Involvement of the ventrolateral medulla in parkinsonism with autonomic failure

Objective: To determine whether patients with PD and autonomic failure (AF) , manifested primarily with orthostatic hypotension (OH), have a consistent loss of tyrosine hydroxylase (TH) neurons in the rostral ventrolateral med ulla (RVLM), similar to that occurring in patients with multiple system atr ophy (MSA) and AF, and to determine whether there is loss of nicotinamide, adenine dinucleotide phosphate (NADPH) diaphorase (NADPH-d) RVLM neurons in both groups of patients. Methods: The numbers of TH and NADPH-d neurons in the RVLM was assessed in brain sections obtained at autopsy from five pati ents with suspected PD and OH, six patients with MSA, two patients with cor ticobasal ganglionic degeneration and no AF, and 10 control subjects with n o history of neurologic disease. Cell numbers were compared among groups an d correlated with their final neuropathologic diagnosis. Results: The numbe r of TH neurons in the RVLM of patients with PD and OH were not significant ly different from control subjects, and there were marked individual variat ions. The TH cell numbers in the RVLM were significantly higher (p < 0.06) in patients with PD than in patients with MSA, despite a similar degree of severity of OH. As a group, patients with PD and OH had reduced numbers of NADPH-d cells in the RVLM compared with control subjects, but again there w ere marked individual variations. NADPH-d cell numbers were reduced consist ently and more markedly in patients with MSA. Conclusion: Unlike the case i n patients with MSA, the number of TH neurons in the RVLM is highly variabl e in patients with PD and is unlikely to contribute significantly to the pa thophysiology of OH. As a group, patients with PD have reduced numbers of N ADPH-d neurons in the RVLM, but some patients had cell counts similar to co ntrol subjects. On the other hand, NADPH-d cell depletion in the RVLM is a consistent finding in MSA and may contribute to cardiorespiratory dysfuncti on in this disorder.