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

Serum matrix metalloproteinase 3 in detecting remitting seronegative symmetrical synovitis with pitting edema syndrome: A case report

We report a case of remitting seronegative symmetrical synovitis with pitting edema(RS3 PE) syndrome in a 71-year-old woman. She referred to our hospital with finger stiffness, edema of both hands and feet, pain of bilateral shoulder, wrist, metacarpophalangeal, proximal interphalangeal, and ankle joints. Rheumatoid factor was negative, human leukocyte antigen-B7 antigen was positive. Moreover, matrix metalloproteinase 3(MMP-3) was high. She was diagnosed with RS3 PE syndrome, and treatment with prednisolone(15 mg/d) was started. One week after prednisolone treatment initiation, CRP decreased to negative, and joint pain was almost completely resolved. However, hand stiffness persisted, and MMP-3 level was still high. Thus, prednisolone dose was increased to 20 mg/d, and the stiffness resolved. Twenty days after treatment initiation, MMP-3 was normalized. MMP-3 was more indicative of RS3 PE syndrome symptoms than CRP. Thus, MMP-3 seems to be more sensitive to RS3 PE syndrome symptoms.

Relationship between MRI pertusion and clinical severity in multiple sclerosis

Perfusion alterations within several brain regions have been shown in multiple sclerosis patients using different magnetic resonance imaging(MRI)techniques.Furthermore,MRI-derived brain perfusion metrics have been investigated in association with multiple sclerosis phenotypes,physical disability,and cognitive impairment.However,a review focused on these aspects is still missing.Our aim was to review all the studies investigating the relationship between perfusion MRI and clinical severity during the last fifteen years to understand the clinical relevance of these findings.Perfusion differences among phenotypes were observed both with 1.5T and 3T scanners,with progressive multiple sclerosis presenting with lower perfusion values than relapsing-remitting multiple sclerosis patients.However,only 3T scanners showed a statistically significant distinction.Controversial results about the association between MRI-derived perfusion metrics and physical disability scores were found.However,the majority of the studies showed that lower brain perfusion and longer transit time are associated with more severe physical disability and worse cognitive performances.

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.

Altered functional connectivity networks of hippocampal subregions in remitted late-onset depression:a longitudinal resting-state study

The regional specifi city of hippocampal abnormalities in late-life depression（LLD） has been demonstrated in previous studies. In this study,we sought to examine the functional connectivity（FC） patterns of hippocampal subregions in remitted late-onset depression（r LOD）,a special subtype of LLD. Fourteen r LOD patients and 18 healthy controls underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging scans at baseline and at ~21 months of follow-up. Each hippocampus was divided into three parts,the cornu ammonis（CA）,the dentate gyrus,and the subicular complex,and then six seed-based hippocampal subregional networks were established.Longitudinal changes of the six networks over time were directly compared between the rL OD and control groups. From baseline to follow-up,the r LOD group showed a greater decline in connectivity of the left CA to the bilateral posterior cingulate cortex/precuneus（PCC/PCUN）,but showed increased connectivity of the right hippocampal subregional networks with the frontal cortex（bilateral medial prefrontal cortex/anterior cingulate cortex and supplementary motor area）. Further correlative analyses revealed thatthe longitudinal changes in FC between the left CA and PCC/PCUN were positively correlated with longitudinal changes in the Symbol Digit Modalities Test（r = 0.624,P = 0.017） and the Digit Span Test（r = 0.545,P = 0.044） scores in the r LOD group. These results may provide insights into the neurobiological mechanism underlying the cognitive dysfunction in r LOD patients.