Abstract: Objective To determine whether valproic acid (VPA) monotherapy influences homocysteine metabolism in patients with epilepsy.  Methods  Articles in English concerning the homocysteine levels in VPA monotherapeutic patients with epilepsy and published from January 1990 to August 2013 were searched through PubMed, Web of Science and EMBASE. Observational case-control studies that evaluated homocysteine levels in subjects with epilepsy compared to controls were selected. Any study lacking information regarding specific effect of VPA on homocysteine in patients with epilepsy was rejected. Definitely, non-controlled design studies, reviews, and animal or in vitro studies were also excluded. Two reviewers independently evaluated the quality of included articles and extracted the data using Newcastle-Ottawa Scale. A Meta-analysis was conducted by using Stata 12.0 software.  Results  A total of 8 eligible studies were enrolled in this Meta-analysis. VPA treated patients with epilepsy (N = 266) and matched healthy controls (N = 489) were included. All included studies reached a total quality score of 6 or higher. Results of the Meta-analysis showed that plasma homocysteine levels in VPA treated patients with epilepsy was significantly higher than healthy controls under a random effect model [standardized mean difference (SMD) = 0.620, 95% CI: 0.320-0.920; P = 0.000]. There was significant heterogeneity in the estimates according to I² test ( I²  = 65.600% , P = 0.005). Further subgroup analysis suggested that no significant difference was present when grouped by ethnicity and age, but the risk of heterogeneity in West-Asian group (I² = 47.400%, P = 0.107) was diminished when compared with overall groups (I² = 65.600%, P = 0.005). Sensitivity analysis was also conducted to evaluate the stability of Meta?analysis. When any single study was deleted, the corresponding pooled SMD was not substantially altered.  Conclusions  VPA monotherapy is associated with the increase of plasma homocysteine levels in patients with epilepsy, and whether this association is influenced by ethnicity needs further research.

Key words: Epilepsy, Valproic acid, Cysteine, Meta-analysis

摘要： 目的 分析癫痫患者血浆同型半胱氨酸水平变化与丙戊酸单药治疗间的关系。方法 选择epilepsy、valproate、homocysteine 和epilep*为检索词，计算机检索1990 年1 月-2013 年8 月美国国立医学图书馆、科学引文索引数据库、荷兰医学文摘等数据库，获得丙戊酸单药治疗与癫痫患者血浆同型半胱氨酸水平间关系的相关英文文献，均为丙戊酸单药治疗的癫痫患者与正常对照受试者血浆同型半胱氨酸水平比较的病例-对照临床研究。通过Newcastle-Ottawa 量表独立进行文献质量评价和数据提取，Stata 12.0 统计软件行Meta 分析。结果 共纳入符合条件的英文文献8 篇，包括266 例行丙戊酸单药治疗的癫痫患者和489 例正常对照受试者，所有纳入文献质量评分均> 6 分。Meta 分析显示，丙戊酸单药治疗组患者血浆同型半胱氨酸水平显著高于正常对照组［标准化均数差（SMD）= 0.620，95%CI：0.320 ~ 0.920；P = 0.000］；经异质性检验存在显著异质性（I² = 65.600%，P = 0.005），根据不同地区和受试者年龄差异行进一步亚组分析，结果显示西亚组癫痫患者异质性风险（I² = 47.400%，P = 0.107）较整体（I² = 65.600%，P = 0.005）降低。采用敏感性分析评价Meta 分析之稳定性，当任何一项研究被剔除后，相应的SMD 值均不发生变化，表明分析结果稳定性良好。结论 丙戊酸单药治疗可显著增加癫痫患者血浆同型半胱氨酸水平，后者是否受种族因素的影响尚待进一步研究。

关键词: 癫痫, 丙戊酸, 半胱氨酸, Meta分析