Biochemical changes in multiple system atrophy detected with positron emission tomography

Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder mani fested by parkinsonism and dysfunction of autonomic, cerebellar, urinary, a nd pyramidal systems. The most frequent presentation is with a combination of parkinsonism and autonomic dysfunction, but cerebellar ataxia with auton omic failure occurs frequently as well. Striatonigral degeneration (SND) an d sporadic olivopontocerebellar atrophy (sOPCA) can progress to include aut onomic failure and thus may be forms of MSA, but it is not known whether al l such cases progress to MSA. Utilizing positron emission tomography (PET) with various ligands, my colleagues and I have investigated the biochemical changes in sOPCB and MSA to understand the relationship between these diso rders. An initial study revealed decreased local cerebral metabolic rates f or glucose in the brainstem, cerebellum, putamen, thalamus and cerebral cor tex in both MSA and sOPCA, suggesting that many sOPCA patients would evolve to develop MSA. Later studies confirmed this by demonstrating decreased mo noaminergic nigrostriatal terminals in both sOPCA and MSA patients. The stu dies suggest that the ligand used might be helpful in determining the risk that an individual patient with sOPCA will progress to develop MSA. An inve stigation of the course of sOPCA patients observed clinically over several years revealed that approximately one-fourth of them progress to MSA within five years. Studies of gamma-aminobutyric acid type A/benzodiazepine neuro transmitter receptors revealed that these sites are largely preserved in sO PCA and MSA. indicating that symptomatic pharmacological therapy may be pos sible in these disorders. (C) 2001 Elsevier Science Ltd. All rights reserve d.