Responses of Arteriovenous Malformations to Radiosurgery: Ultrastructural Changes

Abstract

Abstract OBJECTIVE: To examine the ultrastructural changes in arteriovenous malformations (AVMs) after radiosurgery and to explore the possible mechanisms of posttreatment obliteration and hemorrhage. METHODS: Twenty-two specimens, among them three irradiated AVMs (size, 3–6 cm), 15 nonirradiated AVMs, and four normal controls were processed for ultrastructural study immediately after removal. Transmission electron microscopy was used to compare the vasculature of irradiated AVMs with nonirradiated AVMs and normal controls. RESULTS: Thirty-three months postradiosurgery, partial vaso-occlusion (36–74% lumen) occurred by coagulation of cytoplasmic debris and proteinaceous material leaking from the endothelium. Forty-eight months postradiosurgery, heterogeneous thrombus formation (86–96% lumen) with fibrinoid and proteinaceous materials was observed. Sixty-four months postradiosurgery, complete luminal closure (90–100% lumen) by a fibrin thrombus was seen in vessels with diameters up to 5.5 mm including feeding arteries and draining veins. In occluded vessels, there was extensive degeneration of endothelial cells, subendothelial fibroblasts, and myofibroblasts. Neoproliferation and endothelialization of smooth muscle cells with Weibel-Palade bodies was observed in arteries. CONCLUSION: Radiosurgery causes irreversible cellular damage of the vascular wall. Partial vaso-occlusion that increases blood flow in remaining vessels and degenerative changes on the blood-brain barrier may contribute to hemorrhage at early stage postradiosurgery. Radiosurgery stimulates neoproliferating and endothelializing smooth muscle cells in vessel walls, which might lead to narrowing of the vessel lumina. Complete vaso-occlusion achieved 64 months postradiosurgery suggested a minimum follow-up duration of 5 years to determine final outcome of radiosurgery. Histological end point of vaso-occlusion of AVMs takes longer time than neuroimaging endpoint of complete obliteration.