Neurological issues in children with COVID-19

Lin, Jieru E.; Asfour, Arsenoi; Sewell, Taylor B.; Hooe, Benjamin S.; Pryce, Patrice; Earley, Chelsea; Shen, Min; Kerner-Rossi, Mallory; Thakur, Kiran T.; Vargas, Wendy; Silver, Wendy; Geneslaw, Andrew

doi:10.1016/j.neulet.2020.135567

Cited by 205 publications

(254 citation statements)

References 71 publications

(68 reference statements)

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“…The integrity of the blood-brain barrier may be disrupted by cytokine-driven injury without CNS direct invasion by the virus [ 59 ]. Moreover, the hyperinflammatory state can lead to a pro-coagulable state: initial vasculitis causes the disruption of vascular integrity, the exposure of thrombogenic basement membrane and, finally, the activation of the clotting cascade [ 9 ]. Children with MIS-C exhibit alteration of inflammatory biomarkers (procalcitonin, CRP, fibrinogen, ferritin, D-dimer, IL-6), that suggest a possible involvement of the immune system in the pathogenesis of this syndrome [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

“…Regarding neurological involvement in COVID-19, severe neurological manifestations (encephalopathy, meningoencephalitis, stroke, seizure, Guillain-Barré syndrome, acute disseminated encephalomyelitis) have been reported mainly in adults [ 7 , 8 ], while a few cases have been described in children. Two mechanisms were proposed to explain how SARS-CoV-2 may induce neurological damage: direct viral infection of nervous system through ACE2 receptors and inflammatory injury mediated by cytokines release [ 9 ]; in the latter case, neurological manifestations may be part of a MIS-C [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Neurological complications in pediatric patients with SARS-CoV-2 infection: a systematic review of the literature

Siracusa¹,

Cascio

Giordano³

et al. 2021

Ital J Pediatr

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Objectives To describe clinical characteristics, laboratory tests, radiological data and outcome of pediatric cases with SARS-CoV-2 infection complicated by neurological involvement. Study design A computerized search was conducted using PubMed. An article was considered eligible if it reported data on pediatric patient(s) with neurological involvement related to SARS-CoV-2 infection. We also described a case of an acute disseminated encephalomyelitis (ADEM) in a 5-year-old girl with SARS-CoV-2 infection: this case was also included in the systematic review. Results Forty-four articles reporting 59 cases of neurological manifestations in pediatric patients were included in our review. Most (32/59) cases occurred in the course of a multisystem inflammatory syndrome in children (MIS-C). Neurological disorders secondary to cerebrovascular involvement were reported in 10 cases: 4 children with an ischemic stroke, 3 with intracerebral hemorrhage, 1 with a cerebral sinus venous thrombosis, 1 with a subarachnoid hemorrhage, 1 with multiple diffuse microhemorrhages. Reversible splenial lesions were recognized in 9 cases, benign intracranial hypertension in 4 patients, meningoencephalitis in 4 cases, autoimmune encephalitis in 1 girl, cranial nerves impairment in 2 patients and transverse myelitis in 1 case. Five cases had Guillain-Barré syndrome (GBS) and two, including ours, had ADEM. Radiological investigations were performed in almost all cases (45/60): the most recurrent radiological finding was a signal change in the splenium of the corpus callosum. The presence of SARS-CoV-2 viral nucleic acid in the cerebrospinal fluid was proved only in 2 cases. The outcome was favorable in almost all, except in 5 cases. Conclusions Our research highlights the large range of neurological manifestations and their presumed pathogenic pathways associated with SARS-CoV-2 infection in children. Nervous system involvement could be isolated, developing during COVID-19 or after its recovery, or arise in the context of a MIS-C. The most reported neurological manifestations are cerebrovascular accidents, reversible splenial lesions, GBS, benign intracranial hypertension, meningoencephalitis; ADEM is also a possible complication, as we observed in our patient. Further studies are required to investigate all the neurological complications of SARS-CoV-2 infection and their underlying pathogenic mechanism.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neurological complications in pediatric patients with SARS-CoV-2 infection: a systematic review of the literature

Siracusa¹,

Cascio

Giordano³

et al. 2021

Ital J Pediatr

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“…In adult cases, infection due to COVID-19, venous sinus thrombus, encephalomyelitis, Guillain-Barré syndrome, Miller Fisher syndrome, myelitis, and PRES have been described in the literature (17,18). The neurological findings of COVID 19 and MIS-C in children have been attributed to direct neuronal damage, vascular endothelial damage, and inflammatory and autoimmune damage (19). The neuroradiological findings reported in MIS-C cases in the literature are from a multicenter study (20) and case reports (21)(22)(23) and remain limited.…”

Section: Discussionmentioning

confidence: 99%

Imaging of Multisystem Inflammatory Disease in Children (MIS-C) Associated With COVID-19

et al. 2021

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…A majority had a favorable outcome. More studies are needed in order to elucidate the viral mechanisms of SARS-CoV-2 in CSF.However, most of the neurological studies in COVID-19 are based on the adult population and mainly report neurological symptoms or complications (13-17).Similarly, when reviews are done in the pediatric population, these studies also focus heavily on the pathogenesis or clinical manifestations in the neurological department (18)(19)(20). Analysis of lumbar puncture, a functional diagnostic study that may help differentiate the etiology of infections in the nervous system, is also heavily done in the adult populations (21-23).Besides theories of pathogenesis and clinical manifestations or complications in neurological pediatric COVID-19 cases, there is still a lack of other clinical ndings such as brain imaging, laboratory values, or cerebrospinal uid (CSF) analysis, which may characterize pediatric patients with neurological manifestations in the setting of COVID-19 infection.…”

mentioning

confidence: 99%

“…Similarly, when reviews are done in the pediatric population, these studies also focus heavily on the pathogenesis or clinical manifestations in the neurological department (18)(19)(20). Analysis of lumbar puncture, a functional diagnostic study that may help differentiate the etiology of infections in the nervous system, is also heavily done in the adult populations (21-23).…”

mentioning

confidence: 99%

Analysis of Neurological Clinical Manifestations and Diagnostic Workups in Pediatric COVID-19: A Systematic Review

Octavius

Chandra

Wijaya

et al. 2021

Preprint

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Background While numerous studies report neurological manifestations of COVID-19, there are fewer reviews in the pediatric population, focusing solely on the manifestations.Aim This systematic review aims to describe the clinical manifestations and laboratory findings of pediatric patients with neurological manifestations of COVID-19.Methods We searched Pubmed, Science Direct, Medline, Scielo, Medrxiv, Research Square, SSRN, and Biorxiv with the appropriate keywords. Inclusion criteria include new-onset neurological manifestations with a time correlation to the confirmed COVID-19 with a further diagnostic work-up. We use The Joanna Briggs Institute's (JBI) essential evaluation checklist and Newcastle Ottawa Quality Assessment Scale (NOS) to evaluate the quality of the studies. The protocol for this systematic review has been registered in The international Prospective Register of Systematic Review (PROSPERO) database (CRD42021228671).Results 31 articles were ultimately chosen with 42 patients (26 male) included in this systematic review. The neurological diagnosis was mostly of the CNS classification (38/42) with a predomination of brain disorders (22/38). Most patients had lymphopenia, elevated C-reactive protein, procalcitonin, ferritin, creatinine kinase, blood urea nitrogen, D-dimer, and erythrocyte sedimentation rate. In the CNS group, CSF monocytes (55%; 11–80%), CSF polymorphonuclear (PMN) cells (15%; 0–96%), CSF red blood cells (282 cells/mm3; 2-4000 cells/mm3), and opening pressure (34.5 cm/H2O; 25–100 cm/H2O) were elevated.Conclusions Our systematic review found that neurological manifestations in COVID-19 occurred more often in males, with a majority being CNS disorders. A majority had a favorable outcome. More studies are needed in order to elucidate the viral mechanisms of SARS-CoV-2 in CSF.

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Neurological issues in children with COVID-19

Cited by 205 publications

References 71 publications

Neurological complications in pediatric patients with SARS-CoV-2 infection: a systematic review of the literature

Neurological complications in pediatric patients with SARS-CoV-2 infection: a systematic review of the literature

Imaging of Multisystem Inflammatory Disease in Children (MIS-C) Associated With COVID-19

Analysis of Neurological Clinical Manifestations and Diagnostic Workups in Pediatric COVID-19: A Systematic Review

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