Abstract

Objective

Advanced neuroimaging techniques may offer the potential to monitor disease spreading in amyotrophic lateral sclerosis (ALS). We aim to investigate brain functional and structural magnetic resonance imaging (MRI) changes in a cohort of ALS patients, examined at diagnosis and clinically monitored over 18 months, in order to early discriminate fast progressors (FPs) from slow progressors (SPs). Methods: Resting state functional MRI (RS-fMRI), diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) analyses were performed at baseline in 54 patients with ALS and 22 HCs. ALS patients were classified a posteriori into FPs (n = 25) and SPs (n = 29) based on changes in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score from baseline to the 18-month assessment (ΔALSFRS-R), applying a k-means clustering algorithm. Results: At diagnosis, when compared to HCs, ALS patients showed reduced functional connectivity in both motor and extra-motor networks. When compared to SPs, at baseline, FPs showed decreased function connectivity in paracentral lobule (sensorimotor network), precuneus (in the default mode network), middle frontal gyri (frontoparietal networks) and increased functional connectivity in insular cortices (salience network). Structural analyses did not reveal significant differences in gray and white matter damage by comparing FPs to SPs. Receiver operating characteristic (ROC) curve analysis showed that functional connectivity increase in the left insula at baseline best discriminated FPs and SPs (area under the curve 78%). Conclusions: Impairment of extra-motor networks may appear early in ALS patients with faster disease progression, suggesting that a more widespread functional connectivity damage may be an indicator of poorer prognosis.

中文翻译：

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肌萎缩侧索硬化疾病快速进展的静息状态功能 MRI 脑特征：一项回顾性研究

摘要

客观的

先进的神经影像技术可能提供监测肌萎缩侧索硬化 (ALS) 中疾病传播的潜力。我们的目标是调查一组 ALS 患者的脑功能和结构磁共振成像 (MRI) 变化，在诊断时检查并在 18 个月内进行临床监测，以便及早区分快速进展者 (FP) 和缓慢进展者 (SP)。方法：在基线时对 54 名 ALS 和 22 名 HC 患者进行静息状态功能 MRI (RS-fMRI)、弥散张量成像 (DTI) 和基于体素的形态测量 (VBM) 分析。ALS 患者被后验地分为 FP（n  = 25）和 SP（n = 29) 基于肌萎缩侧索硬化功能评定量表修订版评分从基线到 18 个月评估 (ΔALSFRS-R) 的变化，应用 k 均值聚类算法。结果：在诊断时，与 HC 相比，ALS 患者在运动和运动外网络中表现出功能连接性降低。与 SP 相比，在基线时，FP 在中央旁小叶（感觉运动网络）、楔前叶（在默认模式网络中）、额中回（额顶网络）中的功能连接性降低，而在岛叶皮质（显着性网络）中的功能连接性增加。通过将 FP 与 SP 进行比较，结构分析并未揭示灰质和白质损伤的显着差异。接受者操作特征 (ROC) 曲线分析表明，基线左脑岛的功能连接性增加最能区分 FP 和 SP（曲线下面积 78%）。结论： 在疾病进展较快的 ALS 患者中，运动外网络的损伤可能较早出现，这表明更广泛的功能连接性损伤可能是预后较差的指标。