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BackgroundThe autonomic synucleinopathy multiple system atrophy (MSA) can be difficult to distinguish clinically from Parkinson disease with orthostatic hypotension (PD+OH). 18F-Dopamine positron emission tomography separates these conditions based on cardiac noradrenergic deficiency in PD+OH and not in MSA but is available only at the NIH Clinical Center. 3,4-Dihydroxyphenylglycol (DHPG) is the main neuronal metabolite of norepinephrine. This retrospective observational study examined whether DHPG levels in cerebrospinal fluid (CSF) or plasma differentiate MSA from PD+OH.MethodsWe reviewed CSF and plasma neurochemical data from all patients referred for evaluation at the NIH Clinical Center between 1995 and 2024 for chronic autonomic failure or parkinsonism. A concurrently studied comparison group included healthy volunteers or patients with orthostatic intolerance.ResultsCSF DHPG was decreased in MSA (N = 67, p ConclusionsCSF/plasma ratios of DHPG, cardiac arteriovenous increments in plasma DHPG, and cardiac norepinephrine spillovers separate MSA from PD+OH. On the basis of our results we propose that biomarker combinations involving DHPG in biofluids may enable a clinical laboratory distinction of MSA from PD+OH.
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