Role of non-invasive biomarkers in the diagnosis and prognosis of epilepsy_West China Medical Journal

Authors：

LI Debo ^1,2 , JIN Ling ¹ , ZHANG Jiaxian ¹ , LAI Wanlin ¹ , SHA Leihao ¹ ,  CHEN Lei ¹

1. Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Neurology, First People’s Hospital of Shuangliu District, Chengdu & West China (Airport) Hospital, Sichuan University, Chengdu, Sichuan 610200, P. R. China;

Corresponding author：

CHEN Lei, Email: leilei_25@126.com

Keywords：

Epilepsy; biomarkers; non-invasiveness; prognosis; clinical translation

DOI：

10.7507/1002-0179.202409247

Video：

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Abstract Full text Figures/Tables Video References Cited by

Non-invasive biomarkers, due to their non-invasive and safe characteristics, hold significant potential for the diagnosis and prognosis of epilepsy. This review summarizes the research progress and future directions of non-invasive biomarkers for epilepsy, encompassing electrophysiological, imaging, biochemical, and genetic markers, and discusses biomarkers for specific types of epilepsy, such as structural lesion-related epilepsy, infection and inflammation-related epilepsy, autoimmune epilepsy, endocrine hormone-related epilepsy, and metabolic epilepsy, to facilitate their clinical application.

Citation： LI Debo, JIN Ling, ZHANG Jiaxian, LAI Wanlin, SHA Leihao, CHEN Lei. Role of non-invasive biomarkers in the diagnosis and prognosis of epilepsy. West China Medical Journal, 2025, 40(1): 113-118. doi: 10.7507/1002-0179.202409247 Copy

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2.	陈述花, 郭强, 金丽日, 等. 癫痫中心分级标准(2023 版). 癫痫杂志, 2023, 9(5): 363-368.
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5.	Pitkänen A, Lukasiuk K, Dudek FE, et al. Epileptogenesis. Cold Spring Harb Perspect Med, 2015, 5(10): a022822.
6.	Pitkänen A, Lukasiuk K. Mechanisms of epileptogenesis and potential treatment targets. Lancet Neurol, 2011, 10(2): 173-186.
7.	Pitkänen A, Ekolle Ndode-Ekane X, Lapinlampi N, et al. Epilepsy biomarkers - toward etiology and pathology specificity. Neurobiol Dis, 2019, 123: 42-58.
8.	Kobylarek D, Iwanowski P, Lewandowska Z, et al. Advances in the potential biomarkers of epilepsy. Front Neurol, 2019, 10: 685.
9.	Kanner AM, Mazarati A, Koepp M. Biomarkers of epileptogenesis: psychiatric comorbidities (?). Neurotherapeutics, 2014, 11(2): 358-372.
10.	Pitkänen A, Engel J. Past and present definitions of epileptogenesis and its biomarkers. Neurotherapeutics, 2014, 11(2): 231-241.
11.	Wang I, Oh S, Blümcke I, et al. Value of 7T MRI and post-processing in patients with nonlesional 3T MRI undergoing epilepsy presurgical evaluation. Epilepsia, 2020, 61(11): 2509-2520.
12.	Oluigbo CO, Gaillard WD, Koubeissi MZ. The end justifies the means-a call for nuance in the increasing nationwide adoption of stereoelectroencephalography over subdural electrode monitoring in the surgical evaluation of intractable epilepsy. JAMA Neurol, 2022, 79(3): 221-222.
13.	Labate A, Cherubini A, Tripepi G, et al. White matter abnormalities differentiate severe from benign temporal lobe epilepsy. Epilepsia, 2015, 56(7): 1109-1116.
14.	Guo K, Cui B, Shang K, et al. Assessment of localization accuracy and postsurgical prediction of simultaneous ¹⁸F-FDG PET/MRI in refractory epilepsy patients. Eur Radiol, 2021, 31(9): 6974-6982.
15.	Fierain A, McGonigal A, Lagarde S, et al. Stereoelectroencephalography (SEEG) and epilepsy surgery in posttraumatic epilepsy: a multicenter retrospective study. Epilepsy Behav, 2020, 112: 107378.
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18.	Von EN, Dubeau F, Dudley RWR, et al. “Generalized-to-focal” epilepsy: stereotactic EEG and high-frequency oscillation patterns. Epileptic Disord, 2022, 24(6): 1087-1094.
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26.	Tian Z, Huang S, Wen S, et al. Event-related potentials reveal visual episodic memory deficits in patients with temporal lobe epilepsy. Epilepsy Behav, 2023, 148: 109460.
27.	王盛淋, 邱祥凯, 王汝清, 等. 基于全局图振幅排列熵的 EEG 心算分类研究. 数据采集与处理, 2024, 39(3): 724-735.
28.	Ueda T, Iimura Y, Mitsuhashi T, et al. Chronological changes in phase-amplitude coupling during epileptic seizures in temporal lobe epilepsy. Clin Neurophysiol, 2023, 148: 44-51.
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32.	Bono BC, Ninatti G, Riva M, et al. The role of preoperative [¹¹C] methionine PET in defining tumor-related epilepsy and predicting short-term postoperative seizure control in temporal lobe low-grade gliomas. Neurosurg Focus, 2024, 56(2): E6.
33.	Traub-Weidinger T, Arbizu J, Barthel H, et al. EANM practice guidelines for an appropriate use of PET and SPECT for patients with epilepsy. Eur J Nucl Med Mol Imaging, 2024, 51(7): 1891-1908.
34.	Ngadimon IW, Shaikh MF, Mohan D, et al. Mapping epilepsy biomarkers: a bibliometric and content analysis. Drug Discov Today, 2024, 29(12): 104247.
35.	Filipek A, Leśniak W. S100A6 and its brain ligands in neurodegenerative disorders. Int J Mol Sci, 2020, 21(11): 3979.
36.	Hanin A, Denis JA, Frazzini V, et al. Neuron specific enolase, S100-beta protein and progranulin as diagnostic biomarkers of status epilepticus. J Neurol, 2022, 269(7): 3752-3760.
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38.	卢倩, 张淇, 王秋红, 等. 外泌体在癫痫的诊断与治疗中的应用. 癫痫杂志, 2023, 9(4): 306-309.
39.	Abdel MSS, Rashad AA, Elshaer SS, et al. The emerging role of miRNAs in epilepsy: from molecular signatures to diagnostic potential. Pathol Res Pract, 2024, 254: 155146.
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51.	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.
52.	Simani L, Elmi M, Asadollahi M. Serum GFAP level: a novel adjunctive diagnostic test in differentiate epileptic seizures from psychogenic attacks. Seizure, 2018, 61: 41-44.
53.	Diamond ML, Ritter AC, Failla MD, et al. IL-1β associations with posttraumatic epilepsy development: a genetics and biomarker cohort study. Epilepsia, 2014, 55(7): 1109-1119.
54.	Galovic M, Ferreira-Atuesta C, Abraira L, et al. Seizures and epilepsy after stroke: epidemiology, biomarkers and management. Drugs Aging, 2021, 38(4): 285-299.
55.	Abraira L, Santamarina E, Cazorla S, et al. Blood biomarkers predictive of epilepsy after an acute stroke event. Epilepsia, 2020, 61(10): 2244-2253.
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1. Riney K, Bogacz A, Somerville E, et al. International League Against Epilepsy classification and definition of epilepsy syndromes with onset at a variable age: position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia, 2022, 63(6): 1443-1474.
2. 陈述花, 郭强, 金丽日, 等. 癫痫中心分级标准(2023 版). 癫痫杂志, 2023, 9(5): 363-368.
3. Singh G, Sander JW. The global burden of epilepsy report: implications for low- and middle-income countries. Epilepsy Behav, 2020, 105: 106949.
4. Kalilani L, Sun X, Pelgrims B, et al. The epidemiology of drug-resistant epilepsy: a systematic review and meta-analysis. Epilepsia, 2018, 59(12): 2179-2193.
5. Pitkänen A, Lukasiuk K, Dudek FE, et al. Epileptogenesis. Cold Spring Harb Perspect Med, 2015, 5(10): a022822.
6. Pitkänen A, Lukasiuk K. Mechanisms of epileptogenesis and potential treatment targets. Lancet Neurol, 2011, 10(2): 173-186.
7. Pitkänen A, Ekolle Ndode-Ekane X, Lapinlampi N, et al. Epilepsy biomarkers - toward etiology and pathology specificity. Neurobiol Dis, 2019, 123: 42-58.
8. Kobylarek D, Iwanowski P, Lewandowska Z, et al. Advances in the potential biomarkers of epilepsy. Front Neurol, 2019, 10: 685.
9. Kanner AM, Mazarati A, Koepp M. Biomarkers of epileptogenesis: psychiatric comorbidities (?). Neurotherapeutics, 2014, 11(2): 358-372.
10. Pitkänen A, Engel J. Past and present definitions of epileptogenesis and its biomarkers. Neurotherapeutics, 2014, 11(2): 231-241.
11. Wang I, Oh S, Blümcke I, et al. Value of 7T MRI and post-processing in patients with nonlesional 3T MRI undergoing epilepsy presurgical evaluation. Epilepsia, 2020, 61(11): 2509-2520.
12. Oluigbo CO, Gaillard WD, Koubeissi MZ. The end justifies the means-a call for nuance in the increasing nationwide adoption of stereoelectroencephalography over subdural electrode monitoring in the surgical evaluation of intractable epilepsy. JAMA Neurol, 2022, 79(3): 221-222.
13. Labate A, Cherubini A, Tripepi G, et al. White matter abnormalities differentiate severe from benign temporal lobe epilepsy. Epilepsia, 2015, 56(7): 1109-1116.
14. Guo K, Cui B, Shang K, et al. Assessment of localization accuracy and postsurgical prediction of simultaneous ¹⁸F-FDG PET/MRI in refractory epilepsy patients. Eur Radiol, 2021, 31(9): 6974-6982.
15. Fierain A, McGonigal A, Lagarde S, et al. Stereoelectroencephalography (SEEG) and epilepsy surgery in posttraumatic epilepsy: a multicenter retrospective study. Epilepsy Behav, 2020, 112: 107378.
16. GBD 2016 Epilepsy Collaborators. Global, regional, and national burden of epilepsy, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol, 2019, 18(4): 357-375.
17. 王玮, 梁树立, 杨小枫. 头皮脑电信号中的高频振荡在癫痫诊疗中的应用研究进展. 中华神经医学杂志, 2019, 18(7): 740-744.
18. Von EN, Dubeau F, Dudley RWR, et al. “Generalized-to-focal” epilepsy: stereotactic EEG and high-frequency oscillation patterns. Epileptic Disord, 2022, 24(6): 1087-1094.
19. Li X, Zhang H, Lai H, et al. High-frequency oscillations and epileptogenic network. Curr Neuropharmacol, 2022, 20(9): 1687-1703.
20. 薛苗苗. 颞叶癫痫大鼠海马网络电生理特征研究. 成都: 电子科技大学, 2018.
21. Zhang Y, Lu Q, Monsoor T, et al. Refining epileptogenic high-frequency oscillations using deep learning: a reverse engineering approach. Brain Commun, 2021, 4(1): fcab267.
22. 李陶乐, 许虹. 运用事件相关电位评价颞叶癫痫患者认知功能及其与头颅磁共振和脑电图异常的相关性分析. 中华医学杂志, 2019, 99(27): 2115-2118.
23. Mukheem MMA, Mundlamuri RC, Aravind KR, et al. EEG-based P300 in mesial temporal lobe epilepsy and its correlation with cognitive functions: a case-control study. Epilepsy Behav, 2021, 123: 108279.
24. Wu TQ, Kaboodvand N, McGinn RJ, et al. Multisite thalamic recordings to characterize seizure propagation in the human brain. Brain, 2023, 146(7): 2792-2802.
25. Mogi T, Tsunoda T, Yoshino A. Altered upright face recognition and presence of face inversion effect in temporal lobe epilepsy: an event-related potential study. Psychiatry Clin Neurosci, 2019, 73(5): 269-276.
26. Tian Z, Huang S, Wen S, et al. Event-related potentials reveal visual episodic memory deficits in patients with temporal lobe epilepsy. Epilepsy Behav, 2023, 148: 109460.
27. 王盛淋, 邱祥凯, 王汝清, 等. 基于全局图振幅排列熵的 EEG 心算分类研究. 数据采集与处理, 2024, 39(3): 724-735.
28. Ueda T, Iimura Y, Mitsuhashi T, et al. Chronological changes in phase-amplitude coupling during epileptic seizures in temporal lobe epilepsy. Clin Neurophysiol, 2023, 148: 44-51.
29. Middlebrooks EH, Gupta V, Agarwal AK, et al. Radiologic classification of hippocampal sclerosis in epilepsy. AJNR Am J Neuroradiol, 2024, 45(9): 1185-1193.
30. Li Y, Ran Y, Yao M, Chen Q. Altered static and dynamic functional connectivity of the default mode network across epilepsy subtypes in children: a resting-state fMRI study. Neurobiol Dis, 2024, 192: 106425.
31. Guo J, Guo M, Liu R, et al. Seizure outcome after surgery for refractory epilepsy diagnosed by ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET/MRI): a systematic review and meta-analysis. World Neurosurg, 2023, 173: 34-43.
32. Bono BC, Ninatti G, Riva M, et al. The role of preoperative [¹¹C] methionine PET in defining tumor-related epilepsy and predicting short-term postoperative seizure control in temporal lobe low-grade gliomas. Neurosurg Focus, 2024, 56(2): E6.
33. Traub-Weidinger T, Arbizu J, Barthel H, et al. EANM practice guidelines for an appropriate use of PET and SPECT for patients with epilepsy. Eur J Nucl Med Mol Imaging, 2024, 51(7): 1891-1908.
34. Ngadimon IW, Shaikh MF, Mohan D, et al. Mapping epilepsy biomarkers: a bibliometric and content analysis. Drug Discov Today, 2024, 29(12): 104247.
35. Filipek A, Leśniak W. S100A6 and its brain ligands in neurodegenerative disorders. Int J Mol Sci, 2020, 21(11): 3979.
36. Hanin A, Denis JA, Frazzini V, et al. Neuron specific enolase, S100-beta protein and progranulin as diagnostic biomarkers of status epilepticus. J Neurol, 2022, 269(7): 3752-3760.
37. 冯骄, 黄丽, 侯宁, 等. 丙戊酸通过调控 S100B 蛋白表达对癫痫幼鼠模型的认知功能及 NMDAR1 水平的影响. 卒中与神经疾病, 2023, 30(5): 454-460.
38. 卢倩, 张淇, 王秋红, 等. 外泌体在癫痫的诊断与治疗中的应用. 癫痫杂志, 2023, 9(4): 306-309.
39. Abdel MSS, Rashad AA, Elshaer SS, et al. The emerging role of miRNAs in epilepsy: from molecular signatures to diagnostic potential. Pathol Res Pract, 2024, 254: 155146.
40. Alhusaini S, Whelan CD, Sisodiya SM, et al. Quantitative magnetic resonance imaging traits as endophenotypes for genetic mapping in epilepsy. Neuroimage Clin, 2016, 12: 526-534.
41. Thakran S, Guin D, Singh P, et al. Genetic landscape of common epilepsies: advancing towards precision in treatment. Int J Mol Sci, 2020, 21(20): 7784.
42. Sander T, Toliat MR, Heils A, et al. Association of the 867Asp variant of the human anion exchanger 3 gene with common subtypes of idiopathic generalized epilepsy. Epilepsy Res, 2002, 51(3): 249-255.
43. Layouni S, Buresi C, Thomas P, et al. BRD2 and TAP-1 genes and juvenile myoclonic epilepsy. Neurol Sci, 2010, 31(1): 53-56.
44. Liang J, Zhang Y, Wang J, et al. New variants in the CACNA1H gene identified in childhood absence epilepsy. Neurosci Lett, 2006, 406(1/2): 27-32.
45. Busolin G, Malacrida S, Bisulli F, et al. Association of intronic variants of the KCNAB1 gene with lateral temporal epilepsy. Epilepsy Res, 2011, 94(1/2): 110-116.
46. Balan S, Vellichirammal NN, Banerjee M, et al. Failure to find association between febrile seizures and SCN1A rs3812718 polymorphism in south Indian patients with mesial temporal lobe epilepsy and hippocampal sclerosis. Epilepsy Res, 2012, 101(3): 288-292.
47. Maljevic S, Krampfl K, Cobilanschi J, et al. A mutation in the GABA_A receptor α₁-subunit is associated with absence epilepsy. Ann Neurol, 2006, 59(6): 983-987.
48. Kopczynska M, Zelek WM, Vespa S, et al. Complement system biomarkers in epilepsy. Seizure, 2018, 60: 1-7.
49. Zhu M, Chen J, Guo H, et al. High mobility group protein B1 (HMGB1) and interleukin-1β as prognostic biomarkers of epilepsy in children. J Child Neurol, 2018, 33(14): 909-917.
50. Maiti R, Mishra BR, Jena M, et al. Effect of anti-seizure drugs on serum S100B in patients with focal seizure: a randomized controlled trial. J Neurol, 2018, 265(11): 2594-2601.
51. 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.
52. Simani L, Elmi M, Asadollahi M. Serum GFAP level: a novel adjunctive diagnostic test in differentiate epileptic seizures from psychogenic attacks. Seizure, 2018, 61: 41-44.
53. Diamond ML, Ritter AC, Failla MD, et al. IL-1β associations with posttraumatic epilepsy development: a genetics and biomarker cohort study. Epilepsia, 2014, 55(7): 1109-1119.
54. Galovic M, Ferreira-Atuesta C, Abraira L, et al. Seizures and epilepsy after stroke: epidemiology, biomarkers and management. Drugs Aging, 2021, 38(4): 285-299.
55. Abraira L, Santamarina E, Cazorla S, et al. Blood biomarkers predictive of epilepsy after an acute stroke event. Epilepsia, 2020, 61(10): 2244-2253.
56. Shady JA, Black PM, Kupsky WJ, et al. Seizures in children with supratentorial astroglial neoplasms. Pediatr Neurosurg, 1994, 21(1): 23-30.
57. Shamji MF, Fric-Shamji EC, Benoit BG. Brain tumors and epilepsy: pathophysiology of peritumoral changes. Neurosurg Rev, 2009, 32(3): 275-284.
58. Meldrum BS. The role of glutamate in epilepsy and other CNS disorders. Neurology, 1994, 44(11 Suppl 8): S14-S23.
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West China Medical Journal

Role of non-invasive biomarkers in the diagnosis and prognosis of epilepsy

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