1. Multiple Sclerosis (MS) Presented By: Alyssa Sturm & Brittany Gray December 4, 2012

2. What Are the Symptomsof MS? Primary symptoms ▫Loss of motor skills ▫Loss of senses ▫Physiological fatigue ▫Speech problems ▫Memory impairment Other symptoms depend on patient

3. Figure 1. Th Cell Invasion of Blood-Brain Barrier

4. Figure 2. Unmyelinated vs. Myelinated Axons

5. What is the History of MS? Robert Carswell-1838 ▫Described features of MS Jean-Martin Charcot-19 th century Noted specific symptoms: ▫Memory issues ▫Slowed thinking ▫Intellectual dysfunction

6. Figure 3. Criteria for Diagnosing MS jiroejwi ojfeioje jgeiojgi oerjhds uivh Yes

7. What is the Epidemiology of MS? 400,000 Americans 2.5 million world wide Incidence ▫7 new cases per 100,000 people per year ▫Lifetime risk of 1/400 Onset ▫Twice as likely in females

8. What Are the Risk Factors of MS? Environmental Factors ▫Diet, air pollutants, cigarettes, vitamin-D deficiency, ect. ▫Epstein-Barr Virus, Measels, Mumps Genetic Factors ▫HLA DR15 and DQ6  Different MHC involved  Myelin Proteins

9. What is the Immunopathology of MS? Regulatory lymphocyte defect β-arrestin 1

10. What is the Immunopathology of MS? Inflammation-CD8+ Plaques Myelin basic protein Molecular mimicry

11. What Are Triggers and Risk Factors of MS? Infections High pollution Disease First degree relative with MS

12. What Treatments Are Available? Treatments for Inflammation ▫High-dose methyl prednisolone Treatments for Symptoms: ▫Tremors-Clonazepam, primidone ▫Fatigue-Amantadine, modafinil Treatments for Relapses: ▫Holistic Multi-Professional Therapy

13. Future Treatments? Transplantation therapy: ▫Experimentally induce encephalomyelitis in mice ▫Neural stem cells from humans ▫Stem cell migrate ▫Improve of axonal loss

14. References Benedict RHB, Bobholz JH. 2007. Multiple sclerosis. Seminars in Neurology 27 (1): 78-85. Compston A, Coles A. 2008. Multiple sclerosis. The Lancet 372 (9648): 1502-1517. Kulbatski I, Mothe AJ, Parr AM, Kim H, Kang CE, Bozkurt G, Tator CH. 2008. Glial precursor cell transplantation therapy for neurotrauma and multiple sclerosis 43 (3): 123-176. Vollmer T. 2007. The natural history of relapses of multiple sclerosis. Journal of the Neurological Sciences 256 (1): S5-S13. Wakerley B, Nicholas R, Malik O. 2008. Multiple sclerosis. Medicine 36(12): 2008.

15. Study Questions 1. Why do lymphocytes not typically cross the blood-brain barrier? A. There are low levels of MCH in the brain B. Presence of immunosuppressive hormones and cytokines in the brain C. Immune cells become anergized (Fas, FasL, and Treg) in the brain D. A, B only E. All of the above 2. Why do unmyelinated axons have a slower conduction of action potentials than myelinated axons? A. Myelinated axons only regenerate action potentials at the Nodes of Ranvier B. Unmyelinated axons only regenerate action potentials at the Nodes of Ranvier C. Myelinated axons regenerate action potentials at every ion channel present along the axon D. Unmyelinated axons regenerate action potentials at every ion channel present along the axon

16. Study Questions (Cont.) 3. What is the role of β-arrestin 1, a protein responsible for regulating receptor-mediated immune functions, in Multiple Sclerosis? A. β-arrestin 1 is inhibited and therefore does not activate Th cells B. β-arrestin 1 is over expressed and promotes constant activation of Th cells C. β-arrestin is involved with ineffective Th cell apoptosis upon stimulation by self-antigens D. Both B and C 4. Briefly explain why in patients with Multiple Sclerosis there is an immune response against the myelin basic protein (MBP) even though it is a self protein.