Parkinson`s Disease

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Parkinson’s Disease
Why I Chose This Subject
Common neurodegenerative disorder
120-230/100 000 in Scotland
Expected increase of 25-30% in next 25 yrs
Complex condition which changes with
time
Huge social impact
Uncertainty amongst GP’s re prescribing
New SIGN guideline this year
Clinical Background
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 this
Recommendation that diagnosis should
be made by a hospital clinician in SIGN
Also useful way of getting MDT involved
Differential Diagnosis
Progressive supranuclear palsy
Multi-system atrophy
Alzheimer’s disease
Lewy body dementia
Clues in Differentiating
Up to 20% of those with PD have one relative
affected
30-50% have depressive symptoms
17% hallucinate
80% have ANOSMIA-may precede onset of PD
Investigations
Routine use of imaging not recommended
Functional imaging most useful where
there is uncertainty
SPECT cheapest
Can 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 life
5-10% respond poorly to all medications
Trying to stimulate the dopaminergic
system and control the resulting
excitation in cholinergic pathways
Levodopa
Available for ~40 years
Given with Dopa-decarboxylase inhibitor
Co-beneldopa (Madopar) or
Co-careldopa (Sinemet)
Often get disabling dyskinesias at about 8
years of use
Therefore often kept in reserve, especially
in younger patients
Levodopa
Helps bradykinesia and rigidity (not
really tremor)
Small dose increments every few days
6-18 months to see improvement
Nausea/flushing/sweating/neuropathy
On-off effect
End of dose deterioration
Dopamine Agonists
Ropinorole, Pramipexole, Pergolide
Bromocriptine/Cabergoline now avoided
due to cardiac valvulopathy and pleural,
pericardial and retroperitoneal fibrosis
Again-incremental increases
Similar 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 Treatments
COMT inhibitors
Entacapone provide some benefit in
reducing off time
MAO-B inhibitors
Buccal selegiline or rasagiline can help
motor complications (less commonly used)
Severe PD-can admit for subcutaneous
Apomorphine infusion
New treatments-dopamine pump if others
fail
Antimuscarinics
Orphenadrine-helps drooling
Often drooling is more unpleasant for
family & they are delighted if you can
improve this
Procyclidine
Best in drug-induced Parkinsonism s/e
control
Other Features to Be Aware of
Depression-Citalopram (or Amitriptyline)
Dementia in ~30% with late disease
Treat 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
Park
Stirling FK9 4TU
Tel: 01786 433811 • Helpline: 0808 800 0303
Email: [email protected]
Website: www.parkinsons.org.uk/scotland
Younger Parkinson’s Network
Tel: 01656 663 284
E-mail: [email protected]
Website: www.yap-web.net
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