Publications by authors named "Harald Nyland"

26 Publications

  • Page 1 of 1

Investigating post-stroke fatigue: An individual participant data meta-analysis.

J Psychosom Res 2018 10 16;113:107-112. Epub 2018 Aug 16.

Centre of Research Excellence in Stroke Rehabilitation and Brain Recovery, Australia; School of Health Sciences and Priority Research Centre for Stroke and Brain Injury, University of Newcastle, Callaghan, Australia.

Objective: The prevalence of post-stroke fatigue differs widely across studies, and reasons for such divergence are unclear. We aimed to collate individual data on post-stroke fatigue from multiple studies to facilitate high-powered meta-analysis, thus increasing our understanding of this complex phenomenon.

Methods: We conducted an Individual Participant Data (IPD) meta-analysis on post-stroke fatigue and its associated factors. The starting point was our 2016 systematic review and meta-analysis of post-stroke fatigue prevalence, which included 24 studies that used the Fatigue Severity Scale (FSS). Study authors were asked to provide anonymised raw data on the following pre-identified variables: (i) FSS score, (ii) age, (iii) sex, (iv) time post-stroke, (v) depressive symptoms, (vi) stroke severity, (vii) disability, and (viii) stroke type. Linear regression analyses with FSS total score as the dependent variable, clustered by study, were conducted.

Results: We obtained data from 14 of the 24 studies, and 12 datasets were suitable for IPD meta-analysis (total n = 2102). Higher levels of fatigue were independently associated with female sex (coeff. = 2.13, 95% CI 0.44-3.82, p = 0.023), depressive symptoms (coeff. = 7.90, 95% CI 1.76-14.04, p = 0.021), longer time since stroke (coeff. = 10.38, 95% CI 4.35-16.41, p = 0.007) and greater disability (coeff. = 4.16, 95% CI 1.52-6.81, p = 0.010). While there was no linear association between fatigue and age, a cubic relationship was identified (p < 0.001), with fatigue peaks in mid-life and the oldest old.

Conclusion: Use of IPD meta-analysis gave us the power to identify novel factors associated with fatigue, such as longer time since stroke, as well as a non-linear relationship with age.
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http://dx.doi.org/10.1016/j.jpsychores.2018.08.006DOI Listing
October 2018

The influence of coping styles on long-term employment in multiple sclerosis: A prospective study.

Mult Scler 2017 Jun 6;23(7):1008-1017. Epub 2016 Sep 6.

KG Jebsen MS Research Centre, Institute of Clinical Medicine, University of Bergen, Bergen, Norway/Norwegian Multiple Sclerosis Registry and Biobank, Department of Neurology, Haukeland University Hospital, Bergen, Norway.

Background: The aim was to investigate predictive values of coping styles, clinical and demographic factors on time to unemployment in patients diagnosed with multiple sclerosis (MS) during 1998-2002 in Norway.

Method: All patients ( N = 108) diagnosed with MS 1998-2002 in Hordaland and Rogaland counties, Western Norway, were invited to participate in the long-term follow-up study in 2002. Baseline recordings included disability scoring (Expanded Disability Status Scale (EDSS)), fatigue (Fatigue Severity Scale (FSS)), depression (Beck Depression Inventory (BDI)), and questionnaire assessing coping (the Dispositional Coping Styles Scale (COPE)). Logistic regression analysis was used to identify factors associated with unemployed at baseline, and Cox regression analysis to identify factors at baseline associated with time to unemployment during follow-up.

Results: In all, 41 (44%) were employed at baseline. After 13 years follow-up in 2015, mean disease duration of 22 years, 16 (17%) were still employed. Median time from baseline to unemployment was 6 years (±5). Older age at diagnosis, female gender, and depression were associated with patients being unemployed at baseline. Female gender, long disease duration, and denial as avoidant coping strategy at baseline predicted shorter time to unemployment.

Conclusion: Avoidant coping style, female gender, and longer disease duration were associated with shorter time to unemployment. These factors should be considered when advising patients on MS and future employment.
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http://dx.doi.org/10.1177/1352458516667240DOI Listing
June 2017

[Mapping of function in chronic fatigue syndrome].

Tidsskr Nor Laegeforen 2015 Sep 22;135(17):1540-1. Epub 2015 Sep 22.

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http://dx.doi.org/10.4045/tidsskr.15.0530DOI Listing
September 2015

Longitudinal follow-up of employment status in patients with chronic fatigue syndrome after mononucleosis.

BMJ Open 2014 Nov 26;4(11):e005798. Epub 2014 Nov 26.

Institute of Clinical Medicine, University of Bergen, Bergen, Norway.

Objective: To examine the effect of early clinical and demographic factors on occupational outcome, return to work or awarded permanent disability pension in young patients with chronic fatigue syndrome (CFS).

Design: Longitudinal cohort study.

Intervention: A written self-management programme including a description of active coping strategies for daily life was provided.

Setting, Participants: Patients with CFS after mononucleosis were evaluated at Department of Neurology, Haukeland University Hospital during 1996-2006 (contact 1). In 2009 self-report questionnaires were sent to all patients (contact 2).

Primary And Secondary Outcome Measures: Primary measure was employment status at contact 2. Secondary measures included clinical symptoms, and Fatigue Severity Scale (FSS) scores on both contacts, and Work and Social Adjustment Scale (WSAS) at contact 2.

Results: Of 111 patients at contact 1, 92 (83%) patients returned the questionnaire at contact 2. Mean disease duration at contact 1 was 4.7 years and at contact 2 11.4 years. At contact 1, 9 (10%) were part-time or full-time employed. At contact 2, 49 (55%) were part-time or full-time employed. Logical regression analysis showed that FSS≥5 at contact 2 was associated with depression, arthralgia and long disease duration (all at contact 1).

Conclusions: About half of younger patients with CFS with long-term incapacity for work experienced marked improvement including full-time or part-time employment showing better outcomes than expected. Risk factors for transition to permanent disability were depression, arthralgia and disease duration.
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http://dx.doi.org/10.1136/bmjopen-2014-005798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248085PMC
November 2014

Brain atrophy and disability progression in multiple sclerosis patients: a 10-year follow-up study.

J Neurol Neurosurg Psychiatry 2014 Oct 19;85(10):1109-15. Epub 2014 Feb 19.

Department of Neurology, School of Medicine and Biomedical Sciences, Buffalo Neuroimaging Analysis Center, University at Buffalo, State University of New York, Buffalo, New York, USA MR Imaging Clinical Translational Research Center, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.

Objectives: To identify MRI biomarkers associated with long-term disability progression in patients with multiple sclerosis (MS), and to define the rate of evolution of global, tissue-specific and regional atrophy in patients with MS over long-term.

Methods: MRI of the brain and clinical neurological assessment was performed in 81 patients at time of first visit and after 5 and 10 years of follow-up. MRI was acquired on 1.5 T scanners. T1-lesion and T2-lesion volumes (LVs) were calculated. Global and tissue-specific atrophy changes were longitudinally assessed, using a direct measurement approach, by calculating percentage volume changes between different time points. Regional tissue volumes for the subcortical deep grey matter (SDGM) structures were also obtained. Disability progression was defined as an increase in Expanded Disability Status Scale of ≥ 1.0 compared to baseline at 5-year and 10-year follow-up.

Results: Over 5 years, patients with disability progression showed significantly increased loss of whole brain (-3.8% vs -2.0%, p<0.001), cortical (-3.4% vs -1.8%, p=0.009) and putamen volume changes (-10.6% vs -3.8%, p=0.003) compared to patients with no disability progression. No significant change in white matter (WM) volume was observed when comparing progressing and non-progressing patients. Over 10 years, there was a trend for greater decrease in whole brain volume (-5.5% vs -3.7%, p=0.015) in the progressing patients. No significant changes in LV measures were detected between the patients with and without disability progression.

Conclusion: This long-term study shows that whole brain, cortical and putamen atrophy occurs throughout the 10-year follow-up of this MS cohort and is more pronounced in the group that showed disability progression at 5, but not at 10 years of follow-up. Overall, GM atrophy showed better association with disease progression than WM atrophy over 5-year and 10-year follow-up.
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http://dx.doi.org/10.1136/jnnp-2013-306906DOI Listing
October 2014

C-reactive protein and homocysteine predict long-term mortality in young ischemic stroke patients.

J Stroke Cerebrovasc Dis 2013 Nov 2;22(8):e435-40. Epub 2013 Jun 2.

Department of Neurology, Haukeland University Hospital, Bergen, Norway. Electronic address:

Background: We investigated the relationship between C-reactive protein (CRP) and homocysteine on follow-up and subsequent mortality in young ischemic stroke patients in a population-based study.

Methods: Young ischemic stroke patients were followed-up on average 6 years after the index stroke. CRP and homocysteine levels were measured and risk factors were recorded, including myocardial infarction, diabetes mellitus, hypertension, smoking, alcoholism, and cancer. Stroke outcome was measured using the modified Rankin Scale score. Subsequent survival was obtained by examining the official population registry. Cox regression analyses were performed.

Results: In total, 198 patients were included in this study (82 [41%] women and 116 [59%] men). The mean age on follow-up was 47.8 years. In total, 36 (18.2%) patients died during the subsequent mean follow-up of 12.4 years. Cox regression analysis revealed that mortality was associated with CRP (hazard ratio [HR] 1.05; P=.001) and homocysteine levels (HR 1.04; P=.02) in patients without dissection. Kaplan-Meier curves grouped by dichotomized CRP (CRP≤1 v >1 mg/L) showed increasing separation between the survival curves, and likewise for dichotomized homocysteine (≤9 v >9 μg/L).

Conclusions: There is an independent association between CRP and homocysteine levels obtained several years after ischemic stroke in young adults and subsequent mortality, even when adjusting for traditional risk factors. This association seems to continue for at least 12 years after the measurements.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.04.031DOI Listing
November 2013

Poststroke fatigue and depression are related to mortality in young adults: a cohort study.

BMJ Open 2013 Mar 1;3(3). Epub 2013 Mar 1.

Department of Neurology, Haukeland University Hospital, Bergen, Norway.

Objectives: To investigate the relationship between poststroke fatigue and depression and subsequent mortality in young ischaemic stroke patients in a population-based study.

Design: A prospective cohort study.

Setting: All surviving young ischaemic stroke patients living in Hordaland County.

Participants: Young ischaemic stroke patients aged 15-50 years at the time of the stroke were invited to a follow-up on an average 6 years after the index stroke. Psychosocial factors and risk factors were registered. Fatigue was self-assessed by the Fatigue Severity Scale (FSS). Depression was measured by Montgomery-Åsberg Depression Rating Scale (MADRS).

Intervention: No intervention was performed.

Primary And Secondary Outcome Measure: Mortality on follow-up.

Results: In total, 190 patients were included. The mean age on follow-up was 48 years and subsequent follow-up period was 12 years. Cox regression analysis showed that mortality was associated with FSS score (p=0.005) after adjusting for age (p=0.06) and sex (p=0.19). Cox regression analysis showed that mortality was associated with MADRS score (p=0.006) after adjusting for age (p=0.10) and sex (p=0.11).

Conclusions: Both fatigue and depression are associated with long-term mortality in young adults with ischaemic stroke. Depression may be linked to higher mortality because of psychosocial factors and unhealthy lifestyles whereas the link between fatigue and mortality is broader including connection to diabetes mellitus, myocardial infarction and psychosocial factors.
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http://dx.doi.org/10.1136/bmjopen-2012-002404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612756PMC
March 2013

Poor health-related quality of life is associated with long-term mortality in young adults with cerebral infarction.

J Stroke Cerebrovasc Dis 2013 Oct 9;22(7):e79-83. Epub 2012 Aug 9.

Department of Neurology, Haukeland University Hospital, Bergen, Norway.

Background: Our aim was to investigate the effect of health-related quality of life (HRQOL) on subsequent mortality in young ischemic stroke patients in a population-based study.

Methods: Young ischemic stroke patients were invited to a follow-up on average 6 years after their index stroke. HRQOL was measured by Short-Form 36 (SF-36) and the Nottingham Health Profile (NPH). Data on socioeconomic and functional states were obtained. Subsequent survival was obtained by examining the official population registry. Multivariate analyses were performed.

Results: One hundred eighty-eight patients were included. The mean age on follow-up was 48 years, and the subsequent follow-up period was 12 years. Cox regression analysis revealed that mortality was associated with NHP sum score (P < .001) after adjusting for age (P = .09), sex (P = .11), and alcoholism (P = .04). Cox regression analyses, including subscores of SF-36 or NHP separately, revealed that mortality was associated with pain (P = .05), sleep disturbances (P = .02), and physical function (P = .02) after adjusting for confounders.

Conclusions: Poor HRQOL is associated with subsequent long-term mortality in young adults with ischemic stroke and this may pertain particularly to pain, sleep disturbances and low physical fitness.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2012.06.010DOI Listing
October 2013

Chronic fatigue syndrome after Giardia enteritis: clinical characteristics, disability and long-term sickness absence.

BMC Gastroenterol 2012 Feb 8;12:13. Epub 2012 Feb 8.

Institute of Clinical Medicine, Department of Neurology, and Unit for Gastroenterology, Department for Medicine, Haukeland University Hospital, Bergen, Norway.

Background: A waterborne outbreak of Giardia lamblia gastroenteritis led to a high prevalance of long-lasting fatigue and abdominal symptoms. The aim was to describe the clinical characteristics, disability and employmentloss in a case series of patients with Chronic Fatigue Syndrome (CFS) after the infection.

Methods: Patients who reported persistent fatigue, lowered functional capacity and sickness leave or delayed education after a large community outbreak of giardiasis enteritis in the city of Bergen, Norway were evaluated with the established Centers for Disease Control and Prevention criteria for CFS. Fatigue was self-rated by the Fatigue Severity Scale (FSS). Physical and mental health status and functional impairment was measured by the Medical Outcome Severity Scale-short Form-36 (SF-36). The Hospital Anxiety and Depression Scale (HADS) was used to measure co-morbid anxiety and depression. Inability to work or study because of fatigue was determined by sickness absence certified by a doctor.

Results: A total of 58 (60%) out of 96 patients with long-lasting post-infectious fatigue after laboratory confirmed giardiasis were diagnosed with CFS. In all, 1262 patients had laboratory confirmed giardiasis. At the time of referral (mean illness duration 2.7 years) 16% reported improvement, 28% reported no change, and 57% reported progressive course with gradual worsening. Mean FSS score was 6.6. A distinctive pattern of impairment was documented with the SF-36. The physical functioning, vitality (energy/fatigue) and social functioning were especially reduced. Long-term sickness absence from studies and work was noted in all patients.

Conclusion: After giardiasis enteritis at least 5% developed clinical characteristics and functional impairment comparable to previously described post-infectious fatigue syndrome.
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http://dx.doi.org/10.1186/1471-230X-12-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292445PMC
February 2012

Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.

PLoS One 2011 19;6(10):e26358. Epub 2011 Oct 19.

Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.

Background: Chronic fatigue syndrome (CFS) is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti-CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients.

Methods And Findings: In this double-blind, placebo-controlled phase II study (NCT00848692), 30 CFS patients were randomised to either Rituximab 500 mg/m(2) or saline, given twice two weeks apart, with follow-up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV) was not detected in any of the patients. The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67%) in the Rituximab group and in two out of 15 patients (13%) in the Placebo group (p = 0.003). Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44). Four Rituximab patients had clinical response durations past the study period. General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed), with differences between the Rituximab and Placebo groups between 6-10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative. There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening.

Conclusion: The delayed responses starting from 2-7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses. The present findings will impact future research efforts in CFS.

Trial Registration: ClinicalTrials.gov NCT00848692.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026358PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198463PMC
February 2012

Prevalence and incidence of multiple sclerosis in Oppland County: a cross-sectional population-based study in a landlocked county of Eastern Norway.

Acta Neurol Scand 2011 Oct 10;124(4):250-7. Epub 2010 Dec 10.

Department of Rehabilitation, Sykehuset Innlandet HF, Gjøvik, Norway.

OBJECTIVES - We report the prevalence and incidence rates of multiple sclerosis (MS) in Oppland County, Norway. METHODS - Records from all patients diagnosed with MS at the two Oppland County hospitals, Gjøvik and Lillehammer during 1989-2001 were evaluated. In addition, all general practitioners in Oppland County reported their patients into the study. RESULTS - The age-adjusted prevalence rate of definite MS was 174.4/ 100 000 on the prevalence day 1 January 2002. When the probable cases were included, the prevalence rate rose to 185.6/100 000. The highest prevalence rates were detected in the northern mountain areas, thus corroborating the results from previous local surveys 30-50 years ago. The prevalence of MS was statistically significantly associated with climatic, socioeconomic and geographic variables in the county. The age-adjusted incidence of definite and probable MS in Oppland County was 6.6/100 000 during 1989-1993 increasing to 7.6/100 000 during 1994-1998. DISCUSSION - We found the highest prevalence rates of MS ever reported in Norway. Our findings indicate a possible influence of environmental factors.
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http://dx.doi.org/10.1111/j.1600-0404.2010.01465.xDOI Listing
October 2011

How long can you keep working with benign multiple sclerosis?

J Neurol Neurosurg Psychiatry 2011 Jan 27;82(1):78-82. Epub 2010 Aug 27.

The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.

Objective: To study employment in benign multiple sclerosis (MS), the frequency of employment was analysed and the effect of early clinical and demographic factors on time to disability pension was evaluated in a population based MS cohort. The frequency of depression, cognitive function, fatigue and pain between benign and non-benign MS patients was compared, and their impact on employment in benign MS was studied.

Methods: All 188 patients alive, including 60 benign patients with onset of MS during 1976-1986 in Hordaland County, Western Norway, were interviewed and clinically examined in 2003. The Expanded Disability Status Scale (EDSS), depression (Beck Depression Inventory), cognitive function, fatigue, pain, year of disability pension, employment and type of occupation were registered. Benign MS was defined as an EDSS score ≤3.0 at least 10 years after disease onset.

Results: After a mean disease duration of 22.2 years, 32.4% of the cohort were still employed. A relapsing-remitting course, higher educational level and light physical work were significantly associated with longer time to disability pension in the general MS population. Thirty-nine (65.0%) benign MS patients were employed, independent of light or heavy physical work. Mild depressive symptoms were markedly associated with not being employed in benign MS (OR=7.3).

Conclusions: A relapsing-remitting course, higher educational level and light physical work significantly predicted longer time to disability pension in the total MS population. Among the benign MS patients, depressive symptoms, although mild, were strongly associated with not being employed.
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http://dx.doi.org/10.1136/jnnp.2010.210732DOI Listing
January 2011

Postinfectious and chronic fatigue syndromes: clinical experience from a tertiary-referral centre in Norway.

In Vivo 2010 Mar-Apr;24(2):185-8

Department of Neurology, Haukeland University Hospital, University of Bergen, Bergen, Norway.

Background: We aimed to compare patients reporting acute infection with those reporting no infection at onset of chronic fatigue syndrome (CFS).

Patients And Methods: This study includes 873 patients with CFS referred to a tertiary centre on average 4.8 years after symptom onset. Assessment was by both observer query and self-reports. Antibody analyses against infectious agents including Epstein-Barr virus and enterovirus were performed in a majority of patients.

Results: Females comprised 75.3% of the patient group, and the mean age was 33 years. Initial infection was reported by 77%. There was no difference as to antibody analyses. Logistic regression showed that initial infection was independently associated with acute onset of fatigue, improvement of fatigue at referral, and the following symptoms at referral: fever, tender lymph nodes, and myalgia.

Conclusion: CFS patients with initial infection as a precipitating factor more often report acute onset of fatigue, more frequent accompanying symptoms, and more frequent improvement on referral than do patients without initial infection.
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May 2010

Vaccination as teenagers against meningococcal disease and the risk of the chronic fatigue syndrome.

Vaccine 2009 Jan 5;27(1):23-7. Epub 2008 Nov 5.

Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.

The etiology of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) is unknown. In Norway, a vaccine against Neisseria meningitides group B was administered to teenagers in 1988--1989 in a protection trial. In order to estimate the relative risk of CFS/ME according to vaccine history, we conducted a case-control study in 2007, with 201 cases diagnosed at one of two hospitals and 389 controls. The adjusted odds ratio for CFS/ME was 1.06 (95% CI: 0.67-1.66) for subjects who received the active vaccine contrasted to subjects who did not. Using this design, no statistically significant association between vaccination against meningococcal disease in teenagers and occurrence of CFS/ME could be observed.
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http://dx.doi.org/10.1016/j.vaccine.2008.10.043DOI Listing
January 2009

Vitamin D-dependent rickets as a possible risk factor for multiple sclerosis.

Arch Neurol 2008 Jun;65(6):809-11

Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Background: Vitamin D-dependent rickets type I (VDDR I) (OMIM 264700) is a rare hereditary condition caused by a mutation in CYP27B1. Vitamin D is emerging as an important risk factor for susceptibility to multiple sclerosis (MS), but there have been no studies on the possible association between hereditary rickets and this disease.

Objective: To investigate the association between VDDR I and MS.

Design: Case studies.

Setting: Haukeland University Hospital, Bergen, Norway.

Patients: Three patients in 2 families with a co-occurrence of VDDR I and MS.

Results: All 3 patients had VDDR I verified by genetic testing and fulfilled the Poser criteria for MS. Two of the patients have undergone magnetic resonance imaging, which confirmed the diagnosis of long-lasting MS.

Conclusions: Vitamin D-dependent rickets type I is a very uncommon genetic subtype of rickets. We have identified 3 patients with this disease who later developed MS. We propose that VDDR I and possibly other hereditary rickets mutations that influence vitamin D metabolism could be risk factors for this disease.
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http://dx.doi.org/10.1001/archneur.65.6.809DOI Listing
June 2008

mtDNA nt13708A variant increases the risk of multiple sclerosis.

PLoS One 2008 Feb 13;3(2):e1530. Epub 2008 Feb 13.

Section of Immunogenetics, University of Rostock, Rostock, Germany.

Background: Mitochondrial DNA (mtDNA) polymorphism is a possible factor contributing to the maternal parent-of-origin effect in multiple sclerosis (MS) susceptibility.

Methods And Findings: In order to investigate the role of mtDNA variations in MS, we investigated six European MS case-control cohorts comprising >5,000 individuals. Three well matched cohorts were genotyped with seven common, potentially functional mtDNA single nucleotide polymorphisms (SNPs). A SNP, nt13708 G/A, was significantly associated with MS susceptibility in all three cohorts. The nt13708A allele was associated with an increased risk of MS (OR = 1.71, 95% CI 1.28-2.26, P = 0.0002). Subsequent sequencing of the mtDNA of 50 individuals revealed that the nt13708 itself, rather than SNPs linked to it, was responsible for the association. However, the association of nt13708 G/A with MS was not significant in MS cohorts which were not well case-control matched, indicating that the significance of association was affected by the population structure of controls.

Conclusions: Taken together, our finding identified the nt13708A variant as a susceptibility allele to MS, which could contribute to defining the role of the mitochondrial genome in MS pathogenesis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0001530PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2217590PMC
February 2008

Reduced health-related quality of life in former North Sea divers is associated with decompression sickness.

Occup Med (Lond) 2007 Aug 4;57(5):349-54. Epub 2007 Jun 4.

Department of Occupational Medicine, Haukeland University Hospital, Bergen 5021, Norway.

Background: Diving is associated with long-term effects on several organ systems.

Aim: The objective was to investigate the impact of decompression sickness (DCS) and diving exposure on health-related quality of life (HRQL) in former Norwegian North Sea divers.

Methods: HRQL was recorded by a questionnaire in the cohort of 375 Norwegian North Sea divers registered before 1990. Demographic data, relevant health data and data on diving education, history of DCS and SF-36 were recorded in 230 divers.

Results: All SF-36 sub-scores were significantly reduced compared with Norwegian norms. Reduced scores were seen for all scales among divers who reported previous DCS compared to those without DCS. A decreasing trend in scores was seen when comparing no DCS, skin or joint DCS and neurological DCS. There was a decreasing trend in scores related to number of days in saturation and maximal depth. Stratification on DCS showed that the impact of saturation diving was present only in divers with DCS.

Conclusions: HRQL was reduced in this study sample of divers. Having had DCS during the diving career contributed significantly to the reduction in all SF-36 scales, and apparently neurological DCS has the most pronounced impact. Cumulative diving exposure including days in saturation and maximal depth contributed to a reduced HRQL.
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http://dx.doi.org/10.1093/occmed/kqm032DOI Listing
August 2007

Health-related quality of life among young adults with ischemic stroke on long-term follow-up.

Stroke 2006 May 6;37(5):1232-6. Epub 2006 Apr 6.

Department of Neurology, Haukeland University Hospital, University of Bergen, Bergen, Norway.

Background And Purpose: We sought to compare health-related quality of life (HRQoL) in young adults with ischemic stroke on long-term follow-up with controls and to evaluate HRQoL in clinically relevant patient subgroups.

Methods: HRQoL was determined with the use of the 8 subscales of the Short-Form General Health Survey (SF-36). Subgroups of patients were defined by sex, age, functional status (modified Rankin Scale), marital status, education, depression (Montgomery-Asberg Depression Rating Scale), and fatigue (Fatigue Severity Scale). SF-36 scores among patients were compared with SF-36 scores among age- and sex-matched controls and SF-36 scores available from the general Norwegian population.

Results: SF-36 scores were obtained after a mean follow-up of 6.0 years among 190 young adults with ischemic stroke during 1988-1997 and among 215 responding controls (55%). The difference in HRQoL between patients, controls, and the general Norwegian population was restricted mainly to the 3 subscales physical functioning, general health, and social functioning (P<0.001). Subgroup analysis showed significantly reduced scores for all SF-36 items among patients who were depressed, suffered from fatigue, or unemployed. Linear regression analysis showed that fatigue and depression were major independent variables correlated with low HRQoL.

Conclusions: Compared with controls and the general Norwegian population, low level of HRQoL among young adults with ischemic stroke was most pronounced in regard to physical functioning. Early identification and treatment of depression, fatigue, and physical disability may potentially improve HRQoL among stroke patients.
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http://dx.doi.org/10.1161/01.STR.0000217652.42273.02DOI Listing
May 2006

Fatigue at long-term follow-up in young adults with cerebral infarction.

Cerebrovasc Dis 2005 22;20(4):245-50. Epub 2005 Aug 22.

Department of Neurology, Haukeland University Hospital, University of Bergen, Bergen, Norway.

Background: To study the impact of fatigue in young ischaemic stroke patients.

Methods: The Fatigue Severity Scale score was obtained in 192 patients (mean time 6.0 years after the stroke) and 212 controls.

Results: Fatigue was associated with cerebral infarction in a multivariate analysis of patients and controls (p = 0.002). Fatigue was independently associated with unfavourable functional outcome (p = 0.001), depression (p < 0.001), and basilar artery infarction through interaction with the modified Rankin Scale score (p = 0.047) in patients.

Conclusion: Fatigue is frequent in young adults with cerebral infarction. Stroke-related factors independently associated with fatigue include functional outcome. Stroke location may influence fatigue.
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http://dx.doi.org/10.1159/000087706DOI Listing
November 2005

Concordance for disease course and age of onset in Scandinavian multiple sclerosis coaffected sib pairs.

Mult Scler 2004 Feb;10(1):5-8

Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Background: Investigation of coaffected sib pairs is one method to determine the genetic influence on the clinical presentation of many complex diseases, such as multiple sclerosis (MS). Investigation of the clinical concordance in coaffected sib pairs may be a prerequisite to identify genes that modify the clinical outcome. The aim of this study was to investigate a possible genetic influence on selected demographic and clinical variables among familial Scandinavian MS cases.

Material And Methods: We identified 136 Caucasian Scandinavian families with MS coaffected sib pairs from Denmark, Norway and Sweden. Cohen's kappa coefficient and the intraclass correlation coefficient were used to assess concordances in sib pairs. Furthermore, clinical features and HLA-DR2 carrier status were compared among the probands of sib pairs.

Results: We found significant concordance of the disease course (kappa = 0.28, P < 0.001) and adjusted age of onset (r = 0.23, P = 0.028). Among probands of sib pairs, HLA-DR2 carrier patients had a younger age of onset (P = 0.024).

Conclusion: Analyses of Scandinavian coaffected sib pairs suggest that disease course and age of onset are partly under genetic control. Furthermore, HLA-DR2 in probands of sib pairs suggests importance for age of onset.
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http://dx.doi.org/10.1191/1352458504ms975oaDOI Listing
February 2004

Subpial demyelination in the cerebral cortex of multiple sclerosis patients.

J Neuropathol Exp Neurol 2003 Jul;62(7):723-32

Department of Neurology, Haukeland Hospital, Bergen, Norway.

The extent and pattern of demyelination in the cerebral cortex was determined in 78 tissue blocks from the brains of 20 multiple sclerosis (MS) patients and 28 tissue blocks from 7 patients without neurological disease. Tissue blocks from 4 predetermined areas (cingulate gyrus, frontal, parietal, and temporal lobe) were studied, irrespective of macroscopically evident MS plaques. All tissue blocks contained cerebral cortex and periventricular and/or subcortical white matter. One hundred and nine demyelinating lesions were detected in the cerebral cortex, of which 92 (84.4%) were purely intracortical and 17 (15.6%) were lesions extending through both white and gray matter areas. In 5 of the 20 MS brains, subpial demyelination was extensive in the 4 widely spaced cortical areas studied, thus considered to represent a general cortical subpial demyelination. The percentage of demyelinated area was significantly higher in the cerebral cortex (mean 26.5%, median 14.1%) than in white matter (mean 6.5%, median 0%) (p = 0.001). Both gray and white matter demyelination was more prominent in the cingulate gyrus than in the other areas examined (p < 0.05). These results indicate that the cerebral cortex is likely to be a predilection site for MS lesions and identify general cortical subpial demyelination as a distinct pattern occurring in a significant subpopulation of MS patients.
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http://dx.doi.org/10.1093/jnen/62.7.723DOI Listing
July 2003

TNF-alpha and -beta gene polymorphisms in multiple sclerosis: a highly significant role for determinants in the first intron of the TNF-beta gene.

Autoimmunity 2002 Sep;35(6):377-80

Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.

Tumor necrosis factor (TNF)-alpha and TNF-beta are proinflammatory cytokines that have been implicated in the pathogenesis of several autoimmune diseases. The aim of this investigation was to determine whether a determinant in the first intron of the TNF-beta gene (TNF-beta(+252)) and two promoter-region polymorphisms of the TNF-alpha gene (TNF-alpha(-308) and TNF-alpha(-238)) affect susceptibility to multiple sclerosis (MS). DNA samples from 133 Caucasian MS patients and 148 healthy controls from Norway were genotyped for several polymorphic determinants, using polymerase chain reaction-based restriction fragment length polymorphisms (PCR-RFLP) methods. TNF-beta(+252) genotypes were significantly associated with MS: The frequency of TNF-beta 2,2 was increased (p = 0.00009) while the frequency of TNF-beta 1,2 was decreased (p = 0.0012) in MS patients as compared to controls. TNF-alpha genotypes were not associated with MS. These results suggest that the TNF-beta gene plays a significant role in the etiopathogenesis of MS.
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http://dx.doi.org/10.1080/0891693021000021549DOI Listing
September 2002

[Neurologic decompression sickness in sports divers].

Tidsskr Nor Laegeforen 2002 Jun;122(17):1649-51

Nevrologisk avdeling, Haukeland Sykehus 5021 Bergen.

Background: Sports diving is a popular recreational activity. Sports divers presenting with acute decompression sickness may exhibit residual neurologic and neuropsychological symptoms during follow-up, in spite of appropriate treatment.

Material And Methods: A retrospective review of medical records was carried out for sports divers admitted to the department of neurology at Haukeland University Hospital during 1997.

Results: 11 out of 20 divers experienced residual neurological symptoms after treatment. Five responded poorly to treatment, with 50% or more residual clinical score. These patients tended to be older, had performed deeper dives, and more repetitive diving. Seven divers had increased slow wave activity in EEG on initial recording, in two the EEG changes persisted after treatment.

Interpretation: In this small series of sports divers with decompression sickness and arterial gas embolism, most neurologic symptoms responded to hyperbaric treatment. However, more than one half of the divers had residual neurological symptoms on discharge. Sensory loss and asymmetrical reflexes were the most common residual findings.
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June 2002

Interleukin-10 promoter polymorphisms in patients with multiple sclerosis.

J Neurol Sci 2002 Oct;202(1-2):93-7

The Multiple Sclerosis National Competence Centre, Department of Neurology, Haukeland Hospital, University of Bergen, N-5021 Bergen, Norway.

The expression level of interleukin-10 (IL-10) is related to polymorphisms -1082 (G/A), -819 (T/C) and -592 (A/C) in the promoter region of the IL-10 gene. The distribution of these polymorphisms was analyzed to determine whether they could influence disease susceptibility or clinical course in multiple sclerosis (MS). The -1082 (G/A), -819 (T/C) and -592 (A/C) genotypes were similarly distributed between MS patients and the controls. The primary progressive MS patients with the low IL-10 expression haplotype showed a trend towards a worse clinical outcome than did patients with medium- or high-expression haplotypes (P = 0.056). The polymorphisms did not influence the clinical course in patients with relapsing-remitting MS.
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http://dx.doi.org/10.1016/s0022-510x(02)00246-0DOI Listing
October 2002
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