Finn Sellebjerg

Copenhagen University Hospital - Rigshospitalet · Danish Multiple Sclerosis Center

The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains...

Background Teriflunomide has been associated with an increased risk of hypertension. Real-world studies including adequate control groups are lacking. We hypothesized that patients with multiple sclerosis (MS) treated with teriflunomide would be at higher risk of developing hypertension than those treated with dimethyl fumarate. Methods We conduct...

Background and objectives: Multiple sclerosis (MS) is a CNS disease, characterized by demyelination, inflammation, and neurodegeneration. Recent advances in technology allow measurement of the axonal damage marker neurofilament light chain in peripheral blood. Two studies have shown that patients with MS have elevated neurofilament light levels be...

Currently, there are limited therapeutic options for patients with non-active secondary progressive multiple sclerosis. Therefore, real-world studies have investigated differences between patients with relapsing-remitting multiple sclerosis, non-active secondary progressive multiple sclerosis, and active secondary progressive multiple sclerosis. He...

Human T cells expressing CD20 play an important role in the defense against virus and cancer and are central in the pathogenesis of both malignancies and various autoimmune disorders. Therapeutic modulation of CD20⁺ T cells and the CD20 expression level is therefore of significant interest. In rodents, CD20 on T cells is likely the product of an ac...

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). In MS, CNS-infiltrating monocytes differentiate to tissue resident macrophages which are found in large numbers within the injured areas of the brain where they play a central role in driving disease progression through demyelination and tissue destructio...

It remains elusive whether lesions and inflammation in the sub/juxtacortical white matter reflect cortical and/or meningeal pathologies. Elucidating this could have implications for MRI monitoring as sub/juxtacortical lesions are detectable by routine MRI, while cortical lesions and meningeal inflammation are not. By large‐area microscopy, we quant...

Introduction Multiple sclerosis (MS) causes a broad range of symptoms, with physical function being one of the most disabling consequences according to patients themselves. Exercise effectively improves lower extremity physical function. Nonetheless, it is unknown which exercise modality is most effective and it remains challenging to keep persons...

Background AQP4-antibody seropositive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) may cause reduced work capability due to disability. Here, we evaluated the socioeconomic status of patients with AQP4-Ab+NMOSD in off-label therapy era compared with the general population. Methods A longitudinal nationwide population-based study inclu...

Background and objectives: Cortical lesions contribute to disability in multiple sclerosis (MS), but their impact on regional neurotransmitter levels remains to be clarified. We tested the hypothesis that cortical lesions are associated with regional glutamate and gamma-aminobutyric acid (GABA) concentrations within the affected cortical region....

Background This study investigates clinical and biomarker differences between standard interval dosing (SID) and extended interval dosing (EID) of ocrelizumab therapy in multiple sclerosis (MS). Methods This is a prospective, double-arm, open-label, multi-center study in Denmark. Participants diagnosed with MS on ocrelizumab therapy >12 months wer...

Background Clinicians frequently rely on relapse counts, T2 MRI lesion load (T2L) and Expanded Disability Status Scale (EDSS) scores to guide treatment decisions for individuals diagnosed with multiple sclerosis (MS). This study evaluates how these factors, along with age and sex, influence prognosis during treatment with teriflunomide (TFL). Meth...

Torben Fog was committed to multiple sclerosis (MS) research for more than four decades, starting before the defence of his thesis in 1948 and lasting until his death in 1987. His research was multi-facetted, making him one of the great pioneers in the study of essential parts of the pathology, immunology and treatment of MS. He has contributed wit...

Background and objectives: We 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. Methods: We identified patients with AQP4-Ab+ NMOSD fulfilling the 2015 International Panel for Neuromyelitis Optica Diagnosis...

Introduction Cladribine tablet therapy is an efficacious treatment for multiple sclerosis (MS). Recently, we showed that one year after the initiation of cladribine treatment, T and B cell crosstalk was impaired, reducing potentially pathogenic effector functions along with a specific reduction of autoreactivity to RAS guanyl releasing protein 2 (R...

Objectives: B cells are important in the pathogenesis of multiple sclerosis. It is yet unknown which subsets may be involved, but atypical B cells have been proposed as mediators of autoimmunity. In this study, we investigated differences in B-cell subsets between controls and patients with untreated and anti-CD20-treated multiple sclerosis. Meth...

Background Fingolimod may be associated with risk of developing cardiovascular disease (CVD). Studies including reference groups and long follow-up are scarce. Objectives We hypothesized that patients treated with fingolimod would be at higher risk of developing CVD compared to patients treated with natalizumab. Methods A nationwide 12-year cohor...

Background Treatment switching is a common challenge and opportunity in real-world clinical practice. Increasing diversity in disease-modifying treatments (DMTs) has generated interest in the identification of reliable and robust predictors of treatment switching across different countries, DMTs, and time periods. Objective The objective of this r...

Introduction Multiple sclerosis (MS) is a leading cause of disability among young adults, but standard clinical scales may not accurately detect subtle changes in disability occurring between visits. This study aims to explore whether wearable device data provides more granular and objective measures of disability progression in MS. Methods Remote...

INTRODUCTION Early and accurate diagnosis of neurocognitive disorders including neurodegenerative dementia remains challenging. This study explores the impact of biological factors on serum neurofilament light chain (NfL) levels and clinical usefulness for the detection of neurocognitive disorders in a mixed memory clinic. METHODS Serum samples an...

Information on the pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered cannabis‐based medicine (CBM) in capsule formulation in patient populations is sparse. In this exploratory study, we aimed to evaluate the PK and PD in a probable steady state of CBM in neuropathic pain and spasticity in a population of patients with multiple...

Introduction: In theory, combination of two agents, which are suboptimal when given individually, may result in a significant increase in therapeutic effect. Combination therapies have proven particularly effective against infections such as HIV, cancer, and also chronic autoimmune diseases such as rheumatoid arthritis. Areas covered: The author...

Introduction Multiple sclerosis (MS) is a neurodegenerative disease accumulating disabilities over time. However, the mean age of individuals with MS is increasing, consequently elevating their risk of developing comorbidities. Comorbidities' impact on MS is widely debated. Yet very few countries possess population-based registries, which provide u...

Alemtuzumab is a monoclonal antibody targeting CD52 on the surface of immune cells, approved for the treatment of active relapsing-remitting multiple sclerosis (RRMS). The purpose of this study was to analyze the repopulation of peripheral lymphocytes following alemtuzumab-induced lymphocyte depletion and investigate associations with disease activ...

Importance Cortical lesions contribute to disability in multiple sclerosis (MS) but their impact on regional neurotransmitter levels remains to be clarified. Objective To test the hypothesis that cortical lesions in MS alter the regional concentrations of the main excitatory and inhibitory neurotransmitters, glutamate and gamma-aminobutyric acid (...

Patients with multiple sclerosis (MS) and spinal cord injury (SCI) commonly sustain central neuropathic pain (NP) and spasticity. Despite a lack of consistent evidence, cannabis-based medicine (CBM) has been suggested as a supplement treatment. We aimed to investigate the effect of CBM on NP and spasticity in patients with MS or SCI. We performed a...

The post-translational modification citrullination has been proposed to play a role in the pathogenesis of multiple sclerosis (MS). Myelin basic protein (MBP) is a candidate autoantigen which is citrullinated to a minor extent under physiological conditions and hypercitrullinated in MS. We examined immune cell responses elicited by hypercitrullinat...

Background and Objective Despite accumulating evidence of intrathecal inflammation in patients with primary progressive multiple sclerosis (PPMS), immunomodulatory and suppressive treatment strategies have proven unsuccessful. With this study, we investigated the involvement of CD20 ⁺ T cells and the effect of dimethyl fumarate on CD20 ⁺ T cells in...

Introduction/objectives Multiple sclerosis (MS) leads to physical and cognitive disability, which in turn impacts the socioeconomic status of the individual. The altered socioeconomic trajectory combined with the critical role of aging in MS progression could potentially lead to pronounced differences between MS patients and the general population....

Importance: Ocrelizumab, a humanized monoclonal antibody targeted against CD20+ B cells, reduces the frequency of relapses by 46% and disability worsening by 40% compared with interferon beta 1a in relapsing-remitting multiple sclerosis (MS). Rituximab, a chimeric monoclonal anti-CD20 agent, is often prescribed as an off-label alternative to ocrel...

Cerebrospinal fluid (CSF) soluble CD27 (sCD27) is a sensitive biomarker of intrathecal inflammation. Although generally considered a biomarker of T cell activation, CSF sCD27 has been shown to correlate with biomarkers of B cell activity in multiple sclerosis. We analyzed CSF from 40 patients with relapsing-remitting multiple sclerosis (RRMS) and n...

Introduction Patients with MS are MRI scanned continuously throughout their disease course resulting in a large manual workload for radiologists which includes lesion detection and size estimation. Though many models for automatic lesion segmentation have been published, few are used broadly in clinic today, as there is a lack of testing on clinica...

Objectives: Cladribine tablet therapy is an efficacious treatment for multiple sclerosis (MS), however, its mechanism of action on T and B cell subsets remains unclear. The purpose of this study was to investigate the treatment effects of cladribine on the peripheral pool of T and B cells subsets and reactivity towards central nervous system (CNS)...

Background: Natalizumab is a widely used high-efficacy treatment in multiple sclerosis (MS). Real-world evidence regarding long-term effectiveness and safety is warranted. We performed a nationwide study evaluating prescription patterns, effectiveness, and adverse events. Methods: A nationwide cohort study using the Danish MS Registry. Patients...

Background: The response to cluster headache treatments has a high interindividual variation. To date, treatment response has only been assessed by candidate gene approach and no investigations into metabolic pathways have been performed. To investigate the association between polygenetic risk of cluster headache and treatment response to first li...

Background: The clinical transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS) is often related to a period of diagnostic uncertainty delaying diagnosis. With emerging treatment options for SPMS how to identify RRMS patients at risk of SPMS and when to assign a SPMS diagnosis has become a matter of growin...

Introduction Aerobic exercise has been shown to modify Alzheimer pathology in animal models, and in patients with multiple sclerosis to reduce neurofilament light (NfL), a biomarker of neurodegeneration. Objective To investigate whether a 16-week aerobic exercise program was able to reduce serum NfL in patients with mild Alzheimer’s disease (AD)....

Background: Currently there is an unmet need for a highly standardized blood biomarker test to monitor treatment response in Lyme neuroborreliosis (LNB). Differentiating between active or past infection is challenged by the relatively high frequency of persistent symptoms after the end of antibiotic treatment (estimated 15-20%), variable clinical...

Background Multiple sclerosis is a chronic immune-mediated disease of the brain and spinal cord resulting in physical and cognitive impairment in young adults. It is hypothesized that a disrupted bacterial and viral gut microbiota is a part of the pathogenesis mediating disease impact through an altered gut microbiota-brain axis. The aim of this st...

Introduction Dimethyl fumarate treatment is approved in Europe for patients with relapsing-remitting multiple sclerosis (MS) and in the US for relapsing forms of MS. We recently published the results of the first randomized placebo-controlled trial of 48 weeks of treatment with dimethyl fumarate or placebo in primary progressive MS (PPMS) (clinical...

Background Cladribine is a nucleoside analogue interfering with synthesis and repair of DNA. Treatment with cladribine leads to a preferential reduction in lymphocytes, resulting in profound depletion of B-cells with a rapid recovery of naïve B-cells, while T-cell show a lesser but long-lasting depletion It is approved for treatment of relapsing mu...

Background and Objectives Cladribine tablets cause a reduction in lymphocytes with a predominant effect on B-cell and T-cell counts. The MAGNIFY-MS substudy reports the dynamic changes on multiple peripheral blood mononuclear cell (PBMC) subtypes and immunoglobulin (Ig) levels over 12 months after the first course of cladribine tablets in patients...

Background and Objectives It is unclear to what extent intrathecal inflammation contributes to the pathogenesis in primary progressive multiple sclerosis (PPMS). We conducted an exploratory study to investigate the degree of intrathecal inflammation and its association with biomarkers of disease activity and severity in patients with PPMS. Methods...

Background Ofatumumab is an anti-CD20 monoclonal antibody approved for subcutaneous administration for the treatment of relapsing multiple sclerosis (MS), but intravenously administered ofatumumab has been investigated in a phase 2 trial and used off-label. The objective of the present study was to assess disease activity and side effects in relati...

Objective We investigated whether clinical rebound occurred after fingolimod discontinuation in a complete population of patients with relapsing-remitting multiple sclerosis (RRMS) in Denmark. We further identified clinical and demographical factors associated with disease reactivation after fingolimod discontinuation. Methods The population compr...

Background: Data on pregnancy outcomes following fetal exposure to disease modifying drugs (DMD) in women with multiple sclerosis (MS) is sparse although growing. Methods: Data from The Danish Multiple Sclerosis Registry were linked with nationwide registries enabling an investigation of adverse pregnancy outcomes in newborns to women with MS fo...

Background The role of blood-brain barrier (BBB) in the pathogenesis of Huntington´s disease (HD) is not well understood. We recently found increased frequency of Th17.1 cells in the cerebrospinal fluid (CSF) of HD gene-expansion carriers (HDGECs). The aim of the study was to investigate the BBB integrity as measured by the CSF/plasma albumin ratio...

Background and Objectives Follicular helper T (Tfh) cells play a critical role in protective immunity helping B cells produce antibodies against foreign pathogens and are likely implicated in the pathogenesis of various autoimmune diseases. The purpose of this study was to investigate the role of Tfh cells in the pathogenesis of multiple sclerosis...

Background Motor fatigue is common in multiple sclerosis (MS), but its pathophysiology is still poorly understood. Here we used functional magnetic resonance imaging (fMRI) to delineate how the acute induction of motor fatigue alters functional activity of the motor system and how these activity changes are related to motor fatigue. Method Forty-f...

Background Drivers of differences in disease presentation and symptom duration in Lyme neuroborreliosis (LNB) are currently unknown. Objectives We hypothesized that neurofilament light (NfL) in cerebrospinal fluid (CSF) would predict disease location and sequelae in a historic LNB cohort. Design Using a cross-sectional design and archived CSF sam...

Background and Objectives The anti-CD20 antibody ofatumumab is an efficacious therapy for multiple sclerosis (MS) through depletion of B cells. The purpose of this study was to examine the derivative effects of B cell depletion on the peripheral immune system and a direct treatment effect on T cells expressing CD20. Methods Frequency and absolute...

Background Initiation of disease-modifying therapy early in the disease course of relapsing-remitting multiple sclerosis (RRMS) has demonstrated beneficial effects on clinical outcomes, but socioeconomic outcomes remain largely unexplored. Objective To investigate the association between the delay from disease onset to first treatment and the hazar...

Cortical lesions constitute a key manifestation of multiple sclerosis and contribute to clinical disability and cognitive impairment. Yet it is unknown whether local cortical lesions and cortical lesion subtypes contribute to domain-specific impairments attributable to the function of the lesioned cortex. In this cross-sectional study, we assessed...