Association between serum uric acid level and multiple system atrophy: A meta-analysis

Zhang, Xi; Li, Deshan; An, Chun-Yao; Liu, Yu‑Zhao; Liu, Xiaohong; Zhang, Fang; Ning, Lu‐Ning; Li, Changling; Ma, Chunmei; Hu, Ruiting

doi:10.1016/j.clineuro.2018.03.023

Cited by 8 publications

(13 citation statements)

References 22 publications

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“…In this study, we did not find elevation of oxidative albumin in MSA and PSP patients. However, these patients showed decreased serum UA levels compared with the controls, similar to previous reports . These results might indicate that systemic oxidative stress may be involved in the pathomechanisms of atypical parkinsonism but to a lesser extent than in iPD and PARK2.…”

Section: Discussionsupporting

confidence: 89%

“…However, these patients showed decreased serum UA levels compared with the controls, similar to previous reports. 37,38 These results might indicate that systemic oxidative stress may be involved in the pathomechanisms of atypical parkinsonism but to a lesser extent than in iPD and PARK2. Furthermore, these findings suggest that combining systemic oxidative stress markers, including % HNA and UA, might be useful for diagnosis and understanding the pathomechanisms of iPD, PARK2, and atypical parkinsonism.…”

Section: Discussionmentioning

confidence: 91%

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Nonmercaptalbumin as an oxidative stress marker in Parkinson’s and PARK2 disease

Ueno

Hatano

Okuzumi

et al. 2020

Ann Clin Transl Neurol

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Objective To investigate the oxidized albumin ratio, which is the redox ratio of human nonmercaptalbumin (HNA) to serum albumin (%HNA), as a biomarker in idiopathic Parkinson’s disease (iPD) and related neurodegenerative disorders. Methods This prospective study enrolled 216 iPD patients, 15 patients with autosomal recessive familial PD due to parkin mutations (PARK2), 30 multiple system atrophy (MSA) patients, 32 progressive nuclear palsy (PSP) patients, and 143 healthy controls. HNA was analyzed using modified high‐performance liquid chromatography and was evaluated alongside other parameters. Results iPD and PARK2 patients had a higher %HNA than controls (iPD vs. controls: odds ratio (OR) 1.325, P < 0.001; PARK2 vs. controls: OR 1.712, P < 0.001). Even iPD patients at an early Hoehn & Yahr stage (I and II) showed a higher %HNA than controls. iPD patients had a higher %HNA than MSA and PSP patients (iPD vs. MSA: OR 1.249, P < 0.001, iPD vs. PSP: OR 1.288, P < 0.05). When discriminating iPD patients from controls, %HNA corrected by age achieved an AUC of 0.750; when discriminating iPD patients from MSA and PSP patients, an AUC of 0.747 was achieved. Furthermore, uric acid, an antioxidant compound, was decreased in iPD patients, similar to the change in %HNA. Interpretation %HNA was significantly increased in iPD and PARK2 patients compared with controls, regardless of disease course and severity. Oxidative stress might be increased from the early stages of iPD and PARK2 and play an important role in their pathomechanisms.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 91%

Nonmercaptalbumin as an oxidative stress marker in Parkinson’s and PARK2 disease

Ueno

Hatano

Okuzumi

et al. 2020

Ann Clin Transl Neurol

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“…33 Similarly, modulatory effect of urate on the risk and disease progression in MSA has been observed in male patients. 9,10 However, in this study, the association between serum urate levels and white matter disintegrity was observed in both male and female without significant urate by sex interaction, in spite of difference in the mean serum urate levels between sexes. These results imply that urate may be protective against white matter degeneration in MSA patients irrespective of sex.…”

Section: Discussioncontrasting

confidence: 69%

“…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 levels had slower disease progression than those with lower levels. 11 Although the role of serum urate in the pathogenesis of MSA and its causality are currently unknown, these studies suggest that urate may have a close link to neurodegeneration in MSA, probably via antioxidant effect.…”

Section: Introductionmentioning

confidence: 99%

Urate is closely linked to white matter integrity in multiple system atrophy

Yoo

Chung

Lee

et al. 2020

Ann Clin Transl Neurol

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Objective: We aimed to investigate the association of the serum urate level with cortical thickness and white matter integrity in multiple system atrophy (MSA). Methods: We 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. Results: Serum 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. Interpretation: The 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.

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“…As oxidative stress is increased in MSA and associated with cognitive deterioration, antioxidants might have a beneficial effect on disease progression. Indeed, elevation of uric acid in serum levels positively correlates with motor and cognitive functions in PD and MSA [139][140][141]. Thus, treatment with the antioxidant and uric acid prodrug inosine 5 -monophosphate may be a possible treatment strategy.…”

Section: Targeting Neuronal Lossmentioning

confidence: 99%

Current Symptomatic and Disease-Modifying Treatments in Multiple System Atrophy

Mészáros

Hoffmann

Wihan

et al. 2020

IJMS

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Multiple system atrophy (MSA) is a rare, severe, and rapidly progressive neurodegenerative disorder categorized as an atypical parkinsonian syndrome. With a mean life expectancy of 6–9 years after diagnosis, MSA is clinically characterized by parkinsonism, cerebellar ataxia, autonomic failure, and poor l-Dopa responsiveness. Aside from limited symptomatic treatment, there is currently no disease-modifying therapy available. Consequently, distinct pharmacological targets have been explored and investigated in clinical studies based on MSA-related symptoms and pathomechanisms. Parkinsonism, cerebellar ataxia, and autonomic failure are the most important symptoms targeted by symptomatic treatments in current clinical trials. The most prominent pathological hallmark is oligodendroglial cytoplasmic inclusions containing alpha-synuclein, thus classifying MSA as synucleinopathy. Additionally, myelin and neuronal loss accompanied by micro- and astrogliosis are further distinctive features of MSA-related neuropathology present in numerous brain regions. Besides summarizing current symptomatic treatment strategies in MSA, this review critically reflects upon potential cellular targets and disease-modifying approaches for MSA such as (I) targeting α-syn pathology, (II) intervening neuroinflammation, and (III) neuronal loss. Although these single compound trials are aiming to interfere with distinct pathogenetic steps in MSA, a combined approach may be necessary to slow down the rapid progression of the oligodendroglial associated synucleinopathy.

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Association between serum uric acid level and multiple system atrophy: A meta-analysis

Cited by 8 publications

References 22 publications

Nonmercaptalbumin as an oxidative stress marker in Parkinson’s and PARK2 disease

Nonmercaptalbumin as an oxidative stress marker in Parkinson’s and PARK2 disease

Urate is closely linked to white matter integrity in multiple system atrophy

Current Symptomatic and Disease-Modifying Treatments in Multiple System Atrophy

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