Department of Child Neurology, VU University Medical Centre, 1081 HV Amsterdam, The Netherlands.
Brain. 2011 Nov;134(Pt 11):3333-41. doi: 10.1093/brain/awr254. Epub 2011 Oct 17.
Leucoencephalopathy with brainstem and spinal cord involvement and elevated lactate is a white matter disorder caused by DARS2 mutations. The pathology is unknown. We observed striking discrepancies between improvement on longitudinal conventional magnetic resonance images and clinical deterioration and between large areas of high signal on diffusion-weighted imaging and small areas with low apparent diffusion coefficient values. These observations prompted a longitudinal and quantitative magnetic resonance imaging study. We investigated eight patients (two males, mean age 27 years). Maps of T(2) relaxation times, fractional anisotropy, apparent diffusion coefficients, signal on diffusion-weighted imaging, and axial and radial diffusivities were generated. Brain metabolites, obtained by chemical shift imaging, were quantified. Data analysis focused on: (i) white matter with low apparent diffusion coefficient; (ii) white matter with high T(2) values; (iii) white matter with intermediate T(2) values; and (iv) normal-appearing white matter. The areas were compared with similarly located areas in eight matched controls. In five patients, T(2)-weighted images, spectroscopy, apparent diffusion coefficient maps and diffusion-weighted imaging maps were compared with those obtained 5-7 years ago. In white matter with low apparent diffusion coefficient, axial and radial diffusivities were decreased and fractional anisotropy was high. T(2) values were intermediate. These areas with truly restricted diffusion were small and often observed at the periphery of areas with high T(2) values. In the white matter with high and intermediate T(2) values, apparent diffusion coefficients and axial and radial diffusivities were increased and fractional anisotropy decreased. The signal on diffusion-weighted imaging was highest in white matter with high T(2) values, an effect of T(2) shinethrough. Chemical shift imaging in both white matter types showed increased lactate, increased myo-inositol and decreased N-acetylaspartate, most pronounced in white matter with high T(2) values. Normal-appearing white matter was comparable with white matter of control subjects. Over time, mild decreases in T(2) signal intensities, signal on diffusion-weighted imaging and in extent of the low apparent diffusion coefficient areas were seen. In conclusion, the disease process in leucoencephalopathy with brainstem and spinal cord involvement and elevated lactate is extremely slow. We hypothesize that diffusion restriction is the first stage of the disease caused by intramyelinic water accumulation, followed by slow shift and then loss of the surplus of water. On conventional T(2) images this leads to improvement. We hypothesize that it is loss of water rather than structural restoration that causes the change in T(2) signal intensity, which would be in better agreement with the slow clinical deterioration.
脑桥和脊髓受累伴乳酸性酸中毒的脑白质病是一种由 DARS2 突变引起的脑白质疾病。其病理机制尚不清楚。我们观察到纵向常规磁共振成像上的改善与临床恶化之间，以及弥散加权成像上的大片高信号与表观弥散系数值小的区域之间存在显著差异。这些观察结果促使我们进行了纵向和定量磁共振成像研究。我们研究了 8 名患者（2 名男性，平均年龄 27 岁）。生成 T2 弛豫时间、各向异性分数、表观弥散系数、弥散加权成像信号、轴向和径向弥散度图。通过化学位移成像获得脑代谢物并进行定量分析。数据分析集中在：（i）表观弥散系数低的脑白质；（ii）T2 值高的脑白质；（iii）T2 值中等的脑白质；和（iv）正常外观的脑白质。将这些区域与 8 名匹配对照者的相应区域进行比较。在 5 名患者中，比较了 T2 加权图像、波谱、表观弥散系数图和弥散加权成像图与 5-7 年前获得的图像。在表观弥散系数低的脑白质中，轴向和径向弥散度降低，各向异性分数升高。T2 值中等。这些真正受限制扩散的区域较小，且通常在 T2 值高的区域的外周观察到。在 T2 值高和中等的脑白质中，表观弥散系数以及轴向和径向弥散度增加，各向异性分数降低。在 T2 值高的脑白质中，弥散加权成像信号最高，这是 T2 透过现象的作用。两种脑白质类型的化学位移成像均显示乳酸性酸中毒、肌醇增加和 N-乙酰天冬氨酸减少，T2 值高的脑白质中最为明显。正常外观的脑白质与对照组的脑白质相似。随着时间的推移，T2 信号强度、弥散加权成像信号和低表观弥散系数区域的范围轻度下降。总之，脑桥和脊髓受累伴乳酸性酸中毒的脑白质病的疾病过程非常缓慢。我们假设，弥散受限是由髓鞘内水积聚引起的疾病的第一阶段，随后是缓慢的移位，然后是多余的水丢失。在常规 T2 图像上，这会导致改善。我们假设导致 T2 信号强度变化的是水的丢失而不是结构的恢复，这与缓慢的临床恶化更为一致。
