Lethal Pediatric Cerebral Vasculitis Triggered by Severe Acute Respiratory Syndrome Coronavirus 2 - 17/01/22

Doi : 10.1016/j.pediatrneurol.2021.11.003

Kelsey E. Poisson, MD ^a,^b, Alexander Zygmunt, MD ^a,^b, Daniel Leino, MD ^a,^c, Christine E. Fuller, MD ^a,^c,^d, Blaise V. Jones, MD ^a,^e, David Haslam, MD ^a,^f, Mary Allen Staat, MD, MPH ^a,^f, Gwendolyn Clay, MD ^a,^g, Tracy V. Ting, MD ^a,^g, Kristen Wesselkamper, MD ^a,^b, Barbara Hallinan, MD, PhD ^a,^b, Shannon Standridge, DO ^a,^b, Melissa E. Day, MD ^a,^h, Monica McNeal, MS ^a,^f, Charles B. Stevenson, MD ^a,ⁱ, Marissa Vawter-Lee, MD ^a,^b,^⁎
^a Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
^b Division of Child Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
^c Division of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
^d Department of Pathology, State University of New York, Upstate Medical University, Syracuse, New York
^e Division of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
^f Division of Infectious Disease, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
^g Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
^h Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
ⁱ Division of Neurosurgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

^∗Communications should be addressed to: Dr. Vawter-Lee; Cincinnati Children's Hospital Medical Center; 3333 Burnet Avenue, MLC 2015; Cincinnati, OH 45229.Cincinnati Children's Hospital Medical Center3333 Burnet AvenueMLC 2015CincinnatiOH45229

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Abstract

Background

We report the clinical, radiological, laboratory, and neuropathological findings in support of the first diagnosis of lethal, small-vessel cerebral vasculitis triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric patient.

Patient Description

A previously healthy, eight-year-old Hispanic girl presented with subacute left-sided weakness two weeks after a mild febrile illness. SARS-CoV-2 nasopharyngeal swab was positive. Magnetic resonance imaging revealed an enhancing right frontal lobe lesion with significant vasogenic edema. Two brain biopsies of the lesion showed perivascular and intraluminal lymphohistiocytic inflammatory infiltrate consistent with vasculitis. Despite extensive treatment with immunomodulatory therapies targeting primary angiitis of the central nervous system, she experienced neurological decline and died 93 days after presentation. SARS-CoV-2 testing revealed positive serum IgG and positive cerebrospinal fluid IgM. Comprehensive infectious, rheumatologic, hematologic/oncologic, and genetic evaluation did not identify an alternative etiology. Postmortem brain autopsy remained consistent with vasculitis.

Conclusion

This is the first pediatric presentation to suggest that SARS-CoV-2 can lead to a fatal, postinfectious, inflammatory small-vessel cerebral vasculitis. Our patient uniquely included supportive cerebrospinal fluid and postmortem tissue analysis. While most children recover from the neurological complications of SARS-CoV-2, we emphasize the potential mortality in a child with no risk factors for severe disease.

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Keywords : SARS-CoV-2, COVID-19, Pediatrics, Stroke, Cerebral vasculitis

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Introduction

Patient presentation

Laboratory and imaging studies

Treatment and further evaluation

Postmortem evaluation

Discussion

Conclusion

	Authors' Contributions: All authors contributed to the conception and design of the study, data acquisition and analysis, and drafting the article. Final approval was obtained from all authors before submission.
	Declarations of Interests: None.
	Funding/support: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
	Previous presentation of the information in this manuscript: Our patient was included in very limited detail in the study “Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome,” published in JAMA Neurology in March 2021. In that study's text our patient is the fourth stroke patient who died, and her course is summarized in one sentence within the body of the manuscript. In supplemental e-Table 4 she is presented as Case 3. The authors of that study had limited access to data and no access to imaging on our patient, and their manuscript was published before our patient's postmortem autopsy was performed and the CSF SARS-CoV-2 IgM result was known.
	Disclosures: Authors have no potential, perceived, or real conflicts of interest to report relative to this study. This research was not funded by any sponsor. Study design, collection, analysis and interpretation of data, and all subsequent writing as well as decisions on manuscript submission were made at authors' discretion without undue influence. Drafting and revision of manuscript was performed by all study authors without honorarium, grant, or other form of payment.

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Lethal Pediatric Cerebral Vasculitis Triggered by Severe Acute Respiratory Syndrome Coronavirus 2 - 17/01/22

Abstract

Background

Patient Description

Conclusion

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