Abstract
Multiple system atrophy (MSA) is an adult-onset, sporadic neurodegenerative disease. Because the prognosis of MSA is fatal, neuroprotective or regenerative strategies may be invaluable in MSA treatment. Previously, we obtained clinical and imaging evidence that mesenchymal stem cell (MSC) treatment could have a neuroprotective role in MSA patients. In the present study, we evaluated the effects of MSC therapy on longitudinal changes in subcortical deep gray matter volumes and cortical thickness and their association with cognitive performance. Clinical and imaging data were obtained from our previous randomized trial of autologous MSC in MSA patients. During 1-year follow-up, we assessed longitudinal differences in automatic segmentation-based subcortical deep gray matter volumes and vertex-wise cortical thickness between placebo (n = 15) and MSC groups (n = 11). Next, we performed correlation analysis between the changes in cortical thickness and changes in the Korean version of the Montreal Cognitive Assessment (MoCA) scores and cognitive performance of each cognitive subdomain using a multiple, comparison correction. There were no significant differences in age at baseline, age at disease onset, gender ratio, disease duration, clinical severity, MoCA score, or education level between the groups. The automated subcortical volumetric analysis revealed that the changes in subcortical deep gray matter volumes of the caudate, putamen, and thalamus did not differ significantly between the groups. The areas of cortical thinning over time in the placebo group were more extensive, including the frontal, temporal, and parietal areas, whereas these areas in the MSC group were less extensive. Correlation analysis indicated that declines in MoCA scores and phonemic fluency during the follow-up period were significantly correlated with cortical thinning of the frontal and posterior temporal areas and anterior temporal areas in MSA patients, respectively. In contrast, no significant correlations were observed in the MSC group. These results suggest that MSC treatment in patients with MSA may modulate cortical thinning over time and related cognitive performance, inferring a future therapeutic candidate for cognitive disorders.
Highlights
Multiple system atrophy (MSA) is a sporadic neurodegenerative disease characterized by α-synuclein-positive glial cytoplasmic inclusions (GCIs) with widespread neuronal loss in the basal ganglia, brainstem, cerebellum, and spinal cord
We evaluated the effects of mesenchymal stem cell (MSC) therapy on longitudinal changes in subcortical deep gray matter volumes and cortical thickness and their association with cognitive performance to elucidate whether MSC could modulate pathological processes in the cerebral cortex of MSA patients
There were no significant differences in age at baseline, age at disease onset, gender ratio, disease duration, UMSARS score, Mini-Mental Status Examination (MMSE) score, Montreal Cognitive Assessment (MoCA) score, or education level between the groups
Summary
Multiple system atrophy (MSA) is a sporadic neurodegenerative disease characterized by α-synuclein-positive glial cytoplasmic inclusions (GCIs) with widespread neuronal loss in the basal ganglia, brainstem, cerebellum, and spinal cord. The cardinal features of MSA include autonomic dysfunction, parkinsonism, cerebellar ataxia, and pyramidal signs in any combination, with autonomic dysfunction being an integral component (Stefanova et al, 2009). Accumulating evidence suggests that along with cortical pathology involving frontal and temporal areas, cognitive function is more widely impaired in MSA than initially expected (Kawai et al, 2008; Chang et al, 2009). The precise etiology and pathomechanisms of MSA remain unknown, several mediators including neuroinflammation, oxidative insult, mitochondrial dysfunction, and alterations in the blood–brain barrier have been suggested to play important roles in progression of MSA pathology (Shults et al, 2005; Stefanova et al, 2005; Ubhi et al, 2009; Song et al, 2011b).
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