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COVID-19 is linked to novel seizures and subsequent adverse outcomes, including death, in patients without a previous history of epilepsy, new research shows.
In a retrospective study of more than 900 patients admitted to the hospital with COVID-19, those without a known history of epilepsy had three times greater odds of experiencing novel seizures than those with a known history of epilepsy.
In addition, among patients with new-onset seizures, hospital stays were about 15 days longer ― and mortality rates were significantly higher.
“We’re finding that there are many neurological consequences that can happen with COVID-19 infections, and it’s important for clinicians to keep that in mind as they monitor people long term,” study investigator Neeraj Singh, MD, neurologist and epileptologist with Northwell Health System, Great Neck, New York, told Medscape Medical News.
Singh noted that although seizures “might not be the most common thing we see in people with COVID-19, they seem to be new seizures and not just a seizure we knew would happen in someone with epilepsy.
“So there’s definitely a need now for more prospective research and following people over time to fully understand all the different things that might be newly a problem for them in the long term,” he added.
Singh and Hardik Bhaskar, an undergraduate student at Hunter College, New York City, presented the study findings at the virtual American Academy of Neurology (AAN) 2021 Annual Meeting
Largest Sample to Date
“This study explores the relationship between the incidences of COVID-19 infections and [novel] epileptic seizures in the largest sample to date in a single New York–based hospital system,” the investigators note.
“Novel” seizures included both new-onset and breakthrough seizures. New-onset seizures are those that occur in patients without a previous history of epilepsy, whereas breakthrough seizures occur in patients with such a history.
Singh told meeting attendees that the “early epicenter” of the COVID pandemic was in New York City and occurred from February 29, 2020, to June 1, 2020. Patients with COVID-19 “had multiple neurological sequelae, including seizures, strokes, and encephalopathy,” he said.
However, the effects of COVID-19 on individuals with epilepsy “remain unclear,” Singh said.
For their study, the researchers assessed 917 patients in 13 New York City metropolitan hospitals. All participants had received a confirmed positive test result on PCR for COVID and had received an antiepileptic medication upon admission. The patients were admitted between February 14 and June 14, 2020.
For the study, the patients were first divided into two groups: those with a history of epilepsy (n = 451), and those without such a history (n = 466).
The first group was further divided on the basis of those who presented with breakthrough seizures and those who presented without them. The second group was further divided on the basis of those who presented with new-onset seizures and those who presented without them.
Significant Adverse Outcomes
Results showed that 27% of the patients without a history of epilepsy experienced a novel/new-onset seizure and that 11% of the patients with a history of epilepsy experienced a novel/breakthrough seizure (odds ratio [OR], 3.15; P < .0001).
In addition, participants with new-onset seizures had a longer stay in the hospital (mean, 26.9 days) than the subgroup with a history of epilepsy and no breakthrough seizures (10.9 days) and the subgroup with a history of epilepsy who did experience breakthrough seizures (12.8 days; P < .0001 for both comparisons).
In the group of patients with a history of epilepsy, there were no significant differences in lengths of stay between those with and those without breakthrough seizures (P = .68).
Although mortality rates did not differ significantly between the full group with a history of epilepsy vs the full group without epilepsy (23% vs 25%; OR, 0.9), the mortality rate was significantly higher among patients who experienced novel seizures than among those who did not experience such seizures (29% vs 23%; OR, 1.4; P = .045).
Bhaskar noted that there are “many hypotheses for the mechanism by which COVID-19 might cause seizures.” Those mechanisms include proinflammatory cytokine storms, which may increase the rate of apoptosis, neuronal necrosis, and glutamate concentrations and may disrupt the blood-brain barrier. Another hypothesis is that SARS-CoV-2 infection may lead to hypoxia and abnormal coagulation, resulting in stroke and a subsequent increase in the risk for seizures.
Interestingly, “the presence of antiepileptic medications in patients with epilepsy may confer a protective effect against breakthrough seizures,” Singh said. “However, some subclinical seizures may be misdiagnosed as encephalopathy when patients present with COVID-19 infections.”
He added that further research is needed into the mechanisms linking these infections and new-onset seizures and to “identify subclinical seizures in encephalopathic patients.”
Asked during the question-and-answer session whether the investigators had assessed differences by demographics, such as age or sex, Singh said, “We have not subdivided them that way yet,” but he said he would like to do so in the future. He also plans to look further into which specific medications were used by the participants.
The investigators have reported no relevant financial relationships.
American Academy of Neurology (AAN) 2021 Annual Meeting: Emerging Science session. Presented April 18, 2021.
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