Different relationships between epilepsy syndromes and autoimmune diseases

Objective: Our objective was to study the relationship between epilepsy and autoimmune diseases in two different types of epilepsy: idiopathic generalized epilepsies (IGEs) and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). The contribution of the human leukocyte antigen (HLA) system to this relationship was analyzed. Methods: Adult patients with IGEs and MTLE-HS at a tertiary epilepsy center were consecutively enrolled between January 2016 and December 2020. Results: A total of 664 patients, 422 with IGEs and 242 with MTLE-HS, were included. Patients with IGEs were 15 years younger, on average, than patients with MTLE-HS (p <.001). The frequency of autoimmune diseases was 5.5% (n = 23) and 4.5% (n = 11) in patients with IGEs and MTLE-HS, respectively (p =.716). The mean age of autoimmune disease onset was 20 +/- 15.6 years in patients with IGEs and 36.7 +/- 16.5 years in patients with MTLE-HS (p <.05). Clinical manifestations of autoimmune diseases preceded epilepsy onset in 30.4% of patients with IGEs (i.e., in early childhood); in the other patients, epilepsy appeared before autoimmune disease onset. In all but one patient with MTLE-HS and autoimmune diseases, the autoimmune diseases appeared after epilepsy onset from adolescence onward. Significance: Our study indicates two relationship patterns: a bidirectional association between IGEs and autoimmune diseases and a unidirectional relationship between MTLE-HS and autoimmune diseases. The involvement of genetic susceptibility factors (such as the HLA system), autoinflammatory mechanisms, female sex, and antiseizure medications in these relationships are discussed.