Multiple Sclerosis. Matt Hulvey BL A - 615

Multiple Sclerosis Matt Hulvey BL A - 615

Multiple Sclerosis Multiple Sclerosis (MS) is an idiopathic inflammatory disease of the central nervous system (CNS) MS is characterized by demyelination (lesions) and subsequent axonal degeneration resulting in a loss of axonal conductance

Multiple Sclerosis Physical evidence of the disease exists as lesions or scar tissue Disease is characterized by lesions in more than one location with relapses occurring at least 3 months apart

Common Symptoms Numbness Weakness Loss of balance/vertigo Fatigue Hearing loss Depression Visual Impairment Action tremmor Urinary bladder urgency Affected reflexes

Relapsing/Remitting MS Characterized by relapses Followed by periods of remission Most patients are initially diagnosed with relapsing/remitting MS Exacerbation time

Secondary Progressive Transition from RRMS over time Gradual worsening between relapses After ~10 years 50% of patients with RRMS will be diagnosed with SPMS Exacerbation time

Progressive Relapsing A blend between previous forms Marked by noticeable recovery following relapse, but gradual worsening during remission Exacerbation time

Primary Progressive Characterized by gradual progression from onset with no recovery Onset is typically in late 30 s s or early 40 s Initial disease activity is found in spinal cord Exacerbation time

Other Forms/Similar Conditions Benign MS Malignant MS Marburg s s Variant Transitional/Progressive Devic s disease Optic Neuritis Balo s concentric sclerosis Lyme disease Syphilis Lupus Sarcoidosis Vitamin B 12 deficiency Leukodystrophy

Pathology The exact mechanism and cause of demyelination are unknown Evidence of inflammation is found at sites of MS lesions (macrophages) Myelin can be replaced via oligodendrocytes A loss of oligodendrocytes has been reported in many cases at later stages lending more evidence toward an inflammatory response

Glial Cells The Dark Side of Glia Cells, Science, 2005, 308, 778-781 (May 6 issue)

Demyelination Many believe it is caused by inflammation at myelinated axon Inflammation also leads to loss of oligodendrocytes Over time loss of myelin can lead to axonal degredation Oligodendrocytes provide essential nutrients to axons Axonal degeneration doesn t t seem to occur through inflammation

Demyelination

Neuronal Injury

Autoimmunity Possible Triggers Molecular or epitopic mimicy Pathogen Mediated Epstein-Barr virus, HHV 6, clamydia pneumonia Genetics/Environment Familial and geographical studies Blood-Brain Barrier Degredation Allowing infectious pathogens to pass readily Nitric Oxide Peroxynitrite in cell death and lipid peroxidation NO itself involved in myelin decompaction Augmented glutamate release in oligodendrocytes

Remission During remission, some recovery can take place Axons can develop more sodium channels Myelin can be replaced/repaired New neuronal pathways can be created Astrocytes may form scar tissue

Remyelination

Diagnosis Presence of CNS lesions disseminated in time and space while ruling out all other possibilities Done using a combination of MRI scans and clinical protocols MRI can reveal lesions not clinically detectable Also use Sensory Evoked Potential Testing and Cerebrospinal Fluid (CSF) Analysis

Clinical Diagnosis Romberg s s sign Gait and coordination L Hermittes test Heel Shin Test Muscle strength Reflexes Evoked Potential Test Visual Auditory Sematosensory MRI Spinal Tap

Visually Evoked Potential www.ophth.kpu-m.ac.jp/ research/img/enhj1.jpg

Babinski s Sign Reflex indicating lesions in pyramidal / corticospinal tract Extensor response may indicate neurodegeneration

MRI Based on the principals of NMR Application of external magnetic field will align protons (0.5 T 2 T) Body is primarily made up of fat and water therefore making the body ~63% hydrogen atoms Radio wave frequencies are used to excite protons. Energy released from excited protons is measure to give image via Foruier Transform

MRI Diagnosis

MRI Diagnosis

Immunotherapies Treatment Beta-interferons Glatiramir acetate Monoclonal antibodies Anitoxidants Scavenge NO and other oxidative species Difficult since NO is necessary in proper function Uric acid scavenging ONOO - Anitoxidant vitamins stimulate immune system

Treatment

Benefits of Early Detection Irreversible axonal damage may occur early in RRMS Drug therapies appear to prevent new lesions as opposed to promoting recovery MRI has allowed closer tracking of lesion formation and drug treatment follow-up

Conclusion MS is as mysterious now as ever Developing treatments seem to support multiple pathways Advancing technologies will help early diagnosis Stronger MRI (7 tesla coils) Treatment of early detection makes disease more managable

References (1) Encinas J., M. L. Current Neurology and Neruoscience Reports 2005, 5, 232-238. (2) Freedman, M. Multiple Sclerosis and Demyelinating Diseases; Lippincott, Williams and Wilkins, 2006. (3) Giovannoni G., H. S., Land JM., Thompson EJ. Mutliple Sclerosis 1998, 4, 212-216. (4) Jones, P., 2001; Vol. 2006. (5) Manigar A., G. T. E., Zlexander S., Kelley R. American Society of Neuraoimaging 2004, 14, 5-10. (6) Niepel G., C. C. Hospital Pharmacist 2003, 10, 12-16. (7) Parkinson J., M. B., Merrill J. J. Mol. Med. 1997, 75, 174-186. (8) Rejdak K., E. M. J., et. al. Neruology 2004, 63, 1439-1445. (9) Thiel V., A. K. Antioxidants and Redox Signaling 2001, 3, 273-278.