No evidence of increased oxidative degradation of urate to allantoin in the CSF and serum of patients with multiple sclerosis

Abstract

Sirs: Recent studies have reported an association of low serum levels of the natural antioxidant urate and multiple sclerosis (MS). First, it was shown that MS patients have lower serum levels of urate than controls [3, 6–8] (though there were no significant differences in other studies [1, 4]); second, hyperuricemia (gout) and MS were found to be mutually exclusive [3]; third, serum urate levels correlated negatively with the duration of MS and its severity [1, 8] (but there were no such correlations in another study [6]). Furthermore, a therapeutic effect of urate was observed in the rodent model of MS, experimental allergic encephalomyelitis (EAE) [2, 3]. To date, the interpretation of decreased urate blood levels in MS patients is not clear. Two current explanations are that lower urate blood concentrations predispose to MS or that they are secondary to oxidative degradation of urate [3]. However, its oxidation product allantoin has not so far been measured in MS patients. Accordingly, we determined the concentrations of urate and allantoin in the CSF and serum of MS and control patients. The samples were obtained for diagnostic purposes after obtaining informed consent. All MS patients (n = 70) met the current “McDonald” diagnostic criteria. Forty-four patients had a relapsing-remitting disease course (RRMS). Thirty-six of them had an acute exacerbation and 8 were in remission when the samples were obtained. In 25 of the RRMS patients, cranial MRI was performed at the time of sample collection, gadolinium-enhancing lesions being detected in 18 cases. Twelve patients had a secondary (SPMS) and 14 a primary progressive (PPMS) disease course. Control patients (n = 24) were diagnosed, after extensive diagnostic study, with migraine (12), tension-type headache (7), transient ischemic attack (2), cyclosporine intoxication (1), cervical disc herniation (1), and normal pressure hydrocephalus (1). None of the MS patients or controls had received any immunomodulatory therapy during 6 months prior to the collection of the samples. Urate and allantoin were measured by high pressure liquid chromatography (HPLC) as previously described [5]. Continuous variables were compared by t-test or one-way ANOVA for multiple comparisons. Gender distribution was compared by Fisher’s exact test. Only two-sided tests were used and p < 0.05 was considered significant. When controls and all MS patients were compared, CSF and serum levels of urate or allantoin and allantoin/urate ratios in CSF or serum did not differ significantly (data not shown). When controls, RRMS, SPMS, and PPMS patients were compared with each other (Table) and when RRMS patients with an acute exacerbation and in remission or with and without enhancing lesions on MRI were compared (data not shown), the before-mentioned parameters did not differ either. Our finding of similar serum urate levels in MS patients and controls is in agreement with some previous reports [1, 4], but stands in contrast to others [3, 6–8]. Differences in the MS patient (e. g., course or severity of disease) or control groups (heterogeneous cohorts of patients with other neurological diseases) may perhaps account for the discrepant results. More importantly, in our sample of MS patients we did not detect raised allantoin levels in the CSF or serum. Thus, we could not find any evidence supporting an increased oxidative degradation of urate during MS. LETTER TO THE EDITORS