A Large-Scale Study Indicates Increase in the Risk of Epilepsy in Patients With Different Risk Factors, Including Rheumatoid Arthritis

Abstract

Peripheral neuropathy and inflammatory reactions of the central nervous system may accompany rheumatoid arthritis (RA). Inflammatory processes play a critical role in epilepsy. Therefore, we conducted this study to determine the risk of epilepsy in patients with RA.The RA cohort comprised patients ages 20 years and older who were newly diagnosed with RA between 2000 and 2011, with data obtained from the Registry of Catastrophic Illnesses Patient Database. Patients without RA were frequency matched with an RA cohort at a 1:1 ratio according to age, sex, and year of RA diagnosis.The overall crude hazard ratio (HR) for epilepsy was 1.27-fold higher in the RA cohort compared with that in the controls. After adjustment for age, sex, comorbidities, and medications, the patients with RA were associated with an increased risk of epilepsy compared with those without RA (adjusted HR [aHR] = 1.52, 95% confidence interval [CI] = 1.12–2.07). Compared with the RA patients with ≤ 560 days of nonsteroidal anti-inflammatory drug (NSAID) use, the RA patients with 1181 to 2145 and >2145 days of NSAID use had a significantly lower risk of epilepsy (aHR = 0.35, 95% CI = 0.24–0.52 and aHR = 0.15, 95% CI = 0.09–0.24, respectively).This study provides compelling evidence of an increased risk of epilepsy in patients with RA. The period of NSAID treatment is negatively associated with the risk of epilepsy in RA patients.

The role of inflammation in the development of epilepsy

“…The development of epilepsy within RA patients is 1.27-fold higher than the control patients without RA. Duration of non-steroidal anti-inflammatory drug (NSAID) therapy in RA patients negatively correlated with epilepsy development while patients with minimal NSAID therapy had a greater risk of epilepsy development [ 130 ]. This suggests that limiting the inflammatory process induced by RA reduces risk of epileptogenesis.…”

Seizures as a clinical manifestation in somatic autoimmune disorders

“…RA is the most common form of autoimmune arthritis manifesting as a chronic inflammatory disease with involvement of joints and synovial membrane. Two population-based studies reported an increased risk of epilepsy in people with RA compared with controls [8,86]. The link between RA and epilepsy may be explained by vasculitis [87], CNS infections [88] and the use of methotrexate [89] and sulphasalazine [90].…”

Risk of epilepsy in rheumatoid arthritis: a meta-analysis of population based studies and bioinformatics analysis

“…[32][33][34][35][36][37] Study characteristics Among the six included studies, four of them (n = 3,803,535 in total) were related to the comorbidity of epilepsy and RA [34][35][36][37] and the other two (n = 3,290,578 in total) focused on children born to mothers with RA. 32,33 Chang and colleagues 34 and Ong and colleagues 35 excluded a history of epilepsy before the diagnosis of RA. Téllez-Zenteno and colleagues 36 and Gaitatzis and colleagues 37 provided the prevalence of RA that preceded, cooccurred with, or followed the diagnosis of epilepsy.…”

“…The prevalence of epilepsy in RA and non-RA were extracted or calculated from the four included studies. [34][35][36][37] Since statistical heterogeneity among studies was significant (I 2 = 94.23% and p < 0.001), the random effects model was used. Results showed that RA was associated with an increased risk of epilepsy (0.83% in RA versus 0.44% in non-RA; RR 1.601; 95% CI: 1.089-2.354, p = 0.017; based on n = 3,803,535; Figure 2).…”