Pharmacologic Probes to Differentiate Chronic Autonomic Failure Syndromes

Abstract

Objective: The current clinical classification of chronic autonomic failure (CAF) recognizes four primary forms—pure autonomic failure (PAF), multiple system atrophy (MSA), Parkinson disease (PD), and autoimmune autonomic ganglionopathy (AAG). We provide a pathophysiologic classification scheme, based on neuropharmacologic probes: tyramine (TYR), trimethaphan (TRI) or pentolinium (PEN), yohimbine (YOH), acetylcholine (ACh, quantitative sudomotor axon reflex test, QSART), and 6‐[18F]fluorodopamine (18F‐DA) scanning.Methods: CAF groups received i.v. TYR, TRI/PEN, YOH, or 18F‐DA or ACh by iontophoresis. Blood pressure (BP) and dihydroxyphenylglycol (DHPG) responses were measured.Results: PAF involved low cardiac 18F‐DA‐derived radioactivity and attenuated (Atten.) increments (Inc.) to TYR and YOH and decrements (Dec.) to TRI/PEN, in contrast with normal reponses in AAG and MSA. MSA involved augmented (Aug.) responses to YOH and TRI/PEN and normal (Nl.) cardiac 18F‐DA, in contrast with Atten. in PD+NOH.Conclusions: Pharmacologic probes provide a pathophysiologic classification of chronic autonomic failure that can be utilized in individual patients.