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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引用次数: 0
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.
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.