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PubMed1990

The Second Canadian Conference on Multiple Sclerosis.

The epidemiology of multiple sclerosis (MS) and the planning and i interpretation of clinical therapeutic trials were the subjects of a symposium on MS held on June 13, 1989. Several speakers addressed whether MS is a genetic or an environmental disease. An environmental trigger would resolve the relatively low penetrance of the disease in susceptible individuals, although the alternative hypothesis that MS is a multigenic disease would also account for this observation. Clinical trials have to date failed to confirm the efficacy of any immunosuppressive or other agent in the management of progressive MS. Magnetic resonance imaging (MRI) appears to be highly sensitive for monitoring the activity of MS. Preliminary evidence suggests that MRI activity correlates with longitudinal clinical assessments of disability. Immunologic tests, while valuable in determining pathophysiology of MS, have not been strongly correlated with clinical outcome.

Humans↗

PubMed2005

Spinal and cranial hypertrophic neuropathy in multiple sclerosis.

Two patients with multiple sclerosis developed symptomatic chronic inflammatory demyelinating polyneuropathy with massive spinal or cranial nerve hypertrophy revealed by neuroimaging. Sural nerve biopsy in one showed only moderate demyelination, axonal loss, and onion-bulb formation, illustrating dichotomy between severe proximal and milder distal nerve involvement. Patients with coexistent central and peripheral demyelination usually are symptomatic from dysfunction at one site or the other, but not from both. Our patients showed minimal response to steroids, intravenous immunoglobulin, or azathioprine. These cases suggest that the mechanism of disease in symptomatic central and peripheral demyelination may differ from that of disease in only one region, and that optimal therapy in this situation must be explored further.

Adult↗

PubMed1996

[Modern diagnostic methods in multiple sclerosis].

161 patients with multiple sclerosis were observed according to C. M. Poser's scale. The diagnosis was definite in 73.9% of cases, probable--in 14.9% and doubtful in 11.2% of patients. The diagnostic significance of magnetic resonance tomography (MRT) was estimated as well as of visual evoked potentials (VEPs), mid-latency auditory evoked potentials (MAEPs), viscocontrastoperimetry and pallesthesiometry (vibratory sensation). MRT revealed alterations in 80.3% of 71 cases (97.5% at definite diagnosis). The results of investigation of evoked potentials differed from normal values: VEPs in 100%, MAEPs in 72.6% of 26 patients observed. Visocontrastoperimetry revealed disorders in 75,2% of 113 cases, pallesthesiometry in toes--in 100%, in fingers--in 68.9% of 116 patients observed.

Adult↗

PubMed2000

The prognostic value of age, gender, pregnancy and endocrine factors in multiple sclerosis.

The evolution of multiple sclerosis at the time of diagnosis remains unpredictable since a reliable prognostic marker is not yet available. Nevertheless, a series of useful prognostic indicators have been singled out from epidemiological studies. Young age at onset, female gender, relapsing/remitting course, and sensitive or visual disturbances as initial symptoms are considered favourable prognostic factors. Conversely, late age at onset, male gender, progressive course, and pyramidal or cerebellar symptoms at the first episode predict an unfavourable evolution. Another prognostic indicator has been recognized in pregnancy: although the overall effect of pregnancy on short-term MS course is neutral, in the long-term it seems to protect from disease progression. Most prognostic indicators seem to act through the neuro-endocrine-immune network, modulating the immune response in the context of the Th1/Th2 paradigm.

Adult↗

PubMed2003

A whole genome screen for association with multiple sclerosis in Portuguese patients.

Multiple sclerosis (MS) is common in Europe affecting up to 1:500 people. In an effort to identify genes influencing susceptibility to the disease, we have performed a population-based whole genome screen for association. In this study, 6000 microsatellite markers were typed in separately pooled DNA samples from MS patients (n=188) and matched controls (n=188). Interpretable data was obtained from 4661 of these markers. Refining analysis of the most promising markers identified 10 showing potential evidence for association.

Adolescent↗

PubMed1996

T-cell receptor alpha, beta, gamma, and delta chain gene microsatellites show no association with multiple sclerosis.

Genetic predisposition to multiple sclerosis (MS) is determined, in part, by certain HLA genotypes, but the contribution of T-cell receptor (TCR) germline polymorphisms to MS susceptibility is less clear. Reports of disease associations with restriction fragment length polymorphisms of TCR alpha and beta chain genes have been difficult to confirm, and little data is available on the influence of the TCR gamma delta germline in MS. We investigated the TCR alpha, beta, gamma, and delta chain genes of Northern Irish patients with MS using four microsatellite markers of high heterozygosity. There were similar allele frequencies in patients and controls for all microsatellites studied. We conclude there is no convincing evidence for an association of MS with TCR alpha, beta, gamma, and delta chain gene polymorphisms.

Alleles↗

PubMedDate not supplied

Information for young people when multiple sclerosis enters the family.

Multiple sclerosis (MS) typically affects people aged 20-40 years and, by its very nature, is characterized by unpredictability, uncertainty and variability, and is therefore bound to have an impact on children who have a parent with MS. There has been little work done to assess the needs of young people living with MS in their family. A series of workshops specifically aimed at 9-14-year-olds who have a parent with MS have been successfully conducted. This article reviews the background to setting up the workshop and identifies implications for future MS specialist nurses to help this potentially vulnerable group of people. By breaking the silence and talking about MS with young people, the myths can be removed and the anxieties reduced.

Adaptation, Psychological↗

PubMed1986

Comparison of T8+ cell-mediated suppressor and cytotoxic functions in multiple sclerosis.

Patients with progressive multiple sclerosis (MS) and controls were compared with regard to: (a) in vitro pokeweed mitogen (pwm)-induced IgG secretion, as an indirect measure of T8+ cell-mediated suppressor function; (b) alloantigen-directed cytotoxic activity, a predominantly T8+ cell-mediated function. The MS group had increased IgG secretion (4790 +/- 372 ng/ml vs. 1866 +/- 233 ng/ml, P less than 0.001) compared to controls. In contrast, alloantigen-directed cytotoxic activity did not differ between MS and control groups. These results suggest a selective defect of suppressor cell function in MS rather than a generalized dysfunction of T8+ cells. Defective immunoregulatory control coupled with preserved effector functions may contribute to the autoimmune process, suspected to underlie the pathogenesis of MS.

Adult↗

PubMed1996

Primary progressive multiple sclerosis: a distinct syndrome?

Multiple sclerosis (MS) has long been recognised to have both a relapsing-remitting and progressive course. More recently patients with progressive disease have been further sub-divided into those with a progressive course from onset (primary progressive MS) and those with progressive decline following an initially relapsing-remitting period (secondary progressive MS). Diversity in MS may not however be restricted to clinical course. There is growing evidence that the subgroups of MS also differ with respect to clinical features, epidemiology, pathogenesis, genetics and neuroimaging appearances. In this review we outline the criteria variously applied in the classification of MS patients, addressing the need for a clear nomenclature. We evaluate the proposition that primary progressive MS has a profile distinct from other MS categories, contrasting the separate differential diagnoses and examining the implications for future therapeutic trials.

Disease Progression↗

PubMed2003

[Alpha]B-crystallin genotype has impact on the multiple sclerosis phenotype.

BACKGROUND: Both multiple sclerosis (MS) susceptibility and MS clinical phenotype are in part genetically determined. [Alpha]B-crystallin is a candidate autoantigen in MS, and there are three polymorphisms in the promoter region of the encoding gene (CRYAB): at positions -C249G, -C650G, and -A652G. METHODS: These polymorphisms were studied in sporadic cases of MS, assessing disease susceptibility, clinical phenotype, and MRI appearance. RESULTS: The CRYAB polymorphisms influenced susceptibility as well as disease expression in MS. CONCLUSION: Carriers of the rare allele CRYAB-650*C had an increased likelihood of a noninflammatory, neurodegenerative phenotype characterized by a relatively rapid, primary progressive clinical disease course.

Adult↗

PubMed2006

Fluoxetine increases cerebral white matter NAA/Cr ratio in patients with multiple sclerosis.

Axonal degeneration in multiple sclerosis (MS) may be caused by mitochondrial dysfunction and is associated with decreased levels of N-acetylaspartate (NAA) as measured with 1H-magnetic resonance spectroscopy (MRS). Fluoxetine stimulates astrocytic glycogenolysis, which serves as an energy source for axons. Eleven patients with MS received fluoxetine orally 20 mg a day during the first week, and 40 mg a day during the second week. The mean NAA/Creatine ratio in cerebral white matter of the MS patients increased from 1.77 at baseline to 1.84 at the end of the second week (p=0.007). These findings show evidence for a reversible axonal dysfunction in patients with MS and provide a rationale for investigating whether fluoxetine has neuroprotective effects in MS.

Administration, Oral↗

PubMed1994

Repeated treatment with chimeric anti-CD4 antibody in multiple sclerosis.

We treated 21 multiple sclerosis patients with two to four doses of cM-T412, a chimeric monoclonal antibody against the CD4 antigen found on helper/inducer T lymphocytes. The mean number (+/- standard error) of circulating CD4 lymphocytes decreased from 888 (+/- 81) cells/mm3 at baseline to 246 (+/- 18) after treatment. At 1 year after the last treatment, the CD4 count had recovered to only 335 (+/- 32). The antibody had no effect on CD8 lymphocytes, B lymphocytes, or other leukocytes. Side effects were minimal. Despite the prolonged depletion of CD4 lymphocytes, no opportunistic infections occurred. Only 1 patient had a possible allergic reaction. Most patients were clinically stable, but a few progressed. We conclude that repeated treatment with cM-T412 is effective in reducing the number of circulating CD4 lymphocytes and has no limiting side effects.

Adult↗

PubMed2004

Waldenström's macroglobulinemia developing in a patient with multiple sclerosis: coincidence or association?

Multiple sclerosis (MS) has been reported in association with haematological abnormalities, including monoclonal gammopathies. We present a 54-year-old male patient with a 30-year history of MS who was admitted to our hospital for investigation of anaemia and increased erythrocyte sedimentation rate. A monoclonal IgM protein was detected by serum protein immunofixation, while bone marrow biopsy indicated a 70% infiltration by small lymphoplasmacytoid cells, in the context of a lymphoplasmacytoid immunocytoma, findings compatible to the diagnosis of Waldenström's macroglobulinemia (WM). To our knowledge, this is the first report of WM in a patient with MS. Further to the coexistence of the two diseases observed in the case presented here, there is additional evidence suggesting that the association of MS with plasma cell dyscrasias may not be coincidental.

Bone Marrow↗

PubMed1990

HLA antigens and multiple sclerosis in Northern Ireland.

Multiple sclerosis has been shown to be associated with the presence of certain major histocompatibility (MHC) tissue antigens which are coded on chromosome 6. There are racial differences in the antigens associated with MS. The strength of the associations vary in different communities in Western Europe. We have investigated the association between MS and MCH antigens in Northern Ireland in a group of 104 patients. There is a particularly strong association between MS and HLA-DR2, 65.4% compared with 25.5% in 184 controls. A weaker association has been demonstrated with HLA-A3 (44.2% vs 26.5% in controls). There have been conflicting reports concerning an association of HLA-DW2 and HLA-DR2 with a rapidly progressive form of MS. Our data do not support that hypothesis.

Activities of Daily Living↗

PubMed1976

Pilot study with antilymphocyte globulin in the treatment of multiple sclerosis.

Twenty patients with multiple sclerosis, in whom treatment with azathioprine and steroids had not altered the progression of the disease, were given additional treatment with either antilymphocyte globulin (ALG) (seven patients), thoracic duct drainage (TDD) (five patients) or a combination of both (eight patients). Four of the seven patients treated with the addition of ALG showed remarkable improvement which has lasted little improvement. In the eight patients receiving both had severe allergic reactions to ALG which prevented adequate dosage. TDD alone was performed in patients sensitive to ALG. These five patients showed little improvement. In the eight patients receiving both ALG and TDD there was marked improvement in four patients which has again lasted several years. The main side effect of ALG therapy is allergic reactions. Major infections or tumour formation did not occur in any patients.

Antilymphocyte Serum↗

PubMed2002

Human herpesvirus 6 and Chlamydia pneumoniae as etiologic agents in multiple sclerosis - a critical review.

Multiple sclerosis (MS) is thought by many investigators to have an infectious component, and several microorganisms have been associated with the disease during the last three decades. Recent studies have implicated both human herpesvirus 6 (HHV-6) and the obligate intracellular bacterium Chlamydia pneumoniae in the etiology of MS. As with earlier studies of other potential agents, however, evidence linking either of these organisms to the disease is equivocal. In this article, we review data for and against involvement of HHV-6 and C. pneumoniae in MS, as well as evidence concerning auxiliary factors, such as possession of the APOE epsilon4 allele, which may influence the role of these organisms in pathogenesis. Further, we suggest several lines of investigation that should clarify whether either or both pathogens are associated meaningfully with this disease.

Antigens, Viral↗

PubMed1985

HLA-DR-dependent variation of intrathecal IgG1 (Gm) allotype synthesis in multiple sclerosis.

Genetic susceptibility to multiple sclerosis (MS) in Caucasians was previously shown to be correlated to the presence of given alleles at the HLA-DR and Gm loci. We now demonstrate that the humoral immune response in MS central nervous system (CNS) is modulated by both loci: the levels of IgG1 subclass and IgG1 allotypes in cerebrospinal fluid of MS patients depend on both their Gm genotype and their HLA-DR2 or HLA-DR7 phenotype. That HLA-DR molecules may either participate in a preferential recruitment of IgG1 allotype-producing B cells in MS CNS or act after such a selective homing is discussed. These results demonstrate that both HLA and Gm loci are synergistically involved in the modulation of the humoral immune response.

Disease Susceptibility↗

PubMed1999

Eating patterns in women with multiple sclerosis.

For persons with multiple sclerosis (MS), good nutrition has the potential to enhance quality of life and reduce the risk of lifestyle diseases and secondary conditions. The purpose of this study was to describe nutritional intake of women with MS and to determine what factors influenced their intake. Based on 3-day food diary data, participants had an inadequate intake (< 10% lower than recommended) of carbohydrates, dietary fiber, vitamin E, calcium and zinc. In contrast, they consumed saturated fat, protein, vitamin A, vitamin C, folate and iron at higher levels than recommended. Age was significantly related to nutritional intake with older women consuming fewer calories, total fat and saturated fat. Despite evidence supporting the importance of following recommended nutritional guidelines, nutritional intake for participants in this study was not optimum in many important areas. This study supports the need for interventions to promote good nutrition among persons with MS.

Adult↗