Zielman Ronald, Postma Rudmer, Verhoeven Aswin, Bakels Floor, van Oosterhout Willebrordus P J, Meissner Axel, van den Maagdenberg Arn M J M, Terwindt Gisela M, Mayboroda Oleg A, Ferrari Michel D
Department of Neurology, Leiden University Medical Center, P.O. 9600, 2300 WB, Leiden, The Netherlands.
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
Mol Biosyst. 2016 Nov 15;12(12):3674-3682. doi: 10.1039/c6mb00424e.
Migraine is a common episodic brain disorder. Treatment options and diagnosis are hampered by an incomplete understanding of disease pathophysiology and the lack of objective diagnostic markers. The aim of this study was to identify biochemical differences characteristic for different subtypes of migraine in cerebrospinal fluid (CSF) of migraine patients using an exploratory H-NMR-based metabolomics approach.
CSF was obtained, in between migraine attacks, via lumbar puncture from patients with hemiplegic migraine, migraine with aura, migraine without aura, and healthy controls. Metabolite concentrations were measured by quantitative H-NMR spectroscopy. Multivariate data analysis was used to find the optimal set of predictors, generalized linear models (GLM) were used to ascertain the differential significance of individual metabolites.
In CSF samples from 18 patients with hemiplegic migraine, 38 with migraine with aura, 27 migraine without aura, and 43 healthy controls, nineteen metabolites were identified and quantified. Hemiplegic migraine patients could be discriminated from healthy controls using supervised multivariate modelling with 2-hydroxybutyrate and 2-hydroxyisovalerate as the most discriminant metabolites. Univariate GLM analysis showed 2-hydroxybutyrate to be lower in hemiplegic migraine compared with healthy controls; no significant differences were observed for other metabolites. It was not possible to discriminate migraine with and without aura from healthy controls based on their metabolic profile.
Using an exploratory H-NMR metabolomics analysis we identified metabolites that were able to discriminate hemiplegic migraine patients from healthy controls. The lower levels of 2-hydroxybutyrate found in patients with hemiplegic migraine could indicate a dysregulation of the brain's energy metabolism. An experimental confirmation in vitro or in animal models will be required to confirm or discard this hypothesis. Migraine with and migraine without aura patients did not reveal a metabolic profile different from healthy controls.
偏头痛是一种常见的发作性脑疾病。对疾病病理生理学的不完全理解以及缺乏客观诊断标志物阻碍了治疗选择和诊断。本研究的目的是使用基于氢核磁共振（H-NMR）的探索性代谢组学方法，确定偏头痛患者脑脊液（CSF）中不同偏头痛亚型的生化差异特征。
在偏头痛发作间期，通过腰椎穿刺从偏瘫性偏头痛患者、有先兆偏头痛患者、无先兆偏头痛患者及健康对照者获取脑脊液。通过定量H-NMR光谱法测量代谢物浓度。使用多变量数据分析来寻找最佳预测指标集，使用广义线性模型（GLM）来确定个体代谢物的差异显著性。
在来自18例偏瘫性偏头痛患者、38例有先兆偏头痛患者、27例无先兆偏头痛患者和43例健康对照者的脑脊液样本中，鉴定并定量了19种代谢物。使用以2-羟基丁酸和2-羟基异戊酸为最具鉴别力代谢物的监督多变量建模，可将偏瘫性偏头痛患者与健康对照者区分开来。单变量GLM分析显示，与健康对照者相比，偏瘫性偏头痛患者的2-羟基丁酸水平较低；其他代谢物未观察到显著差异。基于有先兆和无先兆偏头痛患者的代谢谱，无法将其与健康对照者区分开来。
通过探索性H-NMR代谢组学分析，我们鉴定出了能够区分偏瘫性偏头痛患者与健康对照者的代谢物。偏瘫性偏头痛患者中发现的2-羟基丁酸水平较低可能表明大脑能量代谢失调。需要在体外或动物模型中进行实验验证以证实或摒弃这一假设。有先兆偏头痛患者和无先兆偏头痛患者未显示出与健康对照者不同的代谢谱。
