Quantitative objective markers for upper and lower motor neuron dysfunction in ALS
Quantitative objective markers for upper and lower motor neuron dysfunction in ALS
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DOI：
10.1212/01.wnl.0000260065.57832.87
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发表时间：
2007-04-24
期刊：
影响因子：
9.9
通讯作者：
Shungu, D. C.
中科院分区：
文献类型：
--
作者：
Mitsumoto, H.;Ulug, A. M.;Shungu, D. C.
目的：探讨肌萎缩侧索硬化（ALS）患者上、下运动神经元受累的客观生物标志物的价值。研究方法：我们前瞻性研究了64例ALS患者及其亚组，使用临床测量，质子磁共振波谱成像（H-1 MRSI），扩散张量成像，经颅磁刺激和运动单位数量估计（MUNE）在基线和每3个月一次，持续15个月，并将其与对照组进行比较。结果如下：与对照组相比，ALS（p = 0.009）和所有UMN综合征（ALS、家族性ALS [ fALS]和原发性侧索硬化症; p = 0.03）的初级运动皮层N-乙酰天冬氨酸（NAA）浓度的H-1 MRSI测量值显著降低。在ALS（p < 0.0005）和合并UMN综合征（p = 0.001）中，胫骨前肌的中枢运动传导时间延长。与对照组相比，ALS（p < 0.0005）和所有LMN综合征（ALS、fALS和进行性肌萎缩; p = 0.001）的MUNE较低。所有客观标志物与ALS功能评定量表-修订版、手指和足部敲击以及力量测试相关良好，表明这些标志物与疾病活动相关。关于随时间的变化，MUNE变化迅速，而神经影像学标记物变化较慢，与基线相比无显著差异。结论：H-1磁共振波谱成像测量的初级运动皮层N-乙酰天门冬氨酸（NAA）浓度和比率的NAA肌酸，中央运动传导时间的胫骨前肌，和运动单位的数量估计显着不同的ALS，其子集，和对照组，这表明他们有潜力提供洞察这些疾病的病理生物学。
Objective: To investigate the value of objective biomarkers for upper (UMN) and lower (LMN) motor neuron involvement in ALS. Methods: We prospectively studied 64 patients with ALS and its subsets using clinical measures, proton MR spectroscopic imaging (H-1 MRSI), diffusion tensor imaging, transcranial magnetic stimulation, and the motor unit number estimation (MUNE) at baseline and every 3 months for 15 months and compared them with control subjects. Results: H-1 MRSI measures of the primary motor cortex N-acetyl-aspartate (NAA) concentration were markedly reduced in ALS ( p = 0.009) and all UMN syndromes combined ( ALS, familial ALS [ fALS], and primary lateral sclerosis; p = 0.03) vs control values. Central motor conduction time to the tibialis anterior was prolonged in ALS ( p < 0.0005) and combined UMN syndromes ( p = 0.001). MUNE was lower in ALS ( p < 0.0005) and all LMN syndromes combined ( ALS, fALS, and progressive muscular atrophy; p = 0.001) vs controls. All objective markers correlated well with the ALS Functional Rating Scale - Revised, finger and foot tapping, and strength testing, suggesting these markers related to disease activity. Regarding changes over time, MUNE changed rapidly, whereas neuroimaging markers changed more slowly and did not significantly differ from baseline. Conclusions: H-1 MR spectroscopic imaging measures of the primary motor cortex N-acetyl-aspartate ( NAA) concentration and ratio of NAA to creatine, central motor conduction time to the tibialis anterior, and motor unit number estimation significantly differed between ALS, its subsets, and control subjects, suggesting they have potential to provide insight into the pathobiology of these disorders.