Application of cerebrospinal fluid/serum albumin ratio in assessing blood-brain barrier permeability in children with drug-resistant epilepsy

doi:10.3969/j.issn.1672-6731.2025.11.004

Abstract

Abstract: Background The cerebrospinal fluid/serum albumin ratio (QAlb) serves as a critical indicator for assessing blood-brain barrier (BBB) permeability. This study aimed to assess BBB permeability in children with drug-resistant epilepsy (DRE) by calculating QAlb and to investigate its correlation with clinical characteristics, as well as its potential as a biological marker. Methods A total of 35 children diagnosed with DRE (epilepsy group) and 37 children with primary headache (control group) were admitted to The First Affiliated Hospital of Zhengzhou University between June 2018 and June 2023. QAlb values were derived from laboratory test results. Spearman rank correlation analysis was employed to explore the relationship between QAlb and variables such as disease duration, seizure type, seizure frequency, status epilepticus, and the number of antiepileptic seizure medicine (ASM). Results Compared with control group, the QAlb values were elevated [3.29 (2.39, 4.54) ×10³ vs. 2.15 (1.42, 2.59) ×10³; Z=4.616, P=0.000], and the incidence of BBB dysfunction was higher [28.57% (10/35) vs. 2.70% (1/37); χ²=9.299, P=0.002] in epilepsy group. Spearman rank correlation analysis indicated a positive correlation between QAlb and both seizure frequency (r_s=0.587, P=0.000) and the number of ASM (r_s=0.367, P=0.030) in children with DRE. Conclusions Some children with DRE exhibit BBB dysfunction. QAlb is positively correlated with seizure frequency and the number of ASM, suggesting its potential as a biological marker for identifying BBB dysfunction.

Key words: Drug resistant epilepsy, Cerebrospinal fluid, Serum albumin, Blood-brain barrier, Child

摘要： 研究背景 脑脊液/血清白蛋白比值（QAlb）是血脑屏障通透性的评估指标，本研究通过计算QAlb评估药物难治性癫痫患儿血脑屏障通透性，并探讨其与临床特征的相关性及其作为生物学标志物的可行性。方法纳入2018年6月至2023年6月郑州大学第一附属医院收治的35例药物难治性癫痫患儿（癫痫组）和37例原发性头痛患儿（对照组），根据实验室检查结果计算QAlb，Spearman秩相关分析探究其与癫痫病程、发作形式、发作频率、癫痫持续状态和抗癫痫发作药物种类的相关性。结果癫痫组患儿QAlb高于对照组［3.29（2.39，4.54）×10³对2.15（1.42，2.59）×10³；Z=4.616，P=0.000］，血脑屏障功能障碍发生率亦高于对照组［28.57%（10/35）对2.70%（1/37）；χ²=9.299，P=0.002］。Spearman秩相关分析显示，药物难治性癫痫患儿QAlb与癫痫发作频率（r_s=0.587，P=0.000）和抗癫痫发作药物种类（r_s=0.367，P=0.030）呈正相关。结论部分药物难治性癫痫患儿存在血脑屏障功能障碍，QAlb与癫痫发作频率和抗癫痫发作药物种类呈正相关，提示其可作为识别血脑屏障功能障碍的潜在生物学标志物。

关键词: 耐药性癫痫, 脑脊髓液, 血清白蛋白, 血脑屏障, 儿童

WANG Yao, MA Wei, CAI Ao-jie, JIN Pei-na, ZHUO Zhi-hong, WANG Huai-li. Application of cerebrospinal fluid/serum albumin ratio in assessing blood-brain barrier permeability in children with drug-resistant epilepsy[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2025, 25(11): 999-1003.

王瑶, 马威, 蔡奥捷, 靳培娜, 禚志红, 王怀立. 脑脊液与血清白蛋白比值在药物难治性癫痫患儿血脑屏障通透性评估中的应用[J]. 中国现代神经疾病杂志, 2025, 25(11): 999-1003.

/ / Recommend / Download Citations

URL: https://journal11.magtechjournal.com/cjcnn/EN/10.3969/j.issn.1672-6731.2025.11.004

https://journal11.magtechjournal.com/cjcnn/EN/Y2025/V25/I11/999

References

[1] Menon RN, Helen Cross J. Childhood epilepsy[J]. Lancet, 2025, 406:636-649.
[2] Perucca E, Perucca P, White HS, Wirrell EC. Drug resistance in epilepsy[J]. Lancet Neurol, 2023, 22:723-734.
[3] Löscher W. Epilepsy and alterations of the blood-brain barrier:cause or consequence of epileptic seizures or both[J]? Handb Exp Pharmacol, 2022, 273:331-350.
[4] Musaeus CS, Gleerup HS, Høgh P, Waldemar G, Hasselbalch SG, Simonsen AH. Cerebrospinal fluid/plasma albumin ratio as a biomarker for blood-brain barrier impairment across neurodegenerative dementias[J]. J Alzheimers Dis, 2020, 75:429-436.
[5] Nishihara H, Perriot S, Gastfriend BD, Steinfort M, Cibien C, Soldati S, Matsuo K, Guimbal S, Mathias A, Palecek SP, Shusta EV, Pasquier RD, Engelhardt B. Intrinsic blood-brain barrier dysfunction contributes to multiple sclerosis pathogenesis[J].Brain, 2022, 145:4334-4348.
[6] Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Moshé SL, Perucca E, Wiebe S, French J. Definition of drug resistant epilepsy:consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies[J]. Epilepsia, 2010, 51:1069-1077.
[7] Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition[J]. Cephalalgia, 2018, 38:1-211.
[8] Reiber H. External quality assessment in clinical neurochemistry:survey of analysis for cerebrospinal fluid (CSF) proteins based on CSF/serum quotients[J]. Clin Chem, 1995, 41:256-263.
[9] Reiber H, Peter JB. Cerebrospinal fluid analysis:disease-related data patterns and evaluation programs[J]. J Neurol Sci, 2001, 184:101-122.
[10] Chen W, Man X, Zhang Y, Yao G, Chen J. Medial prefrontal cortex oxytocin mitigates epilepsy and cognitive impairments induced by traumatic brain injury through reducing neuroinflammation in mice[J]. Sci Rep, 2023, 13:5214.
[11] van Vliet EA, Aronica E, Gorter JA. Blood-brain barrier dysfunction, seizures and epilepsy[J]. Semin Cell Dev Biol, 2015, 38:26-34.
[12] Cafri N, Mirloo S, Zarhin D, Kamintsky L, Serlin Y, Alhadeed L, Goldberg I, Maclean MA, Whatley B, Urman I, Doherty CP, Greene C, Behan C, Brennan D, Campbell M, Bowen C, Ben-Arie G, Shelef I, Wandschneider B, Koepp M, Friedman A, Benninger F. Imaging blood-brain barrier dysfunction in drug-resistant epilepsy:a multi-center feasibility study[J]. Epilepsia, 2025, 66:195-206.
[13] Weissberg I, Wood L, Kamintsky L, Vazquez O, Milikovsky DZ, Alexander A, Oppenheim H, Ardizzone C, Becker A, Frigerio F, Vezzani A, Buckwalter MS, Huguenard JR, Friedman A, Kaufer D. Albumin induces excitatory synaptogenesis through astrocytic TGF-β/ALK5 signaling in a model of acquired epilepsy following blood-brain barrier dysfunction[J]. Neurobiol Dis, 2015, 78:115-125.
[14] Ivens S, Kaufer D, Flores LP, Bechmann I, Zumsteg D, Tomkins O, Seiffert E, Heinemann U, Friedman A. TGF-beta receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis[J]. Brain, 2007, 130(Pt 2):535-547.
[15] Huang X, Hussain B, Chang J. Peripheral inflammation and blood-brain barrier disruption:effects and mechanisms[J]. CNS Neurosci Ther, 2021, 27:36-47.
[16] Dadas A, Janigro D. Breakdown of blood brain barrier as a mechanism of post-traumatic epilepsy[J]. Neurobiol Dis, 2019, 123:20-26.
[17] Holmes M, Flaminio Z, Vardhan M, Xu F, Li X, Devinsky O, Saxena D. Cross talk between drug-resistant epilepsy and the gut microbiome[J]. Epilepsia, 2020, 61:2619-2628.
[18] Hu NF, Qiu J, Tan LH. Research status of intestinal flora and pathogenesis of epilepsy[J]. Zhonghua Shi Yong Er Ke Lin Chuang Za Zhi, 2022, 37:1589-1592.[胡南非, 仇君, 谭李红. 肠道菌群与癫痫发病机制的研究现状[J]. 中华实用儿科临床杂志, 2022, 37:1589-1592.]
[19] Greene C, Hanley N, Reschke CR, Reddy A, Mäe MA, Connolly R, Behan C, O'Keeffe E, Bolger I, Hudson N, Delaney C, Farrell MA, O'Brien DF, Cryan J, Brett FM, Beausang A, Betsholtz C, Henshall DC, Doherty CP, Campbell M. Microvascular stabilization via blood-brain barrier regulation prevents seizure activity[J]. Nat Commun, 2022, 13:2003.
[20] Rempe RG, Hartz AMS, Soldner ELB, Sokola BS, Alluri SR, Abner EL, Kryscio RJ, Pekcec A, Schlichtiger J, Bauer B. Matrix metalloproteinase-mediated blood-brain barrier dysfunction in epilepsy[J]. J Neurosci, 2018, 38:4301-4315.
[21] van Vliet EA, da Costa Araújo S, Redeker S, van Schaik R, Aronica E, Gorter JA. Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy[J]. Brain, 2007, 130(Pt 2):521-534.
[22] Kimizu T, Takahashi Y, Oboshi T, Horino A, Omatsu H, Koike T, Yoshitomi S, Yamaguchi T, Otani H, Ikeda H, Imai K, Shigematsu H, Inoue Y. Chronic dysfunction of blood-brain barrier in patients with post-encephalitic/encephalopathic epilepsy[J]. Seizure, 2018, 63:85-90.
[23] Tomkins O, Feintuch A, Benifla M, Cohen A, Friedman A, Shelef I. Blood-brain barrier breakdown following traumatic brain injury:a possible role in posttraumatic epilepsy[J]. Cardiovasc Psychiatry Neurol, 2011:ID765923.
[24] van Vliet EA, Aronica E, Gorter JA. Role of blood-brain barrier in temporal lobe epilepsy and pharmacoresistance[J]. Neuroscience, 2014, 277:455-473.
[25] Malter MP, Choi S, Fink GR. Cerebrospinal fluid findings in non-infectious status epilepticus[J]. Epilepsy Res, 2018, 140:61-65.
[26] Süße M, Gag K, Hamann L, Hannich MJ, von Podewils F. Time dependency of CSF cell count, lactate and blood-CSF barrier dysfunction after epileptic seizures and status epilepticus[J]. Seizure, 2022, 95:11-16.
[27] Rüber T, David B, Lüchters G, Nass RD, Friedman A, Surges R, Stöcker T, Weber B, Deichmann R, Schlaug G, Hattingen E, Elger CE. Evidence for peri-ictal blood-brain barrier dysfunction in patients with epilepsy[J]. Brain, 2018, 141:2952-2965.
[28] Soltani Khaboushan A, Yazdanpanah N, Rezaei N. Neuroinflammation and proinflammatory cytokines in epileptogenesis[J]. Mol Neurobiol, 2022, 59:1724-1743.
[29] An J, Li H, Xia D, Xu B, Wang J, Qiu H, He J. The role of interleukin-17 in epilepsy[J]. Epilepsy Res, 2022, 186:107001.
[30] Flammer J, Neziraj T, Rüegg S, Pröbstel AK. Immune mechanisms in epileptogenesis:update on diagnosis and treatment of autoimmune epilepsy syndromes[J]. Drugs, 2023, 83:135-158.

Please choose a citation manager

Content to export