International multicenter cohort study of pediatric brain arteriovenous malformations. Part 1: Predictors of hemorrhagic presentation

Abstract

<jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>Brain arteriovenous malformations (AVMs) are the most common cause of spontaneous intracranial hemorrhage in pediatric patients (age &lt; 18 years). Since the cumulative lifetime risk of AVM hemorrhage is considerable in children, an improved understanding of the risk factors influencing hemorrhagic presentation may aid in the management of pediatric AVMs. The aims of this first of a 2-part multicenter, retrospective cohort study are to evaluate the incidence and determine the predictors of hemorrhagic presentation in pediatric AVM patients.</jats:p></jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>The authors analyzed pooled AVM radiosurgery data from 7 institutions participating in the International Gamma Knife Research Foundation (IGKRF). Patients younger than 18 years at the time of radiosurgery and who had at least 12 months of follow-up were included in the study cohort. Patient and AVM characteristics were compared between unruptured and ruptured pediatric AVMs.</jats:p></jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>A total of 357 pediatric patients were eligible for analysis, including 112 patients in the unruptured and 245 patients in the ruptured AVM cohorts (69% incidence of hemorrhagic presentation). The annual hemorrhage rate prior to radiosurgery was 6.3%. Hemorrhagic presentation was significantly more common in deep locations (basal ganglia, thalamus, and brainstem) than in cortical locations (frontal, temporal, parietal, and occipital lobes) (76% vs 62%, p = 0.006). Among the factors found to be significantly associated with hemorrhagic presentation in the multivariate logistic regression analysis, deep venous drainage (OR 3.2, p &lt; 0.001) was the strongest independent predictor, followed by female sex (OR 1.7, p = 0.042) and smaller AVM volume (OR 1.1, p &lt; 0.001).</jats:p></jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>Unruptured and ruptured pediatric AVMs have significantly different patient and nidal features. Pediatric AVM patients who possess 1 or more of these high-risk features may be candidates for relatively more aggressive management strategies.</jats:p></jats:sec>

Multimodality management and outcomes of brain arterio-venous malformations (AVMs) in children: personal experience and review of the literature, with specific emphasis on age at first AVM bleed

“…In our literature review we report that 82% (95% CI = [77–87]; N  = 267) of children diagnosed with brain AVMs (mean age 11.4 ± 0.4) presented with rupture over the last 22 years included. In spite of a previous report of increased risk of haemorrhage associated with female sex [8], our review revealed a significant difference in gender-related AVM rupture (136 males vs 84 females) ( p  < 0.001). These findings perhaps propose that hormonal changes around puberty may be related, and suggest that the sex difference may be attributable to the hormonal differences too.…”

“…A high percentage of children with AVMs, often more than 60%, present with rupture [7, 8, 15, 17, 25]. In our series, 78.7% presented with haemorrhage.…”

“…The annual risk of AVM haemorrhage in children is approximately 2–6% per annum (assuming presence from birth) and is higher in the first year post rupture [7, 8, 15–18]. However, age-related prevalence of haemorrhage among children diagnosed with brain AVMs is not clear in the literature.…”

“…However, age-related prevalence of haemorrhage among children diagnosed with brain AVMs is not clear in the literature. In spite of the proposed congenital theory of AVMs formation, the number of neonates and young children diagnosed/treated for such pathology is very small [1, 7, 8, 17]. Furthermore, recurrence of brain AVMs after angiographic cure has been reported in a number of cases [19–22].…”

“…In the Blauwblomme et al study, AVMs ruptured at a mean age of 9.7 years (range 7.0–12.7). Furthermore, assuming that AVMs are congenital lesions, they estimated that the annual bleeding risk is 6.3% with significant associations with female sex (49.4% females vs 37.5% males) and annual re-haemorrhage rate of 14.8% [8]. The number of patients that have been diagnosed with AVMs in the neonatal period or infancy is very small [9, 10] and none to date has been diagnosed in utero in spite of the advances in radiological diagnostic techniques, including the now routine use of good quality ultrasound imaging [11].…”