Myriam Abdennadher, MD, Aneeta Saxena, MD
Seizures and Electroencephalogram
- Clinical seizure: subjective symptoms or objective signs due to abnormal excessive or synchronous neuronal activity in the brain .
- Electrographic (subclinical) seizure: electrographic activity apparent only on electroencephalography (EEG) with definitive neurologic examination correlate
- Clinical seizures manifest as behavioral, subjective, or objective signs and symptoms, while subclinical seizures may not have clear clinical signs but rather associated with altered mental state.
- Incidence of clinical and subclinical seizures in patients with COVID-19 patients is unknown.
- Seizures are observed with other types of coronavirus infections. Previous studies on different types of coronavirus found that 6 to 50% of affected children have seizures [2,3]
- Subclinical seizures occur in 10% of critically ill patients and are only identified through EEG 
- One study of a cohort of 214 patients with confirmed COVID19 patients in Wuhan, China, found impaired consciousness in 17.2% of patients; severely affected patients being more affected (14.8% vs 2.4%) . Another study suggests that 5% of patients will become critically ill .
- Seizures have been reported in COVID-19 patients, 2 out of 214 patients in one series  and one patient described in a case of meningo-encephalitis . In one case, focal status epilepticus was the presenting clinical feature of COVID-19 .
- One study of a cohort of 58 severely ill patients with confirmed COVID-19 in Strasbourg, France, reported neurologic findings in 14% on admission to ICU and in 67% after withholding sedation and neuromuscular blockade. EEG showed nonspecific changes in 8 patients who were recorded 
- Unknown in COVID19
- Metabolic derangements and inflammatory response may cause seizures.
- Hypotheses include:
- Direct central nervous system by the virus via direct neurotropic mechanisms i.e. transcribial route via the olfactory bulb (peripheral nervous system)  or hematogenous route via spike protein S1 that enables interaction with CNS ACE2 receptors 
- Novel amino acid substitution in the hemagglutinin gene of influenza A virus 
- Fever alone seemed less likely to be the cause for seizures in other types of coronavirus infections 
- All EEG orders for patients with confirmed or suspected COVID19 must be discussed with EEG service attending prior to ordering test and/or contacting EEG technician.
- All of the below proposed management steps are suggested and can be decided in conjunction with the neuro-critical care attending or the neurology inpatient attending.
- Evaluate for metabolic derangements possibly causing or precipitating seizures, as stated in the Encephalopathy protocol:
- “Evaluate for metabolic etiologies of encephalopathy with complete blood count, coagulation studies, electrolyte panel, and examination of calcium, magnesium, phosphate, glucose, blood urea nitrogen, creatinine, bilirubin, liver enzymes, ammonia, serum osmolality, and arterial blood gases, as metabolic derangements may be common in SARS-CoV2 infected patients”.
- Evaluate for substance intoxication or withdrawal by
Uurine and serum drug screen.
- Obtain neurology e-consult or televisit in case of seizure or suspected seizure.
- Manage acute tonic-clonic seizures (generalized convulsion) and acute convulsive status epilepticus per standard of care :
- Be aware of other organ involvement that may affect antiepileptic drug (AED) use. For patients with liver dysfunction, consider brivaracetam, lacosamide, Levetiracetam, brivaracetam or zonisamide. The EEG service attending physician is available for consultation regarding AED selection.
- Consider continuous EEG for patients with altered mental state with discussion with EEG service attending.
- Consider discontinuation of EEG when EEG interpretation confirms the absence of electrographic seizures or EEG patterns suggestive of imminent seizures (ictal-interictal continuum), typically 48 hours of recording in obtunded or comatose patients and 24 hours of recording in others.
- The 2014 Definition of Epilepsy: A perspective for patients and caregivers. International League Against Epilepsy
- Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X, Li Y, Hu B. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China.JAMA Neurol. 2020 Apr 10
- Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, Ueno M, Sakata H, Kondo K, Myose N, Nakao A, Takeda M, Haro H, Inoue O, Suzuki-Inoue K, Kubokawa K, Ogihara S, Sasaki T, Kinouchi H, Kojin H, Ito M, Onishi H, Shimizu T, Sasaki Y, Enomoto N, Ishihara H, Furuya S, Yamamoto T, Shimada S. A first Case of Meningitis/Encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis. 2020 Apr 3.
- Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, Collange O, Boulay C, Fafi-Kremer S, Ohana M, Anheim M, Meziani F. Neurologic Features in Severe SARS-CoV-2 Infection. N Engl J Med. 2020 Apr 15.
- Yuanyuan Li , Haipeng Li, Ruyan Fan, Bo Wen, Jian Zhang, Xiaoying Cao, Chengwu Wang, Zhanyi Song, Shuochi Li, Xiaojie Li, Xinjun Lv, Xiaowang Qu, Renbin Huang, Wenpei Liu. Coronavirus Infections in the Central Nervous System and Respiratory Tract Show Distinct Features in Hospitalized Children. Intervirology 2016, 59 (3), 163-169.
- Lau SK, Woo PC, Yip CC, Tse H, Tsoi HW, Cheng VC, Lee P, Tang BS, Cheung CH, Lee RA, So LY, Lau YL, Chan KH, Yuen KY. Coronavirus HKU1 and other coronavirus infections in Hong Kong. J Clin Microbiol. 2006 Jun;44(6):2063-71.
- Oddo M, Carrera E, Claassen J, et al. Continuous electroencephalography in the medical intensive care unit. Crit. Care Med. 2009Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X, Li Y, Hu B. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020 Apr 10
- Mao, L., Wang, M., Chen, S., He, Q., Chang, J., Hong, C., Zhou, Y., Wang, D., Li, Y., Jin, H., and Hu, B. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study. medRxiv, 2020.02.22.20026500 (accessed on 2020-02-28).
- Vollono C, Rollo E, Romozzi M, Frisullo G, Servidei S, Borghetti A, Calabresi P. Focal status epilepticus as unique clinical feature of COVID-19: A case report. Seizure. 2020 Apr 21;78:109-112.
- Guan W-J, Ni Z-Y, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med. 2020
- Li Y-C, Bai W-Z, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may be at least partially responsible for the respiratory failure of COVID-19 patients. J. Med. Virol. 2020
- Tassorelli C, Mojoli F, Baldanti F, Bruno R, Benazzo M. COVID-19: what if the brain had a role in causing the deaths? Eur J Neurol. 2020 Apr 25.
- Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chem Neurosci 2020. Mar 13.
- Mori SI, Nagashima M, Sasaki Y, Mori K, Tabei Y, Yoshida Y, Yamazaki K, Hirata I, Sekine H, Ito T, Suzuki S. A novel amino acid substitution at the receptor-binding site on the hemagglutinin of H3N2 influenza A viruses isolated from 6 cases with acute encephalopathy during the 1997-1998 season in Tokyo. Arch Virol. 1999; 144(1):147-55.
- Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016 Jan-Feb; 16(1): 48–61.