Idiopathic Autonomic Neuropathy: Comparison of Cases Seropositive and Seronegative for Ganglionic Acetylcholine Receptor Antibody

Background: The clinical characteristics of autoimmune autonomic neuropathy are only partially defined. More than 50% of patients with high levels of ganglionic acetylcholine receptor (AChR) autoantibodies have a combination of sicca complex (marked dry eyes and dry mouth), abnormal pupillary light response, upper gastrointestinal tract symptoms, and neurogenic bladder. Objective: To compare patients with idiopathic autonomic neuropathy who were seropositive (n=19) and seronegative (n=87) for ganglionic AChR antibodies. Design: Retrospective review of autonomic programmatic database. Setting: Autonomic Disorders Program Project at Mayo Clinic College of Medicine, Rochester, Minn. Patients: We evaluated a cohort of 87 patients with idiopathic autonomic neuropathy who had undergone full autonomic testing and neurological evaluation and who had a complete panel of paraneoplastic and ganglionic AChR antibodies. We compared patients seropositive (n=19) and seronegative (n=87) for ganglionic AChR antibodies. Results: The seropositive group had a significant overrepresentation of abnormal pupillary responses (12/18 [67%] vs 12/87 [14%]; P<.001), sicca complex (9/15 [60%] vs 11/47 [23%]; P=.01), and lower gastrointestinal tract dysautonomia (16/19 [84%] vs 48/85 [56%]; P=.02). A subacute mode of onset was more common in the seropositive group (12/19 [63%] vs 23/84 [27%]; P=.004). Results of quantitative autonomic function tests differed significantly in the 2 groups only in the cardiovagal domain. Because subacute onset was overrepresented in the seropositive group, we analyzed the data separately, controlling for temporal profile (ie, the relationship between antibody status and symptoms while controlling for rate of onset). The relationships between antibody status and clinical profile (eg, presence of sicca complex, pupillary abnormalities, and lower gastrointestinal tract symptoms) generally remained significant regardless of onset rate, indicating that the associations are not due to temporal profile. Conclusions: These observations support the concept that ganglionic AChR antibodies are diagnostically and pathophysiologically important. Patients with orthostatic hypotension and prominent cholinergic dysautonomia are most likely to be seropositive for ganglionic AChR antibody.