Rovaris M, Judica E, Gallo A, Benedetti B, Sormani M P, Caputo D, Ghezzi A, Montanari E, Bertolotto A, Mancardi G, Bergamaschi R, Martinelli V, Comi G, Filippi M
Neuroimaging Research Unit, Department of Neurology, San Raffaele Scientific Institute, Milan, Italy.
Brain. 2006 Oct;129(Pt 10):2628-34. doi: 10.1093/brain/awl222. Epub 2006 Aug 18.
Reliable prognostic markers of primary progressive (PP) multiple sclerosis evolution are still needed. Diffusion tensor (DT) MRI can quantify normal-appearing white matter (NAWM) and grey matter (GM) damage in multiple sclerosis patients. We investigated whether conventional and DT-MRI-derived measures can predict the long-term clinical evolution of PP multiple sclerosis. In 54 PP multiple sclerosis patients, conventional and DT-MRI scans of the brain and T1-weighted scans of the cervical cord were acquired at baseline and after a median follow-up of 15 months. Another clinical evaluation was performed, 56 months after baseline, in 52 patients. Measures of lesion load, brain and cord atrophy were obtained. Histograms of the mean diffusivity (MD) and fractional anisotropy (FA) values from the NAWM and GM were analysed. At follow-up, 35 patients (65%) experienced a confirmed disability progression. Baseline expanded disability status scale score and average GM MD were independent predictors of subsequent clinical deterioration in a multivariable model (Nagelkerke R2: 0.44; discriminating ability: 81%). A lower level of disability and a more severe GM damage identify PP multiple sclerosis patients with an increased risk of disease progression over the subsequent 5 years. These data may be relevant to select patients for future exploratory phase II trials.
原发性进行性（PP）多发性硬化症进展的可靠预后标志物仍有待发现。扩散张量（DT）磁共振成像（MRI）可以量化多发性硬化症患者正常外观白质（NAWM）和灰质（GM）的损伤情况。我们研究了传统MRI和DT-MRI衍生指标是否能够预测PP多发性硬化症的长期临床进展。对54例PP多发性硬化症患者在基线期以及中位随访15个月后进行了脑部的传统MRI和DT-MRI扫描以及颈髓的T1加权扫描。在基线期56个月后，对52例患者进行了另一次临床评估。获取了病灶负荷、脑萎缩和脊髓萎缩的测量值。分析了NAWM和GM的平均扩散率（MD）和各向异性分数（FA）值的直方图。随访时，35例患者（65%）出现了确诊的残疾进展。在多变量模型中，基线期扩展残疾状态量表评分和平均GM MD是后续临床恶化的独立预测因素（Nagelkerke R2：0.44；鉴别能力：81%）。较低的残疾水平和更严重的GM损伤表明PP多发性硬化症患者在随后5年疾病进展风险增加。这些数据可能有助于为未来的探索性II期试验选择患者。
