Rushton David J, Andres Patricia L, Allred Peggy, Baloh Robert H, Svendsen Clive N
From the Board of Governors Regenerative Medicine Institute (D.J.R., P.A., R.H.B., C.N.S.), Department of Biomedical Sciences (D.J.R., C.N.S.), and Neurology (P.A., R.H.B.), Cedars-Sinai Medical Center, Los Angeles, CA; and Neurological Clinical Research Institute (P.L.A.), Massachusetts General Hospital, Boston.
Neurology. 2017 Jul 11;89(2):196-206. doi: 10.1212/WNL.0000000000004105. Epub 2017 Jun 9.
Amyotrophic lateral sclerosis (ALS) progresses at different rates between patients, making clinical trial design difficult and dependent on large cohorts of patients. Currently, there are few data showing whether the left and right limbs progress at the same or different rates. This study addresses rates of decline in specific muscle groups of patients with ALS and assesses whether there is a relationship between left and right muscles in the same patient, regardless of overall progression.
A large cohort of patients was used to assess decline in muscle strength in right and left limbs over time using 2 different methods: The Tufts Quantitative Neuromuscular Exam and Accurate Test of Limb Isometric Strength protocol. Then advanced linear regression statistical methods were applied to assess progression rates in each limb.
This report shows that linearized progression models can predict general slopes of decline with good accuracy. Critically, the data demonstrate that while overall decline is variable, there is a high degree of correlation between left and right muscle decline in ALS. This implies that irrespective of which muscle starts declining soonest or latest, their rates of decline following onset are more consistent.
First, this study demonstrates a high degree of power when using unilateral treatment approaches to detect a slowing in disease progression in smaller groups of patients, thus allowing for paired statistical tests. These findings will be useful in transplantation trials that use muscle decline to track disease progression in ALS. Second, these findings discuss methods, such as tactical selection of muscle groups, which can improve the power efficiency of all ALS clinical trials.
肌萎缩侧索硬化症（ALS）在患者之间的进展速度不同，这使得临床试验设计困难且依赖于大量患者队列。目前，几乎没有数据表明左右肢体的进展速度是否相同。本研究探讨了ALS患者特定肌肉群的衰退速度，并评估了同一患者左右肌肉之间是否存在关联，而不考虑整体进展情况。
使用一大群患者，通过两种不同方法评估左右肢体肌肉力量随时间的衰退情况：塔夫茨定量神经肌肉检查和肢体等长力量精确测试方案。然后应用先进的线性回归统计方法评估每个肢体的进展速度。
本报告表明，线性化进展模型能够以较高的准确性预测衰退的总体斜率。至关重要的是，数据表明，虽然总体衰退情况各不相同，但ALS患者左右肌肉衰退之间存在高度相关性。这意味着，无论哪块肌肉最早或最晚开始衰退，其发病后的衰退速度都更一致。
首先，本研究表明，在使用单侧治疗方法检测较小患者群体中疾病进展放缓时具有高度效力，从而允许进行配对统计检验。这些发现将有助于使用肌肉衰退来跟踪ALS疾病进展的移植试验。其次，这些发现讨论了一些方法，如肌肉群的策略性选择，可提高所有ALS临床试验的效力效率。
