McFarland H F, Frank J A, Albert P S, Smith M E, Martin R, Harris J O, Patronas N, Maloni H, McFarlin D E
Neuroimmunology Branch, National Institute of Neurological Disease and Stroke, Institutes of Health, Bethesda, MD 20892.
Ann Neurol. 1992 Dec;32(6):758-66. doi: 10.1002/ana.410320609.
The highly variable clinical course and the lack of a direct measurement of disease activity have made evaluation of experimental therapies in multiple sclerosis (MS) difficult. Recent studies indicate that clinically silent lesions can be demonstrated by magnetic resonance imaging (MRI) in patients with mild relapsing-remitting MS. Thus, MRI may provide a means for monitoring therapeutic trials in the early phase of MS. We studied 12 patients longitudinally for 12 to 21 months with monthly gadolinium (Gd)-enhanced MRIs. The data have been used to identify the most effective design of a clinical trial using Gd-enhanced lesions as the outcome measure. Frequent ( > 1/mo) Gd-enhancing lesions were observed in 9 of the 12 patients, indicating that the disease is active even during the early phase of the illness. The frequency of the lesions was not constant; there was marked fluctuation in lesion number from month to month. However, the magnitude of the peak number of lesions and the frequency of the peaks varied among patients. Because of this variability, the most effective use of Gd-enhancing lesions as an outcome measure in a clinical trial was a crossover design with study arms of sufficient duration to allow accurate estimation of lesion frequency. Monitoring Gd-enhancing lesions may be an effective tool to assist in the assessment of experimental therapies in early MS.
多发性硬化症（MS）临床病程高度可变，且缺乏对疾病活动的直接测量方法，这使得评估MS的实验性疗法变得困难。最近的研究表明，轻度复发缓解型MS患者可通过磁共振成像（MRI）显示出临床无症状性病变。因此，MRI可能为监测MS早期阶段的治疗试验提供一种方法。我们对12例患者进行了为期12至21个月的纵向研究，每月进行钆（Gd）增强MRI检查。这些数据已用于确定以Gd增强病变作为疗效指标的临床试验的最有效设计。12例患者中有9例观察到频繁（>1/月）的Gd增强病变，这表明即使在疾病的早期阶段，病情也是活跃的。病变的频率并不恒定；每月的病变数量有明显波动。然而，病变峰值数量的大小和峰值频率在患者之间有所不同。由于这种变异性，在临床试验中最有效地将Gd增强病变作为疗效指标的方法是采用交叉设计，各研究组要有足够长的持续时间，以便准确估计病变频率。监测Gd增强病变可能是协助评估MS早期实验性疗法的有效工具。
