Meta-analysis of175 Patients with COVID-19 and Seizures, Status Epilepticus, or Cortical Myoclonus: An Individual Patient Data Analysis

ABSTRACT

Objective: To characterize management and outcomes of seizures, status epilepticus, and cortical myoclonus in COVID-19, with individual patient data analysis of published literature. Background: Seizure disorders in COVID-19 have been sparingly reported. Lack of large-scale studies create challenges in identifying clinically relevant associated factors. Design/Methods: Systematic literature review was conducted in accordance with PRISMA guidelines. Criteria included new-onset seizures, status epilepticus, and/or cortical myoclonus developing prior to or during hospitalization, with concomitant COVID-19. COVID-19 severity was dichotomized into mild and severe cases, based on severity of respiratory symptoms. Good outcome was defined as discharge without severe deficits, and/or return to near baseline. Results: A total of 105 studies reporting 175 patients (male 56.6%;mean age 47.9, SD 25.7) were included. Status epilepticus occurred in 44 patients (25.1%) and myoclonus in 38 (21.7%). Any seizure-like activity on electroencephalography (EEG) was noted in 53/102 patients (52.0%). Abnormal cerebrospinal fluid analysis was reported in 32/83 patients (38.6%). Most common underlying diagnosis was encephalitis (autoimmune or infectious) in 42/175 patients (24.0%), followed by infarct (15/175;8.6%) and intracerebral hemorrhage (ICH) (13/175;7.4%). The most common treatment was levetiracetam (92/130;70.8%). Overall, 106/160 patients (66.3%) had good outcomes while 24/156 died (15.4%). Encephalitis was associated with good outcomes (p=0.005). Severe COVID-19 was associated with more myoclonus, poor outcome, and mortality (all p<0.001), with a trend towards more EEG abnormalities (p=0.066). In multivariate regression, only severe COVID-19 was associated with reduced odds of good outcome (OR=0.095;p=0.006), and higher odds of mortality (OR=4.60, p=0.040). Conclusions: Encephalitis, infarct, and ICH are common underlying etiologies in COVID-19 patients with seizure disorders. Overall, most patients achieved good outcome, thus highlighting the necessity of aggressively treating seizures, and identifying any treatable underlying etiology. Future research should investigate long-term neurocognitive outcomes in COVID-19 patients with seizure disorders.