Multiple Sclerosis
Post on 22-Feb-2016
22 Views
Preview:
DESCRIPTION
Transcript
Multiple SclerosisPresentation by Jacqueline Godin
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
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
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%)
http://www.youtube.com/watch?v=KGzsriXqg6U
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
Mechanism
Mechanism 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
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
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
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
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
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
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
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
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
Treating Exacerbations Managing 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
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
Questions?
top related