Timmers Inge, Zhang Hui, Bastiani Matteo, Jansma Bernadette M, Roebroeck Alard, Rubio-Gozalbo M Estela
Department of Cognitive Neuroscience, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands,
J Inherit Metab Dis. 2015 Mar;38(2):295-304. doi: 10.1007/s10545-014-9780-x. Epub 2014 Oct 25.
White matter abnormalities have been observed in patients with classic galactosemia, an inborn error of galactose metabolism. However, magnetic resonance imaging (MRI) data collected in the past were generally qualitative in nature. Our objective was to investigate white matter microstructure pathology and examine correlations with outcome and behaviour in this disease, by using multi-shell diffusion weighted imaging. In addition to standard diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI) was used to estimate density and orientation dispersion of neurites in a group of eight patients (aged 16-21 years) and eight healthy controls (aged 15-20 years). Extensive white matter abnormalities were found: neurite density index (NDI) was lower in the patient group in bilateral anterior areas, and orientation dispersion index (ODI) was increased mainly in the left hemisphere. These specific regional profiles are in agreement with the cognitive profile observed in galactosemia, showing higher order cognitive impairments, and language and motor impairments, respectively. Less favourable white matter properties correlated positively with age and age at onset of diet, and negatively with behavioural outcome (e.g. visual working memory). To conclude, this study provides evidence of white matter pathology regarding density and dispersion of neurites in these patients. The results are discussed in light of suggested pathophysiological mechanisms.
经典型半乳糖血症是一种先天性半乳糖代谢紊乱疾病，患有该疾病的患者已被观察到存在白质异常。然而，过去收集的磁共振成像（MRI）数据本质上通常是定性的。我们的目标是通过使用多壳扩散加权成像来研究这种疾病中的白质微观结构病理学，并检查其与预后和行为的相关性。除了标准扩散张量成像（DTI）外，神经突方向离散度和密度成像（NODDI）被用于估计一组8名患者（年龄16 - 21岁）和8名健康对照者（年龄15 - 20岁）的神经突密度和方向离散度。发现了广泛的白质异常：双侧前部区域患者组的神经突密度指数（NDI）较低，并且方向离散度指数（ODI）主要在左半球增加。这些特定的区域特征与半乳糖血症中观察到的认知特征一致，分别显示出高阶认知障碍、语言和运动障碍。较差的白质特性与年龄和开始饮食的年龄呈正相关，与行为结果（如视觉工作记忆）呈负相关。总之，本研究提供了这些患者神经突密度和离散度方面白质病理学的证据。根据提出的病理生理机制对结果进行了讨论。
