Multiple Sclerosis: Myhr KM

Sørensen PS, Deisenhammer F, Duda P, Hohlfeld R, Myhr KM, Palace J, Polman C, Pozzilli C, Ross C, Anonymous00318. · Danish Multiple Sclerosis Research Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. · Eur J Neurol. · Pubmed #16241970 No free full text.

Abstract: Therapy-induced binding and neutralizing antibodies is a major problem in interferon (IFN)-beta treatment of multiple sclerosis. The objective of this study was to provide guidelines outlining the methods and clinical use of the measurements of binding and neutralizing antibodies. Systematic search of the Medline database for available publications on binding and neutralizing antibodies was undertaken. Appropriate publications were reviewed by one or more of the task force members. Grading of evidence and recommendations was based on consensus by all task force members. Measurements of binding antibodies are recommended for IFN-beta antibody screening before performing a neutralizing antibody (NAB) assay (Level A recommendation). Measurement of NABs should be performed in specialized laboratories with a validated cytopathic effect assay or MxA production assay using serial dilution of the test sera. The NAB titre should be calculated using the Kawade formula (Level A recommendation). Tests for the presence of NABs should be performed in all patients at 12 and 24 months of therapy (Level A recommendation). In patients who remain NAB-negative during this period measurements of NABs can be discontinued (Level B recommendation). In patient with NABs, measurements should be repeated, and therapy with IFN-beta should be discontinued in patients with high titres of NABs sustained at repeated measurements with 3- to 6-month intervals (Level A recommendation).

Myhr KM. · No affiliation provided · Tidsskr Nor Laegeforen. · Pubmed #15742008 links to  free full text

This publication has no abstract.

Torkildsen O, Brunborg LA, Myhr KM, Bø L. · Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Norway. · Acta Neurol Scand Suppl. · Pubmed #18439226 No free full text.

Abstract: BACKGROUND: Important advances in multiple sclerosis (MS) research have been made as a direct or indirect result of experiments in animal models for the disease, although MS is a disease only affecting humans. The cuprizone model is a model for toxic demyelination. In this model, young mice are fed with the copper chelator cuprizone, leading to oligodendrocyte death and a subsequent reversible demyelination. Spontaneous remyelination can be seen as early as 4 days after withdrawal of cuprizone. MATERIALS AND METHODS: This article reviews previous research on this model and discusses the potential of the model for future application in MS research. DISCUSSION: The cuprizone model correlates with newer histopathological data in MS and is a valuable tool for studies on de- and remyelination. The use of the C57BL/6 strain offers the potential for future studies on transgene and knockout mice.

Pugliatti M, Harbo HF, Holmøy T, Kampman MT, Myhr KM, Riise T, Wolfson C. · Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway. · Acta Neurol Scand Suppl. · Pubmed #18439219 No free full text.

Abstract: OBJECTIVES: Multiple sclerosis (MS) likely results from an interaction between genetic and exogenous factors. While genetics shapes the overall population MS susceptibility, observed epidemiological patterns strongly suggest a role for the environment in disease initiation and modulation. RESULTS: Findings from studies on seasonality in MS patients' birth, disease onset and exacerbations, as well as apparent temporal trends in incidence and gender ratio support an influential effect of viruses, metabolic and lifestyle factors on MS risk. Epstein-Barr virus, vitamin D status, and smoking are factors that may explain such epidemiological patterns. CONCLUSIONS: Further epidemiological investigations are encouraged and opportunities to use data from existing cohort studies as well as the design of new studies should be pursued. In particular, the development of new large multicentre population-based case-control studies which incorporate the study of the role of environment and genetics, including epigenetic mechanisms, in determining MS risk is proposed.

Myhr KM. · Norwegian Multiple Sclerosis National Competence Centre, Department of Neurology, Haukeland University Hospital and Department of Clinical Medicine, University of Bergen, Bergen, Norway. · Acta Neurol Scand Suppl. · Pubmed #18439216 No free full text.

Abstract: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system that usually has onset between 20 and 40 years of age. The causes of MS are unknown, but it probably evolves among genetically susceptible individuals as an infrequent response to environmental factors. The diagnosis is based on careful evaluation of the disease history, clinical examination as well as paraclinical examination, aiming to document disseminated disease in both time and space. No cure is available, but corticosteroids can be used for relapses, various symptomatic treatments exist, and several long-term, disease-modifying therapies are available. This article reviews the diagnosis and treatment of MS, focusing on treatment of relapses and disease-modifying therapies.

Torkildsen O, Vedeler CA, Nyland HI, Myhr KM. · The Multiple Sclerosis National Competence Centre, Department of Neurology, Haukeland University Hospital and Department of Clinical Medicine, Section for Neurology, University of Bergen, Bergen, Norway. · Acta Neurol Scand Suppl. · Pubmed #16637933 No free full text.

Abstract: Receptors for the Fc domain of IgG (FcgammaR) play a key role in the immune system by linking the cellular and humoral immune systems. Despite extensive documentation of CNS-specific antibodies in cerebrospinal fluid and plaques in multiple sclerosis (MS) patients, the role of FcgammaR in this disease remains largely unexplored. Studies indicate however, that polymorphisms in some FcgammaR genes and treatment that induces FcgammaR on immune-competent cells could influence disease progression and treatment response.

Gavasso S, Myhr KM, Vedeler C. · Department of Clinical Medicine, Section of Neurology, University of Bergen and Haukeland University Hospital, Norway. · Acta Neurol Scand Suppl. · Pubmed #16637932 No free full text.

Abstract: Analyzing signaling networks in immune cells is of particular interests in diseases where treatment choices are preferentially immunomodulatory. By combining phospho-specific antibodies with multicolor flow cytometry it is possible to perform quantitative multiparameter analysis of signaling pathways within complex cell populations. Multiplexed phosphoprotein analysis will potentially incorporate environmental factors such as toxins or pathogens and genetic variability of individual patients in a step towards personalized medicine.

Glad S, Nyland H, Myhr KM. · Multiple Sclerosis National Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway. · Acta Neurol Scand Suppl. · Pubmed #16637931 No free full text.

Abstract: A small fraction of patients with multiple sclerosis (MS) have a benign course of the disease. The definition of benign MS has been heavily weighted towards physical disability and in particular ambulation. However, patients who are fully ambulatory may still be heavily disabled by non-motor symptoms like fatigue, pain, depression and cognitive dysfunction. These non-motor symptoms should be considered when defining benign MS.

Myhr KM, Harbo HF. · Nasjonalt kompetansesenter for multippel sklerose, Nevrologisk avdeling, Haukeland Universitetssykehus, 5021 Bergen. · Tidsskr Nor Laegeforen. · Pubmed #14600746 links to  free full text

Abstract: BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, characterised by demyelinisation, gliosis and various degrees of axonal damage. The cause of the disease is unknown though there is evidence that MS is an immune mediated disease in which genetic, environmental and stochastic factors are involved. MATERIAL AND METHODS: Evidence of genetic influence in MS is reviewed. RESULTS: About 20% of patients have other family members with MS. First-degree relatives of MS patients have increased risk (2-5%) of developing MS compared to the risk in the general population (0.1%). The concordance rate in monozygotic twins (25-30%) is higher than in dizygotic twins (2-5%). Genetic analysis has shown association and linkage of MS to the HLA-DR2, DQ6 haplotype. Genome-wide screens have shown chromosome regions of potential importance. CONCLUSION: MS is a complex disease in which several genes are involved. Despite extensive candidate gene studies and genome-wide linkage screens, the HLA-DR2, DQ6 haplotype is the only genetic region that has shown unequivocal association and linkage to the disease. Further studies aimed at defining other MS susceptibility and disease-modifying genes are in progress.

Midgard R, Beiske AG, Celius EG, Jensen D, Hovdal H, Mellgren SI, Myhr KM. · Molde sjukehus/Haukeland Universitetssykehus 6407 Molde. · Tidsskr Nor Laegeforen. · Pubmed #12806674 No free full text.

This publication has no abstract.

Vedeler CA, Myhr KM, Nyland H. · Department of Neurology, Haukeland Hospital, University of Bergen, 5021, Bergen, Norway. · J Neuroimmunol. · Pubmed #11498253 No free full text.

Abstract: Receptors for the Fc part of IgG (FcgammaR) constitute a family of cell-surface molecules expressed on almost every cell of the immune system. They are also present on non-lymphoid cells such as Schwann cells and endothelial cells. By linking humoral and cell-mediated responses, FcgammaR are key in defending against pathogens. Polymorphisms in some FcgammaR genes are associated with infectious and autoimmune diseases. It was found recently that certain FcgammaRIIA and FcgammaRIIIB allotypes are correlated with the disease course of Guillain-Barré syndrome (GBS) and multiple sclerosis (MS). This may imply that clearance of circulating autoantibodies and immune complexes is important in the pathogenesis of these diseases.

Smedal T, Lygren H, Myhr KM, Moe-Nilssen R, Gjelsvik B, Gjelsvik O, Strand LI, Inger L. · National Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway. · Physiother Res Int. · Pubmed #16808091 No free full text.

Abstract: BACKGROUND AND PURPOSE: Patients with multiple sclerosis (MS) tend to have movement difficulties, and the effect of physiotherapy for this group of patients has been subjected to limited systematic research. In the present study physiotherapy based on the Bobath concept, applied to MS patients with balance and gait problems, was evaluated. The ability of different functional tests to demonstrate change was evaluated. METHOD: A single-subject experimental study design with ABAA phases was used, and two patients with relapsing-remitting MS in stable phase were treated. Tests were performed 12 times, three at each phase: A (at baseline); B (during treatment); A (immediately after treatment); and A (after two months). The key feature of treatment was facilitation of postural activity and selective control of movement. Several performance and self report measures and interviews were used. RESULTS: After intervention, improved balance was shown by the Berg Balance Scale (BBS) in both patients, and improved quality of gait was indicated by the Rivermead Visual Gait Assessment (RVGA). The patients also reported improved balance and gait function in the interviews and scored their condition as 'much improved'. Gait parameters, recorded by an electronic walkway, changed, but differently in the two patients. Among the physical performance tests the BBS and the RVGA demonstrated the highest change, while no or minimal change was demonstrated by the Rivermead Mobility Index (RMI) and Ratings of Perceived Exertion (RPE). CONCLUSION: The findings indicate that balance and gait can be improved after physiotherapy based on the Bobath concept, but this should be further evaluated in larger controlled trials of patients with MS.

Wergeland S, Beiske A, Nyland H, Hovdal H, Jensen D, Larsen JP, Marøy TH, Smievoll AI, Vedeler CA, Myhr KM. · The Multiple Sclerosis National Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway. · Eur J Neurol. · Pubmed #15693804 No free full text.

Abstract: The level of interleukin-10 (IL-10) expression is related to polymorphisms -1082 (G/A), -819 (T/C) and -592 (A/C) in the promoter region of the IL-10 gene, which constitute three haplotypes, GCC, ATA, and ACC. The ATA (a non-GCC) haplotype, which is associated with low IL-10 expression, has been shown to improve interferon (IFN) treatment response in hepatitis C. We analysed the distribution of IL-10 promoter haplotype combinations to determine whether they could influence initial IFN treatment response in 63 patients with relapsing-remitting multiple sclerosis (MS). The patients were grouped into non-GCC or GCC haplotypes, and the clinical and magnetic resonance imaging (MRI) disease activity was compared in the two groups. During the first 6 months of treatment, MS patients with non-GCC haplotypes experienced fewer new MRI T1-contrast enhancing lesions [0.77+/-0.36 (SEM)] than patients with the GCC haplotype (2.45+/-0.57) (P=0.05, Mann-Whitney U test). No differences were detected on clinical disease activity. The results suggest an influence of IL-10 promoter polymorphisms on IFN treatment response in MS.

Andersen O, Elovaara I, Färkkilä M, Hansen HJ, Mellgren SI, Myhr KM, Sandberg-Wollheim M, Soelberg Sørensen P. · Institute of Clinical Neuroscience, Sahlgrenska University Hospital, University of Göteborg, Göteborg, Sweden. · J Neurol Neurosurg Psychiatry. · Pubmed #15090564 links to  free full text

Abstract: OBJECTIVE: Interferon (IFN) beta has repeatedly shown benefit in multiple sclerosis (MS) in reducing the rate of relapse, the disease activity as shown with magnetic resonance imaging and, to some degree, the progression of disability; however, it is unknown how much the therapeutic response depends on the dose, the subgroup involved, and the disease stage. This multicentre, double blind, placebo controlled study explored the dose-response curve by examining the clinical benefit of low dose IFN beta-1a (Rebif), 22 micro g subcutaneously once weekly, in patients with secondary progressive MS. METHODS: A total of 371 patients with clinically definite SPMS were randomised to receive either placebo or subcutaneous IFN beta-1a, 22 micro g once weekly, for 3 years. Clinical assessments were performed every 6 months. The primary outcome was time to sustained disability, as defined by time to first confirmed 1.0 point increase on the Expanded Disability Status Scale (EDSS). Secondary outcomes included a sensitive disability measure and relapse rate. RESULTS: Treatment had no beneficial effect on time to confirmed progression on either the EDSS (hazard ratio (HR) = 1.13; 95% confidence interval (CI) 0.82 to 1.57; p = 0.45 for 22 micro g v placebo) or the Regional Functional Status Scale (HR = 0.93; 95% CI 0.68 to 1.28; p = 0.67). Other disability measures were also not significantly affected by treatment. Annual relapse rate was 0.27 with placebo and 0.25 with IFN (rate ratio = 0.90; 95% CI 0.64 to 1.27; p = 0.55). The drug was well tolerated with no new safety concerns identified. No significant gender differences were noted. CONCLUSIONS: This patient population was less clinically active than SPMS populations studied in other trials. Treatment with low dose, IFN beta-1a (Rebif) once weekly did not show any benefit in this study for either disability or relapse outcomes, including a subgroup with preceding relapses. These results add a point at one extreme of the dose-response spectrum of IFN beta therapy in MS, indicating that relapses in this phase may need treatment with higher doses than in the initial phases.

Ulvestad E, Aarseth JH, Vedeler C, Nyland H, Myhr KM. · Department of Microbiology and Immunology, The Gade Institute, Bergen, Norway. · Scand J Immunol. · Pubmed #14723628 No free full text.

Abstract: Multiple sclerosis (MS) patients treated with type I interferon experience reduced disease activity. Because immunoglobulins (Igs), complement and lymphocytes have been given a role in the pathogenesis of MS, we investigated the longitudinal effect of interferon-alpha2a (IFNA) on the variability of these parameters. Patients were treated for 6 months with 4.5 million international units (MIU) IFNA (24 patients), 9.0 MIU IFNA (21 patients) or placebo (23 patients). IFNA induced a significant increase in concentrations of total IgG and IgG subclasses 1, 3 and 4. At 6 months, the mean concentration of IgG had increased by 1.51 g/l (CI: 0.82, 2.21) in the 9.0 MIU IFNA group. There was no significant effect of IFNA treatment on concentrations of IgG2 and IgA, while the effect on IgM was borderline significant. After 6 months, IgM had increased by 0.29 g/l (CI: -0.01, 0.65) in the 9.0 MIU IFNA group. IFNA induced a significant increase in the concentration of C1 inhibitor (INH). At 3 months, the mean concentration of C1 INH had increased by 0.033 g/l (CI: 0.01, 0.05). At 3 months, C4 had increased by 0.05 g/l (CI: 0.01, 0.09) in the 9.0 MIU IFNA group. The effect of IFNA on C4 was inconclusive but indicates an effect during the initial phase of the treatment. C3 showed no significant treatment-mediated change. IFNA induced a significant decrease in lymphocyte concentrations by 0.56 x 106 lymphocytes/ml (CI: -0.81, -0.31) at 3 months. There were no significant associations between changes in immune parameters and changes in clinical and magnetic resonance imaging scores. The results verify that IFNA modulates and activates both the innate and the adaptive arms of the immune system. The observations should be of relevance when evaluating mechanisms of action of IFN treatment in MS.

Nordvik I, Myhr KM, Nyland H, Bjerve KS. · Department of Neurology, Haukeland University Hospital, Bergen, Norway. · Acta Neurol Scand. · Pubmed #10987373 No free full text.

Abstract: OBJECTIVE: To investigate whether supplementation with fish oil given together with dietary advice and vitamin supplementation influenced the clinical outcome in newly diagnosed multiple sclerosis (MS) patients. MATERIAL AND METHODS: Sixteen consecutive, newly diagnosed patients with multiple sclerosis were recruited to an open intervention study. They were given dietary advice and supplemented with 0.9 g/day of long-chain marine fatty acids and vitamins. The patients were followed for 2 years with respect to dietary habits, blood parameters and neurological assessment including exacerbation rate. RESULTS: There was a significant reduction in the mean annual exacerbation rate and the mean Expanded Disability Status Scale (EDSS) as compared to pre-study values. The plasma total phospholipid n-3 fatty acids increased and n-6 fatty acids decreased significantly. CONCLUSIONS: The results suggest that fish oil supplementation given together with vitamins and dietary advice can improve clinical outcome in patients with newly diagnosed MS.

Nortvedt MW, Riise T, Myhr KM, Nyland HI. · Department of Public Health and Primary Health Care, University of Bergen, Norway. · Neurology. · Pubmed #10891905 No free full text.

Abstract: OBJECTIVE: To investigate the predictive value of quality of life on changes in disability measured by the Expanded Disability Status Scale (EDSS). BACKGROUND: There are few good prognostic factors for disease development in MS. Quality of life and self-rated health have been shown to be highly predictive of morbidity and disease development in heart disease and cancer. METHODS: Data on quality of life (SF-36 Health Survey) were ascertained at baseline for 97 relapsing-remitting patients with MS participating in a short-term clinical trial on interferon alpha-2a. These scores were correlated with change in EDSS scores 1 year later, 6 months after treatment ended. RESULTS: Low scores on the SF-36 mental health scale were correlated with increased (worsened) EDSS scores 1 year later (r = -0.29, p = 0.006). The results were not altered by adjusting for disease activity at baseline, which was measured by the number gadolinium-enhanced MRI lesions, relapse rate for the preceding 2 years, and baseline EDSS score. Similar results were found for self-rated health (according to the first question of the SF-36). CONCLUSIONS: These findings reinforce the importance of incorporating the patients' evaluation of their quality of life during treatment. Further, assessing such measures is important in evaluating effects in treatment trials in MS.

Myhr KM, Sadallah S, Mollnes TE, Meri S, Nyland HI, Schifferli J, Vedeler CA. · Department of Neurology, Haukeland University Hospital, University of Bergen, Norway. · Acta Neurol Scand. · Pubmed #10660149 No free full text.

Abstract: OBJECTIVES: To evaluate the treatment effect of recombinant interferon-alpha2a (rIFN-alpha2a) on complement activation and regulation in MS patients. MATERIAL AND METHODS: Plasma levels of the complement activation products C3bc and terminal complement complex (TCC) and serum levels of the complement regulatory proteins, complement receptor 1, CR1 (CD35) and the membrane inhibitor of reactive lysis, protectin (CD59), were determined by enzyme-linked immunosorbent assay (ELISA) in MS patients treated with IFN-alpha2a (14 patients) or placebo (7 patients). RESULTS: The level of soluble CD35 decreased while the level of TCC and to a lesser degree C3bc increased in the IFN-alpha2a treated patients during the initial part of the treatment. There was also a concomitant reduction of leukocytes in the same patients. CONCLUSIONS: The results indicate that complement is activated during the initial phase of rIFN-alpha2a treatment. This could partly be due to a concomitant reduction in soluble CD35.

Nortvedt MW, Riise T, Myhr KM, Nyland HI, Hanestad BR. · Department of Public Health and Primary Health Care, University of Bergen, Ulriksdal 8C, N-5009 Bergen, Norway. · Mult Scler. · Pubmed #10516774 No free full text.

Abstract: The objective of the study was to examine whether the beneficial effect of treatment of interferon alfa-2a on multiple sclerosis seen by magnetic resonance imaging is reflected in a corresponding improvement in the quality of life (QoL) and to address the impact of adverse events related to this treatment on the QoL. The study was a randomised double-blinded placebo-controlled treatment trial including 97 relapsing-remitting multiple sclerosis patients. Thirty-two patients received 4.5 MIU recombinant interferon alfa-2a, 32 patients received 9.0 MIU recombinant interferon alfa-2a and 33 patients received placebo treatment for 6 months. All patients were followed up 6 months after end of treatment. QoL was assessed according to the eight scales of the SF-36 Health Survey and measured at baseline, month 3, 6 and 12. The effect found on MRI was not reflected in a corresponding change in the QoL. We found a relationship between the presence of new enhancing lesions and reduced QoL among the placebo patients, whereas this was not found among the patients treated with interferon. The presence of the adverse events fatigue, myalgia, headache and weakness were significantly negatively correlated to several of the QoL dimensions. Conclusively, the treatment with interferon alfa-2a does not seem to improve the patients' QoL after 6 months of treatment, in spite of a marked effect measured by MRI. The treatment is followed by adverse events that negatively affected the QoL.

Myhr KM, Riise T, Green Lilleås FE, Beiske TG, Celius EG, Edland A, Jensen D, Larsen JP, Nilsen R, Nortvedt MW, Smievoll AI, Vedeler C, Nyland HI. · Department of Neurology, Haukeland University Hospital, University of Bergen, Norway. · Neurology. · Pubmed #10102427 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy and safety of interferon-alpha2a (IFN-alpha2a) in relapsing-remitting MS (RRMS). BACKGROUND: Several immune-modulating therapy regimens of IFN-alpha have shown varying results in MS. A recent pilot study suggested benefits from IFN-alpha2a. METHODS: Ninety-seven patients were randomized to receive subcutaneous injections of placebo (33 patients) or 4.5 million international units (mIU) (32 patients) or 9.0 mIU (32 patients) of IFN-alpha2a three times weekly for 6 months, with a further 6 months of follow-up. Monthly gadodiamide-enhanced MRI was the primary method of evaluating efficacy. RESULTS: IFN-alpha2a treatment resulted in fewer new MRI lesions during the treatment period (p < 0.003). The probability of no new lesions during treatment was >2.5 times higher with 9.0 mIU IFN-alpha2a than with placebo (p < 0.005). The median number of lesions at the end of treatment was lower with IFN-alpha2a treatment than with placebo (p = 0.0004), but the difference disappeared during follow-up. The total number of lesions (mean) increased by 4.78 with placebo, 0.86 with 4.5 mIU IFN-alpha2a, and 0.28 with 9.0 mIU IFN-alpha2a during treatment (p = 0.030). No treatment effect on exacerbation rate, progression of disability, or quality of life was detected. Nine patients discontinued treatment, five because of adverse events. CONCLUSIONS: IFN-alpha2a treatment significantly reduced disease activity as measured by MRI, but the efficacy disappeared within 6 months after discontinuation of treatment. A long-term study of more patients using disability as a primary outcome measure is needed to evaluate the clinical impact.

Myhr KM, Mellgren SI. · Norwegian Multiple Sclerosis National Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway. · Acta Neurol Scand Suppl. · Pubmed #19566504 No free full text.

Abstract: BACKGROUND: Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system (CNS) that usually is clinically characterized by repeated subacute relapses followed by remissions. Therapeutic strategies include corticosteroid treatment of relapses and immunomodulatory- or immunosuppressive treatment to prevent new relapses and progression of disability. OBJECTIVES: To review the evidences for the use of corticosteroids in the treatment of relapses in MS as well as its possible disease modifying potential. MATERIALS & METHODS: Available literature from PubMed search and personal experiences on corticosteroid treatment in multiple sclerosis were reviewed. RESULTS: High dose short-term oral or intravenous methylprednisolone for 3-5 days speed up recovery from relapses, but the treatment has no influence on the occurrence of new relapses or long-term disability. There is also some evidence that pulsed treatment with methylprednisolone have beneficial long-term effects in multiple sclerosis. CONCLUSION: Relapses with moderate to serious disability should be treated with high dose intravenous or oral methylprednisolone. More data is needed to determine long-term disease modifying effects of corticosteroids.

Aarskog NK, Marøy T, Myhr KM, Vedeler CA. · Department of Neurology, Haukeland University Hospital, N-5021 Bergen, Norway. · J Neuroimmunol. · Pubmed #19467718 No free full text.

Abstract: We measured the frequency of binding antibody (BAB) and neutralizing antibody (NAB) against interferon-beta (IFN-beta) in sera from 827 patients with relapsing-remitting multiple sclerosis (RRMS) using various IFN-beta medications. Of the 827 patients, 363 (43.9%) had serum BAB after more than 12 months of IFN-beta treatment. Of the 363 BAB-positive sera, we analyzed 137 for BAB using a myxovirus-resistant protein A (MxA) protein induction assay (ELISA) and an MxA messenger RNA (mRNA) induction assay (real-time polymerase chain reaction (PCR)). We obtained similar results for each serum in both NAB assays, indicating a good correlation between transcription and translation of MxA. We tested all 363 sera by real-time PCR, and NAB was present in 70.8% of BAB-positive sera, or 31.1% of the 827 patients with relapsing-remitting multiple sclerosis (RRMS). Real-time PCR offers several advantages for measuring NAB compared with the MxA protein induction enzyme-linked immunosorbent assay and should be used routinely for NAB among patients with MS using IFN-beta treatment.

Sorensen PS, Mellgren SI, Svenningsson A, Elovaara I, Frederiksen JL, Beiske AG, Myhr KM, Søgaard LV, Olsen IC, Sandberg-Wollheim M. · Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. · Lancet Neurol. · Pubmed #19409854 No free full text.

Abstract: BACKGROUND: Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective, and new more effective and safe strategies are needed. Our aim was to assess the efficacy of oral methylprednisolone as an add-on therapy to subcutaneous interferon beta-1a to reduce the yearly relapse rate in patients with relapsing-remitting multiple sclerosis. METHODS: NORMIMS (NORdic trial of oral Methylprednisolone as add-on therapy to Interferon beta-1a for treatment of relapsing-remitting Multiple Sclerosis) was a randomised, placebo-controlled trial done in 29 neurology departments in Denmark, Norway, Sweden, and Finland. We enrolled outpatients with relapsing-remitting multiple sclerosis who had had at least one relapse within the previous 12 months despite subcutaneous interferon beta-1a treatment (44 microg three times per week). We randomly allocated patients by computer to add-on therapy of either 200 mg methylprednisolone or matching placebo, both given orally on 5 consecutive days every 4 weeks for at least 96 weeks. The primary outcome measure was mean yearly relapse rate. Primary analyses were by intention to treat. This trial is registered, number ISRCTN16202527. FINDINGS: 66 patients were assigned to interferon beta and oral methylprednisolone and 64 were assigned to interferon beta and placebo. A high proportion of patients withdrew from the study before week 96 (26% [17 of 66] on methylprednisolone vs 17% [11 of 64] on placebo). The mean yearly relapse rate was 0.22 for methylprednisolone compared with 0.59 for placebo (62% reduction, 95% CI 39-77%; p<0.0001). Sleep disturbance and neurological and psychiatric symptoms were the most frequent adverse events recorded in the methylprednisolone group. Bone mineral density had not changed after 96 weeks. INTERPRETATION: Oral methylprednisolone given in pulses every 4 weeks as an add-on therapy to subcutaneous interferon beta-1a in patients with relapsing-remitting multiple sclerosis leads to a significant reduction in relapse rate. However, because of the small number of patients and the high dropout rate, these findings need to be corroborated in larger cohorts.

Lode K, Bru E, Klevan G, Myhr KM, Nyland H, Larsen JP. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · Mult Scler. · Pubmed #19299438 No free full text.

Abstract: BACKGROUND: Multiple sclerosis (MS) is a chronic disease with unclear etiology, unpredictable clinical course, and no cure. Patients' ability to cope with MS moderates the adaptation to the disease. OBJECTIVES: To compare coping in patients recently diagnosed with MS and healthy controls and to study the association between depressive symptoms and patients' coping styles. METHODS: A sample of 86 recently diagnosed patients with definite or probable MS and 93 healthy population controls completed questionnaires assessing coping styles and depressive symptoms. RESULTS: Compared with healthy controls, patients with MS used significantly less the problem focused strategies including planning, restraint coping, and seeking social support for instrumental reasons, and they used less the emotion-focused strategies seeking social support for emotional reasons, focusing on and venting of emotions, and positive reinterpretation and growth. The mean Beck Depressive symptoms Inventory scores were 10.8 and 4.7 in patients and controls, respectively. In stress situations connected to MS, depressive symptoms in these patients were related to the problem-focused strategies of restraint coping and planning, the emotion-focused strategy of focusing on and venting of emotions, and the avoidance strategies of behavioral- and mental disengagements, and denial.

Torkildsen Ø, Brunborg LA, Milde AM, Mørk SJ, Myhr KM, Bø L. · Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway. · Clin Nutr. · Pubmed #19042061 No free full text.

Abstract: BACKGROUND & AIMS: Although many patients with multiple sclerosis (MS) use special diets, the data available at present are insufficient to assess any potential benefit of diet modification. Cuprizone induced demyelination is a commonly used animal model for demyelination in the central nervous system. METHODS: The present study was designed to analyse behaviour and activity due to demyelination in mice fed with 0.2% cuprizone on three different diets. The diets consisted of (1) salmon fillets rich in marine n-3 polyunsaturated fatty acids (PUFAs), (2) cod liver oil rich in marine n-3 PUFAs, or (3) a control diet containing soybean oil rich in n-6 PUFAs. After 5 weeks of continuous cuprizone treatment, animal activity was assessed with the elevated plus maze (EPM) test. After 6 weeks the brains were fixated in paraformaldehyde and stained with luxol fast blue (LFB). RESULTS: There was significantly less demyelination in the salmon-cuprizone group than in the two other cuprizone-treatment groups (P<0.0005). The salmon-cuprizone mice had less weight loss (P<0.001) and showed more visits in both open and closed arms of the elevated plus maze than the other cuprizone-treated groups (P<0.0001). In addition they had more entries in the open arms than both the cod liver oil-cuprizone (P<0.02) and the soybean oil-cuprizone-treated mice (P<0.0001). CONCLUSIONS: A diet containing salmon seems to protect against behavioural changes induced by demyelination in the cuprizone model, indicating that a fish diet could have a protective effect in demyelinating diseases.