Shy-Drager syndrome. Neuropathological correlation and response to levodopa therapy

The post-mortem examination of the nervous system of a patient with Shy-Drager syndrome successfully treated with levodopa (Sharpe et al, 1972) revealed features of striato-nigral degeneration and amyotrophic lateral sclerosis, a cerebellar system degeneration and a loss of approximately 75% of sympathetic preganglionic neurons. Lewy bodies were not present and no detectable changes were observed in the sympathetic prevertebral ganglia. While the limited and transient beneficial effect of levodopa on the bradykinesia in our case is possibly due to the progressive loss of striatal dopaminergic receptors seen in striatonigral degeneration, we propose that in Shy-Drager syndrome, levodopa therapy benefits orthostatic hypotension because of a suppression of the central depressor action of this drug. This suppression is attributable to functional disconnection of sympathetic ganglia secondary to the loss of preganglionic neurons or to degeneration of central autonomic catecholaminergic systems.