Structural signature in SCA1: clinical correlates, determinants and natural history.

Abstract

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.