Is Intervention Recommended for Patients With Unruptured AVMs?
Researchers have developed similar prognostication scores for predicting outcomes of radiosurgery and embolization. “These treatments have widely differing efficacies—surgery having the most up-front immediate obliteration rate, which is almost 100%, and endovascular therapy, as a stand-alone, being rarely curative,” she said.
Regarding the 25-year-old wo-man in question, Dr. Amin-Hanjani proposed that clinicians evaluating the patient be “splitters” rather than “lumpers” when considering treatment options and complication rates. “With that 2% per year rupture risk, she’s going to have an approximately 70% to 75% lifetime risk of rupture and a significant risk of a morbidity … defined as a modified Rankin Scale (mRS) score of worse than 2,” she said. “She’s a female, she’s in her childbearing years—and there are some data [suggesting] an eightfold increased risk of hemorrhage in pregnancy.
“All we’ve been told about this case is that she has a grade 3 AVM [that is] 4 cm [large], so it could be [an] AVM that’s in noneloquent territory with deep venous drainage that would do well with surgery, or it could be in eloquent territory and may require treatment with a combination of other modalities like embolization and radiosurgery. But we have some data that support that, either way, you could construct a management strategy that’s going to give her a better-than-90% favorable outcome.”
Dr. Amin-Hanjani recommended referring the 25-year-old woman for interventional treatment. She disagreed with the interpretation of ARUBA that medical therapy is superior for all unruptured AVMs. The investigators had difficulty recruiting participants in the United States, and the study may have been influenced by a pre-enrollment selection bias, Dr. Amin-Hanjani noted. Furthermore, patients who might benefit from treatment (eg, those perceived to have a higher rupture risk based on the features of their AVMs) may have been excluded.
The ARUBA results cannot be applied to all patients with unruptured AVM, including the theoretical 25-year-old, said Dr. Amin-Hanjani. “She’s expected to live 60 years. How can we rely on a study with a mean follow-up of less than three years? We can’t really extrapolate the risk of treating her grade 3 AVM from ARUBA, since the aggregate data are not generalizable, and we can’t determine which treatment to offer her because the study wasn’t designed to compare treatment modalities.”
Patients May Live for Years Without a Hemorrhage
Some patients, however, fare well without interventional therapy. Dr. Mohr described individuals with unruptured AVMs who survived for 20 years or longer without a hemorrhage. One woman presented to his institution in 1973 with her first-ever AVM-related hemorrhage, which doctors decided was too dangerous to operate on. “[They] sent her home hoping that God would be good to her,” Dr. Mohr recalled. “And God was—she had three children, is a grandmother now, and returned with her second hemorrhage in 2008…. She was not considered suitable for treatment then and, with disappointment, went back to Connecticut, asking us [whether we] hadn’t improved the treatment plan in over 30 years.”
Concerns about selection bias in the ARUBA study may be irrelevant, according to Dr. Mohr. Patients with smaller, more easily treated AVMs are indeed overrepresented in the study population, he said. “When we look at the actual outcomes, we can see that the Spetzler–Martin scale predicted quite well the increased degree of complication in the treatment as a function of the larger brain.” But no clear link is evident between Spetzler–Martin grade and outcome in patients in the medical arm who experienced an event, he added.
The mRS scores for patients in the medical arm correlated with small or minor events among those who had such events, but few patients who underwent interventional treatment had subsequent improvement in their mRS scores.
Dr. Mohr and his coinvestigators requested funding for a long-term follow-up of both arms to test whether participants in the medical arm would eventually catch up to the interventional arm and whether mRS scores for the interventional patients who had lesions or other disturbances would return to normal. “To our surprise, the NINDS Study Section … agreed with the ARUBA statisticians and those statisticians who reviewed these data that the long-term follow-up is unlikely to change the statistical outcome,” he said. “So there will be no NINDS-funded follow-up, but we’re still hoping to continue follow-up among the participants for the next few years so we can increase the per-year follow-up rate.”
—Fred Balzac
