Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Multiple Sclerosis, Chronic Progressive”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 505 records · Page 28Linked to original sources
PubMed1989

Multiple sclerosis intra-blood-brain-barrier IgG synthesis: effect of pulse intravenous and intrathecal corticosteroids.

Nine severely disabled clinically definite chronic progressive multiple sclerosis (MS) patients who had at least one determination of intra-blood-brain-barrier (BBB) IgG synthesis rate of greater than 7 mg/day (upper limit of normal = 3.3) participated in this study. Seven patients were given 1 gram of methylprednisolone sodium succinate (MP) by intravenous infusion over 30 minutes once a day for 3 days. Statistically significant (p less than .05) reduction in intra-BBB IgG synthesis (mg/day) was seen in 4/7 patients, but in only 2 were normal levels of synthesis rate (less than 3.3 mg/day) attained. Rebound of IgG synthesis to premedication rates occurred within 30 days in 2/4 patients. There was no change in intensity or pattern of cerebrospinal fluid (CSF) oligoclonal IgG bands by isoelectric focusing, immunofixation, and silver staining. A subsequent course of intrathecal methylprednisolone acetate (MPA) (80 mg twice a week for 5 weeks) was given to 5 of the 7 patients and to 2 additional patients not previously treated. In spite of signs of subarachnoid inflammation, a statistically significant depression of intra-BB synthesis, which far exceeded that from the pulse treatment occurred in all 7, including the 2 patients whose intra-BBB IgG synthesis rates were previously resistant to pulse steroid administration. Normal levels of synthesis were rapidly reached in 4/7 patients; however, an IgG synthesis rebound occurred in 3/7 patients which was just as rapid. One out of 7 patients showed a temporary reduction in the number of cathodic IgG oligoclonal bands in the CSF. Two patients required discontinuation of treatment due to aseptic meningitis in one and progressive weakness in the other. Clinically, these severely afflicted patients with fixed deficits remained unchanged with either treatment protocol. While MPA and ACTH have similar initial effect on the central nervous systems (CNS) inflammatory response in MS, the well documented risk of serious adversities with MPA prohibit its clinical use in MS in its present form.

Adult↗
PubMed1987

Reduction of immunoglobulin G secretion in vitro following long term lymphoblastoid interferon (Wellferon) treatment in multiple sclerosis patients.

Pokeweed-mitogen-induced IgG secretion, Con A suppression and T cell surface markers were measured in 30 chronic progressive multiple sclerosis (MS) patients and 21 healthy controls. Mean IgG secretion was higher in the MS patients than in the controls (2392 +/- 270 vs 1499 +/- 243); Con A suppression was lower (4 +/- 5% vs 24 +/- 4%) and the CD4/CD8 ratio was higher (4.1 +/- 0.4 vs 2.9 +/- 0.4). The above assays were used in vitro to monitor the effects of Wellferon (lymphoblastoid interferon) injections on this group of MS patients. Before treatment the INF-group (n = 14) did not differ from the PLA-group (n = 16). After 1 week of daily injections the level of IgG secreted was dramatically reduced in the INF group (629 +/- 96 ng/ml) compared to the PLA-group (1756 +/- 319 ng/ml). There was no change in either Con A suppression or T cell surface markers. IgG secretion remained lower in the INF-group for the 6 month treatment period. Following cessation of the injections and a 6 month washout period, IgG secretion in the INF-group rose and was equivalent to that observed in the PLA-group. A series of lymphocyte subset mixing experiments implicates the B lymphocyte subset as being directly affected by interferon injections in vitro.

Concanavalin A↗
PubMed1987

Molecular analysis of the CD8 gene in multiple sclerosis.

Analysis of DNA fragments of the CD8 gene following digestion with three restriction enzymes showed no differences between patients with chronic progressive multiple sclerosis (MS), familial MS and controls. These abnormalities suggest that any abnormalities in the expression of CD8 protein in MS are not likely to be due to a gross deletion or rearrangement of the CD8 gene.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

Lumbar cerebrospinal fluid concentrations of somatostatin and neuropeptide Y in multiple sclerosis.

The cerebrospinal fluid (CSF) concentrations of somatostatin and neuropeptide Y were investigated by use of radioimmunoassay in patients suffering from chronic progressive multiple sclerosis. The somatostatin level was significantly decreased in the CSF of patients with multiple sclerosis compared to the control group. The magnitude of this change was more pronounced in patients with severe clinical symptoms of the illness. The CSF neuropeptide Y concentration did not differ from the control values. These findings suggest a selective involvement of somatostatin neurotransmission in multiple sclerosis.

Adult↗
PubMed1986

Serum-mediated oligodendrocyte cytotoxicity in multiple sclerosis patients and controls.

We examined serum-mediated cytotoxicity on cultured rat oligodendrocytes, using serum from patients with acute or chronic progressive multiple sclerosis and normal controls. We found heat-labile serum factors in serum from MS and also in controls. The cytotoxic effects of MS and normal sera were not restored by adding a source of complement. Despite apparent lack of disease specificity, such factors might damage oligodendrocytes if they gained access to these cells through a damaged blood-brain barrier in MS or other disorders.

Adult↗
PubMed1997

The effect of total lymphoid irradiation and low-dose steroids on T lymphocyte populations in multiple sclerosis: correlation with clinical and MRI status.

We have monitored the cell surface phenotypic changes occurring in T, B and NK cells of chronic progressive multiple sclerosis (MS) patients after total lymphoid irradiation (TLI) plus low-dose prednisone (TLI-LDP) therapy in comparison to sham TLI-LDP. TLI-LDP resulted in a marked reduction in the relative and absolute number of total CD3+ T cells, CD4+ helper T cells, CD4+ CD45RA+ naive T cells and CD19+ B cells for at least 1 year after treatment. No change occurred in the percent CD8+ T cells although the number of these cells declined after radiotherapy. The CD4/CD8 T cell ratio was also decreased. The relative percent of CD16+ NK cells increased steadily after TLI-LDP while the number of NK cells transiently declined but returned to baseline values 1 year later. An increase in the percent of CD2+ CD3- cells and a decrease in their number after therapy was also observed. In contrast, no significant changes in the number of T, B or NK cells were seen in the MS patients receiving sham TLI-LDP. These results provide further evidence that radiotherapy causes a reduction of immunocompetent T and B cells and that a population of possibly NK cells and/or immature T cells appears to be repopulating the circulation after TLI. In addition, a correlation was observed between alterations in lymphocyte populations and the presence or absence of contrast enhancing or new T2 lesions on brain magnetic resonance imaging (MRI) in the TLI-LDP treated MS patients. Patients devoid of contrast enhancing or new T2 lesions had a decreased percentage of CD3+ and CD4+ T cells prior to therapy and at six months following TLI-LDP compared to patients with such lesions. An association was also observed between stability in disease activity as determined on the Expanded Disability Status Scale and relative values of CD3 T cells.

Adult↗
PubMed1983

Difference in effect of single immunosuppressive agents (cyclophosphamide, CCNU, 5-FU) on peripheral blood immune cell parameters and central nervous system immunoglobulin synthesis rate in patients with multiple sclerosis.

Cyclophosphamide (CY), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 5-fluorouracil (5-FU) were given in single course schedules to chronic progressive multiple sclerosis (MS) patients clinically stable for 6 months. The following peripheral immune cellular parameters were measured before, during and after each drug administration: white blood count (WBC), polymorphonuclear count (PMN), lymphocyte count, percentage of T cells, T cell response to phytohaemagglutinin (PHA), percentage of B cells, percentage of cells bearing receptors for the Fc portion of immunoglobulin (% FcR cells), killer (K) cell activity defined by antibody-dependent cellular cytotoxicity (ADCC), and natural killer (NK) cell activity. Central nervous system (CNS) immunoglobulin G (IgG) synthesis was also measured. The patients were followed carefully by both quantitative and qualitative methods for any change in their neurologic condition. Selective reduction in NK activity was observed with CY and 5-FU while no significant alteration was seen in %FcR cells and K activity. CY differed from 5-FU in reducing lymphocyte count and B cell percentage while 5-FU decreased the percentage of T cells. CCNU, but not the other drugs, reduced T cell proliferative response to PHA. In addition, CCNU, which is known to penetrate well into the nervous system, caused a modest reduction in CNS IgG synthesis, while 5-FU had an uncertain effect. Clinically the patients were unchanged or continued to progress in their disability. The results suggest an independence of the CNS immune from the systemic immune system in MS in response to many immunosuppressive drugs.

Adult↗
PubMed1995

Evidence for a missed signal to the CD8+ cells in CSF of multiple sclerosis patients.

Peripheral blood (PB) and cerebrospinal fluid (CSF) lymphocyte subpopulations, defined by various T-cell specific monoclonal antibodies and flow cytometry, were analysed in 44 relapsing remitting multiple sclerosis (RRMS) patients (including 21 subjects in the acute phase and 23 in the stable phase), 40 chronic-progressive multiple sclerosis (CPMS) patients, and 24 patients with other neurological diseases (OND), in order to verify the presence of any abnormality in the lymphocyte subset pattern. A significant increase in the total number of T-lymphocytes and the CD4+ subpopulation was found in the PB of the MS patients in comparison with the OND group. Moreover, a not statistically significant increase in CD4+ cells was observed in the CSF of MS patients. A statistically significant increase was also found in the CD4+ Leu 8+ (suppressor inducer) cells in the CSF of all of the MS groups. Finally, the CD8+ (suppressor/cytotoxic) cell levels, were significantly lower in the CSF of CPMS and stable RMS patients than in the CSF of the OND patients. As a whole, our data suggest that the immunosuppressive deficit that seems to be a constant finding in MS is not due to a decrease in suppressor inducer cell levels, as previously suggested, but may be caused by a missed or altered signal from the suppressor inducer to CD8+ suppressor cells.

Adult↗
PubMed1983

T-cell subpopulations in blood and cerebrospinal fluid of multiple sclerosis patients: effect of cyclophosphamide.

Monoclonal antibodies to various lymphocyte surface antigens were used for characterization of cerebrospinal fluid (CSF) and peripheral blood (PB) cells of patients with chronic progressive multiple sclerosis (MS) and of patients with other neurological diseases (OND). The effect of cyclophosphamide on these T-lymphocyte subpopulations in both compartments was studied. In the CSF of all patients 90 +/- 9% of the cells were T lymphocytes. T-helper/inducer (Th) lymphocytes comprised 70 +/- 9% and T-suppressor/cytotoxic (Ts) lymphocytes 31 +/- 10%. No significant differences in the percentages of T-lymphocyte subpopulations in CSF were observed between MS patients and patients with OND. The results obtained with monoclonal antibodies to Ia antigens suggested the presence of activated T cells in CSF of MS as well as OND patients. The mononuclear cell population isolated from PB of all patients contained 64 +/- 13% T lymphocytes, 44 +/- 11% Th cells, and 21 +/- 7% Ts cells. No significant difference in the ratio Th/Ts cells was observed between CSF and PB. The mononuclear cells isolated from the PB of untreated chronic progressive MS patients contained lower percentages of Ts cells (17 +/- 5%) and increased ratios of Th/Ts cells (3.1 +/- 1.6) compared to neurological controls (23 +/- 8% and 1.9 +/- 0.7) and healthy persons (23 +/- 6% and 1.9 +/- 0.5). In both PB and CSF, compared to untreated patients, cyclophosphamide-treated MS patients showed lower percentages of Th lymphocytes, whereas Ts-cell percentages were higher, leading to a normal ratio of Th/Ts cells in both compartments. The percentage of total T lymphocytes in PB was reduced by this treatment.

Antibodies, Monoclonal↗
PubMed1988

Anti-CD4 and anti-CD2 monoclonal antibody infusions in subjects with multiple sclerosis. Immunosuppressive effects and human anti-mouse responses.

The immunologic responses to anti-T4 and anti-T11 mAb infusions were assessed in subjects with chronic progressive multiple sclerosis as part of phase I clinical studies. Eight subjects received five daily infusions (0.2 mg/kg/day) of either anti-T11 (CD2) or anti-T4 (CD4) murine mAb. It was found that in vivo anti-T cell mAb infusions specifically suppress in vitro measurements of the human immune response; anti-T11 mAb blocked T cell activation via the CD2 SRBC-binding protein, and anti-T4 mAb infusions abolished PWM-induced Ig synthesis without lysis of the CD4+ T cell subpopulations. With repeated infusions of the anti-T11 mAb in three subjects, anti-mouse antibodies were found in the circulation. Although the majority of human anti-mouse antibody was not isotype specific, significant anti-idiotypic-like activity was observed after repeated infusions in two of three subjects. The human anti-mouse antibodies were almost exclusively of the IgG isotype. The magnitude of the human anti-mouse response was significantly less after administration of either anti-T11 or anti-T4 as compared with anti-T12 mAb. Murine anti-T cell mAb can provide a specific, benign form of acute immunosuppression in humans. However, repeated administration of these reagents in more chronic diseases can result in anti-Id-like antibodies that block binding of the anti-T cell mAb to the T cell surface.

Animals↗
PubMed2002

Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis.

Blood-brain barrier (BBB) breakdown, demonstrable in vivo by enhanced MRI is characteristic of new and expanding inflammatory lesions in relapsing-remitting and chronic progressive multiple sclerosis (MS). Subtle leakage may also occur in primary progressive MS. However, the anatomical route(s) of BBB leakage have not been demonstrated. We investigated the possible involvement of interendothelial tight junctions (TJ) by examining the expression of TJ proteins (occludin and ZO-1 ) in blood vessels in active MS lesions from 8 cases of MS and in normal-appearing white (NAWM) matter from 6 cases. Blood vessels (10-50 per frozen section) were scanned using confocal laser scanning microscopy to acquire datasets for analysis. TJ abnormalities manifested as beading, interruption, absence or diffuse cytoplasmic localization of fluorescence, or separation of junctions (putative opening) were frequent (affecting 40% of vessels) in oil-red-O-positive active plaques but less frequent in NAWM (15%), and in normal (< 2%) and neurological controls (6%). Putatively "open" junctions were seen in vessels in active lesions and in microscopically inflamed vessels in NAWM. Dual fluorescence revealed abnormal TJs in vessels with pre-mortem serum protein leakage. Abnormal or open TJs, associated with inflammation may contribute to BBB leakage in enhancing MRI lesions and may also be involved in subtle leakage in non-enhancing focal and diffuse lesions in NAWM. BBB disruption due to tight junctional pathology should be regarded as a significant form of tissue injury in MS, alongside demyelination and axonopathy.

Adolescent↗
PubMed2001

Little change in cerebrospinal fluid amino acids in subtypes of multiple sclerosis compared with acute polyradiculoneuropathy.

Levels of free amino acids were determined in randomised, blinded samples of cerebrospinal fluid (CSF) from patients with relapsing-remitting or chronic progressive multiple sclerosis (MS), all in the active phase of disease. The levels were compared with amino acid amounts in patients with an acute polyradiculoneuropathy (Guillain-Barré syndrome (GBS)) and a control population of patients with no known neurological disease or deficit. The data did not indicate any significant changes in amino acid levels between MS subgroups. The only significant differences between MS patients and controls were a modest reduction in glutamate and a slight increase in taurine, but the changes were so small that the biological relevance is dubious. These results contrasted with the marked increases for many amino acids in CSF from patients with acute polyradiculoneuropathy compared with controls. The amino acid profile in cerebrospinal fluid (CSF) does not appear to provide evidence of differential pathology in multiple sclerosis (MS). The increase in hydrophobic amino acids and lysine in CSF from patients with acute polyradiculoneuropathy is consistent with transudation over the blood-CSF barrier following an infection. The increases in glutamine and alanine may reflect increased nitrogen removal from brain.

Acute Disease↗
PubMed1997

Successful treatment of established relapsing experimental autoimmune encephalomyelitis in mice with a monoclonal natural autoantibody.

We postulated that humoral autoimmunity can play a beneficial role in CNS demyelinating diseases such as multiple sclerosis. We previously demonstrated that monoclonal natural autoantibody SCH94.03 suppresses CNS inflammation and promotes remyelination in a virus-induced model of chronic progressive multiple sclerosis. To further investigate the relationship between natural autoimmunity and CNS demyelination, we examined the effect of SCH94.03 treatment on clinical relapses and pathological disease in SJL/J mice with established adoptive-transfer relapsing experimental autoimmune encephalomyelitis. Treatment with SCH94.03 after recovery from the initial episode of clinical disease reduced relapse rates by half, prolonged relapse onset by 6 days and reduced spinal cord demyelination and meningeal inflammation by 40%. These results are consistent with the hypothesized immunomodulatory function of natural autoantibodies, and are the first direct demonstration that natural humoral autoimmunity can be beneficial in an autoimmune T-cell-mediated CNS demyelinating disease.

Animals↗
PubMed1989

A comparison of dementia in Alzheimer's disease and multiple sclerosis.

We compared results of comprehensive neuropsychological testing in 42 patients with clinically diagnosed Alzheimer's disease (AD) and in an equal number of patients with clinically definite chronic-progressive multiple sclerosis. Age, sex, and education were controlled using demographically corrected T scores based on a large normal sample. Both groups showed significant impairment on the test battery, but the degree of dementia was more severe in the patients with AD. A deviation score analysis, controlling for overall level of cognitive impairment, revealed significant differences between the groups. Alzheimer's disease was associated with relatively greater impairment of learning, memory, and verbal skills, whereas the MS group showed greater relative impairment of attention, incidental memory, and psychomotor functions. These data suggest that both the degree and pattern of mental impairement differ in patients with AD and patients with multiple sclerosis. Our results support a distinction between "gray matter" and "white matter" dementia, and may help clarify the issue of "cortical" vs "subcortical" dementia by demonstrating neuropsychological differences based on secure neuropathologic distinctions.

Aged↗
PubMed1993

Multiple sclerosis: remyelination in acute lesions.

Central nervous system (CNS) remyelination has been found by light and electron microscopy and immunocytochemistry within fresh lesions from four cases of acute and chronic progressive multiple sclerosis (MS). The remyelination was sparse and existed in an edematous parenchyma containing oligodendrocytes, macrophages, hypertrophic astrocytes and inflammatory components, but no fibrillary astrogliosis. It is suggested that this type of CNS remyelination in MS is a transient event. Possible underlying factors are discussed.

Acute Disease↗
PubMed1987

Total lymphoid irradiation in multiple sclerosis: blood lymphocytes and clinical course.

We have found a significant relationship between blood lymphocyte count and prognosis in 45 patients receiving either total lymphoid irradiation or sham irradiation for chronic progressive multiple sclerosis. Patients with sustained lymphocyte counts less than 900 mm-3 for prolonged periods after treatment showed less rapid progression over the ensuing 3 years than did patients with multiple sclerosis who had lymphocyte counts above this level (p less than 0.01). Our results suggest that a simple laboratory test, the absolute blood lymphocyte count, may serve as a valuable barometer for monitoring the amount of immunosuppressive therapy needed to prevent progression in patients with multiple sclerosis, and possibly other autoimmune diseases.

Adult↗
PubMed1981

Multiple sclerosis. Oligodendrocyte survival and proliferation in an active established lesion.

Oligodendrocytes have been studied ultrastructurally in relationship to areas of active demyelination in multiple sclerosis. The tissue came from a central nervous system plaque sampled at biopsy during a neurosurgical procedure to correct severe intention tremor in a case of chronic progressive multiple sclerosis. Cells interpreted as oligodendrocytes were abundant within the demyelinated zone, were easily identifiable, and sometimes occurred as nests of cells suggestive of proliferation. Oligodendrocytes were also common within areas of active demyelination where numerous macrophages displayed active phagocytosis of myelin. These oligodendrocytes were paler and perhaps represented residual, surviving cells. In the relatively normal white matter adjacent to the plaque, increased numbers of oligodendrocytes occurred in association with remyelination. In the demyelinated zone, the astrocyte:macrophage:oligodendrocyte ratio was 1:2.25:4.5; within the region of ongoing demyelination, 1:4:4; and in the adjacent white matter, 1:0.1:2.1. On the basis of an apparent proliferation and survival of oligodendrocytes, the findings support the notions that there is no selective depletion of oligodendrocytes either during or shortly following central nervous system demyelination in multiple sclerosis, and that the myelin sheath is the primary target.

Adult↗
PubMed1988

Experience with cyclophosphamide in multiple sclerosis: the cons.

Neurologists in the Kaiser-Permanente Medical Care Program recently designed a study to evaluate the utility of intensive immunosuppression with cyclophosphamide compared with folic acid in 44 patients with chronic progressive multiple sclerosis (MS). Although preliminary results based on incomplete data suggest cyclophosphamide may be safely administered in an outpatient clinic setting and modest benefits cannot be ruled out, it is doubtful that there are very substantial benefits to that therapy. Although several other studies have been cited as evidence of cyclophosphamide's favorable effect on the clinical course of patients with MS, many of these studies have had design shortcomings. If these flaws are considered, the hypothesis that cyclophosphamide has a favorable effect on the course of MS must be considered weak.

Adult↗