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Results for “Multiple Sclerosis, Chronic Progressive”

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PubMed2006

Upregulation of ADAM-17 expression in active lesions in multiple sclerosis.

ADAM-17, a disintegrin and metalloproteinase, is the major proteinase responsible for the cleavage of membrane-bound tumour necrosis factor (TNF) as well as being an active sheddase of other cytokines, cytokine receptors, growth factors and adhesion molecules. TNF is a major proinflammatory cytokine that has been identified as having a pathogenic role in inflammatory diseases within the CNS including multiple sclerosis (MS). Here we report the cellular origin and distribution of ADAM-17 expression within clinically and neuropathologically confirmed MS and normal control white matter, assessed by immunohistochemistry, western blotting and PCR. ADAM-17 expression was associated with the blood vessel endothelium, activated macrophages/microglia and parenchymal astrocytes in MS white matter. Increased levels of ADAM-17 immunoreactivity were displayed in active lesions with evidence of recent myelin breakdown. Further studies into the functional role of ADAM-17 in the pathogenesis of MS and other inflammatory conditions are required.

ADAM Proteins↗
PubMed2006

Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis.

Grey matter hypointensity on T2-weighted magnetic resonance imaging (MRI) scans, suggesting iron deposition, has been described in multiple sclerosis (MS) and is related to physical disability, disease course and brain atrophy. We tested the hypothesis that subcortical grey matter T2 hypointensity is related to cognitive impairment after adjusting for the effect of MRI lesion and atrophy measures. We studied 33 patients with MS and 14 healthy controls. Normalized T2 signal intensity in the caudate, putamen, globus pallidus and thalamus, total brain T1-hypointense lesion volume (T1LV), fluid-attenuated inversion-recovery-hyperintense lesion volume (FLLV) and brain parenchymal fraction (BPF) were obtained quantitatively. A neuropsychological composite score (NCS) encompassed new learning, attention, working memory, spatial processing and executive function. In each of the regions of interest, the normalized T2 intensity was lower in the MS versus control group (all P<0.001). Regression modelling tested the relative association between all MRI variables and NCS. Globus pallidus T2 hypointensity was the only variable selected in the final model (R2 = 0.301, P = 0.007). Pearson correlations between MRI and NCS were T1LV: r = -0.319; FLLV: r = -0.347; BPF: r = 0.374; T2 hypointensity of the caudate: r = 0.305; globus pallidus: r = 0.395; putamen: r = 0.321; and thalamus: r = 0.265. Basal ganglia T2 hypointensity and BPF demonstrated the strongest associations with cognitive impairment on individual cognitive subtests. Subcortical grey matter T2 hypointensity is related to cognitive impairment in MS, supporting the clinical relevance of T2 hypointensity as a biological marker of MS tissue damage. These data implicate a role for basal ganglia iron deposition in neuropsychological dysfunction.

Adult↗
PubMed2006

Sleep and fatigue in multiple sclerosis.

Fatigue is common in multiple sclerosis (MS) and is an important cause of disability. However, the cause of fatigue is poorly understood. This study aimed to describe the frequency and pattern of sleep disturbance in a group of outpatients with MS, and to investigate the relationship between sleep disturbance and fatigue. Sixty outpatients with MS completed the Fatigue Severity Scale (FSS) and the Epworth Sleepiness Scale and kept a sleep diary for seven days. Fatigue and excessive daytime sleepiness were common in this group of patients (64 and 32%). Sleep problems on at least two nights per week occurred frequently, including initial insomnia in 42%, middle insomnia in 53% and terminal insomnia in 58%. The reasons cited for different types of insomnia varied, with anxiety and pain/discomfort being the commonest causes of initial insomnia and nocturia the commonest cause of middle insomnia. Middle insomnia was significantly correlated with daytime fatigue, a relationship that remained after controlling for disability. Sleep disturbance is common in MS and is associated with treatable symptoms, including pain and nocturia. Sleep disturbance may be an important factor contributing to fatigue in patients with MS.

Adult↗
PubMed2004

Similar low frequency of anti-MOG IgG and IgM in MS patients and healthy subjects.

The authors used a liquid-phase radiobinding assay to measure serum anti-myelin oligodendrocyte protein (MOG) immunoglobulin (Ig) G in 87 patients with multiple sclerosis (MS), in 12 patients with encephalomyelitis, and in 47 healthy subjects. Anti-MOG IgM was determined in samples obtained at onset from 40 of 87 patients with MS and in control subjects. The frequency of positive samples with low titers of anti-MOG IgG (< or =5.7%) and IgM (< or =8.3%) was similar in all the groups and subgroups. Binding competition experiments showed that these antibodies had low affinity. Anti-MOG antibodies are not disease specific.

Adolescent↗
PubMed2000

Association between clinical disease activity and Epstein-Barr virus reactivation in MS.

OBJECTIVE: To assess the potential significance of Epstein-Barr virus (EBV) reactivation in disease activity in MS patients. METHODS: The prevalence of antibodies against herpes simplex virus type 1 (HSV-1), HSV-2, EBV, and cytomegalovirus was determined in a group of 108 MS patients and in 163 healthy control subjects. Sera were analyzed using combinations of novel assay systems employing highly purified viral and recombinant antigens. In addition, PCR for the detection of EBV DNA was performed in serial samples. RESULTS: In contrast to the control populations, antibodies against EBV were present in 100% of MS patients. Among the tested human herpesviruses, this high extent of seropositivity was only found for EBV. Primary infection was found exclusively in the control group (3.7%), whereas serologic evidence of EBV reactivation was seen in MS patients (13. 9%) as well as control subjects (17.2%). There was no temporal coincidence between EBV reactivation and disease activity in MS patients. However, in 19 patients followed monthly for 1 year, active viral replication as measured by increased immunoglobulin (Ig) M and IgA responses to EBV early antigens (p54 + p138) and positive serum DNA was seen in 72.7% of patients with exacerbations during the study period and in none of the patients with clinically stable disease. CONCLUSIONS: The results demonstrate an association between EBV reactivation and disease activity in MS patients over time, and suggest that EBV might play an indirect role in MS as an activator of the underlying disease process.

Adult↗
PubMed2003

Complementarity-determining region 3 spectratyping analysis of the TCR repertoire in multiple sclerosis.

Multiple sclerosis (MS) is considered to be an autoimmune disease mediated by T cells reactive with Ags in the CNS. Therefore, it has been postulated that neuroantigen-reactive T cells bearing particular types of TCRs are expanded clonally during the course of the disease. However, there is a controversy with regard to the TCR usage by T cells associated with the development of MS. By the use of complementarity-determining region 3 spectratyping analysis that is shown to be a useful tool for identification of pathogenic TCR in autoimmune disease models, we tried to demonstrate that spectratype was T cells bearing particular types of TCR are activated in MS patients. Consequently, it was found that Vbeta5.2 were often oligoclonally expanded in peripheral blood of MS patients, but not of healthy subjects. Sequence analysis of the complementarity-determining region 3 region of spectratype-derived TCR clones revealed that the predominant TCR clone was different from patient to patient, but that similar results were obtained in a patient examined at different time points. More importantly, examination of cerebrospinal fluid T cells and longitudinal studies of PBLs from selected patients revealed that Vbeta5.2 expansion was detectable in the majority of patients examined. These findings suggest that Vbeta5.2 spectratype expansion is associated with the development of MS and that TCR-based immunotherapy can be applicable to MS patients if the TCR activation pattern of each patient is determined at different stages of the disease.

Adolescent↗
PubMed2003

Immune modulation in multiple sclerosis patients treated with the pregnancy hormone estriol.

The protective effect of pregnancy on putative Th1-mediated autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis, is associated with a Th1 to Th2 immune shift during pregnancy. The hormone estriol increases during pregnancy and has been shown to ameliorate experimental autoimmune encephalomyelitis and collagen-induced arthritis. In addition, estrogens induce cytokine changes consistent with a Th1 to Th2 shift when administered in vitro to human immune cells and in vivo to mice. In a pilot trial, oral estriol treatment of relapsing remitting multiple sclerosis patients caused significant decreases in enhancing lesions on brain magnetic resonance imaging. Here, the immunomodulatory effects of oral estriol therapy were assessed. PBMCs collected longitudinally during the trial were stimulated with mitogens, recall Ags, and glatiramer acetate. Cytokine profiles of stimulated PBMCs were determined by intracellular cytokine staining (IL-5, IL-10, IL-12 p40, TNF-alpha, and IFN-gamma) and cytometric bead array (IL-2, IL-4, IL-5, IL-10, TNF-alpha, and IFN-gamma). Significantly increased levels of IL-5 and IL-10 and decreased TNF-alpha were observed in stimulated PBMC isolated during estriol treatment. These changes in cytokines correlated with reductions of enhancing lesions on magnetic resonance imaging in relapsing remitting multiple sclerosis. The increase in IL-5 was primarily due to an increase in CD4(+) and CD8(+) T cells, the increase in IL-10 was primarily due to an increase in CD64(+) monocytes/macrophages with some effect in T cells, while the decrease in TNF-alpha was primarily due to a decrease in CD8(+) T cells. Further study of oral estriol therapy is warranted in Th1-mediated autoimmune diseases with known improvement during pregnancy.

Adjuvants, Immunologic↗
PubMed2004

Distortion of the self-reactive IgG antibody repertoire in multiple sclerosis as a new diagnostic tool.

To date, none of the myelin-associated Ag targets definitively discriminates between the immune response observed in multiple sclerosis (MS) patients and healthy subjects. However, it has been shown recently that analysis of global immune Ab profiles such as natural autoantibody reactivities can help to distinguish between normal individuals and patients suffering from various immune diseases. The aim of our study was to compare the global IgG immune response against brain self-Ags in sera from 82 MS patients and 27 healthy subjects. The analysis of the immune profiles was performed by Western blotting, and data were subjected to linear discriminant analysis. Particular patterns of IgG reactivity were found in healthy subjects, Sjögren patients, and MS patients. Moreover, this approach separated the three clinical forms of MS with a high concordance rate with the clinical data (kappa value, 77.8%). Our study suggests, for the first time, that serum IgG Ab repertoires are able to distinguish MS patients. In addition, our data suggest that patterns of IgG reactivity could model the pathological processes underlying the various forms of MS. Further characterization of such discriminant Ags could provide useful information regarding their potent role in pathogenesis or regulatory processes in MS.

Adult↗
PubMed1999

Investigation of apparent diffusion coefficient and diffusion tensor anisotrophy in acute and chronic multiple sclerosis lesions.

BACKGROUND AND PURPOSE: The various stages of multiple sclerosis (MS) are characterized by de- and remyelination as well as by inflammation. Diffusion MR imaging is sensitive to tissue water motion, which might correspond to these pathologic processes. Our purpose was to demonstrate differences in apparent diffusion coefficient (ADC) and diffusion tensor anisotropy in acute and chronic MS plaques and in normal-appearing brain. METHODS: Twelve MS patients underwent conventional and full-tensor diffusion MR imaging with B = 1221 s/mm2. Derivation of trace ADC and calculation of anisotropic scalars, including eccentricity, relative anisotropy (RA), and fractional anisotropy (FA) was performed on a per-pixel basis. Regions of interest of plaques and normal structures were determined on coregistered maps. MS lesions were classified as acute, subacute, or chronic on the basis of their appearance on conventional images and in relation to clinical findings. RESULTS: Seven patients had acute plaques with a concentric arrangement of alternating high and low signal intensity on diffusion-weighted images. In nine acute lesions, plaque centers had high ADC with reduced anisotropy compared with rim, normal-appearing white matter (NAWM), and chronic lesions. The thin rim of diffusion-weighted hyperintensity surrounding the center showed variable ADC and anisotropic values, which were not statistically different from NAWM. Subacute and chronic MS lesions had intermediate ADC elevations/anisotropic reductions. Calculated FA pixel maps were superior to eccentricity or RA maps; however, quality was limited by signal-to-noise constraints. CONCLUSION: ADC and diffusion anisotropic scalars reflect biophysical changes in the underlying pathology of the demyelinating process.

Adolescent↗
PubMed2001

Enhancing patterns in multiple sclerosis: evolution and persistence.

BACKGROUND AND PURPOSE: Contrast enhancement on MR images of patients with multiple sclerosis (MS) is known to be associated with abnormalities of the blood-brain barrier (BBB). However, little is known about diagnostic patterns and common features of enhanced MS lesions. This study was designed to evaluate initial enhancement patterns, changes in these enhancing patterns, and duration of enhancement in a cohort of patients with MS. METHODS: Twenty-five patients with clinically definite MS were studied retrospectively. The appearance of enhancing lesions and sequential changes in the appearance on axial contrast-enhanced spin-echo images were evaluated. The enhancing lesions were classified as nodular, ringlike, or "other" (eg, arclike). RESULTS: Of 301 new enhancing lesions, 205 (68%) showed nodular enhancement, 70 (23%) a ring pattern, and 26 (9%) a pattern neither nodular nor ringlike (eg, arclike). Two hundred eighty (93%) of 301 enhancing lesions disappeared within 6 months, and seven (2%) lesions showed persistent enhancement longer than 6 months. The other 14 (5%) lesions, which disappeared by the time of the next scan, were excluded, because the course between two examinations was longer than 6 months. Of nine persisting nodular enhancing lesions on the follow-up images, seven were decreased in size, whereas all of two persisting ringlike enhancing lesions on the follow-up images were larger than before. CONCLUSION: Nodular enhancement is the predominant enhancement pattern for new MS lesions, and the temporal course of enhancement is usually shorter than 6 months. The appreciation of the evolution of MS-enhanced lesions aids in both identifying new MS lesions and distinguishing these lesions from other pathologic entities. This may be helpful in clinically evaluating the stage of MS lesions.

Adult↗
PubMed2001

[The role of MRI in the diagnosis and the natural course of multiple sclerosis].

Magnetic resonance imaging (MRI) is very sensitive in depicting multiple sclerosis (MS) lesions, but its specificity is poor. New sequences such as fast spin echo and FLAIR (fluid attenuated inversion recovery) improve the detection of lesions. The exploration of the whole central nervous system, brain, optic nerves and spinal cord improves sensitivity and specificity. The existence of lesions at different ages responds to temporal dissemination. MRI has also allowed to better understand the natural history of MS, showing 5 to 10 times more radiological than clinical activity. In case of isolated demyelinating syndrome, MRI is the best predictor of the occurrence of definite MS and of the severity of disability in the subsequent 10 years. However, the diagnosis of MS remains clinical, and systematic control MRI are not useful in clinical practice.

Brain↗
PubMed2002

[Multiple sclerosis. Therapeutic nihilism is the wrong approach here].

The standard treatment for acute multiple sclerosis relapses continues to be the intravenous administration of high-dose methylprednisolone. For prophylactic purposes, immunomodulatory therapy with interferon beta or glatiramer acetate, immunoglobulins or azathioprine. Studies have shown that interferon beta not only reduces the frequency of relapses by one-third, but also significantly delays the second relapse, provided it is administrated early, that is, immediately following the first relapse. The reduction in the patient's quality of life caused by the illness can be appreciably improved by a whole series of symptomatic treatments. The ideal situation is a cooperative effort by an interdisciplinary team.

Clinical Trials as Topic↗