Huntingtons Disease (and other Chorea’s)

DDX for chorea

Inherited

· Huntingtons Disease

· (+ many other rare conditions)

Immune mediated:

• Sydenham’s chorea – Rheumatic fever
• SLE
• Anti-phospholipid syndrome

Metabolic

• Hyperglycaemic hemichorea
• Hyperthyroidism

Infective

• HIV

Vascular

· Stroke

· Postcardiac bypass

Toxic

· Carbon monoxide

Medications

• Dopamine blockers
• Levodopa
• Anti-cholinergics
• Phenytoin
• Cocaine
• CNS stimulants
• Oestogens (including pregnancy)
• Lithium

Huntington’s Disease

Epidemiology

• Autosomal dominant
• Onset 25-45yrs
• Prevalence 2-8/100,000
• Full penetrance
• Anticipation (see below)
• More likely if passed on from male

Pathogenesis

• Expansion of CAG (glutamine) repeats in Huntingtin gene on chromosome 4
• Normal gene has 6-34 copies
• >35 is potentially unstable and disease causing
• Full penetrance for disease with copy number >40
• >60 may result in juvenile onset form
• Function of protein in unknown
• Fragments of protein however may be toxic
• Atrophy of caudate nucleus (and putamen) – with enlargement of lateral ventricles
• Later – more diffuse cortical atrophy
• Somatic and germline instability of CAG repeats mean expansion of repeats over successive generations

Clinical manifestations

• Choera - Rapid, non-patterened, semipurposeful involuntary choreform movements
• Initially focal or segmental but progresses to involve multiple regions
• Oculomotor abnormalities are common
• Slowed saccadic movements often first sign
• Bradykinesia
• Postural reflex compromise
• With progression
• Dysarthria, dysphagia
• Reduction in chorea and increased dystonia, rigidity and bradykinesia, myoclonus and spasticity
• Behavioural and cognitive changes
• Frontal lobe type disorder common first
• Depression
• Or “Pseudodepression” with apathy, withdrawal and neglect”
• Aggressive behaviour
• Psychosis
• Or “Pseudopsychopathic” with irritability, impulsivity and disinhibition
• Dementia

· Self-herm and suicide

o Much higher risk

DDx

· Other chorea’s as above

· Benign hereditary chorea

· DRPLA

· Neuroacanthocytosis

· Friedreich ataxia

· CJD

Diagnosis

• Family history and symptoms
• Genetic testing
• MRI has some suggestive features but not diagnostic and used more to rule out alternative diagnosis

Treatment

• Dopamine may reduce chorea but generally not worthwhile
• Treatment of depression and psychosis most important

Prognosis