Multiple System Atrophy

Multiple system atrophy (MSA) is an alpha synuclein glial cytoplasmic inclusion disease causing autonomic failure with parkinsonism (MSA-P) or cerebellar ataxia (MSA-C).

• Prevalence 3 to 5 per 100,000; onset in the 50s; median survival 6 to 10 years.

• Poor response to levodopa; rapid progression.

• Complications: orthostatic hypotension, urinary retention, stridor, sleep disordered breathing, sudden death.

• Autonomic: orthostatic hypotension (drop of 30/15 mmHg), urinary urgency/retention, erectile dysfunction, constipation.

• MSA-P: symmetric bradykinesia, rigidity, postural instability, early falls, antecollis, Pisa syndrome, jerky postural tremor.

• MSA-C: gait ataxia, limb ataxia, dysarthria, nystagmus.

• REM sleep behaviour disorder, inspiratory stridor (vocal cord abduction), cold hands, emotional incontinence.

• Second consensus criteria (probable MSA: autonomic failure plus parkinsonism poorly responsive to levodopa or cerebellar syndrome).

• MRI: putaminal rim sign, hot cross bun sign in pons, middle cerebellar peduncle atrophy, putaminal atrophy.

• Autonomic testing (tilt table), residual urine volume (over 100 mL), anal sphincter EMG; sleep study with video polysomnography; laryngoscopy for stridor.

• DaTscan reduced; FDG PET hypometabolism of putamen/cerebellum; skin biopsy for alpha synuclein; supine plasma noradrenaline normal (differentiates from Parkinson disease).

• Exclude Parkinson disease, PSP, spinocerebellar ataxias, drug-induced parkinsonism.

• No disease modifying therapy.

• Orthostatic hypotension: raise head of bed 10 to 20 degrees, compression stockings, abdominal binder, fluids 2 to 3 L, salt.

• Drugs for orthostatic hypotension: fludrocortisone 0.1 to 0.3 mg daily, midodrine 2.5 to 10 mg three times daily (not at night), droxidopa 100 to 600 mg three times daily, pyridostigmine 30 to 60 mg.

• Treat supine hypertension (nitrate patch at night, elevate head).

• Parkinsonism: levodopa up to 1000 mg daily (response in 30%); amantadine.

• Urinary: antimuscarinics (trospium), mirabegron, intermittent catheterisation, desmopressin nasal spray at night.

• Constipation: macrogol; erectile dysfunction: sildenafil cautiously.

• Stridor and sleep apnoea: CPAP, tracheostomy for severe stridor; REM sleep behaviour: clonazepam 0.5 mg, melatonin 3 to 12 mg.

• Dysphagia: speech therapy, gastrostomy.

• Palliative care and carer support.