Spinocerebellar Ataxia

Spinocerebellar ataxias are a group of dominantly inherited progressive cerebellar ataxias, with over 40 genetic types. The commonest are SCA1, SCA2, SCA3 (Machado-Joseph disease), SCA6, SCA7 and SCA17, caused mostly by CAG repeat expansions that encode polyglutamine.

The overall prevalence is about 3 in every 100,000 people, and varies by region. SCA3 is the commonest worldwide, SCA2 is prominent in Cuba, and SCA10 in Latin America. Onset is usually between 30 and 50 years, with earlier onset and faster progression with longer repeats (anticipation, particularly through paternal transmission).

Features by type. SCA1 (pyramidal signs, bulbar), SCA2 (slow saccades, neuropathy, parkinsonism), SCA3 (spasticity, dystonia, bulging eyes, amyotrophy), SCA6 (pure late onset cerebellar ataxia, downbeat nystagmus), SCA7 (retinal degeneration) and SCA17 (dementia, chorea).

Course. Progressive over 10 to 25 years to loss of walking, with death usually from aspiration pneumonia or complications of immobility.

Pathophysiology.

Polyglutamine expanded proteins form toxic aggregates and disrupt transcription, calcium homeostasis and autophagy, causing degeneration of Purkinje cells, the brainstem and spinal tracts.

Channelopathies (SCA6, SCA13, SCA27) and non-CAG expansions cause other types.

• Progressive gait and limb ataxia, wide based gait and falls.
• Dysarthria, dysphagia, nystagmus, slow saccades and diplopia.
• Type specific signs: spasticity, parkinsonism, dystonia, neuropathy, retinopathy, cognitive impairment, and sleep and mood disturbance.
• Autonomic features (bladder urgency, orthostatic hypotension) in some.
• Family history over several generations, though it can be hidden by anticipation or incomplete history.

Red flags.

• Sudden onset or rapid progression (consider stroke, tumour, paraneoplastic, prion disease).
• Aspiration, weight loss or respiratory failure.
• Depression or suicidal thoughts.

• Detailed family history and examination; MRI of the brain: cerebellar and brainstem atrophy, and pontine "hot cross bun" sign in some.
• Genetic testing: targeted repeat expansion testing for the common SCAs (1, 2, 3, 6, 7, 17), then a broader panel or exome or genome sequencing, and repeat expansion testing for non-coding expansions.
• Exclude treatable and acquired causes: vitamin E and B12 deficiency, hypothyroidism, alcohol, gluten ataxia, paraneoplastic and autoimmune ataxias, multiple system atrophy, and drug toxicity.
• Nerve conduction studies and electrophysiology as needed; ophthalmology (SCA7).
• Genetic counselling with predictive testing only after structured counselling.

Differential diagnosis. Friedreich ataxia, multiple system atrophy, alcoholic cerebellar degeneration, paraneoplastic cerebellar degeneration, ataxia with vitamin E deficiency, gluten ataxia, fragile X tremor ataxia syndrome, mitochondrial disease and episodic ataxia.

• No curative treatment exists; management is supportive and multidisciplinary.
• Physiotherapy: intensive balance and coordination training, aerobic and strength exercise, gait aids and wheelchair provision; occupational therapy, home adaptations and falls prevention.
• Speech and language therapy for dysarthria, with communication aids, and swallowing assessment with texture modification and gastrostomy in severe dysphagia.
• Riluzole has been used for ataxia: 50 mg orally twice daily. Maximum 100 mg daily. Monitor liver function monthly for 3 months then every 3 months, and full blood count if febrile illness occurs (neutropenia). Avoid in hepatic impairment (transaminases over 3 times normal); use caution in renal impairment; avoid in pregnancy and breastfeeding. Evidence is limited.
• Spasticity: baclofen 5 mg orally three times daily, increased by 5 mg every 3 days to a usual 30 to 75 mg daily. Maximum 100 mg daily. Monitor sedation and weakness; withdraw slowly; reduce dose in renal impairment (creatinine clearance under 50 mL/min).
• Parkinsonism in SCA2, SCA3 and SCA17: levodopa test course with co-careldopa equivalent to 50 mg levodopa orally three times daily after food, increased by 100 mg levodopa daily each week to a usual 300 to 600 mg daily in 3 divided doses. Maximum 1000 mg levodopa daily. Assess at 3 months and stop if there is no benefit. Monitor nausea, postural hypotension, hallucinations and dyskinesia. Avoid with non-selective monoamine oxidase inhibitors and in angle closure glaucoma; avoid in pregnancy unless essential.
• Episodic ataxia and SCA6 with episodic features: acetazolamide 250 mg orally twice daily, increased to a maximum of 1000 mg daily in divided doses. Monitor electrolytes, bicarbonate and kidney stones; avoid in severe renal or hepatic impairment and sulphonamide allergy; avoid in pregnancy unless benefit outweighs risk.
• Treat depression, sleep disorders, bladder urgency and orthostatic hypotension; psychological support for patients and families.
• Genetic counselling, predictive testing, prenatal diagnosis and preimplantation genetic testing for at risk families.

Monitoring. Review every 6 to 12 months with an ataxia scale, swallowing, weight, mood and falls; liver tests on riluzole.

Referral and escalation. Neurology and a specialist ataxia clinic; genetics; speech and language therapy; palliative care in late stages.

Special groups. Children: juvenile onset forms need school and developmental support. Women: pregnancy planning and genetic counselling.