key: cord-0782369-wo6dx6w8
authors: Danoun, Omar A.; Zillgitt, Andrew; Hill, Chloe; Zutshi, Deepti; Harris, David; Osman, Gamaleldin; Marawar, Rohit; Rath, Subhendu; Syed, Maryam J.; Affan, Muhammad; Schultz, Lonni; Wasade, Vibhangini S.
title: Outcomes of seizures, status epilepticus and EEG findings in critically ill patient with COVID-19
date: 2021-03-08
journal: Epilepsy Behav
DOI: 10.1016/j.yebeh.2021.107923
sha: 26432e628b201ecee06c7a95068f2039dc937412
doc_id: 782369
cord_uid: wo6dx6w8

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a myriad of neurological manifestations and its effects on the nervous system are increasingly recognized. Seizures and status epilepticus (SE) are reported in the novel coronavirus disease (COVID-19), both new onset and worsening of existing epilepsy, however the exact prevalence is still unknown. The primary aim of this study was to correlate the presence of seizures, status epilepticus, and specific critical care EEG patterns with patient functional outcomes in those with COVID-19. METHODS: This is a retrospective, multicenter cohort of COVID-19 positive patients in Southeast Michigan who underwent electroencephalography (EEG) from March 12(th) through May 15(th), 2020. All patients had confirmed nasopharyngeal PCR for COVID-19. EEG patterns were characterized per 2012 ACNS critical care EEG terminology. Clinical and demographic variables were collected by medical chart review. Outcomes were divided into recovered, recovered with disability, or deceased. RESULTS: Out of the total of 4100 patients hospitalized with COVID-19, 110 patients (2.68%) had EEG during their hospitalization; 64% were male, 67% were African American with mean age of 63 years (range 20-87). The majority (70%) had severe COVID-19 were intubated or had multiorgan failure. The median length of hospitalization was 26.5 days (IQR=15 to 44 days). During hospitalization, of the patients who had EEG, 21.8% had new onset seizure including 7% with status epilepticus, majority (87.5%) with no prior epilepsy. Forty-nine (45%) patients died in the hospital, 46 (42%) recovered but maintained a disability and 15 (14%) recovered without a disability. The EEG findings associated with outcomes were background slowing/attenuation (recovered 60% vs recovered/disabled 96% vs died 96%, p<0.001) and normal (recovered 27% vs recovered/disabled 0% vs died 1%, p<0.001). However, these findings were no longer significant after adjusting for severity of COVID-19. CONCLUSION: In this large multi-center study from Southeast Michigan, one of the early COVID-19 epicenters in the US, none of the EEG findings were significantly correlated with outcomes in critically ill COVID-19 patients. Although seizures and status epilepticus could be encountered in COVID-19, the occurrence did not correlate with the patients’ functional outcome.

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has multiple neurological manifestations. Many patients with COVID-19 are found to have encephalopathy either related to potential direct viral neuroinvasion or as a consequence of multi-organ dysfunction in the context of critical illness [1] .

Over the last few decades, EEG is being utilized to a greater extent in comatose patients in intensive care units, although the effect of seizure recognition and treatment on the overall outcome is debated [2] . Seizures and status epilepticus (SE) have been reported with COVID- 19, with new onset or exacerbation of existing epilepsy and the prevalence of seizures in patients with COVID-19 is still unknown. Multiple studies have recognized electroencephalography (EEG) changes in COVID-19, utilizing short-and long-term EEG recording, though no clear EEG pattern is reliably seen in this patient population [3] . Furthermore, the effects of seizures, clinical or subclinical (electrographic), on the functional outcome in critically ill patients with COVID-19 remains unclear.

During the COVID-19 pandemic, Detroit city and Southeast Michigan were among the early epicenters in the United States [4] . We initiated a collaboration of large medical centers and academic institutions in the region to better characterize EEG findings, assess the prevalence of seizures and status epilepticus in patients with COVID-19 and the functional outcomes grouped as recovered, recovered with disability or deceased.

The primary aim of this study was to correlate the presence of seizures, status epilepticus, and specific critical care EEG patterns in hospitalized patients with COVID-19 who had EEG with their functional outcomes.

This was a retrospective, multicenter cohort study conducted through Henry Ford Health System in Detroit, MI, USA, in collaboration with three other major hospital systems in southeast Michigan that include Beaumont Royal Oak Hospital, Detroit Medical Center, and Michigan

Medicine. The study was approved by the institutional review board (IRB) of all the individual participating institutions.

A retrospective chart review was performed of all patients with COVID-19, confirmed by nasopharyngeal swab polymerase chain reaction (PCR) test, who underwent EEGs in southeast Michigan between March 12 th and May 15 th , 2020 (the first two months of the COVID-19 pandemic). EEG were requested and performed for standard indications (e.g. suspicion for seizures or altered mental status). All patients had at least 21-channel EEG electrodes recording using the international modified 10-20 system. EEGs were performed for a short duration (routine for approximately 20-30 minutes) or were continuous long-term EEGs (> 2 hours).

Patients with presumed COVID-19 who tested negative were excluded from the study. The patients were evaluated and managed at the four major hospital systems in southeast Michigan (Beaumont Royal Oak Hospital, Detroit Medical Center, Henry Ford Health System and Michigan Medicine). Hospital admission and COVID-19 testing results data was used to estimate the total number of patients hospitalized during the study period.

EEG studies were read by a clinical neurophysiology and/or epilepsy board certified neurologist at each institution and classified according to the American Clinical Neurophysiology Society (ACNS) continuous EEG terminology [5] . The EEG reports were reviewed to abstract study data and, if necessary, the EEG tracings were reviewed to confirm the reported findings. The EEG findings were categorized into general background pattern, epileptiform discharges, rhythmic and periodic patterns, and clinical seizures and subclinical seizures, according to the Salzburg criteria [6] .

Patient medical records were reviewed and data was abstracted regarding demographic information (age, sex, race), severity of COVID-19 illness (mild/moderate/severe, defined by the diagnostic criteria used per infectious disease teams: mild was only upper respiratory symptoms and/or low grade fever; moderate was with tachypnea >22 breaths per minute, need for nasal oxygen, high grade fever and leukocytosis; and severe was with endotracheal intubation and/or multiorgan failure), lowest level of consciousness during EEG recording, presence of metabolic disturbances, risk factors for seizures including COVID-19 meningitis or encephalitis, stroke in COVID-19, history of epilepsy and pre-hospitalization seizure control, neuroimaging findings (none, acute, or chronic abnormalities) and location of imaging abnormalities (cortical, white matter, basal ganglia, thalamus, cerebellum, or extra-axial), presence and duration of seizures and status epilepticus, anti-seizure medications (ASMs), indication for EEG, recorded clinical events during EEG, length of stay in the hospital, and length of stay in the intensive care unit (ICU).

The patients were followed until discharge or August 3rd, 2020 and assessed by the Glasgow Outcome Scale (GOS) [7] at discharge. In addition, the disposition (recovery and discharged home, or disabled and discharged to rehabilitation facility) was collected for all patients. Patients were divided into three recovery outcome groups (recovered, recovered with disability, and deceased). For the four patients still hospitalized, the GOS (3 severely disabled and 1 moderately disabled) on the last follow-up day for the study were all classified in the recovered with disability group.

Descriptive statistics were employed to characterize patient demographics, neuroimaging, EEG findings, and functional outcome information. These statistics included number and percentages for the categorical variables, mean and standard deviation for age and median in interquartile ranges (IQR) for the length of stay variables. For the patients with multiple EEGs performed during their hospitalization, an indication, finding, pattern or clinical seizure was coded "yes" for that individual patient if they were observed on any EEG. To assess the association between the patient characteristics and functional outcomes, Fisher's exact tests were performed for the categorical variables and Wilcoxon two sample tests were performed for age and the length of stay variables. Logistic regression analyses were used to assess the association between EEG findings and functional outcome, adjusted for severity of COVID-19 disease. Significance was set at p-value = 0.05. The analysis was performed with SAS version 9.4.

Of the 110 patients with COVID-19 who had EEG, 70 (64%) were male. and total length of stays (p=0.003) when compared to patients who recovered with disability and patients who died (Table 1 ). Table 2 ).

The EEG findings associated with the recovery were background slowing/attenuation (recovered 60% vs recovered with disability 96% vs died 96%, p<0.001) and normal background (recovered 27% vs recovered with disability 0% vs died 1%, p<0.001) ( Table 2 ). However, these differences were no longer significant after adjusting for severity of COVID-19 disease (p=0.119).

Not all the patients with COVID-19 had brain imaging studies performed during the initial surge of pandemic. Of the 110 patients, 67 patients underwent brain imaging (Head CT scan or brain showed acute changes and 5 had cortical involvement. Given the limited imaging data in our patient cohort, further correlation of findings was beyond the scope of this study.

In this large multi-center cohort study, we report outcomes of EEG findings in 110 patients with United Kingdom, respectively [10] [11] [12] . One limitation of the first study is the reliance on limited 8-channel montage, which may miss seizures. No clinical seizures were observed in a large series from China including 304 patients with COVID-19 infection, however EEG was not obtained in any of these patients [13] . On the other hand, the last series reported the occurrence of electrographic seizures in 7-25% of monitored patients [14] [15] [16] [17] consistent with the findings in our cohort (electrographic seizures in 11% of patients and SE in 7% of patients). These rates also match the reported rates of electrographic seizures in the setting of sepsis due to various etiologies which range from 11-17% [18, 19] . There is no evidence so far indicating any greater increase in electrographic seizures specifically with COVID-19 infection.

Similar to previous series, background slowing or attenuation was the most common EEG finding in our cohort, noted in 91% of patients. This was followed by focal slowing or attenuation, observed in 27% of patients. These findings align with previously reported findings from multiple case series [2, [10] [11] [12] [14] [15] [16] [17] . Multiple etiologies can cause diffuse EEG slowing including hypoxia, toxic, metabolic and medication effect such as from anesthetics. Both GPDs with triphasic morphology and GRDA, seen in 21% and 18% or our cohort, respectively, are patterns most commonly seen in the setting of metabolic encephalopathy, though there have been few reports of association between triphasic wave pattern and nonconvulsive status epilepticus [20] [21] [22] [23] [24] [25] . Meanwhile, sporadic interictal epileptiform discharges were noted in 14% of patients, which is largely in concordance with most reported rates in COVID-19 patients, apart from Galanopoulou et al.'s [10] report of occurrence of epileptiform discharges in 40.6% of patients.

However, one major limitation of that study is the reliance on limited channel EEG recordings in the majority of patients. Most of the recorded discharges in their study were bilateral symmetric frontal discharges (which may be confused with eye movement artifacts on limited channel recordings), and no seizures were recorded in any of their patients despite the frequent occurrence of epileptiform discharges [26] . 

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We would like to thank all the EEG technologists, our health care heroes, at the four hospital