Biological markers of status epilepticus_Journal of Epilepsy

Authors：

LIANG Bianbian ¹ , CHENG Xiaojing ² ,  ZHANG Xiaodong ²

1. Changzhi Medical University, Changzhi 046013, China;
2. Department of Neurology, Taiyuan Central Hospital, Taiyuan 0300092, China;

Corresponding author：

ZHANG Xiaodong, Email: 13835195709@163.com

Keywords：

Status epilepticus; Biomarkers; Neuroinflammation; miRNA

DOI：

10.7507/2096-0247.202510001

Video：

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Status epilepticus is a life-threatening neurological emergency with high mortality and disability rates. If not treated promptly and effectively, it can lead to severe brain damage or even death. Currently, diagnosis and prognosis assessment mainly rely on electroencephalogram (EEG) and clinical manifestations, which have delays and subjectivity. Therefore, the search for biomarkers that can rapidly, objectively, and accurately assist in the diagnosis, classification, treatment guidance, and prognosis judgment of status epilepticus has become a research hotspot. Biomarkers can reflect the occurrence and development process of the disease at the molecular level, bringing new hope for the precise diagnosis and treatment of status epilepticus. This review aims to systematically elaborate on potential biomarkers in the field of SE.

Citation： LIANG Bianbian, CHENG Xiaojing, ZHANG Xiaodong. Biological markers of status epilepticus. Journal of Epilepsy, 2025, 11(6): 515-518. doi: 10.7507/2096-0247.202510001 Copy

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2.	Global, regional, and national burden of disorders affecting the nervous system, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol, 2024, 23(4): 344-381.
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4.	Tharmaraja T, Ho J S Y, Neligan A, et al. The etiology and mortality of new-onset refractory status epilepticus (NORSE) in adults: a systematic review and meta-analysis. Epilepsia, 2023, 64(5): 1113-1124.
5.	Alkhachroum A, Der-Nigoghossian CA, Rubinos C, et al. Markers in status epilepticus prognosis. J Clin Neurophysiol, 2020, 37(5): 422-428.
6.	Hanin A, Lambrecq V, Denis JA, et al. Cerebrospinal fluid and blood biomarkers of status epilepticus. Epilepsia, 2020, 61(1): 6-18.
7.	李袁源, 张鸿. 癫痫持续状态诊疗及预后的研究进展. 癫痫杂志, 2025, 11(3): 250-255.
8.	Michetti F, Clementi M E, Di Liddo R, et al. The S100B protein: a multifaceted pathogenic factor more than a biomarker. Int J Mol Sci, 2023, 24(11): 156-162.
9.	Langeh U, Singh S. Targeting S100B protein as a surrogate biomarker and its role in various neurological disorders. Curr Neuropharmacol, 2021, 19(2): 265-277.
10.	Cudna A, Bronisz E, Jopowicz A, et al. Changes in serum blood-brain barrier markers after bilateral tonic-clonic seizures. Seizure, 2023, 106: 129-137.
11.	Hanin A, Denis J A, 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.
12.	Wang M, Yu J, Xiao X, et al. Changes of biochemical biomarkers in the serum of children with convulsion status epilepticus: a prospective study. BMC Neurol, 2022, 22(1): 196.
13.	Tikhonova MA, Shvaikovskaya AA, Zhanaeva SY, et al. Concordance between the in vivo content of neurospecific proteins (BDNF, NSE, VILIP-1, S100B) in the hippocampus and blood in patients with epilepsy. Int J Mol Sci, 2023, 25(1): 658-662.
14.	张芳, 王建忠, 李学超, 等. 血清S100B蛋白联合STESS量表评分对癫痫持续状态患儿近期预后的预测价值. 中南医学科学杂志, 2023, 51(5): 724-726+748.
15.	Park Y, Kc N, Paneque A, et al. Tau, glial fibrillary acidic protein, and neurofilament light chain as brain protein biomarkers in cerebrospinal fluid and blood for diagnosis of neurobiological diseases. Int J Mol Sci, 2024, 25(12): 265-268.
16.	Khalil M, Teunissen CE, Lehmann S, et al. Neurofilaments as biomarkers in neurological disorders - towards clinical application. Nat Rev Neurol, 2024, 20(5): 269-287.
17.	Giovannini G, Bedin R, Ferraro D, et al. Serum neurofilament light as biomarker of seizure-related neuronal injury in status epilepticus. Epilepsia, 2022, 63(1): e23-e29.
18.	Hagberg L, Zetterberg H, Gisslén M. Neurofilament light chain as a biomarker for neuronal injury in CNS infections. Expert Rev Mol Diagn, 2025, 25(8): 419-424.
19.	Thaele A, Barba L, Abu-Rumeileh S, et al. Neurofilament light chain and glial fibrillary acidic protein as diagnostic and prognostic biomarkers in epileptic seizures and epilepsy: A systematic review. Epilepsy Behav, 2025, 165: 110321.
20.	Banote RK, Akel S, Zelano J. Blood biomarkers in epilepsy. Acta Neurol Scand, 2022, 146(4): 362-368.
21.	Babkina AS, Lyubomudrov M A, Golubev M A, et al. Neuron-Specific Enolase-What Are We Measuring? Int J Mol Sci, 2024, 25(9): 653-656.
22.	Sanz P, Rubio T, Garcia-Gimeno M A. Neuroinflammation and epilepsy: from pathophysiology to therapies based on repurposing drugs. Int J Mol Sci, 2024, 25(8): 1159-1168.
23.	Soltani Khaboushan A, Yazdanpanah N, Rezaei N. Neuroinflammation and Proinflammatory Cytokines in Epileptogenesis. Mol Neurobiol, 2022, 59(3): 1724-1743.
24.	Wu L, Zhu Y, Qin Y, et al. Conditional knockout of IL-1R1 in endothelial cells attenuates seizures and neurodegeneration via inhibiting neuroinflammation mediated by nrf2/ho-1/nlrp3 signaling in status epilepticus model. Mol Neurobiol, 2024, 61(7): 4289-4303.
25.	Mohseni-Moghaddam P, Roghani M, Khaleghzadeh-Ahangar H, et al. A literature overview on epilepsy and inflammasome activation. Brain Res Bull, 2021, 172: 229-235.
26.	Yu T, Fu H, Sun J J, et al. miR-106b-5p upregulation is associated with microglial activation and inflammation in the mouse hippocampus following status epilepticus. Exp Brain Res, 2021, 239(11): 3315-3325.
27.	Shigemoto-Mogami Y, Sato K. Central nervous system developmental regulation of microglia via cytokines and chemokines. Yakugaku Zasshi, 2021, 141(3): 359-368.
28.	Hanin A, Cespedes J, Dorgham K, et al. Cytokines in new-onset refractory status epilepticus predict outcomes. Ann Neurol, 2023, 94(1): 75-90.
29.	Di Sapia R, Zimmer T S, Kebede V, et al. CXCL1-CXCR1/2 signaling is induced in human temporal lobe epilepsy and contributes to seizures in a murine model of acquired epilepsy. Neurobiol Dis, 2021, 158: 105468.
30.	Henning L, Antony H, Breuer A, et al. Reactive microglia are the major source of tumor necrosis factor alpha and contribute to astrocyte dysfunction and acute seizures in experimental temporal lobe epilepsy. Glia, 2023, 71(2): 168-186.
31.	Fang W, Chen S, Xia X, et al. Interictal interleukin-6 and tumor necrosis factor α levels are associated with seizure recurrence in adults with epilepsy. Epilepsy Behav, 2024, 155: 109786.
32.	Kamaşak T, Dilber B, Yaman S, et al. HMGB-1, TLR4, IL-1R1, TNF-α, and IL-1β: novel epilepsy markers? Epileptic Disord, 2020, 22(2): 183-193.
33.	Martinez B, Peplow P V. MicroRNAs in mouse and rat models of experimental epilepsy and potential therapeutic targets. Neural Regen Res, 2023, 18(10): 2108-2118.
34.	Liu T, Liu H, Xue S, et al. MiR129-5p-loaded exosomes suppress seizure-associated neurodegeneration in status epilepticus model mice by inhibiting HMGB1/TLR4-mediated neuroinflammation. Mol Biol Rep, 2024, 51(1): 292.
35.	Szydlowska K, Bot A, Nizinska K, et al. Circulating microRNAs from plasma as preclinical biomarkers of epileptogenesis and epilepsy. Sci Rep, 2024, 14(1): 708.
36.	Selvaraj C, Abhirami R, Vijayakumar R, et al. Immunological insights of selectins in human disease mechanism. Adv Protein Chem Struct Biol, 2022, 129: 163-188.
37.	Bronisz E, Cudna A, Wierzbicka A, et al. Blood-brain barrier-associated proteins are elevated in serum of epilepsy patients. Cells, 2023, 12(3): 2256-2261.
38.	Bronisz E, Cudna A, Wierzbicka A, et al. Blood-brain barrier-associated serum proteins as potential diagnostic biomarkers of epilepsy aetiology. Neurol Neurochir Pol, 2025, 59(3): 221-230.
39.	Bronisz E, Cudna A, Wierzbicka A, et al. Serum proteins associated with blood-brain barrier as potential biomarkers for seizure prediction. Int J Mol Sci, 2022, 23(2): 1121-1126.

1. Ascoli M, Ferlazzo E, Gasparini S, et al. Epidemiology and Outcomes of Status Epilepticus. Int J Gen Med, 2021, 14: 2965-2973.
2. Global, regional, and national burden of disorders affecting the nervous system, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol, 2024, 23(4): 344-381.
3. Newton C R. Epidemiology of status epilepticus in children. Dev Med Child Neurol, 2021, 63(9): 1011.
4. Tharmaraja T, Ho J S Y, Neligan A, et al. The etiology and mortality of new-onset refractory status epilepticus (NORSE) in adults: a systematic review and meta-analysis. Epilepsia, 2023, 64(5): 1113-1124.
5. Alkhachroum A, Der-Nigoghossian CA, Rubinos C, et al. Markers in status epilepticus prognosis. J Clin Neurophysiol, 2020, 37(5): 422-428.
6. Hanin A, Lambrecq V, Denis JA, et al. Cerebrospinal fluid and blood biomarkers of status epilepticus. Epilepsia, 2020, 61(1): 6-18.
7. 李袁源, 张鸿. 癫痫持续状态诊疗及预后的研究进展. 癫痫杂志, 2025, 11(3): 250-255.
8. Michetti F, Clementi M E, Di Liddo R, et al. The S100B protein: a multifaceted pathogenic factor more than a biomarker. Int J Mol Sci, 2023, 24(11): 156-162.
9. Langeh U, Singh S. Targeting S100B protein as a surrogate biomarker and its role in various neurological disorders. Curr Neuropharmacol, 2021, 19(2): 265-277.
10. Cudna A, Bronisz E, Jopowicz A, et al. Changes in serum blood-brain barrier markers after bilateral tonic-clonic seizures. Seizure, 2023, 106: 129-137.
11. Hanin A, Denis J A, 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.
12. Wang M, Yu J, Xiao X, et al. Changes of biochemical biomarkers in the serum of children with convulsion status epilepticus: a prospective study. BMC Neurol, 2022, 22(1): 196.
13. Tikhonova MA, Shvaikovskaya AA, Zhanaeva SY, et al. Concordance between the in vivo content of neurospecific proteins (BDNF, NSE, VILIP-1, S100B) in the hippocampus and blood in patients with epilepsy. Int J Mol Sci, 2023, 25(1): 658-662.
14. 张芳, 王建忠, 李学超, 等. 血清S100B蛋白联合STESS量表评分对癫痫持续状态患儿近期预后的预测价值. 中南医学科学杂志, 2023, 51(5): 724-726+748.
15. Park Y, Kc N, Paneque A, et al. Tau, glial fibrillary acidic protein, and neurofilament light chain as brain protein biomarkers in cerebrospinal fluid and blood for diagnosis of neurobiological diseases. Int J Mol Sci, 2024, 25(12): 265-268.
16. Khalil M, Teunissen CE, Lehmann S, et al. Neurofilaments as biomarkers in neurological disorders - towards clinical application. Nat Rev Neurol, 2024, 20(5): 269-287.
17. Giovannini G, Bedin R, Ferraro D, et al. Serum neurofilament light as biomarker of seizure-related neuronal injury in status epilepticus. Epilepsia, 2022, 63(1): e23-e29.
18. Hagberg L, Zetterberg H, Gisslén M. Neurofilament light chain as a biomarker for neuronal injury in CNS infections. Expert Rev Mol Diagn, 2025, 25(8): 419-424.
19. Thaele A, Barba L, Abu-Rumeileh S, et al. Neurofilament light chain and glial fibrillary acidic protein as diagnostic and prognostic biomarkers in epileptic seizures and epilepsy: A systematic review. Epilepsy Behav, 2025, 165: 110321.
20. Banote RK, Akel S, Zelano J. Blood biomarkers in epilepsy. Acta Neurol Scand, 2022, 146(4): 362-368.
21. Babkina AS, Lyubomudrov M A, Golubev M A, et al. Neuron-Specific Enolase-What Are We Measuring? Int J Mol Sci, 2024, 25(9): 653-656.
22. Sanz P, Rubio T, Garcia-Gimeno M A. Neuroinflammation and epilepsy: from pathophysiology to therapies based on repurposing drugs. Int J Mol Sci, 2024, 25(8): 1159-1168.
23. Soltani Khaboushan A, Yazdanpanah N, Rezaei N. Neuroinflammation and Proinflammatory Cytokines in Epileptogenesis. Mol Neurobiol, 2022, 59(3): 1724-1743.
24. Wu L, Zhu Y, Qin Y, et al. Conditional knockout of IL-1R1 in endothelial cells attenuates seizures and neurodegeneration via inhibiting neuroinflammation mediated by nrf2/ho-1/nlrp3 signaling in status epilepticus model. Mol Neurobiol, 2024, 61(7): 4289-4303.
25. Mohseni-Moghaddam P, Roghani M, Khaleghzadeh-Ahangar H, et al. A literature overview on epilepsy and inflammasome activation. Brain Res Bull, 2021, 172: 229-235.
26. Yu T, Fu H, Sun J J, et al. miR-106b-5p upregulation is associated with microglial activation and inflammation in the mouse hippocampus following status epilepticus. Exp Brain Res, 2021, 239(11): 3315-3325.
27. Shigemoto-Mogami Y, Sato K. Central nervous system developmental regulation of microglia via cytokines and chemokines. Yakugaku Zasshi, 2021, 141(3): 359-368.
28. Hanin A, Cespedes J, Dorgham K, et al. Cytokines in new-onset refractory status epilepticus predict outcomes. Ann Neurol, 2023, 94(1): 75-90.
29. Di Sapia R, Zimmer T S, Kebede V, et al. CXCL1-CXCR1/2 signaling is induced in human temporal lobe epilepsy and contributes to seizures in a murine model of acquired epilepsy. Neurobiol Dis, 2021, 158: 105468.
30. Henning L, Antony H, Breuer A, et al. Reactive microglia are the major source of tumor necrosis factor alpha and contribute to astrocyte dysfunction and acute seizures in experimental temporal lobe epilepsy. Glia, 2023, 71(2): 168-186.
31. Fang W, Chen S, Xia X, et al. Interictal interleukin-6 and tumor necrosis factor α levels are associated with seizure recurrence in adults with epilepsy. Epilepsy Behav, 2024, 155: 109786.
32. Kamaşak T, Dilber B, Yaman S, et al. HMGB-1, TLR4, IL-1R1, TNF-α, and IL-1β: novel epilepsy markers? Epileptic Disord, 2020, 22(2): 183-193.
33. Martinez B, Peplow P V. MicroRNAs in mouse and rat models of experimental epilepsy and potential therapeutic targets. Neural Regen Res, 2023, 18(10): 2108-2118.
34. Liu T, Liu H, Xue S, et al. MiR129-5p-loaded exosomes suppress seizure-associated neurodegeneration in status epilepticus model mice by inhibiting HMGB1/TLR4-mediated neuroinflammation. Mol Biol Rep, 2024, 51(1): 292.
35. Szydlowska K, Bot A, Nizinska K, et al. Circulating microRNAs from plasma as preclinical biomarkers of epileptogenesis and epilepsy. Sci Rep, 2024, 14(1): 708.
36. Selvaraj C, Abhirami R, Vijayakumar R, et al. Immunological insights of selectins in human disease mechanism. Adv Protein Chem Struct Biol, 2022, 129: 163-188.
37. Bronisz E, Cudna A, Wierzbicka A, et al. Blood-brain barrier-associated proteins are elevated in serum of epilepsy patients. Cells, 2023, 12(3): 2256-2261.
38. Bronisz E, Cudna A, Wierzbicka A, et al. Blood-brain barrier-associated serum proteins as potential diagnostic biomarkers of epilepsy aetiology. Neurol Neurochir Pol, 2025, 59(3): 221-230.
39. Bronisz E, Cudna A, Wierzbicka A, et al. Serum proteins associated with blood-brain barrier as potential biomarkers for seizure prediction. Int J Mol Sci, 2022, 23(2): 1121-1126.

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Biological markers of status epilepticus

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