Graham and Oppenheimer proposed the term multiple system atrophy (MSA), which has gained wide acceptance. Several large series of cases of this complex syndrome have been published, providing a perspective on the frequency and nature of its component syndromes. Either parkinsonism or cerebellar ataxia may predominate. They are designated as MSA-P and MSA-C, respectively, depending on whether they display predominantly parkinsonism or cerebellar ataxia. More than half of the patients with striatonigral degeneration have orthostatic hypotension, which proves at autopsy to be associated with loss of intermediolateral horn cells and pigmented nuclei of the brainstem. This combined parkinsonian and autonomic disorder, formerly referred to as the Shy-Drager syndrome, was alluded to in Chaps. 17 and 25 and is now termed MSA-A, for multiple system atrophy with autonomic changes. The frequency of MSA-P is higher than for MSA-C and much higher than isolated MSA-A. The exception seems to be in Japan, where the cerebellar type is more frequent than MSA-P and more frequent than in other areas of the world.
Despite the overlap of clinical features in striatonigral degeneration, olivopontocerebellar degeneration, and the Shy-Drager syndrome, each of these disorders can occur in almost isolated clinical form; we therefore remind readers of their original designations. However, experienced clinicians will suspect that an adult onset slowly progressive ataxia is due to MSA-C, or that an unusual parkinsonian syndrome could be MSA-P but will make the diagnosis only confidently when the autonomic features appear some time later.
In addition to orthostatic hypotension, other features of autonomic failure in any of the variants include erectile dysfunction, loss of sweating, dry mouth, miosis, and urinary retention or incontinence. Vocal cord palsy is sometimes an initial manifestation of the disorder; it may cause dysphonia or stridor and airway obstruction requiring tracheostomy. A dusky discoloration of the hands as a sign of this disorder was ascribed to poor control of cutaneous blood flow by Klein and colleagues. Constipation, loss of sweating and sleep apnea occur in many patients as the disease progresses. A diagnostic problem arises in that orthostatic hypotension is also observed in at least 15 percent of patients with Parkinson disease and perhaps a larger proportion in Lewy body disease, a feature that may be exaggerated by medications, but the degree of drop in blood pressure is typically greater and more frequent in patients with this form of multiple system atrophy. These nonmotor aspects have been referred as “prodromal” but are simply initial manifestations of the disease.
In the Brain Tissue Bank of the Parkinson Disease Society of Great Britain, MSA accounted for 13 percent of patients who had been identified during life as having idiopathic Parkinson disease. These cases represent advanced forms of the disease, however, at that stage, all the patients with MSA had one or more symptoms of autonomic failure (postural hypotension, urinary urgency or retention, urinary or fecal incontinence, erectile dysfunction) and dysphonia or stridor. Babinski signs were present in half the patients and cerebellar ataxia in one-third. Tremor was rare. Males were affected more often than females. In a comparable series of 100 patients (67 men and 33 women) studied by Wenning and coworkers (1994), the disease began with a striatonigral-parkinsonian syndrome in approximately half; often it was asymmetrical at the onset. Mild tremor was detected in some but in only a few was it of the “resting” or “pill rolling” Parkinson type. In nearly half, the illness began with autonomic manifestations; orthostatic hypotension occurred eventually in almost all patients, but it was disabling in only a few. Cerebellar features dominated the initial stages of the disease in only 5 percent, but ataxia was eventually obvious in half the larger group. This ataxic clinical presentation of multiple system atrophy will be elaborated further in the section on the degenerative cerebellar ataxias.