Combination Versus Monotherapy in Acute Anti-LGI1 Encephalitis: A Real-World Dose Optimization Analysis

Anti-leucine-rich-glioma-inactivated 1 encephalitis (LGI1e) predominantly affects older adults, who frequently present with chronic comorbidities. Given their heightened susceptibility to adverse effects, optimizing immunotherapy is critical for this high-risk population. Therefore, this study compared the efficacy and safety of intravenous immunoglobulin (IVIg), intravenous methylprednisolone (IVMP) at 500 or 1000 mg/day, and combined IVIg with IVMP to define an optimal efficacy-safety balanced regimen for LGI1e.

A total of 131 LGI1e patients were comprehensively analyzed. The efficacy was assessed through the therapeutic response rate, response latency, and the improvement in the Clinical Assessment Scale for Autoimmune Encephalitis (CASE), the modified Rankin Scale (mRS), the Mini-Mental State Examination (MMSE), and faciobrachial dystonic seizure (FBDS), while safety was evaluated by analyzing the incidence and severity of adverse events (AEs).

Compared with IVIg or IVMP monotherapy, the IVIg+IVMP combination achieved higher response rates, shorter latency, and greater improvements in CASE, mRS, and FBDS. While 1000 mg IVMP reduced response latency and FBDS cessation time versus 500 mg, both doses showed comparable response rates. IVMP-containing regimens increased AEs, especially at 1000 mg. Diabetes was the sole independent AE risk factor during acute immunotherapies. Initial regimens had no long-term outcome association, and cognitive impairment persisted as a major disability contributor.

For LGI1e patients, combined IVIg and corticosteroid demonstrate superior efficacy to monotherapy as first-line treatment, with a starting IVMP dose of 500 mg (vs. 1000 mg) considered optimal. Furthermore, post-immunotherapy cognitive impairment requires sustained management. These findings necessitate validation in larger randomized trials.