From the Neuroimaging Research Unit (E.D.M., A.M., M.F., M.A.R.) and Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience (E.D.M., L.M., M.F., M.A.R.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Multiple Sclerosis Center (A.G.), Ospedale di Gallarate; Pediatric Neurology Unit (P.V.), V. Buzzi Children's Hospital, Milan; and Biomedical and Clinical Science Department (P.V.), University of Milan, Italy.
Neurology. 2019 Apr 9;92(15):e1709-e1723. doi: 10.1212/WNL.0000000000007267. Epub 2019 Mar 13.
To assess, using MRI, the spatial patterns of gray matter (GM) atrophy in pediatric patients with multiple sclerosis (MS), their dynamic changes over time, and their clinical relevance.
Sixty-eight pediatric patients with MS (30 with a clinical and MRI follow-up after 3.5 years) and 26 healthy controls (HC) underwent clinical and MRI evaluation. To overcome difficulties in obtaining longitudinal scans in pediatric HC, a group of 317 pediatric HC from an NIH-funded MRI Study of Normal Brain Development was used to estimate GM developmental trajectories. In pediatric patients with MS, deviations from normative GM volume values at the voxel level were assessed at baseline and during the follow-up, using linear mixed-effects models. Correlations between GM volume deviations and disability, IQ, and white matter (WM) lesion volumes (LV) were estimated.
Pediatric patients with MS showed failures in GM development in several cortical and subcortical regions, as well as GM atrophy progression in most of these regions, which were only partially related to focal WM LV. Significant correlations were found between regional GM atrophy (particularly of deep GM regions) and disability, whereas higher IQ was associated with reduced deviations from age-expected GM volumes of specific GM regions at baseline and during the follow-up.
Impaired GM maturation occurs in pediatric patients with MS, which is only partially driven by WM inflammation, suggesting that early neurodegenerative phenomena contribute to disability. High IQ, a measure of reserve, may offer protection by promoting remodeling of GM pruning in this young age.
利用 MRI 评估多发性硬化症（MS）患儿的灰质（GM）萎缩的空间模式及其随时间的动态变化，并探讨其与临床的相关性。
68 名 MS 患儿（其中 30 名在 3.5 年后进行了临床和 MRI 随访）和 26 名健康对照者（HC）接受了临床和 MRI 评估。为克服在儿科 HC 中获得纵向扫描的困难，使用了一组来自 NIH 资助的正常脑发育 MRI 研究的 317 名儿科 HC 来估计 GM 发育轨迹。在 MS 患儿中，使用线性混合效应模型评估了基线和随访时 GM 体积值与正常 GM 体积值的偏差。估计了 GM 体积偏差与残疾、智商（IQ）和白质（WM）病变体积（LV）之间的相关性。
MS 患儿在几个皮质和皮质下区域表现出 GM 发育失败，以及这些区域中的大多数 GM 萎缩进展，这与局灶性 WM LV 仅部分相关。发现 GM 萎缩（尤其是深部 GM 区域）与残疾之间存在显著相关性，而较高的 IQ 与基线和随访时特定 GM 区域的 GM 体积与年龄预期的偏差降低相关。
MS 患儿存在 GM 成熟受损，这部分是由 WM 炎症驱动的，表明早期神经退行性现象与残疾有关。高 IQ（一种储备的衡量标准）可能通过促进 GM 修剪的重塑来提供保护，从而在这个年轻的年龄发挥作用。
