伴海马硬化的颞叶癫痫患者成簇癫痫发作与皮质醇节律变化的关系

Relationship between seizure cluster of temporal lobe epilepsy with hippocampal sclerosis and cortisol rhythm change

目的探讨伴海马硬化的颞叶癫痫(TLE-HS)患者成簇癫痫发作与皮质醇节律改变的关系,从神经内分泌调节角度了解其发生机制。方法纳入2012年5月1日至2020年12月31日在青海省人民医院确诊的57例单侧TLE-HS患者,根据入院1个月前是否有成簇癫痫发作的病史,将其分为伴有成簇癫痫组(即成簇癫痫组,共纳入27例)和不伴成簇癫痫组(NSC组,共纳入30例)。检测两组的患者同日不同时段的血浆皮质醇浓度,并通过磁共振波谱(MRS)分析海马代谢物浓度,采用独立样本t检验、卡方检验、重复测量方差分析、协方差分析及多因素Logistic回归分析进行两组间数据的统计学分析。结果重复测量方差分析结果显示皮质醇水平的时间效应、组间效应及时间与组间的交互效应均有统计学意义。以年龄为协变量,采用协方差分析发现成簇癫痫组的3个不同时间点(8:00、16:00以及次日0:00)的皮质醇:皮质醇16[(126.22±19.98)μg/L]、皮质醇0[(51.63±21.43)μg/L]及皮质醇8-16浓度变化率(以斜率表示,为-7.78±4.54)高于NSC组[分别为(97.70±18.55)、(31.90±10.73)μg/L和-12.40±4.16],差异有统计学意义(F=5.587、4.320、4.013,均P<0.05)。成簇癫痫组的皮质醇0-8变化率(以斜率表示,17.11±6.32)低于NSC组(20.62±6.54),差异有统计学意义(F=-2.065,P<0.05)。两组不同侧别的海马硬化之间比较差异无统计学意义,且两组病侧海马区的N-乙酰天冬氨酸(NAA)/(胆碱+肌酸)的比值比较差异无统计学意义,但成簇癫痫组病灶对侧海马NAA/(胆碱+肌酸)比值(0.71±0.03)低于NSC组(0.76±0.06),差异有统计学意义(t=4.999,P=0.029)。多因素Logistic回归分析显示,皮质醇16(OR=1.328,95%CI 1.073~1.642,P=0.009)、皮质醇8-16(OR=3.657,95%CI 1.404~9.525,P=0.008)是TLE-HS患者成簇癫痫发作的独立危险因素。结论日间皮质醇节律紊乱可能是TLE-HS患者成簇癫痫发作产生的神经生物学基础。

Objective To explore the relationship between seizure cluster of temporal lobe epilepsy with hippocampal sclerosis(TLE-HS)and cortisol(COR)rhythm,and understand its mechanism from the perspective of neuroendocrine.Methods Fifty-seven patients with unilateral TLE-HS were recruited from the Qinghai Provincial People′s Hospital from May 1st 2012 to December 31st 2020.According to the history of seizure clusters one month before admission,27 patients were enrolled in seizure clusters group(SC group),30 patients were included in without seizures cluster group(NSC group).The clinical characteristics were systematically analyzed and compared between the SC and NSC groups.Plasma COR levels were measured at 8:00,16:00 and 24:00(COR8,COR16 and COR0)on the same day,and bilateral magnetic resonance spectroscopy(MRS)diagnosis was performed in two groups.Independent sample t test,chi-square test,repeated analysis of variance,covariance analysis,and multivariate Logistic regression were used for statistical analysis.Results Time effect,grouping effect and the interaction effect of the time and grouping in the level of COR were statistically significant.Covariance analysis excluded age as an influential factor,COR16,COR0 and the slope of COR8-16 in the SC group[(126.22±19.98)μg/L,(51.63±21.43)μg/L,-7.78±4.54]were higher than the NSC group[(97.70±18.55)μg/L,(31.90±10.73)μg/L,-12.40±4.16],and the difference was statistically significant(F=5.587,4.320,4.013,all P<0.05).The slope of COR0-8 in the SC group(17.11±6.32)was lower than that in the NSC group(20.62±6.54),and the difference was statistically significant(F=-2.065,P<0.05).There was no significant difference in lateralization of hippocampal sclerosis between the two groups,and there was no significant difference in the ratio of N-acetyl aspartic acid(NAA)/[choline(Cho)+creatinine(Cr)]in the unilateral hippocampal sclerosis zone of the two groups,but the NAA/(Cho±Cr)ratio of the contralateral hippocampus in the SC group(0.71±0.03)was lower than that in the NSC group(0.76±0.06),and the difference was statistically significant(t=4.999,P=0.029).Multivariate Logistic regression analysis showed that COR16(OR=1.328,95%CI 1.073-1.642,P=0.009),COR8-16(OR=3.657,95%CI 1.404-9.525,P=0.008)were independent risk factors of seizure clusters in TLE-HS.Conclusion COR rhythm disturbance may be the neuroendocrine basis of seizure clusters in patients with TLE-HS.