Lethal Pediatric Cerebral Vasculitis Triggered by Severe Acute Respiratory Syndrome Coronavirus 2

Poisson, Kelsey E.; Zygmunt, A.; Leino, Daniel; Fuller, Christine; Jones, Blaise V.; Haslam, David B.; Staat, Mary Allen; Clay, Gwendolyn M.; Ting, Tracy V.; Wesselkamper, Kristen; Hallinan, Barbara; Standridge, Shannon; Day, Melissa E.; McNeal, Monica; Stevenson, Charles B.; Vawter-Lee, Marissa

doi:10.1016/j.pediatrneurol.2021.11.003

Cited by 26 publications

(39 citation statements)

References 13 publications

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“…isolated encephalitis without multisystem involvement, and even fewer cases of cerebral vasculitis in children with SARS-CoV-2. Moreover, the clinical, EEG and MRI aspects in the acute phase are rarely well detailed, with little long-term follow-up (2)(3)(4)(5). We present here a well-documented case of an acute encephalitis and cerebral vasculitis without any other organ failure in a teenager who presented consciousness impairment, focal neurological signs, cerebrospinal fluid (CSF) pleiocytosis, electroencephalogram (EEG) and magnetic resonance imaging (MRI) abnormalities associated with a COVID-19 infection.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Acute Corticosteroid Responsive Meningoencephalitis with Cerebral Vasculitis after COVID-19 Infection in a Thirteen-Year-Old

Francois¹,

Cleuziou

Vannod-Michel³

et al. 2022

Neuropediatrics

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Introduction: Various neurologic manifestations have already been described in children during or after severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) infections,. The central nervous system disorders reported in children are mainly encephalopathies during Multisystem inflammatory syndrome (MIS-C). We present here an acute meningo-encephalitis with cerebral vasculitis associated to a COVID-19 infection in a thirteen-year-old girl with a 1-year clinical, EEG and MRI follow-up. Case-report: A thirteen-year-old girl presented acute symptoms of consciousness impairment, frontal headache, hyperthermia and aphasia, with moderate lymphopenia (900/mm3),elevated C-reactive protein (CRP) (17mg/l), cerebrospinal fluid (CSF) pleiocytosis (15 cells/mm3), slow background with frontal focalization on electroencephalogram (EEG), an left frontal ischemic lesion, leptomeningeal enhancement and bilateral limbic FLAIR hyperintensity on cerebral magnetic resonance imaging (MRI). Reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV2 was positive in nasopharyngeal swab and COVID serology was positive for IgM and Ig, whereas extensive auto-immune antibody investigation was negative except for a positive low titre of anti-MOG in CSF and blood. The diagnosis of probable encephalitis associated to cerebral vasculitis after COVID infection was suggested and steroids pulse were started. She recovered within a few days. Six months laters, she had moderate clinical sequels including persistent intermittent headaches, an isolated spatial deficit and focal spikes on the EEG without argument for epilepsia. Conclusion: a teenager without previous medical history presented an acute encephalitis with leptomeningitis and vasculitis after a recent COVID-19 infection. Steroids pulse therapy allowed clinical improvement. Cerebral MRI and EEG helped diagnosis, follow-up of the encephalitis and evolution after treatment

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Section: Accepted Manuscriptmentioning

confidence: 99%

Acute Corticosteroid Responsive Meningoencephalitis with Cerebral Vasculitis after COVID-19 Infection in a Thirteen-Year-Old

Francois¹,

Cleuziou

Vannod-Michel³

et al. 2022

Neuropediatrics

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“…While we identified that as well, we further demonstrated parenchymal perivascular T-cell lymphocytic infiltrates and microglial aggregates, though sparse overall. The 8-year-old described by Poisson et al ( 9 ) raised very interesting points regarding the presumption of underlying SARS-CoV-2-related “vasculitis” as the cause of a middle cerebral artery infarct. Unfortunately, they of necessity had only biopsies of the infarcted regions during life, and on brain autopsy after 93 days described inflammation and vascular changes only within necrotic and reactive areas (which would be expected in an organizing infarct).…”

Section: Discussionmentioning

confidence: 99%

“…Neuropathologic studies are even fewer, but one identified microglial prominence and, rarely, vascular microthrombi (on postmortem needle biopsy only) ( 8 ). A singular case study described an 8-year-old who developed unilateral paresis 2 weeks following a febrile illness and underwent brain biopsies and eventual brain-only autopsy ( 9 ). Unfortunately, the described and illustrated findings from this case were complicated by limited sampling of frankly ischemic and necrotic brain sites; consequently, the authors' interpretation of “brain vasculitis” is open to question.…”

Section: Introductionmentioning

confidence: 99%

Neuropathology of Pediatric SARS-CoV-2 Infection in the Forensic Setting: Novel Application of Ex Vivo Imaging in Analysis of Brain Microvasculature

et al. 2022

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Two years into the COVID-19 pandemic, there are few published accounts of postmortem SARS-CoV-2 pathology in children. We report 8 such cases (4 infants aged 7–36 weeks, 4 children aged 5–15 years). Four underwent ex vivo magnetic resonance neuroimaging, to assist in identification of subtle lesions related to vascular compromise. All infants were found unresponsive (3 in unsafe sleeping conditions); all but 1 had recent rhinitis and/or influenza-like illness (ILI) in the family; 1 had history of sickle cell disease. Ex vivo neuroimaging in 1 case revealed white matter (WM) signal hyperintensity and diffuse exaggeration of perivascular spaces, corresponding microscopically to WM mineralization. Neurohistology in the remaining 3 infants variably encompassed WM gliosis and mineralization; brainstem gliosis; perivascular vacuolization; perivascular lymphocytes and brainstem microglia. One had ectopic hippocampal neurons (with pathogenic variant in DEPDC5). Among the children, 3 had underlying conditions (e.g., obesity, metabolic disease, autism) and all presented with ILI. Three had laboratory testing suggesting multisystem inflammatory syndrome (MIS-C). Two were hospitalized for critical care including mechanical ventilation and extracorporeal membrane oxygenation (ECMO); one (co-infected with adenovirus) developed right carotid stroke ipsilateral to the ECMO cannula and the other required surgery for an ingested foreign body. Autopsy findings included: acute lung injury in 3 (1 with microthrombi); and one each with diabetic ketoacidosis and cardiac hypertrophy; coronary and cerebral arteritis and aortitis, resembling Kawasaki disease; and neuronal storage and enlarged fatty liver. All 4 children had subtle meningoencephalitis, focally involving the brainstem. On ex vivo neuroimaging, 1 had focal pontine susceptibility with corresponding perivascular inflammation/expanded perivascular spaces on histopathology. Results suggest SARS-CoV-2 in infants may present as sudden unexpected infant death, while in older children, signs and symptoms point to severe disease. Underlying conditions may predispose to fatal outcomes. As in adults, the neuropathologic changes may be subtle, with vascular changes such as perivascular vacuolization and gliosis alongside sparse perivascular lymphocytes. Detection of subtle vascular pathology is enhanced by ex vivo neuroimaging. Additional analysis of the peripheral/autonomic nervous system and investigation of co-infection in children with COVID-19 is necessary to understand risk for cardiovascular collapse/sudden death.

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“…However, a biopsy can be done on selected cases as an invasive procedure. Previous reports showed cranial vasculitis in COVID-19 patients, most of them were diagnosed by neuroimaging studies, some also had biopsy ( 8 , 9 ). Inflammatory processes, dysregulated cytokine cascade autoimmunity, possibly had a role in cerebrovascular events in patients with COVID-19 ( 10 ).…”

mentioning

confidence: 99%

Neurologic manifestations in children with COVID-19

Gürlevik

Günbey

Özsürekçi

et al. 2022

European Journal of Paediatric Neurology

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Lethal Pediatric Cerebral Vasculitis Triggered by Severe Acute Respiratory Syndrome Coronavirus 2

Cited by 26 publications

References 13 publications

Acute Corticosteroid Responsive Meningoencephalitis with Cerebral Vasculitis after COVID-19 Infection in a Thirteen-Year-Old

Acute Corticosteroid Responsive Meningoencephalitis with Cerebral Vasculitis after COVID-19 Infection in a Thirteen-Year-Old

Neuropathology of Pediatric SARS-CoV-2 Infection in the Forensic Setting: Novel Application of Ex Vivo Imaging in Analysis of Brain Microvasculature

Neurologic manifestations in children with COVID-19

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