Movement Disorders — Bone Wizardry

Quick — before you learn anything:

A 70-year-old man is referred for tremor. His wife says his right hand shakes when it's resting in his lap during dinner, but it stops when he picks up his fork. He walks with small steps and has a slightly stooped posture. He's been moving more slowly over the past year. He has no family history of tremor.

Essential tremor

Parkinson's disease

Huntington's disease

Drug-induced parkinsonism

Exactly. Resting tremor that stops when he moves = Parkinson's. Add bradykinesia (slowing), shuffling gait, and stooped posture, and this is textbook. Essential tremor is the most common movement disorder, but it's an action tremor — it only shows up when he uses his hand.

Good instinct on tremor, but the location and timing are wrong for ET. Essential tremor is an action tremor — it appears when the hand is being used or held against gravity. This patient's tremor disappears when he reaches for his fork. If it were ET, picking up the fork would make it worse. Also: ET doesn't cause bradykinesia or shuffling gait.

Huntington's causes chorea — random, dance-like, flowing involuntary movements of the whole body, not a focal hand tremor at rest. HD also typically presents in middle age (30-50s) with psychiatric symptoms first, and has autosomal dominant inheritance. No family history here.

Good thought — D2 blockers can cause drug-induced parkinsonism that looks identical to PD. But the question doesn't mention any medications (especially antipsychotics, metoclopramide, prochlorperazine). Always ask about meds, but if no offending drug is present, primary PD is the answer. Drug-induced parkinsonism is reversible when the drug is stopped.

The One Question — Resting vs Action vs Intention▸

Every tremor question starts here

Before any diagnosis, answer: When does the tremor occur?

At rest, disappears with movement → Resting tremor = Parkinson's. The hand shakes while lying in the lap. Pick it up → tremor stops.
With posture or action, NOT at rest → Action/Postural tremor = Essential Tremor. The hand is still at rest. Hold it up or move it → tremor starts.
Worse at the end of a purposeful movement (reaching for something) → Intention tremor = Cerebellar pathology (MS, stroke, spinocerebellar ataxia). Worsens as hand approaches target.

Tremor Type Demo

TREMOR

Resting tremor — present at rest, suppressed by movement. Classic Parkinson's. 4-6 Hz pill-rolling.

Type	When	Diagnosis	Hz
Resting	At rest; stops with movement	Parkinson's disease	4-6 Hz
Action/Postural	During movement or holding posture; absent at rest	Essential Tremor	6-12 Hz
Intention	Worsens as hand approaches target	Cerebellar (MS, stroke)	3-5 Hz

The one board trap: "resting tremor that stops with movement." That four-word phrase = Parkinson's. Essential tremor is the most common movement disorder overall, but Parkinson's is the most tested. Know which is which cold.

Parkinson's Disease — The TRAP▸

The Four Cardinal Features 🔑TRAP: Tremor at rest, Rigidity (cogwheel), Akinesia/bradykinesia, Postural instability. Get one extra credit: T-R-A-P is how you get caught — caught without levodopa.

T — Tremor at rest. Pill-rolling, 4-6 Hz. Unilateral onset. Stops when the patient moves the limb.
R — Rigidity. Cogwheel rigidityCogwheel = ratchety resistance to passive movement. It's the combination of rigidity + the superimposed tremor. Compared to "lead-pipe" rigidity (smooth throughout) seen in other causes of rigidity. — ratchety, catch-and-release resistance to passive limb movement. "Lead pipe" throughout the range.
A — Akinesia / Bradykinesia. slowness of movement. Difficulty initiating. Masked facies (hypomimia). Micrographia (writing gets tiny). Hypophonia.
P — Postural instability. Retropulsion. Festinating gait (shuffling, small steps, stooped forward). Falls. Late feature in PD (if early, think PSP instead).

The Pathology

Loss of dopaminergic neuronsThese neurons project from substantia nigra → striatum (caudate + putamen). Dopamine normally suppresses unwanted movement. Without it: the basal ganglia circuit can't inhibit movement → tremor, rigidity, bradykinesia. in the substantia nigra pars compacta → ↓dopamine in the nigrostriatal pathway.

Histology: Lewy bodies — intracytoplasmic inclusions of alpha-synucleinAlpha-synuclein is a protein that aggregates abnormally in PD. It's also seen in Lewy body dementia and multiple system atrophy. Boards may test: "eosinophilic intracytoplasmic inclusion bodies" = Lewy bodies = PD.. Eosinophilic, round, concentric rings.

Gross pathology: Loss of pigmentation (neuromelanin) in the substantia nigra. Normal brain is dark there; PD brain is pale.

Treatment

Drug	Mechanism	Board Notes
Levodopa / Carbidopa	L-DOPA (dopamine precursor) + peripheral decarboxylase inhibitor (carbidopa blocks conversion outside CNS)	Gold standard. Most effective. "On-off" phenomenon with long-term use. Dyskinesias at high doses.
Dopamine Agonists pramipexole, ropinirole, bromocriptine	Direct D2/D3 agonists	Used as monotherapy in younger patients to delay levodopa and avoid dyskinesias. Side effect: impulse control disorders (gambling, hypersexuality).
MAO-B Inhibitors selegiline, rasagiline	Block breakdown of dopamine in the synapse	Neuroprotective? Modest symptomatic effect. Safe add-on.
COMT Inhibitors entacapone, tolcapone	Prolong levodopa effect by blocking peripheral COMT	Always used WITH levodopa. Extends "on" time. Tolcapone: hepatotoxicity risk.
Anticholinergics benztropine, trihexyphenidyl	Block M receptors to rebalance ACh/DA ratio	Only good for tremor. Useless for bradykinesia. Avoid in elderly → confusion, urinary retention. "Cognitively toxic."
Amantadine	NMDA antagonist, increases DA release	Now primarily used to treat levodopa-induced dyskinesias.

Board Trap: "On-Off" phenomenon. Long-term levodopa use → wearing off (predictable) and random "off" periods. The dose window narrows. Solution: add COMT inhibitor, use extended-release formulations, or switch to continuous infusion. This is a complication of treatment, not the disease.

Board Trap: PSP vs PD. Progressive supranuclear palsy looks like PD but: vertical gaze palsy (can't look up/down), falls backward (not forward), early postural instability (in PD it's late), no tremor, no levodopa response. "The patient falls backward into the exam room" on boards = PSP.

Essential Tremor — Most Common Movement Disorder▸

What It Is 🔑ET phone home — ET holds the phone, tremor only when REACHING (action). If ET were sitting still with his hand in his lap, no tremor. It's the REACH that does it.

Most common movement disorder (more common than PD). Action/postural tremor — bilateral, affects hands and arms. Absent at rest. Worsens with goal-directed movement (pouring coffee, writing, bringing a spoon to mouth).

Classically improves with alcohol (patients self-medicate — worth knowing). Worsens with caffeine, stress, fatigue.

Familial: Autosomal dominant inheritance in many cases. "My dad and his dad had it." Positive family history is a clue.

Head tremor (titubation) and voice tremor can occur. Head tremor = "no-no" or "yes-yes" oscillation.

What It Is NOT

No bradykinesia
No cogwheel rigidity
No postural instability
No masked facies
No resting tremor

If you see these features alongside tremor, reconsider PD or another diagnosis.

Treatment

Drug	Notes
Propranolol (beta-blocker)	First-line. Non-selective beta-blocker. 50-70% see benefit. Avoid in asthma, COPD, bradycardia.
Primidone (anticonvulsant)	First-line alternative. Converted to phenobarbital. Works well. Side effect: initial sedation ("first-dose reaction").
Gabapentin, topiramate	Second-line options.
Deep brain stimulation (DBS)	Thalamic VIM nucleus. For refractory ET. Very effective for tremor.

Boards will give you an elderly patient with bilateral hand tremor "when writing" or "when holding a cup." If there's no bradykinesia, no rigidity, no resting component, and positive family history → Essential tremor. First drug = propranolol.

Huntington's Disease — The Hunt for CAG▸

The Big Picture 🔑Hunting for the CAG — the more CAG repeats you have, the younger it hunts you down (anticipation: earlier onset each generation). >36 repeats = disease. Full penetrance at >40 repeats.

Autosomal dominant. Trinucleotide CAG repeat expansionCAG encodes glutamine. The huntingtin protein (HTT) with a polyglutamine tract that's too long becomes toxic to neurons, especially in the striatum. Normal: ≤26 repeats. Premutation: 27-35. Disease: ≥36 (reduced penetrance), ≥40 (full penetrance). in the huntingtin gene on chromosome 4. Normal ≤26 repeats. Disease ≥36. Anticipation: more repeats in each generation → earlier onset.

Typically presents age 30-50 years. Insidious onset. Progressive. Fatal within 15-20 years of diagnosis. No disease-modifying treatment.

The Classic Progression (Boards Love This Order)

Psychiatric first — depression, personality change, irritability, anxiety. Often before movement symptoms. Many are initially diagnosed with depression or bipolar disorder. Boards may say "depression that won't respond to antidepressants" before the diagnosis is revealed.
Chorea — random, flowing, dance-like involuntary movements. Not purposeful. Not rhythmic. Can look like fidgeting or restlessness early on. Gets worse over time.
Cognitive decline — subcortical dementia. Slow processing, executive dysfunction, memory problems. Eventually severe.
Later: rigidity (chorea paradoxically decreases), dysphagia (aspiration is a major cause of death), severe dementia, total dependence.

Pathology

Atrophy of the caudate nucleus (part of the striatum). Loss of GABA-ergic medium spiny neurons. On MRI: "boxcar ventricles" — the caudate normally bulges into the lateral ventricle; in HD it atrophies and the ventricle widens.

The caudate normally inhibits unwanted movement via the indirect pathway. Without it: uncontrolled, random movement.

Treatment — Palliative Only

Target	Drug	Notes
Chorea	Tetrabenazine (vesicular monoamine transporter inhibitor, depletes dopamine)	FDA-approved for HD chorea. Can worsen depression/suicidality — monitor closely.
Chorea	Deutetrabenazine	Longer-acting version. Better tolerated.
Psychiatric	Antidepressants (SSRIs), antipsychotics (for psychosis/irritability)	Manage symptoms. Standard agents.
Disease	Nothing	No neuroprotective or disease-modifying treatment exists. Palliative care focus. Genetic counseling for family members.

Board Trap: Genetic testing in HD. At-risk individuals (parent with HD) must decide whether to test before symptoms. This is loaded with ethical implications: positive result = certain future disease. Boards may ask about pre-test counseling requirements. You cannot test minors. Genetic counseling is mandatory before testing.

Drug-Induced Parkinsonism & Wilson's Disease▸

Drug-Induced Parkinsonism — The Reversible Mimic

Drugs that block D2 receptorsDopamine D2 receptors in the striatum. Block them pharmacologically → same net effect as losing dopamine neurons → parkinsonism. The key difference: drug-induced is reversible. Primary PD is not. can cause a syndrome identical to PD: bradykinesia, rigidity, tremor.

The culprits (D2 blockers):

Antipsychotics — haloperidol, risperidone, chlorpromazine, any typical or atypical antipsychotic
Metoclopramide — antiemetic. Very commonly tested. Used for nausea/gastroparesis.
Prochlorperazine — antiemetic / vertigo
Promethazine

Key difference from PD: Reversible when the offending drug is stopped. If you see "parkinsonism" in a patient on metoclopramide or antipsychotics → the first step is discontinue the drug.

Board Trap: Tardive dyskinesia (different from drug-induced parkinsonism). Long-term D2 blocker use → repetitive, involuntary orofacial movements (lip smacking, tongue protrusion, chewing). Risk increases with duration and dose. Treatment: tetrabenazine or valbenazine. Prevention: use lowest effective antipsychotic dose.

Wilson's Disease — Young Patient + Everything Wrong

Autosomal recessive. Mutation in ATP7B (copper transporter) → copper accumulates in liver, brain, eyes, kidneys.

Board buzzword cluster: Young patient (teens to 40s) + movement disorder (tremor, dysarthria, chorea, or parkinsonism) + liver disease (hepatitis, cirrhosis) + Kayser-Fleischer rings (copper deposition in Descemet membrane of cornea — golden-brown rings at the limbus) = Wilson's until proven otherwise.

Psychiatric: Personality change, depression, psychosis. Can present primarily psychiatric in young patients.

Lab workup: ↓serum ceruloplasminCeruloplasmin is the copper-carrying protein. In Wilson's it's LOW because the liver can't make it (copper accumulation damages hepatocytes). Serum copper may be low (less ceruloplasmin to carry it) but 24-hour urine copper is HIGH (free unbound copper spills into urine). Both tests are used together. (<20 mg/dL), ↑24-hour urine copper, liver biopsy (gold standard).

Treatment: Penicillamine or trientine (copper chelators). Zinc (blocks intestinal copper absorption). Liver transplant for severe hepatic failure.

Young patient (<40) with movement disorder + liver disease = Wilson's disease until proven otherwise. Order ceruloplasmin + slit-lamp exam (Kayser-Fleischer rings) + 24-hour urine copper. This is the one reversible cause of movement disorder in a young person that boards love to hide.

A patient has a tremor. When does it occur?

At rest — stops or improves when they move the limb

Only with action or holding a position — absent at rest

Worsens as they reach toward a target (finger-nose)

Resting tremor → Parkinson's disease (or Parkinsonism).
Check for the rest of the TRAP: Rigidity (cogwheel), Akinesia/bradykinesia, Postural instability.
Check medications for D2 blockers (drug-induced parkinsonism — reversible).
If patient is young (<40): add Wilson's disease workup (ceruloplasmin, slit-lamp).
If postural instability is the earliest feature + vertical gaze palsy: think PSP.

Action/postural tremor → Essential Tremor.
Bilateral, worse with goal-directed movement (writing, holding a cup), absent at rest.
Ask about family history (autosomal dominant), alcohol (classically improves ET).
No bradykinesia, no rigidity, no postural instability = no PD features.
First-line treatment: propranolol or primidone.

Intention tremor → Cerebellar pathology.
Worsens as hand approaches target. Look for other cerebellar signs: ataxia, dysmetria, dysdiadochokinesia, nystagmus, scanning speech.
Causes: MS (young adult + other demyelinating signs), stroke (posterior circulation), alcohol (cerebellar degeneration), medications (phenytoin, lithium toxicity).
Spinocerebellar ataxias (SCAs) if hereditary.

Side-by-Side — The Three Big Disorders▸

	Parkinson's	Essential Tremor	Huntington's
Tremor type	Resting, 4-6 Hz, pill-rolling	Action/postural, 6-12 Hz	Chorea (not tremor)
Bradykinesia	YES — cardinal feature	NO	Late (rigidity eventually)
Rigidity	YES — cogwheel	NO	Late-stage
Genetics	Mostly sporadic; some LRRK2, PARK mutations	Often autosomal dominant; sporadic common	Autosomal dominant, CAG >36
Onset age	60s-70s (young-onset <50 exists)	Any age; ↑with age	30-50s
Psychiatric sx	Depression, dementia late; DLB overlap	Usually none	FIRST symptom: depression, personality
Pathology	Substantia nigra loss; Lewy bodies	Unclear; mild cerebellar changes	Caudate atrophy; huntingtin aggregates
Treatment	Levodopa/carbidopa	Propranolol, primidone	None (palliative only)
Alcohol effect	No significant change	Improves (classic feature)	No significant change

Quiz — 4 Shaky Patients Walk In▸

4 patients with movement complaints. Don't mix up the tremors. At least try not to give levodopa to the wrong person.