The Role of Infection and Inflammation in the Pathogenesis of Pediatric Arterial Ischemic Stroke

Abstract

Infections play an important role in the pathogenesis of acute ischemic stroke (AIS) in neonates and children. In neonates, chorioamnionitis or intrauterine inflammation has been implicated as a common risk factor for AIS. In infants and children, recent investigations demonstrated that even minor childhood infections are associated with subsequent increased risk for AIS. Post-infectious inflammatory mechanisms following infections with herpesviruses may lead to focal cerebral arteriopathy (FCA), one of the most common causes of AIS in a previously healthy child. Other agents such as parvovirus B19, dengue virus, and SARS-CoV-2 have recently been implicated as other potential triggers. Infections are compelling treatable stroke risk factors, with available therapies for both pathogens and downstream inflammatory effects. However, infections are common in childhood, while stroke is uncommon. The ongoing VIPS II (Vascular effects of Infection in Pediatric Stroke) study aims to identify the array of pathogens that may lead to childhood AIS and whether either unusual strains or unusual combinations of pathogens explain this paradox. Immune modulation with corticosteroids for FCA is another active area of research, with European and U.S. trials launching soon. The results of these new pediatric stroke studies combined with findings emerging from the larger field of immune-mediated post-infectious diseases will likely lead to new approaches to the prevention and treatment of pediatric stroke. This review highlights recent developments from both clinical and animal model research enhancing our understanding of this relationship between infection, inflammation, and stroke in neonates and children.