Georgiou-Karistianis Nellie, Corben Louise A, Lock Eric F, Bujalka Helena, Adanyeguh Isaac, Corti Manuela, Deelchand Dinesh K, Delatycki Martin B, Dogan Imis, Farmer Jennifer, França Marcondes C, Gabay Anthony S, Gaetz William, Harding Ian H, Joers James, Lax Michelle A, Li Jiakun, Lynch David R, Mareci Thomas H, Martinez Alberto R M, Pandolfo Massimo, Papoutsi Marina, Parker Richard G, Reetz Kathrin, Rezende Thiago J R, Roberts Timothy P, Romanzetti Sandro, Rudko David A, Saha Susmita, Schulz Jörg B, Subramony Sub H, Supramaniam Veena G, Lenglet Christophe, Henry Pierre-Gilles
School of Psychological Sciences, The Turner Institute for Brain and Mental Health, Monash University, Clayton, Australia.
Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Parkville, Australia.
Ann Neurol. 2025 Aug;98(2):386-397. doi: 10.1002/ana.27237. Epub 2025 Mar 22.
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.
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).
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.
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;98:386-397.
我们旨在量化弗里德赖希共济失调患者与对照组在大脑和脊髓方面的差异，并按年龄和疾病阶段进行分层，其中首次纳入了幼儿。
TRACK-FA是迄今为止弗里德赖希共济失调领域规模最大的前瞻性、纵向、多模态神经影像学研究。我们在四大洲的7个地点对年龄在5至42岁的弗里德赖希共济失调患者和对照组进行了评估。17项影像学主要结局指标（POMs）是从先前小规模研究中显示出显著纵向变化的指标中选取的。这些指标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（定量磁化率映射）；以及脊髓生物化学（磁共振波谱）。本研究已在ClinicalTrials.gov注册（NCT04349514）。
在2021年2月至2023年8月期间，我们评估了169例弗里德赖希共济失调患者和95例对照组。与对照组相比，弗里德赖希共济失调患者的齿状核和上小脑脚体积较小；脊髓横截面积较小；脊髓和上小脑脚的分数各向异性较低，扩散率较高；脊髓中总N-乙酰天门冬氨酸/肌醇比值较低。儿童期脊髓和上小脑脚的形态测量差异随年龄显著增加，对照组发育迅速，而弗里德赖希共济失调患者则不然。许多影像学POMs与临床严重程度显著相关。
我们的研究结果提供了强有力的影像学证据，表明弗里德赖希共济失调患者在儿童期脊髓和上小脑脚发育受损，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。《神经病学纪事》2025年；98:386 - 397。
