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Results for “SCLEROSIS, MULTIPLE”

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PubMed2001

Human herpesvirus 6 in the pathogenesis of multiple sclerosis.

Multiple sclerosis (MS) is one of the most common disabling neurological diseases affecting young adults. It is a chronic disease characterised by inflammation and demyelination. The aetiology of MS is still unknown, but involvement of viruses has been suspected for many years. Recently much interest has focused on human herpesvirus 6 (HHV-6), since the virus has been detected in MS plaques in the brain and patients with MS have been shown to have an aberrant immune response to HHV-6. Results from different studies are, however, conflicting and in the light of the long list of previous claims to have found the viral aetiology of MS it is necessary to interpret the HHV-6 findings with great caution. Possible mechanisms for virally induced demyelination and autoimmunity are discussed in this review, and the evidence for and against a role for HHV-6 in MS is summarised.

Antigens, CD↗

PubMed1991

No association with germline T cell receptor beta-chain gene alleles or haplotypes in Swedish patients with multiple sclerosis.

Multiple sclerosis (MS) has been reported to be associated with restriction fragment length polymorphism (RFLP)-defined alleles of the T cell receptor (TcR) alpha- and beta-chain genes. One hundred patients with MS, 23 with primarily chronic progressive MS and 77 with relapsing/remitting MS, as well as 100 controls were investigated with RFLP analysis of the V beta 8, V beta 11 and C beta TcR gene segments. No association was found with allelic patterns or, contrary to a previous report (Beall et al. (1989) J. Neuroimmunol. 21, 59-66), TcR beta-chain gene haplotypes. Subgrouping of patients according to clinical form of disease or MS-associated HLA class II alleles also failed to show associations to TcR beta-chain RFLPs. Thus, our results fail to confirm that TcR beta-chain gene haplotypes confer susceptibility to MS.

Gene Rearrangement, beta-Chain T-Cell Antigen Rece↗

PubMed2006

Immunopathogenesis and immunotherapy of multiple sclerosis.

Multiple sclerosis (MS) is a chronic disease of the CNS that is characterized by inflammation, demyelination and axonal injury. Although the etiology of MS is still unknown, many findings point toward a central role for the immune system in the pathogenesis of the disease. This hypothesis is strongly supported by the beneficial effects of immunomodulatory and immunosuppressive therapy on disease activity. Over the past few years, substantial progress has been made in deciphering the immune response in MS. Although animal models have advanced our knowledge of basic mechanisms of immune responses in the CNS, recent studies have also highlighted the differences between MS and its animal equivalent, experimental autoimmune encephalomyelitis. New immunotherapeutic agents have been developed and evaluated in clinical trials. Here, we review current knowledge of the immunopathogenesis of MS and corresponding animal models of disease, and discuss new immunointerventional treatment strategies based on changing pathogenetic concepts.

Animals↗

PubMed1999

[Autotransplantation of hematopoietic progenitor cells in multiple sclerosis].

Multiple sclerosis (MS) is an autoimmune demyelinating disease exhibiting great clinical variability. For control of its primary and secondary progressive variants, treatment has met with limited success. In recent years, increasing experience has been gained with the administration of high dose chemotherapy supported by the autologous infusion of hematopoietic progenitor cells (HPC), in some instances depleted of T cells. The European and International Registry of Hematopoietic Cell Transplantation for Autoimmune Diseases include 43 MS patients. BEAM was the most frequently used conditioning therapy. Treatment related mortality was 7%. The actuarial disease free survival and the overall projected survival at 38 months were 85% and 90% respectively. The inclusion of an increasing number of MS patients into these treatment programs and the growing submission of cases to the Registries will provide useful information to determine if the initial enthusiasm generated by this approach for the control of primary and secondary progressive forms of MS is justified.

Hematopoietic Stem Cell Transplantation↗

PubMed1998

A retrospective review of patients with clinically definite multiple sclerosis.

Multiple sclerosis (MS) is an uncommon disease in Singapore. We retrospectively reviewed our experience from a large single medical institution to identify prominent clinical features and forms of this disease. Of the 21 patients entered into the study, 10 patients developed optic-spinal symptoms over the course of their illness. None of these patients with optic-spinal symptoms had Devic's disease. Unusual clinical manifestations included paroxysmal symptoms either at presentation or during the course of their illness in 3 patients. While cerebrospinal fluid oligoclonal bands were present in only 4 patients, the majority of patients had abnormal neurophysiology and neuroimaging studies. Due to the presence of autoimmune markers in a significant number of cases, we recommend that as part of the initial evaluation for MS, an underlying collagen vascular disorder should be excluded.

Adolescent↗

PubMed2001

Infection and the etiology and pathogenesis of multiple sclerosis.

Multiple sclerosis (MS) currently defies clinical and scientific definitions, and carries a prognosis that remains practically unchanged despite many years of intensive research. Although the prevailing dogma is that MS is an immune-mediated condition, it fulfills none of the criteria of an autoimmune disease. On the other hand, there is enough significant data to suggest that infectious agents(s) could be involved in either direct damage to the white matter or induce inflammatory responses that secondarily affect the brain. Our goal here is to review the data supporting the possibility that infection has a critical role in the disease, examine the list of potential candidates that have been suggested, and outline an approach regarding the potential role of infectious agents in the etiology and pathogenesis of MS.

Adult↗

PubMed2005

Diagnosis and disease modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) refers to scattered areas of hardening found on sectioning central nervous system tissue of affected people, usually after many years of illness. It rarely causes early death but is the commonest cause of neurological disability among young people. Overall results from controlled trials over the past 50 years have been rather disappointing but the comparatively recent licensing of drugs such as interferon beta and glatiramer acetate has led to a reappraisal of many aspects of MS. There are now new diagnostic criteria, which encompass developments in magnetic resonance imaging. Older clinical methods of measuring disease impact are now being re-evaluated to facilitate clinical trials of the approximate 150 new products currently being developed as potential disease modifying agents. The success and failure of agents that should be effective on theoretical grounds, together with advances in neuropathology, have led to fundamental questions regarding our basic understanding of disease pathogenesis being re-addressed.

Adjuvants, Immunologic↗

PubMed2005

Drug insight: using monoclonal antibodies to treat multiple sclerosis.

Multiple sclerosis (MS) is an immunopathological, presumably autoimmune, disease of the CNS. Several immunomodulatory treatments, including various preparations of interferon-beta, glatiramer acetate and mitoxantrone, have been approved for MS therapy. Because these agents are only partially effective, the search for better therapies continues. Therapeutic monoclonal antibodies (mAbs), a class of biotechnological agents, allow the precise targeting of molecules involved in pathological processes. Therapeutic mAbs have shown much promise in the treatment of many disorders, including inflammatory and putative autoimmune diseases such as MS. These agents have intrinsic limitations, however, such as induction of neutralizing 'anti-antibodies', systemic inflammatory reactions and severe adverse effects, some of which remain to be explained. Most notably, natalizumab (Tysabri), a mAb against alpha4 integrin, was very effective in suppressing MS activity, but had to be withdrawn from the market because several treated patients developed progressive multifocal leukoencephalopathy. This article reviews the state of development of various therapeutic mAbs for MS treatment.

Animals↗

PubMed2003

Beta-2 microglobulin and neopterin as markers of disease activity in multiple sclerosis.

Multiple sclerosis (MS) is a predominately T helper 1-mediated autoimmune disease of the central nervous system. Magnetic resonance imaging (MRI) is the most useful tool for monitoring disease activity and progression. However, MRI is an expensive and time-consuming test. Therefore, the ability to measure biological markers in body fluids correlating with MRI disease activity is of great importance. Beta-2 microglobulin (beta2-MG) and neopterin have been found to correlate with disease activity in several autoimmune disorders and are used as pharmacodynamic markers of interferon beta treatment in MS. During the natural course of MS, beta2-MG is stable over time, and thus it is unlikely that monitoring its plasma levels will be a useful marker of disease changes. More controversial results have been found for neopterin evaluations in MS. Urinary excretion of neopterin is higher during a clinical relapse but blood levels of this molecule do not correlate with clinical and MRI measurements.

Biomarkers↗

PubMed2000

Mitochondrial mutations of Leber's hereditary optic neuropathy: a risk factor for multiple sclerosis.

Multiple sclerosis (MS) and Leber's hereditary optic neuropathy (LHON) have been found to occur in combination. Based on an extensive literature search and on a clinical analysis of 55 LHON pedigrees (103 patients) and 40 patients with definite MS, this study concludes that the association of LHON and MS is more than a coincidence, and that carrying a primary LHON mutation is a risk factor for developing MS. All three primary LHON mutations occurring in the European and North American populations have been found to be associated with an MS-like syndrome. The neurological characteristics of MS associated with LHON are indistinguishable from those of MS in general, but the severe and bilateral visual symptoms and signs justify considering these patients as a clinical subgroup of MS and screening them for LHON mutations. However, screening LHON patients for MS appears to be more rewarding.

Adult↗

PubMed1993

Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis.

Multiple sclerosis (MS) is thought to be an autoimmune disease mediated by T lymphocytes that recognize myelin components of the central nervous system. In a 1-year double-blind study, 30 individuals with relapsing-remitting MS received daily capsules of bovine myelin or a control protein to determine the effect of oral tolerization to myelin antigens on the disease. Six of 15 individuals in the myelin-treated group had at least one major exacerbation; 12 or 15 had an attack in the control group. T cells reactive with myelin basic protein were reduced in the myelin-treated group. No toxicity or side effects were noted. Although conclusions about efficacy cannot be drawn from these data, they open an area of investigation for MS and other autoimmune diseases.

Adult↗

PubMed1988

Autoimmunity in multiple sclerosis.

Multiple sclerosis reportedly coexists with disorders of autoimmune origin. The prevalence with which such disorders occur in the MS population has not been adequately investigated. We reviewed the medical records of 828 patients with definite MS and found that 4.8% had a past or present associated disorder in which autoimmune mechanisms presumably play a role. The cumulative prevalence of these disorders was no higher than that estimated for the general population. Serum from 105 patients, without clinical evidence of an associated autoimmune disorder, was tested for the presence of antinuclear, thyroid, parietal cell, smooth muscle, and mitochondrial antibodies. A significantly higher prevalence (p less than 0.01) of generally low titers of one or more autoantibodies was found in serum from the MS group, compared with a control group of 105 patients with other neurologic disorders. The increased frequency of serum autoantibodies probably reflects the existence of a nonspecific B cell overactivity in MS.

Adolescent↗

PubMed2002

Multiple sclerosis.

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system (CNS). Diagnosis rests upon identifying typical clinical symptoms and interpreting supportive laboratory and radiological investigations. The etiology is unknown; however, strong evidence suggests that MS is an autoimmune disease directed against CNS myelin or oligodendrocytes. Genetic factors are important in the development of MS. Contributing environmental determinants (possibly including infectious agents) appear important but remain unidentified. Both cell-mediated and humorally mediated immune mechanisms contribute to pathological injury. Axonal damage occurs in addition to demyelination and may be the cause of later permanent disability. Distinct pathological subtypes may differentiate among patients with MS. Treatment is directed at acute attacks (with corticosteroids) and reduction of attack frequency (primarily with type-1 beta interferons and glatiramer acetate). Research into the causes and treatments of MS has expanded our knowledge of this disease and promises improved care for MS patients in the future.

Atrophy↗

PubMed2006

Interferon after 10 years in patients with multiple sclerosis.

Multiple sclerosis (MS) is a life-long disease that typically affects young adults. The introduction of disease-modifying therapy has changed the clinical and social burden of the disease. Safety, tolerability and efficacy profiles of Interferon beta (IFNbeta) therapy in MS have been widely highlighted both in trial settings and in daily clinical practice. However, there is a relative lack of information on the long-term period: all pivotal trials must be considered short-term in a disease with an average duration of 30-40 years and post-marketing studies suffer from some limitations. Moreover, current available IFNbeta preparations are only partially effective and are difficult to administer, which has led to poor patient compliance. Over the treatment period, a problem could be the development of neutralising antibodies (NAbs) against the drug, which have been related to lessening treatment benefits. Despite these restrictions, IFNbeta still remains the first choice treatment in MS.

Antibodies↗

PubMed2000

Methodological problems in evaluating efficacy of a treatment in multiple sclerosis.

Multiple sclerosis is currently an incurable disease and there is much interest in developing new disease-modifying treatments and testing them in clinical trials. Because therapies are essentially partially effective, neurologists have to develop ways to assess whether the medication they test slows down the course of the disease. Promising treatments selected for Phase III clinical trials are first tested in Phase I/II studies, where preliminary evidence of efficacy is demonstrated in the absence of severe adverse events. Phase III clinical trials are designed to detect significant differences between responses to active therapies and a placebo or a marketed drug. The selection and usage of instruments to detect changes in patients is probably the most important issue in their design. The purpose of this paper is to discuss methodological problems of evaluating drug efficacy in phase III MS trials, including the characteristics of the ideal instrument to measure progression of the disease, the strengths and limitations of existing clinical, radiologic and laboratory outcome measures.

Clinical Trials as Topic↗

PubMed2001

A pathogenic role for myelin-specific CD8(+) T cells in a model for multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) characterized by plaques of infiltrating CD4(+) and CD8(+) T cells. Studies of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, focus on the contribution of CD4(+) myelin-specific T cells. The role of CD8(+) myelin-specific T cells in mediating EAE or MS has not been described previously. Here, we demonstrate that myelin-specific CD8(+) T cells induce severe CNS autoimmunity in mice. The pathology and clinical symptoms in CD8(+) T cell-mediated CNS autoimmunity demonstrate similarities to MS not seen in myelin-specific CD4(+) T cell-mediated EAE. These data suggest that myelin-specific CD8(+) T cells could function as effector cells in the pathogenesis of MS.

Adoptive Transfer↗

PubMed1993

Polyomavirus models of brain infection and the pathogenesis of multiple sclerosis.

Multiple sclerosis (MS) is generally considered to be an autoimmune disorder with myelin as the target and with several unidentified viruses playing ancillary roles, possibly through molecular mimicry. Although this paradigm has led to important progress on potential mechanisms of myelin loss, neither a target antigen in myelin nor a triggering mechanism has yet been identified, leaving the etiology of MS still unknown. Animal models of viral demyelination and studies showing that JC virus (JCV), the polyomavirus which causes progressive multifocal leukoencephalopathy (PML), may be latent in some normal human brains suggest another possibility. A host immune response targeting proteins expressed at low levels from viral DNA latent in the central nervous system (CNS) might underlie a focal demyelinating disease such as MS. A shift from autoimmunity to a latent-virus model is not a trivial substitution of target antigens. This shift would expand the search for a definitive laboratory test for MS and could lead to improved therapeutic and preventive approaches.

Animals↗

PubMedDate not supplied

Management of patients who have relapses in multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurological condition, which disrupts the typical functions and daily activities of those affected. Approximately 80% of those diagnosed will follow a relapsing/remitting disease course at diagnosis. Patients with relapsing/remitting MS can expect to have episodes of relapse or an exacerbation of the disease and its variety of symptoms. Management of such episodes has always been open to the preferences of the healthcare professionals involved. The aim of this article is to review the evidence that exists to support current practice in the management of patients during a relapse and to evaluate how this evidence can be incorporated into patient care. The article begins by giving an overview of MS, and continues by determining what a relapse is and discussing the speculated triggers of relapse. Methods of treating relapse are then explored. It concludes by highlighting the strongest evidence-based method for treating relapses, and by emphasizing the need for further research into the pharmaceutical and non-pharmaceutical management of MS relapses.

Adrenal Cortex Hormones↗