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Results for “Multiple Sclerosis, Chronic Progressive”

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At least 973 records · Page 54Linked to original sources
PubMed1991

Increased interleukin-1 production by peripheral blood mononuclear cells in patients with multiple sclerosis.

The production of interleukin-1 (IL-1) by peripheral blood mononuclear cells (MNC) was assessed in patients with relapsing multiple sclerosis (MS) in both the active and inactive phase, in chronic progressive MS patients, in other neurological diseases, and in healthy subjects. Production was determined by measuring the IL-1 concentration in cultures with MNC supernatants using enzyme-linked immunosorbent assay (ELISA). IL-1 in sera of MS patients and healthy subjects also was investigated. MNC IL-1 alpha production was significantly higher in MS patients (180.2 +/- 177.5 pg/ml) than in healthy subjects (66.2 +/- 66.0 pg/ml) (P less than 0.05). Relapsing MS patients in the active phase had significantly higher MNC IL-1 alpha concentrations (360.1 +/- 130.0 pg/ml) than normal subjects (P less than 0.001), but MNC IL-1 alpha production in patients with relapsing MS in the inactive phase (65.3 +/- 52.8 pg/ml) or chronic progressive MS (80.9 +/- 71.9 pg/ml) was not increased significantly. MNC IL-1 beta production in MS patients was not elevated significantly. IL-1 alpha and -1 beta were not detected in sera of MS patients. The correlation between increased IL-1 alpha production and the clinical course of MS suggests that activated MNC may play a role in the pathogenesis of MS.

Adult↗
PubMed1997

Cerebrospinal fluid lactate and glutamine are reduced in multiple sclerosis.

OBJECTIVES: To analyse various metabolites in human cerebrospinal fluid from healthy controls and patients with multiple sclerosis. PATIENTS AND METHODS: Cerebrospinal fluid was obtained from patients by lumbar puncture, frozen, redissolved, and analysed for metabolites by proton nuclear magnetic resonance spectroscopy. RESULTS: Significantly lower values for lactate and glutamine were found in patients with multiple sclerosis in comparison with controls. No significant differences were found between patients with the relapsing-remitting and chronic progressive forms of the disease for any of the metabolites measured. CONCLUSION: There is a concomitant reduction in both lactate and glutamine in the cerebrospinal fluid of patients with multiple sclerosis compared to controls. This may be related to altered astrocytic metabolism during the disease. The results clearly show the diagnostic potential of magnetic resonance spectroscopy in diseases such as multiple sclerosis.

Adolescent↗
PubMed1976

[Preliminary results of imurek treatment of multiple sclerosis].

The authors, after presenting a survey of the literature on the treatment of multiple sclerosis with immunosuppressants, report their experience with Imurek. Of 53 patients with a chronic and progressive course of the disease, objective improvement could be observed in 17. In 20 patients the symptomatology remained unchanged, although 4 of them reported subjective improvement. In 16 patients, progression of the disease could not be stopped. Better results of treatment could be obtained for those forms of the disease where the course was, first, in the form of what may be referred to as outbursts and, later, in a chronic and progressive form. -Possible side effects are pointed out.

Adult↗
PubMed2006

Purine nucleoside analogs as immunosuppressive and antineoplastic agents: mechanism of action and clinical activity.

The purine nucleoside analogs (PNA) form an important group of cytotoxic drugs active in the treatment of neoplastic and autoimmune diseases. Three of them, fludarabine (FA), cladribine (2-chlorodeoxyadenosine, 2-CdA) and pentostatin (2'-deoxycoformycin, DCF) have established clinical activity in hematological malignancies and have been approved by FDA. These drugs are also investigated in some autoimmune diosorders. Recently four novel PNA: clofarabine (CAFdA), nelarabine, immucillin H (BCX-1777, forodesine) and 8-chloroadenosine (8-Cl-Ado) have been synthesized and introduced into clinical trials. All these drugs have chemical structure similar to adenosine or guanosine, however, the mechanism of their action is different. FA, 2-CdA and CAFdA mainly require phosphorylation by deoxynucleoside salvage pathways. The cytotoxic effect exerts the triphosphate metabolites, which are incorporated into DNA, and finally lead to programmed cell death. In contrast, DCF does not need to be phosphorylated and results in an increase of plasma deoxyadenosine (dAdo) levels and intracellular deoxyadenosine triphosphate (dATP). Nelarabine is an arabinosylguanine (ara-G) prodrug, which after conversion to ara-G is phosphorylated to ara-G triphosphate (ara-GTP). Accumulation of ara-GTP finally leads to apoptosis. Forodesine is a purine nucleoside phosphatase (PNP) inhibitor which blocks intracellular deoxyguanine (dGuo) cleaving to guanine (Guo), but instead converts it to deoxyguanosine triphosphate (dGTP), and similarly to other PNA resulting in apoptosis. 8-chloroadenosine (8-Cl-Ado) is a ribonucleoside analog. The mechanism of its action is quite different from other PNA and remains poorly understood. However, it is known that the drug inhibits RNA synthesis, but not DNA. These agents have significant cytotoxic activity against lymphoid and myeloid malignant cells. Moreover, they have deleterious effects on the normal resting lymphocytes. They result in prolonged lymphocyte depletion especially in the CD4 subset of T-cells. Several clinical trials have demonstrated that PNA used alone or in combination with other cytotoxic drugs or monoclonal antibodies shows good efficacy and acceptable toxicity profile in the treatment of lymphoid malignancies. 2-CdA and DCF are drugs of choice in the treatment of hairy cell leukemia. FA and 2-CdA have significant clinical activity in low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia. 2-CdA exhibits some activity in progressive multiple sclerosis and other autoimmune disorders. This review will summarize current knowledge concerning the mechanism of action, pharmacological properties, clinical activity and toxicity of PNA accepted for use in clinical practice as well as new agents available for clinical trials.

Antineoplastic Agents↗
PubMed1980

Long-term care of patients with multiple sclerosis: a neurologist's perspective.

Multiple sclerosis is a chronic disease with varying degrees of disability and progression. Because there is no known specific therapy, for best care, patients are individualized, with attempts to deal with each patient and each complication separately, thoughtfully, and with psychological support when required. Efforts are directed toward helping the patient adjust to the realities of the disease and to specific disabilities. Ways and means of gaining patient confidence are discussed--and emphasis is placed on the known pathologic processes involved and how information, personalized professional attention, and support might function to aid the body's defense mechanisms for containment of the disease process. Several clinical cases were summarized (at the symposium) to illustrate the favorable and unfavorable effects of personality and emotional characteristics over a long term of care.

Humans↗
PubMed1998

Infrequent detection of human herpesvirus 6 DNA in peripheral blood mononuclear cells from multiple sclerosis patients.

Several studies have suggested an association between human herpesvirus 6 (HHV-6) infection and multiple sclerosis. As HHV-6 is predominantly a T-cell tropic virus, we examined the frequency of detection of HHV-6 genome in peripheral blood mononuclear cells from relapsing-remitting (n = 32) and chronic progressive (n = 14) patients and from healthy (n = 17) and neurological (n = 7) controls. Two sensitive polymerase chain reaction assays were used to target different regions within the HHV-6 genome. Depending on the polymerase chain reaction assay used, the detection of HHV-6 genome ranged from 11.7 to 23.5% (controls), 3.1 to 23.0% (relapsing-remitting), and 14.2 to 28.5% (chronic progressive). Although these observations do not exclude a pathogenic role for HHV-6 in multiple sclerosis, they indicate a lack of correlation between HHV-6 infection of peripheral blood mononuclear cells and the development of multiple sclerosis.

Adult↗
PubMed2004

Progression of multiple sclerosis is associated with exon 1 CTLA-4 gene polymorphism.

OBJECTIVES: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system which is widely believed to have a T-cell-mediated etiology. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) antigen molecule plays a key role in the downregulation of T-cell responses. To examine the genetic association of the CTLA-4 gene locus with MS, we analyzed an exon 1 (A49G) transition. MATERIAL AND METHODS: One hundred and fifty-two MS patients and 154 controls were examined. The A/G transition was genotyped by a polymerase chain reaction followed by labeling with a SNaPshot kit and detection using a capillary genetic analyzer. RESULTS: The genotype, allele and phenotype frequencies did not differ significantly between MS patients and controls. Those MS patients with AA and AG genotypes had 4.36 times greater risk of progressing from the relapsing-remitting to the secondary progressive form of the disease than those with the GG genotype. CONCLUSION: The results of our study indicate that CTLA-4 (A49G) exon 1 polymorphism is associated with MS progression.

Adult↗
PubMed1988

Neutralization of anti-myelin basic protein by cerebrospinal fluid of multiple sclerosis patients in clinical remission.

Autoantibodies to myelin basic protein (anti-MBP) can be detected in the cerebrospinal fluid (CSF) of MS patients using a solid phase radioimmunoassay. Acute relapses of MS are characterized by an elevated, above unity, free (F) to bound (B) anti-MBP ratio; while in contrast, patients with chronic progressing disease have a low, below unity, free to bound ratio of anti-MBP. As patients with acute relapses enter into remission, the F/B anti-MBP ratio gradually decreases and eventually the level of these autoantibodies becomes undetectable. Neutralization of free anti-MBP was observed in intra- and interpatient experiments in which CSF from MS patients in remission was reacted with CSF of patients with acute relapses. Inhibition of anti-MBP neutralization was produced by CSF from MS patients with chronic progressing disease.

Autoantibodies↗
PubMed2000

Temporal development of autoreactive Th1 responses and endogenous presentation of self myelin epitopes by central nervous system-resident APCs in Theiler's virus-infected mice.

Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease is a chronic-progressive, immune-mediated CNS demyelinating disease and a relevant model of multiple sclerosis. Myelin destruction is initiated by TMEV-specific CD4(+) T cells targeting persistently infected CNS-resident APCs leading to activation of myelin epitope-specific CD4(+) T cells via epitope spreading. We examined the temporal development of virus- and myelin-specific T cell responses and acquisition of virus and myelin epitopes by CNS-resident APCs during the chronic disease course. CD4(+) T cell responses to virus epitopes arise within 1 wk after infection and persist over a >300-day period. In contrast, myelin-specific T cell responses are first apparent approximately 50-60 days postinfection, appear in an ordered progression associated with their relative encephalitogenic dominance, and also persist. Consistent with disease initiation by virus-specific CD4(+) T cells, CNS mononuclear cells from TMEV-infected SJL mice endogenously process and present virus epitopes throughout the disease course, while myelin epitopes are presented only after initiation of myelin damage (>50-60 days postinfection). Activated F4/80(+) APCs expressing high levels of MHC class II and B7 costimulatory molecules and ingested myelin debris chronically accumulate in the CNS. These results suggest a process of autoimmune induction in which virus-specific T cell-mediated bystander myelin destruction leads to the recruitment and activation of infiltrating and CNS-resident APCs that process and present endogenous myelin epitopes to autoreactive T cells in a hierarchical order.

Amino Acid Sequence↗
PubMed1977

Spontaneous and PHA stimulated lymphocyte transformation in multiple sclerosis patients during and after acute exacerbations with special reference to steroid therapy.

Spontaneous (SLT) and phytochemagglutinin (PHA) stimulated lymphocyte transformation was studied in multiple sclerosis (MS) patients suffering from acute exacerbations or from the chronic progressive type of MS. The changes in cell-mediated immunity were also observed before, during and after immunosuppressive (prednisone) treatment. A total of 85 venous blood samples from 23 MS patients (11 males, 12 females) were included in the material. The controls consisted of 25 measurements from 17 healthy volunteers who served as normal controls. The pathological controls consisted of 13 patients with neurological diseases other than MS. All these and MS patients were hospitalized. The IUFdR uptake of the cells of MS patients was more rapid than that of the controls at 1-hr incorporation time in SLT. The difference decreased and was eliminated by longer incubation times (2-4 hrs). MS patients also differed from pathological controls in this sense. The reaction to PHA stimulation was lower both in the MS groups (64 per cent from the normal controls) and in the pathological controls. Within the different MS groups, significantly lower values were seen only in the samples of the patients receiving immunosuppressive therapy. Under prednisone (80-100 mg initial dosis) PHA stimulation values rapidly dropped within the first week and slowly returned within 2-4 weeks after the stopping of the corticosteroid treatment. In some cases, however, PHA values remained at a low level for several months. The significance of this finding for the understanding of the underlying pathogenetic mechanisms has to be studied in more detail.

Female↗
PubMed1996

Generation of autonomously pathogenic neo-autoreactive Th1 cells during the development of the determinant spreading cascade in murine autoimmune encephalomyelitis.

Chronic progression of autoimmune disease is accompanied by the acquisition of autoreactivity to new self-determinants. Recent evidence indicates that this process, commonly referred to as determinant spreading, may be pathogenic for chronicity. Our studies on experimental autoimmune encephalomyelitis (EAE), a murine model widely used in multiple sclerosis (MS) studies, have shown that determinant spreading develops as a predictable sequential cascade of neo-autoimmunity during progression to chronic disease. By 7-8 weeks after immunization of (SWR x SJL)F1 mice with the immunodominant myelin proteolipid protein determinant (PLP 139-151), splenocytes consistently respond to the immunodominant myelin basic protein determinant (MBP 87-99). In the present study, we directly address the pathogenicity of neo-autoimmunity resulting from endogenous self-priming during the course of disease. Our results indicate that T cells responding to the spreading MBP 87-99 determinant produce a proinflammatory cytokine profile consistent with type 1 helper T cells (Th1) cells. In addition, splenocytes activated to the spreading MBP 87-99 determinant consistently transfer acute EAE in naive recipients even when T cells reactive to the priming PLP 139-151 immunogen are eliminated by bromodeoxyuridine (BUdR)-mediated photolysis. Our data indicate that endogenous neo-autoantigen priming during chronic autoimmune disease generates type 1 helper T cells (Th1) cells that are autonomously pathogenic. These results provide further evidence supporting the view that determinant spreading is a pathogenic process that leads to chronic progression of autoimmune disease.

Adoptive Transfer↗
PubMed1987

Monocyte-mediated immunosuppression in chronic multiple sclerosis: implications for therapy.

The goal of immunotherapy in multiple sclerosis (MS) is to halt disease progression by correcting an immunologic abnormality. The experiments described here sought an abnormality of immunoregulation. Specifically, the immunosuppressive activity of adherent monocytes in an in vitro assay of immunoglobulin-secreting cells was tested. Although the peak response was slightly lower, the induction, development and shutdown of the response by MS cells reproduced that of control cells. Most importantly, adherent monocytes from patients with MS exerted the same maximal suppression as did monocytes from controls. Further experiments are required to determine if the adherent monocyte is an appropriate target for immunotherapy in MS.

Adult↗
PubMed1999

Primary care management of multiple sclerosis.

Multiple sclerosis is a chronic disease of the central nervous system that affects young adults most often. The course of MS is unpredictable and variable on a day-to-day basis. As chronic problems accumulate, the disease may become more steadily progressive, with fewer or no acute relapses. A diagnosis of multiple sclerosis is a clinical one based on a thorough history and neurologic examination findings and supported by magnetic resonance imaging of the brain and evoked potential studies. Management strategies fall into three general categories: treatment of relapses caused by underlying disease; prevention of progression or reduction of the frequency of relapses; and control of specific symptoms.

Humans↗
PubMed2000

Epitope spreading: a mechanism for progression of autoimmune disease.

Autoimmune diseases are typically characterized by a persistent inflammatory self-recognition process that ultimately leads to chronic progressive disability. Over the past several years we have addressed the fundamental question of why autoimmune diseases are chronic. Our working hypothesis in these studies has been that autoimmunity involves a continuous acquisition of new self-recognition events, thereby providing an inflammatory steady-state that leads to chronicity. This acquired T cell neoautoreactivity is commonly referred to as epitope spreading. By studying multiple sclerosis (MS) and its related animal model, experimental autoimmune encephalomyelitis (EAE), we have found that chronic progression of autoimmune disease is invariably linked to the development of an epitope-spreading process that manifests as a cascade of inflammatory T cell neoautoreactivities to a sequential series of predictable new target self-antigens. However, our most recent observations indicate that the emergence of epitope spreading is accompanied by a concurrent regression of the established primary autoreactivity associated with disease onset. Thus, our studies indicate that progression of autoimmune disease involves a shifting of T cell autoreactivity from primary initiating self-determinants to defined cascades of secondary determinants that sustain the inflammatory self-recognition process during progression to chronicity. Our data support the view that the natural development of self-recognition during autoimmune disease may best be understood when considered in the temporal context of an "epitope du jour" and "moving target" perspective.

Animals↗
PubMed1994

[Charcot. Dates. Legend and reality].

This introductiion to the session devoted to Charcot reviews the important steps in his career: 1848, the internship, followed by the "chef de clinique" state (1852-53); the central hospital office in 1856; the agregation in 1860; the chair of pathological anatomy in 1872; the clinical chair in diseases of the nervous system in 1882. We review as well the milestones in his scientific work. His arrival in 1862 at the Salpêtrière which he would never leave; there in 1866, he started a "free" course which became the point of departure for his reputation. Taking advantage of histology together with a mastery of the anatomical-clinical method permitted him to achieve considerable progress with a few years (associating locomotor ataxia with lesions of the posterior roots and columns; acute and chronic progressive muscular atrophy with those of the anterior horn: separating multiple sclerosis from Parkinson's disease) which culminated in the masterful description of amyotrophic lateral sclerosis (1874), the pathological anatomy and physiology of the spinal cord (1873) and cerebral localisations of motor areas (1875). Beginning in 1878, he applied the nosological method to the study of hysteria, relying on the notion of "analogous anatomy" in seeking a correspondence between organic lesions and "dynamic lesions". In 1883 and 1884, his approach to aphasia led him to introduce beyond the anatomical-clinical fact a new speculative dimension, that of psycho-physiology. This he applied to interpret hysterical ailments and "psychic paralyses". The personality of Charcot is briefly sketched. In the arts as in politics, he was more of a conservative than an opportunist; authoritarian, shy, and brusque, gloomy and taciturn, he nontheless had a remarkable power to attract.

Clinical Medicine↗
PubMed1996

Multiple sclerosis: clinical presentation, diagnosis and treatment.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system and is associated with periods of disability (relapse) alternating with periods of recovery (remission) and often results in progressive neurologic disability. Scientists believe that multiple sclerosis may be a T cell-mediated autoimmune disease. Treatment with high-dose pulses of intravenous methyl-prednisolone is usually associated with a good outcome in the short term. A recent study suggests that interferon beta-1b may decrease the number of relapses in relapsing-remitting multiple sclerosis by 30 percent and also may decrease the development of new central nervous system lesions. Recently, another clinical trial of interferon beta-1a showed a 31 percent reduction in relapse rate and a significant reduction in the average number of active lesions. A third trial showed that 20 mg of copolymer-1, a random polymer of glutamic acid, lysine, alanine and tyrosine, reduced relapses by 21 percent without significant side effects. Further investigation is needed, but these new treatments show great promise in alleviating this difficult clinical problem.

Adrenal Cortex Hormones↗
PubMed1982

Immunonephelometric quantitation of central nervous system IgG daily synthesis in multiple sclerosis. Clinical evaluation using predictive value theory.

With a laser nephelometric immunoassay and an empirical formula for the quantitation of central nervous system (CNS) daily IgG synthesis, we studied prospectively a population of 101 individuals divided into four groups: 31 normals, 25 patients with definite multiple sclerosis (DMS), 18 patients with probable or possible multiple sclerosis (PMS), and 27 patients with neurologic disease other than multiple sclerosis (NMS). By the Kruskal-Wallis, test the results of the DMS and PMS patients were significantly different from the normals and NMS patients (P less than 0.0003). Considering normals, DMS, and NMS patients only, the sensitivity of the test was 96%, the specificity was 98%, the positive predictive value was 96%, the negative predictive value was 98%, and the efficiency was 98%. Based on our study data, we applied the predictive value theory to different hypothetical populations (our Neurology Ward, Northeastern U. S., and patients with optic neuritis and chronic progressive myelopathy). In all these situations, the test gave a diagnostic efficiency for multiple sclerosis greater than 95%.

Adult↗
PubMed1999

Ferritin, transferrin and iron concentrations in the cerebrospinal fluid of multiple sclerosis patients.

The concentrations of ferritin, transferrin and iron were measured in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) and control patients. Ferritin levels were significantly elevated in the CSF of chronic progressive active MS patients (4.71+/-0.54 ng/ml) compared to levels in normal individuals (3.07+/-0.17 ng/ml). MS patients with active or stable relapsing-remitting disease had ferritin levels that were comparable to those found in normal individuals. There were no significant differences in transferrin or iron levels in the CSF between MS and normal individuals. Both ferritin and transferrin levels were elevated in patients that had high CSF IgG values but not in patients with a high IgG index. Since ferritin binds iron, the increase of CSF ferritin levels in chronic progressive MS patients could be a defense mechanism to protect against iron induced oxidative injury. Ferritin levels could be a laboratory measure that helps to distinguish between chronic progressive and relapsing-remitting MS.

Chronic Disease↗