Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece.
Department of Microbiology, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece.
Headache. 2020 Sep;60(8):1508-1534. doi: 10.1111/head.13892. Epub 2020 Jul 2.
Migraine, especially migraine with aura (MA), has been linked to increased risk for ischemic cerebrovascular disease. The possible role of elevated serum homocysteine (Hcy, a cause of thrombophilia) in migraine has been demonstrated by several studies.
The present study aims to review and meta-analyze data from studies investigating the difference of serum Hcy and Hcy lowering vitamins between migraine patients and healthy controls (HC), as well as between patients with MA and migraine without aura (MO).
Literature search involved MEDLINE, Embase, CENTRAL, Google Scholar, and trial registries. The Newcastle-Ottawa Scale was used to evaluate the quality of the retrieved studies. Standardized mean differences (SMDs) and 95% confidence intervals (95%CIs) were calculated. Funnel-plots were utilized for the evaluation of publication bias.
Overall, 29 (28 case-control and 1 cross-sectional) studies were retrieved. Meta-analysis was indicative of higher Hcy concentration in migraine patients vs HC overall [adults and children: 16 studies, I = 81%, SMD = 0.41, 95%CI = (0.20, 0.61)]. Hcy was consistently elevated in adults with migraine [adults: 12 studies, I = 76%, SMD = 0.35, 95%CI = (0.15, 0.54); children: 1 study, SMD = 0.37, 95%CI = (-0.05, 0.79)]. Subgroup analyses reproduced the results for both adults with MA [7 studies, I = 83%, SMD = 0.37, 95%CI = (0.03, 0.71)] and MO [5 studies, I = 84%, SMD = 0.46, 95%CI = (0.03, 0.89)]. Figures for serum folate were lower in the overall comparison of migraine patients with HC [adults and children: 11 studies, I = 87%, SMD = -0.36, 95%CI = (-0.68, -0.05); adults: 8 studies, I = 6%, SMD = -0.11, 95%CI = (-0.22, 0.01); children: 1 study, SMD = -0.71, 95%CI = (-1.14, -0.29); MA adults: 4 studies, I = 44%, SMD = -0.16, 95%CI = (-0.35, 0.04); MO adults: 4 studies, I = 47%, SMD = -0.17, 95%CI = (-0.44, 0.10)]. Serum vitamin B12 levels were not different between migraine patients and HC [adults and children: 11 studies, I = 88%, SMD = -0.24, 95%CI = (-0.57, 0.09); adults: 8 studies, I = 57%, SMD = -0.10, 95%CI = (-0.28, 0.08); children: 1 study, SMD = 0.29, 95%CI = (-0.13, 0.71); MA adults: 4 studies, I = 63%, SMD = -0.14, 95%CI = (-0.48, 0.20); MO adults: 4 studies, I = 59%, SMD = -0.15, 95%CI = (-0.45, 0.15)]. Serum Hcy was lower in MO than MA [adults and children: 10 studies, I = 39%, SMD = 0.30, 95%CI = (0.14, 0.46), adults: 6 studies, I = 29%, SMD = 0.21, 95%CI = (0.09, 0.36), children: 1 study, SMD = 0.51, 95%CI = (0.22, 0.80)]. Serum folate and vitamin B12 did not differ between MA and MO.
Our results suggest that there is a possible link between migraine, mainly MA, and elevated serum Hcy.
偏头痛，尤其是有先兆偏头痛（MA），与缺血性脑血管疾病风险增加有关。几项研究表明，血清同型半胱氨酸（Hcy，血栓形成的一个原因）升高可能在偏头痛中起作用。
本研究旨在回顾和荟萃分析研究偏头痛患者与健康对照组（HC）之间血清 Hcy 和降低 Hcy 维生素差异的研究数据，以及 MA 和无先兆偏头痛（MO）患者之间的差异。
文献检索涉及 MEDLINE、Embase、CENTRAL、Google Scholar 和试验登记处。使用纽卡斯尔-渥太华量表评估检索研究的质量。计算标准化均数差（SMD）和 95%置信区间（95%CI）。使用漏斗图评估发表偏倚。
共检索到 29 项（28 项病例对照和 1 项横断面研究）研究。荟萃分析表明，偏头痛患者的 Hcy 浓度总体较高[成人和儿童：16 项研究，I ²=81%，SMD=0.41，95%CI=（0.20，0.61）]。偏头痛患者的 Hcy 浓度持续升高[成人：12 项研究，I ²=76%，SMD=0.35，95%CI=（0.15，0.54）；儿童：1 项研究，SMD=0.37，95%CI=（-0.05，0.79）]。亚组分析结果与 MA 成人[7 项研究，I ²=83%，SMD=0.37，95%CI=（0.03，0.71）]和 MO 成人[5 项研究，I ²=84%，SMD=0.46，95%CI=（0.03，0.89）]的结果一致。与 HC 相比，偏头痛患者的血清叶酸水平总体较低[成人和儿童：11 项研究，I ²=87%，SMD=-0.36，95%CI=（-0.68，-0.05）；成人：8 项研究，I ²=6%，SMD=-0.11，95%CI=（-0.22，0.01）；儿童：1 项研究，SMD=-0.71，95%CI=（-1.14，-0.29）；MA 成人：4 项研究，I ²=44%，SMD=-0.16，95%CI=（-0.35，0.04）；MO 成人：4 项研究，I ²=47%，SMD=-0.17，95%CI=（-0.44，0.10）]。偏头痛患者与 HC 之间的血清维生素 B12 水平无差异[成人和儿童：11 项研究，I ²=88%，SMD=-0.24，95%CI=（-0.57，0.09）；成人：8 项研究，I ²=57%，SMD=-0.10，95%CI=（-0.28，0.08）；儿童：1 项研究，SMD=0.29，95%CI=（-0.13，0.71）；MA 成人：4 项研究，I ²=63%，SMD=-0.14，95%CI=（-0.48，0.20）；MO 成人：4 项研究，I ²=59%，SMD=-0.15，95%CI=（-0.45，0.15）]。MO 患者的 Hcy 水平低于 MA 患者[成人和儿童：10 项研究，I ²=39%，SMD=0.30，95%CI=（0.14，0.46），成人：6 项研究，I ²=29%，SMD=0.21，95%CI=（0.09，0.36），儿童：1 项研究，SMD=0.51，95%CI=（0.22，0.80）]。MA 和 MO 之间的血清叶酸和维生素 B12 无差异。
我们的结果表明，偏头痛，主要是 MA，与血清 Hcy 升高之间可能存在关联。
