Citations

Abstract Seizures are a well‐recognized and often prominent manifestation of autoimmune encephalitic syndromes. Progress in detection of pathogenic neural autoantibodies has led to increased awareness of autoimmune causes of seizures. Clinical studies of patients with these autoantibodies have improved our understanding of the seizure characteristics, treatments, and seizure prognosis in these disorders. The International League Against Epilepsy (ILAE) Autoimmunity and Inflammation Taskforce proposes conceptual definitions for two main diagnostic entities: (a) acute symptomatic seizures secondary to autoimmune encephalitis, and (b) autoimmune‐associated epilepsy, the latter of which suggests an enduring predisposition to seizures. Such a distinction is relevant when discussing the pathophysiology, treatment, prognosis, and social consequences of these disorders. We discuss the role of biomarkers in the application of these conceptual definitions and illustrate their use in patients cared for by members of the task force.

ObjectiveDrug‐resistant seizures are common in patients with leucine‐rich, glioma‐inactivated 1 (LGI1)‐IgG associated and contactin‐associated protein‐like 2 (CASPR2)‐IgG associated encephalitis. We performed the first randomized double‐blind placebo‐controlled trial to evaluate efficacy of intravenous immunoglobulin (IVIG) in reducing seizure frequency.MethodsOur enrollment goal was 30 LGI1/CASPR2‐IgG–seropositive adult patients with ≥2 seizures per week. Patients were randomized to receive IVIG (0.5g/kg day 1, 1g/kg day 2, 0.6g/kg weeks 3 and 5) or volume‐matched intravenous normal saline. Following the blinded phase, the nonresponders in the placebo group received IVIG. The primary clinical outcome was 50% reduction in seizure frequency from baseline to 5 weeks.ResultsAfter enrollment of 17 patients (LGI1‐IgG, 14; CASPR2‐IgG, 3) over 34 months, the study was terminated due to slow enrollment. Six of 8 patients in the IVIG group were responders, compared to 2 of 9 in the placebo group (p = 0.044, odds ratio = 10.5, 95% confidence interval = 1.1–98.9). For the LGI1‐IgG seropositive subgroup, 6 of 8 patients in the IVIG group were responders, compared to zero of 6 in the placebo group. Two LGI1‐IgG–seropositive patients receiving IVIG, but none receiving placebo, were seizure‐free at the end of the blinded phase. Four of the 6 patients entering the open‐label IVIG arm reported ≥50% reduction in seizure frequency. There were no correlations with LGI1/CASPR2‐IgG1–4 subclasses.InterpretationSuperiority of IVIG to placebo reached statistical significance for the primary endpoint for all patients and the subset with LGI1‐IgG. These results have to be interpreted with the caveat that the study did not reach its originally selected sample size. ANN NEUROL 2020;87:313–323