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At least 163 records · Page 9Linked to original sources
PubMed2005

Effect of mitoxantrone on MRI in progressive MS: results of the MIMS trial.

OBJECTIVE: To evaluate the effects of mitoxantrone (Mx) in progressive multiple sclerosis (MS) on MRI. METHODS: A total of 194 patients with worsening relapsing-remitting or secondary progressive MS were treated with Mx 12 mg/m2 (n = 34), Mx 5 mg/m2 (n = 40), or placebo (n = 36) at 3-month intervals IV over a 2-year period. In preselected MRI centers unenhanced and Gd-enhanced MRI scans were performed at month (M) 0, 12, and 24 in a non-randomized subset of 110 patients and non-selected for MRI criteria. The primary MRI outcome measure was the total number of MRI scans with positive Gd enhancement per group. RESULTS: Twelve mg/m2 Mx failed to reach a significant difference from placebo as measured by the primary MRI outcome at month 12 (p = 0.431) and 24 (p = 0.065). Secondary MRI outcome measures: 5 mg/m2 Mx influenced favorably the number of Gd-enhancing lesions only at month 24 (p = 0.004), but not at month 12 (p = 0.095). Twelve mg/m2 Mx reduced the number of T2-weighted lesions at month 24 (p = 0.027) and showed a positive trend at month 12 (p = 0.069), but not 5 mg/m2 Mx. The number of active MR lesions showed a strong trend toward reduction in the 12 mg/m2 Mx group only at month 24 (p = 0.054). All comparisons are vs placebo, and unadjusted for baseline incidence. CONCLUSIONS: In the MIMS trial 12 mg/m2 Mx does not reduce the number of MRI scans with positive Gd enhancement at month 12 and 24 vs placebo. Results of secondary MRI outcome measures are suggestive of a positive impact of 12 and 5 mg/m2 Mx on some of the Gd enhanced and unenhanced MRI measures as expected from other Mx MRI studies in the past.

Adult↗
PubMed2001

[Beta-interferon clinical trials using MRI in patients with multiple sclerosis].

Magnetic resonance imaging has revolutionized management of patients with multiple sclerosis. This tool provides information on a dynamic process never visualized before, optimizing diagnostic capacities and formalizing the course of the lesion load. Follow-in clinical assessment and performance testing, MRI constitutes a second line tool for following the course of patients with multiple sclerosis in phase II and III trials. We reviewed the correlations between the radiological and clinical findings and the methodology of published trials on beta interferons in remitting, secondarily progressive and early onset multiple sclerosis.

Brain↗
PubMed2006

ADC measurements in various patterns of multiple sclerosis lesions.

OBJECTIVE: To determine the difference of mean apparent diffusion coefficients (ADC) among different patterns of focal multiple sclerosis (MS) lesions, to compare mean lesion ADC between 2 clinical subgroups and to correlate mean lesion ADC with disability. MATERIAL AND METHOD: Thirty seven patients (26 with relapsing-remitting multiple sclerosis (MS) and 11 with secondary-progressive MS) underwent both conventional and diffusion-weighted MR imaging of the brain. After creating ADC maps, region identification was done by using b = 0 images and T2-weighted images. ADC values were measured for MS lesions and (NAWM). RESULTS: A total of 288 lesions were identified on the images. The mean ADC for the lesions was significantly higher than that of NAWM Hypointense T1 lesions (n = 221) had a significantly higher mean ADC than isointense T1 lesions (n = 67) in both nonenhancing lesions (n = 250) and enhancing lesions (n = 38). The enhanced rim of ring-enhancing lesions (n = 18) had lower ADC than the central nonenhanced portions. Confluent lesions (n = 62) had a substantially higher mean ADC than discrete lesion (n = 226). Mean lesion ADC of secondary progressive MS was significantly higher than relapsing remitting MS. No correlation between mean lesion ADC and (EDSS) score was found CONCLUSION: Quantitative diffusion-weighted imaging is useful to elucidate the heterogeneous pathological substrate of MS in different patterns of MS lesions, to differentiate 2 major clinical subgroups.

Adolescent↗
PubMed2004

Methotrexate for multiple sclerosis.

BACKGROUND: Methotrexate is a potent immunosuppressant which in theory could reduce relapse rates and delay disease progression in multiple sclerosis (MS). Subsequently, clinical trials of methotrexate have been conducted in people with MS. OBJECTIVES: To identify and summarise the evidence that methotrexate is beneficial and safe for people with MS. SEARCH STRATEGY: We searched the Cochrane MS Group trials register (searched December 2003), the Cochrane Central Register of Controlled Trails (The Cochrane Library Issue 4, 2003), MEDLINE (Pub Med) (January 1966 to June 2001), EMBASE (January 1988 to June 2001), and reference lists of articles. We also contacted trialists and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials of methotrexate for the prevention of relapses and disease progression in MS. DATA COLLECTION AND ANALYSIS: Two reviewers (OG, GM, ) independently selected articles for inclusion, assessed the trials' quality and extracted the data. Authors of one trial were contacted to obtaining missing information. MAIN RESULTS: One trial involving 60 participants with chronic progressive multiple sclerosis was included. The trial showed a non-significant reduction in sustained EDSS progression and number of relapses in favour of methotrexate therapy. There was no difference in time to first relapse and no data on relapse rate. Minor side-effects were reported frequently in both methotrexate (87.1%) and placebo groups (89.7%), but there were no major side-effects. REVIEWERS' CONCLUSIONS: In progressive MS, the single included trial reveals a non-significant trend in reduction of sustained EDSS progression and number of relapses in favour of methotrexate. A trial of methotrexate in relapsing remitting MS showed non-significant trends in favour of methotrexate but was excluded on methodological grounds. Before drawing further conclusions regarding the efficacy of methotrexate in MS, further trials are required.

Humans↗
PubMed2004

A comparison of the benefits of mitoxantrone and other recent therapeutic approaches in multiple sclerosis.

The approval by the FDA of four immunomodulators (three IFNs and glatiramer acetate) and one immunosuppressant (mitoxantrone; Novantrone) for the treatment of multiple sclerosis is definitely the most important progress in this field since the first description of the disease > 150 years ago. However, both types of immunotherapies raise specific problems. Immunomodulators benefit patients in the relapsing-remitting phase, or patients in the secondary-progressive phase showing clinical and/or radiological signs of active inflammatory processes. Their benefit is modest, but seems to persist with long-term administration, as their tolerance is acceptable. Mitoxantrone is a rescue therapy reserved to patients with an aggressive, rapidly progressive form of the disease. This immunosuppressant is effective on inflammatory processes and pathomechanisms responsible for disability progression. Unfortunately, its cardiotoxicity and potential leukaemogenicity prevent an administration beyond 2 or 3 years. Thus, there is a need to improve on the efficacy of immunomodulators and to reduce the toxicity of immunosuppressants. Combination therapies with immunomodulators and antioxidants or with neuroprotective drugs against excitotoxicity or Na + /Ca 2+ channellopathy are currently being investigated. With regard to immunosuppressants, the development of monoclonal antibodies with fully human protein sequences and the synthesis of a new molecule as effective as mitoxantrone but with a much lower toxicity (pixantrone) seem promising to halt or even to prevent disability progression.

Adjuvants, Immunologic↗
PubMedDate not supplied

[Effect of phlogenzym in long-term treatment of patients with multiple sclerosis].

An assessment was carried out of clinical effectiveness of the drug phlogenzym in 74 patients with remitting, remitting-progressive, and secondary progressive course of multiple sclerosis. Phlogenzym intake for up to one to three years resulted in decline in the incidence of complications, with their degree having come to be lower, duration of remissions longer, progression of the illness slowed down. The data secured suggest to us that phlogenzym is a safe agent. It can, we believe used in a therapeutic regimen for those patients presenting with remitting and remitting-progressive types of the course of the disease.

Adjuvants, Immunologic↗
PubMed2000

A magnetization transfer histogram study of normal-appearing brain tissue in MS.

OBJECTIVE: To evaluate 1) the ability of magnetization transfer ratio (MTR) histogram analysis to detect the extent of changes occurring outside MS lesions seen on conventional scans, 2) whether such changes vary in the different MS clinical phenotypes, 3) whether the changes are associated with the extent and severity of the macroscopic lesion load, and 4) the contribution to brain atrophy. METHODS: Dual-echo, T1-weighted, and MT scans of the brain were obtained from 77 patients with varying MS courses and 20 age- and sex-matched control subjects. To create MT histograms of the normal-appearing cerebral tissue, MS lesions were segmented from dual-echo scans, superimposed automatically, and nulled out from the coregistered and scalp-stripped MTR maps. Average MTR, peak height, and peak position were considered. T2 and T1 lesion loads, average lesion MTR, and brain volume were also measured. RESULTS: Average histogram MTR (p<0.0001) and peak position (p<0.0001) from patients with relapsing-remitting MS (RMMS) were lower than those from control subjects. Patients with primary progressive MS (PPMS) had lower average histogram MTR (p = 0.002) and histogram peak height (p = 0.01) than control subjects. Patients with secondary progressive MS (SPMS) had a lower peak height (p = 0.05) than those with RRMS. Average lesion MTR (p<0.0001) correlated highly with the histogram MTR. Average histogram MTR (p<0.0001) and T2 lesion load (p = 0.001) correlated highly with brain volume. CONCLUSIONS: The amount of microscopic changes account for an important fraction of the lesion load in MS. They may contribute to the development of brain atrophy and tend to be more evident in patients with secondary progressive MS.

Adult↗
PubMed2006

Mitoxantrone-induced cardiotoxicity in patients with multiple sclerosis.

BACKGROUND: There are few treatment options for patients with secondary progressive and worsening relapsing-remitting multiple sclerosis. Mitoxantrone is an antineoplastic drug, recently approved for treatment of multiple sclerosis. Mitoxantrone is, however, associated with dose-related cardiotoxicity, which limits its use. OBJECTIVE: To investigate the possible cardiotoxicity of mitoxantrone in multiple sclerosis. METHODS: We studied 96 patients with worsening relapsing-remitting or secondary progressive multiple sclerosis, to evaluate cardiotoxicity within one year of mitoxantrone therapy. This study was performed in the Multiple Sclerosis Clinic of Isfahan University of Medical Sciences from October 2003 through October 2004. Analysis of mitoxantrone therapy (12 mg/m2), in terms of cardiac toxicity, was conducted on patients who received at least 4 doses. Cardiac assessment was carried out every 6 months with electrocardiogram, as well as a spectral and color-flow Doppler echocardiographic examination at the time of enrollment and 6 and 12 months later. RESULTS: Ninety-six patients were assessed over 12 months. There was no evidence of clinically-significant cardiac dysfunction. Three patients had a left ventricular ejection fraction of <10% of the base-line value and three had <50%. CONCLUSION: Mitoxantrone (12 mg/m2) is effective and generally well tolerated by patients with worsening relapsing-remitting and secondary progressive multiple sclerosis. Our findings suggest that the risk for developing cardiotoxicity is low in patients with multiple sclerosis within one year of the treatment with mitoxantrone.

Adult↗
PubMed2006

Clinical course of progressive multiple sclerosis in Brazilian patients.

OBJECTIVE: To describe the clinical course and outcome of multiple sclerosis with progressive onset in Brazilian patients. A total of 238 medical records were reviewed, 26 cases (10.9%) fulfilled Thompson criteria (2000), and 5.80% classified as primary progressive and 5.04% relapsing progressive according to Lublin and Reingold. STUDY POPULATION: 19 Caucasians and 7 non-Caucasians; male:female ratio 1.2:1, mean age at onset was 34 +/- 7.9 years. RESULTS: Non-Caucasian patients had earlier onset of disease. The most common manifestations at onset were pyramidal and cerebellar (89% and 34.6%). After 11.3 +/- 6.35 years of disease more than 50% of the patients had involvement of most of their functional systems. No statistically significant differences were observed between the subgroups. CONCLUSION: The clinical course and outcome of progressive multiple sclerosis in Brazil, a tropical country with low prevalence, were very similar to those in the multiple sclerosis high prevalence areas.

Adrenal Cortex Hormones↗
PubMed2001

[Therapeutic indications targeting etiology. (With the exception of primary progressive forms)].

On the subject of the treatment of Multiple Sclerosis, JM Charcot stated in 1877 that "the time has not yet come when such a subject can be seriously considered". Fortunately such point of view is no more up to date. This chapter will review the available treatment for relapsing-remitting and secondary progressive Multiple Sclerosis. The immunosuppressive drugs and steroids have been used for many years. Immunomodulation appeared more recently. A review of the evidence on the use of those drugs will be performed.

Adrenal Cortex Hormones↗
PubMed2004

[Immunomodulatory therapy in multiple sclerosis].

During the past decade, several disease-modifying agents have been established and have become available for the treatment of multiple sclerosis. The disease-modifying agents could be grouped into immunomodulatory and immunosuppressive therapies altering the long-term course of multiple sclerosis. Therapy is now available for relapsing-remitting, secondary progressive and progressive-relapsing multiple sclerosis. Different disease-modifying agents became also available for the treatment of relapsing-remitting multiple sclerosis in Hungary which makes the therapeutic decision difficult. This overview might help to give an answer for different questions in the management of multiple sclerosis: Which agent to choose? When to initiate the therapy? Which dose to apply? Are the drugs safe? How long to treat the patients with immunomodulatory drugs? We give a review from the literature to assess the efficacy of disease-modifying therapies and to compare the data from phase three trials of interferon beta1b, two preparations of interferon beta1a or glatiramer acetate for the treatment of multiple sclerosis. We analyzed the efficacy and safety of these agents on physical, inflammatory and cognitive measures of disease activity. Comparison of study results indicated similar effects of immunomodulatory agents on relapse-related and inflammatory measures in relapsing multiple sclerosis. Interferon beta1a slowed the progression of disability in relapsing multiple sclerosis. One interferon beta1a preparation (intramuscularly injected) demonstrated efficacy in slowing progression of cognitive dysfunction. The interferons reduced relapses at early phase of secondary progressive multiple sclerosis, but their efficacy have not yet been proven in the later phase of secondary progressive multiple sclerosis without relapses. Mitoxantrone demonstrated efficacy in slowing the progression of disability in secondary progressive multiple sclerosis. All of the disease modifying agents are safe and tolerable, if the indication is correct and the patients are strictly controlled.

Adjuvants, Immunologic↗
PubMed2002

Interferon-beta therapy for multiple sclerosis induces reciprocal changes in interleukin-12 and interleukin-10 production.

Interleukin-12 is critical to the pathogenesis of experimental autoimmune encephalomyelitis in multiple species. Interleukin-10, a dominant endogenous inhibitor of interleukin-12, is largely protective in these experimental surrogates for multiple sclerosis. Such data have suggested that an interleukin-12/interleukin-10 immunoregulatory circuit is a key determinant of disease expression in experimental autoimmune encephalomyelitis. For multiple sclerosis itself, compatible cytokine data have been reported. The mechanisms underlying the beneficial effects of interferon-beta in multiple sclerosis remain unclear, hampering the search for more effective therapies. Of note, interferon-beta has reciprocal effects on these cytokines in vitro, suppressing interleukin-12 and augmenting interleukin-10 production. To examine the effects of interferon-beta on the interleukin-12/interleukin-10 axis in multiple sclerosis, we characterized the production of these cytokines by peripheral blood mononuclear cells from patients beginning therapy with interferon-beta. Before therapy, multiple sclerosis patients exhibited increased stimulatable interleukin-12 production compared with controls. Interferon-beta therapy leads to inhibition of interleukin-12 and augmentation of interleukin-10 production, significantly elevating the ratio of secreted interleukin-10 to interleukin-12. These effects, observed equally in patients with relapsing-remitting and progressive disease, indicate that interferon-beta affects the interleukin-12/interleukin-10 axis in ways thought to be beneficial to multiple sclerosis patients. More specific therapeutic targeting of these pathways may be warranted.

Adjuvants, Immunologic↗
PubMed2000

Increased cerebrospinal fluid tau protein in multiple sclerosis.

Axonal damage is now being recognized as a common finding in multiple sclerosis (MS) lesions and a cause of irreversible neurological damage. Attempts to identify markers of early axonal damage are of great significance. This prompted us to examine the microtubule-associated protein tau in the cerebrospinal fluid (CSF) of patients with MS vs. controls. Tau was measured by double antibody sandwich ELISA. Increased CSF tau levels were found in MS as compared to controls (medians 249.6 and 135 pg/ml respectively, p<0.001). Half of the MS patients presented with levels above the upper limit of the controls. A significant increase vs. controls was found in both relapsing-remitting and progressive subtypes. These data may indicate axonal impairment in a subpopulation of MS patients and may provide a tool for the estimation of axonal damage during life.

Adult↗
PubMed2001

Matrix metalloproteinases and their tissue inhibitors as markers of disease subtype and response to interferon-beta therapy in relapsing and secondary-progressive multiple sclerosis patients.

Matrix metalloproteinases (MMPs) have recently been implicated in the pathogenesis of multiple sclerosis. Their suggested role includes the disruption of the blood-brain barrier, immune cell transmigration into the central nervous system, and myelin degradation. The present study characterized the mRNA level of a wide spectrum of MMPs and tissue inhibitors of metalloproteinases (TIMPs) expressed by peripheral blood leukocytes from relapsing-remitting (n = 16) and secondary-progressive (n = 12) multiple sclerosis patients. The expression of the same MMPs and TIMPs was evaluated also in a prospective 12-month follow-up of 6 patients randomly chosen from each of the 2 groups during interferon beta-1a treatment. Reverse transcription-polymerase chain reaction assessment demonstrated elevated levels of MT1-MMP and MMP-7 mRNA levels in both groups of patients, and no significant differences in MMP-9 levels, compared with healthy controls. Divergent expression of MMP-2 between relapsing-remitting and secondary-progressive patients compared with controls was observed. Interferon-beta treatment was associated with significant suppression of MMP-9 and MMP-7 mRNA in relapsing-remitting patients, though no significant changes were observed in the secondary-progressive group. These results contribute to the understanding of the IFN-beta-mediated immunomodulatory and therapeutic effects in multiple sclerosis patients and also support evidence for distinct immune mechanism(s) underlying relapsing-remitting versus secondary-progressive multiple sclerosis. The study also suggests that MMPs may be considered as potential biomarkers for response to treatment as well as targets for immunotherapy in multiple sclerosis.

Adjuvants, Immunologic↗
PubMed2006

Tau protein seems not to be a useful routine clinical marker of axonal damage in multiple sclerosis.

BACKGROUND: The descriptions of early axonal damage in patients with multiple sclerosis (MS) prompted the search of body fluid markers. However, the studies addressing this issue in MS present conflicting results. AIM: To assess the levels of tau protein in patients with definite MS. PATIENTS AND METHODS: Cerebrospinal fluid (CSF) samples from 50 patients with definite diagnosis of MS (33 F, 17 M; mean age: 33.6 years) and from 19 age-matched individuals without organic neurological diseases (11 F, 8 M), entered this study. With regard to the clinical course, the MS patients were classified as follows: 32 relapsing-remitting (RR); two secondary progressive (SP), and four primary progressive (PP). Twelve patients had clinical isolated syndromes (CIS). The mean duration was 36.1 months (range: 15 days to 20 years). Tau protein was measured in the CSF by double antibody sandwich ELISA. RESULTS: The median tau and the cut-off values of the controls were 104.9 and 175.3 pg/mL, respectively. We found that most MS patients presented normal values. In addition, the clinical features - course, duration, Expanded Disability Status Scale (EDSS) value, Poser index of progression, Multiple Sclerosis Severity Score - did not significantly influence the tau levels in the MS group. CONCLUSION: Our study showed similar CSF tau concentrations in MS patients with different clinical characteristics. This suggests that tau protein does not seem to be a useful routine clinical marker of axonal damage.

Adolescent↗
PubMedDate not supplied

Lip and tongue function differently affected in individuals with multiple sclerosis.

Clinical dysarthria test scores on lip function and tongue function were compared for 77 dysarthric as well as non-dysarthric subjects with multiple sclerosis (MS) and 15 control subjects. Results show that tongue function was significantly more severely affected than lip function in individuals with MS. Furthermore, tongue function, but not lip function, was significantly more severely affected in the MS individuals with no dysarthria compared to the control group. Test items requiring increased rate of movement (oral and verbal diadochokinesis) were significantly more severely affected than the items requiring range and force of movement, but only in the dysarthric MS subgroup. Moderate correlations were found between tongue and lip function and neurological deficit scores, number of years in disease progression, and perceptually perceived consonant and vowel precision. Consequently, tongue dysfunction can be detected clinically and subclinically using a dysarthria test procedure, and as an early sign of articulatory dysfunction it should be an early target in therapeutic interventions.

Adult↗
PubMed2005

Severe delayed heart failure in three multiple sclerosis patients previously treated with mitoxantrone.

Mitoxantrone is an approved drug for patients with worsening relapsing-remitting, secondary progressive and progressive relapsing multiple sclerosis (MS). From a cohort of 820 MS patients, 52 (6%) were treated with this drug between December 1991 and April 2003. Mitoxantrone was administered at a dose of 12 mg/m(2) once a month for three months and then at three-month intervals to reach a total cumulative dose of 144 mg/m(2). The left ventricular ejection fraction was checked by radionuclide ventriculography prior to treatment and every six months. Treatment was stopped if the ejection fraction was below 50% in two consecutive ventriculographies performed one to three months apart. Cardiotoxicity during the course of the treatment was not observed. However, three patients developed congestive heart failure 24, 39 and 80 months after the last dose of mitoxantrone. Other cardiac causes were excluded. Two of these patients had been treated previously with cyclophosphamide. All patients first recovered on medical treatment, but two worsened a few months later. One patient remained severely symptomatic in spite of optimal medical treatment. Although mitoxantrone is generally well tolerated and reduces progression of disability and clinical exacerbations, our observation of a delayed cardiotoxicity makes necessary a long-term follow-up of MS patients treated with this drug.

Adult↗