Electroencephalographic Abnormalities are Common in COVID-19 and are Associated with Outcomes

Abstract

Objective: The aim was to determine the prevalence and risk factors for electrographic seizures and other electroencephalographic (EEG) patterns in patients with Coronavirus disease 2019 (COVID-19) undergoing clinically indicated continuous electroencephalogram (cEEG) monitoring and to assess whether EEG findings are associated with outcomes.

Methods: We identified 197 patients with COVID-19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns. Multivariate Cox proportional hazards analysis assessed the relationship between EEG patterns and clinical outcomes.

Results: Electrographic seizures were detected in 19 (9.6%) patients, including nonconvulsive status epilepticus (NCSE) in 11 (5.6%). Epileptiform abnormalities (either ictal or interictal) were present in 96 (48.7%). Preceding clinical seizures during hospitalization were associated with both electrographic seizures (36.4% in those with vs 8.1% in those without prior clinical seizures, odds ratio [OR] 6.51, p = 0.01) and NCSE (27.3% vs 4.3%, OR 8.34, p = 0.01). A pre-existing intracranial lesion on neuroimaging was associated with NCSE (14.3% vs 3.7%; OR 4.33, p = 0.02). In multivariate analysis of outcomes, electrographic seizures were an independent predictor of in-hospital mortality (hazard ratio [HR] 4.07 [1.44-11.51], p < 0.01). In competing risks analysis, hospital length of stay increased in the presence of NCSE (30 day proportion discharged with vs without NCSE: HR 0.21 [0.03-0.33] vs 0.43 [0.36-0.49]).

Interpretation: This multicenter retrospective cohort study demonstrates that seizures and other epileptiform abnormalities are common in patients with COVID-19 undergoing clinically indicated cEEG and are associated with adverse clinical outcomes. ANN NEUROL 2021;89:872-883.

FIGURE 1

Examples of electrographic seizures in Coronvirus disease 2019 (COVID‐19) patients. Examples of 19‐channel electroencephalogram from a 63‐year‐old man with no prior history of central nervous system disorders or epilepsy, presenting with acute respiratory distress syndrome attributable to COVID‐19 and multi‐organ failure, who then developed multifocal electrographic seizures after cardiac arrest. An electrographic seizure from the right central region is shown. Anatomical bipolar montage. High‐pass filter 1 Hz, low‐pass filter 70 Hz. Scale bars indicate sensitivity and time scale.

FIGURE 2

Association of electroencephalographic (EEG) findings with mortality and length of stay. (A) Survival curves for the proportion of patients alive over time as a function of presence versus absence of electrographic seizures on EEG; hazard ratio for mortality = 4.06, p < 0.01. (B) Cumulative incidence of discharge without death (competing risk analysis) for patients with versus without epileptiform abnormalities (left) or nonconvulsive status epilepticus (NCSE) (right) on EEG (likelihood of discharge by 30 days in patients without vs with EEG abnormality: 0.45 [0.36–0.53] vs 0.39 [0.26–0.47] for epileptiform abnormalities; 0.43 [0.36–0.49] vs 0.21 [0.03–0.33] for NCSE).