Pandysautonomia associated with impaired ganglionic neurotransmission and circulating antibody to the neuronal nicotinic receptor

Abstract

We report the case of a patient with chronic autonomic failure who had evidence of decreased postganglionic traffic to intact sympathetic nerve terminals. The patient complained mainly of decreased salivation, constipation, dry skin, and orthostatic intolerance. There was no evidence of central neurodegeneration. Autonomic function testing showed orthostatic hypotension without tachycardia and abnormal blood pressure and pulse rate responses to the Valsalva maneuver, indicating combined sympathetic and parasympathetic neurocirculatory failure. In contrast to patients with pure autonomic failure, the patient had normal left ventricular myocardial concentrations of 6-[(18)F]fluorodopamine-derived radioactivity, establishing intact postganglionic sympathetic innervation; and in contrast to patients with multiple system atrophy or baroreflex failure, the patient had a low plasma norepinephrine concentration and brisk norepinephrine response to orthostasis. These findings indicated an impediment to ganglionic neurotransmission. Serologic testing demonstrated a circulating antibody to the ganglionic nicotinic acetylcholine receptor. The findings in this case support the concept that circulating antibodies to this receptor can interfere with ganglionic neurotransmission and produce autoimmune autonomic neuropathy.