Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
High Field Magnetic Resonance, Max-Planck Institute for Biological Cybernetics, Tübingen, Germany.
Clin Neuroradiol. 2021 Dec;31(4):969-980. doi: 10.1007/s00062-020-00975-2. Epub 2020 Nov 23.
T2-weighted signal hyperintensities in white matter (WM) are a diagnostic finding in brain magnetic resonance imaging (MRI) of patients with metachromatic leukodystrophy (MLD). In our systematic investigation of the evolution of T2-hyperintensities in patients with the late-infantile form, we describe and characterize T2-pseudonormalization in the advanced stage of the natural disease course.
The volume of T2-hyperintensities was quantified in 34 MRIs of 27 children with late-infantile MLD (median age 2.25 years, range 0.5-5.2 years). In three children with the most advanced clinical course (age >4 years) and for whom the T2-pseudonormalization was the most pronounced, WM microstructure was investigated using a multimodal MRI protocol, including diffusion-weighted imaging, MR spectroscopy (MRS), myelin water fraction (MWF), magnetization transfer ratio (MTR), T1-mapping and quantitative susceptibility mapping.
T2-hyperintensities in cerebral WM returned to normal in large areas of 3 patients in the advanced disease stage. Multimodal assessment of WM microstructure in areas with T2-pseudonormalization revealed highly decreased values for NAA, neurite density, isotropic water, mean and radial kurtosis, MWF and MTR, as well as increased radial diffusivity.
In late-infantile MLD patients, we found T2-pseudonormalization in WM tissue with highly abnormal microstructure characterizing the most advanced disease stage. Pathological hallmarks might be a loss of myelin, but also neuronal loss as well as increased tissue density due to gliosis and accumulated storage material. These results suggest that a multimodal MRI protocol using more specific microstructural parameters than T2-weighted sequences should be used when evaluating the effect of treatment trials in MLD.
脑磁共振成像（MRI）中脑白质（WM）的 T2 加权信号高信号是黏脂贮积症（MLD）患者的诊断发现。在我们对晚婴型 MLD 患者 T2 高信号演变的系统研究中，我们描述并表征了自然病程晚期 T2 假性正常化。
对 27 例晚婴型 MLD 患儿（中位年龄 2.25 岁，范围 0.5-5.2 岁）的 34 次 MRI 检查中 T2 高信号的体积进行了量化。在 3 名患有最严重临床病程（年龄＞4 岁）的儿童中，对 T2 假性正常化最明显的患儿，采用包括弥散加权成像、磁共振波谱（MRS）、髓鞘水分数（MWF）、磁化传递比（MTR）、T1 映射和定量磁化率映射的多模态 MRI 方案研究了 WM 微观结构。
在疾病晚期，3 名患者的脑 WM 中 T2 高信号在大片区域恢复正常。在 T2 假性正常化区域的 WM 微观结构的多模态评估中，NAA、神经丝密度、各向同性水、平均和径向峰度、MWF 和 MTR 以及径向扩散系数明显降低。
在晚婴型 MLD 患者中，我们在 WM 组织中发现了 T2 假性正常化，其微观结构高度异常，特征为最严重的疾病阶段。病理标志可能是髓鞘丢失，但也可能是神经元丢失以及由于神经胶质增生和积累的储存物质导致的组织密度增加。这些结果表明，在评估 MLD 治疗试验的效果时，应使用多模态 MRI 方案，该方案使用比 T2 加权序列更具体的微观结构参数。
