Le Hua, MD. Disclosures Teaching and Speaking: Teva Neurosciences, Genzyme, Novartis Advisory Board: Genzyme, EMD Serono

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1 Le Hua, MD Le Hua, MD, is a staff neurologist at Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, NV. She is involved in clinical trials assessing new therapies for the treatment of MS and her personal research interests include using advanced MRI techniques to study MS and neurological disorders. Dr. Hua s work has been published in peer reviewed journals and has been presented at the Consortium of Multiple Sclerosis Centers and joint ACTRIMS/ECTRIMsmeetings. Dr. Hua is committed to educating and providing comprehensive care for MS patients and their families with the goal of improving their quality of life. Additionally, she enjoys teaching and has given numerous lectures on topics in neuro-immunology and neurology to medical students and residents in both internal medicine and neurology. Dr. Hua was given a Neurology Clerkship teaching award by the medical students at Stanford School of Medicine. Dr. Hua earned her MD at Keck School of Medicine at the University of Southern California. Subsequently, she completed her internship at Banner Good Samaritan Medical Center in Phoenix and her neurology residency at Stanford University School of Medicine. She went on to complete a clinical fellowship in Neuro-Immunology and MS at the Barrow Neurological Institute and St. Joseph s Hospital and Medical Center in Phoenix. Disclosures Teaching and Speaking: Teva Neurosciences, Genzyme, Novartis Advisory Board: Genzyme, EMD Serono

2 Le Hua, MD Director Mellen Program for MS Cleveland Clinic Lou Ruvo Center for Brain Health Dispelling Myths of MS and Physical Therapy November 2015

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4 History First likely case on record St. Ludwina ( ) 1868 Charcot - First defined la sclerose en plaque disseminee 1916 Dawson described myelin damage and perivenular inflammation 1930s mouse model - EAE 1965 Schumacher criteria DIS and DIT 1980s MRI available 1993 Interferon Beta-1b (Betaseron) FDA approved symptomatic therapy FDA approved DMT Future remyelination, neuroprotection, biomarkers Murray 2005, NMSS 2009

5 Multiple Sclerosis Epidemiology Most common chronic disease of the CNS in young adults Approximately 400,000 cases in the United States The chances of developing MS are ~1: in the general population Estimated 2.5 million cases worldwide Highest incidence in Caucasians though affects all Higher incidence in women (approximately 3:1) Primary progressive MS shows no such gender preference Compston A, et al. Lancet ; Frohman EM. Med Clin N Am Hogancamp WE, et al. Mayo Clin Proc Lage MJ, et al. Work

6 McAlpine 1965

7 Oligodendrocytes and Axons Axons are the major nerve fiber that carries information to other nerve cells or muscle from the cell body.

8 Oligodendrocytes and Axons Oligodendrocytes make myelin which wraps multiple times around the axon (nerve fiber). One cell can provide myelin for numerous axons.

9 Demyelination Causes slowing or blocking of conduction, alters the function of neurons. Sheridan. Nature Biotechnology 2004

10 c c Giesser 2010

11 Pathology Continuum 2013

12 2010 McDonald Criteria Polman 2011

13 MRI

14 Other Paraclinical Data CSF Lymphocytic pleocytosis mildly elevated protein increased IgG index >2 unique OCBs Visual Evoked Potentials/OCT SSEP/BAEP Awad 2010

15 Increasing Disability Relapsing Phases (RIS) Level of Disability Cognitive Dysfunction MRI Burden of Disease Brain Volume Acute MRI Activity Time Trapp, The Neurologist 1999

16 Disability New classification RRMS SPMS PPMS PRMS Time Lublin Neurology 1996, Lublin Neurology 2013

17 Evolution of the Treatment of Multiple Sclerosis Steroids (ACTH, low-dose, high-dose) Mercury Typhoid vaccine Arsenic Tonsillectomy Anticoagulants Polyunsaturated fatty acid regimes Hyperbaric oxygen Nonspecific immunosuppressive (azathioprine, cyclophosphamide) 1993 Interferon β 1b 1996 Glatiramer acetate 1996 Interferon β 1a IM 2002 Interferon β 1a SC 2002 Mitoxantrone 2006 Natalizumab 2010 Fingolimod 2012 Teriflunomide 2013 Dimethyl Fumarate 2014 Pegylated IFN A.D Alemtuzumab

18 Current Disease Modifying Treatments for Relapsing- Remitting MS interferon-β-1a (REBIF) interferon-β-1a (AVONEX) interferon-β-1b (BETASERON, EXTAVIA) PEGylated Interferon β-1a (PLEGRIDY) glatiramer acetate (COPAXONE, COPAXONE 40) natalizumab (TYSABRI) fingolimod (GILENYA) teriflunomide (AUBAGIO) dimethyl fumarate (TECFIDERA) alemtuzumab (LEMTRADA)

19 Efficacy of DMT Goodin, et al, Neurology, 2012;78: Comi, et al. Lancet 2009; 374:

20 multiplesclerosis.net

21 Exercise Myths Worsens the disease Causes relapse Why did this seem to be the case? Heat intolerance due to demyelination Decreased neurological reserve What s the harm of this advice? Promotes deconditioning Contributes to obesity Contributes to osteoporosis Giesser Ther Adv Neurol Disord 2015

22 Exercise benefits Slows down disease progression? anti-inflammatory effect? neuro-protective effect Improves strength, mobility, spasticity, pain, fatigue, mood, cognition Improves quality of life Giesser Ther Adv Neurol Disord 2015

23 Motl and Pilutti, Nat Rev Neur 2012

24 Motl and Pilutti, Nat Rev Neur 2012

25 Learmonth et al, Int J of MS Care 2015

26 How to help my patient with MS? PT/OT/SLP Recovery from relapse Acute weakness and gait difficulty Adjusting to new disability- physical, cognitive Maintain independence as disease progresses Help create exercise program Improve gait and balance Teach stretching/rom, prevent contractures Improve/maintain transfer ability, hand strengthening Evaluate for adaptive equipment, AFOs, electric stimulators, DME Teach energy conservation, compensation Caregiver education Improve quality of life Provide feedback to patient, physician, caregivers Do not take away hope

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