Natalizumab Treatment for Relapsing Multiple Sclerosis Stabilises Normal-Appearing White Matter Microstructure: A One-Year Prospective Ultra-High-Field Quantitative Imaging Study.

(1) Background: Natalizumab dramatically reduces relapses and MRI inflammatory activity (new lesions and enhancing lesions) in multiple sclerosis (MS). Chemical exchange saturation transfer (CEST) MRI can explore brain tissue in vivo with high resolution and sensitivity. We investigated if natalizumab can prevent microstructural tissue damage progression measured with MRI at ultra-high field (7 Tesla) over the first year of treatment. (2) Methods: In this one-year prospective longitudinal study, patients with active relapsing-remitting MS were assessed clinically and scanned at ultra-high-field MRI at the time of their first natalizumab infusion, at 6 and 12 months, with quantitative imaging aimed to detect microstructural changes in the normal-appearing white matter (NAWM), including sequences sensitive to magnetisation transfer (MT) effects from amide proton transfer (MTRAPT) and the nuclear Overhauser effect (MTRNOE). (3) Results: 12 patients were recruited, and 10 patients completed the study. The difference in the T1 relaxation times at month 6 and month 12 of natalizumab treatment was not significant, suggesting the lack of accumulation of tissue damage, while improvements were seen in MTR (MTRAPT and MTRNOE measures) at month 12, suggesting a tissue repair effect. This paralleled the expected lack of clinical and radiological worsening of conventional MRI measures of disease activity (new lesions or gadolinium-enhancing lesions). (4) Conclusion: Natalizumab prevents microstructural brain damage and has effects suggesting an improved white matter microstructure measured at ultra-high field during the first year of treatment.

Natalizumab Treatment of Relapsing Remitting Multiple Sclerosis Has No Long-Term Effects on the Proportion of Circulating Regulatory T Cells.

INTRODUCTION: Natalizumab (NTZ), a monoclonal antibody against the integrin α4ß1 (VLA-4) found on activated T cells and B cells, blocks the interaction of this integrin with adhesion molecules of central nervous system (CNS) endothelial cells and lymphocyte migration through the blood-brain barrier, effectively preventing new lesion formation and relapses in multiple sclerosis (MS). Whether NTZ treatment has additional effects on the peripheral immune system cells, and how its actions compare with other MS disease-modifying treatments, have not been extensively investigated. In particular, its effect on the proportions of circulating regulatory T cells (Treg) is unclear. METHODS: In this study, we investigated the effect of NTZ treatment in 12 patients with relapsing MS, at 6 and 12 months after the start of treatment. We evaluated the proportions of regulatory T cells (Treg), defined by flow cytometry as CD4+ CD25++ FoxP3+ cells and CD4+ CD25++ CD127- cells at these intervals. As an exploratory study, we also investigated the NTZ effects on the proportions of bulk T and B lymphocyte populations, and of those expressing novel the markers CD195 (CCR5), CD196 (CCR6), or CD161 (KLRB1), which are involved in MS pathogenesis but have been studied less in the context of MS treatment. The effects of NTZ were compared to those obtained with 11 patients under interferon-beta-1a (IFN-ß1a) treatment, and against 9 healthy volunteers. RESULTS: We observed a transient increment in the proportion of Treg cells at 6 months, which was not sustained at 12 months. We observed a reduction in the proportion of T cells expressing CD195 (CCR5) and CD161 (KLRB1) subsets of T cells. CONCLUSION: We conclude that NTZ does not have an effect on the proportion of Treg cells over 1 year, but it may affect the expression of molecules important for some aspects MS pathogenesis, in a manner that is not shared with IFN-ß1a.

Prevalence of a history of prior varicella/herpes zoster infection in multiple sclerosis.

Varicella zoster virus (VZV) infection has been implicated in multiple sclerosis (MS), but direct causal involvement has been disputed. Nevertheless, knowledge of VZV exposure is important, given the risk of serious complications of first exposure while undergoing immunosuppressive treatment, in particular with fingolimod. We distributed questionnaires to MS clinic patients, requesting information about history of chickenpox, sibling/household/occupational exposure, history of zoster (shingles), and disease-modifying treatment. A random, proportionally representative sample of 51 patients that included patients with positive, negative, and unknown chickenpox history were selected for determination of VZV IgG by ELISA. Of 1206 distributed questionnaires, 605 were returned (50% response rate). Of these, 86% reported history of chickenpox, 5.6% gave negative history, and 8.5% did not know. Of 594 who answered the zoster question, 78% gave a negative response, 4% did not know, and 104 (17%) answered yes. Of these, 83 reported 1 episode; 12 had 2; 5 had 3; and 1 each reported 5, 6, and 15 episodes. Of 51 patients tested for VZV IgG (44 "yes," 4 "no," and 3 "I don't know" answers to the question of whether they had chickenpox), 48 were seropositive; the 3 seronegative all had reported having had chickenpox. The high rate of MS patients reporting prior chickenpox infection is comparable with previous reports. A substantial proportion of MS patients, estimated to be higher than an age-matched general population, report single or multiple episodes of zoster. These data are useful for consideration of immunosuppressive treatments and/or VZV and zoster vaccination.

[The influence of intermediate physical training on some non-enzyme antioxidants of oxidative stress, in moderate hypertension]. / Influenta antrenamentului fizic recuperator pe termen mediu asupra unor antioxidanti neenzimatici de stres oxidativ în HTA moderata.

A group of patients with moderate hypertension (149-150/90-99 mm Hg) performed physical exercise for 3 months; we determined the oxidative stress in blood samples, by calculating the level of some biochemical markers, non-enzyme antioxidants, glutathione (GSH), total -SH groups (G-STH), nonprotein -SH groups (G-SHNP), their G-SHT/G-SHNP ratio, uric acid, malondialdehyde (MDA) and comparing the results with the values obtained from a group of healthy subjects. We found an increased oxidative stress at the HTA patients, with initial (Vi) decreasing values of GSH and uric acid, and with higher values of MDA. After the 3 months (Vf) of physical training, the oxidative stress improved, with increasing GSH, uric acid and decreasing MDA, compared to normal subjects. The initial values of G-SHT, G-SHNP and their ratio, increased, but decreased after 3 months, with an inverse aspect to GSH. The clinical study proved that after 3 months of physical exercise, there wasn't any increased oxidative stress at the HTA patients; however, the oxidative stress is present, proved by the values of MDA, significantly higher compared to the normal subjects.

[Evaluation of oxidative stress and enzymatic antioxidants in medium physical training of moderate arterial hypertension]. / Evaluarea stresului oxidativ si antioxidantilor enzimatici în antrenamentul fizic recuperator pe termen mediu al HTA moderate.

A group of patients with moderate hypertension (149-150/90-99 mmHg) performed physical exercise for 3 months; we determined the oxidative stress in blood samples, by calculating the level of some antioxidative markers, the enzymes SOD, CAT, GPx, MDA and comparing the results with the values obtained from a group of healthy subjects. We found an increased oxidative stress at the hypertensive patients, with initial higher values of SOD and MDA and with lower values of CAT and GPx, compared to the normal subjects. After the 3 months of physical training, the oxidative stress improved, with decreasing activity of SOD, GPx, MDA and increasing CAT, maintaining the ratio CAT/SOD and GPx/SOD superior compared to normal subjects. The clinical study proved that after 3 months of physical exercise, there wasn't any increased oxidative stress at the hypertensive patients; however, the oxidative stress is present, proved by the values of MDA, significantly higher compared to the normal subjects.

[The effects of the physical training on the hypertensive patients with glycoregulation disorder]. / Efectele antrenamentului fizic la hipertensivii cu tulburari de glicoreglare.

UNLABELLED: The purpose of our clinical study was the evaluation of moderate physical training on hypertensive patients with the impaired glycoregulation, for a determinate period of time. METHODS: The study included 80 patients with moderate hypertension, divided in two groups: group B formed of 40 patients that followed an associated treatment (physical exercises 3-5 times/week, 45-60 min. for one training and antihypertensive drug therapy) and group C formed of 40 patients that followed only drug therapy for controlling blood pressure. The glycoregulation disorder was appreciated by determining a jeune glycemia to all the patients, the oral glucose tolerance test at the patients who were until 60 years old and for which there wasn't any evidence of glucose intolerance a jeune. The uniform pattern of OGTT values was considered due to insulin resistance and hyperinsulinism. We obtained the values of cholesterol, triglycerides, HDL-C, LDL-C and atherogenesis index. RESULTS: The patients with impaired glycoregulation had significant increased values of cholesterol (p = 0.03) and triglycerides (p < 0.001), decreased HDL-C (p = 0.004), compared to the patients without glycoregulation disorder. LDL-C didn't vary significantly (p = 0.2). The patients with impaired glycoregulation had the value of ventricular mass 254.46 +/- 38 g, compared to 239.52 +/- 41 g for the patients without glycoregulation disorder. In group B, we found 14 patients with impaired glycoregulation (35%) and 11 patients in group C (27.5%) with the same metabolic disorder. After 6 month, only 9 patients with glycoregulation disorder (22.5) were left in group B and also 10 patients (25%) with the same disorder in group C. CONCLUSION: Moderate physical exercise associated with antihypertensive therapy induced, besides the decrease of blood pressure values, a good control of lipids and glucose markers of metabolism.