Multiple System Atrophy

Multiple system atrophy is a progressive neurodegenerative disorder that can cause parkinsonism and dysfunction of the pyramidal tracts, cerebellum, and autonomic nervous system. Prominent symptoms may include hypotension, GU dysfunction, constipation, ataxia, rigidity, postural instability, and dystonia. Diagnosis is by history and physical examination. Treatment is symptomatic, with volume expansion, compression garments, and vasoconstrictor drugs.

Geriatric Essentials

• Multiple system atrophy should be considered in elderly patients with severe orthostatic hypotension and some parkinsonian symptoms.
• Nondrug measures can relieve many symptoms; efficacy of drugs is limited.
• End-of-life issues should be discussed.

Multiple system atrophy is a neurodegenerative disorder that affects multiple areas of the CNS. Pathologically, cell loss, gliosis, and cytoplasmic inclusions develop.

Multiple system atrophy occurs sporadically. It affects about twice as many men as women. Mean age at onset is about 53 yr; after symptoms appear, patients live about 10 yr.

Patients with multiple system atrophy were previously thought to have 1 of 3 similar but separate disorders that had subtle clinical and neuroanatomic differences. Shy-Drager syndrome was characterized by degeneration of the central (preganglionic) autonomic, cerebellar, basal ganglia, pyramidal, and spinal motor neurons and by prominent autonomic insufficiency. Striatonigral degeneration affected primarily the substantia nigra and striatum and was characterized by early speech and balance problems, poor response to dopaminergic drugs, mild or absent resting tremor, and dyskinesia. Olivopontocerebellar atrophy was characterized by degeneration of the olivary nucleus, pons, and cerebellum and by prominent cerebellar ataxia; parkinsonian features were mild or absent. These disorders are no longer considered to be separate.

Symptoms and Signs

Multiple system atrophy has parkinsonian features and causes autonomic insufficiency, cerebellar dysfunction, and corticospinal tract dysfunction in various combinations. Parkinsonian features are more prominent than cerebellar dysfunction in 80% of patients; cerebellar dysfunction is more prominent in the other 20%.

Patients with parkinsonian features often develop rigidity, bradykinesia, postural instability, jerky postural tremor, orofacial or craniocervical dystonia, and a high-pitched, quavering dysarthria. Unlike in Parkinson's disease, resting tremor and dyskinesia are uncommon, and symptoms respond poorly and transiently to levodopa or other dopaminergic drugs.

Cerebellar dysfunction includes ataxia, dysmetria, dysdiadochokinesia (difficulty performing rapidly alternating movements), poor coordination, and abnormal eye movements.

Autonomic insufficiency causes wide swings in BP but no change in pulse rate. Orthostatic hypotension is often the most disabling symptom. Patients report dizziness, light-headedness, or syncope when they stand, as well as postexertional weakness, gait unsteadiness, and dimming of vision. Erectile dysfunction (among men), urinary incontinence, and retention are very common. Impaired temperature control, reduced sweating, urinary or fecal incontinence, diarrhea, constipation, nocturnal diuresis, sleep apnea, atrophy of the iris, ocular palsies, Horner's syndrome, and anisocoria may also occur.

In multiple system atrophy, intellectual and emotional function is preserved until late in the disease. However, the disease progresses, and death occurs about 7 to 10 yr after onset of symptoms. Death is usually due to cardiac arrhythmias (caused by autonomic nervous system dysfunction), aspiration, sleep apnea, or pulmonary emboli.

Diagnosis

Multiple system atrophy should be considered in patients with combinations of the typical features: parkinsonian features that respond poorly to dopaminergic drugs (particularly patients with characteristic dystonias, voice abnormalities, and postural instability), autonomic insufficiency (particularly patients with urinary or erectile dysfunction), cerebellar dysfunction, and corticospinal tract dysfunction. Diagnosis is by history and physical examination. Tilt table testing may be helpful in confirming autonomic insufficiency. Electromyography may be helpful in confirming spinal motor neuron degeneration.

Treatment

For autonomic insufficiency, nondrug treatment includes avoidance of extreme heat, alcohol, large meals, getting up rapidly, and excessive straining at stool. Wearing compressive clothing and elastic stockings, increasing salt and fluid intake, drinking caffeinated beverages early in the day, and sleeping in a reverse Trendelenburg's position may ameliorate some orthostatic symptoms.

Fludrocortisone (starting at 0.1 mg po once/day, increased up to 0.4 mg po once/day) can be used to expand plasma volume. Midodrine (starting at 2.5 mg po tid, increased up to 10 mg po tid) may help sustain BP during standing. A -blocker (eg, propranolol 20 mg po bid to qid) may be necessary to keep BP from increasing excessively during recumbency.

Parkinsonian features sometimes respond to dopaminergic drugs, at least to a limited extent. Thus, dopaminergic drugs, beginning with levodopa, are worth trying. Drug therapy is not useful for cerebellar dysfunction.

Physical therapy, occupational therapy, and speech therapy may help relieve symptoms or complications. End-of-life issues should be discussed.

This topic was last updated June 2006.