• Merck Manual
• >
• Health Care Professionals
• >
• Neurologic Disorders
• >
• Autonomic Nervous System
4

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 arginineSome Trade Names
R-GENE
Click for Drug Monograph
vasopressinSome Trade Names
PITRESSIN
Click for Drug Monograph
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 fludrocortisoneSome Trade Names
  FLORINEF
  Click for Drug Monograph
  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
  Click for Drug Monograph
  10 mg po tid may help. However, midodrineSome Trade Names
  ORVATEN
  PROAMATINE
  Click for Drug Monograph
  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 pergolideSome Trade Names
  PERMAX
  
  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, oxybutyninSome Trade Names
  DITROPAN
  Click for Drug Monograph
  chloride 5 mg po tid or tolterodineSome Trade Names
  DETROL
  Click for Drug Monograph
  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
  Click for Drug Monograph
  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

Content last modified November 2009