Department of Neurology, Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, PA.
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Ann Neurol. 2019 Mar;85(3):340-351. doi: 10.1002/ana.25429. Epub 2019 Feb 20.
Central nervous system pathology in multiple sclerosis includes both focal inflammatory perivascular injury and injury to superficial structures, including the subpial region of the cortex, which reportedly exhibits a gradient of damage from the surface inward. We assessed how early in the multiple sclerosis course a "surface-in" process of injury suggesting progressive biology may begin.
We focused on the thalamus, which notably has both a cerebrospinal fluid (CSF) interface and a white matter interface. Thalamic volume trajectories were assessed in a prospectively followed cohort of children from initial presentation with either multiple sclerosis or monophasic acquired demyelination, and healthy controls. Voxelwise volume changes were calculated using deformation-based morphometry, and analyzed in relation to distance from the CSF interface by mixed effects modeling and semiparametric smoothing methods.
Twenty-seven children with multiple sclerosis and 73 children with monophasic demyelination were prospectively followed with yearly brain scans (mean follow-up = 4.6 years, standard deviation = 1.9). A total of 282 healthy children with serial scans were included as controls. Relative to healthy controls, children with multiple sclerosis and children with monophasic demyelination demonstrated volume loss in thalamic regions adjacent to the white matter. However, only children with multiple sclerosis exhibited an additional surface-in gradient of thalamic injury on the ventricular side, which was already notable in the first year of clinical disease (asymptote estimate = 3.01, 95% confidence interval [CI] = 1.44-4.58, p = 0.0002) and worsened over time (asymptote:time estimate = 0.33, 95% CI = 0.12-0.54, p = 0.0021).
Our results suggest that a multiple sclerosis disease-specific surface-in process of damage can manifest at the earliest stages of the disease. ANN NEUROL 2019;85:340-351.
多发性硬化症的中枢神经系统病理学包括局灶性炎症性血管周围损伤和浅表结构损伤，包括皮质的软脑膜下区域，据报道，该区域的损伤从表面向内呈现出梯度分布。我们评估了多发性硬化症病程中，提示进行性生物学的“向表面内”损伤过程何时开始。
我们专注于丘脑，丘脑既有脑脊液（CSF）界面，也有白质界面。在一个前瞻性随访队列中，我们评估了从多发性硬化症或单相获得性脱髓鞘病变初始表现开始的儿童以及健康对照者的丘脑体积轨迹。使用基于变形的形态测量法计算体素体积变化，并通过混合效应模型和半参数平滑方法分析与 CSF 界面距离的关系。
27 例多发性硬化症患儿和 73 例单相脱髓鞘病变患儿进行了前瞻性随访，每年进行一次脑部扫描（平均随访时间为 4.6 年，标准差为 1.9 年）。共有 282 名具有连续扫描的健康儿童作为对照。与健康对照组相比，多发性硬化症患儿和单相脱髓鞘病变患儿的白质相邻的丘脑区域表现出体积损失。然而，只有多发性硬化症患儿在临床疾病的第一年就表现出了丘脑损伤的额外的向表面内梯度，并且随着时间的推移而恶化（渐近估计值=3.01，95%置信区间[CI]：1.44-4.58，p=0.0002）。
我们的研究结果表明，多发性硬化症特异性的向表面内损伤过程可在疾病的最早阶段表现出来。
