COVID-19-Associated Seizures May be Common, Linked to Higher Risk of Death

Study examines the prevalence and risk factors for non-convulsive seizures among patients hospitalized with COVID-19

Boston – COVID-19 can have damaging effects on organs throughout the body, including the brain. A new study led by investigators at Beth Israel Deaconess Medical Center (BIDMC) and Massachusetts General Hospital (MGH) demonstrated that some patients hospitalized with COVID-19 experience non-convulsive seizures, which may put them at higher risk of dying. The findings are published in the Annals of Neurology.

"We found that seizures can happen in patients with severe COVID-19 infections, even those without any prior neurologic history, and that they are associated with worse outcomes," says co-author Mouhsin Shafi, MD, PhD, an investigator in the Department of Neurology at BIDMC, Medical Director of the BIDMC electroencephalogram (EEG) laboratory, and Director of the Berenson-Allen Center for Noninvasive Brain Stimulation. "We know that usually when people are very ill, their brains are impacted even if disease itself isn't primarily neurological. That can have significant consequences for the patient. The purpose of our study is to remind clinicians that seizures happen in this setting and there should be a low threshold for monitoring patients for seizures, whether or not they have a history of seizures."

A common complication in patients with severe critical illnesses, seizures are sudden, uncontrolled electrical disturbances in the brain. While seizures are known to affect about 10 percent of patients admitted to intensive care unit with respiratory infection, most seizures lack obvious physical convulsions and can only be detected with an EEG. It was previously unclear whether such seizures primarily occur in patients who already have a seizure disorder or whether they can arise for the first time because of COVID-19. The effects of such seizures on patients' health were also unknown.

"In the early days of the pandemic, initial reports from China and other countries suggested it was rare to see seizures in patients with COVID-19, but we knew from our previous experience that patients who are critically ill often have seizures that are undetectable without EEG," said co-senior author M. Brandon Westover, MD, PhD, an investigator in the Department of Neurology at MGH and director of Data Science at the MGH McCance Center for Brain Health. "We constructed a study with enough patients to understand how often these events were occurring and whether they were contributing independently to what was happening to patients clinically."

Shafi, Westover and colleagues analyzed medical information for 197 hospitalized patients with COVID-19 who underwent EEG monitoring — a test that measures the brain's electrical activity — for various reasons at nine institutions in North America and Europe. The EEG test detected non-convulsive seizures in 9.6 percent of patients, some of whom had no prior neurological problems. Patients who had seizures remained hospitalized longer that patients who did not, and they were four times more likely to die while in the hospital than patients without seizures — suggesting that neurological complications may be an important contributor to the morbidity and mortality associated with COVID-19.

"Our results suggest that patients with COVID-19 should be monitored closely for non-convulsive seizures. Treatments are available and warranted in patients at high risk; however, further research is needed to clarify how aggressively to treat seizures in COVID-19," said Shafi.

Co-authors included — First author Lu Lin, MD, PhD, Charles Cassasa, MD, Daniel M. Goldenholz, MD, PhD, of Beth Israel Deaconess Medical Center; Abrar Al-Faraj, MD, Myriam Abdennadher, MD, of Boston Medical Center; Neishay Ayub, MD, Sudeshna Das, PhD, Shibani S. Mukerji, MD, PhD, Jing Jin, PhD, Eyal Y. Kimchi, MD, PhD, Sahar Zafar, MD of Massachusetts General Hospital; Pablo Bravo, MD, Nicolas Gaspard, MD, PhD, Emily J. Gilmore, MD, Lawrence J. Hirsch, MD and Jennifer A. Kim, MD, PhD, of Yale University; Lorenzo Ferlini, MD of Hôspital Erasme; Ioannis Karakis, MD, PhD, Harshad S. Ladha, MD, of Emory University; Jong Woo Lee, MD, PhD, Steven Tobochnik, MD, of Brigham and Women's Hospital; Christopher R. Newey, DO, MS of Cleveland Clinic; Jay Pathmanathan, MD, of University of Pennsylvania.

This work was supported by the National Institutes of Health, the Football Players Health Study at Harvard University, the Glenn Foundation for Medical Research and the American Federation for Aging Research, the American Academy of Sleep Medicine, the Department of Defense, and the Eleanor and Miles Shore Fellowship.

All authors report no potential conflicts of interest.

Editor's note: This release is adapted from a press release issued by Massachusetts General Hospital.