1. Multiple Sclerosis Walter Royal, III, MD Associate Professor, Department of Neurology University of Maryland School of Medicine Director, Maryland Center for Multiple Sclerosis Treatment and Research

2. What is Multiple Sclerosis? • Multiple Sclerosis (MS) is an chronic inflammatory demyelinating disease of the brain and spinal cord.

3. Areas affected by MS Brain Spinal cord Optic nerves The Human Nervous System (http://web.lemoyne.edu/~hevern/psy340/lectures/psy340.04.2.ns.structure.html)

4. MS is an Immune-Mediated Disease BBB=blood-brain barrier; APC=antigen-presenting cell. Adapted from Miller et al. Continuum: Multiple Sclerosis (Part A). 1999;5:7.

6. How Common is MS and Who Gets It? • 8,000 – 10,000 new cases are diagnosed annually • Affects nearly 500,000 individuals in the U.S. • Occurs most frequently between ages 25 - 35 • Female: male ratio = 2:1 • More frequent in populations native to areas further away from the equator

7. Risk of Developing MS and Region of Origin

8. What Causes MS? • Genetics • Environmental factors

9. Genetic and the Immune System

10. Monozygotic (identical) twins Dizygotic (non-identical) twins Child of parent with MS Sibling of person with MS 25 – 30% 3 – 4.5% 1.9% 0.9% Family Studies Up to 19% of patients have an affected relative

11. Groups for Which MS Genetic Traits Have Been Identified: • Japanese • African American • Mexican • Arabian • Sardinian (Italy) • Swedish • Norwegian • French Canadian • Multi-ethnic Caucasian • Finnish • Etc.

12. Not Everyone with a Genetic Risk Will Develop MS – Why? • Risk is modified by Environmental factors • Sunlight • Diet (e.g., vitamin D) • Other lifetime experiences (infections?)

13. Initial Presentation of MS

14. Other Common Symptoms of MS

15. Relapsing-remitting Secondary-progressive Disability Disability Disability Disability Time Time Primary-progressive Progressive-relapsing Time Time Multiple Sclerosis Clinical Subtypes Lublin FD et al. Neurology. 1996;46:907-911.

16. How Is MS Diagnosed? • At least two episodes of symptoms • Occur at different points in time • Result from involvement of different areas of the central nervous system • Absence of other treatable causes for the symptoms • Results of neurological testing

17. Examples of MS Onset • Case 1: 26 year old woman • Decreased vision in the right eye in 9/05 • Left leg numbness in 1/06 • Right face numbness, right arm and leg weakness in 4/06 • Left leg weakness in 8/06 • Case 2: 45 year old man • Left arm weakness in 2/93 • Numbness below the waist in 4/07

18. Other Potential Causes ofMS-like Symptoms • Lyme disease • Lupus • Migraine • Non-recurrent inflammatory process • Encephalitis • Stroke • Tumor of the brain or spinal cord

19. How Is MS Diagnosed? • Neurological examination • Magnetic resonance imaging (MRI) Scan • Blood tests • Lumbar Puncture (spinal tap): occasionally performed • Other testing: infrequently performed

21. Assessment of the Appearance of MS Lesions Over time Time lapse = 1 year

22. Images acquired over the course of 7 years from a single person with untreated MS Brain Atrophy (Shrinkage) in Untreated MS

23. Brain Atrophy (Shrinkage) in Untreated MS

24. How is MS Treated and Managed? • Drug therapy • Treat new attacks (exacerbations) • Prevent the occurrence of future attacks • Slow or prevent disease progression • Treat the chronic symptoms of the disease • Physical therapy • Psychosocial support

25. Treatment of New MS Exacerbations • Drug therapy • Corticosteroids • Intravenous immunoglobulin • Plasma exchange • Physical therapy

26. Prevention of Future Attacks and Disease Progression • Immune modulating drugs • Beta-Interferon • Glatiramer acetate • Humanized monoclonal antibodies • Immunosuppressant drugs • Anti-cancer agents • Combination therapies

27. Symptom Management – Examples • Pain control • Management of impaired bladder and bowel function • Anti-spasmodic drugs • Treatment of fatigue • Splinting for contractures • Counseling

28. MS Therapies: What Lies Ahead? • Neural protection • Regenerative therapies • Cell replacement (stem cells) • Dietary approaches (vitamin D)

29. Multiple Sclerosis Research at the University of Maryland • Drug therapies • Injectable drugs with increased efficacy • New oral agents • Cell replacement therapies • Stem cell research • MS “vaccine” • Novel rehabilitation techniques • Robotics • Dietary approaches • Studies of the role of vitamin D in MS

30. Summary • MS is a common inflammatory disease of the CNS that affects females more frequently than males. • The cause of MS appears to be a combination of genetic and environmental factors. • The symptoms of MS can be quite variable. • MRI is a sensitive test for making the diagnosis of MS. • Treatments are available for reducing the number of MS attacks and for slowing MS disease progression.