Neuroimaging Biomarkers for Friedreich Ataxia: A Cross-Sectional Analysis of the TRACK-FA Study.

IF 8.1 1区 医学 Q1 CLINICAL NEUROLOGY
Nellie Georgiou-Karistianis, Louise A Corben, Eric F Lock, Helena Bujalka, Isaac Adanyeguh, Manuela Corti, Dinesh K Deelchand, Martin B Delatycki, Imis Dogan, Jennifer Farmer, Marcondes C França, Anthony S Gabay, William Gaetz, Ian H Harding, James Joers, Michelle A Lax, Jiakun Li, David R Lynch, Thomas H Mareci, Alberto R M Martinez, Massimo Pandolfo, Marina Papoutsi, Richard G Parker, Kathrin Reetz, Thiago J R Rezende, Timothy P Roberts, Sandro Romanzetti, David A Rudko, Susmita Saha, Jörg B Schulz, Sub H Subramony, Veena G Supramaniam, Christophe Lenglet, Pierre-Gilles Henry
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Abstract

Objective: We aimed to quantify differences in the brain and spinal cord between Friedreich ataxia and controls, stratified by age and disease stage, including for the first time in young children.

Methods: TRACK-FA is the largest prospective, longitudinal, multi-modal neuroimaging study in Friedreich ataxia to date. We assessed individuals with Friedreich ataxia and controls, 5 to 42 years, at 7 sites across 4 continents. The 17 imaging primary outcome measures (POMs) were selected from metrics that showed a significant longitudinal change in previous small-scale studies. These included brain and spinal cord morphometry (structural magnetic resonance imaging [MRI]) and microstructure (diffusion MRI); brain iron levels (quantitative susceptibility mapping); and spinal cord biochemistry (magnetic resonance spectroscopy). This study is registered with ClinicalTrials.gov (NCT04349514).

Results: Between February 2021 and August 2023, we assessed 169 individuals with Friedreich ataxia and 95 controls. Compared to controls, individuals with Friedreich ataxia had lower volume of dentate nucleus and superior cerebellar peduncles; smaller cross-sectional area of spinal cord; lower fractional anisotropy and higher diffusivity in spinal cord and superior cerebellar peduncles; and lower total N-acetyl-aspartate/myo-inositol ratio in spinal cord. Morphometric differences in spinal cord and superior cerebellar peduncles increased dramatically with age during childhood, with rapid development in controls, but not in Friedreich ataxia. Many imaging POMs showed significant associations with clinical severity.

Interpretation: Our findings provide strong imaging evidence of impaired development of spinal cord and superior cerebellar peduncles during childhood in Friedreich ataxia and open the way for the use of neuroimaging biomarkers in clinical trials. ANN NEUROL 2025.

弗里德里希共济失调的神经成像生物标志物:TRACK-FA研究的横断面分析。
目的:我们的目的是量化弗里德里希共济失调和对照组之间脑和脊髓的差异,按年龄和疾病分期分层,包括首次在幼儿中进行。方法:TRACK-FA是迄今为止弗里德里希共济失调最大的前瞻性、纵向、多模态神经影像学研究。我们在4大洲的7个地点评估了弗里德里希共济失调患者和对照组,年龄在5至42岁之间。17个影像学主要结局指标(POMs)是从先前小规模研究中显示显著纵向变化的指标中选择的。这些包括脑和脊髓形态测量(结构磁共振成像[MRI])和微观结构(扩散MRI);脑铁水平(定量易感性制图);以及脊髓生物化学(磁共振光谱)。该研究已在ClinicalTrials.gov注册(NCT04349514)。结果:在2021年2月至2023年8月期间,我们评估了169名弗里德赖希共济失调患者和95名对照组。与对照组相比,弗里德赖希共济失调个体的齿状核和小脑上蒂体积较小;脊髓横截面积较小;脊髓和小脑上蒂的分数各向异性较低,弥漫性较高;脊髓总n -乙酰-天冬氨酸/肌醇比值降低。在儿童期,脊髓和小脑上脚的形态差异随着年龄的增长而急剧增加,在对照组中发展迅速,但在弗里德赖希共济失调中没有。许多影像学显示POMs与临床严重程度显著相关。解释:我们的研究结果提供了强有力的影像学证据,证明儿童弗里德赖希共济失调患者的脊髓和小脑上蒂发育受损,并为在临床试验中使用神经影像学生物标志物开辟了道路。Ann neurol 2025。
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来源期刊
Annals of Neurology
Annals of Neurology 医学-临床神经学
CiteScore
18.00
自引率
1.80%
发文量
270
审稿时长
3-8 weeks
期刊介绍: Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.
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