1. Parkinson’s Disease
By Nik Sanyal

2. This = movement disorder caused by degeneration of dopamine pathways in substantia nigra
Characterised by:
TREMOR
RIGIDITY
BRADYKINESIA
+/- postural instability

3. Epidemiology + Risk Factors
Peak age of onset = 55-65
Men > Women
2nd most common neurodegenerative disease after Alzheimer’s
Risk factors:
Age
Gender
Spring birth
Exposure to pesticides e.g. paraquat or Agent Orange

4. Pathogenesis
Most cases = idiopathic PD. Leading to a progressive degeneration + development of Lewy bodies in substantia nigra.
Other pathways – mesocortical, mesolimbic + tubero-hypophyseal
Genetics (lead to early onset):
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.

5. 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.

6. Clinical features
Resting tremor = usually unilateral before it becomes generalised. It is 4-6 Hz pill-rolling. Typically absent during activity.
Rigidity = lead pipe. Cog-wheeling occurs when lead pipe rigidity is broken up by tremor.
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.

7. 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)

8. DDx Wilson’s Lewy Body dementia: get visual hallucinations
CJD: Dementia + myoclonic jerking
Parkinson’s plus
Huntington’s disease
Drug-induced PD
Antipsychotics (APAT side effects: acute dystonia, parkinsonism, akathisia, tardive dyskinesia)
Lithium
Benign essential tremor
Rarely at rest, worse on movement
Family hx

9. NICE criteria for Dx Exclude other causes
Bradykinesia + at least 1 of:
Rigidity
4-6Hz resting tremor
Postural instability
Supportive criteria:
Unilateral
Progressive nature
Asymmetry before bilateral
Response to L-Dopa

10. Investigations Typically a clinical diagnosis Use:
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
Special tests: DAT scan can differentiate between drug-induced + PD.

11. Conservative management
Advice + explanation, consider non-physical 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

12. Medical management
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

13. Dopamine agonists e.g. Pramipexole = good for motor sx
1st 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

14. Surgical Deep brain stimulation
Pallidotomy involves surgical destruction of the globus pallidus to control dyskinesia.

15. Complications Infection Aspiration pneumonia Bed sores Poor nutrition
Falls
PD dementia

16. Prognosis Slowly progressive Mean duration 15 years Variable severity
Earlier age of onset = poorer prognosis
Death usually from complications e.g. pneumonia.

17. Parkinson’s plus syndromes
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

18. Good luck!  Parkinson’s notes Extrapyramidal exam Gait
Extrapyramidal exam
Gait