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11 notes available
1 Last Minute Review 2 Parkinson Disease 3 Atypical Parkinsonism 4 Tremor 5 Dystonia 6 Chorea & Ballism 7 Myoclonus 8 Tics & Tourette Syndrome 9 Wilson Disease & NBIA 10 Hereditary Ataxias 11 Drug-Induced Movement Disorders
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Chorea & Ballism

Chorea & Ballism

What You'll Learn

  • Huntington disease — AD, HTT gene (chromosome 4), CAG ≥36 repeats, caudate atrophy (“boxcar ventricles”), anticipation with paternal transmission
  • Sydenham chorea — post–Group A strep, anti–basal ganglia antibodies, part of rheumatic fever (Jones criteria), self-limiting
  • Hemiballism — large-amplitude flinging movements from contralateral subthalamic nucleus lesion, most commonly vascular
  • Anti-NMDAR encephalitis — young women, ovarian teratoma, psychiatric symptoms + chorea + seizures + dysautonomia
  • Chorea gravidarum, SLE/antiphospholipid chorea, drug-induced chorea (levodopa, OCPs), benign hereditary chorea (NKX2-1)
  • VMAT2 inhibitors (tetrabenazine, deutetrabenazine, valbenazine — all FDA-approved for HD chorea) are the primary pharmacologic treatment for chorea
HighYield Pearls
  • Huntington CAG thresholds: <27 normal, 27–35 intermediate, 36–39 reduced penetrance, ≥40 fully penetrant; paternal transmission drives anticipation (sperm CAG instability).
  • Westphal (juvenile) HD: onset <20, >60 CAG repeats, almost always paternal, rigidity/dystonia/seizures rather than chorea — parkinsonian phenotype.
  • HD non-motor: depression + high suicide risk precedes motor by years; subcortical dementia (recognition > recall); saccadic abnormalities (slow/hypometric); “boxcar ventricles” = caudate atrophy.
  • HD chorea Rx = VMAT2 inhibitors: tetrabenazine (CYP2D6 genotype if >50 mg/day; black-box for depression/suicidality), deutetrabenazine (same boxed warning), valbenazine (FDA-approved Aug 2023, once daily); amantadine adjunct; pridopidine emerging.
  • Sydenham chorea: post–Group A strep, 2–6 mo latency, ASO/anti-DNase B, major Jones criterion (stand-alone), get echo for carditis; treat with valproate first-line, steroids/IVIG/PLEX if severe; long-term penicillin prophylaxis.
  • Chorea gravidarum / OCP-induced → often reactivation of prior Sydenham; self-limited — stop estrogen / await delivery, avoid teratogens.
  • Hemiballism = contralateral STN lesion (most often lacunar stroke); classic board scenario = uncontrolled DM with non-ketotic hyperglycemia + T1-hyperintense putamen → correct glucose.
  • Neuroacanthocytosis (VPS13A/chorein): AR, lip/tongue biting, acanthocytes, ↑CK, caudate atrophy. McLeod (XK): X-linked, absent Kx + weak Kell antigens, cardiomyopathy, ↑CK.
  • Always exclude Wilson in any chorea patient <50: ceruloplasmin, 24-hr urinary copper, slit-lamp for Kayser-Fleischer rings.
  • HD phenocopies when HTT is negative: HDL2 (JPH3, African descent), HDL1 (PRNP), SCA17/HDL4 (TBP), C9orf72 (FTD-ALS-chorea overlap), DRPLA (CAG; chorea + ataxia + myoclonus + dementia, Japanese), benign hereditary chorea (NKX2-1, brain-lung-thyroid, non-progressive).
  • Tardive dyskinesia: chronic dopamine-blocker exposure → orofacial stereotypies; treat with valbenazine or deutetrabenazine (FDA-approved for TD); withdraw offending agent if possible.
🔍 Quick ReferenceClinical · Imaging · Genetics / pathology
Clinical phenotype
  • Milkmaid’s grip + darting tongue (motor impersistence) → Huntington disease or Sydenham chorea
  • Psychiatric decline + chorea + suicidality + family history → Huntington disease
  • Juvenile rigidity-akinesia + seizures + paternal HD → Westphal variant
  • Child with chorea 2–6 mo after sore throat + emotional lability → Sydenham chorea
  • Chorea in pregnancy or on OCPs → chorea gravidarum / estrogen-induced reactivation of Sydenham
  • Acute unilateral large-amplitude flinging limb → hemiballism (contralateral STN stroke)
  • Self-mutilating lip/tongue biting + chorea in adult → chorea-acanthocytosis (VPS13A)
  • Chorea + cardiomyopathy + X-linked male → McLeod syndrome (XK)
  • Orofacial stereotypies after years of antipsychotics → tardive dyskinesia
  • Chorea + ataxia + myoclonus + dementia (Japanese kindred) → DRPLA
Imaging signs
  • “Boxcar ventricles” (caudate atrophy, frontal-horn dilation) → Huntington disease
  • T1-hyperintense contralateral putamen in a diabetic with hemichorea-hemiballism → non-ketotic hyperglycemia
  • Caudate atrophy + acanthocytes on smear → neuroacanthocytosis (and HDL2 phenocopy)
  • Lacunar infarct/hemorrhage in subthalamic nucleus → vascular hemiballism
  • Putaminal “face of the giant panda” / midbrain panda sign → Wilson disease
Genetics / pathology / treatment pearls
  • HTT CAG ≥40 (chromosome 4p16.3), paternal anticipation → Huntington disease
  • JPH3 CTG/CAG expansion, African ancestry → HDL2 (HD phenocopy)
  • TBP CAG/CAA expansion → SCA17 / HDL4 (chorea + ataxia + dementia)
  • PRNP octapeptide insertion → HDL1; C9orf72 GGGGCC hexanucleotide → FTD-ALS-chorea overlap
  • NKX2-1 (TITF1) mutation, brain-lung-thyroid syndrome → benign hereditary chorea
  • VPS13A (chorein) AR / XK (absent Kx + weak Kell) X-linked → chorea-acanthocytosis / McLeod
  • Low ceruloplasmin, ↑24-hr urine copper, Kayser-Fleischer rings → Wilson disease
  • VMAT2 inhibitors — tetrabenazine (CYP2D6, black-box depression/suicidality), deutetrabenazine, valbenazine → HD chorea & tardive dyskinesia
  • Anti–basal ganglia antibodies + elevated ASO/anti-DNase B → Sydenham chorea (valproate first-line; steroids/IVIG/PLEX if severe)
Huntington Disease

Genetics

  • Autosomal dominant — chromosome 4p16.3, HTT gene encoding huntingtin protein
  • Trinucleotide repeat: CAG expansion in exon 1
    • <27 repeats → normal
    • 27–35 → intermediate (unaffected, may expand in offspring)
    • 36–39 → reduced penetrance
    • ≥40 repeats → full penetrance
  • Anticipation: Earlier onset in successive generations — CAG expansion especially with paternal transmission (spermatogenesis instability)

Clinical Features

Motor

  • Chorea: Involuntary, irregular, non-repetitive, flowing movements — hallmark of adult-onset HD
  • Progressive: chorea worsens, then transitions to rigidity and akinesia in advanced stages
  • Motor impersistence: Cannot sustain tongue protrusion or grip (“milkmaid’s grip”)
  • Dystonia, impaired saccades, dysarthria, dysphagia in later disease

Psychiatric & Cognitive

  • Psychiatric symptoms often precede motor by years — depression (most common), high suicide risk, irritability, impulsivity, psychosis
  • Subcortical dementia: Executive dysfunction, slowed processing; recognition > recall (unlike Alzheimer)

Westphal Variant (Juvenile HD)

  • Onset <20 years; >60 CAG repeats — almost always paternal inheritance
  • Rigidity and akinesia predominate (NOT chorea) — parkinsonian phenotype
  • Seizures, cerebellar ataxia, rapid cognitive decline; more aggressive course

Imaging & Pathology

  • MRI: Bilateral caudate atrophy → “boxcar ventricles” (frontal horn dilation)
  • Pathology: Loss of medium spiny neurons (GABA/enkephalin) in caudate and putamen
  • Intranuclear inclusion bodies with mutant huntingtin aggregates

Treatment

  • Chorea — VMAT2 inhibitors (first-line):
    • Tetrabenazine: First FDA-approved for HD chorea; BLACK BOX warning for depression/suicidality; CYP2D6 genotyping required for doses >50 mg/day (to identify poor metabolizers) — NOT universal
    • Deutetrabenazine: Better tolerability, longer half-life; FDA-approved for HD chorea; shares boxed warning for depression/suicidality (same as tetrabenazine)
    • Valbenazine (Ingrezza): FDA-approved Aug 2023 for HD chorea; 40–80 mg/day; once-daily dosing
  • Antipsychotics if chorea + psychiatric features (haloperidol, risperidone, olanzapine) — use with caution: may worsen depression/suicidality and parkinsonism in advanced HD; consider pimozide as alternative
  • Depression: SSRIs/SNRIs; screen regularly given high suicide risk
  • No disease-modifying therapy currently available
💎 Board Pearl
  • CAG ≥40 = full penetrance. Anticipation occurs with paternal transmission. Westphal variant = rigidity (NOT chorea), >60 repeats, paternal.
  • Psychiatric symptoms precede motor by years — depression with suicide risk is the most tested psychiatric feature.
  • “Boxcar ventricles” on imaging = caudate atrophy = Huntington disease.
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