Evaluation of oxidative and nitrosative stress in relapsing remitting multiple sclerosis

Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Several lines of evidence support a role for oxidative and nitrative stress (OS and NS) in pathogenesis of multiple sclerosis. The mechanism of influence of OS and NS on blood-brainbarrier (BBB) has critical importance for evaluating antioxidant therapies. As far as we know, markers of oxidative and nitrative stress in MS patients have been investigated independently for their relationship with the state of the blood-brain-barrier. Blood plasma samples of 58 patients with relapse-remitting MS (RRMS) with normal (Group A, n = 48, 36.2 ± 10.5 years) and damaged BBB (Group B, n = 10, 38.2 ± 11.2 years) and of 44 healthy controls (39.2 ± 14.9 years) were analyzed. TAS (total antioxidant plasma status), lipoperoxides, protein carbonyls, 3-nitrotyrosine and uric acid were evaluated in each group. Our results confirmed decreased TAS (Group A: 1.35 ± 0.55 mmol/l, P e level of lipoperoxidation positively correlated with the state of BBB (P of protein’s carbonyls (A: 0.48 ± 0.11 nmol/mg protein, P nmol/l, P ed damage to plasma proteins, what was confirmed by their positive mutual correlation (P The level of uric acid was physiological and correlated negatively with protein’s carbonyls (P 0.05) while there was no significant relationship with 3-nitotyrosine. The results suggest the role of this antioxidant in the protection of the proteins against OS what was confirmed by its positive correlation with TAS

Sequencing of high-efficacy disease-modifying therapies in multiple sclerosis： perspectives and approaches

Multiple sclerosis（MS） is characterized by chronic inflammation in conjunction with neurodegeneration within the central nervous system. Most individuals with MS begin with a relapsing remitting course that later transitions to secondary progressive MS. Currently available disease-modifying therapies（DMTs） for relapsing MS have been demonstrated to reduce disease activity, however most patients require a change in therapy over the course of their disease. Treatment goals include the prevention of relapses and disability accumulation and to achieve this objective requires careful planning. Sequencing of DMTs for individual patients should be designed in such a way to maximize disease control and minimize risk based on the mechanism of action, pharmacokinetic and pharmacodynamic properties of each therapy. This includes the DMT patients are being switched from to those they are being switched to. The reversibility of immune system effects should be a key consideration for DMT sequence selection. This feature varies across DMTs and should factor more prominently in decision making as newer treatments become available for the prevention of disability accumulation in patients with progressive MS. In this short review, we discuss the landscape of existing therapies with an eye to the future when planning for optimal DMT sequencing. While no cure exists for MS, efforts are being directed toward research in neuroregeneration with the hope for positive outcomes.

Altered birefringence of peripapillary retinal nerve fiber layer in multiple sclerosis measured by polarization sensitive optical coherence tomography

Background:The retina has been used to study the pathophysiology of multiple sclerosis(MS).Peripapillary retinal nerve fiber layer(pRNFL)thinning has been suggested as an ocular biomarker of neurodegeneration in MS.The goal of this project was to determine the birefringence of the pRNFL by measuring the fiber birefringence using polarization sensitive optical coherence tomography(PS-OCT).Methods:Sixty-six MS patients without history of optic neuritis(age:39.9±11.0 yrs.old,53 females and 13 males)and 66 age-and gender-matched normal controls(age:40.7±11.4 yrs.old)were recruited.Custom built PS-OCT was used to measure phase retardation per unit depth(PR/UD,proportional to the birefringence)and pRNFL thickness in each quadrant of the pRNFL.In addition,clinical manifestation was used to correlate with the pRNFL birefringence.Results:The pRNFL was thinner in the temporal and inferior quadrants in MS patients compared with normal controls(P<0.05).The PR/UD of the pRNFL was significantly decreased in MS patients(P<0.05)in all quadrants except for the nasal quadrant.In both groups,the PR/UD from all four quadrants was not related to the averaged pRNFL thickness(P>0.05).In MS patients,the PR/UD was not related to the expanded disability status scale(EDSS)nor disease duration(r ranged from−0.17 to 0.02,P>0.05).Conclusion:This is the first study using PS-OCT to study the pRNFL birefringence in MS patients.Decreased birefringence of the pRNFL may indicate microtubule abnormality,and could be a potential biomarker for detecting early neurodegeneration in MS.