Serum NSE levels in epileptic patients and its correlation with EEG characteristics and recurrence risk
-
摘要:
目的 检测癫痫患者的血清神经元特异性烯醇化酶(NSE)水平,并分析其与脑电图(EEG)特征的相关性,以及癫痫复发风险的预测因素。 方法 选取2021年1月—2023年2月湖州市第一人民医院收治的95例癫痫患者作为研究组,同期选择30例体检健康者作为对照组。采用酶联免疫吸附法检测血清NSE水平,采用Kendall分析血清NSE水平与EEG的相关性;随访1年,根据研究组内癫痫患者是否再次发作分为无复发组(41例)和复发组(52例),采用多因素logistic回归分析癫痫患者复发的影响因素。 结果 研究组血清NSE、甘丙肽(GAL)及肿瘤坏死因子-α(TNF-α)水平均高于对照组(P < 0.05);不同EEG异常组血清NSE、GAL及TNF-α水平比较差异均有统计学意义(P < 0.05)。Kendall相关系数分析显示,NSE、GAL及TNF-α与EEG特征(异常程度)呈正相关关系(P < 0.05)。复发组与无复发组抗癫痫药物服药种数、血清NSE、GAL及TNF-α水平比较差异均有统计学意义(P < 0.05)。多因素logistic回归分析显示:NSE(OR=1.259)及TNF-α(OR=1.097)水平高是癫痫患者复发的独立危险因素(P < 0.05)。ROC曲线结果显示:NSE预测癫痫患者复发的AUC为0.859(95% CI:0.786~0.932),TNF-α的AUC为0.703(95% CI:0.594~0.811)。 结论 血清NSE水平越高,癫痫患者EEG异常程度越高;血清NSE水平对癫痫患者复发风险具有较高的预测价值,可作为癫痫患者复发的独立预测指标。 -
关键词:
- 癫痫 /
- 神经元特异性烯醇化酶 /
- 星形胶质源性蛋白 /
- 脑电图 /
- 复发
Abstract:Objective To detect the level of serum neuron-specific enolase (NSE) in patients with epilepsy, and analyze their correlation with electroencephalogram (EEG) characteristics, as well as identify predictive factors for epilepsy recurrence. Methods A total of 95 epileptic patients admitted to Huzhou First People's Hospital from January 2021 to February 2023 were selected as the research group and 30 healthy people were selected as the control group during the same period. Serum NSE levels were detected by enzyme-linked immunosorbent assay, and the correlation between serum NSE levels and EEG was analyzed by Kendall's correlation. After a one-year follow-up, patients with epilepsy in the research group were divided into a non-recurrence group (n=41) and a recurrence group (n=52). The influencing factors of epilepsy recurrence were analyzed by multivariate logistic regression. Results The levels of serum NSE, galanin (GAL), and TNF-α in the research group were higher than those in the control group (P < 0.05). The levels of serum NSE, GAL, and TNF-α in different EEG abnormal groups were significantly different (P < 0.05). Kendall's correlation analysis showed positive correlations between NSE, GAL, and TNF-α and the degree of EEG abnormality (P < 0.05). The recurrence group showed significant differences in the number of anti-epileptic drugs taken and the levels of serum NSE, GAL, and TNF-α compared to the non-relapse group (P < 0.05). Multivariate logistic regression analysis showed that higher levels of NSE (OR=1.259) and TNF-α (OR=1.097) were independent risk factors for the recurrence of epilepsy (P < 0.05). The ROC curve analysis showed that the AUC of 0.859 (95% CI: 0.786-0.932) for NSE and 0.703 (95% CI: 0.594-0.811) for TNF-α. Conclusion The higher serum NSE levels are associated with higher EEG abnormalities in epileptic patients. Serum NSE levels have a high predictive value for epileptic recurrence and can serve as an independent predictive index of recurrence risk. -
Key words:
- Epilepsy /
- Neuron-specific enolase /
- Astrocyte-derived protein /
- Electroencephalogram /
- Recur
-
表 1 对照组与研究组血清NSE、GAL及TNF-α水平比较(x±s)
Table 1. Comparison of serum NSE, GAL, and TNF-α levels between the control group and the research group (x±s)
组别 例数 NSE(μg/L) GAL(ng/L) TNF-α(μg/L) 对照组 30 15.03±2.14 99.25±7.75 8.56±2.27 研究组 95 53.18±7.68 108.72±20.15 63.20±7.95 t值 43.377 3.780 59.722 P值 < 0.001 0.003 < 0.001 表 2 不同程度EEG异常组癫痫患者血清NSE、GAL及TNF-α水平比较(x±s)
Table 2. Comparison of serum NSE, GAL and TNF-α levels in different EEG abnormal groups (x±s)
组别 例数 NSE(μg/L) GAL(ng/L) TNF-α(μg/L) 轻度EEG异常组 51 48.29±5.18 97.20±18.53 55.76±8.59 中度EEG异常组 20 50.26±4.56 101.54±19.26 61.30±5.42 重度EEG异常组 24 59.03±5.17 114.29±22.15 69.22±7.16 F值 37.490 6.202 25.267 P值 < 0.001 0.003 < 0.001 表 3 癫痫患者实验室指标与EEG特征(异常程度)的相关性分析
Table 3. Correlation analysis between laboratory data and EEG characteristics (abnormal degree) of epileptic patients
项目 r值(95% CI) P值 NSE 0.427(0.305~0.572) < 0.001 GAL 0.194(0.073~0.315) 0.012 TNF-α 0.258(0.112~0.390) < 0.001 表 4 复发组与无复发组癫痫患者一般资料及血清NSE、GAL及TNF-α水平比较
Table 4. Comparison of general data and serum NSE, GAL, and TNF-α levels between the recurrent group and the non-recurrent group
项目 复发组(n=52) 无复发(n=41) 统计量 P值 性别[例(%)] 0.205a 0.651 男性 28(53.85) 24(58.54) 女性 24(46.15) 17(41.46) 年龄(x±s,岁) 46.03±10.22 45.19±9.86 0.401b 0.689 癫痫家族史[例(%)] 1.577a 0.209 有 19(36.54) 10(24.39) 无 33(63.46) 31(75.61) AEDS 服药种数[例(%)] 4.292a 0.038 单药 18(34.62) 23(56.10) 联合用药 34(65.38) 18(43.90) 热惊厥史[例(%)] 0.034a 0.853 有 20(38.46) 15(36.59) 无 32(61.54) 26(63.41) 病程(x±s,年) 5.03±1.35 4.62±1.05 1.647b 0.103 NSE(x±s,μg/L) 62.32±6.14 51.76±6.27 8.138b < 0.001 GAL(x±s,ng/L) 116.20±25.16 105.36±24.29 2.103b 0.038 TNF-α(x±s,μg/L) 65.34±7.56 59.38±7.13 3.897b < 0.001 发作类型[例(%)] 0.997a 0.318 全面性 14(26.92) 15(36.59) 局灶性 38(73.08) 26(63.41) 注:a为χ2值,b为t值。 表 5 癫痫患者复发的多因素logistic回归分析
Table 5. Multivariate logistic regression analysis on recurrence of epilepsy patients
变量 B SE Waldχ2 P值 OR值 95% CI AEDS 服药种数 -1.110 0.604 3.374 0.066 0.329 0.101~1.077 NSE 0.230 0.052 19.219 < 0.001 1.259 1.136~1.395 GAL -0.014 0.015 0.845 0.358 0.987 0.958~1.015 TNF-α 0.093 0.044 4.483 0.034 1.097 1.007~1.196 表 6 血清NSE及TNF-α水平的准确性与预测值
Table 6. Accuracy and predictive value of serum NSE and TNF-α levels
项目 AUC 95% CI 灵敏度
(%)特异度
(%)NSE 0.859 0.786~0.932 78.81 78.04 TNF-α 0.703 0.594~0.811 71.22 61.05 -
[1] LIU J Q, ZHANG P, ZOU Q, et al. Status of epilepsy in the tropics: An overlooked perspective[J]. Epilepsia Open, 2023, 8(1): 32-45. doi: 10.1002/epi4.12686 [2] 刘志敏, 桑琳霞, 李文玲, 等. 难治性癫痫患者外科治疗后延续性护理效果及其复发的影响因素[J]. 实用心脑肺血管病杂志, 2023, 31(12): 134-136, 140.LIU Z M, SANG L X, LI W L, et al. Effect of continuous nursing care for patients with intractable epilepsy after surgical treatment and influencing factors of recurrence[J]. Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease, 2023, 31(12): 134-136, 140. [3] 王满利, 章晓富, 樊玉香, 等. 癫痫患者血清长链非编码RNA母系表达基因3、miR-7-5p表达与认知功能的关系[J]. 中国卫生检验杂志, 2022, 32(24): 2998-3002.WANG M L, ZHANG X F, FAN Y X, et al. Relationship between maternal expression of long-chain noncoding RNA gene 3 and miR-7-5p in serum and cognitive function in epileptic patients[J]. Chinese Journal of Health Laboratory Technology, 2022, 32(24): 2998-3002. [4] 韩长明, 彭福来, 陈财, 等. 基于脑电信号的癫痫发作预测研究进展[J]. 生物医学工程学杂志, 2021, 38(6): 1193-1202.HAN C M, PENG F L, CHEN C, et al. Research progress of epileptic seizure prediction based on EEG[J]. Journal of Biomedical Engineering, 2021, 38(6): 1193-1202. [5] HANIN A, LAMBRECQ V, DENIS J A, et al. Cerebrospinal fluid and blood biomarkers of status epilepticus[J]. Epilepsia, 2020, 61(1): 6-18. doi: 10.1111/epi.16405 [6] KIRMANI B F, AU K, AYARI L, et al. Super-refractory status epilepticus: prognosis and recent advances in management[J]. Aging Dis, 2021, 12(4): 1097-1119. doi: 10.14336/AD.2021.0302 [7] ALKHACHROUM A, DER-NIGOGHOSSIAN C A, RUBINOS C, et al. Markers in status epilepticus prognosis[J]. J Clin Neurophysiol, 2020, 37(5): 422-428. doi: 10.1097/WNP.0000000000000761 [8] 中国抗癫痫协会. 临床诊疗指南-癫痫病分册[M]. 2版. 北京: 人民卫生出版社, 2015: 82.China Anti-Epilepsy Association. Clinical diagnosis and treatment guidelines-epilepsy fascicle[M]. 2nd edition. Beijing: People's Medical Publishing House, 2015: 82. [9] SPECCHIO N, WIRRELL E C, SCHEFFER I E, et al. International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: position paper by the iLAE task force on nosology and definitions[J]. Epilepsia, 2022, 63(6): 1398-1442. doi: 10.1111/epi.17241 [10] VANABELLE P, DE HANDSCHUTTER P, EL TAHRY R, et al. Epileptic seizure detection using EEG signals and extreme gradient boosting[J]. J Biomed Res, 2019, 34(3): 228-239. [11] 刘毅, 郑艳. 济南市癫痫患儿流行病学调查研究与护理防范对策[J]. 护理实践与研究, 2019, 16(12): 8-9.LIU Y, ZHENG Y. Epidemiological investigation and nursing countermeasures of children with epilepsy in Jinan[J]. Nursing Practice and Research, 2019, 16(12): 8-9. [12] 吴雪梅, 王海艳. 癫痫患者共患焦虑和抑郁现状调查及其危险因素分析[J]. 中华全科医学, 2022, 20(11): 1969-1972. doi: 10.16766/j.cnki.issn.1674-4152.002748WU X M, WANG H Y. Investigation of anxiety and depression in epilepsy patients and analysis of risk factors[J]. Chinese Journal of General Practice, 2022, 20(11): 1969-1972. doi: 10.16766/j.cnki.issn.1674-4152.002748 [13] LEE S A, IM K, CHOI E J, et al. Concealment behaviors in Korean adults with epilepsy: their relationships to social anxiety and seizure severity independent of felt stigma[J]. Epilepsy Behav, 2022, 129(1): 108647. DOI: 10.1016/j.yebeh.2022.108647. [14] LONG X Y, WANG S, LUO Z W, et al. Comparison of three administration modes for establishing a zebrafish seizure model induced by N-Methyl-D-aspartic acid[J]. World J Psychiatry, 2020, 10(7): 150-161. doi: 10.5498/wjp.v10.i7.150 [15] KILIÇ H, YILMAZ K, UYUR YALÇIN E, et al. Are interictal discharges associated with neuronal cell loss in electrical status epilepticus in sleep?[J]. Turk Arch Pediatr, 2022, 57(6): 611-615. doi: 10.5152/TurkArchPediatr.2022.22151 [16] KONG Y, CHENG N, DANG N, et al. Application of combined multimodal neuroimaging and video-electroencephalography in intractable epilepsy patients for improved post-surgical outcome prediction[J]. Clin Radiol, 2022, 77(3): e250-e259. doi: 10.1016/j.crad.2021.12.013 [17] DE STEFANO P, SEECK M, ROSSETTI A O. Critical care EEG standardized nomenclature in clinical practice: strengths, limitations, and outlook on the example of prognostication after cardiac arrest[J]. Clin Neurophysiol Pract, 2021, 6(1): 149-154. [18] 阮卫云, 李卫征, 郭燕燕. 脑电图联合血清神经元特异性烯醇化酶、胶质纤维蛋白和S-100β对癫痫病情评估的意义[J]. 中华生物医学工程杂志, 2021, 27(2): 198-200.RUAN W Y, LI W Z, GUO Y Y. The significance of EEG combined with serum neuron-specific enolase, glial fibrillin and S-100β in the evaluation of epilepsy[J]. Chinese Journal of Biomedical Engineering, 2021, 27(2): 198-200. [19] VAN DER LENDE M, ARENDS J B, LAMBERTS R J, et al. The yield of long-term electrocardiographic recordings in refractory focal epilepsy[J]. Epilepsia, 2019, 60(11): 2215-2223. doi: 10.1111/epi.16373 [20] HANIN A, DEMERET S, DENIS J A, et al. Serum neuron-specific enolase: a new tool for seizure risk monitoring after status epilepticus[J]. Eur J Neurol, 2022, 29(3): 883-889. doi: 10.1111/ene.15154 [21] 孙威, 慕洁. 癫痫持续状态的脑脊液和血液生物标志物[J]. 癫痫杂志, 2021, 7(4): 367-378.SUN W, MU J. Cerebrospinal fluid and blood biomarkers in status epilepticus[J]. Journal of Epilepsy, 2021, 7(4): 367-378. [22] CHEN Y, NAGIB M M, YASMEN N, et al. Neuroinflammatory mediators in acquired epilepsy: an update[J]. Inflamm Res, 2023, 72(4): 683-701. [23] 张菲菲, 程艳伟, 石向群. 大鼠癫痫持续状态后海马TNF-α、IL-1β的动态变化[J]. 中国神经精神疾病杂志, 2017, 43(6): 362-367.ZHANG F F, CHENG Y W, SHI X Q. Dynamic changes of TNF-α and IL-1β in hippocampus of rats with epileptic status[J]. Chinese Journal of Nervous and Mental Diseases, 2017, 43(6): 362-367.