STEPTRACKERNERVOUS SYSTEM | PATHOLOGY + PHARMACOLOGY + GENETICS | HIGH-YIELD REVIEW

Movement Disorders

Too little movement or too much — basal ganglia and cerebellar disease, and the drugs that cause and treat it.

FOCUS ON
Parkinson: loss of substantia nigra dopamine neurons, Lewy bodies (α-synuclein) → resting tremor, rigidity, bradykinesia, postural instability; levodopa/carbidopa. Huntington: CAG repeats (AD, anticipation), caudate atrophy, chorea + psychiatric change + dementia. Hemiballismus = contralateral subthalamic nucleus. Drug-induced: acute dystonia, parkinsonism, tardive dyskinesia.
DISORDER
MECHANISM · PATHOLOGY
FEATURES
CLUE · TREATMENT
Parkinson disease
Loss of dopaminergic neurons in substantia nigra pars compacta (depigmented); Lewy bodies (α-synuclein)
Resting pill-rolling tremor, cogwheel rigidity, bradykinesia, postural instability; shuffling gait, masked face, micrographia
Anosmia, constipation, REM behavior disorder precede motor signs
Parkinson — causes & mimics
Mostly sporadic; LRRK2, SNCA, parkin; MPTP toxin
Drug-induced parkinsonism (antipsychotics, metoclopramide) is symmetric, no tremor dominance
MPTP → MPP⁺ via MAO-B
Multiple system atrophy
α-synuclein inclusions in oligodendrocytes
Parkinsonism + severe autonomic failure (orthostasis, impotence, bladder) ± cerebellar ataxia
Poor levodopa response
Progressive supranuclear palsy
Tau accumulation in brainstem and basal ganglia
Vertical gaze palsy, early falls backward, axial rigidity, dementia
Poor levodopa response
Huntington disease
AD CAG repeat in HTT (chr 4); anticipation (paternal); loss of striatal GABAergic neurons → caudate/putamen atrophy
Age 20–50: chorea, irritability, depression (suicide), dementia
↓ GABA, ↓ ACh, ↑ dopamine · tetrabenazine
Hemiballismus
Lesion (often lacunar stroke) of the contralateral subthalamic nucleus
Sudden violent flinging of one arm/leg
Loss of indirect-pathway braking
Essential tremor
Often autosomal dominant
Action/postural tremor of hands and head; better with alcohol
Propranolol, primidone
Drug-induced movement disorders
D2 blockade (antipsychotics, metoclopramide)
Acute dystonia (hours: torticollis, oculogyric crisis) · akathisia (days) · parkinsonism (weeks) · tardive dyskinesia (months: orofacial movements)
Dystonia → benztropine/diphenhydramine · TD → valbenazine
Restless legs syndrome
Dopamine and iron dysfunction; iron deficiency, CKD, pregnancy
Urge to move legs at rest/night, relieved by moving
Iron, dopamine agonists, gabapentin
Cerebellar lesions
Vermis vs hemispheres
Vermis: truncal ataxia, wide gait (alcohol) · hemisphere: ipsilateral limb ataxia, intention tremor, dysdiadochokinesia, dysmetria
Cerebellar signs are ipsilateral
Friedreich ataxia
AR GAA repeat in frataxin (mitochondrial iron) → degeneration of dorsal columns, spinocerebellar tracts, DRG
Child: ataxia, ↓ reflexes, ↓ vibration, Babinski; hypertrophic cardiomyopathy (cause of death), diabetes, kyphoscoliosis, pes cavus
Teen with ataxia and heart failure

Mechanism — basal ganglia circuits

Direct pathwayD1 excitatory
→
↓ GPi inhibition of thalamus
→
More movement
Indirect pathwayD2 inhibitory
→
Subthalamic nucleus drives GPi
→
Less movement

Dopamine loss (Parkinson) → too little movement. Striatal loss (Huntington) or subthalamic loss (hemiballismus) → too much.

Parkinson drugs

DRUG
ACTION
NOTE
Levodopa + carbidopa
Dopamine precursor; carbidopa blocks peripheral decarboxylase
Most effective · dyskinesias, on-off
Pramipexole, ropinirole
D2 agonists
Impulse control disorders
Selegiline, rasagiline
MAO-B inhibitors
Tyramine and serotonergic interactions
Entacapone
COMT inhibitor
Prolongs levodopa
Amantadine
↑ dopamine release, NMDA block
Livedo reticularis
Benztropine, trihexyphenidyl
Antimuscarinic
Tremor; avoid in elderly

How it's tested

COMMON CONFUSIONParkinson tremor is worst at rest and improves with movement; essential tremor appears with action or posture and improves with alcohol; cerebellar tremor worsens approaching a target.
THE TRAPParkinsonism with early falls, vertical gaze palsy, or severe autonomic failure — and a poor response to levodopa — points to PSP or MSA, not Parkinson disease.
YOUR APPROACHToo little vs too much movement → tremor type → onset age and family (repeats, anticipation) → drug exposure → circuit lesion → drug choice.

If you see… think…

Resting pill-rolling tremor, shuffling gait, small handwriting → Parkinson disease
Eosinophilic α-synuclein inclusions in nigral neurons → Lewy bodies
Young IV drug user with sudden parkinsonism → MPTP
Parkinsonism + fainting on standing + impotence → multiple system atrophy
Can't look down, falls backward early → progressive supranuclear palsy
35-year-old with chorea, depression, father affected later in life → Huntington (anticipation)
Sudden flinging of the left arm → right subthalamic nucleus lesion
Head and hand tremor that improves with wine → essential tremor
Neck twisting hours after haloperidol → acute dystonia — benztropine
Teen with ataxia, pes cavus and hypertrophic cardiomyopathy → Friedreich ataxia