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PubMedDate not supplied

Short-term sequential analysis of sex hormones and helper T cells type 1 (Th1) and helper T cells type 2 (Th2) cytokines during and after multiple sclerosis relapse.

Multiple sclerosis (MS) is an immune-mediated disease with a clear sex-bias that may be attributed to sex hormones, sex' linked genes or both. Here we sought to determine the evolution pattern of cortisol and sex hormones at MS relapse and 2-months later in 7 male patients with relapsing remitting MS, and whether there was a correlation with a specific Th1 and Th2 cytokine pattern. Our findings indicate the activation of the hypothalamic-pituitary-adrenal axis and the concomitant upregulation of pro- and anti-inflammatory cytokines during relapse. The further increase of sex hormones, in particular estradiol in our male MS patients suggest their possible implication in the physiopathology of the illness and a putative anti-inflammatory and neuroreparatory effect.

Adult↗
PubMed1991

A correlational study of disabilities, stressors and coping methods in victims of multiple sclerosis.

Twenty multiple sclerosis (MS) patients admitted to the hospital for treatment of exacerbation of their disease were asked to identify stressors and the coping mechanisms they employed to deal with stressors. They completed the MS Stressor Scale (a twenty item Likert-type scale) and the Jalowiec Coping Scale (sixty-item Likert-type scale). Disability level was measured using the Barthel Index. Results showed an overall mean stress score of 1.49 on a scale of 1 to 3. The most stressful items identified were feeling tired, inability to walk and uncertainty about the future. The most prevalent coping theme used was self-reliance and the most prevalent individual coping responses were a sense of humor and trying to learn more. A positive correlation was found between uncertainty about the future and fatalistic coping, and a negative correlation between depression and optimistic coping. No relationship was found between degree of disability and stressors.

Activities of Daily Living↗
PubMed1995

Elevated mast cell tryptase in cerebrospinal fluid of multiple sclerosis patients.

Multiple sclerosis (MS) lesions are associated with infiltration of T lymphocytes and macrophages that appear to mediate myelin destruction and gliosis (scarring). Mast cells are located perivascularly in the brain, are juxtaposed to neurons, and have been shown to secrete vasoactive and inflammatory mediators in response to neuropeptides and direct nerve stimulation. Mast cells have been previously identified in MS lesions, are activated by myelin basic protein, and can participate in the regulation of blood-brain barrier permeability, as well as in myelin destruction. Here, cerebrospinal fluid from MS patients and controls with other neurologic diseases was assayed for histamine, its major metabolite methylhistamine, and the specific mast cell marker tryptase. Histamine and methylhistamine were not elevated in MS. However, the mast cell specific proteolytic enzyme tryptase was significantly elevated in MS, suggesting that mast cell activation may be involved in the pathophysiology of this disease.

Adult↗
PubMed2001

Characterization of the human T cell response against the neuronal protein synapsin in patients with multiple sclerosis.

Although multiple sclerosis (MS) is considered primarily as a demyelinating disease, neuronal damage is abundant and correlates with the neurological deficit. Therefore, we investigated the frequency and characteristics of human T cells specific for synapsin-a neuronal protein highly conserved among species. Synapsin specific T cell responses were detected at a frequency similar to that of MBP specific T cells in MS patients, one patient with acute demyelinating encephalomyelitis (ADEM) and controls. Long-term T cell lines specific for synapsin exhibited a CD3(+), CD4(+), CD8(-) phenotype and produced high amounts of tumor-necrosis-factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) after antigen specific stimulation, whereas lymphotoxin (LT), interleukin-4 (IL-4) and interleukin-10 (IL-10) were detectable in smaller quantities.

Acute Disease↗
PubMed2003

Abnormal response to glutamate of T lymphocytes from multiple sclerosis patients.

Multiple sclerosis (MS) is an immune-mediate, inflammatory and demyelinating disease of the central nervous system (CNS). Since glutamate (Glu) is a modulator of T lymphocyte function and Glu excitotoxicity has been proposed as one of the mechanisms of the demyelination, we studied the responses of T lymphocytes from normal controls (NC), MS or other non-inflammatory neurological disease (ONND) patients to Glu, by measuring phytohemagglutinin-induced intracellular Ca(2+) ([Ca(2+)](i)) rise (Fura-2 method) and cell proliferation (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide colorimetric assay). No differences in the Glu (1 microM)-induced potentiation of the [Ca(2+)](i) rise were measured in T lymphocytes from all groups of subjects, while a significant decrease in the Glu (1 mM)-induced inhibition of cell proliferation was observed in T lymphocytes from MS patients. These data demonstrate that MS T lymphocytes abnormally respond to Glu.

Adult↗
PubMed1979

Pattern and flash visual evoked responses in multiple sclerosis.

In multiple sclerosis (MS), increase of delay may be important, but the earlier change is the behavior of the wave shape; amplitude is always lower even in MS patients without visual subjective symptomatology, provided not only flash but also pattern stimulation is performed. Normal amplitude with pattern stimulation does not necessarily mean normal with flash. Combining both stimulation methods, we obtained lowering of amplitude and change of wave shape in 100% of cases while latency was increased in only 77% of cases. Sectorial ischemic neuropathy, and open angle glaucoma patients show the same findings, which emphasizes that the method is not specific for demyelinating diseases, nor selective for papillomacular bundle involvement, but that VER, considering only its first components, reflects axonal damage somewhere in the visual pathway. Flash and pattern VER might be even more pathognomonic in MS than oligoclonal gammaglobulin fractionation on agar, positive in 75% of cases. It is suggested that subclinical MS cases should be submitted to full electro-ophthalmographic investigation.

Form Perception↗
PubMed2001

Non-conventional MR techniques to monitor the evolution of multiple sclerosis.

In multiple sclerosis (MS), conventional magnetic resonance imaging (MRI) has proved to be sensitive for detecting lesions and their changes over time. However, conventional MRI cannot characterize and quantify the tissue damage within and outside such lesions. Other quantitative MR techniques, including MR spectroscopy (MRS), magnetization transfer imaging (MTI) and diffusion-weighted imaging (DWI) have the potential to overcome this limitation and, as a consequence, to provide complementary information to conventional MRI. MTI- and DWI-derived measurements quantify the structural changes occurring within and outside lesions seen on conventional MRI scans, and MRS adds information on the biochemical nature of such changes. The application of these MR techniques to the study of MS is dramatically increasing our understanding of how MS causes irreversible deficits, and it is likely to provide useful insights into the pathophysiology of other white matter diseases in the future. The present review summarizes the major contributions made by these three MR techniques in the understanding of MS evolution.

Central Nervous System↗
PubMed1999

Herpesviruses--a rationale for antiviral treatment in multiple sclerosis.

In multiple sclerosis (MS), the extensive and long lasting search for viruses or other pathogens has hitherto failed to identify a common etiological agent. However, the beneficial effects by interferon-beta treatment in MS, although suggested to depend mainly on immunomodulation, might lend support to a viral involvement in the pathogenesis. The human herpesviruses have attracted interest since their recurrent modes of infection share some similarity with the relapsing-remitting course of MS, most members are readily detected within the brain, and several of these viruses may induce demyelination within the central nervous system in human hosts as well as in animal models. Accumulated diagnostic and epidemiological data are compatible with a role for the herpesviruses as possible cofactors rather than etiological agents, and recent studies showing early neuronal damage in MS patients focus attention on the neurotropic alpha-herpesviruses. Antiviral treatment trials with safe and effective drugs such as valaciclovir offer a possibility of testing the hypotheses concerning herpesviral involvement in MS.

Acyclovir↗
PubMed2002

Pharmacologic options for the management of multiple sclerosis symptoms.

Multiple sclerosis (MS) is a disease with a wide-ranging impact on physical functioning. Although pharmacotherapy plays an indispensable role in the management of MS symptoms, optimal disease management requires a multidisciplinary approach that combines medication, rehabilitation, and patient education. Successful control of symptoms is critical to quality of life for MS patients. Immunomodulating drugs provide a means of controlling the underlying disease process, but they are not a cure. This places responsibility on health care providers to control a patient's MS-related symptoms to limit disability and delay impairment in the activities of daily living. Owing to the importance of symptom control, comprehensive patient evaluations should be performed at regular intervals to determine the extent of neurological damage and disease progression and to address changing patient needs. The goal of interventions should be not only to treat the primary and secondary symptoms of MS but also to provide access to the psychosocial support that will help MS patients and their families continue to cope as disease status changes.

Adjuvants, Immunologic↗
PubMed2004

[Quality of life and economic cost of multiple sclerosis].

In multiple sclerosis, evaluation of quality of life is important because the patients are usually confronted with a decrease in physical, cognitive and social functioning. Apart from the personal suffering, the financial consequences for these patients and their family and the economic burden for society are enormous. Measurement of health related quality of life is important for the understanding of disease burden and the impact of specific MS treatments. Rising costs associated with new treatments and spending limits have prompted a search for gratter efficiency. Although health economics research can suggest ways to maximize health benefits within fixed budgets it is currently underused in MS. The purpose of this review of the literature is to explain some of the basic principles underlying both quality of life and economic evaluations, and analyse their contribution to understanding and managing patients with MS. Neurologists should not underestimate how dramatic their contributions can be to this maturing field that will influence the future of MS patients care.

Costs and Cost Analysis↗
PubMedDate not supplied

A preliminary study into the dental health status of multiple sclerosis patients.

Multiple sclerosis (MS) is an inflammatory disease of unknown etiology involving the central nervous system. Since MS affects the whole body, orofacial aspects of the disease must be expected, particularly since loss of muscular coordination may result in a diminished ability to maintain oral hygiene. This preliminary study examined the dental health status of 22 volunteer MS patients. A questionnaire collected data regarding medical and dental histories and socio-demographic information. Extra- and intra-oral examinations were carried out on all subjects to determine the particular dental treatment needs of this special group. The DMFT and CPITN scores for this group did not indicate that MS patients were more susceptible to dental caries or periodontal disease. However, the prevalence of trigeminal neuralgia and symptoms of TMJ dysfunction in the group studied indicated that these conditions may be manifest in MS patients and warrant further investigations.

Adult↗
PubMed1996

A phase II trial of anti-CD4 antibodies in the treatment of multiple sclerosis.

In multiple sclerosis (MS) myelin damage is the result of a chronic inflammatory process mediated by CD4 positive T helper/effector cells. In experimental allergic encephalomyelitis (EAE), the animal model of MS, treatment with anti-CD4 antibodies can prevent the onset of disease. Natural history studies have demonstrated that gadolinium enhanced magnetic resonance imaging (MRI) of the brain is more sensitive and objective in assessing inflammatory disease activity in MS than clinical monitoring, so that less patients and shorter studies suffice to reach the same statistical power as compared to trials using clinical outcome parameters. In this paper we describe the design of an exploratory trial of chimeric monoclonal anti-CD4 antibodies in the treatment of MS. For this study we chose the number of active MS lesions on monthly gadolinium enhanced MRI scans as the primary outcome measure.

Adolescent↗
PubMed2003

Metallothionein expression in the central nervous system of multiple sclerosis patients.

Multiple sclerosis (MS) is a major chronic demyelinating and inflammatory disease of the central nervous system (CNS) in which oxidative stress likely plays a pathogenic role in the development of myelin and neuronal damage. Metallothioneins (MTs) are antioxidant proteins induced in the CNS by tissue injury, stress and some neurodegenerative diseases, which have been postulated to play a neuroprotective role. In fact, MT-I+II-deficient mice are more susceptible to developing experimental autoimmune encephalomyelitis (EAE), and treatment of Lewis rats with Zn-MT-II reduces EAE severity. We show here that, as in EAE, MT-I+II proteins were expressed in brain lesions of MS patients. Cells expressing MT-I+II were mainly astrocytes and activated monocytes/macrophages. Interestingly, the levels of MT-I+II were slightly increased in the inactive MS lesions in comparison with the active lesions, suggesting that MTs may be important in disease remission.

Animals↗
PubMedDate not supplied

[The pathogenic role of inflammation in multiple sclerosis].

INTRODUCTION: Multiple sclerosis (MS) is characterized by the presence in the central nervous system (CNS) of perivascular inflammatory infiltrates containing auto-reactive T and B cells and activated macrophages thus indicating that MS is a T cell-mediated CNS-confined chronic inflammatory demyelinating disease in which the ultimate effector cell is the activated macrophage. DEVELOPMENT: The inflammatory process, leading to patchy demyelination and axonal loss, is mainly sustained by pro-inflammatory cytokines that modulate at different levels the pathogenic process underlying MS. Cytokines can 1. Sustain the 'putative' CNS-confined inflammatory process leading to the development of myelin-specific T cells; 2. Activate circulating myelin-specific T cells and shape their repertoire (Th1 versus Th2 pattern); 3. Induce the CNS recruitment of non antigen specific T cells and myelinotoxic effector cells (monocyte/macrophages) from the periphery, and 4. Cause direct oligodendrotoxicity (TNF alpha) or induce the secretion of myelinotoxic substances. The present chapter will focus on the mechanisms sustaining the activity of pro-inflammatory cytokines in MS pathogenesis.

Brain↗
PubMed1998

Awareness of remembering achieved through automatic and conscious processes in multiple sclerosis.

Fifty multiple sclerosis (MS) and forty-one matched control subjects were administered a word stem completion task and the California Verbal Learning. Test (CVLT). As predicted, priming in a conventional "implicit" task did not differ for MS and control groups, and under "explicit" instructions verbal list recall was significantly lower in the MS group with recognition intact. Application of the process dissociation procedure (Jacoby, Toth, & Yonelinas, 1993) to the word stem task demonstrated that conscious and unconscious processes both contribute to remembering in MS. Exploratory analyses found no group differences in words remembered under inclusion nor exclusion conditions, though preliminary estimates for MS automatic processing exceeded those for controls. As predicted, prospective metamemory judgments reflected subsequent performance for both groups in the inclusion but not the exclusion condition. By contrast, retrospective monitoring for both groups reflected memory performance in both conditions. However post hoc analyses demonstrated that those MS subjects who employed more automatic processing were less aware retrospectively of their successful remembering under exclusion than MS subjects who used less automatic processing.

Adult↗
PubMed2001

Neuregulin: an oligodendrocyte growth factor absent in active multiple sclerosis lesions.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) which results in demyelination and axonal injury. Conventional therapy for MS is immune suppression in the absence of agents that promote neural and glial survival or remyelination. Neuregulins are a family of ligands that exert trophic effects on both neurons and glia. Using mice bearing a null mutation in the neuregulin gene, here we demonstrate that neuregulins are necessary for the normal development of oligodendrocytes. In addition, neuregulins are produced in the normal human CNS by astrocytes as well as neurons. Astrocyte-derived neuregulin is functionally active in bioassays and exists in secreted and membrane-associated beta-isoforms. In active and chronic active MS lesions, however, the expression of astrocyte neuregulin is dramatically reduced. The absence of neuregulin in active MS lesions may contribute to the paucity of remyelination in MS.

Adult↗
PubMed2004

Correlations between IL-4, IL-12 levels and CCL2, CCL5 levels in serum and cerebrospinal fluid of multiple sclerosis patients.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Both cytokines and chemokines have been implicated in the pathogenesis of MS. The aim of the study was to assess whether cytokine levels are correlated with chemokine levels during a different stage of relapsing-remitting MS (RR-MS). The study included 53 patients with RR-MS (20 subjects in stable stage and 18 patients with relapse). By ELISA method, the levels of the interleukin-4 (IL-4), interleukin-12 (IL-12), CCL2 and CCL-5 chemokines were measured both in serum and cerebrospinal fluid (CSF) of all patients. The serum IL-4 and IL-12 levels and CSF CCL5 level of patients with stable RR-MS were significantly different from the control level and the IL-12 levels were correlated with CCL5 levels in serum. During the relapse, a significant change in chemokine levels both in serum and CSF and IL-12 in CSF were noted, however no correlations were found between cytokines and chemokines.

Adult↗
PubMed2002

An examination of the association between beta2 adrenergic receptor polymorphisms and multiple sclerosis.

In multiple sclerosis (MS), beta-adrenergic receptor densities on peripheral blood mononuclear cells are enhanced, while the astrocytes present in plaques lack beta2 adrenergic receptor (beta2AR) expression. This differentially altered expression suggests that beta2ARs may influence the pathogenesis of MS. In the present study, we investigated the association of polymorphisms of the beta2AR gene with the occurrence of MS. Our results showed no significant differences in the distribution of the polymorphisms between MS patients overall and control subjects. Furthermore, no association was observed between the presence of beta2AR gene polymorphisms and clinical characteristics, such as age at disease onset and disease severity. While a trend towards an increase of the Gly allele frequency in codon 16 was observed in the secondary-progressive MS, this result was not significantly different from that observed in relapsing-remitting MS patients or control subjects. Together, our findings suggest that the presence of beta2AR gene polymorphisms may be inconclusive in the susceptibility to MS or in the clinical characteristics of Japanese patients with MS and, therefore, need further studies.

Adult↗