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Multiple Sclerosis: HELP
Articles from Ontario
Based on 723 articles published since 2010

These are the 723 published articles about Multiple Sclerosis that originated from Ontario during 2010-2020.
+ 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 Autologous Hematopoietic Cell Transplantation for Treatment-Refractory Relapsing Multiple Sclerosis: Position Statement from the American Society for Blood and Marrow Transplantation. 2019

Cohen, Jeffrey A / Baldassari, Laura E / Atkins, Harold L / Bowen, James D / Bredeson, Christopher / Carpenter, Paul A / Corboy, John R / Freedman, Mark S / Griffith, Linda M / Lowsky, Robert / Majhail, Navneet S / Muraro, Paolo A / Nash, Richard A / Pasquini, Marcelo C / Sarantopoulos, Stefanie / Savani, Bipin N / Storek, Jan / Sullivan, Keith M / Georges, George E. ·Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, Ohio. Electronic address: cohenj@ccf.org. · Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, Ohio. · Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. · Multiple Sclerosis Center, Swedish Neuroscience Institute, Seattle, Washington. · Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. · Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado. · University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. · Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. · Division of Blood and Marrow Transplantation, Stanford University, Stanford, California. · Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio. · Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom. · Blood and Marrow Transplant Program, Colorado Blood Cancer Institute, Denver, Colorado. · Department of Hematology and Oncology, Medical College of Wisconsin and Center for International Blood and Marrow Transplant Research, Milwaukee, Wisconsin. · Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, North Carolina. · Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee. · Blood and Marrow Transplant Program, University of Calgary, Calgary, Alberta, Canada. ·Biol Blood Marrow Transplant · Pubmed #30794930.

ABSTRACT: Multiple sclerosis (MS) is a chronic, disabling, immune-mediated, demyelinating and degenerative disease of the central nervous system. Approved disease-modifying therapies may be incompletely effective in some patients with highly active relapsing disease and high risk of disability. The use of immunoablative or myeloablative therapy followed by autologous hematopoietic cell transplantation (AHCT) has been investigated in retrospective studies, clinical trials, and meta-analyses/systematic reviews as an approach to address this unmet clinical need. On behalf of the American Society for Blood and Bone Marrow Transplantation (ASBMT), a panel of experts in AHCT and MS convened to review available evidence and make recommendations on MS as an indication for AHCT. A review of recent literature identified 8 retrospective studies, 8 clinical trials, and 3 meta-analyses/systematic reviews. In aggregate, these studies indicate that AHCT is an efficacious and safe treatment for active relapsing forms of MS to prevent clinical relapse, magnetic resonance imaging-detectable lesion activity, and worsening disability and to reverse disability without unexpected adverse events. Based on the available evidence, the ASBMT recommends that treatment-refractory relapsing MS with high risk of future disability be considered a "standard of care, clinical evidence available" indication for AHCT. Collaboration of neurologists with expertise in treating MS and transplantation physicians with experience performing AHCT for autoimmune disease is crucial for ensuring appropriate patient selection and optimizing transplantation procedures to improve patient outcomes. Transplantation centers in the United States and Canada are strongly encouraged to report baseline and outcomes data on patients receiving AHCT for multiple sclerosis to the Center for International Blood and Marrow Transplant Research.

2 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.

3 Editorial Vaccination: Not a trigger for MS. 2019

Yeh, E Ann / Graves, Jennifer. ·From the Department of Pediatrics (Neurology) (E.A.Y.), SickKids Research Institute, Division of Neurosciences and Mental Health, Hospital for Sick Children, University of Toronto, Canada · and Department of Neurosciences (J.G.), University of California, San Diego. ·Neurology · Pubmed #31363059.

ABSTRACT: -- No abstract --

4 Editorial Evolution of regional brain atrophy in children with multiple sclerosis: Gray matters. 2019

Yeh, E Ann / Eshaghi, Arman. ·From the Division of Neurology (E.A.Y.), Department of Pediatrics, Division of Neuroscience and Mental Health, SickKids Research Institute, The Hospital for Sick Children, and University of Toronto, Canada · and Queen Square Multiple Sclerosis Centre, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences (A.E.), and Centre for Medical Image Computing, Department of Computer Science (A.E.), University College London, UK. ·Neurology · Pubmed #30867265.

ABSTRACT: -- No abstract --

5 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 --

6 Editorial Another brick in the wall: further evidence supporting the role of haematopoietic stem cell transplantation in treating multiple sclerosis. 2019

Atkins, Harold L. ·The Ottawa Hospital Blood and Marrow Transplant Program, Ottawa, ON K1H 8L6, Canada hatkins@ohri.ca. ·J Neurol Neurosurg Psychiatry · Pubmed #30630958.

ABSTRACT: -- No abstract --

7 Editorial Disease-modifying therapy in multiple sclerosis: Two guidelines (almost) passing in the night. 2018

Marrie, Ruth Ann / Montalban, Xavier. ·Departments of Internal Medicine and Community Health Sciences, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada. · Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron University Hospital, Barcelona, Spain; Division of Neurology, University of Toronto, St Michael's Hospital, Toronto, ON, Canada. ·Mult Scler · Pubmed #29692224.

ABSTRACT: -- No abstract --

8 Editorial Editorial: Lymphocytes in MS and EAE: More Than Just a CD4 2017

Rangachari, Manu / Kerfoot, Steven M / Arbour, Nathalie / Alvarez, Jorge Ivan. ·Department of Neurosciences, Centre de recherche du CHU de Québec - Université Laval, Quebec City, QC, Canada; Department of Molecular Medicine, Université Laval, Quebec City, QC, Canada. · Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University , London, ON , Canada. · Department of Neurosciences, Université de Montréal and CRCHUM , Montréal, QC , Canada. · Department of Pathobiology, University of Pennsylvania , Philadelphia, PA , USA. ·Front Immunol · Pubmed #28243239.

ABSTRACT: -- No abstract --

9 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 --

10 Review The multiple sclerosis gut microbiota: A systematic review. 2020

Mirza, Ali / Forbes, Jessica D / Zhu, Feng / Bernstein, Charles N / Van Domselaar, Gary / Graham, Morag / Waubant, Emmanuelle / Tremlett, Helen. ·Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada. · Department of Internal Medicine, University of Manitoba, University of Manitoba IBD Clinical and Research Centre, Winnipeg, MB, Canada; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada; Department of Laboratory Medicine & Pathobiology, University of Toronto, ON, Canada. · Department of Internal Medicine, University of Manitoba, University of Manitoba IBD Clinical and Research Centre, Winnipeg, MB, Canada. · National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada. · University of California San Francisco, San Francisco, CA, United States. · Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada. Electronic address: helen.tremlett@ubc.ca. ·Mult Scler Relat Disord · Pubmed #32172998.

ABSTRACT: BACKGROUND: To systematically review and synthesize the literature on the multiple sclerosis (MS) gut microbiota composition as compared to persons without MS. METHODS: We systematically searched MEDLINE, EMBASE, and Web of Science databases for relevant published articles (2008-2018). RESULTS: Of 415 articles identified ten fulfilled criteria. All studies used a case-control design, six sourced participants from the US, two Germany, one Italy, and one Japan. Nine focused exclusively on adults and one on children, totaling 286 MS and 296 control participants. Over 90% of cases had relapsing-remitting MS; disease duration ranged from 10.6 ± 6.5 months to 15.3 ± 8.6 years (mean±SD). Nine studies examined stool and one evaluated duodenal mucosa. Diverse platforms were used to quantify microbes: Illumina MiSeq, Roche 454, microarray, and fluorescence in situ hybridization. None of eight studies reported a significant alpha-diversity differences between cases and controls. Two of seven studies reported a difference in beta-diversity (P ≤ 0.002). At the taxa-level, ≥2 studies observed: lower relative abundance of Prevotella, Faecalibacterium prausnitzii, Bacteroides coprophilus, Bacteroides fragilis, and higher Methanobrevibacter and Akkermansia muciniphila in MS cases versus controls. Exposure to an immunomodulatory drug (IMD), relative to no exposure, was associated with individual taxonomic differences in three of three studies. CONCLUSION: Gut microbiota diversity did not differ between MS cases and controls in the majority of studies. However, taxonomic differences were found, with consistent patterns emerging across studies. Longitudinal studies are warranted to elucidate the relationship between IMD exposure and differences in the gut microbiota composition.

11 Review Cannabinoids in Chronic Non-Cancer Pain: A Systematic Review and Meta-Analysis. 2020

Johal, Herman / Devji, Tahira / Chang, Yaping / Simone, Jonathan / Vannabouathong, Christopher / Bhandari, Mohit. ·Center for Evidence-Based Orthopaedics, Division of Orthopaedics, Department of Surgery, McMaster University, Hamilton, ON, Canada. · OrthoEvidence Inc., Burlington, ON, Canada. · Aphria Inc., Leamington, ON, Canada. ·Clin Med Insights Arthritis Musculoskelet Disord · Pubmed #32127750.

ABSTRACT: Background: For patients with chronic, non-cancer pain, traditional pain-relieving medications include opioids, which have shown benefits but are associated with increased risks of addiction and adverse effects. Medical cannabis has emerged as a treatment alternative for managing these patients and there has been a rise in the number of randomized clinical trials in recent years; therefore, a systematic review of the evidence was warranted. Objective: To analyze the evidence surrounding the benefits and harms of medical cannabinoids in the treatment of chronic, non-cancer-related pain. Design: Systematic review with meta-analysis. Data sources: Medline, Embase, CINAHL, SCOPUS, Google Scholar, and Cochrane Databases. Eligibility criteria: English language randomized clinical trials of cannabinoids for the treatment of chronic, non-cancer-related pain. Data extraction and synthesis: Study quality was assessed using the Cochrane risk of bias tool. All stages were conducted independently by a team of 6 reviewers. Data were pooled through meta-analysis with different durations of treatment (2 weeks, 2 months, 6 months) and stratified by route of administration (smoked, oromucosal, oral), conditions, and type of cannabinoids. Main outcomes and measures: Patient-reported pain and adverse events (AEs). Results: Thirty-six trials (4006 participants) were included, examining smoked cannabis (4 trials), oromucosal cannabis sprays (14 trials), and oral cannabinoids (18 trials). Compared with placebo, cannabinoids showed a significant reduction in pain which was greatest with treatment duration of 2 to 8 weeks (weighted mean difference on a 0-10 pain visual analogue scale -0.68, 95% confidence interval [CI], -0.96 to -0.40, Conclusions: There was moderate evidence to support cannabinoids in treating chronic, non-cancer pain at 2 weeks. Similar results were observed at later time points, but the confidence in effect is low. There is little evidence that cannabinoids increase the risk of experiencing serious AEs, although non-serious AEs may be common in the short-term period following use.

12 Review MAGNIMS consensus recommendations on the use of brain and spinal cord atrophy measures in clinical practice. 2020

Sastre-Garriga, Jaume / Pareto, Deborah / Battaglini, Marco / Rocca, Maria A / Ciccarelli, Olga / Enzinger, Christian / Wuerfel, Jens / Sormani, Maria P / Barkhof, Frederik / Yousry, Tarek A / De Stefano, Nicola / Tintoré, Mar / Filippi, Massimo / Gasperini, Claudio / Kappos, Ludwig / Río, Jordi / Frederiksen, Jette / Palace, Jackie / Vrenken, Hugo / Montalban, Xavier / Rovira, Àlex / Anonymous4021135. ·Multiple Sclerosis Centre of Catalonia (Cemcat), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. jsastre-garriga@cem-cat.org. · Section of Neuroradiology and Magnetic Resonance Unit, Department of Radiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. · Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. · Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy. · NMR Research Unit, University College London Queen Square Institute of Neurology, London, UK. · National Institute for Health Research Biomedical Research Centre, University College London Hospitals, London, UK. · Department of Neurology and Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria. · Medical Image Analysis Center (MIAC AG) and Department of Biomedical Engineering, University of Basel, Basel, Switzerland. · Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy. · IRCCS, Ospedale Policlinico San Martino, Genoa, Italy. · Amsterdam Neuroscience, MS Center Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam UMC, Amsterdam, Netherlands. · Institutes of Neurology and Healthcare Engineering, University College London, London, UK. · Lysholm Department of Neuroradiology, University College London Hospitals National Hospital for Neurology and Neurosurgery, University College London Institute of Neurology, London, UK. · Multiple Sclerosis Centre of Catalonia (Cemcat), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. · Vita-Salute San Raffaele University, Milan, Italy. · Multiple Sclerosis Center, Department of Neurosciences, San Camillo-Forlanini Hospital, Rome, Italy. · Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital, University of Basel, Basel, Switzerland. · Department of Neurology, Rigshospitalet-Glostrup and University of Copenhagen, Glostrup, Denmark. · Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. · Division of Neurology, St Michael's Hospital, University of Toronto, Toronto, Canada. · Section of Neuroradiology and Magnetic Resonance Unit, Department of Radiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. alex.rovira.idi@gencat.cat. ·Nat Rev Neurol · Pubmed #32094485.

ABSTRACT: Early evaluation of treatment response and prediction of disease evolution are key issues in the management of people with multiple sclerosis (MS). In the past 20 years, MRI has become the most useful paraclinical tool in both situations and is used clinically to assess the inflammatory component of the disease, particularly the presence and evolution of focal lesions - the pathological hallmark of MS. However, diffuse neurodegenerative processes that are at least partly independent of inflammatory mechanisms can develop early in people with MS and are closely related to disability. The effects of these neurodegenerative processes at a macroscopic level can be quantified by estimation of brain and spinal cord atrophy with MRI. MRI measurements of atrophy in MS have also been proposed as a complementary approach to lesion assessment to facilitate the prediction of clinical outcomes and to assess treatment responses. In this Consensus statement, the Magnetic Resonance Imaging in MS (MAGNIMS) study group critically review the application of brain and spinal cord atrophy in clinical practice in the management of MS, considering the role of atrophy measures in prognosis and treatment monitoring and the barriers to clinical use of these measures. On the basis of this review, the group makes consensus statements and recommendations for future research.

13 Review Too Much on Your "Plate"? Spectrum of Pathologies Involving the Tectal Plate. 2020

Gandhi, Niket / Tsehmaister-Abitbol, Vered / Glikstein, Rafael / Torres, Carlos. ·Department of Radiology, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada. · These authors contributed equally and are co-first authors. ·Can Assoc Radiol J · Pubmed #32063011.

ABSTRACT: The tectal plate comprises the posterior portion of the midbrain, borders the quadrigeminal cistern, and includes the superior and inferior colliculi. Benign and malignant pathologies occurring in this location may lead to aqueductal stenosis, obstructive hydrocephalus, and Parinaud syndrome. Both computed tomography and magnetic resonance imaging can be used to further characterize lesions involving the tectal plate. In this pictorial essay, we review various tectal plate lesions and their imaging features.

14 Review Effects of Mindfulness-based interventions on physical symptoms in people with multiple sclerosis - a systematic review and meta-analysis. 2020

Simpson, Robert / Simpson, Sharon / Ramparsad, Nitish / Lawrence, Maggie / Booth, Jo / Mercer, Stewart W. ·Physical Medicine & Rehabilitation, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Room H390 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada; General Practice and Primary Care, Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom. Electronic address: robert.simpson@sunnybrook.ca. · General Practice and Primary Care, Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom. · Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom. · Nursing and Community Health, Glasgow Caledonian University, Glasgow, United Kingdom. · General Practice and Primary Care, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom. ·Mult Scler Relat Disord · Pubmed #31835209.

ABSTRACT: BACKGROUND: Physical wellbeing is commonly impaired in people with multiple sclerosis (PwMS). This study aims to update our previous systematic review (2014) and conduct a meta-analysis on the efficacy of Mindfulness-based interventions (MBIs) for improving physical symptoms in PwMS. METHODS: In November 2017 we carried out systematic searches for eligible randomised controlled trials (RCTs) in seven major databases, updating our search in July 2018. We used medical subject headings and key words. Two independent reviewers used pre-defined criteria to screen, data extract, quality appraise, and analyse studies. The Cochrane Collaboration risk of bias tool was used to determine study quality. Physical wellbeing was the main outcome of interest. We used the random effects model for meta-analysis, reporting effect sizes as Standardised Mean Difference (SMD). This study is registered with PROSPERO: CRD42018093171. RESULTS: We identified 10 RCTs as eligible for inclusion in the systematic review (including 678 PwMS), whilst seven RCTs (555 PwMS) had data that could be used in our meta-analyses. In general, comorbidity, disability, ethnicity and socio-economic status were poorly reported. MBIs included manualised and tailored interventions, treatment duration 6-9 weeks, delivered face-to-face and online in groups and also individually. For fatigue, against any comparator SMD was 0.24 (0.08 - 0.41), I CONCLUSIONS: MBIs appear to be an effective treatment for fatigue in PwMS. The optimal MBI in this context remains unclear. Further research into MBI optimisation, cost- and comparative-effectiveness is required.

15 Review Functional Electrical Stimulation Cycling Exercise for People with Multiple Sclerosis. 2019

Pilutti, Lara A / Motl, Robert W. ·Interdisciplinary School of Health Sciences, Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada. · Department of Physical Therapy, University of Alabama at Birmingham, 1716 9th Avenue South, Birmingham, AL, 35233, USA. robmotl@uab.edu. ·Curr Treat Options Neurol · Pubmed #31705304.

ABSTRACT: PURPOSE OF REVIEW: There has been substantial interest in the role of exercise for managing impairments, limitations, and disability progression among persons with multiple sclerosis (MS). Despite established benefits of exercise training for persons who have mild-to-moderate MS, the ability to deliver exercise to persons who experience higher disability remains challenging. One promising approach for exercise in this population is functional electrical stimulation (FES) cycling. This review provides a summary of the current evidence for FES cycling as an exercise training modality in persons with MS with respect to prescription, safety, tolerability, and acute and chronic effects. RECENT FINDINGS: We searched the literature for studies involving FES cycling exercise in persons with MS published in English up until July 2019. Eight studies were retrieved: two studies examined acute effects, two studies examined chronic effects, and four studies reported on both acute and chronic effects of FES cycling exercise. The overall quality of the studies was low, with only one, small, randomized controlled trial (RCT). There is limited but promising evidence for the application of FES cycling exercise among persons with MS who have moderate-to-severe disability. Participants were capable of engaging in regular FES cycling exercise (~ 30 min, 2-3×/week), with few, mild adverse events experienced. Preliminary evidence from small, mostly uncontrolled trials supports the potential benefits of FES cycling on physiological fitness, walking mobility, and symptoms of fatigue and pain. High-quality RCTs of FES cycling exercise are necessary for providing recommendations for integrating exercise training in the management of advanced MS.

16 Review Head-to-head drug comparisons in multiple sclerosis: Urgent action needed. 2019

Tur, Carmen / Kalincik, Tomas / Oh, Jiwon / Sormani, Maria P / Tintoré, Mar / Butzkueven, Helmut / Montalban, Xavier. ·From the Department of Neuroinflammation (C.T.), Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, University College London, UK · Neurology/Neuroimmunology Department (C.T., M.T., X.M.), Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain · Department of Medicine (T.K.), CORe, University of Melbourne, Australia · Department of Neurology (T.K.), Royal Melbourne Hospital, Australia · Division of Neurology (J.O., X.M.), University of Toronto, St Michael's Hospital, Canada · Department of Health Sciences (DISSAL) (M.P.S.), University of Genoa, Italy · and Central Clinical School (H.B.), Alfred Centre, Monash University, Melbourne, Australia. ·Neurology · Pubmed #31591277.

ABSTRACT: Disease-modifying drugs are changing the natural history of multiple sclerosis (MS). However, currently available clinical trial data are insufficient to develop accurate personalized treatment algorithms to assign the best possible treatment to each person with MS according to disease features, treatment history, and comorbidities. Such accurate algorithms would require the presence of numerous head-to-head trials of long duration, which is virtually impossible, given the economic costs, required time, and difficulties with attrition. Thus, efforts are being made to compare relative treatment efficacy through observational designs, using large multicenter prospective cohorts or "big MS data," and network meta-analyses. Although such studies can yield useful information, they are liable to biases and their results should be confirmed in other study populations, including smaller, single-center cohorts, where some of these biases can be minimized. In this View article, we analyze the potential benefits and biases of all these strategies alternative to head-to-head trials in MS. Finally, we propose the combination of all these types of studies to obtain reliable head-to-head drug comparisons in the absence of randomized designs.

17 Review Cognitive Fatigability Interventions in Neurological Conditions: A Systematic Review. 2019

Walker, Lisa A S / Lindsay-Brown, Alyssa P / Berard, Jason A. ·Ottawa Hospital Research Institute, Ottawa, Canada. lwalker@toh.ca. · University of Ottawa Brain and Mind Research Institute, Ottawa, Canada. lwalker@toh.ca. · Carleton University, Ottawa, Canada. lwalker@toh.ca. · Ottawa Hospital Research Institute, Ottawa, Canada. ·Neurol Ther · Pubmed #31586303.

ABSTRACT: INTRODUCTION: Although fatigue is a well-studied concept in neurological disease, cognitive fatigability (CF) is less understood. While most studies measure fatigue using subjective self-report, fewer have measured CF objectively. Given the negative impact of CF on quality-of-life, there is a need for targeted interventions. The objective of this review was to determine which procedural, behavioural and pharmacological treatments for objectively measured CF are available to people living with neurological conditions. METHODS: In accordance with the PRISMA guidelines, systematic searches for randomized control trials (RCTs), case-controlled studies and case reports/series were conducted across the Ovid Medline, PsycInfo, EMBASE and Cochrane Library databases. English-language articles published between 1980 and February 2019 were considered for eligibility. Included were those that objectively measured CF in individuals with neurological disease/disorder/dysfunction between the ages of 18 and 65 years. Studies were reviewed using a modified Cochrane Data Extraction Template. Risk of bias was assessed using the Cochrane Risk of Bias tool. The review process was facilitated using Covidence software (www.covidence.org). Two authors reviewed articles independently, with a third resolving conflicts regarding article inclusion. RESULTS: The search identified 450 records. After duplicates were removed and remaining titles/abstracts were screened for eligibility, 28 full-text articles were assessed, and two studies were included in the qualitative synthesis. Studies were a priori divided into those with pharmacological, procedural or behavioural interventions. Two studies met eligibility criteria; both of these included participants with multiple sclerosis. One study utilized a procedural intervention (i.e. transcranial direct current stimulation), while the other utilized a pharmacological intervention (i.e. fampridine-SR). Studies were evaluated for risk of bias, and evidence from both eligible studies was discussed. CONCLUSION: Despite the positive results of the procedural intervention, the paucity of eligible studies and the nascent nature of the field suggests that more studies are required before firm conclusions can be drawn regarding the amenability of CF to treatment. TRIAL REGISTRATION: The review was registered with PROSPERO (CRD42019118706).

18 Review Depression and Suicidality in Multiple Sclerosis: Red Flags, Management Strategies, and Ethical Considerations. 2019

Kalb, Rosalind / Feinstein, Anthony / Rohrig, Amanda / Sankary, Lauren / Willis, Alissa. ·, West Bath, ME, USA. rkalb@cando-ms.org. · Can Do Multiple Sclerosis, Edwards, Avon, CO, USA. rkalb@cando-ms.org. · Department of Psychiatry, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, Canada. · Can Do Multiple Sclerosis, Edwards, Avon, CO, USA. · Horizon Rehabilitation Centers, Omaha, NE, USA. · Cleveland Clinic Center for Bioethics, Cleveland, OH, USA. · Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, USA. ·Curr Neurol Neurosci Rep · Pubmed #31463644.

ABSTRACT: Multiple sclerosis (MS) causes physical, emotional, and cognitive changes that impact function and quality of life (QoL). Risk factors for suicidality in MS patients include a high incidence of depression, increased isolation, and reduced function/independence. PURPOSE OF REVIEW: To describe the epidemiology of depression and suicidality in this population, highlight warning signs for suicidal behavior, provide recommendations and resources for clinicians, and discuss ethical decisions related to patient safety vs. right to privacy. RECENT FINDINGS: Fifty percent of MS patients will experience a major depression related to brain MRI factors and disease-related psychosocial challenges. Nevertheless, depression is under-recognized/treated. The standardized mortality ratio (SMR) indicates a suicide risk in the MS population that is twice that in the general population. Given the prevalence of depression and the increased risk of suicide in the MS population, any clinician providing care for these patients must be prepared to recognize and respond to potential warning signs.

19 Review Behavioural phenotypes in the cuprizone model of central nervous system demyelination. 2019

Sen, Monokesh K / Mahns, David A / Coorssen, Jens R / Shortland, Peter J. ·School of Medicine, Western Sydney University, New South Wales, Australia. · Departments of Health Sciences and Biological Sciences, Faculties of Applied Health Sciences and Mathematics & Science, Brock University, Ontario, Canada. Electronic address: jcoorssen@brocku.ca. · Science and Health, Western Sydney University, New South Wales, Australia. Electronic address: p.shortland@westernsydney.edu.au. ·Neurosci Biobehav Rev · Pubmed #31442519.

ABSTRACT: The feeding of cuprizone (CPZ) to animals has been extensively used to model the processes of demyelination and remyelination, with many papers adopting a narrative linked to demyelinating conditions like multiple sclerosis (MS), the aetiology of which is unknown. However, no current animal model faithfully replicates the myriad of symptoms seen in the clinical condition of MS. CPZ ingestion causes mitochondrial and endoplasmic reticulum stress and subsequent apoptosis of oligodendrocytes leads to central nervous system demyelination and glial cell activation. Although there are a wide variety of behavioural tests available for characterizing the functional deficits in animal models of disease, including that of CPZ-induced deficits, they have focused on a narrow subset of outcomes such as motor performance, cognition, and anxiety. The literature has not been systematically reviewed in relation to these or other symptoms associated with clinical MS. This paper reviews these tests and makes recommendations as to which are the most important in order to better understand the role of this model in examining aspects of demyelinating diseases like MS.

20 Review Improving Outcomes in Pediatric Multiple Sclerosis: Current and Emerging Treatments. 2019

Wilbur, Colin / Yeh, E Ann. ·Department of Pediatrics, Faculty of Medicine and Dentistry, Women and Children's Health Research Institute, University of Alberta, Edmonton, AB, Canada. · Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada. ann.yeh@sickkids.ca. · Division of Neurosciences and Mental Health, SickKids Research Institute, Toronto, ON, Canada. ann.yeh@sickkids.ca. · Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. ann.yeh@sickkids.ca. ·Paediatr Drugs · Pubmed #31155694.

ABSTRACT: Pediatric-onset multiple sclerosis (MS) comprises 2-5% of MS cases, and is known to be associated with high disease activity and the accumulation of disability at an earlier age than their adult-onset counterparts. Appropriate therapy leading to disease control has the potential to alter the known trajectory of adverse long-term physical, cognitive, and psychosocial outcomes in this population. Thus, optimizing treatment for children and adolescents with MS is of paramount importance. The last decade has seen a growing number of disease-modifying therapies approved for relapsing MS in adults, and available agents now include oral, injectable, and infusion therapies. Recently, the development of randomized controlled MS trials in youth has led to the first agent approved by the US FDA for the treatment of pediatric MS-fingolimod. With this, we have entered a new era of knowledge and treatment in this population and ongoing pediatric trials are expected to further inform clinical management. With the emergence of highly effective therapies targeting the inflammatory component of the disease, there has been increased interest in identifying treatment strategies that instead target mechanisms such as remyelination/repair, neuroprotection, or rehabilitation. The potential role for such emerging therapies in the treatment of pediatric MS remains an important area of study. In this review, we discuss current evidence for MS therapies in children including the treatment of acute relapses, disease-modifying therapies, and symptomatic management. We will also discuss evidence for emerging therapies, including remyelinating and neuroprotective agents.

21 Review PET Evaluation of Microglial Activation in Non-neurodegenerative Brain Diseases. 2019

Ghadery, Christine / Best, Laura A / Pavese, Nicola / Tai, Yen Foung / Strafella, Antonio P. ·The Edmond J. Safra Program in Parkinson's Disease & Movement Disorder Unit, Toronto Western Hospital & Krembil Research Institute, University Health Network; Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada. · Clinical Ageing Research Unit, Newcastle University, Campus for Ageing and Vitality, Westgate Road, Newcastle Upon Tyne, UK. Laura.best@newcastle.ac.uk. · Clinical Ageing Research Unit, Newcastle University, Campus for Ageing and Vitality, Westgate Road, Newcastle Upon Tyne, UK. · PET centre, University of Aarhus Denmark, Aarhus, Denmark. · Imperial College London South Kensington Campus, London, UK. ·Curr Neurol Neurosci Rep · Pubmed #31139952.

ABSTRACT: PURPOSE OF THE REVIEW: Microglial cell activation is an important component of neuroinflammation, and it is generally well accepted that chronic microglial activation is indicative of accumulating tissue damage in neurodegenerative conditions, particularly in the earlier stages of disease. Until recently, there has been less focus on the role of neuroinflammation in other forms of neurological and neuropsychiatric conditions. Through this review, we hope to demonstrate the important role TSPO PET imaging has played in illuminating the pivotal role of neuroinflammation and microglial activation underpinning these conditions. RECENT FINDINGS: TSPO is an 18 kDa protein found on the outer membrane of mitochondria and can act as a marker of microglial activation using nuclear imaging. Through the development of radiopharmaceuticals targeting TSPO, researchers have been able to better characterise the spatial-temporal evolution of chronic neurological conditions, ranging from the focal autoimmune reactions seen in multiple sclerosis to the Wallerian degeneration at remote parts of the brain months following acute cerebral infarction. Development of novel techniques to investigate neuroinflammation within the central nervous system, for the purposes of diagnosis and therapeutics, has flourished over the past few decades. TSPO has proven itself a robust and sensitive biomarker of microglial activation and neuroimaging affords a minimally invasive technique to characterise neuroinflammatory processes in vivo.

22 Review Management strategies for female patients of reproductive potential with multiple sclerosis: An evidence-based review. 2019

Coyle, Patricia K / Oh, Jiwon / Magyari, Melinda / Oreja-Guevara, Celia / Houtchens, Maria. ·Department of Neurology, Stony Brook University, Stony Brook, NY, USA. Electronic address: Patricia.Coyle@Stonybrookmedicine.edu. · St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. · Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark. · Hospital Clínico San Carlos, Universidad Complutense de Madrid, IdISSC, Madrid, Spain. · Brigham and Women's Hospital, Harvard Medical School, Brookline, MA, USA. ·Mult Scler Relat Disord · Pubmed #31030020.

ABSTRACT: Multiple sclerosis (MS) is an inflammatory, demyelinating, neurodegenerative, immune-mediated disease primarily diagnosed in early adulthood. Multiple sclerosis mostly impacts women of reproductive potential, with pregnancy and birth outcomes being major concerns for many patients. While there is ample evidence that the disease itself has no impact on pregnancy, many women living with MS still question their ability to have children, and the impact of childbearing on their disease in the short and long term. Such questions emphasize the importance of proper guidance from healthcare professionals, particularly neurologists. Management considerations are also complicated by the growing list of available treatment options. This review will summarize current evidence and expert opinion around the management of female MS patients of reproductive potential, from family planning to the postpartum period. Current guidelines on the use of disease-modifying therapies throughout pregnancy will be discussed, as well as other general medical recommendations, to minimize MS disease activity in the peripartum period.

23 Review Reaching an evidence-based prognosis for personalized treatment of multiple sclerosis. 2019

Rotstein, Dalia / Montalban, Xavier. ·Division of Neurology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. · Division of Neurology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. montalbanx@smh.ca. · Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain. montalbanx@smh.ca. ·Nat Rev Neurol · Pubmed #30940920.

ABSTRACT: Personalized treatment is ideal for multiple sclerosis (MS) owing to the heterogeneity of clinical features, but current knowledge gaps, including validation of biomarkers and treatment algorithms, limit practical implementation. The contemporary approach to personalized MS therapy depends on evidence-based prognostication, an initial treatment choice and evaluation of early treatment responses to identify the need to switch therapy. Prognostication is directed by baseline clinical, environmental and demographic factors, MRI measures and biomarkers that correlate with long-term disability measures. The initial treatment choice should be a shared decision between the patient and physician. In addition to prognosis, this choice must account for patient-related factors, including comorbidities, pregnancy planning, preferences of the patients and their comfort with risk, and drug-related factors, including safety, cost and implications for treatment sequencing. Treatment response has traditionally been assessed on the basis of relapse rate, MRI lesions and disability progression. Larger longitudinal data sets have enabled development of composite outcome measures and more stringent standards for disease control. Biomarkers, including neurofilament light chain, have potential as early surrogate markers of prognosis and treatment response but require further validation. Overall, attainment of personalized treatment for MS is complex but will be refined as new data become available.

24 Review Imaging outcome measures of neuroprotection and repair in MS: A consensus statement from NAIMS. 2019

Oh, Jiwon / Ontaneda, Daniel / Azevedo, Christina / Klawiter, Eric C / Absinta, Martina / Arnold, Douglas L / Bakshi, Rohit / Calabresi, Peter A / Crainiceanu, Ciprian / Dewey, Blake / Freeman, Leorah / Gauthier, Susan / Henry, Roland / Inglese, Mathilde / Kolind, Shannon / Li, David K B / Mainero, Caterina / Menon, Ravi S / Nair, Govind / Narayanan, Sridar / Nelson, Flavia / Pelletier, Daniel / Rauscher, Alexander / Rooney, William / Sati, Pascal / Schwartz, Daniel / Shinohara, Russell T / Tagge, Ian / Traboulsee, Anthony / Wang, Yi / Yoo, Youngjin / Yousry, Tarek / Zhang, Yunyan / Sicotte, Nancy L / Reich, Daniel S / Anonymous951127. ·From the Division of Neurology (J.O.), St. Michael's Hospital, University of Toronto, Canada · Department of Neurology (J.O., P.A.C., B.D., D.S.R.), Johns Hopkins University, Baltimore, MD · Mellen Center for Multiple Sclerosis (D.O.), Cleveland Clinic, OH · Department of Neurology (C.A., D.P.), University of Southern California, Los Angeles · Department of Neurology (E.C.K.), Massachusetts General Hospital, Harvard Medical School, Boston · Translational Neuroradiology Unit (M.A., G.N., P.S., D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD · Brain Imaging Centre (D.L.A., S.N.), Montreal Neurological Institute, McGill University, Canada · Departments of Neurology (R.B.) and Radiology (R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston · Department of Biostatistics (C.C.), Johns Hopkins School of Public Health, Baltimore, MD · Department of Neurology (L.F.), University of Texas Health Science Center at Houston · Department of Neurology (S.G., Y.W.), Weill Cornell Medical College, Cornell University, Ithaca, NY · Department of Neurology (R.H.), University of California at San Francisco · Department of Neurology (M.I., A.T.), Mount Sinai Hospital, New York, NY · Division of Neurology, Department of Medicine (S.K., D.K.B.L.), Department of Radiology (S.K., D.K.B.L., A.R.), Department of Physics and Astronomy (S.K., A.R., A.T., Y.Y.), MS/MRI Research Group (S.K., D.K.B.L., A.T., Y.Y.), MRI Research Centre (S.K., D.K.B.L., A.R.), and Department of Pediatrics (A.R.), University of British Columbia, Vancouver, Canada · A. A. Martinos Center for Biomedical Imaging (C.M.), Department of Radiology, Massachusetts General Hospital, Boston · Centre for Functional and Metabolic Mapping (R.S.M.), Robarts Research Institute, Western University, London, CA · Department of Neurology (F.N.), University of Minnesota, Minneapolis · Advanced Imaging Research Center (W.R., D.S., I.T.), Oregon Health & Science University, Portland · Department of Biostatistics, Epidemiology, and Informatics (R.T.S.), University of Pennsylvania Perelman School of Medicine, Philadelphia · Division of Neuroradiology and Neurophysics (T.Y.), University College London Institute of Neurology, UK · Department of Radiology (Y.Z.) and Department of Clinical Neurosciences and Hotchkiss Brain Institute (Y.Z.), University of Calgary, Canada · and Department of Neurology (N.L.S.), Cedars-Sinai Medical Center, Los Angeles, CA. ·Neurology · Pubmed #30787160.

ABSTRACT: OBJECTIVE: To summarize current and emerging imaging techniques that can be used to assess neuroprotection and repair in multiple sclerosis (MS), and to provide a consensus opinion on the potential utility of each technique in clinical trial settings. METHODS: Clinicians and scientists with expertise in the use of MRI in MS convened in Toronto, Canada, in November 2016 at a North American Imaging in Multiple Sclerosis (NAIMS) Cooperative workshop meeting. The discussion was compiled into a manuscript and circulated to all NAIMS members in attendance. Edits and feedback were incorporated until all authors were in agreement. RESULTS: A wide spectrum of imaging techniques and analysis methods in the context of specific study designs were discussed, with a focus on the utility and limitations of applying each technique to assess neuroprotection and repair. Techniques were discussed under specific themes, and included conventional imaging, magnetization transfer ratio, diffusion tensor imaging, susceptibility-weighted imaging, imaging cortical lesions, magnetic resonance spectroscopy, PET, advanced diffusion imaging, sodium imaging, multimodal techniques, imaging of special regions, statistical considerations, and study design. CONCLUSIONS: Imaging biomarkers of neuroprotection and repair are an unmet need in MS. There are a number of promising techniques with different strengths and limitations, and selection of a specific technique will depend on a number of factors, notably the question the trial seeks to answer. Ongoing collaborative efforts will enable further refinement and improved methods to image the effect of novel therapeutic agents that exert benefit in MS predominately through neuroprotective and reparative mechanisms.

25 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.