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	Faculty
	Statement of Need
	Activity Goal
	Learning Objectives
	Target Audience
	Financial Support
	Credit Information

neuroscienceCME Journal Club

Premiere Date: Monday, January 25, 2010

This activity offers CE credit for:

1. Physicians (ACCME/AMA PRA Category 1)
2. Nurses (CNE)
3. Pharmacists (ACPE)
4. Psychologists (APA)
5. Social Workers (NASW)
6. Certified Case Managers (CCMC)

All other clinicians will either receive a CME Attendance Certificate or may choose any of the types of CE credit being offered.
Credit Expiration Date:
Tuesday, January 25, 2011

Faculty

Aaron Miller, MD (Guest Host) Professor of Neurology Medical Director, Corinne Goldsmith Dickinson Center for Multiple Sclerosis Mount Sinai School of Medicine New York, NY

Fred D. Lublin, MD (Featured Author) Saunders Family Professor of Neurology Director, The Corinne Goldsmith Dickinson Center for Multiple Sclerosis Mount Sinai School of Medicine New York, NY

David H. Mattson, MD, PhD (Content/Peer Reviewer) Professor of Neurology Program Director, Neuroimmunology/Multiple Sclerosis Program Indiana University School of Medicine Bloomington, IN

Statement of Need

Multiple sclerosis (MS) affects 400,000 Americans and is the leading nontraumatic cause of neurological disability in young adults.(1) Although MS is progressive, it is not fatal, and patients generally have a normal lifespan. However, progressive disability imposes increasing limitations and reduced quality of life for these patients. Newly released consensus guidelines offer neurologists and primary care physicians direction to improve the differential diagnosis and develop strategies to facilitate early and accurate diagnosis of MS. A number of factors must be considered when selecting a treatment regimen for patients with MS, including variations in clinical and MRI evidence of disease. The discovery and broad application of MRI in medicine has led to an increased awareness of the number of patients with incidental white matter pathology in the CNS. The natural history or evolution of such individuals with respect to their risk of developing MS is unclear,(2) but a need for further studies on this subject and physician awareness is essential for progression of disease therapy in MS. In this two-part neuroscienceCME Journal Club series, the authors will translate their research and provide insights and application to clinical practice.

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1. Bermel RA, Rudick RA. Interferon-based treatment for multiple sclerosis. Neurotherapeutics 2007;4:633-646.
2. Okuda DT, Mowry EM, Beheshtian A, et al. Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. Neurology 2009;72:800-805.

Featured Article: Miller DH, Weinshenker BG, Filippi M, et al. Differential diagnosis of suspected multiple sclerosis: a consensus approach. Mult Scler 2008;14:1157-1174.
View Abstract
Download Article (PDF format)

Summary: In 2001 an international panel was assembled by the National Multiple Sclerosis Society to review and modify the diagnostic criteria for multiple sclerosis (MS). The panel revised the diagnostic criteria with added use of specific MRI changes to assist in the determination of dissemination in time and dissemination in space criteria that are considered the diagnostic hallmarks of MS. The panel also reduced the results of the diagnostic process to MS, possible MS or not MS; eliminating the prior diagnostic schemas "clinical" and "laboratory supported" prefixes. As before, the 2001 criteria maintained the caveat that there be no better explanation for the associated signs and symptoms. In 2005 the panel reconvened and nuanced the 2001 criteria. However, at the 2005 panel meeting there was recognition that the diagnostic criteria were most useful for diagnosing MS, with very good specificity and sensitivity, but they did not provide sufficient ways to distinguish MS from other diseases that might also produce dissemination in time and space or otherwise resemble features of MS. For this reason, a new panel was convened in 2006 to address the issue of differential diagnosis in MS to assist clinicians in excluding "better explanations."

The new panel, consisting of 18 international experts on demyelinating diseases, convened in 2007 to develop guidelines for MS differential diagnosis based on literature review and expert consensus. The panel focused on three areas: 1) exclusion of MS mimics, 2) diagnosis of common initial clinically isolated syndromes (CIS) and 3) differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. This was accomplished by use of available literature and consensus.

The resultant document contains diagnostic algorithms for MS differential diagnosis, differential diagnosis of patients presenting with demyelinating optic neuritis, differential diagnosis of patients presenting with a demyelinating brain stem syndrome and differential diagnosis of patients presenting with a demyelinating spinal cord syndrome.

The paper provides 79 clinical and paraclinical red flag findings that may be found during a work up for suspected MS. These flags are broken down into major, intermediate or minor designations and as to whether they were clinical or MRI based. A major red flag suggested fairly definitively that a non-MS diagnosis was likely, an intermediate red flag suggested uncertainty for its importance amongst the rating panel, and a minor red flag could be consistent with MS or a non-MS diagnosis. Examples of a major red flag are peripheral neuropathy and persistent gadolinium enhancing lesions. Gastrointestinal symptoms and regional atrophy are examples of intermediate red flags. No spinal cord lesions, and no enhancement are listed as examples of minor red flags.

CIS is defined as a monophasic presentation with suspected underlying inflammatory demyelinating disease. The monophasic onset implies a single clinical presentation at first onset with relatively rapid onset. The prognostic role of MRI at the time of CIS is discussed. CIS is subdivided in the paper by whether it is mono or multifocal or seen on MRI only. The paper also provides a list of CIS features characterized by whether they were typical (e.g., bilateral internuclear ophthalmoplegia), less common (e.g., bilateral simultaneous optic neuritis) or atypical (e.g., third nerve palsy) of an initial onset of MS.

The final task of the panel was to provide guidance in distinguishing MS from other idiopathic inflammatory demyelinating diseases (IIDD), focusing mostly on neuromyelitis optica (NMO) and acute disseminated encephalomyelitis (ADEM). Criteria for diagnosing each of these conditions are provided in a table for classification of the broader category of IIDD.

In summary, this paper provides guidance for the differential diagnosis of CNS disease suggestive of MS in two broad categories: non-IIDD with signs or symptoms that may mimic IIDD, and non-MS IIDD. Through the use of differential features and relative red flags, the diagnosis of MS or its mimics is made easier for the practicing clinician. The authors caution that their conclusions are largely consensus driven and would benefit from prospective clinical studies.

Activity Goal

To translate consensus recommendations on differential diagnosis into effective management of patients with MS, and to increase awareness surrounding the potential risk factor of white matter pathology for the development of MS.

Learning Objectives

At the end of this CE activity, participants should be able to:

• Utilize consensus-based guidelines in determining a more accurate differential diagnosis of MS.

The following learning objectives pertain only to those requesting CNE credit:

• Review the barriers to improved diagnosis of multiple sclerosis (MS).
• Identify established criteria used to diagnose MS.
• Discuss the recommendations of the panel for the use of indicators to improve diagnosis.

Target Audience

Physicians, physician assistants, nurse practitioners, nurses, psychologists, social workers, certified case managers, pharmacists, and other healthcare professionals interested in the management of multiple sclerosis.

Financial Support

This activity is supported by an unrestricted educational grant from Pfizer Inc.

Credit Information

CME Credit (Physicians):
Indiana University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Indiana University School of Medicine designated this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™ Physicians should only claim credit commensurate with the extent of their participation in the activity.
Note to Physician Assistants: AAPA accepts Category I credit from AOACCME, Prescribed credit from AAFP, and AMA Category I CME credit for the PRA from organizations accredited by ACCME.

CNE Credit (Nurses):
This continuing nursing education activity was approved by the New York State Nurses Association, an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation.

It has been assigned approval code 7ZDPTZ-10. 1.0 contact hours will be awarded upon successful completion.

CEP Credit (Psychologists):
CME Outfitters is approved by the American Psychological Association to sponsor continuing education for psychologists. CME Outfitters maintains responsibility for this program and its content. (1.0 CE credits)

NASW Credit (Social Workers):
This program was approved by the National Association of Social Workers (provider #886407722) for 1 continuing education contact hour.

CCMC Credit (Certified Case Managers):
This program has been approved for 1 hour by the Commission for Case Manager Certification (CCMC).

CPE Credit (Pharmacists):
CME Outfitters, LLC, is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. 1.0 contact hours (0.1 CEUs)
Universal Program Number:
376-999-10-003-L01-P (Live)
376-999-10-003-H01-P (Recorded)
Activity type: Knowledge-based

Post-tests, credit request forms, and activity evaluations can be completed online at www.neuroscienceCME.com (click on the Testing/Certification link under the Activities tab–requires free account activation), and participants can print their certificate or statement of credit immediately (80% pass rate required). This website supports all browsers except Internet Explorer for Mac. For complete technical requirements and privacy policy, visit www.neuroscienceCME.com/technical.asp.

This continuing education activity is co-sponsored by Indiana University School of Medicine and by CME Outfitters, LLC.

Disclosure Declaration

In accordance with the Accreditation Council for Continuing Medical Education (ACCME) Standards for Commercial Support, educational programs sponsored by Indiana University School of Medicine (IUSM) and CME Outfitters, LLC, (CMEO) must demonstrate balance, independence, objectivity, and scientific rigor. All faculty, authors, editors, and planning committee members participating in activities sponsored by IUSM and CMEO are required to disclose any relevant financial interest or other relationship with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services that are discussed in an educational activity.
Note: While it offers CME credits, this activity is not intended to provide extensive training or certification in the field.

Dr. Miller has disclosed that he receives grants/research support from Acorda Therapeutics, Genentech, Inc., Genzyme Corporation, Novartis Pharmaceuticals Corporation, Sanofi-aventis, and Teva Pharmaceuticals. He serves as a consultant to Acorda Therapeutics, Biogen Idec, Daiichi Sankyo, EMD Serono, Inc., GlaxoSmithKline, Merk Serono, Novartis Pharmaceuticals Corporation, Ono pharmaceutical Co., Ltd, Sanofi-aventis, and Teva Pharmaceuticals. He serves on the speakers bureaus of Biogen Idec, EMD Serono, Inc., Pfizer Inc., and Teva Pharmaceuticals.

Dr. Lublin has disclosed that he receives grants/research support from Acorda Therapeutics, Biogen Idec, Genentech, Inc., Genzyme Corporation, Novartis Pharmaceuticals Corporation, Sanofi-aventis, and Teva Neuroscience, Inc. He serves as a consultant to, or on the advisory boards of, Acorda Therapeutics, Actelion Pharmaceuticals Ltd, Allozyne, Inc., Bayer HealthCare Pharmaceuticals, Biogen Idec, BioMS Medical Corp., EMD Serono, Inc., Genentech, Inc., Genmab, Medicinova, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., Questcor Pharmaceuticals, Inc., Sanofi-aventis, and Teva Neuroscience, Inc. He serves on the speakers bureaus of EMD Serono, Inc., Pfizer Inc., and Teva Neuroscience, Inc. He owns stock in Cognition Pharmaceuticals, Inc. Dr. Lublin has disclosed that he may discuss unapproved agents that are in the MS developmental pipeline without any recommendation on their use.

Dr. Mattson has disclosed that he receives grants/research support from Acorda Therapeutics Inc., Berlex Laboratories, Biogen Idec, Genentech, Inc., Genzyme Corporation, Lilly USA, LLC, Novartis Pharmaceuticals Corporation, Pfizer Inc., sanofi-aventis, and Teva Pharmaceuticals USA. He serves on the speakers bureaus of Biogen Idec, Merck Serono, Pfizer Inc., and Teva Pharmaceuticals USA. He serves as a consultant to Lilly USA, LLC.

Unlabeled Use Disclosure

Faculty of this CE activity may include discussions of products or devices that are not currently labeled for use by the FDA. The faculty have been informed of their responsibility to disclose to the audience if they will be discussing off-label or investigational uses (any uses not approved by the FDA) of products or devices.

Indiana University School of Medicine, CME Outfitters, LLC, the faculty, and Pfizer Inc. do not endorse the use of any product outside of the FDA labeled indications. Medical professionals should not utilize the procedures, products, or diagnosis techniques discussed during this activity without evaluation of their patient for contraindications or dangers of use.

Questions about this activity? Call us at 877.CME.PROS (877.263.7767).

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