The primary objective of this study was to assess cognitive functioning in participants with relapsing remitting multiple sclerosis (RRMS) using the MicroCog and to compare their performance to that of a demographically matched, healthy control group. It was hypothesized that as a group, participants with RRMS would have worse cognitive function than healthy controls on all Level 1, 2, and 3 Index scores of the MicroCog. Twenty-six participants with RRMS and twenty-nine sex and education matched healthy controls were administered the MicroCog (Standard Form) along with measures of depression and clinical status, and paper-pencil tests of processing speed (Symbol Digit Modalities Test; SDMT and Paced Auditory Serial Addition Test; PASAT). A series of ANCOVAs with depression as a covariate was performed to determine between group differences for each MicroCog Level 3 Index score (General Cognitive Proficiency (GCP) and General Cognitive Functioning (GCF)), Level 2 Index score (Information Processing Accuracy (IPA) and Information Processing Speed (IPS)), and Level 1 Index score (Attention/Mental Control, Memory, Reasoning/Calculation, Spatial Processing, and Reaction Time). Pearson's and point biserial r correlations were calculated in order to assess the degree to which Level 2 and 3 Index scores correlated with clinical and demographic factors (sex, disease duration, depression, and clinical status) and to correlate the MicroCog IPS index score with traditional measures of processing speed. Eight RRMS and two control participants met criteria for cognitive impairment on the MicroCog. ANCOVA results indicated there were significant differences between RRMS and control performance for two MicroCog scores (GCF and IPS). There were not significant differences for GCP, IPS, and all Level 1 scores. A post-hoc analysis performed for the same hypothesis with a group of age equivalent participants suggested a significant RRMS by depression interaction for Level 3 scores. RRMS was not predictive of Level 2 scores after controlling for depression in the age equivalent sample. Correlations for clinical and demographic factors with cognitive outcomes indicated significant relationships for clinical status and depression. There was not a significant relationship detected for disease duration or sex. MicroCog and processing speed measures were significantly related. Post-hoc analyses supported that the criterion validity of the MicroCog is comparable to other cognitive screening tools in RRMS. The results and limitations of our study are discussed, in addition to recommendations for future research.

No description available.

Multiple sclerosis (MS), a demyelinating disorder of the central nervous system (CNS), affects approximately 400,000 individuals in the United States, and 2.5 million people worldwide. It is a leading cause of disability in young adults. Current treatments for MS target the inflammatory aspects of the disease, but do not aid in remyelination. To address remyelination as a therapeutic strategy, it is imperative to identify mechanisms that regulate myelin formation, including epigenetic targets. In this study, we investigate the role of the LMNA, a gene encoding Lamins A and C, intermediate filaments of the nuclear lamina, in regulating oligodendrocyte development and myelination in the CNS. Using electron microscopic analyses, I examined levels of heterochromatin and its distribution in the oligodendrocyte nucleus as an indicator of gene expression, oligodendrocyte maturity, and myelin formation in the absence of A type lamins.. While overall levels of heterochromatin in oligodendrocytes were not altered in the absence of A type lamins, peripherally located heterochromatin was reduced and thinner myelin was observed in the spinal cord. My observations present novel findings for the role of LMNA in oligodendrocytes and myelination.

People with the autoimmune disease multiple sclerosis (MS) have few options for educational activities. Although web-based instruction may be a viable option, little is known about how people with MS perceive this form of learning. The purpose of this qualitative study was to understand the experiences of people with MS regarding web- based instruction. The 3 learning structures--differentiated instruction, collaborative learning, and assistive technology--provided the conceptual framework for this research. Nine volunteers from the Pacific Northwest area of the United States who have MS were individually interviewed for this basic qualitative study. Transcripts were analyzed using open, axial, and selective coding. The results indicated that all participants found personal and professional benefits of their experience with web-based instruction and used course management systems to successfully communicate with instructors or peers. Participants also noted that these management systems did not directly aggravate their MS disease symptoms. Findings from the study may be useful information to individuals with MS for effectively managing their educational choices. This study's results could also be used by learning institutions to improve the access to education and allow individuals with MS to more fully participate in training opportunities.

The present study prospectively examines factors that affect whether self-enhancement exerts favorable or unfavorable effects on both psychological and physical well-being in a context that is less controllable than other contexts in which self-enhancement has been examined (e.g., academic performance), an at risk population of Multiple Sclerosis (MS) patients. In particular, the present study (a) examines whether self-enhancement differentially predicts psychological and physical well-being when self-enhancement is related or unrelated to the well-being outcomes, and (b) whether self-enhancement interacts with severity of circumstances (i.e., course of MS) to predict psychological and physical well-being, as suggested by O’Mara, McNulty, & Karney (2011). In addition to the baseline assessment, participants completed measures of self-enhancement (outcome-related and outcome-unrelated), and psychological and physical well-being every 30 days for 90 days, for a total of four assessments. The pattern of findings suggests that in less controllable contexts, self-enhancement is a doubled-edged sword. Outcome-related self-enhancement was trending towards a positive, cross-sectionally association with physical well-being, and a measure of prior outcome-unrelated self-enhancement (collectivistic tactical self-enhancement) was positively associated with subsequent physical well-being only for individuals with less severe MS. Further, prior outcome-related self-enhancement was associated with better subsequent psychological well-being but worse subsequent physical well-being, and although prior collectivistic tactical self-enhancement is associated with favorable subsequent physical well-being for individuals with less severe MS, it is also associated unfavorable psychological well-being regardless of MS severity. The discussion addresses the contributions of the present study to the literature, strengths and limitations of the present study, and directions for future research.

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.

Vid MS och ALS förekommer depressioner i olika nyanser, vilket är viktigt för 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. / 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.

Multiple sclerosis is a neurodegenerative disorder affecting the central nervous system (CNS). Currently, the disease is incurable and immunomodulating drugs are the only option to control the disease. CD49d is an adhesion receptor expressed on most immune cells. Antibodies that bind to CD49d and block immune cells from trafficking toward the CNS are being pursued as one class of therapeutics. In this work, by combining recombinant antibody and phage display technologies we isolated 10 anti-CD49d single domain antibodies from a synthetic antibody light chain variable domain (VL) phage display library. Isolated VLs (~ 12 kDa) were expressed in Escherichia coli, purified and analysed for biophysical characteristics. The majority were expressed in good yields and were non-aggregating. All 10 VLs bound recombinant CD49d by ELISA, and 7 bound to CD49d-expressing cells in flow cytometry experiments. To empower the VLs for better therapeutic efficacy (thru increasing avidity and half-life), three of the lead VLs were re-engineered as fusions to fragment crystallisable (Fc) of human immunoglobulin gamma (IgG). The engineered hFc-VL fragments (~ 70 – 90 kDa) retained their specificity for CD49d by flow cytometry. With (i) being less immunogenic due to their human nature, (ii) their efficient access to cryptic epitopes (iii) having half-lives comparable to IgGs’ and (iv) being more cost effective compared to IgGs, these novel antibody fragments (monovalent VLs and bivalent hFc-VLs) provide a promising therapeutic platform against multiple sclerosis.

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.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by lesions formed due to demyelination. MS is a complex disease thought to be triggered by environmental factors in genetically predisposed individuals. The strongest associated susceptibility allele is HLA-DRB1*1501. Environmental factors include smoking, latitude and previous infection of Epstein-Barr virus (EBV), a common herpes virus. There is no cure for MS, but several inhibitor and symptomatic drugs. Tysabri® (natalizumab) is the most effective drug, but it may lead to progressive multifocal leukoencephalopathy (PML), a rare but often fatal disease caused by reactivation of JC virus. The aim of this thesis was to replicate previous findings from a genome-wide association study and to find host genetic factors influencing JCV seropositivity and EBNA1 IgG titers in Swedish MS patients and healthy controls. Samples from the EIMS and IMSE studies were genotyped by TaqMan® OpenArray™ PCR, an end-point SNP genotyping analysis. 1143 cases and 556 healthy controls were genotyped. Due to poor call rates, genotype data from an Immunochip study was added. A total of 3408 samples (1664 cases and 1744 controls) were analyzed. EBNA1 IgG antibodies were previously measured as a detection of EBV infection and increased MS risk, and JCV IgG antibodies were measured to find patients potentially at risk for PML. One significant result was found, gene 105 (p = 0.01674, OR 0.68, CI 95% 0.49-0.93), with a protective effect in MS. More significant results might have been found with better loading of the plate, or with a different genotyping method.