肌萎缩侧索硬化．额颞叶痴呆患者的多模态磁共振成像研究

背景：肌萎缩侧索硬化(amyotrophic lateral sclerosis，ALS)和额颞叶痴呆(frontotemporal dementia,FTD)逐渐被认为属于同一谱系疾病。ALS．FTD是一种罕见疾病，特别是中国。ALS．FTD预后较单纯的ALS或FTD更差。有研究发现认知障碍起病的ALS-FTD(cognitive onsetALS．FTD，ALS．FTD．C)中位生存期要显著长于运动障碍起病的患者(motor onsetALS．FTD，ALS．FTD．M)，但两亚组间病理生
理机制的差异尚不明确。
目的：比较认知障碍起病与运动障碍起病ALS．FTD患者生存期、脑灰质结构、脑血流量及脑白质纤维的差异。
方法：本研究纳入2013年7月至2020年lO月北京协和医院诊断为ALS．FTD的26例患者，进行基线临床信息采集、肌电图检查。定期电话随访，采集患者生存状态、改良版ALS功能评分(revisedALS functional rating scale，ALSFRS．R)等信息。采用Kaplan-Meier生存分析比较ALS-FTD．C和ALS-FTD．M的中位生存期。7例ALS．FTD．C、5例ALS．FTD．M及10例年龄、性别、文化程度相匹配的健康对照者
(healthy control，HC)完成磁共振扫描，采集受试者的3D．T1 W脑结构像、3D．伪连续动脉自旋标记图像及弥散张量成像。应用基于体素的分析方法比较两亚组患者的脑灰质萎缩和低灌注，应用基于纤维束示踪的空间统计分析比较两亚组的脑白质纤维束损害。将影像学参数与临床指标进行相关性分析。
结果：ALS．FTD．C中位生存期长于ALS．FTD．M，但未见统计学差异。ALS．FTD．C的运动中位生存期与ALS．FTD．M无显著性差异。脑分割结果显示，ALS．FTD及ALS．FTD．C的相对全脑灰质体积、相对全脑白质体积均低于HC。脑灰质结构的比较显示，ALS．FTD较HC存在双侧运动区、额颞叶、岛叶及前扣带回灰质体积减少。ALS．FTD．C在上述区域存在广泛的灰质体积减少，相反，ALS．FTD．M灰质体
积减少的脑区则局限于右侧额下回、左侧颞叶和双侧岛叶。直接比较发现ALS．FTD．C较ALS．FTD．M存在右侧颞中回、岛叶及角回灰质体积减少。脑血流量的比较显示，ALS．FTD较HC存在双侧背外侧额上回的低灌注，ALS．FTD．C的低灌注区还包括双侧颞叶、前额叶和前扣带回，未发现ALS．FTD．M与HC及ALS．FTD．C与ALS．FTD．M的脑灌注差异。脑白质结构的比较显示，ALS．FTD较HC存在双侧皮质脊髓束、胼胝体辐射线枕部、放射冠及胼胝体等白质纤维受损。ALS．FTD．C较ALS．FTD．M的脑白质纤维受累更广泛。ALS．FTD患者的相关性分析显示，特定区域的灰质体积减少分别与ALSFRS．R、总病程及核磁年龄相关。
结论：本队列ALS．FTD．C的中位生存期数值上长于ALS．FTD．M，但未见统计学差异。ALS．FTD．C出现运动障碍后的生存期与ALS．FTD．M相似，提示影响ALS-FTD患者预后的主要因素可能是运动的受累而非认知损害。多模态影像学研究的结果发现ALS．FTD．C较ALS．FTD．M存在更广泛的脑灰质萎缩、低血流量及白质纤维束损害，初步揭示了两亚组患者上运动神经元和脑运动区外病理基础的差异。

Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are increasingly recognized as belonging to the same disease spectrum. ALS-FTD is a rare disorder, particularly in China. The prognosis of ALS-FTD is worse than that of isolated ALS or FTD. Previous studies have reported that patients with cognitive-onset ALS-FTD (ALS-FTD-C) have a significantly longer median survival time than those with motor-onset ALS-FTD (ALS-FTD-M), yet the differences in pathophysiological mechanisms between these two subgroups remain unclear.

Objective: To compare the differences in survival time, brain gray matter structure, cerebral blood flow, and white matter fibers between cognitive-onset and motor-onset ALS-FTD patients.

Methods: This study enrolled 26 patients diagnosed with ALS-FTD at Peking Union Medical College Hospital from July 2013 to October 2020. Baseline clinical information and electromyography (EMG) examinations were collected for all participants. Regular telephone follow-ups were conducted to obtain data on patients' survival status, revised ALS Functional Rating Scale (ALSFRS-R) scores, and other relevant clinical indicators. Kaplan-Meier survival analysis was utilized to compare the median survival time between ALS-FTD-C and ALS-FTD-M. A total of 7 ALS-FTD-C patients, 5 ALS-FTD-M patients, and 10 age-, sex-, and education-matched healthy controls (HC) completed magnetic resonance imaging (MRI) scans, including 3D T1-weighted brain structural images, 3D pseudo-continuous arterial spin labeling (pCASL) images, and diffusion tensor imaging (DTI). Voxel-based analysis was applied to compare brain gray matter atrophy and hypoperfusion between the two subgroups, while tract-based spatial statistics (TBSS) was used to evaluate white matter fiber tract damage. Correlation analyses were performed between imaging parameters and clinical indicators.

Results: The median survival time of ALS-FTD-C was numerically longer than that of ALS-FTD-M, but no statistically significant difference was observed. The median motor survival time of ALS-FTD-C showed no significant difference compared with that of ALS-FTD-M. Brain segmentation results revealed that the relative total gray matter volume and relative total white matter volume of both ALS-FTD and ALS-FTD-C were lower than those of HC. Comparisons of gray matter structure showed that ALS-FTD patients exhibited reduced gray matter volume in bilateral motor cortices, frontotemporal lobes, insula, and anterior cingulate cortex compared with HC. ALS-FTD-C patients showed widespread gray matter volume reduction in the aforementioned regions, whereas the gray matter volume reduction in ALS-FTD-M patients was restricted to the right inferior frontal gyrus, left temporal lobe, and bilateral insulae. Direct comparison demonstrated that ALS-FTD-C patients had reduced gray matter volume in the right middle temporal gyrus, insula, and angular gyrus compared with ALS-FTD-M. Cerebral blood flow comparisons showed that ALS-FTD patients had hypoperfusion in the bilateral dorsolateral superior frontal gyri compared with HC; the hypoperfusion regions in ALS-FTD-C also included bilateral temporal lobes, prefrontal lobes, and anterior cingulate cortex. No significant differences in cerebral perfusion were found between ALS-FTD-M and HC, nor between ALS-FTD-C and ALS-FTD-M. Comparisons of white matter structure showed that ALS-FTD patients had damaged white matter fibers in bilateral corticospinal tracts, occipital portion of the corpus callosum radiation, corona radiata, and corpus callosum compared with HC. ALS-FTD-C patients had more widespread white matter fiber involvement than ALS-FTD-M. Correlation analyses in ALS-FTD patients revealed that reduced gray matter volume in specific regions was correlated with ALSFRS-R scores, total disease duration, and MRI-estimated brain age, respectively.

Conclusions: In this cohort, the median survival time of ALS-FTD-C was numerically longer than that of ALS-FTD-M, but no statistically significant difference was detected. The survival time after the onset of motor deficits in ALS-FTD-C was similar to that of ALS-FTD-M, suggesting that the main factor affecting the prognosis of ALS-FTD patients may be motor involvement rather than cognitive impairment. The results of the multimodal imaging study revealed that ALS-FTD-C patients had more widespread gray matter atrophy, reduced cerebral blood flow, and white matter fiber tract damage compared with ALS-FTD-M, preliminarily revealing the differences in pathological foundations beyond the upper motor neurons and motor cortex between the two subgroups.

搜集汇总

背景与挑战

背景概述

该数据集是一个针对肌萎缩侧索硬化与额颞叶痴呆共病患者的多模态磁共振成像研究，包含26例患者的临床和影像数据，旨在比较认知障碍起病与运动障碍起病亚组的差异。研究发现两亚组的中位生存期无显著统计学差异，但认知障碍起病患者在脑灰质萎缩、低灌注和白质纤维损害方面表现出更广泛的异常，揭示了不同起病方式的病理基础差异。数据集通过结构像、灌注成像和弥散张量成像等多模态方法，提供了详细的脑结构、血流和白质完整性分析结果。