The management of advanced Parkinson’s disease Dr J Paul Milnes Consultant Physician Airedale NHS Trust

The management of advanced The management of advanced Parkinson’s diseaseParkinson’s disease

Dr J Paul MilnesDr J Paul Milnes

Consultant PhysicianConsultant Physician

Airedale NHS TrustAiredale NHS Trust

Outline of the lectureOutline of the lecture

A few facts about Parkinson’s A few facts about Parkinson’s diseasedisease

The problems encountered as the The problems encountered as the disease progressesdisease progresses

Highlight important management Highlight important management pointspoints

Epidemiology of Epidemiology of Parkinson’s diseaseParkinson’s disease

Approximately 1% of the population Approximately 1% of the population over 60 years has Parkinson’s diseaseover 60 years has Parkinson’s disease

The number of cases increase with ageThe number of cases increase with age The ageing population is expected to The ageing population is expected to

dramatically increase the number of dramatically increase the number of casescases

Parkinson’s disease may affect Parkinson’s disease may affect between 5 and 10% of the nursing between 5 and 10% of the nursing home populationhome population

Changes in the brain in Changes in the brain in Parkinson’s diseaseParkinson’s disease

Loss of dopaminergic neurones from Loss of dopaminergic neurones from the substantia nigra is an essential the substantia nigra is an essential feature of Parkinson’s diseasefeature of Parkinson’s disease

The presence of Lewy bodiesThe presence of Lewy bodies

Changes in the brain in Changes in the brain in Parkinson’s diseaseParkinson’s disease

There’s more to Parkinson’s disease There’s more to Parkinson’s disease than the substantia nigra than the substantia nigra involvementinvolvement

Braak has demonstrated the Braak has demonstrated the progression of abnormalities in the progression of abnormalities in the brain as Parkinson’s disease brain as Parkinson’s disease progresses progresses Mov Disord 2006; 21: Mov Disord 2006; 21: 20422042

The diagnosis of The diagnosis of Parkinson’s diseaseParkinson’s disease

Don’t be afraid to question the Don’t be afraid to question the diagnosis even at a relatively late diagnosis even at a relatively late stagestage

Do all people with Do all people with Parkinson’s disease have Parkinson’s disease have

tremor?tremor? Up to 20% of cases never develop Up to 20% of cases never develop

tremor at any stage of the illnesstremor at any stage of the illness

Do all people with Do all people with Parkinson’s disease have Parkinson’s disease have reduction and slowness of reduction and slowness of

movement?movement?

Hypokinesia and Hypokinesia and bradykinesiabradykinesia

Poverty and slowness of movement Poverty and slowness of movement Must be present to make the diagnosisMust be present to make the diagnosis

Reduced facial expressionReduced facial expression Slow shuffling gaitSlow shuffling gait Reduced arm swingReduced arm swing Reduced swallowingReduced swallowing Difficulty turningDifficulty turning Small handwritingSmall handwriting Difficulty with fine movements affecting the whole Difficulty with fine movements affecting the whole

range of activities of daily livingrange of activities of daily living Usually asymmetricalUsually asymmetrical

UKPDS Brain Bank UKPDS Brain Bank CriteriaCriteria

Step1 Diagnosis of a parkinsonian syndromeStep1 Diagnosis of a parkinsonian syndrome Bradykinesia (slowness of movement) and at Bradykinesia (slowness of movement) and at

least one of the followingleast one of the following Muscular rigidityMuscular rigidity Rest tremor Rest tremor Postural instability unrelated to primary visual, Postural instability unrelated to primary visual,

vestibular or proprioceptive dysfunctionvestibular or proprioceptive dysfunction

Step2 Exclusion criteria for Parkinson’s Step2 Exclusion criteria for Parkinson’s DiseaseDisease

Step3 Supportive criteria for Parkinson’s Step3 Supportive criteria for Parkinson’s DiseaseDisease

Differential diagnosis of Differential diagnosis of Parkinson’s DiseaseParkinson’s Disease

Essential tremorEssential tremor Diffuse Lewy Body Disease Diffuse Lewy Body Disease Cerebrovascular diseaseCerebrovascular disease Progressive supranuclear palsyProgressive supranuclear palsy Multiple system atrophyMultiple system atrophy Trauma or toxin relatedTrauma or toxin related Drug inducedDrug induced OthersOthers

The diagnosis of The diagnosis of Parkinson’s diseaseParkinson’s disease

Don’t be afraid to question the diagnosis Don’t be afraid to question the diagnosis because it can be difficultbecause it can be difficult

Has a specialist been involved?Has a specialist been involved? Up to 25% error rate for non specialist hospital Up to 25% error rate for non specialist hospital

doctorsdoctors

““The diagnosis of Parkinson’s disease The diagnosis of Parkinson’s disease should be reviewed regularly and should be reviewed regularly and reconsidered if atypical features reconsidered if atypical features develop” develop” NICE 2006NICE 2006

The management of The management of Parkinson’s diseaseParkinson’s disease

The management of the The management of the disease can be planned in disease can be planned in

four stagesfour stagesNursing Older People 2004; Nursing Older People 2004;

16:116:1 DiagnosisDiagnosis

MaintenanceMaintenance

ComplexComplex

PalliativePalliative

Audit of 73 cases in Audit of 73 cases in CornwallCornwall

Parkinsonism and related disorders 1999; Parkinsonism and related disorders 1999; 5(S53)5(S53)

Mean duration of the disease 14.6 Mean duration of the disease 14.6 yearsyears

Average duration of the four stagesAverage duration of the four stages Diagnosis 1.5 yearsDiagnosis 1.5 years Maintenance 6 yearsMaintenance 6 years Complex 5 yearsComplex 5 years Palliative 2.2 yearsPalliative 2.2 years

The palliative phase of The palliative phase of Parkinson’s diseaseParkinson’s disease

Patients become increasingly Patients become increasingly disabled and dependantdisabled and dependant

The palliative phase of Parkinson’s The palliative phase of Parkinson’s disease has been defined bydisease has been defined by

Inability to tolerate adequate dopaminergic Inability to tolerate adequate dopaminergic therapytherapy

Unsuitability for surgeryUnsuitability for surgery The presence of advanced co-morbidity The presence of advanced co-morbidity

which is life threatening or disablingwhich is life threatening or disabling

The palliative phase of The palliative phase of Parkinson’s disease Parkinson’s disease

NICE Guidance 2006NICE Guidance 2006 Palliative care does not correlate Palliative care does not correlate

with imminent death in Parkinson’s with imminent death in Parkinson’s diseasedisease

Shift from a therapeutic Shift from a therapeutic pharmacological approach to one pharmacological approach to one which places a greater emphasis on which places a greater emphasis on quality of life issuesquality of life issues

The palliative phase of The palliative phase of Parkinson’s disease Parkinson’s disease

NICE Guidance 2006NICE Guidance 2006 It should be possible to seek advice It should be possible to seek advice

from specialist palliative care teams, from specialist palliative care teams, not just at the end of life, but at any not just at the end of life, but at any stage after diagnosisstage after diagnosis

Recognising the needs of carers at an Recognising the needs of carers at an early stage will enable people to stay at early stage will enable people to stay at home for as long as possiblehome for as long as possible

Many carers will have become “experts Many carers will have become “experts in Parkinson’s disease” themselvesin Parkinson’s disease” themselves

Palliative care and Palliative care and specialist care for PD specialist care for PD

patients in nursing homespatients in nursing homes Between 5 and 10% of nursing home Between 5 and 10% of nursing home

residents have Parkinson’s diseaseresidents have Parkinson’s disease

Many may remain undiagnosed Many may remain undiagnosed

The support from specialist services is The support from specialist services is inadequate and inconsistentinadequate and inconsistent

This population poses huge challenges to us This population poses huge challenges to us allall

NICE Guidance 2006NICE Guidance 2006

The care of people with Parkinson’s The care of people with Parkinson’s disease is best undertaken in a disease is best undertaken in a multidisciplinary way throughout multidisciplinary way throughout each stage of the diseaseeach stage of the disease

Advanced Parkinson’s Advanced Parkinson’s diseasedisease

Motor problemsMotor problems

Non-motor problemsNon-motor problems

Motor problems in Motor problems in advanced disease includeadvanced disease include

Failing mobility and fallsFailing mobility and falls Deterioration in the whole range of Deterioration in the whole range of

activities of daily livingactivities of daily living More frequent “off” periodsMore frequent “off” periods Speech impairmentSpeech impairment Swallowing difficultySwallowing difficulty Dyskinesias – abnormal movements Dyskinesias – abnormal movements

related to drugsrelated to drugs Less predictable response to medicationLess predictable response to medication

Motor problems in Motor problems in advanced disease advanced disease

The delicate balance between the The delicate balance between the benefits and side effects of drug benefits and side effects of drug treatmenttreatment

The crucial role of other The crucial role of other professionals and carersprofessionals and carers

The importance of ensuring the The importance of ensuring the correct timing of medication - correct timing of medication - especially in hospital and care especially in hospital and care homes homes

The crucial role of other The crucial role of other professionals and carersprofessionals and carers

Levodopa (madopar & Levodopa (madopar & sinemet)sinemet)

Levodopa is the most important treatment Levodopa is the most important treatment of the later stages of Parkinson’s diseaseof the later stages of Parkinson’s disease

It is the most effective drug for treating It is the most effective drug for treating motor problemsmotor problems

The side effects are not as extreme as The side effects are not as extreme as some of the other medications some of the other medications

Diet can influence its effect in advanced Diet can influence its effect in advanced Parkinson’s diseaseParkinson’s disease

Protein intake interferes with levodopa therapyProtein intake interferes with levodopa therapy

Levodopa and some amino acids, in protein rich Levodopa and some amino acids, in protein rich foods, compete for the same carriers in the foods, compete for the same carriers in the intestinal mucosa and blood brain barrier intestinal mucosa and blood brain barrier

The data suggest that patients with advanced The data suggest that patients with advanced Parkinson’s disease should adjust daily protein Parkinson’s disease should adjust daily protein intake and shift protein intake to the eveningintake and shift protein intake to the evening

The use of low protein foods to reduce off periods after mealThe use of low protein foods to reduce off periods after mealMov Disord 2006; 21(10): 1682Mov Disord 2006; 21(10): 1682

Beware of an unexpected Beware of an unexpected change in the speed of a change in the speed of a patient’s deteriorationpatient’s deterioration

Beware of an unexpected Beware of an unexpected change in the speed of a change in the speed of a patient’s deteriorationpatient’s deterioration

Consider other contributory factorsConsider other contributory factors

Reassess for intercurrent physical or Reassess for intercurrent physical or mental health problemsmental health problems

Common precipitants includeCommon precipitants include InfectionInfection DepressionDepression Drug side effectsDrug side effects

Case studyCase study

80 year old man with advanced 80 year old man with advanced Parkinson’s diseaseParkinson’s disease

Marked deterioration in his mobility Marked deterioration in his mobility over a 6 week periodover a 6 week period

Recurrent falls and more drowsyRecurrent falls and more drowsy No recent changes in drug treatment No recent changes in drug treatment

or signs of infectionor signs of infection Specialist review and further Specialist review and further

investigationinvestigation

Urgent CT Brain ScanUrgent CT Brain Scan

Neurosurgical treatmentNeurosurgical treatment

Non-motor features in Non-motor features in advanced Parkinson’s advanced Parkinson’s

diseasedisease Are they important?Are they important?

YesYes

Sydney Multicentre Study Sydney Multicentre Study of Parkinson’s Disease of Parkinson’s Disease Hely et al. Hely et al.

Mov Dis 2005; 20(2): 190Mov Dis 2005; 20(2): 190

Report on people with PD who Report on people with PD who survive 15 years from diagnosissurvive 15 years from diagnosis

One third of the 149 people One third of the 149 people recruited had survivedrecruited had survived

Sydney Multicentre StudySydney Multicentre StudyPD survivors at 15 yearsPD survivors at 15 years

81% Falls81% Falls 84% cognitive decline84% cognitive decline 50% hallucinations and depression50% hallucinations and depression 50% choking50% choking 41% urinary incontinence41% urinary incontinence 35% symptomatic postural 35% symptomatic postural

hypotensionhypotension

Sydney Multicentre StudySydney Multicentre StudyPD survivors at 15 yearsPD survivors at 15 years

40% were living in an aged care facility40% were living in an aged care facility

95% experienced L-dopa induced 95% experienced L-dopa induced dyskinesia and end of dose failure of dyskinesia and end of dose failure of medication medication

““The most disabling long-term problems The most disabling long-term problems of Parkinson’s Disease relate to of Parkinson’s Disease relate to symptoms not improved by L-dopa” symptoms not improved by L-dopa”

The non-motor problemsThe non-motor problems


diseasedisease NeuropsychiatricNeuropsychiatric Sleep disordersSleep disorders Autonomic symptomsAutonomic symptoms Gastrointestinal symptomsGastrointestinal symptoms Sensory symptomsSensory symptoms OthersOthers


diseasedisease NeuropsychiatricNeuropsychiatric

DepressionDepression AnxietyAnxiety HallucinationsHallucinations DelusionsDelusions DementiaDementia


diseasedisease Sleep disorders includeSleep disorders include

Restless legsRestless legs REM sleep behaviour disorderREM sleep behaviour disorder Excessive daytime sleepinessExcessive daytime sleepiness Vivid dreams Vivid dreams InsomniaInsomnia


diseasedisease Autonomic symptomsAutonomic symptoms

Bladder disturbancesBladder disturbances SweatingSweating Orthostatic hypotensionOrthostatic hypotension Sexual dysfunctionSexual dysfunction


diseasedisease Gastrointestinal symptomsGastrointestinal symptoms

Dribbling of salivaDribbling of saliva Difficulty with swallowingDifficulty with swallowing Acid refluxAcid reflux Nausea and vomitingNausea and vomiting ConstipationConstipation


diseasedisease Other symptomsOther symptoms

PainPain Loss of smellLoss of smell FatigueFatigue Double visionDouble vision

Screening for non-motor Screening for non-motor symptomssymptoms

A questionnaire has been developedA questionnaire has been developed

This can be downloaded from the This can be downloaded from the Parkinson’s Disease Society websiteParkinson’s Disease Society website

The NMS Quest Study The NMS Quest Study Mov Disord 2006; 21(7): 916Mov Disord 2006; 21(7): 916

International multidisciplinary group of International multidisciplinary group of expertsexperts

Development of a non-motor symptom Development of a non-motor symptom screening tool comprising of 30 itemsscreening tool comprising of 30 items

The number of symptoms correlated closely The number of symptoms correlated closely with advancing age and duration of diseasewith advancing age and duration of disease

Problems previously unknown to health Problems previously unknown to health professionals were frequently highlightedprofessionals were frequently highlighted

Management points for Management points for some common non-motor some common non-motor

symptomssymptoms DepressionDepression

DementiaDementia

HallucinationsHallucinations

Sleep problemsSleep problems

Depression in Parkinson’s Depression in Parkinson’s disease is common and disease is common and easily overlookedeasily overlooked

DepressionDepression

Affects up to 50% of patients with Affects up to 50% of patients with Parkinson’s DiseaseParkinson’s Disease

Low threshold for diagnosing depression Low threshold for diagnosing depression in Parkinson’s diseasein Parkinson’s disease

The strongest predictor of PD quality of The strongest predictor of PD quality of life in several surveyslife in several surveys

J Neurol Neurosurg Psychiatry 1999; 66: 431J Neurol Neurosurg Psychiatry 1999; 66: 431 J Neurol Neurosurg Psychiatry 2000; 69: 308J Neurol Neurosurg Psychiatry 2000; 69: 308

DepressionDepression

Features of depression and Features of depression and Parkinson’s disease overlapParkinson’s disease overlap

The diagnosis can be overlookedThe diagnosis can be overlooked If untreated can affect motor If untreated can affect motor

functionfunction

ManagementManagement

Holistic - multi-disciplinary team Holistic - multi-disciplinary team input input

Liaison with mental health servicesLiaison with mental health services

MedicationMedication

Medication for Medication for depressiondepression

Factors to considerFactors to consider Ensure optimal treatment of the Ensure optimal treatment of the

motor problems motor problems Side effects limit the value of the Side effects limit the value of the

older antidepressant drugsolder antidepressant drugs The presence of anxietyThe presence of anxiety

Treatment of depression - Treatment of depression - NICE Guidance 2006NICE Guidance 2006

There is insufficient evidence from There is insufficient evidence from clinical trials of the efficacy or safety clinical trials of the efficacy or safety of any antidepressant therapy in of any antidepressant therapy in Parkinson’s diseaseParkinson’s disease

There is an urgent need for further There is an urgent need for further research to establish safe and research to establish safe and effective treatments for depression effective treatments for depression in Parkinson’s diseasein Parkinson’s disease

Hallucinations in Hallucinations in Parkinson’s diseaseParkinson’s disease

May begin as visual hallucinations May begin as visual hallucinations which are non-frightening which are non-frightening

As the disease progresses the As the disease progresses the hallucinations may become more hallucinations may become more distressing and paranoid delusions distressing and paranoid delusions may developmay develop

Hallucinations in Hallucinations in Parkinson’s diseaseParkinson’s disease

May be a direct effect of the diseaseMay be a direct effect of the disease

Could be related to drug treatment Could be related to drug treatment

Consider intercurrent illnessConsider intercurrent illness

Impaired vision and environmentImpaired vision and environment

Consider depressionConsider depression

Significant risk of dementiaSignificant risk of dementia

Dementia in Parkinson’s Dementia in Parkinson’s diseasedisease

Dementia is the progressive loss of global Dementia is the progressive loss of global cognitive functioncognitive function

At least half the patients with Parkinson’s At least half the patients with Parkinson’s disease will ultimately develop dementiadisease will ultimately develop dementia

Typically PD dementia affects visuospatial Typically PD dementia affects visuospatial abilities, learning, verbal fluency, working abilities, learning, verbal fluency, working memory and mental flexibilitymemory and mental flexibility

Memory loss is less prominent than in other Memory loss is less prominent than in other common dementiascommon dementias

Management of PD Management of PD dementiadementia

Non-drug strategies – education and Non-drug strategies – education and practical support for patient and carerspractical support for patient and carers

Withdrawal of medication – ultimately Withdrawal of medication – ultimately leaving levodopaleaving levodopa

Treat depressionTreat depression

Use of atypical antipsychotic drugsUse of atypical antipsychotic drugs

Use of cholinesterase inhibitorsUse of cholinesterase inhibitors

Stepwise reduction in drug Stepwise reduction in drug treatmenttreatment

Focus treatment on the most effective Focus treatment on the most effective PD drugs with the least side effects PD drugs with the least side effects

Reduce from the topReduce from the top AnticholinergicsAnticholinergics SelegilineSelegiline AmantadineAmantadine Dopamine agonists (eg ropinirole/ Dopamine agonists (eg ropinirole/

pramipexole)pramipexole) COMT (eg entacapone)COMT (eg entacapone) ApomorphineApomorphine L-dopaL-dopa

Antipsychotic drugsAntipsychotic drugs

Older drugs – “Typical antipsychotic” Older drugs – “Typical antipsychotic” drugs should be avoideddrugs should be avoided

Atypical antipsychotic drugs may helpAtypical antipsychotic drugs may help Quetiapine is often used but little hard dataQuetiapine is often used but little hard data Clozapine is of benefit but rarely used in the UKClozapine is of benefit but rarely used in the UK Caution with Olanzapine and Risperidone in Caution with Olanzapine and Risperidone in

people at risk of strokepeople at risk of stroke

Cholinesterase inhibitorsCholinesterase inhibitors The group of drugs originally introduced The group of drugs originally introduced

to treat Alzheimer’s diseaseto treat Alzheimer’s disease

NICE Guidance 2006NICE Guidance 2006 Used successfully in patients with PD Used successfully in patients with PD

dementiadementia Further research is recommended to identify Further research is recommended to identify

those patients who will benefitthose patients who will benefit

Rivastigmine is currently licensed for the Rivastigmine is currently licensed for the treatment of PD dementiatreatment of PD dementia

Sleep related problems of Sleep related problems of Parkinson’s diseaseParkinson’s disease

Take an accurate historyTake an accurate history

Sleep related problems of Sleep related problems of Parkinson’s disease Parkinson’s disease

Age Ageing 2006; 35: 220Age Ageing 2006; 35: 220 Insomnia directly due to the effects Insomnia directly due to the effects

of Parkinson’s disease on central of Parkinson’s disease on central sleep regulation centres in the brainsleep regulation centres in the brain

Motor function relatedMotor function related Urinary difficultiesUrinary difficulties Neuropsychiatric problemsNeuropsychiatric problems

Management of sleep Management of sleep disordersdisorders

General measuresGeneral measures

Treatment of specific problemsTreatment of specific problems

General measures to cope General measures to cope with insomniawith insomnia

A warm bath 2 hours before bedtimeA warm bath 2 hours before bedtime

Hot milk or a light snack at bedtimeHot milk or a light snack at bedtime

Handrails or satin sheets to help turningHandrails or satin sheets to help turning

Avoid stimulants such as tea and coffee at Avoid stimulants such as tea and coffee at bedtimebedtime

Review other tabletsReview other tablets

Care with hypnotic drugs but sometimes helpfulCare with hypnotic drugs but sometimes helpful

Motor function relatedMotor function related

Restless legsRestless legs Abnormal leg movementsAbnormal leg movements Difficulty turning in bedDifficulty turning in bed

Medication changes may helpMedication changes may help

Urinary problems at night Urinary problems at night include -include -

Nocturia – frequent micturition at Nocturia – frequent micturition at night - is commonnight - is common Is it related to Parkinson’s disease or Is it related to Parkinson’s disease or

another problem?another problem? Exclude active infection and incomplete Exclude active infection and incomplete

bladder emptyingbladder emptying Incontinence related to poor mobilityIncontinence related to poor mobility

Neuropsychiatric causes of Neuropsychiatric causes of sleep disturbancesleep disturbance

Depression is common and treatableDepression is common and treatable

Panic attacksPanic attacks Treatment determined by time of occurrenceTreatment determined by time of occurrence

Cognitive problemsCognitive problems

Distressing dreams and hallucinationsDistressing dreams and hallucinations Review drug treatmentReview drug treatment Consider quetiapine Consider quetiapine

REM Sleep behaviour disorderREM Sleep behaviour disorder

REM Sleep Behaviour REM Sleep Behaviour DisorderDisorder

People enact their dreamsPeople enact their dreams TalkingTalking Shouting Shouting Falling out of bedFalling out of bed Even attacking their partnerEven attacking their partner

Drugs can helpDrugs can help ClonazepamClonazepam OthersOthers

Useful sources of Useful sources of informationinformation

Parkinson’s Disease Society Parkinson’s Disease Society www.parkinsons.org.ukwww.parkinsons.org.uk

2006 NICE Guidance2006 NICE Guidancewww.nice.org.ukwww.nice.org.uk

SummarySummary Parkinson’s disease affects 1% of the population over Parkinson’s disease affects 1% of the population over

60 years old60 years old Specialist support at diagnosis and throughout the Specialist support at diagnosis and throughout the

disease is essentialdisease is essential There is inadequate support for PD patients in There is inadequate support for PD patients in

nursing homesnursing homes The management becomes increasingly complex and The management becomes increasingly complex and

needs input from the whole range of carers and needs input from the whole range of carers and clinical staffclinical staff

Think of other contributory causes if there is an Think of other contributory causes if there is an unexpected deterioration in symptom controlunexpected deterioration in symptom control

The importance of the non-motor symptoms in The importance of the non-motor symptoms in advanced Parkinson’s disease has only recently advanced Parkinson’s disease has only recently received significant attentionreceived significant attention

Documents

The management of advanced Parkinson’s disease Dr J Paul Milnes Consultant Physician Airedale NHS Trust