Multiple system atrophy: pathophysiology and management

Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that usually manifests when an individual is in his/her early fifties and progresses relentlessly with a mean survival of 9 years. Clinically, MSA is dominated by autonomic/urogenital failure which may be associated with either parkinsonism (MSA-P subtype) in 80% of cases or with cerebellar ataxia (MSA-C subtype) in 20% of cases. Pathologically, MSA is characterised by a neuronal multisystem degeneration and abnormal glial cytoplasmic inclusions containing alpha-synuclein aggregates. Autonomic and urogenital features of MSA should be identified early on because they can be treated effectively in many instances. In contrast, pharmacological treatment of motor features is often disappointing, except for a minority of patients with MSA-P who derive transient benefit from levodopa treatment. In the future, neurotransplantation may extend or improve the treatment response in MSA-P, but further preclinical evidence is required prior to clinical application. Neuroprotection strategies may slow down disease progression in MSA and the results of the first double-blind trial of riluzole (an inhibitor of glutamate release) in patients with MSA will be available in 2004.