ArticleNeurosurgical review2026
Incidence of postoperative seizures after clipping of unruptured intracranial aneurysms without prophylactic antiseizure medications: a prospective noninferiority cohort study.
Article in Neurosurgical review, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective to evaluate whether withholding prophylactic antiseizure medications (ASMs) is safe in low-risk patients undergoing microsurgical clipping for unruptured intracranial aneurysms (UIAs) and to identify risk factors of postoperative seizures using a prespecified noninferiority design. Methods this prospective single-center cohort study enrolled adults between January 2019 and June 2023 who were scheduled to undergo clipping for UIAs smaller than 15 mm and had no prior seizures or structural brain injury. Prophylactic ASMs were not administered. The primary endpoint was postoperative seizure within 1 year. Noninferiority was assessed using an exact binomial framework against a prespecified margin of 5.5%. Predictors were evaluated using univariable and multivariable Firth penalized logistic regression. Internal validation was performed with 1,000 bootstrap resamples. Results among 428 patients, postoperative seizures occurred in 7 patients (1.6%). The exact two-sided 95% confidence interval for seizure incidence was 0.66% to 3.34%, and the upper bound remained below the prespecified noninferiority margin of 5.5%. A one-sided exact binomial test confirmed that the seizure rate was significantly below the noninferiority threshold (p < 0.001). Five seizures occurred within 48 h of surgery, and two occurred on postoperative days 25 and 120. In multivariable Firth regression, postoperative infarction showed the strongest association with seizures (adjusted OR 68.63, 95% CI 9.48-468.60), which was supported by bootstrap validation (median OR 72.53, 95% CI 9.32-726.52). dACA location showed a borderline association in the multivariable model (p = 0.085) but demonstrated a consistent positive association in bootstrap resampling (median OR 10.25, 95% CI 2.92-40.21). Conclusion in this prospective non-ASM cohort of low-risk patients undergoing UIA clipping, withholding prophylactic ASMs was noninferior with respect to postoperative seizure incidence, and most seizures were transient. Postoperative infarction showed the most prominent association with postoperative seizure, supporting a selective, risk-adapted strategy rather than routine prophylactic ASM use. Trial Registration clinical Research Information Service (CRIS), KCT0004461, registered on November 22, 2019.
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