Neurocognitive impairment in multiple sclerosis and its association with thiol-disulfide homeostasis and ischemia-modified albumin.

This study aimed to assess the possible association between cognitive impairment and two important biochemical biomarkers of oxidative stress, thiol-disulfide homeostasis (TDH), and ischemia-modified albumin (IMA) in patients with multiple sclerosis (MS). This study included 85 patients with MS (38 treatment-naïve relapsing-remitting MS (RRMS), 31 RRMS on fingolimod therapy, and 16 secondary progressive MS (SPMS)) and 33 healthy controls. Cognitive evaluation was carried out by applying the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) test battery and the scores were adjusted for age and years of education. Plasma TDH was assessed using an automated method and plasma IMA levels were determined using the cobalt-albumin binding assay. Plasma native thiol and total thiol levels were significantly decreased in patients with SPMS when compared with the naïve patients and healthy controls. Cognitive impairment was detected in 47.4% of naïve patients, 64.5% of patients on fingolimod therapy, and 80% of patients with SPMS. Naïve patients or patients on fingolimod therapy who were cognitively impaired had significantly decreased levels of native thiol and total thiol compared to the cognitively normal patients. Logistic regression analysis revealed total thiol and native thiol to be significantly associated with cognitive impairment in naïve patients and patients on fingolimod therapy. Significant correlations were determined between BICAMS scores, TDH, IMA, clinical indices of disease severity (EDSS and MSSS), and magnetic resonance imaging parameters. This study has shown for the first time that plasma TDH parameters are associated with cognitive impairment in MS.

Single nucleotide variants around the connective tissue growth factor (CTGF/CCN2) gene and their association with multiple sclerosis risk, disability scores, and rate of disease progression.

BACKGROUND: This study aimed to explore the possible association of single nucleotide polymorphisms (SNPs) in the upstream (rs9402373) and downstream regions (rs9399005 and rs12526196) of the gene encoding connective tissue growth factor (CTGF/CCN2) with relapsing-remitting multiple sclerosis (RRMS) risk and clinical parameters including disability scores and rate of disability progression. MATERIALS AND METHODS: In total, 200 patients with RRMS and 305 controls were genotyped using real-time PCR (rs1252696 C/T and rs9402373 G/C) or PCR-RFLP (rs9399005 C/T) methods. Furthermore, the association between these genotypes and clinical parameters including Expanded Disability Status Scale (EDSS) score, Multiple Sclerosis Severity Score (MSSS), age at onset, duration of disease, duration of treatment, and presence of contrast-enhancing lesions was analyzed. RESULTS: rs9399005 genotypes TT and CT in the dominant model were significant predictors of RRMS vs. control status by logistic regression analysis (OR = 1.45, 95% CI = 1.01-2.08, P = .04). Moreover, these genotypes for rs9399005 were associated with a MSSS ≥ 2.4 (OR = 3.54, 95% CI = 1.56-8.05, P = .003). In addition, MSSS was lower in patients who had at least one rs12526196C allele than in the corresponding patients with the TT genotype (P = .02). CONCLUSION: To our knowledge, this is the first evidence of the involvement of variants around the CTGF gene in MS risk and disability progression.