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Parkinson Disease Consensus
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2012 Consensus Guidelines
for the Treatment of
Parkinsons Disease
Authors note
4HIS 'UIDELINE WRITTEN BY CLINICIANS EXPERIENCED IN THE MANAGEMENT OF 0ARKINSONS DISEASE 0$
IS INTENDED TO PROVIDE A BRIEF BUT UP
TO
DATE FRAMEWORK FOR DOCTORS INVOLVED IN THE CARE OF PATIENTS
WITH 0$ INCLUDING BUT NOT LIMITED TO GENERAL PRACTITIONERS HOSPITAL MEDICAL OFFICERS PHYSICIANS
GERIATRICIANS REHABILITATION MEDICINE SPECIALISTS PSYCHIATRISTS AND NEUROLOGISTS
3INCE THE PUBLICATION OF THE ORIGINAL h#ONSENSUS ON THE -ANAGEMENT OF 0$v IN SUBSTANTIAL
DEVELOPMENTS HAVE TAKEN PLACE AND THE OPTIMAL MANAGEMENT OF 0$ CONTINUES TO EVOLVE 4HE
CURRENT GUIDELINES HAVE BEEN COMPLETELY REWRITTEN TO REFLECT THESE CHANGES &OR THE READER REQUIRING
MORE IN
DEPTH INFORMATION WE HAVE ALSO CAREFULLY COMPILED A SELECTIVE LIST OF USEFUL REFERENCES FOR
FURTHER READING
!N IMPORTANT DEVELOPMENT HAS BEEN THE INCREASING ROLE THAT EVIDENCE
BASED MEDICINE %"-
PLAYS IN THE PRACTICE OF CLINICAL MEDICINE 4HE RECOMMENDATIONS ADOPTED BY THESE GUIDELINES ARE IN
LINE WITH THIS ADVANCE .EVERTHELESS IT NEEDS TO BE EMPHASIZED THAT THERAPEUTIC RECOMMENDATIONS
SHOULD ALWAYS BE TAILORED TO THE INDIVIDUAL PATIENT BASED NOT ONLY ON AN ACCURATE UNDERSTANDING
OF THE EFFICACY AND SIDE EFFECT PROFILE OF AVAILABLE TREATMENTS THE PRIMARY FOCUS OF GUIDELINES BUT
ALSO THE PHYSICIANS JUDGMENT PATIENT PREFERENCE AND ECONOMIC DETERMINANTS &OR EXAMPLE SOME
TREATMENTS MAY NOT BE AVAILABLE IN LOW
RESOURCE SETTINGS EVEN IF THEIR USEFULNESS IS WELL ESTABLISHED
BY NOW %VEN IN URBAN CENTRES THE COST OF CERTAIN TREATMENTS REMAINS A LIMITING FACTOR AND MANY
PATIENTS WHO MIGHT OTHERWISE BENEFIT FOR EXAMPLE FROM DEEP BRAIN STIMULATION SURGERY OR
INFUSIONAL TREATMENTS ARE CURRENTLY UNABLE TO AFFORD THESE TREATMENTS
!NOTHER DEVELOPMENT HAS BEEN THE ESTABLISHMENT OF THE -OVEMENT $ISORDERS #OUNCIL -$#
UNDER THE AUSPICES OF THE -ALAYSIAN 3OCIETY OF .EUROSCIENCES IN &EBRUARY 4HE -$#
REPRESENTS CLINICIANS NEUROLOGISTS WITH A SPECIAL INTEREST IN 0$ AND OTHER MOVEMENT DISORDERS
AND WAS RECOGNIZED BY THE INTERNATIONAL -OVEMENT $ISORDER 3OCIETY IN AS AN OFFICIAL
!FFILIATE -EMBER 5NDER THE ABLE LEADERSHIP OF 0ROF $ATIN $R .ORLINAH -OHD )BRAHIM THE
INAUGURAL #HAIRPERSON THE -$# HAS IN A RELATIVELY SHORT SPACE OF TIME STAGED SEVERAL SUCCESSFUL
PROGRAMS 4HIS 'UIDELINE IS ONE SUCH INITIATIVE
4HERE IS NO DOUBT THAT SINCE THE INTRODUCTION OF LEVODOPA INTO CLINICAL USE FORTY
PLUS YEARS AGO THE
LIFE EXPECTANCY AND JUST AS IMPORTANTLY THE QUALITY OF LIFE OF PATIENTS WITH 0$ HAVE IMPROVED
CONSIDERABLY )T IS OUR SINCERE HOPE THAT THE SITUATION FOR 0$ PATIENTS IN -ALAYSIA WILL CONTINUE TO
SEE PROGRESS IN THE COMING YEARS !S MEMBERS OF THE -$# WE UNDERTAKE TO ADVANCE THIS AGENDA
TO THE BEST OF OUR ABILITY SO THAT PATIENTS WITH 0$ CAN CONTINUE TO LEAD FULFILLING AND REWARDING
LIVES FOR THE LONGEST TIME POSSIBLE
4HANK YOU BEST WISHES
Prof. Dr. LIM Shen-Yang
ON BEHALF OF ALL CO AUTHORS
From the Movement Disorders Council, Malaysian Society of Neurosciences
Project Leader/Lead author:
s Prof. Dr. Lim Shen-Yang
MBBS (Melbourne), MD (Melbourne), FRACP (Aust), Fellowships in Movement Disorders (Melbourne & Toronto)
#ONSULTANT .EUROLOGIST 0ARKINSONS $ISEASE-OVEMENT $ISORDERS 3PECIALIST $IVISION OF .EUROLOGY
5NIVERSITY OF -ALAYA +UALA ,UMPUR
Co-authors:
s Prof. Datin Dr. Norlinah Mohd. Ibrahim
MBBCH, BAO, BMedSci, MRCP, Fellowship in Movement Disorders (London)
#ONSULTANT .EUROLOGIST AND (EAD OF .EUROLOGY 5NIT 5NIVERSITI +EBANGSAAN -ALAYSIA +UALA ,UMPUR
s Dr. Santhi Datuk Puvanarajah
MBBS (Madras), MRCP (UK), AM (Malaysia)
#ONSULTANT .EUROLOGIST $EPARTMENT OF .EUROLOGY +UALA ,UMPUR (OSPITAL +UALA ,UMPUR
s Dr. Lee Moon Keen
MBBS (Malaya), Dip Clin Neurology (London), FRCP (Edinburgh), FAM (Malaysia)
#ONSULTANT .EUROLOGIST 3UNWAY -EDICAL #ENTRE 3ELANGOR
s Dr. Chee Kok Yoon
MD (USM), MMed(Psych) (Malaysia), Fellowship in Neuropsychiatry (Melbourne)
.EUROPSYCHIATRIST $EPARTMENT OF 0SYCHIATRY AND -ENTAL (EALTH +UALA ,UMPUR (OSPITAL +UALA ,UMPUR
s Dr. Shanthi Viswanathan
MBBS (India), MRCP (Ireland), Fellowship in Neurology (Malaysia)
#ONSULTANT .EUROLOGIST $EPARTMENT OF .EUROLOGY +UALA ,UMPUR (OSPITAL +UALA ,UMPUR
s Dr. Tan Ai Huey
MD (UKM), MRCP (UK)
.EUROLOGY 2EGISTRAR $IVISION OF .EUROLOGY 5NIVERSITY OF -ALAYA -EDICAL #ENTRE +UALA ,UMPUR
s Dr. Chris Chong Kang Tird
MD (UKM), MRCP (UK), Fellowship in Movement Disorders (Monash)
#ONSULTANT .EUROLOGIST 3ABAH -EDICAL #ENTRE (EALTHCARE +OTA +INABALU
s Assoc. Prof. Dr. Kamal Azrin Bin Abdullah @ Kalai Arasu A/L Muthusamy
MBBS (Malaya), MSurg (Malaya), DPhil (Oxon)
#ONSULTANT .EUROSURGEON -OVEMENT $ISORDERS &UNCTIONAL .EUROSURGERY $EPARTMENT OF 3URGERY
5NIVERSITY OF -ALAYA +UALA ,UMPUR
External Reviewers:
s Prof. Emeritus Dr. Niall Quinn MA, MD (Cantab), FRCP (UK), FAAN
.ATIONAL (OSPITAL FOR .EUROLOGY AND .EUROSURGERY 1UEEN 3QUARE ,ONDON
s Assoc. Prof. Dr. Susan H. Fox BSc, MBChB, MRCP (UK), PhD
$IVISION OF .EUROLOGY 4ORONTO 7ESTERN (OSPITAL 4ORONTO
Acknowledgments:
s Ms. Loh Hui Pin 3ECRETARIAT -OVEMENT $ISORDERS #OUNCIL FOR PROVIDING INVALUABLE ADMINISTRATIVE SUPPORT
SINCE THE INCEPTION OF THE #OUNCIL
s Mr. Yap Kian Yong AND Mr. Calvin Kuan #EMERLANG +ASIH 3DN "HD FOR ARTWORK AND DESIGN
1. Introduction - What is Parkinsons disease (PD)?
s 0$ IS A degenerative disease OF THE NERVOUS SYSTEM AFFECTING PRIMARILY THE
BRAIN BUT ALSO OTHER STRUCTURES SUCH AS THE PERIPHERAL AUTONOMIC NERVOUS
SYSTEM
s 0$ IS MORE COMMON IN older PEOPLE AFFECTING ABOUT OF PEOPLE OVER THE
AGE OF BUT YOUNGER INDIVIDUALS CAN ALSO BE AFFECTED )T IS SLIGHTLY MORE
COMMON IN MEN THAN WOMEN
s 4HE COMMON motor PROBLEMS OF 0$ ARE REST TREMOR ALTHOUGH THIS IS NOT
PRESENT IN ALL PATIENTS BRADYKINESIA AND MUSCLE RIGIDITY 4HE DIAGNOSIS OF 0$
IS BASED ON THE PRESENCE OF THESE MOTOR PROBLEMS 4HE BRADYKINESIA OF 0$ IS
OFTEN DESCRIBED BY PATIENTS AS A hWEAKNESSv OF A HAND OR LEG BUT STRENGTH
TESTING REVEALS NO ABNORMALITIES )MBALANCE POSTURAL INSTABILITY WITH FALLS
OCCURS ONLY IN THE LATER STAGES OF THE DISEASE -OST PATIENTS WITH EARLY STAGE
0$ EXPERIENCE MOTOR SYMPTOMS ON ONLY ONE SIDE OF THE BODY (OWEVER
IT SOON SPREADS TO THE OTHER SIDE BUT TYPICALLY REMAINS asymmetric THROUGHOUT
THE DISEASE COURSE
s Non-motor symptoms ALSO OCCUR FREQUENTLY 3OME EXAMPLES INCLUDE
FATIGUE ANXIETY DEPRESSION SLOWNESS OF THINKING DIFFICULTY CONCENTRATING
VISUAL HALLUCINATIONS PAIN OR PARAESTHESIAS CONSTIPATION URINARY FREQUENCY
OR URGENCY POSTURAL LIGHTHEADEDNESS EXCESSIVE SWEATING AND SLEEP DISTURBANCES
EG DREAM ENACTING BEHAVIOURS WITH SHOUTING OR KICKING DURING SLEEP OR
EXCESSIVE SLEEPINESS DURING THE DAY )N SOME PATIENTS NON MOTOR SYMPTOMS
SUCH AS HYPOSMIA 2%- SLEEP BEHAVIOR 2"$ CONSTIPATION AND DEPRESSION
HAVE BEEN FOUND TO PRECEDE MOTOR SYMPTOMS OF 0$
s ! LACK OF THE NEUROTRANSMITTER dopamine IN THE BRAIN IS THE CAUSE OF THE
MOTOR AND POSSIBLY SOME NON MOTOR PROBLEMS IN 0$ (OWEVER THE
UNDERLYING REASON WHY PEOPLE DEVELOP 0$ IS STILL NOT FULLY UNDERSTOOD
HENCE THE TERM hIDIOPATHICv 0$
Contents
)NTRODUCTION
7HAT IS 0ARKINSONS DISEASE
$IAGNOSIS OF 0ARKINSONS DISEASE
)NITIATION OF ANTIPARKINSONIAN MEDICATION
7HEN AND
WHAT TO START
0OTENTIAL SIDE EFFECTS OF ANTIPARKINSONIAN MEDICATIONS
-OTOR RESPONSE COMPLICATIONS MOTOR FLUCTUATIONS
DYSKINESIA
7HAT ARE THEY
13
15
4REATMENT OF MOTOR FLUCTUATIONS DYSKINESIA
!DVANCED THERAPIES FOR DISABLING MOTOR RESPONSE
COMPLICATIONS
18
4HE NON MOTOR SYMPTOMS OF 0ARKINSONS DISEASE
24
20
Appendices
s !PPENDIX
0$ DRUG IDENTIFICATION CHART
s !PPENDIX
0ATIENT DIARY FOR MOTOR FLUCTUATIONS AND
DYSKINESIA
29
31
2. Diagnosis of Parkinsons disease
Diagnosing Parkinsons disease. 0$ IS BY FAR THE COMMONEST CAUSE OF
PARKINSONISM IE A CONSTELLATION OF CLINICAL MANIFESTATIONS INCLUDING BRADYKINESIA
RIGIDITY AND TREMOR 4HE DIAGNOSIS OF 0$ IS BASED ON THE HISTORY AND A CAREFUL
NEUROLOGIC EXAMINATION 4O DATE NO SINGLE TEST HAS BEEN SHOWN TO HAVE
SUFFICIENT SENSITIVITY AND SPECIFICITY TO RELIABLY DIAGNOSE 0$ OR DISTINGUISH 0$
FROM OTHER FORMS OF PARKINSONISM
)N MOST PATIENTS THE DIAGNOSIS IS STRAIGHTFORWARD EG ONSET OF ASYMMETRIC
PARKINSONISM INCLUDING REST TREMOR IN AN INDIVIDUAL IN HIS S OR S WITH A
ROBUST RESPONSE TO DOPAMINERGIC MEDICATION TREATMENT #ERTAIN NON MOTOR
FEATURES SUCH AS HYPOSMIA 2%- SLEEP BEHAVIOR 2"$ OR CONSTIPATION ARE
NON SPECIFIC BUT IN THE APPROPRIATE CONTEXT THE PRESENCE OF THESE FEATURES MAY
LEND FURTHER SUPPORT TO THE DIAGNOSIS
)N A TYPICAL CASE FURTHER INVESTIGATIONS INCLUDING BRAIN IMAGING ARE SELDOM
NECESSARY9
(OWEVER 0$ IS A HETEROGENEOUS DISORDER WITH CLINICAL PRESENTATION VARYING
SUBSTANTIALLY FROM PATIENT TO PATIENT AND OCCASIONALLY IT IS DIFFICULT TO BE
CERTAIN WHETHER A PATIENT HAS 0$ ESPECIALLY EARLY IN THE DISEASE 3OME
DIFFERENTIAL DIAGNOSES THAT ARE REGULARLY ENCOUNTERED IN CLINICAL PRACTICE ARE
DESCRIBED IN 4ABLE
Table 1. $IFFERENTIAL DIAGNOSES OF 0ARKINSONS DISEASE
4HESE -2) ABNORMALITIES ARE
QUITE HIGHLY SPECIFIC FOR -3! 030 BUT SENSITIVITY IS ONLY AROUND
Disorder
Characteristic features
%SSENTIAL
TREMOR
0REDOMINANTLY UPPER LIMB ACTION TREMOR WHICH IS TYPICALLY SYMMETRIC
(EAD AND VOICE MAY ALSO BE AFFECTED 4HERE ARE USUALLY NO OTHER NEUROLOGIC
DEFICITS 4HERE MAY BE A POSITIVE FAMILY HISTORY AND TREMOR MAY IMPROVE
WITH INGESTION OF ALCOHOL
$YSTONIC TREMOR
$YSTONIC POSTURING EG OF THE HANDS WHEN HELD IN A CERTAIN POSITION MAY
BE EVIDENT 4HIS DIAGNOSIS IS OFTEN DIFFICULT TO MAKE
s "OTH GENETIC FACTORS AS WELL AS PROBABLE ENVIRONMENTAL FACTORS CONTRIBUTE TO
THE RISK OF DEVELOPING 0$ (OWEVER ONLY
OF PATIENTS HAVE OTHER
FAMILY MEMBERS ALSO AFFECTED BY THE DISEASE WHICH IS WHY 0$ IS USUALLY
REGARDED AS A sporadic RATHER THAN A FAMILIAL CONDITION
s 4HERE IS no test DURING LIFE CURRENTLY THAT CAN DEFINITELY IDENTIFY 0$ )NSTEAD
THE DIAGNOSIS OF 0$ IS BASED ON THE HISTORY AND A CAREFUL NEUROLOGIC EXAMINATION
4HERE ARE OTHER DISORDERS THAT CAN MIMIC 0$ AND INVESTIGATIONS MAY BE NEEDED
IN SOME PATIENTS EG THOSE WITH ONSET OF SYMPTOMS BELOW THE AGE OF
YEARS OR IF ATYPICAL FEATURES ARE PRESENT TO EXCLUDE SOME OF THESE CONDITIONS
EG 7ILSONS DISEASE
s 4HERE IS CURRENTLY no cure OR PREVENTION FOR 0$ AND THE DISEASE worsens
gradually OVER YEARS .EVERTHELESS MOTOR SYMPTOMS CAN OFTEN BE well controlled
WITH TREATMENT ESPECIALLY IN THE EARLIER STAGES OF THE DISEASE !T PRESENT THESE
TREATMENTS ARE MAINLY BASED ON restoring dopaminergic STIMULATION IN THE
BRAIN 4HERE ARE ALSO EFFECTIVE TREATMENTS FOR SOME OF THE NON
MOTOR SYMPTOMS
OF 0$
s 0$ AFFECTS EVERYONE DIFFERENTLY AND TREATMENTS NEED TO BE tailored TO THE
INDIVIDUAL 4HE BENEFITS OF TREATMENTS NEED TO BE BALANCED AGAINST THEIR
POTENTIAL SIDE EFFECTS 2EFERRAL TO A PHYSICIAN EG NEUROLOGIST WITH A SPECIAL
INTEREST IN 0$ IS RECOMMENDED
)NVESTIGATIONS SHOULD USUALLY BE PERFORMED IF THESE ALTERNATIVE DIAGNOSES ARE
BEING CONSIDERED .EUROIMAGING SHOULD BE OBTAINED IN THOSE WITH ONSET OF
PARKINSONISM BELOW THE AGE OF YEARS OR IF THERE ARE ATYPICAL FEATURES Brain
MRI WHICH IS NORMAL IN 0$ HAS SUBSTANTIALLY GREATER DIFFERENTIAL DIAGNOSTIC
POTENTIAL IN PARKINSONIAN DISORDERS COMPARED TO #4 AND IS PREFERRED
&UNCTIONAL IMAGING POSITRON EMISSION TOMOGRAPHY ;0%4= OR SINGLE
PHOTON
EMISSION COMPUTED TOMOGRAPHY ;30%#4= SCANNING TO ASSESS THE
INTEGRITY OF THE DOPAMINERGIC NIGROSTRIATAL SYSTEM IS NOT WIDELY AVAILABLE AND
IS ALSO NOT SPECIFIC FOR 0$ AS NIGROSTRIATAL DENERVATION ALSO OCCURS IN -3!
AND 030
Staging the severity of PD. 4HE MOST WIDELY USED RATING SCALES TO STAGE THE
SEVERITY OF 0$ ARE THE Hoehn and Yahr (H&Y) stage 4ABLE AND THE
5NIFIED 0$ 2ATING 3CALE 50$23 (9 STAGING IS BRIEFER AND CAN BE
ADMINISTERED IN A FEW MINUTES 4HE MOTOR PART ))) SECTION OF THE 50$23
ASSESSES ITEMS AND TAKES APPROXIMATELY
MINUTES TO ADMINISTER )N
PATIENTS WITH MOTOR FLUCTUATIONS SEE SECTION ON -OTOR RESPONSE COMPLICATIONS
BELOW IT IS IMPORTANT TO CONSIDER THE PATIENTS medication status WHETHER
HE IS h/.v h/&&v OR hSEMI
/.v WHEN ASSESSING MOTOR FUNCTION FOR
EXAMPLE A PATIENT WITH SEVERE FLUCTUATIONS MAY BE (9 STAGE WHEN
h/&&v BUT (9 STAGE WHEN MEDICATION HAS TAKEN FULL EFFECT )T IS IMPORTANT
TO CONSIDER THAT SOMETIMES NON
MOTOR FEATURES EG DEMENTIA MAY HAVE AS
MUCH OR EVEN MORE IMPACT THAN MOTOR FUNCTION ON THE 0$ PATIENTS FUNCTIONAL
STATUS AND QUALITY OF LIFE
Table 2. (OEHN 9AHR STAGING OF 0ARKINSONS DISEASE MOTOR SEVERITY
Hoehn & Yahr stage
Description
5NILATERAL INVOLVEMENT ONLY USUALLY WITH MINIMAL OR NO
FUNCTIONAL DISABILITY
"ILATERAL OR MIDLINE INVOLVEMENT WITHOUT IMPAIRMENT OF BALANCE
"ILATERAL DISEASE; MILD TO MODERATE DISABILITY WITH IMPAIRED
POSTURAL REFLEXES; PHYSICALLY INDEPENDENT
3EVERELY DISABLING DISEASE; STILL ABLE TO WALK OR STAND UNASSISTED
#ONFINEMENT TO BED OR WHEELCHAIR UNLESS AIDED
5
Disorder
$RUG
INDUCED
PARKINSONISM3
#LINICALLY THIS CONDITION MAY APPEAR IDENTICAL TO 0$ EG PRESENTING WITH
UNILATERAL REST TREMOR ! CAREFUL DRUG HISTORY TO EXCLUDE EXPOSURE WITHIN
THE LAST YEAR TO DOPAMINE RECEPTOR BLOCKERS MOST COMMONLY ANTI
PSYCHOTICS OR ANTI EMETICS SUCH AS METOCLOPRAMIDE OR PROCHLORPERAZINE IS
THEREFORE ESSENTIAL
7ILSONS
DISEASE 5
/NSET OF NEUROLOGIC 7ILSONS DISEASE IS USUALLY IN CHILDHOOD OR YOUNG
ADULTHOOD 0ATIENTS MAY PRESENT WITH TREMOR PARKINSONISM ANDOR
DYSTONIA As a general rule, patients presenting with movement
disorders below age 50 should undergo tests to rule out this condition.
0SYCHIATRIC MANIFESTATIONS ARE COMMON INCLUDING BEHAVIOURAL CHANGES
ANXIETY AND PSYCHOSIS )NVESTIGATIONS INCLUDE BRAIN -2) ABNORMAL IN 9
OF CASES; A VARIETY OF ABNORMALITIES MAY BE SEEN EG 4 HYPERINTENSITY OF
THE BASAL GANGLIA SLIT LAMP EXAMINATION BY AN OPHTHALMOLOGIST +AYSER
&LEISCHER RINGS IN ALMOST ALL CASES SERUM CAERULOPLASMIN USUALLY pp AND
HOUR URINARY COPPER USUALLY n
-ANY EXPERTS NOW VIEW THIS DISORDER AS BEING ON A SPECTRUM WITH 0$ )N
0$ DEMENTIA AND VISUAL HALLUCINATIONS ARE TYPICALLY LATE FEATURES WHEREAS
IN $," THESE ARE PRESENT EARLY IN THE DISEASE COURSE PRECEDING OR OCCURRING
WITHIN A YEAR OF MOTOR SYMPTOM ONSET
$EMENTIA WITH
,EWY BODIES
Characteristic features
-ULTIPLE SYSTEM
ATROPHY7 8
4HE MOTOR PROBLEM MAY BE PREDOMINANTLY PARKINSONISM -3! 0 OR
CEREBELLAR EG GAIT OR LIMB ATAXIA -3! # 3IGNIFICANT AUTONOMIC
DYSFUNCTION EG URINARY INCONTINENCE OR SEVERE ORTHOSTATIC HYPOTENSION IS
USUALLY PRESENT 0ATIENTS MAY HAVE SIGNIFICANT DYSARTHRIADYSPHAGIA EARLY IN
THE DISEASE COURSE 5PPER MOTOR NEURON SIGNS EG HYPER REFLEXIA OR
EXTENSOR PLANTAR RESPONSES MAY BE PRESENT "RAIN -2) MAY SHOW CEREBELLAR
OR BRAINSTEM ATROPHY hHOT CROSS BUNv SIGN PUTAMINAL RIM 4 HYPERINTENSITY
ETC
0ROGRESSIVE
SUPRANUCLEAR
PALSY 9
#HARACTERIZED BY VERTICAL GAZE DEFICITS RESTRICTION OR IN EARLIER STAGES
SLOWING OF DOWN SACCADES &ALLS ARE USUALLY AN EARLY FEATURE WITHIN THE ST
YEAR OF SYMPTOM ONSET -AY HAVE AXIAL NECK > LIMB RIGIDITY 0ATIENTS MAY
HAVE SIGNIFICANT DYSARTHRIADYSPHAGIA EARLY IN THE DISEASE COURSE "RAIN -2)
MAY SHOW MIDBRAIN ATROPHY EG hHUMMINGBIRDv SIGN ON MID SAGITTAL
IMAGE
VASCULAR
PARKINSONISM
3
0ARKINSONISM IS USUALLY LOWER
BODY PREDOMINANT 4YPICAL REST TREMOR IS
ABSENT &EATURES OF STROKE MAY BE PRESENT 0ATIENTS USUALLY HAVE SIGNIFICANT
VASCULAR RISK FACTORS AND BRAIN -2) USUALLY SHOWS WIDESPREAD ISCHAEMIC
CHANGES LESS COMMONLY THIS FORM OF PARKINSONISM CAN BE DUE TO A SMALL
STROKE IN A STRATEGIC LOCATION EG IN THE SUBSTANTIA NIGRA
.ORMAL-PRESSURE
HYDROCEPHALUS
0ARKINSONISM IS USUALLY LOWER BODY PREDOMINANT "RAIN IMAGING SHOWS
ENLARGED VENTRICLES OUT OF PROPORTION TO ANY CEREBRAL SULCAL ATROPHY A
POSITIVE hTAP TESTv IMPROVEMENT OF GAIT AFTER LARGE VOLUME REMOVAL OF
CEREBROSPINAL FLUID VIA LUMBAR PUNCTURE AIDS IN THE DIAGNOSIS AND IN
PREDICTING RESPONSE TO A SHUNTING PROCEDURE
$IAGNOSIS
$ECISION TO TREAT
9ES
.O
2EVIEW
%VALUATE PATIENT
CHARACTERISTICS AND DEGREE
OF DISABILITY
-ODERATESEVERE MOTOR
DISABILITY AND AGE
YEARS OR COGNITIVE
IMPAIRMENTOTHER
SIGNIFICANT COMORBIDITY
-ILDMODERATE MOTOR
DISABILITY AND NO COGNITIVE
IMPAIRMENT
-ILD MOTOR DISABILITY AND
NO COGNITIVE IMPAIRMENT
"EGIN LEVODOPA
"EGIN DOPAMINE AGONIST
"EGIN -!/ " INHIBITOR
Figure 1. $ECISION PATHWAY FOR THE INITIATION OF MEDICATION TREATMENT FOR 0$
ADAPTED FROM REFERENCE
3. Initiation of antiparkinsonian medication When and what to start
General approach. 4HE MEDICATIONS CURRENTLY USED TO TREAT 0$ PROVIDE
symptomatic BENEFIT 4HIS MEANS THAT THEY REDUCE 0$ SYMPTOMS SUCH AS
TREMOR BRADYKINESIA AND RIGIDITY 4RADITIONALLY PATIENTS START TAKING MEDICINES
WHEN SYMPTOMS BECOME troublesome EG AT THE POINT WHERE SYMPTOMS
IMPACT NEGATIVELY ON THE PERFORMANCE OF DAILY ACTIVITIES 4HIS IS STILL A POPULAR
APPROACH
.EVERTHELESS SOME EXPERTS HAVE PROPOSED THAT EARLIER INITIATION OF TREATMENT
CAN BE ASSOCIATED WITH BETTER CLINICAL OUTCOMES AND SOME 0$ SPECIALISTS ARE
NOW RECOMMENDING THAT TREATMENT BE STARTED as soon as, or very soon after,
A diagnosis 0$ IS MADE (OWEVER AT PRESENT THERE IS INSUFFICIENT EVIDENCE
TO PROVE THIS HYPOTHESIS AND TREATMENT RECOMMENDATIONS SHOULD TAKE INTO
ACCOUNT THE patients preferences INCLUDING ISSUES RELATED TO MEDICATION SIDE
EFFECTS COST AND THE INCONVENIENCE OF HAVING TO TAKE MEDICATION REGULARLY
/NCE A DECISION HAS BEEN MADE TO INITIATE TREATMENT THERE ARE MULTIPLE
OPTIONS TO CONSIDER &IGURE AND !PPENDIX
! start low, go slow APPROACH CAN HELP TO MINIMIZE THE OCCURRENCE OF
CERTAIN SIDE EFFECTS
!LMOST EVERY PATIENT WITH 0$ WILL EVENTUALLY REQUIRE TREATMENT WITH ,
DOPA
4HE USE OF ,
DOPA should not be inappropriately delayed IF SYMPTOMS ARE
NOT ADEQUATELY CONTROLLED WITH THE LESS POTENT MEDICATIONS
! COMMON misconception IS THAT ,
DOPA SHOULD BE hsaved for laterv OR THAT
hIT ONLY WORKS FOR X NUMBER OF YEARSv !LTHOUGH IT IS TRUE THAT IN MANY
PATIENTS SYMPTOMS BECOME LESS RESPONSIVE TO MEDICATION TREATMENT AFTER
HAVING 0$ FOR MANY YEARS THIS IS PRIMARILY DUE TO A CHANGE IN THE NATURE OF
THE DISEASE WITH THE DEVELOPMENT OF non-dopaminergic LESIONS RATHER
THAN BEING DUE TO LONG
TERM USAGE OF ,
DOPA 4HUS PROBLEMS SUCH AS SLOWNESS
OF LIMB MOVEMENTS ARE DUE PRIMARILY TO A DEFICIENCY OF BRAIN DOPAMINE
WHICH CAN BE ADDRESSED BY RESTORING DOPAMINE LEVELS WITH MEDICATIONS AND
WHICH WILL CONTINUE TO RESPOND OVER TIME (OWEVER SYMPTOMS SUCH AS IMBALANCE
AND FALLS SPEECH OR SWALLOWING DIFFICULTIES AND DEMENTIA THAT TYPICALLY OCCUR
IN THE LATER STAGES OF 0$ ARE USUALLY NOT CAUSED BY DOPAMINE DEFICIENCY
4HEREFORE hMERELYv REPLACING DOPAMINE WITH THE CURRENTLY
AVAILABLE MEDICATIONS
HAS LIMITED EFFECTIVENESS IN TREATING THESE PROBLEMS
Dopamine agonists. 4HESE ARE GENERALLY CONSIDERED THE NEXT MOST POTENT
CLASS OF MEDICATIONS AFTER ,
DOPA IN TERMS OF ANTIPARKINSONIAN EFFICACY
%RGOT DOPAMINE AGONISTS EG BROMOCRIPTINE ARE SELDOM USED NOW IN CLINI
CAL PRACTICE BECAUSE OF THE RISK OF FIBROTIC COMPLICATIONS .ON
ERGOT DOPA
MINE AGONISTS AVAILABLE IN -ALAYSIA ARE LISTED IN 4ABLE )N GENERAL THESE
AGENTS HAVE SIMILAR EFFICACY AND SIDE EFFECT PROFILES .EVERTHELESS IF ONE
RESULTS IN SIDE EFFECTS ANOTHER DOPAMINE AGONIST COULD BE SUBSTITUTED !
PARTICULAR DOPAMINE AGONIST MAY BE PREFERRED IN SELECTED CIRCUMSTANCES EG
THE ONCE
DAILY AGONISTS FOR ADDED CONVENIENCE AND IMPROVED COMPLIANCE OR
ROTIGOTINE IN SITUATIONS WHERE TRANSDERMAL APPLICATION IS DESIRABLE
Levodopa (L-dopa). 4HIS AGENT WHICH HAS BEEN IN CLINICAL USE SINCE THE
S IS STILL the most effective ANTIPARKINSONIAN MEDICATION AVAILABLE
#ONCERNS RAISED IN THE PAST REGARDING THE POSSIBILITY OF A TOXIC EFFECT ON
DOPAMINE NEURONS HAVE LARGELY BEEN DISCOUNTED33 ,
DOPA THERAPY EXTENDS
SURVIVAL IN 0$ LIKELY AS A RESULT OF REDUCTION IN PARKINSONIAN DISABILITY
!S AN EXAMPLE OF THE hSTART LOW GO SLOWv APPROACH ,
DOPA PREPARATIONS CAN
BE started at A DOSE OF 50 mg daily EG TABLET OF -ADOPAR MG
OR TABLET OF 3INEMET MG INCREASING every 3-7 days BY MG TO
AN INITIAL MAINTENANCE DOSE OF
MG X DAILY OR UNTIL A SATISFACTORY
CLINICAL RESPONSE IS OBTAINED )F SIDE EFFECTS OCCUR UP
TITRATION CAN BE CARRIED
OUT EVEN MORE GRADUALLY
Individual doses OF ,
DOPA TYPICALLY RANGE FROM 50-300 mg $AILY DOSAGE
SHOULD RARELY EXCEED MG8
7ITH CHRONIC ,
DOPA THERAPY MOTOR RESPONSE COMPLICATIONS INCLUDING
dyskinesias SEE 3ECTION BELOW ON -OTOR RESPONSE COMPLICATIONS OCCUR
FREQUENTLY AND IN A MINORITY OF PATIENTS MAY BECOME SEVERE WITH
PRONOUNCED INTERFERENCE WITH !$,S ESPECIALLY IN younger PATIENTS35
-ULTIPLE STUDIES HAVE SHOWN THAT THE RISK OF DEVELOPING DYSKINESIA IS HIGHER
WITH ,
DOPA COMPARED FOR EXAMPLE TO DOPAMINE AGONIST THERAPY ESPECIALLY
WHEN USED AT HIGHER DOSES -ODIFIED
RELEASE ,
DOPA PREPARATIONS
CONTROLLED
RELEASE FORMULATIONS OR PREPARATIONS CONTAINING ENTACAPONE DO
NOT DELAY THE DEVELOPMENT OF MOTOR RESPONSE COMPLICATIONS
-ANY DOCTORS DELAY THE USE OF ,
DOPA IN younger patients EG THOSE UNDER
THE AGE OF
YEARS 9 ALTHOUGH RECENTLY OTHERS ARE STARTING ,
DOPA EARLIER
USING THE lowest effective dose -EDICATIONS SUCH AS DOPAMINE AGONISTS
-!/
" INHIBITORS ANTICHOLINERGICS ANDOR AMANTADINE CAN BE USED INITIALLY
INSTEAD (OWEVER THESE AGENTS ARE LESS EFFECTIVE THAN ,
DOPA AND SIDE EFFECTS
MAY LIMIT THEIR USE
Anticholinergic agents. 4HESE INCLUDE trihexyphenidyl OR benzhexol
!PO 4RIHEX AND "ENZHEXOL OR MG X DAILY AND orphenadrine
.ORFLEX MG X DAILY 4HESE AGENTS CAN BE PARTICULARLY HELPFUL FOR
tremor IN SOME PATIENTS BUT THEIR USE IS OFTEN LIMITED BY ANTICHOLINERGIC SIDE
EFFECTS PARTICULARLY IN OLDER PATIENTS AND ESPECIALLY IF THEY HAVE UNDERLYING
COGNITIVE IMPAIRMENT !NTICHOLINERGIC AGENTS MAY ALSO HAVE A ROLE FOR
0$ RELATED dystonia7
Experimental treatments. 3OME SUPPLEMENTS HAVE BEEN STUDIED FOR 0$
0ROBABLY THE BEST KNOWN OF THESE IS #OENZYME 1 !N INITIAL RANDOMIZED
PLACEBO CONTROLLED DOUBLE BLIND TRIAL SHOWED PROMISE FOR THIS AGENT BUT A
MORE RECENT AND LARGER STUDY CONDUCTED IN .ORTH !MERICA BY THE .ATIONAL
)NSTITUTE OF .EUROLOGICAL $ISORDERS AND 3TROKE .).$3 DEMONSTRATED THAT
THIS TREATMENT WAS NOT EFFECTIVE EVEN AT HIGH DOSES UP TO MGDAY THIS
TRIAL WAS TERMINATED AFTER AN INTERIM ANALYSIS7 !NOTHER ANTIOXIDANT 6ITAMIN
% WAS ALSO FOUND TO BE INEFFECTIVE
/THER PURPORTED TREATMENTS HAVE NEVER BEEN SUBJECTED TO PROPER SCIENTIFIC
SCRUTINY IN HUMAN 0$ SUBJECTS 4HESE INCLUDE GINKGO BILOBA EG 4ANAKAN
hSTEM CELL ENHANCERSv EG 3TEM%NHANCE TRADITIONAL HERBAL REMEDIES
BOVINE COW COLOSTRUM ETC 5NPROVEN TREATMENTS THAT ARE COSTLY ANDOR
POTENTIALLY HAZARDOUS SHOULD BE AVOIDED 4HE PLACEBO EFFECT IS WELL RECOGNIZED
IN 0$ AND THEREFORE ANY TREATMENT SHOULD BE SUBJECTED TO RIGOROUS SCIENTIFIC
METHODS TO ESTABLISH EFFICACY AND TO ENSURE THAT PATIENTS ARE RECEIVING THE BEST
VALUE FOR THEIR TIME EFFORT AND HEALTHCARE EXPENDITURE
Non-pharmacologic management. !LLIED HEALTH INVOLVEMENT MAY BE
PARTICULARLY VALUABLE IN ADVANCED 0$ BUT ARE OFTEN ALSO BENEFICIAL FOR EARLIER
STAGE PATIENTS 4HESE INCLUDE physiotherapy STRETCHING AND STRENGTHENING
EXERCISES GAIT AND BALANCE TRAINING INCLUDING USE OF CUEING TECHNIQUES ETC
occupational therapy REHABILITATION TECHNIQUES THAT HELP MAXIMIZE
FUNCTIONAL CAPACITY THROUGH LIFESTYLE ADAPTATIONS AND POSSIBLE USE OF ASSISTIVE
DEVICES THIS MAY INCLUDE ASSESSMENT OF SAFETY IN THE HOME ENVIRONMENT EG
INSTALLATION OF GRAB RAILS SHOWER SEATS ETC speech therapy REHABILITATION
TECHNIQUES TO STRENGTHEN SPEECH FOR IMPROVED COMMUNICATION AND TO
IMPROVE EFFICIENCY OF SWALLOWING WHICH MAY REDUCE THE RISK OF ASPIRATION
11
Table 3. .ON ERGOT ORAL DOPAMINE AGONISTS
DENOTES DOPAMINE AGONISTS THAT ARE
USUALLY ADMINISTERED THREE TIMES DAILY
DENOTES NEWER LONGER
ACTING AGONISTS THAT
ARE ADMINISTERED ONCE DAILY
Usual starting dose
Maximum
recommended dose
0IRIBEDIL 4RIVASTAL 2ETARD
5 MG
3 MGD
2OPINIROLE IMMEDIATE RELEASE
2EQUIP
5 MG
MGD
2OPINIROLE PROLONGED RELEASE
2EQUIP 0$
MG
MGD
2OTIGOTINE .EUPRO
TRANSDERMAL PATCH
MG
MGD
0RAMIPEXOLE IMMEDIATE RELEASE
3IFROL
5 MG
5 MGD
0RAMIPEXOLE EXTENDED RELEASE
3IFROL %2
375 MG
5 MGD
Dopamine agonist
!S EXAMPLES OF THE hSTART LOW GO SLOWv APPROACH ROPINIROLE PROLONGED RELEASE
OR ROTIGOTINE CAN BE STARTED AT A DOSE OF MG DAILY INCREASING EVERY WEEK BY
MG DAILY IE MG DAILY FOR THE FIRST WEEK MG DAILY FOR THE SECOND WEEK
MG DAILY FOR THE THIRD WEEK ETC UNTIL A SATISFACTORY CLINICAL RESPONSE IS
OBTAINED )F SIDE EFFECTS OCCUR UP TITRATION CAN BE CARRIED OUT EVEN MORE
GRADUALLY
Selegiline (e.g., Jumex and Selegos). 4HE USUAL DOSE IS MG IN THE
MORNING IN OR DIVIDED DOSES TAKING THIS AGENT LATER IN THE DAY MAY CAUSE
INSOMNIA 3ELEGILINE HAS A mild antiparkinsonian EFFECT 3OME CLINICIANS
ALSO USE SELEGILINE FOR ITS putative neuroprotective EFFECT BUT THIS IS NOT
PROVEN 4HERE IS ALSO SOME EVIDENCE TO SUGGEST THAT rasagiline !ZILECT
ANOTHER -!/ " INHIBITOR NOT CURRENTLY AVAILABLE IN -ALAYSIA MAY HAVE
NEUROPROTECTIVE POTENTIAL BUT THE RESULTS OF THE RECENT !$!')/ STUDY WERE
INCONCLUSIVE
10
4. Potential side effects of antiparkinsonian
medications
-EDICATIONS USED TO TREAT 0$ CAN CAUSE ADVERSE EFFECTS IN SOME PATIENTS
! hstart low, go slowv APPROACH CAN HELP TO MINIMIZE THE OCCURRENCE OF SOME
SIDE EFFECTS SEE 3ECTION ABOVE FOR EXAMPLES ON HOW THIS CAN BE DONE
Dopaminergic side effects. 4HE POTENTIAL SIDE EFFECTS OF dopaminergic
MEDICATIONS3 , DOPA PREPARATIONS DOPAMINE AGONISTS AND TO A LESSER EXTENT
-!/ " INHIBITORS INCLUDE nausea postural hypotension AND DAYTIME
sleepiness )N PREDISPOSED PATIENTS DEVELOPMENT OR WORSENING OF confusion
hallucinations OR impulse control disorders SUCH AS HYPERSEXUALITY
COMPULSIVE EATING OR PATHOLOGICAL GAMBLING CAN OCCUR PARTICULARLY WITH
DOPAMINE AGONISTS )N MANY CASES MEDICATION ADJUSTMENT CAN ALLEVIATE
THESE SIDE EFFECTS Domperidone MG TAKEN WITH EACH DOSE OF DOPAMINERGIC
MEDICATION CAN HELP TO COUNTERACT NAUSEA AND POSTURAL HYPOTENSION
MAO-B inhibitors. 4HESE AGENTS ARE GENERALLY WELL TOLERATED )N A SURVEY OF
0$ SPECIALISTS ONLY OUT OF PATIENTS ON A COMBINATION OF
SELEGILINE AND AN ANTIDEPRESSANT EXPERIENCED SERIOUS SYMPTOMS POSSIBLY
CONSISTENT WITH serotonin syndrome )N THE !$!')/ STUDY OF RASAGILINE
N WHERE CONCOMITANT TREATMENT WITH ANTIDEPRESSANTS WAS ALLOWED
THERE WAS NOT A SINGLE REPORTED CASE OF SEROTONIN SYNDROME 3IMILARLY THERE
WAS NOT A SINGLE CASE OF TYRAMINE HYPERTENSIVE REACTIONS IN THIS STUDY WHERE
THERE WAS NO RESTRICTION OF DIETARY INTAKE OF TYRAMINE /NE EARLY REPORT FROM
THE 5NITED +INGDOM OF INCREASED MORTALITY WITH SELEGILINE HAD IMPORTANT
METHODOLOGIC LIMITATIONS57 AND HAS BEEN DISCOUNTED BY SUBSEQUENT STUDIES
Anticholinergic medications. 3IDE EFFECTS INCLUDE h!NTI 3,5$v SALIVATION
LACRIMATION URINATION DEFAECATION v EFFECTS DRY MOUTH DRY EYES URINARY
RETENTION CONSTIPATION ALSO CONFUSION AND HALLUCINATIONS
Amantadine. 3IDE EFFECTS INCLUDE CONFUSION AND HALLUCINATIONS LEG SWELLING
LIVEDO RETICULARIS NET LIKE MOTTLING OF THE SKIN USUALLY HARMLESS IN ADDITION
TO ANTICHOLINERGIC EFFECTS 4HERE IS A NEED TO USE THIS MEDICATION WITH CAUTION
IN PATIENTS WITH RENAL DYSFUNCTION
13
AND ADVICE FROM A dietitian UNINTENDED WEIGHT LOSS IS A COMMON FEATURE OF
0$ 0RIMARY CARE PHYSICIANS CAN FACILITATE THIS BY REFERRING PATIENTS TO THE
APPROPRIATE THERAPISTS -ANY COUNTRIES HAVE PD nurse specialists WHO CAN
PROVIDE PSYCHOLOGICAL SUPPORT PRACTICAL ADVICE ON SYMPTOM MANAGEMENT
MONITORING OF MEDICATION ADHERENCE WOUND CARE CARE OF DEVICES EG MEDI
CATION INFUSION PUMPS FEEDING TUBES URINARY CATHETERS HOME VISITS IN CASES
WHERE PATIENTS ARE TOO DISABLED TO COME TO THE HOSPITAL ETC7 -ANY OF THESE
SERVICES ARE CURRENTLY UNDERDEVELOPED IN -ALAYSIA
!LTHOUGH MANY PATIENTS SEEK alternative therapies SUCH AS acupuncture AND
STEM CELL TREATMENTS THERE IS CURRENTLY LITTLE OR NO GOOD SCIENTIFIC EVIDENCE TO
RECOMMEND THESE MODALITIES OF TREATMENT IN 0$
The importance of exercise. &OR ALL PATIENTS IT IS USEFUL TO ENCOURAGE ATTENTION
TO A HEALTHY LIFESTYLE INCLUDING MAINTAINING AN OPTIMISTIC OUTLOOK A HEALTHY
AND BALANCED DIET AND regular exercise EG WALKING OR SWIMMING "ESIDES
THE GENERAL HEALTH BENEFITS OF EXERCISE IMPROVEMENT OF CARDIOVASCULAR AND
CEREBROVASCULAR HEALTH REDUCTION OF OSTEOPOROSISFRACTURE RISK IMPROVEMENT
OF PSYCHOLOGICAL AFFECT THERE IS ACCUMULATING EVIDENCE ALBEIT INDIRECT
SUGGESTING THAT VIGOROUS EXERCISE MAY HAVE A NEUROPROTECTIVE EFFECT IN 0$53
Being informed & being involved. 0ROVISION OF EDUCATION AND VALID
information IS ESSENTIAL TO EMPOWER BOTH PATIENTS AND FAMILIES IN ACTIVELY
PARTICIPATING IN DISEASE MANAGEMENT7 )T SHOULD BE EMPHASIZED THAT WITH THE
RIGHT TREATMENT AND A POSITIVE ATTITUDE PEOPLE LIVING WITH 0$ CAN CONTINUE TO
MAINTAIN A REWARDING LIFESTYLE FOR MANY MORE YEARS FOLLOWING THE DIAGNOSIS
4HE -ALAYSIAN 0$ !SSOCIATION -0$! HAS PUBLISHED ACCURATE AND UP
TO
DATE
information booklets FOR PEOPLE LIVING WITH 0$ WRITTEN BY SENIOR MEMBERS
OF THE -OVEMENT $ISORDERS #OUNCIL 4HESE ARE AVAILABLE IN %NGLISH -ALAY
AND #HINESE AND CAN BE DOWNLOADED FOR FREE FROM THE -0$! WEBSITE
http://www.mpda.org.my
0EOPLE LIVING WITH 0$ CAN ALSO FIND PURPOSE AND SATISFACTION IN LIFE BY BEING
INVOLVED IN A PEER support group SUCH AS THE -0$!7 9OUNG PATIENTS
PARTICULARLY MAY BENEFIT FROM BEING PUT IN TOUCH WITH AN ARTICULATE AND
POSITIVE PATIENT OF SIMILAR AGE WHO IS DOING WELL8
12
5. Motor response complications (motor fluctuations
& dyskinesia) - What are they?
-ANY PATIENTS AFTER THEY HAVE BEEN TAKING DOPAMINERGIC MEDICATIONS FOR
SOME TIME USUALLY YEARS WILL DEVELOP MOTOR FLUCTUATIONS hWEARING OFFv IS THE
COMMONEST TYPE OF MOTOR FLUCTUATION AND DYSKINESIA INVOLUNTARY hWRIGGLINGv
MOVEMENTS
Wearing-off 0ATIENTS EXPERIENCING hWEARING OFF v IMPROVE AFTER TAKING A
DOSE OF 0$ MEDICATION THE hONv MEDICATION STATE TYPICALLY OR HOUR
AFTER MEDICATION INTAKE BUT START TO EXPERIENCE A RECURRENCE OR WORSENING OF
THEIR 0$ SYMPTOMS BEFORE IT IS TIME TO TAKE THE NEXT DOSE OF MEDICATION THE
hOFFv MEDICATION STATE &OR EXAMPLE A PATIENT MAY FEEL THAT EACH MEDICATION
DOSE LASTS FOR ONLY OR HOURS 3OME PATIENTS EXPERIENCING motor fluctuations
ALSO EXPERIENCE non-motor fluctuations EG PAIN MOOD OR PANIC SYMPTOMS
OR SLOWNESS OF THINKING THAT OCCUR OR WORSEN DURING h/&&v PERIODS &IGURE
BELOW DEPICTS THESE FLUCTUATIONS
%VENTUALLY SOME PATIENTS MAY EXPERIENCE MORE unpredictable hON OFF v
FLUCTUATIONS AS WELL 4HESE CAN BE MUCH MORE DIFFICULT TO MANAGE
Symptoms not
adequately
controlled
Symptoms
adequately
controlled
(ON condition)
Peak-dose dyskinesia
s are
tp om ted
ym llevia
a
Symp
to
to re ms be
turn gin
A typical day
(Wearing-off)
Medication
starts to work
PD
medication
PD
medication
Time
PD
medication
(OFF condition)
Figure 2. &LUCTUATIONS h/.v AND h/&&v PERIODS AND DYSKINESIA IN RELATION TO THE
TIMING OF 0$ MEDICATION INTAKE !DAPTED FROM REFERENCE
15
Should medications be taken on an empty stomach or with food? )NITIALLY
AT LEAST DURING THE FIRST SEVERAL MONTHS AFTER INITIATING TREATMENT DOPAMINERGIC
MEDICATIONS SHOULD GENERALLY BE TAKEN WITH FOOD TO REDUCE nausea VOMITING
(OWEVER ONCE THESE MEDICATIONS CAN BE TOLERATED WITHOUT FOOD TAKING THEM
ON AN EMPTY STOMACH IE HOUR PRIOR TO OR HOURS AFTER MEALS ALLOWS FOR
MORE RAPID AND RELIABLE ABSORPTION
2ARELY A PATIENT USUALLY ONE WITH LONG STANDING 0$ AND DISABLING MOTOR
FLUCTUATIONS CAN BE VERY SENSITIVE TO CONCURRENT INTAKE OF DIETARY protein
WHICH MAY DELAY , DOPA FROM REACHING THE BRAIN 4HIS IS BECAUSE PROTEINS ARE
BROKEN DOWN INTO AMINO ACIDS THAT COMPETE WITH , DOPA FOR TRANSPORT FROM
THE GUT INTO THE BLOODSTREAM AND FROM THE BLOODSTREAM INTO THE BRAIN )N
SUCH PATIENTS high-protein foods EG MEAT POULTRY FISH MILK CHEESE AND
EGGS MAY BE redistributed, TYPICALLY TO dinnertime AS PATIENTS ARE USUALLY
LESS ACTIVE IN THE LATER PART OF THE DAY (OWEVER THIS IS NOT AN ISSUE FOR THE VAST
MAJORITY OF PATIENTS WITH 0$ )T SHOULD ALSO BE REMEMBERED THAT MANY
PATIENTS WITH 0$ EXPERIENCE UNINTENDED WEIGHT LOSS SO MAINTAINING A WELL
BALANCED DIET INCLUDING FOODS WITH HIGH PROTEIN EG MILK SHAKES OR
%NSURE IS IMPORTANT
14
4ABLE MAY HELP TO DIFFERENTIATE BETWEEN PEAK
DOSE DYSKINESIA AND BIPHASIC
DYSKINESIA NOTE HOWEVER THAT BOTH ENTITIES MAY BE PRESENT
AND ONE MAY
BLEND INTO THE OTHER
IN THE SAME PATIENT
Table 4. 4YPES OF DYSKINESIAS
Peak-dose dyskinesia
Biphasic dyskinesia
-UCH MORE COMMON
,ESS COMMON
/CCURS AT THE TIME OF PEAK h/.v BENEFIT
FROM A DOSE OF DOPAMINERGIC MEDICATION
/CCURS BEFORE OR AFTER THE TIME OF PEAK
h/.v BENEFIT FROM A DOSE OF DOPAMINERGIC
MEDICATION %ND OF DOSE DYSKINESIA USUALLY
IS MORE PROLONGED DISABLING THAN ONSET
OF DOSE DYSKINESIA
5SUALLY CHOREIFORM
-AY BE BALLISTIC DYSTONIC OR INVOLVE
REPETITIVE PEDALLING MOVEMENTS
/FTEN UPPER BODY IS MORE AFFECTED HEAD
TRUNK UPPER LIMBS BUT MAY BE GENERALIZED
5SUALLY AFFECTS LEGS PRIMARILY
5SUALLY PAINLESS AND PATIENTS ARE OFTEN
UNAWARE OF MILDER DYSKINESIA
/FTEN DISTRESSING; MAY BE PAINFUL
Patient diary. )N SOME PATIENTS DOCUMENTATION OF MOTOR FUNCTION DURING
WAKING HOURS USING AN HOURLY SELF
COMPLETED DIARY CAN BE HELPFUL TO
DETERMINE THE TOTAL DAILY AMOUNT OF h/&&v TIME AND DYSKINESIA AND THE
RELATIONSHIP OF THESE TO THE TIMING OF MEDIATION INTAKE SEE !PPENDIX FOR
AN EXAMPLE FULL VERSIONS IN %NGLISH -ALAY AND #HINESE CAN BE DOWNLOADED
FROM THE -ALAYSIAN 0$ !SSOCIATION WEBSITE ;HTTPWWWMPDAORGMY=
17
Dyskinesia. 4HESE ARE INVOLUNTARY hwrigglingv CHOREIFORM MOVEMENTS THAT
USUALLY OCCUR WHEN PATIENTS ARE h/.v SO CALLED hpeak-dosev DYSKINESIA
&IGURE 4HIS TYPE OF DYSKINESIA IS VERY COMMON OCCURRING IN OF
PATIENTS AFTER YEARS OF TREATMENT WITH ,
DOPA )N MANY PATIENTS IT IS OF LITTLE
CONSEQUENCE IN FACT PATIENTS MAY NOT EVEN BE AWARE OF THE MOVEMENTS IN
MILD CASES OF DYSKINESIA ,ESS COMMONLY DYSKINESIA CAN ALSO OCCUR BEFORE A
DOSE OF MEDICATION TAKES FULL EFFECT ANDOR DURING THE hWEARING
OFF v PHASE SO
CALLED hbiphasicv DYSKINESIA
Figure A. Tremor (shakes).
4HESE ARE OSCILLATORY MOVEMENTS )N 0$ TREMOR MOST COMMONLY
AFFECTS THE HAND ARM BUT SOMETIMES CAN ALSO AFFECT THE LEG OR
HEAD )T IS USUALLY MOST PROMINENT AT REST BUT SOMETIMES CAN ALSO
BE PRESENT WHEN PERFORMING ACTIONS EG WHILST HOLDING A CUP OR
WRITING
A.
B.
Figure B. Dyskinesia (wriggling).
4HESE ARE INVOLUNTARY MOVEMENTS THAT USUALLY OCCUR WHEN A DOSE
OF 0$ MEDICATION HAS TAKEN EFFECT hONv MEDICATION CONDITION
)N THE EXAMPLE SHOWN HERE THE DYSKINESIA IS MORE SEVERE AND
GENERALIZED BUT IN MOST PATIENTS THE MOVEMENTS ARE MILDER
C.
Figure C. Dystonia (twisting).
4HIS MOST COMMONLY AFFECTS THE FOOT WITH THE ANKLE TWISTING IN
OR THE TOES CURLING UP OR DOWN )N MOST PATIENTS IT OCCURS IN THE
hOFFv
MEDICATION CONDITION EG IN THE EARLY MORNING PRIOR TO
TAKING THE ST DOSE OF 0$ MEDICATION
Figure 3. $IFFERENT TYPES OF involuntary movements THAT MAY BE ASSOCIATED WITH
DIFFERENT PHASES OF THE DOPA CYCLE
16
DOSES OF ,
DOPA IF THE BENEFICIAL RESPONSE IS INSUFFICIENT BUT THE ADDITION HAS
BEEN WELL TOLERATED AFTER
DAYS THE FREQUENCY OF ENTACAPONE COULD BE
INCREASED FURTHER TO TABLET X DAILY
Treatment of dyskinesia. 4ROUBLESOME DYSKINESIA CAN SOMETIMES BE MAN
AGED BY REDUCING THE DOSE OF DOPAMINERGIC MEDICATIONS BUT THIS HAS TO BE
BALANCED AGAINST WORSENING CONTROL OF h/&&v PERIODS (OWEVER IT IS A COMMON
misconception THAT PATIENTS HAVE DYSKINESIA DUE TO BEING hoverdosedv ON
MEDICATION 7HILE THIS CAN CERTAINLY HAPPEN IF A PATIENTS DOPAMINERGIC
MEDICATION HAS BEEN INAPPROPRIATELYUNNECESSARILY ESCALATED THE MORE
TYPICAL SCENARIO IS THAT OF A PATIENT WHOSE MEDICATION HAS BEEN GRADUALLY
INCREASED TO ADDRESS PROGRESSIVELY WORSENING h/&&v PERIODS 4O ILLUSTRATE THIS
POINT FURTHER ! PATIENT WHO IS TAKING TABLET OF IMMEDIATE
RELEASE ,
DOPA
EARLY IN THE DISEASE COURSE MAY DEMONSTRATE NO DYSKINESIA AT ALL BUT the exact
same dose GIVEN YEARS LATER WHEN hPLASTICv CHANGES THAT UNDERLIE THE
DYSKINESIA PROCESS HAVE OCCURRED IN THE BRAIN CAN PRECIPITATE SEVERE DYSKINESIA
Amantadine (Pk-Merz). 4HIS AGENT CAN SUPPRESS DYSKINESIA IN MANY
PATIENTS WHILST SIMULTANEOUSLY PROVIDING MILD ANTIPARKINSONIAN BENEFIT
4HE DOSE OF AMANTADINE IS TYPICALLY UPTITRATED GRADUALLY TO MG X DAILY
AS TOLERATED ! RECENT STUDY SHOWED THAT PATIENTS CAN EXPERIENCE A SUSTAINED
ANTI
DYSKINETIC EFFECT FROM AMANTADINE EVEN AFTER MORE THAN YEARS OF
AMANTADINE TREATMENT
Motor response complications that are refractory to adjustment of oral
medications. ! MINORITY OF PATIENTS CONTINUE TO HAVE DISABLING MOTOR
FLUCTUATIONS AND DYSKINESIA DESPITE hOPTIMIZATIONv OF A COMPLEX REGIMEN OF
ORAL 0$ MEDICATIONS 4O ACHIEVE SATISFACTORY CONTROL OF THESE PROBLEMS THESE
PATIENTS MAY REQUIRE MORE INVASIVE ADVANCED TREATMENTS WHICH ARE COVERED
IN THE NEXT SECTION
19
6. Treatment of motor fluctuations & dyskinesia
Treatment of motor fluctuations. 4HERE ARE SEVERAL APPROACHES TO REDUCE
h/&&v PERIODS /NE OPTION IS TO INCREASE THE dose and/or frequency OF 0$
MEDICATIONS EG TAKING , DOPA OR X DAILY INSTEAD OF X DAILY HOWEVER
THIS COMES AT A COST OF INCONVENIENCE IN TERMS OF HAVING TO TAKE FREQUENT
DOSES 7HEN THE FREQUENCY OF , DOPA ADMINISTRATION IS INCREASED IT MAY BE
NECESSARY TO REDUCE INDIVIDUAL DOSAGES OF , DOPA SO AS NOT TO WORSEN SIDE
EFFECTS SUCH AS DYSKINESIA ALTHOUGH THIS CAN SOMETIMES RESULT IN DOSE FAILURES
BECAUSE THE QUANTUM OF , DOPA IS INSUFFICIENT TO EXCEED THRESHOLD AND TURN
THE PATIENT h/.v
/THER APPROACHES TO REDUCE h/&&v PERIODS INCLUDE addition OF A dopamine
agonist entacapone EITHER BY ADDING #OMTAN OR BY SWITCHING FROM
IMMEDIATE RELEASE , DOPA TO 3TALEVO WHICH IS A TABLET COMBINING , DOPA
CARBIDOPA AND ENTACAPONE OR A -!/ " INHIBITOR SELEGILINE OR RASAGILINE
!DDITION OF A DOPAMINE AGONIST IS TYPICALLY MORE EFFECTIVE THAN ADDITION OF
ENTACAPONE OR -!/ " INHIBITOR THERAPY WHICH HAVE COMPARABLE
EFFICACY )N PATIENTS WITH OVERNIGHT WEARING OFF DOPAMINE AGONIST THERAPY
HAS ALSO BEEN SHOWN TO HAVE beneficial effects on night-time sleep
Controlled-release L-dopa 3INEMET #2 OR -ADOPAR ("3 REMAINS USEFUL
IN ADDRESSING OVERNIGHT WEARING OFF EG PATIENTS EXPERIENCING PAINFUL EARLY
MORNING FOOT DYSTONIA (OWEVER THESE AGENTS MAY BE erratically absorbed
RESULTING IN DELAYED h/.v OR NO h/.v RESPONSES AND ARE THEREFORE NOT FIRST
CHOICE TO TREAT MOTOR FLUCTUATIONS )T IS ALSO IMPORTANT TO REMEMBER THAT THE
AMOUNT OF , DOPA ABSORBED IS APPROXIMATELY LESS WITH CONTROLLED RELEASE
COMPARED TO STANDARDIMMEDIATE RELEASE PREPARATIONS THIS SHOULD BE TAKEN
INTO ACCOUNT WHEN SWITCHING BETWEEN PREPARATIONS7
)N GENERAL MEDICATION CHANGES SHOULD BE UNDERTAKEN gradually, especially
in a patient who is at higher risk of side effects EG ALREADY EXPERIENCING
SIGNIFICANT DYSKINESIA OR WHEN COGNITIVE IMPAIRMENT IS PRESENT &OR EXAMPLE
IN A PATIENT WITH SIGNIFICANT WEARING OFF SYMPTOMS ON IMMEDIATE RELEASE
, DOPA X DAILY ENTACAPONE COULD INITIALLY BE ADDED TO THE FIRST AND THIRD
18
MORE THAN THE PATIENTS USUAL MORNING DOSE IS ADMINISTERED SO THAT THE
PATIENTS BEST h/.v CONDITION CAN BE EVALUATED 7HEN SUCCESSFUL $"3 CAN
RESULT IN THE PATIENT SPENDING MUCH MORE TIME IN THIS h/.v CONDITION AND
WITH LESS DYSKINESIA
Other DBS targets. 4HALAMIC $"3 IS MAINLY USEFUL TO TREAT DRUG
RESISTANT
TREMOR AND HAS LIMITED EFFICACY ON OTHER PARKINSONIAN FEATURES 4HE ROLE OF
PEDUNCULOPONTINE NUCLEUS 00. $"3 IS CURRENTLY UNDER INVESTIGATION78
Lesional (ablative) surgery. !LTHOUGH PALLIDOTOMY AND THALAMOTOMY MIGHT
STILL BE PERFORMED IN SELECTED PATIENTS $"3 IS THE SURGICAL TREATMENT OF
CHOICE AS THE LATTER HAS REVERSIBLE EFFECTS AND CAN BE ADJUSTED TO OPTIMIZE THE
INDIVIDUAL PATIENTS RESPONSE AND CAN BE USED BILATERALLY TO IMPROVE
SYMPTOMS7 5NILATERAL PALLIDOTOMY APPEARS TO BE INFERIOR TO $"3 IN TERMS OF
EFFICACY AND IS LIMITED BY SIGNIFICANT SIDE EFFECTS WHICH MAY BE PERMANENT
INCLUDING HYPOPHONIA WHEN PERFORMED BILATERALLY
Apomorphine (APO-go) (subcutaneous infusion or injections).
!POMORPHINE IS THE MOST POTENT DOPAMINE RECEPTOR AGONIST AND IT CAN
PROVIDE SYMPTOM RELIEF SIMILAR TO THAT OF ,
DOPA !POMORPHINE IS RAPIDLY
ABSORBED WITH ONSET OF EFFECT WITHIN
MINUTES OF SUBCUTANEOUS
INJECTION )N THE -$3 %"- GUIDELINES APOMORPHINE SUBCUTANEOUS INJEC
TIONS WAS DESIGNATED hEFFICACIOUSv FOR THE TREATMENT OF MOTOR FLUCTUATIONS
4HE EFFICACY OF CONTINUOUS SUBCUTANEOUS INFUSION OF APOMORPHINE IS
SUPPORTED BY CASE SERIES AND EXTENSIVE CLINICAL EXPERIENCE BUT THERE IS A LACK
OF RANDOMIZED STUDIES
4HE MOST COMMON SIDE EFFECT IS LOCAL SKIN REAC
TIONS BUT THIS TREATMENT IS GENERALLY WELL TOLERATED
Jejunal L-dopa (Duodopa). 4HE ,
DOPACARBIDOPA GEL IS ADMINISTERED
INTO THE JEJUNUM VIA A PERCUTANEOUS ENDOSCOPIC GASTROSTOMY 0%' TUBE )N
THE -$3 %"- GUIDELINES JEJUNAL INFUSION OF ,
DOPA WAS DESIGNATED hLIKELY
EFFICACIOUSv FOR THE TREATMENT OF BOTH MOTOR FLUCTUATIONS AND DYSKINESIA
7ITH THIS TREATMENT MOST PATIENTS ARE ABLE TO COME OFF ALL THEIR ORAL 0$
MEDICATIONS 4ECHNICAL TUBE
RELATED COMPLICATIONS HOWEVER APPEAR TO BE
QUITE COMMON
21
7. Advanced therapies for disabling
motor response complications
When these treatments are used and why. 0ATIENTS WHO EXPERIENCE SEVERE
AND PROLONGED h/&&v PERIODS ANDOR DYSKINESIA DESPITE OPTIMIZATION OF THEIR
ORAL 0$ MEDICATIONS CAN BE CONSIDERED FOR DEEP BRAIN STIMULATION (DBS)
SURGERY OR pump (infusion) therapy USING APOMORPHINE !0/ GO OR
JEJUNAL , DOPA $UODOPA &IGURES 7ELL SELECTED PATIENTS TYPICALLY
EXPERIENCE A marked reduction of OFF periods AND dyskinesia WITH THESE
TREATMENTS (OWEVER THESE TREATMENTS ARE RELATIVELY COSTLY AND MORE
COMPLICATED AND SHOULD BE CARRIED OUT IN SPECIALIZED CENTRES MANAGING A LARGE
VOLUME OF PATIENTS WITH COMPLICATED 0$
Deep brain stimulation (DBS) surgery of the subthalamic nucleus (STN)
or globus pallidus internus (GPi). $"3 HAS BEEN IN CLINICAL USE FOR THE
TREATMENT OF 0$ SINCE THE S )N THE LATEST VERSION OF THE INTERNATIONAL
-OVEMENT $ISORDER 3OCIETY -$3 %VIDENCE "ASED -EDICINE %"-
GUIDELINES FOR THE TREATMENT OF 0$ MOTOR SYMPTOMS $"3 OF THE 34. OR '0I
WAS DESIGNATED hEFFICACIOUSv THE HIGHEST LEVEL OF EFFICACY DESIGNATION AND
hCLINICALLY USEFULv FOR THE TREATMENT OF BOTH MOTOR FLUCTUATIONS AND
DYSKINESIA $"3 RESULTS IN AN AVERAGE IMPROVEMENT IN MOTOR
FLUCTUATIONS AND DYSKINESIA AND IS SUPERIOR TO BEST MEDICAL THERAPY IN
IMPROVING QUALITY OF LIFE IN 0$ PATIENTS 3TUDIES HAVE ALSO DEMONSTRATED
THE EFFECTIVENESS OF $"3 IN IMPROVING , DOPA RESPONSIVE SIGNS AND SYMPTOMS
IN THE LONG TERM
)N GENERAL PATIENTS UNDERGOING $"3 SHOULD BE UNDER THE AGE OF AND
OTHERWISE MEDICALLY FIT WITHOUT MAJOR COGNITIVE IMPAIRMENT OR SEVERE
TREATMENT REFRACTORY PSYCHIATRIC DISORDERS
! hL-dopa challengev MAY BE REQUIRED FOR PROPER EVALUATION OF THE DEGREE OF
BENEFIT A PATIENT IS LIKELY TO GAIN FROM $"377 4HIS INVOLVES OVERNIGHT
WITHDRAWAL OF 0$ MEDICATIONS FOR HOURS SO THAT THE PATIENTS h/&&v
MEDICATION STATUS CAN BE ASSESSED &OLLOWING THIS A DOSE OF , DOPA TYPICALLY
20
Figure 6. 4YPICAL JEJUNAL , DOPA INFUSION SETUP
Percutaneous endoscopic
gastrostomy (PEG)
Infusion pump
Intestinal tubing
Cassette
containing
Duodopa
23
Figure 4. 4YPICAL DEEP BRAIN STIMULATION $"3 SETUP
Tiny electrodes stimulate a deep
part of the brain (subthalamic
nucleus / STN or globus
pallidus internus / GPi)
Wire tunneled
under the skin
Battery
Figure 5. 4YPICAL APOMORPHINE INFUSION SETUP
Apomorphine delivered via very
fine plastic tubing, & butterfly
needle sited under the skin
Cloth pouch containing
apomorphine reservoir
& small infusion pump
22
Evolution of NMS
Medication
effect
)#$S
$$3
PUNDING
3LEEP ATTACKS
2ELATIVE
CONTRIBUTION OF
DOPAMINERGIC
-%$)#A4)/.
VS $)3%A3%
%$3
.ONMOTOR
FLUCTUATIONS
/RTHOSTATIC
HYPOTENSION
Intrinsic to
PD
2"$
#ONSTIPATION
5RINARY URGENCY
%RECTILE
DYSFUNCTION
$EPRESSION
(YPOSMIA
0AIN
VISUAL
HALLUCINATIONS
Modifying factors
(gender, genetic,
etc.)
0)'$ $EMENTIA
E
Disease progression & nAge
,EWY PATHOLOGY PROCEEDS UPWARDS FROM LOWER
BRAINSTEM TO NEOCORTEX /LFACTORY AND PERIPHERAL
AUTONOMIC NEURONS ARE ALSO AFFECTED EARLY
Figure 7. %VOLUTION OF THE NONMOTOR SYMPTOMS .-3 OF 0$ ADAPTED FROM
REFERENCE 3CHEMATIC REPRESENTATION OF THE DEVELOPMENT OF .-3 IN RELATION TO DISEASE COURSE
HORIZONTAL AXIS AND RELATIVE CONTRIBUTION OF DISEASE VS DOPAMINERGIC MEDICATION VERTICAL AXIS "OTH
AXES ARE DIVIDED BY A -IDPOINT TO DENOTE THE HALF
WAY MARK IN THE DISEASE COURSE HORIZONTAL AXIS AND
EQUAL CONTRIBUTION OF DISEASE AND MEDICATION EFFECT IN THE PATHOGENESIS OF THE SYMPTOM VERTICAL
AXIS &OR EXAMPLE ACCORDING TO THIS FIGURE THERE IS A GREATER ROLE FOR DISEASE IN THE DEVELOPMENT OF
VISUAL HALLUCINATIONS AND PATIENTS HAVE GENERALLY PASSED THE HALF
WAY MARK IN THEIR DISEASE COURSE
WHEN THIS SYMPTOM DEVELOPS 4HE OVERLAPPING BOXES FOR 0)'$ AND DEMENTIA INDICATE THAT DEMENTIA
MORE OFTEN OCCURS IN PATIENTS WHO HAVE DEVELOPED AXIAL
PREDOMINANT PARKINSONISM !BBREVIATIONS
$$3 DOPAMINE DYSREGULATION SYNDROME %$3 EXCESSIVE DAYTIME SOMNOLENCE )#$S IMPULSE
CONTROL DISORDERS 0)'$ POSTURAL INSTABILITY AND GAIT DIFFICULTY 2"$ RAPID
EYE
MOVEMENT SLEEP
BEHAVIOUR DISORDER
25
8. The non-motor symptoms of Parkinsons disease
0ATIENTS WITH 0$ CAN EXPERIENCE A VARIETY OF NON MOTOR SYMPTOMS .-3
3TUDIES IN THE LOCAL -ALAYSIAN SETTING CONFIRM A HIGH FREQUENCY OF THESE
SYMPTOMS IN OUR POPULATION OF 0$ PATIENTS .-3 CAN HAVE A large
negative impact ON PATIENTS QUALITY OF LIFE SOMETIMES TO AN EVEN GREATER
EXTENT THAN THE MOTOR SYMPTOMS OF 0$ 4HESE THEREFORE DESERVE GREATER
ATTENTION IN THE ROUTINE MANAGEMENT OF 0$ 3OME OF THESE PROBLEMS WILL
ONLY COME TO LIGHT IF THEY ARE specifically asked about; IN SOME CASES THIS IS
BECAUSE PATIENTS ARE UNAWARE OF THE LINK WITH 0$ OR ITS TREATMENTS EG
CONSTIPATION IN OTHER CASES PATIENTS MAY BE TOO EMBARRASSED TO BRING UP
THESE ISSUES EG SEXUAL DYSFUNCTION
3OME SYMPTOMS ARE DUE PRIMARILY TO THE DISEASE PROCESS ITSELF EG DEMENTIA
SOME ARE THOUGHT TO BE DUE PRIMARILY TO 0$ TREATMENT EG IMPULSE CONTROL
DISORDERS AND OTHERS ARE DUE TO A COMBINATION OF BOTH THE DISEASE AND ITS
TREATMENT EG ORTHOSTATIC HYPOTENSION VISUAL HALLUCINATIONS EXCESSIVE
DAYTIME SOMNOLENCE &IGURE
4ABLE LISTS COMMON .-3 AND A SUGGESTED APPROACH TO THE MANAGEMENT OF
THESE SYMPTOMS
24
Non-motor symptoms
Treatment Options
Comments
Cognitive impairment
#OMPENSATORY STRATEGIES EG CUEING SIMPLIFYING
COMPLEX TASKS
,ESS POTENT 0$ MEDICATIONS SHOULD BE ELIMINATED
SEE ABOVE UNDER 0SYCHOSIS
3 #HOLINESTERASE INHIBITORS RIVASTIGMINE %XELON
5 MG 0/ BID nBY 3 MGD EVERY WEEKS TO MG
BD ACCORDING TO TOLERANCE RIVASTIGMINE PATCH
MGD INCREASE AFTER WEEKS TO 95 MGD ; DONEPEZIL
ARICEPT 5 MGD nAFTER WEEKS TO MGD
-EMANTINE %BIXA HAS CONFLICTING DATA FOR EFFICACY
IN 0$$
s #HOLINESTERASE INHIBITORS GENERALLY WELL
TOLERATED
s 4REMOR MAY nEG IN OF PATIENTS
TAKING RIVASTIGMINE AND MAY BE SEVERE
ENOUGH TO CAUSE DRUG WITHDRAWAL IN <
s -ODEST COGNITIVE BENEFIT OVERALL
Fatigue
%FFECT OF $24 FATIGUE MAY BE LESS LIKELY TO WORSEN
IN PATIENTS TREATED WITH ,
DOPA AND APATHY SCORES
ARE IMPROVED IN ,
DOPA
INDUCED h/.v
STATES
3ELEGILINE JUMEX3ELEGOS MG MORNING
AMANTADINE 0+
-ERZ MG TDS METHYLPHENIDATE
2ITALIN MG TDS OR MODAFINIL 0ROVIGIL
MGD MAY BE TRIED
s /FTEN REFRACTORY TO TREATMENT
s %XCLUDE TREAT CO
MORBID DEPRESSION %$3
ANAEMIA OR HYPOTHYROIDISM
s -ETHYLPHENIDATE AND MODAFINIL ARE WELL
TOLERATED
Insomnia /
Nocturnal sleep disturbance
ATTENTION TO SLEEP HYGIENE EG ESTABLISH A REGULAR
PATTERN OF SLEEP RESTRICT DAYTIME NAPS EXERCISE
AVOID CAFFEINE AND FLUIDS IN EVENING COMFORTABLE
BEDDING AND DARKNESS DURING THE NIGHT
%FFECTS OF $24 ON SLEEP IS VARIABLE; IT MAY HELP TO
AVOID NIGHTTIME DOSING; ON THE OTHER HAND $24
EG CONTROLLED
RELEASE ,
DOPA MAY BENEFIT NOCTURNAL
MOTOR SYMPTOMS PARKINSONISM OR DYSTONIA
3 )DENTIFY AND TREAT UNDERLYING CAUSE EG #0A0 FOR
/3A; LOOK FOR DEPRESSION AND )#$S MAY BE
ASSOCIATED WITH SLEEP DISTURBANCE
3EDATING ANTIDEPRESSANT EG AMITRIPTYLINE
5
MG NOCTE OR MIRTAZAPINE 2EMERON
5 MG
NOCTE; NON
BENZODIAZEPINE HYPNOTIC EG ZOLPIDEM
3TILNOX
MG NOCTE; BENZODIAZEPINE EG
LORAZEPAM ATIVAN
MG NOCTE; ATYPICAL
ANTIPSYCHOTIC EG QUETIAPINE 3EROQUEL IMMEDIATE
RELEASE
5 MG NOCTE CAUTION IS REQUIRED
ESPECIALLY IN ELDERLY PATIENTS DUE TO FALLS RISK
s 0OLYSOMNOGRAPHY REQUIRED IN SOME CASES
EG TO DIAGNOSE /3A
s ,ONG
TERM USE OF BENZODIAZEPINES IS
ASSOCIATED WITH TOLERANCE AND COGNITIVE
IMPAIRMENT
Rapid-eye-movement sleep
behavior disorder (RBD)
-ILD 2"$ MAY NOT NEED MEDICATION 2X; SAFETY OF
THE SLEEPING ENVIRONMENT MAY BE SUFFICIENT EG
REMOVING POTENTIALLY DANGEROUS OBJECTS PLACING
CUSHIONS AROUND THE BED OR MATTRESS ON THE FLOOR
)N MODERATE OR SEVERE CASES EG SLEEP DISRUPTION OR
INJURY TO SELF OR PARTNER MEDICATION 2X IS WARRANTED
EG CLONAZEPAM 2IVOTRIL 5 MG NOCTE n
ACCORDING TO RESPONSE AND TOLERABILITY UP TO MGD
3 #ONSIDER MELATONIN 3 MG NOCTE nBY 3 MG EVERY
WEEK AS NECESSARY AND TOLERATED UP TO MG
Excessive daytime somnolence
(EDS) and Sleep Attacks (SAs)
)MPROVING NIGHTTIME SLEEP MAY OR MAY NOT
IMPROVE %$3
$24 ESPECIALLY $AS SHOULD BE USED AT THE LOWEST
DOSE THAT SATISFACTORILY CONTROLS 0$ SYMPTOMS
3 #ONSIDER MODAFINIL 0ROVIGIL
MGD
WELL
TOLERATED BUT CONFLICTING EVIDENCE FOR EFFICACY
FROM PLACEBO
CONTROLLED 2#4S
)F %$3 OR 3AS PERSIST DESPITE MEDICATION CHANGES
DRIVING SHOULD PREFERABLY BE CURTAILED
3AS FALLING ASLEEP SUDDENLY AND
IRRESISTIBLY WITHOUT WARNING SIGNS
SUCH AS YAWNING GENERALLY
REPRESENT A SUDDEN EXACERBATION
OF ANTECEDENT %$3
s %33 RECOMMENDED FOR MEASURING %$3
SCORE > CONSIDERED ABNORMAL ; IT IS
PARTICULARLY IMPORTANT TO SCREEN PATIENTS
WHO DRIVE ALSO ENQUIRE h$O YOU OR HAVE
YOU IN THE PAST UNINTENTIONALLY AND SUDDENLY
FALLEN ASLEEP DURING THE DAY v
27
Table 5. #OMMONLY USED TREATMENTS FOR .-3
!BBREVIATIONS "48 BOTULINUM
TOXIN INJECTIONS #"4 COGNITIVE
BEHAVIOURAL THERAPY #0!0 CONTINUOUS POSITIVE AIRWAY PRESSURE
$!S DOPAMINE AGONISTS $"0 DIASTOLIC BLOOD PRESSURE $24 DOPAMINE REPLACEMENT THERAPY %#4
ELECTROCONVULSIVE THERAPY %$3 EXCESSIVE DAYTIME SOMNOLENCE %33 %PWORTH SLEEPINESS SCALE ,)$
,
DOPA
INDUCED DYSKINESIA -!/
" MONOAMINE OXIDASE " --3% -INI
-ENTAL 3TATE %XAMINATION
/( ORTHOSTATIC HYPOTENSION /3! OBSTRUCTIVE SLEEP APNOEA 0$$ 0ARKINSONS DISEASE DEMENTIA
2"$ RAPID
EYE
MOVEMENT SLEEP BEHAVIOUR DISORDER 2#4S RANDOMIZED CONTROLLED TRIALS 2O RULE
OUT 2X TREATMENT 3!S SLEEP ATTACKS 3%S SIDE EFFECTS 3"0 SYSTOLIC BLOOD PRESSURE 3, SUBLINGUAL
332)S SELECTIVE SEROTONIN
REUPTAKE INHIBITORS 4520 TRANSURETHRAL RESECTION OF THE PROSTATE 7##
WHITE CELL COUNT PERIPHERAL BLOOD
Non-motor symptoms
26
Treatment Options
Comments
Depression
#ONSIDER EMOTIONAL FLUCTUATIONS ASSOCIATED WITH
h/&&v PERIODS o2EDUCE h/&&v TIME
)NVOLVEMENT OF GERIATRIC OR NEURO
PSYCHIATRIST
ROLE FOR #"4
3 332)S EG ESCITALOPRAM,EXAPRO
MGD
FLUOXETINE 0ROZAC
MGD FLUVOXAMINE
,UVOX 5
3 MGD PAROXETINE 3EROXAT
5 MGD SERTRALINE ZOLOFT 5
MGD
/THERS AGOMELATINEVALDOXAN 5
5 MG NOCTE
AMITRIPTYLINE 5
5 MGD DESVENLAFAXINE
0RISTIQ 5 MGD DULOXETINE #YMBALTA
3
MGD MIRTAZAPINE 2EMERON 5
5 MG
NOCTE VENLAFAXINE %FFEXOR 375
875 MG BD OR
%FFEXOR X2 75
375 MGD
5 0RAMIPEXOLE 3IFROL MAY HAVE ANTIDEPRESSANT
EFFECTS OVER AND ABOVE ITS ANTIPARKINSONIAN EFFECTS
%#4 IN SEVERE REFRACTORY CASES
s 332)S HAVE A FAVORABLE 3% PROFILE AND ARE
TYPICALLY ST CHOICE; THEY DO NOT IN GENERAL
WORSEN THE MOTOR SIGNS OF 0$
s #ONSIDER TARGETING ANTIDEPRESSANT TO
ACCOMPANYING SYMPTOMS EG MIRTAZAPINE
OR AMITRIPTYLINE IF ASSOCIATED INSOMNIA;
ANTICHOLINERGIC 3%S OF AMITRIPTYLINE MAY BE
ADVANTAGEOUS IN PATIENTS WITH DROOLING OR
OVERACTIVE BLADDER
Anxiety / Panic attacks
#ONSIDER EMOTIONAL FLUCTUATIONS ASSOCIATED WITH
h/&&v PERIODS o2EDUCE h/&&v TIME
)NVOLVEMENT OF GERIATRIC OR NEURO
PSYCHIATRIST; ROLE
FOR #"4
3 332)S ALSO TO 2X DEPRESSION WHICH IS HIGHLY
COMORBID WITH ANXIETY
"ENZODIAZEPINES EG ALPRAZOLAM XANAX 5
5 MG 02. LORAZEPAM ATIVAN 5
MG 02.
s 4HERE IS NO CLINICAL TRIAL DATA CONCERNING 2X
CHOICE FOR ANXIETY IN 0$ 4REATMENT IS SIMILAR
TO PATIENTS WITHOUT 0$
s "ENZODIAZEPINES SHOULD BE USED CAUTIOUSLY TO
AVOID DEPENDENCE
Psychosis
2O SECONDARY EG METABOLIC CAUSES; 0$
MEDICATIONS SHOULD BE ELIMINATED IN THE FOLLOWING
ORDER ANTICHOLINERGICS oAMANTADINE o$AS o
-A/ " INHIBITORS , DOPA HAS THE GREATEST MOTOR
EFFECT WITH THE LEAST MENTAL 3%S; THE LOWEST DOSE THAT
SATISFACTORILY CONTROLS 0$ SYMPTOMS SHOULD BE USED
ATYPICAL ANTIPSYCHOTICS FOR PROBLEMATIC PSYCHOSIS
QUETIAPINE 3EROQUEL IMMEDIATE RELEASE
MG NOCTE OR EXTENDED RELEASE 5 MG
NOCTE ; CLOZAPINE #LOZARIL 5 MG NOCTE
3 #HOLINESTERASE INHIBITORS MAY HAVE ANTI PSYCHOTIC
EFFECTS IN 0$
%#4 IN SEVERE REFRACTORY CASES
s .OT ALL HALLUCINATIONS REQUIRE 2X IF MILD AND
WELL TOLERATED BY PATIENT AND FAMILY
s (IGH
POTENCY TYPICAL NEUROLEPTICS EG
HALOPERIDOL SHOULD ./4 BE USED ATYPICAL
ANTIPSYCHOTICS SUCH AS OLANZAPINE AND
RISPERIDONE ALSO WORSEN MOTOR FUNCTION AND
GENERALLY SHOULD NOT BE USED IN 0$
s 1UETIAPINE IS TYPICALLY ST
LINE EVEN THOUGH
THE EVIDENCE BASE FOR THIS IS RELATIVELY WEAK )T
MAY BE ASSOCIATED WITH WORSENING PARKINSONISM
ALTHOUGH TYPICALLY MILD AND USUALLY DOES NOT
WARRANT DISCONTINUATION
s #LOZAPINE IS THE MOST EFFECTIVE AND BEST
TOLERATED
AGENT BUT REQUIRES LONG
TERM BLOOD MONITORING
WEEKLY 7## FOR 8 WEEKS THEN FORTNIGHTLY OR
MONTHLY; < RISK OF AGRANULOCYTOSIS WHICH
MAY OCCUR EVEN ON SMALL DOSES AS AN IDIOSYNCRATIC
3% AND CAN BE FATAL IF NOT DISCOVERED EARLY
#LOZAPINE MAY ALSO SUPPRESS TREMOR AND ,)$
VERY EFFECTIVELY
s 4HERE IS A HIGH RATE OF RELAPSE EVEN WITH CAREFUL
TAPERING OF ANTIPSYCHOTIC
Appendix 1: Parkinsons Disease Drug
Identification Chart
Levodopa-Based Medications
Madopar 100/25mg cap
Levodopa/Benserazide
Madopar 200/50mg tab
Madopar HBS 100/25mg cap
Sinemet 25/100mg tab
Levodopa/Carbidopa
Sinemet 25/250mg tab
Sinemet CR 50/200mg tab
Entacapone
Comtan 200mg tab
Stalevo 50(50/12.5/200mg) tab
Levodopa/Carbidopa/
Entacapone
Stalevo 100(100/25/200mg) tab
Stalevo 150(150/37.5/200mg) tab
Stalevo 200(200/50/200mg) tab
Direct Dopamine Agonists (Ergot)
Bromocriptine
Parlodel 2.5mg tab
0ARKINSONS DISEASE AFFECTS EVERYONE DIFFERENTLY AND TREATMENTS NEED TO BE TAILORED TO THE INDIVIDUAL
29
Non-motor symptoms
Orthostatic hypotension (OH)
$EFINED AS p 3"0 MM (G
ANDOR $"0 MM (G
DURING UPRIGHT POSTURE WITH OR
WITHOUT POSTURAL SYMPTOMS
28
Treatment Options
.ON
PHARMACOLOGICAL nFLUID INTAKE nDIETARY SALT
AVOID ALCOHOL LARGE MEALS FREQUENT SMALL MEALS
INSTEAD EXCESSIVE WARMTH ELEVATE HEAD OF BED
0ATIENTS SHOULD BE ADVISED TO RISE SLOWLY ESPECIALLY
IN MORNING OR AFTER SITTINGLYING FOR A PERIOD OF TIME
$ISCONTINUE UNNECESSARY MEDICATIONS EG
ANTIHYPERTENSIVES
3 &LUDROCORTISONE &LORINEF
MGD
$OMPERIDONE -OTILIUM-OTIDONE
MG
TDS PARTICULARLY EFFECTIVE FOR $!
INDUCED /(
GIVE
3
MINUTES PRIOR TO $24 DOSES
5 -IDODRINE AMATINE0ROAMATINE'UTRON 5 OR
MG TDS
#ONSIDER PYRIDOSTIGMINE -ESTINON 3
MG TDS
Comments
s 3UPINE (4. A POTENTIAL 3% OF FLUDROCORTISONE
AND MIDODRINE
s /BSERVE FOR POSSIBLE HYPOKALAEMIA WHEN USING
HIGHER DOSES OF FLUDROCORTISONE
Constipation
#ONSIDER STOPPING ANTICHOLINERGICS
nDIETARY FIBRE AND FLUID INTAKE EG
8 GLASSES OF
WATERD
ALTHOUGH THIS MAY WORSEN URINARY SYMPTOMS
3 0SYLLIUM EG -ETAMUCIL
,AXATIVES EG LACTULOSE
3 M, DAILY OR BD
MACROGOLS EG &ORLAX
SACHETSD STIMULANT
LAXATIVES SUCH AS BISACODYL $ULCOLAX
5 MG
0/ NOCTE OR MG SUPPOSITORY 02.
Urinary frequency and
urgency, nocturia
(overactive bladder)
AVOID FLUID INTAKE AFTER DINNER FOR NOCTURIA ;
REGULAR VISITS TO THE BATHROOM TO AVOID URGENCY;
BEDSIDE URINAL MAY HELP TO AVOID INCONTINENCE
pINTAKE OF CAFFEINE ALCOHOL
3 ANTICHOLINERGIC AGENTS OXYBUTYNIN VOXYTANE
5 MG
3XD AMITRIPTYLINE TOLTERODINE $ETROL ,A
MGD TROSPIUM 3PASMOLYT MG BD
2EFERRAL FOR UROLOGICAL EVALUATION
MAY REQUIRE 2X
FOR "0(
s 4ROSPIUM DOES NOT SIGNIFICANTLY CROSS THE
BLOOD
BRAIN BARRIER AND THUS MAY BE PREFERRED
IN PATIENTS WITH COGNITIVE IMPAIRMENT
s !VOID SURGERY EG 4520 UNLESS CLEARLY
INDICATED
Erectile dysfunction
4REAT DEPRESSION AND DISCONTINUE POTENTIALLY
OFFENDING DRUGS EG BETA BLOCKERS
3ILDENAFIL VIAGRA 5
MG TAKEN
HOURS
BEFORE SEX
s /( MAY BE UNMASKED BY SILDENAFIL
Drooling
#HEWING GUM OR SUCKING ON HARD CANDY MAY SERVE
AS A CUE TO SWALLOWING MORE FREQUENTLY
ANTICHOLINERGIC AGENTS SUCH AS ORAL BENZHEXOL
APO
4RIHEX"ENZHEXOL 3, ATROPINE
OPHTHALMIC DROPS DROP 5 MG BD IPRATROPIUM
BROMIDE ATROVENT 3 G
SPRAYS INTO
THE MOUTH 3, UP TO QID
3 "4X OF SALIVARY PAROTID SUBMANDIBULAR GLANDS
2ARELY RADIOTHERAPY OR SURGERY REQUIRED
s 3YSTEMIC ANTICHOLINERGIC 3%S WITH ORAL
ANTICHOLINERGICS
s ATROVENT SPRAY WELL
TOLERATED BUT EFFECT MILD
s "4X GENERALLY WELL
TOLERATED
PD-related pain
0AIN IN UNTREATED AND FLUCTUATING 0$ PATIENTS EG
FROZEN SHOULDER AND h/&&v
PERIOD DYSTONIC PAIN
RESPECTIVELY CAN OFTEN BE IMPROVED BY EFFECTIVE 2X
OF UNDERLYING 0$
"4X FOR PAINFUL FOOT DYSTONIA
3 4#AS EG AMITRIPTYLINE ANTIEPILEPTICS EG
GABAPENTIN ;.EURONTIN= DULOXETINE #YMBALTA
OPIOIDS
$EEP BRAIN STIMULATION OF THE SUBTHALAMIC NUCLEUS
GLOBUS PALLIDUS INTERNUS
Appendix 2 - Patient diary (for motor fluctuations
and dyskinesia)
DAY ONE
Time
DATE:
ON
without
dyskinesia
ON with
minor
dyskinesia
ON with
troublesome
dyskinesia
OFF
Asleep
L-dopa intake
(please state
exact time)
%ACH ROW REPRESENTS HOURLY INTERVALS IN A DAY WHILE EACH COLUMN REPRESENTS DIFFERENT MOTOR STATES THAT CAN BE EXPERIENCED BY 0$ PATIENTS WITH
MOTOR FLUCTUATIONS -INOR DYSKINESIA IS WHEN THE ABNORMAL MOVEMENTS DO NOT BOTHER THE PATIENT WHILE TROUBLESOME DYSKINESIA IS WHEN THE
MOVEMENTS INTERFERE WITH DAILY ACTIVITIES &OR EACH ROW THE PATIENT IS INSTRUCTED TO TICK THE BOX /.,9 /.% THAT BEST REPRESENTS HISHER MOTOR
STATUS FOR THAT HOUR 0ATIENTS ARE ALSO ASKED TO RECORD THE EXACT TIME OF ,
DOPA INTAKE
31
Direct Dopamine Agonists (Non-Ergot)
Piribedil
Trivastal Retard 50mg SR tab
Sifrol 0.125mg tab
Pramipexole
Sifrol 1mg tab
Pramipexole extended
release
Sifrol ER 0.375mg tab
Sifrol ER 1.5 mg tab
Requip 0.25mg tab
Ropinirole
Requip 1mg tab
Requip 2mg tab
Ropinirole prolonged
release
Rotigotine transdermal
patch
Requip PD 2mg tab
Requip PD 4mg tab
Neupro
2mg
4mg
Others
Jumex 5mg tab
Selegiline
Selegos 5mg tab
Trihexyphenidyl
hydrochloride
Benzhexol 2mg tab
Orphenadrine
Norflex 100mg tab
Amantadine
PK-Merz 100mg tab
0ARKINSONS DISEASE AFFECTS EVERYONE DIFFERENTLY AND TREATMENTS NEED TO BE TAILORED TO THE INDIVIDUAL
30
6mg
8mg
29. 'ROSSET $ 4AURAH , "URN $* ET AL ! MULTICENTRE LONGITUDINAL OBSERVATIONAL STUDY OF CHANGES IN SELF REPORTED
HEALTH STATUS IN PEOPLE WITH 0ARKINSONS DISEASE LEFT UNTREATED AT DIAGNOSIS *OURNAL OF .EUROLOGY .EUROSURGERY
0SYCHIATRY
30. !MINOFF -* 4REATMENT SHOULD NOT BE INITIATED TOO SOON IN 0ARKINSONS DISEASE !NNALS OF .EUROLOGY
31. 3CHAPIRA !( !LBRECHT 3 "ARONE 0 ET AL )MMEDIATE VERSUS DELAYED START PRAMIPEXOLE IN EARLY 0ARKINSONS DISEASE
4HE 02/5$ STUDY )N TH 7ORLD &EDERATION OF .EUROLOGY 7ORLD #ONGRESS ON 0ARKINSONS $ISEASE AND 2ELATED
-OVEMENT $ISORDERS -IAMI "EACH
32. 3CHAPIRA !(6 4REATMENT OPTIONS IN THE MODERN MANAGEMENT OF 0ARKINSON DISEASE !RCHIVES OF .EUROLOGY
33. ,ANG !% 7HEN AND HOW SHOULD TREATMENT BE STARTED IN 0ARKINSON DISEASE .EUROLOGY 3UPPL 3
34. !HLSKOG *% #HEAPER SIMPLER AND BETTER 4IPS FOR TREATING SENIORS WITH 0ARKINSON DISEASE -AYO #LINIC 0ROCEEDINGS
35. +UMAR . 6AN 'ERPEN *! "OWER *( !HLSKOG *% ,EVODOPA DYSKINESIA INCIDENCE BY AGE OF 0ARKINSONS DISEASE
ONSET -OVEMENT $ISORDERS
36. &OX 3( +ATZENSCHLAGER 2 ,IM 39 ET AL 4HE -OVEMENT $ISORDER 3OCIETY EVIDENCE BASED MEDICINE REVIEW
UPDATE 4REATMENTS FOR THE MOTOR SYMPTOMS OF 0ARKINSONS DISEASE -OVEMENT $ISORDERS 3UPPL 3
37. 4HE 0ARKINSON 3TUDY 'ROUP ,EVODOPA AND THE PROGRESSION OF 0ARKINSONgS DISEASE 4HE .EW %NGLAND *OURNAL OF
-EDICINE
38. 0OEWE 7( 2ASCOL / 1UINN . ET AL %FFICACY OF PRAMIPEXOLE AND TRANSDERMAL ROTIGOTINE IN ADVANCED 0ARKINSONS
DISEASE ! DOUBLE
BLIND DOUBLE
DUMMY RANDOMISED CONTROLLED TRIAL ,ANCET .EUROLOGY
39. (AUSER 2! 3CHAPIRA !(6 2ASCOL / ET AL 2ANDOMIZED DOUBLE
BLIND MULTICENTER EVALUATION OF PRAMIPEXOLE
EXTENDED RELEASE ONCE DAILY IN EARLY 0ARKINSONS DISEASE -OVEMENT $ISORDERS
40. 'ROSSET $ !NTONINI ! #ANESI - ET AL !DHERENCE TO ANTIPARKINSON MEDICATION IN A MULTICENTER %UROPEAN
STUDY -OVEMENT $ISORDERS
41. +ORCZYN !$ 2EICHMANN ( "OROOJERDI " (ACK (
* 2OTIGOTINE TRANSDERMAL SYSTEM FOR PERIOPERATIVE ADMINISTRATION
*OURNAL OF .EURAL 4RANSMISSION
42. 4HE 0ARKINSON 3TUDY 'ROUP %FFECT OF DEPRENYL ON THE PROGRESSION OF DISABILITY IN EARLY 0ARKINSONS DISEASE 4HE
.EW %NGLAND *OURNAL OF -EDICINE
43. (AUSER 2! :ESIEWICZ 4! #LINICAL TRIALS AIMED AT DETECTING NEUROPROTECTION IN 0ARKINSONS DISEASE .EUROLOGY
3UPPL 3
44. 'OETZ #' +OLLER 7# 0OEWE 7 ET AL -ANAGEMENT OF 0ARKINSONS DISEASE !N EVIDENCE
BASED REVIEW
-OVEMENT $ISORDERS 3UPPL 3
3
45. 0ALHAGEN 3 (EINONEN % (AGGLUND * ET AL 3ELEGILINE SLOWS THE PROGRESSION OF THE SYMPTOMS OF 0ARKINSON
DISEASE .EUROLOGY
46. 0ARKINSON 3TUDY 'ROUP ! CONTROLLED RANDOMIZED DELAYED
START STUDY OF RASAGILINE IN EARLY 0ARKINSON DISEASE
!RCHIVES OF .EUROLOGY
47. /LANOW #7 2ASCOL / (AUSER 2 ET AL ! DOUBLE
BLIND DELAYED
START TRIAL OF RASAGILINE IN 0ARKINSONS DISEASE
4HE .EW %NGLAND *OURNAL OF -EDICINE
48. ,EES ! !LTERNATIVES TO ,EVODOPA IN THE INITIAL TREATMENT OF EARLY 0ARKINSONS DISEASE $RUGS !GING
49. 3HULTS #7 /AKES $ +IEBURTZ + ET AL %FFECTS OF #OENZYME 1 IN %ARLY 0ARKINSON $ISEASE %VIDENCE OF
SLOWING OF THE FUNCTIONAL DECLINE !RCHIVES OF .EUROLOGY
50. 4HE 0ARKINSON 3TUDY 'ROUP %FFECTS OF DEPRENYL ON THE PROGRESSION OF DISABILITY IN EARLY 0ARKINSONS DISEASE 4HE
.EW %NGLAND *OURNAL OF -EDICINE
51. 3TOESSL !* DE LA &UENTE
&ERNANDEZ 2 7ILLING ONESELF BETTER ON PLACEBO
EFFECTIVE IN ITS OWN RIGHT ,ANCET
52. $IEDERICH .* 'OETZ #' 4HE PLACEBO TREATMENTS IN NEUROSCIENCES .EW INSIGHTS FROM CLINICAL AND NEUROIMAGING
STUDIES .EUROLOGY
53. !HLSKOG *% $OES VIGOROUS EXERCISE HAVE A NEUROPROTECTIVE EFFECT IN 0ARKINSON DISEASE .EUROLOGY
References
DENOTES REFERENCES OF PARTICULAR INTEREST
1. ,IM 39 &OX 3( ,ANG !% /VERVIEW OF THE EXTRA
NIGRAL ASPECTS OF 0ARKINSON DISEASE !RCHIVES OF .EUROLOGY
2. #HAUDHURI +2 (EALY $' 3CHAPIRA !(6 .ON
MOTOR SYMPTOMS OF 0ARKINSONS DISEASE $IAGNOSIS AND MANAGEMENT
,ANCET .EUROLOGY
3. ,IM 39 ,ANG !% 4HE NONMOTOR SYMPTOMS OF 0ARKINSONS DISEASE !N OVERVIEW -OVEMENT $ISORDERS
3UPPL 3
4. -) .ORLINAH + .OR !FIDAH !4 .ORADINA !3 3HAMSUL B "" (AMIDON 2 3AHATHEVAN !! 2AYMOND 3LEEP
DISTURBANCES IN -ALAYSIAN PATIENTS WITH 0ARKINSONS DISEASE USING POLYSOMNOGRAPHY AND 0$33 0ARKINSONISM
2ELATED $ISORDERS
5. #HENG %- 3WARZTRAUBER + 3IDEROWF !$ !SSOCIATION OF SPECIALIST INVOLVEMENT AND QUALITY OF CARE FOR 0ARKINSONS
DISEASE -OVEMENT $ISORDERS
6. .ATIONAL )NSTITUTE FOR (EALTH AND #LINICAL %XCELLENCE .)#% 0ARKINSONS DISEASE $IAGNOSIS AND MANAGEMENT
IN PRIMARY AND SECONDARY CARE #' ,ONDON .ATIONAL )NSTITUTE FOR (EALTH AND #LINICAL %XCELLENCE
7. 'RIMES $ 'ORDON * 3NELGROVE " ET AL #ANADIAN GUIDELINES ON 0ARKINSONS DISEASE #ANADIAN *OURNAL OF .EUROLOGICAL
3CIENCES 3UPPL 3
8. ,EES !* 0ARKINSONS DISEASE 0RACTICAL .EUROLOGY
9. .UTT *' 7OOTEN '& $IAGNOSIS AND INITIAL MANAGEMENT OF 0ARKINSONgS DISEASE 4HE .EW %NGLAND *OURNAL OF
-EDICINE
10. 4OLOSA % 7ENNING ' 0OEWE 7 4HE DIAGNOSIS OF 0ARKINSONS DISEASE ,ANCET .EUROLOGY
11. $EUSCHL ' "AIN 0 "RIN - !D (OC 3CIENTIFIC #OMMITTEE #ONSENSUS STATEMENT OF THE -OVEMENT $ISORDER
3OCIETY ON TREMOR -OVEMENT $ISORDERS 3UPPL
12. $EUSCHL ' 2AETHJEN * (ELLRIEGEL ( %LBE 2 4REATMENT OF PATIENTS WITH ESSENTIAL TREMOR ,ANCET .EUROLOGY
13. ,ORBERBOYM - 4REVES 4! -ELAMED % ,AMPL 9 (ELLMANN - $JALDETTI 2 ;)= &0#)4 30%#4 IMAGING
FOR DISTINGUISHING DRUG INDUCED PARKINSONISM FROM 0ARKINSONgS DISEASE -OVEMENT $ISORDERS
14. $AS 3+ 2AY + 7ILSONS DISEASE !N UPDATE .ATURE #LINICAL 0RACTICE .EUROLOGY
15. !LA ! 7ALKER !0 !SHKAN + $OOLEY *3 3CHILSKY -, 7ILSONS DISEASE ,ANCET
16. -C+EITH ) $EMENTIA WITH ,EWY "ODIES AND 0ARKINSONS DISEASE WITH DEMENTIA 7HERE TWO WORLDS COLLIDE
0RACTICAL .EUROLOGY
17. 1UINN .0 (OW TO DIAGNOSE MULTIPLE SYSTEM ATROPHY -OVEMENT $ISORDERS 3UPPL 3n
18. 'ILMAN 3 7ENNING '+ ,OW 0! ET AL 3ECOND CONSENSUS STATEMENT ON THE DIAGNOSIS OF MULTIPLE SYSTEM
ATROPHY .EUROLOGY
19. "URN $* ,EES !* 0ROGRESSIVE SUPRANUCLEAR PALSY 7HERE ARE WE NOW ,ANCET .EUROLOGY
20. 7ILLIAMS $2 ,EES !* 0ROGRESSIVE SUPRANUCLEAR PALSY #LINICOPATHOLOGICAL CONCEPTS AND DIAGNOSTIC CHALLENGES
,ANCET .EUROLOGY
21. &ITZ'ERALD 0- *ANKOVIC * ,OWER BODY PARKINSONISM %VIDENCE FOR VASCULAR ETIOLOGY -OVEMENT $ISORDERS
22. :IJLMANS *#- $ANIEL 3% (UGHES !* 2EVESZ 4 ,EES !* #LINICOPATHOLOGICAL INVESTIGATION OF VASCULAR
PARKINSONISM INCLUDING CLINICAL CRITERIA FOR DIAGNOSIS -OVEMENT $ISORDERS
23. +ALRA 3 'ROSSET $' "ENAMER (43 $IFFERENTIATING VASCULAR PARKINSONISM FROM IDIOPATHIC 0ARKINSONS DISEASE
! SYSTEMATIC REVIEW -OVEMENT $ISORDERS
24. %SPAY !* .ARAYAN 2+ $UKER !0 "ARRETT *R %4 DE #OURTEN
-YERS ' ,OWER
BODY PARKINSONISM 2ECONSIDERING
THE THRESHOLD FOR EXTERNAL LUMBAR DRAINAGE .ATURE #LINICAL 0RACTICE .EUROLOGY
25. 'OETZ #' 0OEWE 7 2ASCOL / ET AL -OVEMENT $ISORDER 3OCIETY 4ASK &ORCE REPORT ON THE (OEHN AND 9AHR
STAGING SCALE 3TATUS AND RECOMMENDATIONS -OVEMENT $ISORDERS
26. &AHN 3 %LTON 2, 50$23 PROGRAM MEMBERS 5NIFIED 0ARKINSONS DISEASE RATING SCALE )N &AHN 3 -ARSDEN #$
'OLDSTEIN - #ALNE $" EDITORS 2ECENT DEVELOPMENTS IN 0ARKINSONS DISEASE 6OL &LORHAM 0ARK .* -ACMILLAN
(EALTHCARE )NFORMATION P
27. #HAUDHURI +2 .ON
MOTOR SYMPTOMS ARE THE MAJOR DETERMINANT OF QUALITY OF LIFE IN 0ARKINSONS DISEASE
-OVING !LONG
28. 3CHAPIRA !(6 /BESO * 4IMING OF TREATMENT INITIATION IN 0ARKINSONS DISEASE ! NEED FOR REAPPRAISAL !NNALS OF
.EUROLOGY
78. -ORO % (AMANI # 0OON 9 9 ET AL 5NILATERAL PEDUNCULOPONTINE STIMULATION IMPROVES FALLS IN 0ARKINSONS
DISEASE "RAIN
79. /KUN -3 6ITEK *, ,ESION THERAPY FOR 0ARKINSONS DISEASE AND OTHER MOVEMENT DISORDERS 5PDATE AND
CONTROVERSIES -OVEMENT $ISORDERS
80. !NTONINI ! /DIN 0 0ROS AND CONS OF APOMORPHINE AND , DOPA CONTINUOUS INFUSION IN ADVANCED 0ARKINSONS
DISEASE 0ARKINSONISM AND 2ELATED $ISORDERS 3UPPL 3
81. 'OETZ #' 0OEWE 7 2ASCOL / 3AMPAIO # %VIDENCE BASED MEDICAL REVIEW UPDATE 0HARMACOLOGICAL AND
SURGICAL TREATMENTS OF 0ARKINSONS DISEASE TO -OVEMENT $ISORDERS
82. -ANSON !* 4URNER + ,EES !* !POMORPHINE MONOTHERAPY IN THE TREATMENT OF REFRACTORY MOTOR COMPLICATIONS
OF 0ARKINSONS DISEASE ,ONG TERM FOLLOW UP STUDY OF PATIENTS -OVEMENT $ISORDERS
83. +ATZENSCHLAGER 2 (UGHES ! %VANS ! #ONTINUOUS SUBCUTANEOUS APOMORPHINE THERAPY IMPROVES DYSKINESIAS IN
0ARKINSONS DISEASE ! PROSPECTIVE STUDY USING SINGLE DOSE CHALLENGES -OVEMENT $ISORDERS
84. 4YNE (, 0ARSONS * 3INNOTT ! &OX 3( &LETCHER .! 3TEIGER -* ! YEAR RETROSPECTIVE AUDIT OF LONG TERM
APOMORPHINE USE IN 0ARKINSONS DISEASE *OURNAL OF .EUROLOGY
85. $E 'ASPARI $ 3IRI # ,ANDI ! ET AL #LINICAL AND NEUROPSYCHOLOGICAL FOLLOW UP AT MONTHS IN PATIENTS WITH
COMPLICATED 0ARKINSONS DISEASE TREATED WITH SUBCUTANEOUS APOMORPHINE INFUSION OR DEEP BRAIN STIMULATION OF
THE SUBTHALAMIC NUCLEUS *OURNAL OF .EUROLOGY .EUROSURGERY 0SYCHIATRY
86. $EVOS $ &RENCH $5/$/0! 3TUDY 'ROUP 0ATIENT PROFILE INDICATIONS EFFICACY AND SAFETY OF DUODENAL
LEVODOPA INFUSION IN ADVANCED 0ARKINSONgS DISEASE -OVEMENT $ISORDERS
87. /LANOW #7 3TERN -" 3ETHI + 4HE SCIENTIFIC AND CLINICAL BASIS FOR THE TREATMENT OF 0ARKINSON DISEASE
.EUROLOGY 3UPPL 3
88. 3EPPI + 7EINTRAUB $ #OELHO - ET AL 4HE -OVEMENT $ISORDER 3OCIETY EVIDENCE BASED MEDICINE REVIEW
UPDATE 4REATMENTS FOR THE NON MOTOR SYMPTOMS OF 0ARKINSONgS DISEASE -OVEMENT $ISORDERS
3UPPL 3
89. ,IM 39 &OX 3( !N UPDATE ON THE MANAGEMENT OF 0ARKINSONS DISEASE 'ERIATRICS !GING
90. "OREK ,, !MICK -- &RIEDMAN *( .ON MOTOR ASPECTS OF 0ARKINSONS DISEASE #.3 3PECTRUMS
91. !ARSLAND $ -ARSH , 3CHRAG ! .EUROPSYCHIATRIC SYMPTOMS IN 0ARKINSONS DISEASE -OVEMENT $ISORDERS
92. ,IM 39 %VANS !( #HAPTER 0AIN AND PARESTHESIA IN 0ARKINSONS DISEASE )N /LANOW #7 3TOCCHI & ,ANG
!% EDITORS 0ARKINSONS DISEASE .ON MOTOR AND NON DOPAMINERGIC FEATURES /XFORD "LACKWELL 0UBLISHING
PP
54. ,IM 39 %VANS !( -IYASAKI *- )MPULSE CONTROL AND RELATED DISORDERS IN 0ARKINSONS DISEASE 2EVIEW !NNALS
OF THE .EW 9ORK !CADEMY OF 3CIENCES 4HE 9EAR IN .EUROLOGY
55. ,IM 39 4AN :+ .GAM 0) ET AL )MPULSIVE COMPULSIVE BEHAVIOURS ARE COMMON IN !SIAN 0ARKINSONgS DISEASE
PATIENTS !SSESSMENT USING THE 15)0 0ARKINSONISM 2ELATED $ISORDERS
56. 2ICHARD )( +URLAN 2 4ANNER # ET AL 3EROTONIN SYNDROME AND THE COMBINED USE OF DEPRENYL AND AN
ANTIDEPRESSANT IN 0ARKINSONgS DISEASE .EUROLOGY
57. ,EES !* #OMPARISON OF THERAPEUTIC EFFECTS AND MORTALITY DATA OF LEVODOPA AND LEVODOPA COMBINED WITH
SELEGILINE IN PATIENTS WITH EARLY MILD 0ARKINSONgS DISEASE "RITISH -EDICAL *OURNAL
58. /LANOW #7 -YLLYLA 66 3OTANIEMI +! ET AL %FFECT OF SELEGILINE ON MORTALITY IN PATIENTS WITH 0ARKINSONgS
DISEASE ! META ANALYSIS .EUROLOGY
59. -ONOAMINE OXIDASE TYPE " INHIBITORS IN EARLY 0ARKINSONgS DISEASE -ETA ANALYSIS OF RANDOMISED TRIALS
INVOLVING PATIENTS )VES .* 3TOWE 2, -ARRO * ET AL "RITISH -EDICAL *OURNAL
60. 3TACY - "OWRON ! 'UTTMAN - ET AL )DENTIFICATION OF MOTOR AND NONMOTOR WEARING OFF IN 0ARKINSONS DISEASE
#OMPARISON OF A PATIENT QUESTIONNAIRE VERSUS A CLINICIAN ASSESSMENT -OVEMENT $ISORDERS
61. (AUSER 2! $ECKERS & ,EHERT 0 0ARKINSONS DISEASE HOME DIARY &URTHER VALIDATION AND IMPLICATIONS FOR CLINICAL
TRIALS -OVEMENT $ISORDERS
62. 'OETZ #' +OLLER 7# 0OEWE 7 ET AL -ANAGEMENT OF 0ARKINSONS DISEASE !N EVIDENCE BASED REVIEW
-OVEMENT $ISORDERS 3UPPL 3
63. 2ASCOL / "ROOKS $* -ELAMED % ET AL 2ASAGILINE AS AN ADJUNCT TO LEVODOPA IN PATIENTS WITH 0ARKINSONS DISEASE
AND MOTOR FLUCTUATIONS ,!2'/ ,ASTING EFFECT IN !DJUNCT THERAPY WITH 2ASAGILINE 'IVEN /NCE DAILY STUDY !
RANDOMISED DOUBLE BLIND PARALLEL GROUP TRIAL ,ANCET
64. 0ARKINSON 3TUDY 'ROUP ! RANDOMIZED PLACEBO CONTROLLED TRIAL OF RASAGILINE IN LEVODOPA TREATED PATIENTS WITH
0ARKINSON DISEASE AND MOTOR FLUCTUATIONS 4HE 02%34/ STUDY !RCHIVES OF .EUROLOGY
65. 3TOWE 2 )VES . #LARKE #% ET AL %VALUATION OF THE EFFICACY AND SAFETY OF ADJUVANT TREATMENT TO LEVODOPA THERAPY
IN 0ARKINSON S DISEASE PATIENTS WITH MOTOR COMPLICATIONS #OCHRANE $ATABASE OF 3YSTEMATIC 2EVIEWS *UL
#$
66. 4RENKWALDER # +IES " 2UDZINSKA - ET AL 2OTIGOTINE EFFECTS ON EARLY MORNING MOTOR FUNCTION AND SLEEP IN
0ARKINSONgS DISEASE ! DOUBLE BLIND RANDOMIZED PLACEBO CONTROLLED STUDY 2%#/6%2 -OVEMENT $ISORDERS
67. 7OLF % 3EPPI + +ATZENSCHLAGER 2 ET AL ,ONG TERM ANTIDYSKINETIC EFFICACY OF AMANTADINE IN 0ARKINSONS DISEASE
-OVEMENT $ISORDERS
68. +RINGELBACH -, *ENKINSON . /WEN 3,& !ZIZ 4: 4RANSLATIONAL PRINCIPLES OF DEEP BRAIN STIMULATION .ATURE
2EVIEWS .EUROSCIENCE
69. $EUSCHL ' 3CHADE "RITTINGER # +RACK 0 ET AL ! RANDOMIZED TRIAL OF DEEP BRAIN STIMULATION FOR 0ARKINSONS
DISEASE 4HE .EW %NGLAND *OURNAL OF -EDICINE
70. 3CHUPBACH 7- -ALTETE $ (OUETO *, ET AL .EUROSURGERY AT AN EARLIER STAGE OF 0ARKINSON DISEASE ! RANDOMIZED
CONTROLLED TRIAL .EUROLOGY
71. 7ILLIAMS ! 'ILL 3 6ARMA 4 ET AL $EEP BRAIN STIMULATION PLUS BEST MEDICAL THERAPY VERSUS BEST MEDICAL THERAPY
ALONE FOR ADVANCED 0ARKINSONS DISEASE 0$ 352' TRIAL ! RANDOMISED OPEN LABEL TRIAL ,ANCET .EUROLOGY
72. -ORO % ,OZANO !- 0OLLAK 0 ET AL ,ONG TERM RESULTS OF A MULTICENTER STUDY ON SUBTHALAMIC AND PALLIDAL
STIMULATION IN 0ARKINSONgS DISEASE -OVEMENT $ISORDERS
73. +ISHORE ! 2AO 2 +RISHNAN 3 ET AL ,ONG TERM STABILITY OF EFFECTS OF SUBTHALAMIC STIMULATION IN 0ARKINSONgS
DISEASE )NDIAN EXPERIENCE -OVEMENT $ISORDERS
74. :IBETTI - -EROLA ! 2IZZI , ET AL "EYOND NINE YEARS OF CONTINUOUS SUBTHALAMIC NUCLEUS DEEP BRAIN STIMULATION
IN 0ARKINSONgS DISEASE -OVEMENT $ISORDERS
75. ,ANG !% (OUETO *, +RACK 0 ET AL $EEP BRAIN STIMULATION 0REOPERATIVE ISSUES -OVEMENT $ISORDERS
3UPPL 3
76. ,IM 39 -ORO % ,ANG !% #HAPTER .ON MOTOR SYMPTOMS OF 0ARKINSONS DISEASE AND THE EFFECTS OF DEEP
BRAIN STIMULATION )N #HAUDHURI +2 4OLOSA % 3CHAPIRA ! 0OEWE 7 EDITORS .ON -OTOR 3YMPTOMS OF
0ARKINSONgS $ISEASE /XFORD /XFORD 5NIVERSITY 0RESS PP
77. $EFER ' , 7IDNER ( -ARIE 2 - 2EMY 0 ,EVIVIER - #ONFERENCE 0ARTICIPANTS #ORE ASSESSMENT PROGRAM FOR
SURGICAL INTERVENTIONAL THERAPIES IN 0ARKINSONS DISEASE #!03)4 0$ -OVEMENT $ISORDERS
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