Multiple sclerosis is a chronic autoimmune neurological disease characterized by inflammatory cell infiltration and demyelination in the central nervous system (CNS). It is considered to be mediated by Th1 and Th17 immune responses. Experimental autoimmune encephalomyelitis (EAE) is widely used as a mouse model to study MS as it has features and histopathology similar to that of MS. Tolerogenic dendritic cells (DC) are reported to efficiently prevent sensitization for EAE. In this research, we induced tolerogenic DC (DC10) by differentiating them with IL-10. Compared to immature DC, DC10 did not show increased expression of MHC II or the co-stimulatory molecules CD40, CD80 and CD86, and produced low levels of pro-inflammatory cytokines IL-1â, IL-6, and IL-12 but higher levels of IL-10. This is consistent with their possessing a tolerogenic phenotype. We found that three intraperitoneal (i.p.) injections of DC10 successfully inhibited the signs of established, ongoing EAE: DC10 significantly reduced the clinical scores, demyelination and cell infiltration in the spinal cord, as well as the production of IL-4, IL-6, IL-10, IL-17 and IFN-ã by spleen and lymph node (LN) lymphocytes. DC10 treatments did not significantly affect inflammatory cytokine mRNA levels in the CNS. We found that there was higher FoxP3 expression in the CNS in response to DC10 treatments relative to PBS-treated animals. We also found that DC10 treatments significantly enhanced IgG1, IgG2a and IgG2b production and total spleen and LN lymphocyte proliferation following challenge with myelin oligodendrocyte glycoprotein (MOG) antigen. As far as we know, this is the first report showing the successful therapeutic treatment with tolerogenic DC10 of established EAE in mice.

Syftet med denna systematiska litteraturstudie var att beskriva hur livskvaliteten påverkas hos personer med Multipel Skleros (MS) och vad som kan göras för att öka livskvaliteten. I syftet ingick även att beskriva hur personer med MS upplever fatigue som är ett av huvudsymtomen av sjukdomen samt vad som kan göras för att lindra följderna av fatigue. Artiklarna har sökts i databaserna Elin@Dalarna och Cinahl, tillgängliga via Högskolan Dalarnas proxyserver och granskats med hjälp av en granskningsmall för att säkerställa att de var av en god kvalitet. Sökord som användes var: “multiple sclerosis”, “quality of life”, “nursing” och “fatigue”. Av de artiklar som användes i resultatet var 10 kvantitativa, fyra kvalitativa i en användes båda ansatserna. Resultatet visade att personer med MS generellt sett har en sämre livskvalitet än den övriga befolkningen. Mycket av patienternas livskraft går åt till att bara klara av det dagliga livet. Många personer med MS upplever en stor frustration relaterad till att vilja men inte kunna. Ofta har den försämrade livskvaliteten sin orsak i det sociala livet. Fatigue har ofta en stor påverkan på livet för personer med MS. Det finns en mängd varierande icke farmakologiska behandlingsmetoder som med fördel kan användas för att öka livskvaliteten och minska följderna av fatigue. Exempel på dessa är kylväst, träning och yoga.

Multiple Sclerosis (MS) is the most common demyelinating condition of the central nervous system (CNS), resulting in paralysis and death. The etiology of MS is unknown. However, genetics, exposure to a pathogen, psychological stress and gender are all implicated in the onset and progression of the disease. An animal model of MS, Theiler’s virus (TMEV) infection, causes a biphasic disease. An early CNS viral infection, if allowed to persist within the CNS, is followed by a chronic CNS autoimmune demyelinating condition that is similar to MS. The development of Theiler’s Virus Induced Demyelination (TVID) is under genetic control: SJL mice are highly susceptible to viral persistence and TVID while CBA mice have an intermediate susceptibility. Chronic restraint stress (RST) administered during the first four weeks of TMEV infection influenced the subsequent development of TVID differentially across strain and sex of mice. TVID was exacerbated by RST in male and female SJL mice, but in the CBA strain, TVID was alleviated by RST in male mice only. This pattern of results in SJL and CBA mice could be seen in the chronic phase of TVID on multiple dependent measures: body weights, behavioral signs of the chronic phase, rotarod performance (an automated measure of motor abilities), and inflammation, demyelination, and axonal loss within the spinal cord. The exacerbation of TVID in SJL mice provides some of the first experimental evidence that coincides with reports of stress precipitating the onset of MS in human patients. The sex dependent alleviation of TVID in CBA mice illustrates the complex interaction between genetic predisposition, gender, stress, and exposure to a pathogen that has been proposed for the development of MS.

<p>Vid MS och ALS förekommer depressioner i olika nyanser, vilket är viktigt för</p><p>sjuksköterskan att fånga upp tidigt och ge den omvårdnad individen behöver samt att minska lidandet. För att detta skall kunna uppnås är det viktigt att den som är sjuk känner trygghet och tillit i sin relation till sjuksköterskan. Syftet med studien var att beskriva människors upplevelser av olika symtom i samband med depression som förekommer vid MS och ALS. För att fånga upp människors upplevelser av symtom i samband med depression användes en kvalitativ metod. Data samlades in genom åtta självbiografier som var skrivna på svenska av både kvinnor och män. En kvalitativ metod enligt Dahlberg användes för att tolka dessa data. Resultatet presenterades i varje sjukdom för sig i kategorier och underkategorier. Kategorier i MS var trötthet, förnekelse, skam, rädsla och tankar på döden. Kategorierna i ALS var, de gråter ut sin sorg, att tära på varandra, att behöva ta emot hjälp och tankar på döden. Resultatet visade skillnad i depressioner mellan dessa två sjukdomar. Vid MS är depressionerna djupare och längre då sjukdomen går i skov, medan det i ALS förändras från att vara djupa depressioner i samband med diagnos, till något positivt då de har kort tid kvar i livet.</p> / <p>When having MS and ALS there is also prevalence of depression of varying degree. This is important for the nurse to detect early in order to give the individual the right amount of care, to minimise suffering. In order to achieve this; it is important that the patient feels trust and security in the relation with the nurse. The aim of this study was to describe people's experiences of various symptoms associated with depression in MS and ALS, through the use of autobiographies. A qualitative method was used to gather the individual's experience of depression. Data was collected from eight autobiographies written in Swedish by both women and men. To interpret the data, a qualitative method, according to Dahlberg, was used. The results was separately for the two diseases, and was categorised and sub-categorised. The categories for MS were fatigue, denial, shame, fear and thoughts of death. The categories for ALS was, crying out grief, absume eachothers energy, help dependency and thoughts of death. The results showed differences in the state of depression between the two diseases. For MS, the depression goes deeper and for a longer duration, since the disease progresses in relapse. For ALS, the condition changes from deep depression when diagnosed to somewhat more positive when there are only little time left in life.</p>

Objective: To examine reasons why Multiple Sclerosis (MS) patients may not be adherent to disease-modifying therapies (DMTs). Also, to determine patient perceptions of MS as a disease and DMTs as a source of treatment, and compare these between patients with prior DMT experience and those who were DMT-naïve. Finally, to assess the level of MS symptoms reported in patients taking DMTs, and compare these between DMT users and non-users. Methods: Patients with MS who were affiliated with a regional health plan at any point between January 2005 and December 2010 were asked to fill out a survey, the Multiple Sclerosis Medication Questionnaire (MSMQ). For study purposes, non-adherence was defined as missing any doses in the previous 28 days by the patient. In addition, the MSMQ examined reasons why MS patients do not initiate or discontinue DMT use. For statistical analyses, chi-square tests were performed to detect differences and t-tests and Mann-Whitney U tests to confirm the results. Results: A total of 197 surveys were returned, of which 105 (53.3%) patients were currently on a DMT. Thirty-two (30.5%) of the DMT users were considered non-adherent. Of the non-adherent respondents, the most frequent reason for non-adherence that was at least moderately important was being "too busy" (n=13/29, 44.8%). Amongst patients who were not using a DMT, the most common barrier to DMT use was related to possible side effects of treatment (n=46/79, 58.2%). Analyzing the statements regarding barriers to DMTs revealed significant differences in the proportion of agreement regarding physician's lack of advocacy for DMT use between DMT-naïve patients and those who discontinued DMT use (44.7% vs. 17.1%, respectively, p[less than]0.01), as well as for dislike for using needles (24.3% vs. 46.3%, respectively, p=0.043). In terms of MS symptoms, patients using a DMT generally reported the symptoms posed less of a problem, although significant differences were not seen in chi-square analyses. Conclusion: The injectable nature of most DMTs seems to cause varying degrees of discomfort in MS patients, which may contribute to non-adherence. Reasons given by MS patients for DMT non-adherence in the MSMQ mirror the literature regarding this topic. MS patients who are not currently on DMT may not seek or remain on treatment for various reasons. It appears certain perceptions regarding MS and DMTs are associated with potential DMT use. / text

The purpose of this study was to describe the relationships among common signs/symptoms (depression, fatigue, declines in cognitive function) in women with multiple sclerosis (MS) using a modified version of Braden's Self Help Theoretical Model and evaluate whether depression, fatigue, declines in cognitive function and uncertainty, enabling skills (self-control in this study) and self-management (coping in this study) influence quality of life outcomes in women with MS. MS is one of the most common causes of disability among young adults and is the most prevalent neurological disease among young and middle-aged adults in certain parts of the world. Although research had previously been undertaken with regards to the common symptoms of MS, uncertainty, enabling skills, self-management and quality of life, there had been no studies undertaken that involved all of them. This descriptive study was the first to explore relationships among common symptoms of MS, uncertainty, enabling skills, self-management and quality of life in an MS population using Braden's Learned Response Chronic Illness Self Help Model. A cross-sectional descriptive study was conducted with 106 participants. Measurement tools utilized in the study included: 1) Demographic and Illness Characteristics, 2) The Modified Fatigue Impact Scale, 3) Perceived Deficits Questionnaire, 4) Patient Health Questionnaire-9, 5) Mishel's Uncertainty in Illness Scale- Adult, 6) Rosenbaum's Self-Control Scale- Modified, 7) COPE Inventory-Brief, and 8) SF-36 Health Status Questionnaire. Data analysis involved descriptive statistics, correlations and linear regression to answer the specific aims. The study findings indicate that relationships exist among depression, fatigue, declines in cognitive function, uncertainty, enabling skills and self-management in women with MS. The study findings also indicate that depression, fatigue, declines in cognitive function, uncertainty, enabling skills and self-management influence quality of life outcomes in women with MS. Finally, while only a first study, the research findings indicate using a modified version of Braden's Learned Response Chronic Illness Self Help Model (LRCISHM) is appropriate in a population of women with MS. Future research involving women with MS who meet the inclusion criteria across the contiguous United States as well as male military veterans with MS is recommended. Research involving this modified version of Braden's LRCISHM as well as research incorporating disability levels is recommended. Research to develop interventions to improve quality of life outcomes and minimize distress is also recommended.

Theiler's murine encephalomyelitis virus (TMEV) is classified as a Cardiovirus in the Picornaviridae family. An enteric virus, TMEV, spreads within the mouse population by the fecal-oral route. The neurovirulent GDVII strain of Theiler's virus causes a fatal encephalitis in all strains of mice following intra-cranial infection of the virus. Persistent BeAn strain of Theiler's virus causes a demyelinating disease in susceptible strains of mice, which is similar to the human disease - Multiple Sclerosis (MS). Although a well-recognized model for MS, the route of entry of the virus into the central nervous system (CNS) following natural infection has not been well understood. One of the proposed portals of entry includes the blood-brain barrier (BBB). This report indicates the ability of both the neurovirulent and the persistent strains of Theiler's virus to induce apoptosis in the functional units of the BBB - the cerebrovascular endothelial cells (CVE) both in vitro and in vivo. Induction of apoptosis in CVE was demonstrated by Annexin staining, electron microscopy, DNA fragmentation assay, Hoechst staining and by caspase-3 staining. Corresponding to results by other authors, GDVII is a stronger inducer of apoptosis in CVE compared to BeAn. Induction of apoptosis is dependent on the MOI of the virus. UV-inactivated virus is not capable of inducing apoptosis and induction of apoptosis appears to be an internal event not requiring activation of death receptors. Determining the pathway of induction of apoptosis by TMEV in CVE indicated the involvement of a Ca2+ dependent pathway for apoptosis - the calpain pathway. Involvement of calpain in apoptosis has been reported in MS. Induction of apoptosis in CVE in vivo was also demonstrated following the intra-peritoneal inoculation of Theiler's virus. Induction of apoptosis in CVE following Theiler' virus infection could lead to a breach of the BBB and entry of inflammatory cells as well as virus into the central nervous system. This finding could aid understanding the neuropathogenesis of Theiler's virus.

No description available.

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that is characterized by widespread focal areas of inflammation and demyelination. Although the exact cause of the disease is still not known, myelin-reactive T cells that enter the CNS trigger the disease and lead to the recruitment and activation of macrophages and other immune cells. One set of candidates that could serve to mediate these CNS changes is the family of phospholipase A2 (PLA2) enzymes, which consist of secreted (sPLA2) and cytosolic (cPLA2) forms. These enzymes hydrolyze membrane phospholipids to release free fatty acids (arachidonic acid) that can stimulate complex inflammatory cascades, and lysophospholipids that can induce myelin breakdown and demyelination, the two pathological hallmarks of MS. / For my Ph.D. research I studied the expression and role of different members of the PLA2 family in 'experimental autoimmune encephalomyelitis' (EAE), a widely used animal model of MS. I first generated a relapsing-remitting form of EAE in the C57BL/6 mouse strain that lacks a major form of sPLA2. I showed that cPLA2 is expressed by immune cells in the EAE lesions in the CNS. Furthermore blocking the activity of cPLA2 with a broad-spectrum chemical inhibitor starting at the time of EAE induction reduced the incidence and severity of disease, reduced lesion burden as well as reduced the expression of a number of chemokines and cytokines. Treating mice in the remission phase also prevented further clinical episodes. This showed that some or all members of the cPLA2 family play an important role in the onset and progression of EAE in a strain of mice lacking sPLA2. / I next carried out studies to assess the expression of all 14 members of the sPLA2 and cPLA2 families at the onset, peak and remission stages of EAE in the SJL/J mouse strain that expresses all forms of PLA2. The mRNA expression of only 4 of these PLA2s was increased. These include sPLA2 (groups IIA and V) and cPLA 2 (groups IVA and VIA). The expression of these PLA2s in the CNS was also characterized by double-immunofluorescence. The role of these PLA2s was assessed using selective inhibitors and analysed by monitoring the clinical disability scores, chemokine/cytokine protein arrays, lipomics lipid profiling, and histological analysis. Surprisingly, the sPLA2 inhibitor prevented disease remission and worsened the clinical outcome. This was accompanied by an increase in several pro-inflammatory chemokines. Selective inhibitors of cPLA2 group IVA and the calcium independent foam group VIA (iPLA2) reduced severity of EAE when given starting before onset of disease. The cPLA2 inhibitor treatment was effective only while administered, while iPLA2 inhibitor treatment was effective even after treatment was stopped. Furthermore, only delayed treatment with the iPLA2 inhibitor was effective, suggesting that cPLA2 group IVA only plays a role in the initiation of disease, while iPLA 2 plays a role in both disease onset and progression. These effects were also associated with concomitant reduction in chemokine/cytokine expression, reduction of inflammatory lipid mediators, and increase in protective lipids e.g., omega 3 fatty acids. / This work has allowed us to dissect out the expression and role of different members of the PLA2 family and has revealed the importance of selectively inhibiting some but not others in EAE. These findings may therefore have important implications for the treatment of MS.

Intravenous immunoglobulin (IVIg) has been used to treat a variety of autoimmune disorders including multiple sclerosis (MS); however, its mechanism of action remains elusive. Our results demonstrate a novel finding wherein IVIg treatment induces a dramatic surge (>1000-fold increase) in the levels of IL-11 in the circulation and that the liver is the organ of increased IL-11 transcription. Furthermore, we show that IL-11Rα knockout mice, although initially protected, become resistant to protection by IVIg during experimental autoimmune encephalomyelitis (EAE) and develop disease with a similar incidence and severity as control-treated IL-11Rα-/- mice. The inability of IVIg to prevent EAE in IL-11Rα-/- mice correlated with a failure of this agent to decrease IL-17 production by myelin-reactive T-cells in the draining lymph nodes. Finally, we show that IL-11 can directly inhibit IL-17 production by lymph node cells in culture. Together, these results implicate IL-11 as an important immune effector of IVIg in the amelioration of EAE.