Abstract Details

Outcomes in AAG are heterogeneous, with monophasic, relapsing and progressive courses described. No controlled trials exist to guide immunotherapy choice, duration or expected response. Additional data is needed to help counsel patients on prognosis and long-term immunosuppression requirements.

To describe the clinical course and immunotherapy in patients with ganglionic acetylcholine receptor (gAChR) antibody positive autoimmune autonomic ganglionopathy (AAG).

We conducted a single-center retrospective review of seropositive AAG patients. We included adult patients who had: (1) a clinical presentation consistent with autonomic ganglionopathy; (2) detectable abnormalities on standardized autonomic testing completed between 2000 and 2023; (3) positive gAChR antibody titer ≥0.2 nmol/L; and (4) follow up at minimum 3 months from the initial assessment.

Among the 27 patients included, median Composite Autonomic Scoring Scale (CASS) score at presentation was 8 (1-10) and positively correlated with antibody titers. Twenty-three patients received immunotherapy, and median time from onset to treatment initiation was 13 months (3-144 months). Of those treated, all received at least one course of induction, most commonly intravenous immunoglobulins. Nineteen were treated with maintenance immunotherapy, 10 of which required alternative trials or combinations of multiple agents. Duration of maintenance treatment ranged between 1 and 15 years, and 7 patients had ongoing immunotherapy after their last follow-up. Partial symptomatic improvement was reported in 16 of the treated patients, 7 reported stabilization, and none reached clinical remission. Among untreated patients, 2 slowly progressed and 2 remained stable. Comparing initial and last available autonomic testing (completed a median of 7 years from onset), 11 patients had modestly improved CASS scores, 8 were unchanged and 7 were worse. CASS change did not relate to subjective recovery.

Immunotherapy led to subjective symptomatic improvement in most seropositive AAG patients; however, none achieved remission, objective improvement on autonomic testing was not pronounced, and most required chronic maintenance treatment.