82,403 results match your criteria Multiple Sclerosis


Identification and Preclinical Pharmacology of ((1R,3S)-1-amino-3-((S)-6-(2-methoxyphenethyl)-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol (BMS-986166): A Differentiated Sphingosine-1-Phosphate (S1P1) Receptor Modulator Advanced into Clinical Trials.

J Med Chem 2019 Feb 20. Epub 2019 Feb 20.

Recently, our research group reported the identification of BMS-986104 (2) as a differentiated S1P1 receptor modulator. In comparison to fingolimod (FTY720, 1), a full agonist of S1P1 currently marketed for the treatment of relapse remitting multiple sclerosis (RRMS), 2 offers several potential advantages having demonstrated improved safety multiples in pre-clinical evaluations against undesired pulmonary and cardiovascular effects. In clinical trials, 2 was found to exhibit a pharmacokinetic half-life (T1/2) longer than that of 1, as well as a reduced formation of the phosphate metabolite that is required for activity against S1P1. Read More

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http://dx.doi.org/10.1021/acs.jmedchem.8b01695DOI Listing
February 2019

Immune thrombocytopenia in alemtuzumab-treated MS patients: Incidence, detection, and management.

Mult Scler 2019 Feb 20:1352458518816612. Epub 2019 Feb 20.

Department of Haematology, University Hospitals Leuven, Leuven, Belgium.

Background:: Alemtuzumab is a highly effective therapy for relapsing-remitting multiple sclerosis (RRMS), and immune thrombocytopenia (ITP) has been identified as a risk.

Objective:: To examine ITP incidence, treatment, and outcomes during the clinical development of alemtuzumab for RRMS and discuss postmarketing experience outside clinical trials.

Methods:: CAMMS223 and Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) I and II investigated two annual courses of alemtuzumab 12 mg (or 24 mg in CAMMS223/CARE-MS II) versus subcutaneous interferon beta-1a three times per week. Read More

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http://dx.doi.org/10.1177/1352458518816612DOI Listing
February 2019

Evaluation of body image perception in multiple sclerosis patients without neurological deficit.

Ideggyogy Sz 2019 Jan;72(1-2):49-54

Department of Neurology, Sakarya University, Sakarya Education and Research Hospital, Sakarya, Turkey.

Background And Purpose: There is a lack of research on the association between body image perception (BIP) and multiple sclerosis (MS). The aim of this study was to evaluate BIP in MS patients and its correlation with depression, anxiety, duration of the disease, and sociodemographic characteristics of the patients.

Methods: Fifty patients with MS who applied to our outpatient clinic were examined. Read More

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http://dx.doi.org/10.18071/https://doi.org/10.18071/isz.71.0049DOI Listing
January 2019

The value of anti-JCV antibody index assessment in multiple sclerosis patients treated with natalizumab with respect to demographic, clinical and radiological findings.

Mult Scler Relat Disord 2019 Feb 14;30:187-191. Epub 2019 Feb 14.

Department of Neurology, University Hospital Brno, Czech Republic; Faculty of Medicine, Masaryk University, Brno, Czech Republic. Electronic address:

Background: Natalizumab-related progressive multifocal leukoencephalopathy (PML) is associated with the presence of anti-John Cunningham virus (JCV) antibodies. The aim of this investigation was to evaluate the long-term stability of anti-JCV antibody serum levels and their relation to various demographic, clinical and radiological characteristics in patients suffering from multiple sclerosis (MS).

Methods: Seventy-eight relapsing-remitting MS patients treated with natalizumab and evaluated for the presence of serum anti-JCV antibodies over a time period of 1-6 years (3-11 samples) were included in the study. Read More

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http://dx.doi.org/10.1016/j.msard.2019.02.019DOI Listing
February 2019

Potential mechanisms of action related to the efficacy and safety of cladribine.

Mult Scler Relat Disord 2019 Feb 14;30:176-186. Epub 2019 Feb 14.

BartsMS, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, United Kingdom; Clinical Board:Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London E1 1BB, United Kingdom.

Oral cladribine is a novel treatment for relapsing multiple sclerosis (MS). This appears to be a semi-selective immune-reconstitution therapy that induces long-term therapy from short treatment cycles. It has a relatively good safety profile that currently does not require extensive monitoring associated with some continuous immunosuppressive and relatively non-selective immune reconstitution therapies. Read More

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http://dx.doi.org/10.1016/j.msard.2019.02.018DOI Listing
February 2019

Associations of demographic and clinical factors with depression over 2.5-years in an international prospective cohort of people living with MS.

Mult Scler Relat Disord 2019 Feb 11;30:165-175. Epub 2019 Feb 11.

Neuroepidemiology Unit, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.

Background: Depression is highly prevalent among people with MS, and determinants thereof would be useful.

Objectives: We examined the relationship of demographic and clinical factors with positive depression-screen and change in depression over 2.5 years in people with MS. Read More

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http://dx.doi.org/10.1016/j.msard.2019.02.014DOI Listing
February 2019

Angiopoietin-like proteins in multiple sclerosis.

J Neuroimmunol 2019 Feb 15;330:31-34. Epub 2019 Feb 15.

Division of Neurology, Department of Medicine, Amiri Hospital, Kuwait.

Angiopoietin-like proteins (ANGPTLs) are a group of proteins with functions in lipid metabolism, angiogenesis, and inflammation. Here, we investigated their involvement in multiple sclerosis (MS) progression and response to treatment in 100 MS patients and 77 healthy controls. ANGPTLs significantly associated with MS progression and response to therapy. Read More

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http://dx.doi.org/10.1016/j.jneuroim.2019.02.006DOI Listing
February 2019

VLA-2 blockade in vivo by vatelizumab induces CD4+FoxP3+ regulatory T cells.

Int Immunol 2019 Feb 19. Epub 2019 Feb 19.

Clinic of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.

Integrin α2β1, also known as Very Late Antigen (VLA)-2, is a collagen-binding molecule expressed constitutively on platelets. Vatelizumab, a monoclonal antibody targeting the α2 subunit (CD49b) of VLA-2, was recently investigated for its safety and efficacy during a Phase 2 clinical study in multiple sclerosis patients, as integrin-mediated collagen binding at the site of inflammation is central to a number of downstream pro-inflammatory events. In the course of this study, we could show that VLA-2 is expressed ex vivo on platelets, platelet-T-cell aggregates, as well as a small population of highly activated memory T cells. Read More

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https://academic.oup.com/intimm/advance-article/doi/10.1093/
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http://dx.doi.org/10.1093/intimm/dxz018DOI Listing
February 2019
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Peripheral CD39-expressing T regulatory cells are increased and associated with relapsing-remitting multiple sclerosis in relapsing patients.

Sci Rep 2019 Feb 19;9(1):2302. Epub 2019 Feb 19.

Instituto de Biomedicina de Sevilla, IBiS (Universidad de Sevilla, HUVR, Junta de Andalucía, CSIC), Seville, Spain.

CD39, an ectonucleotidase that hydrolyses pro-inflammatory ATP, is a marker of highly active and suppressive T regulatory cells (Tregs). Although CD39 has a role in Treg suppression and might be important in the control of neuroinflammation in relapsing-remitting multiple sclerosis (RR-MS), to date, there are contradictory reports concerning the Tregs expression of CD39 in RR-MS patients. Thus, our objectives were to assess the activity and expression of CD39, especially in Tregs from peripheral blood mononuclear cells (PBMCs) of relapsing RR-MS patients compared with control subjects and to evaluate the association of CD39+ Tregs with disability and the odds of RR-MS. Read More

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http://www.nature.com/articles/s41598-019-38897-w
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http://dx.doi.org/10.1038/s41598-019-38897-wDOI Listing
February 2019
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Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis.

J Neurol Neurosurg Psychiatry 2019 Feb 19. Epub 2019 Feb 19.

Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia

Objective: To investigate whether lipid-related or body mass index (BMI)-related common genetic polymorphisms modulate the associations between serum lipid levels, BMI and disability progression in multiple sclerosis (MS).

Methods: The association between disability progression (annualised Expanded Disability Status Scale (EDSS) change over 5 years, ΔEDSS) and lipid-related or BMI-related genetic polymorphisms was evaluated in a longitudinal cohort (n=184), diagnosed with MS. We constructed a cumulative genetic risk score (CGRS) of associated polymorphisms (p<0. Read More

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http://dx.doi.org/10.1136/jnnp-2018-319870DOI Listing
February 2019

Trigeminal neuralgia secondary to multiple sclerosis: from the clinical picture to the treatment options.

J Headache Pain 2019 Feb 19;20(1):20. Epub 2019 Feb 19.

Department of Human Neurosciences, Sapienza University, Viale Università 30, 00185, Rome, Italy.

Background: Trigeminal neuralgia is one of the most characteristic and difficult to treat neuropathic pain conditions in patients with multiple sclerosis. The present narrative review addresses the current evidence on diagnostic tests and treatment of trigeminal neuralgia secondary to multiple sclerosis.

Methods: We searched for relevant papers within PubMed, EMBASE and the Cochrane Database of Systematic Reviews, taking into account publications up to December 2018. Read More

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http://dx.doi.org/10.1186/s10194-019-0969-0DOI Listing
February 2019

Setwise comparison: efficient fine-grained rating of movement videos using algorithmic support - a proof of concept study.

Disabil Rehabil 2019 Feb 20:1-7. Epub 2019 Feb 20.

a Department of Neurology , Inselspital, Bern University Hospital, University of Bern , Bern , Switzerland.

Purpose: Clinical ordinal rating scales of movements, e.g., the Expanded Disability Status Scale, have poor intra- and interrater reliability, are insensitive to subtle differences and result in coarse-grained ratings compared to relative comparative rating methods. Read More

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http://dx.doi.org/10.1080/09638288.2018.1563832DOI Listing
February 2019

New Insights on the Nutrition Status and Antioxidant Capacity in Multiple Sclerosis Patients.

Nutrients 2019 Feb 18;11(2). Epub 2019 Feb 18.

Department of Neurology, Ziv Medical Center, Zefat 1311001, Israel.

Background: Multiple sclerosis (MS) is a multifactorial disease with unknown etiology. It is assumed to result from interplay between genetic and environmental factors, including nutrition. We hypothesized that there are differences in nutritional parameters between MS patients and healthy controls. Read More

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http://dx.doi.org/10.3390/nu11020427DOI Listing
February 2019
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Brain Aging and Gut⁻Brain Axis.

Authors:
M Hasan Mohajeri

Nutrients 2019 Feb 18;11(2). Epub 2019 Feb 18.

Department of human medicine, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.

In the last decade, the microbiome in general and the gut microbiome in particular have been associated not only to brain development and function, but also to the pathophysiology of brain aging and to neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), depression, or multiple sclerosis (MS) [... Read More

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http://dx.doi.org/10.3390/nu11020424DOI Listing
February 2019

Psychometric properties of the PHQ-9 depression scale in people with multiple sclerosis: A systematic review.

PLoS One 2019 19;14(2):e0197943. Epub 2019 Feb 19.

Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.

Background: Depression affects approximately 25% of people with MS (pwMS) at any given time. It is however under recognised in clinical practice, in part due to a lack of uptake for brief assessment tools and uncertainty about their psychometric properties. The 9-item Patient Health Questionnaire (PHQ-9) is an attractive candidate for this role. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197943PLOS
February 2019

Impaired Thermoregulatory Function during Dynamic Exercise in Multiple Sclerosis.

Med Sci Sports Exerc 2019 Mar;51(3):395-404

Applied Physiology and Wellness, Southern Methodist University, Dallas, TX.

Introduction: Impairments in sudomotor function during passive whole-body heating have been reported in multiple sclerosis (MS), a demyelinating disease of the CNS that disrupts autonomic function. However, the capability of the thermoregulatory system to control body temperature during exercise has never been assessed in MS. Thus, the aim of the present study was to test the hypothesis that thermoregulatory function is impaired in MS patients compared with healthy controls (CON) exercising at similar rates of metabolic heat production. Read More

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http://dx.doi.org/10.1249/MSS.0000000000001821DOI Listing

Nasal delivery of Fasudil-modified immune cells exhibits therapeutic potential in experimental autoimmune encephalomyelitis.

CNS Neurosci Ther 2019 Feb 18. Epub 2019 Feb 18.

Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China.

Aim: Multiple sclerosis (MS) is a relapsing-remitting inflammatory demyelinating disease that requires long-term treatment. Although Rho kinase inhibitor Fasudil shows good therapeutic effect in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, certain side effects may limit its clinical use. This study aimed at observing the therapeutic potential of Fasudil-modified encephalitogenic mononuclear cells (MNCs) via nasal delivery in EAE and exploring possible mechanisms of action. Read More

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http://dx.doi.org/10.1111/cns.13111DOI Listing
February 2019

Functional deficiency in endogenous interleukin-1 receptor antagonist in patients with febrile infection-related epilepsy syndrome (FIRES).

Ann Neurol 2019 Feb 18. Epub 2019 Feb 18.

Department of Neurology, Mayo Clinic, Rochester, MN, USA, 55905.

Objectives: We recently reported successful treatment of a child with febrile infection-related epilepsy syndrome (FIRES), a subtype of new-onset refractory status epilepticus (NORSE), with the recombinant interleukin-1 (IL1) receptor antagonist (IL1RA) anakinra. On this basis, we tested whether endogenous IL1RA production or function is deficient in FIRES patients.

Methods: Levels of IL1β and IL1RA were measured in serum and CSF. Read More

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http://dx.doi.org/10.1002/ana.25439DOI Listing
February 2019

Passive transfer of allergic encephalomyelitis in rats: a tool for drug mechanism studies and detecting late-acting immunosuppressants.

Inflammopharmacology 2019 Feb 16. Epub 2019 Feb 16.

Department of Medicine, University of California, Los Angeles, CA, 90024, USA.

1. A strategy is described for evaluating drugs against different phases in the development of an auto allergic disease, experimental allergic encephalomyelitis. It is based on a cell transfer technique whereby the disease is passively transferred with lymphoid cells from actively immunized donor rats to normal syngeneic rats = passive recipients. Read More

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http://dx.doi.org/10.1007/s10787-019-00565-wDOI Listing
February 2019

MR findings of uterine PEComa in patients with tuberous sclerosis: report of two cases.

Abdom Radiol (NY) 2019 Feb 18. Epub 2019 Feb 18.

Department of Radiology, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki, 305-8576, Japan.

Tuberous sclerosis complex (TSC), a rare autosomal dominant neurocutaneous disorder, is characterized by the presence of benign congenital tumors in multiple organs. Neoplasms with perivascular epithelioid cell differentiation (PEComas), including angiomyolipoma (AML) and lymphangioleiomyomatosis (LAM), can occur in association with TSC. This report describes two cases of uterine PEComas presenting characteristic MR imaging features reflecting pathological findings. Read More

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http://dx.doi.org/10.1007/s00261-019-01918-3DOI Listing
February 2019

Multi-database study of multiple sclerosis: identification, validation and description of MS patients in two countries.

J Neurol 2019 Feb 18. Epub 2019 Feb 18.

Boston Collaborative Drug Surveillance Program, Lexington, MA, USA.

Objective: To describe the resources and methods used to identify and validate multiple sclerosis (MS) and match non-MS patients in each of the two databases, and to characterize their demographics, comorbidities and concomitant medications.

Methods: This study was conducted in two separate electronic medical databases, the United States Department of Defense (DOD) military health care system and the United Kingdom's Clinical Practice Research Datalink (CPRD) GOLD. We identified patients with a first recorded diagnosis of MS in 2001-2016 (CPRD) or 2004-2017 (DOD) and matched non-MS patients using algorithms appropriate to each database. Read More

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http://dx.doi.org/10.1007/s00415-019-09238-8DOI Listing
February 2019

Nrf2/ARE Pathway Modulation by Dietary Energy Regulation in Neurological Disorders.

Front Pharmacol 2019 4;10:33. Epub 2019 Feb 4.

Laboratory of Neuroendocrinopharmacology and Immunomodulation, Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil.

Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of an array of enzymes with important detoxifying and antioxidant functions. Current findings support the role of high levels of oxidative stress in the pathogenesis of neurological disorders. Given the central role played by Nrf2 in counteracting oxidative damage, a number of studies have targeted the modulation of this transcription factor in order to confer neuroprotection. Read More

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http://dx.doi.org/10.3389/fphar.2019.00033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369171PMC
February 2019

Prodromal symptoms might vary between multiple sclerosis subtypes.

Authors:
Rebecca Kelsey

Nat Rev Neurol 2019 Feb 18. Epub 2019 Feb 18.

Nature Reviews Neurology, .

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http://dx.doi.org/10.1038/s41582-019-0150-zDOI Listing
February 2019

Primary ocular presentation of tuberous sclerosis - A case report.

Indian J Ophthalmol 2019 Mar;67(3):433-435

Department of Ophthalmology, Christian Medical College, Vellore, Tamil Nadu, India.

A 25-year-old man presented with decreased vision in the left eye with hypopigmented elevated subretinal lesion over the optic disk with abnormal vasculature, subretinal and retinal hemorrhages, and fluid in the macula. An area of high spike over the disk with corresponding orbital shadowing was seen on B scan ultrasonography. Fundus fluorescein angiography revealed abnormal vasculature. Read More

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http://dx.doi.org/10.4103/ijo.IJO_925_18DOI Listing

Assessment of expression of RELN signaling pathway in multiple sclerosis patients.

Immunobiology 2019 Feb 12. Epub 2019 Feb 12.

Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. Nearly 85% of MS patients are recognized with relapsing-remitting MS (RRMS), a typical clinical course of disease which is distinguished by several episodes of relapses, separated by remissions of neurological impairment. Failure of repair mechanisms is a main factor in progression of neurological dysfunction in MS. Read More

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http://dx.doi.org/10.1016/j.imbio.2019.02.007DOI Listing
February 2019

Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer's disease.

J Neuroinflammation 2019 Feb 18;16(1):44. Epub 2019 Feb 18.

Neurology Department, Fondazione Istituto Giuseppe Giglio, Cefalù, PA, Italy.

Background: Aβ peptide abnormal production is associated with the development and maintenance of neuroinflammation and oxidative stress in brains from Alzheimer disease (AD) patients. Suppression of neuroinflammation may then represent a suitable therapeutic target in AD. We evaluated the efficacy of IFNβ1a in attenuating cognitive impairment and inflammation in an animal model of AD. Read More

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http://dx.doi.org/10.1186/s12974-019-1417-4DOI Listing
February 2019

Targeting the S1P receptor signaling pathways as a promising approach for treatment of autoimmune and inflammatory diseases.

Pharmacol Res 2019 Feb 15. Epub 2019 Feb 15.

Institute of Pharmacology, University of Bern, Inselspital INO-F, CH-3010 Bern, Switzerland. Electronic address:

The past two decades of intense research have revealed a key role of the sphingolipid molecule sphingosine 1-phosphate (S1P) in regulating multiple physiological and pathophysiological processes including cell proliferation and survival, cell migration, inflammatory mediator synthesis and tissue remodeling. S1P mainly acts through five high-affinity G protein-coupled S1P receptors, which are ubiquitously expressed and mediate a complex network of signaling in a cell type dependent manner. S1P receptors have become an attractive pharmacological target to interfere with S1P-mediated cellular responses, which contribute to various autoimmune and inflammatory diseases. Read More

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http://dx.doi.org/10.1016/j.phrs.2019.02.009DOI Listing
February 2019

Clinical Outcomes of Escalation vs Early Intensive Disease-Modifying Therapy in Patients With Multiple Sclerosis.

JAMA Neurol 2019 Feb 18. Epub 2019 Feb 18.

Institute of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.

Importance: Uncertainty remains about how aggressively to treat early multiple sclerosis. High-efficacy disease-modifying therapies (DMTs) are often reserved for individuals expressing poor prognostic features at baseline.

Objective: To analyze long-term outcomes in a population-based cohort according to initial treatment strategy. Read More

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http://dx.doi.org/10.1001/jamaneurol.2018.4905DOI Listing
February 2019

Methionine Sulfoxide Reductase-B3 Risk Allele Implicated in Alzheimer's Disease Associates with Increased Odds for Brain Infarcts.

J Alzheimers Dis 2019 Feb 11. Epub 2019 Feb 11.

Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA.

Genome-wide association studies identified a single nucleotide polymorphism (SNP) in the MSRB3 gene encoding Methionine Sulfoxide Reductase-B3 (MsrB3) to be associated with the risk for low hippocampal volume and late onset Alzheimer's disease (AD). Subsequently, we identified AD-associated abnormal patterns of neuronal and vascular MsrB3 expression in postmortem hippocampi. The present study investigated the relationship between the MSRB3 SNP rs61921502, G (minor/risk allele) and MRI measures of brain injury including total brain volume, hippocampal volume, and white matter hyperintensities using linear regression models; the presence of brain infarcts using logistic regression models; and the incidence of stroke, dementia, and AD using Cox proportional hazards models in 2,038 Framingham Heart Study Offspring participants with MRI administered close to examination cycle 7 (1998-2001). Read More

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http://dx.doi.org/10.3233/JAD-180977DOI Listing
February 2019

Interference of High Dose Biotin Supplementation with Thyroid Parameters in Immunoassays Utilizing the Interaction between Streptavidin and Biotin: a Case Report and Review of Current Literature.

Clin Lab 2019 Jan;65(1)

Background: Automated immunoassays utilizing the interaction between streptavidin and biotin are widely used. Nonetheless, biotin remains an often overlooked confounder.

Methods: We report the case of a 54-year-old female patient with progressive multiple sclerosis and Hashimoto's thyroiditis who presented herself for a follow-up. Read More

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http://dx.doi.org/10.7754/Clin.Lab.2018.180637DOI Listing
January 2019

Role of immune-pineal axis in neurodegenerative diseases, unraveling novel hybrid dark hormone therapies.

Heliyon 2019 Jan 1;5(1):e01190. Epub 2019 Feb 1.

Department of Research, California Institute of Behavioral Neurosciences and Psychology, 4751, Mangels Boulevard, Fairfield, 94534, CA, USA.

The anti-oxidant effects of melatonin and the immune-pineal axis are well established. However, how they play a role in the pathogenesis of neurodegenerative diseases is not well elucidated. A better understanding of this neuro-immuno-endocrinological link can help in the development of novel therapies with higher efficacy to alleviate symptomatology, slow disease progression and improve the quality of life. Read More

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http://dx.doi.org/10.1016/j.heliyon.2019.e01190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360340PMC
January 2019

Enduring Clinical Value of Copaxone® (Glatiramer Acetate) in Multiple Sclerosis after 20 Years of Use.

Authors:
Daniel R Wynn

Mult Scler Int 2019 15;2019:7151685. Epub 2019 Jan 15.

Director, Clinical Research; Consultants in Neurology, Multiple Sclerosis Center, Northbrook, IL, USA.

Multiple sclerosis (MS) is a chronic progressive neurodegenerative demyelinating disease affecting the central nervous system. Glatiramer acetate (GA; Copaxone®) was the first disease-modifying treatment (DMT) for MS successfully tested in humans (1977) and was approved by the US Food and Drug Administration in December 1996. Since then, there have been numerous developments in the MS field: advances in neuroimaging allowing more rapid and accurate diagnosis; the availability of a range of DMTs including immunosuppressant monoclonal antibodies and oral agents; a more holistic approach to treatment by multidisciplinary teams; and an improved awareness of the need to consider a patient's preferences and patient-reported outcomes such as quality of life. Read More

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http://dx.doi.org/10.1155/2019/7151685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350531PMC
January 2019

Sjögren's syndrome and systemic lupus erythematosus: links and risks.

Open Access Rheumatol 2019 29;11:33-45. Epub 2019 Jan 29.

Rheumatology Division, Hospital das Clinicas, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil,

Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) may coexist, and they are chronic complex disorders, with an autoimmune background, multifactorial etiology, multiple circulating autoantibodies, and variable prognosis. The prominent feature of SS is the impairment of the lacrimal and salivary glands leading to sicca symptoms. This disease may be classified as primary Sjögren's syndrome (pSS), or secondary Sjögren's syndrome (sSS) since it is often associated to other autoimmune disorders, principally SLE, rheumatoid arthritis, and systemic sclerosis. Read More

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http://dx.doi.org/10.2147/OARRR.S167783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357904PMC
January 2019

Diverse Chemical Scaffolds Enhance Oligodendrocyte Formation by Inhibiting CYP51, TM7SF2, or EBP.

Cell Chem Biol 2019 Jan 31. Epub 2019 Jan 31.

Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Electronic address:

Small molecules that promote oligodendrocyte formation have been identified in "drug repurposing" screens to nominate candidate therapeutics for diseases in which myelin is lost, including multiple sclerosis. We recently reported that many such molecules enhance oligodendrocyte formation not by their canonical targets but by inhibiting a narrow range of enzymes in cholesterol biosynthesis. Here we identify enhancers of oligodendrocyte formation obtained by screening a structurally diverse library of 10,000 small molecules. Read More

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http://dx.doi.org/10.1016/j.chembiol.2019.01.004DOI Listing
January 2019

Development of a highly sensitive fluorescence probe for peptidyl arginine deiminase (PAD) activity.

Bioorg Med Chem Lett 2019 Jan 25. Epub 2019 Jan 25.

Graduate School of Pharmaceutical Science, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi, Japan. Electronic address:

Peptidyl arginine deiminases (PADs) catalyze the post-translational deimination of arginine residues to citrulline residues. Aberrant levels of PAD activity are associated with various diseases, such as rheumatoid arthritis, Alzheimer's disease, and multiple sclerosis, so there is a need for simple and convenient high-throughput screening systems to discover PAD inhibitors as candidate therapeutic agents. Here, we report a highly sensitive off/on-type fluorescence probe for PAD activity based on the donor-excited photoinduced electron transfer (d-PeT) mechanism, utilizing the specific cycloaddition reaction between the benzil group of the probe and the ureido group of the PAD product, citrulline, under acidic conditions. Read More

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http://dx.doi.org/10.1016/j.bmcl.2019.01.032DOI Listing
January 2019

SHARQnet - Sophisticated harmonic artifact reduction in quantitative susceptibility mapping using a deep convolutional neural network.

Z Med Phys 2019 Feb 14. Epub 2019 Feb 14.

Centre for Advanced Imaging, The University of Queensland, Building 57 of University Dr, St Lucia, QLD 4072, Brisbane, Australia.

Quantitative susceptibility mapping (QSM) reveals pathological changes in widespread diseases such as Parkinson's disease, Multiple Sclerosis, or hepatic iron overload. QSM requires multiple processing steps after the acquisition of magnetic resonance imaging (MRI) phase measurements such as unwrapping, background field removal and the solution of an ill-posed field-to-source-inversion. Current techniques utilize iterative optimization procedures to solve the inversion and background field correction, which are computationally expensive and lead to suboptimal or over-regularized solutions requiring a careful choice of parameters that make a clinical application of QSM challenging. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09393889183016
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http://dx.doi.org/10.1016/j.zemedi.2019.01.001DOI Listing
February 2019
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Validity of a multi-domain computerized cognitive assessment battery for patients with multiple sclerosis.

Mult Scler Relat Disord 2019 Jan 30;30:154-162. Epub 2019 Jan 30.

South Shore Neurologic Associates, 77 Medford Avenue, Patchogue, NY 11772, USA. Electronic address:

Background: Computerized cognitive batteries may facilitate the integration of neuropsychological assessments into routine clinical care of patients with multiple sclerosis (PwMS).

Objective: To assess the construct and criterion validity of a computerized, multi-domain cognitive assessment battery (CAB, NeuroTrax) in MS.

Methods: 81 PwMS and 15 healthy controls (HC) completed the CAB and a set of traditional neuropsychological tests recommended for MS on the same day. Read More

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http://dx.doi.org/10.1016/j.msard.2019.01.051DOI Listing
January 2019
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Clinical and MRI correlates of CSF neurofilament light chain levels in relapsing and progressive MS.

Mult Scler Relat Disord 2019 Feb 5;30:149-153. Epub 2019 Feb 5.

Department of Neurology, University of Campinas (UNICAMP), Campinas, Brazil.

Backgound: A major aim in MS field has been the search for biomarkers that enable accurate detection of neuronal damage. Besides MRI, recent studies have shown that neuroaxonal damage can also be tracked by neurofilament detection. Nevertheless, before widespread implementation, a better understanding of the principal contributors for this biomarker is of paramount importance. Read More

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http://dx.doi.org/10.1016/j.msard.2019.02.004DOI Listing
February 2019

Effect of dosage reduction on peripheral blood lymphocyte count in patients with multiple sclerosis receiving long-term fingolimod therapy.

Authors:
Kazuya Takahashi

J Clin Neurosci 2019 Feb 13. Epub 2019 Feb 13.

Department of Neurology, Hokuriku Brain and Neuromuscular Disease Center, National Hospital Organization Iou Hospital, Kanazawa, Japan. Electronic address:

Of the 19 cases of fingolimod-associated progressive multifocal leukoencephalopathy (PML) reported worldwide by the end of 2017, 4 cases were from Japan. This may indicate that fingolimod sensitivity is higher in the Japanese population than in the western population because the fingolimod dosage used for the prevention of multiple sclerosis (MS) is the same in both populations. Therefore, the laboratory data of nine patients with MS receiving fingolimod treatment for more than 2 years were retrospectively collected. Read More

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http://dx.doi.org/10.1016/j.jocn.2019.01.034DOI Listing
February 2019

Prolonged cortical silent period is related to poor fitness and fatigue, but not tumor necrosis factor, in Multiple Sclerosis.

Clin Neurophysiol 2019 Feb 4;130(4):474-483. Epub 2019 Feb 4.

Recovery and Performance Laboratory, Faculty of Medicine, L.A. Miller Centre, Memorial University of Newfoundland, St. John's, NL, Canada. Electronic address:

Objective: Poor fitness among people with Multiple Sclerosis (MS) aggravates disease symptoms. Whether low fitness levels accompany brain functioning changes is unknown.

Methods: MS patients (n = 82) completed a graded maximal exercise test, blood was drawn, and transcranial magnetic stimulation determined resting and active motor thresholds, motor evoked potential latency, and cortical silent period (CSP). Read More

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http://dx.doi.org/10.1016/j.clinph.2018.12.015DOI Listing
February 2019
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Trial of intrathecal rituximab in progressive multiple sclerosis patients with evidence of leptomeningeal contrast enhancement.

Mult Scler Relat Disord 2019 Feb 11;30:136-140. Epub 2019 Feb 11.

Department of Neurology, Johns Hopkins University School of Medicine, 600 N Wolfe St, Pathology 627, Baltimore, MD 21287, USA.

Background: Leptomeningeal inflammation is associated with increased cortical damage and worse clinical outcomes in MS. It may be detected on contrast-enhanced T2-FLAIR imaging as focal leptomeningeal contrast-enhancement (LME).

Objective: To assess the safety of intrathecal (IT) rituximab in progressive MS (PMS) and to assess its effects on LME and CSF biomarkers. Read More

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http://dx.doi.org/10.1016/j.msard.2019.02.013DOI Listing
February 2019
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Barriers against a successful MS treatment: The importance of effectiveness beyond efficacy.

Mult Scler Relat Disord 2019 Feb 7;30:129-135. Epub 2019 Feb 7.

Neurology Department, Hospital Italiano y Español de La Plata, La Plata, Argentina.

Current multiple sclerosis (MS) therapeutic options have significantly increased treatment algorithm complexity. This urges physicians to take into account multiple factors in the decision-making process and make an even more thorough analysis of the risk-benefit balance. We carried out a descriptive review aiming to assess some factors that endanger the proper MS treatment fulfillment, focusing mainly on Latin American countries. Read More

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http://dx.doi.org/10.1016/j.msard.2019.01.056DOI Listing
February 2019
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Increased cerebrospinal fluid neurofilament light chain in central nervous system inflammatory demyelinating disease.

Mult Scler Relat Disord 2019 Feb 8;30:123-128. Epub 2019 Feb 8.

Navy Clinical College, Anhui Medical University, Hefei, 230032 Anhui, China; Department of Neurology, The Sixth Medical Centre, Chinese People's Liberation Army General Hospital, Beijing, 100048 China. Electronic address:

Background: Central nervous system (CNS) inflammatory demyelinating disease (IDD) is an immune-mediated disease that is pathologically characterized by demyelination and inflammatory infiltration in the CNS and includes clinically isolated syndrome (CIS), multiple sclerosis (MS), and neuromyelitis optica spectrum disorders (NMOSD). IDD is usually characterized by variable symptoms, multivariate imaging, uncertain reactions to treatment, and a variable prognosis, which makes it difficult to diagnose early. In recent years, the role of the neurofilament light chain (NFL), an axonal injury biomarker, in IDD has become increasingly important. Read More

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http://dx.doi.org/10.1016/j.msard.2019.02.009DOI Listing
February 2019
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Foxp3+ regulatory T cells expression in neuromyelitis optica spectrum disorders.

Mult Scler Relat Disord 2019 Jan 30;30:114-118. Epub 2019 Jan 30.

Department of Neurology and the Multiple Sclerosis Center, the Agnes-Ginges Center for Neurogenetics, Hadassah- Medical Center, Hebrew University, Ein Karem, P.O.B. 12000, Jerusalem 91120, Israel. Electronic address:

Background: Alterations in the frequency or function of regulatory T cells (Tregs), which play a critical role in the maintenance of peripheral immune tolerance, are known to be involved in the pathogenesis of several autoimmune diseases. Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune inflammatory diseases of the central nervous system (CNS), of which the etiology and mechanisms underlying its development are not completely understood. Although there is increasing evidence for the involvement of effector T cells in NMOSD, no data are available regarding the role of Tregs in its pathogenesis. Read More

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http://dx.doi.org/10.1016/j.msard.2019.01.047DOI Listing
January 2019
2 Reads

Acute multiple sclerosis lesion pathology does not predict subsequent clinical course-a biopsy study.

Ir J Med Sci 2019 Feb 15. Epub 2019 Feb 15.

Department of Neuropathology, Beaumont Hospital, Beaumont Road, Dublin, Ireland.

Background: Knowledge of the clinical outcome in tumefactive demyelination remains limited.

Aims: This study aims to characterise the natural history of biopsy-proven, pathogen-free, cerebral demyelination in an adult Irish population.

Methods: We identified all patients with biopsy-proven demyelination in a single neuropathology centre between 1999 and 2017. Read More

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http://dx.doi.org/10.1007/s11845-019-01983-zDOI Listing
February 2019
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Radiomics in multiple sclerosis and neuromyelitis optica spectrum disorder.

Eur Radiol 2019 Feb 15. Epub 2019 Feb 15.

Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.

Objective: To develop and validate an individual radiomics nomogram for differential diagnosis between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD).

Methods: We retrospectively collected 67 MS and 68 NMOSD with spinal cord lesions as a primary cohort and prospectively recruited 28 MS and 26 NMOSD patients as a validation cohort. Radiomic features were extracted from the spinal cord lesions. Read More

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http://dx.doi.org/10.1007/s00330-019-06026-wDOI Listing
February 2019
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The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes.

Nat Commun 2019 Feb 15;10(1):760. Epub 2019 Feb 15.

Institute for Medical Microbiology and Hygiene, Philipps-University Marburg, Marburg, 35043, Germany.

Short-chain fatty acids (SCFAs) have immunomodulatory effects, but the underlying mechanisms are not well understood. Here we show that pentanoate, a physiologically abundant SCFA, is a potent regulator of immunometabolism. Pentanoate induces IL-10 production in lymphocytes by reprogramming their metabolic activity towards elevated glucose oxidation. Read More

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http://dx.doi.org/10.1038/s41467-019-08711-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377655PMC
February 2019
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Health-related quality of life in systemic sclerosis compared with other rheumatic diseases: a cross-sectional study.

Arthritis Res Ther 2019 Feb 15;21(1):61. Epub 2019 Feb 15.

Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.

Background: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by fibrosis of the skin and the involvement of multiple internal organs. Previous studies reported poorer health-related quality of life (HRQoL) in patients with SSc compared with the general population. However, very little is known about how HRQoL in SSc patients compares with that in patients with other systemic autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjogren's syndrome (SjS). Read More

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http://dx.doi.org/10.1186/s13075-019-1842-xDOI Listing
February 2019
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Gut microbiota-dependent CCR9+CD4+ T cells are altered in secondary progressive multiple sclerosis.

Brain 2019 Feb 15. Epub 2019 Feb 15.

Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, Japan.

The mechanism underlying the progression of relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis (SPMS), characterized by accumulating fixed disability, is yet to be fully understood. Although alterations in the gut microbiota have recently been highlighted in multiple sclerosis pathogenesis, the mechanism linking the altered gut environment with the remote CNS pathology remains unclear. Here, we analyse human CD4+ memory T cells expressing the gut-homing chemokine receptor CCR9 and found a reduced frequency of CCR9+ memory T cells in the peripheral blood of patients with SPMS relative to healthy controls. Read More

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http://dx.doi.org/10.1093/brain/awz012DOI Listing
February 2019
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Validation of an algorithm for identifying MS cases in administrative health claims datasets.

Neurology 2019 Feb 15. Epub 2019 Feb 15.

From the Department of Veterans Affairs Post Deployment Health Services (W.J.C., M.T.W.), Multiple Sclerosis Center of Excellence; University of Maryland (W.J.C.), Baltimore; Departments of Internal Medicine and Community Health Sciences (R.A.M., S.L.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Neurology Department (A.L.-G., L.H.C.), Kaiser Permanente Southern California, Los Angeles; Georgetown University School of Medicine (M.T.W.), Washington, DC; University of Colorado (J.C.), Denver; Stanford University School of Medicine (L.M.N.), CA; McKing Consulting Corp (W.E.K., L.W.), Atlanta, GA; Faculty of Medicine (Neurology) and Centre for Brain Health (H.T.), University of British Columbia, Vancouver; College of Pharmacy and Nutrition (C.E.), University of Saskatchewan; Health Quality Council (Saskatchewan) (S.Y.), Saskatoon, Canada; and National Multiple Sclerosis Society (N.G.L.), New York, NY.

Objective: To develop a valid algorithm for identifying multiple sclerosis (MS) cases in administrative health claims (AHC) datasets.

Methods: We used 4 AHC datasets from the Veterans Administration (VA), Kaiser Permanente Southern California (KPSC), Manitoba (Canada), and Saskatchewan (Canada). In the VA, KPSC, and Manitoba, we tested the performance of candidate algorithms based on inpatient, outpatient, and disease-modifying therapy (DMT) claims compared to medical records review using sensitivity, specificity, positive and negative predictive values, and interrater reliability (Youden J statistic) both overall and stratified by sex and age. Read More

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http://dx.doi.org/10.1212/WNL.0000000000007043DOI Listing
February 2019