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.

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

Etiology 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 α-synuclein within oligodendroglial cells.

Symptoms and Signs

Initial symptoms vary but include a combination of parkinsonism unresponsive to levodopa, cerebellar abnormalities, and symptoms due to autonomic insufficiency.

Parkinsonian symptoms: These 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 cause resting tremor and dyskinesia, and symptoms respond poorly and transiently to levodopa.

Cerebellar abnormalities: These abnormalities predominate in olivopontocerebellar atrophy. They include ataxia, dysmetria, dysdiadochokinesia (difficulty performing rapidly alternating movements), poor coordination, and abnormal eye movements.

Autonomic symptoms: Typically, autonomic insufficiency causes orthostatic hypotension (symptomatic fall in BP when a person stands, often with syncope—see Symptoms of Cardiovascular Disorders: Orthostatic Hypotension), 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 arginineSome Trade Names
R-GENE
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vasopressinSome Trade Names
PITRESSIN
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and treatments used to increase blood volume.

Diagnosis

• Clinical evaluation (parkinsonism or cerebellar symptoms that respond poorly to levodopa plus autonomic insufficiency)
• MRI

Diagnosis 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

• MRI shows characteristic changes in the midbrain, pons, or cerebellum.
• MIBG scans show intact innervation of the heart.
• Autonomic tests indicate generalized autonomic failure.

Treatment

• Supportive care

There is no specific treatment, but symptoms are managed as follows:

• Orthostatic hypotension: Treatment includes intravascular volume expansion with salt and water supplementation and sometimes fludrocortisoneSome Trade Names
  FLORINEF
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  0.1 to 0.4 mg po once/day. Use of compression garments for the lower body (eg, abdominal binder, Jobst stockings) and α-adrenoreceptor stimulation with midodrineSome Trade Names
  ORVATEN
  PROAMATINE
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  10 mg po tid may help. However, midodrineSome Trade Names
  ORVATEN
  PROAMATINE
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  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.
• 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, oxybutyninSome Trade Names
  DITROPAN
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  chloride 5 mg po tid or tolterodineSome Trade Names
  DETROL
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  2 mg po bid may be used.
• 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 sildenafilSome Trade Names
  VIAGRA
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  50 mg po prn and various physical means can be used (see Male Sexual Dysfunction: Treatment).

Key Points

• 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.

Last full review/revision April 2013 by Phillip Low, MD

Content last modified May 2013