BACKGROUND AND PURPOSE: Friedreich's ataxia (FRDA) is the most common autosomal-recessive ataxia worldwide. It is characterized by early onset, sensory abnormalities and slowly progressive ataxia. All magnetic resonance imaging (MRI)-based studies have focused on the evaluation of adult patients. Therefore, we designed a cross-sectional multimodal MRI-based study to investigate the anatomical substrates involved in the early stages of FRDA. METHODS: We enrolled 37 patients (12 children) and 38 controls. All subjects underwent MRI in a 3T device to assess gray and white matter. We used measures from FreeSurfer and CERES to evaluate the cerebral and cerebellar cortices. The T1 multiatlas assessed deep gray matter. The diffusion tensor imaging multiatlas was used to investigate microstructural abnormalities in brain white matter and SpineSeg was used to assess the cervical spinal cord. All analyses were corrected for multiple comparisons. RESULTS: Comparison with age-matched controls showed that pediatric patients have spinal cord, inferior cerebellar peduncle and red nucleus damage. In contrast, adult patients showed more widespread white matter damage than pediatric patients. With regard to gray matter, we found cortical thinning at the left central sulcus and volumetric reduction in the thalami and hippocampi only in adult patients. Finally, values of fractional anisotropy in adult patients and radial diffusivity in pediatric patients from the inferior cerebellar peduncle correlated with disease duration and ataxia severity, respectively. CONCLUSIONS: Structural damage in FRDA begins in the spinal cord and inferior cerebellar peduncle as well as the red nucleus, and progresses to cerebral areas in adulthood. These results shed some light on the early stages of FRDA and highlight potential neuroimaging markers for therapeutic trials.
BACKGROUND AND PURPOSE:Friedreich's ataxia (FRDA) is the most common autosomal-recessive ataxia worldwide. It is characterized by early onset, sensory abnormalities and slowly progressive ataxia. All magnetic resonance imaging (MRI)-based studies have focused on the evaluation of adult patients. Therefore, we designed a cross-sectional multimodal MRI-based study to investigate the anatomical substrates involved in the early stages of FRDA. METHODS: We enrolled 37 patients (12 children) and 38 controls. All subjects underwent MRI in a 3T device to assess gray and white matter. We used measures from FreeSurfer and CERES to evaluate the cerebral and cerebellar cortices. The T1 multiatlas assessed deep gray matter. The diffusion tensor imaging multiatlas was used to investigate microstructural abnormalities in brain white matter and SpineSeg was used to assess the cervical spinal cord. All analyses were corrected for multiple comparisons. RESULTS: Comparison with age-matched controls showed that pediatric patients have spinal cord, inferior cerebellar peduncle and red nucleus damage. In contrast, adult patients showed more widespread white matter damage than pediatric patients. With regard to gray matter, we found cortical thinning at the left central sulcus and volumetric reduction in the thalami and hippocampi only in adult patients. Finally, values of fractional anisotropy in adult patients and radial diffusivity in pediatric patients from the inferior cerebellar peduncle correlated with disease duration and ataxia severity, respectively. CONCLUSIONS:Structural damage in FRDA begins in the spinal cord and inferior cerebellar peduncle as well as the red nucleus, and progresses to cerebral areas in adulthood. These results shed some light on the early stages of FRDA and highlight potential neuroimaging markers for therapeutic trials.
Authors: Gary F Egan; Paul M Thompson; Ian H Harding; Sidhant Chopra; Filippo Arrigoni; Sylvia Boesch; Arturo Brunetti; Sirio Cocozza; Louise A Corben; Andreas Deistung; Martin Delatycki; Stefano Diciotti; Imis Dogan; Stefania Evangelisti; Marcondes C França; Sophia L Göricke; Nellie Georgiou-Karistianis; Laura L Gramegna; Pierre-Gilles Henry; Carlos R Hernandez-Castillo; Diane Hutter; Neda Jahanshad; James M Joers; Christophe Lenglet; Raffaele Lodi; David N Manners; Alberto R M Martinez; Andrea Martinuzzi; Chiara Marzi; Mario Mascalchi; Wolfgang Nachbauer; Chiara Pane; Denis Peruzzo; Pramod K Pisharady; Giuseppe Pontillo; Kathrin Reetz; Thiago J R Rezende; Sandro Romanzetti; Francesco Saccà; Christoph Scherfler; Jörg B Schulz; Ambra Stefani; Claudia Testa; Sophia I Thomopoulos; Dagmar Timmann; Stefania Tirelli; Caterina Tonon; Marinela Vavla Journal: Ann Neurol Date: 2021-09-17 Impact factor: 11.274
Authors: Marie Beaudin; Mario Manto; Jeremy D Schmahmann; Massimo Pandolfo; Nicolas Dupre Journal: Nat Rev Neurol Date: 2022-03-24 Impact factor: 42.937
Authors: Juan Sebastian Martin-Saavedra; Sara Reis Teixeira; Cesar Augusto Pinheiro Ferreira Alves; Fabrício Guimarães Gonçalves; Luis Octavio Tierradentro-García; Martin Kidd; Colleen Muraresku; Amy Goldstein; Arastoo Vossough Journal: Cerebellum Date: 2021-05-30 Impact factor: 3.847
Authors: Louisa P Selvadurai; Louise A Corben; Martin B Delatycki; Elsdon Storey; Gary F Egan; Nellie Georgiou-Karistianis; Ian H Harding Journal: Hum Brain Mapp Date: 2020-01-06 Impact factor: 5.038