continuous, abrupt, rapid, brief,unsustained, irregular, random, DANCE-LIKE

movementswhichflowfrom one bodypart toanother.Maybeincorporatedintosemipurposeful activities.Motorimpersistance isacommonfeature - difficultymaintainingsustainedcontractionssuchas tongueprotrusion.

y Athetosis isacontinuousstream ofslow, sinuous,writhing movements, typicallyofthehandsandfeet

y Ballism thrashing motions


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Hyperkinesias - Dystoniay Dystonia - involuntary, sustained (tonic)or

intermittent (spasmodic, clonic), patterned,repetitive musclecontractionswhichfrequentlycause twisting (torticollis), flexingorextending(writerscramp, retrocollis), andsqueezing(blepharospasm)orabnormalposture. Maybe task-specific.

yFocal, segmental, generalized, multifocalandhemidystonia


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Hyperkinesias - Myoclonusy Lightning-like movementssecondaryTO

y briefsuddencontractions (positive myoclonus)

y or muscleinhibition (negative myoclonus). Asterixis:one typeofnegativemyoclonus

y Focal, segmental, multifocal, generalized.

y Cortical, brainstem (reticular), andspinal


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Hyperkinesias - Stereotypies

y Involuntaryorsemi-voluntary(unvoluntary)patterned, repetitive, coordinated, rhythmic,

purposeless thoughseeminglypurposefulorritualistic movement, postureorutterance.

y Examplesincludefoot tapping, bodyrocking, orcomplexrituals.


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Hyperkinesias-Tics

y Relativelybrief, repetitive, nonrhythmic,y movements (motor tics)y sounds (phonic/vocal tics).

y Premonitorysensations - maybelocalized (burning,tension, tightness)orfeelingofanxiety, an urge

y Suppressible toadegree. suppressible yet irresistibley Simple motor tics - sudden, brief, meaningless

movementsinvolveonlyonegroupofmuscles (eyeblinking, head jerkingorshouldershrugging. simple

phonic tic can bealmost anysoundornoise (throatclearing, sniffing, orgrunting)y Complex motor tic - clusterofmovementsandapppear

coordinated. (pullingat clothes, touchingpeople). Vocal echolalia, coprolalia


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Hyperkinesias -Tremorsy Involuntary, rhythmic, oscillatorymovementsabout

a joint secondarytoalternatingorsynchronous

contractionsofantagonist muscles.y Rest - fullysupportedagainst gravity.

y Action - duringvoluntarycontractions.

y Postural, Kinetic (initial, dynamic, terminalor

intention), task- orposition-specific, isometric.


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Anatomy - Basal Ganglia

y 6pairednuclei - caudatenucleus, putamen, globuspallidus, nucleusaccumbens, subthalamicnucleus

andsubstantianigra.y lenticularnucleus - lenslike - putamenandglobus

pallidus.

y GPiand SNr behaveassinglefunctionalunit.


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Anatomy - Basal Ganglia

y striatum - caudateandputamen - composedofstriosomes (limbicsystem projectshere), matrix

(neocorticalfibersproject here).y putamen - motor - receivesinput from

somatosensory, motorandpremotorareas.

y caudate - emotionalandcognitiveprocesses -

posteriorparietaland temporal, frontalassociationareasproject here.


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Anatomy - Basal Gangliay Functions to modulate theamplitudeandvelocityof

movement andin thepreparationfor movement.

ySeediagramsforproposed basalgangliacircuitryinnormalsandin Parkinsonsdisease


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Cortex

PrefrontalInsular

CingulateSensoryMotor

Suppl. MotorPremotor

PremotorPrefrontal

Striatum

D2 D1 ThalamusVA/VL

+ = excitatory

- = inhibitory

BrainstemSC

SNc

SNr

GPi

STN

GPe

-

+

+

+ -

-

--

-

-

+

++

+

+

+

Normal


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Cor ex

re ron ansu ar

Cingu a eensoryo or

upp o orre o or

re o orre ron a

riatu

2 1Thalamus

L

+ = excitatory

= inh ibitory

rainstemSC

SNc

SNri

STN

GPe

++

++++

+

++

+

+

+

Parkinsons isease


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Clinical Features/Cardinal Signs

y 1817: James Parkinson AnEssayon the Shaking Palsy

y

Diagnosis requires 2 of 3:y Bradykinesia

y Rigidity

y Tremor (primarily at rest)

y Othersigns: Maskedface, hypovolemic speech,swallowingdifficulty, micrographia, flexedposture,shufflinggait, start hesitancyandfreezing


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Onsety Insidious, unilateralprogressing to bilateral


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Classification of Parkinson Syndromes in a

Community

y Idiopathic PD ~ 85%ofall PS cases

y Neuroleptic-inducedparkinsonism (DIP)7% - 9%

y Vascularparkinson syndrome ~ 3%y PS due to MPTP, CO, Mn, recurrent head traumais

extremelyrare

y Nonewcasesofpostencephalitic parkinsonism since

1960s


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Epidemiology of Parkinson Syndrome

y Incidence:

- 5-24/100000worldwide (USA/Canada 300/100000)-IncidenceofPS/PD risingslowlywithagingpopulation


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Prevalence

y 57-371/100t. worldwide (USA/Canada 300/100t.)

y 35%-42%ofcasesundiagnosedat anytime


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Onset

y mean PS 61.6years; PD 62.4 years

y rare beforeage 30; 4-10%cases beforeage 40


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Pathology of Parkinsons Disease

y Markedstriatal DAdepletion

Striatal dopaminedeficiencysyndrome

y At death, DAloss > 90%

y


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Parkinsons Disease Risk Factors

y Definite: Oldage

y Highlylikely: MZ co-twinwithearly-onset PD

y Probable: Positivefamilyhistoryy Possible:Herbicides, pesticides, heavymetals,

proximitytoindustry, ruralresidence, wellwater,repeatedhead trauma, etc.

y Possibleprotectiveeffect: Smoking


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Cause of PD

y Unknownin most cases;not acceleratedagingy GenesAD inheritanceveryrare; mutationunknown

mutationofAlphasynucleingene (chromosome 4q)identifiedinonelarge Italian (Contursi)and5 Greekautosomaldominant families

mutationofparkingeneinautosomal-recessive juvenileparkinsonism

y EnvironmentMajorityofcases believedcaused byenvironmentalfactor (s)

but noneidentifiedsofary Genesplusenvironment?


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Early Signs and Symptoms

y CardinalCharacteristics (Requires 2 of3):

y Resting tremor

yBradykinesia

y Rigidity

Andoftenassociatedwith Posturalinstability


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Early Signs and Symptoms

Others

y Micrographia

y

Maskedfacey SlowingofADLs

y Stooped, shufflinggait

y Decreasedarm swingwhenwalking


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Additional Signs and Symptoms

y Difficultyarisingfrom achair

y Difficultyturningin bed

y Hypophonicspeechy Sialorrhea

y Lossofthesenseofsmell

y Foot dystonia


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Clues Suggesting Atypical Parkinsonism

y Earlyonset of, orrapidlyprogressing, dementia

y Rapidlyprogressivecourse

y Supranuclear gazepalsy(impairedverticalgaze,bradykinesia, posturalinstability, frequent falls,incontinence)

y Upper motorneuronsigns (suggestiveofstrokes)

y Cerebellar signsdysmetria, ataxiay Urinaryincontinence (NPH)

y Earlysymptomaticposturalhypotension


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Hereditary disorders associated with

parkinsonism

y Wilsonsdisease

y Huntingtonsdisease

y Dentatorubro-pallidoluysianatrophy(DRPLA)y Machado-Josephdisease (SCA-3)


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Differential Diagnosis of PDy Drug-induced

y Toxin-induced

y Metabolicy Structurallesions (vascularparkinsonism, etc.)

y Hydrocephalus

y Infections


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Drug-Induced Parkinsonism

y Crucial toruleout, since most casesarereversible

y Careful medicationhistorylist drugnames

y Commonoffendingdrug types

y Antipsychotics :haloperidol, chlorpromazine,thioridizine, perphenazine, risperidone, olanzapine

y Antiemeticsmetoclopramide, prochlorperazine

y Dopaminedepletorsmethyldopa, reserpine,

tetrabenaziney Combinationdrugse.g., Triavil (amitriptyline,

perphenazine)

y Treatment: Stopoffending medication


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Metabolic and Infectious Causes of

Parkinsonism

y Metabolicy Oftenreversible

y Hypo- orhyper-thyroidism

y Hypo- orhyper-parathyroidism

y Liverfailure

y Centralpontine myelinolysis

y Infectiousy Post-encephaliticy Creutzfeldt-Jakob disease

y Infectious masses

y HIV


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Toxin-induced Parkinsonism

y MPTP

y Carbon monoxide

y Manganesey Cyanide


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Structural Lesions Causing Parkinsonism

y Acuteorsubacuteonset

y Othersignshemiparesis, hyperreflexia, aphasia,

sensoryloss, seizuresy Brain tumor

y Infectious mass

y Aneurysm


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Vascular Parkinsonism

y Abrupt onset, usuallyunilateral

y Step-wiseornoprogression

y Othersignshemiparesis, aphasia, hyperreflexiay Infarctsonneuroimaginghelpfulinconfirming

diagnosis


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Hydrocephalus-induced Parkinsonism

y Can becommunicatingorobstructive

y Normalpressurehydrocephalusidiopathic

y Clinical triad:y parkinsonism/gait disorder

y urinary/fecalincontinence

y dementia


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Parkinsons Disease vs. Essential Tremory Essential tremorshould be tremorwithnoothersigns

ofparkinsonism

y Bothcanhaveakineticandrest component

y Kinetic tremorcaninterferewith RAM

y Cogwheelrigiditycan befoundinET


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TreatmentOptions

y Preventive treatment -- Nodefinitiveavailable

y Symptomatic treatmenty

Pharmacologicaly Surgical

y Non-motor management

y Restorativeexperimentalonlyy Transplantationy Neurotrophic factors


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Drug Classes in PD

y Dopaminergic agents

y Levodopa

y

Dopamineagonistsy COMT inhibitors

y MAO-Binhibitors

y Anticholinergics

y Amantadine


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Levodopa

y Most effectivedrugforparkinsonian symptoms

y First developedin thelate1960s;rapidlybecame

thedrugofchoicefor PDy Largeneutralaminoacid;requiresactive transport

across thegut-bloodand blood-brain barriers

y Rapidperipheraldecarboxylation todopamine

without adecarboxylase inhibitor (DC

Is:carbidopa, benserazide)

y Sideeffects:nausea, posturalhypotension,dyskinesias, motorfluctuations


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Diagram of LD Metabolism


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Levodopa-Induced Dyskinesiasy Manifestationofexcessivedopaminergic

stimulationy Typicallylateeffect, andwithhigherdosesy Narrowingoftherapeuticwindowy Rarein LD-naivepatientson DA monotherapyy Most commonis peakdosedyskinesia

disappearswithdosereductiony Choreiform, ballisticanddystonic movementsy Most patientsprefersomedyskinesiasover the

alternativeofakinesiaandrigidity


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Dopamine Agonists: Distinguishing Features

y Directlystimulatedopaminereceptorsy No metabolicconversion; bypasses

nigrostriatalneuronsy Noabsorptiondelayfrom competitionwith

dietaryaminoacidsy Longerhalf-life thanlevodopay Monotherapyoradjunct therapyy Maydelayorreduce motorfluctuations &

dyskinesiasassociatedwithlevodopay Maybeneuroprotective


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DAs: Common Adverse Effects

y Nausea, vomitingy Dizziness, posturalhypotensiony Headachey Dizzinessy Drowsiness & somnolencey Dyskinesiasy Confusion, hallucinations, paranoiay Erythromelalgia; pulmonary&retroperitonealfibrosis;pleuraleffusion & pleuralthickening; Raynaudsphenomena. Maybe morecommonwithergotoline DAs


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Apomorphine

y D1/D2 agonist

y Parenteraldelivery(s.c., i.v., sublingual, intranasal,rectal)

y Rapid offperiodrescue 2-5 mgs.c.;peninjectionsystems

y Treatment ofunpredictable, frequent motorfluctuations

continuouss.c. infusionvia mini-pumpy SE:nausea, vomiting, hypotension

trimethobenzamide 250 mg t.i.d.

domperidone 20 mg t.i.d.;not availablein U.S.


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Anticholinergics

y Dopaminergic depletion cholinergicoveractivityy Initiallyusedin the1950sy Effective mainlyfor tremorandrigidityy Commonagents (Start low, goslow):

y Trihexyphenidyl: 2-15 mg/day

y Benztropine:1-8 mg/dayy Ethopropazine:10-200 mg/day

y Sideeffects: Drymouth, sedation, delirium,confusion, hallucinations, constipation, urinaryretention


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Amantadine

y Antiviralagent; PD benefit foundaccidentallyy Tremor, bradykinesia, rigidity& dyskinesiasy Exact mechanism unknown;possibly:

y enhancingreleaseofstoreddopamine

y inhibitingpresynaptic reuptakeofcatecholamines

y dopaminereceptoragonismy NMDAreceptor blockade

y Sideeffectsautonomic, psychiatricy 200-300 mg/day


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EarlyManagement of Parkinsons Disease


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Initial Therapy: Patient Considerationsy Riskofacutedrugintolerance

y Riskoflong-term drug-relatedcomplications

yPolypharmacy

y Comorbidities, especiallydementia

y Patientslifestyle, responsibilities

y Cost ofmedications

y Functionalvs. chronologicalage


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Initial Therapy: The Elderly Patienty Shorter treatment horizon

y Lowerriskoflong-term complications

y

Higherlikelihoodofcomorbiditiesy Levodopa:well tolerated, effective

y Useadjunctive medicationscautiously

y Avoidsedating medications


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Initial Therapy: The Young Patient

y Long-term treatment horizon

y Increasedriskoflong-term complications

y

Increasedpatient responsibilitiesy Dopamineagonist monotherapy

y Levodopa-sparingstrategies

y Putativeneuroprotectivestrategies

y Roleoflevodopaisnot adequatelydefined

:


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Complaint?

SymptomsSymptoms Clinical optionClinical option

No functional impairmentNo functional impairment Delay TherapyDelay Therapy

Mild symptomsMild symptoms Amantadine, SelegilineAmantadine, Selegiline

TremorTremor AnticholinergicAnticholinergic

DepressionDepression AntidepressantAntidepressant

AnxietyAnxiety AnxiolyticAnxiolytic

Functionally disablingFunctionally disabling

symptomssymptoms

Levodopa, DopamineLevodopa, Dopamine

agonist, COMT inhibitoragonist, COMT inhibitor


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Levodopa: Guidelines in Early PD

y Start lowandincreaseslowlyy Titratedosage toefficacy(~200-600 mg/day)y Immediaterelease-morerapidonset-shorterdurationofbenefit-genericavailabley Controlledrelease-longerdurationofbenefit-somepatientspreferlessfrequent dosingy Acutesideeffects:nausea, dizziness, somnolence


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Dopamine Agonists: Guidelines in Early PD

y Effectiveas monotherapyy Lesssymptomatic benefit thanlevodopay Maydelayneedforlevodopaapprox. 12 months

dataup to >3 yearshas beenpresentedy Start lowandincreaseslowlyy Titrate toefficacy-bromocriptine7.5-30 mg/day-pergolide1.5-4.5 mg/day-pramipexole1.5-4.5 mg/day-ropinirole 3-24 mg/dayy Acute SEs:nausea, dizziness, somnolence, confusion


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Dopamine Agonists:Adjunctive Use with L-

dopa

y Bromocriptine, pergolide, pramipexole, ropinirole

y Agonist choiceis moreart thanscience

y Reducelevodopadosagewhenadding theagonist

y Failureofonedoesnot predict failureofanother

y Agonists maybeswitchedeithergraduallyorrapidlytoacomparabledosage


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Managing Early Complications:

AlteredMental States

y Confusion, sedation, dizziness, hallucinations,delusions

y

ReduceoreliminateC

NS-activedrugsoflesserpriorityanticholinergics sedatives

amantadine musclerelaxants

hypnotics urinaryspasmodics

y ReducedosageofDA, COMT inhibitor, or LD


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Late Complications

y Motor

-responsefluctuations, dyskinesias, dystonia, freezing,falls

y Behavioral/neuropsychological

-depression, sleepdisorders, psychosis

y Autonomic

-orthostatichypotension;hyperhidrosis, constipation,impotence, urinaryincontinenceorretention


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LD Response Fluctuationsy Peripheralcauses:

-delayedgastricemptying

-dietaryprotein

-short plasmahalf-life

y Centralcauses:

-pulsatiledeliverytostriatalreceptors

-impairedstoragecapacity-alterationofDAreceptors


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Response Fluctuations: Treatment

y Increase LD dose

y Increase DCI dose

y

Adddopamineagonisty AddCOMT inhibitor

-reduce LD

-liverfunction monitoring

y Apomorphinerescue


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Cognitive Assessment

y Memorydifficulties:11-29%ofPD patients

-Benignforgetfulness

-Delirium

-Alzheimersdisease-Otherdementias

y Evaluation

-Brainimaging

-Lumbarpuncture-EEG

-Bloodworkfor thyroidprofile, vitaminB12, serology,chemistrypanel


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Psychosis

y Features Vividdreams/nightmares, disorientation,hallucinations, delusional thought

y Simplifymedicalregimen Stopunnecessarynon-PD meds Stop:anticholinergicdrugs, amantadine,selegiline, dopamineagonists, COMT inhibitors

y Changefrom CR tostandard

carbidopa/levodopay Tryatypicalantipsychoticagentsy Trylow-potencytraditionalantipsychotic

agents


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Anti-psychotic Agents

y Molindonelow-potencyneuroleptic; mayaggravate PD symptoms, but cansometimesuse5-10 mgat HS

y Risperidone

D3 antagonist; D1/D2 agonist;aggravates PD at doses > 3 mg/d.y Olanzapine

D4 antagonist. D1/D2 inhibition > 10 mg/dy Quetiapine5-HT1-2 antagonist. Dosage 25 - 500 mg/d

y ClozapineD4 antagonist;noconfirmedaggravationofPD orcausationofTDFatalagranulocytosisin 9 patients;weeklyCBC


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Depression

y Reportedin 30-90%ofPD patients

y Difficult todiscernfrom vegetativesymptoms

y Requiresinquiryintodepressionsymptoms

y Usuallyrespondsquicklyto medications

Tricyclicagents

Selectiveserotoninre-uptakeinhibitors

y

IfEC

T needed, will transientlyimprove PD symptoms


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Anxiety/Restlessness

y Primaryanxietydisorder: treat with benzodiazepines

-Associatedwith off-periodsorlow-levodopalevels:

adjust levodopadosingy Restless Leg Syndrome: benzodiazepines, narcotics,

levodopa, dopamineagonists


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Sleep Disorders

y Insomnia

-carefulhistory

-difficultywithsleepinitiation: tricyclicagents,

benzodiazepines, diphenhydramine, chloralhydrate- treat depression

-REM-behavioraldisorder:clonazepam

y Excessivedaytimesleepiness

-Correct poorsleepat night-Discontinueanticholinergics, amantadine

-Reducedopamineagonist, levodopadosagesifpossible

-selegeline;caffeine; methylphenidate5-20 mgs/d


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Orthostatic Hypotension

y Light-headedness, dizziness, fatigue, shoulderorneckpain, bloodpressuredropswhenstanding

y Taperanti-hypertensiveagents

y Tapernon-PD drugsy Increasesalt intake

y Compressionstockings

y Fludrocortisone (0.1-0.4 mg/d)

y Midodrine (2.5 - 20 mg/d)


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Urinary Incontinence/Frequencyy Ruleout urinarytract infection

y Bladderevaluationfor

-detrusorhyperactivity

oxybutinin5 -30 mg/d;propanthaline7.5 - 15 mg/d

-detrusorhypoactivity

phenoxybenzamine;prazosin

y

Urinaryfrequency-avoidfluidpoolinginfeet

-DDAVP inhaler; tolterodine tartrate 2mghs to 2mg tid


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Sexual Dysfunction

y Medicalscreening

-depression, anxiety, iatrogeniccauses

y

Endocrinologicevaluation-prolactin, testosterone, lutenizinghormone, thyroidscreen

y Urologicevaluation

-yohimbine, sildenafil


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Nausea

y Levodopa-related: takewith meals, addcarbidopa, adddomperidone

y Otheranti-PD medications:same.

-Ifnoimprovement:withdrawnewest agent, re-initiateat minimaldoses, slowlyincrease


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Excessive Sweating

y Usuallylevodoparelated, and maybeseenat peakortroughdosedruglevels

-reducelevodopa

-adddopamineagonist orCOMT inhibitor

-addcarbidopa

-addBeta-blocker

The Surgical Treatment of Parkinsons


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The Surgical Treatment of Parkinsons

Disease

y Ablative

-thalamotomy

-pallidotomyy Electricalstimulation

-VIM thalamus, globuspallidusinternus, sub-thalamicnucleus

y Transplant-autologousadrenal, humanfetal, xenotransplants,geneticallyengineered transplants


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Deep Brain Stimulation (DBS)

y Highfrequency, pulsatile, bipolarelectricalstimulation

y Stereotacticallyplacedinto target nucleus

y Can beactivatedanddeactivatedwithanexternalmagnet

y Exact physiologyunknown, but higherfrequencies

mimiccellularablation, not stimulation


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Adjustable Features

y Voltage (1-7volts)

y Pulsewidth (65-450 msec)

y

Frequency(130-180Hz)y Polarity

y Leadlocation (4 leads, each1.5 mm apart)


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Cell Transplants

y Autologousadrenal transplants

-Noefficacy

y Allogenichumanfetal transplants

-Initialencouragingclinicalresults

y Xenogenicfetal transplant (porcineand bovine)

-Preliminaryresultspending

y

Geneticallyengineeredcells-Researchongoing


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Human Fetal Transplants

y Efficacy

-Encouragingpreliminaryresultsinyoung PD pts

-PET studiesconsistent withcellfunctioning

-Autopsies (2)showcellsurvival

y Problems

-4-10embryos


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Problems That May Respond to


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Problems That May Respond to

Nonpharmacological Approaches

y ADL difficultiesy Motor, balance, posture, gait, mobilityy Speechandswallowing:hypophonia,

sialorrhea, dysphagiay Inadequatenutritiony Sleepdisturbancey Autonomicdysfunction:painandconstipationy Skin breakdowny Sexualdysfunctiony Depression


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Nonpharmacologic Treatments

y Patient/caregivereducation

y Physical therapy

y Exercise

y Occupational therapy

y Speech/language therapy

y Diet andnutrition

y Psychosocialinterventions


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Physical Therapy: Goals

y Maintainorincreaseactivitylevel

y Decreaserigidityand bradykinesia

y

Facilitate movement andflexibility;optimizegaity Maximizegross motorcoordinationand balance

y Maximizeindependence, safety, function


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Physical Therapy: Features

y Exercise:e.g., walking (1+ mile/day), swimming, golf,dancing

y Stretchingandstrengthening

y Exaggeratedorpatterned movements

y highstepping, weight shifting, repetition, verbalcues

y Mobilityaids, orthotics, adaptivefootwear

y Transfer techniques


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Occupational Therapy: Features

y Patient andcaregivereducation

goalsofprogram

transfers, tasksimplification, positioning, etc.y Homeexerciseprogram

y Homeandworkplace modifications

y Adaptiveequipment

y Upperextremitysplinting

Adaptive Equipment and


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Adaptive Equipment and

Environmental Modifications

y Customizefordisability, budgety Seating:wheelchairs, cushions, lateralsupports,

etc.y Toilet andhygeine: tub/showerseat, grab bars,etc.

y Feeding:wide-handledutensils, sipcups, etc.y Clothing:velcro, pullovers, shoehorns, etc.y Bed:rails, hospital bed, trapeze, etc.y Equipment: bookholders, large-buttonphone,

keyholders, etc.y Considerdoorsills, throwrugs, otherobstructions


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Speech and Communication Problems

y Maybeoneofthefirst symptomsofPD

y Characterized by:

-soft voiceandimprecisearticulation

-burstsofrapidspeechalternatingwithperiodsofsilence

-lossofinflection

y Can besignificant foremployment

y Dyskinesias mayworsen


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Speech-Language TherapyOptions

y Oftenunderutilized

y Earlytherapyespeciallyeffective

y

At-homeexercises; modificationofdailyactivitiesy Emphasisoncontrolofrespirationandvoice

production

y Amplificationdevicesrarelyuseful


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Techniques to Improve Speech

y Increaseloudness

y Face thelistenerdirectly

y Emphasizekeywords

y Useshort sentences

y Range-of-motionexercisesfor musclesofspeech

y Breathingexercises

y Attendspeech therapy


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Nutritional Risk Factors

y Inactivity

y Foodpreparationproblems

y

Dyskinesiaandfeedingproblemsy Chewingandswallowingproblems

y Increased metabolicneeds

y Medication-relateddietaryrestrictions

y Drugsideeffects:anorexia, nausea, vomiting,constipation

y Depressionanddementia


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Dietary Recommendations

y Eat a balancediet, includingallfoodgroups

y Consumesufficient calories to maintainweight

y C

onsumeadequatefiberandfluids toavoidconstipation

y Takevitamin D andcalcium toprevent osteoporosis

y Reduceprotein to minimum dailyallowance

-concentrateinevening meal


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Miscellaneous Concerns

y Seborrheicdermatitis

-shampoosorlotionswithketoconazole, selenium,pyrithionezinc

y Driving

-assessregularlyforreactionspeed, judgment, mentalstatus

-retakedrivers test


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Education, Support and Counseling

y Patient/caregivereducation:newsletters,Webresources

y Support groups:patient, caregivers

-maybeappropriate towait fordisabilityprogression

-early-onset patients maydesireseparategroup

y Counseling

-bothpatient andcaregiver/family;assessneedsseparately

-anxiety, grief, guilt, anger, isolation, depression


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Community Resources

y Socialworkerintervention:

Social Securityoffice

Medicare, Medicaidy In-homeprograms

MealsonWheels, homevisiting, etc.


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Epidemiologyy Onset is typicallybetween theagesof25and 45years

(range 370years)withaprevalenceoftwo toeightcasesper100,000.


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Etiologyy HD iscaused byanincreasein thenumberof

polyglutamine (CAG)repeats (>40)in thecodingsequenceoftheHuntingtongenelocatedon theshort arm ofchromosome 4. Thegeneencodes thehighlyconservedcytoplasmicproteinhuntingtin.

y Intraneuronalinclusionscontainingaggregatesof

ubiquitinand the mutant proteinhuntingtinarefoundinnucleiofneuronsin thestriatum andcerebralcortex.


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PATHOLOGY AND PATHOGENESISy Impairedglucose metabolism in thecaudatenucleus,

precedingvisibleatrophy

y excessofdopamine (incontrast to Parkinsondisease)

y disturbancesin the metabolism ofotherneurotransmitters (norepinephrine, glutamicaciddecarboxylase, cholineacetyltransferase, GABA,acetylcholine, andsomatostatin)


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CLINICAL FEATURESy The mentaldisorderassumesseveralsubtleformslong

before the moreobviousdeteriorationofcognitivefunctions becomesevident. Inapproximatelyhalfthe

cases, slight andoftenannoyingalterationsofcharacterare thefirst toappear. Patients begin tofindfault witheverything, tocomplainconstantly, and tonagother membersofthefamily


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CLINICAL FEATURESy Theabnormality of movement isat first slight and

most evident in thehandsandface;often thepatient ismerelyconsidered to befidgety, restless, or "nervous."

Slownessofmovement ofthefingersandhands, areducedrateoffinger tapping, anddifficultyinperformingasequenceofhand movementsareearlymotorsigns. Graduallytheseabnormalities becomemorepronounceduntil theentire musculatureis

implicatedwithchorea.


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Diagnosisy It isnowpossible toconfirm orexclude thediagnosis

byanalysisofDNAfrom a bloodsample. Thepresenceofgreater than 39 to 42 CAG repeatsat theHuntington

locusessentiallyconfirmsitspresence


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Huntington's Disease: Treatmenty Treatment involvesa multidisciplinaryapproachwith

medical, neuropsychiatric, social, andgeneticcounselingforpatientsand theirfamilies


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Huntington's Disease: Treatmenty Dopamine-blockingagents maycontrol thechorea but

aregenerallynot recommended becauseoftheirside-effect profileandpotential toaggravate motor

symptoms, and because thechorea tends to beself-limitedandisusuallynot disabling.


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Huntington's Disease: Treatmenty Depressionandanxietycan begreaterproblems, and

patientsshould be treatedwithappropriateantidepressant andantianxietydrugsand monitored

for maniaandsuicidalideations.y Psychosiscan be treatedwithatypicalneuroleptics

suchasclozapine (50600 mg/d), quetiapine (50600mg/d), andrisperidone (28 mg/d)


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Huntington's Disease: Treatmenty Thereisnoadequate treatment for thecognitiveor

motordecline. Aneuroprotective therapythat slowsorstopsdiseaseprogressionis the majorunmet medical

needinHD. Antiglutamateagents, bioenergetics,caspaseinhibitors, inhibitorsofproteinaggregation,intracerebraldeliveryofneurotrophicfactors, andtransplantationoffetalstriatalcellsareallareasofactiveresearch, but nonehasasyet been

demonstrated tohaveadisease-modifyingeffect.

Documents

Movement Disorders - Overview-1