Neuroprotective and Anti-Inflammatory Effects of Dimethyl Fumarate, Monomethyl Fumarate, and Cannabidiol in Neurons and Microglia.

Dimethyl fumarate (DMF) is an immunomodulatory treatment for multiple sclerosis (MS) that can cross the blood-brain barrier, presenting neuroprotective potential. Its mechanism of action is not fully understood, and there is a need to characterize whether DMF or its bioactive metabolite monomethyl fumarate (MMF) exerts neuroprotective properties. Moreover, the combination of adjuvant agents such as cannabidiol (CBD) could be relevant to enhance neuroprotection.

Increased EBNA1-specific antibody response in primary-progressive multiple sclerosis.

Background And Objectives: The impact of viral infections on disease susceptibility and progression has predominantly been studied in patients with relapse-onset MS (RMS). Here, we determined immune responses to ubiquitous viruses in patients with primary progressive MS (PPMS).

Methods: Antibody responses to Epstein-Barr virus (EBV), specifically to the latent EBV nuclear antigen 1 and the lytic viral capsid antigen VCA, human herpesvirus 6 (HHV-6), human cytomegalovirus (HCMV), and measles virus were determined in a cohort of 68 PPMS patients with a mean follow-up of 8 years and compared with 66 healthy controls matched for sex and age.

Response to Fingolimod in Multiple Sclerosis Patients Is Associated with a Differential Transcriptomic Regulation.

Fingolimod is an immunomodulatory sphingosine-1-phosphate (S1P) analogue approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). The identification of biomarkers of clinical responses to fingolimod is a major necessity in MS to identify optimal responders and avoid the risk of disease progression in non-responders. With this aim, we used RNA sequencing to study the transcriptomic changes induced by fingolimod in peripheral blood mononuclear cells of MS-treated patients and their association with clinical response.

Dimethyl fumarate-related immune and transcriptional signature is associated with clinical response in multiple sclerosis-treated patients.

Background And Objective: Dimethyl fumarate (DMF) is an immunomodulatory drug approved for the therapy of multiple sclerosis (MS). The identification of response biomarkers to DMF is a necessity in the clinical practice. With this aim, we studied the immunophenotypic and transcriptomic changes produced by DMF in peripheral blood mononuclear cells (PBMCs) and its association with clinical response.

Endocannabinoid levels in peripheral blood mononuclear cells of multiple sclerosis patients treated with dimethyl fumarate.

The endocannabinoid system (ECS), a signalling network with immunomodulatory properties, is a potential therapeutic target in multiple sclerosis (MS). Dimethyl fumarate (DMF) is an approved drug for MS whose mechanism of action has not been fully elucidated; the possibility exists that its therapeutic effects could imply the ECS. With the aim of studying if DMF can modulate the ECS, the endocannabinoids 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) were determined by liquid chromatography-mass spectrometry in peripheral blood mononuclear cells from 21 healthy donors (HD) and 32 MS patients at baseline and after 12 and 24 months of DMF treatment.

Incidence and prevalence of multiple sclerosis in Spain: a systematic review.

Introduction: Greater understanding of the prevalence and incidence of multiple sclerosis in Spain and their temporal trends is necessary to improve the allocation of healthcare resources and to study aetiological factors.

Methods: We performed a systematic search of the MedLine database and reviewed the reference lists of the articles gathered. We collected studies reporting prevalence or incidence rates of multiple sclerosis in any geographical location in Spain, with no time limits.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain.

Introduction: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis.

Objective: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain.

Development: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017.

Bruton's Tyrosine Kinase Inhibitors: A New Generation of Promising Agents for Multiple Sclerosis Therapy.

B cells play a central role in the pathogenesis of multiple sclerosis (MS), as demonstrated through the success of various B cell-depleting monoclonal antibodies. Bruton's tyrosine kinase (BTK) is a critical molecule in intracellular signaling from the receptor of B cells and receptors expressed in the cells of the innate immune system. BTK inhibitors may be a non-cell-depleting alternative to B cell modulation.

Short-term data on disease activity, cognition, mood, stigma and employment outcomes in a cohort of patients with primary progressive multiple sclerosis (UPPMS study).

Background: Primary progressive multiple sclerosis (PPMS) has long been defined by progressive disability accrual in the absence of initial relapses. However, its underlying neurodegenerative process seems to be accompanied by central nervous system inflammation. A new classification defined multiple sclerosis courses according to clinical/radiological activity and progression.

Brain region volumes and their relationship with disability progression and cognitive function in primary progressive multiple sclerosis.

Background And Purpose: Evidence on regional changes resulting from neurodegenerative processes underlying primary progressive multiple sclerosis (PPMS) is still limited. We assessed brain region volumes and their relationship with disability progression and cognitive function in PPMS patients.

Methods: This was an MRI analysis of 43 patients from the prospective Understanding Primary Progressive Multiple Sclerosis (UPPMS) cohort study.

Multidisciplinary Management of the Adverse Effects of Apremilast.

We present a series of general and specific recommendations based on pathophysiologic considerations for managing the most common adverse effects of apremilast that lead to treatment discontinuation: diarrhea, nausea, and headache. The recommendations are based on a review of the literature and the experience of a multidisciplinary team of 14 experts including dermatologists, rheumatologists, neurologists, gastroenterologists, pharmacists, and nurses. We propose a series of simple algorithms that include clinical actions and suggestions for pharmacologic treatment.

CSF chitinase 3-like-1 association with disability of primary progressive MS.

Objective: To assess the role of CSF chitinase 3-like-1 (CHI3L1), chitinase 3-like-2 (CHI3L2), and neurofilament light chain (NfL) in predicting the course of primary progressive MS (PPMS).

Methods: We analyzed CSF CHI3L1, CHI3L2, and NfL levels in 25 patients with PPMS with disease duration ≤10 years and no disease-modifying therapy for ≥6 months from the prospective Understanding Primary Progressive Multiple Sclerosis cohort study. CSF samples taken at disease diagnosis were analyzed using commercial ELISAs and following the manufacturer's instructions.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain.

Introduction: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis.

Objective: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain.

Development: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017.

Perception of stigma in patients with primary progressive multiple sclerosis.

Stigma associated with neurological disorders may contribute to a poor health-related quality of life. However, limited information is available in primary progressive multiple sclerosis. We investigated the presence and impact of stigma in patients with primary progressive multiple sclerosis.

Criteria heterogeneity in the diagnosis of acute bronchiolitis in Spain.

Introduction: Acute viral bronchiolitis (AB) is one of the most common respiratory diseases in infants. However, diagnostic criteria for AB are heterogeneous and not very well known.

Objective: To identify the diagnostic criteria for AB used by experts and clinical paediatricians in Spain.

[Criteria heterogeneity in the diagnosis of acute bronchiolitis in Spain].

Introduction: Acute viral bronchiolitis (AB) is one of the most common respiratory diseases in infants. However, diagnostic criteria for AB are heterogeneous and not very well known.

Objective: To identify the diagnostic criteria for AB used by experts and clinical paediatricians in Spain.

Immunophenotype and Transcriptome Profile of Patients With Multiple Sclerosis Treated With Fingolimod: Setting Up a Model for Prediction of Response in a 2-Year Translational Study.

Background: Fingolimod is a functional sphingosine-1-phosphate antagonist approved for the treatment of multiple sclerosis (MS). Fingolimod affects lymphocyte subpopulations and regulates gene expression in the lymphocyte transcriptome. Translational studies are necessary to identify cellular and molecular biomarkers that might be used to predict the clinical response to the drug.

Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome.

The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay.

Mechanisms of action of cannabidiol in adoptively transferred experimental autoimmune encephalomyelitis.

Cannabidiol (CBD) is one of the most important compounds in Cannabis sativa, lacks psychotropic effects, and possesses a high number of therapeutic properties including the amelioration of experimental autoimmune encephalomyelitis (EAE). The aim of this study was to analyse the relative efficacy of CBD in adoptively transferred EAE (at-EAE), a model that allows better delineation of the effector phase of EAE. Splenocytes and lymph nodes from mice with actively induced EAE were cultured in the presence of MOG and IL-12 and inoculated intraperitoneally in recipient female C57BL/6J mice.

Anti-CD20 monoclonal antibodies in multiple sclerosis.

The therapeutic utility of the anti-CD20 monoclonal antibodies (mAbs) is currently being evaluated in multiple sclerosis (MS) in line with the better understanding of the role of B lymphocytes in MS pathogenesis. Area covered: We conducted a literature search using Medline/Pub Med database of basic research and available controlled trials about anti-CD20 mAbs in MS. Additionally, ongoing studies were identified in the ClinicalTrials.

Consensus statement on the treatment of multiple sclerosis by the Spanish Society of Neurology in 2016.

With the advent of new disease-modifying drugs, the treatment of multiple sclerosis is becoming increasingly complex. Using consensus statements is therefore advisable. The present consensus statement, which was drawn up by the Spanish Society of Neurology's study group for demyelinating diseases, updates previous consensus statements on the disease.

Looking beyond patients: Can parents' quality of life predict asthma control in children?

Background: Social and family factors may influence the probability of achieving asthma control in children. Parents' quality of life has been insufficiently explored as a predictive factor linked to the probability of achieving disease control in asthmatic children.

Objective: Determine whether the parents' quality of life predicts medium-term asthma control in children.