MacMillan E L, Tam R, Zhao Y, Vavasour I M, Li D K B, Oger J, Freedman M S, Kolind S H, Traboulsee A L
Division of Neurology, Faculty of Medicine, The University of British Columbia, Vancouver, Canada
Department of Radiology, Faculty of Medicine, The University of British Columbia, Vancouver, Canada/UBC MS/MRI Research Group, The University of British Columbia, Vancouver, Canada.
Mult Scler. 2016 Jan;22(1):112-6. doi: 10.1177/1352458515586086. Epub 2015 May 26.
Few biomarkers of progressive multiple sclerosis (MS) are sensitive to change within the two-year time frame of a clinical trial.
To identify biomarkers of MS disease progression with magnetic resonance spectroscopy (MRS) in secondary progressive MS (SPMS).
Forty-seven SPMS subjects were scanned at baseline and annually for two years. Concentrations of N-acetylaspartate, total creatine, total choline, myo-inositol, glutamate, glutamine, and the sum glutamate+glutamine were measured in a single white matter voxel.
Glutamate and glutamine were the only metabolites to show an effect with time: with annual declines of (95% confidence interval): glutamate -4.2% (-6.2% to -2.2%, p < 10(-4)), glutamine -7.3% (-11.8% to -2.9%, p = 0.003), and glutamate+glutamine -5.2% (-7.6% to -2.8%, p < 10(-4)). Metabolite rates of change were more apparent than changes in clinical scores or brain atrophy measures.
The high rates of change of both glutamate and glutamine over two years suggest they are promising new biomarkers of MS disease progression.
在临床试验的两年时间范围内，很少有进展性多发性硬化症（MS）的生物标志物对变化敏感。
利用磁共振波谱（MRS）确定继发进展型多发性硬化症（SPMS）中MS疾病进展的生物标志物。
对47名SPMS受试者在基线时进行扫描，并在两年内每年进行一次扫描。在单个白质体素中测量N-乙酰天门冬氨酸、总肌酸、总胆碱、肌醇、谷氨酸、谷氨酰胺以及谷氨酸+谷氨酰胺总和的浓度。
谷氨酸和谷氨酰胺是仅有的随时间显示出效应的代谢物：每年下降幅度为（95%置信区间）：谷氨酸-4.2%（-6.2%至-2.2%，p<10⁻⁴），谷氨酰胺-7.3%（-11.8%至-2.9%，p = 0.003），谷氨酸+谷氨酰胺-5.2%（-7.6%至-2.8%，p<10⁻⁴）。代谢物变化率比临床评分或脑萎缩测量的变化更明显。
谷氨酸和谷氨酰胺在两年内的高变化率表明它们是MS疾病进展有前景的新生物标志物。
