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 721 records · Page 40Linked to original sources
PubMed2001

Increased nitric oxide products in CSF in primary progressive MS may reflect brain atrophy.

Because nitric oxide (NO) is a putative mediator of oligodendrocyte damage in the primary progressive form of MS (PPMS), the authors analyzed the levels of NO oxidation products in CSF and plasma from 25 patients with PPMS and 15 controls. The levels of nitrite + nitrate (NOx) in CSF were fourfold higher in patients with PPMS than in controls (p < 0.001), whereas the concentrations in plasma were similar. These data suggests involvement of NO in nervous tissue damage in PPMS.

Adult↗
PubMed2003

[Association between DNA antibodies levels in the blood of patients with multiple sclerosis and clinical presentation of the disease].

Multiple sclerosis (MS) as an autoimmune disease is characterized by occurrence of high titres of antibodies (AB) to cell structures and autoantigens. Various AB-mediated effector mechanisms can participate directly in the pathogenesis of demyelinisation damaging myelin, oligodendrocytes and nervous fibres. Antinuclear AB, including anti-DNA AB are an example of activation of humoral immunity in MS. Pathogenetic and clinical value of these AB is investigated insufficiently. The aim of this study was estimation of the AB titers in MS patients from two populations of Russia in relation to clinical features of MS. Results of examination of 83 patients with definite MS from Novosibirsk and Moscow (49 and 34 patients) are analyzed. Groups of comparison consisted of healthy donors and patients with SLE of the same age. Use of identical methods in the analysis of the data received in two various populations made the data objective as much as possible and revealed the strongest clinico-biochemical associations. Levels of AB to both native and denaturated DNA were studied. Comparison of several test-systems showed that the system produced by "Specialized scientific Labs" Company has the best sensitivity. In two populations of MS patients the levels of AB in plasma were similar and associated between each other, higher than in donors, but lower than in SLE patients. In both groups MS patients with secondary progressive MS had higher percent of samples of plasma with average and high levels of AB. In the Novosibirsk group associations of levels of AB with parameters of disease severety (EDSS and a number of FS scales) were seen. In the Moscow group levels of AB to DNA were significantly associated with time from the disease onset to certain level of disability (EDSS 3); both the analysis of average values and the correlation analysis showed a weak association of AB to DNA level and MS duration. The data testify that AB to DNA play a more important role in MS pathogenesis than was considered earlier. Catalytic AB as a part of anti-DNA AB may play a special role.

Adult↗
PubMed2000

One year follow up study of primary and transitional progressive multiple sclerosis.

OBJECTIVE: To document clinical and magnetic resonance imaging (MRI) characteristics of a large cohort of primary and transitional progressive multiple sclerosis (PP and TP MS) patients over one year. INTRODUCTION: Patients with PP or TP MS have been shown to have low brain T2 and T1 lesion loads and slow rates of new lesion formation with minimal gadolinium enhancement, despite their accumulating disability. Serial evaluation of these patients is needed to elucidate the pathological processes responsible for disease progression and to identify clinical and MRI measures which can monitor these processes in treatment trials. METHOD: Patients, recruited from six European centres, underwent two assessments on the expanded disability status scale (EDSS) and MRI of the brain and spinal cord, 1 year apart. RESULTS: Of the 167 patients studied (137 with PP MS and 30 with TP MS), 41 (25%; 35 PP and six TP) showed a one step increase in the EDSS. The mean number of new brain lesions seen was 0.88 in the PP group and 0.47 in the TP MS group. Both groups demonstrated change in T2 lesion load over the year (p< or =0.002), with median percentage changes of 7.3% in the PP group and 10. 8% in the TP MS group. The PP group also showed a significant change in T1 load (p< 0.001, median change 12.6%). The number of new cord lesions seen was small (mean of 0.14 in the PP group and no new cord lesions in the TP group). Both groups demonstrated a decrease in cord cross sectional area (p< 0.001, median changes; PP 3.8%, TP 4. 9%), but only the PP group showed evidence of significant brain atrophy (p<0.001, 0.95%). CONCLUSION: Although the monitoring of disease progression in this patient group is difficult, this study demonstrates changes in both lesion load and atrophy, which, if shown to correlate with clinical change over a longer time will facilitate therapeutic trial design.

Atrophy↗
PubMed2004

Cognitive impairment in relapsing and primary progressive multiple sclerosis: mostly a matter of speed.

Based on the assumption that cognitive impairment in MS is consistent with subcortical dementia, a battery of neuropsychological tests was assembled that included measures of executive function (Tower of London and Wisconsin Card Sorting Test), verbal learning and memory (a paired associates learning test), and speeded information processing (Stroop Color Word Interference Test). The battery was administered to patients with relapsing and primary progressive MS and to healthy controls. Differences between patients and controls occurred on several of the measures. However, when differences with respect to fatigue and depression were statistically controlled, the only differences that remained significant involved measures relating to the speed of information processing. Patients performed more slowly than controls, with the disparity being greater for relapsing patients than for those with primary progressive disease. The slowing was evident on measures of automatic as well as controlled processing and regardless of whether speed was an explicit feature of successful performance or recorded unobstrusively while the patient concentrated on planning a correct solution to a problem. Parallels were noted between cognitive slowing associated with MS and that of normal aging.

Adult↗
PubMed2006

Fatigue in progressive multiple sclerosis is associated with low levels of dehydroepiandrosterone.

BACKGROUND AND OBJECTIVE: Fatigue is one of the most limiting symptoms in multiple sclerosis (MS) and the mechanisms underlying its origin are poorly understood. Our aim was to test whether fatigue in MS is associated with endocrine markers. METHODS: We longitudinally studied 73 progressive MS patients. Fatigue was assessed at baseline and at 3, 6, 12 and 24 months using the Fatigue Severity Scale (FSS). Given the longitudinal design of our study, patients were labelled as sustained fatigued when FSS scores were >5.0 at all time points, and as non-fatigued when FSS scores were < or = 5.0 at all time points. Serum levels of dehydroepiandrosterone (DHEA), its sulphated conjugate (DHEAS) and cortisol were measured at each time point. RESULTS: Twenty-nine patients scored >5.0 in the FSS at all time points, and 9 patients (12.3%) scored 5.0 at all time points. Mean baseline levels of DHEAS and DHEA were lower in MS patients with sustained fatigue when compared to patients without fatigue (P = 0.01 and P = 0.03 respectively). Analysis of DHEAS and DHEA over time showed significantly lower hormone levels in patients with fatigue [F(1,31) = 6.14, P=0.019 for DHEAS; F(1,32) = 6.63, P=0.015 for DHEA]. CONCLUSIONS: Fatigue in progressive MS could be related to low serum levels of DHEA and DHEAS. Our results suggest that these hormones should be considered as biological markers of fatigue in MS patients and that hormone replacement may thus be tested as an option to treat fatigue in MS patients.

Adult↗
PubMed2006

CD24 Ala/Val polymorphism and multiple sclerosis.

CD24 is expressed on a broad range of cells in the immune and central nervous systems and appears to be required for development of experimental autoimmune encephalomyelitis in mice. Association of a CD24 Ala/Val coding polymorphism with susceptibility to and progression of multiple sclerosis was recently reported. We typed this coding polymorphism in a combined cohort of 1,180 cases and 1,168 unrelated and family-based controls from Belgium and the UK, but were unable to confirm either association. Since the CD24 gene is part of a segmental duplication, special care is required for the identification and genotyping of single nucleotide polymorphisms.

Alanine↗
PubMed2001

Inactivation of peroxynitrite in multiple sclerosis patients after oral administration of inosine may suggest possible approaches to therapy of the disease.

Peroxynitrite has been implicated in the pathogenesis of multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis (EAE). Previously, we have shown that administration of uric acid (UA), a peroxynitrite scavenger, is therapeutic in EAE We have also shown that MS patients have lower levels of serum uric acid than healthy individuals or those with other neurological diseases. The aim of this investigation was therefore to raise serum UA levels in MS patients. Oral administration of UA failed to increase low serum UA levels, evidently due to its degradation by gastrointestinal bacteria. However, serum UA could be raised and maintained at elevated levels for a year and more without reported side-effects by oral administration of its precursor inosine. Three of 11 patients given inosine showed some evidence of clinical improvement and there was no sign of disease progression in the remaining patients. Gadolinium-enhanced lesions, observed in two patients before receiving inosine, could not be detected after either 10 or IS months inosine treatment These data provide evidence that serum UA levels can be readily manipulated and that the benefit of higher levels to individuals with MS should be studied further in greater number of patients.

Administration, Oral↗
PubMed2006

Mitoxantrone versus cyclophosphamide in secondary-progressive multiple sclerosis: a comparative study.

Fifty secondary progressive multiple sclerosis (SPMS) patients who had lost one or more EDSS points in the prior two years were selected to receive either cyclophosphamide (25 patients, 13 females, 12 males, F/M = 1.08; mean age: 42.4 years; mean disease duration: 13.3 years; mean EDSS at study entry: 5.7) or mitoxantrone (25 patients, 14 females, 11 males, F/M = 1.27; mean age: 38.2 years; mean disease duration: 11.5 years; mean EDSS at study entry: 5.5). SPMS patients were treated for two years with clinical evaluation (relapse rate, disability progression) every three months and radiological imaging (conventional magnetic resonance imaging) before therapy initiation and at the end of the first and second years of therapy. Safety profile and costs of the two therapeutic protocols were also analysed. In terms of clinical and radiological measures the drugs exerted a quite identical effect on both, and produced a significant reduction in both relapse rate (mitoxantrone Mito): p = 0.001, cyclophosphamide (Cy): p = 0.003) and disability progression (Mito: p = 0.01; Cy: p = 0.01). Subgroups of mitoxantrone- and cyclophosphamide-responding patients were identified (14/25 and 17/25, respectively) and were characterized by a significantly shorter duration of the secondary progressive phase of the disease. In these subgroups, the improvement in the EDSS score at the end of therapy was highly significant (p<0.0001 for Mito, p = 0.0004 for Cy). The safety profiles of both drugs were acceptable; however, the Cy-based therapy protocol was significantly less expensive. We conclude that Cy should be considered as a therapeutic option in rapidly deteriorating SPMS patients.

Adult↗
PubMed2005

Increased disability and MRI lesions after discontinuation of IFN-beta-1a in secondary progressive MS.

OBJECTIVE: To examine neurological and magnetic resonance imaging (MRI) changes following discontinuation of interferon (IFN)-beta-1a treatment in secondary progressive multiple sclerosis (SPMS). METHODS: The study involved 21 SPMS patients who received subcutaneous (s.c.) IFN-beta-1a 44 microg three times weekly (t.i.w.) for 12 months and were thereafter followed up without treatment for a further 12 months. The number of relapses, disability on the Expanded Disability Status Scale (EDSS) and MRI were recorded at baseline, at 12 months of IFN-beta-1a 44 microg t.i.w. and 1 year after discontinuation of treatment. RESULTS: During the 12-month treatment EDSS score and volumes of brain T2- and T1-weighted lesions remained without significant progression, but at 12 months after treatment discontinuation both EDSS score and the volumes of cerebral lesions increased significantly. Cerebrospinal fluid fraction increased significantly both during the treatment and during follow-up. CONCLUSIONS: Discontinuation of IFN-beta-1a 44 microg t.i.w. in SPMS may be associated with an increase in neurological disability and brain lesions on MRI.

Adjuvants, Immunologic↗
PubMed2003

The diagnosis of primary progressive multiple sclerosis.

Primary progressive multiple sclerosis (PPMS) is a rather unique form of the more common relapsing inflammatory demyelinative disease. The absence of attacks that typify relapsing forms of MS imposes special challenges for diagnosis, but also provides an opportunity to study the pathogenesis of the more progressive aspects of the disease process in isolation of confounding transient clinical events. In this review, recent advances in diagnostic approaches are considered in relationship to baseline data from a large multinational study designed to better characterize and treat this clinical phenotype. PPMS subjects with cerebral spinal fluid (CSF) findings consistent with intrathecal immunoglobulin production may have a more tissue destructive disease process than those whose CSF lacks evidence of a B-cell immunopathogenic disease component.

Cerebrospinal Fluid Proteins↗
PubMed2001

Determinants of overall quality of life in secondary progressive MS: a longitudinal study.

Twenty-nine patients with secondary progressive MS underwent monthly assessment with Expanded Disability Status Scale (EDSS), MS Functional Composite (MSFC), MS Quality of Life-54, and cranial MRI over 6 months. Overall quality of life (OQOL) correlated highly with emotional well-being, the mental health composite, health distress, and the physical health composite. In contrast, there was no statistical evidence of consistent correlation between OQOL and EDSS, MSFC, or MR outcome measures.

Adult↗
PubMed2005

Increased accumulations of N-isopropyl-p-[123I]-iodoamphetamine related to tumefactive multiple sclerosis.

We present a 21-year-old woman with tumefactive multiple sclerosis (MS) that exhibited a rapidly progressive course. There were multiple tumor-mimicking contrast-enhance lesions with surrounding edema and mass effect on magnetic resonance imaging. Both early and delayed brain single photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]-iodoamphetamine demonstrated increased accumulations of the tracer and a high retention on the lesions. The SPECT findings represent a diagnostic pitfall for distinguishing MS from malignant brain tumors in patients with intracranial tumor-like lesions.

Adult↗
PubMed2000

Evaluation of mitoxantrone for the treatment of multiple sclerosis.

Mitoxantrone (Novantrone((R))), an antineoplastic agent, has been approved for treating patients with secondary progressive multiple sclerosis (MS). Mitoxantrone, which is usually categorised as an immunosuppressant drug, is now also considered to be a specific immunomodulator. Autoimmune mechanism of pathogenesis of MS is the basis of immunosuppressive therapeutic approaches to MS whereas immunoregulatory abnormalities including defective IFN-alpha production provide the rationale for immunomodulating therapies. Clinical trials have shown that mitoxantrone had a statistically significant impact on reduction of relapse rate and delay in disability progression in these patients. Advantages of mitoxantrone as therapy for MS are: (1) considerable information is available about its pharmacokinetics, metabolism and toxicology from previous use in oncology; (2) it requires administration only once in three months which is not only convenient for the patient but also cost-effective; (3) mitoxantrone is one of the two drugs to be approved for secondary progressive MS (the other is IFN-beta1) which offers an advantage over IFN-beta1a preparations and glatiramer acetate which are indicated only for relapsing remitting MS. However, the duration of therapy is usually limited to two to three years because the maximum cumulative dose recommended is 120 mg/m(2) due to concern for possible cardiotoxicity. Potential market value of the mitoxantrone, based on the cost of treatment per patient and the number of patients likely to be treated in the first year of introduction, is US$210 million.

Animals↗
PubMed2002

Inflammatory demyelinating polyradiculoneuropathy associated with membranous glomerulonephritis and thrombocytopaenia.

A 66-year-old man with secondary progressive multiple sclerosis presented with a flaccid areflexic tetraparesis evolving over a 6-week period. Clinical examination and subsequent investigation confirmed a diagnosis of sub-acute inflammatory demyelinating polyradiculoneuropathy (sub-acute IDP). Nephrotic-range proteinuria and thrombocytopaenia were also noted at the time of presentation-histopathological investigation of the former showed membranous glomerulonephritis as the basis for the protein loss. The IDP, glomerulonephritis and thrombocytopaenia recovered over the same time course. There have been previous reports of either glomerulonephritis or thrombocytopaenia occurring in association with IDP-there are no such reports of all three conditions occurring and resolving simultaneously.

Aged↗
PubMed2005

One-year cyclophosphamide treatment combined with methylprednisolone improves cognitive dysfunction in progressive forms of multiple sclerosis.

We conducted an evaluation of changes in cognition in progressive multiple sclerosis (MS) patients receiving monthly intravenously pulse of cyclophosphamide (700 mg/m2) with methylprednisolone (1g). Twenty-eight consecutive progressive MS patients (10 primary progressive, 18 secondary progressive MS) were evaluated before and after six and 12 months of treatment. The WAIS-R score, memory and executive functions were evaluated. Under treatment we found a significant improvement in global cognitive efficiency, encoding abilities, planning abilities and inhibition after six and 12 months. However, mechanisms of action of the positive effect of these anti-inflammatory and immunosuppressive treatments on cognition remain unclear.

Adult↗
PubMed2006

Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS).

Cognitive impairment occurs in roughly 50% of patients with multiple sclerosis (MS). It is well known that processing speed and episodic memory deficits are the most common neuropsychological (NP) sequelae in this illness. Consensus has emerged about the specific tests that prove most helpful for routine monitoring of MS associated cognitive impairment. The purpose of this study was to examine the validity of the Minimal Assessment of Cognitive Function in MS (MACFIMS), a recommended battery based on the findings of an international conference held in 2001. We tested 291 MS patients and 56 healthy controls. Frequencies of impairment paralleled those reported in previous work for both individual cognitive domains and general impairment. All tests were impaired in the MS group, and distinguished relapsing-remitting (RR) from secondary progressive (SP) course. Principle components analysis showed a distinct episodic memory component. Most of the MACFIMS tests discriminated disabled from employed patients. However, in regression models accounting for all NP tests, those emphasizing verbal memory and executive function were most predictive of vocational status. We conclude that the MACFIMS is a valid approach to routine NP assessment of MS patients. Future work is planned to determine its psychometric properties in a longitudinal study.

Cognition Disorders↗
PubMed2004

Overview of London trial of intramuscular interferon-beta Ia in primary-progressive multiple sclerosis.

This short monograph describes the rationale, design and outcome of a pilot study of beta interferon in patients with primary progressive MS. A total of 50 patients were studied for 2 years using a randomized, double-blinded, placebo-controlled design. There was an emphasis on using MRI measures to evaluate outcome. The study showed that with the numbers studied, useful data could be obtained on safety and on efficacy on certain MRI measures. A larger study would be required to evaluate treatment on disability in this patient cohort and further work is needed to elucidate the relationship between quantitative MR and clinical measures over the longer term.

Adjuvants, Immunologic↗
PubMed2003

A cost-utility analysis of mitoxantrone hydrochloride and interferon beta-1b in the treatment of patients with secondary progressive or progressive relapsing multiple sclerosis.

BACKGROUND: Information on the cost utility of interferon beta-1b and mitoxantrone hydrochloride, 2 disease-modifying agents approved by the US Food and Drug Administration for the treatment of secondary progressive (SP) multiple sclerosis (MS), is limited. OBJECTIVE: The aim of this study was to compare the cost utility of i.v. mitoxantrone hydrochloride administered every 3 months, s.c. interferon beta-1b administered every other day, and routine supportive care from the perspectives of both the insurer and society. METHODS: We used a Markov model with health states based on the Kurtzke Expanded Disability Status Scale (EDSS) scores from both an insurer's and a societal perspective (including direct and total costs, respectively). Theoretical patients entered the model with an EDSS score of 3; their progression was followed for 10 years. Transition probabilities were derived from clinical trial data. Cost and utility inputs were taken from the literature. Sensitivity analyses were conducted on all variables. RESULTS: From the insurer's perspective, the incremental cost-utility ratio of mitoxantrone hydrochloride therapy compared with routine supportive care was 58,272 dollars per quality-adjusted life year (QALY) gained. From a societal perspective, mitoxantrone hydrochloride was more effective and less costly than supportive care. From the perspectives of insurers and society, the cost-utility ratios of interferon beta-1b compared with routine supportive care were 338,738 dollars and 245,700 dollars per QALY gained, respectively. When compared with mitoxantrone hydrochloride, interferon beta-1b had an incremental cost-utility ratio of 741,331 dollars and 658,402 dollars per QALY from the insurer's and society's perspectives, respectively. Cost-utility ratios for mitoxantrone hydrochloride were sensitive to acquisition and administration costs of therapy and to effectiveness at slowing disease progression. Cost-utility ratios for interferon beta-1b were not sensitive to any of the variables included in the model. CONCLUSIONS: Mitoxantrone hydrochloride is likely to be a cost-effective treatment for patients with SPMS or progressive relapsing MS from an insurer' perspective and is cost saving from a societal perspective. Interferon beta-1b is not likely an efficient treatment using conventional comparisons for cost-effectiveness. This analysis has potentially important implications for policy implementation; however, decisions about which agent to use for each patient should consider the treatment's adverse-event profile, the method of administration, and the patient's preferences for these factors.

Adjuvants, Immunologic↗