Although Increased, Risk of Epilepsy and Seizures Following COVID-19 Remain Low

Orrin Devinsky, MD

Recently published findings from a study using electronic health records showed that the risk for developing subsequent seizures or epilepsy 6 months after COVID-19 infection was relatively low, affecting less than 1% of all infected patients. The study also showed that the risk of these outcomes were significantly more raised when compared with influenza.¹

After analyzing 860,934 electronic health records, 2 cohorts of 152,754 patients matched patients infected with either COVID-19 or influenza, were included. The primary outcome, 6-month incidence of the composite end point of epilepsy (ICD-10 code G40) or seizures (ICD-10 code R56), was significantly increased compared with the influenza cohort (cumulative incidence, 0.94% vs 0.60%; hazard ratio [HR], 1.55; 95% CI, 1.40-1.72; P <.0001).

The study investigators, including Orrin Devinsky, MD, director, Comprehensive Epilepsy Center, NYU Langone. Concluded that "As seizures and epilepsy remain relatively rare outcomes following COVID-19, we support continued pooling of data across multiple centers and establishing long-term open access repositories for the reporting of post COVID-19 seizures and epilepsy Transparent reporting of outcomes is crucial to better understanding how COVID-19 may interrelate with seizure disorders."

All told, the between-group differences of COVID-19 and influenza were consistent when separating risk of seizures (0.81% vs 0.51%; HR, 1.55; 95% CI, 1.39-1.74; P <.0001) and epilepsy (0.30% vs 0.17%; HR, 1.87; 95% CI, 1.54-2.28; P <.0001). Additionally, a post-hoc analysis showed that the peak time for the increased risk of seizures or epilepsy was 23 days after infection.

To capture several established and suspected risk factors for COVID-19 and more severe COVID-19 illness, investigators used 58 variables. Additionally, the influence of age was analyzed through a repeated analysis of pediatric (≤16 years old) and adult (>16 years old) populations. To explore whether, and how, associations between COVID-19 and epilepsy or seizures were affected by the severity of the acute infection, Devinsky et al repeated the analysis separately in those who were hospitalized and those not hospitalized within 14 days of either viral diagnosis.

After stratifying patients by age, compared with influenza, there was an increased risk of seizures or epilepsy after COVID-19 infection in both children (1.34% vs 0.69%; HR, 1.85; 95% CI, 1.54-2.22; P <.0001) and adults (0.84% vs 0.54%; HR, 1.56; 95% CI, 1.37-1.77; P <.00001). While markedly higher in children, the moderation of the composite end point by age was not significant (moderation coefficient, 0.20; 95% CI, –0.025 to 0.42; P = .082). Overall, the risk of epilepsy after COVID-19 vs influenza was significantly moderated by age and more marked among children than adults (moderation coefficient, 0.68; 95% CI, 0.23-1.13; P = .0031).

When stratified by hospitalization status and compared with influenza, there was a significant increase in the risk of seizures or epilepsy after COVID-19 in non-hospitalized individuals (0.72% vs 0.48%; HR, 1.44; 95% CI, 1.27-1.63; P <.0001) but not in hospitalized individuals (2.90% vs 2.40%; HR, 1.14; 95% CI, 0.95-1.38; P = .16). Despite this, hospitalization was not considered a significant moderator (moderation coefficient, 0.12; 95% CI, –0.10 to 0.35; P = .28).

When examining the peak of seizures or epilepsy after infection, the peak time for the HR of seizures of epilepsy was 21 days in adults and 50 days in children. At 50 days post-infection, children were almost 3 times more likely to have seizures or epilepsy diagnosed following COVID-19 infection than after influenza. Between either virus, the HR for seizures or epilepsy peaked at 9 days for hospitalized patients vs 41 days for non-hospitalized individuals. At that timepoint, non-hospitalized individuals were more than twice as likely to have seizures or epilepsy diagnosed post COVID-19 compared with influenza.

REFERENCE
1. Taquet M, Devinsky O, Cross JH, Harrison PJ, Sen A. Incidence of epilepsy and seizures over the first 6 months after a COVID-19 diagnosis: a retrospective cohort study. Neurology. Published online November 16, 2022. doi:10.1212/WNL.0000000000201595