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PubMed1977

Effect of encephalitogenic protein on migration in agarose of leukocytes from patients with multiple sclerosis. A longitudinal study of patients with relapsing multiple sclerosis or with cerebral infarction.

Ten patients with MS were studied with leukocyte migration in agarose technique to detect changes in reactivity to encephalitogenic protein in connexion with a relapse. Six showed significant reactivity within a few days after the relapse. It decreased or disappeared during the 2 weeks after the relapse, but sometimes reappeared and was found in tests performed 2-3 months later. Five patients with cerebral infarction were studied in a similar way--in three, marked reactivity was noted within a few days after the stroke; in these, reactivity decreased or disappeared in later tests. In the two other patients, reactivity appeared in the second and/or third test. The possibility of a reactivity as in epiphenomenon due to CNS tissue destruction is discussed, and the need for antigens with a more restricted specificity for such an analysis is stressed.

Cell Migration Inhibition↗
PubMed1996

[Multiple sclerosis: therapy with recombinant beta-1b interferon: initial results with 30 multiple sclerosis patients in northwest Switzerland].

Recombinant interferon beta-1b has been registered with the Swiss health authorities since August 1995. Due to a special arrangement with health insurances it has been possible to prescribe this medication since spring 1995. We report on our experience with the first 30 consecutively treated multiple sclerosis patients. Indication, adverse event profile and clinical response to treatment are described. The most common side effects were local injection site reactions (63%), influenza-like symptoms (50%) and fatigue (33%). As compared to the prestudy period we observed a 49% reduction in the exacerbation rate. Compliance was excellent, possibly due to strict selection and extensive information about possible effects and side effects.

Adjuvants, Immunologic↗
PubMed2005

Use of low-dose mitozantrone to treat aggressive multiple sclerosis: a single-centre open-label study using patient self-assessment and clinical measures of multiple sclerosis status.

BACKGROUND: There is significant evidence supporting the use of mitozantrone in the treatment of multiple sclerosis (MS) but few data on the subtypes of MS that respond or which measures of disease status are most useful. AIMS: To assess the efficacy of low-dose (5 mg/m2 3 monthly) mitozantrone using patient self-assessment questionnaire (SAQ), expanded disability status score (EDSS), multiple sclerosis functional composite score (MSFC), and the fatigue severity scale (FSS). Then, to compare the responses of a subgroup of relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) patients to treatment, and to assess which measures of MS disease status are the most useful in a study of this type. METHOD: Thirty-one patients with definite (McDonald criteria) active MS were commenced on mitozantrone 5 mg/m2 every 3 months. EDSS, MSFC and FSS data collected before treatment and after 12 months were analysed. The SAQ was administered after at least 12 months of therapy. RESULTS: RRMS patients showed significantly more response to mitozantrone than SPMS patients in terms of MSFC (P = 0.02) and SAQ (P = 0.01). CONCLUSIONS: Low-dose mitozantrone was well tolerated and useful in active RRMS in the short term; however, mitozantrone did not display any useful activity in SPMS patients over this time interval or at the mitozantrone dose used. Patient perception of treatment is a worthwhile outcome measure and the MSFC is the most useful objective measure of MS status change in this type of study.

Adult↗
PubMed1998

Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group.

BACKGROUND: Previous trials of interferon beta in multiple sclerosis (MS) have shown efficacy, but the degree of clinical benefit remains uncertain, and the optimum dose is not known. We undertook a double-blind, placebo-controlled study in relapsing/remitting MS to investigate the effects of subcutaneous interferon beta-1a. METHODS: 560 patients with Kurtzke expanded disability status scale (EDSS) scores of 0-5.0, from 22 centres in nine countries, were randomly assigned subcutaneous recombinant interferon beta-1a 22 microg (n=189), or 44 microg (n=184), or placebo (n=187) three times a week for 2 years. Neurological examinations were done every 3 months. All patients had MRI twice yearly and 205 had monthly scans in the first 9 months of treatment. Analysis was by intention to treat. FINDINGS: Clinical data on 533 (95%) patients were available at 2 years. The relapse rate was significantly lower at 1 and 2 years with both doses of interferon beta-1a than with placebo (mean number per patient 1.82 for 22 microg group, 1.73 for 44 microg group vs 2.56 for placebo group: risk reductions 27% [95% CI 14-39] and 33 [21-44]). Time to first relapse was prolonged by 3 and 5 months in the 22 microg and 44 microg groups respectively, and the proportion of relapse-free patients was significantly increased (p<0.05). Interferon beta-1a delayed progression in disability, and decreased accumulated disability during the study. The accumulation of burden of disease and number of active lesions on MRI was lower in both treatment groups than in the placebo group. INTERPRETATION: Subcutaneous interferon beta-1a is an effective treatment for relapsing/remitting MS in terms of relapse rate, defined disability, and all MRI outcome measures in a dose-related manner, and it is well tolerated. Longer-term benefits may become clearer with further follow-up and investigation.

Adult↗
PubMed2006

The Italian Multiple Sclerosis Database Network (MSDN): the risk of worsening according to IFNbeta exposure in multiple sclerosis.

We evaluated the risk of worsening according to the length of exposure to interferon beta (IFNbeta) in a large cohort of 2090 multiple sclerosis patients collected by the Italian MS Database Network. Overall 44,140 patient-visits with a follow-up of 22,143 patient-years were evaluated. Forty-one per cent of patients were exposed to IFNbeta for up to 2 years, 39% for 2-4 years and 20% for more than 4 years. A Cox regression model was used to analyse two clinical outcomes: disability progression and worsening of relapse rate. The technique of propensity score was applied to reduce bias in the comparison of non-randomized groups. The risks of disability progression (HR =0.23; 95% CI: 0.17-0.30) and worsening of relapse rate (HR =0.19; 95% CI: 0.14-0.27) were reduced by about 4-5-fold in patients exposed to IFNbeta for more than four years, compared with patients exposed for up to two years. The propensity score technique confirmed the findings. The proportion of days covered by IFNbeta treatment was lower (P <0.0001) in patients exposed to IFNbeta for up to two years than in other groups. A clinical stabilization over two years of IFNbeta exposure may predict a subsequent good clinical response to treatment.

Adjuvants, Immunologic↗
PubMed1999

[Treatment of multiple sclerosis. The present and the future. Study Group on Diagnosis and Therapy of Multiple Sclerosis].

The last years have produced a plethora of new information including extensive studies, retrospective analysis and new perspectives on data interpretation on multiple sclerosis (MS) treatment. Considering how difficult it is to study a disease such MS with its variability, unpredictability and duration, it seems hard to resemble definite results from this experience. However, corticosteroids have been the mainstay of treatment for the management of acute relapses, showing the capacity to shorten the duration of relapses, accelerate the recovery. At present, interferon beta is generally considered to be the treatment of choice for patients with relapsing remitting disease. Glatiramer acetate is still not available in many parts of Europe, but its results demonstrate a reduction of relapses in 30% of cases. Most European experts only consider as alternative treatment the immunosuppressive drugs, chosen if patients demonstrate unacceptable side effects of interferon or clearly do not respond. Very different and even more confusing data still come from experimental trial in secondary progressive MS, where the target of treatment is to slow the progression of disability. Different drugs (methotrexate, mitoxantrone, linomide, steroids and even interferons) are employed, but the results are still debated. Future therapies are being derived from constantly changing and evolving concept of MS immunopathogenesis: therefore many experimental and clinical trials use anti-integrin antibodies or insulin growth factors, metallo-proteinase inhibitors or T-cell vaccination. Some of the above treatment may have a chance of producing the gaining control of the disease without much inner toxicity.

Adjuvants, Immunologic↗
PubMed2004

Correlations between multiple sclerosis functional composite, expanded disability status scale and health-related quality of life during and after treatment of relapses in patients with multiple sclerosis.

The measurement of the clinical manifestations of multiple sclerosis (MS) is difficult. In the present study, we examined the changes in measurement of functions during and after pulse methylprednisolon (MP) treatment of MS exacerbations using the MSFC and EDSS. Correlation between multiple sclerosis quality of life (MSQoL)-54, EDSS and MSFC were studied. Thirty-six clinically definite MS patients were included in this study. Because of MSFC's repeating feature, we administered the tests to a control group to exclude practise effects. All patients received 1000-mg intravenous MP for 5 days, followed by tappering dose of 100-mg oral prednisolone. All three scales were assessed on day 0. EDSS and two components of MSFC (nine HPT and T25WT) were administered on the other days of pulse MP treatment. PASAT was not applied before the day 5 to exclude the practise effect. MSQoL-54 was assessed again on day 30. Mean EDSS values significantly decreased after the day 2. MSFC score improved from 0.03 +/- 1.71 on day 0 to 0.79 +/- 1.51 on day 5. Improvement continued on day 30. The mean physical health composite score increased from 66.50 +/- 9.3 on day 0 to 74.34 +/- 8.9 on day 30. Mental health composite had also a significant improvement on day 30. Correlation between the baseline overall MSFC and the EDSS was moderately strong. T25WT correlated most strongly with EDSS. Significant positive correlation was found between MSFC and both components of MSQoL-54. It is more prominent for the MSFC and physical health composite correlation. The same correlation was found for the EDSS and MSQoL-54 composites. Changes in EDSS and MSFC scores and MSQoL-54 were found significantly correlated for the overall score on day 30 compared with day 0. In conclusion, MSFC seems to be more sensitive in detecting changes in function than the EDSS. Hence, EDSS is still useful for daily routine practise. When these results combined with the significant correlation between MSFC and MSQoL-54 measures, which indicated the MSFC reflects the severity of MS as perceived by patients, MSFC seems to be the most useful scale for clinical trials.

Adult↗
PubMed2006

[Multifocal central nervous system lesions --multiple sclerosis or neuroborreliosis?].

Multiple sclerosis is the most frequent multifocal disease of the central nervous system, but in a diagnosis of atypical cases about 100 other diseases should be considered. Neuroborreliosis plays a particular role among them, especially in endemic regions. Difficulties result from similarities of clinical symptoms and lack of specific diagnostic investigations. Diagnostic procedures in neuroborreliosis are mostly based on laboratory analyses and serologic examinations of serum and cerebrospinal fluid, in connection with a clinical picture and an epidemiological state. Since the year 2001, multiple sclerosis neurological diagnostic is based on the diagnostic criteria established under the auspices of The US National Multiple Sclerosis Society and International Federation of Multiple Sclerosis Societies. Those recommendations regarding relapsing-remitting MS and primary progressing MS are discussed in this paper. Current knowledge of those diseases warrants cautiousness in the diagnostic of atypical cases.

Central Nervous System Diseases↗
PubMed1995

Epidemiology of multiple sclerosis in US veterans. 6. Population ancestry and surname ethnicity as risk factors for multiple sclerosis.

Previously, we studied the effect of population ancestry on the risk of multiple sclerosis (MS) in US veterans of World War II, comparing by state 1980 US census ancestry data with MS case/control ratios. Here, the joint effects of population ancestry and surname-derived ethnicity on MS risk are examined in the same series. Census data are used again to characterize the population ancestry of the state from which each subject entered active duty (EAD)--that is, the proportions of the populace reporting various ancestries--and subjects were also individually categorized into a single ethnic group, without knowledge of case/control status, based on surname. In this study population, categorized ethnicity was strongly correlated with population ancestry, as expected. Although univariate analyses showed statistically significant associations between MS risk and several surname-derived ethnicities and ethnic groups, when residence at EAD was accounted for as well, there was almost no ethnic variation in MS risk. A logistic regression analysis further showed that variations in MS risk are associated most strongly with latitude and population ancestry group; in particular, subjects who entered military service from states with higher proportions of Swedish or French ancestry had higher risks of MS. After adjustment for characteristics of place, the only significant individual ethnicity factor found was Southern European ethnicity. In general, we conclude that an individual's ethnicity seems to be of less relative importance in determining MS risk than is the population ancestry of the state of EAD. These findings underscore the fact that MS is a disease of place, with 'place' including not only attributes of the locale (e.g., latitude), but also of its populace (e.g., ancestry).

Adult↗
PubMed1984

Hypothesis: multiple sclerosis cerebrospinal fluid IgG multiple bands are derived from one or a few IgG secretor cell clones.

Analytical IEF, immunofixation, and silver nitrate staining of mouse monoclonal, human myeloma, and multiple sclerosis (MS) oligoclonal IgG result in multiple bands. Because the IgG secreted by mouse hybridoma and multiple myeloma are the products of single clones of cells, it is reasonable to propose that MS CSF IgG multiple bands may be derived from one or a small number of clones of IgG secretors.

Antibody Specificity↗