Multiple system atrophy: the putative causative role of environmental toxins.

BACKGROUND Whereas a number of studies have investigated the putative role of environmental toxins in the pathogenesis of idiopathic Parkinson disease, the possibility of such a role in multiple system atrophy has received little attention. DESIGN AND SETTING Review of records of patients examined in the Parkinson's Disease Center and Movement Disorder Clinic, Baylor College of Medicine, Houston, Tex, from July 1, 1977, to February 4, 1998. PATIENTS We reviewed 100 consecutive medical records of patients who satisfied the diagnostic criteria for multiple system atrophy formulated by the Consensus Committee of the American Autonomic Society and the American Academy of Neurology. INTERVENTION The type and amount of toxin exposure were verified by history and examination of records whenever possible. Severity of parkinsonism was assessed by clinical rating scales. MAIN OUTCOME MEASURE Development of multiple system atrophy after environmental toxin exposure. RESULTS Eleven patients had a notable history of heavy exposure to environmental toxins. One patient with multiple system atrophy confirmed by postmortem evaluation was exposed to high concentrations of malathion, diazinon, and formaldehyde, while the other patients with multiple system atrophy had well-documented high exposures to agents including n-hexane, benzene, methyl isobutyl ketone, and pesticides. The case studied pathologically demonstrated extensive advanced glial changes, including glial cytoplasmic inclusions in deep cerebellar white matter, brainstem, cortex (superior frontal, insula) and putamen, with notable cell loss and depigmentation of the substantia nigra and locus ceruleus. CONCLUSION While many studies report a possible role of environmental toxins in Parkinson disease, such a role is even more likely in multiple system atrophy, as this is a sporadic disease.