1. Dallas, TX November 2–4, 2012 Multiple Sclerosis Shirley O’Leary MS NP-C MSCN Texas Neurology Dallas, Texas Mary L. Filipi APRN, PhD Neurology Associates, PC. Lincoln, NE Assistant Professor – College of Nursing University of Nebraska Medical Center Omaha, NE

2. Dallas, TX November 2–4, 2012 MULTIPLE SCLEROSIS Autoimmune CNS disease T-cell mediated Progressive/Degenerative Unpredictable course

3. Dallas, TX November 2–4, 2012 Pathology Characterized by inflammation and demyelination of white matter or myelinated fibers of brain and spinal cord.

4. Dallas, TX November 2–4, 2012 Multiple Sclerosis Inflammatory & degenerative disease of the central nervous system (CNS) that destroys myelin, oligodendrocytes, axons Inflammation may have a dual role in MS: tissue damage and neuroprotection Affects >1 million individuals in North America and Europe Major cause of nontraumatic neurological disability in young adults

5. Dallas, TX November 2–4, 2012 Disease Progression Clinical course is variable Early disease may be subclinical (asymptomatic) Pathogenesis of MS is not fully understood MS may be a single disease or a common endpoint of multiple disease etiologies

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7. ETIOLOGY Autoimmunity –Genetic predisposition –Environmental factors Infection –Molecular mimicry (herpes simplex, Chlamydia).

8. Dallas, TX November 2–4, 2012 MS PATHOLOGY Disease of CNS white matter Multifocal areas (plaques) of axonal demyelination –Moderate loss of axons –Loss of oligodendrocytes –Astroglial scaring Demyelination of axons can reduce speed or block nerve impulses

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10. Demyelination and Axonal Transection

11. Dallas, TX November 2–4, 2012 MOST COMMON SYMPTOMS OF MULTIPLE SCLEROSIS Pyramidal weakness45% Optic neuritis40% Sensory loss35% Brainstem dysfunction30% Cerebellar ataxia and tremor25% Cognitive impairment 34- 65% Sphincter disturbances20%

12. Dallas, TX November 2–4, 2012 MS Abnormal immune response to one or more myelin antigens that occur in genetically susceptible persons after exposure to an as yet undefined casual agent (Hauser)

13. Dallas, TX November 2–4, 2012 DIAGNOSTIC CRITERIA Poser – dissemination in time and place based on history and neurological examination McDonald – combination of MRI and clinical finding to document dissemination - at least one clinical event required

14. Dallas, TX November 2–4, 2012 DIAGNOSIS Brain MRI is commonly over interpreted Diagnosis of MS must be based on clinical findings and MRI information

15. Dallas, TX November 2–4, 2012 Increasing disability Time What Course Might MS Take Over a Lifetime? MS can progress differently in different people The disease may be a combination of relapses, recovery, and progression

16. Dallas, TX November 2–4, 2012 MAJOR CLINICAL COURSES OF MS 5%50%30%15%

17. Dallas, TX November 2–4, 2012 Clinical Disability in MS 510 Years 15 20

18. Dallas, TX November 2–4, 2012 M R I Plaques found: periventricular regions, corpus callosum, brainstem, cerebellum and spinal cord. Hyperintense on T2 and FLAIR sequences sometimes hypointense (black holes) on T1

19. Dallas, TX November 2–4, 2012 Wingerchuk DM, et al. Lab Invest. 2001;81:263-281. Pathophysiologic Features of MS Pathological signature of MS is the white matter (WM) circumscribed areas of demyelination Lesions may occur anywhere in WM but are most commonly seen in –Periventricular regions –Optic nerves –Brain stem –Cerebellum –Spinal cord Lesions may contain varying proportions of immune cells and immunoreactive substances depending on stage of the disease

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23. The Importance of Early Treatment Treatment at diagnosis Later treatment Disease Onset Based on theoretical model

24. Dallas, TX November 2–4, 2012 TREATMENTS Disease modifying agents – CRAB’s Symptomatic treatment Treatment of acute relapses

25. Dallas, TX November 2–4, 2012 PEARLS OF MS TREATMENT All symptoms are not MS related ↑ core temperature ↑ symptoms 40% of flares are pseudo flares

26. Dallas, TX November 2–4, 2012 Fatigue Fatigue is the major debilitating factor in MS

27. Dallas, TX November 2–4, 2012 IV Disease and Flare Treatment Solumedrol 1 gram IV in 250 NS to run 4-6 hrs – may follow with a minimal oral taper Tysabri 300 mg IV in 100 cc NS to run over 1 hour with a one hour wait following infusion – NO EXCEPTIONS Alemtuzumab 12 mg in 100 cc NS or 5% glucose over 4 hours for first dose 3 rd & 4 th dose over 2 hours minimum, 8 hours maximum

28. Dallas, TX November 2–4, 2012 Tysabri 300 mg IV q 28 days to run over 1 hour or more Mix gently invert bag to mix Stable for 8 hours May premedicate with Tylenol, Zantac, and antihistamine Premedication may include Solu-Medrol Must be enrolled in TOUCH prescribing program

29. Dallas, TX November 2–4, 2012 Alemtuzumab IV over 4 hours for first 2 doses – 5 days annually Premedicate with methylprednisolone, tylenol, diphenhydramine, cetirizine hydrochloride, odansetron and famotidine During infusion – tylenol, odansetron and naprelan Post infusion - famotidine

30. Dallas, TX November 2–4, 2012 Alemtuzumab Thyroid problems ITP Will need long term monitoring

31. Dallas, TX November 2–4, 2012 Questions