AHA Scientific Statement Management of Stroke in Infants and Children A Scientific Statement From a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young E. Steve Roach, MD, FAHA, Chair; Meredith R. Golomb, MD, MSc; Robert Adams, MD, MS, FAHA; Jose Biller, MD, FAHA; Stephen Daniels, MD, PhD, FAHA; Gabrielle deVeber, MD; Donna Ferriero, MD; Blaise V. Jones, MD; Fenella J. Kirkham, MB, MD; R. Michael Scott, MD, FAHA; Edward R. Smith, MD Purpose—The purpose of this statement is to review the literature on childhood stroke and to provide recommendations for optimal diagnosis and treatment. This statement is intended for physicians who are responsible for diagnosing and treating infants, children, and adolescents with cerebrovascular disease. Methods—The Writing Group members were appointed by the American Heart Association Stroke Council’s Scientific Statement Oversight Committee. The panel included members with several different areas of expertise. Each of the panel’s recommendations was weighted by applying the American Heart Association Stroke Council’s Levels of Evidence grading algorithm. After being reviewed by panel members, the manuscript was reviewed by 4 expert peer reviewers and by members of the Stroke Council Leadership Committee and was approved by the American Heart Association Science Advisory and Coordinating Committee. We anticipate that this statement will need to be updated in 4 years. Results—Evidence-based recommendations are provided for the prevention of ischemic stroke caused by sickle cell disease, moyamoya disease, cervicocephalic arterial dissection, and cardiogenic embolism. Recommendations on the evaluation and management of hemorrhagic stroke also are provided. Protocols for dosing of heparin and warfarin in children are suggested. Also included are recommendations on the evaluation and management of perinatal stroke and cerebral sinovenous thrombosis in children. (Stroke. 2008;39:000-000.) Key Words: AHA Scientific Statements Ⅲ children Ⅲ stroke troke has been increasingly recognized in children in disturbance of brain function lasting Ͼ24 hours or leading to Srecent years, but diagnosis and management can be death with no obvious nonvascular cause) is far from ideal difficult because of the diversity of underlying risk factors for children. Children with symptoms compatible with a and the absence of a uniform treatment approach. Children transient ischemic attack (TIA), for example, commonly and adolescents with stroke have remarkable differences in have a brain infarction shown by brain imaging despite the presentation compared with older patients. Stroke type also transient nature of their symptoms. Children with cerebral varies according to age. In Western countries, 80% to 85% of venous sinus thrombosis (CVST) commonly present with strokes among adults are ischemic, and the rest are hemor- headache or seizures. “Stroke-like episodes” without an rhagic. In children, Ϸ55% of strokes are ischemic, and the obvious vascular cause may occur in migraine or metabolic remainder are hemorrhagic. disease but may require specific treatment. Prior illness The World Health Organization definition of stroke (a (eg, infection) or events (eg, head trauma) need not clinical syndrome of rapidly developing focal or global preclude a diagnosis of stroke. Although extra-axial hema- The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on April 4, 2008. A single reprint is available by calling 800-242-8721 (US only) or by writing the American Heart Association, Public Information, 7272 Greenville Ave, Dallas, TX 75231-4596. Ask for reprint No. 71-0451. A copy of the statement is also available at http://www.americanheart.org/presenter.jhtml?identifierϭ3003999 by selecting either the “topic list” link or the “chronological list” link. To purchase additional reprints, call 843-216-2533 or e-mail [email protected]. Expert peer review of AHA Scientific Statements is conducted at the AHA National Center. For more on AHA statements and guidelines development, visit http://www.americanheart.org/presenter.jhtml?identifierϭ3023366. Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.americanheart.org/presenter.jhtml? identifierϭ4431. A link to the “Permission Request Form” appears on the right side of the page. © 2008 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.108.189696 1 2 Stroke September 2008 Table 1. Definition of Classes and Levels of Evidence Used in nience of readers who may be unfamiliar with these topics, AHA Stroke Council Recommendations the group’s recommendations emphasize issues regarding Class I Conditions for which there is evidence for treatment. The recommendations in this article represent a and/or general agreement that the consensus of the authors. Because some aspects of stroke in procedure or treatment is useful and children have been studied more thoroughly than others, effective some topics receive more attention than others. Despite major Class II Conditions for which there is conflicting progress in the study of stroke in children in recent years, evidence and/or a divergence of opinion much of the literature remains descriptive. Continued re- about the usefulness/efficacy of a search is essential if we are to better understand the diagnosis procedure or treatment and treatment of stroke in children. Class IIa The weight of evidence or opinion is in favor of the procedure or treatment Overview of the Cause of Childhood Stroke Class IIb Usefulness/efficacy is less well established About half of the children presenting with an acute focal by evidence or opinion neurological deficit have a previously identified risk factor, Class III Conditions for which there is evidence and Ն1 additional risk factors often are uncovered in the and/or general agreement that the remaining patients.1 For arterial ischemic stroke, the most procedure or treatment is not useful/effective and in some cases may be common underlying conditions are sickle cell disease (SCD) harmful and congenital or acquired heart disease. Heart disease and ␤ Therapeutic chronic anemia (including SCD and -thalassemia) also are recommendations risk factors for CVST, but the list of associated conditions Level of Evidence A Data derived from multiple randomized ranges from head and neck infections to systemic conditions clinical trials such as inflammatory bowel disease and autoimmune disor- 2 1,3 Level of Evidence B Data derived from a single randomized trial ders. Head trauma appears to be a trigger for arterial stroke or nonrandomized studies and dehydration for venous stroke,4–6 whereas infections, 1 Level of Evidence C Consensus opinion of experts including Varicella, meningitis, tonsillitis, and otitis media, and anemia, leukocytosis, and prothrombotic disorders are Diagnostic 1,5–7 recommendations probably risk factors for both. It is increasingly evident that many children have multiple risk factors that together Level of Evidence A Data derived from multiple prospective cohort studies using a reference standard determine the risk of stroke or stroke recurrence. applied by a masked evaluator Various factors influencing stroke recurrence risk have Level of Evidence B Data derived from a single grade A study, been documented in individuals with both symptomatic and Ն1 case-control studies, or studies using a idiopathic stroke.5 Some arteriopathies are transient,8 and reference standard applied by an occluded venous sinuses often recanalize.5,6 An estimated unmasked evaluator 10% of intracranial hemorrhages (ICHs) in the young result Level of Evidence C Consensus opinion of experts from CVST. Epidemiology of Childhood Stroke tomas, neonatal intraventricular hemorrhages (IVHs), and After excluding neonatal strokes and strokes related to trauma periventricular leukomalacia arise from cerebrovascular and infection, Schoenberg et al9 found 3 hemorrhagic strokes dysfunction in a broad sense, they are not considered in and 1 ischemic stroke among 15 834 children in Rochester, detail here. Our purpose is to review the literature on stroke in children Minn, between 1965 and 1974. Their estimated annual stroke Ͻ and, whenever possible, to make recommendations for the incidence rate for children 15 years of age was 2.52 per diagnosis and management of these children. Writing Group 100 000 per year or 1.89 per 100 000 per year and 0.63 per members were appointed by the American Heart Association 100 000 per year for hemorrhagic and ischemic strokes, Stroke Council’s Scientific Statement Oversight Committee. respectively. In this population, hemorrhagic strokes occurred The panel included members with several different areas of more often than ischemic strokes, whereas in the Mayo Clinic expertise. The