SEARCH · PubMed Health

Results for “Multiple Sclerosis, Relapsing-Remitting”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources

PubMed1993

Correlation of myelin basic protein-like material in cerebrospinal fluid of multiple sclerosis patients with their response to glucocorticoid treatment.

Predictors and laboratory correlates of the response of patients with multiple sclerosis to glucocorticoids are not well defined. Our study was undertaken to determine if the levels of myelin basic protein (MBP)-like material in cerebrospinal fluid (CSF) might indicate which patients with multiple sclerosis would show a short-term (5 day) or intermediate-term (40 day) improvement of at least a full-grade Kurtzke disability score after initiating treatment with glucocorticoids. A total of 62 patients received 71 courses of treatment consisting of 5 days of intravenous methylprednisolone (500 mg per day) usually followed by a 4-week tapering dose of oral prednisone. CSF was obtained before initiation of treatment and analyzed for MBP-like material by radioimmunoassay. Results were analyzed by chi 2 tests of association and by logistic regression. Individuals having a CSF MBP-like material level of > or = 0.1 ng/ml overall showed a greater likelihood of continued improvement at day 40 (p = 0.014) or further improvement between days 5 and 40 (p = 0.003). Those in the first 15 days of worsening and with an elevated CSF MBP-like level were more likely to respond by day 5. Relapsing-remitting and relapsing-progressive forms of the disease were more likely to respond at both time points than were patients with primary or secondary chronic progressive patterns. The Kurtzke disability score at entry and the major anatomical site of the central nervous system symptomatically affected were not predictive of outcome at either time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Effect of high-dose steroid therapy on T-cell subpopulations. A longitudinal study in MS patients.

Lymphocyte subpopulations, T cell activation antigens, and serum levels of interleukin 2 (IL-2) and soluble IL-2 receptor (sIL2R), were studied in relapsing-remitting MS (RR-MS) patients before and after high-dose steroid therapy. Prior to therapy, a minority of patients showed increased HLA-DR antigen expression, and an increased number of CD16+ and CD19+ cells. Steroid treatment induced a significant increase in HLA-DR and CD19 expression, a significant reduction in CD16+, CD57+, and CD8+ CD57+ cells, and a slight, non-significant, decrease in IL-2 and sIL-2R levels and CD25 expression on CD4+ T lymphocytes.

Adolescent↗

PubMed1994

Betaseron: the new MS treatment.

Betaseron is a new medication that decreases the frequency and severity of exacerbations in persons with relapsing-remitting MS. It is the first to alter the disease itself and has, therefore, generated considerable hope among patients, families and health care providers. Patients who meet the criteria for use of Betaseron will be confronted with a number of decisions and cost factors. Further, they must be willing to prepare and administer Betaseron injections. Potential adverse effects, direct and indirect costs of Betaseron, and administration and monitoring requirements determine the nursing implications. To provide optimum care and education to patients with MS, nurses must maintain current knowledge about this new medication.

Aftercare↗

PubMed1992

Experimental allergic encephalomyelitis in cynomolgus monkeys. Quantitation of T cell responses in peripheral blood.

Chronic relapsing-remitting experimental allergic encephalomyelitis (EAE) was induced in cynomolgus monkeys by a single immunization with a homogenate of human brain white matter (BH) in adjuvant. Proliferative T lymphocyte responses to BH, to myelin basic protein (MBP), but not to proteolipid protein, were detected in peripheral blood mononuclear cells (PBMC) of all animals and persisted until their death or, in surviving animals, for greater than 10 mo postimmunization. Responses of higher magnitude tended to be associated with fatal, compared with nonfatal, episodes of clinical EAE. The frequency of MBP-reactive T cells in PBMC of animals with acute EAE was quantitated with a soft agar colony system; the ratio of T cells that proliferated specifically to MBP was estimated at between 5 and 20 per 10(6) PBMC. A similar frequency of peptide-specific T cells was estimated from PBMC of monkeys immunized with a synthetic 14-mer peptide corresponding to a region near the carboxy terminus of MBP. Thus, autoantigen-reactive T cells can be detected in the circulation throughout the course of chronic EAE, are predictive of disease severity, and occur at a frequency similar to that estimated to be present in humans with multiple sclerosis.

Amino Acid Sequence↗

PubMed1995

Chronic relapsing experimental autoimmune encephalomyelitis with a delayed onset and an atypical clinical course, induced in PL/J mice by myelin oligodendrocyte glycoprotein (MOG)-derived peptide: preliminary analysis of MOG T cell epitopes.

Myelin basic protein (MBP) and proteolipid protein (PLP), the most abundant proteins of central nervous system (CNS) myelin, have been extensively studied as possible primary target antigens in multiple sclerosis (MS), a primary demyelinating autoimmune disease of the CNS. However, there is increasing evidence to suggest that autoimmune reactivity against the quantitatively minor myelin component, myelin oligodendrocyte glycoprotein (MOG), can also play a role in the pathogenicity of MS. We recently demonstrated a predominant response to MOG by peripheral blood lymphocytes from patients with MS tested for their reactivity against various myelin antigens, including MBP and PLP. To ascertain whether or not T cell reactivity to MOG in MS is a potentially pathogenic response, we have tested the ability of synthetic MOG peptides (pMOG) representing potential T cell epitopes, to induce neurological disease in mice. Both strains of mice tested (SJL/J and PL/J mice) were able to mount a primary T cell response to some of the five MOG peptides synthesized, pMOG 1-21, 35-55, 67-87, 104-117 and 202-218. T cell lines could be raised in both strains to pMOG 35-55 and 67-87, but epitope definition revealed that each strain recognized a different minimal epitope within these two peptides. T cell lines to pMOG 1-21 and 202-218 could also be raised in SJL/J and PL/J mice, respectively. T cell reactivity to pMOG 104-117 was not observed in either mouse strain. None of the peptides tested induced detectable clinical signs in SJL/J mice. In contrast, an MS-like chronic relapsing-remitting disease could be induced in PL/J mice with pMOG 35-55. The disease presented with a delayed onset and with clinical signs which differed significantly in their progression and expression from the typical ascending paralysis of experimental autoimmune encephalomyelitis induced with other myelin components, such as MBP and PLP. Histological examination of CNS tissue from mice injected with pMOG 35-55 revealed only mild neuropathological signs with few inflammatory foci in brain and spinal cord. Some myelin splitting and edema were detected upon electron microscopic examination in the spinal cord and cerebellum. Transfer of pMOG 35-55 reactive T cells into naive PL/J mice resulted in pathological changes characterized by inflammatory foci in the brain and spinal cord. This passively induced disease was clinically silent, as was also reported for Lewis rats injected with T cells specific for the same MOG peptide.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed1996

Combinations of drugs.

As a result of recent therapeutic trials, recombinant Interferon beta (rIFN beta)-Ib and -Ia as well as Copolymer I (COP I) and to some extent unspecific immunosuppressants have been accepted as partially efficient treatments of relapsing-remitting MS. In view of partially effective single treatments, the question arises if combination of two or even more-agents could improve efficacy without increasing side effects. The theoretical background of possible combinations is discussed. The selection of combination partners should be based on their proven efficacy as single treatment, on their mode of action and their distinct target in the pathogenetic cascade of events and on their specific side effect profile. Combination regimens selected in this way should undergo evaluation in short term early phase II studies and if the results are positive enter phase III studies. The use of surrogate markers (especially MRI-findings) may help to accelerate this process. Combinations that could enter phase II and III studies in the near future are rIFN beta with unspecific immunosuppressants, e.g. Azathioprine or Methotrexate and rIFN beta with COP I. Combinations including agents just entering phase I and II studies as a single treatment may be more promising for the future.

Clinical Trials as Topic↗

PubMed1995

Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids.

To demonstrate the influence of n-3 PUFA supplementation on cytokine and eicosanoid production in peripheral blood mononuclear cells (PBMCs) of MS patients (MSP), we investigated the impact of a 6-month dietary supplementation with these fatty acids on the levels of interleukin-1 beta (IL-1 beta), IL-2, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the supernatants of stimulated PBMCs and serum soluble IL-2 receptors in a group of 20 relapsing-remitting (R-R) MSP and a group of 15 age-matched control individuals (CI). The production of PGE2 and LTB4 in the stimulated PBMCs was also assessed in patient and control groups supplemented with n-3 PUFAs. In both groups, n-3 PUFA supplementation led to a significant decrease in the levels of IL-1 beta and TNF-alpha, and this reduction was more pronounced in the 3rd and 6th month of supplementation. An analogous decrease was observed in the levels of IL-2 and IFN-gamma produced by stimulated PBMCs, and in the levels of serum soluble IL-2 receptors. n-3 PUFA supplementation also appeared to significantly affect prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production in PBMCs, both in MSP and the control group. The reduced production of these proinflammatory eicosanoids, and the decrease of some cytokines with an immunohenancing effect as a consequence of n-3 PUFA supplementation, could modulate some immune functions which have been demonstrated to be altered in MSP.

Adult↗

PubMed1996

Long term recombinant interferon alpha treatment in MS with special emphasis to side effects.

Twenty relapsing-remitting (RR) clinically definite MS patients were treated with 9 MIU intramuscular recombinant interferon alpha-2a (rIFNA) (Roferon-A, Roche) (n = 12) or placebo (n = 8) every other day for 6 months and followed up for a further 6 months after stopping treatment. Numbers of active lesions at MRI and of patients with clinical-MRI signs of disease activity and lymphocyte interferon gamma production, which were decreased during treatment, returned to values similar to baseline and placebos after stopping treatment. rIFNA chronic therapy seems therefore needed in order to maintain drug efficacy. Side effect profile was monitored, too, for over 1 year in the same 20 patients plus 25 additional RR MS patients. Besides the typical side effects of type I interferon therapy (fever, fatigue, depression, lymphopenia, hepatic enzyme elevation), occurrence of serum autoAbs was noted in 30% patients (in 60% antinuclear and in 80% antithyroid autoAbs). In two patients rIFNA treatment was stopped, in one case for antithyroid autoAbs and hypothyroidism, in the other for antinuclear autoAbs and a five-fold increase of ALT. A careful monitoring of serum autoAbs and of signs of thyroid or liver damage must always precede and accompany longterm type I IFN therapy.

Autoantibodies↗

PubMed1998

Discontinuation of treatment with IFN-beta leads to exacerbation of experimental autoimmune encephalomyelitis in Lewis rats. Rapid reversal of the antiproliferative activity of IFN-beta and excessive expansion of autoreactive T cells as disease promoting mechanisms.

IFN-beta has recently been shown to exert remarkable beneficial effects on disease development in patients with early stage relapsing-remitting MS. The specific immune mechanism(s) by which IFN-beta ameliorates this human demyelinating disease is at present undefined. One potential mechanism may reside in the antiproliferative activity of IFN-beta which may inhibit the expansion of autoaggressive T cells thereby limiting disease progression. In the present study we investigated whether the administration of recombinant rat IFN-beta (rrIFN-beta) to Lewis rats with actively induced experimental autoimmune encephalomyelitis (EAE) inhibits the expansion of encephalitogenic T cells in lymphoid organs and as such may contribute to suppression of disease activity in this widely used animal model for MS. Our data show that daily administrations of > or = 3 x 10(5) u rrIFN-beta to EAE rats, starting two days before MBP sensitization and continued for 10 days led to a dramatic and dose-dependent reduction in encephalitogenic T cells in both spleen and inguinal lymph nodes at day 8 post-immunization (p.i.). However, the rrIFN-beta-mediated reduction in effector T cells did not ameliorate paralytic disease as expected but significantly enhanced the severity of EAE. Analyses of lymphoid organs in the remission phase of EAE revealed strongly elevated numbers of encephalitogenic T cells in rrIFN-beta-treated versus control rats suggesting a rapid reversal of the antiproliferative action of rrIFN-beta followed by an overshoot in the subsequent expansion of these effector T cells. In conformity with higher numbers of encephalitogenic T cells and worsening of disease, animals also showed significantly greater perivascular inflammation in the CNS. The relevance of our findings in relation to the beneficial effects of IFN-beta in MS is discussed.

Adjuvants, Immunologic↗

PubMed1988

Cyclosporine versus azathioprine in the long-term treatment of multiple sclerosis--results of the German multicenter study.

In a double-blind controlled trial of 194 patients with clinically definite active multiple sclerosis, 98 were randomized to treatment with cyclosporine (CyA, 5 mg/kg/day), and 96 to treatment with azathioprine (Aza, 2.5 mg/kg/day). Eighty-five patients in the CyA group and 82 in the Aza group completed a treatment period of 24 to 32 months in accordance with the study protocol. No significant differences could be detected between the two treatment groups at the end of the trial. Assessment was done by serial quantitative neurological examinations and Kurtzke's Expanded Disability Status Scale. Frequency of relapse and patient self-evaluation also failed to show significant differences. Overall deterioration observed in both groups during the trial was only minor. The incidence of side effects in the CyA group was more than two times that in the Aza group. We conclude that CyA as a single agent cannot be the drug of final choice in long-term immunosuppressive treatment of relapsing-remitting and relapsing-progressive multiple sclerosis.

Adolescent↗

PubMed1992

Induction of active and adoptive relapsing experimental autoimmune encephalomyelitis (EAE) using an encephalitogenic epitope of proteolipid protein.

Proteolipid protein (PLP) is a major component of the central nervous system (CNS) myelin membrane and has been shown to induce acute experimental autoimmune encephalomyelitis (EAE) in genetically susceptible animals. Here we describe conditions by which a relapsing-remitting form of EAE can be reliably induced in SJL/J mice either actively immunized with the major encephalitogenic PLP peptide, PLP13-151(S), or following adoptive transfer of PLP139-151(S)-specific T cells. The disease follows a reliable relapsing-remitting course with acute clinical signs first appearing 6-20 days after priming or transfer and relapses first appearing at 30-45 days. The initial onset of disease correlates with delayed-type hypersensitivity (DTH) reactivity specific for PLP139-151(S), in the apparent absence of T cell reactivity to the major myelin basic protein (MBP) peptide. Histologically, both the active and adoptive forms of the disease are characterized by extensive mononuclear cell infiltration and severe demyelination of the CNS. These results suggest that T cell responses specific for PLP139-151(S) are sufficient to induce clinical and histological R-EAE in SJL/J mice. This model should prove useful for examination of the cellular and molecular events involved in clinical relapses and perhaps in determining the role of PLP-specific T cell responses in multiple sclerosis (MS).

Amino Acid Sequence↗

PubMed2026

EBV reactivation priming of the peripheral immune system in multiple sclerosis relapse.

Despite decades of research, the cellular and molecular events preceding multiple sclerosis (MS) relapse remain incompletely understood. Here, in this observational study of longitudinal blood samples from patients with relapsing-remitting MS, we used single-cell RNA sequencing, bulk transcriptomics, multiparameter flow cytometry and targeted viral reverse transcription quantitative polymerase chain reaction (RT-qPCR) to construct a time-resolved atlas of immune perturbations surrounding relapse. A reproducible pre-relapse signature in monocytes and B cells, emerging up to 3 months before clinical onset, was enriched for host genes responsive to Epstein-Barr virus (EBV) lytic reactivation factors. RT-qPCR confirmed elevated EBV LMP-1 transcripts in pre-relapse B cells, and flow cytometry demonstrated expansion of CD11c+ atypical B cell populations displaying EBV surface protein gp350. Pre-relapse transcriptional modules overlapped with MS genome-wide association study (GWAS) risk loci and EBNA-2-bound enhancers, suggesting that inherited MS susceptibility and EBV-responsive programs operate through shared regulatory elements. How this peripheral activation relates to central nervous system lesion formation remains to be established. These findings nonetheless suggest that EBV reactivation, when occurring within a genetically predisposed peripheral immune environment, is a proximal precursor of MS relapse.

Journal Article↗

PubMed1992

CSF myelin basic protein, IgG and IgM levels in 101 MS patients before and after treatment with high-dose intravenous methylprednisolone.

A total of 101 patients (62 women; 39 men) with definite MS were treated with 1000 mg methylprednisolone (MP) intravenously for 10 consecutive days. Immediately before and after MP treatment clinical scoring (Kurtzke's Expanded Disability Status Scale) and CSF analysis were performed. Before MP treatment CSF MBP, IgG and IgM immunoglobulin levels (CSF Ig, index and intrathecal synthesis) were significantly elevated. The mean CSF MBP levels were significantly higher in the relapsing-remitting (RR) and chronic progressive MS patients with relapses (CP + RR) than in the CP group without a RR disease course, respectively 2.1, 2.3 and 1.5 micrograms/l. A weak positive correlation was found between CSF MBP level and EDSS in the RR MS group (r = 0.34). CSF MBP was significantly correlated with IgM index (r = 0.36), IgM synthesis (r = 0.26), but not with the IgG levels. Therefore demyelination seems to be related to intrathecal IgM production. After MP treatment mean (median) EDSS decreased from 4.4 (4.0) to 3.3 (3.0). Except for Q albumin and IgM index, all CSF immunoglobulin levels decreased significantly after MP. The mean CSF MBP returned to reference values. In the RR group the decrease in CSF MBP was significantly correlated with the change in EDSS (r = 0.39). CSF MBP seems to be a good parameter for disease activity in relapsing MS. Following treatment CSF MBP was found to be related with the change in IgM index (r = 0.30). MP treatment reduces CSF MBP and intrathecal IgM in a similar way indicating a relation between these 2 parameters.

Adult↗

PubMed1994

Serial analysis of circulating adhesion molecules and TNF receptor in serum from patients with multiple sclerosis: cICAM-1 is an indicator for relapse.

We determined the serum levels for circulating adhesion molecules (circulating intercellular adhesion molecule-1 [cICAM-1], circulating endothelial leukocyte adhesion molecule-1 [cELAM-1], and circulating L-selectin [cL-selectin]) and circulating tumor necrosis factor receptor (cTNF-R) p60 in 29 patients with relapsing-remitting MS serially over a period of 12 months. During this period there were 27 relapses in 14 patients (48%). There was progression of disease activity in 12/25 patients (48%), as assessed by the occurrence of new lesions on nonenhancing, T2-weighted MRIs of the head. Clinically active patients with relapse or disease progression on MRI (n = 18) had frequent fluctuations in their serum levels for cICAM-1 if compared to patients with stable MS (n = 11). There were significant differences in the cumulative cICAM-1 production between the two groups (502 +/- 218 ng/ml in active versus 225 +/- 82 ng/ml in stable MS patients; p < 0.001). cTNF-R p60 serum levels were higher in patients with stable compared to active disease (2.3 +/- 0.5 ng/ml versus 1.5 +/- 0.6 ng/ml; p < 0.005). A significant increase in cICAM-1 levels was present at the time of a relapse (799 +/- 263 ng/ml versus 449 +/- 95 ng/ml; p < 0.001), whereas the highest serum levels for cTNF-R p60 occurred 4 weeks after the onset of a relapse (1.8 +/- 0.5 ng/ml at relapse versus 2.3 +/- 0.6 ng/ml 4 weeks after a relapse; p < 0.01). Interestingly, the cL-selectin serum levels in all MS patients were significantly higher than in healthy donors, whereas there were no differences for cELAM-1. These results reflect distinct changes of inflammatory variables in serum of patients with MS and revealed that cICAM-1 is an indicator for disease activity and that high serum levels for cTNF-R p60 are associated with remission.

Adult↗

PubMed1998

Intravenous immunoglobulin G reduces MRI activity in relapsing multiple sclerosis.

We wanted to assess whether intravenous immunoglobulin G (IVIG) decreases disease activity on MRI in relapsing MS. Previous trials of IVIG in relapsing-remitting MS demonstrated a reduction of acute relapses, but these studies did not include MRI. We treated 26 patients in a randomized, double-blind, crossover study of IVIG 1 g/kg daily or placebo on 2 consecutive days every month during two 6-month treatment periods. The primary end point was the number of gadolinium-enhancing lesions on monthly serial MRI. Secondary efficacy variables were the occurrence of exacerbations, clinical neurologic ratings, total MS lesion load on T2-weighted MRI, and multimodal evoked potentials. Eighteen patients completed the entire trial; eight patients did not. Twenty-one patients completed the first treatment period and at least two MRI examinations in the second treatment period and were included in the intention-to-treat analysis. On serial MRI, we observed fewer enhancing lesions per patient per scan during IVIG treatment (median, 0.4; range, 0 to 9.3) than during placebo treatment (median, 1.3; range, 0.2 to 25.7; p = 0.03). During IVIG treatment, 15 patients were exacerbation free compared with only 7 on placebo (p = 0.02). The total number of exacerbations in the IVIG period was 11 and in the placebo period, 19 (not significant). None of the remaining secondary efficacy measures were significantly different between the two treatment periods. The number of adverse events, in particular eczema, was significantly higher during IVIG therapy than during placebo treatment. These results suggest that IVIG treatment is beneficial to patients with relapsing MS.

Adolescent↗

PubMed1987

Chronic relapsing necrotizing encephalomyelitis produced by myelin basic protein in mice.

Chronic relapsing experimental autoimmune encephalomyelitis is commonly seen in a number of species after a single injection of whole white matter in adjuvant but not after inoculation with myelin basic protein, the major encephalitogen of central myelin. In the present report on large groups of SJL mice, we describe a form of chronic relapsing experimental autoimmune encephalomyelitis with destructive lesions after a single inoculation of myelin basic protein in complete Freund's adjuvant. This condition was studied for up to 19 months postinoculation and was characterized by a relapsing-remitting or a chronic progressive course, usually with a prolonged latent period. Higher doses of 400 and 800 micrograms of myelin basic protein were more effective in inducing this condition than were lower doses of 100 and 200 micrograms. Large lesions were apparent in the white matter. These comprised widespread destruction and Wallerian degeneration with some demyelination towards the margins. Demyelination was an initial, albeit transient, event which was subsequently masked by nerve fiber destruction. Polymorphonuclear leukocytes were early and prominent components of the inflammatory infiltrate and together with macrophages appeared to be involved in the lysis of myelin and axons. Thus, despite the clinical similarities, these features contrast the model with the more purely demyelinative lesions of chronic relapsing experimental autoimmune encephalomyelitis in other species and multiple sclerosis in man.

Adjuvants, Immunologic↗

PubMed1994

Neuroimaging in multiple sclerosis.

Modern neuroimaging, and in particular magnetic resonance imaging (MRI), has made a major contribution to the assessment of patients with multiple sclerosis. Brain MRI is the single most useful diagnostic investigation, and recent improvements in the quality of spinal cord imaging make MRI of this region a powerful tool in the evaluation of patients with undiagnosed myelopathies or with probable multiple sclerosis but equivocal findings on brain imaging. Putative MR markers of inflammation and axonal loss have, respectively, provided new insights into the mechanisms of relapse and remission on the one hand and persistent disability on the other. Monthly MRI is a powerful method for screening new therapies in relapsing-remitting and relapsing-progressive disease, but because of the uncertain relationship between short-term MRI activity and long-term disability, definitive trials should continue to have primary clinical endpoints.

Diagnostic Imaging↗

PubMed1996

[Course of illness and prognosis of multiple sclerosis. 1: The natural illness course].

This review summarizes the natural history of multiple sclerosis (MS) in terms of disease type, survival, relapse rate and recovery as well as disability. The course of Ms is highly variable and individually difficult to predict. In epidemiological studies, the most common type of MS is the relapsing-remitting form. However, after 10-15 years of disease duration, 30-40% of patients will develop chronic progressive MS. Survival of all MS patients is only mildly affected, but markedly decreased in severely disabled patients mainly due to secondary complications. Suicide is more frequent in MS patients than in normals, especially within the first 5 years of the disease. The mean relapse rate ranges from approximately 0.5 to 0.8 relapses per year and decreases with time. Most patients will recover from relapses within 4 weeks. 50% of patients will require some form of walking aid within 15-18 years from onset. 20-40% of patients have ,,benign" MS, i.e. no or only mild disability after 10 years of MS.

Activities of Daily Living↗