左乙拉西坦单药治疗对偏头痛患者脑内神经递质的作用机制

Mechanism of Levetiracetam Monotherapy on Neurotransmitters in the Brain Regions of Migraine Patients

关键词:  左乙拉西坦  丙戊酸钠  偏头痛  γ-氨基丁酸  单胺类神经递质

Key words:  levetiracetam  sodium valproate  migraine  γ-aminobutyric acid  monoamine neurotransmitter

摘要:

目的 探讨左乙拉西坦单药治疗对偏头痛患者脑内神经递质的作用机制。方法 选取2017年6月—2019年12月温岭市第一人民医院神经内科收治住院治疗的偏头痛患者157例，按照随机数字表法分为丙戊酸钠组（n=64）和左乙拉西坦组（n=93），分别给予丙戊酸钠和左乙拉西坦口服治疗。比较2组患者偏头痛发作频率、持续时间、偏头痛程度，偏头痛残疾程度评估问卷（Migraine Disability Assessment，MIDAS）评分，血清5-羟色胺（5-hydroxytryptamine，5-HT）、多巴胺（dopamine，DA）和去甲肾上腺素（norepinephrine，NE）水平。以年龄±3岁匹配同期于医院进行体检后合格的健康人群作为对照组。磁共振波谱检查测定患者和健康人群前扣带回和后扣带回γ-氨基丁酸（γ-aminobutyric acid，GABA）含量。结果 与治疗前比较，丙戊酸钠组和左乙拉西坦组患者治疗1，2，3个月偏头痛发作频率显著降低，持续时间显著缩短，视觉模拟量表评分显著降低，且左乙拉西坦组效果优于丙戊酸钠组（P<0.05）；与治疗前比较，2组患者治疗3个月MIDAS评分显著降低，且左乙拉西坦组效果优于丙戊酸钠组（P<0.05）；与对照组比较，2组患者治疗前前扣带回和后扣带回GABA含量明显升高，丙戊酸钠组治疗3个月前扣带回和后扣带回GABA含量显著升高（P<0.05）；与治疗前比较，丙戊酸钠组治疗3个月前扣带回和后扣带回GABA含量显著升高，左乙拉西坦组治疗3个月后扣带回GABA含量显著降低（P<0.05）；治疗3个月左乙拉西坦组前扣带回和后扣带回GABA含量显著低于丙戊酸钠组（P<0.05）；与治疗前比较，2组患者治疗1，2，3个月血清5-HT、DA和NE水平显著升高，且左乙拉西坦组效果优于丙戊酸钠组（P<0.05）。结论 左乙拉西坦单药治疗偏头痛疗效确切，与传统抗癫痫药物比较，其机制可能并不是增加脑内GABA含量，而是通过增加血清单胺类神经递质分泌，但GABA有可能成为预测左乙拉西坦治疗偏头痛效果的指标。

Abstract:

OBJECTIVE To investigate the mechanism of levetiracetam monotherapy on neurotransmitters in the brain regions of migraine patients. METHODS A total of 157 migraine patients in the First People's Hospital of Wenling from June 2017 to December 2019 were enrolled. Patients were divided into two groups by random number methods:sodium valproate group(n=64) and levetiracetam group(n=93), sodium valproate and levetiracetam were given orally. The frequency, duration and degree of migraine attack, Migraine Disability Assessment(MIDAS) Questionnaire scores, serum 5-hydroxytryptamine(5-HT), dopamine(DA) and norepinephrine(NE) levels were compared between groups. The healthy people with age ±3 years who passed the physical examination in the hospital during the same period were selected as the control group. The contents of γ-aminobutyric acid(GABA) in anterior cingulate gyrus and posterior cingulate gyrus were measured by Magnetic Resonance Spectroscopy. RESULTS Compared with before treatment, the frequency of migraine attack, duration and visual analogue scale(VAS) score of the two groups were significantly reduced after 1, 2 and 3 months of treatment, and the effect of levetiracetam group was better than that of sodium valproate group(P<0.05). Compared with before treatment, MIDAS scores of the two groups were significantly lower after 3 months of treatment, and the effect of levetiracetam group was better than that of sodium valproate group(P<0.05). Compared with the control group, the levels of GABA in the anterior cingulate gyrus and posterior cingulate gyrus of the two groups were significantly increased before treatment, and the levels of GABA in the anterior cingulate gyrus and posterior cingulate gyrus of the sodium valproate group were significantly increased 3 months after treatment (P<0.05). Compared with before treatment, the content of GABA in cingulate gyrus and posterior cingulate gyrus of sodium valproate group was significantly increased after 3 months of treatment, while the content of GABA in cingulate gyrus of levetiracetam group was significantly decreased(P<0.05). The content of GABA in anterior cingulate gyrus and posterior cingulate gyrus of levetiracetam group was significantly lower than that of sodium valproate group(P<0.05). Compared with before treatment, the serum levels of 5-HT, DA and NE in the two groups were significantly increased after 1 month, 2 months and 3 months of treatment, and the effect of levetiracetam group was better than that of sodium valproate group(P<0.05). CONCLUSION Compared with traditional antiepileptic drugs, levetiracetam is effective in treating migraines. The mechanism may not be related to GABA content increase in brain but the increase in secretion of serum γ-amine neurotransmitters, but GABA may be an indicator to predict the efficacy of levetiracetam in treating migraines.