Good results for early treatment of clinically isolated syndrome prior to multiple sclerosis with interferon beta-1b and glatiramer

Background: The first sign of developing multiple sclerosis is a clinically isolated syndrome that resembles a multiple sclerosis relapse. Objective/methods: The objective was to review the clinical trials of two medicines in clinically isolated syndromes (interferon β and glatiramer acetate) to determine whether they prevent progression to definite multiple sclerosis. Results: In the BENEFIT trial, after 2 years, 45% of subjects in the placebo group developed clinically definite multiple sclerosis, and the rate was lower in the interferon β-1b group. Then all subjects were offered interferon β-1b, and the original interferon β-1b group became the early treatment group, and the placebo group became the delayed treatment group. After 5 years, the number of subjects with clinical definite multiple sclerosis remained lower in the early treatment than late treatment group. In the PreCISe trial, after 2 years, the time for 25% of the subjects to convert to definite multiple sclerosis was prolonged in the glatiramer group. Conclusions: Interferon β-1b and glatiramer acetate slow the progression of clinically isolated syndromes to definite multiple sclerosis. However, it is not known whether this early treatment slows the progression to the physical disabilities experienced in multiple sclerosis.

Oral fingolimod for relapsing-remitting multiple sclerosis

Background: Most people with multiple sclerosis have the relapsing-remitting type. Objective/methods: The objective was to evaluate two clinical trials of fingolimod in relapsing multiple sclerosis. Results: FREEDOMS (FTY720 Research Evaluation Effects of Daily Oral therapy in Multiple Sclerosis), a Phase III placebo-controlled trial, showed that fingolimod (0.5 or 1.25 mg) reduced the relapse rate and disability in multiple sclerosis, compared to placebo. Fingolimod (0.5 or 1.25 mg) has been compared to interferon β-1a in a Phase III clinical trial (TRANSFORMS; Trial Assessing Injectable Interferon versus FTY720 Oral in Relapsing-Remitting Multiple Sclerosis) and shown to be more efficacious than interferon β-1a in reducing relapse rates. However, fingolimod did increase the risk of infections and skin cancers. Conclusions: Only the lower dose of fingolimod (0.5 mg), which possibly has less toxicity, should be considered for prevention of relapses in relapsing-remitting multiple sclerosis.

Mild systemic hypoxia and photopic visual field sensitivity

Purpose: Flickering stimuli increase the metabolic demand of the retina,making it a sensitive perimetric stimulus to the early onset of retinal disease. We determine whether flickering stimuli are a sensitive indicator of vision deficits resulting from to acute, mild systemic hypoxia when compared to standard static perimetry. Methods: Static and flicker visual perimetry were performed in 14 healthy young participants while breathing 12% oxygen (hypoxia) under photopic illumination. The hypoxia visual field data were compared with the field data measured during normoxia. Absolute sensitivities (in dB) were analysed in seven concentric rings at 1°, 3°, 6°, 10°, 15°, 22° and 30° eccentricities as well as mean defect (MD) and pattern defect (PD) were calculated. Preliminary data are reported for mesopic light levels. Results: Under photopic illumination, flicker and static visual field sensitivities at all eccentricities were not significantly different between hypoxia and normoxia conditions. The mean defect and pattern defect were not significantly different for either test between the two oxygenation conditions. Conclusion: Although flicker stimulation increases cellular metabolism, flicker photopic visual field impairment is not detected during mild hypoxia. These findings contrast with electrophysiological flicker tests in young participants that show impairment at photopic illumination during the same levels of mild hypoxia. Potential mechanisms contributing to the difference between the visual fields and electrophysiological flicker tests including variability in perimetric data, neuronal adaptation and vascular autoregulation, are considered. The data have implications for the use of visual perimetry in the detection of ischaemic/hypoxic retinal disorders under photopic and mesopic light levels.

The nature of caregiving in children of a parent with multiple sclerosis from multiple sources and the associations between caregiving activities and youth adjustment overtime

This study explored youth caregiving for a parent with multiple sclerosis (MS) from multiple perspectives, and examined associations between caregiving and child negative (behavioural emotional difficulties, somatisation) and positive (life satisfaction, positive affect, prosocial behaviour) adjustment outcomes overtime. A total of 88 families participated; 85 parents with MS, 55 partners and 130 children completed questionnaires at Time 1. Child caregiving was assessed by the Youth Activities of Caregiving Scale (YACS). Child and parent questionnaire data were collected at Time 1 and child data were collected 12 months later (Time 2). Factor analysis of the child and parent YACS data replicated the four factors (instrumental, social-emotional, personal-intimate, domestic-household care), all of which were psychometrically sound. The YACS factors were related to parental illness and caregiving context variables that reflected increased caregiving demands. The Time 1 instrumental and social-emotional care domains were associated with poorer Time 2 adjustment, whereas personal-intimate was related to better adjustment and domestic-household care was unrelated to adjustment. Children and their parents exhibited highest agreement on personal-intimate, instrumental and total caregiving, and least on domestic-household and social-emotional care. Findings delineate the key dimensions of young caregiving in MS and the differential links between caregiving activities and youth adjustment.

Systemic inflammatory responses to maximal versus submaximal lengthening contractions of the elbow flexors

We compared changes in markers of muscle damage and systemic inflammation after submaximal and maximal lengthening muscle contractions of the elbow flexors. Using a cross-over design, 10 healthy young men not involved in resistance training completed a submaximal trial (10 sets of 60 lengthening contractions at 10% maximum isometric strength, 1 min rest between sets), followed by a maximal trial (10 sets of three lengthening contractions at 100% maximum isometric strength, 3 min rest between sets). Lengthening contractions were performed on an isokinetic dynamometer. Opposite arms were used for the submaximal and maximal trials, and the trials were separated by a minimum of two weeks. Blood was sampled before, immediately after, 1 h, 3 h, and 1-4 d after each trial. Total leukocyte and neutrophil numbers, and the serum concentration of soluble tumor necrosis factor-alpha receptor 1 were elevated after both trials (P < 0.01), but there were no differences between the trials. Serum IL-6 concentration was elevated 3 h after the submaximal contractions (P < 0.01). The concentrations of serum tumor necrosis factor-alpha, IL-1 receptor antagonist, IL-10, granulocyte-colony stimulating factor and plasma C-reactive protein remained unchanged following both trials. Maximum isometric strength and range of motion decreased significantly (P < 0.001) after both trials, and were lower from 1-4 days after the maximal contractions compared to the submaximal contractions. Plasma myoglobin concentration and creatine kinase activity, muscle soreness and upper arm circumference all increased after both trials (P < 0.01), but were not significantly different between the trials. Therefore, there were no differences in markers of systemic inflammation, despite evidence of greater muscle damage following maximal versus submaximal lengthening contractions of the elbow flexors.