Multiple System Atrophy (MSA)
Multiple system atrophy is a relentlessly progressive neurodegenerative disorder causing pyramidal, cerebellar, and autonomic dysfunction. It includes 3 disorders previously thought to be distinct: olivopontocerebellar atrophy, striatonigral degeneration, and Shy-Drager syndrome. Symptoms include hypotension, urinary retention, constipation, ataxia, rigidity, and postural instability. Diagnosis is clinical. Treatment is symptomatic, with volume expansion, compression garments, and vasoconstrictor drugs.
(See also Overview of the Autonomic Nervous System.)
Multiple system atrophy affects about twice as many men as women. Mean age at onset is about 53 yr; after symptoms appear, patients live about 9 to 10 yr.
Etiology of multiple system atrophy is unknown, but neuronal degeneration occurs in several areas of the brain; the area and amount damaged determine initial symptoms. A characteristic finding is cytoplasmic inclusion bodies containing alpha-synuclein within oligodendroglial cells.
Initial symptoms of multiple system atrophy vary but include a combination of
Parkinsonian symptoms predominate in striatonigral degeneration. They include rigidity, bradykinesia, postural instability, and jerky postural tremor. High-pitched, quavering dysarthria is common.
In contrast to Parkinson disease, multiple system atrophy usually does not usually cause resting tremor and dyskinesia, and symptoms respond poorly and transiently to levodopa.
Typically, autonomic insufficiency causes orthostatic hypotension (symptomatic fall in BP when a person stands, often with syncope), urinary retention or incontinence, constipation, and erectile dysfunction.
Other autonomic symptoms, which may occur early or late, include decreased sweating, difficulty breathing and swallowing, fecal incontinence, and decreased tearing and salivation.
REM sleep behavior disorder (eg, speech or skeletal muscle movement during REM sleep) and respiratory stridor are common. Patients are often unaware of REM sleep behavior disorder.
Patients may have nocturnal polyuria; contributing factors may include a circadian decrease in arginine vasopressin and treatments used to increase blood volume.
Diagnosis of multiple system atrophy is suspected clinically, based on the combination of autonomic insufficiency and parkinsonism or cerebellar symptoms. Similar symptoms may result from Parkinson disease, Lewy body dementia, pure autonomic failure, autonomic neuropathies, progressive supranuclear palsy, multiple cerebral infarcts, or drug-induced parkinsonism.
No diagnostic test is definitive, but some (eg, MRI, nuclear imaging with 123I-metaiodobenzylguanidine [MIBG], autonomic tests) help confirm clinical suspicion of multiple system atrophy—for example, if
There is no specific treatment for multiple system atrophy, but symptoms are managed as follows:
Orthostatic hypotension: Treatment includes intravascular volume expansion with salt and water supplementation and sometimes fludrocortisone 0.1 to 0.4 mg po once/day. Use of compression garments for the lower body (eg, abdominal binder, compression stockings) and alpha-adrenoreceptor stimulation with midodrine 10 mg po tid may help. However, midodrine also increases peripheral vascular resistance and supine BP, which may be problematic. Raising the head of the bed about 10 cm reduces nocturnal polyuria and supine hypertension and may reduce morning orthostatic hypotension. Alternatively, droxidopa may be used; its action is similar to that of midodrine, but duration of action is longer.
Parkinsonism: Levodopa/carbidopa 25/100 mg po at bedtime may be tried to relieve rigidity and other parkinsonian symptoms, but this combination is usually ineffective or provides modest benefit.
Urinary incontinence: If the cause is detrusor hyperreflexia, oxybutynin chloride 5 mg po tid or tolterodine 2 mg po bid may be used. Tamsulosin 0.4 to 0.8 mg once/day may be effective for urinary urgency. Alternatively, the beta-3 adrenergic agonist mirabegron 25 to 50 mg once/day can be used; unlike tamsulosin, mirabegron does not worsen orthostatic hypotension.
Urinary retention: Many patients must self-catheterize their bladder.
Constipation: A high-fiber diet and stool softeners can be used; for refractory cases, enemas may be necessary.
Erectile dysfunction: Drugs such as sildenafil 50 mg po prn or tadalafil 2.5 to 5 mg once/day and various physical means can be used.
Multiple system atrophy can include parkinsonian symptoms, cerebellar abnormalities, and autonomic insufficiency in various degrees of severity.
Diagnose this disorder based on clinical, autonomic, and MRI findings, but consider Parkinson disease, Lewy body dementia, pure autonomic failure, autonomic neuropathies, progressive supranuclear palsy, multiple cerebral infarcts, and drug-induced parkinsonism, which can all cause similar symptoms.
Use treatments specific for the symptoms present.