Patients with severe COVID-19 disease are at increased risk for acute symptomatic seizures and a variety of electroencephalographic (EEG) abnormalities. This is the conclusion from the largest study to date of continuous EEG (cEEG) monitoring of patients with COVID-19. A complete report of the series of 22 patients treated at Cleveland Clinic for the novel coronavirus was published online on the preprint server medRxiv on May 28, the same date Neurocritical Care published an online article profiling two cases from the series. In all, five COVID-19 patients developed acute symptomatic seizures; two cases were electrographic only.
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“Knowing that COVID-19 may increase the risk of seizures is important, especially since signs often cannot be detected while patients are heavily sedated on a ventilator,” says Cleveland Clinic neurologist Christopher Newey, DO, MS, a co-author of both articles. “For COVID-19 patients with neurologic changes, continuous EEG monitoring may inform evaluation and management.”
Dearth of EEG evidence in COVID-19
Little is understood about CNS manifestations of COVID-19. Evidence has been emerging from various case reports worldwide that the condition is associated with neurologic effects, although most reports have not included data from cEEG monitoring, and very few have linked the disease to seizures in patients with no history of epilepsy or brain injury.
The case patients at a glance
The case series consisted of 22 adults (8 women; mean age, 66.5 ± 11.2 years) treated for COVID-19 at Cleveland Clinic through May 20, 2020. Nineteen patients underwent cEEG with a 21-channel electrode system for at least 24 hours; three had routine EEG for less than one hour.
Six patients (27.3%) had a history of at least one neurologic comorbidity — i.e., epilepsy (2 patients), stroke (1), headache (1), traumatic brain injury (1) and spinal stenosis (2).
The hospital course involved the following:
- Fever in 15 patients (68.2%)
- Pneumonia in six patients (27.3%)
- Mechanical ventilation in 18 patients (81.8%)
- Hydroxychloroquine use in 16 patients (72.7%)
EEG indications and findings
EEG was ordered for altered mental status in 17 patients and for seizure-like events in five patients. These events consisted of left arm clonic movements, right face twitching (clonic), generalized tonic-clonic seizure and “eyebrow twitching with lip smacking.” Median duration of cEEG monitoring was 2 days (range, 1-6).
Among the 19 patients who underwent cEEG, findings were as follows:
- Acute electrographic seizures were seen in two patients (10.5%).
- Epileptic abnormalities were seen in four patients (15.7%), two of whom were the patients with electrographic seizures noted above. The other two had a history of epilepsy and had generalized polyspikes and right frontal sharp waves.
- Continuous (> 80% of recording) generalized polymorphic delta slowing was seen in all patients.
- Posterior dominant rhythm was absent in eight patients (42.1%), slow (<8 Hz) in nine patients (47.2%) and within normal limits in two.
- Generalized periodic discharges (0.5-1 Hz) were seen in seven patients (36.8%), with triphasic morphology in five and sharply contoured discharges in the other two.
- Intermittent generalized rhythmic delta activity was seen in 10 patients (52.6%), with sharply contoured waveforms in three of these.
Among the three patients who underwent routine EEG (none with a history of epilepsy), findings were as follows:
- Epileptiform abnormalities (left hemispheric lateralized rhythmic delta activity up to 1.5 Hz) were observed in one patient with right-sided jerking movements.
- No patients had posterior dominant rhythms.
By the end of the study period, six patients (27.3%) had died during hospitalization and the rest had been discharged. No statistically significant associations were found between EEG findings and death.
Eighteen patients underwent brain CT and five underwent brain MRI. Except for a single case with acute symptomatic seizure, imaging findings did not correlate with epileptiform abnormalities or electrographic seizures on EEG.
Close-up look at two cases
The report in Neurocritical Care detailed two cases from the series, both of which involved men of advanced age with multiple comorbidities but no history of epilepsy who nevertheless experienced acute symptomatic seizures.
The first case was a 76-year-old who underwent cEEG for episodes of left upper extremity clonic activity and worsening encephalopathy. Monitoring revealed three focal seizures lasting about 30 seconds, each arising from the right centroparietal region. Clinical and EEG seizure activity subsided after levetiracetam initiation. He was ultimately discharged to a long-term acute care hospital.
The second case was an 82-year-old who underwent cEEG for right eyelid and facial twitching. Monitoring showed frequent EEG seizures from the left more than right frontal-temporal regions, which eventually progressed to status epilepticus. Most seizures were nonconvulsive. Seizure frequency improved with levetiracetam, but the patient died after being removed from life support 20 days into his ICU stay.
Possible roles for cEEG in COVID-19 management
These reports reflect greater experience with COVID-19 patients showing evidence of seizures than has been reported elsewhere, Dr. Newey says, adding that this may be due to the long duration of cEEG conducted with a 21-channel electrode system.
The fact that EEG abnormalities correlated with neuroimaging findings in only one case suggests a direct link between COVID-19 and neurologic abnormalities, which Dr. Newey says is likely to involve multiple factors. “Seizures could indicate that COVID-19 is neurotropic or may possibly lead to microthrombi in the brain secondary to hypoxia or inflammation,” he conjectures. “It’s also possible that excessive cytokine activity disrupts the blood-brain barrier.”
Dr. Newey and his co-authors note that these reports also highlight the role of cEEG for evaluating COVID-19 patients with mental status changes and no explanatory neuroimaging findings. This utility may extend to helping guide therapy: Among the series’ six patients who had anti-seizure medications initiated during hospitalization, only two were discharged on them.
“Continuous EEG not only detected abnormal activity not seen by imaging but clarified which patients needed to continue anti-epileptic drugs,” Dr. Newey concludes. “This reduced the rate of unnecessary medication use.”