Biomedical subjects
Publications and source records attributed to K M Myhr.
After a mean of 6 years, the frequencies of later vascular events (recurrent ischemic stroke or myocardial infarction) in 232 young ischemic stroke patients (younger than 50 years) with none to five traditional risk factors were 2.1%, 6%, 19%, 26%, 30%, and 67% (p < 0.001). Long-term secondary preventive medication may not be indicated in young ischemic stroke patients with no risk factor.
OBJECTIVE: To explore the range of psychiatric symptoms in patients with multiple sclerosis (MS) and their association with neurological disability. METHOD: Patients diagnosed with MS during 1998-2000 in Rogaland and Hordaland counties, western Norway, were included. Psychiatric symptoms were assessed by the Neuropsychiatric Inventory (NPI). Patients with systemic lupus erythematosus (SLE) served as controls. RESULTS: Eighty-six of 93 eligible MS patients were included, and 80% showed at least one psychiatric symptom. The most frequent symptoms were depression (59%), sleep disturbance (48%), irritability/emotional lability (42%), and apathy (31%). Depression was associated with higher disability score. MS patients showed significantly higher NPI irritability score (P = 0.002), appetite disturbance score (P < 0.001), and apathy score (P = 0.01) than SLE patients. CONCLUSION: Neuropsychiatric symptoms occur frequently in patients with MS. Irritability and apathy are independent of disability and chronic disease and represent unique disease manifestations.
OBJECTIVE: To calculate the prevalence and incidence of multiple sclerosis (MS) in Nord-Trøndelag County, Norway. MATERIAL AND METHODS: The study comprised everyone diagnosed with MS according to the Poser criteria. On 1 January 2000 a total of 208 were identified: 130 women (62.5%) and 78 men (37.5%). We calculated the crude and age-adjusted annual incidence rates from 1974 to 1999. RESULTS: The prevalence on 1 January 2000 was 163.6 of 100,000, 204.8 of 100,000 for women and 122.6 of 100,000 for men. The age-adjusted annual incidence increased from 3.9 to 5.6 per 100,000 from 1974 to 1999; women from 4.6 to 6.3 and men from 2.2 to 4.4. After 1984, the incidence among women increased most, peaking at 10.2 per 100,000 in 1984-88. CONCLUSIONS: MS incidence is increasing in Nord-Trøndelag County. The prevalence is among the highest ever in Norway.
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Genetic factors influence susceptibility to multiple sclerosis but the responsible genes remain largely undefined, association with MHC class II alleles being the only established genetic feature of the disease. The Nordic countries have a high prevalence of multiple sclerosis, and to further explore the genetic background of the disease, we have carried out a genome-wide screen for linkage in 136 sibling-pairs with multiple sclerosis from Denmark, Finland, Norway and Sweden by typing 399 microsatellite markers. Seventeen regions where the lod score exceeds the nominal 5% significance threshold (0.7) were identified-1q11-24, 2q24-32, 3p26.3, 3q21.1, 4q12, 6p25.3, 6p21-22, 6q21, 9q34.3, 10p15, 10p12-13, 11p15.5, 12q21.3, 16p13.3, 17q25.3, 22q12-13 and Xp22.3. Although none of these regions reaches the level of genome-wide significance, the number observed exceeds the 10 that would be expected by chance alone. Our results significantly add to the growing body of linkage data relating to multiple sclerosis.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) of unknown etiology. Nitric oxide (NO) is a free radical that participates in a variety of biological processes. It is an important mediator in the immune response. Several studies indicate involvement of NO in the pathogenesis of MS. We studied five markers within the three NO synthase genes with regards to susceptibility and disease course in 156 affected sib-pairs and in 96 "benign" and 96 "severe" definite MS patients and 148 controls. We found no significant association or evidence for linkage in our data sets.
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.
BACKGROUND: Myxomas are the most common type of primary cardiac tumours. As they are most often located in the left atrium, primary neurological manifestations are often multiple embolic infarcts in the central nervous system. MATERIAL AND METHODS: We describe a patient with acute aphasia due to left temporal haemorrhage. Later he developed acute ataxia due to right cerebellar infarct. RESULTS: Magnetic resonance also showed multiple supra- and infratentorial infarcts. Echocardiography revealed a myxoma in the left atrium which was treated by surgical excision. There were no signs of myxoma recurrence or embolic infarcts at follow-up. INTERPRETATION: Echocardiography should be included in the diagnostic work-up of patients with cerebrovascular events, especially in young patients with multiple infarcts.
The T cell specific adapter protein (TSAd) encoded by the SH2D2A gene is involved in the control of T cell activation. The gene is located in the 1q21 region, which has been implicated in susceptibility to experimental allergic encephalomyelitis in the mouse. We therefore evaluated whether a polymorphic GA repeat (GA(13)-GA(33)) within the promoter region of the SH2D2A gene shows association to multiple sclerosis (MS). The frequency of the short alleles GA(13-16) was increased among 313 Norwegian MS patients compared to 277 healthy controls (0.332 vs 0.249, OR 1.5, Pc = 0.03). Transmission disequilibrium analysis in 146 Scandinavian families with at least two affected sibs showed increased transmission of GA(16) to MS patients. No linkage or association of MS to four genetic markers flanking the SH2D2A gene was observed. After activation of naive CD4(+) T cells, T cells homozygous for MS associated short alleles displayed lower level of TSAd ex vivo than T cells carrying at least one long allele, which were not associated to MS. Since the SH2D2A protein modulates T cell activation, this may be a mechanism for how short SH2D2A alleles confer susceptibility to develop MS.
Four genomic screens for linkage in multiple sclerosis (MS) have been reported. They confirmed the established role of the human leucocyte antigen (HLA) complex genes in MS and, in addition, suggested the importance of a few other chromosomal segments. Here we report evidence for the importance of 3p14-13 region identified by suggestive linkage in genomic screens from Canada and the United Kingdom. When studying 146 Nordic MS multiplex families, mostly affected sib-pairs, with eight microsatellite markers, spanning a 36-cM region, we observed a two-point non-parametric linkage (NPL) score of 2.39 (P = 0.007) by the GENEHUNTER package for marker D3S1285 and a multipoint NPL score of 1.20 in the same region. Association studies in Swedish MS patients revealed modest allelic associations of uncertain significance not supported by transmission analysis. Analysis of the trinucleotide repeat sequence of the SCA7 gene in Swedish index cases did not reveal expansions. We conclude that support was obtained for the location of a gene or genes with importance for MS susceptibility in 3p14-13 region.
Seventy-seven healthy Ethiopians were genotyped for polymorphisms in the immunoglobulin G Fc receptors (FcgammaR) FcgammaRIIa, FcgammaRIIIa and FcgammaRIIIb, including the SH allele. The genotype and allele frequencies were compared with those of 96 healthy Norwegians. Ethiopians had higher frequencies of the SH-FcgammaRIIIb (P = 0.001), FcgammaRIIIa-158 V (P = 0.026) and FcgammaRIIIb-Na2 (P = 0.046) alleles. The genotype distributions of FcgammaRIIa, FcgammaRIIIa and FcgammaRIIIb, however, did not differ significantly from those of the Norwegians. The data were also compared with those reported from studies on other ethnic groups. The variation of different polymorphisms both within and between ethnic groups may influence differences in the incidence rates of infectious and autoimmune diseases.
OBJECTIVE: To evaluate disability and prognosis in an untreated population-based incidence cohort of multiple sclerosis (MS) patients. METHODS: The Expanded Disability Status Scale (EDSS) score was recorded in 220 MS patients. Disease progression was assessed by life table analysis with different endpoints and multivariate Cox regression analysis was performed for evaluation of prognostic factors. RESULTS: The probability of being alive after 15 years was 94.8 +/- 1.8% (s.e.), of managing without a wheelchair (EDSS < 7.0) 75.8 +/- 3.2%, of walking without walking assistance (EDSS<6.0) 60.3 +/- 3.6%, and of not being awarded a disability pension 46.0 +/- 3.7%. The probability of still having a relapsing-remitting (RR) course after 15 years was 62.0 +/- 4.1%. A RR course and long interval between the initial (onset) and second episode (> 3 years) predicted favorable outcome. There was also a trend towards favorable outcome in patients with optic neuritis, sensory symptoms and low age at onset but these factors were associated with the RR course. Motor symptoms and high age at onset indicated unfavorable outcome, but these factors were associated with the primary progressive course. CONCLUSIONS: A RR course and long inter-episode intervals in the early phase of the disease were associated with a better outcome. Other onset characteristics indicating a favorable outcome were associated with the RR course while characteristics indicating an unfavorable outcome were associated with the PP course.
OBJECTIVE: Physical disability explains only part of the reduced quality of life found among multiple sclerosis (MS) patients. Bladder dysfunction and sexual disturbance are frequent and distressing problems for MS patients. We therefore estimated the relationship between the presence and degree of sexual disturbance/bladder dysfunction and the patients' quality of life as measured by the SF-36 Health Survey. METHODS: We performed a cross-sectional study of all individuals with the onset of MS between 1976 and 1986 in Hordaland County, Norway. The disease duration at examination was 9-19 years; 194 patients (94%) participated. RESULTS: Fifty-three per cent of the patients with low physical disability (Expanded Disability Status Scale (EDSS) < or = 4.0) reported disease-related sexual disturbance and 44% had bladder dysfunction according to the Incapacity Status Scale. The corresponding figures for the patients with a high physical disability (EDSS > 4.0) were 86 and 81% respectively. The patients with sexual disturbance had markedly and significantly reduced scores on all eight SF-36 scales, this was after adjustment for disease development measured by the EDSS. The patients without sexual disturbance scored 0.5 s.d. lower than a normal population on the social functioning scale, whereas those with marked sexual disturbance scored 1.5 s.d. lower. Similar results were found for the patients with bladder dysfunction. CONCLUSION: Bladder and sexual problems are associated with a marked reduction in the quality of life, also among patients with otherwise low disability. This underlines the need for identifying and treating these problems.
Sera from patients with MS treated with recombinant interferon (rIFN) alpha-2a, rIFNbeta-1a, or rIFNbeta-1b were analyzed for cross-reacting neutralizing antibodies (NAB). Because cross-reactivity was not found, switching treatment from rIFNbeta-1a or rIFNbeta-1b to rIFNalpha-2a might provide a secondary treatment response in patients with NAB to rIFNbeta-1a or rIFNbeta-1b. A positive treatment response also might be achieved by switching NAB rIFNalpha-2a-positive patients to rIFNbeta-1a or rIFNbeta-1b.
The authors studied immunoglobulin G (IgG) Fc receptor (FcgammaR) IIA, IIIA, and IIIB polymorphisms in 62 patients with Guillain-Barré syndrome (GBS) and in 89 healthy controls. The FcgammaR genotypes and allele frequencies did not differ significantly between the patients with GBS and the controls. Patients homozygous for the FcgammaRIIIB neutrophil antigen (NA) 1 allele had a significantly less severe disease than patients heterozygous or homozygous for the NA2 allele. The FcgammaRIIIB NA1/NA1 genotype has high affinity for IgG1 and IgG3, and clearance of circulating autoantibodies and immune complexes may therefore be of importance in the pathogenesis of GBS.
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.
Multiple sclerosis (MS) is a multifactorial disease in which genetic and environmental factors apparently have a major influence on the susceptibility and course of the disease. In the present study we have investigated the genetic basis and subclass levels of IgG in MS. Hundred and thirty-six Norwegian patients with MS and 92 controls were genotyped for IgG allotypes of the GM and KM systems. IgG and IgG subclasses were quantified in sera from 115 MS patients and 20 controls. Neither GM nor KM allo-, haplo- or genotypes were significantly correlated with susceptibility, severity or course of the disease. The G1M (3) (3), G2M (23) (23) and G3M (5) (5) allotypes were significantly correlated with high serum levels of IgG3, whereas high IgG2 levels were correlated with G1M (3) (3) and G2M (23) (23) in both patients and controls. Serum levels of IgG subclasses were not significantly correlated with course or severity of the disease. The results indicate no major role for IgG allotypes or IgG subclass levels in the pathogenesis of MS.
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.