In this prospective, population-based observational study, the risk of first-ever or recurrent seizures following AVM treatment did not differ from that seen in conservatively managed adults, irrespective of their mode of presentation. The only variable associated with a greater prospective risk of seizures was increasing hematoma volume in adults who had presented with ICH.
AVM treatment did not influence either the 5-year risk of a recurrent seizure or the chance of achieving 2-year seizure freedom in patients who had presented with an unprovoked seizure. Significantly more of the adults in the treatment group were already being treated with an AED at the start of follow-up, but by the end of follow-up similar proportions were on AEDs (). The risk of a first-ever seizure following AVM treatment for unruptured incidental AVMs appeared higher than with conservative management although this difference was not statistically significant (figure e-3), which is consistent with our previous finding that AVM treatment independently worsens short-term outcome for adults with unruptured AVMs.36
Our study has benefited from multiple overlapping sources of case ascertainment and a median completeness of follow-up of 97%. The crude detection rate of AVMs in the first 2 years of our study in Scotland was not significantly different from the pooled detection rate in a recent meta-analysis.37,38
The population-based design of our study sought to avoid referral and selection biases. Largely because of the logistical and financial constraints involved with studying a geographically dispersed population, we relied on clinicians' evaluations in patients' medical records as well as questionnaire data to patients and their family practitioners, rather than regularly scheduled study visits. The use of 2-year seizure freedom (rather than 1-year seizure freedom) should limit reporting bias that may exist in patients with a long-standing history of epilepsy who may be less inclined to present to medical attention as a result of a seizure, and this outcome measure is directly relevant to clinical practice since AEDs tend not to be withdrawn until a patient is at least 2 years seizure-free.39
Due to the complexities of AVM treatment, we simplified the analysis by starting follow-up from the time of first-ever intervention, and allocating a single mode of intervention to those undergoing multimodality treatment (and consequently the time to first seizure in the surgery group may have been overestimated among patients who received presurgical embolization). AVM treatment obliterated approximately three-quarters of the AVMs, which is similar to the findings of everyday practice at other institutions. The 5-year risk of a seizure did not differ according to whether treatment resulted in complete or incomplete AVM obliteration. We could not perform a multivariable analysis of factors that contribute to the 5-year risk of a recurrent seizure or the chances of achieving 2-year seizure freedom in adults presenting with unprovoked seizures due to the fact that the survival curves did not satisfy the assumptions of the Cox proportional hazards model. However, receipt of AVM treatment did not appear to affect the risk of recurrent seizure or chance of 2-year seizure freedom in adults with AVM-related epilepsy. The effect of AVM treatment may have been modified by the greater proportion of adults on an AED at the start of follow-up (because immediate AED use does in general delay time to first and second seizure, and appears to reduce time to 2-year seizure freedom40
) and such an imbalance would have been expected to favor the AVM treatment group. However, equivalent proportions of adults were on AED by the end of follow-up (). Finally, the lack of statistically significant differences may be due to a type II error on account of sample size, and we have recruited a second 5-year cohort to address this in future analyses.
While AVM treatment may reduce the risk of rebleeding, our observational study could not demonstrate a difference between AVM treatment and conservative management on the clinical course of epileptic seizures. We cannot, however, rule out the influence of confounding in a nonrandomized study. Although the differences were not statistically significant, adults undergoing AVM treatment had higher frequencies of seizures prior to presentation, symptomatic seizures at ICH onset, temporal lobe AVM location, and these adults may have had a higher prospective risk of seizures. Further recruitment and follow-up will improve the precision of our estimates of seizure risk and allow us to expand our multivariable analyses of factors that might influence the development of de novo seizures and predict seizure control. Randomized controlled trials, such as A Randomized trial of Unruptured Brain Arteriovenous Malformations (ARUBA, www.arubastudy.org
, ISRCTN 44013133), are required to confirm or refute our findings.