Silent Intralesional Microhemorrhage as a Risk Factor for Brain Arteriovenous Malformation Rupture

Abstract

Background and Purpose We investigated whether brain arteriovenous malformation (bAVM) silent intralesional microhemorrhage (SIM), i.e., asymptomatic bleeding in the nidal compartment, might serve as a marker for increased risk of symptomatic intracranial hemorrhage (ICH). We evaluated two markers to assess the occurrence of SIM: neuroradiological assessment of evidence of old hemorrhage (EOOH)— imaging evidence of bleeding before the outcome events, and hemosiderin positivity in H&E-stained paraffin block sections. Methods We included cases from a bAVM database with recorded neuroradiological data or available surgical paraffin blocks. Using two endpoints, index ICH and new ICH after diagnosis (censored at treatment, loss to follow-up, or death), we performed logistic or Cox regression to assess EOOH and hemosiderin positivity, adjusting for age, sex, deep-only venous drainage, maximal bAVM size, deep location, and associated arterial aneurysms. Results EOOH was present in 6.5% (n=975) of patients and highly predictive of index ICH (p<0.001; OR=3.97; 95% CI, 2.1-7.5), adjusting for other risk factors. In a multivariable model (n=643), EOOH was an independent predictor of new ICH (HR=3.53; 95% CI=1.35-9.23; p=.010). Hemosiderin positivity was found in 36.2% (29.6% in unruptured; 47.8% in ruptured; p=.04), and associated with index ICH in univariate (OR=2.18; 95%CI 1.03-4.61; p=.042; n=127) and multivariable models (OR=3.64; 95% CI=1.11-12.00; p=.034; n=79). Conclusions The prevalence of SIM is high and there is evidence for an association with both index and subsequent ICH. Further development of means to detect SIM during bAVM evaluation may present an opportunity to improve risk-stratification, especially for unruptured bAVMs.

Distinctive distribution of lymphocytes in unruptured and previously untreated brain arteriovenous malformation

“…Consistent with our published data, [21] hemosiderin deposition was found in 8 out of 19 specimens (42%; 95% CI: 20–67%) [Figure 1]. Hemosiderin positive cells were scattered mainly around the abnormal vessels [Figure 1a].…”

“…[21] Further, histological examination demonstrated that the degree of hemosiderin deposition is positively correlated with the number of macrophages in the lesion. [21] It is not clear, however, whether the macrophage response is specific or whether other inflammatory cells are also correlated with hemosiderin deposition and macrophage. Our previous studies demonstrated that both macrophage and neutrophil may play roles in bAVM pathogenesis.…”

A treatment paradigm for high-grade brain arteriovenous malformations: volume-staged radiosurgical downgrading followed by microsurgical resection

“…Some AVM patients are young with a long life expectancy but they have high-risk features such as silent intralesional hemorrhage, 7 deep location, or deep drainage, all of which increase the risk of future hemorrhage. 5,23,28 For these patients, VS-SRS offers a noninvasive option between resection and observation.…”

Hemorrhage Rates and Risk Factors in the Natural History Course of Brain Arteriovenous Malformations

“…Silent microhemorrhages in unruptured brain AVM patients have been proposed as a novel risk factor for symptomatic hemorrhage [45]. Evidence of old hemorrhage on CT or MR (T1- or T2-weighted sequences) prior to diagnosis but unrelated to any hemorrhage at presentation was present in 6.5% of patients, was highly predictive of hemorrhagic presentation (OR=3.97; 95% CI: 2.1–7.5, P<0.001), and was an independent predictor of new hemorrhage in the natural history course of AVM patients (HR= 3.53, 95% CI=1.35–9.23, P=0.010).…”