癫痫患者血浆同型半胱氨酸水平及多维生素补充疗法的干预效果研究

Effects of multi-vitamin supplement therapy on plasma homocysteine level in patients with epilepsy

摘要:

目的：探讨常用抗癫痫药物（antiepilepsy drugs，AEDs）对癫痫患者血浆同型半胱氨酸（homocysteine，Hcy）的影响，以及多维生素补充疗法对癫痫患者高同型半胱氨酸血症（hyperhomocysteinemia，HHcy）、癫痫发作状态的干预效果。方法：依据服药种类，将105例患者分为卡马西平（carbamazepine，CMZ）组25例、丙戊酸（valproic acid，VPA）组23例，苯妥英钠（phenytoin，PHT）组30例、托吡酯（topiramate，TPM）组12例，拉莫三嗪（lamotrigine，LTG）组15例，选择同期门诊健康体检者30例为健康对照组；并选择同期就诊的未口服AEDs的癫痫患者30例为癫痫对照组，分别对各组患者进行Hcy、叶酸（folacin，Fol）、维生素B12（vitamin B12，VitB12）水平测定，比较各AEDs药物组与健康对照组、癫痫对照组患者间各指标的差异；从HHcy患者中随机选取32例进行叶酸和VitB12补充治疗，随访观察6月，比较患者治疗前、治疗后4周、治疗后6月的Hcy、Fol及VitB12水平；比较维生素辅助治疗患者和单一AEDs治疗患者间癫痫发作改善情况。结果：CMZ组、PHT组、TPM组Hcy水平高于健康对照组和癫痫对照组（FHcy=31.581，P=0.000），VPA组、LTG组Hcy水平与健康对照组和癫痫对照组间均无统计学差异（χ2=0.077，P=0.782）；癫痫对照组、VPA组、LTG组发生HHcy症患者均为2例，分别占6.67%、8.70%和13.33%，3组间无统计学差异（P >0.05）；CMZ组、PHT组、TPM组HHcy患者分别为20例（占80.00%）、20例（占66.67%）、8例（占66.67），发生比例均高于癫痫对照组（χ2=30.556，P=0.000）；30例接受AEDs药物治疗的HHcy患者服用维生素干预后不同时间点Hcy、Fol和VitB１2水平有统计学差异（FHcy=482.541，P=0.000；FFol=48.123，P=0.000；FVitB12=26.286，P=0.000），服药后血浆Hcy明显下降，Fol和VitB１2则明显升高；给予维生素干预治疗的30例HHcy患者中，12例完全控制癫痫的发作，13例显效，3例有效，总有效率为93.33%，1例无效，1例恶化；仅给予AEDs治疗的22例患者中，7例完全控制发作，9例显效，3例有效，总有效率84.34%，2例无效，1例恶化，２组间疗效经非参数检验，差异有统计学意义（Z=-4.426，P=0.001）。结论：服用AEDs可引起HHcy，维生素补充疗法可有效减低癫痫患者Hcy水平，减少患者癫痫发作次数。

Abstract:

Objective：To investigate the plasma homocysteine（Hcy） level in epilepsy patients with common antiepileptic drugs（AEDs） therapy and the intervention effect of multi-vitamin supplement therapy on high homocysteine（HHcy） and seizure status of patients with epilepsy. Methods：According to medication types，105 epileptic patients taking single AEDs were divided into carbamazepine group（CMZ group，n=25），valproate group（VPA group，n=23），phenytoin group（PHT group，n=30），topiramate group（TPM group，n=12），lamotrigine group（LTG group，n=15） and 30 healthy people were selected as healthy control group while 30 epileptic patients not taking AEDs as epileptic control group. The Hcy，folacin（Fol），vitamin B12（VitB12） levels were measured. Comparison on indicators was made among treatment group，healthy control group and epileptic control group. Thirty-two patients with HHcy were randomly se－lected for Fol and VitB12 replacement therapy and Hcy，Fol and VitB12 levels in patients among different time points before treat－ment，at 4 weeks after treatment and at 6 weeks after treatment were followed-up for 6 months and compared. Improvement be－tween patients with multi-vitamin supplement therapy and sin－gle AEDs therapy was compared. Results：Hcy levels were higher in CMZ group，PHT group，TPM group than in healthy control group and epileptic control group（FHcy=31.581，P<0.001）. There were 2 cases of HHcy in epileptic control group，VPA group and LTG group respectively，accounting for 6.67%，8.70% and 13.33% respective－ly，without differences（P<0.05）. There were 20 cases（80.00%） of HHcy in CMZ group，20 cases（66.67%） in PHT group and 8 cases（66.67%） in TPM group，higher than those in epileptic control group（χ2=30.556，P=0.000）. There were differences in Hcy，Fol and VitB12 levels of 30 HHcy patients taking vitamin intervention treatment at different time points after the treatment（FHcy=482.541，P=0.000；FFol=48.123，P=0.000；FVitB12=26.286，P=0.000）；Hcy levels were decreased and Fol and VitB12 levels were increased after the treatment. Among 30 HHcy patients receiving vitamin intervention，12 patients completely controlled seizures，13 patients improved markedly，three patients were effective，with total effective rate of 93.33%；one patient was invalid and one patient was deteriorated. Among 22 patients only took AEDs treatment，seven patients completely controlled seizures，nine patients improved markedly，three cases were effective with total efficiency of 84.34%；two patients ineffective and one patient was deteriorated，with statistically signifi－cant difference（Z=-4.426，P<0.01）. Conclusions：Taking AEDs can cause HHcy while vitamin supplement therapy can be effective in reducing Hcy levels in patients with epilepsy and number of patients with seizures.