Multiple Sclerosis PDF

Multiple Sclerosis 5th stage Multiple Sclerosis INTRODUCTION Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by myelin destruction and axonal damage. Multiple describes the numerous CNS lesions that accrue over time, and sclerosis re...

Multiple Sclerosis 5th stage Multiple Sclerosis INTRODUCTION Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by myelin destruction and axonal damage. Multiple describes the numerous CNS lesions that accrue over time, and sclerosis refers to the demyelination of lesions, also called plaques. It is progressive disease, affect women more than men, between 20-50 years old The cause of MS is unknown, but may be due to a combination of genetic, environmental, immunologic, or infectious factors Symptoms Urinary incontinence or retention Spasticity Optic neuritis Bowel incontinence or constipation Depression Anxiety Cognitive deficits Fatigue Uhthoff phenomenon Tremor Pain Trigeminal neuralgia Lhermitte sign Dysesthetic pain Impaired gait Types of MS Diagnosis Blood tests, to help rule out other diseases with symptoms like MS. Spinal tap (lumbar puncture), in which a small sample of cerebrospinal fluid is removed from your spinal canal for laboratory analysis. This sample can show abnormalities in antibodies that are associated with MS. MRI, which can reveal areas of MS (lesions) on your brain, cervical and thoracic spinal cord. Patient may receive an intravenous injection of a contrast material to highlight lesions that indicate disease is in an active phase. Evoked potential tests that record the electrical signals produced by your nervous system in response to stimuli may be done. An evoked potential test may use visual stimuli or electrical stimuli. There are number of factors can aggravate MS symptoms on the patinets, what are they? What are the symptoms of patients who suffered from aggravating MS? Pathophysiology Treatment Goals of therapy is to prevent permanent neurologic damage and disability progression. First, treat acute relapses with corticosteroids to reduce inflammation and speed recovery. Second, early initiation of disease-modifying therapies (DMT) decreases the number of annual relapses, prevents permanent neurologic damage, and prevents progression of disability. Third, symptomatic treatments can be added to treat common primary symptoms such as pain and spasticity, depression, cognitive dysfunction, and urinary symptoms.  Corticosteroids Pharmacology and Mechanism of Action prevent inflammatory cytokine activation, inhibit T- and B-cell activation, and prevent immune cells from entering the CNS. Corticosteroids hasten functional recovery. Methylprednisolone is given 1000 mg/day IV or orally as one daily dose for 3 to 5 days  Disease-Modifying Therapies These DMTs can reduce annualized relapse rates (ARRs) from 30% to 70%. β-Interferons Pharmacology and Mechanism of Action β-Interferons decrease T cell activation, thereby decreasing cytokine secretion, which prevents upregulation of adhesion molecules on activated T cells, limits T cells’ access to the CNS, and suppresses matrix metalloproteinases (MMPs), thereby maintaining the integrity of the blood–brain barrier. It reduce relapses in RRMS and secondary progressive MS Adverse Effects Adverse effects are common with β-interferons. Flu-like symptoms (fever, fatigue, muscle aches, malaise, and chills) begin a few hours post-injection and dissipate within 24 hrs. How can minimize these adverse effects?  If the patients were suffered from depression, another DMA should tried  Glatiramer Acetate Pharmacology and Mechanism of Action Glatiramer acetate binds to MHC class II, blocking the activation of T cells and activating Th2 cells, preventing inflammation. Activated Th2 cells secrete brain-derived neurotrophic factor, which may be neuroprotective Efficacy Glatiramer acetate reduces relapses by 28% compared with placebo but does not prevent sustained progression of RRMS. It is used in CIS to prevent conversion to CDMS Adverse effects??  Teriflunomide Pharmacology and Mechanism of Action Teriflunomide has a cytostatic effect on rapidly dividing B and T cells, inhibits T-cell activation, entry to the CNS, and secretion of proinflammatory cytokines. Efficacy Teriflunomide reduces relapse rate and progression of disease for relapsing forms of MS. It also prevents CIS from converting to clinically definite MS This drug had serious S.E like: ----------  Fumaric Acid Derivatives Pharmacology and Mechanism of Action Dimethyl fumarate is prodrug These drugs shift cytokine production from a proinflammatory state to an anti- inflammatory state, prevent macrophage entry into the CNS by an unknown mechanism Efficacy Dimethyl fumarate reduced relapses approximately 50% compared to placebo. It slowed RRMS progression in some studies. Some times, this drug can cause itching, besides other GIT side effects, also injection site reactions  Monoclonal antibody Monoclonal antibodies (Mabs) are clones of a single antibody that have been developed as drug therapies. Each one is designed to recognize a specific target protein which may only exist on a single, or a few, cell types. This means that, in theory, treatments can be designed to have a very specific effect.  In MS, this means that, if research identifies the cells that are involved in attacking your nerve cells and causing disease activity, monoclonal antibody treatments could be developed that would only affect those cells. An example is the CD20 marker that is found on the surface of B cells, a type of white blood cell that that is thought to be involved in immune attacks on myelin.  1- Natalizumab Natalizumab be reserved for patients with a highly active disease course who have failed other therapies. Antinatalizumab antibodies develop in 9% to 12% of patients. If patients have anti- bodies 6 months after the start of therapy, relapse rates, disability, and hypersensitivity reaction risk increase.  2- Alemtuzumab Pharmacology and Mechanism of Action Alemtuzumab is a monoclonal antibody that eliminates circulating B and T cells. Repopulation of these cells takes 8 to 35 months. Efficacy Treatment reduced relapse rates compared to interferonβ with 77% of patients relapse free for 2 years. Similar to natalizumab, alemtuzumab is also considered a DMT with higher efficacy.  Anti-CD20 Monoclonal Antibodies Pharmacology and Mechanism of Action rituximab, is monoclonal antibody that specifically target and deplete B cells In RRMS, Rituximab demonstrated significantly reduced ARR and disease progression in patients compared to placebo. How can monitor disease improvement or therapy ?