Kassubek Jan, Roselli Francesco, Witzel Simon, Dorst Johannes, Ludolph Albert C, Rasche Volker, Vernikouskaya Ina, Müller Hans-Peter
Dept. of Neurology, University of Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany.
German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany.
Sci Rep. 2025 Jan 10;15(1):1551. doi: 10.1038/s41598-025-85786-6.
Primary lateral sclerosis (PLS) is a motor neuron disease (MND) which mainly affects upper motor neurons. Within the MND spectrum, PLS is much more slowly progressive than amyotrophic laterals sclerosis (ALS). Classical ALS is characterized by catabolism and abnormal energy metabolism preceding onset of motor symptoms, and previous studies indicated that the disease progression of ALS involves hypothalamic atrophy. Very limited weight loss is observed in patients with PLS, which raises the question of whether there are also less hypothalamic alterations. The purpose of this study was to quantitatively investigate the hypothalamic volume in a group of PLS patients and to compare it with ALS and controls. Recently, we have introduced automatic hypothalamic quantification method based on the use of convolutional neural network (CNN) to reduce human variability and enhance analysis robustness. This CNN of U-Net architecture was applied for automatic segmentation of the hypothalamus and intracranial volume (ICV) to allow adjustments of the hypothalamic volume between subjects with different head sizes respectively. Automatic segmentation and volumetric analysis were performed in high resolution T1 weighted MRI volumes (acquired on a 1.5 T MRI scanner) of 46 PLS patients in comparison to 107 healthy controls and 411 classical ALS patients, respectively. Significant hypothalamic volume reduction was observed in PLS (818 ± 73 mm) when compared to controls (852 ± 77 mm); significant hypothalamic volume reduction was also confirmed in ALS (823 ± 84 mm), in support of previous studies. No significant differences were found in normalized hypothalamic volumes between ALS patients and PLS patients at the group level. This unbiased CNN-based hypothalamus volume quantification study demonstrated similarly reduced hypothalamus volume in PLS and ALS patients, despite the clinical phenotypic differences.
原发性侧索硬化症（PLS）是一种主要影响上运动神经元的运动神经元疾病（MND）。在MND谱系中，PLS的进展比肌萎缩侧索硬化症（ALS）慢得多。“经典”ALS的特征是在运动症状出现之前存在分解代谢和异常能量代谢，先前的研究表明ALS的疾病进展涉及下丘脑萎缩。PLS患者中观察到的体重减轻非常有限，这就提出了一个问题，即下丘脑的改变是否也较少。本研究的目的是定量研究一组PLS患者的下丘脑体积，并将其与ALS患者和对照组进行比较。最近，我们引入了基于卷积神经网络（CNN）的自动下丘脑量化方法，以减少人为差异并增强分析的稳健性。这种U-Net架构的CNN被应用于下丘脑和颅内体积（ICV）的自动分割，以便分别对不同头围大小的受试者之间的下丘脑体积进行调整。对46例PLS患者、107例健康对照和411例“经典”ALS患者的高分辨率T1加权MRI图像（在1.5 T MRI扫描仪上采集）进行了自动分割和体积分析。与对照组（852±77 mm³）相比，PLS患者的下丘脑体积显著减小（818±73 mm³）；ALS患者（823±84 mm³）的下丘脑体积也显著减小，这支持了先前的研究。在组水平上，ALS患者和PLS患者的归一化下丘脑体积没有显著差异。这项基于CNN的无偏倚下丘脑体积量化研究表明，尽管临床表型不同，但PLS患者和ALS患者的下丘脑体积同样减小。
