Characterizing Rates of Post-Radiotherapy Seizure Control in Patients with Cerebral Arteriovenous Malformations: A Systematic Review and Meta-analysis

Introduction: Stereotactic radiosurgery (SRS) is a treatment option for arteriovenous malformations (AVMs), especially for small-to-moderate size (3 cm), unruptured lesions that are deep or adjacent to eloquent brain and possess a compact nidus. However, its potential to decrease AVM-associated seizures or to induce treatment-related seizures remains inadequately explored. As such, the objective of the present review is to evaluate seizure outcomes following SRS for cerebral AVMs.

Methods: Three databases were systematically queried according to PRISMA guidelines for primary studies describing new-onset seizure, seizure progression and/or seizure freedom following SRS for treatment of patients with AVMs. Meta-analysis was performed with mixed effects modeling, and p-values 0.05 were considered statistically significant.

Results: Of 196 unique articles, 33 studies comprising 4,381 patients were included. Seventy-seven percent (n = 3,391) underwent GKRS and 10% (n = 411) received hypofractionated radiotherapy delivered via LINAC. The remaining 13% underwent proton beam therapy (PBT). Among the 1,711 patients with available follow-up data, 41% (n = 701) had initially presented with seizures while 26% experienced seizures (unresolved, worsened, or new-onset) post-treatment. In total, 730/1,711 (42.7%) patients were seizure-free at last follow-up. Furthermore, seizure frequency remained at pre-intervention levels for 357 (20.9%) patients and seizure status worsened for 91 (5.3%) patients. Finally, 533 patients (29.6%) exhibited partial improvement. Seizure worsening—defined as an increase in events on the same treatment regimen or the need for treatment escalation—occurred in 5.3% of patients. Additionally, there were 108 (6.3%) instances of new-onset seizure following treatment with SRS. SRS was not associated with the likelihood of seizure freedom (post-SRS rate = 0.427, p = 0.06), though this could have been the result of high reported effect heterogeneity (I ²=95%) of the data, and the result is therefore not conclusive. As far as the efficacy of the AVM treatment itself is concernd, across all SRS modalities, complete AVM obliteration was described in 65% of patients (1,240/1,909). Finally, seven studies comprising 409 patients with seizure at presentation (prior to radiotherapy) provided further stratification of post-SRS seizure freedom status by patient, AVM, and radiological follow-up characteristics. In this cohort, 302 patients (73.8%) became seizure free, while 107 patients (26.2%) did not become seizure free. Variable-specific cohort sizes varied from 110 to 336 patients. Sex, pre-SRS hemorrhage, Spetzler-Martin grade, cerebral hemispheric laterality, history of prior AVM resection or embolization, radiation-induced changes on follow-up, and post-radiotherapy cyst formation failed to predict the likelihood of seizure freedom at follow-up. However, the odds of post-SRS seizure freedom were significantly reduced when AVMs were characterized by superficial versus deep venous drainage (OR: 0.53, 95% CI: 0.28–0.98, p = 0.05).

Conclusion: SRS is a common therapeutic option for the obliteration of small cerebral AVMs presenting in eloquent brain. The present meta-analysis finds that while SRS treatment of AVMs is associated with increased seizure freedom, the correlation is not statistically significant. Finally, only superficial (versus deep) venous drainage emerged as a significant predictor of reduced likelihood for post-SRS seizure freedom.

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Artikel online veröffentlicht:
07. Februar 2025