Histopathology of brain AVMs part I: microhemorrhages and changes in the nidal vessels

Abstract

Background: Arteriovenous malformations of the brain (bAVM) may rupture from aneurysms or ectasias of the feeding, draining, or nidal vessels. Moreover, they may rupture from the immature, fragile nidal vessels that are characteristic to bAVMs. How the histopathological changes of the nidal vessels associate with clinical presentation and hemorrhage of the lesion is not well known.

Materials and methods: We investigated tissue samples from surgically treated bAVMs (n = 85) using standard histological and immunohistochemical stainings. Histological features were compared with the clinical presentation of the patient.

Results: Microhemorrhages from nidal vessels were found both in bAVMs with a history of clinically evident rupture and in bAVMs considered unruptured. These microhemorrhages were associated with presence of immature, pathological nidal vessels (p = 0.010) and perivascular inflammation of these vessels (p = 0.001), especially with adhesion of neutrophils (p < 0.001). In multivariate analysis, perivascular inflammation (OR = 19, 95% CI 1.6 to 230), neutrophil infiltration of the vessel wall (OR = 13, 95% CI 1.9 to 94), and rupture status (OR = 0.13, 95% CI 0.017 to 0.92) were significantly associated with microhemorrhages.

Conclusions: Clinically silent microhemorrhages from nidal vessels seem to be very common in bAVMs, and associate with perivascular inflammation and neutrophil infiltration. Further studies on the role of perivascular inflammation in the clinical course of bAVMs are indicated.

Keywords: Arteriovenous malformation; Brain; Inflammation; Microhemorrhage; Rupture; Vascular degeneration.

Fig. 1

An abnormal vessel typical to bAVMs. The structure of the vessel resembles a capillary with no smooth muscle in spite of diameter much larger than that of a capillary. The endothelial layer is marked with arrows and the lumen with *

Fig. 2

Two small bAVM vessels which have bled into their immediate surroundings. The endothelium of the vessels (marked with arrows) is thin in comparison with the size of the lumen (marked with asterisks). A typical example of microhemorrhage in bAVM samples

Fig. 3

Light (a) and strong (b) recruitment and adhesion of neutrophils (marked with arrows) to the luminal surface (marked with asterisks) of a bAVM vessel and the vessel wall

Fig. 4

Dense perivascular inflammation (marked with arrows) around a bAVM vessel. The inflammation consists of mononuclear lymphocytes

Fig. 5

A bAVM vessel with a high degree of perivascular mononuclear inflammation (marked with arrows). The vessel has also hemorrhaged into its immediate surroundings