Spinocerebellar Ataxia Type 1: One-Year Longitudinal Study to Identify Clinical and MRI Measures of Disease Progression in Patients and Presymptomatic Carriers.

Spinocerebellar ataxias type 1 (SCA1) is an autosomal dominant disease usually manifesting in adulthood. We performed a prospective 1-year longitudinal study in 14 presymptomatic mutation carriers (preSCA1), 11 ataxic patients, and 21 healthy controls. SCA1 patients had a median disease duration of 6 years (range 2-16) and SARA score of 7 points (range 3.5-20). PreSCA1 had an estimated time before disease onset of 9.7 years (range 4-30), and no signs of ataxia. At baseline, SCA1 patients significantly differed from controls in SARA score (Scale for Assessment and Rating of Ataxia), cognitive tests, and structural MRI measures. Significant volume loss was found in cerebellum, brainstem, basal ganglia, and cortical thinning in frontal, temporal, and occipital regions. PreSCA1 did not differ from controls. At 1-year follow-up, SCA1 patients showed significant increase in SARA score, and decreased volume of cerebellum (- 0.6%), pons (- 5.5%), superior cerebellar peduncles (- 10.7%), and midbrain (- 3.0%). Signs of disease progression were also observed in preSCA1 subjects, with increased SARA score and reduced total cerebellar volume. Our exploratory study suggests that clinical scores and MRI measures provide valuable data to monitor and quantify the earliest changes associated with the preclinical and the symptomatic phases of SCA1 disease.