1. Multiple Sclerosis Presentation by Jacqueline Godin

2. What is MS?  Pathophysiologic condition where nerve fibers in CNS lose their myelin  Causes slow transmission of impulses  Autoimmune disease  Body’s own immune system attacks the myelin sheath  Arises from combination of genetic and environmental factors  Genetic predisposition causes increased susceptibility to environmental factors that may cause the disease  Some possible environmental factors: viral infections, environmental toxins, and vitamin D deficiency  Not generally fatal, but chronic and disabling for some  Currently no cure

3. Symptoms  Common  Fatigue  Numbness  Balance & Coordination Problems  Depression  Vision Problems  Dizziness and Vertigo  Spasticity  Pain  Gradual Paralysis  Less Common  Respiration/Breathing Problems  Swallowing Problems  Headache  Speech Disorders  Tremors  Hearing Loss  Seizures The disruption of nerve signals produces the primary symptoms of MS, which vary depending on where the damage has occurred

4. Four Courses  Relapsing-Remitting  Clearly defined attacks (exacerbations) of worsening neurologic function followed by partial or complete remissions (85%)  Primary-Progressive  Slowly worsening neurologic function from the start with no distinct relapses or remissions (10%)  Secondary-Progressive  Following an initial period of Relapsing-Remitting in which the disease worsens more steadily, with or without occasional remissions or flare-ups  Progressive-Relapsing  Steadily worsening disease from the start with clear attacks of worsening neurologic function along the way; disease continues to progress without remissions (5%)

5. http://www.youtube.com/watch?v= KGzsriXqg6U

6. The Process  Characterized by local infiltration of T cells and macrophages into the nerve tissue, local multiple areas of inflammation in this tissue, activation of the glia (astrocytes and microglia), damage to oligodendrocytes, demyelination of nerve fibers, and injury of axons  A hardened scar (sclerosis) forms at the sites of myelin damage  These scars interfere with and can eventually block the propagation of action potentials in these axons

7. Mechanism

8.  Normally blood-brain barrier (BBB) is impermeable to blood cells, but infiltration by T cells causes the appearance of inflammation and development of demyelination  This can be initiated by the penetration of viral and bacterial factors in the nerve tissue, which results in the appearance of their proteins on the membranes of oligodendrocytes and myelin sheaths  A subsequent autoimmune response is then directed against myelin antigens, which leads to disorders of recognition of these antigens  The viral/bacterial proteins exposed on the surface cause antigen-presenting cells to induce primary activation of autoreactive T cells circulating in the vascular system  T lymphocytes proliferate and express cell adhesion molecules (CAMs) and cytokines, intensifying damage to the BBB and causing an abnormal increase in its permeability

9. Mechanism  Then the endothelial leukocyte-connected CAMs with the participation of metalloproteinases of the external matrix (MEMs) promote passing of T cells, B cells, plasmocytes, and activated microphages via the basal membrane of the BBB in the CNS  Then T cells in the presence of local autoantigens induce the development of scattered foci of inflammation in the CNS  T cell-synthesized proinflammatory cytokines (interleukin 2, lymphotoxin, γ-interferon, and tumor necrosis factor (TNF-α)) promote the continued intensification of the BBB permeability  Under these conditions, B cells and antibodies present in the blood migrate in the CNS much more intensely and, via activation of the complement system, form membrane-attacking complexes that damage myelin and oligodendrocytes

10. Mechanism  In addition, cytokines trigger the processes of activation of microglial cells, macrophages, and astrocytes  As a result, microglial cells begin to secrete inflammatory cytokines, MEMs, and increased amounts of free radicals  Also, microglia frequently play the role of antigen-presenting cells in the CNS, which intensify the development of a pathological immune response in MS  Astrocytes also acquire the properties typical of immune effector cells, producing a few cytokines, antigens, CAMs, and immunomodulators  Therefore, microglia together with astrocytes form the abnormal immune response in the cerebral tissue

11. Mechanism  As a result of the previously stated local auto-immune response and local vascular inflammation, the myelin sheaths are subjected to destruction, while oligodendrocytes are injured  This leads to demyelination and degeneration of the axons with subsequent formation of sclerotic plaques  The damaged myelin is then phagocytized and destroyed by microglia-activated astrocytes and macrophages penetrating the CNS

12. Mechanism  Secretion of chemokines is activated by proinflammatory cytokines  In MS, endothelial cells synthesize MCP-3; activated perivascular T cells synthesize RANTES; macrophages synthesize MIP-1β; astrocytes synthesize RANTES, MCP-1,2,3, and MIP-1β; microglial units synthesize MIP-1β  Chemokines mediate humoral and cellular immune reactions and can contribute to the intensification and distribution of the inflammatory reaction and process of demyelination

13. Mechanism  MEMs synthesized by activated T cells, monocytes, astrocytes, and microglia in MS promote invasion of inflammatory cells in the CNS after damage to the basal membrane of the BBB and extracellular matrix  They are also directly involved in the process of destruction of myelin  With the development of MS, the impairment of the process of lipid peroxidation results in the production of increased amounts of free radicals, which promote extensive injury to the myelin and oligodendrocytes

14. Mechanism Summary  The autoimmune response and the vascular inflammation causes demyelination and degeneration of axons, formation of sclerotic plaques (lesions), and injury of oligodendrocytes  The damaged myelin on the axons is then phagocytized by astrocytes and macrophages

15. Treatments  *As neural inflammation resolves, some remyelination can occur along with some recovery of function, however this may be due to neural plasticity  No cure, but some effective strategies include modifying the disease course, treating exacerbations, managing symptoms, improving functioning and safety, and providing emotional support

16. Treatment: Modifying Disease Course  Some modifying agents include Copaxone, Gilenya, and Rebif  The drug Gilenya, for example, acts by retaining certain lymphocytes in the lymph nodes, thereby preventing those cells from crossing the BBB into the CNS  This reduces inflammatory damage to nerve cells

17. Treating ExacerbationsManaging Symptoms Treatments  Exacerbation is caused by inflammation in the CNS that causes damage to the myelin and slows or blocks the transmission of nerve impulses  Most commonly treated with high-dose corticosteroids to reduce the inflammation  Symptoms are highly variable from person to person and from time to time, but most can be managed through medication, self-care techniques, rehabilitation, or use of assistive devices

18. Promoting Function Through Rehabilitation Role of Complementary and Alternative Medicine Treatments  Rehab programs focus on helping improve or maintain ability to perform effectively and safely at home and work  Focus on overall fitness and energy management, while addressing problems with accessibility and mobility, speech and swallowing, and memory  Important at all stages of the disease  Includes everything from exercise and diet to food supplements, stress management strategies, and lifestyle changes  Examples: Yoga, hypnosis, relaxation techniques, etc.  Complementary = used in conjunction with conventional medical treatments  Alternative = instead of

19. Questions?