Seizure control and cognitive improvement via immunotherapy in late onset epilepsy patients with paraneoplastic versus GAD65 autoantibody-associated limbic encephalitis

•Corticosteroids are an effective treatment for paraneoplastic limbic encephalitis.•Verbal memory scores correlate with hippocampal size in paraneoplastic limbic encephalitis.•Subiculum and amygdala were larger in GAD65 than in paraneoplastic limbic encephalitis.•GAD65 and paraneoplastic limbic encephalitis appear to differ in their immunopathology.

ObjectiveTo determine the efficacy of immunotherapy in limbic encephalitis (LE) associated epilepsies with autoantibodies against intracellular antigens in the forms of paraneoplastic autoantibodies versus glutamic acid decarboxylase 65 (GAD)-autoantibodies.MethodsEleven paraneoplastic-antibodies + and eleven age- and gender-matched GAD-antibodies + patients with LE were compared regarding EEG, seizure frequency, MRI volumetry of the brain, and cognition. All patients received immunotherapy with corticosteroids add-on to antiepileptic therapy. A few patients underwent additional interventions like immunoglobulins or immunoadsorption.ResultsImmunotherapy led to a significantly greater proportion of seizure-free patients in the paraneoplastic antibodies + (55%) as compared to GAD-antibodies + (18%) patients (p < 0.05). Impaired cognition was evident initially (total cognitive performance score based on attentional-executive function, figural/verbal memory and word fluency) in 100% of the paraneoplastic-antibodies + and 73% of the GAD-antibodies + group. After therapy, cognition improved significantly in the paraneoplastic-antibodies +, but not in the GAD-antibodies + patients (p < 0.05). Cognitive change did not correlate with the change in the number of antiepileptic drugs over time. MRI showed larger and unchanged volumes of the amygdala, presubiculum and subiculum in GAD-antibodies + as compared to paraneoplastic-antibodies + patients (p < 0.05) over time.ConclusionsOur data provide evidence of a beneficial effect of immunotherapy added to antiepileptic drugs on seizure frequency and cognition only in the paraneoplastic-antibodies + subgroup of LE presenting autoantibodies against intracellular antigens.