Abstract
ObjectiveWe aimed to investigate the association of the serum urate level with cortical thickness and white matter integrity in multiple system atrophy (MSA).MethodsWe recruited 75 MSA patients and 42 controls who underwent brain MRI and measured serum urate level at baseline. Using cortical thickness and tract‐based spatial statistics analyses, we investigated the correlation between serum urate levels and cortical thickness or diffusion tensor imaging (DTI) measures in controls and MSA patients. Interaction effects were analyzed to find different patterns of correlation according to sex and clinical subtype. We evaluated the relationship between serum urate levels, DTI measures, and total UMSARS score, using path analysis.ResultsSerum urate levels showed a positive correlation with FA values in the corpus callosum and a negative correlation with MD values in widespread regions including cerebellar, brainstem, and cerebral white matter in patients with MSA. Both sexes showed a negative correlation between serum urate levels and MD values without significant interaction effect. In subgroup analysis according to subtype, patients with cerebellar subtype showed a negative correlation. Serum urate levels did not correlated with cortical thickness. Path analysis showed that MD values in middle and inferior cerebellar peduncle mediated the association between serum urate level and total UMSAR score.InterpretationThe present study demonstrated that serum urate levels played a pivotal role in white matter disintegrity and clinical disability in MSA. It would provide an evidence of the role of urate as a potential neuroprotective factor against white matter neurodegeneration in MSA.
Highlights
multiple system atrophy (MSA) is an adult-onset and sporadic neurodegenerative disease that manifests as progressive autonomic failure, parkinsonism, cerebellar syndrome, and pyramidal features in various combinations.[1]
In the present study, using the analyses of cortical thickness and track-based spatial statistics (TBSS), we explored the relationship between serum urate levels and cortical thickness or quantitative white matter metrics such as fractional anisotropy (FA) and mean diffusivity (MD) in patients with MSA
In patients with MSA-P, serum urate levels showed no correlation with FA and MD values or cortical thickness (Fig. 3B)
Summary
MSA is an adult-onset and sporadic neurodegenerative disease that manifests as progressive autonomic failure, parkinsonism, cerebellar syndrome, and pyramidal features in various combinations.[1]. MSA is a relentlessly progressive disease with median disease duration of 7.5 years from the onset of symptoms to death.[2]. Despite extensive research and clinical trials, disease-modifying candidates except stem cell therapy are not available.[3]. White matter alterations in supratentorial and infratentorial areas were extensively detected in patients with MSA, suggesting prominent dysfunction of myelin connecting multiple brain systems throughout the cerebral regions.[5–7]. A natural antioxidant, has been reported to have an association with the risk and progression of neurodegenerative diseases.[8]. A meta-analysis reported that low serum urate levels were associated with an increased risk of MSA.[9,10]. Patients with MSA having high serum urate a 2020 The Authors.
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