Movement Disorders

Parkinson's Disease - Dopamine Deficit

• Pathophysiology: Loss of dopaminergic neurons in Substantia Nigra pars compacta (SNpc) leading to ↓ dopamine in striatum. Pathological hallmark: Lewy bodies (abnormal α-synuclein aggregates).
• Cardinal Motor Features (📌 TRAP):
  • Tremor: At rest, "pill-rolling," often unilateral onset.
  • Rigidity: Cogwheel or lead-pipe.
  • Akinesia/Bradykinesia: Slowness, difficulty initiating movement.
  • Postural instability: Later sign, risk of falls.
• Key Non-Motor Symptoms: Anosmia, constipation, REM sleep behavior disorder (RBD), depression, anxiety.
• Treatment Principles:
  • Mainstay: Levodopa/Carbidopa (most effective for motor symptoms).
  • Dopamine Agonists (e.g., Pramipexole, Ropinirole).
  • MAO-B Inhibitors (e.g., Selegiline, Rasagiline) for mild symptoms or as adjunct.

⭐ The presence of Lewy bodies containing α-synuclein is a pathological hallmark of Parkinson's Disease.

Tremors & Ataxias - Unsteady States

• Tremor Types:
  • Resting (e.g., Parkinson's).
  • Postural (holding position).
  • Action/Kinetic (during movement).
  • Intention (target approach, cerebellar).
• Essential Tremor:
  • Bilateral, postural/action. Improves with alcohol. Family Hx.
  • Rx: Propranolol, Primidone.

  ⭐ Essential tremor is the most common movement disorder; often improves with small alcohol amount.

• Cerebellar Tremor:
  • Intention tremor, ipsilateral cerebellar signs.
• Friedreich's Ataxia (AR):
  • GAA repeat (FXN gene). Onset < 25 yrs.
  • Ataxia, dysarthria, HOCM, diabetes, scoliosis.
  • 📌 Friedreich is Fratastic (Frataxin): AR, stumbling (ataxia), slurring (dysarthria), big heart (HOCM), sweet tooth (diabetes).

Hyperkinetic Disorders - Wild Wobbles

• Huntington's Disease (HD)

  • AD; CAG repeats (HTT gene, Chr 4).
  • 3 C's: Chorea, Cognitive decline, Crazy (psychiatric).
  • 📌 HUNT: Huntington gene, Uncontrolled movements, Neuropsychiatric, Trinucleotide.
  • CAG repeats: Normal <26; Full penetrance ≥40.

  ⭐ Genetic anticipation in HD (earlier, severe onset in generations) often via paternal CAG expansion.

• Wilson's Disease (WD)

  • AR; ATP7B gene (Chr 13) → Cu accumulation.
  • Hepatic, Neurological, Psychiatric. Kayser-Fleischer (KF) rings.
  • Labs: ↓ Serum ceruloplasmin (<20 mg/dL), ↑ urinary Cu (>100 mcg/24h).
  • 📌 Mnemonic (Wilson's): Weird Involuntary movements, Liver problems, Serum ceruloplasmin low, Ocular (KF rings), Neurological.

• Dystonia

  • Sustained muscle contractions → abnormal postures.
  • Focal (torticollis, blepharospasm), segmental, generalized.

• Myoclonus

  • Brief, shock-like, involuntary muscle jerks.

• Tics & Tourette Syndrome (TS)

  • Tics: Sudden, nonrhythmic motor/vocal.
  • TS: Multiple motor & ≥1 vocal tics >1 yr, onset <18 yrs. Premonitory urge. Coprolalia not essential.

Other Key Syndromes - Mixed Bag Moves

• Drug-Induced Movement Disorders (DIMDs):
  • Acute Dystonia (oculogyric crisis, torticollis): Rx: Anticholinergics/Antihistamines.
  • Akathisia: Rx: Propranolol, Benzos.
  • Parkinsonism: Rx: Reduce drug, Anticholinergics.
  • Tardive Dyskinesia (TD): Orobuccolingual. Rx: VMAT2 inhibitors (valbenazine, deutetrabenazine).
• Restless Legs Syndrome (RLS):
  • 📌 URGE: Urge to move, Rest worsens, Gets better with activity, Evening/night worsening.
  • Iron deficiency. Rx: Dopamine agonists, Gabapentinoids.
• Gait Disorders: Parkinsonian, Ataxic, Spastic, Waddling, Apraxic.

⭐ Tardive Dyskinesia is a serious, potentially irreversible side effect of long-term dopamine receptor blocking agents, particularly typical antipsychotics.

High‑Yield Points - ⚡ Biggest Takeaways

• Parkinson's Disease: TRAP features (Tremor, Rigidity, Akinesia, Postural instability) & Lewy bodies.
• Huntington's Disease: Autosomal Dominant, CAG trinucleotide repeats, chorea & dementia.
• Wilson's Disease: ATP7B defect, Kayser-Fleischer rings, low ceruloplasmin, ↑ urinary copper.
• Essential Tremor: Postural/action tremor, often improves with alcohol; propranolol is key treatment.
• Restless Legs Syndrome: Urge to move legs, worse at rest/night; treat with dopamine agonists.
• Tourette Syndrome: Multiple motor and at least one vocal tic; associated with ADHD/OCD.