Objective: Correlate clinical measures of ataxia and spasticity in a SCA7 cohort with the pattern and severity of atrophy of grey matter (GM) and white matter (WM) structures as quantified by structural imaging metrics.

Background: SCA7 is a neurodegenerative disease characterized by progressive cerebellar ataxia, retinal degeneration, ophthalmoplegia, and spasticity[1]. Postmortem analysis reveals widespread atrophy of the brain stem and cerebellum[1], but our understanding of the evolution of this pathology is limited. Methods that quantify differences in brain structure such as voxel-based morphometry[2] (VBM) and diffusion tensor imaging (DTI) tractography[3] may be used to assess these neurodegenerative changes in vivo and correlate them with clinical measures as the disease progresses. Spasticity is also poorly understood. Correlating structural changes with an index of spasticity can provide useful pathophysiologic insights.

Methods: Appendicular ataxia was measured using the 9-hole pegboard test and a keyboard dexterity test, axial ataxia was assessed using the Timed Up and Go test, and both types were quantified using the SARA scale[4]. Spasticity was quantified using the vibration inhibition index (VII), which is a measure of H reflex suppression due to vibration. VBM was used to localize and quantify Cerebral and Cerebellar GM volumes. DTI tractography was used to determine fractional anisotropy (FA) in various descending motor and cerebellar tracts. Imaging was performed in controls for comparison. A correlation analysis was conducted between the clinical measures of axial/appendicular ataxia and spasticity and structural imaging metrics calculated from VBM and DTI tractography.

Results: Atrophy of the Flocculonodular lobe correlated with axial ataxia while atrophy of the lateral cerebellar hemispheres (notably Crus II) correlated with appendicular ataxia. Measures of ataxia and spasticity correlated with the FA of various descending WM tracts, including the corticospinal, reticulospinal, vestibulospinal, and cerebellofugal tracts.

Conclusions: This study provides insight into the evolution of SCA7 pathology by correlating clinical characteristics with structural imaging metrics. To our knowledge, this is the first investigation correlating a physiological index of spasticity with pathways implicated in its pathophysiology.

References: 1. Horton, L.C., et al., Spinocerebellar ataxia type 7: clinical course, phenotype-genotype correlations, and neuropathology. Cerebellum, 2013. 12(2): p. 176-93. 2. Ashburner, J. and K.J. Friston, Voxel-based morphometry–the methods. Neuroimage, 2000. 11(6 Pt 1): p. 805-21. 3. Basser, P.J., et al., In vivo fiber tractography using DT-MRI data. Magn Reson Med, 2000. 44(4): p. 625-32. 4. Schmitz-Hubsch, T., et al., Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology, 2006. 66(11): p. 1717-20.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pathophysiologic-insights-into-ataxia-and-spasticity-through-structural-imaging-of-a-spinocerebellar-ataxia-type-7-sca7-cohort/