Developmental and neurodegenerative damage in Friedreich's ataxia

Autor(es)

Rezende, T. J. R. ^{[1, 2]} ; Martinez, A. R. M. ^{[1, 2]} ; Faber, I. ^{[1, 2]} ; Girotto Takazaki, K. A. ^{[1, 2]} ; Martins, M. P. ^{[1, 2]} ; de Lima, F. D. ^{[1, 2]} ; Lopes-Cendes, I. ^[3] ; Cendes, F. ^{[1, 2]} ; Franca, M. C. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Sch Med Sci, Neuroimaging Lab, Campinas, SP - Brazil

^[2] Univ Campinas UNICAMP, Dept Neurol, Rua Tessalia Vieira de Camargo, BR-13083887 Campinas, SP - Brazil

^[3] Univ Campinas UNICAMP, Sch Med Sci, Dept Med Genet, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF NEUROLOGY; v. 26, n. 3, p. 483-489, MAR 2019.
• Citações Web of Science: 2

Resumo

Background and purposeFriedreich'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. MethodsWe 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. ResultsComparison 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. ConclusionsStructural 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. (AU)

• Processo FAPESP: 13/26410-0 - Estudo clínico, imunológico e neurofisiológico nas neuronopatias sensitivas
• Beneficiário: Alberto Rolim Muro Martinez
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 14/19786-7 - Cálculo automatizado dos tempos de relaxação transversal: identificação de depósitos de ferro no cérebro
• Beneficiário: Thiago Junqueira Ribeiro de Rezende
• Modalidade de apoio: Bolsas no Brasil - Doutorado