Multiple System Atrophy

Definition

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by parkinsonism, cerebellar dysfunction, and autonomic disturbances.

Description

MSA causes a wide range of symptoms, in keeping with its name of "multiple system" atrophy. Parkinsonian symptoms include tremor, rigidity and slowed movements; cerebellar symptoms include incoordination and unsteady gait; and autonomic symptoms include orthostatic hypotension (drop in blood pressure upon standing) and urinary incontinence. Because of this wide variety of symptoms, it was originally thought of as three distinct diseases: striatonigral degeneration (parkinsonian symptoms), olivopontocerebellar atrophy (cerebellar symptoms) and Shy-Drager syndrome (autonomic symptoms). Further study showed the overlap among these conditions was best explained by considering them as a single disease with symptoms clustered into three groups. Historically, confusion about the disease was made even worse because olivopontocerebellar atrophy is also the name of an unrelated genetically inherited disease. It is hoped that widespread use of the name MSA will clear up some of this confusion.

Demographics

Because MSA is often misdiagnosed, figures on its prevalence are not known with certainty. It is estimated there are between 25,000 and 100,000 people in the United States with MSA. Onset is usually in the early fifties, and men are slightly more likely to be affected than women.

Causes and symptoms

The cause or causes of MSA are unknown. No genes have been found for MSA. Some evidence indicates that toxins may be responsible, but no specific agents have been identified. The brains of MSA patients reveal that cells called glia undergo characteristic changes. Glia are supportive cells for neurons, brain cells that conduct electrical signals. In MSA, glia develop tangles of proteins within them, called glial cytoplasmic inclusions. It is not known whether these actually cause MSA, or are caused by some other problem that is the real culprit.

The symptoms of MSA fall into three separate areasparkinsonism, cerebellar symptoms, and autonomic disturbances. The distribution and severity of individual symptoms varies among patients. MSA is a progressive disease, and symptoms worsen over time.

Parkinsonism is the initial symptom in almost half of all patients. The classic symptoms of Parkinson's disease (PD)—tremor, stiffness or rigidity, and slowed move-ments—are seen in MSA, although tremor is not as common, and is jerkier than the tremor of PD.

Cerebellar symptoms are the initial feature in very few MSA patients, but occur in about half of patients at some point during the disease. The cerebellum is an important center for coordination, and degeneration of the cerebellum in MSA leads to loss of balance, incoordination in the limbs, and loss of smooth eye movements. A person with cerebellar dysfunction in MSA typically walks with a wide stance to improve stability, and may lose the hand-eye coordination that makes so many simple activities possible.

Autonomic symptoms refer to those involving the autonomic nervous system. The autonomic nervous system controls a variety of "automatic" body functions, including blood pressure, heart rate, sweating, and bladder function. Autonomic symptoms are the initial complaint in half or more of all MSA patients. The most common initial problem is urinary dysfunction in women, and erectile dysfunction in men. Urinary dysfunction may be incontinence, or inability to void the bladder. Other autonomic symptoms include lack of sweating, constipation, and fecal incontinence.

Orthostatic hypotension is a common autonomic symptom. It refers to a significant drop in blood pressure shortly after standing. It can cause dizziness, lightheadedness, fainting, weakness, fatigue, yawning, slurred speech, headache, neck ache, cognitive impairment, and blurred vision.

Other symptoms may also occur in MSA. These may include:

• vocal cord paralysis, leading to hoarseness
• swallowing difficulty
• sleep apnea
• spasticity
• myoclonus
• Raynaud's phenomenon (cold extremities)

Diagnosis

The diagnosis of MSA is difficult, because it is easily mistaken in its earlier stages for Parkinson's disease, which is much more common. Autonomic disturbance also occurs in PD, but is much more pronounced in MSA. MSA is the more likely diagnostic choice when disease progression is rapid, and when the patient responds mildly or poorly to levodopa, the mainstay of PD treatment. Some centers use electromyography of the anal sphincter (the muscles surrounding the anus) in order to confirm the diagnosis of MSA. Abnormal results indicate MSA rather than PD, although this method is not universally recognized as valid.

Neuroimaging may be used to rule out other causes of similar symptoms, such as lesions in the brain or normal pressure hydrocephalus.

Treatment team

The treatment team includes the neurologist, possibly a movement disorders specialist, a urologist, and a speech/language pathologist.

Treatment

There are no treatments that halt or slow the degeneration of brain cells that causes MSA. Treatment is aimed at relieving symptoms.

Treatment of parkinsonian symptoms is attempted with standard PD drugs, namely levodopa and the dopamine agonists. Unfortunately, these are rarely as effective in MSA as they are in PD, although about one-third of patients have at least a moderate response. In the best case, treatment relieves stiffness, tremor and slowed movements, allowing increased activities of daily living.

Orthostatic hypotension is treated with medications to increase retention of fluids (fludrocortisone), compressive stockings to keep blood from pooling in the legs, increasing fluids, and increasing salt intake. Midodrine, a drug that helps maintain blood pressure is often prescribed.

A urologist may be needed to define the type of urinary dysfunction the patient has, and to manage treatment. A bedside commode or condom catheter may be helpful for urge incontinence, or inability to hold urine once the urge to urinate occurs. If incomplete voiding is the problem, intermittent catheterization may be needed. Detrusor hyperreflexia, in which the bladder muscle undergoes spasms, may be treated with drugs to reduce these spasms.

Male erectile dysfunction may be treated with sildenafil or other medications.

Anhidrosis, or lack of sweating, can be dangerous in an active patient, because of the risk of overheating. Awareness of the problem and avoidance of prolonged exercise are helpful.

Gait ataxia may require a mobility aid, such as a cane, walker, or eventually a wheelchair.

Speech and swallowing problems are dealt with by a speech/language pathologist, who may work with the patient to develop swallowing strategies, and instruct in the use of assistive communication devices. Sleep apnea may be treated with continuous positive airway pressure ventilation.

Clinical trials

Clinical trials for MSA are usually directed toward better diagnosis, or symptomatic treatment. Until researchers develop a better understanding of the causes of the disease, little progress can be expected in development of treatments to slow its progression.

Prognosis

The average survival after diagnosis is 9-10 years. Death usually occurs from pneumonia or suddenly from insufficient respiration, due to degeneration of the respiratory centers in the brain.

PERIODICALS

Wenning, G. K., et al. "Multiple System Atrophy." Lancet Neurology 3 (2004): 93-103.

WEBSITES

Shy-Drager Syndrome/Multiple System Atrophy Support Group. <www.shy-drager-syndrome.org>.

WE MOVE. <www.wemove.org>.

Richard Robinson