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Role of reduced ADAMTS13 in arterial ischemic stroke: a pediatric cohort study.

ABSTRACT: Previous studies in adults and mice have implicated ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), also known as von Willebrand factor (VWF)-cleaving protease, as a protective factor for stroke. Here we investigated ADAMTS13 in 208 pediatric patients with arterial ischemic stroke (AIS) and 125 population-based control children in a frequency-matched case-control study.The proportion of patients/controls with ADAMTS13 activity levels below and above the 10th percentile was compared. Additionally, in a quintile comparison, the proportion of patients versus controls in the lowest ADAMTS13 quintile was compared to those in the 2nd to 5th quintiles. Adjustment was performed for VWF antigen (VWF:Ag), factor VIII activity (FVIII:C), blood group, and age.Forty-six of 208 patients (22%) showed ADAMTS13 levels below the 10th percentile, compared with 5 of 125 controls (4%; p < 0.001). Odds ratios/95% confidence intervals were 7.30/2.73-19.50 for the lowest percentile and 2.44/1.15-5.16 in the quintile comparison after adjustment for VWF:Ag, FVIII:C, blood group, and age. Comparing the proportion of patients with ADAMTS13 activity below the 10th percentile within the different stroke subtypes (undetermined, cardioembolic, steno-occlusive arteriopathies), no statistically significant differences were found (undetermined, 16 of 89; cardioembolic, 6 of 40; steno-occlusive arteriopathies, 24 of 79; p = 0.08). ADAMTS13 levels did not significantly differ among stroke subtypes (p = 0.29).Our findings implicate reduced ADAMTS13 activity as a risk factor for pediatric AIS, and support the concept that ADAMTS13 has a role in the pathogenesis of pediatric AIS.

SUBMITTER: Lambers M

PROVIDER: S-EPMC3703929 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Role of reduced ADAMTS13 in arterial ischemic stroke: a pediatric cohort study.

Lambers Moritz M Goldenberg Neil A NA Kenet Gili G Kirkham Fenella J FJ Manner Daniela D Bernard Timothy T Mesters Rolf M RM Junker Ralf R Stoll Monika M Nowak-Göttl Ulrike U

Annals of neurology 20121207 1

<h4>Objective</h4>Previous studies in adults and mice have implicated ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), also known as von Willebrand factor (VWF)-cleaving protease, as a protective factor for stroke. Here we investigated ADAMTS13 in 208 pediatric patients with arterial ischemic stroke (AIS) and 125 population-based control children in a frequency-matched case-control study.<h4>Methods</h4>The proportion of patients/controls with ADAMTS1 ...[more]

PMID: 23225307

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Project description:Background and purposeTo assess whether initial imaging characteristics independently predict 1-year neurological outcomes in childhood arterial ischemic stroke patients.MethodsWe used prospectively collected demographic and clinical data, imaging data, and 1-year outcomes from the VIPS study (Vascular Effects of Infection in Pediatric Stroke). In 288 patients with first-time stroke, we measured infarct volume and location on the acute magnetic resonance imaging studies and hemorrhagic transformation on brain imaging studies during the acute presentation. Neurological outcome was assessed with the Pediatric Stroke Outcome Measure. We used univariate and multivariable ordinal logistic regression models to test the association between imaging characteristics and outcome.ResultsUnivariate analysis demonstrated that infarcts involving uncinate fasciculus, angular gyrus, insular cortex, or that extended from cortex to the subcortical nuclei were significantly associated with poorer outcomes with odds ratios ranging from 1.95 to 3.95. All locations except the insular cortex remained significant predictors of poor outcome on multivariable analysis. When infarct volume was added to the model, the locations did not remain significant. Larger infarct volumes and younger age at stroke onset were significantly associated with poorer outcome, but the strength of the relationships was weak. Hemorrhagic transformation did not predict outcome.ConclusionsIn the largest pediatric arterial ischemic stroke cohort collected to date, we showed that larger infarct volume and younger age at stroke were associated with poorer outcomes. We made the novel observation that the strength of these associations was modest and limits the ability to use these characteristics to predict outcome in children. Infarcts affecting specific locations were significantly associated with poorer outcomes in univariate and multivariable analyses but lost significance when adjusted for infarct volume. Our findings suggest that infarcts that disrupt critical networks have a disproportionate impact upon outcome after childhood arterial ischemic stroke.

Dataset Information

Role of reduced ADAMTS13 in arterial ischemic stroke: a pediatric cohort study.

Publications

Role of reduced ADAMTS13 in arterial ischemic stroke: a pediatric cohort study.

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