Multiple Systems Atrophy/Shy-Drager Syndrome
Introduction
In multiple system atrophy, there is widespread autonomic failure associated with impairment in other neurological systems. The other neurological systems may be cerebellar, extrapyramidal, neuromuscular, or pyramidal. The pathological hallmark of MSA is neuronal loss and gliosis within multiple sites in the brain.
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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
In order to diagnose multiple system atrophy, thoughtful and careful evaluation should be undertaken. Posture studies with blood pressure and heart rate monitoring with catecholamine levels in the supine and upright position should be done. Other potential evaluations include autonomic function testing, MRI, consultation by physicians that specialize in movement and/or blood pressure disorders, a sleep study, urodynamic testing, and blood pressure monitoring throughout sleep to evaluate for supine hypertension, or a high blood pressure with lying. This testing can be helpful in suggesting whether a patient has multiple system atrophy, but true diagnosis can only be accomplished by examination of the brain post-mortem.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.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
Click here to find details about how to become a Vanderbilt ADC Research Volunteer and about ongoing studies designed to better understand this disorder.
