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At least 487 records · Page 27Linked to original sources
PubMed1987

Administration of monthly-pulse cyclophosphamide in multiple sclerosis patients. Effects of long-term treatment on immunologic parameters.

Eleven patients with chronic progressive multiple sclerosis received monthly pulses of cyclophosphamide (CY) for approximately one year. During the final 9 months the monthly dose ranged between 1000 mg/m2 and 2000 mg/m2. This resulted in a marked (47% or greater) reduction in CD4 (T helper/inducer) cells a less striking (22%) decrease in CD8 (T suppressor/cytotoxic) cells and a decline in the CD4/CD8 ratio. The magnitude of the decrease in CD4 cells correlated with the total dose received (r = 0.88, P less than 0.05). B cells were reduced 50% and FcR+ lymphocytes were reduced 48% without comparable reduction in natural killer cells or antibody-dependent cellular cytotoxicity. Proliferative responses to PHA were suppressed. Two patients improved, seven stabilized and two continued to worsen. Monthly pulses of CY can achieve substantial and differential reduction in immune parameters and appear to slow the disease progression in some MS patients.

Cyclophosphamide↗
PubMed2000

Serial magnetic resonance imaging in multiple sclerosis: correlation with attacks, disability, and disease stage.

Serial MRI and clinical testing was performed on 45 well-defined untreated multiple sclerosis patients in different categories of disease (relapsing-remitting, progressive, stable). Up to 24 MRIs were scheduled over a 1-year period for each patient. Clinical evaluation was performed monthly and at times of attacks using the Expanded Disability Status Scale (EDSS) and the Ambulation Index (AI). MRI scans were performed both with and without gadolinium enhancement. MRI lesion volume was determined by computerized analysis and gadolinium-enhancing lesions were counted by radiologists. We observed an increase in lesion volume over 1 year in all patient groups except those classified clinically as stable. In relapsing-remitting patients there were correlations between increases in the number of gadolinium enhancing lesions and increases in EDSS and the occurrence of attacks. In chronic progressive patients, increases in lesion volume were correlated with both increases in EDSS and AI. These results demonstrate a linkage between MRI and clinical disease that depends both on the stage of MS and the MRI measures used and support the use of MRI as a surrogate marker of clinical disability in the study of multiple sclerosis.

Adult↗
PubMed1997

Clinical and magnetic resonance imaging changes correlate in a clinical trial monitoring cyclosporine therapy for multiple sclerosis. The MS Study Group.

Magnetic resonance imaging (MRI) was used to monitor cyclosporine therapy for chronic progressive multiple sclerosis in a multicenter clinical trial and an analysis was performed to determine whether there was a correlation between clinical changes and MRI changes. MRI was performed on 163 patients at the onset and completion of the 2-year study. Burden of disease (BOD, lesion load) was quantitated by a single observer using a computer program. Active lesions were also identified. The Expanded Disability Status Scale (EDSS) score was determined every 3 months MRI data did not show any effect of cyclosporine treatment on BOD progression (mean 24.5% increase/yr) or lesion activity. However, there was a statistically significant positive correlation between the baseline total BOD value and the baseline EDSS score (r = 0.221, p = 0.005) and a positive correlation between the percent changes in BOD from baseline to exit and EDSS score (r = 0.186, p = 0.018). The study supports the concepts that MRI is a useful technique in monitoring therapeutic trials and that MRI is a direct measure of pathology.

Brain↗
PubMed1993

Magnetic fields normalize visual evoked potentials and brainstem auditory evoked potentials in multiple sclerosis.

The present communication concerns a 46 year old woman with a 10 year history of chronic progressive multiple sclerosis (MS) in whom external application of magnetic fields (MF) (7.5 picoTesla; 5 Hz) during a period of remission resulted in a rapid and dramatic improvement in symptoms including vision, cerebellar symptomatology (ataxia and dysarthria), mood, sleep, bowel and bladder functions as well as fatigue. Improvement in the patient's symptoms was associated with normalization of the pretreatment latencies of the visual evoked potentials and brainstem auditory evoked potential responses within a week after initiation of magnetic treatment. This report demonstrates that treatment with picoTesla MF is an effective, nonpharmacological modality in the management of MS and for the first time documents reversal of abnormal evoked potential responses by this treatment. The pineal gland is a magnetosensor. As MF affect the release of the pineal gland's principal hormone, melatonin, it is hypothesized that the effects of picoTesla MF in MS are partly mediated by the pineal gland which has recently been implicated in the pathogenesis of MS (Sandyk, 1992 a; b).

Electromagnetic Fields↗
PubMed2006

Drug Insight: interferon treatment in multiple sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS. Between 1987 and 1997, clinical trials of three preparations of recombinant interferon-beta were conducted in patients with MS, ushering in a new therapeutic era. These medications have demonstrable benefits and seem to be safe; they represent an important advance in MS treatment. All three formulations of interferon-beta had modest effects on relapses and short-term progression of disability, but the effects on MRI lesion parameters were more substantial. The benefits were greater in clinically isolated syndromes and relapsing-remitting MS than in secondary progressive MS. Although these drugs have been shown to be effective, however, their long-term impact on clinically relevant disability progression is uncertain, and there are many areas of controversy in the MS field regarding the use of these products. There is still a need for more effective treatments, which might include new agents or combination therapies.

Antibodies↗
PubMed1993

Thymectomy as treatment of autoimmune diseases other than myasthenia gravis.

This paper reviews the different series of thymectomies performed in patients with autoimmune diseases other than myasthenia gravis. It is possible that thymectomy can decrease the activity of T-helper lymphocytes or, alternatively, it may enhance the activity of T-suppressor lymphocytes, whose function is depressed in autoimmune diseases. Thymectomy was performed empirically for systemic lupus erythematosus and rheumatoid arthritis. The therapeutic benefits were questionable. Conflicting results were reported for thymectomy against autoimmune hemolytic anemia. Several trials were conducted to assess the therapeutic value of thymectomy in multiple sclerosis. Benefits were achieved only in relapsing-remitting but not in chronic-progressive multiple sclerosis. The effect of thymectomy in autoimmune diseases associated with myasthenia gravis were also reported. The authors conclude that thymectomy as treatment for autoimmune diseases other than myasthenia gravis is not elective therapeutic choice and it is acceptable only in selected cases.

Anemia, Hemolytic, Autoimmune↗
PubMed1992

Successful treatment of multiple sclerosis with magnetic fields.

The present communication concerns a 50 year-old woman with a 15 year history of chronic-progressive multiple sclerosis (MS) in whom extracranial application of picoTesla magnetic fields (MF) produced a dramatic and sustained improvement in disability. In contrast, administration of melatonin (3 mg, P.O.) produced in this patient a rapid exacerbation of disability which was reversed subsequently by treatment with MF. It is hypothesized that the therapeutic effects of picoTesla MF involve the mediation of the pineal gland which is known to act as a magnetosensor. The report demonstrates, for the first time, the remarkable efficacy of weak MF in the symptomatic treatment of chronic-progressive MS and underscores the pivotal role of the pineal gland in the pathophysiology of MS. If confirmed by a larger cohort of patients, extracranial application of picoTesla MF may prove as an extremely efficacious, nonpharmacological modality for the treatment of MS.

Brain↗
PubMed2003

Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R+WIN55,212.

Theiler murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is a mouse model of chronic-progressive multiple sclerosis (MS) characterized by Th1-mediated CNS demyelination and spastic hindlimb paralysis. Existing MS therapies reduce relapse rates in 30% of relapsing-remitting MS patients, but are ineffective in chronic-progressive disease, and their effects on disability progression are unclear. Experimental studies demonstrate cannabinoids are useful for symptomatic treatment of spasticity and tremor in chronic-relapsing experimental autoimmune encephalomyelitis. Cannabinoids, however, have reported immunosuppressive properties. We show that the cannabinoid receptor agonist, R+WIN55,212, ameliorates progression of clinical disease symptoms in mice with preexisting TMEV-IDD. Amelioration of clinical disease is associated with downregulation of both virus and myelin epitope-specific Th1 effector functions (delayed-type hypersensitivity and IFN-gamma production) and the inhibition of CNS mRNA expression coding for the proinflammatory cytokines, TNF-alpha, IL1-beta, and IL-6. Clinical trials investigating the therapeutic potential of cannabinoids for the symptomatic treatment of MS are ongoing, and this study demonstrates that they may also have potent immunoregulatory properties.

Animals↗
PubMed1999

Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study.

In experimental animal models of multiple sclerosis demyelinating antibody responses are directed against the myelin oligodendrocyte glycoprotein (MOG). We have investigated whether a similar antibody response is also present in multiple sclerosis patients. Using the recombinant human extracellular immunoglobulin domain of MOG (MOG-Ig) we have screened the sera and CSFs of 130 multiple sclerosis patients, 32 patients with other inflammatory neurological diseases (OIND), 30 patients with other non-inflammatory neurological diseases (ONND) and 10 patients with rheumatoid arthritis. We report that 38% of multiple sclerosis patients are seropositive for IgG antibodies to MOG-Ig compared with 28% seropositive for anti-myelin basic protein (MBP). In contrast, OIND are characterized by similar frequencies of serum IgG antibody responses to MOG-Ig (53%) and MBP (47%), whereas serum IgG responses to MOG-Ig are rare in ONND (3%) and rheumatoid arthritis (10%). Anti-MBP IgG antibodies, however, are a frequent finding in ONND (23%) and rheumatoid arthritis (60%). Our results provide clear evidence that anti-MOG-Ig antibodies are common in CNS inflammation. However, in OIND these antibody responses are transient, whereas they persist in multiple sclerosis. We demonstrate that the serum anti-MOG-Ig response is already established in early multiple sclerosis (multiple sclerosis-R0; 36%). In later multiple sclerosis stages frequencies and titres are comparable with early multiple sclerosis. In contrast, the frequency of anti-MBP antibodies is low in multiple sclerosis-R0 (12%) and increases during disease progression in relapsing-remitting (32%) and chronic progressive multiple sclerosis (40%), thus suggesting that anti-MBP responses accumulate over time. Finally we provide evidence for intrathecal synthesis of IgG antibodies to MOG-Ig in multiple sclerosis.

Adult↗
PubMed1993

Increased high affinity beta-adrenergic receptor densities and cyclic AMP responses of CD8 cells in multiple sclerosis.

Beta-adrenergic receptor (beta R) density is increased on suppressor T-cells (Ts) from patients with chronic progressive multiple sclerosis (CPMS). We investigated the contribution of high-affinity (kh) beta R to cAMP responses of nongranular leukocyte subsets from CPMS patients and normal individuals (NL). CD8 beta R density was 1930 receptors/cell in CPMS compared to only 1020 receptors/cell in NL (t(18) = 2.73, P < 0.02). beta R densities on monocytes, B cells, and CD4 cells did not differ between groups. The increased density of beta R on CD8 cells in CPMS was entirely the result of an increase in the number of high affinity receptors. Basal level of cAMP in CD8 lymphocytes were 7.8 pmol/10(6) cells in CPMS and 3.5 pmol/10(6) cells in NL. Isoproterenol stimulation elevated cAMP levels in CD8 cells to 49.9 pmol/10(6) cells in CPMS patients and to 25.7 pmol/10(6) cells in NL (difference after activation: t(18) = 3.23, P < 0.005). No differences between groups were found in cAMP levels of other cell subsets. We also measured circulating catecholamine levels. Supine and standing epinephrine levels were not different between CPMS and NL. Supine norepinephrine (NE) levels were higher in CPMS (411 pg/ml) than in NL (268 pg/ml) (P < 0.03); upon standing, significant increases in NE occurred in both groups to 573 pg/ml in CPMS and to 494 pg/ml in NL. These results extend our previous findings of peripheral sympathetic dysregulation in CPMS and suggest a means whereby Ts function, hypothesized to play a role in the immune pathogenesis of CPMS, may be altered.

Adult↗
PubMed1988

Effect of total lymphoid irradiation on functional status in chronic multiple sclerosis: importance of lymphopenia early after treatment--the pros.

To determine whether immunosuppression by total lymphoid irradiation (TLI) slowed deterioration of chronic progressive multiple sclerosis (MS), functional impairment score and blood lymphocyte counts were compared at 6-month intervals through 4 years following treatment of MS patients by either TLI (n = 27) or sham irradiation (n = 21). At each interval, 20 to 30% fewer TLI-treated patients had deteriorated (p less than 0.05 at 6, 12, and 18 months), and the difference in mean functional impairment score between groups became progressively greater (p less than 0.01 at 42 and 48 months). Benefit accrued principally to the 17 TLI-treated patients with absolute blood lymphocyte counts less than 900/mm3 3 months after treatment, whose mean functional impairment score remained within 0.6 units of baseline (p = NS), whereas the ten TLI patients with higher post-treatment lymphocyte counts had progressive deterioration (p less than 0.05 to p less than 0.001 versus TLI-treated patients with lower lymphocyte counts at all intervals except 30 months) and had deteriorated by more than 5 functional scale units by 42 and 48 months. Side effects were minor and complications rare in TLI-treated patients, but one TLI-treated patient developed staphylococcal sepsis. Thus, TLI slows deterioration of chronic progressive MS, with what appears to be enduring benefit through 4 years compartmented to patients with greater induced lymphopenia. Modification of lymphoid irradiation regimens to increase the proportion of MS patients who achieve a favorable degree of lymphopenia and to avert functional hyposplenism may further improve the benefit/risk ratio.

Adult↗
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↗