These criteria represent current knowledge and are expected to enhance future assessments of PHACE syndrome. It is understood that modifications are to be expected over time to incorporate new research findings.

Background Cerebral arteriopathies, including an idiopathic focal cerebral arteriopathy of childhood (FCA), are common in children with arterial ischemic stroke (AIS) and strongly predictive of recurrence. To better understand these lesions, we measured predictors of arteriopathy within a large international series of children with AIS. Methods and Results Between 1/2003 and 7/2007, 30 centers within the International Pediatric Stroke Study (IPSS) enrolled 667 children (29 days-19 years of age) with AIS and abstracted clinical and radiographic data. Cerebral arteriopathy and its subtypes were defined using published definitions; FCA was defined as cerebral arterial stenosis not attributed to specific diagnoses such as moyamoya, arterial dissection, vasculitis, or post-varicella angiopathy. We used multivariate logistic regression techniques to determine predictors of arteriopathy and FCA among those subjects who received vascular imaging. The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written. Of 667 subjects, 525 had known vascular imaging results, and 53% of those (n=277) had an arteriopathy. The most common arteriopathies were FCA (n=69, 25%), moyamoya (n=61, 22%), and arterial dissection (n=56; 20%). Predictors of arteriopathy include early school age (5-9 years), recent upper respiratory infections (URI), and sickle cell disease, while prior cardiac disease and sepsis reduced the risk of arteriopathy. The only predictor of FCA was recent URI. Conclusions Arteriopathy is prevalent among children with AIS, particularly those presenting in early school age, and those with a history of sickle cell disease. Recent URI predicted cerebral arteriopathy, and FCA in particular, suggesting a possible role for infection in the pathogenesis of these lesions.

PHACE (OMIM no. 606519) is a neurocutaneous syndrome that refers to the association of large, plaque-like, "segmental" hemangiomas of the face, with one or more of the following anomalies: posterior fossa brain malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, eye anomalies, and ventral developmental defects, specifically sternal defects and/or supraumbilical raphe. The etiology and pathogenesis of PHACE is unknown, and potential risk factors for the syndrome have not been systematically studied. The purpose of this study was thus to determine (1) the incidence of PHACE and associated anomalies among a large cohort of hemangioma patients, (2) whether certain demographic, prenatal or perinatal risk factors predispose infants to this syndrome, and (3) whether the cutaneous distribution of the hemangioma can be correlated to the types of anomalies present. We undertook a prospective, cohort study of 1,096 children with hemangiomas, 25 of whom met criteria for PHACE. These 25 patients represented 20% of infants with segmental facial hemangiomas. Compared to previous reports, our PHACE patients had a higher incidence of cerebrovascular and cardiovascular anomalies. Two developed acute arterial ischemic stroke during infancy, while two with cardiovascular anomalies showed documented evidence of normalization, suggesting that both progressive and regressive vascular phenomena may occur in this syndrome. Correlation to the anatomic location of the hemangioma appears to be helpful in determining which structural abnormalities might be present. A comparison of demographic and perinatal data between our PHACE cases and the hemangioma cohort overall showed no major differences, except a trend for PHACE infants to be of slighter higher gestational age and born to slightly older mothers. Eighty-eight percent were female, a finding which has been noted in multiple other reports. Further research is needed to determine possible etiologies, optimal evaluation, and outcomes.

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