Parkinson’s disease is caused by degeneration of the dopaminergic neurons in the substantia nigra (part of the basal ganglia). This results in rigidity, tremor, bradykinesia and postural instability.

Clinical features tetrad

Rigidity	Lead pipe rigidity, cogwheel rigidity, festinant gait
Tremor	Resting, pill-rolling
Bradykinesia	Slow shuffling gait, flexed trunk, slow monotonous speech, expressionless face, reduced blink rate, micrographia
Postural instability	Falls

Differential diagnosis of Parkinsonism

• Parkinson’s disease
• Vascular parkinsonism
• Parkinson-plus syndromes
  • Multi-system atrophy (cerebellar signs, autonomic problems)
  • Progressive supranuclear palsy (vertical gaze palsy, axial rigidity)
  • Corticobulbar degeneration (apraxia, dementia, aphasia)
  • Lewy body dementia (dementia with some parkinsonian features)
• Other causes
  • Iatrogenic, e.g. secondary medications
  • Wilson’s disease
  • Communicating hydrocephalus
  • Supratentorial tumours

Investigation

Parkinson’s disease is a clinical diagnosis – however, investigations may be required if the diagnosis is unclear:

• Structural MRI: may be used to exclude some other causes of parkinsonism
• Single-photon emission CT: may be used to differentiate Parkinson’s disease from other causes of tremor
• Serum caeruloplasmin or 24-hour urinary copper excretion: to exclude Wilson’s disease

Management

Pharmacological

Low potency:

• Monoamine oxidase B inhibitors (e.g. rasagiline, selegiline) 
  • For mild symptoms (no functional disability)

Moderate potency:

• Dopamine agonists (e.g. ropinirole, pramipexole)
  • For moderate symptoms (most at diagnosis)
  • Take several weeks to work
  • Notable side effects: sleep attacks, impulse control disorders

High potency:

• Levodopa (e.g. Madopar, Sinemet)
  • For severe symptoms/elderly
  • Given with peripheral decarboxylase inhibitor (e.g. carbidopa) to prevent peripheral conversion to dopamine
  • Notable side effects: ‘on-off’/’wearing off’ phenomenon (increased immobility before the next dose is due after prolonged levodopa use); dyskinesias

Adjuncts to levodopa:

• Dopamine agonists – reduce motor complications and levodopa dosage needs 
• Monoamine oxidase B inhibitors – reduce ‘off time’
• COMT inhibitors (e.g. entacapone) – reduce ‘off time’
• Apomorphine (subcutaneous) – for rescue therapy during ‘off time’
• Amantadine (glutamate antagonist) – for levodopa-induced dyskinesias

Non-pharmacological

• Multidisciplinary approach: input from neurologist, physiotherapist, occupational therapist, specialist nurse, GP, speech and language therapist
• Supervised exercise
• Home modifications
• Consider associated conditions: dementia, depression, psychosis, sleep disturbance

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