Inflammatory Biomarkers in Childhood Arterial Ischemic Stroke

Abstract

Background and Purpose Among children with arterial ischemic stroke (AIS), those with arteriopathy have the highest recurrence risk. We hypothesized that arteriopathy progression is an inflammatory process, and that inflammatory biomarkers would predict recurrent AIS. Methods In an international study of childhood AIS, we selected cases classified into one of the three most common childhood AIS etiologies: definite arteriopathic (N=103), cardioembolic (N=55), or idiopathic (N=78). We measured serum concentrations of high sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), myeloperoxidase (MPO), and tumor necrosis factor alpha (TNF-α). We used linear regression to compare analyte concentrations across the subtypes, and Cox proportional hazards models to determine predictors of recurrent AIS. Results Median age at index stroke was 8.2 years (IQR 3.6, 14.3); serum samples were collected at median 5.5 days post-stroke (IQR 3, 10 days). In adjusted models (including age, infarct volume, and time to sample collection) with idiopathic as the reference, the cardioembolic (but not arteriopathic) group had higher concentrations of hsCRP and MPO, while both cardioembolic and arteriopathic groups had higher SAA. In the arteriopathic (but not cardioembolic) group, higher hsCRP and SAA predicted recurrent AIS. Children with progressive arteriopathies on follow-up imaging had higher recurrence rates, and a trend towards higher hsCRP and SAA, compared to children with stable or improved arteriopathies. Conclusion Among children with AIS, specific inflammatory biomarkers correlate with etiology and—in the arteriopathy group—risk of stroke recurrence. Interventions targeting inflammation should be considered for pediatric secondary stroke prevention trials.

Transient Cerebral Arteriopathy, Postvaricella Arteriopathy, and Focal Cerebral Arteriopathy or the Unique Susceptibility of the M1 Segment in Children With Stroke

“…7,9,17,18 Classical determinants for stroke and biomarkers reflecting endothelial injury and repair can also predict outcome. 17,19,20,21 There is also a trend for a better outcome 6 and few recurrences 17 in children treated with aspirin. In our former report of TCA, recurrence occurred in 3 of 4 children without treatment versus only one of 11 who received aspirin.…”

Recurrent Stroke: The Role of Thrombophilia in a Large International Pediatric Stroke Population

“…[1][2][3][4][5] Prior diagnoses in children with symptomatic AIS are multiple and include cardiac disorders, haematological conditions (sickle cell anaemia, prothrombotic disorders), collagen tissue diseases, metabolic disorders, other chronic diseases, and acute illnesses. [6][7][8] Childhood infections, including Varicella Zoster virus, have been shown to be associated with an increased risk of AIS, with routine vaccinations being protective against AIS. 9,10 In addition, the presence of prothrombotic risk factors has been found in small case series and case control studies to be associated with ischaemic stroke in children, with this association confirmed by meta-analysis.…”

“…[15][16][17][18][19][20] Several of these studies have identified vasculopathy, in particular moyamoya, as an important factor in predicting recurrent stroke. 8,15,20 There are some early data to suggest that prothrombotic states may also enhance the risk of recurrence, but many of these studies are limited by size and scope. 7,11,15,16,21 We therefore investigated in an international cohort study the relevance of prothrombotic risk factors, as well as underlying stroke subtypes, to a second stroke in paediatric patients.…”

Clinical trials in childhood stroke: from consensus to reality

“…2 The condition appears to have an inflammatory component: levels of serum inflammatory markers among children with arteriopathy predict recurrence. 3 Prior research has suggested that herpesvirus infections, and particularly varicella zoster virus (VZV), cause progressive cerebral vasculopathy. 4 In recent work from VIPS, moreover, herpesviruses other than VZV were also associated with stroke of multiple etiologies.…”