Study finds electroencephalographic abnormalities common in patients with COVID‐19, associated with adverse outcomes

Seizures and other epileptiform abnormalities were common in patients with coronavirus disease 2019 (COVID-19) undergoing clinically indicated continuous electroencephalogram (cEEG) and were associated with adverse clinical outcomes, according to a study published in Annals of Neurology.

“In the largest study to date of cEEG findings, conducted in a single academic hospital system, electrographic seizures were reported in 7% of patients, demonstrating that seizures are a possible complication of COVID-19,” wrote Lu Lin, MD, Harvard Medical School, Boston, Massachusetts, and colleagues. “To date, however, there have been no published multicentre studies with sufficient sample size to determine the rate of seizures and other epileptiform abnormalities with statistical confidence across institutions or to investigate their impact on patient outcomes.”

To provide insights, researchers retrospectively reviewed medical records and EEG reports of 197 patients with COVID‐19 referred for cEEG between March 1 and May 21, 2020 at 9 participating hospitals. The median age of the cohort was 65 years. A prior history of intracranial neurologic disease was present in 67 (34.0%) patients, including 32 (16.2%) with a prior history of epilepsy. EEGs were performed on median day 7 of hospitalisation, and patients remained on cEEG for a median of 25 hours.

Of the 197 patients, 27 (13.7%) presented to the hospital with witnessed seizures or seizure‐like events, and 11 more patients (5.6%) had clinical seizures or seizure‐like events during their hospitalisation before EEG. Of these 38 patients, 22 (57.9%) had a prior history of CNS disorders, including 12 (31.6%) with a history of epilepsy. Of the 16 patients without prior history of CNS disorders, the majority had either intracranial lesions (acute or remote) detected on brain CT or MRI or other risk factors for seizures.

Meanwhile, electrographic seizures were detected in 19 (9.6%) patients, including nonconvulsive status epilepticus (NCSE) in 11 (5.6%) patients. Of the 19 patients with electrographic seizures, 14 (73.7%) had either a history of a central nervous system (CNS) disorder (including 6 with history of epilepsy) or acute/chronic intracranial lesions. Therefore, the rate of electrographic seizures was 12.6% among the 111 patients with either a history of CNS disorders or intracranial lesions, compared to 5.8% among 86 patients without a history of CNS disorders or intracranial lesions.

The researchers found that patients who had preceding clinical seizures during hospitalisation were more likely to have both electrographic seizures (36.4% vs 8.1%, odds ratio [OR] 6.51, P = 0.01) and and NCSE (27.3% vs 4.3%, OR 8.34, P = 0.01) compared with those who did not have preceding clinical seizures during hospitalisation. A pre-existing intracranial lesion on neuroimaging was also found to be associated with NCSE (14.3% vs 3.7%; OR 4.33, P = 0.02).

Further, the study also showed that epileptiform EEG abnormalities (either ictal or interictal) were common in this study cohort, occuring in 96 (48.7%) patients. Significant univariate associations for any epileptiform abnormalities, noted the authors, included the presence of an old intracranial lesion (OR = 2.34), maximal CRP value during hospitalisation (OR = 1.48), and the day after admission on which the first positive COVID‐19 testing was done (OR = 1.46), suggesting that delayed positive COVID‐19 testing was associated with a greater risk of these findings.

Overall, death occurred in 63 of 178 (35.4%) patients without electrographic seizures compared to 10 of 19 (52.7%) patients with electrographic seizures. In multivariate analysis of outcomes, electrographic seizures were observed to be an independent predictor of in-hospital mortality (hazard ratio [HR] 4.07, 95% confidence interval [CI] 1.44–11.51, P< 0.01).

Meanwhile, in competing risk analysis, the estimated probability of hospital discharge by 30 days after the time of initiating EEG monitoring was significantly lower for patients with NCSE compared with those without NCSE (0.21 [95% CI 0.03–0.33] vs 0.43 [95% CI 0.36–0.49]).

“In conclusion, we found that seizures were not uncommon in patients with COVID‐19 undergoing cEEG, particularly in patients with a prior history of neurologic disease or significant abnormalities on neuroimaging,” the authors noted. “Furthermore, epileptiform abnormalities were common, occurring in almost 50% of monitored patients, indicating that the impact of COVID‐19 on cerebral physiology might be greater than is generally appreciated.”

“Notably, seizures were associated with increased mortality, and NCSE was associated with prolonged length of stay, both of which suggest that the neurologic complications of COVID‐19 might be an important contributor to the observed disease mortality and morbidity,” the authors added. “These findings thus strongly support the need for more careful neurologic assessment, including cEEG in many patients, and long‐term follow‐up in these patients.”