MULTIPLE SCLEROSIS Mercedes P Jacobson, MD, Department of Neurology Temple University School of Medicine

Transcription

1 MULTIPLE SCLEROSIS 2015 Mercedes P Jacobson, MD, Department of Neurology Temple University School of Medicine

2 Disclosure Research support, Sunovion and Marinus for epilepsy research

3 Goals and Objectives Definition of MS Associated terms and syndromes: Optic Neuritis, Neuromyelitis optic (NMO) Epidemiology Clinical/behavioral presentation Pathophysiology Diagnostic tools Management/treatment Patient Education

4 Key points in 2015: Pathophysiology Genetics and environment play a role: Multiple sclerosis (MS) can be considered an immunogenetic disease. Genetic predisposition to MS has been documented, and epidemiologic studies implicate environmental factors. Although still elusive, environmental factors appear to act as triggers in the context of genetic predisposition, which leads to immune dysregulation and MS. The immunopathogenesis of MS involves inflammation, demyelination, and axonal loss This is a degenerative disease Neurology Exchange: Exploring the Latest Advances in Multiple Sclerosis Diagnosis and Management Suhayl Dhib-Jalbut, MD; Aaron E. Miller, MD Medscape CME 04/28/2014

5 Key points in 2015: Treatment Initiate a DMD (Disease modifying Drugs) as soon after definitive diagnosis as soon as possible and considering DMD therapy in select high-risk patients with a first attack. The initiation of this treatment is frequently delayed or skipped entirely. Increasingly, earlier diagnosis and initiation of therapy is found to delay disability and lessen the overall impact of MS. Patient focused treatment is essential Neurology Exchange: Exploring the Latest Advances in Multiple Sclerosis Diagnosis and Management Suhayl Dhib-Jalbut, MD; Aaron E. Miller, MD Medscape CME 04/28/2014

6 Key points in 2015: Management/Wellness Complex DMTs (disease modifying therapies) mandate an active role for the practitioner Management of symptoms, and treatment of comorbid issues can enhance quality of life and may play a role in ameliorating disability.

7 Multiple Sclerosis Is a chronic immune mediated/inflammatory disease of the central nervous system The salient pathology in but not limited to the white matter; both axons and neurons are affected Inflammation leads to demyelination, then axonal loss and neurodegeneration Classic teaching: lesions in time and space

8 Multiple Sclerosis vocabulary CIS: clinically isolated syndrome 90% of MS at presentation at present RIS: Radiologically isolated syndrome Optic Neuritis Transverse Myelitis NMO: Neuromyleitis Optica or Devic s disease Associated with Aquaporin 4 antibody, an integral membrane protein Different medical management than typical RRMS

9 MS vocabulary: Relapse: Relapse rate is important, but relapse severity also important RRR=Relapse Rate Reduction Severity of relapse may lead to greater disability Disability Scores: EDSS (Expanded Disability Status Scale (EDSS) MRI findings: Active lesions enhance (Gad images) WM changes: Dawson s fingers McDonald Criteria: Refers to MRI findings Can make Dx of MS with CIS and appropriate MRI findings that demonstrate active and prior attacks Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69:

10 Progressive-relapsing MS: Steady decline since onset with superimposed attacks Secondary Progressive MS: Initial relapsing-remitting then sudden decline without remission Primary progressive MS: Steady increase in disability without attacks Relapsing-remitting MS: Unpredictable attacks which may or may not leave permanent deficits followed by periods of remission

11 Epidemiology: Who? A disease of the young, with the age of onset from 15 to 55 years. One million world-wide & 75, ,000 people with multiple sclerosis in the US Female to Male ratio 3:1 The MS prevalence ratio of women to men has increased markedly during the last decades Prevalent in the northern hemispheres. Ther Adv Neurol Disord Jul; 6(4): doi: /

12 What causes Multiple Sclerosis No one specific cause NOT preventable Factors include: Environment Lower socioeconomic status is protective Genetics- 15% HLA type Epstein Barr virus exposure Smoking Obesity Gender Low vitamin D level Drinking fewer than 4-6 cups of coffee per day Gourraud P., Harbo H., Hauser S., Baranzini S. (2012) The genetics of multiple sclerosis: an up-todate review. Immunol Rev 248:

13 Pathophysiology of Multiple Sclerosis Myelin or microbial antigens presented by antigen-presenting cells and B-cells trigger MS by activating peripheral proinflammatory Th1 cells, Th17 cells, and B- cells. Immune cells (CD4) are activated Activated cells cross the blood-brain barrier This causes cell mediated and humoral mediated damage to the oligodendroglia and astrocytes

14 Clinical presentation 2015 Attacks or exacerbations of multiple sclerosis (MS) are characterized by symptoms that reflect central nervous system (CNS) involvement CIS most common in 2015(Lublin) Motor or sensory deficits Ataxia Optic neuritis: 20% Acute transverse myelitis- spinal cord involvement MS is a heterogeneous disease! Multiple Sclerosis Clinical Presentation Author: Christopher Luzzio, MD; Chief Editor: B Mark Keegan,

15 Common complaints over time Sensory loss an early complaint Spinal cord symptoms: cramps, bowel, bladder, sexual dysfunction Fatigue: 75% Cognition: 40-70% Coordination Depression Pain - Occurs in 30-50% Heat intolerance Sensory loss Visual- optic Neuritis 40% Spasticity

16 Making the diagnosis Clinical features: history and exam Imaging Evoked Potentials CSF examination Blood studies: Excluding the lookalikes Collagen vascular disease and other rheumatologic conditions Infections (ie, Lyme disease, syphilis) Endocrine abnormalities (eg, thyroid disease) Vitamin B12 deficiency Vitamin D level Sarcoidosis Vasculitis (ANA, ESRR) Subject looks at checkerboard pattern Conduction time to cortex, P100 measured

17 Optic Neuritis

18 MRI findings Brain MRI shows brain abnormalities in 90-95% of MS patients MRI + spinal cord lesions in up to 75%patients. T2WI= chronic disease, T1WI show black holes=death of axons. These T2WI show involvement of corpus callosum and Dawson s fingers

19 MRI in Multiple Sclerosis ects/ms Christian Barillot, PhD 2011 Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69:

20 Principles of pharmacotherapy T-regulatory cells (Th2, Tr1, Th3, Foxp3 cells), which are generated in the periphery and cross the BBB, down regulate the inflammatory process, resulting in remission of MS. This paradigm is consistent with the mechanisms of action of MS therapies, including interferon, glatiramer acetate (GA), natalizumab, fingolimod, teriflunomide (TF), and dimethyl fumarate (BG-12). Neurology Exchange: Exploring the Latest Advances in Multiple Sclerosis Diagnosis and Management Suhayl Dhib-Jalbut, MD; Aaron E. Miller, MD Medscape CME 04/28/2014

21 Drugs used in treatment of MS ABC s of Injectables Beta interferon, Avonex, Rebif Copaxone Relapse Rate Reduction: (RRR) 30-35% Potential to develop neutralizing antibodies Small molecules oral meds Terflunomide or Aubagio 31% Relapse Risk Reduction, Pregnancy Category X Fingolimod or Gilenya EKG monitoring, labs & vax status RRR: 54-60% Dimethyl fumarate (BG-12) Tecfidera 49% 2 year RRR Natalizumab or Tysabri JC virus exposure status and PML risk patients w/o combined disease activity: 45.59% during the first two successive years of treatment; 17% drop out rate. Chemo agents, Mitoxantrone and Bone marrow TX A prospective observational post-marketing study of natalizumab-treated multiple sclerosispatients: clinical, radiological and biological features and adverse events. The BIONAT cohort. Eur J Neurol Jun 12. doi: /ene [Epub ahead of print]

22 The importance of early treatment blogspot com/ archive html Koch 2013

23 Signs of breakthrough disease include the following: 1 moderate/severe clinical relapse over 1 year; mild clinical relapses over 2 years; 1 to 2 gadolinium-enhancing brain lesions over 1 year; Two T2 lesions over 2 years; Functionally significant worsening in cognition, ambulation, upper extremity function.

24 Measuring disability Expanded Disability Status Scale (EDSS)

25 Wellness in Multiple Sclerosis Vitamin D analog helpful for fatigue Stop smoking: reduce risk of progressing EDSS Appropriate exercise (Yoga, Tai Chi, core, aquatics) Avoid overheating ROS in MS is always + Ask directed questions-do you have frequency, urgency, etc Avoid obesity Emotions Connect your patient: MS society, Mayo, MSF MSAA

26 Conclusions New Treatments, new strategies Initiate a DMD (Disease modifying Drugs) as soon after definitive diagnosis as soon as possible Considering DMD therapy in select high-risk patients with a first attack. The initiation of this treatment is frequently delayed or skipped entirely. Early treatment is found to delay disability and lessen the overall impact of MS. Patient focused treatment is essential Wellness, active role of multiple practioners, team based care Neurology Exchange: Exploring the Latest Advances in Multiple Sclerosis Diagnosis and Management Suhayl Dhib-Jalbut, MD; Aaron E. Miller, MD Medscape CME 04/28/2014