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Results for “Multiple Sclerosis, Chronic Progressive”

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PubMed1988

Borrelia burgdorferi antibodies in patients with relapsing/remitting form and chronic progressive form of multiple sclerosis.

Sera of 106 multiple sclerosis patients and 103 closely matched controls were examined for Borrelia burgdorferi antibodies. The prevalence rate in multiple sclerosis patients was 14.2%, in controls 25.2%. Overall prevalence was 20.1%. Mean IgG antibody level was insignificantly higher in controls than in multiple sclerosis patients. Patients with a chronic progressive course of multiple sclerosis had an insignificantly higher mean borrelia antibody level, when compared with those suffering from relapsing/remitting form of disease.

Adolescent↗

PubMed1987

The prevalence of locally-synthesized virus antibodies in various forms of multiple sclerosis.

In 125 patients with multiple sclerosis, intrathecally synthesized antibodies against measles, rubella and zoster viruses were determined with an ELISA. 70% of patients with chronic progressive disease synthesized measles antibodies in comparison to 50% with a relapsing course. Women suffering from chronic progressive multiple sclerosis exhibited zoster antibodies 3 times as frequent as the other patients. These data indicate that relapsing and chronic progressive forms of multiple sclerosis exhibit different antiviral responses within the central nervous system which remain stable during the course of the disease.

Adolescent↗

PubMed1989

Serum antibodies to HTLV-I in Thai patients with chronic progressive myelopathy, multiple sclerosis, myopathy and in HIV-seropositive intravenous drug abusers.

Antibodies to HTLV-I were assayed in sera of 9 patients with progressive myelopathy, 11 with multiple sclerosis, 5 with myopathy and in 10 HIV-seropositive intravenous heroin abusers. Clinical features in 9 cases with progressive myelopathy were not different from those previously described in tropical spastic paraparesis associated with HTLV-I infection. No detectable HTLV-1 antibody was found in the sera of any of the 35 patients studied.

Adult↗

PubMedDate not supplied

Immunosuppression in progressive multiple sclerosis with high dose intravenous cyclophosphamide and monoclonal antibodies.

Our work with multiple sclerosis has demonstrated a favorable effect on the course of chronic progressive multiple sclerosis in two-thirds of patients treated with cyclophosphamide/ACTH. However, alternative methods of therapy, or repeated treatments with cyclophosphamide and ACTH are required for longer term control of the illness. We are attempting to assess the efficacy of outpatient maintenance cyclophosphamide, but do not as yet have any data to support the use of this form of treatment. Cyclophosphamide and ACTH can be given to multiple sclerosis patients without significant serious toxicity. Monoclonal antibody therapy of multiple sclerosis is in its beginning stages. The treatment appears to be safe and has produced some interesting data indicating that rapid entry of some labeled lymphocytes into the nervous system can be measured by this technique. Since these are phase one pilot trials designed to assess immune parameters and only small numbers of patients have been treated, no clinical results have been obtained. No adverse effects of monoclonal antibody therapy were observed.

Adrenocorticotropic Hormone↗

PubMed1988

Total lymphoid irradiation for multiple sclerosis.

Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferior margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one. Our data suggest that this modified TLI regimen has clinical efficacy and sufficiently low toxicity to make it suitable for investigative immunosuppressive treatment of patients with progressive MS or other non-malignant conditions.

Adult↗

PubMed1990

Clinical and demographic predictors of cognitive performance in multiple sclerosis. Do diagnostic type, disease duration, and disability matter?

Patients with chronic progressive multiple sclerosis often perform more poorly on cognitive tasks than do patients with the relapsing-remitting form of this disease. Whether these differences reflect an independent influence of disease type on cognitive performance is uncertain. We used multiple regression techniques to determine how well performance on a number of tasks done poorly by groups of patients with multiple sclerosis could be predicted by disease type and its confounds: age, disease duration, and disability status as well as other demographic variables. Disease types were assigned longitudinally, based on serial neurological examinations at 6-month intervals over a minimum of 2 years. None of the demographic or clinical variables predicted cognitive performance with more than minimal accuracy. These findings fail to provide support for the assertion that disease type is an important independent determinant of cognitive impairment in multiple sclerosis.

Adult↗

PubMed1993

Immunoglobulin G immunosuppression of multiple sclerosis. Suppression of all three major lymphocyte subsets.

Six patients with relapsing chronic progressive multiple sclerosis were treated on 2 consecutive days with large amounts of IgG to induce immunosuppression. Peripheral blood lymphocyte subsets were monitored for 5 weeks after IgG treatment to determine immunosuppression. Decreased numbers of B, T, and natural killer lymphocytes were detected after treatment. Lymphocyte numbers were at a nadir 1 week after treatment, but an immunosuppressive effect continued to be present after 5 weeks. Although clinical efficacy was not evident in this brief open trial, the decrease of peripheral lymphocyte numbers and the apparent safety of the procedure warrant further study.

Adult↗

PubMed1994

Adherence-mediated T cell activation in multiple sclerosis and other neurological disorders.

Peripheral blood T cells were isolated from chronic progressive multiple sclerosis patients using a stepwise protocol of density gradient centrifugation, erythrocyte rosetting and adherent cell depletion, after which T cells were cultured with no added stimulus. These cultures exhibited as much as 10-fold higher 'background' proliferative activity (designated hyperactivity) than similarly prepared cultures from normal healthy control individuals. Hyperactivity was also found with T cell cultures from patients with other neurological disorders, i.e. namely, Guillain-Barré syndrome, acute stroke, myasthenia gravis or seizures. Characterizing the hyperactivity, kinetic studies showed that it was not evident until 6 days and became maximal in 8-10 day cultures; it occurred concomitantly with an increase in activated cells; and it was inhibited by anti-HLA-DR antibody, implicating the role of CD4+ T cells. Taken together, these results suggest that the hyperactivity was the result of in vitro stimulation. In further support of this view, hyperactivity was dependent on the adherence step used in the T cell isolation procedure. Although the T cell stimulus and the mechanism underlying the adherence effect is currently speculative, the hyperactivity appears to be the result of a feature common to the diseases in which it was found. The possible roles of inflammatory events in vivo and an autologous mixed lymphocyte response in vitro are discussed.

Antigens, CD↗

PubMed1988

Oligoclonal T lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis.

We have investigated the T cell populations in the cerebrospinal fluid (CSF) of chronic progressive multiple sclerosis (MS) patients. Individual T cells from the CSF and blood were cloned before expansion and their clonotypes were defined by analysis of rearranged T cell receptor beta chain and gamma chain genes. 87 T cell clones from blood and CSF of two patients with chronic progressive MS were examined for common TCR gene rearrangement patterns. In one patient, 18 of 28 CSF-derived T cell clones demonstrated common TCR gene rearrangements indicating oligoclonal T cell populations; in the blood, two patterns were found twice among 26 T cell clones. In another patient, 5 of 27 CSF-derived clones had common TCR gene rearrangement patterns. In contrast, no common beta chain rearrangement pattern was found among 67 T cell clones derived from the blood or CSF of a patient with subacute sclerosing panencephalitis, among 20 clones from the CSF of a patient with herpes zoster meningoencephalitis, or among 66 clones from a normal subject. A subject with atypical, fatal MS of 8-mo duration was also studied and did not have oligoclonal T cells in the CSF or blood. These results demonstrate that distinct oligoclonal T cell populations can be found in the CSF immune compartment of subjects with nonmalignant inflammatory disease and they can create a new avenue for the investigation of the specificity of the T cell response within the central nervous system.

Cerebrospinal Fluid↗

PubMed2005

Cortical demyelination and diffuse white matter injury in multiple sclerosis.

Focal demyelinated plaques in white matter, which are the hallmark of multiple sclerosis pathology, only partially explain the patient's clinical deficits. We thus analysed global brain pathology in multiple sclerosis, focusing on the normal-appearing white matter (NAWM) and the cortex. Autopsy tissue from 52 multiple sclerosis patients (acute, relapsing-remitting, primary and secondary progressive multiple sclerosis) and from 30 controls was analysed using quantitative morphological techniques. New and active focal inflammatory demyelinating lesions in the white matter were mainly present in patients with acute and relapsing multiple sclerosis, while diffuse injury of the NAWM and cortical demyelination were characteristic hallmarks of primary and secondary progressive multiple sclerosis. Cortical demyelination and injury of the NAWM, reflected by diffuse axonal injury with profound microglia activation, occurred on the background of a global inflammatory response in the whole brain and meninges. There was only a marginal correlation between focal lesion load in the white matter and diffuse white matter injury, or cortical pathology, respectively. Our data suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter. With chronicity, diffuse inflammation accumulates throughout the whole brain, and is associated with slowly progressive axonal injury in the NAWM and cortical demyelination.

Acute Disease↗

PubMed2000

Autologous stem cell transplantation in progressive multiple sclerosis--an interim analysis of efficacy.

Based on the good results of experimental transplantation in animal models of multiple sclerosis and of other autoimmune diseases, we have treated 24 patients suffering from chronic progressive multiple sclerosis with high-dose chemotherapy (BEAM regimen) followed by autologous blood stem cell rescue and antithymocyte globulin. Blood stem cells were mobilised with cyclophosphamide at 4g/m2 and G- (or GM-) CSF. In 9 cases, additional CD34+ cell-selection of the graft was performed. Here we update previously published results of this novel treatment, mainly with regard to clinical efficacy, as the median follow-up time has reached 40 months (range, 21-51). Infections were the principal toxicity early after the procedure, with death of a patient from aspergillosis 65 days post stem cell infusion. No serious late events occurred apart from a case of autoimmune thyroiditis that developed 11 months after transplant in a patient who had received a CD34+ cell-depleted graft. Mild and transient neurotoxicity was observed in 10 patients (42%), most probably associated with fever and infections. Eighteen patients (18/23; 78%) responded to the treatment, i.e., they were improved or stabilized, while five patients progressed, of which 4 had primary progressive disease. Of those improved or stabilised (18), 9 patients have maintained stable condition whereas 9 developed relapses or they slowly resumed progression, although their disability scores have not gotten worse than they were before transplantation. The probability of progression-free survival (compared to entry status) at 3 years is 92% for patients with secondary progressive disease and 39% for the primary progressive type. CD34+ cell-selection did not seem to yield better results except for a delay in progression or in relapse after transplantation. These results appear better than those achieved by any other treatment of progressive multiple sclerosis, including beta-interferon, but they need to be confirmed by other open or controlled studies in view of the well-known difficulty of judging objectively the effect of a treatment in patients with this disease.

Adult↗

PubMed1992

A prospective study of depression and immune dysregulation in multiple sclerosis.

This study examined psychologic distress and immune function in patients with chronic-progressive multiple sclerosis participating in a placebo-control trial of cyclosporine. Immune measures included percentages and absolute numbers of CD2+, CD4+, CD8+, Leu-11-b+, HLA-DR (IA+), and transferrin-receptor-positive cells, which were evaluated by immunofluorescence using monoclonal antibodies. Distress was measured with self-report scales. The Expanded Disability Status Scale assessed neurologic disability. Subjects were followed up for 2 years, and their high-depressed and low-depressed times were compared. Times of greater depression were associated with lower CD8+ cell numbers and CD8+%, and a higher CD4/CD8 ratio. CD4+ cell numbers and percent were also higher when subjects were depressed, but only in the placebo group. There were no differences in Expanded Disability Status Scale when subjects were more depressed. Evaluation of a single subject revealed that Ia+ and transferrin-receptor-positive lymphocytes increased 3 months before distress increased. It was concluded that distress is associated with immune dysregulation in multiple sclerosis, although the mechanisms of this association have yet to be delineated.

Adult↗

PubMed1988

Serial immune evaluation of cyclosporine- and placebo-treated multiple sclerosis patients.

During an ongoing clinical trial of cyclosporine (CsA) immunosuppression therapy for chronic progressive multiple sclerosis (MS), a comparison was made of the immune responses of 18 CsA- and 18 placebo (P)-treated MS patients. Patients randomized to receive either CsA or P had identical entry immune profiles. However, these MS patients displayed significantly increased T-helper:T-suppressor (TH:TS) ratios (P less than 0.01), percentage (%) active-T (P less than 0.01), % Ia+-T (P less than 0.05) and % Ta1+-T (P less than 0.01) cell phenotypes when compared to age-matched normal controls. Further, the MS-P-treated patients displayed significant increases (all P less than 0.01) in % pan-T, % helper-T, % active-T and % Ta1+-T cell phenotypes as well as panel mixed lymphocyte culture (panel MLC) functional responsiveness from entry to cumulative 12-month study data. In contrast, the MS-CsA-treated patients only displayed an increased % pan-T cell phenotype. The cumulative 12-month follow-up data showed that the MS-P-treated patients displayed significantly higher immune parameters than the MS-CsA-treated patients for % pan-T (P less than 0.05), % helper-T (P less than 0.01), TH:TS ratio (P less than 0.05), % active-T (P less than 0.01), % Ta1+-T cells (P less than 0.01) and panel MLC stimulation index (P less than 0.01). Thus, MS-CsA-treated patients did not display the progressive immune activation seen on serial evaluation during the follow-up time period that characterized the placebo-treated MS group.

Acute Disease↗

PubMed2003

Working memory deficits in multiple sclerosis: a controlled study with auditory P600 correlates.

BACKGROUND: Recently, the P600 component of event related potentials, a waveform that is conceived to be generated and/or modulated by basal ganglia and cingulate area has been considered an index of the completion of any synchronised operation after target detection, having much in common with working memory operation. Moreover, dysfunction of these brain structures as well as working memory deficits have been implicated in the pathophysiology of multiple sclerosis. The aim of this study was to investigate the patterns of P600 elicited during a working memory test in multiple sclerosis patients compared with healthy controls. METHODS: Twenty two definite, chronic progressive multiple sclerosis patients, with recent exacerbation of their illness, and 20 normal subjects matched for age, sex, and educational level, were studied with a computerised version of the digit span test of Wechsler batteries. Auditory P600 were measured during the anticipatory period of this test. RESULTS: The patient group, as compared with healthy controls, showed significantly reduced latencies of P600 at left frontal areas and reduced P600 amplitudes at left temporoparietal region. Moreover, memory performance of patients was significantly more impaired when compared with healthy controls. CONCLUSIONS: These findings may indicate that multiple sclerosis is associated with abnormal features of the completion of synchronised operation after target detection, as they are reflected by P600 amplitudes and latencies. Dysfunction of this mechanism may contribute to the identification of basic cognitive processes that could account for the cognitive deficits in multiple sclerosis.

Adult↗

PubMedDate not supplied

Hyperbaric oxygen therapy in the treatment of multiple sclerosis. A clinical and electrophysiological study in a 2 year follow-up.

15 patients with chronic progressive Multiple Sclerosis were treated with Hyperbaric Oxygen Therapy at 2.0 atmospheres absolute for a total of 20 daily exposures followed by 2 exposures every month. The treatment was carried out for a 24 months follow-up. No objective benefit resulted from Hyperbaric Oxygen Therapy at the completion of the study while a subjective improvement in bladder control was reported in the short and in the long-term follow-up by 8 and by 5 patients respectively. No significant variations in the electrophysiological results were observed after the first 20 consecutive exposures. It is concluded from this trial that a long-term Hyperbaric Oxygen Treatment cannot moderate the progression of Multiple Sclerosis. However, an improvement in the quality of life can be obtained in some patients resulting from a better control of bladder function.

Adult↗

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↗