Progression of Brain Atrophy in Spinocerebellar Ataxia Type 2: A Longitudinal Tensor-Based Morphometry Study

Abstract

Spinocerebellar ataxia type 2 (SCA2) is the second most frequent autosomal dominant inherited ataxia worldwide. We investigated the capability of magnetic resonance imaging (MRI) to track in vivo progression of brain atrophy in SCA2 by examining twice 10 SCA2 patients (mean interval 3.6 years) and 16 age- and gender-matched healthy controls (mean interval 3.3 years) on the same 1.5 T MRI scanner. We used T1-weighted images and tensor-based morphometry (TBM) to investigate volume changes and the Inherited Ataxia Clinical Rating Scale to assess the clinical deficit. With respect to controls, SCA2 patients showed significant higher atrophy rates in the midbrain, including substantia nigra, basis pontis, middle cerebellar peduncles and posterior medulla corresponding to the gracilis and cuneatus tracts and nuclei, cerebellar white matter (WM) and cortical gray matter (GM) in the inferior portions of the cerebellar hemisphers. No differences in WM or GM volume loss were observed in the supratentorial compartment. TBM findings did not correlate with modifications of the neurological deficit. In conclusion, MRI volumetry using TBM is capable of demonstrating the progression of pontocerebellar atrophy in SCA2, supporting a possible role of MRI as biomarker in future trials.

Progression of Microstructural Damage in Spinocerebellar Ataxia Type 2: A Longitudinal DTI Study

“…Finally, we preliminarily explored whether longitudinal DTI changes were correlated with clinical progression in patients with SCA2. The lack of a significant correlation between longitudinal DTI changes and clinical deterioration in our study (which has been observed also for morphometry findings in patients with SCA2 7 and those with SCA1, SCA3, or SCA6 58 ) might reflect the small sample size, but in our opinion, supports the role of DTI metrics as potential biomarkers of the progression of disease-related microstructural alterations that may precede the evolution of clinical disease manifestations. However, we did not obtain a structured assessment of cognitive or behavioral changes in our patients.…”

Spinocerebellar ataxia type 2: Measures of saccade changes improve power for clinical trials

“…The progression of saccade abnormalities reflects the neurodegenerative pattern of SCA2, specifically at the pontocerebellar level, where regional brain volume declines with disease duration and clinical scores, as has been demonstrated in cross‐sectional and longitudinal studies by imaging data.…”

Brain atrophy measures in preclinical and manifest spinocerebellar ataxia type 2

“…Magnetic resonance imaging (MRI) data are sparse and often comprise only small sample sizes in this orphan disease. The available structural MRI data have so far confirmed the neuropathological findings showing atrophy of the brainstem and cerebellum,6, 7, 8 but there is also some evidence for cortical brain atrophy and microstructural abnormalities in SCA2 patients 9, 10, 11, 12, 13. For preclinical SCA2 mutation carriers, only two structural MRI studies exist.…”