Department of Radiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Neurobiol Aging. 2013 Jun;34(6):1700-7. doi: 10.1016/j.neurobiolaging.2012.12.001. Epub 2013 Jan 5.
Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset movement disorder affecting FMR1 premutation carriers, is associated with cerebral and cerebellar lesions. The aim of this study was to test whether computational anatomy can detect similar patterns in asymptomatic FMR1 premutation carriers (mean age 46.7 years) with qualitatively normal -appearing grey and white matter on brain MRI. We used a multimodal imaging protocol to characterize brain anatomy by automated assessment of gray matter volume and white matter properties. Structural changes in the hippocampus and in the cerebellar motor network with decreased gray matter volume in lobule VI and white matter alterations of the corresponding afferent projections through the middle cerebellar peduncles are demonstrated. Diffuse subcortical white matter changes in both hemispheres, without corresponding gray matter alterations, are only identified through age × group interactions. We interpret the hippocampal fimbria and cerebellar changes as early alterations with a possible neurodevelopmental origin. In contrast, progression of the diffuse cerebral hemispheric white matter changes suggests a neurodegenerative process, leading to late-onset lesions, which may mark the imminent onset of FXTAS.
脆性 X 相关震颤/共济失调综合征（FXTAS）是一种影响 FMR1 前突变携带者的迟发性运动障碍，与脑和小脑病变有关。本研究旨在测试计算解剖学是否可以检测到大脑 MRI 上表现为正常的无症状 FMR1 前突变携带者（平均年龄 46.7 岁）中是否存在类似的模式。我们使用多模态成像方案通过自动评估灰质体积和白质特性来描述大脑解剖结构。研究结果表明，海马体和小脑运动网络存在结构变化，表现为 VI 小叶灰质体积减少，以及通过中脑小脑脚的相应传入投射的白质改变。通过年龄×组相互作用仅识别出双侧弥漫性皮质下白质变化，而没有相应的灰质改变。我们将海马体的伞部和小脑的改变解释为具有潜在神经发育起源的早期改变。相比之下，弥漫性大脑半球白质变化的进展表明存在神经退行性过程，导致迟发性病变，这可能标志着 FXTAS 的即将发作。
