Clinical implications of free triiodothyronine levels and diagnostic revisions in antibody-negative autoimmune encephalitis.

Background and objective: Low triiodothyronine (T3) syndrome has been associated with initial clinical severity and poor long-term functional outcomes in autoimmune encephalitis (AE). However, its prognostic implications in antibody-negative AE remain unclear. The objective of this study was to explore the clinical significance of low T3 syndrome in patients with antibody-negative AE, and to assess the clinical characteristics of patients reclassified with alternative diagnoses during follow-up. Methods: We conducted a retrospective cohort study of patients initially diagnosed with antibody-negative AE between January 2016 and June 2024. Patients were divided into two groups based on the presence or absence of low T3 syndrome. Demographics, clinical features, and ancillary test results were compared between the subgroups. Modified Rankin Scale (mRS) scores were used to evaluate neurological function during hospitalization and at the 12-month follow-up. In addition, we analyzed reclassified patients and their clinical outcomes to improve clinical management of antibody-negative AE. Results: Of the 84 patients initially diagnosed with antibody-negative AE at discharge, eight were reclassified during their disease course (non-autoimmune encephalitis, n=4; paraneoplastic encephalitis, n=3; neuropsychiatric systemic lupus erythematosus, n=1; these eight patients were defined as reclassified group) and were excluded from the antibody-negative AE group. A total of 76 patients were ultimately enrolled. Of these, 23.68% presented with low T3 syndrome during the acute phase. Subgroup analysis further showed that patients with low T3 syndrome had a higher incidence of consciousness disturbances (p = 0.048), more frequent motor impairments, and higher scores on the modified Rankin Scale (mRS) throughout hospitalization. Overall, 61.84% (47/76) of patients achieved a favorable prognosis, whereas 38.16% (29/76) had an unfavorable outcome. Notably, low T3 syndrome was associated with poor prognosis in univariable analysis but not after multivariable adjustment. Discharge mRS was an independent predictor of unfavorable outcome (OR 0.293, 95% CI 0.103-0.834, p = 0.021). Furthermore, the reclassified group demonstrated a higher recurrence rate compared with the antibody-negative AE group. Conclusion: Acute-phase low T3 syndrome is common in antibody-negative AE but appears to reflect disease severity rather than serving as an independent prognostic biomarker; discharge mRS is a more reliable predictor. Larger prospective studies are needed to clarify the prognostic role of thyroid hormone alterations in this population. Furthermore, a subset of patients (8/84, 9.5%) initially diagnosed with antibody-negative AE received alternative diagnoses after 12 months of follow-up, highlighting diagnostic uncertainty and the urgent need to identify clinical red flags for re-evaluation.