Movement Disorders

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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.

Substantia Nigra and Amygdala Histopathology in PD

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. Basal ganglia and cerebellar pathways diagram
  • 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). Anticholinergic Use for Drug-Induced Movement Disorders
  • 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.

Practice Questions: Movement Disorders

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All the following apply to Parkinson disease except

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Flashcards: Movement Disorders

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_____ disease often presents with neuropsychiatric manifestations, due to copper deposition and resultant cystic degeneration in the putamen and other adjacent structures

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_____ disease often presents with neuropsychiatric manifestations, due to copper deposition and resultant cystic degeneration in the putamen and other adjacent structures

Wilson

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