Untreated brain arteriovenous malformation

Abstract

Objective: To identify risk factors for intracranial hemorrhage in the natural history course of brain arteriovenous malformations (AVMs) using individual patient data meta-analysis of 4 existing cohorts.Methods: We harmonized data from Kaiser Permanente of Northern California (n 5 856), University of California San Francisco (n 5 787), Columbia University (n 5 672), and the Scottish Intracranial Vascular Malformation Study (n 5 210). We censored patients at first treatment, death, last visit, or 10-year follow-up, and performed stratified Cox regression analysis of timeto-hemorrhage after evaluating hemorrhagic presentation, sex, age at diagnosis, deep venous drainage, and AVM size as predictors. Multiple imputation was performed to assess impact of missing data.Results: A total of 141 hemorrhage events occurred during 6,074 patient-years of follow-up (annual rate of 2.3%, 95% confidence interval [CI] 2.0%-2.7%), higher for ruptured (4.8%, 3.9%-5.9%) than unruptured (1.3%, 1.0%-1.7%) AVMs at presentation. Hemorrhagic presentation (hazard ratio 3.86, 95% CI 2.42-6.14) and increasing age (1.34 per decade, 1.17-1.53) independently predicted hemorrhage and remained significant predictors in the imputed dataset. Female sex (1.49, 95% CI 0.96-2.30) and exclusively deep venous drainage (1.60, 0.95-2.68, p 5 0.02 in imputed dataset) may be additional predictors. AVM size was not associated with intracerebral hemorrhage in multivariable models (p . 0.5). Conclusion:This large, individual patient data meta-analysis identified hemorrhagic presentation and increasing age as independent predictors of hemorrhage during follow-up. Additional AVM cohort data may further improve precision of estimates, identify new risk factors, and allow validation of prediction models. Brain arteriovenous malformations (BAVMs) are the most common cause of intracranial hemorrhage in younger people, who are at risk of long-term morbidity and mortality. The most common presentation is hemorrhage (approximately 50%), followed by seizures and neurologic deficits.Understanding hemorrhage risk in the natural history course of BAVM is crucial when making treatment decisions. However, obtaining accurate estimates is challenging because of short follow-up times from censoring by treatment, low event rates, and low prevalence of disease, which are major limitations of all BAVM longitudinal studies. Current BAVM annual hemorrhage rates range from 2%-4% overall 1-9 to 1%-3% among unruptured patients, 1,4,6,9 but vary †Deceased.

Radiosurgery for Cerebral Arteriovenous Malformations in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA)-Eligible Patients

“…Patients with <12 months follow-up who developed complications were also included. To select patients for the ARUBA-eligible cohort, the following exclusion criteria were applied 1 : Previous AVM hemorrhage, 2 any previous AVM intervention including embolization or microsurgery 3 age <18 years, 4 life expectancy <10 years (age >66 years for men or >71 years for women), 5 and Spetzler-Martin grade V AVMs. 12 …”

“…The annual hemorrhage risk of the conservatively managed patients in ARUBA was 2.2%, which is consistent with previous natural history studies but higher than the 0.9% annual hemorrhage rate observed during the latency period of our cohort. 2,18,19 Because 30% of the patients with in this study were determined to have an unfavorable outcome (incomplete AVM obliteration, hemorrhage during the latency period, or permanent treatment-related complication), we estimate that patients who undergo radiosurgery would have superior outcomes to observation after 17 years of follow-up. This estimate does not account for other neurological sequelae originating from a patent AVM, such as seizures and focal deficits secondary to chronic vascular steal.…”

“…13 Despite these criticisms, the ARUBA trial was interpreted to indicate that patients with unruptured AVMs should be observed. The aims of this retrospective, multicenter cohort study 1 are to determine the outcomes of ARUBA-eligible patients, who uniformly received treatment with radiosurgery 2 and define the predictors of AVM radiosurgery outcomes in ARUBAeligible patients.…”

Periventricular Location as a Risk Factor for Hemorrhage and Severe Clinical Presentation in Pediatric Patients with Untreated Brain Arteriovenous Malformations

“…[8][9][10][11][12][13] A recent angiographic study revealed that the angioarchitectural features of BAVM, some of which confer a higher risk for future hemorrhage in adults, differ between children and adults. 7 However, only a few studies have specifically been conducted to assess the risk of pediatric BAVM hemorrhage and provide a prognosis before treatment (On-line Table 3).…”

“…[8][9][10] Meta-analyses of natural history studies and large-scale cohort studies failed to reach a consensus regarding the role of other factors such as nidus size, exclusive deep venous drainage, associated arterial aneurysm, and deep location. [11][12][13] A periventricular location has also been found to correlate positively with the risk of hemorrhage before the treatment of BAVMs. 14,15 However, this feature, although amenable to analysis with imaging, has not been studied carefully in the risk assessment of interventional-versus-observational treatment.…”