Prevalence and clinical correlates of autoimmune and infection-related antibodies in unexplained seizures in western China

Unexplained seizures represent a substantial diagnostic and therapeutic challenge in clinical neurology. Immune-mediated mechanisms coupled with prior infections are increasingly recognized as pivotal etiological contributors, yet large-scale epidemiological data from western China remain scarce. This retrospective cohort study enrolled 471 patients with unexplained seizures from eight provinces in western China between January 2017 and June 2022. Serum and cerebrospinal fluid samples were tested for neural-specific autoantibodies, thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TgAb), antinuclear antibody (ANA), and immunoglobulin M/G antibodies against Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes simplex virus. Patients were stratified into definite autoimmune-associated seizures (AAS), probable AAS, and non-AAS subgroups. This trial was registered with the Chinese Clinical Trial Registry (ChiCTR1900027074) on October 30, 2019, and was retrospectively registered as the first participant was enrolled in January 2017. Overall, 14.65% of patients tested positive for neural-specific autoantibodies, with N-methyl-D-aspartate receptor antibody (NMDAR-Ab) being the most prevalent subtype (accounting for 46.38% of antibody-positive patients), and leucine-rich glioma-inactivated 1 antibody (LGI1-Ab) predominantly detected in patients with recurrent seizures. The positive rates of TPO-Ab, TgAb, and ANA were significantly higher in the definite AAS group than in the non-AAS group (all P < 0.01). No significant differences in pathogen-specific IgM levels were observed among subgroups, while serum HSV-IgG and T. gondii-IgG levels were markedly lower in the non-AAS group (both P < 0.0001). CSF white blood cell count was significantly elevated in the definite AAS group ( P = 0.036). Combined detection of neural autoantibodies, systemic autoimmune antibodies, and infection-related serological markers facilitates etiological diagnosis and identification of candidates for early immunotherapy in patients with unexplained seizures in western China.