Parkinson's disease

Overview

Classic triad: bradykinesia + resting tremor + rigidity - onset is asymmetrical (unilateral first)
Bradykinesia - slowness/difficulty initiating movement; cardinal feature required for diagnosis
Resting tremor - 3-5 Hz 'pill-rolling'; present at rest, suppressed by intentional movement
Rigidity - cogwheel rigidity (ratchet-like) on passive movement
Gait - shuffling, small steps (festination), freezing of gait
Other motor: hypomimia (masked facies), micrographia, hypophonia
Non-motor (may precede motor symptoms): anosmia, REM sleep behaviour disorder, depression/anxiety, constipation, orthostatic hypotension, cognitive impairment
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PD tremor is a RESTING tremor that IMPROVES with intentional movement. Essential tremor is an ACTION/POSTURAL tremor that WORSENS with movement - no bradykinesia or rigidity. Essential tremor is managed with propranolol.

Investigations

Clinical diagnosis - made by a movement disorder specialist; investigations support, not replace, clinical judgement
Routine bloods (FBC, TFTs, U&Es) - exclude metabolic/endocrine causes of tremor
Gold standard - DaTscan (iodine-123-labelled ioflupane SPECT) - confirms loss of dopaminergic neurones; differentiates PD/atypical parkinsonism (reduced uptake) from essential tremor and drug-induced parkinsonism (normal uptake); performed 3-6 hours after injection
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In primary care: do NOT arrange a DaTscan and do NOT start treatment before specialist assessment. The GP's only role is to recognise the syndrome and refer URGENTLY to neurology.

Differential diagnosis

PD vs Essential tremor vs Drug-induced parkinsonism
FeatureParkinson's diseaseEssential tremorDrug-induced
Tremor typeResting, pill-rollingAction/posturalResting or mixed
Bradykinesia/rigidityPresentAbsentPresent
OnsetAsymmetricBilateral/symmetricSymmetric
DaTscanAbnormalNormalNormal
TreatmentSpecialist-led, levodopaPropranololStop offending drug / procyclidine

Management

GP action: refer URGENTLY to neurology (movement disorder specialist) - do not start medications in primary care
First-line (specialist-initiated): co-careldopa (levodopa + carbidopa) - most effective symptomatic treatment; does NOT slow disease progression
Psychosis in PD: reduce dopaminergic drugs first; if antipsychotic needed use quetiapine or clozapine only - never typical antipsychotics or risperidone
Nausea in PD: domperidone preferred (peripheral D2 antagonism only); metoclopramide is contraindicated (crosses blood-brain barrier, worsens parkinsonism)

Complications

Motor fluctuations - 'wearing off' and 'on-off' phenomena; consequence of long-term levodopa
Peak-dose dyskinesia - involuntary writhing movements at peak levodopa levels
Impulse control disorders - gambling, hypersexuality, binge eating; associated with dopamine agonist therapy
Neuroleptic malignant syndrome - precipitated by abrupt withdrawal of anti-parkinsonian medication; never stop medications suddenly
Aspiration pneumonia - bulbar involvement in later disease; leading cause of death

Drugs that worsen Parkinson's disease - avoid

Avoid in Parkinson's disease (dopamine antagonists / D2 blockers)
Metoclopramide - contraindicated antiemetic
Prochlorperazine - dopamine antagonist
Haloperidol - typical antipsychotic
Chlorpromazine - typical antipsychotic
Risperidone - high D2-affinity atypical antipsychotic
Lithium - worsens tremor
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Haloperidol and other typical antipsychotics block D2 receptors and can cause severe deterioration in PD motor symptoms and precipitate neuroleptic malignant syndrome. Never use in PD.