Barkhof Frederik, Calabresi Peter A, Miller David H, Reingold Stephen C
Department of Radiology and Amsterdam MS Center, VU University Medical Center, Amsterdam, The Netherlands.
Nat Rev Neurol. 2009 May;5(5):256-66. doi: 10.1038/nrneurol.2009.41.
Multiple sclerosis (MS) is commonly regarded as an inflammatory disease, but it also has a neurodegenerative component, which represents an additional target for treatment. The use of MRI to evaluate the inflammatory disease component in 'proof-of concept' clinical trials is well established, but no systematic assessment of imaging outcomes to evaluate neuroprotection or repair in MS has been performed. In this Review, we examine the potential of traditional and novel imaging parameters to serve as primary outcomes in phase II clinical trials of neuroprotective and reparative strategies in MS. We present the conclusions of an international meeting of imaging, clinical and statistical experts, as well as a review of relevant literature. The available imaging techniques are appraised in five categories of performance: pathological specificity, reproducibility, sensitivity to change, clinical relevance, and response to treatment. At present, the three most promising primary outcomes in phase II trials of neuroprotective and/or reparative strategies in MS are: changes in whole-brain volume to gauge general cerebral atrophy; T1 hypointensity and magnetization transfer ratio to monitor the evolution of lesion damage; and optical coherence tomography findings to evaluate the anterior visual pathway. Power calculations show that these outcome measures can be applied with attainable sample sizes.
多发性硬化症（MS）通常被视为一种炎症性疾病，但它也有神经退行性病变的成分，这是另一个治疗靶点。在“概念验证”临床试验中，使用MRI评估炎症性疾病成分已经很成熟，但尚未对MS中评估神经保护或修复的影像学结果进行系统评估。在本综述中，我们研究了传统和新型成像参数在MS神经保护和修复策略II期临床试验中作为主要结果的潜力。我们展示了影像学、临床和统计专家国际会议的结论，以及相关文献的综述。从病理特异性、可重复性、对变化的敏感性、临床相关性和对治疗的反应这五类性能方面对现有的成像技术进行了评估。目前，MS神经保护和/或修复策略II期试验中最有前景的三个主要结果是：测量全脑体积变化以评估总体脑萎缩；通过T1低信号和磁化传递率监测病变损伤的演变；以及通过光学相干断层扫描结果评估前视觉通路。功效计算表明，这些结果测量方法可以应用于可达到的样本量。
