Gro Owren Nygaard

• Serkland, Trond Trætteberg; Oma, Anna-Kristina Fredheim; Hallin, Erik Ingmar; Øverås, Mathias Herstad; Nygaard, Gro Owren & Myhr, Kjell-Morten [Vis alle 9 forfattere av denne artikkelen] (2026). Pharmacokinetic-Pharmacodynamic Modelling of Repeated Ocrelizumab Dosing in Relapsing-Remitting Multiple Sclerosis. Clinical Pharmacokinetics. ISSN 0312-5963. doi: 10.1007/s40262-026-01692-8. Fulltekst i vitenarkiv Vis sammendrag

  Background and Objective Ocrelizumab (OCR) is an anti-CD20 monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Although the standard regimen consists of fixed 6-monthly infusions, therapeutic duration may vary between patients, highlighting the need for individualized dosing strategies. The objective of this study was to develop a pharmacokinetic-pharmacodynamic (PKPD) model able to predict patient-specific treatment responses, as a step towards a clinically applicable tool for optimizing OCR dosing precision in RRMS. Methods Serum OCR concentrations and CD19⁺ lymphocyte counts from 11 treatment-naïve patients with newly diagnosed RRMS were analyzed. Samples were collected over 24 weeks following the first and second OCR infusions. Data were analyzed using a nonlinear mixed-effects population modelling approach in Monolix Suite 2023R1, with parameter estimation performed via the stochastic approximation expectation-maximization algorithm. Several structural models were evaluated, and model performance was assessed by fit statistics and visual predictive checks. Results The resultant two-compartment PKPD model successfully described OCR disposition and CD19⁺ lymphocyte depletion/repopulation. The final model included clearance of OCR without target-mediated elimination and described the effect of OCR on the dynamics of CD19⁺ lymphocyte counts. Simulations demonstrated the ability of the model to estimate the time to CD19⁺ lymphocyte repopulation and to explore optimal time for follow-up measurements. Conclusion A novel PKPD model for OCR in RRMS that integrates drug exposure and CD19⁺ lymphocyte kinetics is presented. Although a small number of patients is included in the current study, this framework represents an important step toward clinically applicable, model-informed dosing strategies, with the potential to enhance treatment precision and support personalized therapy in RRMS.

• Korbmacher, Max; Lie, Ingrid Anne; Wesnes, Kristin; Westman, Eric; Espeseth, Thomas & Andreassen, Ole [Vis alle 13 forfattere av denne artikkelen] (2026). Regional patterns of grey matter volume decline in relapsing-remitting multiple sclerosis relative to healthy ageing. NeuroImage. ISSN 1053-8119. 338, s. 1–9. doi: 10.1016/j.neuroimage.2026.122118. Fulltekst i vitenarkiv Vis sammendrag

  Background: Grey matter volume loss (GM-VL) is an accurate marker of multiple sclerosis (MS)-related progression. However, long-term comparisons of GM-VL between MS and healthy controls (HC) are rare, and the brain regions with most significant GM-VL and their clinical importance still need robust and longitudinal validation. Methods: This multi-cohort longitudinal observational study used two relapsing remitting MS (RRMS) cohorts (N = 386, T1w-scans=940) sampled for up-to-12 years to localise grey matter volume loss (GM-VL) and disease progression (Expanded Disability Status Scale (EDSS), Paced Auditory Serial Addition Test (PASAT), Fatigue Severity Scale (FSS)). The identified region-specific significant GM-VL was compared with 2163 HCs (T1w-scans=4326). Results: The strongest, replicable, significant patterns of brain GM-VL in RRMS were found in the frontal lobes, specifically, in the superior frontal cortex (SFC, βage≤-0.27), pars orbitalis (βage≤-0.25), and thalami (βage≤-0.20). Compared with healthy controls (HCs) >20 years older, MS showed greater GM-VL in the right SFC, caudal-middle frontal cortex, caudate, and left frontal pole (all Z > 2.08, p < 0.019). The overlap of associations between volumetric and clinical outcome changes was limited to EDSS, which was significantly related to left hippocampal volumes βEDSS≤-0.19 in both cohorts. Conclusions: Our findings indicate GM-VL in people with RRMS comparable to 20-year older HC, and stronger in the SFC and thalamus, and cohort-specific relationships with disability-progression.

• Torkildsen, Øivind; Brustad, Hilde Kjelgaard; Høgestøl, Einar August; Alstadhaug, Karl Bjørnar; Bhan, Alok & Flemmen, Heidi Øyen [Vis alle 22 forfattere av denne artikkelen] (2026). Rituximab versus Ocrelizumab in Newly Diagnosed Relapsing Multiple Sclerosis. New England Journal of Medicine. ISSN 0028-4793. 395(1), s. 44–53. doi: 10.1056/nejmoa2600993. Fulltekst i vitenarkiv Vis sammendrag

  BACKGROUND Anti-CD20 monoclonal antibodies are effective for relapsing multiple sclerosis. However, data from head-to-head trials are lacking. METHODS In this phase 3, multicenter, double-blind, noninferiority trial, we randomly assigned adults with newly diagnosed relapsing multiple sclerosis and recent disease activity in a 3:2 ratio to receive rituximab or ocrelizumab every 6 months for 24 months. The primary end point was the absence of new or enlarging lesions on T2-weighted magnetic resonance imaging (MRI) from month 6 to month 24. Noninferiority was defined as a lower limit of the 95% confidence interval for the risk difference (ritux- imab minus ocrelizumab) of greater than or equal to −10 percentage points. Secondary end points included efficacy and safety. RESULTS A total of 218 participants underwent randomization; 216 received treatment (132 assigned to the rituximab group and 84 assigned to the ocrelizumab group). Between months 6 and 24, the estimated probability of having no new or enlarging lesions detected on T2-weighted MRI was 92.2% with rituximab and 94.8% with ocrelizumab, corresponding to a risk difference of –2.6 percentage points (95% confidence interval, –9.4 to 4.3), which met the prespecified noninferiority criterion. Relapse rates, dis- ability outcomes, and cognitive-performance profiles appeared to be similar in the two groups. Infections were more common in the rituximab group than in the ocreliz- umab group (in 82% vs. 69% of participants), although the percentage of participants with serious adverse events was similar in the two groups (8% and 7%, respectively). CONCLUSIONS In participants with newly diagnosed relapsing multiple sclerosis and recent disease activity, rituximab was noninferior to ocrelizumab in suppressing disease activity as detected by MRI from 6 to 24 months, with a similar incidence of serious adverse events.

• 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.

• Breedt, Lucas C.; Pontillo, Giuseppe; Santos, Fernando A.N.; Vriend, Chris; Prados, Ferran & Wink, Alle Meije [Vis alle 38 forfattere av denne artikkelen] (2026). Structure–function multilayer network integration and cognition in multiple sclerosis. Network Neuroscience. doi: 10.1162/NETN.a.545. Fulltekst i vitenarkiv
• 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
• 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.

• 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
• Rød, Brit Ellen; Høgestøl, Einar August; Torkildsen, Øivind; Bjørnevik, Kjetil; Gran, Jon Michael & Øverås, Mathias Herstad [Vis alle 10 forfattere av denne artikkelen] (2025). Comparative effectiveness of rituximab and cladribine in relapsing–remitting multiple sclerosis: A target trial emulation. Multiple Sclerosis. ISSN 1352-4585. 31(8), s. 975–984. doi: 10.1177/13524585251342727. Fulltekst i vitenarkiv Vis sammendrag

  Background: Head-to-head comparisons of high-efficacy therapies for relapsing–remitting multiple sclerosis (RRMS) are lacking. We conducted a target trial emulation to compare the long-term effectiveness of rituximab and cladribine. Methods: We estimated the effect of initiating treatment with rituximab versus cladribine using observational data from the Norwegian MS Registry and Biobank at two university hospitals with different treatment strategies. Cumulative incidence and risk differences (RDs) were estimated using weighted Kaplan-Meier estimators, adjusting for baseline covariates. The primary outcome was magnetic resonance imaging (MRI) disease activity, with secondary outcomes including relapses and safety. Results: The study included 285 patients, 159 receiving rituximab and 126 cladribine, with a median follow-up of 4.5 years (interquartile range (IQR): 4.2–4.7). The 4-year risk of new MRI disease activity was 17% (95% confidence interval (CI): 11–23) for rituximab-treated patients and 57% (95% CI: 44–66) for cladribine-treated patients, yielding an RD of 40 percentage-points (95% CI: 28–50). The 4-year RD for relapse was 12 percentage-points (95% CI: 4–19). The incidence of hospitalizations related to potential adverse events was 6.0 per 100 person-years for rituximab and 4 per 100 person-years for cladribine. Conclusion: These findings suggest that rituximab has superior effectiveness compared to cladribine during a median follow-up of 4.5 years.

• Pontillo, Giuseppe; Prados, Ferran; Wink, Alle Meije; Kanber, Baris; Bisecco, Alvino & Broeders, Tommy A. A. [Vis alle 43 forfattere av denne artikkelen] (2025). More Than the Sum of Its Parts: Disrupted Core Periphery of Multiplex Brain Networks in Multiple Sclerosis. Human Brain Mapping. ISSN 1065-9471. 46(1). doi: 10.1002/hbm.70107. Fulltekst i vitenarkiv
• Pontillo, Giuseppe; Prados, Ferran; Colman, Jordan; Kanber, Baris; Abdel-Mannan, Omar & Al-Araji, Sarmad [Vis alle 62 forfattere av denne artikkelen] (2024). Disentangling Neurodegeneration From Aging in Multiple Sclerosis Using Deep Learning: The Brain-Predicted Disease Duration Gap. Neurology. ISSN 0028-3878. 103(10). doi: 10.1212/WNL.0000000000209976. Fulltekst i vitenarkiv Vis sammendrag

  Background and Objectives Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS. Methods In this retrospective study, we collected 3D T1-weighted brain MRI scans of PwMS to build (1) a cross-sectional multicentric cohort for age and disease duration (DD) modeling and (2) a longitudinal single-center cohort of patients with early MS as a clinical use case. We trained and evaluated a 3D DenseNet architecture to predict DD from minimally preprocessed images while age predictions were obtained with the DeepBrainNet model. The brain-predicted DD gap (the difference between predicted and actual duration) was proposed as a DD-adjusted global measure of MS-specific brain damage. Model predictions were scrutinized to assess the influence of lesions and brain volumes while the DD gap was biologically and clinically validated within a linear model framework assessing its relationship with BAG and physical disability measured with the Expanded Disability Status Scale (EDSS). Results We gathered MRI scans of 4,392 PwMS (69.7% female, age: 42.8 ± 10.6 years, DD: 11.4 ± 9.3 years) from 15 centers while the early MS cohort included 749 sessions from 252 patients (64.7% female, age: 34.5 ± 8.3 years, DD: 0.7 ± 1.2 years). Our model predicted DD better than chance (mean absolute error = 5.63 years, R2 = 0.34) and was nearly orthogonal to the brain-age model (correlation between DD and BAGs: r = 0.06 [0.00–0.13], p = 0.07). Predictions were influenced by distributed variations in brain volume and, unlike brain-predicted age, were sensitive to MS lesions (difference between unfilled and filled scans: 0.55 years [0.51–0.59], p < 0.001). DD gap significantly explained EDSS changes (B = 0.060 [0.038–0.082], p < 0.001), adding to BAG (ΔR2 = 0.012, p < 0.001). Longitudinally, increasing DD gap was associated with greater annualized EDSS change (r = 0.50 [0.39–0.60], p < 0.001), with an incremental contribution in explaining disability worsening compared with changes in BAG alone (ΔR2 = 0.064, p < 0.001). Discussion The brain-predicted DD gap is sensitive to MS-related lesions and brain atrophy, adds to the brain-age paradigm in explaining physical disability both cross-sectionally and longitudinally, and may be used as an MS-specific biomarker of disease severity and progression.

• 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.

• Tran, Trung; Vaage, Eline Benno; Mehta, Adi; Chopra, Adity; Tietze, Lisa & Kolderup, Heidi Anette [Vis alle 40 forfattere av denne artikkelen] (2022). Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants. npj Vaccines. 7(1). doi: 10.1038/s41541-022-00586-7. Fulltekst i vitenarkiv Vis sammendrag

  Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 serum samples. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.

• Riise, Jon; Meyer, Saskia; Blaas, Isaac; Chopra, Adity; Tran, Trung & Delic-Sarac, Marina [Vis alle 22 forfattere av denne artikkelen] (2022). Rituximab-treated patients with lymphoma develop strong CD8 T-cell responses following COVID-19 vaccination. British Journal of Haematology. ISSN 0007-1048. 197(6), s. 697–708. doi: 10.1111/bjh.18149. Fulltekst i vitenarkiv Vis sammendrag

  B-cell depletion induced by anti-cluster of differentiation 20 (CD20) monoclonal antibody (mAb) therapy of patients with lymphoma is expected to impair humoral responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, but effects on CD8 T-cell responses are unknown. Here, we investigated humoral and CD8 T-cell responses following two vaccinations in patients with lymphoma undergoing anti-CD20-mAb therapy as single agent or in combination with chemotherapy or other anti-neoplastic agents during the last 9 months prior to inclusion, and in healthy age-matched blood donors. Antibody measurements showed that seven of 110 patients had antibodies to the receptor-binding domain of the SARS-CoV-2 Spike protein 3–6 weeks after the second dose of vaccination. Peripheral blood CD8 T-cell responses against prevalent human leucocyte antigen (HLA) class I SARS-CoV-2 epitopes were determined by peptide-HLA multimer analysis. Strong CD8 T-cell responses were observed in samples from 20/29 patients (69%) and 12/16 (75%) controls, with similar median response magnitudes in the groups and some of the strongest responses observed in patients. We conclude that despite the absence of humoral immune responses in fully SARS-CoV-2-vaccinated, anti-CD20-treated patients with lymphoma, their CD8 T-cell responses reach similar frequencies and magnitudes as for controls. Patients with lymphoma on B-cell depleting therapies are thus likely to benefit from current coronavirus disease 2019 (COVID-19) vaccines, and development of vaccines aimed at eliciting T-cell responses to non-Spike epitopes might provide improved protection.

• König, Marton; Torgauten, Hilde Marie; Tran, Trung; Holmøy, Trygve; Vaage, John T. & Lund-Johansen, Fridtjof [Vis alle 7 forfattere av denne artikkelen] (2022). Immunogenicity and Safety of a Third SARS-CoV-2 Vaccine Dose in Patients with Multiple Sclerosis and Weak Immune Response after COVID-19 Vaccination. JAMA Neurology. ISSN 2168-6149. 79(3), s. 307–309. doi: 10.1001/jamaneurol.2021.5109. Fulltekst i vitenarkiv
• 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.

• Høgestøl, Einar August; Ghezzo, Samuele; Nygaard, Gro Owren; Espeseth, Thomas; Sowa, Piotr & Beyer, Mona K. [Vis alle 10 forfattere av denne artikkelen] (2021). Functional connectivity in multiple sclerosis modelled as connectome stability: A 5-year follow-up study. Multiple Sclerosis. ISSN 1352-4585. s. 1–9. doi: 10.1177/13524585211030212. Fulltekst i vitenarkiv Vis sammendrag

  Background: Brain functional connectivity (FC) in multiple sclerosis (MS) is abnormal compared to healthy controls (HCs). More longitudinal studies in MS are needed to evaluate whether FC stability is clinically relevant. Objective: To compare functional magnetic resonance imaging (fMRI)-based FC between MS and HC, and to determine the relationship between longitudinal FC changes and structural brain damage, cognitive performance and physical disability. Methods: T1-weighted MPRAGE and resting-state fMRI (1.5T) were acquired from 70 relapsing-remitting MS patients and 94 matched HC at baseline (mean months since diagnosis 14.0 ± 11) and from 60 MS patients after 5 years. Independent component analysis and network modelling were used to measure longitudinal FC stability and cross-sectional comparisons with HC. Linear mixed models, adjusted for age and sex, were used to calculate correlations. Results: At baseline, patients with MS showed FC abnormalities both within networks and in single connections compared to HC. Longitudinal analyses revealed functional stability and no significant relationships with clinical disability, cognitive performance, lesion or brain volume. Conclusion: FC abnormalities occur already at the first decade of MS, yet we found no relevant clinical correlations for these network deviations. Future large-scale longitudinal fMRI studies across a range of MS subtypes and outcomes are required.

• Brune, Synne; Høgestøl, Einar August; Cengija, Vanja; Berg-Hansen, Pål; Sowa, Piotr & Nygaard, Gro Owren [Vis alle 8 forfattere av denne artikkelen] (2020). LesionQuant for assessment of MRI in multiple sclerosis—A promising supplement to the visual scan inspection. Frontiers in Neurology. 11:546744, s. 1–10. doi: 10.3389/fneur.2020.546744. Fulltekst i vitenarkiv Vis sammendrag

  Background and Goals: Multiple sclerosis (MS) is a central nervous system inflammatory disease where magnetic resonance imaging (MRI) is an important tool for diagnosis and disease monitoring. Quantitative measurements of lesion volume, lesion count, distribution of lesions, and brain atrophy have a potentially significant value for evaluating disease progression. We hypothesize that utilizing software designed for evaluating MRI data in MS will provide more accurate and detailed analyses compared to the visual neuro-radiological evaluation. Methods: A group of 56 MS patients (mean age 35 years, 70% females and 96% relapsing-remitting MS) was examined with brain MRI one and 5 years after diagnosis. The T1 and FLAIR brain MRI sequences for all patients were analyzed using the LesionQuant (LQ) software. These data were compared with data from structured visual evaluations of the MRI scans performed by neuro-radiologists, including assessments of atrophy, and lesion count. The data from LQ were also compared with data from other validated research methods for brain segmentation, including assessments of whole brain volume and lesion volume. Correlations with clinical tests like the timed 25-foot walk test (T25FT) were performed to explore additional value of LQ analyses. Results: Lesion count assessments by LQ and by the neuro-radiologist were significantly correlated one year (cor = 0.92, p = 2.2 × 10 −16 ) and 5 years (cor = 0.84, p = 2.7 × 10 −16 ) after diagnosis. Analyzes of the intra- and interrater variability also correlated significantly (cor = 0.96, p &amp;lt; 0.001, cor = 0.97, p &amp;lt; 0.001). Significant positive correlation was found between lesion volume measured by LQ and by the software Cascade (cor = 0.7, p &amp;lt; 0.001. LQ detected a reduction in whole brain percentile &amp;gt;10 in 10 patients across the time-points, whereas the neuro-radiologist assessment identified six of these. The neuro-radiologist additionally identified five patients with increased atrophy in the follow-up period, all of them displayed decreasing low whole brain percentiles (median 11, range 8–28) in the LQ analysis. Significant positive correlation was identified between lesion volume measured by LQ and test performance on the T25FT both at 1 and 5 years after diagnosis. Conclusion: For the number of MS lesions at both time-points, we demonstrated strong correlations between the assessments done by LQ and the neuro-radiologist. Lesion volume evaluated with LQ correlated with T25FT performance. LQ-analyses classified more patients to have brain atrophy than the visual neuro-radiological evaluation. In conclusion, LQ seems like a promising supplement to the evaluation performed by neuro-radiologists, providing an automated tool for evaluating lesions in MS patients and also detecting early signs of atrophy in both a longitudinal and cross-sectional setting.

• 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.

• Høgestøl, Einar August; Kaufmann, Tobias; Nygaard, Gro Owren; Beyer, Mona K.; Sowa, Piotr & Nordvik, Jan Egil [Vis alle 11 forfattere av denne artikkelen] (2019). Cross-sectional and longitudinal MRI brain scans reveal accelerated brain aging in multiple sclerosis. Frontiers in Neurology. 10:450, s. 1–9. doi: 10.3389/fneur.2019.00450. Fulltekst i vitenarkiv Vis sammendrag

  Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system. By combining longitudinal MRI-based brain morphometry and brain age estimation using machine learning, we tested the hypothesis that MS patients have higher brain age relative to chronological age than healthy controls (HC) and that longitudinal rate of brain aging in MS patients is associated with clinical course and severity. Seventy-six MS patients [71% females, mean age 34.8 years (range 21–49) at inclusion] were examined with brain MRI at three time points with a mean total follow up period of 4.4 years (±0.4 years). We used additional cross-sectional MRI data from 235 HC for case-control comparison. We applied a machine learning model trained on an independent set of 3,208 HC to estimate individual brain age and to calculate the difference between estimated and chronological age, termed brain age gap (BAG). We also assessed the longitudinal change rate in BAG in individuals with MS. MS patients showed significantly higher BAG (4.4 ± 6.6 years) compared to HC (Cohen's D = 0.69, p = 4.0 × 10−6). Longitudinal estimates of BAG in MS patients showed high reliability and suggested an accelerated rate of brain aging corresponding to an annual increase of 0.41 (SE = 0.15) years compared to chronological aging (p = 0.008). Multiple regression analyses revealed higher rate of brain aging in patients with more brain atrophy (Cohen's D = 0.86, p = 4.3 × 10−15) and increased white matter lesion load (WMLL) (Cohen's D = 0.55, p = 0.015). On average, patients with MS had significantly higher BAG compared to HC. Progressive brain aging in patients with MS was related to brain atrophy and increased WMLL. No significant clinical associations were found in our sample, future studies are warranted on this matter. Brain age estimation is a promising method for evaluation of subtle brain changes in MS, which is important for predicting clinical outcome and guide choice of intervention.

• Høgestøl, Einar August; Nygaard, Gro Owren; Alnæs, Dag; Beyer, Mona K.; Westlye, Lars Tjelta & Harbo, Hanne Flinstad (2019). Symptoms of fatigue and depression is reflected in altered default mode network connectivity in multiple sclerosis. PLOS ONE. 14(4). doi: 10.1371/journal.pone.0210375. Fulltekst i vitenarkiv Vis sammendrag

  Background Fatigue and depression are frequent and often co-occurring symptoms in multiple sclerosis (MS). Resting-state functional magnetic resonance imaging (rs-fMRI) represents a promising tool for disentangling differential associations between depression and fatigue and brain network function and connectivity. In this study we tested for associations between symptoms of fatigue and depression and DMN connectivity in patients with MS. Materials and methods Seventy-four MS patients were included on average 14 months after diagnosis. They underwent MRI scanning of the brain including rs-fMRI, and symptoms of fatigue and depression were assessed with Fatigue Severity Scale (FSS) and Beck Depression Inventory II (BDI). A principal component analysis (PCA) on FSS and BDI scores was performed, and the component scores were analysed using linear regression models to test for associations with default mode network (DMN) connectivity. Results We observed higher DMN connectivity with higher scores on the primary principal component reflecting common symptom burden for fatigue and depression (Cohen’s f2 = 0.075, t = 2.17, p = 0.03). The secondary principal component reflecting a pattern of low fatigue scores with high scores of depression was associated with lower DMN connectivity (Cohen’s f2 = 0.067, t = -2.1, p = 0.04). Using continuous mean scores of FSS we also observed higher DMN connectivity with higher symptom burden (t = 3.1, p = 0.003), but no significant associations between continuous sum scores of BDI and DMN connectivity (t = 0.8, p = 0.4). Conclusion Multivariate decomposition of FSS and BDI data supported both overlapping and unique manifestation of fatigue and depression in MS patients. Rs-fMRI analyses showed that symptoms of fatigue and depression were reflected in altered DMN connectivity, and that higher DMN activity was seen in MS patients with fatigue even with low depression scores.

• Lindland, Elisabeth Margrete Stokke; Solheim, Anne Marit; Andreassen, Silje; Paulsen, Else Quist; Eikeland, Randi & Ljøstad, Unn [Vis alle 12 forfattere av denne artikkelen] (2018). Imaging in Lyme neuroborreliosis. Insights into Imaging. 9(5), s. 833–844. doi: 10.1007/s13244-018-0646-x. Fulltekst i vitenarkiv Vis sammendrag

  Lyme neuroborreliosis (LNB) is a tick-borne spirochetal infection with a broad spectrum of imaging pathology. For individuals who live in or have travelled to areas where ticks reside, LNB should be considered among differential diagnoses when clinical manifestations from the nervous system occur. Radiculitis, meningitis and facial palsy are commonly encountered, while peripheral neuropathy, myelitis, meningoencephalitis and cerebral vasculitis are rarer manifestations of LNB. Cerebrospinal fluid (CSF) analysis and serology are key investigations in patient workup. The primary role of imaging is to rule out other reasons for the neurological symptoms. It is therefore important to know the diversity of possible imaging findings from the infection itself. There may be no imaging abnormality, or findings suggestive of neuritis, meningitis, myelitis, encephalitis or vasculitis. White matter lesions are not a prominent feature of LNB. Insight into LNB clinical presentation, laboratory test methods and spectrum of imaging pathology will aid in the multidisciplinary interaction that often is imperative to achieve an efficient patient workup and arrive at a correct diagnosis. This article can educate those engaged in imaging of the nervous system and serve as a comprehensive tool in clinical cases.

• 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.

• Benavent, Sigrid Aune de Rodez; Nygaard, Gro Owren; Harbo, Hanne Flinstad; Tønnesen, Siren; Sowa, Piotr & Landrø, Nils Inge [Vis alle 13 forfattere av denne artikkelen] (2017). Fatigue and cognition: Pupillary responses to problem-solving in early multiple sclerosis patients. Brain and Behavior. 7(7). doi: 10.1002/brb3.717. Fulltekst i vitenarkiv Vis sammendrag

  Introduction In early multiple sclerosis (MS) patients, cognitive changes and fatigue are frequent and troublesome symptoms, probably related to both structural and functional brain changes. Whether there is a common cause of these symptoms in MS is unknown. In theory, an altered regulation of central neuropeptides can lead to changes in regulation of autonomic function, cognitive difficulties, and fatigue. Direct measurements of central neuropeptides are difficult to perform, but measurements of the eye pupil can be used as a reliable proxy of function. Methods This study assesses pupil size during problem-solving in early MS patients versus controls. A difference in pupil size to a cognitive challenge could signal altered activity within the autonomic system because of early functional brain changes associated with cognitive load. We recruited MS patients (mean disease duration: 2.6 years, N = 41) and age-matched healthy controls (N = 43) without eye pathology. Neurological impairment, magnetic resonance imaging, visual evoked potentials, depression, and fatigue were assessed in all of the patients. In both groups, we assessed processing speed and retinal imaging. Pupil size was recorded with an eye-tracker during playback of multiplication tasks. Results Both groups performed well on the cognitive test. The groups showed similar pupillary responses with a mean of 0.55 mm dilation in patients and 0.54 mm dilation in controls for all the tasks collapsed together. However, controls (N = 9) with low cognitive scores (LCS) had an increased pupillary response to cognitive tasks, whereas LCS MS patients (N = 6) did not (p < .05). There was a tendency toward a smaller pupillary response in patients with fatigue. Conclusions This is the first study to investigate pupillary responses to cognitive tasks in MS patients. Our results suggest that MS-related changes in cognition and fatigue may be associated with changes in arousal and the autonomic regulation of task-related pupillary responses. This supports the theory of a link between cognition and fatigue in MS.

• Gustavsen, Marte Wendel; Celius, Elisabeth Gulowsen; Winsvold, Bendik K S; Moen, Stine Marit; Nygaard, Gro Owren & Berg-Hansen, Pål [Vis alle 9 forfattere av denne artikkelen] (2016). Migraine and frequent tension-type headache are not associated with multiple sclerosis in a Norwegian case-control study. Multiple Sclerosis Journal, Experimental, Translational and Clinical. 2, s. 1–4. doi: 10.1177/2055217316682976. Fulltekst i vitenarkiv Vis sammendrag

  Background Inconsistent results have been obtained with regard to headache comorbidity in multiple sclerosis (MS). Objective Investigate the one-year prevalence of migraine and tension-type headache (TTH) in Norwegian MS patients and relate this to clinical parameters. Methods A questionnaire concerning headache was administered to 756 MS patients and 1090 controls and used to determine the one-year prevalence of migraine and frequent TTH. Results No significant differences were seen between patients and controls or between patients with different disease course. Less migraine was observed in patients with Expanded Disability Status Scale score (EDSS) ≥4.0. Conclusions This case-control study does not support an association between migraine or TTH and MS.

• Nygaard, Gro Owren; Benavent, Sigrid Aune de Rodez; Harbo, Hanne Flinstad; Laeng, Bruno; Sowa, Piotr & Damangir, Soheil [Vis alle 13 forfattere av denne artikkelen] (2015). Eye and hand motor interactions with the Symbol Digit Modalities Test in early multiple sclerosis. Multiple Sclerosis and Related Disorders. ISSN 2211-0348. 4(6), s. 585–589. doi: 10.1016/j.msard.2015.08.003. Fulltekst i vitenarkiv Vis sammendrag

  Purpose Eye and hand motor dysfunction may be present early in the disease course of relapsing-remitting multiple sclerosis (RRMS), and can affect the results on visual and written cognitive tests. We aimed to test for differences in saccadic initiation time (SI time) between RRMS patients and healthy controls, and whether SI time and hand motor speed interacted with the written version of the Symbol Digit Modalities Test (wSDMT). Methods Patients with RRMS (N=44, age 35.1±7.3 years), time since diagnosis <3 years and matched controls (N=41, age 33.2±6.8 years) were examined with ophthalmological, neurological and neuropsychological tests, as well as structural MRI (white matter lesion load (WMLL) and brainstem lesions), visual evoked potentials (VEP) and eye-tracker examinations of saccades. Results SI time was longer in RRMS than controls (p<0.05). SI time was not related to the Paced Auditory Serial Addition Test (PASAT), WMLL or to the presence of brainstem lesions. 9 hole peg test (9HP) correlated significantly with WMLL (r=0.58, p<0.01). Both SI time and 9HP correlated negatively with the results of wSDMT (r=−0.32, p<0.05, r=−0.47, p<0.01), but none correlated with the results of PASAT. Conclusions RRMS patients have an increased SI time compared to controls. Cognitive tests results, exemplified by the wSDMT, may be confounded by eye and hand motor function.

• Gustavsen, Marte Wendel; Celius, Elisabeth Gulowsen; Moen, Stine Marit; Bjølgerud, Anja; Berg-Hansen, Pål & Nygaard, Gro Owren [Vis alle 9 forfattere av denne artikkelen] (2015). No association between multiple sclerosis and periodontitis after adjusting for smoking habits. European Journal of Neurology. ISSN 1351-5101. 22(3), s. 588–590. doi: 10.1111/ene.12520. Fulltekst i vitenarkiv
• Nygaard, Gro Owren; Celius, Elisabeth Gulowsen; Benavent, Sigrid Aune de Rodez; Sowa, Piotr; Gustavsen, Marte Wendel & Fjell, Anders Martin [Vis alle 9 forfattere av denne artikkelen] (2015). A longitudinal study of disability, cognition and gray matter atrophy in early multiple sclerosis patients according to evidence of disease activity. PLOS ONE. 10(8). doi: 10.1371/journal.pone.0135974. Fulltekst i vitenarkiv Vis sammendrag

  New treatment options may make “no evidence of disease activity” (NEDA: no relapses or disability progression and no new/enlarging MRI lesions, as opposed to “evidence of disease activity” (EDA) with at least one of the former), an achievable goal in relapsing-remitting multiple sclerosis (RRMS). The objective of the present study was to determine whether early RRMS patients with EDA at one-year follow-up had different disability, cognition, treatment and gray matter (GM) atrophy rates from NEDA patients and healthy controls (HC). RRMS patients (mean age 34 years, mean disease duration 2.2 years) were examined at baseline and one-year follow-up with neurological (n = 72), neuropsychological (n = 56) and structural MRI (n = 57) examinations. Matched HC (n = 61) were retested after three years. EDA was found in 46% of RRMS patients at follow-up. EDA patients used more first line and less second line disease modifying treatment than NEDA (p = 0.004). While the patients groups had similar disability levels at baseline, they differed in disability at follow-up (p = 0.010); EDA patients progressed (EDSS: 1.8–2.2, p = 0.010), while NEDA patients improved (EDSS: 2.0–1.7, p<0.001). Cognitive function was stable in both patient groups. Subcortical GM atrophy rates were higher in EDA patients than HC (p<0.001). These results support the relevance of NEDA as outcome in RRMS and indicate that pathological neurodegeneration in RRMS mainly occur in patients with evidence of disease activity.

• Nygaard, Gro Owren; Walhovd, Kristine B; Sowa, Piotr; Chepkoech, Joy-Loi; Bjørnerud, Atle & Due-Tønnessen, Paulina [Vis alle 14 forfattere av denne artikkelen] (2015). Cortical thickness and surface area relate to specific symptoms in early relapsing−remitting multiple sclerosis. Multiple Sclerosis. ISSN 1352-4585. 21(4), s. 402–414. doi: 10.1177/1352458514543811. Fulltekst i vitenarkiv
• Sowa, Piotr; Bjørnerud, Atle; Nygaard, Gro Owren; Damangir, Soheil; Spulber, Gabriela & Celius, Elisabeth Gulowsen [Vis alle 9 forfattere av denne artikkelen] (2015). Reduced perfusion in white matter lesions in multiple sclerosis. European Journal of Radiology. ISSN 0720-048X. 84(12), s. 2605–2612. doi: 10.1016/j.ejrad.2015.09.007. Fulltekst i vitenarkiv
• Gustavsen, Marte Wendel; Page, Christian; Moen, Stine Marit; Bjølgerud, Anja; Berg-Hansen, Pål & Nygaard, Gro Owren [Vis alle 10 forfattere av denne artikkelen] (2014). Environmental exposures and the risk of multiple sclerosis investigated in a Norwegian case-control study. BMC Neurology. 14(1). doi: 10.1186/s12883-014-0196-x. Fulltekst i vitenarkiv Vis sammendrag

  Background: Several environmental exposures, including infection with Epstein-Barr virus, low levels of vitamin D and smoking are established risk factors for multiple sclerosis (MS). Also, high hygienic standard and infection with parasites have been proposed to influence MS risk. The aim of this study was to investigate the influence of various environmental exposures on MS risk in a Norwegian cohort, focusing on factors during childhood related to the hygiene hypothesis. Methods: A questionnaire concerning environmental exposures, lifestyle, demographics and comorbidity was administrated to 756 Norwegian MS patients and 1090 healthy controls. Logistic regression was used to calculate odds ratio (OR) with 95% confidence interval (CI) for the risk of MS associated with the variables infectious mononucleosis, severe infection during childhood, vaccination and animals in the household during childhood. Age, gender, HLA-DRB1*15:01, smoking and infectious mononucleosis were included as covariates. General environmental exposures, including tobacco use, were also evaluated. Results: Infectious mononucleosis was confirmed to be significantly associated with increased MS risk, also after adjusting for the covariates (OR?=?1.79, 95% CI: 1.12-2.87, p?=?0.016). The controls more often reported growing up with a cat and/or a dog in the household, and this was significant for ownership of cat also after adjusting for the covariates (OR?=?0.56, 95% CI: 0.40-0.78, p?=?0.001). More patients than controls reported smoking and fewer patients reported snuff use. Conclusions: In this Norwegian MS case-control study of environmental exposures, we replicate that infectious mononucleosis and smoking are associated with increased MS risk. Our data also indicate a protective effect on MS of exposure to cats during childhood, in accordance with the hypothesis that risk of autoimmune diseases like MS may increase with high hygienic standard.

• Fremeau, R.T Jr; Troyer, M. D.; Pahner, I; Nygaard, Gro Owren; Tran, C. H. & Reimer, R.J. [Vis alle 10 forfattere av denne artikkelen] (2001). The expression of vesicular glutamate transporters defines two classes of excitatory synapse. Neuron. ISSN 0896-6273. 31(2), s. 247–260. Fulltekst i vitenarkiv

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• König, Marton; Holmøy, Trygve; Nygaard, Gro Owren; Riise, Jon; Midtvedt, Karsten & Goll, Guro Løvik [Vis alle 11 forfattere av denne artikkelen] (2026). Vaccination of immunosuppressed patients. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. doi: 10.4045/tidsskr.25.0555. Fulltekst i vitenarkiv
• Høgestøl, Einar August; Sowa, Piotr; Holmøy, Trygve; Bø, Lars; Nygaard, Gro Owren & Wergeland, Stig (2025). Oppdaterte diagnosekriterier for multippel sklerose. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 145(15). doi: 10.4045/tidsskr.25.0592. Fulltekst i vitenarkiv
• Nygaard, Gro Owren & Holmøy, Trygve (2024). Norsk helsevesen børtilby stamcellebehandling mot multippel sklerose. 144(2). doi: 10.4045/tidsskr.23.0770. Fulltekst i vitenarkiv
• Skattebøl, Lars; Øverås, Mathias Herstad; Nordhøy, Wibeke; Harbo, Hanne Flinstad; Sowa, Piotr & Lundby, Rigmor [Vis alle 8 forfattere av denne artikkelen] (2023). Brain Age and Quantitative Susceptibility Mapping of Chronic Active Lesions in Relapsing Multiple Sclerosis. Fulltekst i vitenarkiv
• Tran, Trung; Vaage, Eline Benno; Mehta, Adi; Chopra, Adity; Tietze, Lisa & Kolderup, Heidi Anette [Vis alle 40 forfattere av denne artikkelen] (2023). Author Correction: Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants (npj Vaccines, (2022), 7, 1, (174), 10.1038/s41541-022-00586-7). npj Vaccines. 8(1). doi: 10.1038/s41541-023-00600-6. Fulltekst i vitenarkiv
• 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
• Skattebøl, Lars; Nygaard, Gro Owren; Sowa, Piotr; Olsrud, Ellen Regine & Nordhøy, Wibeke (2022). Clinical integration of an automated QSM pipeline for multiple sclerosis on a 3 T MRI. Fulltekst i vitenarkiv
• 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
• Nygaard, Gro Owren (2017). Hjerneslag i sykehus. 137(19), s. 1–1. doi: 10.4045/tidsskr.17.0634. Fulltekst i vitenarkiv
• Moen, Stine Marit; Harbo, Hanne Flinstad; Celius, Elisabeth Gulowsen; Sowa, Piotr; Nygaard, Gro Owren & Beyer, Mona K. (2016). S.M. Moen og medarbeidere svarer. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 136(20), s. 1702–1702. doi: 10.4045/tidsskr.16.0865. Fulltekst i vitenarkiv
• Moen, Stine Marit; Harbo, Hanne Flinstad; Sowa, Piotr; Celius, Elisabeth Gulowsen; Nygaard, Gro Owren & Beyer, Mona K. (2016). MR-undersøkelser ved multippel sklerose. 136(16), s. 1373–1376. doi: 10.4045/tidsskr.15.1361. Fulltekst i vitenarkiv
• Moen, Stine Marit; Harbo, Hanne Flinstad; Celius, Elisabeth Gulowsen; Sowa, Piotr; Nygaard, Gro Owren & Beyer, Mona K. (2016). S.M. Moen og medarbeidere svarer. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 136(19), s. 1608–1608. doi: 10.4045/tidsskr.16.0826. Fulltekst i vitenarkiv
• Nygaard, Gro Owren; Harbo, Hanne Flinstad; Celius, Elisabeth Gulowsen & Landro, N. I. (2013). Does the Brief International Cognitive Assessment for MS (BICAMS) catch the cognitive problems of a sample of well-educated recently diagnosed MS patients in Oslo? Multiple Sclerosis. ISSN 1352-4585. 19(7), s. 970–971. Fulltekst i vitenarkiv
• Benavent, S.A. de Rodez; Nygaard, Gro Owren; Tønnesen, Siren; Celius, Elisabeth Gulowsen; Landro, N. I. & Laeng, Bruno (2013). Pupillometry indicates increased cognitive effort in response to easy cognitive tasks in newly diagnosed MS patients. Multiple Sclerosis. ISSN 1352-4585. 19(7), s. 988–989. Fulltekst i vitenarkiv

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