A chromosome study in multiple sclerosis

Summary Chromosome studies of 30 patients with multiple sclerosis and 30 controls have been made. The results show that there is no significant increase in the frequency of structural aberrations in the multiple sclerosis patients. It is suggested that previously reported differences may have been due to technical factors, the nature of which is discussed.

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Zusammenfassung Bei 30 Patienten mit multipler Sklerose und 30 Kontrollen wurden die Chromosomen untersucht. Es fand sich bei den Patienten kein signifikanter Anstieg in der Häufigkeit struktureller Aberrationen. Vielleicht wurden früher mitgeteilte Unterschiede durch technische Faktoren, die im einzelnen diskutiert werden, vorgetäuscht.

     

Elevated frequencies of 6-thioguanine-resistant lymphocytes in multiple sclerosis patients treated with cyclophosphamide: a prospective study

An autoradiographic assay for 6-thioguanine-resistant (TGr) lymphocytes was used to determine the frequency of in vivo derived variant T lymphocytes in peripheral blood from multiple sclerosis (MS) patients treated with monthly intravenous infusions of 750 mg/m2 of cyclophosphamide (CP). To analyze the time-course of response to CP, the MS patients were studied prospectively. Samples were obtained from the patients before the beginning of CP therapy, 4-5 times during the course of treatment, and, finally, 2 or 3 months after the completion of therapy. 2 weeks after the first CP infusion, the variant frequencies (Vfs) of the MS patients were significantly increased (p less than 0.05) above their pre-treatment values, but by 4 weeks following the first CP infusion the Vfs had fallen to normal or near-normal levels. After subsequent treatments, the frequencies of variant TGr cells were again higher than pre-treatment Vfs. However, within 7-13 weeks after the cessation of CP therapy, the Vfs of all subjects had returned to normal levels. The transient nature of the response indicates rapid in vivo selection against CP-induced TGr mutant cells. The mean pre-treatment Vf of the 4 MS patients who were cigarette smokers was 6.56 X 10(-6) which was significantly greater (p less than 0.05) than the mean Vf (1.52 X 10(-6) of the 4 MS patients who were non-smokers. The mean Vf from 8 assays of healthy non-smokers was 1.92 X 10(-6).     

Anomalously warm weather and acute care visits in patients with multiple sclerosis: A retrospective study of privately insured individuals in the US

BackgroundAs the global climate changes in response to anthropogenic greenhouse gas emissions, weather and temperature are expected to become increasingly variable. Although heat sensitivity is a recognized clinical feature of multiple sclerosis (MS), a chronic demyelinating disorder of the central nervous system, few studies have examined the implications of climate change for patients with this disease.Methods and findingsWe conducted a retrospective cohort study of individuals with MS ages 18–64 years in a nationwide United States patient-level commercial and Medicare Advantage claims database from 2003 to 2017. We defined anomalously warm weather as any month in which local average temperatures exceeded the long-term average by ≥1.5°C. We estimated the association between anomalously warm weather and MS-related inpatient, outpatient, and emergency department visits using generalized log-linear models. From 75,395,334 individuals, we identified 106,225 with MS. The majority were women (76.6%) aged 36–55 years (59.0%). Anomalously warm weather was associated with increased risk for emergency department visits (risk ratio [RR] = 1.043, 95% CI: 1.025–1.063) and inpatient visits (RR = 1.032, 95% CI: 1.010–1.054). There was limited evidence of an association between anomalously warm weather and MS-related outpatient visits (RR = 1.010, 95% CI: 1.005–1.015). Estimates were similar for men and women, strongest among older individuals, and exhibited substantial variation by season, region, and climate zone. Limitations of the present study include the absence of key individual-level measures of socioeconomic position (i.e., race/ethnicity, occupational status, and housing quality) that may determine where individuals live—and therefore the extent of their exposure to anomalously warm weather—as well as their propensity to seek treatment for neurologic symptoms.ConclusionsOur findings suggest that as global temperatures rise, individuals with MS may represent a particularly susceptible subpopulation, a finding with implications for both healthcare providers and systems.     

A randomised controlled trial of an exercise plus behaviour change intervention in people with multiple sclerosis: the step it up study protocol

Background

Exercise has consistently yielded short-term, positive effects on health outcomes in people with multiple sclerosis (MS). However, these effects have not been maintained in the long-term. Behaviour change interventions aim to promote long-term positive lifestyle change. This study, namely, “Step it Up” will compare the effect of an exercise plus Social Cognitive Theory (SCT)-based behaviour change intervention with an exercise plus control education intervention on walking mobility among people with MS.

Methods/design

People with a diagnosis of MS who walk independently, score of 0–3 on the Patient Determined Disease Steps, who have not experienced an MS relapse or change in their MS medication in the last 12 weeks and who are physically inactive will be randomised to one of two study conditions. The experimental group will undergo a 10-week exercise plus SCT-based behavioural change intervention. The control group will undergo a 10-week exercise plus education intervention to control for contact. Participants will be assessed at weeks 1, 12, 24 and 36. The primary outcome will be walking mobility. Secondary outcomes will include: aerobic capacity, lower extremity muscle strength, participant adherence to the exercise programme, self-report exercise intensity, self-report enjoyment of exercise, exercise self-efficacy, outcome expectations for exercise, goal-setting for exercise, perceived benefits and barriers to exercise, perceptions of social support, physical and psychological impact of MS and fatigue. A qualitative evaluation of Step it Up will be completed among participants post-intervention.

Discussion

This randomised controlled trial will examine the effectiveness of an exercise plus SCT-based behaviour change intervention on walking mobility among people with MS. To this end, Step it Up will serve to inform future directions of research and clinical practice with regard to sustainable exercise interventions for people with MS.

Trial registration

ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02301442

     

A novel needle for subcutaneous injection of interferon beta-1a: effect on pain in volunteers and satisfaction in patients with multiple sclerosis

Background  

To reduce injection pain and improve satisfaction, a thinner (29-gauge [29G]), sharper (5-bevel) needle than the 27G/3-bevel needle used previously to inject interferon (IFN) beta-1a, 44 or 22 mcg subcutaneously (sc) three times weekly (tiw), was developed for use in multiple sclerosis (MS).     

Masitinib treatment in patients with progressive multiple sclerosis: a randomized pilot study

ABSTRACT: BACKGROUND: Treatment options for patients suffering from progressive forms of multiple sclerosis (MS) remain inadequate. Mast cells actively participate in the pathogenesis of MS, in part because they release large amounts of various mediators that sustain the inflammatory network. Masitinib, a selective oral tyrosine kinase inhibitor, effectively inhibits the survival, migration and activity of mast cells. This exploratory study assessed the safety and clinical benefit of masitinib in the treatment of primary progressive MS (PPMS) or relapse-free secondary progressive MS (rfSPMS). METHODS: Multicenter, randomized, placebo-controlled, proof-of-concept trial. Masitinib was administered orally at 3 to 6 mg/kg/day for at least 12 months, with dose adjustment permitted in event of insufficient response with no toxicity. The primary response endpoint was the change relative to baseline in the multiple sclerosis functional composite score (MSFC). Clinical response was defined as an increase in MSFC score relative to baseline of > 100%. RESULTS: Thirty-five patients were randomized to receive masitinib (N = 27) or placebo (N = 8). Masitinib was relatively well tolerated with the most common adverse events being asthenia, rash, nausea, edema, and diarrhea. The overall frequency of adverse events was similar to the placebo group, however, a higher incidence of severe and serious events was associated with masitinib treatment. Masitinib appeared to have a positive effect on MS-related impairment for PPMS and rfSPMS patients, as evidenced by an improvement in MSFC scores relative to baseline, compared with a worsening MSFC score in patients receiving placebo; +103% +/- 189 versus -60% +/- 190 at month-12, respectively. This positive albeit non-statistically significant response was observed as early as month-3 and sustained through to month-18, with similar trends seen in the PPMS and rfSPMS subpopulations. A total of 7/17 (41%) assessable masitinib patients reported clinical response following 12 months of treatment (according to the modified intent-to-treat population, observed cases) compared with none in the placebo group. The Expanded Disability Status Scale remained stable for both treatment groups. CONCLUSION: These data suggest that masitinib is of therapeutic benefit to PPMS and rfSPMS patients and could therefore represent an innovative avenue of treatment for this disease. This exploratory trial provides evidence that may support a larger placebo-controlled investigation.     

Incidence of multiple myeloma in Kailuan cohort: A prospective community-based study in China

BackgroundPrevious retrospective studies showed that the incidence and mortality rates for MM in China were lower than those in western countries. A large-scale prospective study on incidence and mortality rates of MM is still lacking.MethodsBased on the prospective Kailuan Cohort study in China, we included all patients with MM in Kailuan Cohort from June 1, 2008 to December 31, 2016. Using the numbers of diagnosed cases and deaths during the study period as the numerators and the corresponding observed person-years as the denominators respectively, we calculated crude incidence and mortality rates. The 95% confidence intervals for crude incidence rate and mortality rate were estimated base on Poisson distribution. Rates were standardized by direct standardization according to the China population in 2000 and Segi’ world standard population.ResultsA total of 22 members from Kailuan Cohort were first diagnosed with MM between 2008 and 2016. The calculated crude incidence rates were 2.8 (95% CI, 1.7–4.2) per 100,000 person-years for all participants. The standardized incidence rate was 0.9 per 100,000 person-years (95% CI, 0.5–2.1) when standardized by 2000 China population census data, and 1.0 per 100,000 person-years (95% CI, 0.6–1.8) when standardized by Segi’s world standard population (WSP). The calculated crude mortality rates were 2.3 (95% CI, 1.4–3.6) per 100,000 person-years. The mortality standardized by 2000 China population census data was 0.7 per 100,000 person-years (95% CI, 0.3–1.9), and 0.9 per 100,000 population (95% CI, 0.5–1.7) when standardized by Segi’s WSP. Both incidence and mortality for males were higher than that for females almost in all age groups. Both rates increased steadily with age.ConclusionIn this community-based prospective cohort study, we found that the incidence of MM in China was far lower than that in American and Europe.     

Self-reported physical activity correlates in Swedish adults with multiple sclerosis: a cross-sectional study

Background

The benefits of physical activity in persons with Multiple Sclerosis (MS) are considerable. Knowledge about factors that correlate to physical activity is helpful in order to develop successful strategies to increase physical activity in persons with MS. Previous studies have focused on correlates to physical activity in MS, however falls self-efficacy, social support and enjoyment of physical activity are not much studied, as well as if the correlates differ with regard to disease severity. The aim of the study was to examine associations between physical activity and age, gender, employment, having children living at home, education, disease type, disease severity, fatigue, self-efficacy for physical activity, falls self-efficacy, social support and enjoyment of physical activity in a sample of persons with MS and in subgroups with regard to disease severity.

Methods

This is a cross-sectional survey study including Swedish community living adults with MS, 287 persons, response rate 58.2%. The survey included standardized self-reported scales measuring physical activity, disease severity, fatigue, self-efficacy for physical activity, falls self-efficacy, and social support. Physical activity was measured by the Physical Activity Disability Survey – Revised.

Results

Multiple regression analyzes showed that 59% (F(6,3)?=?64.9, p?=?0.000) of the variation in physical activity was explained by having less severe disease (β?=??0.30), being employed (β?=?0.26), having high falls self-efficacy (β?=?0.20), having high self-efficacy for physical activity (β?=?0.17), and enjoying physical activity (β?=?0.11). In persons with moderate/severe MS, self-efficacy for physical activity explained physical activity.

Conclusions

Consistent with previous research in persons with MS in other countries this study shows that disease severity, employment and self-efficacy for physical activity are important for physical activity. Additional important factors were falls self-efficacy and enjoyment. More research is needed to confirm this and the subgroup differences.

     

Impact of natalizumab on cognitive performances and fatigue in relapsing multiple sclerosis: a prospective, open-label, two years observational study

Background and Objectives

Natalizumab reduces the relapse rate and magnetic resonance imaging activity in patients with Relapsing-Remitting Multiple Sclerosis (RRMS). So far the influence of natalizumab on cognitive functions and fatigue in MS remains uncertain. The aim of this prospective, open-label, observational study was to evaluate the possible effects of natalizumab on cognition and fatigue measures in RRMS patients treated for up to two years.

Methods

Cognitive performances were examined by the Rao''s Brief Repeatable Battery (BRB), the Stroop test (ST) and the Cognitive Impairment Index (CII), every 12 months. Patients who failed in at least 3 tests of the BRB and the ST were classified as cognitively impaired (CI). Fatigue Severity Scale (FSS) was administered every 12 months to assess patient''s self-reported fatigue. One hundred and 53 patients completed 1 and 2 year-natalizumab treatment, respectively.

Results

After 1 year of treatment the percentage of CI patients decreased from 29% (29/100) at baseline to 19% (19/100) (p = 0.031) and the mean baseline values of CII (13.52±6.85) and FSS (4.01±1.63) scores were significantly reduced (10.48±7.12, p<0.0001 and 3.61±1.56, p = 0.008). These significant effects were confirmed in the subgroup of patients treated up to two years.

Conclusions

These results demonstrate that a short-term NTZ treatment may significantly improve cognitive performances and fatigue in RRMS patients.