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PubMed2006

Effects of pregnancy and childbirth on the incidence of urinary disorders in multiple sclerosis.

OBJECTIVE: Women with multiple sclerosis frequently pose questions to physicians regarding the potential negative impact of pregnancy, especially on urinary disorders. About 50 to 80% of patients suffer from urinary disorders during the course of the disease. Trauma to the pelvic floor and the urethral sphincter during vaginal delivery may lead to the development of stress urinary incontinence. The purpose of this work was to study the consequences of pregnancy and childbirth on urinary problems. STUDY DESIGN: An inception cohort of 368 consecutive women suffering from multiple sclerosis (MS), according to the Poser criteria, were included in the study between June 1999 and June 2000. For each patient a full urological and obstetrical record was obtained. RESULTS: Two hundred and seventy-three women (74%) had had at least one pregnancy. The parous women were older at the time of the study (mean age: 45.5 years vs 35.5 years), and were older at MS onset (mean age: 32.8 years vs 25.7 years). The nulliparous women were more rapidly disabled, with a shorter time to reach an EDSS score of 3 from MS onset (mean time of 5.9 years versus 8.2 years in parous women). In parous women, 259 (95%) had had at least one vaginal delivery and 14 (5%) had had a caesarean only. Delivery modalities had no influence on urinary disorder frequency or the type of problems. CONCLUSION: On the basis of these data, there is actually no clear argument for systematically performing caesarean section in MS women. Urinary disorders in these women were mostly linked to the duration and the severity of the disease but not to pregnancy or delivery modalities. From our point of view, caesarean section must be decided only on classic obstetrical criteria as for healthy women independently of multiple sclerosis. However our data were open and retrospective.

Adult↗
PubMed1997

The lived experience of relapsing multiple sclerosis: a phenomenological study.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that is well known but poorly understood by the medical and nursing community as well as the general public. The myriad neurological symptoms result from an autoimmune attack on the insulating myelin of the nerves which cause a disruption of nerve impulses in the brain and spinal cord. MS most often affects young adults and may be broadly categorized as either a relapsing or a chronic progressive disease course. Until recently, research has focused on the progressive form of MS though it accounts for less than half of the cases. People who are diagnosed with relapsing MS are cared for in the same way as those with the debilitating progressive form. Relapsing MS affects individuals periodically with exacerbations from which they often recover completely, whereas chronic MS results in a progressive functional deterioration. People with relapsing MS are not given a realistic prediction of what to expect in their future nor are they left with any hope for normalcy in their lives. The purpose of this study was to provide a description of the lived experience of people who have relapsing MS. To answer the question, "What is the lived experience of people with relapsing multiple sclerosis?" this study was conducted using hermeneutic phenomenology. A sample of 10 patients with relapsing MS was interviewed over a seven month period. Interviews began with the question, "What is it like for you living with multiple sclerosis?" The interviews were tape recorded and transcribed verbatim. Data were analyzed using the Colaizzi method of hermeneutic phenomenology. Themes that emerged from the data were combined and abstracted into twelve dimensions that described the lived experience of people with relapsing MS. Participants' social networks served as either positive or negative influences in their adjustment process and led to conflicts for some. Coping with recurrent symptoms and social situations related to the MS was facilitated by maintaining control and a sense of hope. Most expressed a sense of relief with diagnosis because they had secretly feared their symptoms were a result of a fatal illness or psychological instability. Uncertainty surfaced as a major theme due to the unpredictability of relapsing MS. Participants also experienced fear and loss. Getting to know MS was an integral part of the experience often made difficult by concealment of facts. Participants experienced acts of revealing and concealing throughout their illness process and often attempted to conceal their illness from a society that did not understand. Nurses should be aware of the relapsing MS experience when providing care and teaching to patients and families with MS. The nurse should also reflect on the importance of maintaining hope and open communication.

Activities of Daily Living↗
PubMedDate not supplied

[Somatic types of patients with multiple sclerosis].

In 129 patients with multiple sclerosis (61 men and 68 women) anthropometric measurements were taken and 5 somatic indices calculated. The types of somatic constitution and the so-called somatic composition were determined using the method of reference points of Wanke. The results were compared with those in a control group representing the Polish population and with a group of patients with psoriasis. The usual male patient with multiple sclerosis was of athletic-pyknic constitution with very strongly expressed (in relation to the control group) features of dysplastic type (A). The typical male individual from the control group had pyknic-athletic constitution. The typical female patient with multiple sclerosis had leptosomic-dysplastic constitution, while the typical control female was leptosomic-pyknic. Male and female patients with multiple sclerosis had the hyperbrachycephalic skull configuration while the control group was branchycephalic. There was no difference between controls and patients with multiple sclerosis with regard to blood groups A1, A2, B, O and Rh.

Adolescent↗
PubMed1995

High resolution proton NMR spectroscopy of multiple sclerosis lesions.

Tissue from postmortem multiple sclerosis and normal control brains was extracted with perchloric acid and analysed using proton NMR spectroscopy. The content of N-acetyl-derived groups (the sum of N-acetyl-aspartate, acetate, and N-acetylaspartylglutamate) was decreased in multiple sclerosis plaques compared with normal control white matter (mean, 4.36 vs. 6.64 mumol/g wet weight). In normal appearing white matter adjacent to plaques a corresponding decrease was seen, with no change in white matter distant from plaques. A decrease in the content of total creatine was observed in multiple sclerosis plaques in comparison with normal control white matter (mean, 4.64 vs. 6.56 mumol/g wet weight), which correlated strongly with the decrease in N-acetyl-derived groups. No changes in other metabolites such as total choline or myo-inositol were seen. The decreases in content of N-acetyl-derived groups are in agreement with observations from in vivo proton NMR spectroscopy in multiple sclerosis patients. The decrease in total creatine is in contrast to most of the observations made in vivo where total creatine is assumed to be unchanged and metabolite levels are often expressed as a total creatine ratio. The use of a total creatine ratio in vivo could lead to an underestimation of reductions in N-acetylaspartate and an apparent increase in other metabolites in the multiple sclerosis lesion.

Adult↗
PubMed2005

CXC chemokine receptors on human oligodendrocytes: implications for multiple sclerosis.

Subsequent to demyelination in multiple sclerosis, myelin repair occurs but, as lesions age, the ability to remyelinate diminishes. Molecular pathways underlying oligodendrocyte behaviour during CNS remyelination remain to be elucidated. In this study, we report for the first time constitutive expression of the CXC/alpha chemokine receptors, CXCR1, CXCR2 and CXCR3, on oligodendrocytes in normal adult human CNS tissue, the levels of which were upregulated in multiple sclerosis and other neurological diseases (OND). In addition, both immature (A2B5+/O4+) and more mature (CNPase+) human oligodendrocytes in vitro expressed the same three receptors. The respective ligands to CXCR1, CXCR2 and CXCR3 [i.e. CXCL8/IL-8, CXCL1/GRO-alpha and CXCL10/IP-10), were absent in CNS tissue from normals and subjects with OND, but were present at high levels on hypertrophic (reactive) astrocytes at the edge of active (but not silent) multiple sclerosis lesions. Astrocytes in vitro could be induced to express chemokines following stimulation with pro-inflammatory cytokines. CXCL8 and CXCL1 production by human astrocytes at both the RNA and protein levels could be induced by interleukin (IL)-1beta, while CXCL10 was induced by both IL-1beta and interferon-gamma. Since these cytokines are integral to inflammatory events occurring at the margins of active multiple sclerosis lesions, their upregulation in these regions may underlie the dynamics of chemokine expression observed herein. The simultaneous expression of different CXC chemokine receptors on oligodendrocytes, and their ligands on astrocytes around multiple sclerosis lesions, may bespeak novel functional roles for these immune system molecules in the recruitment of oligodendrocytes and remyelination.

Adult↗
PubMed1975

Pathologic-anatomical findings and cerebral localization in stereotactic treatment of extrapyramidal motor disturbances in multiple sclerosis.

Two postmortem case of multiple sclerosis treated by sterotactic operations for the intention shaking of limbs, trunk, and head, and for the action myoclonus are analyzed to determine the location of the substrate of myoclonic and ballistic movements, the location of the coagulations for relief of these movements, and whether fresh demyelinating foci are elicited by intracerebral interventions. In the first case of a clinically typical multiple sclerosis, the foci responsible for the severe action myoclonus and intention ataxia of the trunk are demyelinations in the right and left red nucleus resulting in nerve cell damage and loss and an almost complete destruction of myelinated fibers. The restricted foci in the white matter of the cerebellum which do not involve the cerebellar nuclei are not extensive enough or old enough to be the cause of the action myoclonus but may, perhaps, sustain the pathogenesis. - In the second case of cerebral palsy and combined multiple sclerosis (detected post mortem), the combination of the severe damage of putamen and caudate nucleus by status marmoratus and the extensive nerve cell and fiber damage due to demyelinating foci in the substantia nigra are probably the substrate of the jactitation and intention myoclonus of the left limbs. The stereotactic coagulation of the dentatothalamic and pallidothalamic fibers in the base of V. o.p. and V.o.a. at the point where they pass through the zona incerta (location confirmed post mortem) resulted in a nearly complete relief of hyperkinetic movements. In the first case, fresh demyelinating foci are present in both hemispheres with stereotactic interventions; these foci are located, amongother places, around the coagulation and the electrode track. In the second case, post mortem serial brain sections demonstrate that stereotactic operations even in subacute multiple sclerosis can be carried out without eliciting any exacerbation of demyelination foci. Therefore, the danger exists that stereotactic intervention in cases of multiple sclerosis may precipitate fresh demyelinating foci. As our clinical experience [Riechert and Richter, 1972a, b] indicates, however, this occurred in markedly less than 10% of the cases.

Adult↗
PubMed2001

The range of multiple sclerosis associated with neurofibromatosis type 1.

Multiple sclerosis associated with neurofibromatosis type 1 (NF1) is a very rare event. Seven patients with multiple sclerosis and NF1 are described in the literature, and all were reported to have the primary progressive form of multiple sclerosis. Three new patients with NF1 that developed multiple sclerosis are described and it is shown that the range of multiple sclerosis associated with NF1 includes the relapsing forms of the disease. The risk of having both NF1 and multiple sclerosis in north east Italy is higher than would be expected based on the prevalence rates of the two diseases.

Adult↗
PubMed2002

Markers for different glial cell responses in multiple sclerosis: clinical and pathological correlations.

Disease progression in multiple sclerosis occurs within the interface of glial activation and gliosis. This study aimed to investigate the relationship between biomarkers of different glial cell responses: (i) to disease dynamics and the clinical subtypes of multiple sclerosis; (ii) to disability; and (iii) to cross-validate these findings in a post-mortem study. To address the first goal, 51 patients with multiple sclerosis [20 relapsing remitting (RR), 21 secondary progressive (SP) and 10 primary progressive (PP)] and 51 neurological control patients were included. Disability was assessed using the ambulation index (AI), the Expanded Disability Status Scale score (EDSS) and the 9-hole PEG test (9HPT). Patients underwent lumbar puncture within 7 days of clinical assessment. Post-mortem brain tissue (12 multiple sclerosis and eight control patients) was classified histologically and adjacent sites were homogenized for protein analysis. S100B, ferritin and glial-fibrillary acidic protein (GFAP) were quantified in CSF and brain-tissue homogenate by ELISA (enzyme-linked immunosorbent assay) techniques developed in-house. There was a significant trend for increasing S100B levels from PP to SP to RR multiple sclerosis (P < 0.05). S100B was significantly higher in RR multiple sclerosis than in control patients (P < 0.01), whilst ferritin levels were significantly higher in SP multiple sclerosis than in control patients (P < 0.01). The S100B : ferritin ratio discriminated patients with RR multiple sclerosis from SP, PP or control patients (P < 0.05, P < 0.01 and P < 0.01, respectively). Multiple sclerosis patients with poor ambulation (AI > or =7) or severe disability (EDSS >6.5) had significantly higher CSF GFAP levels than less disabled multiple sclerosis or control patients (P < 0.01 and P < 0.001, respectively). There was a correlation between GFAP levels and ambulation in SP multiple sclerosis (r = 0.57, P < 0.01), and between S100B level and the 9HPT in PP multiple sclerosis patients (r = -0.85, P < 0.01). The post-mortem study showed significantly higher S100B levels in the acute than in the subacute plaques (P < 0.01), whilst ferritin levels were elevated in all multiple sclerosis lesion stages. Both GFAP and S100B levels were significantly higher in the cortex of multiple sclerosis than in control brain homogenate (P < 0.001 and P < 0.05, respectively). We found that S100B is a good marker for the relapsing phase of the disease (confirmed by post-mortem observation) as opposed to ferritin, which is elevated throughout the entire course. GFAP correlated with disability scales and may therefore be a marker for irreversible damage. The results of this study have broad implications for finding new and sensitive outcome measures for treatment trials that aim to delay the development of disability. They may also be considered in future classifications of multiple sclerosis patients.

Adult↗
PubMed1993

Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. UBC MS/MRI Study Group and the IFNB Multiple Sclerosis Study Group.

We performed yearly MRI analyses on 327 of the total 372 patients in a multicenter, randomized, double-blind, placebo-controlled trial of interferon beta-1b (IFNB). Clinical results are presented in the preceding companion paper. Baseline MRI characteristics were the same in all treatment groups. Fifty-two patients at one center formed a cohort for frequent MRIs (one every 6 weeks) for analysis of disease activity. The MRI results support the clinical results in showing a significant reduction in disease activity as measured by numbers of active scans (median 80% reduction, p = 0.0082) and appearance of new lesions. In addition, there was an equally significant reduction in MRI-detected burden of disease in the treatment as compared with placebo groups (mean group difference of 23%, p = 0.001). These results demonstrate that IFNB has made a significant impact on the natural history of MS in these patients.

Adult↗
PubMed2005

Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy?

Multiple sclerosis afflicts more than 1 million individuals worldwide and is widely considered to be an autoimmune disease. Traditionally, CD4(+) T helper cells have almost exclusively been held responsible for its immunopathogenesis, partly because certain MHC class II alleles clearly predispose for developing multiple sclerosis and also, because of their importance in inducing experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. However, several strategies that target CD4(+) T cells beneficially in EAE have failed to ameliorate disease activity in multiple sclerosis, and some have even triggered exacerbations. Recently, the potential importance of CD8(+) T cells has begun to emerge. Physiologically, CD8(+) T cells are essential for detecting and eliminating abnormal cells, whether infected or neoplastic. In multiple sclerosis, genetic associations with MHC class I alleles have now been established, and CD8(+) as well as CD4(+) T cells have been found to invade and clonally expand in inflammatory central nervous system plaques. Recent animal models induced by CD8(+) T cells show interesting similarities to multiple sclerosis, in particular, in lesion distribution (more inflammation in the brain relative to the spinal cord), although not all of the features of the human disease are recapitulated. Here we outline the arguments for a possible role for CD8(+) T cells, a lymphocyte subset that has long been underrated in multiple sclerosis and should now be considered in new therapeutic approaches.

Animals↗
PubMed2002

HLA-DR 15 is associated with female sex and younger age at diagnosis in multiple sclerosis.

BACKGROUND: The association between multiple sclerosis and class II alleles of the major histocompatibility complex, in particular the DRB1*1501-DQB1*0602 haplotype, is well established but their role in determining specific features of this clinically heterogeneous disease is unknown as few studies involving large sample sizes have been performed. METHODS: 729 patients with multiple sclerosis were typed for the HLA DR15 phenotype. All patients underwent clinical assessment and a detailed evaluation of their clinical records was undertaken. RESULTS: The presence of DR15 was associated with younger age at diagnosis and female sex but there was no association with disease course (relapsing-remitting or secondary progressive v primary progressive type), disease outcome, specific clinical features (opticospinal v disseminated form), diagnostic certainty (clinically and laboratory supported definite v clinically probable multiple sclerosis), and paraclinical investigations including the presence of oligoclonal bands in the CSF or characteristic abnormalities on MRI imaging of the central nervous system. CONCLUSION: Even though DR15 carriers are more likely to be female and prone to an earlier disease onset, the results indicate that there is no association with other specific clinical outcomes or laboratory indices examined here. This suggests that DR15 exerts a susceptibility rather than disease modifying effect in multiple sclerosis.

Adolescent↗
PubMedDate not supplied

Multiple sclerosis: immunologic aspects.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). Although the causes are not known, the pathogenesis likely involves complex relationships between autoimmunity, immunogenetics, immunologic deficiency and viral infection. The evidence for such interrelationships is discussed.

Autoimmune Diseases↗
PubMedDate not supplied

[In vivo T-lymphocyte activation in patients with multiple sclerosis].

Patients with multiple sclerosis present changes in lymphocyte subtypes in the peripheral blood. In this study, the authors demonstrate that patients with clinical activity or under an episode show marked increases in the percentages of activate lymphocytes detected through monoclonal antibodies against transferrin and interleukin 2 receptors.

Antibodies, Monoclonal↗
PubMed2006

Gastroparesis with multiple sclerosis.

Symptomatology in multiple sclerosis (MS) depends on the areas of demyelination which can be situated anywhere in the white matter of central nervous system (CNS). Upper gastrointestinal tract symptoms are rarely reported. We recently saw a patient with MS who had disabling gastroparesis and dysphagia.

Adult↗
PubMed2006

Interferon-beta modulates bone-associated cytokines and osteoclast precursor activity in multiple sclerosis patients.

PURPOSE: Multiple sclerosis (MS) patients have a high risk of low bone density. The purpose of this study was to examine the molecular mechanisms potentially capable of modulating bone homeostasis in response to interferon-beta-1a (IFN-beta-1a) treatment and the focus was the bone-modulating system comprised of receptor activator of nuclear factor-kappaB (RANK), its ligand RANKL and its decoy receptor, osteoprotegerin (OPG). METHODS: In this open-label pharmacodynamic study, peripheral blood was obtained from relapsing-remitting MS patients just prior to and at multiple time points after intramuscular injection of 30 microg IFN-beta-1a. Samples were analysed for RANKL, tumour necrosis factor related apoptosis-inducing ligand (TRAIL), OPG and macrophage inflammatory protein-1 alpha/beta expression. Osteoclast precursor differentiation from peripheral blood cells of MS patients in the presence of exogenously added IFN-beta-1a was also assessed. Additionally, the changes in plasma levels of osteocalcin and the C-telopeptides after 1 year of treatment were measured as surrogate markers of bone formation and degradation, respectively. RESULTS: IFN-beta-1a treatment modulated RANKL and OPG in a selective, time-dependent manner. The levels of OPG protein decreased 25% at the 8-h time point, then increased 43% at the 24-h time point. The levels of free RANKL reached a maximum at the 8-h time point. Increases in the levels of macrophage inflammatory protein-1beta (MIP-1beta), a chemokine that increases osteolysis, were observed. The levels of the bone formation marker, osteocalcin, were lower in MS patients compared to controls and increased after one year of treatment. Ex vivo treatment of peripheral blood lymphocytes with IFN-beta resulted in a marked reduction of osteoclast-like cells in the presence of RANKL and macrophage colony stimulating factor. CONCLUSIONS: IFN-beta treatment induces complex, specific and time-dependent changes in multiple proteins and mRNAs related to bone homeostasis in MS patients.

Adult↗
PubMedDate not supplied

Increasing awareness of services for people with multiple sclerosis.

Awareness of multiple sclerosis has been increasing in recent years. However, there are still many issues which the MS Society will be highlighting during MS Week. This year there are three main MS Week themes. These include funding for research, a volunteer recruitment drive, and promotion of the NICE guideline for MS.

Awareness↗