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Vanderbilt Autonomic Dysfunction Center

Multiple System Atrophy/Shy-Drager Syndrome

Introduction

Multiple system atrophy (MSA) is a rare neurodegenerative disease marked by a combination of symptoms affecting movement, blood pressure, and other body functions; hence the label "multiple system" atrophy.  According to the American Autonomic Society, Multiple System Atrophy (MSA) is a sporadic, progressive, adult-onset disorder characterized by autonomic dysfunction, parkinsonism and ataxia (a failure of muscular coordination) in any combination

Clinical Manifestations

The average age of onset is in the sixth decade of life. Men are affected twice as frequently as women are. In some patients, chronic orthostatic hypotension may be a presenting symptom, but in other cases, extrapyramidal symptoms or cerebellar symptoms may predominate in the early stages. When the chronic orthostatic hypotension antedates other neurological involvement, it may be very difficult to differentiate MSA from the more benign pure autonomic failure (PAF). Patients complain of impotence, change in writing style, slurred speech, sleep apnea, difficulty with urination, frequent urinary tract infections, a hoarse voice, passing out, headache, neck pain, dimming of vision and yawning. Syncope, or passing out, is most frequently associated with orthostatic hypotension, or a low blood pressure with standing, even though blood pressure while lying down may be very high. There are several unusual features of multiple system atrophy that are often missed, but may be important in making this diagnosis. Patients frequently note emotional lability, with short (sometimes only one or two minutes) episodes of crying due to happiness or sadness in response to relatively minor environmental stimulus, such as a song, a television program, or a movie. This is usually self-limited, but may be a harbinger of depression. Patients sometimes have periodic gasping respirations punctuating the medical interview. They only last a few seconds, are not generally deep, but seem labored. Finally, many patients will discontinue the use of nicotine-containing products at the onset of their disease. It sometimes appears that they no longer enjoy the nicotine. Ultimately, nicotine may provoke worsened tremor in some of these patients. A final symptom which occurs in occasional patients with multiple system atrophy is diplopia, not unlike that seen in multiple sclerosis. Pathologically, there is involvement of multiple sites within the brain and spinal cord. A glial cytoplasmic inclusion has been found to occur intracellularly in both glial cells and neurons of involved portions of the brain. This has been seen in patients carrying the clinical diagnosis of Shy-Drager syndrome, sporadic oligopontocerebellar atrophy, striatonigral degeneration, and corticobasal degeneration. These inclusions contain ubiquitin, but are quite distinct from Lewy bodies, which also contain ubiquitin. The glial cytoplasmic inclusions tend to be irregular in outline in contrast to the target-shaped concentric circular Lewy bodies. Some investigators have suggested a relationship between the Shy-Drager syndrome and Parkinson's disease, although this is not supported by the pathologic data accumulated to date. Lewy bodies have been absent in several careful autopsies of Shy-Drager patients (Heieren, 1972). At least one family has been reported in whom four members had a Shy-Drager-like syndrome (Lewis, 1964), but there is no other suggestion of a strong genetic component in the disease, and the actual diagnosis in this reported family may not have been MSA.

Blood and urinary levels of norepinephrine are often near normal in the unstimulated state in patients with MSA, but they do not rise appropriately on assumption of the upright posture (Ziegler et al., 1977). Peripheral norepinephrine levels tend to be higher in MSA than in PAF. Catecholamine metabolites reflect the central nature of the neurological defect (Polinsky et al., 1981; Kopin et al., 1983; Polinsky et al., 1984; Polinsky et al., 1987). It is noteworthy that there is also biochemical evidence of central abnormalities in the dopamine, acetylcholine and serotonin systems (Polinsky et al., 1988; Polinsky et al., 1989).

Diagnosis

 

Diagnosis of MSA can be challenging because there is no test that can make or confirm the diagnosis in a living patient. Certain signs and symptoms of MSA also occur with other disorders, such as Parkinson's disease, making the diagnosis more difficult.

If your doctor suspects multiple system atrophy, he or she will obtain a medical history and perform a physical examination. You may receive a referral to a neurologist or other specialist for specific evaluations that can help in making the diagnosis.

Tests that may be helpful in making a diagnosis include:

  • Tilt table test - In this procedure, your blood pressure is monitored while you are on a special table that will tilt you to an almost upright position. This allows the physician to record blood pressure irregularities, and information about whether they occur with a change in physical position.
  • Blood tests
  • A sweat test to evaluate perspiration
  • Tests to assess your bladder and bowel function
  • Electrocardiogram to track the electrical signals of your heart
  • Brain-imaging tests, particularly a magnetic resonance imaging (MRI) scan, to determine if another condition might be triggering symptoms
  • Pharmacological challenge tests (administering certain medications and observing the patient’s body’s reaction to them, in controlled clinical settings)
  • True diagnosis can only be accomplished by examination of the brain post-mortem.

For patients with sleep irregularities, particularly if they involve interrupted breathing or snoring, physicians may recommend an evaluation in a sleep laboratory to determine if there is an underlying and treatable sleep disorder, such as sleep apnea.

Prognosis

The prognosis is more guarded in the multiple system atrophy patient than in pure autonomic failure. It is rare for a patient to survive 10 years. The autonomic abnormalities are seldom the direct cause of death A significant number of patients develop laryngeal stridor and difficulty swallowing, which can lead to pneumonia. In addition, many patients with MSA experience Cheyne-Stokes or periodic respiration and in some cases this may lead to a critical loss of respiratory drive, so called Ondine's curse (Craddock et al., 1987). Pulmonary hypertension may occur during apnea (Guilleminault et al., 1977). The most common causes of death in patients with MSA are pulmonary embolus, apnea, and intercurrent infection.

Management

There is no known cure for multiple system atrophy, so management involves treating specific problems in this patient population. This includes treatment of the depression, tremor and gait disturbances, supine hypertension, orthostatic hypotension, and possible self-catheterization.

Shy-Drager Syndrome Support Group Listserver

In May 1995, the Vanderbilt Autonomic Dysfunction Center initiated a free Shy-Drager Syndrome electronic mail list so that patients with multiple system atrophy (MSA) and their caregivers could communicate with each other throughout the world. The electronic mail list is open to patients, caregivers, and others who are interested in the Shy-Drager syndrome. Through use of the electronic 'party line', anyone can ask a question, answer a question, post information on medication and treatments, share the good and the bad times, etc. A person with a computer and access to email can join the list by subscribing or by having a friend or relative subscribe and relay messages to the list. The list has evolved over time and now contains over 900 subscribers. To subscribe to the mail list, simply click on the hypertext below and follow directions:

 

Participate in Research Protocols

 

A clinical trial of the drug Rifampicin is being conducted by the Autonomic Disorders Consortium.

Click here to find details about how to become a Vanderbilt ADC Research Volunteer and about ongoing studies designed to better understand this disorder.

Symptoms of MSA

Symptoms of MSA include:

  • Orthostatic hypotension,or a significant fall in blood pressure when standing, causing dizziness, lightheadedness, fainting, or blurred vision
  • urinary difficulties or constipation
  • motor control symptoms, including tremor, rigidity, and loss of muscle coordination, loss of balance
  • male impotence (inability to achieve or maintain an erection)
  • speech or swallowing difficulties

This page was last updated June 22, 2010 and is maintained by