School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Clayton Campus, Clayton, VIC, 3800, Australia.
The Australian E-Health Research Centre, CSIRO, Melbourne, Australia.
J Neurol. 2021 Nov;268(11):4178-4189. doi: 10.1007/s00415-021-10512-x. Epub 2021 Apr 15.
Friedreich ataxia is an inherited neurodegenerative disease, with cerebral and cerebellar pathology evident. Despite an increased understanding of its neuropathology, disease progression in this disease remains poorly understood. This study aimed to characterise longitudinal change in brain structure using a multi-modal approach across cerebral and cerebellar grey and white matter.
T1-weighted, diffusion-tensor, and magnetisation transfer magnetic resonance images were obtained from 28 individuals with Friedreich ataxia and 29 age- and gender-matched controls at two time-points, 2 years apart. Region-of-interest and exploratory between-group comparisons assessed changes in brain macrostructure (cerebellar lobule volume, cerebral cortical thickness/gyrification, brain white matter volume) and microstructure (white matter fractional anisotropy, mean/axial/radial diffusivity, magnetisation transfer ratio). Rates of change were correlated against change in neurological severity, Time 1 severity, and onset age.
Individuals with Friedreich ataxia had a greater rate of white matter volume loss than controls in the superior cerebellar peduncles and right peri-thalamic/posterior cerebral regions, and greater reduction in left primary motor cortex gyrification. Greater cerebellar/brainstem white matter volume loss and right dorsal premotor gyrification loss was observed amongst individuals with less severe neurological symptoms at Time 1. Conversely, cerebral atrophy and changes in axial diffusivity were observed in individuals with more severe Time 1 symptoms. Progression in radial diffusivity was more pronounced amongst individuals with earlier disease onset. Greater right ventral premotor gyrification loss correlated with greater neurological progression.
Heterogeneity in Friedreich ataxia progression is observed at the neurobiological level, with evidence of earlier cerebellar and later cerebral degeneration.
弗里德里希共济失调是一种遗传性神经退行性疾病，大脑和小脑的病理变化明显。尽管对其神经病理学有了更多的了解，但这种疾病的疾病进展仍知之甚少。本研究旨在使用多模态方法研究大脑和小脑灰质和白质的结构纵向变化。
从 28 名弗里德里希共济失调患者和 29 名年龄和性别匹配的对照者中获得 T1 加权、弥散张量和磁化传递磁共振图像，时间间隔为 2 年。感兴趣区域和探索性组间比较评估了大脑宏观结构（小脑叶体积、大脑皮质厚度/脑回、脑白质体积）和微观结构（白质各向异性分数、平均/轴向/径向弥散度、磁化传递比）的变化。变化率与神经严重程度的变化、Time1 严重程度和发病年龄相关。
与对照组相比，弗里德里希共济失调患者的上小脑脚和右侧丘脑周围/大脑后区域的白质体积损失速度更快，左侧初级运动皮层脑回减少更多。在 Time1 时神经症状较轻的患者中，观察到小脑/脑干白质体积损失更大和右侧背侧运动前区脑回损失更大。相反，在 Time1 时症状更严重的患者中观察到大脑萎缩和轴向弥散度变化。在发病较早的患者中，径向弥散度的进展更为明显。右侧腹侧运动前区脑回损失越大，神经进展越大。
在神经生物学水平上观察到弗里德里希共济失调进展的异质性，有早期小脑和晚期大脑退化的证据。
Zotero 插件