Patients older than 60 years with unruptured brain arteriovenous malformations faced a twofold higher risk of intracranial hemorrhage compared with those diagnosed before age 20, according to a study published in JAMA Neurology.

In the Multicenter Arteriovenous Malformation Research Study, the annual risk of intracranial hemorrhage (ICH) among patients with unruptured brain arteriovenous malformations (AVMs) was 1.4 per 100 person-years—significantly lower than the 2% to 4% rate often cited in clinical practice. A total of 159 ICH events occurred over 11,339 person-years of follow-up. Increasing age, associated arterial aneurysms, and cerebellar or deep supratentorial AVM locations were identified as independent predictors of first ICH. The presence of an associated arterial aneurysm increased risk by 66%, and cerebellar or deep supratentorial location raised risk by 87%. Each additional risk factor increased hemorrhage risk by 65%.

“Increasing age, flow-associated arterial aneurysms, and cerebellar or deep supratentorial brain AVM location were independent risk factors for first ICH in the untreated course,” noted the lead author Helen Kim, PhD, of the Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, and colleagues.

The Multicenter Arteriovenous Malformation Research Study was an international, multicenter cohort study conducted from 2017 to 2023 to define the rate and risk factors for first ICH in patients with unruptured brain AVMs. The analysis included 3,030 patients from 9 cohorts with confirmed unruptured AVMs. The mean follow-up time was 3.7 years, with the longest follow-up extending to 50 years. Data were collected both retrospectively and prospectively, harmonized through standardized definitions, and entered into a centralized REDCap database. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data guidelines.

Participants had a median age of 38 years, and 50% were female. Seizures were the most common presenting symptom (45%). The median maximal AVM diameter was 3.1 cm. Among patients, 10% had exclusively deep venous drainage, 11% had AVMs located in deep supratentorial or cerebellar regions, and 19% had associated arterial aneurysms. Kaplan-Meier survival analyses and Cox proportional hazards models were used to evaluate time to first ICH, with stratification by cohort to account for baseline hazard differences. Missing data were imputed using multiple chained equations, and sensitivity analyses produced consistent findings across models.

This study was supported by the National Institutes of Health and international funding partners. Investigators reported receiving grants from the National Institutes of Health and industry sources. The funders had no role in the study design, data acquisition, analysis, interpretation, or decision to publish the findings.

Source: JAMA Neurology