Multiple sclerosis (OMIM 126200) is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability.1 Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals;2,3 and systematic attempts to identify linkage in multiplex families have confirmed that variation within the Major Histocompatibility Complex (MHC) exerts the greatest individual effect on risk.4 Modestly powered Genome-Wide Association Studies (GWAS)5-10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects play a key role in disease susceptibility.11 Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the Class I region. Immunologically relevant genes are significantly over-represented amongst those mapping close to the identified loci and particularly implicate T helper cell differentiation in the pathogenesis of multiple sclerosis.
The SF-36 captures the broad effects of MS, and the results showed that patients also are bothered frequently with health problems such as bodily pain and low vitality. These problems, which are not reflected in the Expanded Disability Status Scale, should be given more attention in the treatment of MS and when evaluating interventions.
Background and purposeThere is still no curative treatment for multiple sclerosis (MS), but during the last 20 years eight different disease-modifying compounds have been approved for relapsing−remitting MS (RRMS).MethodsA literature search was conducted on published randomized controlled phase III trials indexed in PubMed on the approved medications until 21 May 2015.ResultsIn this review the mode of action, documented treatment effects and side effects of the approved MS therapies are briefly discussed.ConclusionsBased on current knowledge of risk−benefit of the approved MS medications, including factors influencing adherence, it is suggested that oral treatment with dimethyl fumarate or teriflunomide should be preferred as a starting therapy amongst the first-line preparations for de novo RRMS. In the case of breakthrough disease on first-line therapy, or rapidly evolving severe RRMS, second-line therapy with natalizumab, fingolimod or alemtuzumab should be chosen based on careful risk−benefit stratification.
The cuprizone model correlates with newer histopathological data in MS and is a valuable tool for studies on de- and remyelination. The use of the C57BL/6 strain offers the potential for future studies on transgene and knockout mice.
Most multiple sclerosis (MS) patients experience some sexual, bladder and/or bowel dysfunction during the course of the disease--one of MS most disabling features. This study estimated the frequency of these problems among patients, two to five years after diagnosis, and investigated how these problems are associated with health-related quality of life (using the Multiple Sclerosis Quality of Life-54 questionnaire). The study population comprised a cohort of patients (n = 56), diagnosed in a three-year period, in Hordaland County, Norway. The patients were examined clinically, including scoring of the Expanded Disability Status Scale (EDSS), and completed questionnaires related to bowel and bladder dysfunction, sexual problems and health-related quality of life. More than half the patients had bladder and sexual problems. The frequency of self-reported bladder problems corresponded to the relatively high levels of residual urine found. The presence of these problems was associated with lower scores on the quality of life scales. Further, the bowel problems reported were markedly associated with the quality of life scores. Since treatments and preventive strategies can manage many of these problems, we suggest increasing the focus on these aspects of the disease when consulting patients, including at early stages.
We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
Therapy‐induced binding and neutralizing antibodies is a major problem in interferon (IFN)‐β treatment of multiple sclerosis. The objective of this study was to provide guidelines outlining the methods and clinical use of the measurements of binding and neutralizing antibodies. Systematic search of the Medline database for available publications on binding and neutralizing antibodies was undertaken. Appropriate publications were reviewed by one or more of the task force members. Grading of evidence and recommendations was based on consensus by all task force members. Measurements of binding antibodies are recommended for IFN‐β antibody screening before performing a neutralizing antibody (NAB) assay (Level A recommendation). Measurement of NABs should be performed in specialized laboratories with a validated cytopathic effect assay or MxA production assay using serial dilution of the test sera. The NAB titre should be calculated using the Kawade formula (Level A recommendation). Tests for the presence of NABs should be performed in all patients at 12 and 24 months of therapy (Level A recommendation). In patients who remain NAB‐negative during this period measurements of NABs can be discontinued (Level B recommendation). In patient with NABs, measurements should be repeated, and therapy with IFN‐β should be discontinued in patients with high titres of NABs sustained at repeated measurements with 3‐ to 6‐month intervals (Level A recommendation).
Background: To study the impact of fatigue in young ischaemic stroke patients. Methods: The Fatigue Severity Scale score was obtained in 192 patients (mean time 6.0 years after the stroke) and 212 controls. Results: Fatigue was associated with cerebral infarction in a multivariate analysis of patients and controls (p = 0.002). Fatigue was independently associated with unfavourable functional outcome (p = 0.001), depression (p < 0.001), and basilar artery infarction through interaction with the modified Rankin Scale score (p = 0.047) in patients. Conclusion: Fatigue is frequent in young adults with cerebral infarction. Stroke-related factors independently associated with fatigue include functional outcome. Stroke location may influence fatigue.
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