Fecal microbiota transplantation is safe and tolerable in patients with multiple sclerosis: A pilot randomized controlled trial.

Background: Patients with MS have an altered gut microbiota compared to healthy individuals, as well as elevated small intestinal permeability, which may be contributing to the development and progression of the disease.

Objective: We sought to investigate if fecal microbiota transplantation was safe and tolerable in MS patients and if it could improve abnormal intestinal permeability.

Methods: Nine patients with MS were recruited and provided monthly FMTs for up to six months.

Long-term outcomes of peginterferon beta-1a in multiple sclerosis: results from the ADVANCE extension study, ATTAIN.

Background: ADVANCE was a phase III trial of the efficacy and safety of subcutaneous peginterferon beta-1a 125 µg every 2 or 4 weeks in patients with relapsing-remitting multiple sclerosis (RRMS). ATTAIN was a 2-year extension study of ADVANCE. The aim was to evaluate the long-term safety, tolerability, and efficacy of peginterferon beta-1a 125 µg every 2 or 4 weeks in ATTAIN.

Common variation near IRF6 is associated with IFN-β-induced liver injury in multiple sclerosis.

Multiple sclerosis (MS) is a disease of the central nervous system treated with disease-modifying therapies, including the biologic, interferon-β (IFN-β). Up to 60% of IFN-β-exposed MS patients develop abnormal biochemical liver test results, and 1 in 50 experiences drug-induced liver injury. Since genomic variation contributes to other forms of drug-induced liver injury, we aimed to identify biomarkers of IFN-β-induced liver injury using a two-stage genome-wide association study.

Predictive validity of NEDA in the 16- and 21-year follow-up from the pivotal trial of interferon beta-1b.

Background: Long-term follow-up from the randomized trial of interferon beta-1b (IFNB-1b) permitted the assessment of different definitions of no evidence of disease activity (NEDA) for predicting long-term outcome in multiple sclerosis (MS).

Objective: To examine the predictive validity of different NEDA definitions.

Methods: Predictive validity for negative disability outcomes (NDOs) at 16 years and survival at 21 years post-randomization were assessed.

Effect of Treating Acute Optic Neuritis With Bioequivalent Oral vs Intravenous Corticosteroids: A Randomized Clinical Trial.

Importance: Intravenous (IV) administration of corticosteroids is the standard of care in the treatment of acute optic neuritis. However, it is uncertain whether a bioequivalent dose of corticosteroid administered orally, which may be more cost-efficient and convenient for patients, is as effective as IV administration in the treatment of acute optic neuritis.

Objective: To determine whether recovery of vision following treatment of acute optic neuritis with a high-dose IV corticosteroid is superior to that with a bioequivalent dose of an oral corticosteroid.

Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis.

Background: On the basis of encouraging preliminary results, we conducted a randomized, controlled trial to determine whether minocycline reduces the risk of conversion from a first demyelinating event (also known as a clinically isolated syndrome) to multiple sclerosis.

Methods: During the period from January 2009 through July 2013, we randomly assigned participants who had had their first demyelinating symptoms within the previous 180 days to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of multiple sclerosis was established or until 24 months after randomization, whichever came first.

Breaking down the gut microbiome composition in multiple sclerosis.

Background: The gut microbiome, which consists of a highly diverse ecologic community of micro-organisms, has increasingly been studied regarding its role in multiple sclerosis (MS) immunopathogenesis. This review critically examines the literature investigating the gut microbiome in MS.

Methods: A comprehensive search was performed of PubMed databases and ECTRIMS meeting abstracts for literature relating to the gut microbiome in MS.

Canadian Experience with Fingolimod: Adherence to Treatment and Monitoring.

Background: The Canadian GILENYA® Go ProgramTM provides education and support to people with relapsing-remitting multiple sclerosis during fingolimod treatment.

Methods: Data were collected and analyzed from the time of the first individual enrolled in March 2011 to March 31, 2014. Individuals were excluded if they withdrew from the program prior to receiving the first dose, or had not completed the first dose observation (FDO) at the time of data cut-off.

Consensus Management of Gastrointestinal Events Associated with Delayed-Release Dimethyl Fumarate: A Delphi Study.

Introduction: Delayed-release dimethyl fumarate (DMF, also known as gastro-resistant DMF) is indicated for the treatment of patients with relapsing multiple sclerosis. Gastrointestinal (GI) adverse events (AEs) occur with DMF therapy.

Methods: We used a Delphi process to reach consensus among North American clinicians on effective real-world management strategies for GI AEs associated with DMF.

Factors influencing long-term outcomes in relapsing-remitting multiple sclerosis: PRISMS-15.

Aim: An exploratory study of the relationship between cumulative exposure to subcutaneous (sc) interferon (IFN) β-1a treatment and other possible prognostic factors with long-term clinical outcomes in relapsing-remitting multiple sclerosis (RRMS).

Methods: Patients in the original PRISMS study were invited to a single follow-up visit 15 years after initial randomisation (PRISMS-15). Outcomes over 15 years were compared in the lowest and highest quartile of the cumulative sc IFN β-1a dose groups, and according to total time receiving sc IFN β-1a as a continuous variable per 5 years of treatment.

Autonomic dysfunction in multiple sclerosis.

Autonomic dysfunction is a prevalent and significant cause of disability among patients with multiple sclerosis. Autonomic dysfunction in multiple sclerosis is usually explained by lesions within central nervous system regions responsible for autonomic regulation, but novel evidence suggests that other factors may be involved as well. Additionally, the interactions between the autonomic nervous system and the immune system have generated increased interest about the role of autonomic dysfunction in the pathogenesis of multiple sclerosis.

Evolving role of MRI in optimizing the treatment of multiple sclerosis: Canadian Consensus recommendations.

Background: Magnetic resonance imaging (MRI) is increasingly important for the early detection of suboptimal responders to disease-modifying therapy for relapsing-remitting multiple sclerosis. Treatment response criteria are becoming more stringent with the use of composite measures, such as no evidence of disease activity (NEDA), which combines clinical and radiological measures, and NEDA-4, which includes the evaluation of brain atrophy.

Methods: The Canadian MRI Working Group of neurologists and radiologists convened to discuss the use of brain and spinal cord imaging in the assessment of relapsing-remitting multiple sclerosis patients during the treatment course.

Systematic review of efficacy of TENS for management of central pain in people with multiple sclerosis.

Background: Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological therapy that can be used for central pain (CP) management without the side effects of pharmacological interventions. Currently, the efficacy of TENS for management of CP in people living with multiple sclerosis (MS) is considered questionable.

Methods: Relevant electronic databases were searched from their inception to November 2014 using appropriate terms for case-control (CC) studies or randomized controlled trials (RCTs) utilizing TENS for management of CP in MS.

Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: a randomized, placebo-controlled, multiple-dose study.

Background: Infusion of PDA-001, a preparation of mesenchymal-like cells derived from full-term human placenta, is a new approach in the treatment of patients with multiple sclerosis.

Objective: This safety study aimed to rule out the possibility of paradoxical exacerbation of disease activity by PDA-001 in patients with multiple sclerosis.

Methods: This was a phase 1b, multicenter, randomized, double-blind, placebo-controlled, 2-dose ranging study including patients with relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis.

Bilateral trochlear nerve palsy in a patient with neuromyelitis optica.

We present a unique case of isolated bilateral simultaneous cranial nerve (CN) IV palsy in a patient with neuromyelitis optica (NMO). Although some CN IV abnormalities have been described in multiple sclerosis (MS), no case of isolated bilateral simultaneous CN IV has been reported, to our knowledge, in either NMO or MS.

Increased deep gray matter iron is present in clinically isolated syndromes.

Objective: Abnormal iron accumulation in MS has been known for decades, however it remains to be established whether iron reflects a cause or epiphenomenon of pathology. The objective of the present study is to determine if iron is increased in the brains of patients with clinically isolated syndromes (CIS) suggestive of early MS.

Methods: Twenty-two patients with a CIS and 16 age- and sex-matched controls underwent 3T MRI studies.

Impact of prior treatment status and reasons for discontinuation on the efficacy and safety of fingolimod: Subgroup analyses of the Fingolimod Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study.

Background: Fingolimod is a once-daily, oral sphingosine 1-phosphate receptor modulator approved for the treatment of relapsing multiple sclerosis.

Objective: This post-hoc analysis of phase 3 FREEDOMS data assessed whether the effects of fingolimod are consistent among subgroups of patients defined by prior treatment history.

Methods: Annualized relapse rate and safety profile of treatment with fingolimod 0.

Cardiovascular autonomic dysfunction in multiple sclerosis: a meta-analysis.

Background And Objective: The definition of cardiovascular autonomic dysfunction in patients with multiple sclerosis is controversial. Thus, its true prevalence is unknown. We performed a systematic review and meta-analysis to compare the proportion of patients with multiple sclerosis that would be diagnosed with cardiovascular dysautonomia using a definition of at least one abnormal cardiac autonomic test vs.

Characteristics associated with drug-induced liver injury from interferon beta in multiple sclerosis patients.

Objective: To identify and characterize drug-induced liver injury (DILI) associated with IFN-β in multiple sclerosis (MS) using recommended criteria.

Methods: This retrospective, mixed methods design included a cohort of IFN-β exposed MS patients from British Columbia (BC), Canada and a series of DILI cases from other Canadian provinces and two adverse drug reaction (ADR) networks (USA and Sweden). Associations between sex, age and IFN-β product, and DILI were explored in BC cohort using Cox proportional hazard analyses.

Multiple sclerosis: improved identification of disease-relevant changes in gray and white matter by using susceptibility-based MR imaging.

Purpose: To evaluate the potential of quantitative susceptibility (QS) and R2* mapping as surrogate biomarkers of clinically relevant, age-adjusted demyelination and iron deposition in multiple sclerosis (MS).

Materials And Methods: All study participants gave written informed consent, and the study was approved by the institutional review board. Quantitative maps of the magnetic resonance imaging susceptibility parameters (R2* and QS) were computed for 25 patients with either clinically isolated syndrome (CIS) or relapsing-remitting MS, as well as for 15 age- and sex-matched control subjects imaged at 7 T.

Pegylated interferons: a nurses' review of a novel multiple sclerosis therapy.

Most multiple sclerosis (MS) therapies are injectable drugs, and the frequency of injections has been shown to be inversely proportional to overall compliance. One method of improving therapeutic compliance and thus clinical outcomes is to develop medications that require less frequent dosing. One of the most promising modification techniques to extend the bioavailability of a drug is poly(ethylene glycol) conjugation (pegylation), which increases the size of a molecule by attaching polyethylene glycol moieties to the parent compound, resulting in slower clearance and metabolism.

Venocentric Lesions: An MRI Marker of MS?

From the earliest descriptions of multiple sclerosis (MS), the venocentric characteristic of plaques was noted. Recently, numerous magnetic resonance imaging (MRI) studies have proposed this finding as a prospective biomarker for MS, which might aid in differentiating MS from other diseases with similar MRI findings. High-field MRI studies have shown that penetrating veins can be detected in most MS lesions using T2(∗) weighted or susceptibility-weighted imaging.