A Postmortem Study of a Patient with Low Titer Nicotinic Acetylcholine Receptor Ganglionic Antibody: Implications for Clinical Neurologic Disease

Abstract

Small fiber polyneuropathy is a well-recognized syndrome mitigated by somatic sensory afferent and autonomic efferent nerve fibers that respectively mediate pain, heat and cold temperature afferent and autonomic efferent function in the skin. A patient with low serum titers of neuronal acetylcholine receptor ganglionic antibodies and autonomic failure had symptomatic small fiber polyneuropathy late in life in the setting of autoimmune dementia and encephalopathy and prostate cancer. Large and small fiber polyneuropathy and dysautonomia were detected in routine electrodiagnostic and autonomic laboratory studies, and epidermal nerve fiber analysis of the calf and thigh. Clinical improvement for one year concomitant with intravenous immune globulin therapy preceded a clinical decline in neurocognitive function and death. Postmortem examination showed typical features of Alzheimer disease with neuropathic neuropathological changes in the peripheral nervous system, and viable autonomic ganglia consistent with a channelopathy mechanism involving postsynaptic neuronal nAChRs.