Introduction

Editor’s Note: On March 2, 2018, Biogen and AbbVie announced the voluntary withdrawal of daclizumab (Zinbryta) from the global market due to reports of inflammatory brain disorders associated with use of the drug in patients with MS. Readers should be aware of this development when reading the information provided in this activity, which was published before the announcement.

In recent years, the treatment options for multiple sclerosis (MS) have increased in number and in efficacy. These new therapies—coupled with our emerging understanding of the nature of the disease state itself—provide clinicians with more options to better control the inflammatory aspects of MS that are often associated with disability.
The benefit from disease-modifying therapies (DMTs) is likely greatest early in the disease course. However, before treatment can begin, a careful, accurate, and timely diagnosis must be made. Despite advances in our understanding of MS and in the tools available for identifying it, misdiagnosis of MS remains a problem.^1-3
That challenges exist in the correct identification of MS is not surprising, given that fulfillment of the current (and still-evolving) criteria for the condition can be subjective.

These include⁴:

Demonstrationofdisseminationoflesionsinspace(DIS)
Demonstrationofdisseminationoflesionsintime(DIT)
Exclusion of alternative diagnoses

Imminent updates to the McDonald diagnostic criteria for MS are likely to refine the ways in which the aforementioned steps can be satisfied.⁵ The publication outlining those updates is in press at the time of this writing, in the fall of 2017. However, briefings at the October 2017 meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) indicate that the presence of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) can be substituted for demonstration of DIT to warrant diagnosis of MS in a patient who otherwise might be considered to have clinically isolated syndrome (CIS).⁵ While these and other refinements to the criteria will affect clinical practice, the principles that guide early, precise MS diagnosis and the continued emphasis on characteristic clinical symptoms of demyelinating disease will remain in place.

A Current Snapshot of MS Diagnosis: Where We Are and Where We Need to Be

This activity is intended for neurologists, physician assistants, nurse practitioners, and registered nurses involved in the diagnosis and management of patients with multiple sclerosis (MS). Primary care physicians who manage and/or treat a high volume of patients with neurological conditions will benefit as well.

Start CME/CE Activity

Supported by an educational grant from:

Genentech, Inc.

Activity Information

Original Release Date: December 31, 2017
Expiration Date: December 31, 2018
Estimated Time to Complete Activity: 1.0 hour

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Method of Participation

Participants should read the activity information, review the activity in its entirety, and complete the online post-test and evaluation. Upon completing this activity as designed and achieving a passing score on the post-test, you will be directed to a Web page that will allow you to receive your certificate of credit via e-mail or you may print it out at that time.
For information about the accreditation of this program, please contact Global Education Group at 303-395-1782 or inquire@global-educationgroup.com.

Physician Accreditation Statement

This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Global Education Group (Global) and Global Academy for Medical Education. Global Education Group is accredited by the ACCME to provide continuing medical education for physicians.

Physician Credit Designation

Global Education Group designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit^TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Nursing Continuing Education

Nursing Global Education Group is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s COA.
This educational activity for 1.0 contact hours is provided by Global Education Group. Nurses should claim only the credit commensurate with the extent of their participation in the activity.

Faculty

stephen_krieger.png	Stephen Krieger, MD Associate Professor of Neurology Corinne Goldsmith Dickinson Center for MS Director, Neurology Residency Program Icahn School of Medicine at Mount Sinai New York, New York
andrew_solomon.png	Andrew J. Solomon, MD Assistant Professor of Neurological Sciences Division Chief, Multiple Sclerosis University of Vermont College of Medicine Burlington, Vermont

Educational Needs

The recent approval and availability of a multitude of new options for MS management has led clinicians to reconsider their approach to the diagnosis of the disease, as well as the timing, approach, and aggressiveness of initial treatment. MS symptoms may often be subclinical or incorrectly attributed to another cause, potentially delaying treatment until the disease has already begun to progress. Earlier and more accurate diagnosis to guide treatment offers opportunities to improve patient outcomes and quality of life.

Learning Objectives

At the conclusion of this program, participants should be better able to:

Discuss the role of radiologically isolated syndromes (RIS) and clinically isolated syndromes (CIS) in diagnosing and monitoring MS
Describe recent updates to established MS disease phenotypes and discuss their application in clinical practice
Recognize the importance of early diagnosis and treatment in reducing disability progression
Identify important risk factors impacting the onset, severity, and progression of MS
Understand and apply recent discoveries and emerging therapies in the management of patients with MS

Joint Providership Statement

This activity is jointly provided by Global Education Group and Global Academy for Medical Education.

Term of Offering

This activity was released on December 1, 2017, and is valid for 1 year. Requests for credit must be made no later than December 31, 2018.

Global Education Group Contact Information

For information about the accreditation of this activity, please contact Global Education Group at 303-395-1782 or inquire@globaleducationgroup.com.

Instructions for Obtaining Credit

In order to receive credit, participants must complete the online evaluation and post-test at the end of this activity. Participants must also score at least a 65% on the post-test. Statements of credit will be issued upon completion of the evaluation and post-test.

Fee Information and Refund/Cancellation Policy

There is no fee for this educational activity.

Disclosure of Conflicts of Interest

Global Education Group (Global) requires instructors, planners, managers, and other individuals and their spouse/life partner who are in a position to control the content of this activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly vetted by Global Education Group for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations.

The faculty reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME/CE activity:
Stephen Krieger, MD, FAAN: Consultant: Acorda, Bayer, Biogen, EMD Serono, Genentech, Genzyme, Mallinckrodt, MedDay, Novartis, Teva, TG Therapeutics. Speakers Bureau: Biogen
Andrew J. Solomon, MD: Consultant: Biogen, EMD Serono, Genentech. Grant/Research Support: Biogen

The planners and managers reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME activity:
Global Academy for Medical Education Staff: Sylvia H. Reitman, MBA, DipEd; Mike LoPresti; Shirley V. Jones, MBA; Ron Schaumburg; and Tom Garry hereby state that they or their spouse/life partner do not have any financial relationships or relationships to products or devices with any commercial interest related to the content of this activity of any amount during the past 12 months.

Global Education Group (Global): The following planners and managers, Ashley Marostica, RN, MSN; Andrea Funk; Liddy Knight have nothing to disclose.

Off-Label/Investigational Use Disclosure

This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the US Food and Drug Administration. The planners of this activity do not recommend the use of any agent outside of the labeled indications.

The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of any organization associated with this activity. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Disclaimer

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed in this activity should not be used by clinicians without evaluation of patient conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

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References

Solomon AJ, Klein EP, Bourdette D. “Undiagnosing” multiple sclerosis: The challenge of misdiagnosis in MS. Neurology. 2012;78:1986-1991.
Solomon AJ, Bourdette DN, Cross AH, et al. The contemporary spec- trum of multiple sclerosis misdiagnosis: A multicenter study. Neurology. 2016;87:1393-1399.
Solomon AJ, Corboy JR. The tension between early diagnosis and misdiagnosis of multiple sclerosis. Nat Rev Neurol. 2017;13:567-572.
Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple scle- rosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69:292-302.
Fiore K. Revised McDonald diagnostic criteria revealed. MedPage Today. October 26, 2017. https://www.medpagetoday.com/meetingcoverage/ectrims/68804. Accessed November 7, 2017.
Dilokthornsakul P, Valuck RJ, Nair KV, Corboy JR, Allen RR, Campbell JD. Multiple sclerosis prevalence in the United States commercially insured population. Neurology. 2016;86:1014-1021.
National Multiple Sclerosis Society. Who gets MS (epidemiology). https://www.nationalmssociety.org/What-is-MS/Who-Gets-MS#section-0. Accessed October 6, 2017.
Freedman MS. Evidence for the efficacy of interferon beta-1b in delaying the onset of clinically definite multiple sclerosis in individuals with clinically isolated syndrome. Ther Adv Neurol Disord. 2014;7:279-288.
Langer-Gould A, Brara SM, Beaber BE, Zhang JL. The incidence of clinically isolated syndrome in a multi-ethnic cohort. J Neurol. 2014;261:1349-1355.
OkudaDT, SivaA, KantarciO, etal. Radiologically isolated syndrome: 5-year risk for an initial clinical event. PLoS One. 2014;9:e90509.
Mealy MA, Wingerchuk DM, Greenberg BM, Levy M. Epidemiology of neuro myelitis optica in the United States: A multicenter analysis. Arch Neurol. 2012;69:1176-1180.
Glisson CC. Neuromyelitis optica spectrum disorders. UpToDate. August 22, 2017. https://www.uptodate.com/contents/neuromyelitis-optica-spectrum-disorders. Accessed October 16, 2017.
National Multiple Sclerosis Society. Multiple sclerosis FAQs. https://www.nationalmssociety.org/What-is-MS/MS-FAQ-s. Accessed November 19, 2017.
Noonan CW, Williamson DM, Henry JP, et al. The prevalence of multiple sclerosis in 3 US communities. Prev Chronic Dis. 2010;7:A12. https://www.cdc.gov/. Accessed October 14, 2017.
GruenewaldD, BrodkeyM, ClaytonReitmanN, DelBeneM. Openingdoors: The palliative care continuum in multiple sclerosis. National Multiple Sclerosis Society Clinical Bulletin. https://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Clinical_Bulletin_Opening-Doors-The-Palliative-Care-Continuum-in-MS.pdf. Published 2012. Accessed October 14, 2017.
National Multiple Sclerosis Society. MS symptoms. https://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms. Accessed October 8, 2017.
Kessler R, Mealy M, Levy M. Clinical predictors of death in neuromyelitis optica spectrum disorder. Neurology. 2017;88(suppl):P2.329.
Marcus JF, Waubant EL. Updates on clinically isolated syndrome and diagnostic criteria for multiple sclerosis. Neurohospitalist. 2013;3:65-80.
Ford CC. Best practices for using MS disease modifying therapies. Presented at: 2015 Annual Meeting of the Consortium of Multiple Sclerosis Centers; May 27-30, 2015; Indianapolis, IN.
Giovannoni G, Butzkueven H, Dhib-Jalbut S, et al. Brain health: Time matters in multiple sclerosis. Mult Scler Relat Disord. 2016;9:S5-S48.
Goodin DS, Reder AT, Ebers GC, et al. Survival in MS: A randomized cohort study 21 years after the start of the pivotal IFNb-1b trial. Neurology. 2012;78:1315-1322.
Rebif [prescribing information]. Rockland, MA: EMD Serono Inc; revised November 2015.
Tysabri [prescribing information]. Cambridge, MA: Biogen Inc; revised August 2017.
Avonex [prescribing information]. Cambridge, MA: Biogen Inc; revised March 2016.
Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: The 2013 revisions. Neurology. 2014;83:278-286.
Traboulsee A, Simon JH, Store L, et al. Revised recommendations of the Consortium of MS Centers Task Force for a standardized MRI protocol and clinical guidelines for the diagnosis and follow-up of multiple sclerosis. AJNR Am J Neuroradiol. 2016;37:394-401.
O’Gorman C, Lucas R, Taylor B. Environmental risk factors for multiple sclerosis: A review with a focus on molecular mechanisms. Int J Mol Sci. 2012;13:11718-11752.
National Multiple Sclerosis Society. Diagnosingtools. https://www.nationalmssociety.org/Symptoms-Diagnosis/Diagnosing-Tools. Accessed November 19, 2017.
Forslin Y, Granberg T, Jumah AA, et al. Incidence of radiologically isolated syndrome: A population-based study. AJNR Am J Neuroradiol. 2016;37:1017-1022.
Thormann A, Sørensen PS, Koch-Henriksen N, Laursen B, Magyari M. Comorbidity in multiple sclerosis is associated with diagnostic delays and increased mortality. Neurology. 2017;89:1668-1675.
Marrie RA, Horwitz R, Cutter G, Tyry T, Campagnolo D, Vollmer T. Comorbidity delays diagnosis and increases disability at diagnosis in MS. Neurology. 2009;72:117-124.
Sicras-Mainar A, Ruiz-Beato E, Navarro-Artieda R, Maurino J. Comorbidity and metabolic syndrome in patients with multiple sclerosis from Asturias and Catalonia, Spain. BMC Neurol. 2017;17:134.
Consortium of Multiple Sclerosis Centers. Proposed 2017 revised guidelines. Updated January 2017. www.mscare.org/MRI. Accessed October 14, 2017.
Okuda DT, Mowry EM, Beheshtian A, et al. Incidental MRI anomalies suggestive of MS: The radiologically isolated syndrome. Neurology. 2009;72:800-805.
Etemadifar M, Janghorbani M, Koushki MM, Etemadifar F, Esfahani MF. Conversion from radiologically isolated syndrome to multiple sclerosis. Int J Prev Med. 2014;5:1379-1386.
Granberg T, Martola J, Aspelin P, Kristoffersen-Wiberg M, Fredrikson S. Radiologically isolated syndrome: An uncommon finding at a university clinic in a high-prevalence region for multiple sclerosis. BMJ Open. 2013;3:e003531.
Stankiewicz JM, Glanz BI, Healy BC, et al. Brain MRI lesion load at 1.5T and 3T vs. clinical status in multiple sclerosis. J Neuroimaging. 2011;21:e50-e56.
Freedman MS, Thompson EJ, Deisenhammer F, et al. Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: A consensus statement. Arch Neurol. 2005;62:865-870.
KriegerSC,CookK,DeNinoS,FletcherM.The topographical model of multiple sclerosis. A dynamic visualization of disease course. Neurol Neuroimmunol Neuroinflamm. 2016;3:e279.
KatzSandI,KriegerS,FarrellC,MillerAE.Diagnostic uncertainty during the transition to secondary progressive multiple sclerosis. Mult Scler. 2014;20:1654-1657.
National Multiple Sclerosis Society. Symptoms and diagnosis of NMO. https://www.nationalmssociety.org/What-is-MS/Related-Conditions/Neuromyelitis-Optica-(NMO)/Symptoms-and-Diagnosis. Accessed October 8, 2017.
Ocrevus [prescribing information]. South San Francisco, CA: Genentech Inc; revised March 2017.
Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376:221-234.
Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376:209-220.
Zinbryta [prescribing information]. Cambridge, MA: Biogen Inc; revised August 2017.
Benedict RH, Cohan S, Lynch SG, et al. Improved cognitive outcomes in patients with relapsing-remitting multiple sclerosis treated with daclizumab beta: Results from the DECIDE study. Mult Scler. 2017 May 1:1352458517707345. [Epub ahead of print]
Radue EW, Sprenger T, Vollmer T, et al. Daclizumab high-yield process reduced the evolution of new gadolinium-enhancing lesions to T1 black holes in patients with relapsing-remitting multiple sclerosis. Eur J Neurol. 2016;23:412-415.
De Ridder D, Van Der Aa F, Debruyne J, et al. Consensus guidelines on the neurologist’s role in the management of neurogenic lower urinary tract dysfunction in multiple sclerosis. Clin Neurol Neurosurg. 2013;115:2033-2040.