Timothy C. Hain, MD -- Chicago, USA
Last update: 12/15/2002
Please read our disclaimer
Multiple system atrophy is a rare neurological disorder characterized by a combination of parkinsonism, cerebellar and pyramidal signs, and autonomic dysfunction. The term "Multiple System Atrophy" is synonymous with striatonigral degeneration (SND) when Parkinsonism predominates, olivopontocerebellar atrophy (OPCA) when cerebellar signs predominate, and Shy-Drager syndrome when autonomic failure is dominant. The incidence (new case per 100,000 person years) for ages 50 to 99 years is 3.0 (Bower et al, 1997), or about half as frequent as progressive supranuclear palsy (PSP). The mean age of onset is 54.
The Parkinsonism of MSA is generally an akinetic rigid syndrome, similar to that of PSP. Rest tremor may occur but is not a predominant feature. Postural instability is common. Parkinsonism is generally the most common initial sign and eventually develops in about 90% of all patients.
The cerebellar signs inlude finger-to-nose or heel-shin dysmetria, gait ataxia, intention tremor and nystagmus. Cerebellar signs are the first feature on only about 5% of patients. Cerebellar signs are observed in 50% of cases (Ben-Shlomo et al, 1997). Sporadic OPCA evolves into MSA in roughly 25% of cases within 5 years.
Autonomic dysfunction includes impotence (the most common male sign), postural hypotension with syncope, urinary incontinence and retention, and fecal incontinence.
Disease progression in MSA is quicker than in Parkinsonism but similar or slightly slower to that of PSP (Bower, 1997). Albost 80% of patients are disabled within 5 years of onset of the motor symptoms, and only 20% survive past 12 years. The mean survival is roughly 6 years.
There is neuronal loss and gliosis in the inferior olives, pons, cerebellum, substantia nigra, locus ceruleus, striatum and the intermediolateral column of the spinal cord. Typical but not specific to MSA are argyrophilic inclusions containing accumulations of tubules. Alpha-synuclein has recently been shown to be accumulated in glial cytoplasmic incusions. Alpha synuclein is also a component of Lewy bodies in sporadic Parkinsonism, dementia with Lewy bodies, and a rare variant of Alzheimer's disease with abundant Lewy bodies (Tu and others, 1998). This is in distinction to the "tau" rich inclusion bodies found in most types of Alzheimer's disease and PSP. Depletion of catecholamine neurons in the rostral ventrolateral medulla is a consistant finding in patients with MSA and autonomic failure. (Bennaroch et al, 1998).
The most difficult diagnosis is between Parkinsons disease and levodopa-responsive striato-niagral degeneration-type MSA. PSP is generally detected by eye-movement abnormalities. In early stages, Cortico-basal-ganglionic degeneration may be impossible to distinguish from MSA but as more cortical signs develop in later stages, the disorders may be possible to separate.
According to Goldstein and others (2000), orthostatic hypotension that occurs in Parkinsonism is due to cardiac sympathetic denervation, while in MSA, it caused by central regulatory disturbances. According to Kraft and others (2002), T2 MRI distinguishes MSA from Parkinsonism by the finding of low-intensity areas, attributed to iron deposition, on T2 gradiant echo.
A case of valproic acid toxicity has been described mimicking MSA (Shill and Fife, 2000).
MSA patients either do not respond or respond poorly to levodopa. Doses of 1 to 1.5 gram per day must be used before unresponsiveness is declared, but generally only about 1/3 of patients respond. Autonomic failure can be treated with salt supplements, florinef, and mitodrine. It has been suggested that MSA patients may benefit from replacement of central norepinephrine or epinephrine with precursors such as dihidroxyphenylserine (Benarroch et al, 1998). There is no effective treatment for the cerebellar disturbance.
Many patients with MSA develop sleep-disordered breathing with stridor, due to bilateral vocal fold paresis. For this reason, patients with MSA should get a sleep study. Treatment of the sleep disorder may include continuous positive airway pressure (CPAP) or tracheostomy. (Blumin JH, Berke GS, 2002)
The American Parkinson's Disease Association (800-223-9776) is a good source of information for patients.