Departments of Radiology, Stony Brook Medicine, Stony Brook, NY 11794, United States; Department of Neurology, New York University School of Medicine, New York, NY, United States.
Departments of Radiology, Stony Brook Medicine, Stony Brook, NY 11794, United States; Department of Neurology, New York University School of Medicine, New York, NY, United States.
Mult Scler Relat Disord. 2019 Jun;31:101-105. doi: 10.1016/j.msard.2019.03.020. Epub 2019 Mar 30.
Fatigue is one of the most commonly experienced symptoms in multiple sclerosis (MS). The neural correlates of fatigue in MS, in general and specifically in early onset, remain poorly understood. This study employed resting-state fMRI (rsfMRI) to investigate the functional connectivity of fatigue in MS patients with early age onset.
Twenty-seven relapsing-remitting MS patients (20 ± 7yo at the age of diagnosis and 26.0 ± 5.5yo at the time of study) were recruited and 22 patients were studied. Structural and rsfMRI sequences were performed on a 3-Tesla Seimens MRI scanner. Seed-based analysis was performed using CONN Functional Connectivity Toolbox for Statistic Parametric Mapping. The Fatigue Severity Scale (FSS) and the Modified Fatigue Impact scale (MFIS) as well as EDSS, Beck Depression Inventory, and symptomatology were measured. Non-fatigued (N = 12) and fatigued patients (N = 10) were separated based on FSS scores, with a score of 5 or greater being classified as fatigued. Group differences in rsfMRI between non-fatigued and fatigued patients were analyzed. Correlations between these functional connectivity differences and behavioral fatigue scores were also analyzed.
Ages, disease duration, lesion load, lesion volume, and neurologic disability were not significantly different between non-fatigued and fatigued patients (p > 0.05). Fatigued patients showed significantly stronger connectivity between the right thalamus and right precentral gyrus (T = 4.58, p = 0.015), and a trending increase in connectivity between the left hippocampus and left precentral gyrus (T = 7.55, p = 0.051). Patients with fatigue showed significantly reduced connectivity between the right thalamus and left parietal operculum (T= -4.28, p = 0.0002), left thalamus and right superior frontal gyrus (T=-5.54, p = 0.046), and between the left insula and posterior cingulate (T=-9.4, p = 0.003). The connectivity between the left insula and posterior cingulate was significantly correlated with the cognitive score of MFIS (R = -0.471, p = 0.027) and FSS (R = -0.719, p = 0.0001). The connectivity between the right thalamus and left parietal operculum was significantly correlated with MFIS cognitive scores (R = -0.431, p = 0.045) and with FSS scores (R = 0.402, p = 0.006). Correlations remained significant after accounting for depression scores.
rsfMRI identified Alterations in two distinct connections (the connectivity between insula and posterior cingulate gyrus and between the right thalamus and right precentral gyrus) that differed between fatigued and non-fatigued patients, as well as correlated with cognitive fatigue severity. These findings suggest that disruption of sensorimotor, high-order motor, and non-motor executive function likely contributes to the neural mechanism of fatigue in MS. Knowledge of the neural mechanisms of underlying MS fatigue could inform more effective treatment strategies.
疲劳是多发性硬化症（MS）中最常见的症状之一。MS 患者疲劳的神经相关性，一般来说，尤其是在早期发病时，仍知之甚少。本研究采用静息态 fMRI（rsfMRI）来研究发病年龄较早的 MS 患者的疲劳的功能连接。
招募了 27 名复发缓解型 MS 患者（诊断时的年龄为 20±7 岁，研究时的年龄为 26.0±5.5 岁），并对 22 名患者进行了研究。在 3 特斯拉西门子 MRI 扫描仪上进行结构和 rsfMRI 序列。使用 CONN 功能连接工具包进行基于种子的分析，用于统计参数映射。使用疲劳严重程度量表（FSS）和改良疲劳影响量表（MFIS）以及 EDSS、贝克抑郁量表和症状学来测量。根据 FSS 评分将非疲劳（N=12）和疲劳（N=10）患者分开，FSS 评分为 5 或更高者被归类为疲劳。分析非疲劳和疲劳患者之间 rsfMRI 之间的组间差异，并分析这些功能连接差异与行为疲劳评分之间的相关性。
非疲劳和疲劳患者之间的年龄、疾病持续时间、病灶负荷、病灶体积和神经残疾无显著差异（p>0.05）。疲劳患者的右侧丘脑与右侧中央前回之间的连接明显增强（T=4.58，p=0.015），左侧海马与左侧中央前回之间的连接呈增加趋势（T=7.55，p=0.051）。疲劳患者的右侧丘脑与左侧顶叶岛盖之间的连接明显减弱（T=-4.28，p=0.0002），左侧丘脑与右侧额上回之间的连接减弱（T=-5.54，p=0.046），左侧岛叶与后扣带回之间的连接减弱（T=-9.4，p=0.003）。左侧岛叶与后扣带回之间的连接与 MFIS 的认知评分显著相关（R=-0.471，p=0.027）和 FSS（R=-0.719，p=0.0001）。右侧丘脑与左侧顶叶岛盖之间的连接与 MFIS 认知评分显著相关（R=-0.431，p=0.045）和 FSS 评分（R=0.402，p=0.006）。在考虑抑郁评分后，相关性仍然显著。
rsfMRI 确定了疲劳和非疲劳患者之间存在两个不同连接（岛叶和后扣带回之间的连接以及右侧丘脑和右侧中央前回之间的连接）的改变，这些改变与认知疲劳的严重程度相关。这些发现表明，感觉运动、高级运动和非运动执行功能的中断可能是 MS 疲劳的神经机制。对 MS 潜在疲劳的神经机制的了解可以为更有效的治疗策略提供信息。
