A Multi-center Exploration of Efficacious Treatment Approaches in LGI1-Ab Encephalitis

ObjectiveTo identify efficacious immunotherapy strategies in patients with LGI1-antibody encephalitis (LGI1-Ab-E). BackgroundIn the 15 years since the initial descriptions, knowledge of LGI1-Ab-E and its pathognomonic feature, faciobrachial dystonic seizures, appears well disseminated amongst neurologists. The disorder is largely reported as immunotherapy-responsive, yet immunotherapy regimens are highly variable. Furthermore, despite immunotherapy, up to 1/3 of patients relapse and residual cognitive and functional deficits are increasingly reported. Management strategies that minimize symptom burden have not been systematically investigated although it is widely believed that steroids and plasma exchange are effective, and rituximab appears ineffective. Design/MethodsNeurologists retrospectively databased the clinical phenotypes, pharmacological management, and functional outcomes of 181 patients affected by LGI1-Ab-AE from five international autoimmune neurology clinics to better define the natural history of treated and untreated LGI1-Ab-E. ResultsTreatment approaches varied widely across centers and included combinations of steroids, IVIG, PLEX, rituximab, tocilizumab, and seizure medications with a median exposure to 4 immunotherapies and 1 seizure medication. Relapses were observed in 61/181 patients and associated with decreased recovery, defined by mRS score >=2 at 2, 4, and 6 years post-onset, and by both patient-reported and physician-reported quality of life metrics. Immunotherapy exposure decreased the frequency of relapses by ∼33%; hazard ratios of relapse significantly favored various combinatorial strategies. Steroids provided the most rapid benefit in seizure frequency and cognition but, surprisingly, rituximab most strongly associated with relapse reduction and favorable long-term outcomes. Immunotherapies were associated with a disproportionately high level of adverse effects (129/181 patients), in particular with steroids (96/129 patients). ConclusionsCombinatorial immunotherapy strategies utilizing steroids for early seizure control, and steroid sparing agents for longer term remission are most efficacious in LGI1-Ab-E.