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Results for “Multiple Sclerosis, Chronic Progressive”

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PubMed1991

Antibodies to brain tissue in sera of patients with chronic progressive multiple sclerosis.

Using a blind indirect immunofluorescence assay we examined the sera of 30 multiple sclerosis (MS) patients and 30 age- and sex-matched controls for autoantibodies to brain tissue. Binding was found in 33% of the patients' sera and in only 3% of the controls' sera. Positive and negative patients differed significantly in the course of MS, since eight of the ten positive patients showed a chronic progressive form. None of the patients with a large deficit in a chronic state showed antibodies to brain tissue, while eight of the 11 active chronic progressive cases were positive. Therefore it seems possible that these brain antibodies could be used as an activity parameter, at least for this form of the disease.

Adult↗
PubMed1987

Cyclophosphamide 'pulses' in chronic progressive multiple sclerosis. A preliminary clinical trial.

To our knowledge, this is the first clinical trial in multiple sclerosis (MS) demonstrating the feasibility of directing immunomodulating therapy by monitoring immunologic results. Cyclophosphamide was administered at monthly intervals, escalating the dose until there was a significant reduction in both the number of blood B lymphocytes and helper/inducer (CD4) T cells of 14 patients with chronic progressive MS. The frequency and severity of adverse effects led us to conclude that the regimen is too toxic for the long-term treatment of patients with MS.

Adult↗
PubMed1988

Experience with use of plasmapheresis in chronic progressive multiple sclerosis: the pros.

Based on the assumptions that multiple sclerosis (MS) is an autoimmune disorder and that plasmapheresis (PP) is an effective means of removing antibodies and other proteins from the circulation, several uncontrolled studies were undertaken to ascertain the role of PP in MS. Since MS is a chronic and persistent rather than monophasic illness, PP has been used in MS in conjunction with a variety of immunosuppressive drug regimens, theoretically to prevent the rebound reformation of the offending protein being removed. Careful analysis of the uncontrolled studies shows wide variance in the types of patients treated; the extent, duration and activity of their disease; and the methodology of PP and the adjunctive immunosuppressive treatment. Nevertheless, the conclusion we reached from this analysis was that prolonged treatment with PP, in conjunction with corticosteroid and other immunosuppressive drug treatment, may have a major clinical effect in patients severely disabled with chronic progressive MS. This in itself is a remarkable conclusion, since it is drawn from data about a form of MS which, by definition, rarely if ever improves spontaneously: more than one-half of the patients reported improvement.

Adult↗
PubMed1999

A double-blind, placebo-controlled trial of extracorporeal photopheresis in chronic progressive multiple sclerosis.

Extracorporeal photopheresis is a safe therapy for cutaneous T-cell lymphoma and may have efficacy in certain autoimmune disorders. We performed a randomized, double-blinded, placebo-controlled trial of monthly photopheresis therapy in 16 patients with clinically definite multiple sclerosis (MS). All patients had progressed during the preceding year with entry Expanded Disability Status Scale (EDSS) scores between 3.0 and 7.0. Patients received photopheresis or sham therapy for 1 year and were followed for an additional 6 to 12 months. Patients were clinically evaluated by three disability scales: (1) EDSS; (2) Ambulation index and (3) Scripp's quantitative neurologic assessment. No serious side effects occurred in either group. There were no differences between the photopheresis and sham therapy groups by the disability measures. Additionally, there were no differences in progression of MRI plaque burden or evoked potential latencies. In this limited study, photopheresis was found to be safe but did not significantly alter the course of chronic progressive MS.

Adult↗
PubMed1990

Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. The Multiple Sclerosis Study Group.

Patients with clinically definite multiple sclerosis, mild to moderately severe neurological disability (entry score on the Expanded Disability Status Scale (EDSS) between 3.0 and 7.0), and a progressive course defined by an increase in the EDSS of between 1 and 3 grades in the year prior to entry were randomized to receive either cyclosporine (n = 273) or placebo (n = 274) in a 2-year, double-blinded, multicenter trial. Treatment groups at entry proved balanced for age, gender, duration of illness, and neurological disability. Cyclosporine dosage was adjusted for toxicity and a median trough whole-blood level was maintained between 310 and 430 ng/ml. The mean increase in EDSS score was 0.39 +/- 1.07 grades for cyclosporine-treated patients and 0.65 +/- 1.08 grades for placebo-treated patients from entry until the time of early withdrawal or completion of the study (p = 0.002). Of three primary efficacy criteria, cyclosporine delayed the time to becoming wheelchair bound (p = 0.038; relative risk, 0.765), but statistically significant effects were not observed for "time to sustained progression" or on a composite score of "activities of daily living." Active treatment did have a favorable effect on several secondary measures of disease outcome. A large and differential withdrawal rate (44% for cyclosporine-treated patients, 32% for placebo-treated patients) complicated the analysis but did not appear to explain the observed effect of cyclosporine in delaying disease progression. Multivariate analysis did not show institutional effects but did demonstrate substantial effects of baseline neurological disability on outcome. Nephrotoxicity and hypertension were common troublesome toxicities and accounted for most of the excess loss of patients in the cyclosporine arm of the study. Thus, chronic cyclosporine therapy was associated with a statistically significant but clinically modest delay of progression of disability in a group of patients with multiple sclerosis selected for moderately severe and progressive disease. Close supervision by physicians familiar with cyclosporine is mandatory to minimize known adverse effects, particularly nephrotoxicity, when considering the use of this immunosuppressant.

Adult↗
PubMed1983

Immunohistological analysis of T lymphocyte subsets in the central nervous system in chronic progressive multiple sclerosis.

In an analysis of pooled data, we have found that cytotoxic-suppressor T cells outnumber the helper-inducer subset and also the population of cells bearing the pan-T cell marker in specimens of CNS from patients dying with MS (Booss et al. 1983). In the present study of individual data, we have reviewed the case histories to determine if these findings were consistent in various clinical settings. Variables examined included disease duration, tempo of evolution, immunosuppressive therapy, and other potentially immunomodulating features such as tumours. The predominance of the cytotoxic-suppressor subset was not found to be altered by any of these variables. We also present an individual data analysis of cases dying without known CNS disease and of cases with chronic non-inflammatory CNS disease. We found that the low but consistently observed number of T cells was apparently unrelated to the age of the individual or the site of the CNS sampled. Analysis of selected perivascular infiltrates showed, in contrast to the CNS parenchyma, that the pan-T cells and each of the subsets were approximately equal in proportion. Consideration of this observation and of the cytotoxic-suppressor subset preponderance in the parenchyma is compatible with the possibility of antigenic modulation of the T cell differentiation antigens. Finally, the potential contribution of perivascular infiltrates to the CSF pleocytosis is considered.

Aged↗
PubMed1994

Clinical and pathological features of an autosomal dominant, adult-onset leukodystrophy simulating chronic progressive multiple sclerosis.

OBJECTIVE: To study the clinical and pathological features of a kindred with an adult-onset autosomal dominant leukodystrophy. PATIENTS: Five symptomatic and nine asymptomatic at-risk members of the kindred. INTERVENTIONS: Subjects underwent detailed histories and general and neurologic examinations. Further evaluation included electroencephalography, evoked potentials, electromyography, autonomic testing, and analysis of serum, urine, and cerebrospinal fluid. One patient underwent sural nerve biopsy and analysis. Another, previously studied patient, underwent a limited autopsy. RESULTS: Cerebellar and pyramidal dysfunction began in the fourth and fifth decades of life; subtle autonomic symptoms were often present years earlier. Frontal lobe dysfunction and abnormalities of the central visual pathways were mild and of late onset. Sensorineural hearing loss was common. The peripheral nervous system was spared. Autopsy results of one patient revealed severe degeneration of the white matter at all levels of the neuraxis, but most prominent in the frontoparietal and cerebellar regions, with sparing of the subcortical U fibers. Histological and ultrastructural examinations failed to show evidence of a specific pathogenetic mechanism or etiology. CONCLUSION: This disorder seems to be a distinct type of hereditary leukodystrophy, but its exact nature remains unknown.

Chronic Disease↗
PubMed1989

The germline repertoire of T cell receptor beta-chain genes in patients with chronic progressive multiple sclerosis.

The T cell receptor (TcR) beta-chain germline gene repertoire of multiple sclerosis (MS) patients was compared to that of 100 normal individuals. No differences in the number of gene segments defined by probes representing 14 different human V beta subfamilies and the constant region genes were found. The distribution of haplotypes defined by restriction fragment length polymorphism (RFLP) alleles detected with V beta 8, V beta 11, and C beta probes in the MS patients was significantly different from that found in normal individuals. Because 84% of the MS patients were DR2+, the findings in these patients were compared to a second group of 43 normals who were DR2+. The distribution of TcR haplotypes in MS patients was also significantly different from that in the DR2+ normals. The data suggest that an MS susceptibility gene(s) may be located in the region of the TcR beta-chain gene complex.

Alleles↗
PubMed1991

Immunologic effects of cyclophosphamide/ACTH in patients with chronic progressive multiple sclerosis.

We examined immune function and changes in T cell populations over a 1-year period in a series of progressive multiple sclerosis (MS) patients treated with different regimens of cyclophosphamide/ACTH as part of the Northeast Multiple Sclerosis Treatment Group. Our studies were designed to determine the effect of different cyclophosphamide/ACTH regimens on T cell populations and functional immune assays and to determine whether immune measures could be identified to predict which patients responded favorably to treatment. Cyclophosphamide/ACTH infusions significantly decreased the proportion of peripheral blood CD4+ T cells at 2, 6 and 12 months following treatment while there was a tendency for increased CD8 expression. This was associated with significant decreases of CD4/CD8 ratios at 2, 6 and 12 months following treatment compared to pretreatment. No changes in CD3+ T cells were observed while there were increased percentages of CDw26 (Ta1) positive and IL-2 positive T cells following treatment. The only T cell populations predictive of improvement were percentages of either CD3+ or CD4+ cells where increased percentages of either these populations at 2 months following cyclophosphamide/ACTH infusions were associated with improvement at both 6 and 12 months. In terms of functional immune measures, we found that cyclophosphamide/ACTH treatment decreased the level of proliferation in the allogeneic mixed lymphocyte reaction (MLR) at 2 months and of spontaneous proliferation of mononuclear cells at 12 months following therapy. Changes in spontaneous proliferation were predictive of clinical improvement at 12 months in that subjects with improved scores on the disability status scale (DSS) had decreases in spontaneous proliferation at 12 months as compared to pretreatment, whereas those stable or worse did not change significantly. Thus, our studies have demonstrated specific alterations in immune function following immunosuppression with cyclophosphamide/ACTH and suggest that certain immune measures may be linked to a positive clinical response and thus associated with disease progression in MS.

Adrenocorticotropic Hormone↗
PubMed1989

Frontal lobe dysfunction and memory impairment in patients with chronic progressive multiple sclerosis.

Deficits in semantic encoding have been described in patients with frontal lobe disease who also show memory impairments. As a group, patients with multiple sclerosis (MS) exhibit memory impairment, fail to make effective use of semantic encoding to aid memory, and perform poorly on verbal fluency and concept formation tests which are sensitive to frontal lobe damage. In the present study the semantic encoding capacity of MS patients was measured using a modification of Wicken's release from proactive interference (PI) paradigm. Individual patients varied considerably in the severity of their impairments on verbal fluency, verbal recognition memory and on Wisconsin Card Sorting Task, but even patients who evidenced both memory impairment and signs of frontal lobe dysfunction showed normal release from PI after a categorical shift. Memory disturbances in MS are unlikely to result from an incapacity for semantic encoding, which seems preserved in MS, but may arise instead from deficits in processing information rapidly.

Adult↗