Parkinson's disease
Exam Tips
- For OSCEs, diagnose parkinsonism only when bradykinesia is present with tremor and/or rigidity; postural instability alone is not enough early on.
- Early frequent falls, rapid progression, poor levodopa response, early severe autonomic failure, or vertical gaze palsy suggest atypical parkinsonism rather than idiopathic Parkinson's disease.
- Do not stop dopaminergic therapy abruptly in admitted patients; this can precipitate life-threatening hyperpyrexia-rigidity syndrome.
- When counselling on dopamine agonists, always mention impulse-control risk and driving implications from sudden sleep episodes.
- Use the 'motor plus non-motor' framing in vivas: constipation, REM sleep behaviour disorder, hyposmia, depression, and cognitive change can predate or dominate motor symptoms.
Definition
Parkinson's disease is a chronic, progressive neurodegenerative disorder in which dopaminergic neurons in the substantia nigra are lost, causing dopamine depletion in basal ganglia motor circuits. Clinically it presents as a parkinsonian syndrome (bradykinesia plus tremor and/or rigidity, later postural instability), with important non-motor features including cognitive, autonomic, sleep, and psychiatric symptoms.
Pathophysiology
Core pathology is degeneration of nigrostriatal dopaminergic neurons with intraneuronal alpha-synuclein aggregation (Lewy body pathology), leading to impaired modulation of direct and indirect basal ganglia pathways and reduced thalamocortical motor drive. Motor symptoms usually emerge only after substantial dopaminergic loss (roughly half or more of nigral dopaminergic function). Extra-nigral involvement explains non-motor disease (autonomic dysfunction, mood disorder, sleep disturbance, cognitive decline). See Figure: basal ganglia direct/indirect pathway diagram in your movement-disorders textbook chapter.
Risk Factors
- Increasing age
- Male sex
- Family history of Parkinson's disease (especially early-onset cases)
- Monogenic variants in a minority of patients (for example LRRK2, PRKN)
- Likely multifactorial genetic susceptibility with environmental contributions
Clinical Features
Symptoms
- Slowness of movement affecting daily tasks (dressing, turning in bed, reduced dexterity)
- Rest tremor (often unilateral at onset, 'pill-rolling')
- Gait difficulty, freezing episodes, and falls (typically later)
- Non-motor symptoms: constipation, anosmia, sleep disturbance (including REM sleep behaviour disorder), fatigue, pain
- Neuropsychiatric symptoms: depression, anxiety, apathy, hallucinations, impulse-control behaviours
Signs
- Bradykinesia (required for parkinsonism diagnosis)
- Rigidity (lead-pipe or cogwheel)
- Resting tremor (4-6 Hz)
- Postural instability (usually later in idiopathic disease)
- Hypomimia, reduced blink rate, hypophonia, micrographia
- Shuffling gait with reduced arm swing and en bloc turning
Investigations
Management
Lifestyle Modifications
- Early multidisciplinary care: Parkinson's nurse specialist, physiotherapy, occupational therapy, speech and language therapy, dietetic input
- Regular exercise (aerobic, balance, strength, cueing strategies) to maintain mobility and reduce falls risk
- Falls prevention and home hazard review; swallowing assessment if cough/choking or weight loss
- Advance care planning and carer support in progressive disease
Pharmacological Treatment
Levodopa preparations (first choice when motor symptoms affect quality of life)
- Co-careldopa (levodopa/carbidopa) 12.5 mg/50 mg three times daily initially, titrate gradually
- Co-beneldopa (levodopa/benserazide) 12.5 mg/50 mg or 25 mg/100 mg three times daily initially, titrate to response
Most effective symptomatic treatment. Use lowest effective dose, divide dosing through day. Adverse effects: nausea, postural hypotension, hallucinations, dyskinesia, motor fluctuations with long-term use.
Dopamine agonists
- Pramipexole 88 micrograms three times daily initially (immediate-release), titrate slowly
- Ropinirole 250 micrograms three times daily initially, increase weekly
- Rotigotine transdermal patch 2 mg/24 h once daily initially, titrate by response
Useful in earlier disease or as adjunct. Safety warnings: impulse-control disorders (gambling, hypersexuality, shopping, binge eating), excessive daytime sleepiness/sudden sleep attacks, hallucinations, oedema, orthostatic hypotension. Caution in older/frail patients and cognitive impairment.
MAO-B inhibitors
- Rasagiline 1 mg once daily
- Selegiline 5 mg once daily, may increase to 10 mg/day in divided doses
Can be used for mild symptoms or adjunct to reduce wearing-off. Watch for serotonergic interactions (for example SSRIs/SNRIs, tramadol) and neuropsychiatric adverse effects.
COMT inhibitors (adjunct to levodopa for end-of-dose wearing off)
- Entacapone 200 mg with each levodopa dose (maximum 2 g/day)
- Opicapone 50 mg at night
Not used as monotherapy. Can worsen dyskinesia; may need levodopa dose reduction. Entacapone may cause diarrhoea and orange urine discoloration.
Other adjuncts for motor complications
- Amantadine 100 mg once daily then 100 mg twice daily (dose-adjust in renal impairment)
- Apomorphine subcutaneous intermittent rescue or infusion (specialist initiation)
Amantadine may reduce dyskinesia; adverse effects include confusion, hallucinations, ankle oedema, livedo reticularis. Apomorphine requires specialist supervision; antiemetic planning needed.
Surgical / Interventional
- Deep brain stimulation (usually subthalamic nucleus or globus pallidus internus) for selected patients with disabling motor fluctuations/dyskinesia despite optimized medical therapy
- Device-aided therapies in advanced disease (for example levodopa-carbidopa intestinal gel infusion, continuous apomorphine infusion) via specialist movement-disorder services
Complications
- Motor fluctuations (wearing-off, on-off phenomena, dose failures)
- Levodopa-induced dyskinesia (choreiform or dystonic)
- Freezing of gait and recurrent falls
- Depression, anxiety, apathy
- Cognitive impairment and Parkinson's disease dementia
- Psychosis (visual hallucinations, delusions)
- Impulse-control disorders related to dopaminergic therapy
- Autonomic dysfunction: orthostatic hypotension, constipation, urinary and sexual dysfunction, drooling
- Dysphagia, weight loss, aspiration pneumonia, pressure ulcers
- Neuroleptic malignant syndrome/parkinsonism-hyperpyrexia syndrome risk with abrupt dopaminergic withdrawal
Prognosis
Progression is typically gradual but heterogeneous. Older age at onset and non-tremor-predominant presentations are linked to faster motor decline and greater non-motor burden; early-onset disease often delays cognitive and motor complications. Long-term risks include postural instability, dementia, institutional care needs, and increased mortality versus age-matched controls, though a subgroup retains relatively preserved function for many years.
Sources & References
🏥BMJ Best Practice(4)
✅NICE Guidelines(1)
- Parkinson's disease[overview]