Kjell-Morten Myhr | University of Bergen (original) (raw)
Papers by Kjell-Morten Myhr
Physiotherapy Research International, 2006
Background and Purpose. Patients with multiple sclerosis (MS) tend to have movement difficulties,... more 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 pati...
Acta Neurologica Scandinavica, 2008
Having found positive the research for anti-Bordetella antibodies in the 95.47% of 92 patients af... more Having found positive the research for anti-Bordetella antibodies in the 95.47% of 92 patients affected by defined multiple sclerosis and in the 100% of 55 patients affected by non-patched neuropathies (amyotrophic lateral sclerosis and correlated neuropathies), I reassessed the pathogenesis of the neuropathies from Bordetella pertussis. In the two categories of neuropathies (with and without patches), the beginning pathogenetic mechanisms are the same: 1) pertussis re-infection in patients with mucociliary barrier defect; 2) pertussis toxins passage in the blood; and 3) formation of circulating immune complexes. In multiple sclerosis, astrocytes produce class II human leukocyte antigens, the endothelia of the small brain vessels show the "adhesion molecules," and the immune complexes fall in the central nervous system (patches are formed). In amyotrophic lateral sclerosis and in the other non-patched neuropathies, the astrocytes do not produce the class II human leukocyte antigens, the endothelia do not show adhesion molecules, and immune complexes do not fall in the central nervous system; but they increase in blood until they inhibit the ulterior antibodies production. For relative antibodies lack, pertussis toxins fix directly on neuro-epithelia; their pathogenic power and physiopathologic astrocytes role in the central nervous system produce the damage. With a blood sample, we can assess Bordetella etiology. In all these neuropathies, an extended antibiotic therapy to clear mucosae and to prevent reinfections is necessary.
Tidsskrift for Den norske lægeforening, Mar 27, 2023
Expert Opinion on Pharmacotherapy, 2017
has received speakers honoraria and research grants from Merck, Biogen, Genzyme, Novartis and Tev... more has received speakers honoraria and research grants from Merck, Biogen, Genzyme, Novartis and Teva; speakers honoraria from Santen, and served on advisory board for Genzyme, Merck and Biogen. Ø Torkildsen has served on advisory boards and received travel grants and speakers honoraria form Biogen Idec, Merck and Genzyme, and received speakers honoraria and travel grants from Novartis. K M Myhr has received unrestricted research grants to his institution and scientific advisory board or speakers honoraria from Biogen Novartis, Merck and Teva; speakers honoraria from Amirall; and has participated in clinical trials organized by Biogen, Merck and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
CNS Drugs, 2016
Alemtuzumab (Lemtrada TM) is a humanized monoclonal antibody approved in more than 50 countries. ... more Alemtuzumab (Lemtrada TM) is a humanized monoclonal antibody approved in more than 50 countries. Within the European Union, alemtuzumab is indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) with active disease defined by clinical or imaging features; in the USA, the indication states that alemtuzumab should generally be reserved for the treatment of patients with relapsing forms of multiple sclerosis who have had an inadequate response to two or
Neurology, Jan 27, 2005
Using data from the compulsory Medical Birth Registry of Norway, the authors investigated the eff... more Using data from the compulsory Medical Birth Registry of Norway, the authors investigated the effect of maternal multiple sclerosis (MS) on pregnancy, delivery, and birth outcome in 649 births by MS mothers and 2.1 million control births. The mothers with MS had a higher proportion of neonates small for gestational age and also more frequent induction and operative interventions during delivery.
Multiple sclerosis (Houndmills, Basingstoke, England), Jan 13, 2015
We explored which clinical and biochemical variables predict conversion from clinically isolated ... more We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year ...
PLoS ONE, 2014
Objective: To investigate demographic and clinical factors associated with employment in MS. Meth... more Objective: To investigate demographic and clinical factors associated with employment in MS. Methods: The study included 213 (89.9%) of all MS patients in Sogn and Fjordane County, Western Norway at December 31 st 2010. The patients underwent clinical evaluation, structured interviews and completed self-reported questionnaires. Demographic and clinical factors were compared between patients being employed versus patients being unemployed and according to disease course of MS. Logistic regression analysis was used to identify factors independently associated with current employment. Results: After a mean disease duration of almost 19 years, 45% of the population was currently full-time or part-time employed. Patients with relapsing-remitting MS (RRMS) had higher employment rate than patients with secondary (SPMS) and primary progressive (PPMS). Higher educated MS patients with lower age at onset, shorter disease duration, less severe disability and less fatigue were most likely to be employed. Conclusions: Nearly half of all MS patients were still employed after almost two decades of having MS. Lower age at onset, shorter disease duration, higher education, less fatigue and less disability were independently associated with current employment. These key clinical and demographic factors are important to understand the reasons to work ability in MS. The findings highlight the need for environmental adjustments at the workplace to accommodate individual 's needs in order to improve working ability among MS patients.
PLoS ONE, 2012
Background: Poor sleep is a frequent symptom in patients with multiple sclerosis (MS). Sleep may ... more Background: Poor sleep is a frequent symptom in patients with multiple sclerosis (MS). Sleep may be influenced by MSrelated symptoms and adverse effects from immunotherapy and symptomatic medications. We aimed to study the prevalence of poor sleep and the influence of socio-demographic and clinical factors on sleep quality in MS-patients. Methods: A total of 90 MS patients and 108 sex-and age-matched controls were included in a questionnaire survey. Sleep complaints were evaluated by Pittsburgh Sleep Quality Index (PSQI) and a global PSQI score was used to separate good sleepers (#5) from poor sleepers (.5). Excessive daytime sleepiness, the use of immunotherapy and antidepressant drugs, symptoms of pain, depression, fatigue and MS-specific health related quality of life were registered. Results were compared between patients and controls and between good and poor sleepers among MS patients. Results: MS patients reported a higher mean global PSQI score than controls (8.6 vs. 6.3, p = 0.001), and 67.1% of the MS patients compared to 43.9% of the controls (p = 0.002) were poor sleepers. Pain (p = 0.02), fatigue (p = 0.001), depression (p = 0.01) and female gender (p = 0.04) were associated with sleep disturbance. Multivariate analyses showed that female gender (p = 0.02), use of immunotherapy (p = 005) and a high psychological burden of MS (p = 0.001) were associated with poor sleep among MS patients. Conclusions: Poor sleep is common in patients with MS. Early identification and treatment of modifiable risk factors may improve sleep and quality of life in MS.
PLoS ONE, 2014
Background: Anti interferon-beta (IFN-b) neutralizing antibodies (NAb) affect efficacy of treatme... more Background: Anti interferon-beta (IFN-b) neutralizing antibodies (NAb) affect efficacy of treatment of multiple sclerosis patients, but exactly when the detrimental effects of NAbs offset therapeutic efficacy is debated. Quantification of intracellular pathway-specific phosphorylation by phospho-specific flow cytometry (phosphoflow) is a promising tool for evaluation of these effects in primary immune cells from treated patients at the single-cell level. Method: Samples for phosphoflow and gene expression changes were collected before administration of IFN-b and at four, six, and eight hours thereafter. Patients were NAb negative (n = 3) or were NAb positive with low/medium (n = 1) or high (n = 2) NAb titers. Levels of phosphorylation of six Stat transcription factors (pStat) in seven cell subtypes and expression levels of 71 pathway-specific genes in whole blood were measured. The data was subjected to principal component analysis (PCA), fifty-fifty MANOVA, ANOVA, and partial least square regression (PLSR). Results: PCA of pStat levels clustered patients according to NAb class independently of time. PCA of gene expression data clustered patients according to NAb class but was affected by time and treatment. In the fifty-fifty MANOVA, NAb class was significant for both pStat levels and gene expression data. The ANOVA identified pStat1 protein in several cell subtypes as significantly affected by NAb class. The best fitting model for NAb prediction based on PLSR included pStat1 in monocytes, T cells, or lymphocytes and pStat3 in monocytes (r = 0.97). Gene expression data were slightly less predictive of NAb titers. Conclusion: Based on this proof of concept study, we hypothesize that NAb effects can be monitored by evaluation of a single biomarker, pStat1, in either monocytes or T cells by phosphoflow directly after IFN-b administration. The method will significantly reduce cost relative to labor intensive in vitro methods and offers a patient-specific approach to NAb evaluation.
Neurology, 2012
Objective: Studies based on deseasonalized vitamin D levels suggest that vitamin D may influence ... more Objective: Studies based on deseasonalized vitamin D levels suggest that vitamin D may influence the disease activity in multiple sclerosis (MS), and high doses are suggested as add-on treatment to interferon- (IFN-). Seasonal fluctuation of vitamin D varies between individuals, thus the relationship to disease activity should preferentially be studied by repeated and simultaneous vitamin D and MRI measurements from each patient. Methods: This was a cohort study comprising 88 patients with relapsing-remitting MS who were followed for 6 months with 7 MRI and 4 25-hydroxyvitamin D measurements before initiation of IFN-, and for 18 months with 5 MRI and 5 25-hydroxyvitamin D measurements during IFN- treatment. Results: Prior to IFN- treatment, each 10 nmol/L increase in 25-hydroxyvitamin D was associated with 12.7% (p ϭ 0.037) reduced odds for new T1 gadolinium-enhancing lesions, 11.7% (p ϭ 0.044) for new T2 lesions, and 14.1% (p ϭ 0.024) for combined unique activity. Patients with the most pronounced fluctuation in 25-hydroxyvitamin D displayed larger proportion of MRI scans with new T1 gadolinium-enhancing lesions (51% vs 23%, p ϭ 0.004), combined unique activity (60% vs 32%, p ϭ 0.003), and a trend for new T2 lesions (49% vs 28%, p ϭ 0.052) at the lowest compared to the highest 25-hydroxyvitamin D level. No association between 25-hydroxyvitamin D and disease activity was detected after initiation of IFN-. HLA-DRB1*15 status did not affect the results. Conclusion: In untreated patients with MS, increasing levels of 25-hydroxyvitamin D are inversely associated with radiologic disease activity irrespective of their HLA-DRB1*15 status. Neurology ® 2012;79:267-273 GLOSSARY 25(OH)D ϭ 25-hydroxyvitamin D; CI ϭ confidence interval; CUA ϭ combined unique activity; EDSS ϭ Expanded Disability Status Scale; IFN- ϭ interferon-; MS ϭ multiple sclerosis; RRMS ϭ relapsing-remitting MS.
Multiple Sclerosis Journal, 2007
Background Patients with multiple sclerose (MS) live with their disease for many years. The cause... more Background Patients with multiple sclerose (MS) live with their disease for many years. The cause of the disease is unknown and there are no curative therapies. Patients' adaption to chronic disease is dependent on the effectiveness of coping behaviour. Objectives To explore the correlation between the quality of perceived disease information and to estimate the correspondance between the quality of perceived disease information and later coping styles applied by MS-patients in stress situations related to their disease. Methods Of a total of 108 patients recently diagnosed with MS, 93 agreed to participate in the study and 86 of these completed two different questionnaires, one assessing quality of the perceived information and the other asessing coping styles (the COPE scale). Results 43.2% of the patients were dissatisfied or very dissatisfied with the information by the time of diagnosis. MS-related coping styles were influenced by general coping styles and the most frequent...
Multiple Sclerosis Journal, 2012
Background: The placebo-controlled phase of the PreCISe study showed that glatiramer acetate dela... more Background: The placebo-controlled phase of the PreCISe study showed that glatiramer acetate delayed onset of clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome and brain lesions on MRI. Objective: To compare the effects of early versus delayed glatiramer acetate treatment in the open-label phase of PreCISe. Methods: Patients with a clinically isolated syndrome suggestive of MS with unifocal manifestation and ≥2 T2-weighted brain lesions were randomized to receive glatiramer acetate 20 mg/d (early-treatment, n=198) or placebo (delayed-treatment, n=211) for 36 months or until conversion to CDMS, followed by open-label glatiramer acetate treatment for two years. Results: Early glatiramer acetate treatment reduced CDMS conversion risk by 41% (hazard ratio 0.59, 95% confidence interval 0.44–0.80; p=0.0005) versus delayed-treatment, and was associated with a 972-day delay (185%) in conversion to CDMS, less brain atrophy (−28%, p=0.0209), fewer new...
Multiple Sclerosis Journal, 2014
Background: The immunogenicity of influenza vaccines in MS patients undergoing immunomodulatory t... more Background: The immunogenicity of influenza vaccines in MS patients undergoing immunomodulatory treatment is not well studied. Objectives: This explorative study investigated the influence of immunomodulatory treatment on MS patients receiving pandemic H1N1 (swine flu) vaccination in 2009 and seasonal influenza vaccination in 2010. Methods: We investigated the immune response to pandemic H1N1 vaccination among 113 MS patients and 216 controls during the pandemic of 2009. We also investigated the serological response to seasonal influenza vaccination (2010 – 2011 season) among 49 vaccinated and 62 non-vaccinated MS patients, versus 73 controls. We evaluated these vaccine responses by haemagglutination inhibition assay. Results: MS patients receiving immunomodulatory treatment had reduced protection (27.4%), compared to controls (43.5%) ( p = 0.006), after pandemic H1N1 vaccination (2009). The rates of protection were not influenced by interferon beta treatment (44.4% protected), but ...
Multiple Sclerosis Journal, 2011
Background: In the clinical trials about 9% of natalizumab treated multiple sclerosis (MS) patien... more Background: In the clinical trials about 9% of natalizumab treated multiple sclerosis (MS) patients generated anti-natalizumab antibodies, of which 6% were persistent and 3% transient. The occurrence of antibodies reduced serum levels of natalizumab, decreased bio-efficacy, and abrogated the therapeutic efficacy. Objective: The objective was to assess the frequency of anti-natalizumab antibodies in an unselected cohort of patients from four different countries. Methods: We measured anti-natalizumab antibodies in a large cohort of 4881 unselected patients from four MS centres that systematically measured antibodies in patients treated with natalizumab. We applied the same ELISA assay developed by Biogen Idec and used in the pivotal trials of natalizumab. Results: Antibodies occurred in 4.5% (95% confidence interval, CI: 4.0–5.1%) of the patients, and were persistent in 3.5% (95% CI: 3.0–4.0%) and transient in 1.0% (95% CI: 0.7–1.3%) of the patients. The frequencies of permanently ant...
The Lancet, 2009
developmental assessment without having a creatinine kinase level having been performed. The latt... more developmental assessment without having a creatinine kinase level having been performed. The latter is an easy, sensitive, and inexpensive test that is unfortunately underused in patients who have early signs and symptoms that can be compatible with DMD. In this series, only about one-third of youngsters with motor or global developmental delay had a creatine kinase (CK) obtained at the time of their initial evaluation. In another quarter of children, referral was made to physical, occupational, or speech therapy or to a developmental evaluation program without any diagnostic testing for DMD. A delay in diagnosis would simply be an academic or intellectual faux pas were it not for the fact that shortening the time to diagnosis in fact does have importance. Delay in diagnosis can result in a second pregnancy affected with DMD absent identification of the disorder. In addition to reproductive planning information, some children with DMD will have improvement in their quality of life with specific targeted therapies, albeit noncurative ones. Newborn screening has been advocated for by some as the best solution for the early detection of DMD. Absent that, only an increased awareness on our part will help. The report of Ciafaloni et al shows us how important this heightened awareness of DMD is.
Journal of Neurology, Neurosurgery & Psychiatry, 2007
Nature, Jan 11, 2011
Multiple sclerosis is a common disease of the central nervous system in which the interplay betwe... more Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require ...
Physiotherapy Research International, 2006
Background and Purpose. Patients with multiple sclerosis (MS) tend to have movement difficulties,... more 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 pati...
Acta Neurologica Scandinavica, 2008
Having found positive the research for anti-Bordetella antibodies in the 95.47% of 92 patients af... more Having found positive the research for anti-Bordetella antibodies in the 95.47% of 92 patients affected by defined multiple sclerosis and in the 100% of 55 patients affected by non-patched neuropathies (amyotrophic lateral sclerosis and correlated neuropathies), I reassessed the pathogenesis of the neuropathies from Bordetella pertussis. In the two categories of neuropathies (with and without patches), the beginning pathogenetic mechanisms are the same: 1) pertussis re-infection in patients with mucociliary barrier defect; 2) pertussis toxins passage in the blood; and 3) formation of circulating immune complexes. In multiple sclerosis, astrocytes produce class II human leukocyte antigens, the endothelia of the small brain vessels show the "adhesion molecules," and the immune complexes fall in the central nervous system (patches are formed). In amyotrophic lateral sclerosis and in the other non-patched neuropathies, the astrocytes do not produce the class II human leukocyte antigens, the endothelia do not show adhesion molecules, and immune complexes do not fall in the central nervous system; but they increase in blood until they inhibit the ulterior antibodies production. For relative antibodies lack, pertussis toxins fix directly on neuro-epithelia; their pathogenic power and physiopathologic astrocytes role in the central nervous system produce the damage. With a blood sample, we can assess Bordetella etiology. In all these neuropathies, an extended antibiotic therapy to clear mucosae and to prevent reinfections is necessary.
Tidsskrift for Den norske lægeforening, Mar 27, 2023
Expert Opinion on Pharmacotherapy, 2017
has received speakers honoraria and research grants from Merck, Biogen, Genzyme, Novartis and Tev... more has received speakers honoraria and research grants from Merck, Biogen, Genzyme, Novartis and Teva; speakers honoraria from Santen, and served on advisory board for Genzyme, Merck and Biogen. Ø Torkildsen has served on advisory boards and received travel grants and speakers honoraria form Biogen Idec, Merck and Genzyme, and received speakers honoraria and travel grants from Novartis. K M Myhr has received unrestricted research grants to his institution and scientific advisory board or speakers honoraria from Biogen Novartis, Merck and Teva; speakers honoraria from Amirall; and has participated in clinical trials organized by Biogen, Merck and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
CNS Drugs, 2016
Alemtuzumab (Lemtrada TM) is a humanized monoclonal antibody approved in more than 50 countries. ... more Alemtuzumab (Lemtrada TM) is a humanized monoclonal antibody approved in more than 50 countries. Within the European Union, alemtuzumab is indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) with active disease defined by clinical or imaging features; in the USA, the indication states that alemtuzumab should generally be reserved for the treatment of patients with relapsing forms of multiple sclerosis who have had an inadequate response to two or
Neurology, Jan 27, 2005
Using data from the compulsory Medical Birth Registry of Norway, the authors investigated the eff... more Using data from the compulsory Medical Birth Registry of Norway, the authors investigated the effect of maternal multiple sclerosis (MS) on pregnancy, delivery, and birth outcome in 649 births by MS mothers and 2.1 million control births. The mothers with MS had a higher proportion of neonates small for gestational age and also more frequent induction and operative interventions during delivery.
Multiple sclerosis (Houndmills, Basingstoke, England), Jan 13, 2015
We explored which clinical and biochemical variables predict conversion from clinically isolated ... more We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year ...
PLoS ONE, 2014
Objective: To investigate demographic and clinical factors associated with employment in MS. Meth... more Objective: To investigate demographic and clinical factors associated with employment in MS. Methods: The study included 213 (89.9%) of all MS patients in Sogn and Fjordane County, Western Norway at December 31 st 2010. The patients underwent clinical evaluation, structured interviews and completed self-reported questionnaires. Demographic and clinical factors were compared between patients being employed versus patients being unemployed and according to disease course of MS. Logistic regression analysis was used to identify factors independently associated with current employment. Results: After a mean disease duration of almost 19 years, 45% of the population was currently full-time or part-time employed. Patients with relapsing-remitting MS (RRMS) had higher employment rate than patients with secondary (SPMS) and primary progressive (PPMS). Higher educated MS patients with lower age at onset, shorter disease duration, less severe disability and less fatigue were most likely to be employed. Conclusions: Nearly half of all MS patients were still employed after almost two decades of having MS. Lower age at onset, shorter disease duration, higher education, less fatigue and less disability were independently associated with current employment. These key clinical and demographic factors are important to understand the reasons to work ability in MS. The findings highlight the need for environmental adjustments at the workplace to accommodate individual 's needs in order to improve working ability among MS patients.
PLoS ONE, 2012
Background: Poor sleep is a frequent symptom in patients with multiple sclerosis (MS). Sleep may ... more Background: Poor sleep is a frequent symptom in patients with multiple sclerosis (MS). Sleep may be influenced by MSrelated symptoms and adverse effects from immunotherapy and symptomatic medications. We aimed to study the prevalence of poor sleep and the influence of socio-demographic and clinical factors on sleep quality in MS-patients. Methods: A total of 90 MS patients and 108 sex-and age-matched controls were included in a questionnaire survey. Sleep complaints were evaluated by Pittsburgh Sleep Quality Index (PSQI) and a global PSQI score was used to separate good sleepers (#5) from poor sleepers (.5). Excessive daytime sleepiness, the use of immunotherapy and antidepressant drugs, symptoms of pain, depression, fatigue and MS-specific health related quality of life were registered. Results were compared between patients and controls and between good and poor sleepers among MS patients. Results: MS patients reported a higher mean global PSQI score than controls (8.6 vs. 6.3, p = 0.001), and 67.1% of the MS patients compared to 43.9% of the controls (p = 0.002) were poor sleepers. Pain (p = 0.02), fatigue (p = 0.001), depression (p = 0.01) and female gender (p = 0.04) were associated with sleep disturbance. Multivariate analyses showed that female gender (p = 0.02), use of immunotherapy (p = 005) and a high psychological burden of MS (p = 0.001) were associated with poor sleep among MS patients. Conclusions: Poor sleep is common in patients with MS. Early identification and treatment of modifiable risk factors may improve sleep and quality of life in MS.
PLoS ONE, 2014
Background: Anti interferon-beta (IFN-b) neutralizing antibodies (NAb) affect efficacy of treatme... more Background: Anti interferon-beta (IFN-b) neutralizing antibodies (NAb) affect efficacy of treatment of multiple sclerosis patients, but exactly when the detrimental effects of NAbs offset therapeutic efficacy is debated. Quantification of intracellular pathway-specific phosphorylation by phospho-specific flow cytometry (phosphoflow) is a promising tool for evaluation of these effects in primary immune cells from treated patients at the single-cell level. Method: Samples for phosphoflow and gene expression changes were collected before administration of IFN-b and at four, six, and eight hours thereafter. Patients were NAb negative (n = 3) or were NAb positive with low/medium (n = 1) or high (n = 2) NAb titers. Levels of phosphorylation of six Stat transcription factors (pStat) in seven cell subtypes and expression levels of 71 pathway-specific genes in whole blood were measured. The data was subjected to principal component analysis (PCA), fifty-fifty MANOVA, ANOVA, and partial least square regression (PLSR). Results: PCA of pStat levels clustered patients according to NAb class independently of time. PCA of gene expression data clustered patients according to NAb class but was affected by time and treatment. In the fifty-fifty MANOVA, NAb class was significant for both pStat levels and gene expression data. The ANOVA identified pStat1 protein in several cell subtypes as significantly affected by NAb class. The best fitting model for NAb prediction based on PLSR included pStat1 in monocytes, T cells, or lymphocytes and pStat3 in monocytes (r = 0.97). Gene expression data were slightly less predictive of NAb titers. Conclusion: Based on this proof of concept study, we hypothesize that NAb effects can be monitored by evaluation of a single biomarker, pStat1, in either monocytes or T cells by phosphoflow directly after IFN-b administration. The method will significantly reduce cost relative to labor intensive in vitro methods and offers a patient-specific approach to NAb evaluation.
Neurology, 2012
Objective: Studies based on deseasonalized vitamin D levels suggest that vitamin D may influence ... more Objective: Studies based on deseasonalized vitamin D levels suggest that vitamin D may influence the disease activity in multiple sclerosis (MS), and high doses are suggested as add-on treatment to interferon- (IFN-). Seasonal fluctuation of vitamin D varies between individuals, thus the relationship to disease activity should preferentially be studied by repeated and simultaneous vitamin D and MRI measurements from each patient. Methods: This was a cohort study comprising 88 patients with relapsing-remitting MS who were followed for 6 months with 7 MRI and 4 25-hydroxyvitamin D measurements before initiation of IFN-, and for 18 months with 5 MRI and 5 25-hydroxyvitamin D measurements during IFN- treatment. Results: Prior to IFN- treatment, each 10 nmol/L increase in 25-hydroxyvitamin D was associated with 12.7% (p ϭ 0.037) reduced odds for new T1 gadolinium-enhancing lesions, 11.7% (p ϭ 0.044) for new T2 lesions, and 14.1% (p ϭ 0.024) for combined unique activity. Patients with the most pronounced fluctuation in 25-hydroxyvitamin D displayed larger proportion of MRI scans with new T1 gadolinium-enhancing lesions (51% vs 23%, p ϭ 0.004), combined unique activity (60% vs 32%, p ϭ 0.003), and a trend for new T2 lesions (49% vs 28%, p ϭ 0.052) at the lowest compared to the highest 25-hydroxyvitamin D level. No association between 25-hydroxyvitamin D and disease activity was detected after initiation of IFN-. HLA-DRB1*15 status did not affect the results. Conclusion: In untreated patients with MS, increasing levels of 25-hydroxyvitamin D are inversely associated with radiologic disease activity irrespective of their HLA-DRB1*15 status. Neurology ® 2012;79:267-273 GLOSSARY 25(OH)D ϭ 25-hydroxyvitamin D; CI ϭ confidence interval; CUA ϭ combined unique activity; EDSS ϭ Expanded Disability Status Scale; IFN- ϭ interferon-; MS ϭ multiple sclerosis; RRMS ϭ relapsing-remitting MS.
Multiple Sclerosis Journal, 2007
Background Patients with multiple sclerose (MS) live with their disease for many years. The cause... more Background Patients with multiple sclerose (MS) live with their disease for many years. The cause of the disease is unknown and there are no curative therapies. Patients' adaption to chronic disease is dependent on the effectiveness of coping behaviour. Objectives To explore the correlation between the quality of perceived disease information and to estimate the correspondance between the quality of perceived disease information and later coping styles applied by MS-patients in stress situations related to their disease. Methods Of a total of 108 patients recently diagnosed with MS, 93 agreed to participate in the study and 86 of these completed two different questionnaires, one assessing quality of the perceived information and the other asessing coping styles (the COPE scale). Results 43.2% of the patients were dissatisfied or very dissatisfied with the information by the time of diagnosis. MS-related coping styles were influenced by general coping styles and the most frequent...
Multiple Sclerosis Journal, 2012
Background: The placebo-controlled phase of the PreCISe study showed that glatiramer acetate dela... more Background: The placebo-controlled phase of the PreCISe study showed that glatiramer acetate delayed onset of clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome and brain lesions on MRI. Objective: To compare the effects of early versus delayed glatiramer acetate treatment in the open-label phase of PreCISe. Methods: Patients with a clinically isolated syndrome suggestive of MS with unifocal manifestation and ≥2 T2-weighted brain lesions were randomized to receive glatiramer acetate 20 mg/d (early-treatment, n=198) or placebo (delayed-treatment, n=211) for 36 months or until conversion to CDMS, followed by open-label glatiramer acetate treatment for two years. Results: Early glatiramer acetate treatment reduced CDMS conversion risk by 41% (hazard ratio 0.59, 95% confidence interval 0.44–0.80; p=0.0005) versus delayed-treatment, and was associated with a 972-day delay (185%) in conversion to CDMS, less brain atrophy (−28%, p=0.0209), fewer new...
Multiple Sclerosis Journal, 2014
Background: The immunogenicity of influenza vaccines in MS patients undergoing immunomodulatory t... more Background: The immunogenicity of influenza vaccines in MS patients undergoing immunomodulatory treatment is not well studied. Objectives: This explorative study investigated the influence of immunomodulatory treatment on MS patients receiving pandemic H1N1 (swine flu) vaccination in 2009 and seasonal influenza vaccination in 2010. Methods: We investigated the immune response to pandemic H1N1 vaccination among 113 MS patients and 216 controls during the pandemic of 2009. We also investigated the serological response to seasonal influenza vaccination (2010 – 2011 season) among 49 vaccinated and 62 non-vaccinated MS patients, versus 73 controls. We evaluated these vaccine responses by haemagglutination inhibition assay. Results: MS patients receiving immunomodulatory treatment had reduced protection (27.4%), compared to controls (43.5%) ( p = 0.006), after pandemic H1N1 vaccination (2009). The rates of protection were not influenced by interferon beta treatment (44.4% protected), but ...
Multiple Sclerosis Journal, 2011
Background: In the clinical trials about 9% of natalizumab treated multiple sclerosis (MS) patien... more Background: In the clinical trials about 9% of natalizumab treated multiple sclerosis (MS) patients generated anti-natalizumab antibodies, of which 6% were persistent and 3% transient. The occurrence of antibodies reduced serum levels of natalizumab, decreased bio-efficacy, and abrogated the therapeutic efficacy. Objective: The objective was to assess the frequency of anti-natalizumab antibodies in an unselected cohort of patients from four different countries. Methods: We measured anti-natalizumab antibodies in a large cohort of 4881 unselected patients from four MS centres that systematically measured antibodies in patients treated with natalizumab. We applied the same ELISA assay developed by Biogen Idec and used in the pivotal trials of natalizumab. Results: Antibodies occurred in 4.5% (95% confidence interval, CI: 4.0–5.1%) of the patients, and were persistent in 3.5% (95% CI: 3.0–4.0%) and transient in 1.0% (95% CI: 0.7–1.3%) of the patients. The frequencies of permanently ant...
The Lancet, 2009
developmental assessment without having a creatinine kinase level having been performed. The latt... more developmental assessment without having a creatinine kinase level having been performed. The latter is an easy, sensitive, and inexpensive test that is unfortunately underused in patients who have early signs and symptoms that can be compatible with DMD. In this series, only about one-third of youngsters with motor or global developmental delay had a creatine kinase (CK) obtained at the time of their initial evaluation. In another quarter of children, referral was made to physical, occupational, or speech therapy or to a developmental evaluation program without any diagnostic testing for DMD. A delay in diagnosis would simply be an academic or intellectual faux pas were it not for the fact that shortening the time to diagnosis in fact does have importance. Delay in diagnosis can result in a second pregnancy affected with DMD absent identification of the disorder. In addition to reproductive planning information, some children with DMD will have improvement in their quality of life with specific targeted therapies, albeit noncurative ones. Newborn screening has been advocated for by some as the best solution for the early detection of DMD. Absent that, only an increased awareness on our part will help. The report of Ciafaloni et al shows us how important this heightened awareness of DMD is.
Journal of Neurology, Neurosurgery & Psychiatry, 2007
Nature, Jan 11, 2011
Multiple sclerosis is a common disease of the central nervous system in which the interplay betwe... more Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require ...