The pathophysiology of parkinsonism in multiple system atrophy

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Abstract
Parkinsonism is the principal motor disorder of multiple system atrophy (MSA). In order to explore the pathophysiology of parkinsonism in MSA, we analysed 182 pathological reports from the literature and 35 from the United Kingdom Parkinson's Disease Society Brain Bank, and have also examined published post-mortem and in vivo neurochemical data. This review indicates that the brains of MSA patients who had parkinsonism in life show degeneration principally in anatomically related regions of the nigrostriatal dopaminergic pathway and of the striatum as well as in the globus pallidus. This degeneration affects both "direct" and "indirect" striatal outflow pathways. The degree of dopaminergic response in any one subject at any one point in the evolution of the disease probably relates both to the severity and extent of striatal pathology and also to the balance between degeneration in "indirect" and "direct" striatal outflow pathways and in the pallidum, especially its external part Abnormal oligodendroglial cytoplasmic inclusions are also found in large numbers in most of the basal ganglia structures that show cell loss and gliosis. The precise consequences of their additional presence in motor cortex remain unknown, but disturbance of function in supplementary motor area could also contribute to the extrapyramidal syndrome of MSA.

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