Movement Disorders

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. clinical medicine 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

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

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 (clinical medicine Love This Order)

1. Psychiatric first · depression, personality change, irritability, anxiety. Often before movement symptoms. Many are initially diagnosed with depression or bipolar disorder. clinical medicine may say "depression that won't respond to antidepressants" before the diagnosis is revealed.
2. Chorea · random, flowing, dance-like involuntary movements. Not purposeful. Not rhythmic. Can look like fidgeting or restlessness early on. Gets worse over time.
3. Cognitive decline · subcortical dementia. Slow processing, executive dysfunction, memory problems. Eventually severe.
4. 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

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.

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.

Spot the Pattern

Brand-new, one-sided, big flinging movements of an arm or leg in a vasculopath (HTN, diabetes, smoker). Hyperkinetic. Proximal, not finger-twitchy. Goes away when the patient sleeps. One word: ballistic.

The Chain · Why a Tiny Stroke Causes a Whole Arm to Fling 🔑Brake-failure mnemonic: the STN is the brake pedal that tells GPi to slow movement down. Knock out the brake → thalamus floors the gas → motor cortex over-fires → arm flies through the air. Pathways crossed at the brainstem, so the side opposite the stroke flings.

The lesion is a lacunar stroke of the contralateral subthalamic nucleus (STN). Tiny penetrating arteries off the basilar/PCA become diseased from chronic HTN/diabetes (lipohyalinosis) and finally clot off. The STN dies. Here is what that does:

1. Normal STN sends excitatory glutamate to GPi (globus pallidus internus). GPi is the basal ganglia's brake on movement: it tonically inhibits the thalamus.
2. Lose STN → GPi loses its drive → GPi underactive.
3. Thalamus loses its inhibition → thalamus disinhibited → floods motor cortex with excitatory drive.
4. Motor cortex over-fires on the side opposite the lesion (corticospinal fibers cross at the medulla) → wild flinging arm.

In one line: kill the brake, the gas pedal floors itself.

Direct vs Indirect Pathway Recap (One Sentence Each)

• Direct pathway · D1 receptors. Striatum inhibits GPi → thalamus disinhibited → more movement. Dopamine turns this ON.
• Indirect pathway · D2 receptors. Striatum inhibits GPe → STN unleashed → GPi over-driven → less movement. Dopamine turns this OFF.
• Dopamine increases movement two ways: stimulates D1 (GO louder) AND blocks D2 (STOP quieter). Net result: more movement.

Now anchor each disease on the same circuit:

• Parkinson · SNc dopamine dies → both pathways skew toward LESS movement → hypokinetic.
• Huntington · caudate GABA neurons die → indirect pathway broken at the striatum → STOP signal lost → chorea (more movement).
• Hemiballismus · STN lacunar lesion → indirect pathway broken at the next node → same net effect: STOP signal lost, but bigger and more proximal → flinging.

The Move · Treatment

• Calm the storm: dopamine antagonists. Haloperidol short-term, or tetrabenazine / valbenazine (VMAT2 inhibitors) for ongoing chorea-like movement.
• Fix the soil: aggressive BP control, glycemic control, statin, antiplatelet. The same vasculopathy that took out the STN is going for the next penetrating artery.
• Wait it out: a single isolated STN lacune often resolves over weeks to months as adjacent circuitry compensates. Refractory cases → pallidotomy or DBS to GPi.
• Do NOT reach for levodopa · this is too much movement, not too little. Adding dopamine pours gas on the fire.