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Multiple Sclerosis: HELP
Articles from Ontario
Based on 478 articles published since 2008
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These are the 478 published articles about Multiple Sclerosis that originated from Ontario during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13 · 14 · 15 · 16 · 17 · 18 · 19 · 20
1 Guideline Revised Recommendations of the Consortium of MS Centers Task Force for a Standardized MRI Protocol and Clinical Guidelines for the Diagnosis and Follow-Up of Multiple Sclerosis. 2016

Traboulsee, A / Simon, J H / Stone, L / Fisher, E / Jones, D E / Malhotra, A / Newsome, S D / Oh, J / Reich, D S / Richert, N / Rammohan, K / Khan, O / Radue, E-W / Ford, C / Halper, J / Li, D. ·From the Department of Medicine (Neurology) (A.T.), University of British Columbia, Vancouver, Canada t.traboulsee@ubc.ca. · Portland VA Research Foundation and Oregon Health and Sciences University (J.H.S.), Portland, Oregon. · Mellen Center for MS Treatment and Research (L.S.), Cleveland Clinic, Cleveland, Ohio. · Department of Biomedical Engineering, Cleveland Clinic (E.F.). Cleveland, Ohio. · Department of Neurology, University of Virginia (D.E.J.), Charlottesville, Virginia. · Department of Radiology and Biomedical Imaging, Yale University (A.M.), New Haven, Connecticut. · Department of Neurology (S.D.N.), Johns Hopkins School of Medicine, Baltimore, Maryland. · St. Michael's Hospital (J.O.), University of Toronto, Toronto, Ontario, Canada. · Translational Neuroradiology Unit (D.S.R.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. · Biogen Idec (N.R.), Cambridge, Massachusetts. · University of Miami Multiple Sclerosis Center (K.R.), Miami, Florida. · Department of Neurology (O.K.), Wayne State University School of Medicine, Detroit, Michigan. · Department of Radiology (E.-W.R.), University Hospital, Basel, Switzerland. · University of New Mexico Health Science Center (C.F.), Albuquerque, New Mexico. · Consortium of Multiple Sclerosis Centers (J.H.), Hackensack, New Jersey. · Departments of Radiology (D.L.), University of British Columbia, Vancouver, British Columbia Canada. ·AJNR Am J Neuroradiol · Pubmed #26564433.

ABSTRACT: An international group of neurologists and radiologists developed revised guidelines for standardized brain and spinal cord MR imaging for the diagnosis and follow-up of MS. A brain MR imaging with gadolinium is recommended for the diagnosis of MS. A spinal cord MR imaging is recommended if the brain MR imaging is nondiagnostic or if the presenting symptoms are at the level of the spinal cord. A follow-up brain MR imaging with gadolinium is recommended to demonstrate dissemination in time and ongoing clinically silent disease activity while on treatment, to evaluate unexpected clinical worsening, to re-assess the original diagnosis, and as a new baseline before starting or modifying therapy. A routine brain MR imaging should be considered every 6 months to 2 years for all patients with relapsing MS. The brain MR imaging protocol includes 3D T1-weighted, 3D T2-FLAIR, 3D T2-weighted, post-single-dose gadolinium-enhanced T1-weighted sequences, and a DWI sequence. The progressive multifocal leukoencephalopathy surveillance protocol includes FLAIR and DWI sequences only. The spinal cord MR imaging protocol includes sagittal T1-weighted and proton attenuation, STIR or phase-sensitive inversion recovery, axial T2- or T2*-weighted imaging through suspicious lesions, and, in some cases, postcontrast gadolinium-enhanced T1-weighted imaging. The clinical question being addressed should be provided in the requisition for the MR imaging. The radiology report should be descriptive, with results referenced to previous studies. MR imaging studies should be permanently retained and available. The current revision incorporates new clinical information and imaging techniques that have become more available.

2 Editorial Stem Cell Transplantation to Treat Multiple Sclerosis. 2019

Atkins, Harold. ·Ottawa Hospital Blood and Marrow Transplant Program, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada. ·JAMA · Pubmed #30644971.

ABSTRACT: -- No abstract --

3 Editorial Are we in need of NEDA? 2016

Freedman, Mark S. ·Division of Neurology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada mfreedman@toh.on.ca. ·Mult Scler · Pubmed #26552731.

ABSTRACT: -- No abstract --

4 Review Multiple sclerosis and faecal microbiome transplantation: are you going to eat that? 2019

Wing, A C / Kremenchutzky, M. ·1 University of Western Ontario, 339 Windermere Rd, London, ON N6A 5A5, Canada. ·Benef Microbes · Pubmed #30525949.

ABSTRACT: Gut microbiome interaction goes beyond commensal function as vitamin production or support nutrients digestion. It also interplays with the host immune system and may be related to the development of immune-mediated diseases. Multiple sclerosis patients have dysbiosis compared to healthy individuals. But how this relates to disease development and severity is still uncertain. Dietary change including probiotic mixtures or ketogenic regimen has proven to change microbiome in multiple sclerosis (MS) subjects to one similar to healthy controls. However, proof of clinical benefits is lacking. We dissert on current knowledge about immune system and gut bacteria interactions. We discuss faecal microbial transplantation as a potential intervention to ameliorate gut dysbiosis in MS as well as the caveats of a clinical trial design.

5 Review Multiple sclerosis: clinical aspects. 2018

Oh, Jiwon / Vidal-Jordana, Angela / Montalban, Xavier. ·Division of Neurology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. · Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Servei de Neurologia-Neuroinmunologia, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain. ·Curr Opin Neurol · Pubmed #30300239.

ABSTRACT: PURPOSE OF REVIEW: Multiple sclerosis is a chronic, predominantly immune-mediated disease of the central nervous system, and one of the most common causes of neurological disability in young adults globally. This review will discuss the epidemiology, diagnosis, disease course, and prognosis of multiple sclerosis and will focus on recent evidence and advances in these aspects of the disease. RECENT FINDINGS: Multiple sclerosis is increasing in incidence and prevalence globally, even in traditionally low-prevalence regions of the world. Recent revisions have been proposed to the existing multiple sclerosis diagnostic criteria, which will facilitate earlier diagnosis and treatment in appropriate patients. Classifying multiple sclerosis into distinct disease phenotypes can be challenging, and recent refinements have been proposed to clarify existing definitions. The prognosis of multiple sclerosis varies substantially across individual patients, and a combination of clinical, imaging, and laboratory markers can be useful in predicting clinical course and optimizing treatment in individual patients. SUMMARY: A number of recent advances have been made in the clinical diagnosis and prognostication of multiple sclerosis patients. Future research will enable the development of more accurate biomarkers of disease categorization and prognosis, which will enable timely personalized treatment in individual multiple sclerosis patients.

6 Review Exploring the role of physical activity and exercise for managing vascular comorbidities in people with multiple sclerosis: A scoping review. 2018

Ewanchuk, Benjamin W / Gharagozloo, Marjan / Peelen, Evelyn / Pilutti, Lara A. ·Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada. · Program of Immunology, Department of Pediatrics, CR-CHUS, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada. · Neuroimmunology Unit, The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC H2X 0A9, Canada; Department of Neuroscience, Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada. · Interdisciplinary School of Health Sciences, Brain and Mind Research Institute, University of Ottawa, Ottawa, ON K1N 6N5, Canada. Electronic address: lpilutti@uottawa.ca. ·Mult Scler Relat Disord · Pubmed #30216755.

ABSTRACT: INTRODUCTION: Vascular comorbidities are prevalent among people with multiple sclerosis (MS) and have adverse disease-related consequences. In the general population, physical activity (PA) and exercise training have proven beneficial at all levels of vascular disease risk management. People with MS exhibit particularly low rates of PA; therefore, PA represents a modifiable health behavior for potentially managing vascular comorbidity risk in MS, and in turn, reducing disease burden. However, points of evidence justifying such an approach have yet to be summarized. OBJECTIVE: To conduct a scoping review of existing evidence linking PA and exercise training to potential modification of vascular comorbidities and related risk factors in people with MS. METHODS: We searched five electronic databases (PubMed, Ovid MEDLINE, Embase, PsycINFO, and CINAHL Plus) from inception to November 2017, for articles involving relevant vascular comorbidities (obesity, hyperlipidemia, heart disease, hypertension, and diabetes) in people with MS in conjunction with measures of PA, physical fitness, sedentary behavior, or exercise training. Studies were limited to English-language and primary research articles. Data were extracted and summarized by comorbidity type and study design (observational vs. interventional). RESULTS: Our initial search identified 1028 articles; subsequent screening resulted in 34 articles meeting the final inclusion criteria, including both observational (n = 17) and interventional (n = 17) studies. Most of the articles reported on obesity (n = 29), although evidence surrounding hyperlipidemia (n = 5), arterial function and hypertension (n = 5), and diabetes (n = 5) was also identified. Data supporting a beneficial role for PA or exercise training could be drawn from each comorbidity category. Overall, 14 of the 17 observational studies identified (82.4%) reported an association between higher levels of PA or cardiorespiratory fitness, or decreased sedentary behavior, and better function of at least one risk factor related to vascular comorbid conditions in people with MS. The efficacy of exercise training in limiting vascular comorbidity risk and burden was dependent upon intervention type and duration, with 9 of 17 interventional studies (52.9%) reporting improvement in at least one relevant measure of vascular comorbidity in participants with MS. CONCLUSIONS: Evidence points to a potential relationship between PA and exercise and risk factors related to vascular comorbidities in people with MS. PA and exercise training interventions may represent an effective therapeutic strategy for managing vascular comorbidities in people with MS, justifying further investigation.

7 Review Managing Multiple Sclerosis: Treatment Initiation, Modification, and Sequencing. 2018

Freedman, Mark S / Selchen, Daniel / Prat, Alexandre / Giacomini, Paul S. ·1Division of Neurology,Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute,Ottawa,ON,Canada. · 4St. Michael's Hospital,University of Toronto,Toronto,ON,Canada. · 3CRCHUM and Department of Neuroscience, Faculty of Medicine,Université de Montréal,Montréal,QC,Canada. · 2Montreal Neurological Institute,McGill University,Montréal,QC,Canada. ·Can J Neurol Sci · Pubmed #29893652.

ABSTRACT: Recent therapeutic advances in the management of multiple sclerosis (MS) have raised questions about the selection of appropriate patient candidates for various treatments and, if the plan is to move from one treatment to another, the appropriate sequencing of these therapies. The selected approach should provide optimal disease management without limiting future therapeutic options based on safety concerns, and recognize potential future treatments and the possibility of combination therapies. Additional challenges include incorporation of patient needs and preferences into the overall therapeutic approach, in order to ensure optimal outcomes in the short and long term. The objective of this manuscript is to provide an overview of what is currently known regarding the impact of various therapies for MS on future therapeutic choices (sequencing). In this context, we reviewed the available evidence in support of various treatments and, based on the presence of disease activity, suggested a scheme for switching or escalating therapy with the main focus on sequencing of therapeutic approaches.

8 Review The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis. 2018

Morris, Gerwyn / Stubbs, Brendon / Köhler, Cristiano A / Walder, Ken / Slyepchenko, Anastasiya / Berk, Michael / Carvalho, André F. ·Tir Na Nog, Bryn Road Seaside 87, Llanelli, SA152LW, Wales, United Kingdom. · Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, SE5 8AZ, United Kingdom; Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience King's College London, De Crespigny Park, London, SE5 8AF, United Kingdom. · Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil. · Deakin University, The Centre for Molecular and Medical Research, School of Medicine, P.O. Box 291, Geelong, 3220, Australia. · Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, 100 West 5th Street, Suite C124, Hamilton, ON, L8N 3K7, Canada; MiNDS Neuroscience Graduate Program, McMaster University, 1280 Main St. W., Hamilton, ON, Canada. · Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, P.O. Box 291, Geelong, 3220, Australia; Orygen Youth Health Research Centre and the Centre of Youth Mental Health, The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, 3052, Australia; Department of Psychiatry, University of Melbourne, Parkville, 3052, Australia. · Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada. Electronic address: andrefc7@hotmail.com. ·Sleep Med Rev · Pubmed #29759891.

ABSTRACT: Sleep and circadian abnormalities are prevalent and burdensome manifestations of diverse neuro-immune diseases, and may aggravate the course of several neuropsychiatric disorders. The underlying pathophysiology of sleep abnormalities across neuropsychiatric disorders remains unclear, and may involve the inter-play of several clinical variables and mechanistic pathways. In this review, we propose a heuristic framework in which reciprocal interactions of immune, oxidative and nitrosative stress, and mitochondrial pathways may drive sleep abnormalities across potentially neuroprogressive disorders. Specifically, it is proposed that systemic inflammation may activate microglial cells and astrocytes in brain regions involved in sleep and circadian regulation. Activated glial cells may secrete pro-inflammatory cytokines (for example, interleukin-1 beta and tumour necrosis factor alpha), nitric oxide and gliotransmitters, which may influence the expression of key circadian regulators (e.g., the Circadian Locomotor Output Cycles Kaput (CLOCK) gene). Furthermore, sleep disruption may further aggravate oxidative and nitrosative, peripheral immune activation, and (neuro) inflammation across these disorders in a vicious pathophysiological loop. This review will focus on chronic fatigue syndrome, bipolar disorder, and multiple sclerosis as exemplars of neuro-immune disorders. We conclude that novel therapeutic targets exploring immune and oxidative & nitrosative pathways (p.e. melatonin and molecular hydrogen) hold promise in alleviating sleep and circadian dysfunction in these disorders.

9 Review Chronobiological regulation of psychosocial and physiological outcomes in multiple sclerosis. 2018

De Somma, Elisea / Jain, Rajiv W / Poon, Kelvin W C / Tresidder, Kaitlyn A / Segal, Julia P / Ghasemlou, Nader. ·Department of Psychology, York University, Toronto, Ontario, Canada. · Department of Microbiology & Immunology, University of Western Ontario, London, Ontario, Canada. · Hotchkiss Brain Institute, University of Calgary, Alberta, Canada. · Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada. · Department of Biomedical & Molecular Sciences, Queen's University, Kingston, Ontario, Canada. · Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada; Department of Biomedical & Molecular Sciences, Queen's University, Kingston, Ontario, Canada; Department of Anesthesiology & Perioperative Medicine, Queen's University, Kingston, Ontario, Canada. Electronic address: nader.ghasemlou@queensu.ca. ·Neurosci Biobehav Rev · Pubmed #29548931.

ABSTRACT: There is mounting scientific evidence showing the importance of innate biological rhythms on disease onset and progression. Perhaps the most important of these is the circadian rhythm, a cycle of oscillations lasting approximately 24 h. Recent work has shown that circadian rhythms are intrinsically linked to the immune system in a bidirectional fashion, and that disruption of these cycles can contribute to changes in pathology and quality of life (including fatigue, mood, and disability). This is particularly true in diseases of the nervous and immune systems. We review here the current preclinical and clinical literature to highlight interactions between circadian rhythms and multiple sclerosis, as well as its animal model, experimental autoimmune encephalomyelitis. We highlight potential benefits of chronotherapy (the temporal administration of immunomodulatory drugs) in an effort to increase treatment efficacy and reduce the negative side-effects of the drugs that often burden those suffering from the disease.

10 Review Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. 2018

Thompson, Alan J / Banwell, Brenda L / Barkhof, Frederik / Carroll, William M / Coetzee, Timothy / Comi, Giancarlo / Correale, Jorge / Fazekas, Franz / Filippi, Massimo / Freedman, Mark S / Fujihara, Kazuo / Galetta, Steven L / Hartung, Hans Peter / Kappos, Ludwig / Lublin, Fred D / Marrie, Ruth Ann / Miller, Aaron E / Miller, David H / Montalban, Xavier / Mowry, Ellen M / Sorensen, Per Soelberg / Tintoré, Mar / Traboulsee, Anthony L / Trojano, Maria / Uitdehaag, Bernard M J / Vukusic, Sandra / Waubant, Emmanuelle / Weinshenker, Brian G / Reingold, Stephen C / Cohen, Jeffrey A. ·Faculty of Brain Sciences, University College London, London, UK. · Division of Neurology, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · Institute of Healthcare Engineering, University College London, London, UK; Institute of Neurology, University College London, London, UK; Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands. · Neurology Department, Sir Charles Gairdner Hospital, Perth, WA, Australia. · National Multiple Sclerosis Society, New York, NY, USA. · Department of Neurology, Vita-Salute San Raffaele University-Ospedale San Raffaele, Milan, Italy. · Institute for Neurological Research Dr. Raúl Carrea, FLENI, Buenos Aires, Argentina. · Department of Neurology, Medical University of Graz, Graz, Austria. · The Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University-Ospedale San Raffaele, Milan, Italy. · Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada. · Department of Multiple Sclerosis Therapeutics, School of Medicine, Fukushima Medical University, Fukushima, Japan; Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research Institute for Neuroscience, Koriyama, Fukushima, Japan. · Department of Neurology, New York University Langone Medical Center, New York, NY, USA. · Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany. · Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland. · Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, NY, USA. · Departments of Internal Medicine and Community Health Sciences, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada. · Queen Square Multiple Sclerosis Centre, University College London, London, UK. · Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron University Hospital, Barcelona, Spain; Division of Neurology, University of Toronto, St Michael's Hospital, Toronto, ON, Canada. · Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. · Danish Multiple Sclerosis Center, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark. · Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron University Hospital, Barcelona, Spain. · Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada. · Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy. · Department of Neurology, VU University Medical Center, Amsterdam, Netherlands. · Service de neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation, Hôpital Neurologique, Hospices Civils de Lyon, Bron, France; Centre des Neurosciences de Lyon, INSERM 1028 et CNRS UMR5292, Lyon, France; Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Est, Villeurbanne, Auvergne-Rhône-Alpes, France. · Department of Neurology, University of California at San Francisco, San Francisco, CA, USA. · Department of Neurology, Mayo Clinic, Rochester, MN, USA. · Scientific and Clinical Review Associates LLC, Salisbury, CT, USA. · Neurologic Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: cohenj@ccf.org. ·Lancet Neurol · Pubmed #29275977.

ABSTRACT: The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.

11 Review Spinal Cord MRI in Multiple Sclerosis. 2018

Muccilli, Alexandra / Seyman, Estelle / Oh, Jiwon. ·Division of Neurology, St. Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada; Division of Neurology, Centre Hospitalier de L'Université de Montréal, Université de Montréal, 1058 Saint-Denis Street, Montreal, Quebec H2X 3J4, Canada. · Division of Neurology, St. Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada. · Division of Neurology, St. Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada; Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. Electronic address: ohjiw@smh.ca. ·Neurol Clin · Pubmed #29157403.

ABSTRACT: Spinal cord (SC) MRI in multiple sclerosis (MS) has significant usefulness in clinical and investigational settings. Conventional MRI of the SC is used in clinical practice, because it has both diagnostic and prognostic value. A number of advanced, quantitative SC MRI measures that assess the structural and functional integrity of the SC have been evaluated in investigational settings. These techniques have collectively demonstrated usefulness in providing insight into microstructural and functional changes relevant to disability in MS. With further development, these techniques may be useful in clinical trial settings as biomarkers of neurodegeneration and protection, and in day-to-day clinical practice.

12 Review An overview of biosimilars and non-biologic complex drugs in Europe, the United States, and Canada and their relevance to multiple sclerosis. 2017

Gran-Ruaz, Sophia / Mani, Arvind / O'Quinn, Sherry. ·MORSE Consulting Inc, Toronto, ON, Canada. ·Mult Scler · Pubmed #29095099.

ABSTRACT: The advent of biological medicines has significantly transformed the landscapes of many disease spaces and improved the lives of millions around the world. However, the structural complexity and sensitivity of such products result in a high price tag, adding to already financially strained healthcare systems. As these and other expensive complex drugs lose market exclusivity, stakeholders eagerly await the arrival of lower cost alternatives, such as biosimilars and subsequent entry non-biological complex drugs (NBCDs). Nevertheless, stakeholders remain uncertain about key issues which have resulted in heterogeneous reimbursement policies and varying levels of biosimilar uptake and subsequent entry NBCD approval processes between different markets. With the imminent introduction of both subsequent entry NBCDs and biosimilars for multiple sclerosis (MS), it is important to get a better understanding of this new class of products and how healthcare systems have been adapting to their use. This article defines biosimilars and subsequent entry NBCDs and provides an overview of how these products have been introduced in Europe, the United States, and Canada from a regulatory, health technology, and reimbursement perspective. In addition, this article briefly explores the potential impact and outlook of biosimilar and NBCD products related to MS.

13 Review Non-invasive brain stimulation interventions for management of chronic central neuropathic pain: a scoping review protocol. 2017

Chen, Mei Lin / Yao, Lin / Boger, Jennifer / Mercer, Kathryn / Thompson, Benjamin / Jiang, Ning. ·Department of Systems Design Engineering, Faculty of Engineering, University of Waterloo, Waterloo, Canada. · School of Pharmacy, University of Waterloo, Waterloo, Canada. · Department of Optometry and Vision Science, University of Waterloo, Waterloo, Canada. ·BMJ Open · Pubmed #29042375.

ABSTRACT: INTRODUCTION: Pain can affect people regardless of age, gender or ethnicity. Chronic central neuropathic pain (CCNP) is a debilitating condition that affects populations such as stroke survivors, amputees, spinal cord injury patients and patients with multiple sclerosis, with prevalence rates between 30% and 80%. This condition can be caused by a lesion or disease affecting the somatosensory system. CCNP is notoriously drug resistant, and few effective CCNP treatment or management strategies exist. The emergence of non-invasive brain stimulation and neuromodulation techniques provide novel avenues for managing chronic central neuropathic pain. This scoping review aims to systematically identify the methods and effectiveness of non-invasive brain stimulation techniques for treating and managing chronic central neuropathic pain. METHODS AND ANALYSIS: The following databases will be searched systematically: PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Institute of Electric and Electronic Engineers (IEEE), Association of Computing Machinary (ACM) and Scopus. Additional literature will be identified by searching the reference lists of identified studies. Studies will include reviews and original research in both published and grey literatures. Two reviewers will independently screen identified studies for final inclusion. A quantitative analysis on the intervention type, application and efficacy will be synthesised along with a qualitative analysis to describe the effectiveness of each intervention. ETHICS AND DISSEMINATION: No primary data will be collected and hence formal ethics review is not required. The results of the scoping review will be presented at relevant national and international conferences, published in a peer-reviewed journal and provided to the stakeholders with plain language to be posted on their websites. This scoping review will provide a foundation to guide the development of future primary research on non-invasive brain stimulation and CCNP.

14 Review Exercise in patients with multiple sclerosis. 2017

Motl, Robert W / Sandroff, Brian M / Kwakkel, Gert / Dalgas, Ulrik / Feinstein, Anthony / Heesen, Christoph / Feys, Peter / Thompson, Alan J. ·Department of Physical Therapy, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: robmotl@uab.edu. · Department of Physical Therapy, University of Alabama at Birmingham, Birmingham, AL, USA. · Department of Rehabilitation Medicine, VU University Medical Centre, Amsterdam Movement Sciences and Amsterdam Neuroscience, Amsterdam, Netherlands; Department of Physical Therapy and Human Movement Sciences, Northwestern University, Chicago, IL, USA. · Section of Sport Science, Department of Public Health, Aarhus University, Aarhus, Denmark. · Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. · Institute of Neuroimmunology and Department of Neurology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany. · Rehabilitation Research Center, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium. · Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK. ·Lancet Neurol · Pubmed #28920890.

ABSTRACT: Exercise can be a beneficial rehabilitation strategy for people with multiple sclerosis to manage symptoms, restore function, optimise quality of life, promote wellness, and boost participation in activities of daily living. However, this population typically engages in low levels of health-promoting physical activity compared with adults from the general population, a fact which has not changed in the past 25 years despite growing evidence of the benefits of exercise. To overcome this challenge, the main limitations to promoting exercise through the patient-clinician interaction must be addressed. These limitations are the inadequate quality and scope of existing evidence, incomplete understanding of the mechanisms underlying the beneficial effects of exercise in people with multiple sclerosis, and the absence of a conceptual framework and toolkit for translating the evidence into practice. Future research to address those limitations will be essential to inform decisions about the inclusion of exercise in the clinical care of people with multiple sclerosis.

15 Review Cannabinoids for spasticity due to multiple sclerosis or paraplegia: A systematic review and meta-analysis of randomized clinical trials. 2017

da Rovare, Victoria P / Magalhães, Gabriel P A / Jardini, Guilherme D A / Beraldo, Matheus L / Gameiro, Mariel O / Agarwal, Arnav / Luvizutto, Gustavo José / Paula-Ramos, Lucas / Camargo, Samira Esteves Afonso / de Oliveira, Luciane Dias / Bazan, Rodrigo / El Dib, Regina. ·São Paulo State University (Unesp), Botucatu Medical School, São Paulo, Brazil. Electronic address: victoriarovare@gmail.com. · São Paulo State University (Unesp), Botucatu Medical School, São Paulo, Brazil. Electronic address: beelz.magalhaes@gmail.com. · São Paulo State University (Unesp), Botucatu Medical School, São Paulo, Brazil. Electronic address: guilhermejardini@gmail.com. · São Paulo State University (Unesp), Botucatu Medical School, São Paulo, Brazil. Electronic address: beraldoa@hotmail.com. · São Paulo State University (Unesp), Botucatu Medical School, São Paulo, Brazil. Electronic address: marielorsi@gmail.com. · Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada; Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: arnav.mcmaster@gmail.com. · São Paulo State University (Unesp), Department of Neurology, Botucatu Medical School, Brazil. Electronic address: gustavo.luvizutto@uftm.edu.br. · São Paulo State University (Unesp), Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo, Brazil. Electronic address: lucas93paula@hotmail.com.br. · São Paulo State University (Unesp), Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo, Brazil. Electronic address: samira@ict.unesp.br. · São Paulo State University (Unesp), Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo, Brazil. Electronic address: luciane@ict.unesp.br. · São Paulo State University (Unesp), Department of Neurology, Botucatu Medical School, Brazil. Electronic address: bazan.r@terra.com.br. · São Paulo State University (Unesp), Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo, Brazil; São Paulo State University (Unesp), Department of Anesthesiology, São Paulo, Brazil; McMaster Institute of Urology, McMaster University, St. Joseph's Healthcare, Hamilton, Canada. Electronic address: eldib@fmb.unesp.br. ·Complement Ther Med · Pubmed #28917371.

ABSTRACT: OBJECTIVES: Spasticity remains highly prevalent in patients with spinal cord injury and multiple sclerosis. To summarize the effects of cannabinoids compared with usual care, placebo for spasticity due to multiple sclerosis (MS) or paraplegia. METHODS: Searches of MEDLINE, EMBASE, CENTRAL and LILACS to March 2017 were performed to identify randomized controlled trials. The primary outcomes were spasticity and spasm frequency. The criteria were any patient with MS and spasticity affecting upper or lower limbs or both, and that had a confirmed diagnosis of MS based on validated criteria, or however defined by the authors of the included studies. RESULTS: 16 trials including 2597 patients were eligible. Moderate-certainty evidence suggested a non-statistically significant decrease in spasticity (standardized mean difference (SMD) 0.36 [confidential interval (CI) 95% -0.17 to 0.88; p=0.18; I2=88%]), and spasm frequency (SMD 0.04 [CI 95% -0.15 to 0.22]). There was an increase in adverse events such as dizziness (risk ratio (RR) 3.45 [CI 95% 2.71-4.4; p=0.20; I2=23%]), somnolence (RR 2.9 [CI 95% 1.98-4.23; p=0.77; I2=0%]), and nausea (RR 2.25 [CI 95% 1.62-3.13; p=0.83; I2=0%]). CONCLUSIONS: There is moderate certainty evidence regarding the impact of cannabinoids in spasticity (average 0.36 more spasticity; 0.17 fewer to 0.88 more) due to multiple sclerosis or paraplegia, and in adverse events such as dizziness (419 more dizziness/1000 over 19 weeks), somnolence (127 more somnolence/1000 over 19 weeks), and nausea (125 more somnolence/1000 over 19 weeks).

16 Review Five Questions Answered: A Review of Autologous Hematopoietic Stem Cell Transplantation for the Treatment of Multiple Sclerosis. 2017

Atkins, Harold L / Freedman, Mark S. ·The Ottawa Hospital, 501 Smyth Rd., Mailstop 926, Ottawa, Ontario, K1H 8L6, Canada. hatkins@ohri.ca. · The Ottawa Hospital, 501 Smyth Rd., Mailstop 926, Ottawa, Ontario, K1H 8L6, Canada. ·Neurotherapeutics · Pubmed #28822119.

ABSTRACT: Multiple sclerosis (MS) is thought to be an autoimmune disease targeting the central nervous system leading to demyelination, and axonal and neuronal damage, resulting in progressive disability. More intensive therapies such as immunodepletion with hematopoietic stem-cell rescue are being used at a time prior to patients becoming irreversibly disabled. Over the last 15 years, there has been a shift away from using autologous hematopoietic stem-cell transplants (aHSCT) to treat patients with progressive MS, towards treating those with active inflammation and relapses. There is an increasing body of evidence that aHSCT improves all measured MS outcomes, including burden of disease on MRI, clinical relapses, accumulation of disability, and quality of life of patients with active MS not controlled with standard therapy. Importantly, the progression-free survival curves of these patients plateau after the first few years demonstrating the impact that aHSCT has in changing the natural history of MS, potentially freeing patients from the relentless accumulation of disability. Concurrently there has been a reduction in procedure-related mortality. The results of randomized trials will likely spur further development of this field.

17 Review The effect of exercise training in adults with multiple sclerosis with severe mobility disability: A systematic review and future research directions. 2017

Edwards, Thomas / Pilutti, Lara A. ·Department of Kinesiology & Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, USA. · Interdisciplinary School of Health Sciences, University of Ottawa, 200 Lees Avenue, Ottawa, Ontario, Canada K1N 6N5. Electronic address: lpilutti@uottawa.ca. ·Mult Scler Relat Disord · Pubmed #28755682.

ABSTRACT: INTRODUCTION: There is evidence for the benefits of exercise training in persons with multiple sclerosis (MS). However, these benefits have primarily been established in individuals with mild-to-moderate disability (i.e., Expanded Disability Status Scale [EDSS] scores 1.0-5.5), rather than among those with significant mobility impairment. Further, the approaches to exercise training that have been effective in persons with mild-to-moderate MS disability may not be physically accessible for individuals with mobility limitations. Therefore, there is a demand for an evidence-base on the benefits of physically accessible exercise training approaches for managing disability in people with MS with mobility impairment. OBJECTIVE: To conduct a systematic review of the current literature pertaining to exercise training in individuals with multiple sclerosis (MS) with severe mobility disability. METHODS: Four electronic databases (PubMed, EMBASE, OvidMEDLINE, and PsychINFO) were searched for relevant articles published up until October 2016. The review focused on English-language studies that examined the effect of exercise training in people with MS with severe mobility disability, characterized as the need for assistance in ambulation or EDSS score ≥ 6.0. The inclusion criteria involved full-text articles that: (i) included participants with a diagnosis of MS; (ii) included primarily participants with a reported EDSS score ≥ 6.0 and/or definitively described disability consistent with this level of neurological impairment; and (iii) implemented a prospective, structured exercise intervention. Data were analyzed using a descriptive approach and summarized by exercise training modality (conventional or adapted exercise training), and by outcome (disability, physical fitness, physical function, and symptoms and participation). RESULTS: Initially, 1164 articles were identified and after removal of duplicates, 530 articles remained. In total, 512 articles did not meet the inclusion criteria. 19 articles were included in the final review. Five studies examined conventional exercise training (aerobic and resistance training), and thirteen studies examined adapted exercise modalities including body-weight support treadmill training (BWSTT), total-body recumbent stepper training (TBRST), and electrical stimulation cycling (ESAC). Outcomes related to mobility, fatigue, and quality of life (QOL) were most frequently reported. Two of five studies examining conventional resistance exercise training reported significant improvements in physical fitness, physical function, and/or symptomatic and participatory outcomes. Nine of 13 studies examining adapted exercise training reported significant improvements in disability, physical fitness, physical function, and/or symptomatic and participatory outcomes. CONCLUSIONS: There is limited, but promising evidence for the benefits of exercise training in persons with MS with severe mobility disability. Considering the lack of effective therapeutic strategies for managing long-term disability accumulation, exercise training could be considered as an alternative approach. Further research is necessary to optimize the prescription and efficacy of exercise training for adults with MS with severe mobility disability.

18 Review Multiple sclerosis and suicide. 2017

Feinstein, Anthony / Pavisian, Bennis. ·Department of Psychiatry, Sunnybrook Health Sciences Centre and University of Toronto, Toronto, ON, Canada. ·Mult Scler · Pubmed #28327056.

ABSTRACT: Mortality rates are elevated in people with multiple sclerosis (MS) relative to the general population. There is, however, some uncertainty whether suicide contributes to this. Epidemiological data suggest that the standardized mortality ratio (SMR) for suicide in MS is approximately twice that of the general population with younger males in the first few years following diagnosis most at risk. Rates of suicidal intent, a potential harbinger of more self-destructive behavior, are also elevated, but the frequency with which intent is followed by suicide is not known. Depression, severity of depression, social isolation, and alcohol abuse are associated with thoughts of suicide. The variables linked with suicide and suicidal intent are therefore well defined and should be readily available from routine clinical inquiry. While vigilance on the part of clinicians is required, particularly in the context of high-risk patients, it is also recognized that prevention is dependent on full disclosure of intent.

19 Review Patient education for people with multiple sclerosis-associated fatigue: A systematic review. 2017

Wendebourg, Maria Janina / Heesen, Christoph / Finlayson, Marcia / Meyer, Björn / Pöttgen, Jana / Köpke, Sascha. ·Institute of Neuroimmunology and Department of Neurology, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany. · School of Rehabilitation Therapy, Queen's University, Kingston, Ontario, Canada. · GAIA AG, Hamburg, Germany. · Nursing Research Unit, Institute of Social Medicine and Epidemiology, University of Lübeck, Lübeck, Germany. ·PLoS One · Pubmed #28267811.

ABSTRACT: BACKGROUND: Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease often causing decreased quality of life, social withdrawal and unemployment. Studies examining the effect of pharmacological interventions demonstrated only minor effects, whereas non-pharmacological interventions as e.g. patient education programs have shown promising results. OBJECTIVE: We aim to systematically review the literature to determine the effect of patient education programs on fatigue in MS. METHODS: We conducted a comprehensive search in PubMed for randomized controlled trials (RCTs) that evaluated patient education programs for MS-related fatigue. Interventions evaluating physical exercise and/or pharmacological treatments were not included. Meta-analyses were performed using the generic inverse variance method. RESULTS: The search identified 856 citations. After full-text screening we identified ten trials that met the inclusion criteria. Data of 1021 participants were analyzed. Meta-analyses showed significant positive effects on fatigue severity (weighted mean difference -0.43; 95% CI -0.74 to -0.11) and fatigue impact (-0.48; -0.82 to -0.15), but not for depression (-0.35 (95% CI -0.75 to 0.05; p = 0.08). Essentially, we categorized patient education programs into two types: firstly, interventions with a focus on cognitive-behavioral therapy (CBT) and secondly, interventions that teach patients ways of managing daily fatigue. CBT-based approaches seem to generate better results in reducing patient-reported fatigue severity. Analysing CBT studies only, the pooled weighted mean difference for fatigue severity was -0.60 (95% CI; -1.08 to -0.11) compared to non-CBT approaches (-0.20; 95% CI; -0.60 to -0.19). Furthermore, interventions employing an individual approach seem to reduce fatigue more effectively than group-based approaches (pooled weighted mean difference for fatigue severity in face-to-face studies was -0.80 (95% CI; -1.13 to -0.47) compared to group-based studies with -0,17 (95% CI; -0,39 to 0,05). Longest follow-up data were available for 12 months post-intervention. CONCLUSION: Overall, included studies demonstrated that educational programs and especially CBT-based approaches have a positive effect on reducing fatigue. Since fatigue is thought to be a multidimensional symptom, it should be treated with a multidimensional approach targeting patients' behavior as well as their emotional and mental attitude towards fatigue. However, the clinical relevance of the treatment effects i.e. the relevance for patients' daily functioning remains unclear and long-term effects, i.e. sustainability of effects beyond 6 months, warrants further work. This review has been registered in the PROSPERO international prospective register of systematic reviews data base (Registration number: CRD42014014224).

20 Review Modifiable Psychosocial Constructs Associated With Physical Activity Participation in People With Multiple Sclerosis: A Systematic Review and Meta-Analysis. 2017

Casey, Blathin / Coote, Susan / Shirazipour, Celina / Hannigan, Ailish / Motl, Robert / Martin Ginis, Kathleen / Latimer-Cheung, Amy. ·Department of Clinical Therapies, Faculty of Education and Health Sciences, University of Limerick, Limerick, Ireland. Electronic address: blathin.casey@ul.ie. · Department of Clinical Therapies, Faculty of Education and Health Sciences, University of Limerick, Limerick, Ireland. · School of Kinesiology & Health Studies, Queen's University, Kingston, Ontario, Canada. · Graduate Entry Medical School, Faculty of Education and Health Sciences, University of Limerick, Limerick, Ireland. · Department of Physical Therapy, University of Alabama at Birmingham, Birmingham, AL. · Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada. ·Arch Phys Med Rehabil · Pubmed #28254635.

ABSTRACT: OBJECTIVE: To synthesize current knowledge of the modifiable psychosocial constructs associated with physical activity (PA) participation in people with multiple sclerosis. DATA SOURCES: A search was conducted through October 2015 in 8 electronic databases: CINAHL, PubMed, SPORTDiscus, Web of Knowledge, MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and PsycINFO. STUDY SELECTION: Cohort and intervention studies were included if they (1) included an objective or subjective measure of PA; (2) measured at least 1 modifiable psychosocial construct; and (3) reported bivariate correlations (or these could be extracted) between the PA and psychosocial construct measures. A total of 13,867 articles were screened for inclusion, and 26 were included in the final analysis. DATA EXTRACTION: Meta-analyses of correlations were conducted using the Hedges-Olkin method. Where a meta-analysis was not possible, results were reported descriptively. DATA SYNTHESIS: Meta-analyses indicated a pooled correlation coefficient between (1) objective PA and self-efficacy (n=7) of r=.30 (P<.0001), indicating a moderate, positive association; (2) subjective PA and self-efficacy (n=7) of r=.34 (P<.0001), indicating a moderate, positive association; (3) subjective PA and goal-setting (n=5) of r=.44 (P<.0001), indicating a moderate-to-large positive association; and 4) subjective PA and outcome expectancies (n=4) (physical: r=.13, P=.11; social: r=.19, P<.0001; self-evaluative: r=.27, P<.0001), indicating small-moderate positive associations. Other constructs such as measures of health beliefs, enjoyment, social support, and perceived benefits and barriers were reported to be significantly correlated with PA in individual studies, but the number of studies was not sufficient for a meta-analysis. CONCLUSIONS: Future PA interventions should continue to focus on the psychosocial constructs of self-efficacy and goal-setting. However, there is a need to explore the associations between other constructs outside those reported in this review.

21 Review Public Funding and Open Access to Research: A Review of Canadian Multiple Sclerosis Research. 2017

Bakker, Caitlin / Stephenson, Carol / Stephenson, Erin / Chaves, Debbie. ·Health Sciences Libraries, University of Minnesota, Minneapolis, MN, United States. · Council of Prairie and Pacific University Libraries, Vancouver, BC, Canada. · Hotchkiss Brain Institute and the Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada. · Library, Wilfrid Laurier University, Waterloo, ON, Canada. ·J Med Internet Res · Pubmed #28242594.

ABSTRACT: BACKGROUND: Multiple sclerosis (MS), a progressive demyelinating disease of the brain and spinal cord, is the leading cause of nontraumatic neurological damage in young adults. Canada has one of the highest reported incidents of MS, with estimates between 55 and 240 per 100,000 individuals. Between 2009 and 2014, the MS Society of Canada provided over Can $90 million to researchers and, since 2013, has encouraged researchers to make both current and previous research products openly available. OBJECTIVE: The goal of the study was to determine the open access (OA) cost implications and repository policies of journals frequently used by a sample of MS researchers. This study benchmarked current publishing preferences by MS Society of Canada researchers by examining the OA full-text availability of journal articles written by researchers funded between 2009 and 2014. METHODS: Researchers were identified from the 2009 to 2014 annual MS Society of Canada Research Summaries. Articles were identified through searches in Web of Science, Scopus, Medline and Embase (both via OVID). Journal level analysis included comparison of OA policies, including article processing charges (APCs) and repository policies. Data were analyzed using descriptive statistics. RESULTS: There were 758 articles analyzed in this study, of which 288 (38.0%) were OA articles. The majority of authors were still relying on journal policies for deposit in PubMed Central or availability on publisher websites for OA. Gold OA journals accounted for 10.2% of the journals in this study and were associated with significantly lower APCs (US $1900) than in hybrid journals (US $3000). Review of the journal self-archiving options highlighted the complexity of stipulations that authors would have to navigate to legally deposit a version of their article. CONCLUSIONS: This study found that there are currently researcher- and publisher-imposed barriers to both the gold and green roads to OA. These results provide a current benchmark against which efforts to enhance openness can be measured and can serve as a reference point in future assessments of the impact of OA policies within this field. With funding agencies worldwide releasing OA mandates, future success in compliance will require changes to how researchers and publishers approach production and dissemination of research.

22 Review Potential pathophysiological pathways that can explain the positive effects of exercise on fatigue in multiple sclerosis: A scoping review. 2017

Langeskov-Christensen, Martin / Bisson, Etienne J / Finlayson, Marcia L / Dalgas, Ulrik. ·Section of Sport Science, Department of Public Health, Aarhus University, Aarhus C, Denmark. Electronic address: mach@ph.au.dk. · School of Rehabilitation Therapy, Queen's University, Kingston, Canada. · Section of Sport Science, Department of Public Health, Aarhus University, Aarhus C, Denmark. ·J Neurol Sci · Pubmed #28131211.

ABSTRACT: BACKGROUND: Fatigue is one of the most common and most disabling symptoms of multiple sclerosis (MS). It is a multidimensional and complex symptom with multifaceted origins, involving both central and peripheral fatigue mechanisms. Exercise has proven to be safe for people with MS, with cumulating evidence supporting significant reductions in fatigue. However, the potential pathophysiological pathways that can explain the positive effects of exercise on fatigue in MS remain elusive. OBJECTIVES: The objectives were, in PwMS (1) to update the knowledge on the pathophysiology underlying primary and secondary fatigue, and (2) to discuss potential pathophysiological pathways that can explain the positive effects of exercise on MS fatigue. METHODS: A comprehensive literature search of six databases (PubMed, Embase, Cochrane Library, PEDro, CINAHL and SPORTDiscus) was performed. To be included, the study had to 1) enroll participants with definite MS according to defined criteria, 2) assess explicit pathophysiological mechanisms related to MS fatigue, 3) be available in English, Danish or French, and 4) had undergone peer-review. RESULTS: A total of 234 studies fulfilled the inclusion criteria. Primary MS fatigue mainly originated from a dysfunction of central nervous system neuronal circuits secondary to increased inflammation, reduced glucose metabolism, brain atrophy and diffuse demyelination and axonal lesions. Secondary MS fatigue was linked with sleep disturbances, depression, cognitive impairments, and deconditioning. Cardiovascular, immunologic, neuroendocrine, and neurotrophic changes associated with exercise may alleviate primary MS fatigue while exercise may improve secondary MS fatigue through symptomatic improvement of deconditioning, sleep disorders, and depression. CONCLUSIONS: >30 primary and secondary pathophysiological fatigue pathways were identified underlining the multidimensionality and complexity of MS fatigue. Though the underlying key cellular and molecular cascades still have to be fully elucidated, exercise holds the potential to alleviate MS fatigue, through both primary and secondary fatigue pathways.

23 Review Breaking down the gut microbiome composition in multiple sclerosis. 2017

Budhram, Adrian / Parvathy, Seema / Kremenchutzky, Marcelo / Silverman, Michael. ·Department of Clinical Neurological Sciences, Division of Neurology, University Hospital, London, ON, Canada. · Division of Infectious Diseases, St. Joseph's Health Care, London, ON, Canada. ·Mult Scler · Pubmed #27956557.

ABSTRACT: 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. Controlled studies examining the gut microbiome in patients with MS were included for review. RESULTS: Identified studies were predominantly case-control in their design and consistently found differences in the gut microbiome of MS patients compared to controls. We examine plausible mechanistic links between these differences and MS immunopathogenesis, and discuss the therapeutic implications of these findings. CONCLUSIONS: Review of the available literature reveals potential immunopathogenic links between the gut microbiome and MS, identifies avenues for therapeutic advancement, and emphasizes the need for further systematic study in this emerging field.

24 Review Radiologically isolated syndrome: watchful waiting vs. active treatment. 2017

Alshamrani, Foziah / Alnajashi, Hind / Freedman, M. ·a University of Dammam , Dammam , Saudi Arabia. · b King Abdulaziz University Hospital , Jeddah , Saudi Arabia. · c Faculty of Medicine , University of Ottawa , Ottawa , ON , Canada. ·Expert Rev Neurother · Pubmed #27830953.

ABSTRACT: INTRODUCTION: Neurologists are frequently consulted for patients who have white matter lesions discovered incidentally on their brain MRI, performed for reasons other than suspecting a demyelinating disease. The referring physician will question if the person has multiple sclerosis (MS). If the MRI is typical for MS but there are no clinical symptoms or signs suggestive of a demyelinating disorder, patients are diagnosed as having a Radiologically Isolated Syndrome (RIS). Areas covered: This is a timely review on RIS with a focus on treatment considerations. Expert commentary: Multiple studies have tried to identify common predictive factors for conversion of RIS to clinical MS, the strongest thus far being an asymptomatic cervical spinal cord lesion. Treatment of RIS is highly controversial, but early treatment in carefully selected patients might improve long term outcome.

25 Review Correlation of geographic distributions of haptoglobin alleles with prevalence of multiple sclerosis (MS) - a narrative literature review. 2017

Bamm, Vladimir V / Geist, Arielle M / Harauz, George. ·Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada. · Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada. gharauz@uoguelph.ca. ·Metab Brain Dis · Pubmed #27807673.

ABSTRACT: We have proposed that the myelin damage observed in multiple sclerosis (MS) may be partly mediated through the long-term release and degradation of extracellular hemoglobin (Hb) and the products of its oxidative degradation [Cellular and Molecular Life Sciences, 71, 1789-1798, 2014]. The protein haptoglobin (Hpt) binds extracellular Hb as a first line of defense, and can serve as a vascular antioxidant. Humans have two different Hpt alleles: Hpt1 and Hpt2, giving either homozygous Hpt1-1 or Hpt2-2 phenotypes, or a heterozygous Hpt1-2 phenotype. We questioned whether those geographic regions with higher frequency of the Hpt2 allele (conversely, lower frequency of Hpt1 allele) would correlate with an increased incidence of MS, because different Hpt phenotypes will have variable anti-oxidative potentials in protecting myelin from damage inflicted by extracellular Hb and its degradation products. To test this hypothesis, we undertook a systematic analysis of the literature on reported geographic distributions of Hpt alleles to compare them with data reported in the World Health Organization Atlas of worldwide MS prevalence. We found the frequency of the Hpt1 allele to be low in European and North American countries with a high prevalence of MS, consistent with our hypothesis. However, this correlation was not observed in China and India, countries with the lowest Hpt1 frequencies, yet low reported prevalence of MS. Nevertheless, this work shows the need for continued refinement of geographic patterns of MS prevalence, including data on ethnic or racial origin, and for new clinical studies to probe the observed correlation and evaluate Hpt phenotype as a predictor of disease variability and progression, severity, and/or comorbidity with cardiovascular disorders.

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