The Risk of Epilepsy in Systemic Autoimmune Diseases: A Population-based Study in Olmsted County, Minnesota
Shemonti Hasan1, Adam Nguyen4, Sara Achenbach2, Hannah Langenfeld2, Michelle Devine5, Eoin Flanagan1, Cynthia Crowson3, Divyanshu Dubey1
1Department of Neurology, 2Department of Quantitative Health Sciences, 3Department of Quantitative Health Sciences, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, 4Edward Via College of Osteopathic Medicine, 5Olmsted Medical Center
Objective:
Determine the risk and etiology of epilepsy among systemic autoimmune conditions including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)
Background:
Population-based epidemiology studies evaluating a link between epilepsy and systemic autoimmune diseases are lacking.
Design/Methods:
Using the Rochester Epidemiology Project medical records-linkage system, we identified incident cases matched to comparators by age and sex within Olmsted County, Minnesota of RA from 1980-2013, and SLE from 1976-2018. We reviewed the records to identify seizures and their etiologies following the incidence of RA or SLE. Cox models were used to compare development of epilepsy by RA status, adjusted for age, sex and index year.  
Results:
Among the 1063 identified RA patients and 1063 comparators, 27 cases and 13 comparators developed seizures following the index date with a hazard ratio of 2.33 (95% CI 1.20-4.53). Most common seizure etiology for RA cases was stroke (9/27, 33%). None of the patients had autoimmune encephalitis. Among RA patients with seizures, 26/27 (96%) developed long-term epilepsy. EEG was abnormal in 14/23 (61%) RA patients, but only nine demonstrated epileptiform discharges. Among the 188 SLE patients and 188 comparators, five SLE patients and three comparators developed seizures following the index date. A hazard ratio was not calculated due to the small number of patients with seizures. Only one of the five SLE patients with seizures had features of seronegative probable autoimmune encephalitis. Among those with seizures, 3/5 (60%) SLE patients developed long-term epilepsy. EEG was abnormal in 3/3 (100%) cases and two had focal epileptiform discharges.

Conclusions:
RA was associated with an increased risk of epilepsy, mostly secondary to comorbidities. Epilepsy frequency among the SLE population was not high enough to significantly suggest a relationship. Seizure secondary to autoimmune encephalitis was not a common cause of seizures among these populations.
10.1212/WNL.0000000000206254