Arterial ischemic stroke (AIS) is a common and devastating disorder of childhood. In spite of this, there is little evidence regarding etiology or outcomes with which to inform treatment. This proposal aims to support the early career development of an academic pediatric neurologist focusing upon the investigation of prognostic factors in childhood-onset AIS. Specifically, we are investigating the role of stroke subtype and biomarkers upon the risk of recurrent stroke. Preliminary results suggest that acutely elevated biomarkers of hypercoagulability are likely associated with specific subtypes in childhood-onset AIS. Further, these biomarkers may be prognostic or recurrent AIS and/or adverse neurological outcome. Certain stroke subtypes, such as arteriopathy, are also associated with recurrent AIS. Therefore, we seek to explore the combined prognostic significance of subtype and biomarkers of hypercoagulability upon recurrent AIS in children with stroke. To that end, our initial aim is to confirm the reliability of a consensus based classification system in childhood- onset AIS. This analysis will be performed as an ancillary study of an established NIH database of over 100 consecutively enrolled patients with childhood-onset AIS. In a separate, four-center cohort of prospectively enrolled children with childhood onset AIS, we will evaluate the relationship between stroke subtype and acutely elevated biomarkers of hypercoagulability. Finally, we will evaluate the prognostic significance of biomarkers of hypercoagulability, stroke subtype, and systemic inflammation for recurrent cerebrovascular events in childhood-onset AIS.

Public Health Relevance

Childhood stroke is a poorly understood disease. The most prevalent risk factors identified to date include stroke subtype and coagulation abnormalities. The systematic collection of the proposed biomarkers may provide insight into 1) the pathophysiology of childhood stroke, 2) the prediction of recurrent stroke, and 3) the identification of patients who need more aggressive therapies.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1-CSR-R (M1))
Program Officer
Scott, Jane
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Colorado Denver
Schools of Medicine
United States
Zip Code
Bernard, Timothy J; Beslow, Lauren A; Manco-Johnson, Marilyn J et al. (2016) Inter-Rater Reliability of the CASCADE Criteria: Challenges in Classifying Arteriopathies. Stroke 47:2443-9
Bernard, Timothy J; Rivkin, Michael J; Scholz, Kelley et al. (2014) Emergence of the primary pediatric stroke center: impact of the thrombolysis in pediatric stroke trial. Stroke 45:2018-23
Goldenberg, Neil A; Bernard, Timothy J; Hillhouse, Jasper et al. (2013) Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children. Haematologica 98:802-7
Goldenberg, Neil A; Jenkins, Sarah; Jack, Jessica et al. (2013) Arteriopathy, D-dimer, and risk of poor neurologic outcome in childhood-onset arterial ischemic stroke. J Pediatr 162:1041-6.e1
Joachim, Emily; Goldenberg, Neil A; Bernard, Timothy J et al. (2013) The methylenetetrahydrofolate reductase polymorphism (MTHFR c.677C>T) and elevated plasma homocysteine levels in a U.S. pediatric population with incident thromboembolism. Thromb Res 132:170-4
Bernard, Timothy J; Armstrong-Wells, Jennifer; Goldenberg, Neil A (2013) The institution-based prospective inception cohort study: design, implementation, and quality assurance in pediatric thrombosis and stroke research. Semin Thromb Hemost 39:10-4
Pearson, Virginia; Ruzas, Chris; Krebs, Nancy F et al. (2013) Overweight and obesity are increased in childhood-onset cerebrovascular disease. J Child Neurol 28:517-9
Lambers, Moritz; Goldenberg, Neil A; Kenet, Gili et al. (2013) Role of reduced ADAMTS13 in arterial ischemic stroke: a pediatric cohort study. Ann Neurol 73:58-64
Bernard, Timothy J; Manco-Johnson, Marilyn J; Lo, Warren et al. (2012) Towards a consensus-based classification of childhood arterial ischemic stroke. Stroke 43:371-7
Beslow, Lauren A; Kasner, Scott E; Smith, Sabrina E et al. (2012) Concurrent validity and reliability of retrospective scoring of the Pediatric National Institutes of Health Stroke Scale. Stroke 43:341-5

Showing the most recent 10 out of 16 publications