The Nuts and Bolts of Multiple Sclerosis. Rebecca Milholland, M.D., Ph.D. Center for Neurosciences

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1 The Nuts and Bolts of Multiple Sclerosis Rebecca Milholland, M.D., Ph.D. Center for Neurosciences

2 Objectives Discuss which patients are at risk for Multiple Sclerosis Discuss the diagnostic criteria for the diagnosis of Multiple Sclerosis Discuss the types of and progression of Multiple Sclerosis Discuss treatment options for Multiple Sclerosis.

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5 Multiple Sclerosis - Epidemiology Smoking increased over all risk and prognosis Vitamin D Deficiency Genetic o 0.1% general population o Monozygotic twins 30% correlation o Dizygotic twins 4% o Sons 1% o Daughters 4% o Sex, 3 Women: 1 Man Age 20-50

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8 Diagnosis Cardinal Features of Multiple Sclerosis Attack Neurological Examination with Deficits MRI brain and total spine, with and without contrast CSF: oligoclonal bands and IgG index elevation Somatosensory, Visual Evoked Potentials Watch for Multiple Sclerosis Mimics

9 MacDonald Criteria; separation in time and space Revised 2010, and updated 2011 By MRI o Simultaneous presence of asymptomatic enhancing and non-enhancing lesions o OR new T2 lesion or gad-enhancing lesion on follow up MRI By clinical Exam AND MRI o Typical lesions on MRI o History of at least one exacerbation with typical deficits

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16 Multiple Sclerosis Mimics Migraine Vascular Disease Vasculitis Radiologically Isolated Syndrome/Clinically Isolated Syndrome ADEM (Acute Disseminated Encephalomyelitis)

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19 Vasculitis

20 o Acute CNS demyelinating disease o Follows infection o Accompanied by a mental status change and fever o Predominance in children o Occurs over days to weeks Acute Disseminated Encephalomyelitis Date: 22 Nov 2011Pages: 15, Chapter Category:Neurodegenerative Disease Taken from the Book: Neurodegenerative Diseases, Book Series: Special Books Edited by: Shamim I. Ahmad

21 Radiographic Isolated Syndrome Lesion typical for Multiple Sclerosis found as an incidental finding on MRI without clinical symptoms % convert to clinically isolated syndrome within 2-3 years. 90% demonstrate a diagnosis of Multiple Sclerosis by current criteria.

22 Clinically Isolated Syndrome Clinical syndrome typical for multiple sclerosis with a corresponding T2 lesion MRI % convert to multiple sclerosis within 5 years. Most often lesions in the optic nerve, brain stem, and spine.

23 Forms of Multiple Sclerosis Relapsing Remitting: o Repeated clinical attacks with stability between. Secondary Progressive MS: o Progressive impairment between or in the absence of attacks o Disease modifiers no clear effect. NO history of attacks with resolution o Progressive myelopathy with accompanying dysfunction. NMO neuromyelitis optica: o Large initial lesion in the cervical spine o More aggressive form of Multiple Sclerosis o anti-aquiporin 4 antibodies

24 Determination of Therapeutic Goals Reduce the frequency of relapses. Reduce the numbers of lesions forming over time. Reduce disability accumulation. Avoid long-term disability.

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29 Fingolimod (FTY720) Mechanism of Action o Prevents T cell entry into CNS by trapping them in the peripheral lymph nodes. Monitoring o o o o Baseline CBC and liver panel Opthalmological examination Cardiac Status Varicella Immune Status Initiation: 6 hr observation, for first dose bradycardia o o o CBC, Hepatic Panel Opthalmologic Exam 3-4 months Monitor BP

30 PML Risk With Natalizumab Progressive multifocal leukoencephalopathy o Subacute progressive demyelinating disease caused by JC virus. o Symptoms: Progressive hemiparesis Speech disturbance Visual field cut Cognitive dysfunction confusion and personality changes o Prognosis poor, usually death o MRI findings, extensive, confluent lobar areas of T2 signal change

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33 BG12 Nrf 2 activation, possibly activating apoptosis. Oral agent Side Effects o Flushing o Diarrhea o Nausea o Abdominal pain o Leukopenia, not associated with adverse effects Monitoring CBC and CMP after 3 months

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37 Knowledge Assessment 1. What percentage of clinically isolated syndrome patients convert to MS? a) 5% b) 10% c) 20% d) > 30% 2. The standard treatment for a pregnant MS patient is no treatment. a) True b) False 3. Existing MS therapies include a) Intravenous b) Infusions c) Oral Medications d) All of the above

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