Lucan · Conditions

Parkinson's disease

Australian guidance: eTG Neurology — Parkinson Disease

1. Definition and epidemiology

Parkinson's disease is a progressive neurodegenerative disorder characterised by dopaminergic neuronal loss in the substantia nigra pars compacta, leading to the cardinal motor triad of tremor, rigidity, and bradykinesia. In Australia, prevalence is approximately 1% of adults over 60 years, rising to 3 to 4% beyond 75 years, with roughly 80,000 Australians currently living with the condition. Incidence is approximately 20 per 100,000 person-years overall, with a male preponderance of roughly 1.5 to 1.

2. Pathophysiology

The cardinal pathological lesion is degeneration of dopaminergic neurones in the substantia nigra pars compacta, with resulting depletion of dopamine in the striatum (Robbins Ch 28). The hallmark microscopic finding is the Lewy body: an eosinophilic cytoplasmic inclusion composed predominantly of aggregated alpha-synuclein protein surrounded by a pale halo. Lewy neurites are dystrophic neuronal processes containing the same fibrillar alpha-synuclein aggregates. Current evidence supports a prion-like propagation model, in which misfolded alpha-synuclein spreads in a caudorostral pattern through connected neural circuits; this is systematised in the Braak staging scheme (stages 1 to 6), with motor symptoms emerging around stage 3 to 4 when substantia nigra involvement is substantial. Neuronal loss becomes clinically manifest once approximately 60 to 70% of dopaminergic neurones and 80% of striatal dopamine are lost. Secondary pathology includes noradrenergic degeneration in the locus coeruleus, serotonergic loss in the raphe nuclei, and cholinergic loss in the nucleus basalis of Meynert, accounting for non-motor features. Reactive gliosis accompanies the degenerating regions without prominent inflammatory infiltrate.

3. Clinical presentation and diagnostic criteria

The UK Parkinson's Disease Society Brain Bank (PDSBB) criteria are the most widely used clinical standard. Diagnosis requires bradykinesia plus at least one of: muscular rigidity, 4 to 6 Hz rest tremor, or postural instability not due to primary visual, vestibular, cerebellar, or proprioceptive dysfunction, with features supporting idiopathic disease rather than secondary or atypical causes.

Typical presentation is insidious onset in the sixth or seventh decade with unilateral resting tremor (often the "pill-rolling" thumb-index pattern at 4 to 6 Hz), cogwheel rigidity, bradykinesia (slowed fine movements, micrographia, hypomimia, hypophonia), and shuffling festinant gait. Postural instability is a later feature. Non-motor symptoms often precede motor features by years: hyposmia, REM sleep behaviour disorder, constipation, and depression are recognised prodromal markers. Autonomic dysfunction (orthostatic hypotension, sialorrhoea, urinary urgency) and neuropsychiatric features (hallucinations, dementia in later disease, impulse control disorders linked to dopamine agonists) are clinically important.

A sustained levodopa response (greater than 30% improvement in UPDRS motor score) supports the diagnosis of idiopathic Parkinson's disease and helps distinguish it from atypical parkinsonian syndromes (multiple system atrophy, progressive supranuclear palsy, corticobasal syndrome).

4. Investigations and AU-specific cutoffs

Parkinson's disease is a clinical diagnosis and no investigation is required to confirm it in typical presentations. The following workup is used to exclude mimics and guide management:

• MRI brain: Not diagnostic for Parkinson's disease but indicated to exclude structural causes (normal pressure hydrocephalus, vascular parkinsonism, space-occupying lesions). The "hummingbird sign" on sagittal MRI suggests progressive supranuclear palsy. In Australia, MRI is bulk-billed under Medicare for a clinical indication of suspected parkinsonism.
• DaTscan (FP-CIT SPECT): Dopamine transporter imaging demonstrating reduced striatal uptake supports a neurodegenerative parkinsonian syndrome (sensitivity approximately 78 to 88%) but cannot distinguish Parkinson's disease from atypical parkinsonism. Access in Australia is limited to tertiary neurology centres; not routinely funded by Medicare.
• Levodopa challenge: A single oral dose of levodopa 200 mg with carbidopa 50 mg, with UPDRS motor assessment before and 60 to 90 minutes after, is used diagnostically and to guide therapy initiation. Response greater than 30% improvement indicates dopamine-responsive parkinsonism.
• Baseline bloods: Thyroid function, copper studies (to exclude Wilson's disease in onset under 50 years), and metabolic panel are checked at first presentation.
• Autonomic testing: Tilt-table testing is used in specialist centres if significant orthostatic hypotension complicates management.

There are no AU-specific laboratory cutoffs that differ from international standards for this condition.

5. Management

Management in Australia follows the eTG Neurology (Parkinson Disease) guidelines and is coordinated by a neurologist, ideally in a multidisciplinary team including physiotherapy, occupational therapy, speech pathology, and social work.

Pharmacological initiation: For most patients with functional impairment, levodopa remains the most effective symptomatic therapy and the drug of first choice, particularly in older patients (over 70 years) or those with cognitive impairment (eTG Neurology). In younger patients (typically under 65 years), dopamine agonists may be trialled first to delay levodopa initiation and reduce early motor complications, with the understanding that agonists carry higher rates of neuropsychiatric adverse effects and impulse control disorders. The decision must be individualised.

Non-pharmacological: Exercise, particularly aerobic and resistance training, has robust evidence for slowing functional decline and is considered a core component of management. Physiotherapy for gait and balance, speech pathology for hypophonia and dysphagia, and occupational therapy for activities of daily living are all recommended.

Motor fluctuations and dyskinesia: As disease progresses, patients on levodopa develop wearing-off phenomenon and peak-dose dyskinesia. Management includes dose timing optimisation, addition of a catechol-O-methyltransferase (COMT) inhibitor (entacapone), addition of a monoamine oxidase B (MAO-B) inhibitor (selegiline or rasagiline), or controlled-release levodopa preparations. Amantadine reduces peak-dose dyskinesia.

Advanced disease: Deep brain stimulation (DBS) of the subthalamic nucleus or globus pallidus internus is appropriate for patients with refractory motor fluctuations who retain good cognitive function. Referral to a DBS centre (available in all major Australian capital cities) should occur before severe motor disability develops.

6. Pharmacology and AU PBS notes

Levodopa/carbidopa (co-careldopa): First-line for most patients. Carbidopa inhibits peripheral decarboxylation, reducing nausea and increasing central levodopa availability. Available in Australia as Sinemet (25/100 mg, 25/250 mg) and generic equivalents. PBS listed (Streamlined Authority not required at initiation for neurologist-prescribed treatment; Schedule 3 restriction applies to GP repeat prescribing after specialist initiation).

Dopamine agonists: Pramipexole (Sifrol) and ropinirole (Requip) are PBS listed. Cabergoline is no longer recommended due to cardiac valve fibrosis risk. Rotigotine transdermal patch (Neupro) is available for patients with swallowing difficulty. Apomorphine subcutaneous infusion is used in advanced disease as a continuous dopaminergic stimulus; it is available in Australia through specialist centres and requires domperidone pretreatment to prevent nausea.

MAO-B inhibitors: Selegiline and rasagiline are adjunct therapies; rasagiline has modest disease-modifying evidence. Both are PBS listed. Interactions with serotonergic drugs (SSRIs, SNRIs, meperidine) require vigilance.

COMT inhibitors: Entacapone (Comtan) is PBS listed as adjunct to levodopa for wearing-off. Opicapone is an alternative with once-daily dosing.

Amantadine: Used for levodopa-induced dyskinesia. PBS listed. Dose reduction required in renal impairment.

7. Complications and monitoring

Motor complications: Wearing-off and peak-dose dyskinesia affect the majority of patients after 5 or more years of levodopa therapy. Regular UPDRS-III assessment at each specialist visit tracks motor fluctuations.

Falls and fracture: Postural instability and freezing of gait markedly increase fall risk. Bone mineral density should be assessed given immobility risk; calcium and vitamin D supplementation recommended if deficient.

Dementia: Parkinson's disease dementia occurs in up to 80% of patients by 20 years. Rivastigmine (a cholinesterase inhibitor) has PBS approval for Parkinson's disease dementia; memantine is not PBS listed for this indication.

Neuropsychiatric: Hallucinations are managed initially by withdrawing anticholinergics, amantadine, and dopamine agonists in that order. Clozapine (low dose, with mandatory haematological monitoring) or quetiapine are used for refractory psychosis; other antipsychotics worsen parkinsonism and are contraindicated.

Autonomic dysfunction: Orthostatic hypotension is managed with volume loading, compression garments, and fludrocortisone or midodrine if needed. Constipation is addressed with dietary fibre and macrogol laxatives. Sialorrhoea may respond to low-dose glycopyrrolate or botulinum toxin to the parotid glands.

Monitoring schedule: Neurologist review every 3 to 6 months in established disease. Annual cognitive screening with MoCA. Physiotherapy reassessment annually or with functional decline. Ophthalmology review if symptoms of diplopia arise (to exclude progressive supranuclear palsy).

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.