Despite increasing awareness of autoimmune encephalitis (AE), real-world, population-based epidemiological data are scarce. Using 15 years of nationwide, centralized testing data, we aimed to (1) characterize all Danish patients with neuronal cell-surface antibodies (NSAbs), GAD65, and GFAP; (2) estimate AE incidence in Denmark; and (3) assess temporal trends in treatment strategies. Nationwide testing data from 2009 to 2023 were obtained from the Danish centralized antibody test center, and the medical records for antibody-positive patients were reviewed. National and regional incidence rates were calculated using census data, and trends in testing, incidence, and treatment were analyzed. A total of 198 patients were included. The most prevalent antibody was NMDAR (n = 79), followed by LGI1 (n = 37), GAD65 (n = 20), and CASPR2 (n = 19). The national average crude incidence rate (IR) in 2019–2023 was 2.8 cases per million person-years. Incidence increased by 10

Background: Little is known about the involvement of gut microbiota in the disease course of diverticulitis and the potential benefits of manipulating the gut milieu. We propose to conduct a randomised placebo-controlled feasibility trial of faecal microbiota transplantation (FMT) given as capsules to patients with acute uncomplicated diverticulitis. Objectives: The objective is primarily to investigate the feasibility of clinical safety, explore efficacy associated with FMT in this patient population, and examine changes in patient-reported quality of life and the composition and function of the gut microbiota. Design: Study protocol for a randomised placebo-controlled trial. Methods and analysis: Participants with acute, uncomplicated diverticulitis, as confirmed by computed tomography (CT) scan, will be recruited from Odense University Hospital (Denmark) and randomly assigned to either the intervention group or the control group. The intervention group will consist of 20 patients who receive encapsulated FMT. The control group will also consist of 20 patients, receiving placebo capsules. Primary safety endpoint : Patient safety is monitored by (a) the number of re-admissions and (b) the number of adverse events within 3 months of FMT/placebo; Primary efficacy endpoint : Reduction in the proportion of patients treated with antibiotics within 3 months following FMT/placebo; Secondary outcome : Change from baseline to 3 months in the GI-QLI questionnaire. Results will be analysed using an intention-to-treat approach. Adverse events or unintended consequences will be reported. Ethics and discussion: This is the first study to investigate the safety and efficacy of FMT in patients with acute uncomplicated diverticulitis. The project has the potential to broaden the knowledge and literature on the role of the intestinal microbiota in diverticulitis, and we believe it will elevate our understanding of cause and effect. Trial registration: Informed consent is obtained from all participants. The study is approved by the regional ethics committee (ref. S-20230023) and the Danish Data Protection Agency (ref. 24/2435). The trial was registered on clinicaltrials.gov (NCT06254625) on 10th February 2024.

Objective Fecal microbiota transplantation (FMT) holds promises as a beneficial supplement to methotrexate in patients with psoriatic arthritis (PsA). We therefore investigated how gut bacterial signatures in patients and donor strain engraftment were associated with long-term response to FMT.Methods This exploratory study is based on the FLORA trial cohort, encompassing 31 patients with moderate-to-high PsA disease activity and four FMT donors. Of the 15 patients receiving one single-donor FMT, 13 were included in the per-protocol (PP) population. Stool samples were collected before and after FMT (week 4, 12, and 26). We performed shotgun metagenomics to characterize gut microbiota features.Results At baseline, 17 patients (55%) had a gut microbiota community type dominated by the Bacteroides genus (B-type), whereas 14 (45%) had a Prevotella-driven community type (P-type). The B- and P-type patients did not differ in disease activity or demographics, but the B-type had a significantly higher species diversity compared to the P-type (P = 0.005). In the PP population, five of seven B-type patients versus none of six P-type patients (P = 0.021) achieved a long-term clinical beneficial response at week 26. Bacterial strain richness increased significantly from baseline to week 4 and week 26 in B-type (P = 0.016), but not in P-type, patients. Eighteen engrafted strains persisted only in B-type recipients by week 26, including a Bacteroides clarus strain, which demonstrated a negative effect size regarding arthritis pain and the patients' global assessment of disease.Conclusion Recipients with a Bacteroides-dominated community structure were more likely to achieve long-term beneficial response following one FMT.

Objective The primary objective was to assess the prevalence of anti-ribosomal-P protein antibodies (anti-Rib-P) in a well-characterised Danish adult SLE cohort. Secondary objectives included (1) assessing any association between anti-Rib-P and neuropsychiatric SLE (NPSLE), (2) assessing any association between anti-Rib-P and characteristics of Danish patients with SLE and (3) assessing potential associations between selected autoantibodies and NPSLE.Method This cross-sectional study included 198 Danish patients with SLE from a population-based cohort. Patients meet the American College of Rheumatology’s 1997 revised classification criteria for SLE and were 18 years of age or older. Anti-Rib-P were detected in serum using fluorescence enzyme immunoassay. ANA patterns were tested using indirect immunofluorescence on HEp-2 cells. Anti-double-stranded DNA antibody was examined by manual ELISA, and antibodies targeting Ro/SSA, La/SSB, Sm, RNP, Scl-70, Jo-1, Centromer B and Histone were examined on a Luminex instrument.Results We identified 14 (7.1%) patients with anti-Rib-P positive SLE, and 3 anti-Rib-P positive patients were diagnosed with NPSLE (21% of patients with NPSLE). There was no statistically significant association between anti-Rib-P and NPSLE. The mean anti-Rib-P titres in the patients with NPSLE did not differ significantly from patients without NPSLE patients’ titres. We observed a significant association between anti-Rib-P positivity and disease activity measured by the SLEDAI-2K (SLE Disease Activity Index 2000) score. A stepwise logistic regression found an association between NPSLE and SLEDAI-2K and SLICC DI (SLE International Collaborating Clinics Damage Index) score.Conclusion This study could not confirm a role for anti-Rib-P in the identification of NPSLE. On the other hand, anti-Rib-P was associated with SLE disease activity as well as organ damage.

The culture performance of Fastidious Anaerobe Agar (FAA-HB) was evaluated for fecal samples and candidate-species for EUCAST antimicrobial susceptibility testing (AST). Thirty-six anaerobic species were cultured from fecal samples and most EUCAST candidate-species exhibited confluent growth within 16-20 h. The FAA-HB performed excellent for both culture and AST of a broad spectrum of anaerobic bacteria.

Four published case reports have proposed Lyme neuroborreliosis (LNB) as a trigger for anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. In this study, we examined the prevalence of anti-NMDAR antibodies in a well-characterized cohort of patients with LNB. In this retrospective cohort study, archived cerebrospinal fluid (CSF) samples from patients diagnosed with LNB between 2001 and 2012 were analyzed for anti-NMDAR IgG using a standard commercial cell-based assay. LNB diagnosis followed the European Federation of Neurological Societies guidelines. To identify potential later development of anti-NMDAR encephalitis, an infectious disease specialist systematically reviewed medical records in 2021, and the national reference center for neural autoantibody testing verified testing history in 2025. We included 82 patients with a median age of 52 years (interquartile range [IQR]: 34–63); 55

The immune system of neonates is immature and therefore knowledge of possible early-life protection against SARS-CoV-2 infection, such as breastfeeding, is of great importance. Few studies have investigated the presence and duration of SARS-CoV-2 antibodies in breastmilk in relation to the trimester of maternal infection during pregnancy, and none with successful participation from all three trimesters. This study has dual objectives (1) in relation to the trimester of infection to examine the frequency, concentration and duration of IgA and IgG antibodies in breastmilk and blood serum in the third and sixth month post-partum in former SARS-CoV-2-infected mothers and (2) to examine the association in pediatric emergency admission of children within the first six months of life compared to children of non-SARS-CoV-2-infected women. The first objective is based on a prospective cohort and the second is based on a nested case-control design. The study participants are women with a former SARS-CoV-2 infection during pregnancy, whose serology IgG tests at delivery were still positive. Maternal blood and breastmilk samples were collected at three and six months postpartum. Serum IgA frequency three months pp was 72.7% (50%, 90% and 60% in the first, second and third trimester) and 82% six months pp (67%, 91% and 82% in the first, second and third trimester). Breastmilk IgA frequency three months pp was 27% (16.6%, 36% and 20% in first, second and third trimester) and 28% six months pp (0%, 38% and 28% in the first, second and third trimester). The highest IgA concentration in breastmilk was found six months post-partum with infection in the third trimester. Serum IgA was detectable more than 400 days post infection, and serum IgG above threshold was found 430 days after date of infection. We found no correlation between serum IgA and breastmilk IgA, nor between serum IgG and breastmilk IgA regardless of the trimester of infection.

Background and ObjectivesWe aimed to evaluate the mortality of patients with AQP4 antibody-seropositive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) in Denmark compared with that in the general population.MethodsWe identified patients with AQP4-Ab+ NMOSD fulfilling the 2015 International Panel for Neuromyelitis Optica Diagnosis (IPND) criteria from multiple sources (laboratories and the Danish Multiple Sclerosis Registry). We obtained detailed information about patients from hospital records and about the general population matched on age, sex, and calendar year from Statistics Denmark. We calculated standardized mortality ratio (SMR), excess number of deaths per 1,000 person-years (EDR), and life expectancies compared with those of the matched general population. We examined predictive factors of mortality and the cause of death.ResultsOf 66 patients with AQP4-Ab+ NMOSD between 2008 and 2020, 15 died. Overall, the SMR was 2.54 (95% CI 1.47-4.09), and the EDR was 16.8 (95% CI 4.6-34.3). The median life expectancy for patients with AQP4-Ab+ NMOSD was 64.08 years (95% CI 53.02-83.9), compared with 83.07 years for the general population. Risk of death over time was increased in the patient population with a hazard ratio (HR) of 2.22 (1.34-3.68; p = 0.002). The cause of death was directly related to NMOSD in 93% of the cases. The age at disease onset was an independent predictor of death (HR 1.042; 95% CI 1.006-1.079; p = 0.02).DiscussionAQP4-Ab+ NMOSD is associated with increased mortality and shorter life expectancy compared with that in the general population, underlining the need for highly effective treatment approaches.

It is well known that N-methyl-D-aspartate receptor encephalitis (NMDARE) can be triggered by infectious encephalitis such as herpes simplex virus 1 encephalitis (HSE). However, the incidence of post-HSE NMDARE in Denmark is unknown. We reviewed literature cases and compared these to retrospectively identified cases of post-HSE NMDARE in Denmark, using a national cohort database of autoimmune encephalitis (AE) and two regional databases of infectious encephalitis patients. We identified 80 post-HSE NMDARE cases in the literature, 66% being children, who more often presented movement disorders, decreased consciousness, and sleep disturbances compared to adults. Eight patients with post-HSE NMDARE were identified from the national cohort database of AE, none being children. Forty-four HSE patients were identified from the regional infectious encephalitis databases. Of these, 16 (36%) fulfilled the Graus criteria for probable/definite NMDARE, and eight (18%) presented a prolonged/relapsing disease course. Ten (23%) were tested for AE during hospitalization. Six (14%) had leftover cerebrospinal fluid available for retrospective autoantibody testing. One out of these six patients (17%) harbored NMDARE antibodies. Thus, in total, nine post-HSE NMDARE patients have been identified in Denmark from 2009 to 2021. Comparing the adult Danish patients to the literature, Danish patients were older, but the clinical phenotype and paraclinical findings were similar. Overall, the incidence of adult post-HSE NMDARE in the Region of Southern Denmark was 0.17 per million people per year and only 7% of adult HSE patients in the region were diagnosed with post-HSE NMDARE. Our findings suggest that adult patients are still underdiagnosed and the absence of pediatric cases diagnosed with post-HSE NMDARE in Denmark is highly concerning.

Background This study examines the humoral and cellular response in multiple sclerosis (MS) patients on anti-CD20 therapy before and after the 1st to 4th BNT162b2 mRNA SARS-CoV-2 vaccination and the relationship with breakthrough infection.Methods Participants with McDonald 2017 MS that were treated with ocrelizumab were included. The study duration was throughout the COVID-19 pandemic until four months after fourth mRNA SARS-CoV-2 vaccination (BNT162b2). Longitudinal blood samples were analysed for: IgG antibodies of SARS-CoV-2 spike anti-receptor binding domain (anti-RBD), nucleocapsid IgG antibodies (anti-N) and activation induced marker expressing CD4+, CD8+ T-cells and concentration of ocrelizumab and anti-drug antibodies. Incidences of breakthrough infection were confirmed with SARS-CoV-2 PCR tests.Results The rate of anti-RBD positive participants increased substantially between the third and fourth vaccination from 22.2% to 55.9% (median 54.7 BAU/mL; IQR: 14.5 - 221.2 BAU/mL and 607.7 BAU/mL; IQR: 29.4 - 784.6 BAU/mL, respectively). Within the same period 75% of participants experienced breakthrough infection. The fourth vaccination resulted in an additional increase in seropositive individuals (64.3%) (median 541.8 BAU/mL (IQR: 19.1-1007 BAU/mL). Breakthrough infection did not influence the cellular response without a significant change after the fourth vaccination. During the study period two participants had detectable anti-N, both after the fourth vaccination. No correlation was found between serum concentration of ocrelizumab and the humoral and cellular response.Discussion Low levels or absence of specific anti-RBD following vaccination, with a significant increase after breakthrough infections and boosted by the fourth vaccination. T-cell reactivity remained sustained and unaffected by breakthrough infections.

Objectives The gut microbiota can mediate both pro and anti-inflammatory responses. In patients with psoriatic arthritis (PsA), we investigated the impact of faecal microbiota transplantation (FMT), relative to sham transplantation, on 92 inflammation-associated plasma proteins.Methods This study relates to the FLORA trial cohort, where 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate treatment, were included in a 26-week, double-blind, randomised, sham-controlled trial. Participants were allocated to receive either one gastroscopic-guided healthy donor FMT (n=15) or sham (n=16). Patient plasma samples were collected at baseline, week 4, 12 and 26 while samples from 31 age-matched and sex-matched healthy controls (HC) were collected at baseline. Samples were analysed using proximity extension assay technology (Olink Target-96 Inflammation panel).Results Levels of 26 proteins differed significantly between PsA and HC pre-FMT (adjusted p<0.05), of which 10 proteins were elevated in PsA: IL-6, CCL20, CCL19, CDCP1, FGF-21, HGF, interferon-γ (IFN-γ), IL-18R1, monocyte chemotactic protein 3, and IL-2. In the FMT group, levels of 12 proteins changed significantly across all timepoints (tumour necrosis factor (TNF), CDCP1, IFN-γ, TWEAK, signalling lymphocytic activation molecule (SLAMF1), CD8A, CD5, Flt3L, CCL25, FGF-23, CD6, caspase-8). Significant differences in protein levels between FMT and sham-treated patients were observed for TNF (p=0.002), IFN-γ (p=0.011), stem cell factor (p=0.024), matrix metalloproteinase-1 (p=0.038), and SLAMF1 (p=0.042). FMT had the largest positive effect on IFN-γ, Axin-1 and CCL25 and the largest negative effect on CCL19 and IL-6.Conclusions Patients with active PsA have a distinct immunological plasma protein signature compared with HC pre-FMT. FMT affects several of these disease markers, including sustained elevation of IFN-γ.Trial registration number NCT03058900.

AbstractIntroductionSmall‐cell lung cancer (SCLC) may be associated with neuronal autoantibodies and paraneoplastic neurological syndromes. It has been suggested that neuronal autoantibodies, especially antineuronal nuclear antibody type 1 (Hu) autoantibodies, are associated with longer survival of patients with SCLC. The objective of this study was to determine the frequency and distribution of neuronal autoantibodies at the time of diagnosis of SCLC patients and assess survival rates in relation to autoimmunity.MethodsIn this retrospective study, serum from 40 patients with biopsy‐proven SCLC at the time of diagnosis was studied prior to treatment. The sera originated from a cancer registry at the Oncology Department, Vejle Hospital from 2007 to 2010. The sera were analyzed blindly to clinical status for the presence of neuronal autoantibodies. Medical records were reviewed for neurological symptoms.ResultsNeuronal autoantibodies were detected in 22/40 (55%) of the SCLC patients. A broad range of neurological symptoms was recorded in 28/40 (70%) patients, of which 14/28 (50%) were positive for neuronal autoantibodies. The most frequently detected autoantibodies were Hu (7/40, 17.5%) followed by GAD65 (6/22, 15.0%). Striational and P/Q‐ or N‐type voltage‐gated calcium channel antibodies were less common, with each found in five patients (12.5%). Eight patients (20%) had coexisting autoantibodies. Autoantibody‐positivity was not associated with survival.ConclusionNeuronal autoantibodies were at time of diagnosis found in approximately half of the treatment‐naïve SCLC patients. Neither autoantibody positivity at diagnosis nor neurological manifestations correlated with survival and their clinical importance requires further studies in larger, prospective cohorts.

BackgroundFecal Microbiota Transplant (FMT) is an effective treatment for recurring Clostridioides Difficile Infections (rCDI). FMT administered via oral capsules (caFMT) offers several practical advantages to conventional liquid FMT. We began using caFMT in 2021 imported from an external institution. Based on similar production methods, we began our own caFMT production in 2022. We aimed to evaluate the quality of our caFMT.Study Design and MethodsWe created a database of all FMT treatments (n = 180) provided by our institution. Quality of all FMT was evaluated by treatment success rates. We compared our caFMT to the imported caFMT.ResultsOur caFMT yielded similar success rates compared to that of the imported caFMT, 65% (CI 95% 58-72%) and 72% (CI 95% 66-79%) respectively. FMT administered via colonoscopy had a significantly higher success rate, 79% (CI 95% 73-85%) than own our caFMT and other routes of administration. The combined success rate of treatments increased notably for all routes of administration when repeating FMT after prior failure.DiscussionThe fact that our caFMT compared similarly to the imported caFMT was viewed as a success in terms of quality assurance. Our caFMT had a slightly lower success rates compared to data from other studies, but could be affected by several other factors than our FMT-production methods. A lower success rate of caFMT compared to FMT via colonoscopy is acceptable due to the practical advantages offed by caFMT. Our study serves as a practical example, proving that of the standardization of caFMT production is indeed viable.

Objective We investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate‐treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT). Methods This exploratory study is based on the FLORA trial cohort, in which 31 patients with moderate‐to‐high peripheral PsA disease activity, despite at least 3 months of methotrexate‐treatment, were included in a 26‐week, double‐blind, 1:1 randomized, sham‐controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n = 15) or sham (n = 16) via gastroscopy. The primary trial end point was the proportion of treatment failures through 26 weeks. We performed a lactulose‐to‐mannitol ratio (LMR) test at baseline (n = 31) and at week 26 (n = 26) to assess small intestinal permeability. Metabolomic profiles in fecal, plasma, and urine samples collected at baseline, weeks 4, 12, and 26 were measured using 1H Nuclear Magnetic Resonance. Results Trial failures (n = 7) had significantly higher LMR compared with responders (n = 19) at week 26 (0.027 [0.017‐0.33]) vs. 0.012 [0‐0.064], P = 0.013), indicating increased intestinal permeability. Multivariate analysis revealed a significant model for responders (n = 19) versus failures (n = 12) at all time points based on their fecal (P < 0.0001) and plasma (P = 0.005) metabolomic profiles, whereas urine metabolomic profiles did not differ between groups (P = 1). Fecal N‐acetyl glycoprotein GlycA correlated with Health Assessment Questionnaire Disability Index (coefficient = 0.50; P = 0.03) and fecal propionate correlated with American College of Rheumatology 20 response at week 26 (coefficient = 27, P = 0.02). Conclusion Intestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder.

Objective: To investigate the rate of breakthrough SARS-CoV-2 infection and clinical outcomes in a cohort of MS patients who were treated with ocrelizumab before first, second, and third BNT162b2 mRNA vaccinations. Background: The study included participants from three MS clinics in Denmark and the University of California, San Francisco in the United States when omicron BA.1 and BA.2 were the dominating subtypes of SARS-CoV-2. Reduced humoral response is associated with ocrelizumab treatment of multiple sclerosis (MS). Design/Methods: The study was a prospective nonrandomized controlled observational multicenter trial. Participants were diagnosed with MS and received ocrelizumab treatment for >12 months prior to the three BNT162b2 mRNA vaccinations. The follow-up period was from January 2021 to May 2022. Clinical outcomes were evaluated using WHO progression scale. The humoral and cellular immunogenicity in participants were correlated with PCR confirmed breakthrough infection. Results: Out of 54 participants, 32 (59.3%) developed a positive SARS-CoV-2 PCR test in the study period. Mild infections were observed in all infected participants. After the third vaccination, the non-infected participants had higher mean antibody levels compared to the infected participants (54.3 vs. 26.5 BAU/mL, p=0.030). The difference in reactivity between spike-specific CD4+ and CD8+ T-lymphocytes in the two groups were non-significant. Additional results regarding levels of ocrelizumab, anti-ocrelizumab antibodies and SARS-CoV-2 nucleocapsid protein, together with the immunological effects of fourth vaccination will be presented at the conference. Conclusions: Our results demonstrate high rates of breakthrough infections, along with mild disease courses after 3rd SARS-CoV-2 mRNA vaccination in ocrelizumab treated MS participants. This suggests that vaccination of B-cell depleted patients provides low protection against breakthrough infection. The study findings point to the need for better prophylactic options or more specific vaccines to allow for better clinical protection. Disclosure: Dr. Novak has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi A/S. Mr. Bajwa has nothing to disclose. The institution of Prof. Coia has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tillotts. The institution of Prof. Coia has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Tillotts. The institution of Prof. Coia has received research support from Tillotts. Dr. Nilsson has received publishing royalties from a publication relating to health care. Dr. Nielsen has nothing to disclose. Mrs. Holm has nothing to disclose. Dr. Ostergaard has nothing to disclose. Miss Hvidt has nothing to disclose. Mr. BYG has nothing to disclose. Prof. Johansen has nothing to disclose. Ms. Mittl has nothing to disclose. William Rowles has nothing to disclose. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Genzyme. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Genentech. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Alexion. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme Sanofi. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jansen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Bove has received research support from Biogen. The institution of Dr. Bove has received research support from Roche Genentech. The institution of Dr. Bove has received research support from Novartis. Dr. Sabatino has received research support from Novartis. Dr. Sabatino has received research support from Roche/Genentech. Dr. Sabatino has received personal compensation in the range of $500-$4,999 for serving as a CME course instructor with eMultiple Sclerosis Review. Dr. Sabatino has received personal compensation in the range of $500-$4,999 for serving as a CME course instructor with Physician Education Resource. Tobias Sejbaek has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen, Merck, Novartis, Roche. Tobias Sejbaek has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen, Merck, Novartis, Teva. The institution of Tobias Sejbaek has received research support from Biogen, Merck, Novartis, Roche.