Multiple system atrophy (MSA) is a sporadic, adult-onset, relentlessly progressive
neurodegenerative disorder, clinically characterized by various combinations of autonomic
failure, parkinsonism and ataxia. The neuropathological hallmark of MSA are glial
cytoplasmic inclusions consisting of misfolded alpha-synuclein. Selective atrophy
and neuronal loss in striatonigral and olivopontocerebellar systems underlie the division
into two main motor phenotypes of MSA-parkinsonian type and MSA-cerebellar type. Isolated
autonomic failure and REM sleep behavior disorder are common premotor features of
MSA. Beyond the core clinical symptoms, MSA manifests with a number of non-motor and
motor features. Red flags highly specific for MSA may provide clues for a correct
diagnosis, but in general the diagnostic accuracy of the second consensus criteria
is suboptimal, particularly in early disease stages. In this chapter, the authors
discuss the historical milestones, etiopathogenesis, neuropathological findings, clinical
features, red flags, differential diagnosis, diagnostic criteria, imaging and other
biomarkers, current treatment, unmet needs and future treatments for MSA.
