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At least 937 records · Page 52Linked to original sources
PubMed2005

A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis.

Genetic susceptibility to multiple sclerosis is associated with genes of the major histocompatibility complex (MHC), particularly HLA-DRB1 and HLA-DQB1 (ref. 1). Both locus and allelic heterogeneity have been reported in this genomic region. To clarify whether HLA-DRB1 itself, nearby genes in the region encoding the MHC or combinations of these loci underlie susceptibility to multiple sclerosis, we genotyped 1,185 Canadian and Finnish families with multiple sclerosis (n = 4,203 individuals) with a high-density SNP panel spanning the genes encoding the MHC and flanking genomic regions. Strong associations in Canadian and Finnish samples were observed with blocks in the HLA class II genomic region (P < 4.9 x 10(-13) and P < 2.0 x 10(-16), respectively), but the strongest association was with HLA-DRB1 (P < 4.4 x 10(-17)). Conditioning on either HLA-DRB1 or the most significant HLA class II haplotype block found no additional block or SNP association independent of the HLA class II genomic region. This study therefore indicates that MHC-associated susceptibility to multiple sclerosis is determined by HLA class II alleles, their interactions and closely neighboring variants.

Canada↗
PubMed1999

Problems in designing and recruiting to therapeutic trials in primary progressive multiple sclerosis.

Patients with primary progressive multiple sclerosis have atypical clinical and magnetic resonance imaging (MRI) characteristics which present unique problems in designing and recruiting to therapeutic trials. The first randomised controlled therapeutic trial specifically for primary progressive multiple sclerosis is now underway. Although only an exploratory phase II study, it has provided further insight into difficulties in diagnosis, classification and choice of clinical and MRI outcome measures. Patients with primary progressive multiple sclerosis have a wide differential diagnosis and do not readily conform to the Poser criteria. They may therefore present diagnostic uncertainty, particularly as their classification often relies on a retrospective history. This was highlighted during the recruitment to this study of interferon-beta1a. Of the 138 patients referred with a definite diagnosis of primary progressive multiple sclerosis only 50 were enrolled in the study. Of the 88 patients not included, 50% either did not have primary progressive multiple sclerosis, or the diagnosis was not secure. Outcome measures pose particular problems. Clinically the focus must be on progression, and the measure should be both responsive and reliable. In relation to MRI, the currently recommended measures for therapeutic trials in relapsing/remitting and secondary progressive multiple sclerosis show little change in primary progressive multiple sclerosis, and therefore more pathologically specific MRI measures are required. Strict clinical guidelines and further developments in clinical and MRI measures are required to facilitate future therapeutic trials in primary progressive multiple sclerosis.

Brain↗
PubMed2002

Gender prevalence in childhood multiple sclerosis and myasthenia gravis.

Multiple sclerosis and myasthenia gravis are the most common autoimmune diseases affecting the nervous system, with generally a female predominance in adults. To determine the gender distribution in childhood, we reviewed 28 patients with definite multiple sclerosis and 44 patients with myasthenia gravis with onset before 16 years. In myasthenia gravis, a significant female preponderance was observed only with onset after 10 years of age; earlier disease showed no gender difference. Multiple sclerosis tended to affect boys more than girls before age 10 years and both sexes equally after this age. Gender prevalence in childhood multiple sclerosis and myasthenia gravis is different than in adult series; these results may provide insight into pathogenesis or clinical approach.

Adolescent↗
PubMedDate not supplied

[Young-onset multiple sclerosis].

INTRODUCTION: Young onset multiple sclerosis is an infrequent situation which may present with atypical symptoms and uncertain outcome. OBJECTIVE: Our aim was to assess the clinical presentation and course in young onset multiple sclerosis, and analyze eventual data which might be helpful in establishing its prognosis. PATIENTS AND METHODS: We have retrospectively reviewed the clinical protocols of 17 patients with young onset multiple sclerosis, defined as presentation of symptoms before 21 years. Diagnosis was made according to Poser's criteria including clinical features, magnetic resonance imaging, cerebrospinal fluid findings, and evoked potentials. RESULTS: The mean age at onset was 16.9 +/- 4.4 and median time to diagnosis was four weeks. The clinical course was relapsing-remitting in 76.5% and secondary progressive in 23.5%. The mean annual exacerbation rate was 1.5 +/- 0.9 and median time to second exacerbation was 12 months. The actual Expanded Disability Status Scale score is 2.6 +/- 2 after a mean disease duration of 11.4 +/- 8.0 years. The correlation between the Expanded Disability Status Scale score and the mean disease duration was the only statistically significant result. CONCLUSIONS: These results are similar to other studies, namely, age at onset did not correlate with final neurological disability. However, we must emphasize that any primary progressive form was found in our study. We conclude that in young onset multiple sclerosis, progression is not dependent on the age of onset and does not necessarily lead to an unfavorable outcome.

Adolescent↗
PubMed2004

Intravenous immunoglobulin and interferon: successful treatment of optic neuritis in pediatric multiple sclerosis.

Optic neuritis is a common clinical condition that causes loss of vision. It can be clinically isolated or can occur as one of the manifestations of multiple sclerosis. Multiple sclerosis is a severe disabling demyelinating disease of the central nervous system, which is rare among children. The treatment of optic neuritis has been investigated in several trials, the results of which have shown that corticosteroids speed up the recovery of vision without affecting the final visual outcome. Treatment of neurologic disorders with intravenous immunoglobulin is an increasing feature of our practice for an expanding range of indications, including multiple sclerosis. Owing to its anti-inflammatory properties, intravenous immunoglobulin can be beneficial in the treatment of acute relapses and in the prevention of new relapses of multiple sclerosis. To our knowledge, there is only one experience of treatment of optic neuritis with intravenous immunoglobulin in multiple sclerosis, even if therapeutic trials are used in the therapy of multiple sclerosis. We report on a girl with optic neuritis and multiple sclerosis in whom treatment with intravenous immunoglobulin at first alone and subsequently associated with interferon achieved great improvement in visual acuity.

Adjuvants, Immunologic↗
PubMed2001

Oligoclonal band number as a marker for prognosis in multiple sclerosis.

The natural course of disease in multiple sclerosis varies. Multiple sclerosis that is clinically apparent but causes minimal disability over time has been labeled benign multiple sclerosis. The ability to predict the subsequent clinical course of multiple sclerosis on the basis of clinical and other supportive data at presentation would be invaluable. In this article we report our findings based on a retrospective analysis of 1800 patients diagnosed as having multiple sclerosis, of which 44 patients met our inclusion criteria. There was a suggestion that a low or absent number of oligoclonal bands in the cerebrospinal fluid at the time of diagnosis predicts a better prognosis. However, quantification of oligoclonal bands in cerebrospinal fluid remains an insensitive prognostic indicator and must not be used to influence decisions regarding therapeutic options.

Adult↗
PubMed2005

CD30 antigen and multiple sclerosis: CD30, an important costimulatory molecule and marker of a regulatory subpopulation of dendritic cells, is involved in the maintenance of the physiological balance between TH1/TH2 immune responses and tolerance. The role of IFNbeta-1a in the treatment of multiple sclerosis.

OBJECTIVES: The immunological effect of CD30 on dendritic cells (DCs) was examined in a comparative study of patients with relapsing-remitting multiple sclerosis (RRMS). The patients were divided into two groups on the basis of interferon (IFN)beta-1a treatment: IFNbeta-1a-treated patients and untreated patients. We have already shown that CD30 is a marker of cells involved in the regulation of the balance between TH1 and TH2 immune responses and so the aim of this study was to confirm this role in DCs and, consequently, to clarify the immunopathological mechanisms of MS and the causes of immunosuppressive drug failure. METHODS: We studied network interactions between soluble (s) CD30 and TH1/TH2 cytokines in the supernatants of CD14+-derived immature DC (IDC) and DC cultures from treated and untreated patients. Network interactions between the sCD30 and cytokines in IDC and DC supernatants were also evaluated in relation to TH1/TH2 cytokine serum levels. RESULTS: Our overall results show that CD30 is expressed on IDCs and DCs, indicating an immunological role in resting and activated physiological conditions. This role would appear to be the regulation of the resting and activated physiological balance between the TH1/TH2 immune functions as abnormal increases in sCD30 levels result in impaired regulation. Further studies are undoubtedly required to clarify this situation. IFNbeta-1a treatment was found to determine a fall in sCD30 levels, leading to the restoration of the normal functional selection of IDCs from progenitor cells and the regulation of the TH1/TH2 network balance. However, IFNbeta-1a treatment may also be responsible for the in vivo suppression of CD30-mediated TH1-DC functions in immune activation. TH1-DC functions are involved in the induction of T-regulatory cells for the physiological deletion of self-aggressive cells. CONCLUSION: We conclude that CD30 is an important costimulatory molecule and marker of a regulatory subpopulation of DCs which induces and modulates immune cells involved in the maintenance of the physiological balance between TH1/TH2 immune responses and tolerance. Elucidating the mechanisms restoring DC and T-regulatory cell function could lead to more effective therapy and strategies for the prevention and treatment of immunopathological conditions such as autoimmunity, transplant rejection, allergy and tumors.

Adult↗
PubMed2004

Treatment optimization in multiple sclerosis.

The treatment of multiple sclerosis has finally become possible with the advent of the current disease-modifying therapies (DMTs) that have had a significant impact on those living with this disease. Though demonstrating clear efficacy on a number of short-term outcome measures, unfortunately, these agents are not "cures" and many patients with multiple sclerosis continue to experience disease activity in spite of treatment. Clinicians are becoming more comfortable initiating therapy with DMTs, but it is now important to focus attention on monitoring the results of the chosen therapy and deciding whether or not a patient is responding well to treatment. At present, however, clinicians lack criteria for defining optimal versus suboptimal responses to DMTs as well as evidence-based guidelines on how to improve treatment outcomes. Using a recently published model as a framework, The Canadian Multiple Sclerosis Working Group developed practical recommendations on how neurologists can assess the status of patients on DMTs and decide when it may be necessary to modify treatment in order to optimize outcomes. The Canadian Multiple Sclerosis Working Group's recommendations are based on monitoring relapses, neurological progression and MRI activity. Other possible causes of suboptimal treatment responses or treatment failure are also considered.

Decision Support Techniques↗
PubMed2001

Improved detection of differential information-processing speed deficits between two disease-course types of multiple sclerosis.

Patients with multiple sclerosis (MS) frequently demonstrate impairments of information-processing speed (IPS) on measures such as the Paced Auditory Serial Addition Test (PASAT; D. M. A. Gronwall, 1977). The authors have previously shown that their new PASAT scoring method (mean dyad score) is better correlated in comparison with more traditional PASAT scoring method(s), with magnetic resonance imaging measurement of the total area (mm2) of white-matter sclerotic lesions (P. J. Snyder & J. C. Cappelleri, 2001). The present study reports that the mean dyad score discriminated 20 relapsing-remitting MS (RRMS) patients from 15 secondary-progressive MS (SPMS) patients noticeably better than did the standard scoring method(s). Mean dyad scores < 4.13 classified patients as having SPMS with 73% accuracy (sensitivity), whereas scores > or = 4.13 classified patients as having RRMS with 80% accuracy (specificity).

Adult↗
PubMed2003

Impact of clinical nurse specialists in multiple sclerosis--synthesis of the evidence.

BACKGROUND: Multiple sclerosis is a chronic neurological condition demanding a broad range of interventions and support. Multiple sclerosis nurse specialists are emerging as a leading force in providing care to this group of patients. AIM: This review aimed to identify and synthesize the evidence on the role of clinical nurse specialists in meeting the care needs of people with multiple sclerosis. METHODS: A systematic review of the literature addressing the role of the multiple sclerosis nurse specialist was undertaken. The review examined both the appropriateness and effectiveness of the multiple sclerosis nurse specialist role. The content of each item identified in the review was analysed, examining the structure, process and outcomes variables associated with the role. Materials containing an explicit methodology were critically appraised using established schedules and graded as strong, moderate or weak. The data were then synthesized in tables, thematically and using a quasi-judicial approach called the 'System of Reasoning'. FINDINGS: Fifty-five items were examined and most (53%; n = 18) were descriptive in nature. There was insufficient evidence to demonstrate that the multiple sclerosis nurse role makes a difference to care. However, evidence was found to support current descriptions of the role - meaning? and there appeared to be a good fit between the role and the care needs of people with multiple sclerosis. CONCLUSION: A systematic overview of the attributes of the multiple sclerosis nurse role is provided which should help service providers, nurses and other professionals consider how multiple sclerosis nurse specialists roles can contribute to the care of people with this condition. While there is little current evidence of effectiveness for the multiple sclerosis nurse specialist role, there is evidence for its appropriateness, although more rigorous primary research is required to test this.

Humans↗
PubMed1979

Increased frequency of HLA--DRw2 and DRw3 in multiple sclerosis.

Previous studies of multiple sclerosis patients showed the existence of a positive association between multiple sclerosis and HLA--A3 and --B7, as well as a negative association with B12. These observations have been confirmed. In addition, a more marked association has been observed with two recently identified B-cell antigens, DRw2 and DRw3, closely related to the HLA--D locus. The presence of cold lymphocytotoxic antibodies was found to bear no relationship with those two specificities. These results suggest that two genes of the HLA--DR region may play a role in the pathogenesis of multiple sclerosis.

Epitopes↗
PubMed1978

[HLA-DRW antigens and multiple sclerosis].

Previous studies of multiple sclerosis patients showed the existence of a positive association between multiple sclerosis and HLA-A3 and B7, as well as a negative association with B12, These observations have been confirmed. In addition, a more marked association has been observed with two recently identified B-cell antigens, DRW2 and DRW3, closely related to HLA-D locus. The presence of cold lymphocytotoxic antibodies was found to bear no relationship with those two specificities. These results suggest that two genes of the HLA-DR region may play a role in the pathogenesis of multiple sclerosis.

Adolescent↗