新型冠状病毒感染伴发癫痫及其发病机制与脑电图改变_Journal of Epilepsy

Authors：

 殷全喜

菏泽市第三人民医院神经电生理室（菏泽 274031）;

Corresponding author：

殷全喜, Email: hzyqx@126.com

Keywords：

新型冠状病毒感染; 癫痫; 脑电图; 癫痫样放电; 发病机制

DOI：

10.7507/2096-0247.202205008

Video：

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新型冠状病毒感染（Corona virus disease 2019，COVID-19）是一种由冠状病毒（SARS-CoV-2）导致的新型传染性疾病。关于COVID-19与癫痫之间的关系，有研究认为癫痫发作和COVID-19无明显关系；但也有不少学者认为，癫痫发作是COVID-19的继发症状，甚至是早期症状。COVID-19患者中癫痫发作发生率为0.08%～1.9%。COVID-19出现癫痫发作的直接发病机制是，SARS-COV-2能够直接进入并感染中枢神经系统，引起脑膜炎和脑炎，从而引起癫痫发作。间接发病机制包括：中枢神经系统炎症（细胞因子风暴）、血-脑屏障的破坏、凝血异常、脑卒中、线粒体功能异常、电解质紊乱。新发作和频发癫痫发作的患者可能导致预后更差，死亡率更高。COVID-19伴发癫痫患者中脑电图（Electroencephalogram，EEG）改变的主要表现为：基本节律不同程度的慢化、节律性慢活动、癫痫样放电（包括周期性放电和散在性棘波、尖波等）。癫痫患者EEG的异常部位主要分布在额叶，然而，异常EEG表现并无特异性。

Citation： 殷全喜. 新型冠状病毒感染伴发癫痫及其发病机制与脑电图改变. Journal of Epilepsy, 2023, 9(1): 53-58. doi: 10.7507/2096-0247.202205008 Copy

1.	Kuroda N. Epilepsy and COVID-19: associations and important considerations. Epilepsy & Behavior, 2020, 108: 107122.
2.	Rodrigo-Armenteros P, Uterga-Valiente JM, Zabala-Del-Arco J, et al. Non-convulsive status epilepticus in a patient with COVID-19 infection. Clinical Neurophysiology, 2020, 131(11): 2588-2590.
3.	Besnard S, Nardin C, Lyon E, et al. Electroencephalographic abnormalites in SARS-CoV-2 patients. Frontiers in Neurology. 2020, 11: 582794.
4.	Kubota T, Kuroda N. Exacerbation of neurological symptoms and COVID-19 severity in patients with preexisting neurological disorders and COVID-19: a systematic review. Clinical Neurology and Neurosurgery, 2021, 200: 106349.
5.	Asadi-Pooya AA, Simani L, Shahisavandi M, et al. COVID-19, de novo seizures, and epilepsy: a systematic review. Neurological Sciences, 2021, 42(2): 415-431.
6.	Mao L, Jin HJ, Wang MD, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurology, 2020, 77(6): 683-690.
7.	Asadi-Pooya AA. Seizures associated with coronavirus infections. Seizure, 2020, 79: 49-52.
8.	Ding H, Yin SY, Cheng YH, et al. Neurologic manifestations of nonhospitalized patients with COVID-19 in Wuhan, China. MedComm, 2020, 1(2): 1-4.
9.	Pan RG, Zhang QR, Anthony SM , et al. Oligodendrocytes that survive acute coronavirus infection induce prolonged inflammatory responses in the CNS. Proceedings of the National Academy of Sciences, 2020, 117(27): 15902-15910.
10.	Sugrue W, Yozawitz E, Mehler MF, et al. Response: epileptic discharges in acutely ill patients investigated for SARS-CoV-2/COVID-19 and the absence of evidence. Epilepsia Open, 2020, 5: 618-621.
11.	Kuroda N. Epilepsy and COVID-19: updated evidence and narrative review. Epilepsy & Behavior, 2021, 116: 107785.
12.	Danoun OA, Zillgitt A, Hill C, et al. Outcomes of seizures, status epilepticus, and EEG findings in critically ill patient with COVID-19. Epilepsy & Behavior, 2021, 118: 107923.
13.	Cabezudo-García P, Lundahl N, Petersen C, et al. Incidence and case fatality rate of COVID-19 in patients with active epilepsy. Neurology. 2020, 95 (10): e1417-e1425.
14.	Emami A, Fadakar N, Akbari A, et al. Seizure in patients with COVID-19. Neurological Sciences, 2020, 41(11): 3057-3061.
15.	Anand P, Al-Faraj A, Sader E, et al. Seizure as the presenting symptom of COVID-19: a retrospective case series. Epilepsy & Behavior, 2020, 112: 107335.
16.	Sun MX, Ruan XY, Li YY, et al. Clinical characteristics of 30 COVID-19 patients with epilepsy: a retrospective study in Wuhan. International Journal of Infectious Diseases, 2021, 103: 647-653.
17.	Ji WJ, Huh KG, Kang MS, et al. Effect of underlying comorbidities on the infection and severity of covid-19 in Korea: a nationwide case-control study. Journal of Korean Medical Science, 2020, 35(25): e237.
18.	Lu L, Xiong WX, Liu D, et al. New onset acute symptomatic seizure and risk factors in coronavirus disease 2019: a retrospective multicenter study. Epilepsia, 2020, 61(6): e49-e53.
19.	Granata T, Bisulli F, Arzimanoglou A, et al. Did the COVID-19 pandemic silence the needs of people with epilepsy? Epileptic Disord, 2020, 22 (4): 439-442.
20.	Zeng C, Meng HM, Zhu YL, et al. Correlation of seizure increase and COVID-19 outbreak in adult patients with epilepsy: findings and suggestions from a nationwide multi-centre survey in China. Seizure, 2021, 88: 102-108.
21.	Huang SS, Wu CM, Jia YC. et al. COVID-19 outbreak:the impact of stress on seizures in patients with epilepsy. Epilepsia, 2020, 61(9): 1884-1893.
22.	Assenza G, Lanzone J, Brigo F, et al. Epilepsy care in the time of COVID-19 pandemic in Italy: risk factors for seizure worsening. Frontiers in Neurology, 2020, 11: 737.
23.	Alkhotani A, Siddiqui MI, Almuntashri F, et al. The effect of COVID-19 pandemic on seizure control and self-reported stress on patient with epilepsy. Epilepsy & Behavior, 2020, 112: 107323.
24.	Lin L, Al-Faraj A, Ayub N, et al. Electroencephalographic abnormalities are common in COVID-19 and are associated with outcomes. American Neurological Association, 2021, 89(5): 872-882.
25.	Pellinen 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(10): 2097-2105.
26.	Hepburn M, Mullaguri N, George P, et al. Acute symptomatic seizures in Critically Ⅲ patients with COVID-19: is there an association? Neurocritical Care, 2021, 34(1): 139-143.
27.	Vollonoa C, Rollob E, Romozzi M, et al. Focal status epilepticus as unique clinical feature of COVID-19: a case report. Seizure, 2020, 78: 109-112.
28.	Louis S, Dhawan A, Newey C, et al. Continuous electroencephalography characteristics and acute symptomatic seizures in COVID-19 patients. Clinical Neurophysiology, 2020, 131(11): 2651-2656.
29.	Carroll E, Melmed KR, Frontera J, et al. Cerebrospinal fluid findings in patients with seizure in the setting of COVID-19: a review of the literature. Seizure, 2021, 89: 99-106.
30.	Saeed A, Shorafa E. Status epilepticus as a first presentation of COVID-19 infection in a 3 years old boy: case report and review the literature. IDCases, 2020, 22: e00942.
31.	Niguet JP, Tortuyaux R, Garcia B, et al. Neurophysiological findings and their prognostic value in critical COVID-19 patients: an observational study. Clinical Neurophysiology, 2021, 132(5): 1009-1017.
32.	Narula N, Joseph R, Katyal N, et al. Seizure and COVID-19: association and review of potential mechanism. Neurology, Psychiatry and Brain Research, 2020, 38: 49-53.
33.	Aristea SG, Ferastraoaru V, Daniel JC, et al. EEG findings in acutely ill patients investigated for SARS-CoV-2/COVID-19: a small case series preliminary report. Epilepsia Open, 2020, 5: 314-324.
34.	Antony AR, Haneef Zulfi. Systematic review of EEG findings in 617 patients diagnosed with COVID-19. Seizure, 2020, 83: 234-241.
35.	Haddad S, Tayyar R, Risch L, et al. Encephalopathy and seizure activity in a COVID-19 well controlled HIV patient. IDCases, 2020, 21: e00814.
36.	Lambrecq V, Hanin A, Pharm D, et al. Association of clinical, biological, and brain magnetic resonance imaging findings with electroencephalographic findings for patients with COVID-19. JAMA Network Open, 2021, 4(3): e211489.
37.	Sohal S, Mansur M. COVID-19 presenting with seizures. IDCases, 2020, 20: e00782.
38.	Ayub N, Cohen J, Jing J, et al. Clinical electroencephalography findings and considerations in hospitalized patients with coronavirus SARS-CoV-2. Neurohospitalist, 2021, 11(3): 204-213.
39.	Chen WD, Toprani S, Werbaneth K, et al. Status epilepticus and other EEG findings in patients with COVID-19: a case series. Seizure, 2020, 81: 198-200.
40.	Skorin I, Carrillo R, Carmen P, et al. EEG findings and clinical prognostic factors associated with mortality in a prospective cohort of inpatients with COVID-19. Seizure, 2020, 83: 1-4.
41.	Scullen T, Keen J, Mathkour M, et al. Coronavirus 2019 (COVID-19) associated encephalopathies and cerebrovascular disease: the new orleans experience. World Neurosurgery, 2020, 141: e437-e446.
42.	Roberto KT, Adrian IE, Marc LL, et al. Electroencephalographic findings in COVID-19 patients: a systematic review. Seizure, 2020, 82: 17-22.
43.	Vellieux G, Sonneville R, Vledouts S, et al. COVID-19-associated neurological manifestations: an emerging electroencephalographic literature. Frontiers in Physiology, 2021, 11: 622466.
44.	Kubota T, Gajera PK, Kuroda N. Meta-analysis of EEG findings in patients with COVID-19. Epilepsy & Behavior, 2021, 115: 107682.
45.	Zeynep BG, Atakli HD. Effect of the COVID-19 pandemic on drug compliance and stigmatization in patients with epilepsy. Epilepsy & Behavior, 2021, 114: 107610.
46.	Gelisse P, Rossetti AO, Genton P , et al. How to carry out and interpret EEG recordings in COVID-19 patients in ICU? Clinical Neurophysiology, 2020, 131(8): 2023-2031.
47.	Balloy G, Leclair-Visonneau L, Yann PP, et al. Non-lesional status epilepticus in a patient with coronavirus disease 2019. Clinical Neurophysiology, 2020, 131(8): 2059-2061.
48.	Vohora D, Jain S, Tripathi Manjari, et al. COVID-19 and seizures: is there a link? Epilepsia, 2020, 61(8): 1840–1853.
49.	Nikbakht F, Mohammadkhanizadeh A, Mohammadi E, et al. How does the COVID-19 cause seizure and epilepsy in patients? The potential mechanisms. Multiple Sclerosis and Related Disorders, 2020, 46: 102535.
50.	Pati S, Toth E, Chaitanya G. Quantitative EEG markers to prognosticate critically ill patients with COVID-19: a retrospective cohort study. Clinical Neurophysiology, 2020, 131(8): 1824-1826.

1. Kuroda N. Epilepsy and COVID-19: associations and important considerations. Epilepsy & Behavior, 2020, 108: 107122.
2. Rodrigo-Armenteros P, Uterga-Valiente JM, Zabala-Del-Arco J, et al. Non-convulsive status epilepticus in a patient with COVID-19 infection. Clinical Neurophysiology, 2020, 131(11): 2588-2590.
3. Besnard S, Nardin C, Lyon E, et al. Electroencephalographic abnormalites in SARS-CoV-2 patients. Frontiers in Neurology. 2020, 11: 582794.
4. Kubota T, Kuroda N. Exacerbation of neurological symptoms and COVID-19 severity in patients with preexisting neurological disorders and COVID-19: a systematic review. Clinical Neurology and Neurosurgery, 2021, 200: 106349.
5. Asadi-Pooya AA, Simani L, Shahisavandi M, et al. COVID-19, de novo seizures, and epilepsy: a systematic review. Neurological Sciences, 2021, 42(2): 415-431.
6. Mao L, Jin HJ, Wang MD, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurology, 2020, 77(6): 683-690.
7. Asadi-Pooya AA. Seizures associated with coronavirus infections. Seizure, 2020, 79: 49-52.
8. Ding H, Yin SY, Cheng YH, et al. Neurologic manifestations of nonhospitalized patients with COVID-19 in Wuhan, China. MedComm, 2020, 1(2): 1-4.
9. Pan RG, Zhang QR, Anthony SM , et al. Oligodendrocytes that survive acute coronavirus infection induce prolonged inflammatory responses in the CNS. Proceedings of the National Academy of Sciences, 2020, 117(27): 15902-15910.
10. Sugrue W, Yozawitz E, Mehler MF, et al. Response: epileptic discharges in acutely ill patients investigated for SARS-CoV-2/COVID-19 and the absence of evidence. Epilepsia Open, 2020, 5: 618-621.
11. Kuroda N. Epilepsy and COVID-19: updated evidence and narrative review. Epilepsy & Behavior, 2021, 116: 107785.
12. Danoun OA, Zillgitt A, Hill C, et al. Outcomes of seizures, status epilepticus, and EEG findings in critically ill patient with COVID-19. Epilepsy & Behavior, 2021, 118: 107923.
13. Cabezudo-García P, Lundahl N, Petersen C, et al. Incidence and case fatality rate of COVID-19 in patients with active epilepsy. Neurology. 2020, 95 (10): e1417-e1425.
14. Emami A, Fadakar N, Akbari A, et al. Seizure in patients with COVID-19. Neurological Sciences, 2020, 41(11): 3057-3061.
15. Anand P, Al-Faraj A, Sader E, et al. Seizure as the presenting symptom of COVID-19: a retrospective case series. Epilepsy & Behavior, 2020, 112: 107335.
16. Sun MX, Ruan XY, Li YY, et al. Clinical characteristics of 30 COVID-19 patients with epilepsy: a retrospective study in Wuhan. International Journal of Infectious Diseases, 2021, 103: 647-653.
17. Ji WJ, Huh KG, Kang MS, et al. Effect of underlying comorbidities on the infection and severity of covid-19 in Korea: a nationwide case-control study. Journal of Korean Medical Science, 2020, 35(25): e237.
18. Lu L, Xiong WX, Liu D, et al. New onset acute symptomatic seizure and risk factors in coronavirus disease 2019: a retrospective multicenter study. Epilepsia, 2020, 61(6): e49-e53.
19. Granata T, Bisulli F, Arzimanoglou A, et al. Did the COVID-19 pandemic silence the needs of people with epilepsy? Epileptic Disord, 2020, 22 (4): 439-442.
20. Zeng C, Meng HM, Zhu YL, et al. Correlation of seizure increase and COVID-19 outbreak in adult patients with epilepsy: findings and suggestions from a nationwide multi-centre survey in China. Seizure, 2021, 88: 102-108.
21. Huang SS, Wu CM, Jia YC. et al. COVID-19 outbreak:the impact of stress on seizures in patients with epilepsy. Epilepsia, 2020, 61(9): 1884-1893.
22. Assenza G, Lanzone J, Brigo F, et al. Epilepsy care in the time of COVID-19 pandemic in Italy: risk factors for seizure worsening. Frontiers in Neurology, 2020, 11: 737.
23. Alkhotani A, Siddiqui MI, Almuntashri F, et al. The effect of COVID-19 pandemic on seizure control and self-reported stress on patient with epilepsy. Epilepsy & Behavior, 2020, 112: 107323.
24. Lin L, Al-Faraj A, Ayub N, et al. Electroencephalographic abnormalities are common in COVID-19 and are associated with outcomes. American Neurological Association, 2021, 89(5): 872-882.
25. Pellinen 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(10): 2097-2105.
26. Hepburn M, Mullaguri N, George P, et al. Acute symptomatic seizures in Critically Ⅲ patients with COVID-19: is there an association? Neurocritical Care, 2021, 34(1): 139-143.
27. Vollonoa C, Rollob E, Romozzi M, et al. Focal status epilepticus as unique clinical feature of COVID-19: a case report. Seizure, 2020, 78: 109-112.
28. Louis S, Dhawan A, Newey C, et al. Continuous electroencephalography characteristics and acute symptomatic seizures in COVID-19 patients. Clinical Neurophysiology, 2020, 131(11): 2651-2656.
29. Carroll E, Melmed KR, Frontera J, et al. Cerebrospinal fluid findings in patients with seizure in the setting of COVID-19: a review of the literature. Seizure, 2021, 89: 99-106.
30. Saeed A, Shorafa E. Status epilepticus as a first presentation of COVID-19 infection in a 3 years old boy: case report and review the literature. IDCases, 2020, 22: e00942.
31. Niguet JP, Tortuyaux R, Garcia B, et al. Neurophysiological findings and their prognostic value in critical COVID-19 patients: an observational study. Clinical Neurophysiology, 2021, 132(5): 1009-1017.
32. Narula N, Joseph R, Katyal N, et al. Seizure and COVID-19: association and review of potential mechanism. Neurology, Psychiatry and Brain Research, 2020, 38: 49-53.
33. Aristea SG, Ferastraoaru V, Daniel JC, et al. EEG findings in acutely ill patients investigated for SARS-CoV-2/COVID-19: a small case series preliminary report. Epilepsia Open, 2020, 5: 314-324.
34. Antony AR, Haneef Zulfi. Systematic review of EEG findings in 617 patients diagnosed with COVID-19. Seizure, 2020, 83: 234-241.
35. Haddad S, Tayyar R, Risch L, et al. Encephalopathy and seizure activity in a COVID-19 well controlled HIV patient. IDCases, 2020, 21: e00814.
36. Lambrecq V, Hanin A, Pharm D, et al. Association of clinical, biological, and brain magnetic resonance imaging findings with electroencephalographic findings for patients with COVID-19. JAMA Network Open, 2021, 4(3): e211489.
37. Sohal S, Mansur M. COVID-19 presenting with seizures. IDCases, 2020, 20: e00782.
38. Ayub N, Cohen J, Jing J, et al. Clinical electroencephalography findings and considerations in hospitalized patients with coronavirus SARS-CoV-2. Neurohospitalist, 2021, 11(3): 204-213.
39. Chen WD, Toprani S, Werbaneth K, et al. Status epilepticus and other EEG findings in patients with COVID-19: a case series. Seizure, 2020, 81: 198-200.
40. Skorin I, Carrillo R, Carmen P, et al. EEG findings and clinical prognostic factors associated with mortality in a prospective cohort of inpatients with COVID-19. Seizure, 2020, 83: 1-4.
41. Scullen T, Keen J, Mathkour M, et al. Coronavirus 2019 (COVID-19) associated encephalopathies and cerebrovascular disease: the new orleans experience. World Neurosurgery, 2020, 141: e437-e446.
42. Roberto KT, Adrian IE, Marc LL, et al. Electroencephalographic findings in COVID-19 patients: a systematic review. Seizure, 2020, 82: 17-22.
43. Vellieux G, Sonneville R, Vledouts S, et al. COVID-19-associated neurological manifestations: an emerging electroencephalographic literature. Frontiers in Physiology, 2021, 11: 622466.
44. Kubota T, Gajera PK, Kuroda N. Meta-analysis of EEG findings in patients with COVID-19. Epilepsy & Behavior, 2021, 115: 107682.
45. Zeynep BG, Atakli HD. Effect of the COVID-19 pandemic on drug compliance and stigmatization in patients with epilepsy. Epilepsy & Behavior, 2021, 114: 107610.
46. Gelisse P, Rossetti AO, Genton P , et al. How to carry out and interpret EEG recordings in COVID-19 patients in ICU? Clinical Neurophysiology, 2020, 131(8): 2023-2031.
47. Balloy G, Leclair-Visonneau L, Yann PP, et al. Non-lesional status epilepticus in a patient with coronavirus disease 2019. Clinical Neurophysiology, 2020, 131(8): 2059-2061.
48. Vohora D, Jain S, Tripathi Manjari, et al. COVID-19 and seizures: is there a link? Epilepsia, 2020, 61(8): 1840–1853.
49. Nikbakht F, Mohammadkhanizadeh A, Mohammadi E, et al. How does the COVID-19 cause seizure and epilepsy in patients? The potential mechanisms. Multiple Sclerosis and Related Disorders, 2020, 46: 102535.
50. Pati S, Toth E, Chaitanya G. Quantitative EEG markers to prognosticate critically ill patients with COVID-19: a retrospective cohort study. Clinical Neurophysiology, 2020, 131(8): 1824-1826.

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新型冠状病毒感染伴发癫痫及其发病机制与脑电图改变

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