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 703 records · Page 39Linked to original sources

Overview of primary progressive multiple sclerosis (PPMS): similarities and differences from other forms of MS, diagnostic criteria, pros and cons of progressive diagnosis.

Patients with the primary progressive form of multiple sclerosis (PPMS) have a unique clinical course and demonstrate additional demographic and imaging features, which separate them from the relapsing/remitting form of the condition. Whether these features indicate a fundamental difference in the underlying pathogenesis of the condition or simply reflect opposite ends of a clinical spectrum is unclear. What is clear, however, is that this form of MS provides a valuable model of progression, which has the potential to explain this most disabling component of the disease process. The lack of the hallmark relapses and remissions in PPMS poses diagnostic difficulties, some of which have been addressed by recently published diagnostic criteria. Following diagnosis, the need for information, specific to this form of MS, must be recognized and addressed.

Diagnosis, Differential↗

Cognitive impairment in primary and secondary progressive multiple sclerosis.

The aim of this study was to use neuropsychological data to characterize two subtypes of multiple sclerosis (MS) patients in a large patient sample. We studied patients with primary-progressive MS (PPMS) and secondary-progressive MS (SPMS). A group of 121 MS patients (36 PPS, 85 SPMS) and 40 healthy controls were administered a brief battery of cognitive tests. Executive functioning, memory and attention were studied. Results demonstrate that PPMS patients exhibited slightly more impairment than patients with SPMS, although this difference is not significant (50% vs 37%). However, PPMS patients revealed a significantly poorer performance in verbal learning (p < 0.05) and in verbal fluency (p < 0.05). Whereas PPMS patients had significantly shorter disease durations (p < 0.05), there was no statistical difference in disability between both groups. We conclude from our study that cognitive deficits in progressive MS are frequent. Patients with PPMS tend to be more frequently and severely affected than SPMS patients. Our findings of high prevalence of cognitive involvement in PPMS have not been reported previously

Adult↗

No effect of intravenous immunoglobulins on cytokine-producing lymphocytes in secondary progressive multiple sclerosis.

Intravenous immunoglobulins (IVIG) have been effective in reducing multiple sclerosis (MS) disease activity and improving disability scores. However, the mechanism by which this beneficial effect is achieved remains unclear. An effect of IVIG on pro- and anti-inflammatory cytokines which are thought to play a role in the disease process - has been postulated in a number of animal and ex vivo studies. Hence, we performed a study on 34 patients with secondary progressive (SP) MS being treated with monthly IVIG or placebo for two years according to the protocol of the ESIMS study. Clinical outcome measures and cytokine production (interferon gamma, tumour necrosis factor alpha, interleukin-4 and -10) were recorded in all patients and compared with respect to the treatment group. Against our expectations, IVIG did not reduce the relapse rate or the progression of disability or cytokine production. Our data argue against an enduring immunomodulating effect of IVIG, at least in SPMS.

Adult↗

Serum S100B in primary progressive multiple sclerosis patients treated with interferon-beta-1a.

S100B belongs to a family of calcium-binding proteins implicated in intracellular and extracellular regulatory activities. This study of serum S100B in primary progressive multiple sclerosis (PPMS) is based on data obtained from a randomized, controlled trial of Interferon beta-1a in subjects with PPMS. The key questions were whether S100B levels were associated with either disability or MRI findings in primary progressive MS and whether Interferon beta-1a has an effect on their S100B levels. Serial serum S100B levels were measured using an ELISA method. The results demonstrated that serum S100B is not related to either disease progression or MRI findings in subjects with primary progressive MS given Interferon beta-1a. Furthermore there is no correlation between S100B levels and the primary and secondary outcome measures.

Adult↗

Cladribine followed by autologous stem-cell transplantation in progressive multiple sclerosis.

We studied the safety of autologous peripheral blood stem-cell transplantation (PBSCT) in four patients with progressive multiple sclerosis. Clinical and magnetic resonance imaging outcomes were secondary end-points. Cladribine administration preceded filgrastim-primed PBSC collection, aiming for lymphocyte depletion. Conditioning was with antithymocyte globulin and cyclophosphamide. The procedure was well tolerated, but without obvious clinical benefit. The study was terminated when other therapeutic options with lower morbidity became available.

Adult↗

Mitoxantrone in secondarily progressive multiple sclerosis: a series of 18 patients.

Mitoxantrone hydrochloride (Novantrone) is an anthracenedione that has been used as one of the latest in a long line of general immunosuppresive agents studied in multiple sclerosis (MS). We reviewed the clinical, laboratory, neuroimaging and echocardiography data of 18 patients from February 2001 to March 2004 out of a total number of 100 patients with definite MS. Fourteen patients were women (77.7%) and four were men. The mean age of the patients was 41.6 +/- 10 years old (confidence intervals 95%: 36.4-46.7 years old). The mean duration of disease was 10.5 +/- 6.3 years. Fourteen patients had the secondarily progressive form of MS, and four had the relapsing-remitting form. Mitoxantrone is an useful and clinically effective drug in MS and its major limitation is the potencial cardiotoxicity due to cumulative dose (140 mg).

Adult↗

[Immunologic therapy for secondary and primary progressive multiple sclerosis].

Immunological treatments of progressive multiple sclerosis are discussed. Recent trials of interferon-beta 1b(IFN beta-1b) and IFN beta-1a in secondary progressive MS (SPMS) have demonstrated treatment benefits on relapse rate and accumulation of MRI lesions, and one trial of IFN beta-1b showed significant slowing of disability progression. In another recent study, mitoxantrone, a potent immunosuppressive agent, was reported to reduce progression of disability in SPMS. As regards primary progressive MS, there is currently no convincing disease-modifying treatment. Pathologic studies have revealed that axonal injury is prominent in MS and may be the explanation for irreversible disability. It is hoped that therapeutic strategies will be aimed at axonal loss as well as inflammation and demyelination.

Adjuvants, Immunologic↗

Brain tissue loss occurs after suppression of enhancement in patients with multiple sclerosis treated with autologous haematopoietic stem cell transplantation.

To assess whether brain tissue loss occurs after profound and sustained suppression of magnetic resonance imaging (MRI) enhancement, we measured brain volume changes from 10 patients with rapidly evolving secondary progressive multiple sclerosis (MS) treated with autologous haematopoietic stem cell transplantation and followed up for 24 months. An average yearly decrease of brain volume of about 1.9% was observed despite only five enhancing lesions seen on triple dose follow up scans of two patients. This indicates that, in MS, progressive loss of tissue can occur independently of concomitant MRI-visible inflammation.

Artifacts↗

The PROMiSe trial: baseline data review and progress report.

The PROMiSe trial is a multinational, multicentre, double-blind, placebo-controlled trial evaluating the effects of glatiramer acetate treatment over 3 years in patients with primary progressive multiple sclerosis (PPMS). A total of 943 patients were enrolled, and all those remaining on-study had completed at least 24 months as of October 2002. Baseline clinical and MRI characteristics and select correlations are reported here. A total of 3.9% of patients exhibited confirmed relapse over 1904 patient-years of exposure, indicating success of efforts to exclude relapsing MS types. Of the 26.3% of patients who have prematurely withdrawn from the study, only 36% discontinued after meeting the study primary endpoint of disease progression. The progression rate in patients in the low Expanded Disability Status Scale (EDSS) stratum (3.0-5.0) observed thus far is markedly lower than the 50% annual progression rate estimate used for determining size and statistical power of the trial; progression was observed in 16.1% of patients with 12 months of study exposure. These early findings raise some concern about the ability of the trial to demonstrate a significant treatment effect, and suggest that the short-term natural history of PPMS may not be as aggressive as previously assumed.

Adjuvants, Immunologic↗

Interferon beta1a and depression in secondary progressive MS: data from the SPECTRIMS Trial.

Depression is a suspected side effect of treatment with interferon beta1a in MS. However, an association with depression has not been confirmed by rigorous studies. During the SPECTRIMS clinical trial of interferon beta1a (Rebif) in secondary progressive MS, depression ratings were obtained from 365 subjects treated either with interferon beta1a or with placebo. No significant differences between groups emerged during 36 months of follow-up. These data suggest that depression is not a side effect of interferon beta1a.

Adjuvants, Immunologic↗

Sex differences in proinflammatory cytokine profiles of progressive patients in multiple sclerosis.

The objective of this article is to evaluate the presence of sex differences in expression of cytokines in both CD4+ and CD8+ T cells derived from peripheral blood of untreated multiple sclerosis (MS) patients. The predominance of females in MS and other autoimmune diseases may be related to their differential responses in many immunological settings. Recent data show beneficial effect of sex hormones on proinflammatory cytokine levels and on magnetic resonance imaging in MS. Better understanding of gender differences is warranted. In this study 124 MS subjects (M:F; 56:68) and 34 healthy controls (M:F; 12:22) were included. Stimulated peripheral blood-derived CD4+ and CD8+ T cells were analysed for interferon-gamma, interleukin (IL)-2, tumour necrosis factor alpha, IL-4, IL- 10 and IL- 13 production. There were no significant differences for these cytokines between male and female MS subjects in the whole group. Compared to males, female patients had higher proinflammatory cytokine levels in the progressive phase of the disease. In conclusion, the data presented indicate that cytokine production and sex differences in cytokine production might differ between disease phases, probably related to underlying disease mechanisms.

Adult↗

[Therapeutic indications targeting etiology of progressive multiple sclerosis].

The indication for a long-term treatment in secondary or primary progressive multiple sclerosis is raised in more than half of the patients with MS. The fact that the pathogenic mechanisms involved in these two entities are unknown makes it difficult to predict the clinical course. The still insufficient knowledge of the MRI parameters is another obstacle to overcome. Nevertheless, the results of a certain number of clinical trials have, despite the methodological inadequacies, provided some insight. Immunomodulators, such as interferon-beta, have shown some efficacy, particularly in patients with a still inflammatory form of secondary progressive MS. Massive short-term immunosuppression does not appear to affect the course of progression but prolonged immunosuppression appears to be able to retard progression, at least in certain patients. This points out the importance of starting treatment as early as possible, before the development of irreversible damage. A better analysis of results already published, and most importantly, of results currently under way, should be most helpful in terms of therapeutic management if not in terms of our understanding of the pathophysiological processes involved.

Clinical Trials as Topic↗

Randomized study of antibodies to IFN-gamma and TNF-alpha in secondary progressive multiple sclerosis.

Studies of cytokines in multiple sclerosis (MS) have shown that immune mechanisms connected with disturbance of the synthesis of cytokines probably play critical roles in the initiation and prolongation of MS. In a double-blind, placebo-controlled trial, 45 patients with active secondary progressive MS were randomized to three groups of 15 patients, each receiving a short course of antibodies to IFN-gamma, to tumor necrosis factor (TNF)-alpha, or a placebo. After 12 months with analysis of disability (Expanded Disability Status Scale scores), accompanied by interval determinations of lymphocyte subpopulations, cytokine production levels, MRI, and evoked potentials, it was found that only patients who received antibodies to IFN-gamma showed statistically significant improvement compared to the placebo group--a significant increase in the number of patients without confirmed disability progression. This was supported by MRI data (a decrease in the number of active lesions) and systemic changes in cytokine status (a decrease in IL-1beta, TNF-alpha, and IFN-gamma concentrations in supernatants of actvated blood cells of these MS patients and an increase in TGF-beta production). Neutralization of IFN-gamma could be a new approach to treating secondary progressive MS. Long-term administration of humanized monoclonal antibodies to IFN-gamma and simultaneous use of antibodies to IFN-gamma together with IFN-beta products are planned.

Animals↗

Overview of European pilot study of interferon beta-Ib in primary progressive multiple sclerosis.

This short monograph describes a trial of interferon beta-1b in patients with primary progressive multiple sclerosis (PPMS) or transitional MS. Designed as a randomized, placebo-controlled pilot, the trial randomly placed 73 eligible patients into two groups, placebo or interferon beta-1b 8 MIU given subcutaneously every other day for two years. Significant differences favouring interferon beta-1b in the MSFC score, T2 lesion volume and TI lesion volume at 24 months were observed. Further study of interferon beta-Ib therapy in PPMS patients in warranted.

Adjuvants, Immunologic↗

Evidence of involvement of leptin and IL-6 peptides in the action of interferon-beta in secondary progressive multiple sclerosis.

Leptin is a peptide hormone which acts on cells of immune system by influencing the production of cytokines. Serum leptin levels and cytokine production by peripheral blood mononuclear cells (PBMC) were measured in 18 secondary progressive multiple sclerosis (SPMS) patients under IFN-beta-1b treatment. There were no overall effects on leptin, interleukin-6 (IL-6), IL-10 and IL-12 p40 after 2, 6 and 12 months of treatment. However, leptin and IL-6 decreased after 6 and 12 months of treatment in 12 patients who did not show progression of disability. Thus, our pilot data show that the beneficial effect of IFN-beta on some SPMS patients might be associated with the reduced levels of leptin and reduced IL-6 production by PBMC.

Adult↗

Benefit of interferon beta-1a on MSFC progression in secondary progressive MS.

BACKGROUND: Interferon beta-1a (IFNbeta-1a, Avonex) is efficacious in relapsing forms of MS. Studies of other IFNbeta preparations in secondary progressive MS (SPMS) yielded conflicting results. This study was undertaken to determine whether IFNbeta-1a slowed disease progression in SP-MS. METHODS: A total of 436 subjects with SPMS and Expanded Disability Status Scale (EDSS) score 3.5 to 6.5 were randomized to receive IFNbeta-1a (60 micro g) or placebo by weekly intramuscular injection for 2 years. The primary outcome measure, used for the first time in a large-scale MS trial, was baseline to month 24 change in the MS Functional Composite (MSFC), comprising quantitative tests of ambulation (Timed 25-Foot Walk), arm function (Nine-Hole Peg Test [9HPT]), and cognition (Paced Auditory Serial Addition Test [PASAT]). RESULTS: Median MSFC Z-score change was reduced 40.4% in IFNbeta-1a subjects (-0.096 vs -0.161 in placebo subjects, p = 0.033), an effect driven mainly by the 9HPT and PASAT. There was no discernible benefit on the EDSS, which in this range principally reflects walking ability. IFNbeta-1a subjects had 33% fewer relapses (p = 0.008). There was significant benefit on eight of 11 MS Quality of Life Inventory subscales. New or enlarging T2-hyperintense brain MRI lesions and gadolinium-enhancing lesions were reduced at months 12 and 24 (both p < 0.001). IFNbeta-1a was well tolerated by the majority of subjects. Neutralizing antibodies developed in 3.3% of IFNbeta-1a-treated subjects. CONCLUSIONS: IFNbeta-1a demonstrated benefit on MSFC progression, relapses, quality of life, and MRI activity in SPMS.

Adjuvants, Immunologic↗

Serum and cerebrospinal fluid soluble Fas levels in clinical subgroups of multiple sclerosis.

Elevated sFas levels have been described in multiple sclerosis (MS) patients with active disease. The aim of this study was to assess the diagnostic potential of serum and cerebrospinal fluid (CSF) sFas measurements in differentiating clinically defined MS patient subgroups. Levels of sFas and sFas indices were determined in patients with stable relapsing-remitting MS (RRMS), active RRMS, primary progressive MS (PPMS), secondary progressive MS (SPMS) and patients with inflammatory (IND) and noninflammatory neurological diseases (NIND). Serum sFas modulation over 32 weeks IFN-beta1a therapy was also investigated. Serum and CSF sFas levels and sFas indices were elevated in MS compared to NIND and IND patients. Within the MS group, serum and CSF sFas levels were highest in PPMS, with active RRMS patients demonstrating the highest sFas indices. This may reflect an ongoing disease process which is occurring acutely (active disease) or incessantly (progressive disease). IFN-beta1a induced a transient increase in circulating sFas following initiation of therapy. Whilst evidence was provided for variable sFas expression in clinical subgroups of MS, there was insufficient definition between the respective groups to advocate sFas measurements as a diagnostic marker of clinical subgroups of MS.

Adolescent↗

Primary progressive multiple sclerosis: increasing clarity but many unanswered questions.

Heterogeneity in the clinical course of multiple sclerosis (MS) is well recognised and patients following a primary progressive course, 10-15% of the MS population, have a distinct clinical and paraclinical phenotype. This review examines recent advances in our understanding of this subgroup of patients and examines the new criteria to be applied in diagnosis. It also highlights developments in genetic, immunological, magnetic resonance and pathological aspects of the disease, whilst also outlining the results of recent therapeutic trials.

Controlled Clinical Trials as Topic↗