In vivo assessment of neurodegeneration in Spinocerebellar Ataxia type 7

Abstract

Highlights DTI study reveals brain-wide differences between SCA7 patients and controls. DTI dual-compartment model controls for increased CSF-like free water in patients. Tensor-based deformations show SCA7 tissue loss extends beyond cerebellum. Focal atrophy, but global microstructural abnormalities were observed in SCA7.

Structural and connectivity parameters reveal spared connectivity in young patients with non-progressive compared to slow-progressive cerebellar ataxia

“…It should be noted, however, that few cerebral regions of the sensorimotor system (i.e., left paracentral lobule, right middle cingulum, right postcentral gyrus, right middle temporal pole, and right cuneus) show smaller volumes in NonP patients compared to SlowP. This result is in agreement with recent works that detected either gray matter atrophy or microstructural alterations in sensorimotor cortices, motor association areas, and temporal regions of patients with ataxia ( 19 , 23 , 36 ). Even though, since no specific studies have investigated these alterations in patients with Joubert syndrome, it is hard to infer the mechanisms underlying the different volumetric pattern that we revealed in NonP and SlowP patients.…”

“…In particular, Olivito et al ( 21 ) showed a specific pattern of WM microstructural damage resulting in a cerebro-cerebellar dysregulation associated with the neurodegenerative processes of spinocerebellar ataxia (SCA), while Friedreich ataxia patients showed a significant reduction in the number of streamlines of cerebro-cerebellar tracts, which led to secondary effects in other cortical areas, such as the supplementary motor area, cingulate and frontal cortex, and subcortical nuclei ( 22 ). Fractional Anisotropy (FA) and Mean Diffusivity (MD) maps, derived from diffusion tensor imaging (DTI), also demonstrated the degeneration of the cerebro-cerebellar loop by revealing microstructural abnormalities comparable to those found by neuropathology in SCA7 ( 23 ), and monitoring ataxia severity through alterations of the cortico-ponto-cerebellar pathway in adult-onset ataxic neurodegenerative patients ( 24 ). Furthermore, disruption of WM integrity in ataxic patients with respect to HC may be used to monitor the progression of pathology since these microstructural changes strongly correlated with clinical severity of one of the most frequent inherited cerebellar ataxias ( 25 ).…”

Longitudinal MRI and 1H-MRS study of SCA7 mouse forebrain reveals progressive multiregional atrophy and early brain metabolite changes indicating early neuronal and glial dysfunction

“…Atrophy of hippocampus is observed from 24 weeks, while the volume of midbrain and brain stem decreases at 30 weeks. Loss of grey matter tissue has been previously described in various brain regions in clinical SCA7, including the putamen and thalamus [ 28 ] using voxel-wise analysis. Diffusion tensor imaging has also demonstrated microstructural deficiencies in these structures [ 28 ].…”

“…Loss of grey matter tissue has been previously described in various brain regions in clinical SCA7, including the putamen and thalamus [ 28 ] using voxel-wise analysis. Diffusion tensor imaging has also demonstrated microstructural deficiencies in these structures [ 28 ]. Further investigation is needed to conclude on the nature of these defects, which can be attributed to either demyelination, neuronal death, or gliosis, as shown recently in a mouse model of Alzheimer’s disease [ 29 ].…”

Structural and connectivity parameters reveal compensation patterns in young patients with non-progressive and slow-progressive cerebellar ataxia

“…In particular, Olivito and colleagues (2017) showed a specific pattern of WM microstructural damage resulting in a cerebrocerebellar dysregulation associated with the neurodegenerative processes of spinocerebellar ataxia (SCA), while Friedreich ataxia patients showed a significant reduction in the number of streamlines of cerebro-cerebellar tracts, which led to secondary effects in other cortical areas, such as the supplementary motor area, cingulate and frontal cortex, and subcortical nuclei (Zalesky et al, 2014). Fractional Anisotropy (FA) and Mean Diffusivity (MD) maps, derived from diffusion tensor imaging (DTI), also demonstrated the degeneration of the cerebro-cerebellar loop by revealing microstructural abnormalities comparable to those found by neuropathology in SCA7 (Parker et al, 2021), and monitoring ataxia severity through alterations of the cortico-ponto-cerebellar pathway in adult-onset ataxic neurodegenerative patients (Kitamura et al, 2008). Furthermore, disruption of WM integrity in ataxic patients with respect to HC may be used to monitor the progression of pathology since these microstructural changes strongly correlated with clinical severity of one of the most frequent inherited cerebellar ataxias (Kang et al, 2014).…”