Giorgio Antonio, Zhang Jian, Stromillo Maria Laura, Rossi Francesca, Battaglini Marco, Nichelli Lucia, Mortilla Marzia, Portaccio Emilio, Hakiki Bahia, Amato Maria Pia, De Stefano Nicola
Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Anna Meyer Children's University Hospital, Florence, Italy.
Front Neurol. 2017 Nov 14;8:608. doi: 10.3389/fneur.2017.00608. eCollection 2017.
Pediatric-onset multiple sclerosis (POMS) may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS) patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability ( = 15) in comparison with age- and disability-matched AOMS patients ( = 14) and to normal controls (NC, = 20). We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC) (analysis of variance, ≤ 0.01, corrected for multiple comparisons across space). POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities) and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term.
儿童期多发性硬化症（POMS）可能代表了人类大脑活跃成熟阶段易受损伤的一种模式。尽管在短期至中期内，POMS患者的大脑似乎会出现适应性机制，但自然史研究表明，这些患者尽管疾病进展较慢，但在比成人期多发性硬化症（AOMS）患者显著年轻的年龄就会出现不可逆转的残疾。我们首次测试了与年龄和残疾匹配的AOMS患者（n = 14）以及正常对照（NC，n = 20）相比，POMS患者在成年早期且无残疾或残疾程度轻微（n = 15）时是否已经出现了显著的脑部改变。我们采用了多模态MRI方法，通过使用FSL进行建模，以体素方式测量白质束的微观结构完整性、灰质体积以及网络内和网络间的功能连接（FC）（方差分析，p≤0.01，经跨空间多重比较校正）。与NC和AOMS患者相比，POMS患者的扩散张量成像测量结果发生了改变（分数各向异性降低和/或扩散率增加），并且在诸如放射冠后部等对身体残疾具有临床明确意义的区域出现病变的概率更高。此外，与其他两组相比，POMS患者在静息功能MRI评估中，默认模式网络和次级视觉网络之间的远程FC降低，这两个网络的相互作用对诸如空间注意力和视觉学习等重要认知功能起着重要作用。总体而言，成年早期无临床残疾或残疾程度轻微的POMS患者的这种结构损伤和脑连接中断模式可能解释了他们长期不良的临床结局。
