Increasing age of multiple sclerosis onset from 1920 to 2022: a population-based study.

OBJECTIVE: To study the age at onset of relapsing-remitting multiple sclerosis (RRMS) during the past century. METHODS: This is a population-based cohort study of persons diagnosed with RRMS in Hordaland, Møre, and Romsdal counties, Western Norway, from 1920 to 2022. Individual patient data were available and assessed from previously conducted prevalence and incidence studies in addition to hospital records up until October 31, 2022. Participants were categorized according to onset period and analyzed for temporal trends in age at onset, time from onset to diagnosis, and distribution of onset over time. RESULTS: We identified 3364 persons with confirmed RRMS. The mean age at onset significantly increased (p < 0.001) throughout the study period, despite a decrease in time from symptom onset to diagnosis (p < 0.001). The proportion of persons with MS onset after 50 years of age increased from 2.6% before 1970 to 11.9% after 2010. We also found a trend toward a bimodal distribution of age at onset that peaked at around 30 years and 40-45 years of age in the latest period. CONCLUSION: Age at onset of MS significantly increased throughout the study period. This was mainly due to an increasing number of persons with MS, predominantly female, experiencing onset after 40-45 years of age. This bimodal distribution could indicate different susceptibility periods of MS or changes in exposure to risk factors during the observation period.

A 60-year follow-up of the incidence and prevalence of multiple sclerosis in Hordaland County, Western Norway.

OBJECTIVE: Investigate the incidence of multiple sclerosis during 1953-2013 and estimate the prevalence rate of MS on 1 January 2003 and 2013 in Hordaland County, Western Norway. METHODS: All patients with onset of disease in Hordaland 1953-2013 were identified in files from previous studies until 2003 and from patient records at the departments of Neurology, Haukeland University Hospital and Haugesund Hospital during 2003-2013. 1558 patients were assessed and 1402 of these were included, of whom 1035 were alive and living in Hordaland at prevalence day 1 January 2013. Annual incidence rates were calculated for 1953-2013. RESULTS: On 1 January 2003, the crude prevalence rate was 191/100 000 population and on 1 January 2013, the crude prevalence rate was 211.4 (95% CI 198.3 to 224.2) per 100 000; 270.9 (95% CI 250.6 to 292.3) for women and 151.8 (95% CI 136.8 to 167.9) for men. Prevalence peaked at ages 55-59 years for women and 60-64 years for men. The annual incidence rate increased from 1.9 (95% CI 1.2 to 2.6) per 100 000 during 1953-1957 to 7.2 (95% CI 6.0 to 8.5) during 1978-1982 and to 8.5 (95% CI 7.3 to 9.7) during 2003-2007, thus indicating a stabilising incidence over the past 35 years. The female/male ratio ranged from 1.2:1 to 1.8:1 (p=0.381) during the period. CONCLUSIONS: Stabilising rather than increasing incidence combined with the stable female/male ratio are indicative of non-fluctuating environmental factors in a geographical area otherwise characterised by lack of vitamin D effective sun exposure. The rising prevalence of MS could result from improved survival and follow-up methodology.

The Norwegian Multiple Sclerosis Registry and Biobank.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with unknown cause and various benefits from disease modifying therapies. Systematic recording of data into national MS registries is therefore needed to optimize treatment and define the pathogenesis of the disease. The Norwegian MS Registry and Biobank was established for systematic collection of clinical and epidemiological data, as well as biological samples. Data collection is based on informed consent from the individual patients and recordings by treating neurologists. All researchers have, by application, access to data and biological samples from the Norwegian Multiple Sclerosis Registry and Biobank. By this combined effort from both patients and healthcare personnel, the Registry and Biobank aims to facilitate research for improved understanding of disease mechanisms and improved health care in MS.

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.

Stoppers and non-starters of disease-modifying treatment in multiple sclerosis.

OBJECTIVES: To explore the frequency of non-starters and stoppers of disease-modifying therapy (DMT) in a cohort of people recently diagnosed with multiple sclerosis (MS) and to identify reasons for non-starting or stopping DMT measured by demographic variables, social support [The Interpersonal Support Evaluation List (ISEL)] and disease-related stress [The Impact of Event Scale (IES)]. MATERIALS AND METHODS: A multicentre retrospective cohort study using postal surveys completed by people with MS was performed, comprising all patients diagnosed with MS during 2000-2007 at four university clinics in Norway. RESULTS: Of the 424 respondents, 180 (42%) were still using the first prescribed DMT, 83 (20%) were using DMT after switching DMT at least once, 53 (12.5%) had ended DMT, and 108 (25.5%) had never started DMT. The risk of non-starting DMT was associated with increasing age at diagnosis, the region, disease-related stress and avoidant trauma coping. The risk factors for stopping therapy after the first prescribed DMT were adverse events and high education. CONCLUSIONS: Disease-related stress, avoidant trauma coping, age at diagnosis and education should be considered when motivating people with MS to use DMT. Hence, the challenges to starting and continuing treatment will probably also remain a problem with orally administered DMT.

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.

A need for national registries and international collaborative research in multiple sclerosis.

OBJECTIVE: There is a growing need to identify biomarkers for early diagnosis and treatment in multiple sclerosis (MS). Such markers may also be involved in the cause and pathogenesis of the disease. METHODS: Established national MS registries have through several decades allowed data collection to facilitate MS research. The European MS Registry (EUReMS) is a recent international collaborative effort to ultimately promote MS research and quality in health care across European countries. International collaborations based on such initiatives can facilitate studies on new biomarkers in MS. RESULTS: Important studies on data from MS registries, as well as national- and international collaboration networks have been conducted. CONCLUSION: The symposium "National MS Registries--to improve health care and research in Multiple Sclerosis" held in Bergen, Norway, earlier this year aimed to highlight the need and benefit from national MS registries and promote international collaborative research in MS.

The Norwegian Multiple Sclerosis Registry and Biobank.

UNLABELLED: OBJEVTIVES: Multiple sclerosis is a chronic inflammatory disease of the central nervous system with unknown cause and without any curable treatment. Research aiming at defining the pathogenesis of the disease is therefore needed. METHODS: The Norwegian Multiple Sclerosis Registry and Biobank has been established for systematic collection of clinical and epidemiological data as well as biological samples. Data collection is based on informed consent from the individual patients and recordings by the treating neurologists. RESULTS: All researchers have, by application, access to data and biological samples from the Norwegian Multiple Sclerosis Registry and Biobank. CONCLUSION: By this combined effort from both patients and health care personnel, the Registry and Biobank aims to facilitate research for improved understanding of disease mechanisms and improved health care in multiple sclerosis.

Health-related quality of life and disease-modifying treatment behaviour in relapsing-remitting multiple sclerosis--a multicentre cohort study.

OBJECTIVES: To assess the overall health-related quality of life (HRQoL) in a population-based cohort of patients recently diagnosed with multiple sclerosis (MS) compared with the general Norwegian population, to compare HRQoL among MS patients continuing, switching, stopping or not starting disease-modifying treatment (DMT) and to assess the motivation for DMT according to HRQoL. MATERIALS AND METHODS: A multicentre retrospective survey completed by patients recently diagnosed with relapsing-remitting MS (relapsing-remitting multiple sclerosis, RRMS) during 2001-2007 at four university clinics in Norway was performed. HRQoL was measured by the SF-36 version 2 Health Survey and standardized according to the general population with a mean of 50 and a standard deviation of 10. Motivation for DMT was assessed using Visual Analogue Scale (VAS). RESULTS: The mean age at diagnosis was 37 years. Patients had reduced mean scores for all eight dimensions of the SF-36 with lowest scores on social functioning (mean = 31.1), mental health (mean = 32.7), general health (mean = 39.7) and vitality (mean = 40.9) compared with the general population. Continuers scored higher on mental summary scale (mean = 37.9) and lower on physical summary scale (mean = 43.8) compared with non-starters. Non-starters scored highest on physical summary scale (mean = 45.2, P = 0.007) and lowest on mental summary scale (36.1, P = 0.01) compared with continuers, stoppers and switchers. Patients with high SF-36 physical health summary score and low SF-36 mental health summary score were less motivated for using DMT. CONCLUSION: The association of HRQoL and motivation to DMT emphasizes the need for health care personnel to inform and motivate patients to DMT, especially among patients with low mental health and otherwise high physical health and functioning.

Fatigue in multiple sclerosis: associations with health-related quality of life and physical performance.

BACKGROUND AND PURPOSE: fatigue is a common, but still one of the least understood symptoms in multiple sclerosis (MS). We aimed to investigate whether fatigue was associated with demographic-, clinical-, health-related quality of life (HRQoL)- and physical performance variables, and whether change in fatigue after treatment was associated with changes in HRQoL and physical performance. METHODS: sixty patients were included for inpatient physiotherapy. Fifty-six patients completed the study and were available for analysis. Fatigue (Fatigue Severity Scale; FSS), HRQoL (Multiple Sclerosis Impact Scale; MSIS-29) and physical performance (walking ability and balance) were assessed at screening, baseline, after treatment and at follow-up after 3 and 6 months. We analysed possible associations between fatigue and other variables at baseline by regression models, and between change in fatigue versus changes in both HRQoL and physical performance variables after physiotherapy by correlation analysis. RESULTS: fatigue at baseline was associated with HRQoL (explained 21.9% of variance), but not with the physical performance tests. Change in fatigue was correlated with change in HRQoL, but not with changes in physical performance. All measures were improved after treatment (P ≤ 0.001). While improvements in fatigue and HRQoL were lost at follow-up, improvements in physical performance tests were maintained for at least 6 months (P ≤ 0.05). CONCLUSIONS: fatigue was associated with HRQoL at baseline. Improvement in fatigue seemed to be related to other factors than improvement in physical performance. A broader strategy including both physical and psychological dimensions seems to be needed to improve fatigue over the long-term.

The influence of warm versus cold climate on the effect of physiotherapy in multiple sclerosis.

OBJECTIVE: To compare the effect of inpatient physiotherapy in a warm versus cold climate in short- and long-term perspectives. METHODS: Sixty multiple sclerosis (MS) patients with gait problems, without heat intolerance, were included in a randomized cross-over study of 4-week inpatient physiotherapy in warm (Spain) and cold (Norway) climate. The primary outcome, 6-min walk test (6MWT), and secondary physical performance and self-reported measures were scored at screening, baseline, after treatment and at 3 and 6 months of follow-up. Treatment effects were analysed by mixed models. RESULTS: After treatment, the mean walking distance had increased by 70 m in Spain and 49 m in Norway (P = 0.060). Improvement in favour of warm climate was demonstrated at 6 months of follow-up, 43 m (Spain) compared to 20 m (Norway) (P = 0.048). The patients reported less exertion after walking (6MWT) in favour of treatment in Spain at all time points (P < 0.05). No significant differences in change were detected for the other physical performance measures. Most self-reported measures showed more improvement after treatment in Spain, but these improvements were not sustained at follow-up. CONCLUSION: The results indicate that MS patients without heat intolerance have additional benefits from physiotherapy in a warm climate.

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

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

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.

Depression and anxiety amongst multiple sclerosis patients.

The aim of this study was to investigate the prevalence of symptoms of depression and anxiety amongst multiple sclerosis (MS) patients, and the associations with demographic and clinical characteristics. The current treatment for depression and anxiety was also evaluated amongst the MS patients. A total of 140 MS patients from Eastern Norway underwent neuropsychiatric and clinical examinations, with registration of symptoms of depression and anxiety (Hopkins Symptom Checklist-25), as well as information about any help seeking for depression were obtained. A total of 31.4% patients reported symptoms of depression, whilst 19.3% reported anxiety; both symptoms were significantly higher than that amongst the general population (P < 0.001). Fatigue and younger age at onset were significantly associated with symptoms of depression, whilst fatigue and pain, lower Expanded Disability Status Scale score and younger age at onset were associated with symptoms of anxiety. The proportion of reported treatment of depression was 15.9% and for anxiety 11.1%. Of untreated patients with symptoms, 18.2% expressed the need for treatment. A greater focus on depression and anxiety amongst MS patients is needed to establish the appropriate treatment for patients suffering from MS.

Focal epileptiform activity described by a large computerised EEG database.

OBJECTIVE: To study the age-related topographical tendency of expressing epileptiform activity, and the effect of focal epileptiform activity (FEA) on the general cortical brain activity. METHODS: 1647 consecutive routine EEGs containing FEA were visually assessed for FEA location and asymmetry. Background activity was compared with that in normal EEGs from 3268 drug-free outpatient controls. RESULTS: FEA localisation was age-related (p<0.0005) except for the temporal region (p=0.22) where FEA was found equally often in the young and the old. The left hemisphere was more prone to FEA (p=0.018). The left-right asymmetry varied by age (p=0.013). FEA asymmetry occurred most frequently in EEGs from patients older than 80 years, and least frequent in the age-group 20-39 years. FEA was associated with lower alpha rhythm (AR) frequencies (p=0.0041) and higher AR amplitudes (p=0.0023), as well as higher general background activity (GBA) amplitude (p<0.0005), while GBA frequencies were the same (p=0.96). CONCLUSIONS: Topographical localisation of FEA was age-dependent. There was an overall left dominance, but the side asymmetry was modest and varied by age. FEA was associated with changes in AR and GBA. SIGNIFICANCE: The results demonstrate that FEA is associated with cerebral cortical dysfunction also distant from the epileptic focus.

Health-related quality of life in secondary progressive multiple sclerosis.

Common disability scales in multiple sclerosis (MS) are often weighted towards physical disability. Non-motor symptoms such as depression, fatigue and pain substantially influence wellbeing in MS. Health-related quality of life (HRQoL) measures the broader impact of MS and might indicate less obvious disease burdens. We analysed HRQoL, using the Nottingham Health Profile Part I (NHP-I), among 345 secondary progressive MS (SPMS) patients participating in a randomized trial of interferon-beta1a (IFN-beta1a), 22 mug subcutaneously weekly, or matching placebo. The results did not reveal any beneficial effect of IFN-beta1a in any outcome measure. NHP-I sub- and sum scores were compared for 217 population controls and correlated with demographic and clinical disease variables. SPMS patients had lower NHP-I sum and all subscores than the controls. Patients experiencing disease progression reported worse NHP-I sum scores. Increased fatigue, Expanded Disability Status Scale (EDSS) and Arm Index scores were independently associated with reduction in several NHP-I subscores. SPMS patients had significantly lower HRQoL than controls and physical disability (EDSS and Arm Index), disease progression and fatigue strongly influenced this. MS.

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.

Yo antibodies in ovarian and breast cancer patients detected by a sensitive immunoprecipitation technique.

Onconeural antibodies are found in patients with cancer and are associated with paraneoplastic neurological syndromes (PNS). The objective of the present study was to assess the frequency of Yo antibodies in ovarian and breast cancer using a sensitive immunoprecipitation technique, and to look for any association of Yo antibodies with neurological symptoms and prognostic factors. A multiwell adapted fluid-phase immunoassay using radiolabelled recombinant cerebellar degeneration related protein (cdr2), produced by coupled in vitro transcription/translation was used for the detection of Yo antibodies. This technique combines high specificity and sensitivity with high sample analysing capacity for the antibody in question. Sera or EDTA-blood from 810 ovarian (n = 557) and breast cancer (n = 253) patients were analysed for Yo antibodies by immunoprecipitation, as well as immunofluorescence and immune blots. Two hundred healthy blood donors and sera from 17 patients with paraneoplastic cerebellar degeneration and Yo antibodies served as controls. Immunoprecipitation was more sensitive in detecting Yo antibodies than immunofluorescence and immune blots. The prevalence of Yo antibodies was 13/557 (2.3%) in ovarian cancer and 4/253 (1.6%) in breast cancer using immunoprecipitation. Yo antibodies were not correlated with specific histological subgroups. The Yo index of ovarian cancer patients in FIGO stage IV was higher compared to FIGO stage I-III. The prevalence of Yo antibodies was 3 times higher in patients with stage III breast cancer than in stage I and II. Only 2/17 (11.8%) patients with Yo antibodies detected during the screen of 810 cancer patients had PNS. The results show that the prevalence of Yo antibodies is low in ovarian and breast cancer. Yo antibodies may be associated with advanced cancer, but less often with PNS.

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.