Májovská Jitka, Nestrašil Igor, Ahmed Alia, Bondy Monica T, Klempíř Jiří, Jahnová Helena, Schneider Susanne A, Horáková Dana, Krásenský Jan, Ješina Pavel, Vaneckova Manuela, Nascene David R, Whitley Chester B, Jarnes Jeanine R, Magner Martin, Dušek Petr
Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital Prague, Prague, Czech Republic.
Division of Clinical Behavioral Neuroscience, Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, Minnesota, USA.
J Inherit Metab Dis. 2024 Mar;47(2):327-339. doi: 10.1002/jimd.12700. Epub 2023 Dec 19.
Cerebellar atrophy is a characteristic sign of late-onset Tay-Sachs disease (LOTS). Other structural neuroimaging abnormalities are inconsistently reported. Our study aimed to perform a detailed whole-brain analysis and quantitatively characterize morphometric changes in LOTS patients. Fourteen patients (8 M/6F) with LOTS from three centers were included in this retrospective study. For morphometric brain analyses, we used deformation-based morphometry, voxel-based morphometry, surface-based morphometry, and spatially unbiased cerebellar atlas template. The quantitative whole-brain morphometric analysis confirmed the finding of profound pontocerebellar atrophy with most affected cerebellar lobules V and VI in LOTS patients. Additionally, the atrophy of structures mainly involved in motor control, including bilateral ventral and lateral thalamic nuclei, primary motor and sensory cortex, supplementary motor area, and white matter regions containing corticospinal tract, was present. The atrophy of the right amygdala, hippocampus, and regions of occipital, parietal and temporal white matter was also observed in LOTS patients in contrast with controls (p < 0.05, FWE corrected). Patients with dysarthria and those initially presenting with ataxia had more severe cerebellar atrophy. Our results show predominant impairment of cerebellar regions responsible for speech and hand motor function in LOTS patients. Widespread morphological changes of motor cortical and subcortical regions and tracts in white matter indicate abnormalities in central motor circuits likely coresponsible for impaired speech and motor function.
小脑萎缩是迟发性泰-萨克斯病（LOTS）的一个特征性体征。其他结构性神经影像学异常的报道并不一致。我们的研究旨在进行详细的全脑分析，并对LOTS患者的形态学变化进行定量表征。这项回顾性研究纳入了来自三个中心的14例LOTS患者（8例男性/6例女性）。对于脑形态学分析，我们使用了基于变形的形态学、基于体素的形态学、基于表面的形态学和空间无偏小脑图谱模板。全脑形态学定量分析证实了LOTS患者存在严重的脑桥小脑萎缩，其中小脑小叶V和VI受影响最严重。此外，主要参与运动控制的结构出现萎缩，包括双侧腹侧和外侧丘脑核、初级运动和感觉皮层、辅助运动区以及包含皮质脊髓束的白质区域。与对照组相比，LOTS患者右侧杏仁核、海马以及枕叶、顶叶和颞叶白质区域也出现萎缩（p < 0.05，FWE校正）。构音障碍患者和最初表现为共济失调的患者小脑萎缩更严重。我们的结果表明，LOTS患者中负责言语和手部运动功能的小脑区域存在主要损伤。运动皮层和皮层下区域以及白质束的广泛形态学变化表明，中枢运动回路异常可能共同导致言语和运动功能受损。
