Kappos L, Moeri D, Radue E W, Schoetzau A, Schweikert K, Barkhof F, Miller D, Guttmann C R, Weiner H L, Gasperini C, Filippi M
Department of Neurology, Kantonsspital, Basel, Switzerland.
Lancet. 1999 Mar 20;353(9157):964-9. doi: 10.1016/s0140-6736(98)03053-0.
Reliable prognostic factors are lacking for multiple sclerosis (MS). Gadolinium enhancement in magnetic resonance imaging (MRI) of the brain detects with high sensitivity disturbance of the blood-brain barrier, an early event in the development of inflammatory lesions in MS. To investigate the prognostic value of gadolinium-enhanced MRI, we did a meta-analysis of longitudinal MRI studies.
From the members of MAGNIMS (European Magnetic Resonance Network in Multiple Sclerosis) and additional centres in the USA, we collected data from five natural-course studies and four placebo groups of clinical trials completed between 1992 and 1995. We included a total of 307 patients, 237 with relapsing disease course and 70 with secondary progressive disease course. We investigated by regression analysis the relation between initial count of gadolinium-enhancing lesions and subsequent worsening of disability or impairment as measured by the expanded disability status scale (EDSS) and relapse rate.
The relapse rate in the first year was predicted with moderate ability by the mean number of gadolinium-enhancing lesions in monthly scans during the first 6 months (relative risk per five lesions 1.13, p=0.023). The predictive value of the number of gadolinium-enhancing lesions in one baseline scan was less strong. The best predictor for relapse rate was the variation (SD) of lesion counts in the first six monthly scans which allowed an estimate of relapse in the first year (relative risk 1.2, p=0.020) and in the second year (risk ratio=1.59, p=0.010). Neither the initial scan nor monthly scans over six months were predictive of change in the EDSS in the subsequent 12 months or 24 months. The mean of gadolinium-enhancing-lesion counts in the first six monthly scans was weakly predictive of EDSS change after 1 year (odds ratio=1.34, p=0.082) and 2 years (odds ratio=1.65, p=0.049).
Although disturbance of the blood-brain barrier as shown by gadolinium enhancement in MRI is a predictor of the occurrence of relapses, it is not a strong predictor of the development of cumulative impairment or disability. This discrepancy supports the idea that variant pathogenetic mechanisms are operative in the occurrence of relapses and in the development of long-term disability in MS.
多发性硬化症（MS）缺乏可靠的预后因素。脑部磁共振成像（MRI）中的钆增强可高灵敏度检测血脑屏障的破坏，这是MS炎症性病变发展中的早期事件。为了研究钆增强MRI的预后价值，我们对纵向MRI研究进行了荟萃分析。
我们从MAGNIMS（欧洲多发性硬化症磁共振网络）成员及美国的其他中心收集了1992年至1995年间完成的五项自然病程研究和四项临床试验安慰剂组的数据。我们共纳入307例患者，其中237例为复发型病程，70例为继发进展型病程。我们通过回归分析研究了钆增强病灶初始计数与随后残疾或功能障碍恶化之间的关系，残疾或功能障碍恶化通过扩展残疾状态量表（EDSS）和复发率来衡量。
通过前6个月每月扫描中钆增强病灶的平均数量，对第一年的复发率有中等程度的预测能力（每五个病灶的相对风险为1.13，p = 0.023）。一次基线扫描中钆增强病灶数量的预测价值较弱。复发率的最佳预测指标是前六个月每月扫描中病灶计数的变化（标准差），这可以估计第一年（相对风险1.2，p = 0.020）和第二年（风险比 = 1.59，p = 0.010）的复发情况。初始扫描和六个月的每月扫描均不能预测随后12个月或24个月内EDSS的变化。前六个月每月扫描中钆增强病灶计数的平均值对1年后（优势比 = 1.34，p = 0.082）和2年后（优势比 = 1.65，p = 0.049）的EDSS变化有较弱的预测作用。
尽管MRI中钆增强显示的血脑屏障破坏是复发发生的一个预测指标，但它并不是累积功能障碍或残疾发展的强有力预测指标。这种差异支持了这样一种观点，即不同发病机制在MS的复发发生和长期残疾发展中起作用。
