DEPLETION OF CATECHOLAMINERGIC NEURONS OF THE ROSTRAL VENTROLATERAL MEDULLA IN MULTIPLE SYSTEMS ATROPHY WITH AUTONOMIC FAILURE

The ventrolateral portion of the intermediate reticular formation of t he medulla (ventrolateral medulla, VLM), including the C1/A1 groups of catecholaminergic neurons, is thought to be involved in control of sy mpathetic cardiovascular outflow, cardiorespiratory interactions, and reflex control of vasopressin release. As all these functions are affe cted in patients with multiple systems atrophy (MSA) with autonomic fa ilure, we sought to test the hypothesis that catecholaminergic (tyrosi ne hydroxylase [TH]-positive) neurons of the VLM are depleted in these patients. Medullas were obtained at autopsy from 4 patients with MSA with prominent autonomic failure and 5 patients with no neurological d isease. Patients with MSA had laboratory evidence of severe adrenergic sudomotor and cardiovagal failure. Tissue was immersion fixed in 2% p araformaldehyde at 4 degrees C for 24 hours and cut into l-cm blocks i n the coronal plane from throughout the medulla Serial 50-mu m section s were collected and one section every 300 mu m was stained for TH. Th ere was a pronounced depletion of TH neurons in the rostral VLM in all cases of MSA. There was also significant reduction of TH neurons in t he caudal VLM in 3 MSA patients compared with 3 control subjects. In 2 MSA cases and in 2 control subjects, the thoracic spinal cord was ava ilable for study. There was also depletion of TH fibers and sympatheti c preganglionic neurons (SPNs) in the 2 MSA cases examined, Thus, depl etion of catecholaminergic neurons in the VLM may provide a substrate for some of the autonomic and endocrine manifestations of MSA.