Effects of cladribine on intrathecal and peripheral B and plasma cells.

Introduction: Cladribine is a deoxyadenosine analogue that can penetrate the blood-brain barrier. It is used to treat multiple sclerosis (MS). However, the mechanistic understanding of the effect of this highly effective therapy on B cells and plasma cells in the central nervous system compartment is limited.

Assessing the landscape and charting paths: UK neurology trainees' opinions on neuroinflammation subspecialty.

Therapeutics of neuroinflammatory disorders including multiple sclerosis is one of the fastest growing areas in neurology. However, pressures on higher specialty training in neurology together with an expanding curriculum have led to challenges in adequately preparing trainees for a subspecialist career. In this study we set out to understand current perceptions and barriers to training in neuroinflammatory disorders among neurology trainees in the UK.

Cladribine tablets in relapsing-remitting multiple sclerosis preferentially target B-cells.

Recent studies demonstrate the efficacy of B cell-targeting therapies in managing multiple sclerosis (MS) activity, emphasizing the critical role of B cells in MS pathogenesis. CladB study aimed to quantify the temporal changes in peripheral immune cells and their activity over 96 weeks of Cladribine tablets (CladT) treatment in relapsing-remitting MS (RRMS). Ten participants (3 males, 7 females) had blood samples collected at multiple intervals (Day 0, 1, 5, then weekly for 8 weeks, biweekly for up to 24 weeks, and monthly for up to 96 weeks) for immune cell analysis, compared to a historical alemtuzumab-treated cohort.

Engaging a community to focus on upper limb function in people with multiple sclerosis: the ThinkHand campaign case study.

Background: Solving complex research challenges requires innovative thinking and alternative approaches to traditional methods. One such example is the problem of arm and hand, or upper limb function in multiple sclerosis (MS), a neurological condition affecting approximately 2.9 million people worldwide and more than 150,000 in the United Kingdom.

MS care: integrating advanced therapies and holistic management.

Lifestyle and environmental factors are key determinants in disease causality and progression in neurological conditions, including multiple sclerosis (MS). Lack of exercise, poor diet, tobacco smoking, excessive alcohol intake, social determinants of health, concomitant medications, poor sleep and comorbidities can exacerbate MS pathological processes by impacting brain health and depleting neurological reserves, resulting in more rapid disease worsening. In addition to using disease-modifying therapies to alter the disease course, therapeutic strategies in MS should aim to preserve as much neurological reserve as possible by promoting the adoption of a "brain-healthy" and "metabolically-healthy" lifestyle.

Neutropenia following immune-depletion, notably CD20 targeting, therapies in multiple sclerosis.

Neutropenia serves as a risk factor for severe infection and is a consequence of some immune-depleting immunotherapies. This occurs in people with multiple sclerosis following chemotherapy-conditioning in haematopoietic stem cell transplantation and potent B cell targeting agents. Whilst CD52 is expressed by neutrophils and may contribute to early-onset neutropenia following alemtuzumab treatment, deoxycytidine kinase and CD20 antigen required for activity of cladribine tablets, off-label rituximab, ocrelizumab, ofatumumab and ublituximab are not or only weakly expressed by neutrophils.

Disease activity 4.5 years after starting cladribine: experience in 264 patients with multiple sclerosis.

Background: Cladribine is an effective immunotherapy for people with multiple sclerosis (pwMS). Whilst most pwMS do not require re-treatment following standard dosing (two treatment courses), disease activity re-emerges in others. The characteristics of pwMS developing re-emerging disease activity remain incompletely understood.

Parakinesia Brachialis Oscitans in a Patient With a First Manifestation of Multiple Sclerosis.

Objectives: Parakinesia brachialis oscitans (PBO) is the involuntary movement of an otherwise paretic upper limb triggered by yawning. We describe the first case of PBO in a patient with a first manifestation of tumefactive multiple sclerosis (MS).

Methods: A 35-year-old man presented to the emergency department with a first episode of generalized seizure.

Risk of COVID-19 in people with multiple sclerosis who are seronegative following vaccination.

Background: People with multiple sclerosis (pwMS) treated with certain disease-modifying therapies (DMTs) have attenuated IgG response following COVID-19 vaccination; however, the clinical consequences remain unclear.

Objective: To report COVID-19 rates in pwMS according to vaccine serology.

Methods: PwMS with available (1) serology 2-12 weeks following COVID-19 vaccine 2 and/or vaccine 3 and (2) clinical data on COVID-19 infection/hospitalisation were included.

Decision Making About Disease-Modifying Treatments for Relapsing-Remitting Multiple Sclerosis: Stated Preferences and Real-World Choices.

Background: People with relapsing-remitting multiple sclerosis can benefit from disease-modifying treatments (DMTs). Several DMTs are available that vary in their efficacy, side-effect profile and mode of administration.

Objective: We aimed to measure the preferences of people with relapsing-remitting multiple sclerosis for DMTs using a discrete choice experiment and to assess which stated preference attributes correlate with the attributes of the DMTs they take in the real world.

A plain language summary of the impact of vaccines against flu and chickenpox in people with multiple sclerosis treated with cladribine tablets.

What Is This Summary About?: This is a summary of an article originally published in the . Cladribine tablets (MAVENCLAD) are an oral (taken by mouth) medication, approved for the treatment of people with relapsing forms of multiple sclerosis (MS, with episodes of new or worsening symptoms). They are administered for a maximum of 10 days per year, over a period of 2 years.

The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination.

Background: Sphingosine-one phosphate receptor (S1PR) modulation inhibits S1PR1-mediated lymphocyte migration, lesion formation and positively-impacts on active multiple sclerosis (MS). These S1PR modulatory drugs have different: European Union use restrictions, pharmacokinetics, metabolic profiles and S1PR receptor affinities that may impact MS-management. Importantly, these confer useful properties in dealing with COVID-19, anti-viral drug responses and generating SARS-CoV-2 vaccine responses.

Multiple sclerosis and the risk of infection: Association of British Neurologists consensus guideline.

Infection in people with multiple sclerosis (MS) is of major concern, particularly for those receiving disease-modifying therapies. This article explores the risk of infection in people with MS and provides guidance-developed by Delphi consensus by specialists involved in their management-on how to screen for, prevent and manage infection in this population.

Early Reduction of MRI Activity During 6 Months of Treatment With Cladribine Tablets for Highly Active Relapsing Multiple Sclerosis: MAGNIFY-MS.

Background And Objectives: The onset of action for high-efficacy immunotherapies in multiple sclerosis (MS) is an important parameter. This study (MAGNIFY-MS) evaluates the onset of action of cladribine tablets by observing changes in combined unique active (CUA) MRI lesion counts during the first 6 months of treatment in patients with highly active relapsing MS.

Methods: MRI was performed at screening, baseline, and at months 1, 2, 3, and 6 after initiating treatment with cladribine tablets 3.

Response to COVID-19 booster vaccinations in seronegative people with multiple sclerosis.

Background: People with MS treated with anti-CD20 therapies and fingolimod often have attenuated responses to initial COVID-19 vaccination. However, uncertainties remain about the benefit of a 3rd (booster) COVID-19 vaccine in this group.

Methods: PwMS without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate.

Neuropsychological evaluation and rehabilitation in multiple sclerosis (NEuRoMS): protocol for a mixed-methods, multicentre feasibility randomised controlled trial.

Background: Cognitive problems affect up to 70% of people with multiple sclerosis (MS), which can negatively impact mood, ability to work, and quality of life. Addressing cognitive problems is a top 10 research priority for people with MS. Our ongoing research has systematically developed a cognitive screening and management pathway (NEuRoMS) tailored for people with MS, involving a brief cognitive evaluation and rehabilitation intervention.

Seroconversion following COVID-19 vaccination: can we optimize protective response in CD20-treated individuals?

Although there is an ever-increasing number of disease-modifying treatments for relapsing multiple sclerosis (MS), few appear to influence coronavirus disease 2019 (COVID-19) severity. There is concern about the use of anti-CD20-depleting monoclonal antibodies, due to the apparent increased risk of severe disease following severe acute respiratory syndrome corona virus two (SARS-CoV-2) infection and inhibition of protective anti-COVID-19 vaccine responses. These antibodies are given as maintenance infusions/injections and cause persistent depletion of CD20+ B cells, notably memory B-cell populations that may be instrumental in the control of relapsing MS.

The Expression of Active CD11b Monocytes in Blood and Disease Progression in Amyotrophic Lateral Sclerosis.

Monocytes expressing the inflammation suppressing active CD11b, a beta2 integrin, may regulate neuroinflammation and modify clinical outcomes in amyotrophic lateral sclerosis (ALS). In this single site, retrospective study, peripheral blood mononuclear cells from 38 individuals living with ALS and 20 non-neurological controls (NNC) were investigated using flow cytometry to study active CD11b integrin classical (CM), intermediate (IM) and non-classical (NCM) monocytes during ALS progression. Seventeen ALS participants were sampled at the baseline (V1) and at two additional time points (V2 and V3) for longitudinal analysis.

Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients.

Objective: To report on safety and effectiveness of subcutaneous cladribine (Litak) in multiple sclerosis (MS) patients.

Methods: Litak was offered to MS-patients irrespective of disease course. Litak 10 mg was administered for 3-4 days during week 1.

High-resolution quantitative MRI of multiple sclerosis spinal cord lesions.

Purpose: Validation of quantitative MR measures for myelin imaging in the postmortem multiple sclerosis spinal cord.

Methods: Four fixed spinal cord samples were imaged first with a 3T clinical MR scanner to identify areas of interest for scanning, and then with a 7T small bore scanner using a multicomponent-driven equilibrium single-pulse observation of T and T protocol to produce apparent proton density, T , T , myelin water, intracellular water, and free-water fraction maps. After imaging, the cords were sectioned and stained with histological markers (hematoxylin and eosin, myelin basic protein, and neurofilament protein), which were quantitatively compared with the MR maps.