RESUMEN
Spinocerebellar ataxia type 1 is an autosomal dominant disorder caused by a CAG repeat expansion in ATXN1, characterized by progressive cerebellar and extracerebellar symptoms. MRI-based studies in SCA1 focused in the cerebellum and connections, but there are few data about supratentorial/spinal damage and its clinical relevance. We have thus designed this multimodal MRI study to uncover the structural signature of SCA1. To accomplish that, a group of 33 patients and 33 age-and gender-matched healthy controls underwent MRI on a 3T scanner. All patients underwent a comprehensive neurological and neuropsychological evaluation. We correlated the structural findings with the clinical features of the disease. In addition, we evaluated the disease progression looking at differences in SCA1 subgroups defined by disease duration. Ataxia and pyramidal signs were the main symptoms. Neuropsychological evaluation disclosed cognitive impairment in 53% with predominant frontotemporal dysfunction. Gray matter analysis unfolded cortical thinning of primary and associative motor areas with more restricted impairment of deep structures. Deep gray matter atrophy was associated with motor handicap and poor cognition skills. White matter integrity loss was diffuse in the brainstem but restricted in supratentorial structures. Cerebellar cortical thinning was found in multiple areas and correlated not only with motor disability but also with verbal fluency. Spinal cord atrophy correlated with motor handicap. Comparison of MRI findings in disease duration-defined subgroups identified a peculiar pattern of progressive degeneration.
Asunto(s)
Ataxias Espinocerebelosas/diagnóstico por imagen , Adulto , Atrofia , Encéfalo/diagnóstico por imagen , Estudios de Cohortes , Imagen de Difusión Tensora , Progresión de la Enfermedad , Femenino , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Tamaño de los Órganos , Fenotipo , Médula Espinal/diagnóstico por imagen , Ataxias Espinocerebelosas/fisiopatología , Ataxias Espinocerebelosas/psicologíaRESUMEN
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant disorder caused by a CAG repeat expansion, characterized by progressive cerebellar ataxia and pyramidal signs. Non-motor and extracerebellar symptoms may occur. MRI-based studies in SCA1 focused in the cerebellum and connections, but there are no data about cord damage in the disease and its clinical relevance. To evaluate in vivo spinal cord damage in SCA1, a group of 31 patients with SCA1 and 31 age- and gender-matched healthy controls underwent MRI on a 3T scanner. We used T1-weighted 3D images to estimate the cervical spinal cord area (CA) and eccentricity (CE) at three C2/C3 levels based on a semi-automatic image segmentation protocol. The scale for assessment and rating of ataxia (SARA) was used to quantify disease severity. The groups were significantly different regarding CA (47.26 ± 7.4 vs. 68.8 ± 5.7 mm2, p < 0.001) and CE values (0.803 ± 0.044 vs. 0.774 ± 0.043, p < 0.05). Furthermore, in the patient group, CA presented significant correlation with SARA scores (R = -0.633, p < 0.001) and CAGn expansion (R = -0.658, p < 0.001). CE was not associated with SARA scores (p = 0.431). In the multiple variable regression, CA was strongly associated with disease duration (coefficient -0.360, p < 0.05) and CAGn expansion (coefficient -1.124, p < 0.001). SCA1 is characterized by cervical cord atrophy and anteroposterior flattening. Morphometric analyses of the spinal cord MRI might be a useful biomarker in the disease.