Pro-tumorigenic electrochemical synapses between neurons and brain tumor cells in pre-clinical studies suggest unfavorable effects of epilepsy on patient survival. We investigated associations of epilepsy and survival in three cohorts of brain tumor patients (meningioma, glioblastoma, brain metastases). Cohorts were segregated into three groups for comparative analyses: (i) no epilepsy, (ii) epilepsy without status epilepticus and (iii) status epilepticus. Status epilepticus was considered a surrogate of extensive neuronal hyperexcitability. Main outcome was progression-free survival (meningioma) and overall survival (glioblastoma and brain metastases), adjusted for established prognostic factors and onset of epilepsy by time-dependent multivariate Cox modeling. The primary analysis population comprised 1792 patients (742 meningioma, 249 glioblastoma, 801 brain metastases). Epilepsy was associated with favorable prognostic factors. On multivariate analyses, status epilepticus was however associated with inferior overall survival of patients with glioblastoma (status epilepticus vs no epilepsy multivariate HR 3.72, CI 1.78-7.76, P<0.001) and brain metastases (status epilepticus vs no epilepsy HR 2.30, CI 1.10-4.79, P=0.026). Among brain metastases patients, but not among patients with meningioma or glioblastoma, epilepsy was similarly associated with inferior overall survival (epilepsy vs no epilepsy HR 2.16, CI 1.60-2.93, P<0.001). We conclude that epilepsy may convey inferior survival of patients with malignant brain tumors.
Keywords: brain metastases; brain tumor; epilepsy; glioblastoma; status epilepticus.
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