Tackling clinical heterogeneity across the amyotrophic lateral sclerosis-frontotemporal dementia spectrum using a transdiagnostic approach.
Tackling clinical heterogeneity across the amyotrophic lateral sclerosis-frontotemporal dementia spectrum using a transdiagnostic approach.
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DOI：
10.1093/braincomms/fcab257
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发表时间：
2021
影响因子：
4.8
通讯作者：
Rohrer JD
中科院分区：
文献类型：
--
作者：
Ahmed RM;Bocchetta M;Todd EG;Tse NY;Devenney EM;Tu S;Caga J;Hodges JR;Halliday GM;Irish M;Kiernan MC;Piguet O;Rohrer JD
肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTD）的疾病综合征显示出相当大的临床，遗传和病理重叠，但越来越多的证据表明，在进展和生存的实质性差异。到目前为止，已经有有限的检查，如何配置文件的脑萎缩可能不同的临床表型。在这里，我们解决了这个长期存在的差距，在文献中，通过评估皮质和皮质下的灰色和白色物质的体积结构MRI在一个大的队列209名参与者。使用Addenbrooke认知检查和剑桥行为量表评估认知和行为变化。相对于58例对照组，行为变异FTD（n = 58）和ALS-FTD（n = 41）患者显示额岛、扣带回、颞叶和运动皮质广泛萎缩，海马、杏仁核、丘脑和纹状体明显皮质下萎缩，后一组萎缩进一步扩展至脑干、脑桥和小脑。在另一端的频谱，纯ALS患者（n = 52）显示相当大的额顶叶萎缩，包括右岛叶和运动皮质和脑桥和脑干区域。皮质下区域包括双侧苍白球和壳核，但程度低于ALS-FTD和行为变体FTD组。在整个范围内，所有三个组中受影响最严重的区域是小脑，特别是前部（比对照组低76-90%）。患者组的直接比较显示，相对于纯ALS，ALS-FTD的颞叶萎缩和广泛的皮质下受累不成比例。相比之下，纯ALS表现出显着更大的顶叶萎缩。行为变体FTD和ALS-FTD的特征均为额叶体积相对于纯ALS减少。运动皮层和小脑皮质是临床综合征之间的区别结构，与单纯ALS相比，ALS-FTD的双侧运动皮层萎缩更明显，相对于行为变体FTD，左侧运动皮层和小脑皮质萎缩更严重。采用跨诊断方法，我们发现异常行为与涉及杏仁核、纹状体和丘脑的主要额岛叶网络中的体积损失之间存在显着相关性。我们的研究结果表明，在ALS-FTD谱中存在不同的萎缩特征，关键结构包括运动皮质和小脑。值得注意的是，我们的研究结果指出，皮质下参与行为障碍的起源，可能占整个频谱通常观察到的显着的表型变异。Ahmed等人'研究结果表明，在ALS-FTD谱中存在不同的萎缩特征，关键结构包括运动皮质和小脑。皮质下受累可能是行为障碍的起源，可能解释了在ALS-FTD谱中通常观察到的显著表型变异性。
The disease syndromes of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) display considerable clinical, genetic and pathological overlap, yet mounting evidence indicates substantial differences in progression and survival. To date, there has been limited examination of how profiles of brain atrophy might differ between clinical phenotypes. Here, we address this longstanding gap in the literature by assessing cortical and subcortical grey and white matter volumes on structural MRI in a large cohort of 209 participants. Cognitive and behavioural changes were assessed using the Addenbrooke’s Cognitive Examination and the Cambridge Behavioural Inventory. Relative to 58 controls, behavioural variant FTD (n = 58) and ALS–FTD (n = 41) patients displayed extensive atrophy of frontoinsular, cingulate, temporal and motor cortices, with marked subcortical atrophy targeting the hippocampus, amygdala, thalamus and striatum, with atrophy further extended to the brainstem, pons and cerebellum in the latter group. At the other end of the spectrum, pure-ALS patients (n = 52) displayed considerable frontoparietal atrophy, including right insular and motor cortices and pons and brainstem regions. Subcortical regions included the bilateral pallidum and putamen, but to a lesser degree than in the ALS–FTD and behavioural variant FTD groups. Across the spectrum the most affected region in all three groups was the insula, and specifically the anterior part (76–90% lower than controls). Direct comparison of the patient groups revealed disproportionate temporal atrophy and widespread subcortical involvement in ALS–FTD relative to pure-ALS. In contrast, pure-ALS displayed significantly greater parietal atrophy. Both behavioural variant FTD and ALS–FTD were characterized by volume decrease in the frontal lobes relative to pure-ALS. The motor cortex and insula emerged as differentiating structures between clinical syndromes, with bilateral motor cortex atrophy more pronounced in ALS–FTD compared with pure-ALS, and greater left motor cortex and insula atrophy relative to behavioural variant FTD. Taking a transdiagnostic approach, we found significant associations between abnormal behaviour and volume loss in a predominantly frontoinsular network involving the amygdala, striatum and thalamus. Our findings demonstrate the presence of distinct atrophy profiles across the ALS–FTD spectrum, with key structures including the motor cortex and insula. Notably, our results point to subcortical involvement in the origin of behavioural disturbances, potentially accounting for the marked phenotypic variability typically observed across the spectrum. Ahmed et al.’s findings demonstrate the presence of distinct atrophy profiles across the ALS–FTD spectrum, with key structures including the motor cortex and insula. Subcortical involvement is likely the origin of behavioural disturbances, potentially accounting for the marked phenotypic variability typically observed across the ALS-FTD spectrum.
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