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Objective: The most common genetic cause of amyotrophic lateral sclerosis (ALS) is the C9orf72 expansion. A high incidence of this expansion has been detected in Sweden and Finland. This Norwegian population-based study aimed to identify the prevalence, geographic distribution, ancestry, and relatedness of ALS patients with a C9orf72 expansion (C9 pos ). Further, we compared C9 pos and C9 neg patients' clinical presentation, family history of ALS and other neurodegenerative disorders, and sociodemographic status., Methods: We recruited ALS patients from all 17 Departments of neurology in Norway. Blood samples and questionnaires regarding clinical characteristics, sociodemographic status and family history of ALS, and other neurodegenerative disorders were collected. The C9orf72 expansion was examined for all patients., Results: The study enrolled 500 ALS patients, 8.8% of whom were C9 pos , with half being sporadic ALS cases. The proportion of C9 pos cases differed between regions, ranging from 17.9% in the Northern region to 1.9% in the Western region. The majority of C9 pos patients had non-Finnish European descent and were not closely related. C9 pos patients exhibited a significantly shorter mean survival time, had a higher frequency of relatives with ALS or dementia, and were more often unmarried/single and childless than C9 neg patients., Conclusion: C9 pos patients constitute a large portion of the Norwegian ALS population. Ancestry and relatedness do not adequately explain regional differences. Relying on clinical information to identify C9 pos patients has proven to be challenging. Half of C9 pos patients were reported as having sporadic ALS, underlining the importance of carefully assessing family history and the need for genetic testing.

Genetic repeat expansions cause neuronal degeneration in amyotrophic lateral sclerosis as well as other neurodegenerative disorders such as spinocerebellar ataxia, Huntington's disease and Kennedy's disease. Repeat expansions in the same gene can cause multiple clinical phenotypes. We aimed to characterize repeat expansions in a Norwegian amyotrophic lateral sclerosis cohort. Norwegian amyotrophic lateral sclerosis patients ( n = 414) and neurologically healthy controls adjusted for age and gender ( n = 713) were investigated for repeat expansions in AR , ATXN1 , ATXN2 and HTT using short read exome sequencing and the ExpansionHunter software. Five amyotrophic lateral sclerosis patients (1.2%) and two controls (0.3%) carried ≥36 repeats in HTT ( P = 0.032), and seven amyotrophic lateral sclerosis patients (1.7%) and three controls (0.4%) carried ≥29 repeats in ATXN2 ( P = 0.038). One male diagnosed with amyotrophic lateral sclerosis carried a pathogenic repeat expansion in AR , and his diagnosis was revised to Kennedy's disease. In ATXN1 , 50 amyotrophic lateral sclerosis patients (12.1%) and 96 controls (13.5%) carried ≥33 repeats ( P = 0.753). None of the patients with repeat expansions in ATXN2 or HTT had signs of Huntington's disease or spinocerebellar ataxia type 2, based on a re-evaluation of medical records. The diagnosis of amyotrophic lateral sclerosis was confirmed in all patients, with the exception of one patient who had primary lateral sclerosis. Our findings indicate that repeat expansions in HTT and ATXN2 are associated with increased likelihood of developing amyotrophic lateral sclerosis. Further studies are required to investigate the potential relationship between HTT repeat expansions and amyotrophic lateral sclerosis., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Fatigue affects 60-90% of people with multiple sclerosis (MS). It reduces quality of life and the ability to work. The cause of fatigue in MS remains unknown. Several disease-modifying treatments (DMTs) slow the disease process in relapsing MS by suppressing neuroinflammation. We aimed to investigate if treatment with a DMT is associated with lower rates of fatigue., Methods: In this cross-sectional study of the MS population in three counties in Norway, we used the Fatigue Scale for Motor and Cognitive Functions (FSMC) and the Hospital Anxiety and Depression Scale (HADS) to assess patient-reported fatigue, anxiety and depression. Clinical data were retrieved from the electronic patient record system. We categorized DMTs as high-efficacy therapy or moderate-efficacy therapy. High-efficacy drugs included fingolimod, natalizumab, ocrelizumab, rituximab, alemtuzumab, daclizumab, and autologous hematopoietic stem cell transplantation. Moderate-efficacy drugs included interferons, glatiramer acetate, dimethyl fumarate, and teriflunomide. We included persons with relapsing MS only., Results: Of 1142 patients, 80% had fatigue. Fifty-six percent of the patients were on DMTs (25% on moderate-efficacy treatment and 30% on high-efficacy treatment), 18% had discontinued treatment and 26% had never received any DMT. Sex, level of disability as measured by the Multiple Sclerosis Severity Score, anxiety and depression were independently associated with fatigue. Moderate-efficacy treatment was associated with less fatigue, but not after adjustment for other variables. There was no association between high-efficacy treatment and fatigue., Conclusion: We found no independent relationship between the use of disease-modifying treatment and fatigue in MS., Competing Interests: Declaration of Competing Interest LB has received unrestricted research grants from Sanofi, and advisory board honoraria from Sanofi, Merck and Biogen CSS has received unrestricted research grants from Sanofi and Novartis, and advisory board and/or speaker honoraria from Sanofi, Merck, BMS, Novartis and Biogen HØF has received unrestricted research grants from Biogen and Novartis, and advisory board and/or speaker honoraria Sanofi, Merck and Biogen PBH has received funding for travel or speaker's fees from Novartis, UCB, Biogen, Teva and Sanofi. HO has no conflicts of interest. CB has no conflicts of interest. EGC has received unrestricted research grants from Sanofi, and advisory board and/or speaker honoraria from Biogen, BMS, Janssen, Merck, Novartis, Roche, Sanofi and Teva., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: No evidence of disease activity with three components (NEDA-3) is achieved if the person with MS (pwMS) has no new MRI lesions, no new relapses and no change in Expanded disability status scale (EDSS) over 1 year. Whether NEDA-3 is a good tool in measuring disease activity is up for discussion, but it is superior to the individual parameters separately and user-friendly. There is disagreement on whether NEDA-3 is a good predictor of long-term disability., Methods: This is a retrospective cohort study using real-world data with limited selection bias from the complete MS population at two hospitals in the southeast of Norway. We included pwMS diagnosed between 2006 and 2017 who had enough information to determine time to failure of NEDA-3 after diagnosis., Results: Of 536 pwMS, only 38% achieved NEDA 1 year after diagnosis. PwMS achieving NEDA were more likely to be started on a high efficacy drug as the initial drug, but there were no demographic differences. Mean time to NEDA failure was 3.3 (95% CI 2.9-3.7) years. Starting a high efficiacy therapy was associated with an increased risk of sustaining NEDA as compared to those receiving moderate efficacy therapy. PwMS who achieved NEDA at year one had a mean time to EDSS 6 of 33.8 (95% CI 30.9-36.8) years vs. 30.8 (95% CI 25.0-36.6) years in pwMS who did not achieve NEDA, p < 0.001. When rebaselining NEDA 1 year after diagnosis, 52.2% achieved NEDA in the 1st year after rebaseline, mean time to NEDA failure was 3.4 (95% CI 3.0-3.7) years and mean time to EDSS 6 was 44.5 (95% CI 40.4-48.5) years in pwMS achieving NEDA vs. 29.6 (95% CI 24.2-35.0) years in pwMS not achieving NEDA, p < 0.001. After rebaseline, pwMS with a high efficacy therapy as the initial drug had a mean time from diagnosis to NEDA fail of 4.8 years (95% CI 3.9-5.8) vs. 3.1 years (95% CI 2.7-3.5) in pwMS started on a moderate efficacy therapy, p < 0.001. In pwMS with NEDA failure at year one, 70% failed one, 28% failed two and 2% failed three components. New MRI lesions were the most common cause of NEDA failure (63%), followed by new relapses (50%) and EDSS change (25%)., Conclusion: NEDA-3 from rebaseline after 1 year, once treatment is stabilized, can predict the long-term disease course in MS. Starting a high efficacy DMT is associated with longer time to NEDA failure than moderate therapies. Finally, most pwMS only fail one component and new MRI lesions are the most likely cause of NEDA failure., Competing Interests: Author CS has received personal compensation for lectures and/or serving on scientific advisory boards from Sanofi, Merck, Novartis, BMS, and Biogen Idec and received unrestricted research grants from Sanofi and Novartis. Author HF has received unrestricted research grants from Biogen Idec and Novartis. Author KB has received personal compensation for lectures and/or serving on advisory boards from Biogen, Novartis, and Merck. Author LB has received unrestricted research grants from Sanofi, and advisory board honoraria from Sanofi, Merck, and Biogen. Author PB-H has received advisory board and/or speaker honoraria from Novartis, UCB, Teva, Merck, and Biogen Idec. Author EC has received personal compensation for lectures and / or serving on scientific advisory boards for Almirall, Biogen, BMS, Janssen, Genzyme, Merck, Novartis, Roche, and Teva. Her department has received unrestricted research grants from Biogen, Novartis, Merck, and Genzyme. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Simonsen, Flemmen, Broch, Brekke, Brunborg, Berg-Hansen and Celius.)

Objectives: Fatigue is one of the leading causes of reduced quality of life and inability to work in people with multiple sclerosis (pwMS). Currently, no treatment effectively ameliorates fatigue. We still know little about what causes fatigue and which factors may contribute to fatigue. Knowledge about socioeconomic factors' role in fatigue might help us recognize strategies for the management of fatigue. Our aim was to explore whether socioeconomic factors are associated with the presence or level of perceived fatigue., Methods: This is a cross-sectional study of the MS population in three Norwegian counties. We used the Fatigue Scale for Motor and Cognitive Functions to assess self-reported fatigue, and obtained socioeconomic data from Statistics Norway and questionnaires. To assess self-reported anxiety and depression, we employed the Hospital Anxiety and Depression Scale. Clinical data were gathered from the hospital record system., Results: The response rate was 64% (1599/2512). Seventy percent of the respondents were female, and the mean age was 52 years. Higher levels of education were associated with lower levels of fatigue. Receiving a disability pension, being divorced and having children were all factors associated with higher levels of fatigue, as were low parental education, low income, current smoking, and autoimmune comorbidities. We found a higher prevalence of anxiety and depression in pwMS with fatigue compared to those without fatigue CONCLUSION: Female sex, high level of disability, anxiety, depression and socioeconomic factors were independently associated with fatigue in contemporary patients with MS. These factors should be considered when devising management strategies., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: There is limited evidence regarding optimal duration of antibiotic treatment in neuroborreliosis. We aimed to compare efficacy and safety of oral doxycycline for 2 and 6 weeks in European Lyme neuroborreliosis (LNB)., Methods: The trial had a randomised, double-blinded, placebo-controlled, non-inferiority design. Patients with LNB were recruited from eight Norwegian hospitals and randomised to doxycycline 200 mg once daily for 2 weeks, followed by 4 weeks of placebo, or doxycycline 200 mg once daily for 6 weeks. The primary endpoint was clinical improvement as measured by difference in a Composite Clinical Score (0-64 points) from baseline to 6 months. The non-inferiority margin was predetermined to 0.5 points., Results: One hundred and twenty-one patients were included. Fifty-two treated for 2 weeks and 53 for 6 weeks were included in the intention-to-treat analyses, and 52 and 51 in per-protocol analysis. Mean difference in clinical improvement between the groups was 0.06, 95% CI -1.2 to 1.2, p=0.99 in the intention-to-treat population, and -0.4, 95% CI -1.4 to 0.7, p=0.51 in the per-protocol population and non-inferiority could not be established. There were no treatment failures and no serious adverse events. The groups did not differ in secondary outcomes including clinical scores at 10 weeks and 12 months, cerebrospinal fluid data and patient-reported outcome measures. Patients receiving 6 weeks doxycycline reported slightly more side effects in week 5., Conclusion: Our results strongly indicate that there are no benefits of doxycycline treatment beyond 2 weeks in European LNB., Trial Registration Number: 2015-001481-25., Competing Interests: Competing interests: SB has received honoraria for lecturing from Biogen and Novartis., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Several studies report an impact of socioeconomic factors on access to disease modifying treatment (DMT) in multiple sclerosis (MS), with a trend of less access to more deprived persons. We investigated the impact of socioeconomic status (SES) on access to treatment in a well-defined Norwegian MS cohort., Methods: This is a study of a population-based Norwegian MS cohort. We collected detailed information on disease development, progression, and DMT administered. Socioeconomic data was obtained from Statistics Norway and a questionnaire., Results: We included 1314 persons with relapsing remitting MS at the prevalence date 01/01/2018. The population ever treated with DMTs is younger at onset, has shorter time from onset to diagnosis and lower expanded disability status score (EDSS) at diagnosis. The persons with MS (pwMS) with the highest levels of education, and those who are married are more likely to be ever treated with DMT. In the subgroup treated with a high efficacy DMT as a first drug, the pwMS are younger at prevalence date (39.9 years (SD 12.1)) compared with those who are not treated with a high efficacy DMT as first drug (43.8 years (SD 10.3)). The subgroup treated with a high efficacy DMT as a first drug has a 0.5 point higher EDSS at diagnosis compared to those not treated with a high efficacy DMT as a first drug. The level of education, household income and marital status are inversely related to access to high efficacy DMT as a first drug. None of the above differences persist when analyzing the subgroup diagnosed within the last six years (2012-2017)., Conclusions: Since 2012, the pwMS in this Norwegian cohort are treated equally with DMT in terms of different measures of socioeconomic position., (Copyright © 2022. Published by Elsevier B.V.)

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons. In Europe, disease-causing genetic variants have been identified in 40-70% of familial ALS patients and approximately 5% of sporadic ALS patients. In Norway, the contribution of genetic variants to ALS has not yet been studied. In light of the potential development of personalized medicine, knowledge of the genetic causes of ALS in a population is becoming increasingly important. The present study provides clinical and genetic data on familial and sporadic ALS patients in a Norwegian population-based cohort., Methods: Blood samples and clinical information from ALS patients were obtained at all 17 neurological departments throughout Norway during a 2-year period. Genetic analysis of the samples involved expansion analysis of C9orf72 and exome sequencing targeting 30 known ALS-linked genes. The variants were classified using genotype-phenotype correlations and bioinformatics tools., Results: A total of 279 ALS patients were included in the study. Of these, 11.5% had one or several family members affected by ALS, whereas 88.5% had no known family history of ALS. A genetic cause of ALS was identified in 31 individuals (11.1%), among which 18 (58.1%) were familial and 13 (41.9%) were sporadic. The most common genetic cause was the C9orf72 expansion (6.8%), which was identified in 8 familial and 11 sporadic ALS patients. Pathogenic or likely pathogenic variants of SOD1 and TBK1 were identified in 10 familial and 2 sporadic cases. C9orf72 expansions dominated in patients from the Northern and Central regions, whereas SOD1 variants dominated in patients from the South-Eastern region., Conclusion: In the present study, we identified several pathogenic gene variants in both familial and sporadic ALS patients. Restricting genetic analysis to only familial cases would miss more than 40 percent of those with a disease-causing genetic variant, indicating the need for genetic analysis in sporadic cases as well., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: The duration and features of the multiple sclerosis (MS) prodrome are not well defined. We aimed to ascertain whether people with a future MS diagnosis have more days of absence and perform worse in upper secondary school than age, gender and county-matched controls., Methods: Using registry data from the southeast of Norway, we identified people with MS born ≥1978. Statistics Norway provided information on grades and days of absence in cases and matched controls. We looked at absence in the three years of upper secondary school and grades in the compulsory subjects Norwegian, English, mathematics and physical education., Results: We identified 107 cases with disease onset one year or more after graduation and 626 controls. There were no significant differences in absence or grades achieved in the population as a whole or in those with disease onset within four years of diagnosis, and no association between time to disease onset and days of absence or grades., Conclusion: There was no difference in days of absence or grades achieved in upper secondary school in the four years leading up to disease onset in cases compared to controls. A potential prodrome may not affect cognition enough to impact school achievements., (Copyright © 2021. Published by Elsevier B.V.)

Objective: The identification of potential risk factors for disease severity is of great importance in the treatment of multiple sclerosis. The influence of socioeconomic status on progression in multiple sclerosis (MS) is sparsely investigated. Our aim was to investigate how socioeconomic status in adolescence influences disease progression in later life., Methods: A total of 1598 patients with multiple sclerosis from a well-defined population in Norway were included. Detailed information on disease progression, measured by expanded disability status scale (EDSS) and multiple sclerosis severity score (MSSS), were combined with data on socioeconomic factors. We used residency and parental level of education at patients' age 16 and exposure to second-hand smoking as a measure of socioeconomic status in adolescence, adjusting for the same variables as well as use of disease modifying treatments at prevalence date 01.01.18., Results: High maternal level of education at patients' age 16 was significantly associated with less pronounced disease progression measured by MSSS (β-coefficient -0.58, p = 0.015), younger age and lower EDSS at disease onset, and shorter time from onset to diagnosis. No significant associations were found for paternal education level and MSSS. The use of any disease modifying treatment before prevalence date was significantly associated with disease progression (β-coefficient -0.49, p=0.004), while residence, current and second-hand smoking were not., Conclusion: This study on a population-based, real-world cohort shows that the parental level of education has a significant impact on a timely diagnosis of MS. In addition to disease modifying treatment, maternal level of education also had an impact on disease progression in later life., (Copyright © 2021. Published by Elsevier B.V.)

Background: Moderate and high efficacy disease modifying therapies (DMTs) have a profound effect on disease activity. The current treatment guidelines only recommend high efficacy DMTs for patients with highly active MS. The objective was to examine the impact of initial treatment choice in achieving no evidence of disease activity (NEDA) at year 1 and 2. Methods: Using a real-world population-based registry with limited selection bias from the southeast of Norway, we determined how many patients achieved NEDA on moderate and high efficacy DMTs. Results: 68.0% of patients who started a high efficacy DMT as the first drug achieved NEDA at year 1 and 52.4% at year 2 as compared to 36.0 and 19.4% of patients who started a moderate efficacy DMT as a first drug. The odds ratio (OR) of achieving NEDA on high efficacy drugs compared to moderate efficacy drugs as a first drug at year 1 was 3.9 (95% CI 2.4-6.1, p < 0.001). The OR for high efficacy DMT as the second drug was 2.5 (95% CI 1.7-3.9, p < 0.001), and was not significant for the third drug. Patients with a medium or high risk of disease activity were significantly more likely to achieve NEDA on a high efficacy therapy as a first drug compared to moderate efficacy therapy as a first drug. Conclusions: Achieving NEDA at year 1 and 2 is significantly more likely in patients on high-efficacy disease modifying therapies than on moderate efficacy therapies, and the first choice of treatment is the most important. The immunomodulatory treatment guidelines should be updated to ensure early, high efficacy therapy for the majority of patients diagnosed with MS., Competing Interests: CS has received unrestricted research grant from Sanofi and Novartis, advisory board and/or speaker honoraria from Sanofi, Merck, Novartis, and Biogen Idec. HF has received unrestricted research grant Biogen Idec and Novartis, advisory board and/or speaker honoraria Sanofi, Merck, and Biogen Idec. LB has received an unrestricted grant from Sanofi Genzyme and advisory board honoraria from Merck. PB-H has received advisory board and/or speaker honoraria from Novartis, UCB, Sanofi, Merck, and Biogen Idec. EC has received unrestricted research grants from Novartis and Sanofi, advisory boards and/or speaker honoraria (Almirall, Biogen Idec, Merck, Roche, Novartis, Sanofi, and Teva). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Simonsen, Flemmen, Broch, Brunborg, Berg-Hansen, Moen and Celius.)

Objective: To assess the occurrence of perinatal depression and anxiety in women before and after diagnosis of multiple sclerosis (MS)., Methods: A total of 114,629 pregnant women were included in the Norwegian Mother, Father and Child Cohort study (1999-2008). We assessed depression and anxiety by questionnaires during and after pregnancy. Women with MS were identified from national health registries and hospital records and grouped into (1) MS diagnosed before pregnancy (n = 140) or MS diagnosed after pregnancy with (2) symptom onset before pregnancy (n = 98) or (3) symptom onset after pregnancy (n = 308). Thirty-five women were diagnosed with MS in the postpartum period. The reference group (n = 111,627) consisted of women without MS., Results: Women with MS diagnosed before pregnancy had an adjusted odds ratio of 2.0 (95% confidence interval, 1.2-3.1) for depression in the third trimester. Risk factors were adverse socioeconomic factors and history of psychiatric disease and physical/sexual abuse. The risk of anxiety was not increased. Women diagnosed with MS in the postpartum period had especially high risk of postpartum depression. Women with MS symptom onset within 5 years after pregnancy had increased risk of both depression and anxiety during pregnancy, whereas women with more than 5 years until symptom onset did not., Conclusion: Women diagnosed with MS have increased risk of perinatal depression. Women with MS symptom onset within 5 years after pregnancy have increased risk of both depression and anxiety during pregnancy., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objectives: Over the past few decades, there has been an improvement in the rate of disability progression in multiple sclerosis (MS) patients, and most studies relate this evolvement to the introduction of disease-modifying therapies. However, several other factors have changed over this period, including access to MRI and newer diagnostic criteria. The aim of this study is to investigate changes in the natural course of MS over time in a near-complete and geographically well-defined population from the south-east of Norway., Methods: We examined disease progression and demographics over two decades and assessed the effect of disease-modifying therapies using linear mixed-effect models., Results: In a cohort of 2097 patients, we found a significant improvement in disability as measured by the Expanded Disability Status Scale (EDSS) stratified by age, and the improvement remained significant after adjusting for time on disease-modifying medications, gender and progressive MS at onset. The time from disease onset to EDSS 6 in the total cohort was 29.8 years (95% CI 28.5-31.1) and was significantly longer in patients diagnosed after 2006 compared to patients diagnosed before. There are significant differences between patient demographics, as well as time to EDSS 6, in the near-complete, geographically well-defined population compared to an additional cohort from the capital Oslo and its suburbs., Conclusion: The natural course of MS is improving, but the improvement seen in disease progression has multifaceted explanations. Our study underlines the importance of completeness of data, relevant timeframes and demographics when comparing different MS populations. Studies on incomplete populations should be interpreted with caution.

Objective: The prevalence of multiple sclerosis (MS)-related fatigue may have changed due to new diagnostic criteria and new disease modifying drugs. We aimed to assess the prevalence of fatigue in a contemporary MS cohort, and to explore associations between fatigue and clinical and demographic factors., Methods: This is a cross-sectional study of the MS population in three Norwegian counties. Fatigue was assessed with the Fatigue Scale for Motor and Cognitive Functions (FSMC). We also assessed self-reported anxiety, depression and daytime sleepiness., Results: The response rate was 64% (1599/2512). The mean age of the participants was 52 ± 13 years, median EDSS was 2.5 (IQR 1.5-3.0) and median disease duration from onset was 16 years (IQR 8-25). We found a prevalence of fatigue of 81%. Women had a higher prevalence of fatigue than men (83% vs 78%, p = 0.02). The prevalence increased with age (p < 0.001) and with increasing disease severity (p < 0.001), but in multivariate analyses, only sex and disease severity remained independent determinants of fatigue. Anxiety, depression, and daytime sleepiness were more prevalent in patients with fatigue than in those without fatigue (all p-values < 0.001)., Conclusion: The prevalence of fatigue is high in contemporary patients with MS. Fatigue is associated with female sex and level of disability, as well as with anxiety, depression and excessive daytime sleepiness., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Objective: To explore the trends in prevalence and incidence of multiple sclerosis (MS) in Telemark, Norway (latitude 58.7-60.3˚N), over the past two decades, with focus on differences between rural and urban areas., Methods: Data from all patients with a confirmed diagnosis of MS in Telemark since 1993 were prospectively recorded and collected in a retrospective chart review. Prevalence estimates on January 1 st 1999, 2009 and 2019, and incidence rates at five-year intervals between 1999 and 2018 were calculated and all results were adjusted to the European Standard Population. The study population was divided into urban and rural residency using a Norwegian governmental index., Results: We registered 579 patients with MS in Telemark between 1999 and 2019. The adjusted prevalence estimates for January 1 st 1999, 2009 and 2019 were 105.8/10 5 , 177.1/10 5 and 260.6/10 5 , respectively. In 2019, the prevalence estimates were 250.4/10 5 in urban and 316.2 /10 5 in rural areas. Between 1999 and 2018, the yearly incidence increased from 8.4/10 5 to 14.4/10 5 ., Conclusions: The prevalence of MS in Telemark is among the highest ever reported in Norway, consistent with an increasing incidence in the county over the past twenty years. The even higher prevalence in the rural areas is unlikely to be explained by possible risk factors like latitude, exposure to sunlight and diet. Further studies on differences between urban and rural areas are required to reveal possible new risk factors., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To chart patient-reported outcome measures (PROMs) in Norwegian patients treated for definite neuroborreliosis (NB)., Material and Methods: Adult patients treated for definite NB 1-10 years earlier supplied demographics, symptoms and treatment during NB, and answered validated questionnaires; Fatigue Severity Scale (FSS), Hospital Anxiety and Depression Scale (HADS), health-related quality of life questionnaire (RAND-36), and Patient Health Questionnaire (PHQ-15)., Results: A higher proportion of NB-treated persons reported severe fatigue, defined as FSS score ≥ 5, than in Norwegian normative data, but when removing persons with confounding fatigue associated comorbidities (n = 69) from the analyses, there was no difference between groups. Physical health-related quality of life (RAND-36 PCS), mean FSS score, proportions of persons reporting moderate or severe somatic symptom burden (PHQ-15 score ≥ 10), anxiety (HADS-A ≥ 8), or depression (HADS-D ≥ 8) did not differ between NB-treated persons and reference scores. Mental health-related quality of life (RAND-36 MCS) was poorer than in normative data (47.1 vs. 53.3), but associated with anxiety, depression and current moderate or severe somatic symptom burden, and not with NB characteristics., Conclusions: Results on validated PROM questionnaires measuring fatigue, anxiety, depression, self-reported somatic symptom burden, and physical health-related quality did not differ between persons treated for definite NB 1-10 years earlier and reference scores. NB-treated persons tended to report a slightly poorer mental health-related quality of life than found in normative data, but when adjusting for confounders the causative connection is questionable. Overall, the long-term prognosis of definite NB seems to be good., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Background: Diagnostic criteria for multiple sclerosis have been developed to guide the diagnostic process. In the latest revision of the McDonald criteria, the presence of oligoclonal bands may replace the need for dissemination in time. The aim of this study is to investigate if the less time-consuming analysis of immunoglobulin G index in cerebrospinal fluid can safely predict the findings of oligoclonal bands., Methods: This is a retrospective study of patients with multiple sclerosis at three hospitals in South-East Norway where lumbar puncture is performed routinely. We included patients diagnosed with multiple sclerosis after 2005 with known oligoclonal band status and an immunoglobulin G index score., Results: Of 1295 patients diagnosed during or after 2005, 93.8% were oligoclonal band positive at diagnosis. Of 842 multiple sclerosis patients with known immunoglobulin G index and oligoclonal band status, 93.3% were oligoclonal band positive and 76.7% had an elevated immunoglobulin G index. The positive predictive value of a high immunoglobulin G index when oligoclonal bands are positive was 99.4% (95% confidence interval 98.4-99.8%). The negative predictive value of a normal immunoglobulin G index when oligoclonal bands are negative was 26.5% (95% confidence interval 23.5-29.9%)., Conclusion: An immunoglobulin G index >0.7 has a positive predictive value >99% for oligoclonal bands. An elevated immunoglobulin G index adds diagnostic value versus oligoclonal bands and saves time in the diagnostic process., (© The Author(s) 2020.)

Evidence-based guidelines, published in 2010, equate the efficacy of oral and intravenous antibiotics and recommend treatment duration of 2 weeks in early Lyme neuroborreliosis (LNB) without encephalitis or myelitis. Further, the Norwegian health authorities give a general advice to choose oral rather than intravenous administration when proven effective, due to lower costs, fewer risks, and reduced patient inconvenience. In this study we aimed to chart LNB treatment practice in Norway and compare it to these recommendations. Adult patients diagnosed with definite LNB between 2007 and 2013 in 11 different hospitals in the four health regions in Norway were invited to answer a questionnaire regarding duration and administration of antibiotic treatment. A total of 253 patients answered. Median age at diagnosis was 59 years (range 19-83), and 125 (49%) were women. Duration of treatment was 1 week in 7 (3%) patients, 2 weeks in 81 (32%), 3 weeks in 62 (25%), 4 weeks in 48 (19%), 5 weeks in 12 (5%), ≥6 weeks in 29 (12%), and unknown in 14 (6%). Treatment was given orally in 77 (30%) patients, intravenously in 110 (44%), both orally and intravenously in 65 (26%), and unknown in one. Treatment practices differed between the health regions (p = 0.002). During the study period, there were no significant time trend neither with respect to proportion of patients treated for only 2 weeks (OR 0.899, p = 0.109) nor with respect to proportion of patients treated exclusively with oral antibiotics (OR 1.131, p = 0.074). In conclusion, there seem to be a gap between evidence-based recommendations and treatment practice of LNB in Norway.