Callosal tissue loss in multiple system atrophy--a one-year follow-up study

Abstract

Multiple system atrophy (MSA) is a neurodegenerative disease not only affecting the basal ganglia, brainstem, cerebellum, and intermediolateral cell columns of the spinal cord but also the cerebral cortex. Clinically, cerebellar (MSA-C) and parkinsonian variants of MSA (MSA-P) are distinguished. We investigated 14 MSA patients (10 MSA-C, 4 MSA-P, men: 7, women: 7; age: 61.1 ± 3.3 years) and 14 matched controls (men: 7, women: 7; age: 58.6 ± 5.1 years) with voxel-based morphometry (VBM) to analyze gray and white matter differences both at baseline and at follow-up, 1 year later. Baseline comparisons between patients and controls confirmed significantly less gray matter in MSA in the cerebellum and cerebral cortex, and significantly less white matter in the cerebellar peduncles and brainstem. Comparisons of tissue-loss profiles (i.e., baseline versus follow-up) between patients and controls, revealed white matter reduction in MSA along the middle cerebellar peduncles, reflecting degeneration of the ponto-cerebellar tract as a particularly prominent and progressive morphological alteration in MSA. Comparisons between baseline and follow-up, separately performed in patients and controls, revealed additional white matter reduction in MSA along the corpus callosum at follow-up. This was replicated through additional shape-based analyses indicating a reduced callosal thickness in the anterior and posterior midbody, extending posteriorly into the isthmus. Callosal atrophy may possibly reflect a disease-specific pattern of neurodegeneration and cortical atrophy, fitting well with the predominant impairment of motor functions in the MSA patients.

Figure 1. Differences in callosal thickness

The two top panels illustrate the decreased callosal thickness in MSA patients compared to controls at baseline (panel A) and at follow-up (panel B). The two bottom panels illustrate the decreased callosal thickness at follow-up compared to baseline in MSA patients (panel C) and in controls (panel D). Group and time effects are color-coded and projected onto the average callosal surface map. Spectral colors indicate uncorrected significance (large callosal maps); red indicates FDR-corrected significance (small callosal maps).