Parkinson’s Disease

Why I Chose This Subject

Common neurodegenerative disorder120-230/100 000 in ScotlandExpected increase of 25-30% in next 25 yrs

Complex condition which changes with time

Huge social impactUncertainty amongst GP’s re prescribingNew SIGN guideline this year

ClinicalBackground

PD-syndrome consisting of bradykinesia plus at least one of rigidity, resting tremor and postural disorder

Parkinsonism-broader term but could be different aetiology from PD

Average time from diagnosis to death is 13 years

Pathophysiology

Motor system-fine balance of inhibitory and excitatory inputs of basal ganglia and cerebellum

Cerebellar output is excitatory, basal ganglia is inhibitory

Pathophysiology

Apoptosis of dopaminergic neurons in substantia nigra-leads to decrease in inhibition

Disruption of signals to motor cortex via thalamus

Smooth, coordinated movement is lost

Diagnosis Is Difficult

As is progressive disorder-can be hard in initial stages to diagnose accurately

Poor specificity-advise pt & family thisRecommendation that diagnosis should

be made by a hospital clinician in SIGNAlso useful way of getting MDT involved

Differential Diagnosis

Progressive supranuclear palsyMulti-system atrophyAlzheimer’s diseaseLewy body dementia

Clues in Differentiating

Up to 20% of those with PD have one relative affected

30-50% have depressive symptoms17% hallucinate80% have ANOSMIA-may precede onset of PD

Investigations

Routine use of imaging not recommendedFunctional imaging most useful where

there is uncertaintySPECT cheapestCan potentially detect very early disease

as you can lose up to ~50% of dopamine receptors before showing signs of PD

Drug therapy

Does not slow or prevent disease progression

Improves quality of life5-10% respond poorly to all medicationsTrying to stimulate the dopaminergic

system and control the resulting excitation in cholinergic pathways

Levodopa

Available for ~40 yearsGiven with Dopa-decarboxylase inhibitorCo-beneldopa (Madopar) or

Co-careldopa (Sinemet)Often get disabling dyskinesias at about 8

years of useTherefore often kept in reserve,

especially in younger patients

Levodopa

Helps bradykinesia and rigidity (not really tremor)

Small dose increments every few days6-18 months to see improvementNausea/flushing/sweating/neuropathyOn-off effectEnd of dose deterioration

Dopamine Agonists

Ropinorole, Pramipexole, PergolideBromocriptine/Cabergoline now avoided

due to cardiac valvulopathy and pleural, pericardial and retroperitoneal fibrosis

Again-incremental increasesSimilar s/e profile, less motor

complications but less improvement

Dopamine Agonists

If you initiate this you must tell patient about impulse control disorders and excessive daytime somnolence

Hypotension particularly in first few days of treatment

Good evidence in advanced PD to improve off time-transdermal Rotigotine

Amantadine-weak dopamine agonist

However…

Increasing Dopamine Agonists often worsens hallucinations

Patient preference

Other TreatmentsCOMT inhibitors

Entacapone provide some benefit in reducing off time

MAO-B inhibitorsBuccal selegiline or rasagiline can help

motor complications (less commonly used)Severe PD-can admit for subcutaneous

Apomorphine infusionNew treatments-dopamine pump if others

fail

Antimuscarinics

Orphenadrine-helps droolingOften drooling is more unpleasant for

family & they are delighted if you can improve this

ProcyclidineBest in drug-induced Parkinsonism s/e

control

Other Features to Be Aware of

Depression-Citalopram (or Amitriptyline)

Dementia in ~30% with late diseaseTreat as per dementia guideline

Psychosis-low dose Clozapine or Quetiapine if monitoring impractical

Contacts

Parkinson’s Disease Society (Scottish Office)Forsyth House, Lomond Court, Castle Business

ParkStirling FK9 4TUTel: 01786 433811 • Helpline: 0808 800 0303Email: pds.scotland@parkinsons.org.ukWebsite: www.parkinsons.org.uk/scotland

Younger Parkinson’s NetworkTel: 01656 663 284E-mail: alunmorgan@btinternet.comWebsite: www.yap-web.net