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's 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 arginine vasopressin and treatments used to increase blood volume.

Diagnosis

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

Diagnosis is suspected clinically, based on the combination of autonomic failure and parkinsonism or cerebellar symptoms. Similar symptoms may result from Parkinson's 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 MRI abnormalities in the striatum, pons, and cerebellum strongly suggest the disorder. Multiple system atrophy can be diagnosed antemortem based on these findings plus symptoms of generalized autonomic failure and lack of response to levodopa.

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 fludrocortisone 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 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.
• Parkinsonism: Levodopa/carbidopa 25/100 mg po at bedtime or pergolide 0.1 mg po once/day, titrated upward to 0.25 to 1.0 mg tid, may be tried to relieve rigidity and other parkinsonian symptoms, but these drugs are usually ineffective or provide 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.
• 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 and various physical means can be used (see Male Sexual Dysfunction: Treatment).

Last full review/revision November 2009 by Phillip Low, MD