癫痫发作期相关生物标志物的研究进展_Journal of Epilepsy

Authors：

刘磊 ¹ , 马维宁 ² ,  李少一 ³

1. ;
2. ;
3. ;

Corresponding author：

李少一, Email: lishaoyi2097@163.com

Keywords：

癫痫发作期; 生物标记物; 相关蛋白; 激素; 炎症因子

DOI：

10.7507/2096-0247.202205004

Video：

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癫痫是一种由多种病因引起的慢性脑部疾病，以脑神经元过度放电导致反复性、发作性和短暂性的中枢神经系统功能失常为特征。临床上癫痫致病的原因及机制较为复杂，癫痫的诊断需要症状学及脑电图的支持。但是由于癫痫发作早期症状学较为隐匿且容易与其他发作性疾病相混淆，脑电图也可能表现为正常，因此，癫痫的早期诊断一般较为困难。回顾既往的研究报道，以癫痫发作期是否存在诊断性生物标志物为出发点，阐述与发作相关的血清学及脑脊液标记物，本综述主要关注癫痫发作期相关的蛋白、激素及炎症因子等方面，目的在于筛选出具有代表性的癫痫发作期相关生物标记物，为癫痫的早期诊断提供新的思路。

Citation： 刘磊, 马维宁, 李少一. 癫痫发作期相关生物标志物的研究进展. Journal of Epilepsy, 2022, 8(5): 453-456. doi: 10.7507/2096-0247.202205004 Copy

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18.	Grafe LA, Bhatnagar S. Orexins and stress. Front Neuroendocrinol, 2018 , 51: 132-145.
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22.	Roundtree HM, Simeone TA, Johnson C, et al. Orexin receptor antagonism improves sleep and reduces seizures in kcna1-null mice. Sleep, 2016, 39(2): 357-368.
23.	Samzadeh M, Papuć E, Furtak-Niczyporuk M, et al. Decreased cerebrospinal fluid orexin-a (hypocretin-1) concentrations in patients after generalized convulsive status epilepticus. J Clin Med, 2020 , 19(10): 3354.
24.	Rana A, Musto AE. The role of inflammation in the development of epilepsy. J Neuroinflammation, 2018, 15(1): 144.
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28.	Sanz P, Garcia-Gimeno MA. Reactive glia inflammatory signaling pathways and epilepsy. Int J Mol Sci, 2020 , 21(11): 4096.
29.	Aronica E, Ravizza T, Zurolo E, et al. Astrocyte immune responses in epilepsy. Glia, 2012 , 60(8): 1258-1268.
30.	Vezzani A, Balosso S, Ravizza T. Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy. Nat Rev Neurol, 2019, 15(8): 459-472.
31.	Vega-García A, Feria-Romero I, García-Juárez A, et al. Cannabinoids: a new perspective on epileptogenesis and seizure treatment in early life in basic and clinical studies. Front Behav Neurosci, 2021, 12(1): 14: 610484.
32.	Alapirtti T, Lehtimäki K, Nieminen R, et al. The production of IL-6 in acute epileptic seizure: a video-EEG study. Neuroimmunol, 2018, 316(15): 50-55.
33.	Kamaşak T, Dilber B, Yaman SÖ, et al. HMGB-1, TLR4, IL-1R1, TNF-α, and IL-1β: novel epilepsy markers? Epileptic Disord, 2020, 22(2): 183-193.

1. Bertran F. L’épilepsie aujourd’hui [Epilepsy today]. Rev Infirm, 2018, 67(243): 14-16.
2. Thijs RD, Surges R, O'Brien TJ, et al. Epilepsy in adults. Lancet, 2019, 393(10172): 689-701.
3. Ding D, Zhou D, Sander JW, et al. Epilepsy in China: major progress in the past two decades. Lancet Neurol, 2021, 20(4): 316-326.
4. Hampel KG, Garces-Sanchez M, Gomez-Ibanez A, et al. Desafios diagnosticos en epilepsia [Diagnostic challenges in epilepsy]. Rev Neurol, 2019, 68(6): 255-263.
5. RavizzaT, Onat FY, Brooks-Kayal AR, Depaulis A, et al. WONOEP appraisal: biomarkers of epilepsy-associated comorbidities. Epilepsia, 2017, 58(3): 331-342.
6. Ravizza T, Vezzani A. Pharmacological targeting of brain inflammation in epilepsy: therapeutic perspectives from experimental and clinical studies. Epilepsia Open, 2018, 3(Suppl 2): 133-142.
7. Whitlock JH, Soelter TM, Williams AS, et al. Liquid biopsies in epilepsy: biomarkers for etiology, diagnosis, prognosis, and therapeutics. Hum Cell, 2022, 35(1): 15-22.
8. da Rosa MI, Simon C, Grande AJ, et al. Serum S100B in manic bipolar disorder patients: systematic review and meta-analysis. J Affect Disord, 2016, 206: 210-215.
9. Astrand R, Undén J. Clinical use of the calcium-binding s100b protein, a biomarker for head injury. Methods Mol Biol, 2019, 1929: 679-690.
10. Calik M, Abuhandan M, Kandemir H, et al. . Interictal serum S-100B protein levels in intractable epilepsy: a case-control study. Neurosci Lett, 2014 , 13(8): 58-61.
11. 王晶, 殷亮, 吕涌涛, 冯肖亚. S100B在癫痫患者脑脊液和血清中的表达. 实用医学杂志, 2016, 32(20): 3422-3424.
12. Liang KG, Mu RZ, Liu Y, Jiang D, et al . Increased serum s100b levels in patients with epilepsy: a systematic review and meta-analysis study. Front Neurosci, 2019, 16(5): 13: 456.
13. Li Y, Wang Z, Zhang B, et al . Cerebrospinal fluid ubiquitin C-terminal hydrolase as a novel marker of neuronal damage after epileptic seizure. Epilepsy Res, 2013, 2, 103(2-3): 205-210.
14. Asadollahi M, Simani L. The diagnostic value of serum UCHL-1 and S100-B levels in differentiate epileptic seizures from psychogenic attacks. Brain Res, 2019, 1704: 11-15.
15. Pollard JR, Eidelman O, Mueller GP, et al. The TARC/sICAM5 ratio in patient plasma is a candidate biomarker for drug resistant epilepsy. Front Neurol, 2013, 3(1): 181.
16. Cabrera-Reyes EA, Limón-Morales O, Rivero-Segura NA, et al. Prolactin function and putative expression in the brain. Endocrine, 2017 , 57(2): 199-213.
17. Wang YQ, Wen Y, Wang MM, et al. Prolactin levels as a criterion to differentiate between psychogenic non-epileptic seizures and epileptic seizures: a systematic review. Epilepsy Res, 2021 , 169: 106508.
18. Grafe LA, Bhatnagar S. Orexins and stress. Front Neuroendocrinol, 2018 , 51: 132-145.
19. Razavi BM, Farivar O, Etemad L, et al. Suvorexant, a dual orexin receptor antagonist, protected seizure through interaction with GABAA and glutamate receptors. Iran J Pharm Res, 2020, 19(2): 383-390.
20. Çikriklar HI, Kotan D, Yücel M, Ceylan M, et al. The role of Orexin-A levels in epileptic seizure. Neurosci Lett, 2020, 24(8): 734: 135097.
21. Ng MC. Orexin and epilepsy: potential role of rem sleep. Sleep, 2017, 1(3): 1-3.
22. Roundtree HM, Simeone TA, Johnson C, et al. Orexin receptor antagonism improves sleep and reduces seizures in kcna1-null mice. Sleep, 2016, 39(2): 357-368.
23. Samzadeh M, Papuć E, Furtak-Niczyporuk M, et al. Decreased cerebrospinal fluid orexin-a (hypocretin-1) concentrations in patients after generalized convulsive status epilepticus. J Clin Med, 2020 , 19(10): 3354.
24. Rana A, Musto AE. The role of inflammation in the development of epilepsy. J Neuroinflammation, 2018, 15(1): 144.
25. Alyu F, Dikmen M. Inflammatory aspects of epileptogenesis: contribution of molecular inflammatory mechanisms. Acta Neuropsychiatr, 2017 , 29(1): 1-16.
26. Vezzani A, Aronica E, Mazarati A, et al. Epilepsy and brain inflammation. Exp Neurol, 2013, 244: 11-21.
27. Vezzani A. Epilepsy and inflammation in the brain: overview and pathophysiology. Epilepsy Curr, 2014 , 14(Suppl 1): 3-7.
28. Sanz P, Garcia-Gimeno MA. Reactive glia inflammatory signaling pathways and epilepsy. Int J Mol Sci, 2020 , 21(11): 4096.
29. Aronica E, Ravizza T, Zurolo E, et al. Astrocyte immune responses in epilepsy. Glia, 2012 , 60(8): 1258-1268.
30. Vezzani A, Balosso S, Ravizza T. Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy. Nat Rev Neurol, 2019, 15(8): 459-472.
31. Vega-García A, Feria-Romero I, García-Juárez A, et al. Cannabinoids: a new perspective on epileptogenesis and seizure treatment in early life in basic and clinical studies. Front Behav Neurosci, 2021, 12(1): 14: 610484.
32. Alapirtti T, Lehtimäki K, Nieminen R, et al. The production of IL-6 in acute epileptic seizure: a video-EEG study. Neuroimmunol, 2018, 316(15): 50-55.
33. Kamaşak T, Dilber B, Yaman SÖ, et al. HMGB-1, TLR4, IL-1R1, TNF-α, and IL-1β: novel epilepsy markers? Epileptic Disord, 2020, 22(2): 183-193.

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