We report an immunohistochemical investigation of the striatal efferents in the striatum, globus pallidus, and substantia nigra of five patients with
multiple system atrophy (MSA):
olivopontocerebellar atrophy (2),
striatonigral degeneration (2), and
Shy-Drager syndrome (1). All patients manifested
parkinsonism during the
clinical course of their illness. The administration of
levodopa improved the symptoms of two patients, but not of the other three. Brain tissues from five age-matched neurologically normal subjects served as controls. Immunohistochemical assays were carried with
antibodies against
met-enkephalin,
substance P, and
calbindin-D28k. Irrespective of the clinical form of
multiple system atrophy, the immunoreactivity with the
antibodies was reduced at the dorsolateral portion of the striatum and the ventrolateral portions of the globus pallidus and of the substantia nigra. The woolly fiber arrangement of reaction product deposits seen in both segments of the globus pallidus of normal individuals was totally absent in the ventrolateral portions of the three patients who did not have a response to
levodopa. By contrast, there were positively stained woolly fibers in globus pallidum segments of the two
levodopa-responsive patients, even though their number and size were decreased in comparison with controls. These results indicate that the three clinical forms of
multiple system atrophy share common topographic alterations of the striatal efferent system and that the severity of the involvement correlates with the clinically observed effect of
levodopa on the
parkinsonism.