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At least 1,711 records · Page 95Linked to original sources
PubMed2001

Expression of urokinase plasminogen activator receptor on monocytes from patients with relapsing-remitting multiple sclerosis: effect of glatiramer acetate (copolymer 1).

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system in which peripheral blood monocytes play an important role. We have previously reported that patients with chronic progressive MS (CPMS) have significantly increased numbers of circulating monocytes which express the urokinase plasminogen activator receptor (uPAR). In the present study, we examined the expression of uPAR on monocytes in patients with relapsing-remitting multiple sclerosis (RRMS) not currently participating in a clinical trial and in patients with RRMS who were enrolled in a double-blind multicenter clinical trial designed to examine the effect of glatiramer acetate (copolymer 1; Copaxone) on relapsing disease. Patients with CPMS have sustained high levels of circulating uPAR-positive (uPAR(+)) monocytes. In comparison, patients with RRMS displayed variable levels of circulating uPAR(+) monocytes. Mean values for uPAR in patients with RRMS were above those seen for controls but were not as high as those observed for patients with secondary progressive MS. Patients with RRMS in the clinical trial also had variable levels of monocyte uPAR. However, patients in the treatment group displayed lower levels following 2 years of treatment. In both placebo-treated and glatiramer acetate-treated patients, the percentage of circulating uPAR(+) monocytes, as well as the density of uPAR expressed per cell (mean linear fluorescence intensity), increased just prior to the onset of a clinically documented exacerbation. Values fell dramatically with the development of clinical symptoms. uPAR levels in all groups correlated with both clinical activity and severity. Results indicate that monocyte activation is impatient in MS and that glatiramer acetate may have a significant effect on monocyte activation in patients with RRMS.

Antibodies, Monoclonal↗
PubMedDate not supplied

Effects of an energy conservation course on fatigue impact for persons with progressive multiple sclerosis.

OBJECTIVE: Fatigue is a common, troublesome symptom for persons with multiple sclerosis. This study evaluated the effects of an energy conservation course on fatigue impact for persons with multiple sclerosis whose symptoms cause moderate to severe disability. METHODS: Thirty-seven persons with progressive multiple sclerosis participated in an 8-week experimental energy conservation course treatment and an 8-week control period of traditional treatment using a crossover design. The Fatigue Impact Scale (FIS) was used to assess fatigue impact before and after the experimental and control periods, and 8 weeks post-energy conservation course. RESULTS: After participation in the energy conservation course, the average FIS total score and physical, cognitive, and psychosocial subscale scores decreased significantly, whereas the total and subscale scores did not change significantly during the control period. Additionally, decreased fatigue impact was maintained 8 weeks after course completion for evaluated participants. CONCLUSION: This study provides evidence that this energy conservation course can be a beneficial intervention for persons with progressive multiple sclerosis.

Activities of Daily Living↗
PubMed2006

Clinical characteristics of cortical multiple sclerosis.

There are several articles in this special issue in which authors eloquently describe neurobehavioural and cognitive complications of multiple sclerosis with relevant neuropsychological assessments and neuroimaging findings. However behavioural and cognitive presentation of multiple sclerosis remains poorly understood. Two years ago, we reported a series of patients with multiple sclerosis who presented with neurobehavioural symptoms and had neuropsychological deficits consistent with cortical dysfunction. Based on previous case reports, pathological studies of cerebral cortex in multiple sclerosis and advanced neuroimaging studies we suggested that neurobehavioural presentation of multiple sclerosis represents a new variant called "cortical multiple sclerosis". The condition is characterised by predominant or exclusive cortical pathology presenting with neurobehavioural symptoms, such as depression, amnesia or distinct cortical syndromes. Since the publication of our report, there has been further neuroimaging and neuropathological findings that further supported the above concept. In addition, observation of more patients with this condition helped us to formulate a logical approach in the detection of these patients. This article focuses on their clinical characteristics.

Behavioral Symptoms↗
PubMedDate not supplied

Gray matter N-acetyl aspartate deficits in secondary progressive but not relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Spectroscopic examination of multiple sclerosis (MS) patients has revealed abnormally low N-acetyl-aspartate (NAA) signal intensity, even in brain tissue that appears normal on high-resolution structural MR images but has yielded inconclusive evidence to distinguish the well-documented clinical differences between MS subtypes. This study used proton MR spectroscopic imaging (MRSI) and high-resolution MR imaging to characterize metabolite profiles in normal-appearing brain tissue of relapsing-remitting multiple sclerosis (RRMS) and secondary progressive (SP) MS. METHODS: Volumetric spiral MRSI was used together with high-resolution MR imaging to derive absolute measures of metabolite concentrations separately in normal-appearing supratentorial cerebral gray matter and white matter in five RRMS patients, five SPMS patients, and nine age-matched controls. Structural MR images were segmented into compartments of gray matter, white matter, CSF, and lesions, and metabolite signals per unit of tissue volume were calculated for gray matter and white matter separately. RESULTS: Only the SPMS group had significantly lower NAA concentrations in normal-appearing gray matter compared with concentrations in controls. NAA in normal-appearing white matter was equally reduced in RRMS and SPMS patients. The functional relevance of this brain metabolite measure was suggested by the observed but statistically nonsignificant correlation between higher disability scores on the Expanded Disability Status Scale and lower gray matter NAA concentrations. CONCLUSION: The otherwise occult abnormality in supratentorial gray matter in SPMS but not RRMS may explain the more severe physical and cognitive impairments afflicting patients with SPMS that do not correlate well with visible lesion burden.

Adult↗
PubMed2005

Inapparent visual field defects in multiple sclerosis patients.

To assess inapparent visual field defects in patients with multiple sclerosis free from optic neuritis. During 5 years period 120 patients with multiple sclerosis were examined at the University Department of Ophthalmology, Zagreb University Hospital Center. They were divided into three groups with 40 patients each: patients with acute unilateral optic neuritis, referred to ophthalmologist and treated with pulsed steroid therapy; patients with subjective feeling of blurred vision, normal visual acuity and no signs of acute optic neuritis; and patients free from subjective signs of visual impairment. Study patients underwent standard ophthalmologic examination and visual field testing in photopia by use of quantitative kinetic Goldmann perimetry. The initial and control examination by visual field testing were performed at least 6 months apart. Study results showed 65% of multiple sclerosis patients to have visual field defects without subjective signs of impaired vision. The most common defects were mild to moderate visual field narrowing with blind spot enlargement and depression from above. The following results were recorded: acute optic neuritis group: normal in 13/40 (32.5%) for the affected eyes and 27/40 (67.5%) for fellow eyes; mild visual field narrowing in 4/40 (10%) for the affected eyes and 10/40 (25%) for fellow eyes; moderate visual field narrowing with blind spot enlargement in 14/40 (35%) for the affected eyes and 1/40 (2.5%) for fellow eyes; and paracentral and arcuate scotomata in 9/40 (22.5%) for the affected eyes and 2/40 (5%) for fellow eyes; subjective symptom group: normal in 8/40 (20%) for the affected eyes and 11/40 (27.5%) for fellow eyes; mild visual field narrowing in 11/40 (27.5%) for the affected eyes and 16/40 (40%) for fellow eyes; moderate visual field narrowing with blind spot enlargement in 18/40 (45%) for the affected eyes and 10/40 (25%); andparacentral and arcuate scotomata in 3/40 (7.5%) for both affected and fellow eyes; and subjective symptom-free group: normal in 24/80 (30%), mild visual field narrowing in 22/80 (27.5%) moderate visual field narrowing with blind spot enlargement in 24/80 (30%); and paracentral and arcuate scotomata in 10/80 (12.5%). The presence of subclinical form of optic nerve involvement could be demonstrated in a very early stage of multiple sclerosis by the introduction of visual field testing in the standard examination protocol.

Adolescent↗
PubMed1999

Development of a multiple sclerosis functional composite as a clinical trial outcome measure.

The primary clinical outcome measure for evaluating multiple sclerosis in clinical trials has been Kurtzke's expanded disability status scale (EDSS). New therapies appear to favourably impact the course of multiple sclerosis and render continued use of placebo control groups more difficult. Consequently, future trials are likely to compare active treatment groups which will most probably require increased sample sizes in order to detect therapeutic efficacy. Because more responsive outcome measures will be needed for active arm comparison studies, the National Multiple Sclerosis Society's Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis appointed a Task Force that was charged with developing improved clinical outcome measures. This Task Force acquired contemporary clinical trial and historical multiple sclerosis data for meta-analyses of primary and secondary outcome assessments to provide a basis for recommending a new outcome measure. A composite measure encompassing the major clinical dimensions of arm, leg and cognitive function was identified and termed the multiple sclerosis functional composite (MSFC). The MSFC consists of three objective quantitative tests of neurological function which are easy to administer. Change in this MSFC over the first year of observation predicted subsequent change in the EDSS, suggesting that the MSFC is more sensitive to change than the EDSS. This paper provides details concerning the development and testing of the MSFC.

Clinical Trials as Topic↗
PubMed1986

Acute optic neuritis: a prospective study of risk factors for multiple sclerosis.

Eighty two patients with isolated optic neuritis were studied prospectively to determine the frequency with which multiple sclerosis developed and the factors which increased its risk. Patients were followed for 6 to 264 months (mean, 57 months). Twenty six patients (32%) developed clinically definite or probable multiple sclerosis during the period of follow-up. Actuarial analysis predicted that 42% would develop multiple sclerosis by 7 years. Of those patients who developed multiple sclerosis, 92% had symptoms within 4 years of the first attack of optic neuritis. The highest incidence of multiple sclerosis occurred in the 21-40 year age group. There was an increased risk of MS in patients with HLA-DR2 and HLA-B7 tissue types. The frequency of HLA-DR4 was increased in patients with optic neuritis alone compared to controls and to patients with multiple sclerosis, but further studies are required to confirm this finding.

Acute Disease↗
PubMedDate not supplied

Physiologic and thermal responses of male and female patients with multiple sclerosis to head and neck cooling.

Personal cooling systems are used to alleviate symptoms of multiple sclerosis and to prevent increased core temperature during daily activities. The objective of this study was to determine the thermal and physiologic responses of patients with multiple sclerosis to short-term maximal head and neck cooling. A Life Support Systems, Inc. Mark VII portable cooling system and a liquid cooling helmet were used to cool the head and neck regions of 24 female and 26 male patients with multiple sclerosis in this study. The subjects, seated in an upright position at normal room temperature (approximately 22 degrees C), were cooled for 30 min by the liquid cooling garment, which was operated at its maximum cooling capacity. Oral, right, and left ear temperatures and cooling system parameters were logged manually every 5 min. Forearm, calf, chest, and rectal temperatures, heart rate, and respiration rate were recorded continuously on a U.F.I., Inc. Biolog ambulatory monitor. This protocol was performed during the winter and summer to investigate the seasonal differences in the way patients with multiple sclerosis respond to head and neck cooling. No significant differences were found between the male and female subject group's mean rectal or oral temperature responses during any phase of the experiment. The mean oral temperature decreased significantly (P < 0.05) for both groups approximately 0.3 degrees C after 30 min of cooling and continued to decrease further (approximately 0.1-0.2 degrees C) for a period of approximately 15 min after removal of the cooling helmet. The mean rectal temperatures decreased significantly (P < 0.05) in both male and female subjects in the winter studies (approximately 0.2-0.3 degrees C) and for the male subjects during the summer test (approximately 0.2 degrees C). However, the rectal temperature of the female subjects did not change significantly during any phase of the summer test. These data indicate that head and neck cooling may, in general, be used to reduce the oral and body temperatures of both male and female patients with multiple sclerosis by the approximate amount needed for symptomatic relief as shown by other researchers. However, thermal response of patients with multiple sclerosis may be affected by gender and seasonal factors, which should be considered in the use of liquid cooling therapy.

Activities of Daily Living↗
PubMed2000

Decreased stability of alpha2-macroglobulin purified from patients with multiple sclerosis.

OBJECTIVES: To investigate conformational properties of alpha2-macroglobulin from multiple sclerosis patients. MATERIALS AND METHODS: alpha2-macroglobulin was purified to homogeneity from plasma of 4 multiple sclerosis patients and 5 healthy controls. The plasma and the purified alpha2-macroglobulin from each individual were investigated using polyacrylamide gel electrophoresis. RESULTS: Impaired stability of purified alpha2-macroglobulins from multiple sclerosis patients was demonstrated with spontaneous conversion to an electrophoretic "fast" form upon purification and following storage not ascribable to bait region cleavage. CONCLUSION: alpha2-macroglobulin from multiple sclerosis patients displays altered stability. Possible functional impairments of proteinase inhibition mechanisms are discussed.

Adult↗
PubMed2003

Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level in patients with multiple sclerosis.

Free radical-mediated peroxidation of biological molecules, especially of lipids, is implicated in the pathogenesis of a number of diseases like multiple sclerosis. Low concentration of antioxidant vitamins: beta carotene, retinol, alpha tocopherol and ascorbic acid have been observed in serum or cerebrospinal fluid of multiple sclerosis patients. On the basis of these observations, we studied the potential lipoprotein oxidation and total antioxidant capacity in the pathogenesis of multiple sclerosis. Lipoprotein oxidizability for plasma in vitro, serum levels of autoantibodies against oxidized low-density lipoproteins, plasma total homocysteine levels with vitamin B12 and folate, and plasma total antioxidant capacity were measured in twenty four patients with multiple sclerosis and twenty four healthy sex- and age-matched person as control. In multiple sclerosis patients during an attack, a significant increase in both in vitro lipid oxidizability for plasma and in the levels of autoantibodies against oxidized low-density lipoproteins, and a strong decrease in plasma total antioxidant capacity were detected. Plasma total homocysteine levels were significantly higher in multiple sclerosis patients whose plasma vitamin B12 and folate levels were lower but not statistically significant, than controls. The present study indicates that lipoprotein oxidation may be important factor in the course of multiple sclerosis and in vitro measurements of plasma oxidation kinetics as an indication for lipoprotein oxidation might be useful as an additional tool for the clinical diagnosis of multiple sclerosis.

Adult↗
PubMed1999

Cranial polyneuropathies in multiple sclerosis: case report and literature review.

Although cranial neuropathies are common disorders in multiple sclerosis patients, multiple cranial nerve involvement is an unusual occurrence. Correlation of clinical symptoms with magnetic resonance imaging evidence of demyelinating central nervous system lesions can confirm the diagnosis. The authors report on the case of a 43-year-old woman who initially was thought to have suffered a brainstem infarct but, in fact, had developed multiple cranial nerve functional deficits. Treatment of multiple sclerosis remains primarily supportive in nature, with corticosteroids used for acute exacerbations and chronic progression.

Adult↗
PubMed1997

Transitional progressive multiple sclerosis: a clinical and imaging study.

OBJECTIVE: To study the prevalence and the natural course of transitional progressive multiple sclerosis (TPMS). This clinical form is defined by a progressive course beginning many years after an isolated bout. METHODS: 214 consecutive outpatients with definite or probable multiple sclerosis were studied. The prevalence of TPMS was established. Patients with TPMS were compared with patients with other progressive forms of multiple sclerosis according to the clinical course. A prospective one year follow up study was performed in a subgroup of patients to compare progression of the disease using clinical indices and MRI. RESULTS: In this clinical population of 214 outpatients with multiple sclerosis, 55 had secondary progressive multiple sclerosis (SPMS), 38 primary progressive multiple sclerosis (PPMS), and 12 TPMS. Retrospective analysis of the clinical data of these patients shows that TPMS is very similar to SPMS at the beginning of the disease (age at onset, time before progression, clinical symptoms at onset, progression index). In addition a cohort of patients was prospectively followed up clinically and by MRI for one year. CONCLUSIONS: The results did not show any significant differences between the three forms during this follow up. However, all data showed a concordant trend suggesting that at this progressive stage, TPMS is closer to PPMS in terms of progression of disability and new MRI lesions.

Brain↗
PubMed2006

A rapid screening tool for fatigue impact in multiple sclerosis.

BACKGROUND: Fatigue is a common complaint in multiple sclerosis (MS) and often interferes with daily functioning. Both clinicians and researchers may need to detect high levels of fatigue impact using a time and effort efficient tool. This study evaluates the psychometric properties of a rapid screening instrument for fatigue impact in multiple sclerosis. METHODS: Three visual analogue scales (VAS) for assessing the impact of fatigue were developed. Sixty two subjects with definite MS (mean age 52 +/- 10.5 years; 29 women) and 24 healthy controls (mean age 52 +/- 14 years; 13 women) completed all VAS scales (range 0-100), the Fatigue Severity Scale (FSS) (range 7-63), the Modified Fatigue Impact Scale (MFIS) (range 0-84) and the Guy's Neurological Disability Scale (GNDS) (range 0-5). All tests were repeated with an interval of maximum three days. To evaluate the reproducibility, intraclass correlations (ICC) were calculated, based on one-way analysis of variance for repeated measurements. Validity was considered by means of correlation coefficients. ROC analysis was used to determine the accuracy of the VAS scales. RESULTS: The ICC of the VAS scales ranged from 0.68 to 0.69. VAS scales showed low to moderate correlation with FSS, MFIS and GNDS (Kendall's tau 0.23-0.45) and were not related with physical or cognitive performance, or with depression. All VAS scales were able to discriminate between subjects with MS and controls. Twenty five subjects with MS had a Fatigue Severity Scale score of 36 or more and were classified into the "fatigue" group. ROC analysis showed that VAS_1 is most useful to classify subjects in the "fatigue" group. A cut-off value of VAS_1 of 59 displayed 76% sensitivity and 72% specificity. When using the MFIS score of 40 or more to classify the groups, VAS_1 remained the strongest tool, with 81% sensitivity and 77% specificity at a cut-off value of 59. CONCLUSION: The VAS for the impact of fatigue on daily life (VAS_1) is a moderately reliable, though valid and useful tool to screen rapidly for fatigue impact in multiple sclerosis. A cut-off value of 59 satisfactorily classifies individuals having severe fatigue with a high impact on daily life. In clinical practice, a more comprehensive assessment of fatigue and the impact on daily life is recommended.

Adult↗
PubMed2006

Relations between social support, appraisal and coping and both positive and negative outcomes for children of a parent with multiple sclerosis and comparisons with children of healthy parents.

OBJECTIVE: To examine adjustment in children of a parent with multiple sclerosis within a stress and coping framework and compare them with those who have 'healthy' parents. SUBJECTS: A total of 193 participants between 10 and 25 years completed questionnaires; 48 youngsters who had a parent with multiple sclerosis and 145 youngsters who reported that they did not have a parent with an illness or disability. METHOD: A questionnaire survey methodology was used. Variable sets included caregiving context (e.g. additional parental illness, family responsibilities, parental functional impairment, choice in helping), social support (network size, satisfaction), stress appraisal, coping (problem solving, seeking support, acceptance, wishful thinking, denial), and positive (life satisfaction, positive affect, benefits) and negative (distress, health) adjustment outcomes. RESULTS: Caregiving context variables significantly correlated with poorer adjustment in children of a parent with multiple sclerosis included additional parental illness, higher family responsibilities, parental functional impairment and unpredictability of the parent's multiple sclerosis, and less choice in helping. As predicted, better adjustment in children of a parent with multiple sclerosis was related to higher levels of social support, lower stress appraisals, greater reliance on approach coping strategies (problem solving, seeking support and acceptance) and less reliance on avoidant coping (wishful thinking and denial). Compared with children of 'healthy' parents, children of a parent with multiple sclerosis reported greater family responsibilities, less reliance on problem solving and seeking social support coping, higher somatization and lower life satisfaction and positive affect. CONCLUSIONS: Findings delineate the key impacts of young caregiving and support a stress and coping model of adjustment in children of a parent with multiple sclerosis.

Adaptation, Psychological↗
PubMed2006

Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research.

In view of disease heterogeneity of multiple sclerosis and limited access to ex vivo specimens, different approaches must be undertaken to better understand disease pathogenesis and new therapeutic challenges. Here, we critically discuss models of experimental autoimmune encephalomyelitis (EAE) that reproduce specific features of the histopathology and neurobiology of multiple sclerosis and their shortcomings as tools to investigate emerging therapeutic approaches. By using EAE models we have understood mechanisms of T-cell mediated immune damage of the CNS, and the associated effector cascade of innate immunity. Also, the importance of humoral components of the immune system for demyelination has been delineated in EAE, before it was applied therapeutically to subtypes of multiple sclerosis. Yet, similar to multiple sclerosis, EAE is also heterogeneous and influenced by the selected autoantigen, species and the genetic background. In particular, the relevance of cytotoxic CD8 T cells for human multiple sclerosis has been underestimated in most EAE models, and no EAE model exists that mimics primary progressive disease courses of multiple sclerosis. Seventy years after the first description of EAE and the publication of >7000 articles, we are aware of the obvious limitations of EAE as a model of multiple sclerosis, but feel strongly that when used appropriately it will continue to provide a crucial tool for improving our understanding and treatment of this devastating disease.

Animals↗
PubMed2004

Association of protein kinase C alpha (PRKCA) gene with multiple sclerosis in a UK population.

Twin, family and adoption studies suggest that susceptibility to multiple sclerosis is substantially mediated by genetic factors. Linkage to human chromosome 17q, homologous to a locus linked to experimental animal models of multiple sclerosis, has been widely replicated and the region likely to harbour a multiple sclerosis susceptibility gene has recently been refined to a 2.5 Mb region of 17q22-24. The candidate multiple sclerosis susceptibility gene, protein kinase C alpha (PRKCA), maps within this interval and association with 35 single-nucleotide polymorphism (SNP) markers, spanning the gene with a median spacing of 7.8 kb, was tested using a case-control approach. Single-marker genotype and estimated haplotype frequencies were compared in UK unrelated cases with multiple sclerosis (n = 184) and healthy controls (n = 340) in order to investigate association with susceptibility to disease. A haplotype of two SNPs mapping to the proximal region of the gene showed evidence for association with susceptibility (Bonferroni-corrected P value = 1.1 x 10(-5)). These findings suggest that further investigation of the PRKCA gene is warranted, particularly in cohorts with evidence of linkage to 17q22. Most of the SNPs investigated in this study were intronic and screening to identify disease-associated functional mutations is now required. Our results suggest that the promoter and proximal gene region should be not only included but prioritized in any screening strategy.

Adult↗
PubMed1999

Benign multiple sclerosis? Clinical course, long term follow up, and assessment of prognostic factors.

OBJECTIVE: To establish the characteristics of patients following a benign course of multiple sclerosis and evaluate the importance of potential prognostic factors. Also, an assessment of the value of the Kurtzke EDSS as a prognostic indicator has been undertaken in patients previously determined to have benign multiple sclerosis, after 10 years of follow up. METHODS: A prevalence study in the Coleraine, Ballymena, Ballymoney, and Moyle districts of Northern Ireland used the Kurtzke expanded disability scale score (EDSS) in 259 patients with multiple sclerosis. Of these, 181 had had multiple sclerosis for>/=10 years, 36 having benign disease (EDSS</=3.0) >/=10 years after onset. Clinical and demographic details of the various patient groups, including the minimal record of disability, were compared. The 1987 study in Northern Ireland identified 33 patients with benign multiple sclerosis. Twenty eight were available for follow up in 1996 along with 42 contemporary non-benign patients. RESULTS: Patients with benign multiple sclerosis were predominantly women (ratio 4.1:1 v 2.1:1) and younger at onset (25.8 v 31.2 years). Commonest symptoms at onset were sensory and optic neuritis (33.3% each). Patients with late onset (older than 40 years) were less likely to have a benign course, more likely to have a progressive course from onset, significantly more likely to have motor disturbance at presentation, and had a lesser female predominance. Optic neuritis was significantly more common in those with a younger age at onset. In the follow up study, patients with benign multiple sclerosis continued to have a more favourable course than non-benign counterparts but progression of disability and to the secondary progressive phase remained significant. CONCLUSIONS: The association of female sex, early onset, and presentation with optic neuritis and sensory symptoms with a favourable course is confirmed. However, although the EDSS does provide a useful indicator of prognosis, the label "benign multiple sclerosis" is often temporary as apparently benign disease often becomes disabling.

Adult↗