Association of Cortical Lesions With Regional Glutamate, GABA, -Acetylaspartate, and Myoinositol Levels in Patients With Multiple Sclerosis.

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.

Methods: In this cross-sectional study, we used structural 7T MRI to segment cortical lesions and 7T proton MR-spectroscopy of the bilateral sensorimotor hand areas to quantify regional GABA, glutamate, -acetylaspartate, and myoinositol concentrations in patients with MS (inclusion criteria: diagnosis of relapsing-remitting [RR] or secondary progressive MS [SPMS]; age 18-80 years) and age and sex-matched healthy controls.

Neoehrlichiosis associated with ocrelizumab in a patient with multiple sclerosis: A case report.

Objective: To describe a case of neoehrlichiosis, an emerging opportunistic tick-borne infection, in a patient with multiple sclerosis (MS) treated with ocrelizumab.

Methods: This is a case study.

Results: Our patient developed clinical infection over several months while on ocrelizumab and was ultimately diagnosed with neoehrlichiosis, caused by the bacteria .

Autologous hematopoietic stem cell transplantation of patients with aggressive relapsing-remitting multiple sclerosis: Danish nation-wide experience.

Background: Autologous hematopoietic stem cell treatment (AHSCT) is considered an effective treatment option for patients with aggressive relapsing-remitting multiple sclerosis (RRMS). Still there are few randomized and controlled studies of AHSCT to shed light on the safety and efficacy of the treatment, and therefore experiences from single centers are important.

Aim: To describe the Danish experience with AHSCT regarding patient characteristics, safety, and efficacy.

Comparison of Translocator Protein Expression Between Tumefactive Multiple Sclerosis and Glioblastoma.

This figure presents a comparison of molecular imaging of the translocator protein (TSPO) and contrast-enhanced MRI in 2 patients with tumefactive multiple sclerosis and glioblastoma, respectively. In the case of the tumefactive multiple sclerosis patient, TSPO uptake is primarily located centrally, while in the glioblastoma patient, TSPO uptake is predominantly situated peripherally to the central necrotic area. These findings suggest that TSPO imaging could be a noninvasive imaging technique for distinguishing between these 2 diagnoses.

Mapping grip-force related brain activity after a fatiguing motor task in 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-four right-handed mildly disabled patients with relapsing-remitting MS and 25 healthy controls performed a maximal tonic precision grip with their right hand until they developed motor fatigue.

Oligoclonal bands, age 11-17 years, occipital lesion, and female sex differentiate pediatric multiple sclerosis from acute disseminated encephalomyelitis: A nationwide cohort study.

Background: Our aim was to propose criteria to distinguish multiple sclerosis (MS) from acute disseminated encephalomyelitis (ADEM) at onset based on age at onset, sex, cerebrospinl fluid (CSF)-specific oligoclonal bands, and MRI.

Methods: A neuroradiologist undertook retrospective evaluation of the baseline magnetic resonance imaging (MRI) in a nationwide cohort of children with medical record-validated MS (n = 67) and monophasic ADEM (n = 46). Children with ADEM had at least 5 years of follow-up for relapse.

Blood-brain barrier permeability changes in the first year after alemtuzumab treatment predict 2-year outcomes in relapsing-remitting multiple sclerosis.

Background: In relapsing-remitting multiple sclerosis (RRMS), early disease control reduces the risk of permanent disability. The blood-brain barrier (BBB) is compromised in MS, and its permeability is a potential biomarker.

Objective: To investigate BBB permeability measured by MRI as a marker of alemtuzumab efficacy.

Linking lesions in sensorimotor cortex to contralateral hand function in multiple sclerosis: a 7 T MRI study.

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 how cortical lesions in the primary sensorimotor hand area relate to corticomotor physiology and sensorimotor function of the contralateral hand.

Magnetic resonance imaging criteria at onset to differentiate pediatric multiple sclerosis from acute disseminated encephalomyelitis: A nationwide cohort study.

Background: MRI of the nervous system is the critical in distinguishing pediatric MS from acute disseminated encephalomyelitis (ADEM). Our aim was to propose MRI criteria to distinguish MS from monophasic ADEM based on the first MRI and to validate previously proposed MRI criteria.

Methods: A neuroradiologist undertook retrospective evaluation of the MRI at the first demyelinating event in children (<18 years) with medical record-validated MS and ADEM in Denmark during 2008-15.

Employment, health visits, mental health, and mortality in parents with a chronically ill child: a Danish nationwide population-based cohort study.

Unlabelled: Chronic diseases in children can impact their parents; this may be overlooked in a clinical setting. Our aim was to investigate associations of chronic diseases in children with their parents' employment, health care utilization, mental health, and mortality. In a matched cohort study using nationwide and population-based data in Denmark, we included parents to children (< 18 years) with acute disseminated encephalomyelitis, multiple sclerosis, type 1 diabetes, inflammatory bowel disease, and rheumatoid arthritis/juvenile idiopathic arthritis during 2008-2015.

Validation of MRI radiological reports in pediatric MS according to the McDonald 2017 criteria: A Danish nationwide multicenter cohort study.

Background: MRI allows demonstration of dissemination in space and time at the first demyelinating event. However, no pediatric MS study has investigated the validity of MS-specific outcomes described in MRI radiological reports that clinicians rely on to make the MS diagnosis and to assess the MS treatment effect. Our aim was to validate MS-specific outcomes in hospital MRI reports in pediatric MS by comparing MS-specific outcomes in MRI reports with secondary MRI review.

Safety, tolerability, and activity of mesenchymal stem cells versus placebo in multiple sclerosis (MESEMS): a phase 2, randomised, double-blind crossover trial.

Background: Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells, have been proposed as a promising therapeutic option for people with multiple sclerosis on the basis of their immunomodulatory and neuroprotective properties. The MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study was devised to evaluate the safety, tolerability, and activity of autologous MSCs derived from bone marrow and infused intravenously in patients with active multiple sclerosis.

Methods: MESEMS is a randomised phase 2 trial done at 15 sites in nine countries.

Ocrelizumab treatment in multiple sclerosis: A Danish population-based cohort study.

Background And Purpose: Real-world evidence regarding the effectiveness and safety of ocrelizumab for the treatment of multiple sclerosis (MS) is limited. The aim was to evaluate the effectiveness and safety of ocrelizumab treatment for MS in a real-world setting.

Methods: A nationwide population-based cohort study was conducted where clinical and magnetic resonance imaging data of MS patients enrolled prospectively in the Danish Multiple Sclerosis Registry who initiated ocrelizumab treatment between January 2018 and November 2020 were analyzed.

Dimethyl Fumarate Treatment in Patients With Primary Progressive Multiple Sclerosis: A Randomized, Controlled Trial.

Background And Objective: To study whether dimethyl fumarate is superior to placebo in decreasing CSF concentrations of neurofilament light chain (NFL) in patients with primary progressive MS (PPMS).

Methods: In the double-blind, placebo-controlled phase 2 study dimethyl FUMArate treatment in Progressive Multiple Sclerosis (FUMAPMS), patients with PPMS were randomly assigned to treatment with 240 mg dimethyl fumarate or placebo in a 1:1 ratio for 48 weeks. The primary endpoint was change in concentration of NFL in the CSF.

Anti-CD20 antibody therapy and risk of infection in patients with demyelinating diseases.

Background: Anti-CD20 antibody therapy may be associated with an increased risk of infections. We therefore investigated risk factors for infection in patients with demyelinating diseases treated with anti-CD20 antibody therapy.

Methods: In this retrospective uncontrolled study, patients ever treated with anti-CD20 antibodies at an academic clinic were identified through the Danish Multiple Sclerosis Registry (DMSR).

Magnetic resonance imaging at baseline and follow-up to differentiate between pediatric monophasic acquired CNS demyelination and MS.

Background: It is essential to distinguish acute disseminated encephalomyelitis (ADEM) from MS early. Our aim was to determine MRI features at baseline and follow-up to distinguish pediatric ADEM from MS stratified according to age at onset.

Methods: Using hospital ICD-10 codes for acquired demyelinating syndromes from a nationwide register and subsequent chart review, we identified 52 children (<18 years) with ADEM and 66 children with MS.

Increased socioeconomic burden in patients with primary progressive multiple sclerosis: A Danish nationwide population-based study.

Background: Primary progressive multiple sclerosis (PPMS) is characterized by development of more chronic neurological manifestations from disease onset compared with relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) but the following socioeconomic consequences have never been described in a nation-wide patient population.

Objective: To determine if socioeconomic burden of PPMS is increased compared with RRMS and SPMS.

Methods: We included patients from The Danish Multiple Sclerosis Registry diagnosed between 1998 and 2015.

School performance, psychiatric comorbidity, and healthcare utilization in pediatric multiple sclerosis: A nationwide population-based observational study.

Background: Pediatric multiple sclerosis (MS) may hamper educational achievements due to psychiatric comorbidity and cognitive impairment. Our aims were to investigate school performance, psychiatric comorbidity, and healthcare utilization following pediatric MS and to differentiate between disability in MS and that arising from a non-brain-related chronic disease.

Methods: We included all children (<18 years) with MS onset during 2008-2015 in Denmark with a medical record-validated MS diagnosis.

Disentangling white-matter damage from physiological fibre orientation dispersion in multiple sclerosis.

Multiple sclerosis leads to diffuse damage of the central nervous system, affecting also the normal-appearing white matter. Demyelination and axonal degeneration reduce regional fractional anisotropy in normal-appearing white matter, which can be routinely mapped with diffusion tensor imaging. However, the standard fractional anisotropy metric is also sensitive to physiological variations in orientation dispersion of white matter fibres.

Motor fatigue is associated with asymmetric connectivity properties of the corticospinal tract in multiple sclerosis.

Multiple Sclerosis (MS) is characterized by demyelination and neurodegeneration of the central nervous system and causes excessive fatigue in more than 80% of the patients. The pathophysiologic mechanisms causing fatigue are still largely unknown. In 46 right-handed patients with relapsing-remitting MS and 25 right-handed controls, we performed diffusion MRI and applied streamline based probabilistic tractography to derive unilateral anatomical connectivity maps for the white matter of the right and left hemispheres.

Long term effect of delayed treatment on disability in patients with paediatric onset multiple sclerosis: A prospective Danish cohort study.

Background: A consensus of early treatment with disease-modifying therapies (DMT) in multiple sclerosis (MS) has been reached based on several observational and experimental studies in adults. However, paediatric onset (PO)MS appears phenotypically different from adult onset MS, characterized by increased relapse rate and pronounced radiological activity on MRI. The objective of this study was to investigate the long-term consequences of delayed treatment start in POMS on disability in a real-world, population-based setting.

Anti-CD20 Monoclonal Antibodies for Relapsing and Progressive Multiple Sclerosis.

Multiple sclerosis (MS) was previously thought to be a T-cell-mediated, demyelinating disease of the central nervous system. Disease-modifying therapies targeting T cells have, indeed, shown remarkable efficacy in patients with relapsing-remitting MS. However, these therapies do also target B cells, and a B-cell-depleting monoclonal antibody (ocrelizumab) has recently been approved for MS therapy and is efficacious not only in relapsing forms of MS but also in some patients with primary progressive MS.

Clinical characteristics and use of disease modifying therapy in the nationwide Danish cohort of paediatric onset multiple sclerosis.

Background: Several disease-modifying therapies (DMT) are being used in paediatric patients with multiple sclerosis (MS) despite the limited number of randomised controlled clinical trials leading to approved indication in children.

Objectives: The aim of this study was to describe clinical characteristics of the Danish population of paediatric onset MS, and the patterns of DMT utilisation in patients who started treatment before the age of 18 years.

Methods: We conducted a nationwide population-based cohort study, including 347 children with paediatric-onset MS (<18 years).

School performance and psychiatric morbidity 6 years after pediatric acute disseminated encephalomyelitis: A nationwide population-based cohort study.

Background: Acute disseminated encephalomyelitis (ADEM) can cause cognitive impairment in children. However, long-term consequences for school performance and psychiatric morbidity have never been characterized. Our aim was to investigate long-term school performance and psychiatric morbidity after pediatric ADEM (<18 years).

[Autologous haematopoietic stem cell transplantation of patients with multiple sclerosis].

Immunosuppression with chemotherapy followed by autologous haematopoietic stem cell transplantation has proven to be an effective long-term treatment for younger patients with relapsing-remitting multiple sclerosis and clinical as well as radiological evidence of high disease activity. The conditioning regimen can be of either high, intermediate or low intensity. Due to the safety profile and favourable efficacy measures, the low intensity regimen cyclophosphamide + anti-thymocyte globulin is currently used in Denmark as standard regimen.