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PubMed1989

Cognitive and psychiatric abnormalities in multiple sclerosis.

In multiple sclerosis, behavioral changes, including alterations in cognitive functions and psychiatric abnormalities, have been recognized with increasing frequency in recent years. Multiple sclerosis formerly was thought to be primarily a disorder of the brain stem and spinal cord; however, functional changes that can be attributed, at least in part, to cerebral dysfunction are being recognized. Certain cognitive functions such as memory and conceptual processes seem to be preferentially impaired. The degrees of impairment of other functions such as attention and visuospatial skills are now being evaluated. Psychiatrically, affective disorders seem to be the most common diagnoses, and debate exists about whether these abnormalities are a function of the demyelinating process itself or are a reaction to the disability produced by the disorder.

Dementia↗
PubMed1994

On the pathogenesis of multiple sclerosis. A revised model of the cause(s) of multiple sclerosis, especially based on epidemiological data.

Data from an epidemiological study are used to analyse the course of multiple sclerosis. It could be proved that the course of MS is not as haphazard as was often supposed. In general the course is described as being a chronic progressive one, in the majority of patients preceded by a relapsing-remitting period. In contrast to the relapsing-remitting phase the chronic progressive phase of the course does not show marks of being an autoimmune process. From recent data obtained by MRI and NMR spectroscopy it can be concluded that the chronic progression of handicaps in multiple sclerosis is related to neuronal and axonal damage. The relation between these different pathogenetic processes should be the aim of further research.

Adult↗
PubMed1999

Mechanisms of demyelination and tissue damage in multiple sclerosis.

Although multiple sclerosis is generally believed to be a T-cell mediated inflammatory disease of the central nervous system, recent experimental and neuropathological studies show that additional pathogenetic factors are required to induce widespread primary demyelination and secondary tissue damage, such as axonal loss. This review summarises experimental evidence for multiple pathogenetic pathways, that can be responsible for myelin destruction in this disease. Furthermore, recent data are discussed which show that different immunopathological pathways seem to be involved in different patient subgroups. The pathogenetic heterogeneity of multiple sclerosis suggests that immunomodulatory treatment of this disease may be more complex than previously anticipated.

Demyelinating Diseases↗
PubMed2002

Large-scale gene-expression studies and the challenge of multiple sclerosis.

In multiple sclerosis, a complex neurodegenerative disorder, a combination of genetic and environmental factors results in inflammation and myelin damage. Recent transcription-profiling studies have found distinct gene-expression patterns in diseased tissue; such large-scale studies at different stages of the disease are contributing to understanding multiple sclerosis and developing effective therapy.

Gene Expression Profiling↗
PubMed2006

Clinical outcomes after autologous haematopoietic stem cell transplantation in patients with progressive multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a continuously disabling disease and it is unresponsive to high dose steroid and immunomodulation with disease progression. The autologous haematopoietic stem cell transplantation (ASCT) has been introduced in the treatment of refractory forms of multiple sclerosis. In this study, the clinical outcomes followed by ASCT were evaluated for patients with progressive MS. METHODS: Twenty-two patients with secondary progressive MS were treated with ASCT. Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony stimulating factor. Etoposide, melphalan, carmustin and cytosine arabinoside were administered as conditioning regimen. Outcomes were evaluated by the expanded disability status scale and progression free survival. No maintenance treatment was administered during a median follow-up of 39 months (range, 6 to 59 months). RESULTS: No death occurred following the treatment. The overall confirmed progression free survival rate was 77% up to 59 months after transplantation which was significantly higher compared with pre-transplantation (P = 0.000). Thirteen patients (59%) had remarkable improvement in neurological manifestations, four (18%) stabilized their disability status and five (23%) showed clinical recurrence of active symptoms. CONCLUSIONS: ASCT as a therapy is safe and available. It can improve or stabilize neurological manifestations in most patients with progressive MS following failure of conventional therapy.

Adult↗
PubMedDate not supplied

[Symptomatic treatment of multiple sclerosis].

INTRODUCTION: Multiple sclerosis is a chronic neurological disorder which affects middle aged adults. It usually means serious physical, psychological, social and employment problems for the patients concerned. METHOD: From the anatomo pathological point of view, it is characterized by demyelination and axon damage in the central nervous system. The clinical features are variable, depending on the course of the disease, its clinical form and the sites of the lesions. Symptoms may appear in bouts, as relapses of the disorder or as a result of incomplete recovery from these episodes and cause severe disability. CONCLUSION: We review the physiopathology and most widely used treatment for management of the commonest symptoms of multiple sclerosis.

Ataxia↗
PubMed2004

Aging with multiple sclerosis.

Although multiple sclerosis (MS) does not typically reduce life expectancy, there has been relatively little systematic investigation of the experiences and health-related concerns of people aging with this disease. A current search of the database CINAHL produced no articles when the search terms "multiple sclerosis," "nursing" and "aging" were used. To initiate more dialogue about the role of nurses in addressing the issues and concerns of people aging with MS, a cross-sectional descriptive study was conducted using both qualitative interviews and the administration of standardized instruments to elicit information about the health concerns and service needs of 27 people with MS 55 years of age and older. Qualitatively, participants perceived that they had less freedom and required more assistance than same age peers who do not have MS. Scores from standardized instruments support these perceptions. Participants expressed unmet needs in the areas of housework, physical therapy, MS support groups, religious service attendance, information and referral, check-in services, assistive technology use, social activities, personal care, and care coordination. To address these perceptions and needs, neuroscience nurses need to be aware of and sensitive to the challenges of aging with MS. In addition, nurses must be prepared to discuss and provide information, resources, and referrals on a wide range of health, social, and wellness-related services.

Activities of Daily Living↗
PubMed2005

Impact of the Asp299Gly polymorphism in the toll-like receptor 4 (tlr-4) gene on disease course of multiple sclerosis.

In multiple sclerosis patients, infection is often associated with disease deterioration. Lipopolysaccharide (LPS) from gram-negative bacteria signals via the toll-like receptor 4 (TLR-4) pathway. Therefore, we investigated the role of an Asp299Gly mutation in the TLR-4 receptor in 890 MS patients with multiple sclerosis and 350 healthy controls. No association of different genotypes with MS susceptibility, MS subtypes, or disease severity was found. In vitro LPS stimulation studies showed a significantly lower proliferation of PBMCs from donors heterozygous for the Asp299Gly mutation in comparison to PBMCs from individuals with the wild-type genotype (p=0.01). However, these functional changes seem not to have any impact on the clinical presentation of MS patients with different TLR-4 genotypes.

Adolescent↗
PubMedDate not supplied

Antibodies against the paramyxovirus SV5 in the cerebrospinal fluids of some multiple sclerosis patients.

Multiple sclerosis is a demyelinating disease of the central nervous system and although there is little doubt that an infectious agent (or agents) is involved it has not been possible to demonstrate this unequivocally by any direct relationship to a given agent. Here we show that a significant proportion of patients with multiple sclerosis have antibodies against the paramyxovirus SV5 (simian virus 5) in their cerebrospinal fluid and in some of these such antibodies form a major proportion of the total immunoglobulin content. Further, we have been able to demonstrate that the oligoclonal bands displayed on electrophoresis of the cerebrospinal fluid of these patients can be removed by prior absorption with SV5 virus antigen.

Antibodies, Viral↗
PubMed1977

Effect of body temperature on visual evoked potential delay and visual perception in multiple sclerosis.

Seven multiple sclerosis patients were cooled and four heated, but evoked potential delay changed in only five out 11 experiments. Control limits were set by cooling eight and heating four control subjects. One patient gave anomalous results in that although heating degraded perceptual delay and visual acuity, and depressed the sine wave grating MTF, double-flash resolution was improved. An explanation is proposed in terms of the pattern of axonal demyelination. The medium frequency flicker evoked potential test seems to be a less reliable means of monitoring the progress of demyelination in multiple sclerosis patients than is double-flash campimetry or perceptual delay campimetry, although in some situations the objectivity of the evoked potential test would be advantageous.

Body Temperature↗
PubMed1988

[Early detection of multiple sclerosis: MR findings in the initial manifestations of multiple sclerosis].

The MR results in 21 patients showing the initial manifestations of multiple sclerosis (MS) were compared with those in 45 patients with a long history of MS. As in the old cases, MR proved a very sensitive technique during the early manifestations, with abnormal findings in 20 out of the 21 patients. The relatively characteristic MR findings in long-standing MS (predominant peri-ventricular involvement with a relatively typical pattern) was seen in the early stages is only rare cases. The value of MR during the initial manifestations of MS is in cases where the clinical findings are not conclusive and laboratory diagnosis (evoked potentials, CSF findings) are indefinite. In these patients the findings of multiple lesions in the brain can confirm the suspected diagnosis of MS.

Adult↗
PubMed1990

Cellular immune response in multiple sclerosis plaques.

Multiple sclerosis plaques were immunohistochemically stained to exhibit cells expressing immune-system antigens. Human leukocyte antigen (HLA)-DR-positive cells formed dense rings around all plaque regions. The majority were reactive microglia/macrophages. Counterstaining with oil red O revealed heavy myelin debris within these cells. They were distinct from astrocytes, which were identified with an antibody to glial fibrillary acidic protein (GFAP) and which did not contain oil red O myelin debris. Numerous leukocytes and microglia were stained with antibody to leukocyte common antigen (LCA). Lymphocytes in cuffs around vessels, along the margins of capillary walls, and, sparingly, in the tissue matrix of affected areas, were stained with antibodies to CD4 (T-helper/inducer) and CD8 (T-cytotoxic/suppressor). In experimental allergic encephalomyelitis (EAE) induced in Lewis rats, a similar proliferation of Ia-positive (OX6, OX17) cells displaying reactive microglia/macrophage morphology was observed. These Ia-positive cells also were easily distinguished from GFAP-positive astrocytes. The results suggest that macrophages/reactive microglia, and not astrocytes, express class II MHC antigens in multiple sclerosis and EAE plaques.

Animals↗
PubMed1998

Oligodendrocyte progenitors are present in the normal adult human CNS and in the lesions of multiple sclerosis.

In multiple sclerosis, partial remyelination is conspicuous in many lesions, but widespread and lasting myelin repair ultimately fails as disability and handicap accumulate. Thus far, the precise identity of the cell responsible for limited spontaneous myelin repair has remained obscure. In the rodent, the proliferative oligodendrocyte progenitor is the most efficient remyelinating cell; this has now been identified in cultures prepared from normal human brain, but has proved difficult to demonstrate in situ. We adapted techniques using antibodies against the human platelet-derived growth factor-alpha receptor to identify oligodendrocyte progenitors in human tissue sections. Small numbers of oligodendrocyte progenitors were found in normal adult human white matter. Progenitors were also demonstrable in acute and chronic lesions from patients dying with multiple sclerosis, but with no evidence of any marked reactive increase in cell numbers. Understanding the biology of the remyelinating cell, and in particular the reason for its apparent failure to repopulate demyelinated lesions, is important for the development of remyelination treatments.

Adult↗
PubMed1999

Interferon beta treatment in relapsing-remitting multiple sclerosis: a post-marketing study in Lombardia, Italy. Multiple Sclerosis Centers of Lombardia, Italy.

The aim of the study was to evaluate the efficacy of interferon beta-1a (IFN-beta-1a) and beta-1b (IFN-beta-1b) in clinical practice for the treatment of relapsing-remitting multiple sclerosis (RR MS). Patients were selected and prospectively monitored according to a predefined protocol. An appropriate form was prepared to collect clinical data of multiple sclerosis patients attending the MS Centers of Lombardia, Italy. On 30 June 1998, 317 patients were treated with IFN-beta-1b and 156 with IFN-beta-1a. Basal expanded disability status scale (EDSS) and relapse frequency were similar in both groups of patients. The annual relapse rate consistently decreased from 1.76 to 0.63 at 1 year and to 0.51 at 2 years for the IFN-beta-1b group and from 1.6 to 1.0 at 1 year for the IFN-beta-1a group. Disability remained stable in most patients. Dropouts (20.5%) were affected by more active disease compared to patients who continued to be treated. This study confirms the efficacy of both treatments, showing a more marked effect than expected from the clinical trials' results, probably due to differences in selection criteria and exclusion of dropouts.

Adjuvants, Immunologic↗
PubMed2002

Cyclophosphamide for multiple sclerosis.

BACKGROUND: Multiple sclerosis is a presumed cell-mediated autoimmune disease of the central nervous system. Cyclophosphamide (CFX) is a cytotoxic and immunosuppressive agent, used in systemic autoimmune diseases. Controversial results have been reported on its efficacy in MS. We conducted a systematic review of all relevant trials, evaluating the CFX efficacy in patients with progressive MS. OBJECTIVES: The main objectives were to determine whether CFX slows the disease progression. SEARCH STRATEGY: Electronic databases (including MEDLINE, EMBASE, Cochrane Controlled Trials Register) were systematically searched. References list of retrieved studies and conference abstracts on the main meetings on Multiple Sclerosis were handsearched. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating the clinical effect of CFX treatment in patients affected by clinically definite progressive MS. CFX had to be administered alone or in combination with ACTH or steroids. The comparison group had to be placebo or no treatment or the same co intervention (ACTH or steroids) The main outcome criteria were : progression of disability (defined as an increase of 0.5 point in Kurtzke Extended Disability Status Scale (EDSS) for patients with baseline EDSS > or = 6 and 1 for EDSS < or = 5.5), differences of disability between treatment-control groups and the number of patients with side effects. DATA COLLECTION AND ANALYSIS: The identified references were reviewed by two reviewers who independently decided the eligibility of the study, extracted and summarized data and assessed the trial's quality. The statistical analysis was performed using the Cochrane RevMan software and analyzed using Cochrane MetaView. MAIN RESULTS: Of the 326 identified references, 80 were selected for full review, only four RCTs were selected for the final analysis. Intensive immunosuppression with CFX (alone or associated with ACTH or prednisone) in patients with progressive MS compared to placebo or no-treatment (152 participants) did not prevent the long -term (12-18-24 months) risk to evolution to a next step of EDSS. However, the mean change in disability (final disability subtracted from the baseline) significantly favoured the treated group at 12 (effect size - 0.21; C. I. - 0.24, - 0.17) and 18 months (- 0.19; C. I. - 0.24, - 0.14). We were not able to verify the efficacy of other schedules. Five patients died; sepsis and amenorrhea frequently occurred in treated patients (descriptive analysis). REVIEWER'S CONCLUSIONS: Only limited objectives were reached. This review shows a role of CFX in the treatment of progressive MS, but less toxic schedules must be considered, before its use in the clinical practice.

Cyclophosphamide↗
PubMed2005

Relationships between brain water content and diffusion tensor imaging parameters (apparent diffusion coefficient and fractional anisotropy) in multiple sclerosis.

Fifteen multiple sclerosis patients were examined by diffusion tensor imaging (DTI) to determine fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in a superventricular volume of interest of 8 x 8 x 2 cm(3) containing gray matter (GM) and white matter (WM) tissue. Point resolved spectroscopy 2D-chemical shift imaging of the same volume was performed without water suppression. The water contents and DTI parameters in 64 voxels of 2 cm(3) were compared. The water content was increased in patients compared with controls (GM: 244+/-21 vs. 194+/-10 a.u.; WM: 245+/-32 vs. 190+/-11 a.u.), FA decreased (GM: 0.226+/-0.038 vs. 0.270+/-0.020; WM: 0.337+/-0.044 vs. 0.402+/-0.011) and ADC increased [GM: 1134+/-203 vs. 899+/-28 (x10(-6) mm(2)/s); WM: 901+/-138 vs. 751+/-17 (x10(-6) mm(2)/s)]. Correlations of water content with FA and ADC in WM were strong (r=-0.68, P<0.02; r=0.75; P<0.01, respectively); those in GM were weaker (r=-0.50, P<0.05; r=0.45, P<0.1, respectively). Likewise, FA and ADC were more strongly correlated in WM (r=-0.88; P<0.00001) than in GM (r=-0.69, P<0.01). The demonstrated relationship between DTI parameters and water content in multiple sclerosis patients suggests a potential for therapy monitoring in normal-appearing brain tissue.

Anisotropy↗