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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 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 autonomic symptoms.
Parkinsonian symptoms (predominant in striatonigral degeneration) include rigidity, bradykinesia, postural instability, and jerky postural tremor. High-pitched, quavering dysarthria is common. In contrast to Parkinson's disease, resting tremor and dyskinesia are uncommon, and symptoms respond poorly and transiently to levodopa.
Symptoms of cerebellar dysfunction (predominant in olivopontocerebellar atrophy) include ataxia, dysmetria, dysdiadochokinesia (difficulty performing rapidly alternating movements), poor coordination, and abnormal eye movements.
Typical symptoms of autonomic failure are orthostatic hypotension (symptomatic fall in BP when a person stands, often with syncope—see Approach to the Cardiac Patient: Orthostatic Hypotension), urinary retention or incontinence, constipation, and erectile dysfunction.
Other autonomic symptoms, which may occur early or late, include decreased sweating, problems with breathing and swallowing, fecal incontinence, and decreased tearing and salivation. Sleep apnea and respiratory stridor are common.
Diagnosis
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 are highly suggestive. Multiple system atrophy can be diagnosed antemortem based on these findings plus symptoms of generalized autonomic failure and lack of response to levodopa.
Treatment
There is no specific treatment, but symptoms are managed.
Treatment of orthostatic hypotension includes intravascular volume expansion with salt and water supplementation; sometimes fludrocortisone 0.1 to 0.4 mg po once/day is used. 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.
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. Urinary incontinence secondary to detrusor hyperreflexia may be treated with oxybutynin chloride 5 mg po tid or tolterodine 2 mg po bid. Many patients must self-catheterize their bladder. Constipation can be treated with a high-fiber diet and stool softeners; for refractory cases, enemas may be necessary. Erectile dysfunction can be treated with drugs such as sildenafil 50 mg po prn and with various physical means (see Male Reproductive Endocrinology: Treatment).
Last full review/revision November 2005
Content last modified November 2005
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