Top

Published in:

01-03-2022 | SARS-CoV-2 | Review

SARS-CoV-2-associated acute disseminated encephalomyelitis: a systematic review of the literature

Authors: Yumin Wang, Yanchao Wang, Liang Huo, Qiang Li, Jichao Chen, Hongquan Wang

Published in: Journal of Neurology | Issue 3/2022

Abstract

The literature on cases of acute disseminated encephalomyelitis (ADEM) associated with SARS-CoV-2 infection has been rapidly increasing. However, the specific clinical features of ADEM associated with SARS-CoV-2 (SARS-CoV-2-ADEM) have not been previously evaluated. We screened all articles resulting from a search of PubMed and Web of Science databases looking for reports of ADEM published between December 01, 2019, and June 5, 2021. Of the 48 ADEM cases identified from 37 studies, 34 (71%) had ADEM while 14 (29%) were of AHLE. RT-PCR for SARS-CoV-2 was positive in 83% (n = 19) of patients. 26 patients (54%) were male, and 18 patients (38%) were female, with a male to female sex ratio of 1.4:1; median age was 44 (1.4–71) years. 9 patients (19%, 9/48) were children. Of the 9 children patients, their median age was 9 years (range 1.4–13 years), 6 patients (67%) were female, and 2 patients (22%) were male, with a female to male sex ratio of 3:1.39 patients (81%) was performed CSF analysis. PCR for SARS-CoV-2 tested positive in 3 patients (14%, 3/22) on CSF sample. 31 (64%) of patients had a poor outcome on discharge from hospital. Five (10%) patients died in hospital. Compared to classic ADEM, SARS-CoV-2-ADEM have a more longer duration between the onset of the antecedent infective symptoms and the start of ADEM symptoms, the older age distribution of the patients, relatively poor outcome, a lower full recovery rate, a more frequently brain lesions involved the periventricular white matter and corpus callosum, and less frequently affected the deep gray matter. Taken together, the present comprehensive review reveals that although rare, ADEM can be associated with SARS-CoV-2 infection. SARS-CoV-2-ADEM seems to share most features of classic ADEM, with moderate discrepancies from the classical ADEM.

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395:497–506CrossRefPubMedPubMedCentral

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 (2020) Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 77:683–690PubMed

Camargo-Martínez W, Lozada-Martínez I, Escobar-Collazos A, Navarro-Coronado A, Moscote-Salazar L, Pacheco-Hernández A, Janjua T, Bosque-Varela P (2021) Post-COVID 19 neurological syndrome: implications for sequelae’s treatment. J Clin Neurosci 88:219–225PubMedPubMedCentral

Elmashala A, Chopra S, Garg A (2020) The neurologic manifestations of coronavirus disease 2019. J Neurol Res 10:107–112PubMedPubMedCentral

Gaddam S (2020) Implications of COVID-19 in neurological disorders. J Neurol Res 10:160–163PubMedPubMedCentral

Koralnik IJ, Tyler KL (2020) COVID-19: a global threat to the nervous system. Ann Neurol 88:1–11PubMed

Nordvig AS, Fong KT, Willey JZ, Thakur KT, Boehme AK, Vargas WS, Smith CJ, Elkind M (2021) Potential neurologic manifestations of COVID-19. Neurol Clin Pract 11:e135-135e146PubMedPubMedCentral

Li X, Wang Y, Wang H, Wang Y (2021) SARS-CoV-2-associated Guillain-Barré syndrome is a para-infectious disease. QJM. https://doi.org/10.1093/qjmed/hcab157CrossRefPubMed

Pohl D, Alper G, Van Haren K, Kornberg AJ, Lucchinetti CF, Tenembaum S, Belman AL (2016) Acute disseminated encephalomyelitis: updates on an inflammatory CNS syndrome. Neurology 87:S38-45PubMed

10.

Sriwastava S, Tandon M, Podury S, Prasad A, Wen S, Guthrie G, Kakara M, Jaiswal S, Subedi R, Elkhooly M, Lisak RP (2021) COVID-19 and neuroinflammation: a literature review of relevant neuroimaging and CSF markers in central nervous system inflammatory disorders from SARS-COV2. J Neurol. https://doi.org/10.1007/s00415-021-10611-9CrossRefPubMedPubMedCentral

11.

Koh JS, De Silva DA, Quek A, Chiew HJ, Tu TM, Seet C, Hoe R, Saini M, Hui AC, Angon J, Ker JR, Yong MH, Goh Y, Yu WY, Lim T, Tan B, Ng K, Yeo L, Pang YZ, Prakash KM, Ahmad A, Thomas T, Lye D, Tan K, Umapathi T (2020) Neurology of COVID-19 in Singapore. J Neurol Sci 418:117118PubMedPubMedCentral

12.

Pilotto A, Masciocchi S, Volonghi I, Crabbio M, Magni E, De Giuli V, Caprioli F, Rifino N, Sessa M, Gennuso M, Cotelli MS, Turla M, Balducci U, Mariotto S, Ferrari S, Ciccone A, Fiacco F, Imarisio A, Risi B, Benussi A, Premi E, Focà E, Caccuri F, Leonardi M, Gasparotti R, Castelli F, Zanusso G, Pezzini A, Padovani A (2021) Clinical presentation and outcomes of severe acute respiratory syndrome coronavirus 2-related encephalitis: the ENCOVID multicenter study. J Infect Dis 223:28–37PubMed

13.

Sawlani V, Scotton S, Nader K, Jen JP, Patel M, Gokani K, Denno P, Thaller M, Englezou C, Janjua U, Bowen M, Hoskote C, Veenith T, Hassan-Smith G, Jacob S (2021) COVID-19-related intracranial imaging findings: a large single-centre experience. Clin Radiol 76:108–116PubMed

14.

Paterson RW, Brown RL, Benjamin L, Nortley R, Wiethoff S, Bharucha T, Jayaseelan DL, Kumar G, Raftopoulos RE, Zambreanu L, Vivekanandam V, Khoo A, Geraldes R, Chinthapalli K, Boyd E, Tuzlali H, Price G, Christofi G, Morrow J, McNamara P, McLoughlin B, Lim ST, Mehta PR, Levee V, Keddie S, Yong W, Trip SA, Foulkes A, Hotton G, Miller TD, Everitt AD, Carswell C, Davies N, Yoong M, Attwell D, Sreedharan J, Silber E, Schott JM, Chandratheva A, Perry RJ, Simister R, Checkley A, Longley N, Farmer SF, Carletti F, Houlihan C, Thom M, Lunn MP, Spillane J, Howard R, Vincent A, Werring DJ, Hoskote C, Jäger HR, Manji H, Zandi MS (2020) The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain 143:3104–3120PubMedPubMedCentral

15.

Zanin L, Saraceno G, Panciani PP, Renisi G, Signorini L, Migliorati K, Fontanella MM (2020) SARS-CoV-2 can induce brain and spine demyelinating lesions. Acta Neurochir (Wien) 162:1491–1494

16.

Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4:1PubMedPubMedCentral

17.

Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 350:g7647PubMed

18.

Manzo ML, Galati C, Gallo C, Santangelo G, Marino A, Guccione F, Pitino R, Raieli V (2021) ADEM post-Sars-CoV-2 infection in a pediatric patient with Fisher-Evans syndrome. Neurol Sci. https://doi.org/10.1007/s10072-021-05311-1CrossRefPubMedPubMedCentral

19.

Kumar A, Olivera A, Mueller N, Howard J, Lewis A (2020) Delayed SARS-COV-2 leukoencephalopathy without severe hypoxia. J Neurol Sci 418:117146PubMedPubMedCentral

20.

Shahmirzaei S, Naser Moghadasi A (2021) Association of COVID-19 and acute disseminated encephalomyelitis (ADEM) in the absence of pulmonary involvement. Autoimmun Rev 20:102753PubMedPubMedCentral

21.

Assunção FB, Fragoso DC, Donoso Scoppetta T, Martins Maia AC (2020) COVID-19-associated acute disseminated encephalomyelitis-like disease. AJNR Am J Neuroradiol 42:E21-23PubMed

22.

Abdi S, Ghorbani A, Fatehi F (2020) The association of SARS-CoV-2 infection and acute disseminated encephalomyelitis without prominent clinical pulmonary symptoms. J Neurol Sci 416:117001PubMedPubMedCentral

23.

Utukuri PS, Bautista A, Lignelli A, Moonis G (2020) Possible acute disseminated encephalomyelitis related to severe acute respiratory syndrome coronavirus 2 infection. AJNR Am J Neuroradiol 41:E82-82E83PubMedPubMedCentral

24.

Espíndola OM, Brandão CO, Gomes Y, Siqueira M, Soares CN, Lima M, Leite A, Torezani G, Araujo A, Silva M (2021) Cerebrospinal fluid findings in neurological diseases associated with COVID-19 and insights into mechanisms of disease development. Int J Infect Dis 102:155–162PubMed

25.

Parsons T, Banks S, Bae C, Gelber J, Alahmadi H, Tichauer M (2020) COVID-19-associated acute disseminated encephalomyelitis (ADEM). J Neurol 267:2799–2802PubMedPubMedCentral

26.

Hanafi R, Roger PA, Perin B, Kuchcinski G, Deleval N, Dallery F, Michel D, Hacein-Bey L, Pruvo JP, Outteryck O, Constans JM (2020) COVID-19 neurologic complication with CNS vasculitis-like pattern. AJNR Am J Neuroradiol 41:1384–1387PubMedPubMedCentral

27.

Walker JM, Gilbert AR, Bieniek KF, Richardson TE (2021) COVID-19 patients with CNS complications and neuropathologic features of acute disseminated encephalomyelitis and acute hemorrhagic leukoencephalopathy. J Neuropathol Exp Neurol 80:628–631PubMed

28.

Green C, Morrison H, Smith P, Golestani F, Rice C, Coulthard E, Searle J, Lyburn I (2021) Teaching neuroimages: COVID-19-associated acute disseminated encephalomyelitis with corpus callosal hemorrhage. Neurology 96:e307-307e308PubMed

29.

Yong MH, Chan Y, Liu J, Sanamandra SK, Kheok SW, Lim KC, Sewa DW (2020) A rare case of acute hemorrhagic leukoencephalitis in a covid-19 patient. J Neurol Sci 416:117035PubMedPubMedCentral

30.

Reichard RR, Kashani KB, Boire NA, Constantopoulos E, Guo Y, Lucchinetti CF (2020) Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology. Acta Neuropathol 140:1–6PubMedPubMedCentral

31.

Mehra B, Aggarwal V, Kumar P, Kundal M, Gupta D, Kumar A, Dugaya SK (2020) COVID-19-associated severe multisystem inflammatory syndrome in children with encephalopathy and neuropathy in an adolescent girl with the successful outcome: an unusual presentation. Indian J Crit Care Med 24:1276–1278PubMedPubMedCentral

32.

Zoghi A, Ramezani M, Roozbeh M, Darazam IA, Sahraian MA (2020) A case of possible atypical demyelinating event of the central nervous system following COVID-19. Mult Scler Relat Disord 44:102324PubMedPubMedCentral

33.

Novi G, Rossi T, Pedemonte E, Saitta L, Rolla C, Roccatagliata L, Inglese M, Farinini D (2020) Acute disseminated encephalomyelitis after SARS-CoV-2 infection. Neurol Neuroimmunol Neuroinflamm 7:e797PubMedPubMedCentral

34.

Vraka K, Ram D, West S, Chia W, Kurup P, Subramanian G, Tan HJ (2021) Two paediatric patients with encephalopathy and concurrent COVID-19 infection: two sides of the same coin. Case Rep Neurol Med 2021:6658000PubMedPubMedCentral

35.

Wang CX (2021) Assessment and management of acute disseminated encephalomyelitis (ADEM) in the pediatric patient. Paediatr Drugs 23:213–221PubMed

36.

Cole J, Evans E, Mwangi M, Mar S (2019) Acute disseminated encephalomyelitis in children: an updated review based on current diagnostic criteria. Pediatr Neurol 100:26–34PubMed

37.

Tenembaum S, Chamoles N, Fejerman N (2002) Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients. Neurology 59:1224–1231PubMed

38.

Atzori M, Battistella PA, Perini P, Calabrese M, Fontanin M, Laverda AM, Suppiej A, Drigo P, Grossi P, Rinaldi L, Gallo P (2009) Clinical and diagnostic aspects of multiple sclerosis and acute monophasic encephalomyelitis in pediatric patients: a single centre prospective study. Mult Scler 15:363–370PubMed

39.

Mikaeloff Y, Caridade G, Husson B, Suissa S, Tardieu M (2007) Acute disseminated encephalomyelitis cohort study: prognostic factors for relapse. Eur J Paediatr Neurol 11:90–95PubMed

40.

Alper G, Heyman R, Wang L (2009) Multiple sclerosis and acute disseminated encephalomyelitis diagnosed in children after long-term follow-up: comparison of presenting features. Dev Med Child Neurol 51:480–486PubMed

41.

de Seze J, Debouverie M, Zephir H, Lebrun C, Blanc F, Bourg V, Wiertlewski S, Pittion S, Laplaud D, Le Page E, Deschamps R, Cabre P, Pelletier J, Malikova I, Clavelou P, Jaillon V, Defer G, Labauge P, Gout O, Boulay C, Edan G, Vermersch P (2007) Acute fulminant demyelinating disease: a descriptive study of 60 patients. Arch Neurol 64:1426–1432PubMed

42.

Dale RC, de Sousa C, Chong WK, Cox TC, Harding B, Neville BG (2000) Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. Brain 123(Pt 12):2407–2422PubMed

43.

Berzero G, Cortese A, Ravaglia S, Marchioni E (2016) Diagnosis and therapy of acute disseminated encephalomyelitis and its variants. Expert Rev Neurother 16:83–101PubMed

44.

ZhR I, Boldyreva MN, Dekonenko EP, Malishev NA, Leontyeva IY, Martinenko IN, Petrukhin AS (2003) Acute disseminated encephalomyelitis in children: clinical features and HLA-DR linkage. Eur J Neurol 10:537–546

45.

Massa S, Fracchiolla A, Neglia C, Argentiero A, Esposito S (2021) Update on acute disseminated encephalomyelitis in children and adolescents. Children (Basel) 8:280

46.

Varadan B, Shankar A, Rajakumar A, Subramanian S, Sathya AC, Hakeem AR, Kalyanasundaram S (2021) Acute hemorrhagic leukoencephalitis in a COVID-19 patient-a case report with literature review. Neuroradiology 63:653–661PubMedPubMedCentral

47.

de Miranda Henriques-Souza AM, de Melo A, de Aguiar Coelho Silva Madeiro B, Freitas LF, Sampaio Rocha-Filho PA, Gonçalves FG (2021) Acute disseminated encephalomyelitis in a COVID-19 pediatric patient. Neuroradiology 63:141–145PubMed

48.

Langley L, Zeicu C, Whitton L, Pauls M (2020) Acute disseminated encephalomyelitis (ADEM) associated with COVID-19. BMJ Case Rep 13:e239597PubMed

49.

McLendon LA, Rao CK, Da Hora CC, Islamovic F, Galan FN (2021) Post-COVID-19 acute disseminated encephalomyelitis in a 17-month-old. Pediatrics 147:e2020049678PubMed

50.

Brun G, Hak JF, Coze S, Kaphan E, Carvelli J, Girard N, Stellmann JP (2020) COVID-19-White matter and globus pallidum lesions: demyelination or small-vessel vasculitis. Neurol Neuroimmunol Neuroinflamm 7:e777PubMedPubMedCentral

51.

Haqiqi A, Samuels TL, Lamb FJ, Moharrum T, Myers AE (2021) Acute haemorrhagic leukoencephalitis (Hurst disease) in severe COVID-19 infection. Brain Behav Immun Health 12:100208PubMedPubMedCentral

52.

Chalil A, Baker CS, Johnston RB, Just C, Debicki DB, Mayich MS, Bosma KJ, Steven DA (2021) Acute hemorrhagic encephalitis related to COVID-19. Neurol Clin Pract 11:e147-147e151PubMedPubMedCentral

53.

Karapanayiotides T, Geka E, Prassopoulos P, Koutroulou I, Kollaras P, Kiourtzieva E, Pourzitaki C, Veroniki F, Sintila SA, Astreinidis A, Tsivgoulis G, Grigoriadis N (2020) Concentric demyelination pattern in COVID-19-associated acute haemorrhagic leukoencephalitis: a lurking catastrophe. Brain 143:e100PubMed

54.

Handa R, Nanda S, Prasad A, Anand R, Zutshi D, Dass SK, Bedi PK, Pahuja A, Shah PK, Sharma B (2020) Covid-19-associated acute haemorrhagic leukoencephalomyelitis. Neurol Sci 41:3023–3026PubMedPubMedCentral

55.

Fitouchi S, Heger B, Kremer L, Kremer S, Ohlmann P (2020) A case of acute disseminate encephalomyelitis after SARS-CoV-2 related acute respiratory distress syndrome. J Neuroradiol. https://doi.org/10.1016/j.neurad.2020.11.001CrossRefPubMedPubMedCentral

56.

McCuddy M, Kelkar P, Zhao Y, Wicklund D (2020) Acute demyelinating encephalomyelitis (ADEM) in COVID-19 infection: a case series. Neurol India 68:1192–1195PubMed

57.

Siracusa L, Cascio A, Giordano S, Medaglia AA, Restivo GA, Pirrone I, Saia GF, Collura F, Colomba C (2021) Neurological complications in pediatric patients with SARS-CoV-2 infection: a systematic review of the literature. Ital J Pediatr 47:123PubMedPubMedCentral

58.

Kelley B, Mixis B, Beinlich B, Chagharvand S, Allen S (2021) Tumefactive acute disseminated encephalomyelitis after recent COVID-19 infection: a case report. Neurology 96(15 Supplement):2121

59.

Naik S, Bokka SK, Tareen TK, Naik S, Sagi V, Remmel K (2021) COVID-19 associated acute disseminated encephalomyelitis in adult. Neurology 96(15 Supplement):5002

60.

Gonzalez N, Lorenzo J, Wang C (2021) Refractory acute disseminated encephalomyelitis-like findings in a pediatric patient in the setting of SARS-CoV-2 with histopathology. Neurology 96(15 Supplement):4942

61.

Sahlas DJ, Miller SP, Guerin M, Veilleux M, Francis G (2000) Treatment of acute disseminated encephalomyelitis with intravenous immunoglobulin. Neurology 54:1370–1372PubMed

62.

Keegan M, Pineda AA, McClelland RL, Darby CH, Rodriguez M, Weinshenker BG (2002) Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology 58:143–146PubMed

63.

Ketelslegers IA, Visser IE, Neuteboom RF, Boon M, Catsman-Berrevoets CE, Hintzen RQ (2011) Disease course and outcome of acute disseminated encephalomyelitis is more severe in adults than in children. Mult Scler 17:441–448PubMed

Title: SARS-CoV-2-associated acute disseminated encephalomyelitis: a systematic review of the literature
Authors: Yumin Wang
Yanchao Wang
Liang Huo
Qiang Li
Jichao Chen
Hongquan Wang
Publication date: 01-03-2022
Publisher: Springer Berlin Heidelberg
Keywords: SARS-CoV-2
COVID-19
Published in: Journal of Neurology / Issue 3/2022
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-021-10771-8

2024 ASCO Annual Meeting

Springer Medicine

SARS-CoV-2-associated acute disseminated encephalomyelitis: a systematic review of the literature

Abstract

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2022

COVID-19 manifestations in people with Parkinson’s disease: a USA cohort

Gastrointestinal dysfunction in Parkinson’s disease: molecular pathology and implications of gut microbiome, probiotics, and fecal microbiota transplantation

Neuroimaging studies in persistent postural–perceptual dizziness and related disease: a systematic review

Retina thickness in atypical parkinsonism: a systematic review and meta-analysis

Susac’s syndrome as an autoimmune complication of alemtuzumab-associated immune reconstitution

Anti-CD20 therapies for multiple sclerosis: current status and future perspectives