The R2eD Arteriovenous Malformation Score: A Novel Predictive Tool for Arteriovenous Malformation Presentation With Hemorrhage

Abstract

INTRODUCTION The management of unruptured brain arteriovenous malformations (AVMs) remains unclear. This study aims to develop a predictive tool that could guide hemorrhage risk stratification. METHODS A database of 789 AVM patients presenting to our institution between 1990 and 2017 was used. A hold-out method of model building and validation was employed whereby the data was randomly split in half into training and validation datasets. Factors significantly associated with hemorrhage presentation at the univariable level in the training dataset were used to construct a model based on multivariable logistic regression. Model performance was assessed using receiver operating curves (ROC) on the training, validation, and complete datasets. The model predictors and the complete dataset were then used to derive a formula for risk prediction and a practical scoring system according to the model coefficients. RESULTS In 755 patients with complete data on presentation status, 272 (36%) presented with hemorrhage. After model building and validation, the final model contained the following risk factors: non-white race (odds ratio [OR] = 2.49, P < .01), deep location (OR = 1.68, P = .02), small AVM size (<3 cm, OR = 1.63, P < .01), exclusive deep venous drainage (OR = 1.73, P = .02), and “monoarterial” feeding (OR = 1.58, P = .02). Area under the curve from ROC analysis was 0.702, 0.698, and 0.685 for the training, validation, and complete datasets, respectively. Every risk factor was worth 1 point except race, which was worth 2 points. The factors are summarized by the acronym R2eD AVM (total score varies from 0 to 6). In the entire study population, the predicted probability of hemorrhagic presentation increased in a stepwise manner from 16% for patients with no risk factors (score of 0) to 78% for patients having all the risk factors (score of 6) with around a 10% increase in risk per added point. CONCLUSION This risk can be used as a predictive tool that supplements clinical judgement and aids in patient counselling.

A novel online calculator predicting short-term postoperative outcomes in patients with metastatic brain tumors

“…Naïve c-statistics for our extended LOS, nonroutine discharge, and high hospital charges models were 0.824, 0.870, and 0.833, respectively. Optimism-corrected c-statistics for LOS (0.810), nonroutine discharge (0.851), and high hospital charges models (0.817) indicated that our three models all had clinically-useful discrimination [ 23 , 24 ]. Our LOS, nonroutine discharge, and high hospital charges models had Hosmer–Lemeshow test p-values of 0.97, 0.70, and 0.64, respectively, indicating adequate model calibration (p > 0.05).…”

“…Model discrimination was assessed using the c-statistic. In the present study, a c-statistic cutoff of ≥ 0.7 defined a model with clinically-useful predictive ability [ 23 , 24 ]. A naïve c-statistic was calculated by fitting our model to the entire dataset, and 2000 bootstrap samples were used to calculate an optimism-corrected c-statistic [ 25 ].…”

Cellular loci involved in the development of brain arteriovenous malformations

“…Embryos harboring homozygous mutations in EphrineB2 and EphB4 exhibited vascular defects and AVMs ( Krebs et al, 2010 ). It was shown in an in vitro model of HHT2 that loss of ALK1 gene blocked BMP9 signaling, resulting in reduced EphrinB2 expression, enhanced VEGFR2 expression and dysregulated ECs sprouting and anastomosis ( Feghali et al, 2019 ).…”

Review of treatment and therapeutic targets in brain arteriovenous malformation

“…There is no established natural history scoring system, though a number of series have noted increased ICH risks for deep seated lesions, those with a single or deep draining vein, the presence of nidal or peri-nidal aneurysm, and infratentorial location. 11 For patients with a prior history of hemorrhage, treatment is often recommended given the elevated observed rate of secondary hemorrhage, particularly within the first year of ictus. 12 As a general rule, smaller (< 3 cm), well-circumscribed lesions with fewer arterial afferents and venous efferents centered in non-eloquent locations respond more favorably to any intervention.…”