Mortality and cause of death in multiple sclerosis in western Norway 1950-2021: a registry-based linkage study.

BACKGROUND: Persons with multiple sclerosis (pwMS) have higher risk of mortality compared with the general population. Longitudinal studies are important for understanding the evolution of survival in pwMS. OBJECTIVE: Examine changes in mortality among pwMS during the past seven decades. METHODS: We followed pwMS from Hordaland and Møre and Romsdal in Western Norway, with disease onset from before 1950, identified from population-based epidemiological surveys and the Norwegian MS Registry and Biobank, until 1 January 2021. Data were linked to the Norwegian Cause of Death Registry to obtain underlying cause of death. We examined all-cause, and cause-specific mortality using standardised mortality ratios (SMR) and excess death rates (EDR). We calculated life expectancies and assessed survival stratified by sex, age and disease phenotype at onset. We compared hazard ratios (HRs) for mortality, in pwMS diagnosed before and after the era of disease-modifying treatment (DMT). RESULTS: Of 3624 pwMS, 964 (55.5% women) had died, predominantly of multiple sclerosis (49.0%). Median life expectancy for pwMS was 74.3 years (95% CI 73.3 to 75.3), compared with 83.1 years for the general population (p<0.001). From disease onset, pwMS survived 14.6 years shorter than the general population (p<0.001). Overall, SMR was 2.3 (95% CI 2.13 to 2.42) and EDR was 6.8 (95% CI 6.42 to 7.09) for pwMS. Treatment-eligible pwMS diagnosed in the DMT era had the lowest risk of mortality, HR 0.49 (95% CI 0.34 to 0.70,p<0.001). CONCLUSION: Excess mortality among pwMS declined during the past seven decades, possibly due to improved diagnostics, better symptomatic treatment and access to DMTs.

Serum neurofilament as a predictor of 10-year grey matter atrophy and clinical disability in multiple sclerosis: a longitudinal study.

BACKGROUND: The predictive value of serum neurofilament light chain (sNfL) on long-term prognosis in multiple sclerosis (MS) is still unclear. OBJECTIVE: Investigate the relation between sNfL levels over a 2-year period in patients with relapsing-remitting MS, and clinical disability and grey matter (GM) atrophy after 10 years. METHODS: 85 patients, originally enrolled in a multicentre, randomised trial of ω-3 fatty acids, participated in a 10-year follow-up visit. sNfL levels were measured by Simoa quarterly until month 12, and then at month 24. The appearance of new gadolinium-enhancing (Gd+) lesions was assessed monthly between baseline and month 9, and then at months 12 and 24. At the 10-year follow-up visit, brain atrophy measures were obtained using FreeSurfer. RESULTS: Higher mean sNfL levels during early periods of active inflammation (Gd+ lesions present or recently present) predicted lower total (ß=-0.399, p=0.040) and deep (ß=-0.556, p=0.010) GM volume, lower mean cortical thickness (ß=-0.581, p=0.010) and higher T2 lesion count (ß=0.498, p=0.018). Of the clinical outcomes, higher inflammatory sNfL levels were associated with higher disability measured by the dominant hand Nine-Hole Peg Test (ß=0.593, p=0.004). Mean sNfL levels during periods of remission (no Gd+ lesions present or recently present) did not predict GM atrophy or disability progression. CONCLUSION: Higher sNfL levels during periods of active inflammation predicted more GM atrophy and specific aspects of clinical disability 10 years later. The findings suggest that subsequent long-term GM atrophy is mainly due to neuroaxonal degradation within new lesions.

Risk of cancer among multiple sclerosis patients, siblings, and population controls: A prospective cohort study.

BACKGROUND: Risk of cancer in multiple sclerosis (MS) patients compared to their siblings is unknown. OBJECTIVE: The objective was to prospectively investigate the risk of cancer among MS patients compared to siblings without MS and to population controls. METHODS: We retrieved data on MS patients born between 1930 and 1979 from the Norwegian Multiple Sclerosis Registry and population studies and on cancer diagnosis from the Cancer Registry of Norway. We used adjusted Cox proportional hazard regression to estimate cancer risk among 6883 MS patients, 8918 siblings without MS, and 37,919 population controls. RESULTS: During 65 years of follow-up, cancer risk among MS patients was higher than that among population controls (hazard ratio (HR) = 1.14, 95% confidence interval (CI): 1.05-1.23) in respiratory organs (HR = 1.66, 95% CI: 1.26-2.19), urinary organs (HR = 1.51, 95% CI: 1.12-2.04), and the central nervous system (HR = 1.52, 95% CI: 1.11-2. 09). Siblings had higher risk of hematological cancers compared with MS patients (HR = 1.82, 95% CI: 1.21-2.73) and population controls (HR = 1.72, 95% CI: 1.36-2.18). CONCLUSION: MS patients were associated with increased risk of cancer compared to population controls. Siblings had increased risk of hematological cancer. This indicates that MS and hematological cancer could share a common etiology.

Factors influencing employment after minor stroke and NSTEMI.

AIM: To study the effect of cognitive function, fatigue and emotional symptoms on employment after a minor ischemic stroke compared to non-ST-elevation myocardial infarction (NSTEMI). MATERIAL AND METHODS: We included 217 patients with minor ischemic stroke and 133 NSTEMI patients employed at baseline aged 18-70 years. Minor stroke was defined as modified Rankin scale (mRS) 0-2 at day seven or at discharge if before. Included NSTEMI patients had the same functional mRS. We applied a selection of cognitive tests and the patients completed questionnaires measuring symptoms of anxiety, depression and fatigue at follow up. Stroke patients were tested at three and 12 months and NSTEMI at 12 months. RESULTS: The patients still employed at 12 monthswere significantly younger than the unemployed patients and the NSTEMI patients employed were significantly older than the stroke patients (59 vs 55 years, p < .001). In total, 82 % of stroke patients and 90 % of the NSTEMI patients employed at baseline were still employed at 12 months (p = 06). Stroke patients at work after 12 months had higher education than unemployed patients. There were no difference between employed and unemployed patients in risk factors or location of cerebral ischemic lesions. Cognitive function did not change significantly in the stroke patients from three to 12 months. For stroke patients, we found a significant association between HADS-depression and unemployment at 12 months (p = 04), although this association was not present at three months. Lower age and higher educational level were associated with employment at 12 months for all patients. DISCUSSION AND CONCLUSION: Age and education are the main factors influencing the ability to stay in work after a minor stroke. Employed stroke patients were younger than the NSTEMI patients, but there was no difference in the frequencies in remaining employed. The employment rate at 12 months was high despite the relatively high prevalence of cognitive impairment in both groups.

α-Linolenic acid is associated with MRI activity in a prospective cohort of multiple sclerosis patients.

BACKGROUND: The plant-based ω-3 fatty acid α-linolenic acid (ALA) has been associated with lower MS risk. It is currently unknown whether ALA affects disease activity. OBJECTIVE: To investigate the association between ALA levels and disease activity. METHODS: We conducted a cohort study including 87 multiple sclerosis (MS)-patients who originally participated in a randomized trial of ω-3 fatty acids (the OFAMS study). We measured serum levels of ALA during follow-up and used random intercept logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association between ALA levels, new magnetic resonance imaging (MRI) lesions, Expanded Disability Status Scale (EDSS) progression and new relapses adjusting for age at inclusion, sex, and use of interferon beta-1a. RESULTS: In continuous (per 1-SD increase) multivariable-adjusted analyses, higher ALA levels were significantly associated with lower odds of new T2-lesions (OR: 0.59, 95% CI: 0.37-0.95) during follow-up. The effect estimates were similar for new T1Gd + lesions (OR: 0.73, 95% CI: 0.48-1.11), EDSS-progression (OR: 0.62, 95% CI: 0.34-1.16) and new relapses (OR: 0.49, 95% CI: 0.22-1.10), but these estimates did not reach statistical significance. Further adjustment for vitamin D and tobacco use did not materially change the results. CONCLUSION: We found that higher levels of ALA were associated with lower disease activity in MS-patients.

The development of cognitive and emotional impairment after a minor stroke: A longitudinal study.

OBJECTIVES: To study the development of cognitive and emotional symptoms between 3 and 12 months after a minor stroke. MATERIAL AND METHODS: We included patients from stroke units at hospitals in the Central Norway Health Authority and from Haukeland University Hospital. We administered a selection of cognitive tests, and the patients completed a questionnaire 3 and 12 months post-stroke. Cognitive impairment was defined as impairment of ≥2 cognitive tests. RESULTS: A total of 324 patients completed the 3-month testing, whereas 37 patients were lost to follow-up at 12 months. The results showed significant improvement of cognitive function defined as impairment of ≥2 cognitive tests (P = .03) from months 3 to 12. However, most patients still showed cognitive impairment at 12 months with a prevalence of 35.4%. There is significant association between several of the cognitive tests and hypertension and smoking (P = .002 and .05). The prevalence of depression, but not anxiety, increased from 3 to 12 months (P = .04). The prevalence of fatigue did not change and was thus still high with 29.5% after 12 months. CONCLUSIONS: This study shows that an improvement of cognitive function still occurs between 3 and 12 months. Despite this, the prevalence of mostly minor cognitive impairment still remains high 12 months after the stroke. The increasing prevalence of depressive symptoms highlights the importance of being vigilant of depressive symptoms throughout the rehabilitation period. Furthermore, high prevalence of fatigue persisted.

Preclinical disease activity in multiple sclerosis: A prospective study of cognitive performance prior to first symptom.

OBJECTIVE: To prospectively investigate potential signs of preclinical multiple sclerosis (MS) activity and when they are present prior to first symptom using data from a historical cohort. METHODS: We linked the cognitive performance of all Norwegian men born 1950-1995 who underwent conscription examination at age 18 to 19 years to the Norwegian MS registry to identify those later developing MS, and randomly selected controls frequency-matched on year of birth from the Norwegian Conscript Service database. In this nested case-control study, cognitive test scores were available for 924 male cases and 19,530 male controls. We estimated mean score differences among cases and controls (Student t test) and the risk of developing MS comparing lower to higher scores (Cox regression) in strata of years to clinical onset. RESULTS: Men developing first clinical MS symptoms up to 2 years after the examination scored significantly lower than controls (Δ = 0.80, p = 0.0095), corresponding to a 6 intelligence quotient (IQ)-point difference. Those scoring lowest, that is, >1 standard deviation below the controls' mean, had an increased MS risk during the 2 following years (relative risk = 2.81, 95% confidence interval = 1.52-5.20). Whereas results were similar for relapsing-remitting MS cases (RRMS), those developing primary-progressive MS (PPMS) scored a significant 4.6 to 6.9 IQ points lower than controls up to 20 years prior to first progressive symptoms. INTERPRETATION: RRMS may start years prior to clinical presentation, and disease processes in PPMS could start decades prior to first apparent progressive symptoms. Cognitive problems could be present in both MS forms before apparent symptoms. Apart from potential implications for clinical practice and research, these findings challenge our thinking about the disease. Ann Neurol 2016;80:616-624.

Level of education and multiple sclerosis risk over a 50-year period: Registry-based sibling study.

BACKGROUND: The conflicting results from studies on socioeconomic status (SES) and multiple sclerosis (MS) risk might be due to a change in the distribution of environmental exposures over time or to methodological limitations in previous research. OBJECTIVE: To examine the association between SES and MS risk during 50 years. METHODS: We included patients registered in Norwegian MS registries and prevalence studies born between 1930 and 1979, and identified their siblings and parents using the Norwegian Population Registry. Information on education was retrieved from the National Education Registry, categorized into four levels (primary, secondary, undergraduate and graduate) and compared in patients and siblings using conditional logistic regression. RESULTS: A total of 4494 MS patients and 9193 of their siblings were included in the analyses. Level of education was inversely associated with MS risk ( p trend < 0.001) with an odds ratio (OR) of 0.73 (95% confidence interval (CI): 0.59-0.90) when comparing the highest and lowest levels. The effect estimates did not vary markedly between participants born before or after the median year of birth (1958), but we observed a significant effect modification by parental education ( p = 0.047). CONCLUSION: Level of education was inversely associated with MS risk, and the estimates were similar in the earliest and latest birth cohorts.

Antibodies to Epstein-Barr virus and MRI disease activity in multiple sclerosis.

BACKGROUND: Previous reports indicate an association between Epstein-Barr virus (EBV) antibody levels and multiple sclerosis (MS) disease activity, but the results have been conflicting. OBJECTIVES: The objective of this paper is to study if EBV antibody levels reflect MRI disease activity in MS and examine the potential for EBV antibody levels as biomarkers for treatment response. METHODS: A total of 87 MS patients were followed for two years prior to and during interferon beta (IFNB) treatment, with MRI examinations and serum measurement of IgM and IgG antibodies to viral capsid antigen (VCA), EBV nuclear antigen 1 (EBNA-1) and early antigen (EA). Associations between EBV antibody levels and MRI activity were assessed by a logistic regression model. RESULTS: Higher anti-EBNA-1 IgG levels were associated with increased MRI activity, OR = 2.95 (95% CI 1.07-8.10; p = 0.036) for combined unique activity (CUA; the sum of T1Gd+ lesions and new or enlarging T2 lesions). Although most patients were anti-VCA IgM negative, there was an inverse association, OR = 0.32 (95% CI 0.12-0.84; p = 0.021) with CUA during IFNB treatment. CONCLUSIONS: This study supports an association between anti-EBNA-1 IgG levels and MS disease activity. We also found an inverse association with anti-VCA IgM levels during IFNB treatment not previously described, indicating anti-VCA IgM as a possible biomarker for IFNB treatment response.

Retinol levels are associated with magnetic resonance imaging outcomes in multiple sclerosis.

BACKGROUND: Vitamin A has immunomodulatory properties and may regulate the transcription of genes involved in remyelination. OBJECTIVE: To investigate the association between retinol and disease activity in multiple sclerosis (MS). METHODS: Cohort study of 88 relapsing-remitting MS patients, originally included in a randomised placebo-controlled trial of omega-3 fatty acids in MS (the OFAMS study), followed prospectively for 24 months with repeated assessments of serum-retinol and magnetic resonance imaging (MRI). All patients were initiated on interferon ß-1a after month 6. RESULTS: Each 1 µmol/L increase in serum-retinol reduced the odds (95% confidence interval) for new T1 gadolinium enhanced (Gd(+)) lesions by 49 (8-70)%, new T2 lesions by 42 (2-66)%, and combined unique activity (CUA) by 46 (3-68)% in simultaneous MRI scans, and 63 (25-82)% for new T1Gd(+) lesions, 49 (3-73)% for new T2 lesions and 43 (12-71)% for CUA the subsequent month. Serum-retinol also predicted new T1Gd(+) and T2 lesions six months ahead. The associations were not affected by HLA-DRB1*15, or serum levels of 25-hydroxyvitamin D, eicosapentaenoic acid or docosahexaenoic acid. CONCLUSION: Serum retinol is inversely associated with simultaneous and subsequent MRI outcomes in RRMS.

Month of birth as a latitude-dependent risk factor for multiple sclerosis in Norway.

OBJECTIVE: We aimed to determine if the risk of Multiple Sclerosis (MS) is associated with month of birth in Norway and to explore a possible latitudinal gradient. METHODS: All patients with MS born between 1930 and 1979 registered in the Norwegian MS Registry or ascertained in Norwegian prevalence studies were included (n = 6649). The latitude gradient was divided in Southern, Middle and Northern Norway, according to the estimated regional yearly mean vitamin D effective UV dose. RESULTS: Risk of MS was 11% higher for those born in April (p = 0.045), and 5% higher for those born in May (p = 0.229), 5% lower for those born in November (p = 0.302) and 12% lower for those born in February (p = 0.053) compared with the corresponding population, unaffected mothers and siblings. In Southern Norway the odds ratio of MS births in April and May was 1.05 (0.98-1.24), in Middle Norway 1.11 (0.97-1.27) and in Northern Norway 1.28 (1.0-1.63) compared with the other months. CONCLUSIONS: This study confirms previous reports of increased MS births in spring and decreased MS births in the winter months. This could support the role of decreased sunlight exposure during pregnancy and vitamin D deficiency in prenatal life in MS.

Cancer related mortality in multiple sclerosis. A population based cohort study.

BACKGROUND: Cancer is a major cause of death, but how cancer influences mortality risk in Multiple Sclerosis (MS) is unclear. OBJECTIVES: Determine all-cause mortality and mortality following a cancer diagnosis among MS patients compared with matched population controls. METHODS: Norwegian MS patients born 1930 - 1979 (n= 6950) followed-up 1953 - 2016, were matched with 37 922 controls. We compared incident cancer diagnosis from the Cancer Registry of Norway, date of death from the Cause of Death Registry, education from the National Education Database, by multivariate Cox proportional hazard regression. RESULTS: Hazard ratio (HR) and 95% confidence interval (CI) for all-cause mortality among MS patients was 4.97 (4.64 - 5.33), and 2.61 (2.29 - 2.98) for mortality following a cancer diagnosis. Mortality in MS was highest following urinary- (2.53: 1.55 - 4.14), colorectal- (2.14: 1.47 - 3.11), hematological- (1.76: 1.08 - 2.88), ovarian - 2.30 (1.73-3.06) and breast cancer diagnosis (2.61: 1.85 - 3.68), compared to controls. High education was inversely associated with mortality among MS patients. CONCLUSIONS: All-cause mortality was five- fold and mortality following a cancer diagnosis was two- fold increased among MS patients. Mortality following specific cancers raises the possibility of diagnostic neglect.

The Effect of Smoking on Long-term Gray Matter Atrophy and Clinical Disability in Patients with Relapsing-Remitting Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: The relationship between smoking, long-term brain atrophy, and clinical disability in patients with multiple sclerosis (MS) is unclear. Here, we assessed long-term effects of smoking by evaluating MRI and clinical outcome measures after 10 years in smoking and nonsmoking patients with relapsing-remitting MS (RRMS). METHODS: We included 85 treatment-naive patients with RRMS with recent inflammatory disease activity who participated in a 10-year follow-up visit after a multicenter clinical trial of 24 months. Smoking status was decided for each patient by 2 separate definitions: by serum cotinine levels measured regularly for the first 2 years of the follow-up (during the clinical trial) and by retrospective patient self-reporting. At the 10-year follow-up visit, clinical tests were repeated, and brain atrophy measures were obtained from MRI using FreeSurfer. Differences in clinical and MRI measurements at the 10-year follow-up between smokers and nonsmokers were investigated by 2-sample t tests or Mann-Whitney tests and linear mixed-effect regression models. All analyses were conducted separately for each definition of smoking status. RESULTS: After 10 years, smoking (defined by serum cotinine levels) was associated with lower total white matter volume (ß = -21.74, p = 0.039) and higher logT2 lesion volume (ß = 0.22, p = 0.011). When defining smoking status by patient self-reporting, the repeated analyses found an additional association with lower deep gray matter volume (ß = -2.35, p = 0.049), and smoking was also associated with a higher score (higher walking impairment) on the log timed 25-foot walk test (ß = 0.050, p = 0.039) after 10 years and a larger decrease in paced auditory serial addition test (attention) scores (ß = -3.58, p = 0.029). DISCUSSION: Smoking was associated with brain atrophy and disability progression 10 years later in patients with RRMS. The findings imply that patients should be advised and offered aid in smoking cessation shortly after diagnosis, to prevent long-term disability progression.

Risk of MS is not associated with exposure to crude oil, but increases with low level of education.

BACKGROUND: Offshore workers in the Norwegian upstream petroleum industry are exposed to a number of chemicals such as organic solvents, mineral oils and other hydrocarbons, possibly contributing to an increased risk of multiple sclerosis (MS). OBJECTIVE: To estimate the risk of MS in this population compared with the general working population in Norway, adjusting for education. METHODS: Using the Norwegian Registry of Employers and Employees we included all 27,900 offshore workers registered from 1981 to 2003 and 366,805 referents from the general working population matched by gender, age and community of residence. The cohort was linked to the Norwegian MS Registry and the Norwegian Education Registry. RESULTS: There was no increased risk of MS among the offshore workers. We found a marked and linear inverse relationship between level of education and the risk of MS in the total study population, with a rate ratio of 0.48 (95% CI, 0.53 to 0.88) for workers with a graduate degree compared to workers with elementary school only. CONCLUSIONS: These findings do not support a major aetiological role of petroleum-based products, but rather point to smoking and other lifestyle factors related to the level of education as being important for the risk of MS.

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

Incidence of cancer in multiple sclerosis before and after the treatment era- a registry- based cohort study.

BACKGROUND: Whether disease-modifying therapies (DMTs) influence cancer in multiple sclerosis (MS) is uncertain. OBJECTIVES: Assess incidence of cancer diagnosis among Norwegian MS patients compared to the general population in 1953 to 1995 and 1996 to 2017-reflecting era before and after introduction of DMTs. METHODS: We performed a nationwide cohort study comprising 6949 MS patients and 37,922 controls, matched on age, sex and county. The cohort was linked to Norwegian Cancer Registry, Cause of Death Registry and National Educational database. We used Poisson regression to calculate incidence rate ratio (IRR) of cancer. RESULTS: During 1953-1995 MS patients had similar cancer frequency compared to controls (IRR: 1.11 (95% Confidence Intervals (CI): 0.90-1.37)), although MS patients had increased frequency of cancer in endocrine glands (IRR: 2.51 (1.27-4.93). During 1996-2017 we identified significant increased frequency of cancer among MS patients compared to controls (IRR: 1.38 (95% CI: 1.28-1.52): in brain (IRR: 1.97 (1.41-2.78)), meninges (IRR: 2.44 (1.54-3.77)), respiratory organs (IRR: 1.96 (1.49-2.63)). The excess cancer diagnosis was most frequent among MS patients ≥ 60 years of age (HR 1.30 (1.15-1.47)). CONCLUSION: Incidence of cancer among MS patients compared to controls was higher in 1996 to 2017, corresponding in time to the introduction of DMT for MS. This was observed more frequently among MS patients older than 60 years of age.

Low vitamin D, but not tobacco use or high BMI, is associated with long-term disability progression in multiple sclerosis.

BACKGROUND: Low vitamin D levels, tobacco use and high body mass index (BMI) have been linked to adverse disease outcomes in multiple sclerosis (MS), but their influence on long-term disability progression remains unclear. Therefore, we explored whether these modifiable lifestyle factors were associated with 10-year clinical disability progression in patients with MS. METHODS: In this prospective study, a cohort of 88 patients with relapsing-remitting MS completed a randomized controlled study on ω-3 fatty acids between 2004 and 2008. During 24 months, serum 25-hydroxyvitamin D (25(OH)D), serum cotinine (nicotine metabolite), and BMI were repeatedly measured. In 2017, a follow-up study was conducted among 80 of the participants, including disability assessment by the Expanded Disability Status Scale (EDSS). Linear regression was used to explore associations between the lifestyle factors and the EDSS change over 10 years. RESULTS: Higher seasonally adjusted 25(OH)D levels were associated with lower 10-year EDSS progression (change in EDSS per 1 SD increase in 25(OH)D in a model adjusted for sex, age and baseline EDSS: -0.45 point, 95% CI: -0.75 to -0.16, p=0.003). Further adjustments for potential confounders related to lifestyle and disease status gave similar results. The association was mainly driven by low 25(OH)D levels during spring, as well as seasonally adjusted levels below 80 nmol/L. No clear association was found for BMI and cotinine. CONCLUSION: Lower 25(OH)D levels, but apparently not tobacco use or higher BMI, were significantly associated with worse long-term disability progression in MS.

Spasticity, gait, and balance in patients with multiple sclerosis: A cross-sectional study.

OBJECTIVE: More than 80% of people with multiple sclerosis (MS) are affected by spasticity. Spasticity is known to reduce quality of life and contribute to additional symptoms, such as pain and reduced mobility, but the association between spasticity, balance, and mobility has not yet been established. Our aim was to examine whether a relationship exists between spasticity in the lower limbs, balance, and gait, as well as to explore the involvement of different muscle groups. METHODS: This study employed a cross-sectional design. Thirty patients with MS were included. The Modified Ashworth Scale (MAS) was used to examine spasticity in the ankle plantar flexors, knee extensors, and hip adductors. Balance was measured using the Mini-Balance Evaluation Systems Test, and gait with the 2-Minute Walk Test. The participants were tested once with no additional follow-up. Spearman's correlation, recursive partitioning, and linear regression analyses were used to explore the association. RESULTS: A significant correlation between gait distance and spasticity in the ankle plantar flexors (ρ = -.69, p < .001) and knee extensors (ρ = -.45, p = .012) was observed. Balance significantly correlated with spasticity in ankle plantar flexors (ρ = -.69, p < .001), knee extensors (ρ = -.52, p = .003), and hip adductors (ρ = -.5, p = .005). The relationship between spasticity in ankle plantar flexors and hip adductors was significant, even from low levels of spasticity, whereas MAS score ≥ 2 was clinically correlated with a decrease in gait and balance function. Adjustments for sex, age, or years since diagnosis had only minor impact on the results. CONCLUSIONS: This study indicates that spasticity in the lower limbs is clinically significantly associated with mobility in people with MS.

High incidence and prevalence of MS in Møre and Romsdal County, Norway, 1950-2018.

OBJECTIVE: To determine prevalence and longitudinal trends in incidence of MS in Møre and Romsdal County, Western Norway, from 1950 to 2018. METHODS: Retrospective longitudinal population-based observational study. All patients diagnosed, or living, with MS in Møre and Romsdal were identified as incident or prevalent cases from local, regional, and national sources. We compiled the data in the Norwegian Multiple Sclerosis Registry and Biobank and used the aggregated data set to calculate incidence and prevalence rates using population measures obtained from Statistics Norway. RESULTS: On January 1, 2018, the estimated prevalence was 335.8 (95% CI, 314.1-358.5) per 100,000 inhabitants, with a female:male ratio of 2.3. From 1950 through 2017, we observed a considerable (p < 0.001) increase in average annual incidence rates from 2.1 (95% CI, 1.3-3.3) to 14.4 (95% CI, 11.9-17.3) per 100,000. From 2005 through 2017, the incidence among women increased from 17.1 (95% CI, 14.0-20.7) to 23.2 (95% CI, 18.7-28.5) per 100,000, whereas the incidence among men declined from 10.3 (95% CI, 7.9-13.2) to 5.9 (95% CI, 3.4-8.8) per 100,000. CONCLUSION: Møre and Romsdal County in Western Norway has the highest prevalence of MS reported in Norway. The incidence has steadily increased since 1950, and during the latest 15 years, we observed opposing trends in sex-specific incidence rates.

Anxiety and depression in multiple sclerosis. A comparative population-based study in Nord-Trøndelag County, Norway.

Anxiety and depression are widely distributed symptoms among multiple sclerosis patients and in the general population. We assessed the prevalence of anxiety and depression in the multiple sclerosis population in Nord-Trøndelag County, Norway compared with Norway's general population. The Hospital Anxiety and Depression Scale questionnaire was completed by 172 MS patients and 56,000 controls. A cut-off of > or =8 was used to define significant symptoms of anxiety and depression. Fatigue was measured using Krupp's Fatigue Severity Scale, with a mean cut-off of >4. Among men, 31.1% of the multiple sclerosis patients reported anxiety, while only 12.1% of the control population reported this symptom (p = 0.002). For women, the prevalence of anxiety was 29.7% versus 17.4% (p < 0.001). Depression was reported by 26.2% of the men with multiple sclerosis compared with 10.8% of the controls (p < 0.001). The corresponding figures for women were 25.2% versus 10.4% (p < 0.001). Anxiety and depression were not correlated with duration of disease or disability measured by the Expanded Disability Status Scale. Among women, fatigue was associated with anxiety (p < or = 0.010) and depression (p = 0.007). No such association was found among men. Anxiety and depression occur more frequently in multiple sclerosis patients than in the general population. Fatigue was associated with these neuropsychiatric manifestations in only women.