Health related quality of life in patients recently diagnosed with multiple sclerosis.

OBJECTIVE: To describe a representative population of patients recently diagnosed with MS in terms of both motor and non-motor disability. In particular we wanted to examine the HRQoL in this population to get a better understanding of what impact various clinical features have on the patients' experience of distress in the early phase of the disease. METHODS: Ninety three patients diagnosed with MS in Hordaland and Rogaland county in 1998-2000 and 96 healthy controls were examined through questionnaires on HRQoL (SF-36), depression (Beck's depression inventory), fatigue (fatigue severity scale) and apathy (Starkstein's apathy scale). The patients also underwent neurological examination including the expanded disability status scale and the Multiple Sclerosis Functional Composite, as well as the symbol digit memory test and the selective reminder test. RESULTS: Patients with MS reported a lower HRQoL than the controls with a mean physical health summary score of 57.3 compared to 84.5 (P < 0.001), and a mental health summary score of 66.4 vs 79.2 (P < 0.001). The controls scored significantly higher on all SF-36 sub scores except for bodily pain. The incidence of fatigue was 71% in patients compared to 27% in controls (P < 0.001), whereas 46% of patients vs 18% of controls reported depression (P < 0.001). The mean score for apathy was significantly higher among patients. CONCLUSIONS: Patients with recently diagnosed MS reported significantly lower on both physical and mental aspects of HRQoL compared with controls. Depression, fatigue and apathy were more common and more severe in MS. We found no correlation between cognitive decline and HRQoL scores.

Risk factor burden predicts long-term mortality in young patients with arterial cerebral infarction.

OBJECTIVE: The aim was to investigate risk factors separately and in sum in relation to long-term mortality after arterial cerebral infarction in young adults. MATERIALS AND METHODS: Mortality in relation to the number of risk factors (smoking, hypertension, hypercholesterolemia, diabetes mellitus, myocardial infarction, angina pectoris, and intermittent claudication known at the time of the index stroke) and etiology was studied in a population of young adults with first-ever arterial ischemic stroke at an age < 50 years. Cox regression analyses were performed. RESULTS: After a mean follow-up time of 18 years (the longest follow-up study after cerebral infarction in young adults), 12.5% with no risk factor had died while the corresponding frequencies in patients with 1-3 or more risk factors were 18.5%, 25.4%, and 53.1%, respectively (P < 0.001). The number of risk factors was associated with mortality on Cox regression analysis [hazard ratio (HR) = 1.6, P = 0.001]. A separate Cox regression analysis showed mortality to be associated with diabetes mellitus (HR = 3.0, P = 0.001), myocardial infarction (HR = 3.1, P = 0.001), and alcoholism (HR = 6.3, P < 0.001). CONCLUSION: Increasing number of traditional risk factors is associated with long-term mortality in young adults with cerebral infarction indicating aggressive long-term secondary preventive treatment in selected patients.

The cost of multiple sclerosis in Norway.

Health economic aspects have been increasingly important during introduction of new treatments for multiple sclerosis. As a partial response for Norway, a cost-of-illness study was carried out to estimate the yearly cost of the illness to society and relate costs and patients' quality of life to illness severity. Estimated cost to society was Euro 439 million in 2002 exclusive of the cost of reduced quality of life. The cost per patient was close to Euro 65,000. Account taken of methodological differences, the results compare to results for Sweden, Norway's closest neighboring country. The illness reduced patients' quality of life with 0.26. More patients were early retired because of their MS in Norway than in any of nine other European countries comprised by a recent European study, illustrating a liberal practice in Norway. The Norwegian cost of unpaid assistance was almost identical to the Swedish cost that was the lowest found across the countries in the European study. When related to illness severity, the cost per patient increased, and the patients' experienced quality of life decreased with increasing EDSS levels in line with what has been found for other countries. Cost-of-MS studies have been carried out for a number of countries. Together they contribute to our understanding of the economic consequences of multiple sclerosis and, if their results are related to illness severity, also provide valuable information for further economic analyses of treatment and medication. Our study adds to this.

Benign multiple sclerosis: a need for a consensus.

OBJECTIVES: To investigate the impact of different definitions on the frequency of benign multiple sclerosis (MS) in patients with a long follow-up, and to study the presence of non-motor symptoms and employment across the definitions. MATERIALS AND METHODS: All patients alive (n = 188) with disease onset during 1976-1986 in Hordaland County, Norway, were clinically examined including the Expanded Disability Status Scale (EDSS) in 2003. Non-motor symptoms which included depression, cognitive impairment, fatigue and pain, and employment status were also registered. Three definitions of benign MS were used based on the following EDSS cut-off values: 2.0, 3.0 and 4.0. Two additional definitions were added using an EDSS

Coping with multiple sclerosis: a 5-year follow-up study.

OBJECTIVES: To examine how coping styles among patients with multiple sclerosis (MS) change over time and how patients' coping styles after 5 years are associated with disability pension. MATERIALS AND METHODS: Seventy-six MS patients and 94 healthy controls were included in this study. The patients were examined at baseline and 5 years later. This included a neurological examination and information on disability pension and a questionnaire assessing coping (the COPE scale). Controls were registered at baseline only. RESULTS: Compared to healthy controls, MS patients were more passive in coping with disease related distress. This was even more pronounced 5 years later. Disability pensioned patients employed more social support, venting of emotions and behavioural disengagement at follow-up. CONCLUSION: This study shows that patients with MS employ coping styles that may be inadequate and this is not improved by adaption over time. Although patients also use strategies to enhance their lives, these findings suggest that there may be a potential for improving the lives of patients with MS through interventions that may enhance adequate coping with the disease.

Long-term follow-up of benign multiple sclerosis in Hordaland County, Western Norway.

OBJECTIVE: To study the frequency of benign multiple sclerosis (MS) after 20 years disease duration and identify early clinical and demographic prognostic factors of a benign course. METHODS: A population-based cohort including all 230 MS patients with clinical disease onset during 1976-1986 in Hordaland County, Western Norway was followed up with clinical examination in 1995 and 2003. Benign MS was defined as an Expanded Disability Status Scale (EDSS) score

Depressive symptoms and coping in newly diagnosed patients with multiple sclerosis.

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

Relationship of cognitive impairment to psychiatric symptoms in multiple sclerosis.

Psychiatric and cognitive changes are common in patients with multiple sclerosis (MS), but their relationship has not received much attention. We studied the relationship between psychiatric symptoms and verbal memory, working memory, and mental speed in 78 patients with MS and 40 healthy control subjects using linear regression analyses. The MS group exhibited impaired performance on all cognitive tests. Apathy was associated with intrusions and depression with impaired memory and mental speed. The association between apathy and intrusions supports the hypothesis that lesions in frontal areas or frontal connections contribute to a specific neuropsychiatric syndrome in patients with MS.

Survival and cause of death in multiple sclerosis: results from a 50-year follow-up in Western Norway.

BACKGROUND: Survival time among patients with multiple sclerosis (MS) has varied considerably according to previous reports. OBJECTIVES: Survival and cause of death were analyzed among all patients with MS (878) with onset of MS in Hordaland County, Western Norway during 1953-2003, of whom 198 were dead at follow-up on January 1, 2005. METHODS: Standardized mortality ratios (SMRs) and relative mortality ratios (RMRs) were calculated based on observed mortality in MS and expected mortality. RESULTS: Median survival from onset was 41 years versus 49 years in the corresponding population, and mortality (SMR) was 2.7-fold increased in MS. The median survival was 43 years among women and 36 years among men, but women had higher relative mortality, when compared with the corresponding population, than men (RMR = 1.40). The median survival time was 45 years among young-onset patients (21-30 years) and 23 years among older-onset patients (51-60 years), but young-onset patients had higher relative mortality than older-onset patients, as shown by a significant reduction by 10-year interval of age at onset (RMR = 0.65). Median survival from onset was longer (43 years) among relapsing-remitting MS than primary progressive MS ([PPMS]; 49 years), and the relative mortality was higher in the PPMS group, (RMR = 1.55). According to death certificates, 57% died from MS. CONCLUSION: Female patients and patients with young onset had longer median time to death but higher relative risk of dying compared with the corresponding population. PPMS had both shorter median time to death from onset and a higher relative risk of dying.

Epstein-Barr virus reactivation and multiple sclerosis.

Infection with Epstein-Barr virus (EBV) is considered one of the possible key environmental factors in the aetiology of multiple sclerosis (MS). Whether EBV plays an underlying role as an activator of MS remains, however, controversial. Sixty-one patients with definite relapsing-remitting multiple sclerosis (RRMS) according to the Poser criteria were followed for 1 year. Blood samples were drawn at baseline, months 3, 6 and 12, and in case of any clinical exacerbation. Twenty-three baseline-paired exacerbation samples in the same set were quantitatively analysed to examine whether exacerbations in MS were associated with a change in anti-diffuse component of the EBV-early antigen (EA-D) IgG ratio. All the 61 patients (100%) were anti-viral capsid antigen (VCA) IgG positive, one (2%) was anti-VCA IgM positive and 60 (98%) were anti-EBV nuclear antigen IgG positive. Mean anti-EA-D IgG at baseline was 0.57 (range 0.12-2.70) and at the time of exacerbations 0.61 (range 0.11-2.70). Wilcoxon signed rank test revealed no differences between the 23 baseline and paired exacerbation samples (P = 0.58). Our findings suggest that reactivation of latent EBV infection does not play a significant role for exacerbations in RRMS.

Patient information and coping styles in multiple sclerosis.

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 frequently employed strategies were ;positive reinterpretation and growth', ;planning' and ;restraint coping' while ;denial' was the most infrequently employed strategy. Patients who were satisfied with the information employed avoidance coping to a lesser extent and more actively both plan and seek information about the situation. CONCLUSION: Optimizing the information process in the early phase of the disease may induce coping styles that produce a better adaption to living with MS.

Prevalence of bladder, bowel and sexual problems among multiple sclerosis patients two to five years after diagnosis.

Most multiple sclerosis (MS) patients experience some sexual, bladder and/or bowel dysfunction during the course of the disease--one of MS most disabling features. This study estimated the frequency of these problems among patients, two to five years after diagnosis, and investigated how these problems are associated with health-related quality of life (using the Multiple Sclerosis Quality of Life-54 questionnaire). The study population comprised a cohort of patients (n = 56), diagnosed in a three-year period, in Hordaland County, Norway. The patients were examined clinically, including scoring of the Expanded Disability Status Scale (EDSS), and completed questionnaires related to bowel and bladder dysfunction, sexual problems and health-related quality of life. More than half the patients had bladder and sexual problems. The frequency of self-reported bladder problems corresponded to the relatively high levels of residual urine found. The presence of these problems was associated with lower scores on the quality of life scales. Further, the bowel problems reported were markedly associated with the quality of life scores. Since treatments and preventive strategies can manage many of these problems, we suggest increasing the focus on these aspects of the disease when consulting patients, including at early stages.

The Norwegian Multiple Sclerosis National Competence Centre and National Multiple Sclerosis registry -- a resource for clinical practice and research.

The Norwegian Multiple Sclerosis National Competence Centre was established at the Department of Neurology, Haukeland University Hospital, Bergen in 1996. Promotion of research, supervision and education of doctors and other health care professionals in Norway are the main responsibilities of the Centre. The centre has established national networks for MS care and research and has provided supervision and education of doctors and other health care professionals in Norway. Guidelines for diagnosis and treatment of MS have been established. The National Multiple Sclerosis Registry was established in 1998 and includes by January 2006 50-60% of all MS patients in Norway. Through a national collaboration, the registry aims for inclusion of a biobank unit for collection of cerebrospinal fluid and serum, DNA, and tissue samples.

Benign multiple sclerosis.

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

FcgammaR and multiple sclerosis: an overview.

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

A 50-year follow-up of the incidence of multiple sclerosis in Hordaland County, Norway.

OBJECTIVE: To assess longitudinal follow-up of the incidence of multiple sclerosis (MS) through five decades and estimate the prevalence rate in Hordaland County, Norway, on January 1, 2003. METHODS: All patients with MS diagnosed from 1953 to 2003 were identified in the patient records of the Department of Neurology, Haukeland University Hospital, Bergen, Norway. The diagnostic criteria of Poser et al. were applied and only patients with definite and probable MS were included. The study comprises 912 patients, and 666 patients with MS were living in Hordaland on January 1, 2003. The annual incidence rates for the years 1953 to 2003 were calculated. RESULTS: The total crude prevalence rate on January 1, 2003, was 150.8 per 100,000 population: 191.3 per 100,000 among women and 109.8 per 100,000 among men. The annual incidence of MS increased from 1.8 per 100,000 in 1953 to 1957 to 6.0 per 100,000 in 1993 to 1997. CONCLUSIONS: Hordaland County, Norway, has changed from a low-risk to a high-risk area for multiple sclerosis (MS) during the last 50 years. During the last 25 years, the incidence of MS has been stable rather than increasing. Systematic longitudinal follow-up studies are essential to calculate reliable prevalence and incidence rates in MS. The results suggest that both methodologic and environmental factors are essential in determining the distribution of MS.

Neuropsychiatric symptoms in patients with multiple sclerosis.

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.

Do all young ischemic stroke patients need long-term secondary preventive medication?

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.

High dose methylprednisolone induces FcgammaRI on granulocytes in MS-patients.

Immune complexes impinge on receptors for the Fc domain of IgG (FcgammaR) and may thus influence the disease course in multiple sclerosis (MS). We analyzed FcgammaR distribution on monocytes and granulocytes in twenty relapsing-remitting MS patients at baseline, immediately after a five day course of high dose intravenous methylprednisolone (IVMP) treatment and after two months. After a five day course of IVMP the proportion of granulocytes with FcgammaRI was increased, P=0,002. There was no change in FcgammaRII and FcgammaRIII expression. The effect of IVMP on FcgammaRI expression could be important for the clearance of immune complexes in MS.

IL-10 promoter haplotype influence on interferon treatment response in multiple sclerosis.

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