Evidence of axonal damage in cerebellar peduncles without T2-lesions in multiple sclerosis

Abstract

Background and aim: Cerebellar peduncles (CP) can be probed by diffusion tensor imaging (DTI) to evaluate the integrity of cerebellar afferent and efferent networks. Damage to the CP in multiple sclerosis (MS) could lead to serious cognitive and mobility impairment. The aim of this study was to investigate the extent and the clinical impact of CP damage in MS.

Methods: Sixty-eight MS patients were included in this study along with 27 healthy controls (HC) and underwent an MRI on a 1.5T including T1, T2, FLAIR and DTI. Using DTI, the microstructural integrity within the CP regions (superior (SCP), inferior (ICP) and middle (MCP)) was probed while controlling for focal T2-lesions presence or absence. A general linear model was performed to test for associations between clinical scores and DTI metrics for each CP.

Results: Significantly decreased fractional anisotropy (FA) and increased radial diffusivity (RD) were found in the CP of all MS patients compared to those of HC, but to a lesser extent in non-lesioned CP than those with lesions. Axial diffusivity (AD) was significantly and similarly increased in both non-lesioned and lesioned CP, but only in the SCP and ICP. Expanded disability status scale (EDSS) significantly correlated with MCP's FA (p < 0.05) and RD (p < 0.05), while MS functional composite (MSFC) significantly correlated with SCP's FA (p < 0.01) and RD (p < 0.01).

Conclusion: The diffusion changes (FA and RD) measured in lesioned CP are probably directly related to the presence of inflammatory and/or demyelinating lesions. In contrast, the microstructural alterations reflected by AD increase in non-lesioned CP may result either from remote effects of cerebral white matter injury (diaschisis) or primary axonal degeneration, that are associated with cognitive, sensory and motor impairments of MS patients.

Keywords: Axial diffusivity (AD); Diffusion tensor imaging (DTI); Inferior cerebellar peduncles (ICP); Middle cerebellar peduncles (MCP); Multiple sclerosis (MS); Superior cerebellar peduncles (SCP).