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J Pediatr Intensive Care
DOI: 10.1055/s-0042-1757478
Original Article

The Clinical Characteristics and Prognosis of Children Presenting with New Onset Refractory Status Epilepticus in COVID-19 Related Multisystem Inflammatory Syndrome

Suman Das 
1   Department of Neurology, Bangur Institute of Neurology, Kolkata, West Bengal, India
,
Kaushani Chatterjee
2   Department of Pediatric Medicine, Dr. B.C. Roy Post Graduate Institute of Pediatric Sciences, Kolkata, West Bengal, India
,
Gobinda Mondal
2   Department of Pediatric Medicine, Dr. B.C. Roy Post Graduate Institute of Pediatric Sciences, Kolkata, West Bengal, India
,
Dilip Kumar Paul
2   Department of Pediatric Medicine, Dr. B.C. Roy Post Graduate Institute of Pediatric Sciences, Kolkata, West Bengal, India
,
Lopamudra Mishra
3   Department of Pediatric Medicine, Calcutta National Medical College, Kolkata, West Bengal, India
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Abstract

Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory process leading to multiorgan failure and shock, occurring during the acute or post-infectious stage of severe acute respiratory syndrome coronavirus (SARS-CoV-2), and has two subtypes: para-infectious and post-infectious varieties. The new onset of refractory status epilepticus has rarely been described as the presenting feature of MIS-C. This retrospective study, conducted at Dr. B.C. Roy Post Graduate Institute of Pediatric Sciences, included children hospitalized between August 1, 2020 and July 31, 2021, with new-onset refractory status epilepticus (NORSE) and subsequently diagnosed to have MIS-C. Their clinico-demographic variables, treatment courses during hospital stays, laboratory reports, radiological and electrophysiological findings, and outcomes at discharge and follow-up over 1 year were recorded. At their 12 month visits, their motor disabilities (primary) and continuation of anti-epileptic drugs, and persistence of magnetic resonance imaging (MRI) brain abnormalities (secondary) were the outcome measures. The characteristics of the patients in the para-infectious and post-infectious groups were compared using the Mann-Whitney U test for continuous variables and the Chi-square test for categorical variables. There were eight and 10 patients in groups A and B, respectively. Patients in group B had significantly higher age, more prolonged refractory status epilepticus (RSE), use of anesthetics and ventilation, and longer pediatric intensive care unit (PICU) stay, while other clinical and laboratory parameters and short and long-term outcomes were not significantly different between the two groups. Eight patients developed hemiparesis, while two had quadriparesis in the acute stage, but 15 (83%) patients had complete recovery from their motor deficits by 1 year. At 1-year follow-up, 33 and 39% of patients, respectively, had abnormal MRI and electroencephalogram (EEG). Acute disseminated encephalitis and acute leukoencephalopathy were the most commonly observed MRI abnormalities in the acute phase, with prolonged persistence of cerebritis in patients in the post-infectious group, warranting long-term immunomodulation. Combined immunotherapy with intravenous immunoglobulin and steroids was effective in the acute phase. However, long-term anti-epileptic therapy was needed in both groups.

Keywords

MIS-C - SARS-CoV-2 - NORSE - MRI - follow-up - immunomodulators


Publication History

Received: 07 August 2022

Accepted: 28 August 2022

Article published online:
11 October 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
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  • References

  • 1 Laçinel Gürlevik S, Günbey C, Ozsurekci Y. et al. Neurologic manifestations in children with COVID-19 from a tertiary center in Turkey and literature review. Eur J Paediatr Neurol 2022; 37: 139-154
    CrossrefPubMedGoogle Scholar
  • 2 Fink EL, Robertson CL, Wainwright MS. et al; Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) Investigators. Prevalence and risk factors of neurologic manifestations in hospitalized children diagnosed with acute SARS-CoV-2 or MIS-C. Pediatr Neurol 2022; 128: 33-44
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 4 Abdel-Mannan O, Eyre M, Löbel U. et al. Neurologic and radiographic findings associated with COVID-19 infection in children. JAMA Neurol 2020; 77 (11) 1440-1445
    CrossrefPubMedGoogle Scholar
  • 5 Maury A, Lyoubi A, Peiffer-Smadja N, de Broucker T, Meppiel E. Neurological manifestations associated with SARS-CoV-2 and other coronaviruses: a narrative review for clinicians. Rev Neurol (Paris) 2021; 177 (1-2): 51-64
    CrossrefPubMedGoogle Scholar
  • 6 Mishra D, Sharma S, Sankhyan N. et al; Multi-disciplinary Group on Management of Status Epilepticus in Children in India. Consensus guidelines on management of childhood convulsive status epilepticus. Indian Pediatr 2014; 51 (12) 975-990
    CrossrefPubMedGoogle Scholar
  • 7 Sahoo T, Aradhya AS, Gulla KM. International guidelines 2020 for the management of septic shock in children. Indian Pediatr 2020; 57 (07) 671-675
    CrossrefPubMedGoogle Scholar
  • 8 Ellul MA, Benjamin L, Singh B. et al. Neurological associations of COVID-19. Lancet Neurol 2020; 19 (09) 767-783
    CrossrefPubMedGoogle Scholar
  • 9 Chacko F, Rohith PS. NORSE following viral infections like COVID 19. BMH Med J 2021; 8 (04) 132-134
    PubMedGoogle Scholar
  • 10 Nawfal O, Toufaili H, Dib G, Dirani M, Beydoun A. New-onset refractory status epilepticus as an early manifestation of multisystem inflammatory syndrome in adults after COVID-19. Epilepsia 2022; 63 (05) e51-e56
    CrossrefPubMedGoogle Scholar
  • 11 Leelamani V, Ali MR. Immune responsive NORSE in a patient with COVID 19 infection. BMH Med J 2021; 8 (04) 135-137
    PubMedGoogle Scholar
  • 12 Manganotti P, Furlanis G, Ajčević M. et al. Intravenous immunoglobulin response in new-onset refractory status epilepticus (NORSE) COVID-19 adult patients. J Neurol 2021; 268 (10) 3569-3573
    CrossrefPubMedGoogle Scholar
  • 13 Dono F, Carrarini C, Russo M. et al. New-onset refractory status epilepticus (NORSE) in post SARS-CoV-2 autoimmune encephalitis: a case report. Neurol Sci 2021; 42 (01) 35-38
    CrossrefPubMedGoogle Scholar
  • 14 Carroll E, Neumann H, Aguero-Rosenfeld ME. et al. Post-COVID-19 inflammatory syndrome manifesting as refractory status epilepticus. Epilepsia 2020; 61 (10) e135-e139
    CrossrefPubMedGoogle Scholar
  • 15 Chen TH. Neurological involvement associated with COVID-19 infection in children. J Neurol Sci 2020; 418: 117096
    CrossrefPubMedGoogle Scholar
  • 16 Kwak JH, Lee SY, Choi JW. Korean Society of Kawasaki Disease. Clinical features, diagnosis, and outcomes of multisystem inflammatory syndrome in children associated with coronavirus disease 2019. Clin Exp Pediatr 2021; 64 (02) 68-75
    CrossrefPubMedGoogle Scholar
  • 17 Gupta Dch S, Chopra Md N, Singh Md A. et al. Unusual clinical manifestations and outcome of multisystem inflammatory syndrome in children (MIS-C) in a tertiary care hospital of North India. J Trop Pediatr 2021; 67 (01) fmaa127
    CrossrefPubMedGoogle Scholar
  • 18 Paterson RW, Brown RL, Benjamin L. , et al for the UCL Queen Square National Hospital for Neurology and Neurosurgery COVID-19 Study Group. The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain 2020; 143 (10) 3104-3120
    CrossrefPubMedGoogle Scholar
  • 19 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
    CrossrefPubMedGoogle Scholar
  • 20 Stoian A, Stoian M, Bajko Z. et al. Autoimmune Encephalitis in COVID-19 infection: our experience and systematic review of the literature. Biomedicines 2022; 10 (04) 774
    CrossrefPubMedGoogle Scholar
  • 21 Panciani PP, Saraceno G, Zanin L. et al. SARS-CoV-2: “Three-steps” infection model and CSF diagnostic implication. Brain Behav Immun 2020; 87: 128-129
    CrossrefPubMedGoogle Scholar
  • 22 Leven Y, Bösel J. Neurological manifestations of COVID-19 - an approach to categories of pathology. Neurol Res Pract 2021; 3 (01) 39
    CrossrefPubMedGoogle Scholar
  • 23 Patel P, DeCuir J, Abrams J, Campbell AP, Godfred-Cato S, Belay ED. Clinical characteristics of multisystem inflammatory syndrome in adults. JAMA Netw Open 2021; 4 (09) e2126456
    CrossrefPubMedGoogle Scholar
  • 24 Nakra NA, Blumberg DA, Herrera-Guerra A, Lakshminrusimha S. Multi-system inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection: review of clinical presentation, hypothetical pathogenesis, and proposed management. Children (Basel) 2020; 7 (07) 69
    PubMedGoogle Scholar
  • 25 Vogel TP, Top KA, Karatzios C. et al. Multisystem inflammatory syndrome in children and adults (MIS-C/A): case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 2021; 39 (22) 3037-3049
    CrossrefPubMedGoogle Scholar
  • 26 Zubair AS, McAlpine LS, Gardin T, Farhadian S, Kuruvilla DE, Spudich S. Neuropathogenesis and neurologic manifestations of the coronaviruses in the age of coronavirus disease 2019: a review. JAMA Neurol 2020; 77 (08) 1018-1027
    CrossrefPubMedGoogle Scholar
  • 27 Graus F, Titulaer MJ, Balu R. et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016; 15 (04) 391-404
    Google Scholar
  • 28 Ouldali N, Toubiana J, Antona D. et al; French Covid-19 Paediatric Inflammation Consortium. Association of intravenous immunoglobulins plus methylprednisolone vs immunoglobulins alone with course of fever in multisystem inflammatory syndrome in children. JAMA 2021; 325 (09) 855-864
    CrossrefPubMedGoogle Scholar
  • 29 McMurray JC, May JW, Cunningham MW, Jones OY. Multisystem inflammatory syndrome in children (MIS-C), a post-viral myocarditis and systemic vasculitis – a critical review of its pathogenesis and treatment. Front Pediatr 2020; 8: 626182
    CrossrefPubMedGoogle Scholar
  • 30 Sculier C, Barcia Aguilar C, Gaspard N. et al; pSERG. Clinical presentation of new onset refractory status epilepticus in children (the pSERG cohort). Epilepsia 2021; 62 (07) 1629-1642
    CrossrefPubMedGoogle Scholar
  • 31 Wu J, Lan X, Yan L. et al. A retrospective study of 92 children with new-onset refractory status epilepticus. Epilepsy Behav 2021; 125: 108413
    CrossrefPubMedGoogle Scholar
  • 32 Hirsch LJ, Gaspard N, van Baalen A. et al. Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions. Epilepsia 2018; 59 (04) 739-744
    CrossrefPubMedGoogle Scholar