Neurosurgery Unit, Sainte-Anne Hospital, Paris, France; Paris Descartes University, Paris, France.
Epilepsia. 2013 Dec;54 Suppl 9:30-4. doi: 10.1111/epi.12440.
Gliomas are the most frequent primary brain tumors and most glioma patients have seizures. The origin and mechanisms of human glioma-related epilepsy are multifactorial and an intermix of oncologic and neuronal processes. In this brief review, we show that the infiltrated peritumoral neocortex appears to be the key structure for glioma-related epileptic activity, which depends on the interactions between the tumor per se and the surrounding brain. We shed light on the underlying mechanisms from two different "tumorocentric" and "epileptocentric" approaches, with a special emphasis on the glioma-related glutamatergic and γ-aminobutyric acid (GABA)ergic changes leading to epileptogenicity. Because gliomas use the neurotransmitter glutamate as a "tumor growth factor" to enhance glioma cell proliferation and invasion with neurotoxic, proinvasive, and proliferative effects, glutamate homeostasis is impaired, with elevated extracellular glutamate concentrations. Such excitatory effects contribute to the generation of epileptic activity in the peritumoral neocortex. GABAergic signaling is also involved both in tumor growth and in paradoxical excitatory effects mediated by alterations in neuronal and tumor cell Cl(-) homeostasis related to cotransporter changes. Local excitability may also be affected by an increase in extracellular K(+) concentration, the alkalization of peritumoral neocortex, and alterations of gap-junction functioning. Finally, the tumor itself may mechanically affect locally neuronal behavior, connections, and networks. Better understanding of glioma-related oncologic and epileptologic processes are crucial for development of combined therapeutic strategies, but so far, the surgical management of gliomas should comprise a maximally safe surgical resection encompassing peritumoral neocortex.
神经胶质瘤是最常见的原发性脑肿瘤，大多数神经胶质瘤患者都有癫痫发作。人类神经胶质瘤相关癫痫的起源和机制是多因素的，涉及肿瘤和神经元过程的混合。在这篇简短的综述中，我们表明浸润性肿瘤周围新皮层似乎是与神经胶质瘤相关的癫痫活动的关键结构，这取决于肿瘤本身与周围大脑之间的相互作用。我们从两种不同的“肿瘤中心”和“癫痫中心”方法来探讨潜在的机制，特别强调与神经胶质瘤相关的谷氨酸能和γ-氨基丁酸（GABA）能变化导致致痫性。由于神经胶质瘤将神经递质谷氨酸用作“肿瘤生长因子”，以增强神经胶质瘤细胞的增殖和侵袭，具有神经毒性、侵袭性和增殖性作用，因此谷氨酸稳态受到损害，细胞外谷氨酸浓度升高。这种兴奋作用有助于肿瘤周围新皮层中癫痫活动的产生。GABA 能信号也参与肿瘤生长和神经元和肿瘤细胞 Cl(-)稳态改变介导的矛盾兴奋作用，与共转运体改变有关。局部兴奋性也可能受到细胞外 K(+)浓度增加、肿瘤周围新皮层碱化以及缝隙连接功能改变的影响。最后，肿瘤本身可能会对局部神经元行为、连接和网络产生机械影响。更好地理解神经胶质瘤相关的肿瘤学和癫痫学过程对于开发联合治疗策略至关重要，但到目前为止，神经胶质瘤的手术治疗应包括最大限度地安全切除肿瘤周围新皮层。
