Focal Cerebral Arteriopathy in a Pediatric Patient with COVID-19.

Introduction

The neuroinvasive mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not fully understood. SARS-CoV-2 may enter the central nervous system hematogenously, with other proposed routes, including the olfactory and trigeminal nerves, cerebral spinal fluid (CSF), and lymphatic system (1). Neurologic manifestations in pediatric patients with coronavirus disease 2019 (COVID-19) have uncommonly been reported. Herein, we report a presumptive case of ischemic stroke due to focal cerebral arteriopathy (FCA) associated with COVID-19.

Case Presentation

A previously healthy 12-year-old-boy with a new onset of generalized seizures was initially treated with diazepam. Shortly thereafter, he developed right-sided hemiparesis and dysarthria. There was no previous history of fever, cough, shortness of breath, skin rash, hemoglobinopathy, or recent trauma. No one in his family had a known history of COVID-19 infection.

The diagnosis of COVID-19 was made according to the presence of SARS-CoV-2 viral nucleic acid in the nasopharyngeal swab using 2019 novel coronavirus real-time reverse-transcriptase polymerase chain reaction assay. Test results for the presence of SARS-CoV-2 viral nucleic acid in the CSF were also positive. Viral genome was extracted using a viral RNA kit (High Pure; Roche, Basel, Switzerland), with a multiplex one-step reverse-transcriptase real-time polymerase chain reaction test (Pishtaz Teb Zaman Diagnostics, Tehran, Iran) to amplify COVID-19 E, N, and ORF1ab and/or RdRp genes. A CSF bacterial culture showed no growth after 3 days, and tests for herpes simplex viruses 1 and 2 and varicella-zoster virus (QIAGEN, Hilden, Germany) were negative. The serum ferritin level was 86.7 ng/L, the C-reactive protein level was 3 mg/L, and the erythrocyte sedimentation rate was 45 mm/h. CSF analysis demonstrated 21 mg/dL of protein, 62 mg/dL of glucose, 100 red blood cells per cubic millimeter (using traumatic lumbar puncture), and no white blood cells. The CSF opening pressure was 25 mm of H2O. d-dimer level was not obtained. The platelet count was 285×103/µL, the prothrombin time was 12.1 seconds, the international normalized ratio was 0.9, and the partial thromboplastin time was 27 seconds. The antinuclear antibody level was normal.

Low-dose CT scans of the lung had normal findings. Color Doppler US performed of the carotid artery and echocardiography performed of the heart had normal findings. MRI depicted findings consistent with acute infarction without microhemorrhages (Figure, parts a–c), along with focal irregular narrowing and banding of the proximal M1 segment of the left middle cerebral artery with a slightly reduced distal flow (Figure, part d). High-resolution contrast material–enhanced vessel wall imaging was not performed.

(a–c) Axial T2-weighted (a) and fluid-attenuated inversion recovery (b) MRI scans show diffuse hyperintense signal and edema of caudate nucleus head, putamen, anterior limb of internal capsule, and parts of external capsule and insula on left side, with corresponding low values on axial apparent diffusion coefficient map (c), in keeping with an acute infarction. (d) Maximal intensity projection reformatted image from time-of-flight MR angiography shows focal irregular narrowing and banding of proximal left M1 segment of middle cerebral artery with slightly reduced distal flow in middle cerebral artery (arrows).

There were no symptoms of other system involvement, cervical enlarged lymph nodes, cutaneous or mucosal rash, or redness. The patient had no respiratory abnormalities. The patient received conservative management. Upon discharge, the patient is still hemiparetic at home and is undergoing rehabilitation.

Discussion

The major imaging finding in this patient is the presence of unilateral focal vasculopathy, characterized by focal irregular narrowing and banding of the proximal left middle cerebral artery associated with left basal ganglia and insula acute infarction. There are many potential differential considerations in a child with acute stroke, including FCA, arterial dissection, embolic or thrombotic stroke, cerebral vasculitis in the context of systemic disease (including Kawasaki disease), and genetic disorders with arteriopathy, among others. Our leading diagnosis is FCA, one of the most common causes of childhood arterial ischemic stroke, which is defined by Wintermark et al (2) as a “unifocal and unilateral stenosis/irregularity of the large intracranial arteries of the anterior circulation (distal internal carotid artery and/or its proximal branches).” Varicella-zoster virus vasculopathy is a well-known cause of FCA. Other infectious agents less commonly associated with FCA include other herpesviruses, human immunodeficiency virus, parvovirus B19, influenza A, enteroviruses, and Mycoplasma pneumoniae.

According to the patient’s history and lack of thrombotic processes outside the central nervous system, embolic stroke and dissection were considered less likely than FCA. Recent reports of an elevated immune response and an inflammatory syndrome have been reported in children with COVID-19 infection (3). Reports have described typical vasculitis findings in other organ systems, including Kawasaki disease–like presentations (4,5). No evidence suggests a multisystem inflammatory syndrome or a Kawasaki disease–like presentation, as the patient did not show any of the classic clinical physical findings. The CSF from lumbar puncture was not inflammatory. To our knowledge, Kawasaki disease–like illnesses do not manifest as FCA. The presence of SARS-CoV-2 material from the nasopharynx swab is evidence that the patient had COVID-19, and the presence of the virus in the CSF, although uncommon, further corroborates central nervous system involvement.