基于中医药祛瘀化痰理论的祛瘀定痫镇痛合剂防治癫痫合并认知障碍临床观察

Clinical Observation and Research on Prevention and Treatment of Epilepsy Complicated with Cognitive Impairment by Quyu Dingxian Zhengtong Mixture for Dispelling Stasis and Resolving Phlegm

目的:采用随机双盲安慰剂平行对照法观察具有祛瘀化痰作用的祛瘀定痫镇痛合剂联合西药治疗癫痫合并认知障碍的临床疗效及安全性。方法:选择2020年10月至2021年10月上海中医药大学附属龙华医院脑病科病房及门诊收治的癫痫合并认知障碍患者123例,采用随机数字表法分为对照组(卡马西平+安慰剂)62例和治疗组(卡马西平+祛瘀定痫镇痛合剂)61例;其中治疗组脱落和剔除4例;对照组脱落3例;最终纳入治疗组57例,对照组59例,两组总疗程均为12周,观察比较两组临床疗效、中医症状疗效、不良反应发生率;治疗前后癫痫发作频率、脑电图异常率、认知功能评分、血清同型半胱氨酸(Hcy)、叶酸、维生素B_(12)(B_(12))水平的变化情况。结果:治疗12周,治疗组临床疗效总有效率92.98%(53/57),明显优于对照组79.66%(47/59,χ^(2)=4.327,P<0.05);治疗组中医症状疗效96.49%(55/57),明显优于对照组84.75%(50/59,χ^(2)=4.660,P<0.05);治疗组癫痫发作频率改善差值情况显著尤于对照组(Z=-3.938,P<0.01);治疗组认知功能蒙特利尔认知评估量表(MoCA)及简易智力状态检查量表(MMSE)评分改善差值情况显著尤于对照组(t=4.333,t=9.531,P<0.01);治疗组患者血清HCY、叶酸、B_(12)水平变化差值显著小于对照组(t=-7.233,t=-7.972,t=-6.871,P<0.01);治疗组治疗后脑电图异常率低于对照组(χ^(2)=4.437,P<0.05);治疗组不良反应发生率1.75%(1/57)低于对照组的13.56%(8/59,校正χ^(2)=4.116,P<0.05)。结论:祛瘀化痰作用的中药联合西药治疗癫痫合并认知障碍的临床疗效和安全性优于单纯应用西药,其临床疗效及中医症状疗效、癫痫发作频率、脑电图异常率及认知功能改善情况、对于患者血清叶酸、B_(12)、HCY水平的影响及不良反应发生均优于单纯西药组。祛瘀化痰作用的中药可能通过癫痫合并认知障碍患者的血清叶酸、B_(12)、HCY代谢的改变从而改善临床疗效和安全性。

Objective:To observe the clinical efficacy and safety of Chinese medicinal mixture for dispelling stasis and resolving phlegm combined with western medicine in the treatment of epilepsy combined with cognitive impairment by randomized,double-blind,placebo-controlled,parallel-group trial.Method:A total of 123 inpatients and outpatients with epilepsy complicated with cognitive impairment admitted to the department of neurology at Longhua Hospital from October 2020 to October 2021 were randomly assigned into a control group(62 cases,carbamazepine+placebo)and a treatment group(61 cases,carbamazepine+Quyu Dingxian Zhengtong mixture)by random number table method.In the treatment group,4 cases were exfoliated and eliminated.In the control group,3 cases fell off.Finally,57 cases in the treatment group and 59 cases in the control group were included.The total course of treatment for both groups was 12 weeks.The clinical efficacy,efficacy for traditional Chinese medicine(TCM)syndromes,and incidence of adverse reactions were compared between two groups.The changes of seizure frequency,abnormal rate of electroencephalogram(EEG),cognitive function score,serum homocysteine(HCY),folic acid,and vitamin B_(12)(B_(12))were measured and compared before and after treatment.Result:After 12 weeks of treatment,the treatment group had higher clinical efficacy[92.98%(53/57)vs 79.66%(47/59),χ^(2)=4.327,P<0.05]and efficacy for TCM syndromes[96.49%(55/57)vs 84.75%(50/59),χ^(2)=4.660,P<0.05]than the control group.The treatment group was superior to the control group in reducing the seizure frequency(Z=-3.938,P<0.01)and improving the Montreal cognitive assessment(MoCA)score(t=4.333,P<0.01)and mini-mental state examination(MMSE)score(t=9.531,P<0.01).The variations in serum HCY,folic acid,and B_(12)in the treatment group were less than those in the control group(t=-7.233,t=-7.972,t=-6.871,P<0.01).After treatment,the abnormal rate of EEG in the treatment group was lower than that in the control group(χ^(2)=4.437,P<0.05).The incidence of adverse reactions in the treatment group(1.75%,1/57)was lower than that(13.56%,8/59)in the control group(correctedχ^(2)=4.116,P<0.05).Conclusion:Chinese medicinal mixture for dispelling stasis and resolving phlegm in combination with western medicine had better efficacy and safety than western medicine alone in the treatment of epilepsy complicated with cognitive impairment.Specifically,the combination outperformed western medicine alone in terms of clinical efficacy,efficacy for TCM syndromes,reduction in seizure frequency,abnormal rate of EEG,adverse reactions,improvement of cognitive function,and variations in serum folic acid,B_(12),and HCY values.Chinese medicinal mixture for dispelling stasis and resolving phlegm may improve the clinical efficacy and safety by changing the metabolism of folic acid,B_(12),and HCY in serum of the patients with epilepsy complicated with cognitive impairment.