Electroencephalographic Abnormalities are Common in COVID-19 and are Associated with Outcomes
Lu Lin MD, PhD
Beth Israel Deaconess Medical Center, Department of Neurology, Harvard Medical School, Boston, MA
Search for more papers by this authorAbrar Al-Faraj MD
Boston Medical Center, Department of Neurology, Boston, MA
Shared second authorship.
Search for more papers by this authorNeishay Ayub MD
Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA
Shared second authorship.
Search for more papers by this authorPablo Bravo MD
Department of Neurology, Yale University, New Haven, CT
Shared second authorship.
Search for more papers by this authorSudeshna Das PhD
Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA
Shared second authorship.
Search for more papers by this authorLorenzo Ferlini MD
Hôspital Erasme, Département de Neurologie, Université Libre de Bruxelles, Bruxelles, Belgium
Shared second authorship.
Search for more papers by this authorIoannis Karakis MD, PhD
Department of Neurology, Emory University, Atlanta, GA
Shared second authorship.
Search for more papers by this authorJong Woo Lee MD, PhD
Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, , MA
Shared second authorship.
Search for more papers by this authorShibani S. Mukerji MD, PhD
Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA
Shared second authorship.
Search for more papers by this authorChristopher R. Newey DO, MS
Department of Neurology, Cleveland Clinic, Cleveland, OH
Shared second authorship.
Search for more papers by this authorJay Pathmanathan MD
Department of Neurology, University of Pennsylvania, Philadelphia, PA
Shared second authorship.
Search for more papers by this authorMyriam Abdennadher MD
Boston Medical Center, Department of Neurology, Boston, MA
Search for more papers by this authorCharles Casassa MD
Beth Israel Deaconess Medical Center, Department of Neurology, Harvard Medical School, Boston, MA
Search for more papers by this authorNicolas Gaspard MD, PhD
Department of Neurology, Yale University, New Haven, CT
Hôspital Erasme, Département de Neurologie, Université Libre de Bruxelles, Bruxelles, Belgium
Search for more papers by this authorDaniel M. Goldenholz MD, PhD
Beth Israel Deaconess Medical Center, Department of Neurology, Harvard Medical School, Boston, MA
Search for more papers by this authorEmily J. Gilmore MD
Department of Neurology, Yale University, New Haven, CT
Search for more papers by this authorJin Jing PhD
Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA
Search for more papers by this authorJennifer A. Kim MD, PhD
Department of Neurology, Yale University, New Haven, CT
Search for more papers by this authorEyal Y. Kimchi MD, PhD
Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA
Search for more papers by this authorHarshad S. Ladha MD
Department of Neurology, Emory University, Atlanta, GA
Search for more papers by this authorSteven Tobochnik MD
Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, , MA
Search for more papers by this authorSahar Zafar MD
Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA
Search for more papers by this authorLawrence J. Hirsch MD
Department of Neurology, Yale University, New Haven, CT
Search for more papers by this authorCorresponding Author
M. Brandon Westover MD, PhD
Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA
Address correspondence to Dr Westover, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114. E-mail: [email protected]
Dr Shafi, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215. E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Mouhsin M. Shafi MD, PhD
Beth Israel Deaconess Medical Center, Department of Neurology, Harvard Medical School, Boston, MA
Address correspondence to Dr Westover, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114. E-mail: [email protected]
Dr Shafi, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215. E-mail: [email protected]
Search for more papers by this authorLu Lin MD, PhD
Beth Israel Deaconess Medical Center, Department of Neurology, Harvard Medical School, Boston, MA
Search for more papers by this authorAbrar Al-Faraj MD
Boston Medical Center, Department of Neurology, Boston, MA
Shared second authorship.
Search for more papers by this authorNeishay Ayub MD
Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA
Shared second authorship.
Search for more papers by this authorPablo Bravo MD
Department of Neurology, Yale University, New Haven, CT
Shared second authorship.
Search for more papers by this authorSudeshna Das PhD
Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA
Shared second authorship.
Search for more papers by this authorLorenzo Ferlini MD
Hôspital Erasme, Département de Neurologie, Université Libre de Bruxelles, Bruxelles, Belgium
Shared second authorship.
Search for more papers by this authorIoannis Karakis MD, PhD
Department of Neurology, Emory University, Atlanta, GA
Shared second authorship.
Search for more papers by this authorJong Woo Lee MD, PhD
Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, , MA
Shared second authorship.
Search for more papers by this authorShibani S. Mukerji MD, PhD
Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA
Shared second authorship.
Search for more papers by this authorChristopher R. Newey DO, MS
Department of Neurology, Cleveland Clinic, Cleveland, OH
Shared second authorship.
Search for more papers by this authorJay Pathmanathan MD
Department of Neurology, University of Pennsylvania, Philadelphia, PA
Shared second authorship.
Search for more papers by this authorMyriam Abdennadher MD
Boston Medical Center, Department of Neurology, Boston, MA
Search for more papers by this authorCharles Casassa MD
Beth Israel Deaconess Medical Center, Department of Neurology, Harvard Medical School, Boston, MA
Search for more papers by this authorNicolas Gaspard MD, PhD
Department of Neurology, Yale University, New Haven, CT
Hôspital Erasme, Département de Neurologie, Université Libre de Bruxelles, Bruxelles, Belgium
Search for more papers by this authorDaniel M. Goldenholz MD, PhD
Beth Israel Deaconess Medical Center, Department of Neurology, Harvard Medical School, Boston, MA
Search for more papers by this authorEmily J. Gilmore MD
Department of Neurology, Yale University, New Haven, CT
Search for more papers by this authorJin Jing PhD
Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA
Search for more papers by this authorJennifer A. Kim MD, PhD
Department of Neurology, Yale University, New Haven, CT
Search for more papers by this authorEyal Y. Kimchi MD, PhD
Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA
Search for more papers by this authorHarshad S. Ladha MD
Department of Neurology, Emory University, Atlanta, GA
Search for more papers by this authorSteven Tobochnik MD
Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, , MA
Search for more papers by this authorSahar Zafar MD
Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA
Search for more papers by this authorLawrence J. Hirsch MD
Department of Neurology, Yale University, New Haven, CT
Search for more papers by this authorCorresponding Author
M. Brandon Westover MD, PhD
Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA
Address correspondence to Dr Westover, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114. E-mail: [email protected]
Dr Shafi, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215. E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Mouhsin M. Shafi MD, PhD
Beth Israel Deaconess Medical Center, Department of Neurology, Harvard Medical School, Boston, MA
Address correspondence to Dr Westover, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114. E-mail: [email protected]
Dr Shafi, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215. E-mail: [email protected]
Search for more papers by this authorAbstract
Objective
The aim was to determine the prevalence and risk factors for electrographic seizures and other electroencephalographic (EEG) patterns in patients with Coronavirus disease 2019 (COVID-19) undergoing clinically indicated continuous electroencephalogram (cEEG) monitoring and to assess whether EEG findings are associated with outcomes.
Methods
We identified 197 patients with COVID-19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns. Multivariate Cox proportional hazards analysis assessed the relationship between EEG patterns and clinical outcomes.
Results
Electrographic seizures were detected in 19 (9.6%) patients, including nonconvulsive status epilepticus (NCSE) in 11 (5.6%). Epileptiform abnormalities (either ictal or interictal) were present in 96 (48.7%). Preceding clinical seizures during hospitalization were associated with both electrographic seizures (36.4% in those with vs 8.1% in those without prior clinical seizures, odds ratio [OR] 6.51, p = 0.01) and NCSE (27.3% vs 4.3%, OR 8.34, p = 0.01). A pre-existing intracranial lesion on neuroimaging was associated with NCSE (14.3% vs 3.7%; OR 4.33, p = 0.02). In multivariate analysis of outcomes, electrographic seizures were an independent predictor of in-hospital mortality (hazard ratio [HR] 4.07 [1.44–11.51], p < 0.01). In competing risks analysis, hospital length of stay increased in the presence of NCSE (30 day proportion discharged with vs without NCSE: HR 0.21 [0.03–0.33] vs 0.43 [0.36–0.49]).
Interpretation
This multicenter retrospective cohort study demonstrates that seizures and other epileptiform abnormalities are common in patients with COVID-19 undergoing clinically indicated cEEG and are associated with adverse clinical outcomes. ANN NEUROL 2021;89:872–883
Potential Conflicts of Interest
Nothing to report.
References
- 1 World Health Organization. COVID-19 weekly epidemiological update - 2 February. 2021.
- 2Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395: 1054–1062. https://doi.org/10.1016/S0140-6736(20)30566-3.
- 3Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020; 77: 683–690.
- 4Helms J, Kremer S, Merdji H, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med 2020; 382: 2268–2270.
- 5Moriguchi T, Harii N, Goto J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 2020; 94: 55–58. https://doi.org/10.1016/j.ijid.2020.03.062.
- 6Hepburn M, Mullaguri N, George P, et al. Acute symptomatic seizures in critically ill patients with COVID-19: is there an association? Neurocrit Care 2021; 34: 139–143.
- 7Somani S, Pati S, Gaston T, et al. De novo status Epilepticus in patients with COVID-19. Ann Clin Transl Neurol 2020; 7: 1240–1244.
- 8Lu L, Xiong W, Liu D, et al. New-onset acute symptomatic seizure and risk factors in Corona virus disease 2019: a retrospective multicenter study. Epilepsia 2020; 61: e49–e53.
- 9Claassen J, Mayer SA, Kowalski RG, et al. Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. Neurology 2004; 62: 1743–1748.
- 10Westover MB, Shafi MM, Bianchi MT, et al. The probability of seizures during EEG monitoring in critically ill adults. Clin Neurophysiol 2015; 126: 463–471. https://doi.org/10.1016/j.clinph.2014.05.037.
- 11Ruiz AR, Vlachy J, Lee JW, et al. Association of periodic and rhythmic electroencephalographic patterns with seizures in critically ill patients. JAMA Neurol 2017; 74: 181–188.
- 12Abend NS, Arndt DH, Carpenter JL, et al. Electrographic seizures in pediatric ICU patients: cohort study of risk factors and mortality. Neurology 2013; 81: 383–391.
- 13Payne ET, Zhao XY, Frndova H, et al. Seizure burden is independently associated with short term outcome in critically ill children. Brain 2014; 137: 1429–1438.
- 14Wagenman KL, Blake TP, Sanchez SM, et al. Electrographic status epilepticus and long-term outcome in critically ill children. Neurology 2014; 82: 396–404.
- 15De Marchis GM, Pugin D, Meyers E, et al. Seizure burden in subarachnoid hemorrhage associated with functional and cognitive outcome. Neurology 2016; 86: 253–260.
- 16Zafar SF, Postma EN, Biswal S, et al. Effect of epileptiform abnormality burden on neurologic outcome and antiepileptic drug management after subarachnoid hemorrhage. Clin Neurophysiol 2018; 129: 2219–2227. https://doi.org/10.1016/j.clinph.2018.08.015.
- 17Tabaeizadeh M, Aboul Nour H, Shoukat M, et al. Burden of Epileptiform activity predicts discharge neurologic outcomes in severe acute ischemic stroke. Neurocrit Care 2020; 32: 697–706. https://doi.org/10.1007/s12028-020-00944-0.
- 18Herman ST, Abend NS, Bleck TP, et al. Consensus statement on continuous EEG in critically ill adults and children, part I: indications. J Clin Neurophysiol 2015; 32: 87–95.
- 19Pellinen J, Carroll E, Friedman D, et al. Continuous EEG findings in patients with COVID-19 infection admitted to a New York academic hospital system. Epilepsia 2020; 61: 2097–2105.
- 20Hirsch LJ, Laroche SM, Gaspard N, et al. American clinical neurophysiology society's standardized critical care EEG terminology: 2012 version. J Clin Neurophysiol 2013; 30: 1–27.
- 21Gaspard N, Hirsch LJ, LaRoche SM, et al. Interrater agreement for critical care EEG terminology. Epilepsia 2014; 55: 1366–1373.
- 22Beniczky S, Hirsch LJ, Kaplan PW, et al. Unified EEG terminology and criteria for nonconvulsive status epilepticus. Epilepsia 2013; 54: 28–29.
- 23Vakulenko-Lagun B, Magdamo C, Charpignon M-L, Bang Zheng MA, Das S. causalCmprsk: nonparametric and cox-based estimation of average treatment effects in competing risks. R package version 1.0.0. 2020.Available at: https://github.com/Bella2001/causalCmprsk
- 24Oddo M, Carrera E, Claassen J, et al. Continuous electroencephalography in the medical intensive care unit. Crit Care Med 2009; 37: 2051–2056.
- 25Gilmore EJ, Gaspard N, Choi HA, et al. Acute brain failure in severe sepsis: a prospective study in the medical intensive care unit utilizing continuous EEG monitoring. Intensive Care Med 2015; 41: 686–694.
- 26Kamel H, Betjemann JP, Navi BB, et al. Diagnostic yield of electroencephalography in the medical and surgical intensive care unit. Neurocrit Care 2013; 19: 336–341.
- 27Viarasilpa T, Panyavachiraporn N, Osman G, et al. Electrographic seizures in patients with acute encephalitis. Neurocrit Care 2019; 30: 207–215.
Citing Literature
