Jeffrey Russ, MD, PhD
Traditionally, arteriovenous malformations (AVMs) were thought of as isolated, static anomalies of vascular development, and complete surgical resection was, therefore, considered curative. A commonly employed treatment approach was for patients to undergo microsurgical resection of their AVM followed shortly thereafter by post-operative digital subtraction angiogram (DSA), which could provide gold-standard confirmation of a complete resection. Because DSA-proven resection is typically presumed to be curative, subsequent surveillance imaging has not been undertaken across institutions in any systematic way, if it is even performed at all.1 While AVM recurrence remains rare, accumulating evidence suggests that AVMs do recur in a subset of patients, the vast majority of which are pediatric patients.1
Copelan et al. present a thorough analysis to specifically address AVM recurrence risk in the pediatric population. The authors review retrospective data from a cohort of 115 children and young adults, from ages 3 to 25, who underwent microsurgical resection of an AVM at a single institution. Based on institution-specific guidelines, patients with no evidence of residual nidus on post-operative DSA then underwent surveillance angiography 6 months later only if residual arteriovenous shunting had been identified; otherwise, repeat DSA was performed at 5 years.
Of the total cohort, 12 (10.4%) patients experienced AVM recurrence, all of whom initially presented with intracranial hemorrhage (ICH). ICH at presentation was a significant risk factor for AVM recurrence, since no patient experienced recurrence from the subgroup 25 years or younger without initial ICH (Figure 3). Only half of those patients with recurrence were symptomatic at the time, and the mean time to recurrence was about 4.5 years. The 5-year recurrence rate from the entire cohort was 13.1%, but when calculated for the enriched population of children 18 years or younger who presented with ICH, about one-fifth (21.4%) ultimately experienced recurrence within 5 years. Finally, regression analysis suggested that for every year older a patient was at their initial resection, their risk of recurrence was lower by 14%.
In all, the significant risk factors associated with AVM recurrence included hemorrhage at presentation and younger age at resection, with a suggestion that deep venous drainage and left hemispheric location may also increase recurrence risk. The pathophysiology contributing to increased risk of recurrence in this subpopulation of patients is not clear. The authors invoke a number of possible mechanisms: 1) developmental — angiogenic factors may be more prevalent in the cerebrovascular milieu of children, and enhanced growth factor expression has been noted in recurrent AVMs; 2) genetic — gene mutations that upregulate cell signaling involved in vascular remodeling have been reported in some AVMs; 3) hemodynamic — deep venous drainage appears to be associated with higher risk of recurrence (Figure), and it has also been hypothesized that some vessels might be obscured on the original DSA by “steal” from the AVM nidus, which then become recruited after nidus removal; and 4) anatomic — hemorrhage in the pediatric brain may differentially contribute to thrombosis or compression of the microvasculature, making detection of the complete AVM more challenging. Also, caution with language cortex leading to less aggressive resection may underly the left sided predominance of recurrence. Ultimately, further clinical studies, as well as cellular and molecular characterization from either rodent models or human pathology specimens, will help to answer these questions.
Nevertheless, Copelan et al. effectively conclude that a systematic approach to follow up angiography in children who undergo AVM resection is critical, particularly in younger children who present with hemorrhage and have deep venous drainage of their AVM. They recommend that for pediatric AVMs, surveillance DSA should be repeated by at least five years post-resection if not sooner.
References:
- Weil AG, Li S, and Zhao JZ. Recurrence of a cerebral arteriovenous malformation following complete surgical resection: a case report and review of the literature. Surg Neurol Int. 2011;2:175.
