Predictors of epilepsy as presenting symptom of cerebral cavernomas

Background: Cerebral cavernous malformations (CCMs) are vascular lesions frequently presenting with seizures on presentation. Studies have widely analyzed topography as a determinant of epileptogenesis. However, the association between lesion volumetry and epileptic risk remains poorly investigated, as no objective volumetric thresholds have been established to stratify seizure risk. Methods: We conducted a multicentric case-control study including 230 adult patients with CCMs. Patients were grouped according to their initial presentation: epileptic (n=75) versus non-epileptic (n=155). We calculated the volumes of the lesions using the ABC/2 method and categorized them into quartiles. Subsequently, we run a multivariate logistic regression assessing independent predictors of epilepsy, adjusting for demographic, clinical, and radiological factors. We also estimated the diagnostic accuracy of lesion volume thresholds (>11.9 mm³, >80 mm³, >300 mm³). Results: Lesion volume was significantly associated with epilepsy risk. Lesions ≥80 mm³ were shown to have higher odds of seizures on presentation (OR 86.4, 95% CI 9.94–751). We found hemorrhagic presentation (OR 60.3, 95% CI 6.50–558) and frontal or temporal location (OR 6.34, 95% CI 2.99–113.4) to be also independent predictors of epilepsy. Differently, demographic and pharmacologic factors were not independently predictive. Conclusions: Lesion volume, hemorrhage, and cortical location were found to be the major predictors of epilepsy as first manifestation. Therefore, incorporating volumetric assessment into routine MRI evaluation may improve individualized risk stratification and guide early management decisions.