Arteritis and Large Vessel Occlusive Strokes in Children after COVID-19 Infection

Dec 18, 2020

By Brian Appavu and Todd Abruzzo.

In the summer of 2020 the Phoenix Children’s Hospital pediatric stroke team encountered a previously healthy 8 year-old child with severe clinical stroke secondary to acute large vessel occlusion. The child, who had a history of recent upper respiratory infection and exposure to multiple family members with COVID-19 presented with dense aphasia and right hemiplegia. Brain MRI showed infarction in the middle cerebral artery territory bilaterally, ruling out focal cerebral arteriopathy, a vascular abnormality commonly seen in children, and initially raising suspicion of a cardiogenic process. MR angiography showed a left middle cerebral artery proximal occlusion. Mechanical thrombectomy was performed with successful clot removal and cerebral reperfusion. Notably, catheter directed cerebral angiography and subsequent magnetic resonance vessel wall imaging both demonstrated unexpected findings of large to medium size vessel cerebral arteritis. Unfortunately, the patient re-occluded her MCA within a few hours of her embolectomy procedure, likely a consequence of underlying vascular inflammation and hypercoagulability. Although the patient’s COVID-19 PCR was negative, COVID-19 antibodies were subsequently found to be elevated.

At the time that this case presented to us, emerging data was being reported about large vessel occlusive strokes in young adults from New York after mild or asymptomatic COVID-19 infection. The authors publishing those reports noted the specific contribution of hypercoagulability to the pathogenesis of these unusual strokes. Additionally, multisystem inflammatory syndrome in children (MIS-C), was increasingly recognized as a cause of morbidity in pediatric patients after COVID-19 infection. Within the same timeframe, Dr. Michael Dowling at the UT Southwestern Medical Center informed us of a previously healthy child with evidence of multi-system arteritis and large-vessel occlusive stroke 3 weeks after COVID-19 infection. We recognized that both of our index cases represented unique circumstances in which multifocal cerebral arteritis and large vessel occlusive strokes were components of a systemic inflammatory process developing in previously healthy children after COVID-19 infection.

We published our findings in the journal, Pediatrics to increase awareness amongst pediatric healthcare providers that COVID-19 and MIS-C are risk factors for childhood stroke. While our cases represent serious life-threatening manifestations of pediatric COVID-19 infection, it is important to note that large vessel occlusive strokes are rare in children after COVID-19. Although our sample size is too small to make any generalizations, both of our patients expressed signs of systemic illness in the days between their COVID-19 infection and their stroke onset (iron deficiency anemia requiring blood transfusion in one patient, and fatigue with progressive lethargy in the other patient).We published our report with the hope that pediatricians and pediatric subspecialists will be better able to recognize stroke early in pediatric COVID patients. In particular, we want to raise awareness that COVID 19 infection and MIS-C are risk factors for childhood stroke, and that cerebral arteritis is the underlying mechanism. We believe the process is often (but not always) multifocal, potentially involves multiple organ systems and is usually characterized by marked vascular inflammation and hypercoagulability. Although one of our patients received a short course of anti-inflammatory therapy with steroids, the benefit remains speculative at best. Nonetheless, we hope that our report meaningfully informs stroke and neurocritical care treatment decisions in the pediatric population with COVID-19.

Literature published by members of the IPSO community have helped elucidate that respiratory infections transiently increase stroke risk. The IPSS-run VIPS (Vascular effects of Infection in Pediatric Stroke) II study is actively enrolling new pediatric stroke cases to identify specific pathogens that may trigger childhood stroke. Through this work as well as other biomarker-based investigations, we will be able to better understand what places children at risk for stroke after infection. In the meanwhile, we hope that through our report, the pediatric medical community can remain vigilant regarding recognition of early stroke symptoms in children.

Links to Relevant Scientific Publications:

Brian Appavu, MD

Brian Appavu, MD

Phoenix Children's Hospital

Dr. Brian Appavu is a clinical neurophysiologist and is a Clinical Assistant Professor of Child Health and Neurology at the University of Arizona College of Medicine Phoenix and Director of the Pediatric Neurocritical Care Fellowship at the Barrow Neurological Institute at Phoenix Children’s Hospital.

Todd Abruzzo, MD

Todd Abruzzo, MD

Phoenix Children's Hospital

Dr. Todd Abruzzo is an interventional neuroradiologist and Professor of Radiology and Child Health at the University Of Arizona College Of Medicine – Phoenix and serves as Co-Director of the Vascular Diseases and Therapeutics Section at the Barrow Neurological Institute at Phoenix Children’s Hospital.

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