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Results for “Multiple Sclerosis, Chronic Progressive”

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PubMed1994

Total lymphoid irradiation in multiple sclerosis.

Following a report of the efficacy of total lymphoid irradiation (TLI) in the treatment of chronic progressive multiple sclerosis a further randomised double-blind placebo-controlled study was undertaken with the intention of entering 56 patients. In the event it was possible to recruit only 27 patients in a 2.5 year period. Three patients received active treatment openly and 24 were randomised to either active (14) or sham (10) treatment. Treatment was 1980 cGy to the lymphoid system and spleen or sham treatment after full simulation. The primary outcome measure was a comparison of the mean rates of change between treatment groups on the expanded Kurtzke disability scale (EDSS) over the two year follow up period. Patients were also assessed on other clinical outcome measures, psychometry, and serial MRI of the brain. Active treatment resulted in a profound and prolonged fall in T lymphocytes especially those with the CD4 marker and a reversal in CD4:CD8 ratio. No significant benefit was demonstrated on the rate of clinical disease progression (EDSS). A small but significant benefit was found on a score of bladder function. No significant benefit was demonstrated on other clinical or psychometric indices or on subjective visual analogue scales. There was a small but significant difference in the rate of accumulation of lesions on brain MRI favouring the treatment group. The treated group had a higher incidence of clinically relevant side effects, notably amenorrhoea and infections: three deaths (one in the TLI group, two in the sham treated group) occurred. A post hoc calculation indicates that the study had a possible 35% risk of a false negative result using the principal outcome measure. The study fails to confirm the previously reported clinical benefit of TLI although there may be a minor benefit on disease progression as indicated by MRI lesion counts. It is concluded that TLI cannot be recommended for the routine treatment of chronic progressive multiple sclerosis but the beneficial effect on MRI lesions, though modest, suggests that further research into immune modulation of this condition may be worthwhile.

Adult↗

PubMed1991

Importance of intrathecal synthesis of IgD in multiple sclerosis. A combined clinical, immunologic, and magnetic resonance imaging study.

There is increasing evidence that soluble IgD has a certain role in the humoral immune response within the central nervous system. We report herein the results of a combined clinical, magnetic resonance imaging, and immunopathologic study to determine the clinical importance of intrathecal IgD synthesis. Intrathecal synthesis of IgD (detected through the calculation of index values) was studied in 64 patients with multiple sclerosis and in 50 neurologic control patients and normal subjects. Locally secreted IgD was detected in 30% of patients with clinically active multiple sclerosis, including two in whom magnetic resonance images of brain and spinal cord were normal and who had no evidence of intrathecal IgG synthesis. No intrathecal IgD production was detected in patients with clinically stable multiple sclerosis or those suffering from chronic progressive multiple sclerosis, while it significantly correlated with the interval from the last relapse and with the total duration of the disease process in patients with relapsing, remitting multiple sclerosis. Intrathecal IgD synthesis also correlated with the degree of cerebrospinal fluid pleocytosis and with the presence of free kappa and lambda light chain bands in cerebrospinal fluid. Present results supplement and expand earlier data and suggest that intrathecally secreted IgD is a putatively important part of the immune response in clinically active relapsing, remitting multiple sclerosis.

Adult↗

PubMed1993

Failure to detect genomic material of HTLV-I or HTLV-II in mononuclear cells of Italian patients with multiple sclerosis and chronic progressive myelopathy.

To contribute to the undecided question if a retrovirus of the human T-cell lymphotropic virus (HTLV) family may be involved in the development of multiple sclerosis (MS), we investigated by the polymerase chain reaction (PCR) the presence of HTLV-I and HTLV-II sequences in the peripheral blood mononuclear cell DNAs from 30 patients affected by MS and 15 by chronic progressive myelopathy. Moreover a control group of 14 blood donors was examined. All these patients were devoid of anti-HTLV-I antibody in the serum and cerebrospinal fluid at ELISA. For the PCR, primers and probes specific for the tax region common to HTLV-I and HTLV-II, for the pol region of HTLV-I, and for the pol region of HTLV-II were used. In spite of the high sensitivity of the technique used, the three groups of subjects were negative for HTLV-I and HTLV-II genomic sequences.

Adult↗

PubMed1989

Immunosuppressive treatment of multiple sclerosis.

Multiple sclerosis is thought, by many investigators, to be an immunologic disease. Therefore, a rationale exists for treating this disease by immunosuppressive therapy. In exacerbating-remitting multiple sclerosis, corticosteroids and adrenocorticotropic hormone are the most widely used drugs; high doses of intravenously administered methylprednisolone have recently gained favor. Chronic progressive multiple sclerosis has been treated with a number of immunosuppressive regimens, several of which have shown promise to date. Cyclophosphamide and azathioprine have been used most often and are reviewed in this report, as are other agents currently under investigation. No firm guidelines for the treatment of chronic progressive multiple sclerosis can be offered, but an approach to immunosuppressive therapy is suggested in this review.

Adrenal Cortex Hormones↗

PubMed1994

Defective CD3 mediated proliferation and LPS responsiveness in multiple sclerosis.

Multiple sclerosis [MS] is a chronic inflammatory disease of the central nervous system which has been postulated to be a T cell mediated disease. We examined proliferation of mononuclear cells to OKT3 mAb, Con A, ionomycin plus PMA and human myelin basic protein in subjects with relapsing-remitting and chronic progressive multiple sclerosis. Age and sex matched controls demonstrated a good proliferation to anti-CD3 mAb whereas subjects with relapsing-remitting multiple sclerosis showed a significantly decreased anti-CD3 mAb response. There was no difference in mitogen, ionomycin plus PMA or human MBP proliferation between controls and MS subjects. There was also a trend for decreasing anti-CD3 mAb proliferation in patients with chronic progressive multiple sclerosis compared to controls. LPS significantly decreased anti-CD3 mAb proliferation in controls but not in the MS subjects. An abnormality of signal transduction via the CD3 T-cell receptor complex in T cells and responsiveness to the immunomodulatory effect of IFN inducers may exist in multiple sclerosis.

CD3 Complex↗

PubMedDate not supplied

Nursing assessment of positive adjustment for individuals with multiple sclerosis.

The chronic, progressive nature of multiple sclerosis (MS) often interferes with effective psychosocial adjustment. When presented with physical limitations and/or cognitive impairment, the client with MS may experience problems such as depression, family dissolution, and loss of important roles. However, some persons are able to adjust positively and enjoy life. This article explains a model for assessing psychosocial adjustment of those with MS and describes its practical application for the rehabilitation nurse.

Adaptation, Psychological↗

PubMed1998

Immunoadsorption--a new therapeutic possibility for multiple sclerosis?

A 46 year old woman suffers from chronic progressive multiple sclerosis. She was diagnosed in 1993. Because of many complications seen in conservative treatment, plasma exchange was started. The expanded disability status scale by Kurtzke could be improved but the interval between the treatments became shorter and shorter. It was therefore decided to commence protein A immunoadsorption treatment. With this treatment the patient shows good and stable improvement in neurological and functional status with an acceptable treatment frequency of once every 3 weeks.

Chronic Disease↗

PubMedDate not supplied

[IgG synthesis in the cerebrospinal fluid in patients with the chronic progressive phase of multiple sclerosis treated with cyclophosphamide and ACTH].

In 30 cases of multiple sclerosis in the chronic-progressive phase treated with cyclophosphamide (total dose 4000 mg) and ACTH (total dose 1050 units) IgG and albumin were determined in the serum and cerebrospinal fluid by Mancini's method. From these determination the IgG, albumin ratio and the IgG index were calculated as markers of IgG synthesis in CSF spaces. As a result of these investigations it is suggested that the treatment of patients with multiple sclerosis in chronic-progressive phase with short-lasting intensive immunosuppression using cyclophosphamide and ACTH causes no significant changes in IgG synthesis in CSF spaces.

Adrenocorticotropic Hormone↗

PubMed1987

Correlation of clinical and immunologic states in multiple sclerosis.

Cyclophosphamide was administered to 14 patients with chronic progressive multiple sclerosis on an intermittent escalating dosage schedule adjusted to maintain numbers of peripheral blood B lymphocytes and helper/inducer (CD4) T cells below the fifth percentile of the normal population. Peripheral blood B cells, T cells, suppressor/cytotoxic (CD8) T cells, CD4 cells, and FcR+-bearing cell numbers and percentages were monitored at one-week to two-week intervals. Clinical status was assessed by neurologic examinations at approximately four-week intervals. Regression analysis revealed a statistically significant correlation between changes in immunologic status and changes in clinical state. The immunologic changes preceded the neurologic changes. Increases in percent of CD8 cells and decreases in percent of CD4 cells forecast improved clinical course. These findings, coupled with other studies, strongly suggest a pathogenetic role for helper and suppressor T cells in the production of clinical signs of multiple sclerosis.

B-Lymphocytes↗

PubMed2005

Hypothalamo-pituitary-adrenal axis activity predicts disease progression in multiple sclerosis.

Clinical studies have shown that groups of multiple sclerosis (MS) patients exhibit a chronically activated hypothalamo-pituitary-adrenal (HPA) axis. However, the association of HPA axis activity and disease progression in MS is unknown. In this longitudinal study over a 3-year follow-up period, we report that patients who exhibited stronger HPA reactivity at baseline were significantly more likely to experience progression as measured by the Expanded Disability Status Scale (EDSS) during the follow-up period. Furthermore, HPA axis activity correlated with progression ratings and cognitive impairment three years later. Tests of HPA axis activity may be useful biomarkers for disease progression in MS.

Adrenocorticotropic Hormone↗

PubMed1984

Lymphocyte subpopulations in multiple sclerosis: spontaneous and mitogen-induced activity.

Lymphocytes of chronic progressive multiple sclerosis (MS) patients and healthy persons were isolated by nylon-wool column filtration followed by density centrifugation. Incubating part of these lymphocytes with 2- aminoethyliso thiouronium bromide hydrobromide-treated sheep erythrocytes resulted in two other subfractions, the rosette-forming (E+) lymphocytes and the nonrosette -forming (E-) lymphocytes. Increased spontaneous activity was observed with the nonfractionated lymphocyte populations and with the E+- and E- -cell fractions of MS patients compared to the corresponding cell populations of controls following a culture period of one or several days. Phytohemagglutinin- and pokeweed mitogen-induced stimulation of these different lymphocyte fractions was the same in MS patients and controls. No influence of disease activity could be found on the immune parameters. Characterization of the different lymphocyte populations with monoclonal anti-human T-cell antibodies demonstrated a prevalence for helper T cells in forming rosettes.

Adult↗

PubMed1980

Plasmapheresis in multiple sclerosis: preliminary study.

In six of eight patients with chronic progressive multiple sclerosis (MS) who were previously unresponsive to corticosteroid medication, moderate but unequivocal improvement occurred after short-term plasmapheresis, prednisone, and azathioprine therapy. In four patients, improvement gradually disappeared in the 2 to 3 months after therapy, and two patients have remained improved. There were no exacerbations during the treatment period. No consistent improvement in evoked response batteries was seen after plasmapheresis; IgG levels in cerebrospinal fluid were lowered by plasmapheresis. A controlled trial to determine the efficacy of plasmapheresis in the treatment of MS is warranted.

Adult↗

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↗

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↗