Department of Neurology, Clinical Neuroscience Center and Brain Tumor Center, University and University Hospital Zurich, 8091 Zurich, Switzerland.
Brain. 2021 Dec 16;144(11):3322-3327. doi: 10.1093/brain/awab188.
Pro-tumorigenic electrochemical synapses between neurons and brain tumour cells in preclinical studies suggest unfavourable effects of epilepsy on patient survival. We investigated associations of epilepsy and survival in three cohorts of brain tumour patients (meningioma, glioblastoma and 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. The 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 modelling. The primary analysis population comprised 1792 patients (742 meningioma, 249 glioblastoma, 801 brain metastases). Epilepsy was associated with favourable prognostic factors. However, on multivariate analyses, status epilepticus was associated with inferior overall survival of patients with glioblastoma [status epilepticus versus no epilepsy multivariate hazard ratio (HR) 3.72, confidence interval (CI) 1.78-7.76, P < 0.001] and brain metastases (status epilepticus versus 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 versus 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 tumours.
在临床前研究中,神经元与脑肿瘤细胞之间的促肿瘤电化学突触表明癫痫对患者生存的不利影响。我们研究了癫痫与脑肿瘤患者(脑膜瘤、胶质母细胞瘤和脑转移瘤)三个队列之间的相关性。为了进行比较分析,将队列分为三组:(i)无癫痫;(ii)无癫痫持续状态的癫痫;和(iii)癫痫持续状态。癫痫持续状态被认为是广泛神经元过度兴奋的替代指标。主要结果是无进展生存期(脑膜瘤)和总生存期(胶质母细胞瘤和脑转移瘤),通过时间依赖性多变量 Cox 建模,针对既定的预后因素和癫痫发作时间进行调整。主要分析人群包括 1792 名患者(742 名脑膜瘤、249 名胶质母细胞瘤、801 名脑转移瘤)。癫痫与有利的预后因素相关。然而,在多变量分析中,癫痫持续状态与胶质母细胞瘤患者的总生存期较差相关[癫痫持续状态与无癫痫的多变量危险比(HR)3.72,95%置信区间(CI)1.78-7.76,P < 0.001]和脑转移瘤患者(癫痫持续状态与无癫痫的 HR 2.30,CI 1.10-4.79,P = 0.026)。在脑转移瘤患者中,但不在脑膜瘤或胶质母细胞瘤患者中,癫痫与总生存期较差相关(癫痫与无癫痫的 HR 2.16,CI 1.60-2.93,P < 0.001)。我们的结论是,癫痫可能会导致恶性脑肿瘤患者的生存状况恶化。