Brain and Spine Institute, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France.
Epilepsy Unit (VL, VN) and Neuro-Intensive care Unit (SD), Neurology Department, AP-HP, GH Pitié-Salpêtrière-Charles Foix, Paris, France.
Epilepsia. 2020 Jan;61(1):6-18. doi: 10.1111/epi.16405. Epub 2019 Dec 11.
Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms that lead to abnormally prolonged seizures and require urgent administration of antiepileptic drugs. Refractory status epilepticus requires anesthetics drugs and may lead to brain injury with molecular and cellular alterations (eg, inflammation, and neuronal and astroglial injury) that could induce neurologic sequels and further development of epilepsy. Outcome scores based on demographic, clinical, and electroencephalography (EEG) condition are available, allowing prediction of the risk of mortality, but the severity of brain injury in survivors is poorly evaluated. New biomarkers are needed to predict with higher accuracy the outcome of patients admitted with status in an intensive care unit. Here, we summarize the findings of studies from patients and animal models of status epilepticus. Specific protein markers can be detected in the cerebrospinal fluid and the blood. One of the first described markers of neuronal death is the neuron-specific enolase. Gliosis resulting from inflammatory responses after status can be detected through the increase of S100-beta, or some cytokines, like the High Mobility Group Box 1. Other proteins, like progranulin may reflect the neuroprotective mechanisms resulting from the brain adaptation to excitotoxicity. These new biomarkers aim to prospectively identify the severity and development of disability, and subsequent epilepsy of patients with status. We discuss the advantages and disadvantages of each biomarker, by evaluating their brain specificity, stability in the fluids, and sensitivity to external interferences, such as hemolysis. Finally, we emphasize the need for further development and validation of such biomarkers in order to better assess patients with severe status epilepticus.
癫痫持续状态是一种由导致癫痫发作终止的机制失效或引发导致异常延长的癫痫发作的机制启动的情况，需要紧急给予抗癫痫药物。难治性癫痫持续状态需要使用麻醉药物，并可能导致分子和细胞改变的脑损伤（例如炎症、神经元和星形胶质细胞损伤），这可能导致神经后遗症和进一步发展为癫痫。基于人口统计学、临床和脑电图（EEG）条件的预后评分可用，允许预测死亡率风险，但幸存者的脑损伤严重程度评估不佳。需要新的生物标志物来更准确地预测入住重症监护病房的癫痫持续状态患者的预后。在这里，我们总结了癫痫持续状态患者和动物模型研究的结果。特定的蛋白质标志物可以在脑脊液和血液中检测到。神经元特异性烯醇化酶是最早描述的神经元死亡标志物之一。癫痫持续状态后炎症反应引起的神经胶质增生可以通过 S100-beta 或某些细胞因子（如高迁移率族蛋白 1）的增加来检测。其他蛋白质，如颗粒蛋白可能反映了大脑对兴奋性毒性的神经保护机制。这些新的生物标志物旨在前瞻性地识别癫痫持续状态患者的严重程度和残疾发展以及随后的癫痫发作。我们通过评估它们的脑特异性、在液体中的稳定性以及对溶血等外部干扰的敏感性，讨论了每种生物标志物的优缺点。最后，我们强调需要进一步开发和验证这些生物标志物，以便更好地评估严重癫痫持续状态患者。
