HISTOPATHOLOGY OF ARTERIOVENOUS-MALFORMATIONS AFTER GAMMA-KNIFE RADIOSURGERY

Stereotactic radiosurgery effectively obliterates many arteriovenous m alformations (AVMs). Hemodynamic changes in AVMs after radiosurgery ha ve been illustrated using magnetic resonance imaging and angiography, but there have been no detailed reports describing the underlying hist opathological changes. This study examines AVMs at various times after gamma knife radiosurgery (GKRS) and describes the histopathological c hanges that lead to vessel occlusion. The authors examined nine AVM sp ecimens obtained 10 months to more than 5 years after GKRS, by using r outine histopathological stains as well as immunohistochemical techniq ues to detect smooth-muscle actin, factor VIII, and type IV collagen. Blood vessels within the AVMs showed progressive changes leading to na rrowing or obliteration of the lumen. The earliest changes after gamma knife irradiation appear to be damage to endothelial cells, followed by progressive thickening of the intimal layer caused by proliferation of smooth-muscle cells that elaborate an extracellular matrix that in cludes type IV collagen. Finally, cellular degeneration and hyaline tr ansformation occur. For statistical correlation analyses, the specimen s were graded according to the degree of histopathological change and the relative number of vessels showing such changes. Both of these par ameters were significantly correlated with time after GKRS and with AV M size reduction shown on follow-up imaging studies. Gamma knife radio surgery of AVMs causes endothelial damage, which induces the prolifera tion of smooth-muscle cells and the elaboration of extracellular colla gen by these cells, which leads to progressive stenosis and obliterati on of the AVM nidus. This series of pathological changes in AVMs after GKRS is essentially similar to the response-to-injury model of athero sclerosis.