Extensive White Matter Alterations and Its Correlations with Ataxia Severity in SCA 2 Patients

Abstract

Background: Previous studies of SCA2 have revealed significant degeneration of white matter tracts in cerebellar and cerebral regions. The motor deficit in these patients may be attributable to the degradation of projection fibers associated with the underlying neurodegenerative process. However, this relationship remains unclear. Statistical analysis of diffusion tensor imaging enables an unbiased whole-brain quantitative comparison of the diffusion proprieties of white matter tracts in vivo.

Methods: Fourteen genetically confirmed SCA2 patients and aged-matched healthy controls participated in the study. Tract-based spatial statistics were performed to analyze structural white matter damage using two different measurements: fractional anisotropy (FA) and mean diffusivity (MD). Significant diffusion differences were correlated with the patient's ataxia impairment.

Results: Our analysis revealed decreased FA mainly in the inferior/middle/superior cerebellar peduncles, the bilateral posterior limb of the internal capsule and the bilateral superior corona radiata. Increases in MD were found mainly in cerebellar white matter, medial lemniscus, and middle cerebellar peduncle, among other regions. Clinical impairment measured with the SARA score correlated with FA in superior parietal white matter and bilateral anterior corona radiata. Correlations with MD were found in cerebellar white matter and the middle cerebellar peduncle.

Conclusion: Our findings show significant correlations between diffusion measurements in key areas affected in SCA2 and measures of motor impairment, suggesting a disruption of information flow between motor and sensory-integration areas. These findings result in a more comprehensive view of the clinical impact of the white matter degeneration in SCA2.

Fig 1. TBSS significant differences in diffusion measurements between SCA2 and healthy controls.

a) Fractional anisotropy. b)Mean diffusivity. Warm and cold colors indicate an increase and decrease of these measures in the patients with SCA2, respectively.

Fig 2. Significant correlations between abnormal diffusivity measurements and SARA scores.

a) Fractional anisotropy. b) Mean diffusivity. For r and p values see Table 1. LSPG = left superior parietal gyrus; LSCR = left superior corona radiata; RML = right medial lemniscus; RMOFG = right medial orbitofrontal gyrus; RMSFG = right medial superior frontal gyrus; RSCR = right superior corona radiata; LCIV = left cerebellum lobule IV; PCT = Pontine crossing tract; RCST = right corticospinal tract; MCP = middle cerebellar peduncle; RCIV = right cerebellum lobule IV; RCCII = right cerebellum crus II.