Electroencephalographic Seizures Are Common in COVID-19, Linked to Increased Mortality Risk

Seizures are known to be a potential complication of COVID-19. However, many centers have limited continuous electroencephalography (cEEG) for patients with the disease because of scarce resources and concerns about transmission.

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M. Brandon Westover, MD, PhD, neurologist and director of the Clinical Data Animation Center at Massachusetts General Hospital, Mouhsin M. Shafi MD, PhD, of Beth Israel Deaconess Medical Center, and colleagues have conducted the first multicenter retrospective study with sufficient sample size to determine the incidence of epileptiform abnormalities in COVID-19 patients. In the Annals of Neurology, they present data suggesting cerebral dysfunction may substantially contribute to adverse COVID-19 outcomes.

Study Methods

The team retrospectively examined data on 197 adults who tested positive for COVID-19 and had clinical indications for cEEG monitoring. The patients were treated between March 1 and May 21, 2020, at eight centers in the northeastern U.S. and one in Belgium.

Clinical Seizures

39 patients (20%) presented to the hospital with witnessed seizures/seizure-like events or had seizures/seizure-like events during hospitalization before EEG. All but one of these patients had a prior history of central nervous system (CNS) disorder, intracranial lesions detected on neuroimaging or a risk factor for seizures. The exception was a 47-year-old man with COVID-19 pneumonia who presented with bilateral tonic–clonic seizure.

Thus, although clinical seizures in COVID-19 patients are not uncommon, a directly epileptogenic process is unlikely.

cEEG Findings

• 96 patients (49%) had epileptiform abnormalities, including electrographic seizures in 19 patients (10%) and nonconvulsive status epilepticus in 11 (6%)
• Electrographic seizures were present in 6% of patients with no prior history of CNS disorders and no structural lesions on neuroimaging
• Five patients with electrographic seizures (26%) had no motor manifestations of their seizures

Clinical Outcomes

37% of patients died. Factors significantly associated with mortality were:

• Electrographic seizures (HR, 4.07; P<0.01)
• Higher maximal ferritin level (HR, 1.39; P<0.05)

Clinical seizures as a presenting symptom were not associated with increased mortality.

In an analysis that considered death as a competing event, the probability of hospital discharge within 30 days after cEEG initiation was substantially lower for patients with nonconvulsive status epilepticus than those without (21% vs. 43%).

The Necessity of cEEG

Significant cerebral dysfunction leading to cortical hyperexcitability might be present more commonly in COVID-19 than is generally appreciated or clinically apparent. The high percentage of patients with no motor correlates to their electrographic seizures supports the importance of cEEG in this population. That conclusion is bolstered by the 6% incidence of electrographic seizures in patients with no history of CNS disorders and no structural brain lesions.

Clinical seizures as a presenting symptom might reflect cortical hyperexcitability in the presence of otherwise mild disease, whereas electrographic seizures might reflect severe COVID-19 systemic disease. It remains to be seen whether electrographic seizures are a modifiable risk factor for mortality.

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