Background: Frontotemporal Spectrum Disorder (FTSD) and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases often considered as a continuum from clinical, epidemiologic and genetic perspectives. We used localized brain volume alterations to evaluate common and specific features of FTSD, FTSD-ALS and ALS patients to further understand this clinical continuum. Methods: We used voxel-based morphometry on structural MRI images to localize volume alterations in group comparisons: patients (20 FTSD, seven FTSD-ALS, 18 ALS) versus healthy controls (39 CTR), and patient groups between themselves. We used mean whole-brain cortical thickness (CT) to assess whether its correlations with local brain volume could propose mechanistic explanations of the heterogeneous clinical presentations. We also assessed whether volume reduction can explain cognitive impairment, measured with frontal assessment battery, verbal fluency and semantic fluency. Results: Common (mainly frontal) and specific areas with reduced volume were detected between FTSD, FTSD-ALS and ALS patients, confirming suggestions of a clinical continuum, while at the same time defining morphological specificities for each clinical group (e.g. a difference of cerebral and cerebellar involvement between FTSD and ALS). CT values suggested extensive network disruption in the pathological process, with indications of a correlation between cerebral and cerebellar volumes and CT in ALS. The analysis of the neuropsychological scores indeed pointed towards an important role for the cerebellum, along with fronto-temporal areas, in explaining impairment of executive and linguistic functions. Conclusions: We identified common elements that explain the FTSD-ALS clinical continuum, while also identifying specificities of each group, partially explained by different cerebral and cerebellar involvement.

中文翻译：

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额叶和小脑萎缩支持FTSD-ALS临床连续体

背景：额颞频谱障碍（FTSD）和肌萎缩性侧索硬化症（ALS）是神经退行性疾病，从临床，流行病学和遗传学角度来看通常被视为连续体。我们使用局部脑容量改变来评估FTSD，FTSD-ALS和ALS患者的共有和特定特征，以进一步了解该临床连续性。方法：我们在结构MRI图像上使用基于体素的形态计量学来确定组比较中的体积变化：患者（20 FTSD，7 FTSD-ALS，18 ALS）与健康对照（39 CTR），以及两组之间的患者组。我们使用平均全脑皮质厚度（CT）来评估其与局部脑容量的相关性是否可以提出异质临床表现的机械解释。我们还评估了体量的减少是否可以解释认知障碍，可以通过额头评估，口语流利度和语义流利度来衡量。结果：在FTSD，FTSD-ALS和ALS患者之间检测到了常见的（主要是额叶）和特定的体积缩小的区域，证实了临床连续性的建议，同时定义了每个临床组的形态学特异性（例如，大脑的差异以及FTSD和ALS之间的小脑受累）。CT值表明在病理过程中存在广泛的网络中断，提示ALS的脑小脑容量与CT之间存在相关性。对神经心理学得分的分析确实指出了小脑以及额颞区的重要作用，在解释执行和语言功能的损害。结论：我们确定了解释FTSD-ALS临床连续性的共同因素，同时也确定了每个组的特异性，部分原因是由于不同的脑部和小脑受累。