Medicine chapters
Parkinson disease and parkinsonism
Parkinson disease is a degenerative loss of dopamine neurones in the substantia nigra causing slowness, rest tremor and rigidity; this chapter covers its features, treatment and the other causes of parkinsonism.
- Parkinson disease is loss of dopamine neurones in the substantia nigra pars compacta with Lewy bodies (α-synuclein); symptoms appear when about 70% of these cells are gone.
- The core signs are bradykinesia (essential), rest (pill-rolling) tremor, lead-pipe or cogwheel rigidity and later postural instability, starting on one side.
- Levodopa with a decarboxylase inhibitor (carbidopa or benserazide) is the most effective drug; long-term use brings wearing off and dyskinesias.
On this page
Overview
Parkinsonism is a clinical syndrome: bradykinesia plus at least one of rest tremor, rigidity or postural instability. The commonest cause is idiopathic Parkinson disease (PD); others are drugs, vascular disease and the "Parkinson-plus" degenerations.
PD affects about 150 per 100 000 people, rises steeply with age, and is slightly commoner in men (1.5 : 1). MCQs test the pathology, the signs, levodopa pharmacology and how to recognise the mimics.
Basal ganglia in one paragraph
Dopamine from the substantia nigra pars compacta reaches the striatum (caudate and putamen). It excites the direct pathway (D1) and inhibits the indirect pathway (D2), both of which make movement easier. Lose dopamine and the internal globus pallidus over-inhibits the motor thalamus, so movement becomes slow and small. The relative excess of acetylcholine in the striatum explains why antimuscarinics help tremor.
Aetiology and risk factors
- Increasing age is the strongest risk.
- Environment: rural living, well water and pesticides slightly raise the risk; the toxin MPTP (a contaminant of illicit opioids) causes severe parkinsonism. Smokers have a lower risk, an unexplained finding.
- Genes: most PD is sporadic. Monogenic forms explain many early-onset cases (onset before 40): α-synuclein (PARK1, dominant), parkin (PARK2, recessive, the commonest cause of juvenile PD), PINK1, and LRRK2 (dominant, clinically identical to sporadic PD).
Pathology
- Loss of pigmented dopaminergic neurones in the substantia nigra (pars compacta), so the nigra looks pale at post-mortem.
- Lewy bodies: round eosinophilic inclusions in neurones made of α-synuclein and ubiquitin. They spread from the lower brainstem and olfactory bulb up to the midbrain and finally the cortex.
- About 70% of nigral cells are already lost when motor symptoms first appear.
Lewy bodies = α-synuclein. In Alzheimer disease the tangles are tau and the plaques β-amyloid.
Clinical features
Before the motor signs (prodrome, often years)
Loss of smell (very common, the olfactory bulb is affected early), REM sleep behaviour disorder (acting out dreams), constipation, depression and anxiety, urinary urgency and postural hypotension.
Motor features (usually one-sided at first)
| Feature | What you see |
|---|---|
| Bradykinesia (akinesia) | Slowness and progressive decrease in speed and size on repeated finger tapping; difficulty starting movement and rising from a chair; micrographia (small writing that tails off); mask-like face, reduced blinking; quiet monotonous speech |
| Rest tremor | 3–6 Hz, "pill-rolling" between thumb and finger; present at rest, reduced by movement, worse with stress; starts in one hand, spreads to the leg on the same side, later the other side; presenting symptom in about 70% |
| Rigidity | Lead-pipe (uniform through the range, same in flexors and extensors, not velocity-dependent); cogwheel when tremor is superimposed |
| Posture and gait | Stooped, flexed posture; shuffling, small steps, reduced arm swing, festination (hurrying steps), freezing, turning "en bloc"; postural instability is late (pull test) |
Rigidity in PD is the same at any speed of passive movement. Spasticity (upper motor neurone) increases with speed and shows clasp-knife release.
Falls in the first year or two are not typical of PD; they suggest progressive supranuclear palsy.
Non-motor features later
Depression, dementia (common in late disease), visual hallucinations and psychosis (often provoked by drugs), constipation, urinary problems, postural hypotension, drooling, swallowing difficulty and sleep disorders. Death is usually from bronchopneumonia after 10–20 years.
Diagnosis
- Clinical. No blood test; MRI is normal in PD (used only if the picture is atypical).
- A clear, sustained response to levodopa supports the diagnosis.
- DaT (dopamine transporter) SPECT shows loss of striatal nerve terminals. It separates PD from essential tremor and drug-induced parkinsonism (both normal scans), but not PD from the Parkinson-plus disorders.
Tremor comparison
| Feature | Parkinson tremor | Essential tremor | Cerebellar tremor |
|---|---|---|---|
| When | At rest | Posture and action (holding a cup) | Intention (worse near target) |
| Side | Asymmetric | Bilateral, may involve head and voice | Same side as the lesion |
| Family history | Uncommon | Often autosomal dominant | - |
| Alcohol | No effect | Improves | - |
| Treatment | Dopaminergic drugs | Propranolol, primidone | Treat cause |
Management
General
Education, exercise, physiotherapy, occupational and speech therapy, and treating non-motor problems (depression, constipation, sleep). Start dopaminergic drugs when symptoms interfere with life.
Drugs
| Drug | How it works | Key points |
|---|---|---|
| Levodopa + decarboxylase inhibitor (co-careldopa = with carbidopa; co-beneldopa = with benserazide) | Levodopa crosses the blood-brain barrier and is turned into dopamine. Carbidopa blocks peripheral dopa decarboxylase and does not enter the brain | Most effective drug; every patient eventually needs it. Fewer peripheral effects (nausea, hypotension). Start low (e.g. 50 mg levodopa three times daily, rising to 100 mg three times daily). Take about 40 minutes before protein-rich meals |
| Dopamine agonists: ropinirole, pramipexole, rotigotine patch; apomorphine (subcutaneous) | Act directly on D2/D3 receptors | First choice in younger patients; fewer motor complications but weaker and less well tolerated. Impulse control disorders (gambling, shopping, hypersexuality), sleepiness, hallucinations, oedema. Ergot agonists (bromocriptine, cabergoline, pergolide) are avoided: fibrosis of heart valves, lungs, retroperitoneum |
| MAO-B inhibitors: selegiline, rasagiline | Reduce dopamine breakdown in the brain | Mild effect early or as add-on |
| COMT inhibitors: entacapone (200 mg with each levodopa dose) | Block peripheral breakdown of levodopa | Prolong each dose; for wearing off; orange urine |
| Amantadine | Releases dopamine; NMDA antagonist | Mainly to reduce dyskinesias |
| Antimuscarinics: trihexyphenidyl (benzhexol), procyclidine, orphenadrine | Rebalance acetylcholine | Help tremor in young patients; cause confusion in the elderly, glaucoma and urinary retention |
Use domperidone for nausea in PD. It barely crosses the blood-brain barrier. Metoclopramide and prochlorperazine block central D2 receptors and worsen parkinsonism.
Never stop levodopa suddenly (e.g. nil by mouth after surgery). It can cause severe rigidity and a neuroleptic malignant-like syndrome. If the patient cannot swallow, use a rotigotine patch or a nasogastric tube.
Long-term motor complications of levodopa
About 10% of patients a year develop:
- Wearing off: each dose lasts a shorter time (fewer surviving neurones to store dopamine).
- Peak-dose dyskinesias: writhing (choreiform) movements at peak levels.
- On-off phenomenon: sudden unpredictable switches between mobility and freezing.
Management: smaller, more frequent levodopa doses; add entacapone, an MAO-B inhibitor or a dopamine agonist; amantadine for dyskinesia; slow-release levodopa at night; apomorphine injections or infusion; levodopa intestinal gel; and deep brain stimulation.
Deep brain stimulation
For selected, usually younger patients with disabling fluctuations. Targets: subthalamic nucleus (commonest; levodopa doses can be reduced), globus pallidus internus (reduces dyskinesia), thalamus (tremor only).
"TRAP" = Tremor, Rigidity, Akinesia, Postural instability.
Other causes of parkinsonism
Drug-induced parkinsonism
- Caused by dopamine blockers: typical antipsychotics (haloperidol, chlorpromazine), metoclopramide, prochlorperazine; dopamine depleters (reserpine, tetrabenazine); also sodium valproate, flunarizine.
- Usually symmetrical, with less tremor; DaT scan normal.
- Stop or reduce the culprit; antimuscarinic (procyclidine, trihexyphenidyl) helps. Among antipsychotics, clozapine (and quetiapine) causes least parkinsonism.
Parkinson-plus (atypical) syndromes
| Disorder | Clues | Pathology |
|---|---|---|
| Progressive supranuclear palsy (Steele-Richardson-Olszewski) | Early backward falls, vertical (especially downgaze) supranuclear gaze palsy, axial rigidity, staring face, pseudobulbar palsy, frontal dementia | Tau |
| Multiple system atrophy | Parkinsonism or cerebellar ataxia plus marked autonomic failure (postural hypotension, bladder, erectile dysfunction); poor levodopa response | α-synuclein in glial cells |
| Corticobasal degeneration | Very asymmetric rigidity, alien limb, apraxia, myoclonus, cortical sensory loss | Tau |
| Dementia with Lewy bodies | Dementia first or within a year of parkinsonism, fluctuating attention, visual hallucinations, severe sensitivity to antipsychotics | Cortical Lewy bodies |
Red flags for atypical parkinsonism: symmetrical onset, no tremor, poor response to levodopa, early falls, early autonomic failure or dementia, and extra neurological signs. These conditions progress faster and usually cause death within about a decade.
Other secondary causes
- Vascular parkinsonism: multiple small-vessel strokes; "lower-body" parkinsonism with gait problems, little tremor, poor drug response.
- Repeated head injury (boxers), post-encephalitic, toxins (carbon monoxide, manganese, MPTP).
- Normal pressure hydrocephalus: gait apraxia, urinary incontinence and dementia.
- Wilson disease: see below.
Wilson disease (brief)
- Autosomal recessive defect in copper excretion; copper builds up in the liver, basal ganglia and cornea.
- Young patients with tremor (wing-beating), dystonia, parkinsonism, dysarthria, psychiatric change and liver disease; Kayser-Fleischer rings.
- Screen anyone under about 50 with an unexplained movement disorder or cirrhosis: low serum caeruloplasmin, high urinary copper.
- Treat with chelation (penicillamine, trientine) or zinc; early treatment can reverse neurological damage. (More detail in the hepatology chapter on Wilson disease.)
Expect: the site of degeneration (substantia nigra pars compacta, nigrostriatal pathway) and Lewy bodies (α-synuclein); the cardinal signs and which is essential (bradykinesia); rest versus essential versus intention tremor; lead-pipe rigidity versus spasticity; diagnosis being clinical; why carbidopa is added; side-effects of dopamine agonists (impulse control disorders) and ergot agonists (fibrosis); entacapone for wearing off, amantadine for dyskinesia; domperidone as the safe antiemetic; drug-induced parkinsonism and its treatment; the clues to PSP and MSA; screening young patients for Wilson disease.
Quick revision
- PD: nigral dopamine cell loss, Lewy bodies (α-synuclein); about 70% lost before symptoms.
- Signs: bradykinesia + rest tremor (3–6 Hz, pill-rolling) + lead-pipe/cogwheel rigidity; postural instability late; asymmetric onset.
- Prodrome: anosmia, REM sleep behaviour disorder, constipation, depression.
- Diagnosis clinical; MRI normal; DaT scan abnormal in PD, normal in essential tremor and drug-induced parkinsonism.
- Levodopa + carbidopa/benserazide is the most effective drug; dopamine agonists in younger patients (impulse control disorders).
- Wearing off: entacapone, MAO-B inhibitor, more frequent doses; dyskinesia: amantadine; DBS of the subthalamic nucleus.
- Domperidone is safe; metoclopramide and typical antipsychotics worsen PD.
- PSP: early falls, vertical gaze palsy. MSA: autonomic failure. Young patient: exclude Wilson disease.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine).
FAQ
What is the essential feature for diagnosing parkinsonism?
Bradykinesia, with slowing and shrinking of repeated movements, plus rest tremor, rigidity or postural instability.
Why is carbidopa combined with levodopa?
Carbidopa blocks dopa decarboxylase outside the brain, so less levodopa becomes dopamine in the blood; this reduces nausea and hypotension and lets more levodopa reach the brain.
Which antiemetic should be used in a patient with Parkinson disease?
Domperidone, because it barely enters the brain; metoclopramide and prochlorperazine block brain dopamine receptors and worsen symptoms.
What suggests progressive supranuclear palsy instead of Parkinson disease?
Falls early in the illness, difficulty looking down (vertical gaze palsy), symmetrical axial stiffness and a poor response to levodopa.