Journal of Pediatric Neurology 2022; 20(05): 310-318
DOI: 10.1055/s-0042-1751265
Review Article

Cerebrovascular Complications in Pediatric Patients with COVID-19 Infection

Thymur Ali Chaudhry
1   Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
,
Figen Palabiyik
2   Department of Pediatric Radiology, Health Science University, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
,
Sarah J. Moum
3   Department of Medical Imaging, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, United States
› Author Affiliations

Abstract

Since the onset of the coronavirus disease 2019 pandemic, a variety of neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in patients, of which one of the most concerning is stroke. This review aims to summarize the current literature and evolving understanding of pediatric cerebrovascular complications in the setting of SARS-CoV-2.



Publication History

Received: 01 June 2022

Accepted: 01 June 2022

Article published online:
02 August 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Mallick AA, Ganesan V, Kirkham FJ. et al. Childhood arterial ischaemic stroke incidence, presenting features, and risk factors: a prospective population-based study. Lancet Neurol 2014; 13 (01) 35-43
  • 2 Mittal SO, ThatiGanganna S, Kuhns B, Strbian D, Sundararajan S. Acute ischemic stroke in pediatric patients. Stroke 2015; 46 (02) e32-e34
  • 3 LaRovere KL, Riggs BJ, Poussaint TY. et al; Overcoming COVID-19 Investigators. Neurologic involvement in children and adolescents hospitalized in the United States for COVID-19 or multisystem inflammatory syndrome. JAMA Neurol 2021; 78 (05) 536-547
  • 4 Ray STJ, Abdel-Mannan O, Sa M. et al; CoroNerve study group. Neurological manifestations of SARS-CoV-2 infection in hospitalised children and adolescents in the UK: a prospective national cohort study. Lancet Child Adolesc Health 2021; 5 (09) 631-641
  • 5 Tsze DS, Valente JH. Pediatric stroke: a review. Emerg Med Int 2011; 2011: 734506
  • 6 Ferriero DM, Fullerton HJ, Bernard TJ. et al; American Heart Association Stroke Council and Council on Cardiovascular and Stroke Nursing. Management of stroke in neonates and children: a scientific statement from the American Heart Association/American Stroke Association. Stroke 2019; 50 (03) e51-e96
  • 7 Siracusa L, Cascio A, Giordano S. et al. Neurological complications in pediatric patients with SARS-CoV-2 infection: a systematic review of the literature. Ital J Pediatr 2021; 47 (01) 123
  • 8 Beslow LA, Linds AB, Fox CK. et al; International Pediatric Stroke Study Group. Pediatric ischemic stroke: an infrequent complication of SARS-CoV-2. Ann Neurol 2021; 89 (04) 657-665
  • 9 Oxley TJ, Mocco J, Majidi S. et al. Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med 2020; 382 (20) e60
  • 10 Mao L, Jin H, Wang M. et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020; 77 (06) 683-690
  • 11 Yaghi S, Ishida K, Torres J. et al. SARS-CoV-2 and stroke in a New York healthcare system. Stroke 2020; 51 (07) 2002-2011
  • 12 Rothstein A, Oldridge O, Schwennesen H, Do D, Cucchiara BL. Acute cerebrovascular events in hospitalized COVID-19 patients. Stroke 2020; 51 (09) e219-e222
  • 13 Siegler JE, Cardona P, Arenillas JF. et al. Cerebrovascular events and outcomes in hospitalized patients with COVID-19: the SVIN COVID-19 multinational registry. Int J Stroke 2021; 16 (04) 437-447
  • 14 Centers for Disease Control and Prevention. . (2020). Demographic trends of COVID-19 cases and deaths in the US reported to CDC. COVID data tracker. Accessed 12 March 2022 at: https://covid.cdc.gov/covid-data-tracker/#demographics
  • 15 Mirzaee SMM, Gonçalves FG, Mohammadifard M, Tavakoli SM, Vossough A. Focal cerebral arteriopathy in a pediatric patient with COVID-19. Radiology 2020; 297 (02) E274-E275
  • 16 Tiwari L, Shekhar S, Bansal A, Kumar S. COVID-19 associated arterial ischaemic stroke and multisystem inflammatory syndrome in children: a case report. Lancet Child Adolesc Health 2021; 5 (01) 88-90
  • 17 Shen MY, Dugue R, Maldonado-Soto AR, Thakur KT, Zyskind I, Vargas WS. Acute ischemic stroke in a pediatric patient with known exposure to COVID-19 and positive serology. Pediatr Neurol 2021; 116: 39-40
  • 18 Appavu B, Deng D, Dowling MM. et al. Arteritis and large vessel occlusive strokes in children after COVID-19 infection. Pediatrics 2021; 147 (03) e2020023440
  • 19 Lehman LL, Beslow LA, Steinlin M, Kossorotoff M, Mackay MT. What will improve pediatric acute stroke care?. Stroke 2019; 50 (02) 249-256
  • 20 Fullerton HJ, Wu YW, Zhao S, Johnston SC. Risk of stroke in children: ethnic and gender disparities. Neurology 2003; 61 (02) 189-194
  • 21 Oleske DM, Cheng X, Jeong A, Arndt TJ. Pediatric acute ischemic stroke by age-group: a systematic review and meta-analysis of published studies and hospitalization records. Neuroepidemiology 2021; 55 (05) 331-341
  • 22 Abou-Ismail MY, Diamond A, Kapoor S, Arafah Y, Nayak L. The hypercoagulable state in COVID-19: incidence, pathophysiology, and management. Thromb Res 2020; 194: 101-115
  • 23 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; 11 (07) 995-998
  • 24 Miller EH, Namale VS, Kim C. et al. Cerebrospinal analysis in patients with COVID-19. Open Forum Infect Dis 2020; 7 (11) ofaa50
  • 25 Lewis A, Frontera J, Placantonakis DG. et al. Cerebrospinal fluid in COVID-19: a systematic review of the literature. J Neurol Sci 2021; 421: 117316
  • 26 Al Saiegh F, Ghosh R, Leibold A. et al. Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke. J Neurol Neurosurg Psychiatry 2020; 91 (08) 846-848
  • 27 Bikdeli B, Madhavan MV, Jimenez D. et al; Global COVID-19 Thrombosis Collaborative Group, Endorsed by the ISTH, NATF, ESVM, and the IUA, Supported by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and followup: JACC state-of-the-art review. J Am Coll Cardiol 2020; 75 (23) 2950-2973
  • 28 O'Loughlin L, Alvarez Toledo N, Budrie L, Waechter R, Rayner J. A systematic review of severe neurological manifestations in pediatric patients with coexisting SARS-CoV-2 infection. Neurol Int 2021; 13 (03) 410-427
  • 29 Schober ME, Robertson CL, Wainwright MS, Roa JD, Fink EL. COVID-19 and the pediatric nervous system: global collaboration to meet a global need. Neurocrit Care 2021; 35 (02) 283-290
  • 30 Sharma C, Ganigara M, Galeotti C. et al. Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison. Nat Rev Rheumatol 2021; 17 (12) 731-748
  • 31 Feldstein LR, Rose EB, Horwitz SM. et al; Overcoming COVID-19 Investigators, CDC COVID-19 Response Team. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med 2020; 383 (04) 334-346
  • 32 Haidar MA, Shakkour Z, Reslan MA. et al. SARS-CoV-2 involvement in central nervous system tissue damage. Neural Regen Res 2022; 17 (06) 1228-1239
  • 33 Matschke J, Lütgehetmann M, Hagel C. et al. Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. Lancet Neurol 2020; 19 (11) 919-929
  • 34 Buzhdygan TP, DeOre BJ, Baldwin-Leclair A. et al. The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood-brain barrier. Neurobiol Dis 2020; 146: 105131
  • 35 Khosravi B, Moradveisi B, Abedini M, Behzadi S, Karimi A. Stroke in a child with SARS-CoV-2 infection: a case report. eNeurologicalSci 2021; 23: 100345
  • 36 Becker RC. COVID-19-associated vasculitis and vasculopathy. J Thromb Thrombolysis 2020; 50 (03) 499-511
  • 37 Iadecola C, Anrather J, Kamel H. Effects of COVID-19 on the nervous system. Cell 2020; 183 (01) 16-27.e1
  • 38 Lou M, Yuan D, Liao S, Tong L, Li J. Potential mechanisms of cerebrovascular diseases in COVID-19 patients. J Neurovirol 2021; 27 (01) 35-51
  • 39 Lindan CE, Mankad K, Ram D. et al; ASPNR PECOBIG Collaborator Group. Neuroimaging manifestations in children with SARS-CoV-2 infection: a multinational, multicentre collaborative study. Lancet Child Adolesc Health 2021; 5 (03) 167-177
  • 40 Ippolito Bastidas H, Márquez-Pérez T, García-Salido A. et al. Cerebral venous sinus thrombosis in a pediatric patient with COVID-19. Neurol Clin Pract 2021; 11 (02) e208-e210
  • 41 de Marcellus C, Dupic L, Roux CJ. et al. Case report: cerebrovascular events associated with bacterial and SARS-CoV-2 infections in an adolescent. Front Neurol 2021; 12: 606617
  • 42 Reiff DD, Meyer CG, Marlin B, Mannion ML. New onset ANCA-associated vasculitis in an adolescent during an acute COVID-19 infection: a case report. BMC Pediatr 2021; 21 (01) 333
  • 43 Fireizen Y, Shahriary C, Imperial ME, Randhawa I, Nianiaris N, Ovunc B. Pediatric P-ANCA vasculitis following COVID-19. Pediatr Pulmonol 2021; 56 (10) 3422-3424
  • 44 Hoskins B, Keeven N, Dang M, Keller E, Nagpal R. A child with COVID-19 and immunoglobulin A vasculitis. Pediatr Ann 2021; 50 (01) e44-e48
  • 45 Orman G, Desai NK, Kralik SF. et al. Neuroimaging offers low yield in children positive for SARS-CoV-2. AJNR Am J Neuroradiol 2021; 42 (05) 951-954
  • 46 Wintermark M, Hills NK, DeVeber GA. et al; VIPS Investigators. Clinical and imaging characteristics of arteriopathy subtypes in children with arterial ischemic stroke: results of the VIPS study. AJNR Am J Neuroradiol 2017; 38 (11) 2172-2179
  • 47 Fullerton HJ, Wintermark M, Hills NK. et al; VIPS Investigators. Risk of recurrent arterial ischemic stroke in childhood: a prospective international study. Stroke 2016; 47 (01) 53-59
  • 48 Mackay MT, Wiznitzer M, Benedict SL, Lee KJ, Deveber GA, Ganesan V. International Pediatric Stroke Study Group. Arterial ischemic stroke risk factors: the International Pediatric Stroke Study. Ann Neurol 2011; 69 (01) 130-140
  • 49 Roach ES, Golomb MR, Adams R. et al; American Heart Association Stroke Council. Council on Cardiovascular Disease in the Young. Management of stroke in infants and children: a scientific statement from a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young. Stroke 2008; 39 (09) 2644-2691
  • 50 Fullerton HJ, Elkind MS, Barkovich AJ. et al. The Vascular effects of Infection in Pediatric Stroke (VIPS) Study. J Child Neurol 2011; 26 (09) 1101-1110
  • 51 Fullerton HJ, Hills NK, Elkind MS. et al; VIPS Investigators. Infection, vaccination, and childhood arterial ischemic stroke: results of the VIPS study. Neurology 2015; 85 (17) 1459-1466
  • 52 Wintermark M, Hills NK, deVeber GA. et al; VIPS Investigators. Arteriopathy diagnosis in childhood arterial ischemic stroke: results of the vascular effects of infection in pediatric stroke study. Stroke 2014; 45 (12) 3597-3605
  • 53 Gulko E, Overby P, Ali S, Mehta H, Al-Mufti F, Gomes W. Vessel wall enhancement and focal cerebral arteriopathy in a pediatric patient with acute infarct and COVID-19 infection. AJNR Am J Neuroradiol 2020; 41 (12) 2348-2350
  • 54 Foster CH, Vargas AJ, Wells E, Keating RF, Magge SN. Cerebral vasculopathy and strokes in a child with COVID-19 antibodies: illustrative case. J Neurosurg Case Lessons 2021; 2 (03) 21160
  • 55 Poisson KE, Zygmunt A, Leino D. et al. Lethal pediatric cerebral vasculitis triggered by severe acute respiratory syndrome coronavirus 2. Pediatr Neurol 2022; 127: 1-5
  • 56 Salik I, Jacoby M. Carotid artery dissection and hemorrhagic stroke in the setting of multisystem inflammatory syndrome in children. Cureus 2021; 13 (03) e13640
  • 57 Munoz AC, Tasayco J, Morales W. et al. High incidence of stroke and mortality in pediatric critical care patients with COVID-19 in Peru [published online ahead of print, May 3, 2021]. Pediatr Res DOI: 10.1038/s41390-021-01547-x.
  • 58 Sánchez-Morales AE, Urrutia-Osorio M, Camacho-Mendoza E. et al. Neurological manifestations temporally associated with SARS-CoV-2 infection in pediatric patients in Mexico. Childs Nerv Syst 2021; 37 (07) 2305-2312
  • 59 Jillella DV, Philbrook B, Ortolani E. et al. Successful endovascular therapy in COVID-19 associated pediatric ischemic stroke. J Stroke Cerebrovasc Dis 2021; 30 (12) 106152
  • 60 Al Haboob AA. Miller Fischer and posterior reversible encephalopathy syndromes post COVID-19 infection. Neurosciences (Riyadh) 2021; 26 (03) 295-299
  • 61 Korkmazer B, Ozogul M, Hikmat E. et al. Posterior reversible encephalopathy syndrome in a pediatric COVID-19 patient. Pediatr Infect Dis J 2021; 40 (06) e240-e242
  • 62 Basirjafari S, Rafiee M, Shahhosseini B, Mohammadi M, Neshin SAS, Zarei M. Association of pediatric COVID-19 and subarachnoid hemorrhage. J Med Virol 2021; 93 (02) 658-660
  • 63 Kaushik S, Ahluwalia N, Gangadharan S. et al. ECMO support in SARS-CoV2 multisystem inflammatory syndrome in children in a child. Perfusion 2021; 36 (05) 524-528
  • 64 Kihira S, Morgenstern PF, Raynes H, Naidich TP, Belani P. Fatal cerebral infarct in a child with COVID-19. Pediatr Radiol 2020; 50 (10) 1479-1480
  • 65 Schupper AJ, Yaeger KA, Morgenstern PF. Neurological manifestations of pediatric multi-system inflammatory syndrome potentially associated with COVID-19. Childs Nerv Syst 2020; 36 (08) 1579-1580