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

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.

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

FIGURE 1

Imaging findings. (A) Axial T1-weighted magnetic resonance image with contrast through the frontal lobes shows an enhancing lesion with diffusion restriction centered in the right corona radiata, including extension into the precentral gyrus, with extensive surrounding edema. The cortical component had hemorrhagic staining. Examination performed two weeks later (B) shows increased size of the enhancing component, with central nonenhancement. (C) Contrast-enhanced image six weeks after presentation demonstrates further progression of the lesion, with enhancement extending throughout much of the entire cerebral hemisphere. (D) Ten weeks after presentation the lesion had spread throughout the right hemisphere, with substantial extension across the corpus callosum into the left hemisphere, with noncontiguous peripheral lesions apparent (arrow).

FIGURE 2

Brain biopsies and autopsy findings. (A-D) Initial biopsy. (A) Relatively bland ischemic necrosis with cellular loss of nuclear basophilia along with perivascular inflammation. (B) Patchy areas of intraparenchymal inflammation and gliosis. (C) CD3 (brown) and CD20 (red) dual chromogen immunohistochemistry revealing predominance of CD3-positive T lymphocytes in the vascular walls and perivascular infiltrates. (D) CD163 highlights vascular and intraparenchymal histiocytes. (E-G) Second biopsy. (E) Similar findings to previous biopsy including transmural and perivascular inflammation, but also with areas of cystic change and foamy histiocytes (right upper corner). (F) CD163 highlighting histiocytes. (G) CD3 highlighting T lymphocytes. (H) Coronal section of brain at autopsy revealing confluent areas of necrosis from cortex to corpus callosum and basal ganglia, hemorrhage near previous biopsy. Microscopic images are 400× magnification. The color version of this figure is available in the online edition.

FIGURE 3

Cerebrospinal fluid (CSF) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. CSF testing showing strong SARS-CoV-2 IgM positivity on left and negative SARS-CoV-2 IgG on right. The color version of this figure is available in the online edition.