7 - Multiple system atrophy

Abstract

This chapter discusses the epidemiology, pathogenesis, and molecular biology of multiple system atrophy (MSA). The α-synuclein pathway appears to be the key pathway to selective loss of glia and neurons in MSA. The differential distribution of α-synuclein deposits and associated neuronal pathology suggests variability of pathogenetic mechanisms underlying the multifaceted disease process of MSA. Glial inclusion formation is a prominent feature of MSA pathology. In case of striatonigral degeneration, the striatonigral system is the main site of pathology, but less severe degeneration can be widespread and usually includes the olivopontocerebellar system. In case of olivopontocerebellar atrophy the brunt of pathology is in the olivopontocerebellar system, whereas the involvement of the striatum and substantia nigra is less severe. Autonomic failure in MSA is caused by dysfunction of central and preganglionic efferent autonomic activity, neuronal networks in the brainstem controlling cardiovascular and respiratory function, and the neuroendocrine component of the autonomic regulation via the hypothalamic–pituitary axis. The combination of nigral and striatal degeneration is the core pathology underlying Parkinsonism in MSA (MSA-P). The degenerative process affects nigrostriatal dopaminergic transmission at both presynaptic and postsynaptic sites. The discovery of glial cytoplasmic inclusions (GCIs) in MSA brains firmly established glial pathology as a biological hallmark of this disorder. Clinical features of MSA include Parkinsonism, dysautonomia, cerebellar disorder, and pyramidal signs. Clinical diagnosis of MSA and clinical diagnostic criteria for MSA are also discussed in the chapter.