Intrinsic and extrinsic risk factors in tumor-related epilepsy

This study consolidated evidence on the association of tumor-intrinsic and investigated the underexplored association of tumor-extrinsic factors with tumor-related epilepsy, aiming to contribute to the overall risk assessment for clinical management in tumor-related epilepsy.

Over a period of one year (2020), we prospectively collected imaging and clinical data of 373 patients with histopathologically confirmed brain tumors. Assessed tumor-intrinsic factors included histopathology, diameter and anatomical location, with the central lobe comprising the precentral, postcentral and subcentral gyrus and paracentral lobule. Tumor-extrinsic factors comprised sex, age, BMI, smoking, alcohol abuse, and Na⁺/K⁺ imbalances. We applied univariable and multivariable binary logistic regression to characterize the associations between tumor-intrinsic and tumor-extrinsic factors with tumor-related epilepsy.

Preoperative seizures occurred in 29.5% (n = 110) of patients, with cortical locations - particularly the central lobe (91.3%, n = 21) - posing the highest seizure incidence among all factors. In univariable analysis, compared to WHO grade 3/4 gliomas, WHO grade 1/2 neuroepithelial tumors exhibited moderately higher, whereas pituitary adenomas/ craniopharyngiomas and schwannomas showed lower incidences of preoperative seizures. In multivariable analysis, the central lobe (OR 58.15), other cortical locations (OR 3.47-3.76), male sex (OR 1.77), low BMI (OR 4.61) and smoking (OR 1.013 per pack-year), revealed significant associations (p = < 0.05).

Cortical location, especially in the central lobe, male sex, low BMI and smoking, are independently associated with tumor-related epilepsy. Our findings support the importance of considering both tumor-intrinsic and tumor-extrinsic factors to develop a holistic seizure-risk assessment and highlight the need for larger, prospective studies to refine clinical management and potentially pharmacological seizure prophylaxis.