Hallmarks of spinal cord pathology in multiple sclerosis.

A disparity exists between spinal cord and brain involvement in multiple sclerosis (MS), each independently contributing to disability. Underlying differences between brain and cord are not just anatomical in nature (volume, white/grey matter organization, vascularization), but also in barrier functions (differences in function and composition of the blood-spinal cord barrier compared to blood-brain barrier) and possibly in repair mechanisms. Also, immunological phenotypes seem to influence localization of inflammatory activity.

Improvements in quality of life over 2 years with cladribine tablets in people with relapsing multiple sclerosis: The CLARIFY-MS study.

Background: Multiple sclerosis (MS) negatively affects health-related quality of life (HRQoL).

Objective: To evaluate HRQoL in people with highly active relapsing MS treated with cladribine tablets (CladT; 3.5 mg/kg cumulative dose over 2 years) in CLARIFY-MS.

Effect of disease-modifying treatment on spinal cord lesion formation in multiple sclerosis: A retrospective observational study.

Background: Spinal cord lesions in multiple sclerosis (MS) are an important contributor to disability. Knowledge on the effect of disease-modifying treatment (DMT) on spinal lesion formation in MS is sparse, as cord outcome measures are seldom included in MS treatment trials. We aim to investigate whether intermediate- or high-efficacy DMTs (i/hDMT) can reduce spinal lesion formation, compared with low-efficacy DMTs (lDMT) and/or no treatment.

Efficacy of prolonged-release fampridine placebo on walking ability, dynamic and static balance, physical impact of multiple sclerosis, and quality of life: an integrated analysis of MOBILE and ENHANCE.

Background: MOBILE and ENHANCE were similarly designed randomized trials of walking-impaired adults with relapsing-remitting or progressive multiple sclerosis (MS) who received placebo or 10 mg prolonged-release (PR)-fampridine twice daily for 24 weeks. Both studies showed sustained and clinically meaningful improvement in broad measures of walking and balance over 24 weeks of PR-fampridine treatment.

Objective: To evaluate the functional benefits and safety of PR-fampridine placebo using a integrated efficacy analysis of MOBILE and ENHANCE data.

Treatment satisfaction, safety, and tolerability of cladribine tablets in patients with highly active relapsing multiple sclerosis: CLARIFY-MS study 6-month interim analysis.

Background Multiple sclerosis (MS) is a chronic disabling disease that is associated with negative effects on health-related quality of life (HRQoL) due to reduced physical and psychosocial functioning. Cladribine tablets 10 mg (3.5 mg/kg cumulative dose over 2 years) have been approved for the treatment of adult patients with highly active relapsing multiple sclerosis (RMS).

Ultra-high field spinal cord MRI in multiple sclerosis: Where are we standing? A literature review.

Magnetic resonance imaging (MRI) is a cornerstone in multiple sclerosis (MS) diagnostics and monitoring. Ultra-high field (UHF) MRI is being increasingly used and becoming more accessible. Due to the small diameter and mobility of the spinal cord, imaging this structure at ultra-high fields poses additional challenges compared to brain imaging.

Vitamin D related genetic polymorphisms affect serological response to high-dose vitamin D supplementation in multiple sclerosis.

Introduction: A poor 25-hydroxyvitamin D (25(OH)D) status is a much replicated risk factor for developing multiple sclerosis (MS), and several vitamin D-associated single nucleotide polymorphisms (SNPs) have been associated with a higher risk of MS. However, studies on the benefit of vitamin D supplementation in MS show inconclusive results. Here, we explore whether vitamin D-associated SNPs and MS risk alleles confound serological response to vitamin D supplementation.

Proportions of circulating transitional B cells associate with MRI activity in interferon beta-treated multiple sclerosis patients.

B-cells contribute to MS pathogenesis. The association of circulating B-cell phenotypes with combined unique active lesions (CUA) on MRI at 48 weeks follow-up was investigated in 50 interferon beta-treated MS patients. Transitional B-cell proportions were lower in participants with CUA at week 0 and 48 [p = 0.

Vitamin D supplementation in multiple sclerosis: an expert opinion based on the review of current evidence.

Introduction: Vitamin D has long been known for its immune-modulating effects, next to its function in calcium metabolism. As a consequence, poor vitamin D status has been associated with many diseases including multiple sclerosis (MS). Epidemiological studies suggest an association between a poor vitamin D status and development of MS and a poor vitamin D status is associated with more relapses and faster progression after patients are diagnosed with MS.

Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis.

Objective: To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort.

Methods: Using data from the MSBase Registry, we included pregnancies conceived after 31 Dec 2010 from women with relapsing-remitting MS or clinically isolated syndrome. Predictors of intrapartum relapse, and postpartum relapse and disability progression were determined by clustered logistic regression or Cox regression analyses.

Risk of requiring a wheelchair in primary progressive multiple sclerosis: Data from the ORATORIO trial and the MSBase registry.

Background And Purpose: Reaching Expanded Disability Status Scale (EDSS) ≥7.0 represents the requirement for a wheelchair. Here we (i) assess the effect of ocrelizumab on time to EDSS ≥7.

NK/T cell ratios associate with interleukin-2 receptor alpha chain expression and shedding in multiple sclerosis.

NK/T-cell ratios predict disease activity in relapsing remitting multiple sclerosis (RRMS). We investigated in 50 RRMS patients whether interleukin-2 receptor alpha-chain (IL-2Rα) expression and shedding associates with NK/T-cell balance, as suggested by daclizumab-trials in RRMS. A subsample (N = 31) was genotyped for IL2RA-associated MS risk SNPs.

Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years.

Objective: To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients.

Methods: We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods.

Prognostic value of natural killer cell/T cell ratios for disease activity in multiple sclerosis.

Background And Purpose: Natural killer (NK) cells may play a role in multiple sclerosis (MS). Ratios of NK cells to CD4 T cells have been proposed as a biomarker for the therapeutic effect of stem cell transplantation in MS. The objectives here were to explore the relevance of this ratio in MS patients by analysing NK and T cell subsets, as well as their prognostic value for disease activity.

Treatment Response Score to Glatiramer Acetate or Interferon Beta-1a.

Objective: To compare the effectiveness of glatiramer acetate (GA) vs intramuscular interferon beta-1a (IFN-β-1a), we applied a previously published statistical method aimed at identifying patients' profiles associated with efficacy of treatments.

Methods: Data from 2 independent multiple sclerosis datasets, a randomized study (the Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis [CombiRx] trial, evaluating GA vs IFN-β-1a) and an observational cohort extracted from MSBase, were used to build and validate a treatment response score, regressing annualized relapse rates (ARRs) on a set of baseline predictors.

Results: The overall ARR ratio of GA to IFN-β-1a in the CombiRx trial was 0.

Delay from treatment start to full effect of immunotherapies for multiple sclerosis.

In multiple sclerosis, treatment start or switch is prompted by evidence of disease activity. Whilst immunomodulatory therapies reduce disease activity, the time required to attain maximal effect is unclear. In this study we aimed to develop a method that allows identification of the time to manifest fully and clinically the effect of multiple sclerosis treatments ('therapeutic lag') on clinical disease activity represented by relapses and progression-of-disability events.

Association of Sustained Immunotherapy With Disability Outcomes in Patients With Active Secondary Progressive Multiple Sclerosis.

Importance: It is unclear whether relapses and disease-modifying therapies are associated with the rate of disability accumulation in patients with secondary progressive multiple sclerosis (SPMS).

Objective: To examine the association of relapses with the rate of disability accumulation in patients with SPMS and to assess whether treatment before or during the secondary progressive phase can slow the progression of disability accumulation.

Design, Setting, And Participants: In this observational cohort study, patient data were prospectively collected from the MSBase international registry between January 1, 1995, and February 1, 2018.

Prediction of on-treatment disability worsening in RRMS with the MAGNIMS score.

Background: The magnetic resonance imaging in multiple sclerosis (MAGNIMS) score combines relapses and magnetic resonance imaging (MRI) lesions to predict disability outcomes in relapsing-remitting multiple sclerosis (RRMS) treated with interferon-β.

Objective: To validate the MAGNIMS score and extend to other disease-modifying therapies (DMTs). To examine the prognostic value of gadolinium contrast-enhancing (Gd+) lesions.

Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis.

Background: Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear.

Objective: The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms.

Methods: This study used data from MSBase registry.

Early clinical markers of aggressive multiple sclerosis.

Patients with the 'aggressive' form of multiple sclerosis accrue disability at an accelerated rate, typically reaching Expanded Disability Status Score (EDSS) ≥ 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive multiple sclerosis, but less research has focused on clinical markers that are present in the first year of disease. The development of early predictive models of aggressive multiple sclerosis is essential to optimize treatment in this multiple sclerosis subtype.

Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study.

Background: High-efficacy therapies in multiple sclerosis are traditionally used after unsuccessful treatment with first-line disease modifying therapies. We hypothesised that early commencement of high-efficacy therapy would be associated with reduced long-term disability. We therefore aimed to compare long-term disability outcomes between patients who started high-efficacy therapies within 2 years of disease onset with those who started 4-6 years after disease onset.