From the Université Paris Cité (J.P., A.R., A.M., A.E., E.G., C.O., M.G., M.Z.), Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266; Departments of Neurosurgery (J.P., A.R., A.M., O.A., A.E., E.P., M.Z.), Neurophysiology (E.G., M.G.), Neuroradiology (C.O.), Neuropathology (A.T.-E., F.C.), and Neurology (G.H.), Hôpital Fondation Adolphe de Rothschild; and Neuroglial Interactions in Cerebral Physiopathology (G.H.), Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 7241, INSERM U1050, Université PSL Paris, France.
Neurology. 2024 Jan 9;102(1):e207902. doi: 10.1212/WNL.0000000000207902. Epub 2023 Dec 13.
Tumor-related epilepsy is a well-known symptom of glioblastoma. However, the particular characteristics of epileptic seizures related to glioblastoma, ()-wild-type is almost unexplored longitudinally during the whole course of the disease. We assessed tumor-related epilepsy and seizure control during tumor evolution and the prognostic significance of tumor-related epilepsy.
We performed an observational, retrospective single-center study at one tertiary referral neuro-oncology surgical center (2000-2020). We included adult patients treated for a newly diagnosed supratentorial glioblastoma, -wild-type with available preoperative and postoperative MRI and with available epileptic seizure status at diagnosis. To determine factors associated with tumor-related epilepsy or seizure control, univariate analyses were performed using the χ or Fisher exact tests for categorical variables and the unpaired test or Mann-Whitney rank-sum test for continuous variables. Predictors associated with tumor-related epilepsy and seizure control in unadjusted analysis were entered into backward stepwise logistic regression models.
One thousand six patients were enrolled. The cumulative incidence of tumor-related epilepsy increased during tumor evolution (33.1% at diagnosis, 44.7% after oncologic treatment, 52.4% at progression, and 51.8% at the end-of-life phase) and is related to tumor features (cortex involvement, no necrosis, and small volume). Uncontrolled epileptic seizures increased during tumor evolution (20.1% at diagnosis, 32.0% after oncologic treatment, 46.7% at progression, and 41.1% at the end-of-life phase). Epileptic seizure control after oncologic treatment was related to seizure features (uncontrolled before oncologic treatment and focal-to-bilateral tonic-clonic seizures) and to the extent of resection. Epileptic seizure control at tumor progression was related to seizure features (presence at diagnosis and uncontrolled after oncologic treatment) and to the time to progression. Tumor-related epilepsy at diagnosis was a predictor of a longer overall survival (adjusted hazard ratio, 0.78; 95% CI 0.67-0.90; < 0.001) independent of age, Karnofsky Performance Status score, tumor location and volume, extent of resection, standard combined chemoradiotherapy, levetiracetam use, and promoter methylation.
The progression of tumor-related epilepsy with the evolution of glioblastoma, -wild-type and the effects of surgery on seizure control argue for proper antiseizure medication and maximal safe resection. Tumor-related epilepsy is an independent predictor of a longer survival.
肿瘤相关性癫痫是胶质母细胞瘤的一种常见症状。然而,与胶质母细胞瘤相关的癫痫发作的特殊特征,在疾病的整个过程中几乎没有进行过 ()-野生型的纵向研究。我们评估了肿瘤相关性癫痫和肿瘤演变过程中的癫痫发作控制情况,以及肿瘤相关性癫痫的预后意义。
我们在一家三级转诊神经肿瘤外科中心(2000-2020 年)进行了一项观察性、回顾性单中心研究。我们纳入了新诊断为幕上胶质母细胞瘤,-野生型,且术前和术后 MRI 均可用,且在诊断时具有癫痫发作状态的成年患者。为了确定与肿瘤相关性癫痫或癫痫发作控制相关的因素,我们使用 χ 或 Fisher 确切检验对分类变量进行了单变量分析,使用未配对 t 检验或 Mann-Whitney 秩和检验对连续变量进行了分析。在未调整分析中与肿瘤相关性癫痫和癫痫发作控制相关的预测因素被纳入向后逐步逻辑回归模型。
共纳入 1600 例患者。肿瘤相关性癫痫的累积发生率在肿瘤演变过程中增加(诊断时为 33.1%,肿瘤治疗后为 44.7%,进展时为 52.4%,生命终末期为 51.8%),且与肿瘤特征(皮层受累、无坏死和体积小)有关。肿瘤演变过程中未控制的癫痫发作增加(诊断时为 20.1%,肿瘤治疗后为 32.0%,进展时为 46.7%,生命终末期为 41.1%)。肿瘤治疗后癫痫发作控制与发作特征(治疗前未控制和局灶性至双侧强直阵挛性发作)和切除范围有关。肿瘤进展时的癫痫发作控制与发作特征(诊断时存在且肿瘤治疗后未控制)和进展时间有关。诊断时的肿瘤相关性癫痫是总生存时间更长的预测因素(调整后的危险比为 0.78;95%CI 0.67-0.90;<0.001),独立于年龄、Karnofsky 表现状态评分、肿瘤位置和体积、切除范围、标准联合放化疗、左乙拉西坦的使用以及 启动子甲基化。
随着 ()-野生型胶质母细胞瘤的发展,肿瘤相关性癫痫的进展以及手术对癫痫发作控制的影响,都需要进行适当的抗癫痫药物治疗和最大限度的安全切除。肿瘤相关性癫痫是总生存时间更长的独立预测因素。