Ravizza Teresa, Onat Filiz Y, Brooks-Kayal Amy R, Depaulis Antoine, Galanopoulou Aristea S, Mazarati Andrey, Numis Adam L, Sankar Raman, Friedman Alon
Department of Neuroscience, IRCCS-"Mario Negri" Institute for Pharmacological Research, Milano, Italy.
Department of Medical Pharmacology, Epilepsy Research Center, School of Medicine Marmara University, Istanbul, Turkey.
Epilepsia. 2017 Mar;58(3):331-342. doi: 10.1111/epi.13652. Epub 2016 Dec 30.
Neurologic and psychiatric comorbidities are common in patients with epilepsy. Diagnostic, predictive, and pharmacodynamic biomarkers of such comorbidities do not exist. They may share pathogenetic mechanisms with epileptogenesis/ictogenesis, and as such are an unmet clinical need. The objectives of the subgroup on biomarkers of comorbidities at the XIII Workshop on the Neurobiology of Epilepsy (WONOEP) were to present the state-of-the-art recent research findings in the field that highlighting potential biomarkers for comorbidities in epilepsy. We review recent progress in the field, including molecular, imaging, and genetic biomarkers of comorbidities as discussed during the WONOEP meeting on August 31-September 4, 2015, in Heybeliada Island (Istanbul, Turkey). We further highlight new directions and concepts from studies on comorbidities and potential new biomarkers for the prediction, diagnosis, and treatment of epilepsy-associated comorbidities. The activation of various molecular signaling pathways such as the "Janus Kinase/Signal Transducer and Activator of Transcription," "mammalian Target of Rapamycin," and oxidative stress have been shown to correlate with the presence and severity of subsequent cognitive abnormalities. Furthermore, dysfunction in serotonergic transmission, hyperactivity of the hypothalamic-pituitary-adrenocortical axis, the role of the inflammatory cytokines, and the contributions of genetic factors have all recently been regarded as relevant for understanding epilepsy-associated depression and cognitive deficits. Recent evidence supports the utility of imaging studies as potential biomarkers. The role of such biomarker may be far beyond the diagnosis of comorbidities, as accumulating clinical data indicate that comorbidities can predict epilepsy outcomes. Future research is required to reveal whether molecular changes in specific signaling pathways or advanced imaging techniques could be detected in the clinical settings and correlate with epilepsy-associated comorbidities. A reliable biomarker will allow a more accurate diagnosis and improved treatment of epilepsy-associated comorbidities.
神经和精神共病在癫痫患者中很常见。目前尚不存在此类共病的诊断、预测和药效学生物标志物。它们可能与癫痫发生/发作机制有共同的发病机制，因此是尚未满足的临床需求。在第十三届癫痫神经生物学研讨会（WONOEP）上，共病生物标志物小组的目标是介绍该领域的最新研究成果，突出癫痫共病的潜在生物标志物。我们回顾了该领域的最新进展，包括在2015年8月31日至9月4日于土耳其伊斯坦布尔海贝利阿达岛举行的WONOEP会议上讨论的共病的分子、影像学和遗传生物标志物。我们进一步强调了共病研究的新方向和概念，以及用于预测、诊断和治疗癫痫相关共病的潜在新生物标志物。各种分子信号通路的激活，如“Janus激酶/信号转导子和转录激活子”、“雷帕霉素哺乳动物靶点”和氧化应激，已被证明与随后认知异常的存在和严重程度相关。此外，血清素能传递功能障碍、下丘脑-垂体-肾上腺皮质轴功能亢进、炎症细胞因子的作用以及遗传因素的贡献，最近都被认为与理解癫痫相关的抑郁和认知缺陷有关。最近的证据支持影像学研究作为潜在生物标志物的实用性。此类生物标志物的作用可能远远超出共病的诊断，因为越来越多的临床数据表明共病可以预测癫痫的预后。未来的研究需要揭示在临床环境中是否可以检测到特定信号通路的分子变化或先进的影像学技术，并与癫痫相关共病相关联。可靠的生物标志物将有助于更准确地诊断和改善癫痫相关共病的治疗。
