Clinical efficacy and immunomodulation of double-filtration plasmapheresis in autoimmune encephalitis: A prospective study highlighting the importance of timely initiation.

Background and purpose: Double-filtration plasmapheresis (DFPP) has emerged as a plasma-saving alternative to therapeutic plasma exchange for autoimmune encephalitis (AE), but prospective evidence regarding its dual effects on both clinical efficacy and immunomodulation remains limited. This study aimed to evaluate the clinical and immunological effects of DFPP in AE. Methods: In this prospective single-center cohort study, 57 patients diagnosed with AE according to international criteria were enrolled between 2018 and 2023. Participants received DFPP (median 3-5 sessions), either alone or combined with immunotherapies. The primary outcome was neurological improvement, measured by the change in modified Rankin Scale (ΔmRS). Secondary outcomes included symptomatic change (ΔCASE score), immunological parameter shifts, and adverse events. Subgroup analyses were conducted based on antibody type, treatment timing, and combination therapies. Results: The cohort had a median age of 47 years (IQR: 24-65), with 49.1 % being female. DFPP significantly reduced median mRS scores from 3.00 to 1.00 (p < 0.001) and CASE scores from 3.00 to 1.00 (p < 0.001). The overall functional improvement rate was 71.9 %. Initiation of DFPP within 14 days of symptom onset was associated with significantly higher response rates (100 % vs. 63.6 %, p < 0.05) and greater neurological improvement (p < 0.05). Combination with IVMP or IVIG did not enhance efficacy compared to DFPP alone (p = 0.600). Immunological profiling revealed significant reductions in IgG (77.55 %), IgA (76.11 %), and IgM (79.96 %), along with modulation of lymphocyte subsets and cytokine levels. Adverse events occurred in 28.1 % of patients, predominantly mild catheter-related thrombosis. Conclusions: DFPP is an effective and well-tolerated treatment for autoimmune encephalitis, significantly improving neurological function modulates immune responses.