This first autopsy report of AAG demonstrates preserved sympathetic nerve fibers despite reduced MIBG uptake, supporting a postsynaptic channelopathy mechanism rather than neurodegeneration.
Abstract Introduction Autoimmune autonomic ganglionopathy (AAG) is a rare disorder characterized by widespread autonomic failure due to antibodies targeting the ganglionic nicotinic acetylcholine receptor (gAChR). Although the clinical manifestations of AAG have been widely reported, autopsy findings in human cases remain undocumented. Methods We examined the clinical course, imaging data, and autopsy findings of a patient with AAG who survived for 14 years. Clinical symptoms, cardiac MIBG scintigraphy results, treatment response, and histological features of sympathetic ganglia and cardiac nerve fibers were analyzed. Results: The patient initially showed markedly reduced MIBG cardiac uptake, which improved with intravenous immunoglobulin therapy. After a prolonged clinical course with recurrent infections and nutritional decline, he died at age 78. Autopsy revealed preserved thoracic sympathetic ganglia and intact postganglionic sympathetic fibers in the heart. Mild perivascular lymphocytic infiltration was observed, but no neuronophagia or dense inflammatory infiltrates. Phosphorylated α‐synuclein was absent in the central and peripheral nervous systems. The enteric plexus was preserved, without overt neuronal loss. Age‐associated tau pathology was confined to the entorhinal cortex. Conclusion Despite functional sympathetic impairment evident in reduced MIBG uptake and severe gastrointestinal dysmotility, there was no histologic evidence of sympathetic nerve degeneration or neuronal loss in the enteric plexus, supporting a postsynaptic channelopathy mechanism in AAG. The mild inflammation observed may reflect systemic illness rather than primary autoimmune pathology. This is the first report correlating longitudinal clinical data, imaging, and postmortem pathology in AAG.
Taniguchi et al. (Wed,) studied this question.