How Parkinson disease is tested on Step 1
Link the lost neurons to the circuit and the signs.
- Motor signs: resting tremor that improves with movement, cogwheel rigidity, bradykinesia, stooped shuffling gait, reduced arm swing, masked face, micrographia.
- Non-motor signs: loss of smell, constipation, REM sleep behavior disorder (often years earlier), depression, orthostatic hypotension, and later dementia.
Drug treatment
Every drug class either replaces dopamine, mimics it, slows its breakdown, or rebalances acetylcholine.
Other movement disorders
Location of the lesion predicts the movement.
| Disorder | Lesion or cause | Key features |
|---|---|---|
| Huntington disease | Caudate atrophy; CAG repeat; autosomal dominant | Chorea, depression, dementia; anticipation |
| Essential tremor | Often familial | Action tremor of hands and head; improves with alcohol; propranolol |
| Drug-induced parkinsonism | D2 blockade (haloperidol, metoclopramide) | Symmetric; treat by stopping the drug or with benztropine |
| Hemiballismus | Contralateral subthalamic nucleus | Wild flinging of one arm |
| Wilson disease | Copper in basal ganglia (ATP7B) | Tremor, dystonia, psychiatric change, Kayser-Fleischer rings |
| Lewy body dementia | Cortical Lewy bodies | Parkinsonism, visual hallucinations, fluctuating attention |
Cerebellar tremor appears with intention (finger-to-nose) rather than at rest.
Pathology and causes
Most cases are sporadic.
- Lewy bodies: round eosinophilic inclusions of α-synuclein; the substantia nigra loses its dark pigment.
- Toxins: MPTP, a contaminant of illicit opioid synthesis, destroys nigral neurons and causes rapid parkinsonism.
Worked example
Explain a drug combination.
functions Worked example — why add carbidopa?
A 66-year-old with resting tremor and bradykinesia starts levodopa alone and has severe nausea with little improvement. Carbidopa is added. Why does this help?
- Dopamine itself cannot cross the blood-brain barrier, so levodopa is given.
- Peripheral DOPA decarboxylase converts much of the levodopa to dopamine outside the brain.
- Peripheral dopamine stimulates the chemoreceptor trigger zone (outside the barrier), causing nausea.
- Carbidopa blocks peripheral decarboxylation without entering the brain, so more levodopa reaches the CNS.
Answer. Carbidopa inhibits peripheral DOPA decarboxylase, increasing brain levodopa and reducing nausea.