Parkinsonism. Multiple system atrophy.

Abstract

Over the last decade multiple system atrophy (MSA) has been confirmed as a distinct clinicopathological entity. For a long time, overlapping pathology in individual cases with striatonigral degeneration (SND), sporadic olivopontocerebellar atrophy (OPCA) or Shy-Drager syndrome (SDS) had often been a source of confusion. The recently discovered glial and neuronal inclusions indeed confirm that these three disorders represent manifestations of the same disease. Parkinsonism is the most frequent motor disorder of MSA. Early diagnosis of these patients is difficult but important, particularly in clinical trials of potential therapies. Patients with only parkinsonism (+/- autonomic failure) account for much of this diagnostic difficulty, particularly early on. Some features that have been associated with SND such as symmetry or absence of tremor are not helpful, and insistence on a poor levodopa response will miss a sizeable minority of patients. A number of further clinical 'red flags' may be helpful. MRI, MRS, PET and SPECT scanning, autonomic function tests and, especially, external sphincter EMG, may also help differentiate between idiopathic Parkinson's disease (IPD) and MSA. Available medical treatments are usually disappointing, so that good therapy services are all the more important. Better animal models of MSA and evaluation of novel treatment strategies are urgently required, and grafting techniques currently applied to IPD and Huntington's disease (HD) patients might be usefully combined in MSA. Epidemiological and case-control studies are needed to determine the prevalence, incidence and risk factors of MSA. The pathogenesis of MSA remains uncertain. Until the discovery of glial cytoplasmic inclusions (GCIs) previous studies had failed to identify abnormalities relevant to pathogenesis rather than reflecting secondary change. The abundance of GCIs points to a fundamental cytoskeletal alteration in glial cells that may eventually result in neuronal degeneration. Mechanisms of formation and distribution of GCIs as well as disordered glial-neuronal interactions should be studied in more detail in MSA brains.