Transcript Parkinson`s Disease

Parkinson’s
Disease
By Nik Sanyal
 This
= movement disorder caused by
degeneration of dopamine pathways in
substantia nigra
 Characterised
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by:
TREMOR
RIGIDITY
BRADYKINESIA
+/- postural instability
Epidemiology + Risk Factors
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Peak age of onset = 55-65
Men > Women
2nd most common neurodegenerative
disease after Alzheimer’s
Risk factors:
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Age
Gender
Spring birth
Exposure to pesticides e.g. paraquat or Agent
Orange
Pathogenesis
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Most cases = idiopathic PD. Leading to a
progressive degeneration + development of
Lewy bodies in substantia nigra.
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Other pathways – mesocortical, mesolimbic +
tubero-hypophyseal
Genetics (lead to early onset):
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mutations in c’some 6 = AR PD
Alpha synuclein mutation
Parkin gene
Dopamine has a role in disinhibition of motor activity
hence why reduced levels leads to dyskinesia.
Pathophysiology
 Cell
death in substantia nigra (particularly
pars compacta) leads to reduced
dopamine secreting cells.
 Dopamine acts to facilitate release of
inhibition and as such in PD there is
greater exertion required to initiate a
movement as there is less release of
inhibition.
Clinical features
1)
Resting tremor = usually unilateral before it
becomes generalised. It is 4-6 Hz pill-rolling.
Typically absent during activity.
2)
Rigidity = lead pipe. Cog-wheeling occurs
when lead pipe rigidity is broken up by tremor.
3)
Bradykinesia = festinant gait (slow to start +
small shuffling steps + difficult turns) Has
diminished arm swing = leads to recurrent falls.
You also get reduction in amplitude of repetitive
movements.
Other features
 Progressive
decline over years
 Mask-like face
 Impaired swallowing – drooling, choking
on food
 Cognitive decline = depression +
dementia
 Quiet voice progressing to dysarthria
 Micrographia (small + spidery writing)
DDx
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Wilson’s
Lewy Body dementia: get visual hallucinations
CJD: Dementia + myoclonic jerking
Parkinson’s plus
Huntington’s disease
Drug-induced PD
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Antipsychotics (APAT side effects: acute
dystonia, parkinsonism, akathisia, tardive
dyskinesia)
Lithium
Benign essential tremor
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Rarely at rest, worse on movement
Family hx
NICE criteria for Dx
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Exclude other causes
Bradykinesia + at least 1 of:
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Rigidity
4-6Hz resting tremor
Postural instability
Supportive criteria:
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Unilateral
Progressive nature
Asymmetry before bilateral
Response to L-Dopa
Investigations
 Typically
a clinical diagnosis
 Use:
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Bedside: BP lying + standing, urine dip
Bloods: Genetic testing for Huntington’s or
caeruloplasmin for Wilson’s
Imaging: CT/MRI
 Fail
to respond to L-Dopa
 Can visualise structural defects
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Special tests: DAT scan can differentiate
between drug-induced + PD.
Conservative management
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Advice + explanation, consider nonphysical problems (depression, poor sleep,
dementia).
Limited time frame for meds so start when
really needed + started by neurologist!
MDT: specialist nurses, OT, SALT, psychiatrist,
GP, neurologist, dietician
Inform DVLA
REHAB
Medical management
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Drugs alter the natural progression – they just improve
symptoms.
Levodopa
 Is
the most effective drug.
 It crosses the BBB and enters the nigrostriatal neurones
and is converted to dopamine.
 Give with dopa-decarboxylase inhibitor e.g. carbidopa
to inhibit peripheral metabolism.
S/E = N+V, confusion, on-off phenomena, wearing off +
dyskinesia, hallucination
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Dopamine agonists e.g. Pramipexole = good for
motor sx
 1st
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line in younger patients
MAO-B inhibitors = selegiline = block dopamine
breakdown. Good for motor sx.
COMT inhibitors = entacapone = inhibits peripheral
break down. S/E = hepatotoxic, N+V, confusion.
Amantadine: can be used as monotherapy in
early PD but has poor evidence base. Enhances
dopamine release.
Apomorphine can reduce off periods given as s/c
injection. S/E confusion + hallucinations
Surgical
 Deep
brain stimulation
 Pallidotomy involves surgical destruction
of the globus pallidus to control
dyskinesia.
Complications
 Infection
 Aspiration
 Bed
pneumonia
sores
 Poor nutrition
 Falls
 PD dementia
Prognosis
 Slowly
progressive
 Mean duration 15 years
 Variable severity
 Earlier age of onset = poorer prognosis
 Death usually from complications e.g.
pneumonia.
Parkinson’s plus syndromes
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Disorders with parkinsonism + additional
features + specific pathology.
Vascular dementia
Orthotic hypotension = multi-system atrophy
gives insomnia, somnolence, restless legs,
hallucinations. Use fludrocortisone for BP
Dementia + vertical gaze palsy= progressive
supra-nuclear palsy
Kayser-Fleischer rings = Wilson’s
Apraxic gait – communicating hydrocephalus
Good luck! 
 Parkinson’s
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notes
http://www.patient.co.uk/doctor/parkinson
ism-and-parkinsons-disease
 Extrapyramidal
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exam
http://youtu.be/6PDxANv_ME8
 Gait
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http://youtu.be/7SyTpEdhBLw