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Results for “Multiple Sclerosis, Relapsing-Remitting”

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PubMed1992

Using gadolinium-enhanced magnetic resonance imaging lesions to monitor disease activity in multiple sclerosis.

The highly variable clinical course and the lack of a direct measurement of disease activity have made evaluation of experimental therapies in multiple sclerosis (MS) difficult. Recent studies indicate that clinically silent lesions can be demonstrated by magnetic resonance imaging (MRI) in patients with mild relapsing-remitting MS. Thus, MRI may provide a means for monitoring therapeutic trials in the early phase of MS. We studied 12 patients longitudinally for 12 to 21 months with monthly gadolinium (Gd)-enhanced MRIs. The data have been used to identify the most effective design of a clinical trial using Gd-enhanced lesions as the outcome measure. Frequent ( > 1/mo) Gd-enhancing lesions were observed in 9 of the 12 patients, indicating that the disease is active even during the early phase of the illness. The frequency of the lesions was not constant; there was marked fluctuation in lesion number from month to month. However, the magnitude of the peak number of lesions and the frequency of the peaks varied among patients. Because of this variability, the most effective use of Gd-enhancing lesions as an outcome measure in a clinical trial was a crossover design with study arms of sufficient duration to allow accurate estimation of lesion frequency. Monitoring Gd-enhancing lesions may be an effective tool to assist in the assessment of experimental therapies in early MS.

Adult↗

PubMedDate not supplied

[Lipid peroxides in the sera of patients with multiple sclerosis].

Serum lipid peroxides (LPX) were determined in 24 patients with multiple sclerosis and in 30 healthy controls. Patients with relapses or chronic progression had significantly higher serum LPX level than healthy controls: mean 3.09 +/- 0.15 nmol/ml versus 2.30 nmol/ml, p less than 0.01. Relapsing-remitting patients showed slightly higher LPX level than slowly progressive patients. It is supposed that lipid peroxides are unspecific mediators of the inflammatory reaction in multiple sclerosis.

Adult↗

PubMed1992

Prevalence of multiple sclerosis in Barrhead County, Alberta, Canada.

A prevalence study of multiple sclerosis (MS) was carried out in the town of Barrhead and surrounding county of Barrhead, in Alberta, Canada. The prevalence rate for clinically probable/definite multiple sclerosis on January 1, 1990 was 196/100,000. The average annual incidence rates for patients living in the area at onset were 1.31/100,000 for 1950-59, 4.97/100,000 for 1960-69, 3.77/100,000 for 1970-79, and 4.22/100,000 for 1980-89. Fifty percent of the patients were relapsing-remitting. Sixty percent were still walking without assistance. The female-to-male ratio was 1:1. Mean current age, age at onset and duration of illness were 49, 27 and 22 years respectively. The majority of patients (40%) experienced multiple symptom onset. Fifty percent were of single ethnic origin (either British or German); the rest were predominantly North European combinations. Forty percent of patients reported another MS relative. MS had affected the work status of 60% of the patients, 15% of whom were confined to an extended care centre.

Adult↗

PubMed1991

Multiple sclerosis: an immune system activation disease.

Two-color flow-cytometric analysis on peripheral blood lymphocytes of 46 untreated multiple sclerosis patients (MS), 36 other medical disease patients (OMD) and 19 healthy control subjects (HC) was performed to know the relationships between T and B cell subpopulations. In MS patients we observed an increase of total lymphocyte count and an increase of CD4+CD29+ cells, which are adjuvant to B cell in antibody production. We hypothesized this change is related to the reduction of CD21+ cells, expressing B2 antigen which disappears after B cell activation. The unperfect balance of immune system in MS was also demonstrated by the increased level of CD25+ cells in relapsing-remitting patients and by the decreased level of CD4+ CD45RA+ (suppressor inducer) cells in progressive patients.

Adult↗

PubMed1991

Increased free light chains in the urine from patients with multiple sclerosis.

We quantitated free kappa (kappa) and lambda light (L) chains in coded urine specimens from subjects with clinically definite multiple sclerosis (MS) (N = 56), other neurologic diseases (OND) (N = 30), and age-matched normal controls (N = 28). Urine from MS patients showed statistically significant increases in free L chains compared with the other groups, although there was overlap between MS patients and OND patients. The ratio of kappa/creatinine was significantly greater in the relapsing-remitting MS group than in patients with clinically stable MS, OND, and normal controls. Elevated free L chains were usually independent of urinary albumin and beta 2-microglobulin levels. Serial studies showed that urinary free kappa/creatinine ratios were elevated during periods of clinical worsening in seven of eight MS patients and subsequently decreased during clinical recovery. The measurement of free L chains in urine obtained at intervals from MS patients may be useful as a marker to monitor disease activity.

Albuminuria↗

PubMed1990

Long-term follow-up of MS: disease activity detected clinically and by MRI.

Prospective clinical and magnetic resonance imaging (MRI) studies were performed over a period of 2-3 years on 51 MS patients. Comparing cerebral MRI and neurological evaluation for sensitivity in detecting disease activity, follow-up MRI turned out to be superior to standardized clinical assessment. In particular, an interval during which the clinical findings remain stable may not necessarily indicate that there is no florid inflammatory activity during this time. The morphological progression demonstrated a preference towards periventricular localization around the posterior horns of the lateral ventricles, and non-periventricularly in the frontal white matter. Longitudinal MRI studies of the disease activity can be an aid in obtaining a more definite diagnosis. Patients having had the disease for a longer period showed a more rapid clinical and morphological progression. Clinical progression and an increase in periventricular involvement were observed more often in the primary unremitting-progressive form of MS than in the relapsing-remitting form.

Adolescent↗

PubMed1991

The relationship of interleukin-2 and soluble interleukin-2 receptors to intrathecal immunoglobulin synthesis in patients with multiple sclerosis.

The in vivo relationship of interleukin-2 (IL-2) to the local humoral immune response within the central nervous system (CNS) in patients with multiple sclerosis (MS) is hitherto largely unknown. Intrathecal levels of IL-2 and soluble IL-2 receptors (sIL-2R) were correlated to the local CNS synthesis of immunoglobulin G, A, D, and M isotypes in 70 patients with clinically definite MS. Levels were also determined in 19 normal control subjects to establish normal reference limits. High cerebrospinal fluid levels of IL-2 and sIL-2R were detected mainly in patients with acute relapsing-remitting MS and were significantly higher than corresponding serum levels. Intrathecal levels of IL-2 significantly correlated with local CNS synthesis of IgD and IgM, while no correlation was found with either IgG or IgA. Similarly, intrathecal sIL-2R levels significantly correlated with local CNS production of IgD and IgM, but not IgG or IgA. These findings further extend previous reports and also suggest that IL-2 and sIL-2R are involved in the early intrathecal humoral immune response in MS.

Female↗

PubMed1979

Lymphoblastic transformation in response to viral antigens in multiple sclerosis.

The blastogenic response of lymphocytes to pokeweed mitogen and a battery of viral antigens was studied in healthy individuals, patients with multiple sclerosis (MS), and patients with other neurologic disorders. The multiple sclerosis patients exhibited a diminished response to pokeweed mitogen and to mumps, parainfluenza, and poliomyelitis I antigens when compared with healthy individuals. However, there was no significant difference between the multiple sclerosis patients and the neurologic control group, except that the MS patients had a better response to measles antigen. The three groups did not differ with regard to herpes antigen. Blocking factors were found in the autologous plasma of all three groups with approximately equal frequency, but were not responsible for the decreased responses noted. A significant inverse correlation was found between disease severity and the blastogenic response to pokeweed mitogen and herpes, parainfluenza, and measles antigens. These findings indicate that the decreased cell-mediated immune response in some MS patients is not specific for any of the viruses tested, and is probably a nonspecific effect of chronic disease. Patients with the relapsing-remitting form of the disease had a higher response to measles antigen and a lower response to pokeweed mitogen than patients with the chronic progressive form of the disease, suggesting that these variants differ immunologically as well as clinically.

Adult↗

PubMed1990

Multiple sclerosis: relations between MRI and CT findings, cerebrospinal fluid parameters and clinical features.

Cerebral MRI and CT findings were compared with various cerebrospinal fluid (CSF) parameters and clinical features in 75 patients with multiple sclerosis (MS). There were positive correlations between CSF albumin as a parameter of blood-brain barrier function and morphological parameters, namely the number of nonperiventricular foci and periventricular involvement demonstrated by MRI and ventricular enlargement as shown by CT. Apart from positive correlations between the number of nonperiventricular foci and CSF levels of IgA and IgG, including the IgG synthetic rate, no other correlations were found between CSF parameters (leucocyte count and immunoglobulin concentrations) and morphological findings. The unremitting-progressive type of MS was distinguished from the relapsing-remitting form by a lower CSF leucocyte count and a higher degree of disability, but there was no difference between the morphological findings in the two forms. Positive correlations were found between degree of disability and both periventricular involvement in the MRI and CT evidence of ventricular enlargement. In terms of correlations with the duration of disease, cerebral MRI proved to be far superior to CSF evaluations.

Adolescent↗

PubMed1992

Clinically isolated lesions of the type seen in multiple sclerosis: a cognitive, psychiatric, and MRI follow up study.

There is a dearth of longitudinal studies on psychometric and psychiatric change in multiple sclerosis (MS) particularly on the evolution of these abnormalities early in the disease process. A 4 1/2 year follow up study documenting magnetic resonance imaging (MRI), psychometric, and psychiatric abnormalities was undertaken in a group of 48 patients with clinically isolated lesions--for example, optic neuritis--which are frequently the harbinger of MS. At follow up about half the subjects had developed clinically definite MS, with memory deficits becoming apparent. Deficits in attention documented at initial assessment were present but unchanged in those subjects who still had a clinically isolated lesion status. However, after MS was categorised into a relapsing-remitting or chronic progressive course, patients with a chronic progressive course were found to have significantly deteriorated with regard to auditory attention tasks. T1 relaxation times in apparently normal white matter correlated with certain indices of cognitive impairment. In developing a model to explain the pathogenesis of intellectual and emotional change in MS, the interaction of organic, psychological, and social factors needs to be emphasised.

Adult↗

PubMedDate not supplied

[Multiple sclerosis--studies of the correlations between selected parameters of immune response and the clinical course of the disease].

In the paper the following immune response parameters were analyzed: number of leucocytes in the cerebrospinal fluid, IgG index, presence and number of oligoclonal IgG bands. The correlation between these parameters and between the parameters and clinical course of multiple sclerosis was studied. Oligoclonal bands were present in the cerebrospinal fluid in 92% cases of MS, and that was the most frequent abnormality among immune response parameters studied. There was a correlation between IgG index, number of leucocytes in the cerebrospinal fluid and number of oligoclonal IgG bands in patients with relapsing-remitting course of the disease. We did not find any statistical differences between the number of leucocytes in the cerebrospinal fluid, the frequency of pleocytosis and the type of the disease, relapsing remitting or chronic progressive. The type of the disease, its duration and number of relapses did not significantly influence the IgG index values and number of IgG oligoclonal bands in the cerebrospinal fluid.

Adult↗

PubMed1991

Increased lymphocyte beta-adrenergic receptor density in progressive multiple sclerosis is specific for the CD8+, CD28- suppressor cell.

Beta-adrenergic receptor density on T cells from healthy humans is greatest on suppressor cells (CD8+, CD28-) and the effect of catecholamines, secreted by the sympathetic nervous system, predominates on this subset. The sympathetic skin response, a measure of sympathetic nervous system function, is absent in most patients with chronic progressive multiple sclerosis (MS). We measured beta-adrenergic receptor density on suppressor cells, cytotoxic cells, and monocytes from patients with chronic progressive MS and healthy control subjects. Control receptor density on suppressor cells was 2.8 +/- 0.3 fmol/10(6) cells versus a density of 5.1 +/- 0.7 fmol/10(6) cells for patients. Cytotoxic cell (CD8+, CD28+) receptor density was 1.4 +/- 0.4 fmol/10(6) cells in control subjects and 0.9 +/- 0.3 fmol/10(6) cells in the patients. Monocytes displayed beta-adrenergic receptor densities of 2.6 +/- 0.4 fmol/10(6) cells in normal individuals and 2.7 +/- 0.4 fmol/10(6) cells in the patient group. CD8 lymphocyte beta-adrenergic receptor densities in patients with relapsing-remitting and those with stable MS were not different from control values, yet were significantly less than the values for patients with chronic progressive MS. We find that mononuclear cells from healthy control subjects and patients with chronic progressive MS proliferate in response to 200 units/ml of recombinant human interleukin-2 (IL-2) similarly. However, IL-2 treatment increased beta-adrenergic receptor density on normal mononuclear cells, but failed to increase it on mononuclear cells from patients with chronic progressive MS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Tumor necrosis factor alpha production as a possible predictor of relapse in patients with multiple sclerosis.

No biological parameter is currently available as a specific marker of multiple sclerosis (MS) activity. The aim of this study was to determine whether an evolution of the neurological disability is associated with a modified profile of cytokine production. Clinical disease activity was quantitated by the Kurtzke's expanded disability status scale (EDSS). Whole blood was stimulated with phytohemagglutinin (PHA) for 2 hours at 37 degrees C and the activated plasma was assayed for Tumor necrosis factor alpha (TNF-alpha) and Interleukin-1 beta (IL-1 beta). Relapsing-remitting MS patients enduring a relapse (RRMS, in relapse) (721 +/- 58 pg/ml, n = 27) and chronic progressive MS (CPMS) patients (516 +/- 33 pg/ml, n = 17) had an higher TNF-alpha production capacity as compared to healthy subjects (143 +/- 25 pg/ml, n = 17), RRMS, stable patients, (123 +/- 11 pg/ml, n = 26) or other neurological diseases (OND) without immunological or inflammatory disease in the peripheral immune compartment (131 +/- 24 pg/ml, n = 14) (t test: p < 0.0001). IL-1 beta production was also significantly higher but to a lesser extent in the same conditions. Concentration of TNF-alpha was also found to be significantly higher in the cerebrospinal fluid (CSF) of CPMS patients (199 +/- 7.8 pg/ml, n = 7, p < 0.0001) but also in RRMS, in relapse (149 +/- 5.7 pg/ml, n = 11, p < 0.05) as compared to RRMS, stable (130 +/- 4.4 pg/ml, n = 7) or OND without inflammatory or immunological disease of the central nervous system (CNS) (142 +/- 6.2 pg/ml, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2026

Prevalence of Slowly Expanding Lesions in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Chronic active lesions (CALs) reflect chronic inflammation in multiple sclerosis (MS). Slowly expanding lesions (SELs) are CALs identified on conventional MRI by linear, concentric expansion over time, while paramagnetic rim lesions (PRLs) are CALs characterized by a paramagnetic rim on susceptibility-sensitive MRI. However, the prevalence of SELs and their overlap with PRLs remain unclear. The aims of this study were to (1) estimate the proportion of SELs among all T2 lesions and the proportion of patients with at least 1 SEL and (2) assess the proportion of SELs overlapping with PRLs. METHODS: We systematically searched PubMed, Scopus, Web of Science, and Embase on February 1, 2026, for studies evaluating SELs in MS. At least 2 authors independently assessed study eligibility. Primary outcomes were the pooled proportion of SELs among T2 lesions and the proportion of patients with at least 1 SEL. We estimated mean per-patient volumes of SELs and total T2 lesions and the proportion of SELs overlapping with PRLs. Random-effects generalized linear mixed-effects models and inverse-variance methods were used, with between-study heterogeneity assessed using τ2 and I2 and robustness using sensitivity analyses. Univariable meta-regression explored heterogeneity. PROSPERO: CRD42024603778. RESULTS: Of 5,980 records, 20 studies comprising 4,786 patients with MS were included (mean age: 43.6 ± 6.3 years; 63.7% female). Sample sizes varied by outcome. SELs accounted for 14% (95% CI 10-21) of all T2 lesions, and 78% (67-85) of patients had at least 1 SEL. After sensitivity analysis, per-patient mean volumes were 1.42 mL (0.79-2.06) for SELs and 10.6 mL (8.53-12.67) for total T2 lesions. In total, 11% (6-20) of SELs overlapped with PRLs. In subgroup analyses, proportions of SELs were similar in relapsing-remitting and progressive MS (15%), but the proportion of patients with at least 1 SEL was higher in progressive MS. Between-study heterogeneity was high across analyses with no significant sources identified. DISCUSSION: Although SELs represent a minority of T2 lesions, most patients have at least 1 SEL and a subset overlaps with PRLs, suggesting a partial correspondence between these 2 imaging markers of chronic inflammatory activity. Limitations include possible publication bias, high unexplained heterogeneity, differences in SEL identification methods, and differences in MRI time point number/timing.

Humans↗

PubMed1991

Hyperprolactinemia in multiple sclerosis.

In order to clarify endocrine abnormalities due to hypothalamic involvement in multiple sclerosis (MS), serum prolactin levels were measured in 27 patients with MS and 22 healthy subjects. The presence of hypothalamic lesions was also studied by magnetic resonance imaging (MRI). Serum prolactin levels were found to be significantly higher in MS patients than in healthy controls in both sexes. Although only one patient had galactorrhea, one-third of the MS patients had mild to moderate hyperprolactinemia, which was a 4-13-fold increase over the mean value of healthy subjects. The results of thyrotropin-releasing hormone, sulpiride, L-DOPA and bromocriptine loading tests suggested a hypothalamic dysfunction, rather than pituitary prolactinoma in MS patients. Four of eight patients with hyperprolactinema had diencephalic hypothalamic lesion(s) contiguous with the third ventricle on the brain MRI, while none of the normoprolactinemic patients had any lesions in the diencephalon. All relapsing-remitting patients with hyperprolactinemia showed a rise in prolactin levels in the acute stage of the relapse and a decrease during the recovering stage and the following remission phase. Our findings suggest that latent hyperprolactinemia due to hypothalamic dysfunction occurs frequently in MS patients in relapse. The increase of serum prolactin is considered to be a sensitive indicator for hypothalamic lesions in MS.

Adult↗

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↗

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↗