Urate Oxidation in CSF and Blood of Patients with Inflammatory Disorders of the Nervous System

Bf, Becker; Kastenbauer, Stefan; Ködel, Uwe; Kiesl, David; Hw, Pfister

doi:10.1081/ncn-200027469

Cited by 15 publications

(14 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, Becker et al found normal UA concentrations in blood and CSF of 18 patients with MS (33). In a recent study by Zamani et al (29), CSF and serum UA concentrations were measured in 12 patients with MS and 10 controls.…”

Section: Discussionmentioning

confidence: 98%

Cerebrospinal fluid and serum uric acid levels in patients with multiple sclerosis

Dujmović¹,

Gazibara²,

Obrenović³

et al. 2009

Clinical Chemistry and Laboratory Medicine

View full text Add to dashboard Cite

Background: Peroxynitrite was hypothesized to be involved in the pathogenesis of multiple sclerosis (MS) through its various neurotoxic effects. Uric acid (UA) was shown to be a strong peroxynitrite scavenger. Methods: We analyzed cerebrospinal fluid (CSF) and serum UA concentrations in 30 MS patients and 20 controls with non-inflammatory neurological diseases (NIND) and correlated these findings with demographic and clinical characteristics of MS patients. Disease activity was assessed by brain magnetic resonance imaging (MRI) and the CSF/serum albumin quotient as an indicator of the state of blood-brainbarrier (BBB). Results: Serum UA concentrations were found to be significantly lower in MS patients compared with controls (ps0.019). CSF UA concentrations were lower in MS patients as compared to controls, as well as in patients with active MS (clinical and/or MRI activity) in comparison to patients with inactive MS or controls, but these differences were not statistically significant. Significant correlation was found between CSF and serum UA concentrations (ps0.016) in MS patients, but not in controls; and between CSF UA concentrations and the CSF/serum albumin quotient in MS patients (ps0.043), but not in controls. Conclusions: Our results support the significance of UA in the pathogenesis of MS. Decreased serum UA concentrations in MS patients might be due to both intrinsically reduced antioxidant capacity and increased UA consumption in MS. CSF UA concentrations may not be a reliable marker of disease activity in MS since its concentration is dependent on leakage

show abstract

Section: Discussionmentioning

confidence: 98%

Cerebrospinal fluid and serum uric acid levels in patients with multiple sclerosis

Dujmović¹,

Gazibara²,

Obrenović³

et al. 2009

Clinical Chemistry and Laboratory Medicine

View full text Add to dashboard Cite

show abstract

“…[8]–[27] Furthermore, most of these studies [12], [16], [18]–[22], [25], [27] were conducted on small cohorts of MS patients and did not control urate levels for significant determinants of serum urate, particularly for renal function. Only one study [15] evaluated serum urate concentrations at the earliest stage of MS (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…In the last ten years several studies evaluated serum urate levels in patients with MS, reporting conflicting results; [8]–[27] some case-control studies found lower, [8]–[15] but others reported higher [16]–[18] serum urate levels in MS patients than in neurological [16], [19], [20] and healthy controls [10], [16]–[19]; finally, other studies found no difference between the MS and neurological, [21], [22] and healthy controls. [23]–[27] A recent metanalysis was in favour of lower serum urate levels in MS than in healthy subjects and neurological controls [28] Furthermore, in a recent clinical trial, the combination of interferon beta and inosine was safe and well tolerated but did not provide any additional benefit on accumulation of disability compared with interferon beta alone.…”

Section: Introductionmentioning

confidence: 99%

Low Serum Urate Levels Are Associated to Female Gender in Multiple Sclerosis Patients

et al. 2012

View full text Add to dashboard Cite

BackgroundUrate is a natural antioxidant and may prevent CNS tissue damage and the clinical manifestations of experimental autoimmune encephalitis. Results from clinical studies are conflicting and the contribution of urate to the pathogenesis of Multiple Sclerosis (MS) remains uncertain.ObjectiveTo evaluate serum urate levels in MS patients and their relationships with clinical, demographic and MRI variables.MethodsLevels of non-fasting serum uric acid and creatinine were determined by an automated enzymatic assay and glomerular filtration rate was assessed in 245 MS patients, in 252 age/sex-matched neurological controls (NC) and in 59 Healthy controls (HC).ResultsMedian serum urate levels did not differ between MS patients (3.8 mg/dL), HC (4.0 mg/dl) and NC (4.0 mg/dL). Serum urate levels were lower in females than in males in all groups (p = <0.0001). In female-MS, serum urate levels (3.2 mg/dL) were lower compared to those in female HC (3.8; p = 0.01) and NC (3.5 mg/dL; p = 0.02), whereas in male-MS they(4.8 mg/dL) did not differ from those in male HC (4.5 mg/dl) and NC (4.8 mg/dL). Urate concentrations trended to be lower in Clinically isolated syndromes suggestive of MS (3.7 mg/dL) and in relapsing MS (3.7 mg/dL), compared to patients with progressive MS (4.4 mg/dL; p = 0.06), and in patients with an annual relapse rate (ARR) >2 (3.3 mg/dL) than in those with an ARR ≤2: 3.9 mg/dL; p = 0.05). Significant lower serum urate levels were found in females than in males in all clinical MS subtypes (p<0.01), separately evaluated. Female sex (beta: −0.53; p<0.00001) was the most significant determinant of serum urate concentrations in MS patients on multivariate regression analysis.ConclusionsOur findings suggest that low urate levels could be of significance in predominantly inflammatory phases of MS even at the early stage and mainly in females.

show abstract

“…Levels of serum urate are closely correlated with levels of urate in the cerebrospinal fluid (CSF) and CSF urate is typically 10% of peripheral levels. This suggests that CSF levels of urate are in part dependent on serum uric acid levels [7]. It has been suggested that uric acid may have neuroprotective influence as a scavenger of reactive nitrogen and oxygen radicals.…”

Section: Introductionmentioning

confidence: 99%

Clinical associations between gout and multiple sclerosis, Parkinson’s disease and motor neuron disease: record-linkage studies

et al. 2015

View full text Add to dashboard Cite

BackgroundUric acid has antioxidant effects on neurons. Abnormally high levels of uric acid are, however, associated with gout. Previous studies have suggested that high levels of uric acid (and the presence of gout) may exert a protective effect against the risk of developing some neurological diseases. We aimed to investigate this hypothesis in a large database of hospital admissions in England.MethodsWe analysed a database of linked statistical records of hospital admissions and death registrations in England (1999–2012). A cohort of people with gout was constructed and followed for development of multiple sclerosis (MS), Parkinson’s disease (PD) or motor neuron disease (MND). Then, conversely, cohorts of all people in the database with MS, PD or MND were constructed and followed for subsequent gout. Rate ratios (RRs) were determined, comparing these cohorts with people in a reference cohort.ResultsIn the gout cohort, we observed a modest elevation of the overall risk of subsequent MS, PD and MND (respectively, RR = 1.27 (95% confidence interval 1.03-1.55), 1.11 (1.05-1.17) and 1.28 (1.11-1.48) which was largely attributable to an increased risk observed in the early years after hospitalisation for gout. The increased risk of neurological disease did not remain after 5 years. In the cohorts of people with MS or PD, there was a significantly reduced risk of subsequent gout admission (RR = 0.79 (0.69-0.89) and 0.83 (0.79-0.87), respectively). This inverse association was sustained over time. There was also a reduced risk of MND following gout which only emerged more than five years following initial gout admission (RR at 5+ years 0.35 (0.15-0.68)).ConclusionsThis study investigated the epidemiological evidence for a protective role of high serum concentration of uric acid, for which we used gout as a proxy, in the aetiology of MS, PD or MND. Our observations do not support this hypothesis. However, when the order was reversed, and we retrospectively followed up patients with MS, PD and MND for a number of years, we found a statistically significant deficit of gout. This suggests that there is relationship between some aspects of these neurodegenerative diseases and metabolism of uric acid.

show abstract

Urate Oxidation in CSF and Blood of Patients with Inflammatory Disorders of the Nervous System

Cited by 15 publications

References 5 publications

Cerebrospinal fluid and serum uric acid levels in patients with multiple sclerosis

Cerebrospinal fluid and serum uric acid levels in patients with multiple sclerosis

Low Serum Urate Levels Are Associated to Female Gender in Multiple Sclerosis Patients

Clinical associations between gout and multiple sclerosis, Parkinson’s disease and motor neuron disease: record-linkage studies

Contact Info

Product

Resources

About