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PubMed2003

Emerging disease modifying therapies for multiple sclerosis.

Multiple sclerosis (MS), the most common central nervous system (CNS) demyelinating disease, is thought to be mediated in part by CNS autoantigen-specific T cells. The aetiology of the disease is unclear, but includes genetic and environmental factors. The disease onset often occurs in young adults and is characterised by bouts of neurological symptoms such as numbness, weakness, imbalance or visual difficulties that may not be recovered from. Sometimes the course is more progressive. Since the disease can be disabling, several treatments have been developed that reduce the risk of relapse and progression of sustained disability. Although earlier treatment is encouraged, currently approved disease modifying therapies for MS are only partially effective, administered parenterally and associated with significant side effects and potential toxicities. Therefore, many promising new therapies are under development that target various goals, including immunosuppression, immunomodulation, cell traffic through the blood-brain barrier (BBB), neuroprotection and enhancement of CNS repair.

Adjuvants, Immunologic↗

PubMed2000

Early onset multiple sclerosis.

Multiple sclerosis (MS) onset is usually in adult life (age 20-40 years). Discordant data have been reported concerning the frequency of early onset MS (EOMS) that ranges from 2.7% to 5%, whereas there is a general agreement on prevalence of female sex, particularly after puberty. The initial symptoms in EOMS are frequently characterized by visual loss whereas the other functional systems are involved with a variable frequency. Literature data show that EOMS tends to have a relapsing-remitting course, a high rate of recovery from the initial attack, a long time interval between the first and second attacks and a slow progression rate. A poor prognosis is reported in a few cases of EOMS and seems to be related to number of relapses and to the delay between the first and second attacks.

Adolescent↗

PubMed2000

Viruses and multiple sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system whose cause is still unknown. Many findings suggest an infectious etiology or, at least, that infectious agents in association with host genetic factors may play a role in the pathogenesis of this disease. Accumulating data, including animal models, human models of virus induced demyelination, epidemiologic, and laboratory findings, demonstrate that viruses and host genetic factors can interact to cause immune-mediated demyelination. While many viruses have been postulated as a possible cause of MS, to date, no "MS virus" has been definitively shown to be associated with this disease. Alternatively, ubiquitous viruses are being considered as the environmental "triggers" that have been postulated to be involved in the MS disease process. We will focus on recent studies with human herpesvirus 6 and MS as how a common virus may be associated with this disorder in a subset of infected individuals.

Animals↗

PubMed1990

High-resolution NMR spectroscopy of cerebral white matter in multiple sclerosis.

Multiple sclerosis (MS) lesions have been shown by conventional methods to have major alterations in water and myelin lipid contents. To characterize these abnormalities more efficiently, NMR spectroscopy was used to evaluate water content by measuring relaxation times at 0.5 and 2.0 T. Subsequently, cholesterol content was obtained by using 1H NMR spectroscopy, while 31P NMR spectroscopy allowed measurement of the four main phospholipids and the inorganic phosphate concentrations in normal and pathological cerebral white matter samples. The relaxation times were significantly prolonged in MS lesions relative to normal white matter. Measured in different sample types, T1 and T2 times increased with water content. Moreover, the T2 of normal-appearing white matter was considerably lengthened. Analysis of white matter lipid composition using this method gave accurate values, which showed a significant decrease in phospholipids and cholesterol content in MS samples.

Body Water↗

PubMed2004

A putative role for Toxocara species in the aetiology of multiple sclerosis.

Multiple sclerosis (MS) is a disease of unknown aetiology. The finding of monoclonal antibodies in MS has been attributed to various infectious agents. Nematodes, such as Toxocara species have not been explored as possible aetiologic agents of MS. Some epidemiological studies have found an association between exposure to stress and household pets prior to the diagnosis of MS. In a case known to the authors, slight malaise and eosinophilia in peripheral blood preceded the diagnosis of MS by one year in a middle-aged man who lived in rural surroundings with cats in the household. The ubiquitary parasite Toxocara catis or canis is prevalent and serum antibodies are found regularly in populations examined. It is able to develop into the larval stage in human beings. The hypothesis presented here is that MS could be initiated by such infections in previously unexposed subjects under conditions of long-term stress.

Animals↗

PubMed2002

Sex differences in cognitive impairment in multiple sclerosis.

Multiple sclerosis (MS) is twice as prevalent in females as in males, but the possibility of sex differences in the cognitive sequellae of the disease has not been considered. In this study male patients with MS performed more poorly than female patients on tests of verbal and nonverbal memory, visuospatial construction, and on the Mini Mental State Exam (MMSE) and the Wisconsin Card Sorting Test (WCST). The groups of male and female patients were similar in age, education, and on several measures of neurologic and emotional disturbance. Among normals there are no sex differences on the MMSE and WCST. Sex differences on the memory and visuospatial construction tests were larger in magnitude for the patients than for normal controls, implying that male patients are somehow especially vulnerable to cognitive deficits. Reanalysis of existing databases could clarify questions about the existence and source of cognitive sex differences in MS.

Cognition Disorders↗

PubMed2005

Inflammatory demyelination is not central to the pathogenesis of multiple sclerosis.

Multiple sclerosis is a disease of the central nervous system that destroys myelin, oligodendrocytes, neurons and axons. Historically considered to be caused by an autoimmune process mainly affecting myelin and oligodendrocytes in the white matter, recent data provide evidence that a generalized, diffuse neurodegenerative process plays an important role in the pathogenesis of MS. There is a high density of axonal transections in active demyelinating lesions, but also persistent low-level axonal damage in inactive plaques and diffuse axonal and neuronal loss throughout the nervous system. Initial axonal injury appears to be closely related to inflammation, but is not restricted to the lesions themselves. Damage may be propagated throughout the nervous system by anterograde Wallerian, retrograde or transynaptic degeneration. Cumulative tissue loss in the grey and white matter, especially of axons, is important and probably the principal determinant of accumulation of irreversible neurological disability and of conversion to a progressive disease course.

Axons↗

PubMed2003

Upregulation of the apoptosis regulators cFLIP, CD95 and CD95 ligand in peripheral blood mononuclear cells in relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a chronic disease involving an inflammatory reaction within the white matter of the CNS, mediated by T cells, B cells and macrophages. The pathogenesis of MS may involve impaired activation-induced cell death of activated myelin-specific mature T cells. We investigated the mRNA expression of the apoptosis mediators cellular FLICE-inhibitory protein (cFLIP), caspase-8, CD95 and CD95L in peripheral blood mononuclear cells (PB MNCs) from MS patients using real-time PCR. The overall increased expression of the four key players in the CD95 pathway in relapsing-remitting MS suggests their involvement in the inflammatory process in this disease.

Adult↗

PubMed1997

Genetics of multiple sclerosis.

Multiple Sclerosis (MS) is a common chronic central nervous system disease in young adults. Relative familial risk appears to be determined largely by genes while population risk is strongly influenced by environmental factors. This is supported by genetic epidemiological studies which also suggest an oligogenic inheritance of susceptibility. The HLA DRB1*1501, DQA1*0102, DQB1 0602 haplotype is associated with the disease but HLA contributes only modestly to overall susceptibility. The results of three genomic searches are concordant with the genetic epidemiology and imply a number of genes with interacting effects will be found. Importantly, no single region has been identified with a major influence on familial risk.

Adult↗

PubMed2004

A multimodal approach to managing the symptoms of multiple sclerosis.

Multiple sclerosis (MS) is a disease of the CNS with a challenging clinical course characterized by heterogeneous symptoms related to inflammation and demyelination. Disease-modifying agents (DMAs) are used to treat the related neuronal degradation. Certain symptoms occur regularly, although with variable frequency, regardless of treatment with DMAs. Because there is no cure for MS at this time, symptom management is critically important to quality of life. Symptoms commonly seen are spasticity, fatigue, sexual dysfunction, bladder dysfunction, pain, and cognitive dysfunction. Other symptoms include depression, bowel dysfunction, paroxysmal symptoms, and weakness. The symptom management model that provides optimal results for patients with MS is a multimodal approach using effective communication, patient education, physical modalities and activities, occupational and other therapies, and pharmacologic interventions. Individualizing treatment for each patient involves gaining control of symptoms as early as possible to prevent cycles of symptoms from developing.

Cognition Disorders↗

PubMed1999

Cognitive profile of patients with relapsing remitting multiple sclerosis.

Multiple sclerosis (MS) is a common disease in Western countries of temperate/cold climate, but in tropical countries an increasing number of cases have been diagnosticated. Moved by the lack of information about cognitive dysfunction of Brazilian MS patients, the present study attempted to describe features of neuropsychological alterations in patients with relapsing remitting MS living in the city of São Paulo. They were compared to healthy volunteers, matched for age and education. In the absence of global intellectual deterioration, the patients had a deficit: a) in learning and verbal long-term memory tasks and in visual long-term memory of complex figure; b) in timed tasks, accounted for by a slowness of mental processes; c) in tasks with a motor component. Tendency to depression was observed; anxiety levels were normal.

Adolescent↗

PubMed2003

[Susceptibility genes for multiple sclerosis].

Multiple lines of evidence support the role of genetic factors for susceptibility to multiple sclerosis (MS), although unknown environmental factors must play an important role in developing MS. In this paper, we review the reports studied for the possible associations between Japanese MS and candidate genes by using case-control method. As for HLA alleles, HLA-DRB1*1501 and -DPB1*0501 allele have been confirmed to be associated with conventional MS and opticospinal MS, respectively. Some polymorphisms of vitamin D receptor gene, estrogen receptor gene, CTLA-4 gene, and osteopontin gene were reported to be associated with conventional MS. Appropriate case ascertainment and collection as well as proper statistical method are needed to isolate the susceptibility genes for MS.

Alleles↗

PubMed2004

IFN-beta treatment modulates the CD28/CTLA-4-mediated pathway for IL-2 production in patients with relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system probably mediated by Th1 lymphocytes. IFN-beta is an established therapy for relapsing MS patients, although the mechanisms underlying its efficacy are yet to be well characterized. We determined IL-2 production, CD25 expression and T-cell proliferation from relapsing-remitting MS patients before and three months after starting therapy. A decrease in the percentage of CD80-induced IL-2-producing cells was observed after in vivo IFN-beta treatment. These data support that one of the immunomodulatory effects of IFN-beta treatment in MS may be a limitation of the autoimmune response modifying the CD80:CD28/CTLA-4 pathway.

Adjuvants, Immunologic↗

PubMed2004

Current approved options for treating patients with multiple sclerosis.

Multiple sclerosis (MS), a neurologic disorder that affects 400,000 persons in the United States, consists of an inflammatory and a neurodegenerative phase. Treatment options now approved by the FDA specifically target the inflammatory phase of MS and include immunomodulators (i.e., interferon betas and glatiramer acetate) and an immunosuppressant, mitoxantrone. This article discusses the methods of monitoring disease progression using disability scales and MRI and reviews the clinical efficacy and tolerability of the FDA-approved therapies. All of the immunomodulators are approved for the treatment of relapsing forms of MS. Only mitoxantrone is approved for the treatment of worsening relapsing-remitting MS, secondary progressive MS, and progressive-relapsing MS. Early treatment with these disease-modifying agents is desirable to reduce the progression of the disease and to limit long-term disability.

Clinical Trials as Topic↗

PubMedDate not supplied

Managing bladder symptoms in people with multiple sclerosis.

Multiple sclerosis is a chronic disease of the central nervous system (brain and spinal cord). The cause is still unknown but there is evidence that suggests there is an autoimmune component to the disease that causes damage to the myelin sheath, a complex material that surrounds the axon of myelinated nerves (Fig 1). It affects 100-120 people per 100,000 population, approximately 75 per cent of whom will develop urinary symptoms (NICE, 2003). Bladder problems usually occur when the disease involves the spinal cord (Fig 2) and these can get worse as the disease progresses and the patient becomes less mobile. Bladder symptoms affect many aspects of daily life and their management is extremely important. As the disease progresses and symptoms worsen, a well-planned strategy can offer patients the most effective pathway to manage their bladder problems.

Activities of Daily Living↗

PubMed1994

Human leukocyte antigen studies in multiple sclerosis.

Multiple sclerosis (MS) has been associated with HLA-DR2 for more than 20 years, and a large number of studies have addressed the relation between MS and the HLA class II genes, which are our major immune-response genes. This has produced a complex and confusing picture that is difficult to interpret. With the advent of reliable and comprehensive DNA-based typing techniques, it is now possible to extract a coherent pattern from this mass of data. The associated haplotype has been specified to HLA-Dw2 in cellular typing nomenclature, which equals DR15,DQ6 by serology, and DRB1*1501,DQA1*0102,DQB1*0602 in sequence-based terminology. This haplotype is increased among groups of MS patients worldwide, although most strongly in North and West Europeans, and it is the only haplotype with a clear importance in MS. Attempts to map this association within the haplotype have not been successful.

Alleles↗

PubMed2006

Clinical and imaging metrics for monitoring disease progression in patients with multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the CNS leading to clinical disability in 250,000-350,000 young adults in the USA and Europe. The disease affects both white matter (WM) and gray matter (GM) tissues of the brain and spinal cord. While WM disease is easily quantified using currently available magnetic resonance imaging (MRI) techniques, identification and quantification of GM disease present a daily challenge. Nonconventional brain and spinal cord MRI techniques, including magnetization transfer, MRI spectroscopy and diffusion tensor imaging, have improved our understanding of MS pathology in the deep GM. The sensitivity of high-resolution MRI obtained at a high magnetic field will improve the detection of spinal cord and brain cortical GM disease. The appropriate use of the above-mentioned techniques has the potential to more accurately explain the level of disability in MS patients.

Cognition Disorders↗

PubMed2006

The role of MRS and fMRI in multiple sclerosis.

Multiple sclerosis is now recognized as more than simply a disease of inflammation and demyelination in the brain and spinal cord. Conventional MRI has been established as the most important paraclinical tool in the diagnostic assessment of patients with suspected MS, and in the monitoring of treatment efficacy in clinical trials, at least in relapsing disease. Magnetization-transfer, diffusion-weighted MRI, 1H-MRS, and fMRI improve our ability to quantify the pathological changes in MS in vivo. Although we have gained some insight into the disease and are starting to uncover some of the structural and physiological substrates for the disability that develops in MS patients, we are far from understanding what causes MS and how to prevent its progression. Imaging can be used as a tool to better understand the pathophysiology of MS and ultimately improve on the treatment of MS.

Central Nervous System↗