Cheong Ian, Marjańska Małgorzata, Deelchand Dinesh K, Eberly Lynn E, Walk David, Öz Gülin
Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota, 2021 6th St. S.E., Minneapolis, MN, 55455, USA.
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, USA.
Neurochem Res. 2017 Jun;42(6):1833-1844. doi: 10.1007/s11064-017-2248-2. Epub 2017 Apr 3.
A major hurdle in the development of effective treatments for amyotrophic lateral sclerosis (ALS) has been the lack of robust biomarkers for use as clinical trial endpoints. Neurochemical profiles obtained in vivo by high field proton magnetic resonance spectroscopy (H-MRS) can potentially provide biomarkers of cerebral pathology in ALS. However, previous H-MRS studies in ALS have produced conflicting findings regarding alterations in the levels of neurochemical markers such as glutamate (Glu) and myo-inositol (mIns). Furthermore, very few studies have investigated the neurochemical abnormalities associated with ALS early in its course. In this study, we measured neurochemical profiles using single-voxel H-MRS at 7 T (T) and glutathione (GSH) levels using edited MRS at 3 T in 19 subjects with ALS who had relatively high functional status [ALS Functional Rating Scale-Revised (ALSFRS-R) mean ± SD = 39.8 ± 5.6] and 17 healthy controls. We observed significantly lower total N-acetylaspartate over mIns (tNAA/mIns) ratio in the motor cortex and pons of subjects with ALS versus healthy controls. No group differences were detected in GSH at 3 and 7 T. In subjects with ALS, the levels of tNAA, mIns, and Glu in the motor cortex were dependent on the extent of disease represented by El Escorial diagnostic subcategories. Specifically, combined probable/definite ALS had lower tNAA than possible ALS and controls (both p = 0.03), higher mIns than controls (p < 0.01), and lower Glu than possible ALS (p < 0.01). The effect of disease stage on MRS-measured metabolite levels may account for dissimilar findings among previous H-MRS studies in ALS.
肌萎缩侧索硬化症（ALS）有效治疗方法开发中的一个主要障碍是缺乏可靠的生物标志物作为临床试验终点。通过高场质子磁共振波谱（H-MRS）在体内获得的神经化学图谱有可能提供ALS脑病理学的生物标志物。然而，先前关于ALS的H-MRS研究在谷氨酸（Glu）和肌醇（mIns）等神经化学标志物水平变化方面产生了相互矛盾的结果。此外，很少有研究在ALS病程早期调查与之相关的神经化学异常。在本研究中，我们对19名功能状态相对较高[修订的ALS功能评定量表（ALSFRS-R）均值±标准差=39.8±5.6]的ALS患者和17名健康对照者，使用7T的单体素H-MRS测量神经化学图谱，并使用3T的编辑磁共振波谱测量谷胱甘肽（GSH）水平。我们观察到，与健康对照相比，ALS患者运动皮层和脑桥中的总N-乙酰天门冬氨酸与肌醇（tNAA/mIns）比值显著降低。在3T和7T时，未检测到两组之间GSH的差异。在ALS患者中，运动皮层中tNAA、mIns和Glu的水平取决于El Escorial诊断亚类所代表的疾病程度。具体而言，可能/确诊的ALS合并症患者的tNAA低于可能的ALS患者和对照组（均p=0.03），mIns高于对照组（p<0.01），Glu低于可能的ALS患者（p<0.01）。疾病阶段对磁共振波谱测量的代谢物水平的影响可能解释了先前ALS的H-MRS研究中不同的结果。
