Elisabeth Gulowsen Celius

• Mäki-Marttunen, V.; Nerland, S.; Jørgensen, K. N.; Høgestøl, E. A.; Rokicki, J. & Alnæs, D. [Vis alle 36 forfattere av denne artikkelen] (2026). Thalamic nuclei volumes across psychiatric and neurological disorders: a multi-site magnetic resonance imaging study. Translational Psychiatry. 16(1). doi: 10.1038/s41398-026-04076-5. Fulltekst i vitenarkiv
• Myklebust, Harald; Grønnestad, Erik; Peel, Geoffrey; Flemmen, Heidi Øyen; Brekke, Kamilla & Broch, Line [Vis alle 9 forfattere av denne artikkelen] (2026). The Norwegian NBSS-SF: Psychometric Properties in People With Multiple Sclerosis Treated With Natalizumab. Acta Neurologica Scandinavica. ISSN 0001-6314. 2026(1). doi: 10.1155/ane/7868813. Fulltekst i vitenarkiv Vis sammendrag

  Introduction Neurogenic lower urinary tract dysfunction (NLUTD) is common in neurological disease. Patient reported outcome measures (PROMs) can be useful for evaluating NLUTD and are recommended by guidelines. The Neurogenic Bladder Symptom Score–Short form (NBSS‐SF) is a 10‐item questionnaire that measures symptom burden and bladder‐related quality of life due to NLUTD. The aim of this study is to translate and validate the Norwegian version of the NBSS‐SF. Methods The translation of the NBSS‐SF was done in accordance with international guidelines for cross‐cultural adaptation of questionnaires. Ten people with multiple sclerosis (pwMS) pilot‐tested the pre‐final version and the final version was made. We assessed the psychometric properties of the Norwegian NBSS‐SF in pwMS treated with natalizumab (NTZ). They completed the Norwegian NBSS‐SF and International Prostate Symptom Score (IPSS) at baseline and repeated the NBSS‐SF at second visit. Patient data was gathered from health records. Results A total of 69 pwMS were recruited. Mean age was 46.7 years (SD 11.6), median disease duration of 10 years, and median Expanded Disability Status Scale score (EDSS) of 2.0 (range 0–8). Median NBSS‐SF‐score was 4 (range 1–19). There was good correlation ( S p e a r m a n ’ s   r h o = 0.51, p < 0.001) between NBSS‐SF and IPSS. NBSS‐SF‐score correlated with EDSS ( S p e a r m a n ’ s   r h o = 0.46). Patients treated for NLUTD had higher scores ( p < 0.001). The Norwegian NBSS‐SF has good internal consistency ( C r o n b a c h ’ s   a l p h a = 0.88) and test–retest reliability ( i n t r a c l a s s   c o r r e l a t i o n   c o e f f i c i e n t = 0.88). Conclusion The Norwegian NBSS‐SF proved valid and reliable for measuring symptoms of NLUTD in a cohort of pwMS treated with NTZ.

• Høgset, Anne; Simonsen, Cecilia Smith; Flemmen, Heidi Øyen; Brunborg, Cathrine; Broch, Line & Berg-Hansen, Pål [Vis alle 7 forfattere av denne artikkelen] (2026). Differences in Income Growth Between People With Multiple Sclerosis and Controls: A Norwegian Cohort Study. European Journal of Neurology. ISSN 1351-5101. 33(6). doi: 10.1111/ene.70638. Fulltekst i vitenarkiv Vis sammendrag

  Objectives: The aim of this study was to determine if people with MS (pwMS) experience a different income development from controls, and if so, at what age, and at what time in the disease course. Methods: We examined income development for pwMS compared to matched controls in a Norwegian cohort. We assessed the impact of both age and time from diagnosis on income using linear mixed‐effects models. Results Men with MS (mwMS) had, on average, a lower income trajectory compared to controls at an earlier age than women with MS (wwMS) (49 vs. 55 years). For men, the gap was increasing throughout the entire working age, while women were catching up with their controls close to retirement age. Although the absolute difference from controls is larger for mwMS than wwMS from age 50, the difference between the sexes is only statistically significant from age 60. The income increase rate was lower for both mwMS and wwMS compared to controls after being diagnosed with MS. For mwMS, the difference is evident 2 years after diagnosis, and for wwMS, 5 years after diagnosis. The average income loss experienced by mwMS was double that of women from 6 years after diagnosis, but the difference was not statistically significant when comparing the sexes. Conclusions: PwMS have lower income development than controls. Men lose income earlier in life and earlier in the disease course than women.

• Rasmussen, Tilde Harridsleff; Schikora-Rustad, Stine; Lorentzen, Åslaug Rudjord; Tran, Trung; Øverås, Mathias Herstad & Myhr, Kjell-Morten [Vis alle 22 forfattere av denne artikkelen] (2026). Low risk of severe COVID-19 in vaccinated people with multiple sclerosis: a nationwide Norwegian study. BMJ Neurology Open. 8(1). doi: 10.1136/bmjno-2026-001556. Fulltekst i vitenarkiv Vis sammendrag

  Background: We aimed to assess antibody responses and COVID-19 outcomes after vaccination in people with multiple sclerosis (pwMS) receiving disease-modifying therapies. Methods: NevroVAX is a Norwegian multicentre cohort study including 3559 pwMS and 449 healthy controls (HCs) who received at least one dose of BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna) or ChAdOx1 (AstraZeneca/Oxford) between January 2021 and December 2022. Data from records, registries, questionnaires and blood samples collected June 2021–November 2023 were analysed. Primary outcomes were humoral immune responses assessed by seroconversion (anti-spike and anti-receptor-binding domain (RBD) IgG ≥5 binding antibody units/mL). Secondary outcomes included quantitative anti-RBD IgG levels, breakthrough SARS-CoV-2 infection, COVID-19-related hospitalisation and death. Associations with breakthrough infection were evaluated using multivariable logistic regression. Results: Among 3559 pwMS, 1201 received anti-CD20 monoclonal antibodies and 324 sphingosine-1-phosphate receptor (S1PR) modulators. After three vaccine doses, seroconversion was observed in 43.0% of anti-CD20-treated patients and 48.4% of S1PR-treated patients. In multivariable analysis, seroconversion was associated with lower risk of breakthrough infection (OR 0.67, 95% CI 0.58 to 0.78). During follow-up, 58 pwMS (1.6%) were hospitalised for COVID-19; 4 (0.1%) required non-invasive ventilatory support, no patients required invasive ventilation and no deaths occurred. Conclusions: Humoral vaccine responses were impaired in pwMS receiving anti-CD20 or S1PR therapies, but severe COVID-19 was rare. These findings support continued vaccination programmes and tailored protective measures for immunomodulated populations.

• Høgestøl, Einar August; Brustad, Åge Winje; Celius, Elisabeth Gulowsen; Meling, Martine; Berg-Hansen, Pål & Kro, Grete Anette Birkeland [Vis alle 13 forfattere av denne artikkelen] (2026). Serum drug levels and JCV assay discrepancies after switching from originator to biosimilar natalizumab. BMJ Neurology Open. 8(1). doi: 10.1136/bmjno-2025-001477. Fulltekst i vitenarkiv
• Fox, Robert J.; Bar-Or, Amit; Traboulsee, Anthony; Oreja-Guevara, Celia; Giovannoni, Gavin & Vermersch, Patrick [Vis alle 13 forfattere av denne artikkelen] (2025). Tolebrutinib in Nonrelapsing Secondary Progressive Multiple Sclerosis. New England Journal of Medicine. ISSN 0028-4793. 392(19), s. 1892–1892. doi: 10.1056/nejmoa2415988. Fulltekst i vitenarkiv
• Skattebøl, Lars; Nygaard, Gro Owren; Leonardsen, Esten Høyland; Kaufmann, Tobias Herbert; Moridi, Thomas & Stawiarz, Leszek [Vis alle 23 forfattere av denne artikkelen] (2025). Brain age in multiple sclerosis: a study with deep learning and traditional machine learning. Brain Communications. 7(3). doi: 10.1093/braincomms/fcaf152. Fulltekst i vitenarkiv Vis sammendrag

  ‘Brain age’ is a numerical estimate of the biological age of the brain and an overall effort to measure neurodegeneration, regardless of disease type. In multiple sclerosis, accelerated brain ageing has been linked to disability accrual. Artificial intelligence has emerged as a promising tool for the assessment and quantification of the impact of neurodegenerative diseases. Despite the existence of numerous AI models, there is a noticeable lack of comparative imaging data for traditional machine learning versus deep learning in conditions such as multiple sclerosis. A retrospective observational study was initiated to analyse clinical and MRI data (4584 MRIs) from various scanners in a large longitudinal cohort (n = 1516) of people with multiple sclerosis collected from two institutions (Karolinska Institute and Oslo University Hospital) using a uniform data post-processing pipeline. We conducted a comparative assessment of brain age using a deep learning simple fully convolutional network and a well-established traditional machine learning model. This study was primarily aimed to validate the deep learning brain age model in multiple sclerosis. The correlation between estimated brain age and chronological age was stronger for the deep learning estimates (r = 0.90, P &lt; 0.001) than the traditional machine learning estimates (r = 0.75, P &lt; 0.001). An increase in brain age was significantly associated with higher expanded disability status scale scores (traditional machine learning: t = 5.3, P &lt; 0.001; deep learning: t = 3.7, P &lt; 0.001) and longer disease duration (traditional machine learning: t = 6.5, P &lt; 0.001; deep learning: t = 5.8, P &lt; 0.001). No significant inter-model difference in clinical correlation or effect measure was found, but significant differences for traditional machine learning-derived brain age estimates were found between several scanners. Our study suggests that the deep learning-derived brain age is significantly associated with clinical disability, performed equally well to the traditional machine learning-derived brain age measures, and may counteract scanner variability.

• Cortese, Rosa; Sforazzini, Francesco; Gentile, Giordano; Mauro, Anna De; Luchetti, Ludovico & Amato, Maria Pia [Vis alle 55 forfattere av denne artikkelen] (2025). Deep Learning Modeling to Differentiate Multiple Sclerosis From MOG Antibody–Associated Disease. Neurology. ISSN 0028-3878. 105(6). doi: 10.1212/wnl.0000000000214075. Fulltekst i vitenarkiv Vis sammendrag

  Background and Objectives Multiple sclerosis (MS) is common in adults while myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) is rare. Our previous machine-learning algorithm, using clinical variables, ≤6 brain lesions, and no Dawson fingers, achieved 79% accuracy, 78% sensitivity, and 80% specificity in distinguishing MOGAD from MS but lacked validation. The aim of this study was to (1) evaluate the clinical/MRI algorithm for distinguishing MS from MOGAD, (2) develop a deep learning (DL) model, (3) assess the benefit of combining both, and (4) identify key differentiators using probability attention maps (PAMs). Methods This multicenter, retrospective, cross-sectional MAGNIMS study included scans from 19 centers. Inclusion criteria were as follows: adults with non-acute MS and MOGAD, with high-quality T2-fluid-attenuated inversion recovery and T1-weighted scans. Brain scans were scored by 2 readers to assess the performance of the clinical/MRI algorithm on the validation data set. A DL-based classifier using a ResNet-10 convolutional neural network was developed and tested on an independent validation data set. PAMs were generated by averaging correctly classified attention maps from both groups, identifying key differentiating regions. Results We included 406 MRI scans (218 with relapsing remitting MS [RRMS], mean age: 39 years ±11, 69% F; 188 with MOGAD, age: 41 years ±14, 61% F), split into 2 data sets: a training/testing set (n = 265: 150 with RRMS, age: 39 years ±10, 72% F; 115 with MOGAD, age: 42 years ±13, 61% F) and an independent validation set (n = 141: 68 with RRMS, age: 40 years ±14, 65% F; 73 with MOGAD, age: 40 years ±15, 63% F). The clinical/MRI algorithm predicted RRMS over MOGAD with 75% accuracy (95% CI 67–82), 96% sensitivity (95% CI 88–99), and specificity 56% (95% CI 44–68) in the validation cohort. The DL model achieved 77% accuracy (95% CI 64–89), 73% sensitivity (95% CI 57–89), and 83% specificity (95% CI 65–96) in the training/testing cohort, and 70% accuracy (95% CI 63–77), 67% sensitivity (95% CI 55–79), and 73% specificity (95% CI 61–83) in the validation cohort without retraining. When combined, the classifiers reached 86% accuracy (95% CI 81–92), 84% sensitivity (95% CI 75–92), and 89% specificity (95% CI 81–96). PAMs identified key region volumes: corpus callosum (1872 mm3), left precentral gyrus (341 mm3), right thalamus (193 mm3), and right cingulate cortex (186 mm3) for identifying RRMS and brainstem (629 mm3), hippocampus (234 mm3), and parahippocampal gyrus (147 mm3) for identifying MOGAD. Discussion Both classifiers effectively distinguished RRMS from MOGAD. The clinical/MRI model showed higher sensitivity while the DL model offered higher specificity, suggesting complementary roles. Their combination improved diagnostic accuracy, and PAMs revealed distinct damage patterns. Future prospective studies should validate these models in diverse, real-world settings. Classification of Evidence This study provides Class III evidence that both a clinical/MRI algorithm and an MRI-based DL model accurately distinguish RRMS from MOGAD.

• Skattebøl, Lars; Lundby, Rigmor; Øverås, Mathias H.; Sowa, Piotr; Celius, Elisabeth G. & Harbo, Hanne-Cathrin Flinstad [Vis alle 9 forfattere av denne artikkelen] (2025). Quantitative susceptibility mapping of paramagnetic rim lesions in early multiple sclerosis: A cross-sectional study of brain age and disability. Neuroimage: Reports. 5(3), s. 100277–100277. doi: 10.1016/j.ynirp.2025.100277. Fulltekst i vitenarkiv
• Alroughani, Raed; Celius, Elisabeth G.; Gray, Helen; Kasilingam, Elisabeth; Kruger, Paola & Montague, Amanda [Vis alle 12 forfattere av denne artikkelen] (2025). Guiding Multiple Sclerosis Care: An Update to the 2013 Consensus Statement from the MS in the 21st Century Steering Group. Neurology and Therapy. ISSN 2193-8253. doi: 10.1007/s40120-025-00849-0. Fulltekst i vitenarkiv
• Bungudo, Binyam Bogale; Solem, Ingrid Konstanse Ledel; Larsen, Anna Grøndahl; Celius, Elisabeth Gulowsen & Halvorsrud, Ragnhild (2025). Patient Pathways Inefficiencies in Neurology Care: Providers’ Perspectives. I Househ, Mowafa S.; Tariq, Zain Ul Abideen; Al-Zubaidi, Mahmood; Shah, Uzair & Huesing, Elaine (Red.), MEDINFO 2025 — Healthcare Smart × Medicine Deep: Proceedings of the 20th World Congress on Medical and Health Informatics. IOS Press. ISSN 9781643686080. s. 1676–1677. doi: 10.3233/SHTI251159. Fulltekst i vitenarkiv Vis sammendrag

  Care for diseases of the nervous system spans multiple providers and levels, often marked by coordination and communication inefficiencies. This study employed a validated pathways assessment tool to explore healthcare workers’ views on current patient pathways, revealing inefficiencies in care coordination, unmet patient information needs, fragmented and siloed digital systems.

• Simonsen, Cecilia Smith; Flemmen, Heidi Øyen; Broch, Line; Brekke, Kamilla; Myklebust, Harald & Berg-Hansen, Pål [Vis alle 8 forfattere av denne artikkelen] (2025). Reduced childbirth rates in multiple sclerosis from the prodromal phase: Evidence from a population-based cohort study. Multiple Sclerosis. ISSN 1352-4585. 31(4), s. 398–407. doi: 10.1177/13524585251315077. Fulltekst i vitenarkiv Vis sammendrag

  Background: The age of multiple sclerosis (MS) onset coincides with fertile age, and both improved prognosis and treatment may influence birth rates in people with MS (pwMS). Objectives: To investigate birth rates over time in pwMS compared with controls. Methods: This cohort study included pwMS from three hospitals in the southeast of Norway. Clinical data were collected prospectively. Statistics Norway provided year of live births and marital status in pwMS and controls matched for age, sex, and place of residence at age 16. Results: We included 1599 pwMS (1118 women with MS (wMS) and 481 men with MS (mMS)) and 23,855 controls. The mean number of live births was 1.5 (standard deviation (SD) 1.2) for pwMS versus 1.8 (SD 1.2) for controls (p < 0.001). Birth rates in wMS declined significantly starting 3 years before onset, with 4.5% giving birth versus 8.4% of controls 2 years before onset (p = 0.046). Birth rates were also lower 1 year after onset (p = 0.002). mMS showed a dip 2 years before onset (p = 0.002), but otherwise had rates similar to controls. There were no differences in marital status. Conclusion: wMS have reduced rates of childbirth compared with controls. This is significant already in the prodromal phase.

• Høgestøl, Einar August; Rinker, Daniel Allen; Maximov, Ivan; Sowa, Piotr; Celius, Elisabeth Gulowsen & Hope, Tuva Roaldsdatter [Vis alle 26 forfattere av denne artikkelen] (2025). A cross-sectional multicentre study of multishell diffusion MRI in multiple sclerosis. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 98. doi: 10.1016/j.msard.2025.106435. Fulltekst i vitenarkiv Vis sammendrag

  Background and objectives White matter (WM) microstructural properties from advanced multishell diffusion MRI (dMRI) have been linked to clinical disability in multiple sclerosis (MS). This multicentre study used multishell dMRI to compute WM metrics and test for differences between people with MS (pwMS) and healthy controls (HCs). Methods We included multishell dMRI data from 251 pwMS or clinically isolated syndrome (CIS) (mean age 40.7 years, 72.4 % women, 88.8 % relapsing remitting MS) at six MAGNIMS centres and 543 HCs. Eleven scalar metric maps were estimated from multishell dMRI sequences, based on diffusion tensor imaging (DTI) and restriction spectrum imaging (RSI). The maps were analysed using tract-based spatial statistics (TBSS). The diffusion output was submitted to paired sampled t-tests to test for case-control differences and linear regression models to test for associations with Expanded Disability Status Scale (EDSS) scores, while accounting for confounders. In a sub-sample from Oslo, we tested for correlations between EDSS and dMRI metrics within WM lesions. Results Significant group differences were found in nine out of eleven dMRI metrics. Linear regression models revealed significant correlations between EDSS and fractional anisotropy (FA) fast (β=-4.54, p = 0.01) and apparent diffusion coefficient (ADC) fast (β=10.92, p = 8.7 × 10−3). Conclusions Diffusion MRI based on clinically feasible multishell sequences uncovers WM group differences between pwMS and HCs, but only a selection of the advanced multishell parameters were sensitive to disability, and no statistically significant correlations with disability remained after Bonferroni correction.

• Simonsen, Cecilia Smith; Flemmen, Heidi Øyen; Broch, Line; Myklebust, Harald; Berg-Hansen, Pål & Brunborg, Cathrine [Vis alle 7 forfattere av denne artikkelen] (2024). The influence of menopause on multiple sclerosis. European Journal of Neurology. ISSN 1351-5101. 32(1). doi: 10.1111/ene.16566. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Introduction One third of the multiple sclerosis (MS) population consists of peri‐ or postmenopausal women. Many symptoms of menopause overlap those of MS. Some studies show increased speed of disability progression after menopause, while others indicate an unaltered trajectory. Objective Determine the association between menopause and MS disease course. Methods Cohort study with clinical data collected prospectively. Self‐reported age of menopause, smoking and parity collected retrospectively. Results We included 559 peri−/postmenopausal women and 386 similarly aged men. There was no significant difference in EDSS progression (slope coef 0.03, 0.02–0.08, p  = 0.208) or annual relapse rate (ARR) (0.10, 0.29–0.10, p  = 0.324) in the 5 years before and after menopause. Women's EDSS progressed slower than men's after menopause (coef −0.02, 95% CI −0.04 to −0.002, p  = 0.032), but there was no difference in ARR [coef. −0.01, 95% CI −0.04 to −0.01, p  = 0.262]. Women who reached menopause before MS onset had shorter time to diagnosis than women who reached menopause after onset (3.1 years (3.1) vs. 7.4 years (8.1), p  < 0.001). Women who reached menopause before diagnosis had an even longer time to diagnosis (8.8 (9.3) vs. 5.5 (6.3), p  < 0.001). Conclusions There were no significant differences in EDSS progression or ARR before and after menopause. In fact, men progressed faster than women, suggesting there is no negative impact of menopause on disease progression, as measured by EDSS and relapses.

• Bungudo, Binyam Bogale; Solem, Ingrid Konstanse Ledel; Celius, Elisabeth Gulowsen & Halvorsrud, Ragnhild (2024). Visual Modeling of Multiple Sclerosis Patient Pathways: The Healthcare Workers’ Perspectives. I Särestöniemi, Mariella; Keikhosrokiani, Pantea; Singh, Daljeet; Harjula, Erkki; Tiulpin, Aleksei; Jansson, Miia; Isomursu, Minna; Gils, Mark van; Saarakkala, Simo & Reponen, Jarmo (Red.), Digital Health and Wireless Solutions: First Nordic Conference​, NCDHWS 2024, Oulu, Finland, May 7–8, 2024, Proceedings, Part I. Springer. ISSN 9783031590801. s. 303–317. doi: 10.1007/978-3-031-59080-1_22. Fulltekst i vitenarkiv Vis sammendrag

  Multiple Sclerosis (MS) necessitates tailored care along intricate pathways throughout a patient's lifetime. Visualizing these pathways enhances the collective understanding of care processes and fosters collaboration among stakeholders. This study employed a qualitative study to map and the Customer Journey Modeling Language (CJML) to model MS patient pathways. A total of six purposefully selected healthcare professionals working in specialized healthcare, at a hospital and separate rehabilitation center, contributed to the care process mapping, participating in both pre- and post-modeling in-depth interviews. CJML, designed to capture planned and actual journeys from the service users’ perspective was adapted in this study to showcase the service provider's viewpoints, revealing insights into the existing organization of MS care. Involving more than one service provision level in mapping and modeling care processes requires dealing with handovers and its associated challenges. The final visualizations illustrate potential areas for improvement, including the need for more standardized procedures, potentially leading to variations in the quality of care and/or inefficient processes. However, the mapping process highlighted the difficulties in visualizing the MS care pathway due to its highly personalized nature, including challenges with creating personas or case groups that would allow for a unified service model. Participants’ feedback on the visualizations was essential, illustrating the importance of member checking when dealing with complex concepts such as patient pathways and organization of care.

• Simonsen, Cecilia Smith; Flemmen, Heidi Øyen; Broch, Line; Myklebust, Harald; Berg-Hansen, Pål & Brunborg, Cathrine [Vis alle 7 forfattere av denne artikkelen] (2024). The influence of menopause on multiple sclerosis. European Journal of Neurology. ISSN 1351-5101. doi: 10.1111/ene.16566. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: One third of the multiple sclerosis (MS) population consists of peri- or postmenopausal women. Many symptoms of menopause overlap those of MS. Some studies show increased speed of disability progression after menopause, while others indicate an unaltered trajectory. Objective: Determine the association between menopause and MS disease course. Methods: Cohort study with clinical data collected prospectively. Self-reported age of menopause, smoking and parity collected retrospectively. Results: We included 559 peri-/postmenopausal women and 386 similarly aged men. There was no significant difference in EDSS progression (slope coef 0.03, 0.02-0.08, p = 0.208) or annual relapse rate (ARR) (0.10, 0.29-0.10, p = 0.324) in the 5 years before and after menopause. Women's EDSS progressed slower than men's after menopause (coef -0.02, 95% CI -0.04 to -0.002, p = 0.032), but there was no difference in ARR [coef. -0.01, 95% CI -0.04 to -0.01, p = 0.262]. Women who reached menopause before MS onset had sh

• Bungudo, Binyam Bogale; Vesinurm, Märt; Lillrank, Paul; Celius, Elisabeth Gulowsen & Halvorsrud, Ragnhild (2024). Visual Modeling Languages in Patient Pathways: Scoping Review. Interactive Journal of Medical Research. 13. doi: 10.2196/55865. Fulltekst i vitenarkiv Vis sammendrag

  Background: Patient pathways (PPs) are presented as a panacea solution to enhance health system functions. It is a complex concept that needs to be described and communicated well. Modeling plays a crucial role in promoting communication, fostering a shared understanding, and streamlining processes. Only a few existing systematic reviews have focused on modeling methods and standardized modeling languages. There remains a gap in consolidated knowledge regarding the use of diverse visual modeling languages. Objective: This scoping review aimed to compile visual modeling languages used to represent PPs, including the justifications and the context in which a modeling language was adopted, adapted, combined, or developed. Methods: After initial experimentation with the keywords used to describe the concepts of PPs and visual modeling languages, we developed a search strategy that was further refined and customized to the major databases identified as topically relevant. In addition, we consulted gray literature and conducted hand searches of the referenced articles. Two reviewers independently screened the articles in 2 stages using preset inclusion criteria, and a third reviewer voted on the discordance. Data charting was done using an iteratively developed form in the Covidence software. Descriptive and thematic summaries were presented following rounds of discussion to produce the final report. Results: Of 1838 articles retrieved after deduplication, 22 satisfied our inclusion criteria. Clinical pathway is the most used phrase to represent the PP concept, and most papers discussed the concept without providing their operational definition. We categorized the visual modeling languages into five categories: (1) general purpose–modeling language (GPML) adopted without major extension or modification, (2) GPML used with formal extension recommendations, (3) combination of 2 or more modeling languages, (4) a developed domain specific modeling language (DSML), and (5) ontological modeling languages. The justifications for adopting, adapting, combining, and developing visual modeling languages varied accordingly and ranged from versatility, expressiveness, tool support, and extensibility of a language to domain needs, integration, and simplification. Conclusions: Various visual modeling languages were used in PP modeling, each with varying levels of abstraction and granularity. The categorization we made could aid in a better understanding of the complex combination of PP and modeling languages. Standardized GPMLs were used with or without any modifications. The rationale to propose any modification to GPMLs evolved as more evidence was presented following requirement analyses to support domain constructs. DSMLs are infrequently used due to their resource-intensive development, often initiated at a project level. The justifications provided and the context where DSMLs were created are paramount. Future studies should assess the merits and demerits of using a visual modeling language to facilitate PP communications among stakeholders and use evaluation frameworks to identify, modify, or develop them, depending on the scope and goal of the modeling need.

• Cortese, Rosa; Battaglini, Marco; Prados, Ferran; Gentile, Giordano; Luchetti, Ludovico & Bianchi, Alessia [Vis alle 47 forfattere av denne artikkelen] (2024). Grey Matter Atrophy and its Relationship with White Matter Lesions in Patients with Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease, Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder, and Multiple Sclerosis. Annals of Neurology. ISSN 0364-5134. 96(2), s. 276–288. doi: 10.1002/ana.26951. Fulltekst i vitenarkiv Vis sammendrag

  Objective To evaluate: (1) the distribution of gray matter (GM) atrophy in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD), and relapsing–remitting multiple sclerosis (RRMS); and (2) the relationship between GM volumes and white matter lesions in various brain regions within each disease. Methods A retrospective, multicenter analysis of magnetic resonance imaging data included patients with MOGAD/AQP4+NMOSD/RRMS in non-acute disease stage. Voxel-wise analyses and general linear models were used to evaluate the relevance of regional GM atrophy. For significant results (p < 0.05), volumes of atrophic areas are reported. Results We studied 135 MOGAD patients, 135 AQP4+NMOSD, 175 RRMS, and 144 healthy controls (HC). Compared with HC, MOGAD showed lower GM volumes in the temporal lobes, deep GM, insula, and cingulate cortex (75.79 cm3); AQP4+NMOSD in the occipital cortex (32.83 cm3); and RRMS diffusely in the GM (260.61 cm3). MOGAD showed more pronounced temporal cortex atrophy than RRMS (6.71 cm3), whereas AQP4+NMOSD displayed greater occipital cortex atrophy than RRMS (19.82 cm3). RRMS demonstrated more pronounced deep GM atrophy in comparison with MOGAD (27.90 cm3) and AQP4+NMOSD (47.04 cm3). In MOGAD, higher periventricular and cortical/juxtacortical lesions were linked to reduced temporal cortex, deep GM, and insula volumes. In RRMS, the diffuse GM atrophy was associated with lesions in all locations. AQP4+NMOSD showed no lesion/GM volume correlation. Interpretation GM atrophy is more widespread in RRMS compared with the other two conditions. MOGAD primarily affects the temporal cortex, whereas AQP4+NMOSD mainly involves the occipital cortex. In MOGAD and RRMS, lesion-related tract degeneration is associated with atrophy, but this link is absent in AQP4+NMOSD. ANN NEUROL 2024;96:276–288

• Prosperini, Luca; Arrambide, Georgina; Celius, Elisabeth Gulowsen; Goletti, Delia; Killestein, Joep & Kos, Daphne [Vis alle 12 forfattere av denne artikkelen] (2024). COVID-19 and multiple sclerosis: challenges and lessons for patient care. The Lancet Regional Health - Europe. 44. doi: 10.1016/j.lanepe.2024.100979. Fulltekst i vitenarkiv Vis sammendrag

  During the COVID-19 pandemic, people with multiple sclerosis (MS) and their healthcare providers have faced unique challenges related to the interaction between SARS-CoV-2, underlying neurological disease and the use of disease-modifying treatments (DMTs). Key concerns arose, primarily related to the possibility that SARS-CoV-2 infection could trigger the initial demyelinating event or exacerbate disease activity. Another major concern was the safety and efficacy of the COVID-19 vaccines, especially for patients undergoing specific treatments that could weaken their antibody responses. In the post-infection phase, identifying long COVID in patients with MS has been complicated due to the large overlap between post-infection sequelae and MS symptoms. In addition, disruptions in health and rehabilitation services have made it difficult for MS patients to access care. This Series article explores current evidence on the interaction between MS and SARS-CoV-2, identifies the challenges posed by the COVID-19 pandemic in the care of patients with MS, and discusses the significant adoption of digital health solutions, including telemedicine and new technology-based rehabilitation approaches. Based on lessons learned, recommendations and future directions are offered for managing patients with MS, rethinking healthcare systems and improving health outcomes in the post-COVID-19 pandemic era.

• Berg-Hansen, Pål; Moen, Stine Marit; Klyve, Thomas Dahl; Sanchez, Victor Evaristo Gonzalez; Seeberg, Trine Margrethe & Celius, Elisabeth Gulowsen [Vis alle 8 forfattere av denne artikkelen] (2023). The instrumented single leg stance test detects early balance impairment in people with multiple sclerosis. Frontiers in Neurology. 14. doi: 10.3389/fneur.2023.1227374. Fulltekst i vitenarkiv Vis sammendrag

  Balance impairment is frequent in people with multiple sclerosis (pwMS) and affects risk of falls and quality of life. By using inertial measurement units (IMUs) on the Single Leg Stance Test (SLS) we aimed to discriminate healthy controls (HC) from pwMS and detect differences in balance endurance and quality. Thirdly, we wanted to test the correlation between instrumented SLS parameters and self-reported measures of gait and balance. Fifty-five pwMS with mild (EDSS&amp;lt;4) and moderate disability (EDSS≥4) and 20 HC performed the SLS with 3 IMUs placed on the feet and sacrum and filled the Twelve Item Multiple Sclerosis Walking Scale (MSWS-12) questionnaire. A linear mixed model was used to compare differences in the automated balance measures. Balance duration was significantly longer in HC compared to pwMS ( p  &amp;lt; 0.001) and between the two disability groups ( p  &amp;lt; 0.001). Instrumented measures identified that trunk stability (normalized mediolateral and antero-posterior center of mass stability) had the strongest association with disability (R 2 marginal 0.30, p  &amp;lt; 0.001) and correlated well with MSWS-12 ( R  = 0.650, p  &amp;lt; 0.001). PwMS tended to overestimate own balance compared to measured balance duration. The use of both self-reported and objective assessments from IMUs can secure the follow-up of balance in pwMS.

• Broch, Line; Flemmen, Heidi Øyen; Simonsen, Cecilia Smith; Berg-Hansen, Pål; Ormstad, Heidi & Brunborg, Cathrine [Vis alle 7 forfattere av denne artikkelen] (2023). “No association between disease modifying treatment and fatigue in multiple sclerosis”. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 79. doi: 10.1016/j.msard.2023.104993. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Wolf, Asia-Sophia Fumika Michaela; Ravussin, Anthony; König, Marton; Øverås, Mathias Herstad; Solum, Guri & Kjønstad, Ingrid Fadum [Vis alle 18 forfattere av denne artikkelen] (2023). T cell responses to SARS-CoV-2 vaccination differ by disease-modifying therapy for multiple sclerosis. JCI Insight. 8(12), s. 1–14. doi: 10.1172/jci.insight.165111. Fulltekst i vitenarkiv Vis sammendrag

  Immune responses in people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have been of significant interest throughout the COVID-19 pandemic. Lymphocyte-targeting immunotherapies, including anti-CD20 treatments and sphingosine-1-phosphate receptor (S1PR) modulators, attenuate Ab responses after vaccination. Evaluation of cellular responses after vaccination, therefore, is of particular importance in these populations. In this study, we used flow cytometry to analyze CD4 and CD8 T cell functional responses to SARS-CoV-2 spike peptides in healthy control study participants and pwMS receiving 5 different DMTs. Although pwMS receiving rituximab and fingolimod therapies had low Ab responses after both 2 and 3 vaccine doses, T cell responses in pwMS taking rituximab were preserved after a third vaccination, even when an additional dose of rituximab was administered between vaccine doses 2 and 3. PwMS taking fingolimod had low detectable T cell responses in peripheral blood. CD4 and CD8 T cell responses to SARS-CoV-2 variants of concern Delta and Omicron were lower than to the ancestral Wuhan-Hu-1 variant. Our results indicate the importance of assessing both cellular and humoral responses after vaccination and suggest that, even in the absence of robust Ab responses, vaccination can generate immune responses in pwMS.

• Harroud, Adil; Stridh, Pernilla; McCauley, Jacob L.; Saarela, Janna Saija; Bosch, Aletta M. R. van den & Engelenburg, Hendrik J. [Vis alle 120 forfattere av denne artikkelen] (2023). Locus for severity implicates CNS resilience in progression of multiple sclerosis. Nature. ISSN 0028-0836. 619(7969), s. 323–331. doi: 10.1038/s41586-023-06250-x. Fulltekst i vitenarkiv
• Eid, Karine; Torkildsen, Øivind; Aarseth, Jan Harald; Aalstad, Mari; Bhan, Alok & Celius, Elisabeth Gulowsen [Vis alle 16 forfattere av denne artikkelen] (2022). Association of adverse childhood experiences with the development of multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry. ISSN 0022-3050. 93(6), s. 645–650. doi: 10.1136/jnnp-2021-328700. Fulltekst i vitenarkiv Vis sammendrag

  Objective: To study whether exposure to childhood emotional, sexual or physical abuse is associated with subsequent multiple sclerosis (MS) development. Methods: A nationwide, prospective cohort study based on participants in the Norwegian Mother, Father and Child cohort study. Enrolment took place 1999-2008, with follow-up until 31 December 2018. Childhood abuse before age 18 years was obtained from self-completed questionnaires. We identified MS diagnoses through data-linkage with national health registries and hospital records. The Cox model was used to estimate HRs for MS with 95% CIs, adjusting for confounders and mediators. Results: In this prospective cohort study, 14 477 women were exposed to childhood abuse and 63 520 were unexposed. 300 women developed MS during the follow-up period. 71 of these (24%) reported a history of childhood abuse, compared with 14 406 of 77 697 (19%) women that did not develop MS. Sexual abuse (HR 1.65, 95% CI 1.13 to 2.39) and emotional abuse (HR 1.40, 95% CI 1.03 to 1.90) in childhood were both associated with an increased risk of developing MS. The HR of MS after exposure to physical abuse was 1.31 (95% CI 0.83 to 2.06). The risk of MS was further increased if exposed to two (HR 1.66, 95% CI 1.04 to 2.67) or all three abuse categories (HR 1.93, 95% CI 1.02 to 3.67). Interpretation: Childhood sexual and emotional abuse were associated with an increased risk of developing MS. The risk was higher when exposed to several abuse categories, indicating a dose-response relationship. Further studies are needed to identify underlying mechanisms. Keywords: multiple sclerosis; trauma, psychol seque. © 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.

• Berg-Hansen, Pål; Moen, Stine Marit; Austeng, Andreas; Gonzalez, Victor; Klyve, Thomas Dahl & Negård, Henrik [Vis alle 9 forfattere av denne artikkelen] (2022). Sensor-based gait analyses of the six-minute walk test identify qualitative improvement in gait parameters of people with multiple sclerosis after rehabilitation. Journal of Neurology. ISSN 0340-5354. 269, s. 3723–3734. doi: 10.1007/s00415-022-10998-z. Fulltekst i vitenarkiv Vis sammendrag

  The aim of this work was to determine whether wearable inertial measurement units (IMUs) could detect gait improvements across different disability groups of people with Multiple Sclerosis (pwMS) by the six-minute walk test (6MWT) during a rehabilitation stay in a specialized rehabilitation center. Forty-six pwMS and 20 healthy controls (HC) were included in the study. They performed the 6MWT with two inertial measurement units (IMUs) placed on the feet. Thirty-two of the pwMS were retested at the end of the stay. PwMS were divided in a mild-disability and a moderate-disability group. The 6MWT was divided in six sections of 1 min each for technical analysis, and linear mixed models were used for statistical analyses. The comparison between the two disability groups and HC highlighted significant differences for each gait parameter (all p 

• Eid, Karine; Torkildsen, Øivind; Aarseth, Jan Harald; Celius, Elisabeth Gulowsen; Cortese, Marianna & Holmøy, Trygve [Vis alle 12 forfattere av denne artikkelen] (2022). Abuse and revictimization in adulthood in multiple sclerosis: a cross-sectional study during pregnancy. Journal of Neurology. ISSN 0340-5354. 269, s. 5901–5909. doi: 10.1007/s00415-022-11249-x. Fulltekst i vitenarkiv Vis sammendrag

  Background: Knowledge concerning exposure to abuse in adulthood and in pregnancy in people with multiple sclerosis (MS) is sparse. Objective: To determine the occurrence of adult abuse and abuse in relation to pregnancy in women with MS and their risk of revictimization (repeated abuse as adults after childhood abuse). Methods: This cross-sectional study comprised pregnant women from the Norwegian Mother, Father and Child Cohort study. Information on abuse was acquired through self-completed questionnaires. We used logistic regression to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results: We identified 106 women with MS at enrollment through linkage with national health registries. The reference group consisted of 77,278 women without MS. Twenty-seven women (26%) with MS reported any adult abuse compared to 15,491 women (20%) without MS, aOR 1.33 (0.85–2.09). Twenty-two (21%) women with MS reported systematic emotional abuse compared to 13% without MS, aOR 1.75 (1.08–2.83). Ten women (10%) with MS reported sexual abuse, compared to 6% without MS, aOR 1.72 (0.89–3.33). More women with MS reported rape as an adult, aOR 2.37 (1.02–5.49). Women with MS had higher risk of revictimization as adults, after childhood abuse, aOR 2.23 (1.22–4.10). The risk of abuse during pregnancy or 6 months preceding pregnancy was similar between the groups. Conclusions: Women with MS had increased occurrence of systematic emotional abuse, rape, and revictimization as adults, compared to women without MS.

• Broch, Line; Flemmen, Heidi Øyen; Simonsen, Cecilia Smith; Berg-Hansen, Pål; Ormstad, Heidi & Brunborg, Cathrine [Vis alle 7 forfattere av denne artikkelen] (2022). Fatigue in multiple sclerosis is associated with socioeconomic factors. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 64, s. 1–9. doi: 10.1016/j.msard.2022.103955. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Grytten, Nina; Myhr, Kjell-Morten; Celius, Elisabeth Gulowsen; Benjaminsen, Espen; Midgard, Rune & Vatne, Anita [Vis alle 9 forfattere av denne artikkelen] (2022). Cancer related mortality in multiple sclerosis. A population based cohort study. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 69, s. 1–6. doi: 10.1016/j.msard.2022.104417. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Flemmen, Heidi Øyen; Simonsen, Cecilia Smith; Broch, Line; Brunborg, Cathrine; Berg-Hansen, Pål & Moen, Stine Marit [Vis alle 8 forfattere av denne artikkelen] (2022). The influence of socioeconomic factors on access to disease modifying treatment in a Norwegian multiple sclerosis cohort. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 61, s. 1–10. doi: 10.1016/j.msard.2022.103759. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Simonsen, Cecilia Smith; Flemmen, Heidi Øyen; Broch, Line; Brekke, Kamilla; Brunborg, Cathrine & Berg-Hansen, Pål [Vis alle 7 forfattere av denne artikkelen] (2022). Rebaseline no evidence of disease activity (NEDA-3) as a predictor of long-term disease course in a Norwegian multiple sclerosis population. Frontiers in Neurology. 13, s. 1–10. doi: 10.3389/fneur.2022.1034056. Fulltekst i vitenarkiv Vis sammendrag

  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

• Cortese, Rosa; Battagili, Marco; Prados, Ferran; Boanchi, Alessia; Haider, Lukas & Jacob, Anu [Vis alle 47 forfattere av denne artikkelen] (2022). Clinical and MRI measures to identify non-acute MOG-antibody disease in adults. Brain. ISSN 0006-8950. 146(6), s. 2489–2501. doi: 10.1093/brain/awac480. Fulltekst i vitenarkiv Vis sammendrag

  Abstract MRI and clinical features of myelin oligodendrocyte glycoprotein (MOG)-antibody disease may overlap with those of other inflammatory demyelinating conditions posing diagnostic challenges, especially in non-acute phases and when serologic testing for MOG-antibodies is unavailable or shows uncertain results. We aimed to identify MRI and clinical markers that differentiate non-acute MOG-antibody disease from aquaporin4 (AQP4)-antibody neuromyelitis optica spectrum disorder and relapsing remitting multiple sclerosis, guiding in the identification of MOG-antibody disease patients in clinical practice. In this cross-sectional retrospective study, data from 16 MAGNIMS centres were included. Data collection and analyses were conducted from 2019 to 2021. Inclusion criteria were: diagnosis of MOG-antibody disease, AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis, brain and cord MRI at least 6 months from relapse, EDSS on the day of MRI. Brain white matter T2 lesions, T1-hypointense lesions, cortical and cord lesions were identified. Random-forest models were constructed to classify patients as MOG-antibody disease/AQP4-neuromyelitis optica spectrum disorder/multiple sclerosis; a leave one out cross-validation procedure assessed the performance of the models. Based on the best discriminators between diseases, we proposed a guide to target investigations for MOG-antibody disease. One hundred sixty-two patients with MOG-antibody disease (99F, mean age: 41 [±14] years, median EDSS: 2 [0-7.5]), 162 with AQP4-neuromyelitis optica spectrum disorder (132F, mean age: 51 [±14] years, median EDSS: 3.5 [0-8]), 189 with multiple sclerosis (132F, mean age: 40 [±10] years, median EDSS: 2 [0-8]) and 152 healthy controls (91F) were studied. In young patients (&amp;lt;34 years), with low disability (EDSS &amp;lt; 3), the absence of Dawson’s fingers, temporal lobe lesions and longitudinally extensive lesions in the cervical cord pointed towards a diagnosis of MOG-antibody disease instead of the other two diseases (accuracy: 76%, sensitivity: 81%, specificity: 84%, p &amp;lt; 0.001). In these non-acute patients, a number of brain lesions &amp;lt; 6 predicted MOG-antibody disease versus multiple sclerosis (accuracy: 83%, sensitivity: 82%, specificity: 83%, p &amp;lt; 0.001). An EDSS &amp;lt; 3 and the absence of longitudinally extensive lesions in the cervical cord predicted MOG-antibody disease versus AQP4-neuromyelitis optica spectrum disorder (accuracy: 76%, sensitivity: 89%, specificity: 62%, p &amp;lt; 0.001). A workflow with sequential tests and supporting features has been proposed to guide a better identification of MOG-antibody disease patients. Adult non-acute MOG-antibody disease patients showed distinctive clinical and MRI features when compared to AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis. A careful inspection of the morphology of brain and cord lesions together with clinical information, can guide for further analyses towards diagnosis of MOG-antibody disease in clinical practice.

• Nes, Dragana; Berg-Hansen, Pål; Benavent, Sigrid Aune de Rodez; Høgestøl, Einar August; Beyer, Mona K. & Rinker, Daniel Allen [Vis alle 12 forfattere av denne artikkelen] (2022). Exploring Retinal Blood Vessel Diameters as Biomarkers in Multiple Sclerosis. Journal of Clinical Medicine. 11(11). doi: 10.3390/jcm11113109. Fulltekst i vitenarkiv Vis sammendrag

  We aimed to determine whether retinal vessel diameters and retinal oxygen saturation in newly diagnosed patients with multiple sclerosis (pwMS) are different from those of a healthy population. Retinal blood vessel diameters were measured using imaging with a spectrophotometric non-invasive retinal oximeter. Twenty-three newly diagnosed untreated relapsing-remitting MS (RRMS) patients (mean age: 32.2 ± 7.5 years, age range = 18–50 years, 56.5% female) were measured and compared to 23 age- and sex-matched healthy controls (HCs) (mean age: 34.8 ± 8.1 years). Patients with Optic Neuritis were excluded. Retinal venular diameter (143.8 µm versus 157.8 µm: mean; p = 0.0013) and retinal arteriolar diameter (112.6 µm versus 120.6 µm: mean; p = 0.0089) were smaller in pwMS when compared with HCs, respectively. There was no significant difference in the oxygen saturation in retinal venules and arterioles in pwMS (mean: 60.0% and 93.7%; p = 0.5980) compared to HCs (mean: 59.3% and 91.5%; p = 0.8934), respectively. There was a significant difference in the median low contrast visual acuity (2.5% contrast) between the pwMS and the HC groups (p = 0.0143) Retinal arteriolar and venular diameter may have potential as objective biomarkers for MS.

• Leonardsen, Esten Høyland; Peng, Han; Kaufmann, Tobias; Agartz, Ingrid; Andreassen, Ole & Celius, Elisabeth Gulowsen [Vis alle 19 forfattere av denne artikkelen] (2022). Deep neural networks learn general and clinically relevant representations of the ageing brain. NeuroImage. ISSN 1053-8119. 256. doi: 10.1016/j.neuroimage.2022.119210. Fulltekst i vitenarkiv Vis sammendrag

  The discrepancy between chronological age and the apparent age of the brain based on neuroimaging data — the brain age delta — has emerged as a reliable marker of brain health. With an increasing wealth of data, approaches to tackle heterogeneity in data acquisition are vital. To this end, we compiled raw structural magnetic resonance images into one of the largest and most diverse datasets assembled (n=53542), and trained convolutional neural networks (CNNs) to predict age. We achieved state-of-the-art performance on unseen data from unknown scanners (n=2553), and showed that higher brain age delta is associated with diabetes, alcohol intake and smoking. Using transfer learning, the intermediate representations learned by our model complemented and partly outperformed brain age delta in predicting common brain disorders. Our work shows we can achieve generalizable and biologically plausible brain age predictions using CNNs trained on heterogeneous datasets, and transfer them to clinical use cases.

• Oreja-Guevara, Celia; Brownlee, Wallace; Celius, Elisabeth Gulowsen; Centonze, Diego; Giovannoni, G. & Hodgkinson, Suzanne [Vis alle 15 forfattere av denne artikkelen] (2022). Expert opinion on the long term use of cladribine tablets for multiple sclerosis: Systematic literature review of real Word evidence. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 69(104459), s. 1–13. doi: 10.1016/j.msard.2022.104459. Fulltekst i vitenarkiv Vis sammendrag

  Background Treatment with cladribine tablets (CladT), an immune reconstitution therapy for relapsing multiple sclerosis (RMS), involves two short courses of treatment in Year 1 and Year 2. Most patients achieve sustained efficacy with CladT, but a small proportion may experience new disease activity (DA). Following completion of the indicated dose, physicians may have questions relating to the long-term management of these patients. Since the EU approval of CladT over 5 years ago, real-world evidence (RWE) is increasing and may provide some insights and guidance for clinical practice. We describe a systematic literature review (SLR) of RWE and provide expert opinions relating to six questions regarding the long-term use of CladT. Methods Pertinent clinical questions were developed by a steering committee (SC) of 14 international multiple sclerosis (MS) experts regarding breakthrough DA in Year 1, new DA after 2 years or more of treatment, long-term management of stable patients, and whether additional courses of CladT may be required or safe. An SLR was performed in EMBASE and PubMed using the population, intervention, comparators, outcomes, study design (PICOS) framework to identify relevant studies within the last 15 years. Searches of key congress proceedings for the last 2–3 years were also performed. Following review of the results and RWE, the SC drafted and agreed on expert opinion statements for each question. Results A total of 35 publications reporting RWE for CladT were included in this review. In the real world, breakthrough DA in Year 1 is of low incidence (1.1–21.9%) but can occur, particularly in patients switching from anti-lymphocyte trafficking agents. In most patients, this DA did not lead to treatment discontinuation. Reported rates of DA after the full therapeutic effect of CladT has been achieved (end of Year 2, 3 or 4) range from 12.0 to 18.7% in the few studies identified. No RWE was identified to support management decisions for stable patients in Year 5 or later. Views among the group were also diverse on this question and voting on expert opinion statements was required. Only two studies reported the administration of additional courses of CladT, but detailed safety outcomes were not provided. Conclusions RWE for the long-term use of CladT in the treatment of RMS is increasing, however, gaps in knowledge remain. Where possible, the RWE identified through the SLR informed expert statements, but, where RWE is still lacking, these were based solely on experiences and opinion, providing some guidance on topics and questions that occur in daily clinical practice. More real-world studies with longer-term follow-up periods are needed and highly anticipated.

• Broch, Line; Simonsen, Cecilia Smith; Flemmen, Heidi Øyen; Berg-Hansen, Pål; Skardhamar, Åshild & Ormstad, Heidi [Vis alle 7 forfattere av denne artikkelen] (2021). High prevalence of fatigue in contemporary patients with multiple sclerosis. Multiple Sclerosis Journal, Experimental, Translational and Clinical. 7(1). doi: 10.1177/2055217321999826. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Grytten, Nina; Myhr, Kjell-Morten; Celius, Elisabeth Gulowsen; Benjaminsen, Espen; Kampman, Margitta & Midgard, Rune [Vis alle 10 forfattere av denne artikkelen] (2021). Incidence of cancer in multiple sclerosis before and after the treatment era– a registry- based cohort study. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 55:103209, s. 1–7. doi: 10.1016/j.msard.2021.103209. Fulltekst i vitenarkiv Vis sammendrag

  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.

• König, Marton; Lorentzen, Åslaug Rudjord; Torgauten, Hilde Marie; Tran, Trung; Schikora-Rustad, Stine & Vaage, Eline Benno [Vis alle 22 forfattere av denne artikkelen] (2021). Humoral immunity to SARS-CoV-2 mRNA vaccination in multiple sclerosis: the relevance of time since last rituximab infusion and first experience from sporadic revaccinations. Journal of Neurology, Neurosurgery and Psychiatry. ISSN 0022-3050. doi: 10.1136/jnnp-2021-327612. Fulltekst i vitenarkiv Vis sammendrag

  Introduction The effect of disease-modifying therapies (DMT) on vaccine responses is largely unknown. Understanding the development of protective immunity is of paramount importance to fight the COVID-19 pandemic. Objective To characterise humoral immunity after mRNA-COVID-19 vaccination of people with multiple sclerosis (pwMS). Methods All pwMS in Norway fully vaccinated against SARS-CoV-2 were invited to a national screening study. Humoral immunity was assessed by measuring anti-SARS-CoV-2 SPIKE RBD IgG response 3–12 weeks after full vaccination, and compared with healthy subjects. Results 528 pwMS and 627 healthy subjects were included. Reduced humoral immunity (anti-SARS-CoV-2 IgG <70 arbitrary units) was present in 82% and 80% of all pwMS treated with fingolimod and rituximab, respectively, while patients treated with other DMT showed similar rates as healthy subjects and untreated pwMS. We found a significant correlation between time since the last rituximab dose and the development of humoral immunity. Revaccination in two seronegative patients induced a weak antibody response. Conclusions Patients treated with fingolimod or rituximab should be informed about the risk of reduced humoral immunity and vaccinations should be timed carefully in rituximab patients. Our results identify the need for studies regarding the durability of vaccine responses, the role of cellular immunity and revaccinations. This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

• Hammerstad, Sara Salehi; Celius, Elisabeth Gulowsen; Husby, Henrik; Sørensen, Ingvild M. & Norheim, Ingrid (2021). Management of Severe Graves' Hyperthyroidism in Pregnancy Following Immune Reconstitution Therapy in Multiple Sclerosis. Journal of the Endocrine Society (JES). 5(6). doi: 10.1210/jendso/bvab044. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Context Alemtuzumab (ALZ), a CD52 monoclonal antibody, is highly efficacious in multiple sclerosis; however, side effects are common. Autoimmune thyroid disease (Graves’ disease and Hashimoto thyroiditis) is a well-known complication of ALZ. Treatment of ALZ-induced Graves’ disease can be challenging, and even more difficult during pregnancy. Case description We present a case of severe ALZ-induced Graves’ disease with a rapid increase in thyrotropin receptor antibodies (TRAb 240 IU/L) and thyrotoxicosis in early pregnancy. Treatment with high doses of antithyroid medication was needed. There was high risk of both fetal and neonatal thyrotoxicosis. Serial fetal sonography showed normal development. The newborn baby presented high levels of TRAb (240 IU/L) and developed neonatal thyrotoxicosis on day 8. Adequate monitoring, treatment, and follow-up of the newborn baby ensured normal thyroid function until disappearance of TRAb 6 weeks after birth. Conclusion Multiple sclerosis patients treated with ALZ may develop severe Graves’ disease with an increased risk of both fetal and neonatal thyrotoxicosis. Close follow-up with a multidisciplinary approach is needed to ensure a healthy outcome.

• Flemmen, Heidi Øyen; Simonsen, Cecilia Smith; Broch, Line; Brunborg, Cathrine; Berg-Hansen, Pål & Moen, Stine Marit [Vis alle 8 forfattere av denne artikkelen] (2021). Maternal education has significant influence on progression in multiple sclerosis. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 53, s. 1–10. doi: 10.1016/j.msard.2021.103052. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Celius, Elisabeth Gulowsen; Thompson, Heidi; Pontaga, Maija; Langdon, Dawn; Laroni, Alice & Potra, Stanca [Vis alle 12 forfattere av denne artikkelen] (2021). Disease Progression in Multiple Sclerosis: A Literature Review Exploring Patient Perspectives. Patient Preference and Adherence. 15, s. 15–27. doi: 10.2147/PPA.S268829. Fulltekst i vitenarkiv Vis sammendrag

  Purpose: Multiple sclerosis (MS) prognosis is often uncertain. This literature review considers patients’ understanding of, and perspectives on, MS progression to better comprehend the unmet needs of people with MS (PwMS), in order to improve treatment adherence and quality of life (QoL). Methods: Literature searches for peer-reviewed papers concerning patient perspectives on the progression of MS and comparable conditions, published between January 2000 and January 2020, were conducted. Results: Little qualitative evidence exists that examines PwMS’ perspectives on MS progression. The understanding and meaning ascribed to terms such as “disease progression” vary. Some PwMS find disease labels stigmatizing, confusing, and disconnected from reality. The lack of a clear definition of progression and discrepancies between PwMS and healthcare professional (HCP) perspectives may contribute to misunderstanding and poor communication. Patient descriptions of progression and relapses include symptoms in addition to those evaluated by standard severity and disability measures. Compared with HCPs, PwMS are still focused on relapse prevention but place higher priority on QoL and ascribe different relative importance to the causes of poor adherence to treatment plans. PwMS want to discuss progression and likely prognosis. Such communication needs to be personalized and delivered with sensitivity, at an appropriate time. Poor treatment adherence may arise from a lack of understanding and poor communication, particularly around treatment goals. The few studies that directly considered patient perspectives on the progression of comparable conditions supported and extended the perspectives of PwMS. Lack of adequate communication by HCPs was the most common theme. Conclusion: Patient perspectives on disease progression in MS and other chronic progressive conditions are under-investigated and under-reported. The limited evidence available highlights the importance of providing adequate information and effective HCP communication. While further studies are needed, the current evidence base offers information and insights that may help HCPs to enhance patient care, well-being, and treatment adherence.

• Saposnik, Gustavo; Andhavarapu, Sanketh; Fernández, Oscar; Kim, Ho Jin; Wiendl, Heinz & Foss, Mona [Vis alle 19 forfattere av denne artikkelen] (2021). Factors associated with treatment escalation among MS specialists and general neurologists: Results from an International cojoint study. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. doi: 10.1016/j.msard.2021.103404. Fulltekst i vitenarkiv
• Saposnik, Gustavo; Andhavarapu, Sanketh; Fernández, Oscar; Kim, Ho Jin; Wiendl, Heinz & Foss, Mona [Vis alle 19 forfattere av denne artikkelen] (2021). Effect of desire for pregnancy on decisions to escalate treatment in multiple sclerosis care: Differences between MS specialists and non-MS specialists. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. s. 1–1. doi: 10.1016/j.msard.2021.103389. Fulltekst i vitenarkiv
• Simonsen, Cecilia Smith; Flemmen, Heidi Øyen; Broch, Line; Brunborg, Cathrine; Berg-Hansen, Pål & Moen, Stine Marit [Vis alle 7 forfattere av denne artikkelen] (2021). Early High Efficacy Treatment in Multiple Sclerosis Is the Best Predictor of Future Disease Activity Over 1 and 2 Years in a Norwegian Population-Based Registry. Frontiers in Neurology. 12, s. 1–13. doi: 10.3389/fneur.2021.693017. Fulltekst i vitenarkiv Vis sammendrag

  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

• Simonsen, Cecilia Smith; Flemmen, Heidi Øyen; Broch, Line; Brunborg, Cathrine; Berg-Hansen, Pål & Moen, Stine Marit [Vis alle 7 forfattere av denne artikkelen] (2021). No significant differences in absenteeism or academic achievements in a Norwegian multiple sclerosis case control study. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. doi: 10.1016/j.msard.2021.103141. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Oh, Jiwon; Achiron, Anat; Celius, Elisabeth Gulowsen; Chambers, Christina; Derwenskus, Joy & Devonshire, Virginia [Vis alle 19 forfattere av denne artikkelen] (2020). Pregnancy outcomes and postpartum relapse rates in women with RRMS treated with alemtuzumab in the phase 2 and 3 clinical development program over 16 years. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 43. doi: 10.1016/j.msard.2020.102146. Fulltekst i vitenarkiv Vis sammendrag

  Background Relapsing-remitting multiple sclerosis (RRMS) is frequently diagnosed in women of reproductive age. Because the use of disease-modifying therapies (DMTs) early in the disease course is increasing, it is important to evaluate the safety of DMTs in pregnant women and their developing fetuses. Alemtuzumab, approved for the treatment of relapsing forms of MS, is administered as 2 courses of 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. Alemtuzumab is eliminated from the body within approximately 30 days after administration; it is recommended that women of childbearing potential use effective contraception during and for 4 months after treatment. Here, we report pregnancy outcomes in alemtuzumab-treated women from the phase 2 and 3 clinical development program over 16 years. Methods We followed 972 women who had alemtuzumab in phase 2 (CAMMS223 [NCT00050778]) and phase 3 (CARE-MS I [NCT00530348], CARE-MS II [NCT00548405]) studies, and/or in 2 consecutive extension studies (NCT00930553; NCT02255656 [TOPAZ]). In the extension studies, patients could receive additional alemtuzumab (12 mg/day on 3 days; ≥12 months apart) as needed for disease activity. All women who received alemtuzumab in the clinical development program were included. Pregnant or lactating patients were followed up for safety. Results As of November 26, 2018, 264 pregnancies occurred in 160 alemtuzumab-treated women, with a mean age at conception of 32.6 years, and mean time from last alemtuzumab dose to conception of 35.9 months. Of the 264 pregnancies, 233 (88%) were completed, 11 (4%) were ongoing, and 20 (8%) had unknown outcomes; 16 (6%) conceptions occurred within 4 months, and 5 conceptions within 1 month of the last alemtuzumab dose. Of the 233 completed pregnancies with known outcomes, there were 155 (67%) live births with no congenital abnormalities or birth defects, 52 (22%) spontaneous abortions, 25 (11%) elective abortions, and 1 (0.4%) stillbirth. Maternal age was associated with an increased risk of spontaneous abortion in alemtuzumab-treated patients (<35 years: 15%; ≥35 years: 37%; relative risk [RR], 2.46 [95% CI: 1.53–3.95], p=0.0002). Risk of spontaneous abortion was not increased in patients becoming pregnant ≤4 months versus >4 months since alemtuzumab exposure (19% vs 23%; RR, 1.08 [95% CI: 0.41–2.85], p=0.88). Autoimmune thyroid adverse events did not increase risk for spontaneous abortion (patients with vs without thyroid adverse events, 23.7% vs 21.3%; RR, 1.11 [95% CI: 0.69–1.80], p=0.75). Annualized relapse rate was 0.10 and 0.12 in the 2 years prior to pregnancy (post alemtuzumab), and was 0.22, 0.12, and 0.12 in each of the first 3 years postpartum, respectively. Conclusion Normal live births were the most common outcome in women exposed to alemtuzumab 12 mg or 24 mg in clinical studies. Spontaneous abortion rate in alemtuzumab-treated patients was comparable with rates in the general population and treatment-naive MS patients, and was not increased in women with pregnancy onset within 4 months of alemtuzumab exposure. There was a minimal increase in postpartum relapses.

• Ormstad, Heidi; Simonsen, Cecilia Smith; Broch, Line; Maes, Dr Michael; Anderson, George & Celius, Elisabeth Gulowsen (2020). Chronic fatigue and depression due to multiple sclerosis: Immune-inflammatory pathways, tryptophan catabolites and the gut-brain axis as possible shared pathways. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 46, s. 1–9. doi: 10.1016/j.msard.2020.102533. Fulltekst i vitenarkiv Vis sammendrag

  Chronic fatigue and major depression (MDD)-like symptoms are common manifestations of multiple sclerosis (MS), both with huge impact on quality of life. Depression can manifest itself as fatigue, and depressive symptoms are often mistaken for fatigue, and vice versa. The two conditions are sometimes difficult to differentiate, and their relationship is unclear. Whether chronic fatigue and depression occur primarily, secondarily or coincidentally with activated immune-inflammatory pathways in MS is still under debate. We have carried out a descriptive review aiming to gain a deeper understanding of the relationship between chronic fatigue and depression in MS, and the shared pathways that underpin both conditions. This review focuses on immune-inflammatory pathways, the kynurenine pathway and the gut-brain axis. It seems likely that proinflammatory cytokines, tryptophan catabolites (the KYN pathway) and the gut-brain axis are involved in the mechanisms causing chronic fatigue and MDD-like symptoms in MS. However, the evidence base is weak, and more research is needed. In order to advance our understanding of the underlying pathological mechanisms, MS-related fatigue and depression should be examined using a longitudinal design and both immune-inflammatory and KYN pathway biomarkers should be measured, relevant clinical characteristics judiciously registered, and self-report instruments for both fatigue and depression should be used.

• Flemmen, Heidi Øyen; Simonsen, Cecilia Smith; Berg-Hansen, Pål; Moen, Stine Marit; Kersten, Hege & Heldal, Kristian [Vis alle 7 forfattere av denne artikkelen] (2020). Prevalence of multiple sclerosis in rural and urban districts in Telemark county, Norway. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 45. doi: 10.1016/j.msard.2020.102352. Fulltekst i vitenarkiv Vis sammendrag

  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 1st 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 1st 1999, 2009 and 2019 were 105.8/105, 177.1/105 and 260.6/105, respectively. In 2019, the prevalence estimates were 250.4/105 in urban and 316.2 /105 in rural areas. Between 1999 and 2018, the yearly incidence increased from 8.4/105 to 14.4/105. 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.

• Brorson, Ina Skaara; Eriksson, Anna Maria; Leikfoss, Ingvild Sørum; Vitelli, Valeria; Celius, Elisabeth Gulowsen & Luders, Torben [Vis alle 10 forfattere av denne artikkelen] (2020). CD8 + T cell gene expression analysis identifies differentially expressed genes between multiple sclerosis patients and healthy controls. Multiple Sclerosis Journal, Experimental, Translational and Clinical. doi: 10.1177/2055217320978511. Fulltekst i vitenarkiv Vis sammendrag

  Background: Genetic and clinical observations have indicated T cells are involved in MS pathology. There is little insight in how T cells are involved and whether or not these can be used as markers for MS. Objectives: Analysis of the gene expression profiles of circulating CD8þ T cells of MS patients compared to healthy controls. Methods: RNA from purified CD8þ T cells was sequenced and analyzed for differential gene expression. Pathway analyses of genes at several p-value cutoffs were performed to identify putative pathways involved. Results: We identified 36 genes with significant differential gene expression in MS patients. Four genes reached at least 2-fold differences in expression. The majority of differentially expressed genes was higher expressed in MS patients. Genes associated to MS in GWAS showed enrichment amongst the differentially expressed genes. We did not identify enrichment of specific pathways amongst the differentially expressed genes in MS patients. Conclusions: CD8þ T cells of MS patients show differential gene expression, with predominantly higher activity of genes in MS patients. We do not identify specific biological pathways in our study. More detailed analysis of CD8þ T cells and subtypes of these may increase understanding of how T cells are involved in MS.

• Simonsen, Cecilia Smith; Flemmen, Heidi Øyen; Broch, Line; Brunborg, Cathrine; Berg-Hansen, Pål & Moen, Stine Marit [Vis alle 7 forfattere av denne artikkelen] (2020). The course of multiple sclerosis rewritten: a Norwegian population-based study on disease demographics and progression. Journal of Neurology. ISSN 0340-5354. s. 1–12. doi: 10.1007/s00415-020-10279-7. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Elvsåshagen, Torbjørn; Bahrami, Shahram; Meer, Dennis van der; Agartz, Ingrid; Alnæs, Dag & Barch, Deanna M. [Vis alle 76 forfattere av denne artikkelen] (2020). The genetic architecture of human brainstem structures and their involvement in common brain disorders. Nature Communications. 11. doi: 10.1038/s41467-020-17376-1. Fulltekst i vitenarkiv Vis sammendrag

  Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson’s disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.

• Celius, Elisabeth Gulowsen (2020). Normal antibody response after COVID-19 during treatment with cladribine. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 46(102476). doi: 10.1016/j.msard.2020.102476. Fulltekst i vitenarkiv
• Simonsen, Cecilia Smith; Flemmen, Heidi Øyen; Lauritzen, Trine; Berg-Hansen, Pål; Moen, Stine Marit & Celius, Elisabeth Gulowsen (2020). The diagnostic value of IgG index versus oligoclonal bands in cerebrospinal fluid of patients with multiple sclerosis. Multiple Sclerosis Journal, Experimental, Translational and Clinical. 6(1). doi: 10.1177/2055217319901291. Fulltekst i vitenarkiv Vis sammendrag

  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. 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. 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%). 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.

• Bertolotto, Antonio; Arroyo, Rafael; Celius, Elisabeth Gulowsen; Comi, Giancarlo; Havrdova, Eva & Honeycutt, William David [Vis alle 18 forfattere av denne artikkelen] (2020). Quality of Life Improves with Alemtuzumab Over 6 Years in Relapsing-Remitting Multiple Sclerosis Patients with or without Autoimmune Thyroid Adverse Events: Post Hoc Analysis of the CARE-MS Studies. Neurology and Therapy. ISSN 2193-8253. 9(2), s. 443–457. doi: 10.1007/s40120-020-00191-7. Fulltekst i vitenarkiv Vis sammendrag

  Introduction In clinical trials of alemtuzumab, autoimmune thyroid adverse events (AEs) were frequent. Here, we assess the impact of thyroid AEs on health-related quality of life (HRQL) in alemtuzumab-treated patients with relapsing-remitting multiple sclerosis (RRMS). Methods In phase 3 CARE-MS I (NCT00530348) and II (NCT00548405) trials, patients with RRMS were administered alemtuzumab 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. Patients could participate in an extension study (NCT00930553) through year 6. HRQL was assessed at baseline and annually using the Functional Assessment of Multiple Sclerosis (FAMS), EuroQoL-5 Dimension Visual Analog Scale (EQ-5D VAS), and 36-Item Short-Form Survey (SF-36) questionnaires. Outcomes were analyzed in patients with or without thyroid AEs (nonserious or serious). A subset of patients with thyroid AEs was analyzed to assess HRQL before and during the onset of thyroid AEs. Results A total of 811 CARE-MS patients were treated with alemtuzumab. Of these, 342 (42%) patients experienced thyroid AEs over 6 years; serious thyroid AEs occurred in 44 (5%) patients. At year 6, HRQL outcomes generally remained slightly improved or similar to core study baseline in alemtuzumab-treated patients with or without thyroid AEs: FAMS (least-squares mean change from baseline without thyroid AEs, 0.7; with nonserious thyroid AEs, 5.1; with serious thyroid AEs, − 5.3), EQ-5D VAS (2.0; 3.0; − 6.8), SF-36 mental component summary (MCS [0.6; 1.6; − 2.8]), SF-36 physical component summary (PCS [0.8; 1.0; 1.1]). Over 6 years, 63–82% of patients in each group had improved/stable SF-36 MCS and PCS scores. Among patients with thyroid AE onset in year 3 (peak incidence), there were minimal differences between HRQL outcomes before onset (year 2) and after onset (year 3). Conclusion Autoimmune thyroid AEs (serious and nonserious) had minimal impact on HRQL in alemtuzumab-treated patients. These data may aid therapeutic decisions in patients with relapsing MS.

• Sá, María José; Reis, Ricardo Soares dos; Altintas, Ayse; Celius, Elisabeth Gulowsen; Chien, Claudia & Comi, Giancarlo [Vis alle 18 forfattere av denne artikkelen] (2020). State of the Art and Future Challenges in Multiple Sclerosis Research and Medical Management: An Insight into the 5th International Porto Congress of Multiple Sclerosis. Neurology and Therapy. ISSN 2193-8253. 9, s. 281–300. doi: 10.1007/s40120-020-00202-7. Fulltekst i vitenarkiv Vis sammendrag

  The 5th International Porto Congress of Multiple Sclerosis took place between the 14th and 16th of February 2019 in Porto, Portugal. Its intensive programme covered a wide-range of themes—including many of the hot topics, challenges, pitfalls and yet unmet needs in the field of multiple sclerosis (MS)—led by a number of well-acknowledged world experts. This meeting review summarizes the talks that took place during the congress, which focussed on issues in MS as diverse as the development and challenges of progressive MS, epidemiology, differential diagnosis, medical management, molecular research and imaging tools.

• Brorson, Ina Skaara; Eriksson, Anna Maria; Leikfoss, Ingvild Sørum; Celius, Elisabeth Gulowsen; Berg-Hansen, Pål & Barcellos, Lisa F [Vis alle 9 forfattere av denne artikkelen] (2019). No differential gene expression for CD4+ T cells of MS patients and healthy controls. Multiple Sclerosis Journal, Experimental, Translational and Clinical. 5(2). doi: 10.1177/2055217319856903. Fulltekst i vitenarkiv
• Rhead, Brooke; Brorson, Ina Skaara; Berge, Tone; Adams, Cameron; Quach, H. & Moen, Stine Marit [Vis alle 18 forfattere av denne artikkelen] (2019). Increased DNA methylation of SLFN12 in CD4+ and CD8+ T cells from multiple sclerosis patients. PLOS ONE. doi: 10.1371/journal.pone.0206511. Fulltekst i vitenarkiv
• Grytten, Nina; Myhr, Kjell-Morten; Celius, Elisabeth Gulowsen; Benjaminsen, Espen; Kampman, Margitta Theodora & Midgard, Rune [Vis alle 10 forfattere av denne artikkelen] (2019). Risk of cancer among multiple sclerosis patients, siblings, and population controls: A prospective cohort study. Multiple Sclerosis. ISSN 1352-4585. 26(2), s. 1569–1580. doi: 10.1177/1352458519877244. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Brorson, Ina Skaara; Eriksson, Anna; Leikfoss, Ingvild Sørum; Celius, Elisabeth Gulowsen; Berg-Hansen, Pål & Barcellos, Lisa F. [Vis alle 9 forfattere av denne artikkelen] (2019). No differential gene expression for CD4+ T cells of MS patients and healthy controls. Multiple Sclerosis Journal, Experimental, Translational and Clinical. 5(2). doi: 10.1177/2055217319856903. Fulltekst i vitenarkiv Vis sammendrag

  Background: Multiple sclerosis-associated genetic variants indicate that the adaptive immune system plays an important role in the risk of developing multiple sclerosis. It is currently not well understood how these multiple sclerosis-associated genetic variants contribute to multiple sclerosis risk. CD4þ T cells are suggested to be involved in multiple sclerosis disease processes. Objective: We aim to identify CD4þ T cell differential gene expression between multiple sclerosis patients and healthy controls in order to understand better the role of these cells in multiple sclerosis. Methods: We applied RNA sequencing on CD4þ T cells from multiple sclerosis patients and healthy controls. Results: We did not identify significantly differentially expressed genes in CD4þ T cells from multiple sclerosis patients. Furthermore, pathway analyses did not identify enrichment for specific pathways in multiple sclerosis. When we investigated genes near multiple sclerosis-associated genetic variants, we did not observe significant enrichment of differentially expressed genes. Conclusion: We conclude that CD4þ T cells from multiple sclerosis patients do not show significant differential gene expression. Therefore, gene expression studies of all circulating CD4þ T cells may not result in viable biomarkers. Gene expression studies of more specific subsets of CD4þ T cells remain justified to understand better which CD4þ T cell subsets contribute to multiple sclerosis pathology.

• Halvorsrud, Ragnhild; Røhne, Mette; Celius, Elisabeth Gulowsen; Moen, Stine Marit & Strisland, Frode (2019). Application of Patient Journey Methodology to Explore Needs for Digital Support A Multiple Sclerosis Case Study. I Granja, Conceição & Solvoll, Terje (Red.), Proceedings of the 17th Scandinavian Conference on Health Informatics 2019. Linköping University Electronic Press. ISSN 9789179299576. s. 148–153. Fulltekst i vitenarkiv Vis sammendrag

  Multiple sclerosis (MS) is a chronic disease with a highly variable course, and patients face a large number of health professionals during treatment and follow-up. We introduce a methodology for detailed analysis and visualisation of patient journeys. The purpose was to gain insight into MS-patients' needs, experiences, and desires. A case study with three patients over a period of 4-6 weeks revealed how they interact with health professionals in managing their disease. We have identified several areas where digital tools may improve the patients' quality of life, and support health professionals in their follow-up and treatment of MS.

• Barclay, Kate; Carruthers, R; Traboulsee, A; Bass, AD; LaGanke, C & Bertolotto, Antonio [Vis alle 20 forfattere av denne artikkelen] (2019). Best practices for long-term monitoring and follow-up of alemtuzumab-treated MS patients in real-world clinical settings. Frontiers in Neurology. 10. doi: 10.3389/fneur.2019.00253. Fulltekst i vitenarkiv Vis sammendrag

  Multiple sclerosis (MS) is a chronic autoimmune neurological disease that typically affects young adults, causing irreversible physical disability and cognitive impairment. Alemtuzumab, administered intravenously as 2 initial courses of 12 mg/day (5 consecutive days at baseline, and 3 consecutive days 12 months later), resulted in significantly greater improvements in clinical and MRI outcomes vs. subcutaneous interferon beta-1a over 2 years in patients with active relapsing-remitting MS (RRMS) who were either treatment-naive (CARE-MS I; NCT00530348) or had an inadequate response to prior therapy (CARE-MS II; NCT00548405). Efficacy with alemtuzumab was maintained over 7 years in subsequent extension studies (NCT00930553; NCT02255656), in the absence of continuous treatment and with a consistent safety profile. There is an increased incidence of autoimmune events in patients treated with alemtuzumab (mainly thyroid events, but also immune thrombocytopenia and nephropathy), which imparts a need for mandatory safety monitoring for 4 years following the last treatment. The risk management strategy for alemtuzumab-treated patients includes laboratory monitoring and a comprehensive patient education and support program that enables early detection and effective management of autoimmune events, yielding optimal outcomes for MS patients. Here we provide an overview of tools and techniques that have been implemented in real-world clinical settings to reduce the burden of monitoring for both patients and healthcare providers, including customized educational materials, the use of social media, and interactive online databases for managing healthcare data. Many practices are also enhancing patient outreach efforts through coordination with specialized nursing services and ancillary caregivers. The best practice recommendations for safety monitoring described in this article, based on experiences in real-world clinical settings, may enable early detection and management of autoimmune events, and help with implementation of monitoring requirements while maximizing the benefits of alemtuzumab treatment for MS patients.

• Madireddy, Lohith; Patsopoulos, Nikolaos A.; Cotsapas, Chris; Bos, Steffan Daniel; Beecham, Ashley & McCauley, Jacob [Vis alle 64 forfattere av denne artikkelen] (2019). A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis. Nature Communications. 10:2236, s. 1–12. doi: 10.1038/s41467-019-09773-y. Fulltekst i vitenarkiv Vis sammendrag

  Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intraindividual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available.

• Benavent, Sigrid Aune de Rodez; Nygaard, Gro Owren; Nilsen, Kristian Bernhard; Etholm, Lars; Sowa, Piotr & Gustavsen, Marte Wendel [Vis alle 11 forfattere av denne artikkelen] (2019). Neurodegenerative interplay of cardiovascular autonomic dysregulation and the retina in early multiple sclerosis. Frontiers in Neurology. 10, s. 1–9. doi: 10.3389/fneur.2019.00507. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Autonomic nervous system (ANS) symptoms are prevalent in multiple sclerosis (MS) as is neurodegeneration. Our aim was to explore the occurrence of ANS symptoms and retinal neurodegeneration in a newly diagnosed MS population with tools available in a clinical setting. Methods: Forty-three MS patients and 44 healthy controls took part in the study. We employed a bedside cardiovascular ANS test battery together with classical pupillometry, optical coherence tomography (OCT) evaluation of retinal neurodegeneration in eyes without previous optic neuritis (MSNON) and patients' self-report forms on fatigue, orthostatic and ANS symptoms. Results: Half of the patients presented with ANS symptoms and a high level of fatigue. There was a significant difference in ganglion cell layer thickness (mean GCIPL) evaluated by OCT in MSNON compared to healthy control eyes. We found a negative linearity of mean GCIPL on group level with increasing disease duration. Three patients fulfilled the criteria of postural orthostatic tachycardia syndrome (POTS). Conclusion: Our results demonstrate retinal neurodegeneration in MSNON, a high frequency of fatigue and a high prevalence of ANS symptoms in newly diagnosed patients. Whether neurodegeneration precedes ANS dysfunction or vice versa is still open to debate, but as unveiled by the presence of POTS in this MS population, differences in stress-response regulation add to the understanding of variation in onset-time of ANS dysfunction in early MS.

• Kaufmann, Tobias; Meer, Dennis van der; Doan, Nhat Trung; Schwarz, Emanuel; Lund, Martina Jonette & Agartz, Ingrid [Vis alle 84 forfattere av denne artikkelen] (2019). Common brain disorders are associated with heritable patterns of apparent aging of the brain. Nature Neuroscience. ISSN 1097-6256. 22(10), s. 1617–1623. doi: 10.1038/s41593-019-0471-7. Fulltekst i vitenarkiv Vis sammendrag

  Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3–96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.

• Patsopoulos, Nikolaos A.; Baranzini, Sergio E.; Santaniello, Adam; Shoostari, Parisa; Cotsapas, Chris & Wong, Garrett [Vis alle 154 forfattere av denne artikkelen] (2019). Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science. ISSN 0036-8075. 365:eaav7188(6460), s. 1–12. doi: 10.1126/science.aav7188. Fulltekst i vitenarkiv Vis sammendrag

  We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses

• Rhead, Brooke; Brorson, Ina Skaara; Berge, Tone; Adams, Cameron; Quach, Hong & Moen, Stine Marit [Vis alle 18 forfattere av denne artikkelen] (2018). Increased DNA methylation of SLFN12 in CD4+ and CD8+ T cells from multiple sclerosis patients. PLOS ONE. 13(10). doi: 10.1371/journal.pone.0206511. Fulltekst i vitenarkiv Vis sammendrag

  DNA methylation is an epigenetic mark that is influenced by environmental factors and is associated with changes to gene expression and phenotypes. It may link environmental exposures to disease etiology or indicate important gene pathways involved in disease pathogenesis. We identified genomic regions that are differentially methylated in T cells of patients with relapsing remitting multiple sclerosis (MS) compared to healthy controls. DNA methylation was assessed at 450,000 genomic sites in CD4+ and CD8+ T cells purified from peripheral blood of 94 women with MS and 94 healthy women, and differentially methylated regions were identified using bumphunter. Differential DNA methylation was observed near four loci: MOG/ZFP57, HLA-DRB1, NINJ2/LOC100049716, and SLFN12. Increased methylation of the first exon of the SLFN12 gene was observed in both T cell subtypes and remained present after restricting analyses to samples from patients who had never been on treatment or had been off treatment for more than 2.5 years. Genes near the regions of differential methylation in T cells were assessed for differential expression in whole blood samples from a separate population of 1,329 women with MS and 97 healthy women. Gene expression of HLA-DRB1, NINJ2, and SLFN12 was observed to be decreased in whole blood in MS patients compared to controls. We conclude that T cells from MS patients display regions of differential DNA methylation compared to controls, and corresponding gene expression differences are observed in whole blood. Two of the genes that showed both methylation and expression differences, NINJ2 and SLFN12, have not previously been implicated in MS. SLFN12 is a particularly compelling target of further research, as this gene is known to be down-regulated during T cell activation and up-regulated by type I interferons (IFNs), which are used to treat MS.

• Hobart, Jeremy; Bowen, Amy; Pepper, George; Crofts, Harriet; Eberhard, Lucy & Berger, Thomas [Vis alle 27 forfattere av denne artikkelen] (2018). International consensus on quality standards for brain health-focused care in multiple sclerosis. Multiple Sclerosis. ISSN 1352-4585. s. 1–10. doi: 10.1177/1352458518809326. Fulltekst i vitenarkiv
• Kular, Lara; Liu, Yun; Ruhrmann, Sabrina; Zheleznyakova, Galina; Marabita, Francesco & Gomez-Cabrero, David [Vis alle 48 forfattere av denne artikkelen] (2018). DNA methylation as a mediator of HLA-DRB1 15:01 and a protective variant in multiple sclerosis. Nature Communications. 9(1), s. 1–15. doi: 10.1038/s41467-018-04732-5. Fulltekst i vitenarkiv Vis sammendrag

  The human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here, we find that DRB1*15:01 is hypomethylated and predominantly expressed in monocytes among carriers of DRB1*15:01. A differentially methylated region (DMR) encompassing HLA-DRB1 exon 2 is particularly affected and displays methylation-sensitive regulatory properties in vitro. Causal inference and Mendelian randomization provide evidence that HLA variants mediate risk for MS via changes in the HLA-DRB1 DMR that modify HLA-DRB1 expression. Meta-analysis of 14,259 cases and 171,347 controls confirms that these variants confer risk from DRB1*15:01 and also identifies a protective variant (rs9267649, p < 3.32 × 10−8, odds ratio = 0.86) after conditioning for all MS-associated variants in the region. rs9267649 is associated with increased DNA methylation at the HLA-DRB1 DMR and reduced expression of HLA-DRB1, suggesting a modulation of the DRB1*15:01 effect. Our integrative approach provides insights into the molecular mechanisms of MS susceptibility and suggests putative therapeutic strategies targeting a methylation-mediated regulation of the major risk gene.

• Sowa, Piotr; Harbo, Hanne Flinstad; White, Nathan S.; Celius, Elisabeth Gulowsen; Bartsch, Hauke & Berg-Hansen, Pål [Vis alle 12 forfattere av denne artikkelen] (2018). Restriction spectrum imaging of white matter and its relation to neurological disability in multiple sclerosis. Multiple Sclerosis. ISSN 1352-4585. s. 1–12. doi: 10.1177/1352458518765671. Fulltekst i vitenarkiv Vis sammendrag

  Background: Restriction spectrum imaging (RSI) is a recently introduced magnetic resonance imaging diffusion technique. The utility of RSI in multiple sclerosis (MS) is unknown. Objective: To investigate the association between RSI-derived parameters and neurological disability in MS. Methods: Seventy-seven relapsing-remitting MS patients were scanned with RSI on a 3-Tesla scanner. RSI-derived parameters: fast and slow apparent diffusion coefficient (sADC), fractional anisotropy, restricted fractional anisotropy, neurite density (ND), cellularity, extracellular water fraction and free water fraction were obtained in white matter lesions (WML) and normal appearing white matter (NAWM). Patients were divided into three groups according to their expanded disability status scale (EDSS): with minimal, low and substantial disability (<2.5, 2.5–3 and >3, respectively). Group comparisons and correlation analyses were performed. Results: All tested RSI-derived parameters differed between WML and NAWM (p<0.001 for all pairwise comparisons). The sADC in WML showed largest difference across disability subgroups (ANOVA: F=5.1, η2=0.12 p=0.008). ND in NAWM showed strongest correlation with disability (ϱ=-0.39, p<0.001). Conclusion: The strongest correlation with EDSS of ND obtained in NAWM indicates that processes outside lesions are important for disability in MS. Our study suggests that RSIderived parameters may help understand the “clinico-radiological paradox” and improve disease monitoring in MS.

• Celius, Elisabeth Gulowsen & Vila, Carlos (2018). The influence of THC:CBD oromucosal spray on driving ability in patients with multiple sclerosis-related spasticity. Brain and Behavior. 8(5), s. 1–11. doi: 10.1002/brb3.962. Fulltekst i vitenarkiv Vis sammendrag

  Background: Driving ability is a key function for the majority of patients with multiple sclerosis (MS) to help maintain daily interactions. Both physical and cognitive disability, as well as treatments, may affect the ability to drive. Spasticity is a common symptom associated with MS, and it may affect driving performance either directly or via the medications used to treat it. In this article, we review the evidence relating the antispasticity medicine, Δ9 -tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex®), and its potential impact on driving performance. Methods: Articles were identified by searching PubMed from 1/1/2000 to 30/6/2017 using a specified list of search terms. The articles identified using these search terms were augmented with relevant references from these papers and other articles known to the authors. Results: The results from THC:CBD oromucosal spray driving studies and real-world registries did not show any evidence of an increase in motor vehicle accidents associated with THC:CBD oromucosal spray. The majority of patients reported an improvementin driving ability after starting THC:CBD oromucosal spray, and it was speculated that this may be related to reduced spasticity and/or better cognitive function. It should be noted that THC blood levels are significantly lower than the levels associated with recreational use of herbal cannabis. Conclusions: THC:CBD oromucosal spray was shown not to impair driving performance. However, periodic assessment of patients with MS driving ability is recommended, especially afterrelapses andchanges intreatment.BloodTHCmeasurements might be above authorized thresholds for some countries following administration of THC:CBD oromucosal spray, thus specific knowledge of each country’s driving regulations and a medical certificate are recommended.

• Mitrovic, Mitja; Patsopoulos, Nikolaos A.; Beecham, Ashley H.; Dankowski, Theresa; Goris, An & Dubois, Benedicte [Vis alle 52 forfattere av denne artikkelen] (2018). Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk. Cell. ISSN 0092-8674. 175(6), s. 1679–1687. doi: 10.1016/j.cell.2018.09.049. Fulltekst i vitenarkiv Vis sammendrag

  Multiple sclerosis is a complex neurological disease, with ∼20% of risk heritability attributable to common genetic variants, including >230 identified by genome-wide association studies. Multiple strands of evidence suggest that much of the remaining heritability is also due to additive effects of common variants rather than epistasis between these variants or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that up to 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common-variant signals, highlighting key pathogenic roles for regulatory T cell homeostasis and regulation, IFNγ biology, and NFκB signaling. As low-frequency variants do not show substantial linkage disequilibrium with other variants, and as coding variants are more interpretable and experimentally tractable than non-coding variation, our discoveries constitute a rich resource for dissecting the pathobiology of MS.

• Bjørnevik, Kjetil; Riise, Trond; Benjaminsen, Espen; Celius, Elisabeth Gulowsen; Dahl, Ole-Petter & Kampman, Margitta Theodora [Vis alle 12 forfattere av denne artikkelen] (2017). Level of education and multiple sclerosis risk over a 50-year period: Registry-based sibling study. Multiple Sclerosis. ISSN 1352-4585. 23(2), s. 213–219. doi: 10.1177/1352458516646863. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Olafsson, Sigurgeir; Olafsson, S.; Stridh, Pernilla; Stridh, P.; Bos, Steffan Daniel & Ingason, Andrés [Vis alle 72 forfattere av denne artikkelen] (2017). Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations. NPJ GENOMIC MEDICINE. 2. doi: 10.1038/s41525-017-0027-2. Fulltekst i vitenarkiv Vis sammendrag

  A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 x 10(-7), 4.3 x 10(-9)) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.

• Celius, Elisabeth Gulowsen (2017). Infections in patients with multiple sclerosis: Implications for disease-modifying therapy. Acta Neurologica Scandinavica. ISSN 0001-6314. 136, s. 34–36. doi: 10.1111/ane.12835. Fulltekst i vitenarkiv
• Sowa, Piotr; Nygaard, Gro Owren; Bjørnerud, Atle; Celius, Elisabeth Gulowsen; Harbo, Hanne Flinstad & Beyer, Mona K. (2017). Magnetic resonance imaging perfusion is associated with disease severity and activity in multiple sclerosis. Neuroradiology. ISSN 0028-3940. 59(7), s. 655–664. doi: 10.1007/s00234-017-1849-4. Fulltekst i vitenarkiv Vis sammendrag

  Purpose The utility of perfusion-weighted imaging in multiple sclerosis (MS) is not well investigated. The purpose of this study was to compare baseline normalized perfusion measures in subgroups of newly diagnosed MS patients. We wanted to test the hypothesis that this method can differentiate between groups defined according to disease severity and disease activity at 1 year follow-up. Methods Baseline magnetic resonance imaging (MRI) including a dynamic susceptibility contrast perfusion sequence was performed on a 1.5-T scanner in 66 patients newly diagnosed with relapsing-remitting MS. From the baseline MRI, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps were generated. Normalized (n) perfusion values were calculated by dividing each perfusion parameter obtained in white matter lesions by the same parameter obtained in normal-appearing white matter. Neurological examination was performed at baseline and at follow-up approximately 1 year later to establish the multiple sclerosis severity score (MSSS) and evidence of disease activity (EDA). Results Baseline normalized mean transit time (nMTT) was lower in patients with MSSS >3.79 (p = 0.016), in patients with EDA (p = 0.041), and in patients with both MSSS >3.79 and EDA (p = 0.032) at 1-year follow-up. Baseline normalized cerebral blood flow and normalized cerebral blood volume did not differ between these groups. Conclusion Lower baseline nMTT was associated with higher disease severity and with presence of disease activity 1 year later in newly diagnosed MS patients. Further longitudinal studies are needed to confirm whether baseline-normalized perfusion measures can differentiate between disease severity and disease activity subgroups over time.

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• Simonsen, Cecilia Smith; Moen, Mette Haase & Celius, Elisabeth Gulowsen (2025). Lower threshold for hormone therapy in women with multiple sclerosis. doi: 10.4045/tidsskr.25.0070. Fulltekst i vitenarkiv
• Simonsen, Cecilia Smith; Flemmen, Heidi Øyen; Broch, Line; Myklebust, Harald; Berg-Hansen, Pål & Brunborg, Cathrine [Vis alle 7 forfattere av denne artikkelen] (2024). The influence of menopause on multiple sclerosis. Fulltekst i vitenarkiv
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• Nygaard, Gro Owren; Torgauten, Hilde Marie; Skattebøl, Lars; Høgestøl, Einar August; Sowa, Piotr & Myhr, Kjell-Morten [Vis alle 8 forfattere av denne artikkelen] (2022). Risk of fingolimod rebound after switching to cladribine or rituximab in multiple sclerosis. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 62. doi: 10.1016/j.msard.2022.103812. Fulltekst i vitenarkiv
• Rasmussen, Tilde; König, Marton; Lorentzen, Åslaug Rudjord; Schikora-Rustad, Stine; Berge, Tone & Holmøy, Trygve [Vis alle 17 forfattere av denne artikkelen] (2022). Safety of a third SARS CoV 2 mRNA vaccine dose in people with multiple sclerosis. Fulltekst i vitenarkiv
• König, Marton; Wolf, Asia-Sophia Fumika Michaela; Ravussin, Anthony; Chopra, Adity; Tran, Trung & Torgauten, Hilde Marie [Vis alle 28 forfattere av denne artikkelen] (2022). Immunogenicity and efficacy of mRNA-COVID-19 vaccines in people with multiple sclerosis. Fulltekst i vitenarkiv
• Tsivgoulis, Georgios; Deftereos, Spyros; Gobbi, Claudio; Celius, Elisabeth Gulowsen; Kulakowska, Alina & Maniscalco, Giorgia [Vis alle 8 forfattere av denne artikkelen] (2022). Oral Cladribine in Patients who Change From First-Line Disease Modifying Treatments for Multiple Sclerosis: Protocol of a Prospective Effectiveness and Safety Study (CLAD CROSS). Journal of central nervous system disease. 14, s. 1–8. doi: 10.1177/11795735211069441. Fulltekst i vitenarkiv Vis sammendrag

  Background Recently, the number of available disease modifying therapies for multiple sclerosis (MS) has increased. However, a proportion of patients treated with these agents continue to experience relapses and disease progression. Cladribine tablets, approved in 2017 for highly active relapsing MS, comprise a sparsely administered oral treatment which exerts its therapeutic effect through a reduction and subsequent repletion of the lymphocyte population. Purpose/Study Sample Here we describe the design of CLAD CROSS, a prospective, non-interventional, multicenter, Phase IV study in patients with a confirmed diagnosis of RRMS who switch from first-line disease modifying drugs (DMDs) to treatment with cladribine tablets in routine clinical practice. 242 adult patients will be recruited in 61 sites (6 countries) over 30 months and will be followed up for 2 years following prescription of cladribine tablets per the decision of the treating physicians. Research Design The primary endpoint is the change in annualized relapse rate (ARR) between the 12-month pre-baseline period and over the 12-month period before end of study. Secondary endpoints are the percentage of patients with 6-month disability progression or improvement at the end of the study, measured by the Expanded Disability Status Scale, Timed 25 Foot Walk and 9-Hole Peg Test scales and quality of life, treatment satisfaction, and healthcare resource utilization, measured through the MSIS-29, TSQM 1.4, and EQ-5D-3L scales, respectively. MRI lesions will be compared in the exploratory setting between the 12-month pre-baseline period, baseline, and at years 1 and 2. Adverse events will be monitored throughout the study. Interim analyses are pre-planned when 30% and 60% of patients will complete the 12-month follow-up visit. Conclusions CLAD CROSS will provide efficacy data on cladribine tablets, used as a follow-up treatment to first-line DMDs in the real-world setting, will further establish its safety profile and will collect information to support pharmacoeconomic studies.

• Nygaard, Gro Owren; Schikora-Rustad, Stine; Lie, Ingeborg Haugesag; Aase, Audun; Leiknes, Ingvild Jullum & König, Marton [Vis alle 15 forfattere av denne artikkelen] (2021). Humoral immune response to the influenza vaccine in multiple sclerosis patients treated with cladribine or rituximab. Fulltekst i vitenarkiv
• König, Marton; Lorentzen, Åslaug Rudjord; Torgauten, Hilde Marie; Tran, The Trung; Schikora-Rustad, Stine & Vaage, Eline Benno [Vis alle 22 forfattere av denne artikkelen] (2021). Humoral Immunity to SARS-CoV-2 mRNA Vaccination in People with Multiple Sclerosis using High-Efficacy Disease Modifying Therapies. Fulltekst i vitenarkiv
• Berg-Hansen, Pål; Moen, Stine Marit; Austeng, Andreas; Gonzales, Victor; Klyve, Thomas Dahl & Negård, Henrik [Vis alle 9 forfattere av denne artikkelen] (2021). Sensor-based gait analyses identify qualitative improvement in gait parameters after short-time rehabilitation in a Norwegian MS rehabilitation unit. Fulltekst i vitenarkiv
• Berg-Hansen, Pål; Moen, Stine Marit; Jahren, Silje Ekroll; Klyve, Thomas; Meyer, Fredrik & Strisland, Frode [Vis alle 10 forfattere av denne artikkelen] (2020). Use of sensors in MS rehabilitation - a pilot study. Fulltekst i vitenarkiv
• Kaufmann, Tobias; Meer, Dennis van der; Doan, Nhat Trung; Schwarz, Emanuel; Lund, Martina Jonette & Agartz, Ingrid [Vis alle 97 forfattere av denne artikkelen] (2020). Publisher Correction: Common brain disorders are associated with heritable patterns of apparent aging of the brain (Nature Neuroscience, (2019), 22, 10, (1617-1623), 10.1038/s41593-019-0471-7). Nature Neuroscience. ISSN 1097-6256. 23(2), s. 295–295. doi: 10.1038/s41593-019-0553-6. Fulltekst i vitenarkiv
• Jahren, Silje Ekroll; Seeberg, Trine Margrethe; Berg-Hansen, Pål; Celius, Elisabeth Gulowsen & Moen, Stine Marit (2020). Det hun gjør her kan hjelpe folk med MS. Magasinet Tekna. ISSN 1502-704X. Fulltekst i vitenarkiv
• Halvorsrud, Ragnhild; Røhne, Mette; Celius, Elisabeth Gulowsen; Moen, Stine Marit & Strisland, Frode (2019). Application of Patient Journey Methodology to Explore Needs for Digital Support. A Multiple Sclerosis Case Study. Fulltekst i vitenarkiv
• Richter, Stephan; Wagner, Bert & Celius, Elisabeth Gulowsen (2019). Two cases of diabetes mellitus type 1 after alemtuzumab treatment for multiple sclerosis: another probable secondary autoimmune disease. Journal of Neurology. ISSN 0340-5354. 266(5), s. 1270–1271. doi: 10.1007/s00415-019-09257-5. Fulltekst i vitenarkiv
• Seeberg, Trine Margrethe; Benjaminsen, Christina; Sandbakk, Øyvind & Celius, Elisabeth Gulowsen (2019). Langrennsløpernes gulloppskrift hjelper også MS-pasienter. Gemini. ISSN 0802-085X. Fulltekst i vitenarkiv
• Seeberg, Trine Margrethe; Benjaminsen, Christina; Sandbakk, Øyvind & Celius, Elisabeth Gulowsen (2019). Disse dingsene kan hjelpe både skiløpere og MS-pasienter. Forskning.no. ISSN 1891-635X. Fulltekst i vitenarkiv
• Bos, Steffan Daniel; Brorson, Ina Skaara; Eriksson, Anna; Leikfoss, Ingvild Sørum; Vitelli, Valeria & Celius, Elisabeth Gulowsen [Vis alle 10 forfattere av denne artikkelen] (2019). Differential gene expression analysis of CD8+ T cells from multiple sclerosis patients and healthy controls. Fulltekst i vitenarkiv
• Madireddy, Lohith; Patsopoulos, Nikolaos A.; Cotsapas, Chris; Bos, Steffan Daniel; Beecham, Ashley H. & McCauley, Jacob [Vis alle 64 forfattere av denne artikkelen] (2019). Author Correction: A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis (Nature Communications, (2019), 10, 1, (2236), 10.1038/s41467-019-09773-y). Nature Communications. 10(1). doi: 10.1038/s41467-019-10951-1. Fulltekst i vitenarkiv
• Leikfoss, Ingvild Sørum; Bos, Steffan Daniel; Berg-Hansen, Pål; Berge, Tone; Beyer, Mona K. & Celius, Elisabeth Gulowsen [Vis alle 8 forfattere av denne artikkelen] (2018). The EU Horizon2020 Project MultipleMS: Improved Personalized Medicine for Multiple Sclerosis. Fulltekst i vitenarkiv
• Brorson, Ina Skaara; Rhead, Brooke; Berge, Tone; Adams, Cameron; Quach, Hong & Sangurdekar, Dipen [Vis alle 18 forfattere av denne artikkelen] (2018). SLFN12 is differentially methylated in multiple sclerosis CD4+ and CD8+ T cells. Fulltekst i vitenarkiv
• Celius, Elisabeth Gulowsen (2018). Undervisning har lav status innen akademia. 138(12). doi: 10.4045/tidsskr.18.0341. Fulltekst i vitenarkiv
• Røhne, Mette; Halvorsrud, Ragnhild; Strisland, Frode; Moen, Stine Marit & Celius, Elisabeth Gulowsen (2018). Digital oppfølging og støtte for personer med multippel sklerose. Erfaringer fra prosjektet MS-DOS. SINTEF Digital. ISSN 9788214069051. Fulltekst i vitenarkiv Vis sammendrag

  MS-DOS er et forprosjekt som undersøker muligheter for at personer med multippel sklerose (MS) og relevante helseaktører kan ta i bruk digitale hjelpemidler for bedre oppfølging, behandling og mestring av sykdommen. Målet for MS-DOS er å samle informasjon om hvilke utfordringer personer med MS opplever på grunn av sin sykdom, og vurdere i hvilken grad digitale verktøy kan gjøre livet bedre for denne gruppen. Denne rapporten gir et overblikk over helsetilbudet til personer med MS. Deretter presenteres resultater fra en dybdestudie hvor vi følger tre personer med MS over en periode på seks uker. Metoden vi har brukt er observasjon og intervjuer, samt kartlegging av planlagte og reelle pasientforløp ved hjelp av Customer Journey Modelling Language. Rapporten presenterer til slutt muligheter for bruk av digitale støtteverktøy, og forslag til videre studier Oppdragsgiver: Helsedirektoratet ved Innomed

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