2019 June AANnews by American Academy of Neurology

VOLUME 33 · ISSUE 6 · June 2019

FALL CONFERENCE REGISTRATION OPENS THIS MONTH Features Pre-conference for APPs Registration opens later this month for the 2019 Fall Conference. Visit AAN.com/view/19FC to learn more and to secure your spot for the hottest topics in the world of neurology, real-world issues in practice management, and innovative science—plus valuable end-of-year CME. Returning to The Cosmopolitan of Las Vegas this October 18 through 20, this year’s conference will offer new programming to help advanced practice providers and business administrators excel. A Thursday, October 17, pre-conference will provide advanced practice providers with everything from neurology fundamentals to clinical case studies on headache and multiple sclerosis. And a practice management curriculum geared towards both business administrators and neurologists will take place on Friday and Saturday and be co-led by expert business administrator faculty.

Continued on page 40

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June 20 Is Advance Registration and Hotel Deadlines for Sports Concussion Conference

Meet Your New President and Board of Directors

June 20 is the last chance for AAN members to book their hotel and save up to $100 with advance registration discounts to the 2019 Sports Concussion Conference returning to the NCAA’s hometown of Indianapolis, IN, July 26 through 28. The conference is the leading voice in shaping the sportsrelated concussion conversation for all clinicians, scientists, Continued on page 40

10 Axon Registry Helps User

Increase Performance Scores

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James C. Stevens, MD, FAAN, a private practice neurologist in Fort Wayne, IN, became the 36th president of the AAN following the Annual Meeting in Philadelphia, succeeding Ralph L. Sacco, MD, MS, FAHA, FAAN. During the annual business meeting on May 4, members elected new officers and members of the Board of Directors for the 2019–2021 term. Stevens has been a participant, co-author, and/or principal investigator in over 80 clinical trials dealing with a wide variety of neurologic diseases. He has also been involved with the development, authorship, and/or

11 New AAN Guideline on

Tourette and Chronic Tics

Continued on page 21

34 Philly Full of Neurology

During 2019 Annual Meeting

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In Multiple

Sclerosis —

GREY MATTERS, TOO

AANnews · June 2019

CONTENTS

News Briefs

Cover Fall Conference Registration Opens This Month

Conferences & Community Philly Full of Neurology During 2019 Annual Meeting · ·34

June 20 Is Advance Registration and Hotel Deadlines for Sports Concussion Conference

Women’s Leadership Program Graduate Rises to New Heights in Medical Career, Military · · · · · · · · · ·36

Meet Your New President and Board of Directors

Congratulations New Fellows of the American Academy of Neurology! · · · · · · · · · · · · ·39

President’s Column Enhancing Career Satisfaction · 4 From the Chief Executive Officer From Solid to Exceptional: 20 Years of AAN Growth · · · · · · · 5 Tools & Resources Members Love New Practice Management Webinar Format · 8 Accident Motivated Estefan’s Support for Paralysis Research 8 Brain & Life and Neurology Today Recognized with Awards · 9 Axon Registry Helps User Increase Measure Performance Scores · · · · · · · 10 Policy & Guidelines New AAN Guideline on Tourette and Chronic Tics Shared at Annual Meeting Press Conference · · · · · · · · 11

Missed the Annual Meeting? There’s Still Time to Order Annual Meeting On Demand · · 39 Careers · · · · · · · · · · · · · · · 41 Education & Research June Continuum Examines Latest Information on MS Diagnosis and Treatment · · · ·48 New Letter of Intent Requirement for Education Research Grants and Medical Education Research Training Fellowship Program · · · · · · ·48 Fisher Succeeds Józefowicz as New UCNS Chair · · · · · · · 49

Palatucci Advocacy Leadership Forum (PALF) Advocate of the Year Award Glynnis Zieman, MD, FAHS, received the 2018 award at the PALF Graduate Reception at the Annual Meeting, highlighting her accomplishments in raising awareness of concussions in domestic violence victims on a national level and her commitment to AAN advocacy.

Kenneth M. Viste, Jr., MD, Patient Advocate of the Year Award Aaron Berkowitz, MD, PhD, of Brigham and Women’s Hospital in Boston, MA received the 2019 award in Philadelphia. As the director of BWH’s Global Neurology Program, Berkowitz has been a tireless advocate for the people of Haiti. He regularly travels to the Caribbean nation, with a population of nearly 11 million people, to offer training and support to local doctors. 

UCNS Releases Details on New Continuous Certification Model · · · · · · · 49 Dates & Deadlines · · · · · · · · 50

Passion for Advocacy Is Springboard to Leadership Role · 12 Capitol Hill Report · · · · · · · · 13

The Vision of the AAN is to be indispensable to our members. The Mission of the AAN is to promote the highest quality patient-centered neurologic care and enhance member career satisfaction. Contact Information

For advertising rates, contact:

American Academy of Neurology 201 Chicago Avenue Minneapolis, MN 55415

Eileen R. Henry Wolters Kluwer Health | Medical Research Lippincott, Williams & Wilkins

Phone: (800) 879-1960 (toll free) (612) 928-6000 (international) Email:

memberservices@aan.com

Website: AAN.com

Phone: (732) 778-2261 Email: Eileen.Henry@wolterskluwer.com

AAN Chief Executive Officer: Catherine M. Rydell, CAE Editor-in-Chief: John D. Hixson, MD Managing Editor: Angela Babb, CAE Editor: Tim Streeter Writers: Ryan Knoke and Sarah Parsons Designer: Jim Hopwood Email: aannews@aan.com

AANnews is published monthly by the American Academy of Neurology for its 36,000 members worldwide. Access this magazine and other AAN publications online at AAN.com. The American Academy of Neurology ’ s registered trademarks and service marks are registered in the United States and various other countries around the world. “American Brain Foundation” is a registered service mark of the American Brain Foundation and is registered in the United States.

President’s Column

Enhancing Career Satisfaction It is with great humility and excitement that I welcome the opportunity to serve as your 36th president of the Stevens American Academy of Neurology. For those members I have yet to meet, I think it is important to tell you a bit about my background. I have worked as a private practicing neurologist for the past 32 years at the Fort Wayne (Indiana) Neurological Center. I have specialty board certification in sleep disorders medicine but spend a majority of my clinical hours practicing general neurology. I see patients on a daily basis either in my office, an out-of-town clinic, perform consults and rounds in my community hospitals, provide telestroke services for our 27-hospital network, teach medical students and residents, participate in clinical trial research, help run the business of my practice, and absolutely love it all! I liken my days to Forrest Gump and his box of chocolates; when I walk into the exam room (aka open the box of chocolates), I never know what I am going to find, but am extremely excited over the possibilities. I am fully aware, however, that things are not quite as “rosy” for many of my colleagues. The house of medicine and our specialty, in particular, have not been without significant challenges. Over the past two decades, the landscape of medical practice has changed dramatically with the institution of electronic health records, the regulatory burdens for participation and documentation with an alphabet soup number of programs such as HIPAA, ACA, MIPS, QPP, MOC, RVUs, etc. These have come at a time when additional practice resources have been required for pre-authorization (just to get done what we want for our patients), increased costs of pharmaceuticals, procedures, and hospitalizations, while seeing cuts in neurology-specific

AANnews • June 2019

services such as nerve conductions, sleep, and EEG studies—all while suffering the indignity of having cognitive services undervalued—which constitute the majority of what our specialty provides! It is no surprise to discover that many of my colleagues have become disheartened, disillusioned, and dissatisfied with their careers. Many have expressed a sense they are powerless to achieve the profession they envisioned when they were completing their training. This issue is critically important and why the AAN has placed in its mission statement “…to enhance member career satisfaction” as part of an overarching strategic objective. This includes understanding the needs and finding solutions for members in clinical practice, educators, research scientists, administrators, business managers, and advanced practice providers who share a connecting thread of passion for neurology and neuroscience. As a practicing clinical neurologist, the essence of my career has been the opportunity to listen and examine, using my knowledge-base and skills, in order to affect a positive change for those patients seeking my help. In my own practice, I have intentionally worked to reduce, and in some instances eliminate, the “noise” (as outlined in the paragraph above) that interferes with my ability to achieve this daily goal. It has not been easy, and for many this perhaps seems an impossibility, but it is a priority of the AAN to preserve the sanctity of the physician-patient relationship. For the past 27 years, I have had the privilege to work in various capacities as a volunteer physician with the AAN

(how that all began is another story I will share in an upcoming column). I have chosen to give so much of my personal time to the organization due to the fact the AAN has been so effective in “getting things done.” This is in no small part owed to the expertise of the AAN executive leadership, the exceptional talent of the AAN staff, and the inspiring excellence of the volunteer members of the organization. I have great confidence that the AAN has the culture, governance, and resources to tackle the challenges facing our profession. I consider it my responsibility to have a thorough understanding of the issues important to our membership in order to prioritize the use of our talent and resources in order to accomplish our goals. It is my fervent hope during my tenure as your president that the percentage of our members finding fulfillment and professional satisfaction in their career choice increases significantly. I hope that every day can be met with the hope of what the “box of chocolates” might bring. I look forward to hearing from you and having the good fortune of meeting many of you in the years to come. 

James C. Stevens, MD, FAAN President, AAN jstevens@aan.com @JimStevensMD on Twitter

From the Chief Executive Officer

From Solid to Exceptional: 20 Years of AAN Growth 2019 marks my 20th year at the AAN, and I want to take this opportunity to thank the literally thousands of members I have met and worked with these two decades. As I’ve reflected on the evolution of the Academy and the field of neurology over this time, I am humbled to have been selected, in Rydell 1999, as the third executive director of the AAN—and the first woman to hold the position. But stronger now is the feeling of pride at what has been accomplished over the last 20 years.

why seizures can recur after surgery Page 23

organization of today. As programs and services for members grew, we expanded staff led by a competent and innovative executive staff team. In recent years, continual strategic planning has become the norm, backed by data, member input, and environmental scans that tipped us off to new trends and concerns on the horizon. This enabled us to be more proactive, rather than reactive, which is critical in this rapidly shifting health care environment.

Based on what we learned from the data and environment, the board approved additional resources to significantly expand the AAN’s ability to meet the I feel now is a good time for me needs of our members. In 2005, to make way for new leadership we established a permanent for our organization, and I plan office in Washington, DC, from to step down as chief executive which we deploy our federal officer effective in May 2020. A advocacy and regulatory affairs CEO Search Committee, chaired staff to Capitol Hill as well as by Past President Ralph L. the headquarters of the FDA The AAN staff of 1999 Sacco, MD, MS, FAHA, FAAN, and Centers for Medicare & has selected a search firm and Medicaid Services to fight for recruitment for a new CEO will fair reimbursement and access begin in summer 2019. The timing to care for our patients. The of this will help us ensure a board approved the creation of smooth transition. BrainPAC, the only political action committee solely for neurology, I credit the exceptional growth and the Axon Registry ®, vitally of the AAN during my tenure important to analyzing patient in great part to the scores of care data to help ensure our member leaders who have clinicians are meeting the served on the boards of the AAN health needs of their patients and AAN Institute as officers The AAN staff of 2018 by providing the highest quality and directors. The volunteer patient centered care. And the board gave the go-ahead to build time they have given the AAN and the field of neurology is a new, permanent headquarters in downtown Minneapolis astounding. In the early years of the AAN, when there was little that has been our or no staff support, the neurologist volunteer leaders captained home since 2012. We the ship. When I arrived at the Academy in 1999, the board had successfully launched just approved its first strategic plan but was focused more on several spoke journals operations and less on strategy. With the help of some key from our flagship board members, we were able to evolve scientific journal this governing body to be much more Neurology ® and began strategically focused. The board’s high Neurology Today ® expectations and commitment to drive the to keep members AAN forward have moved us from a solid informed about news organization in 1999 to the exceptional in their profession. is the thalamus really the Key to the arousal Pathway? Page 28

the official ne ws source of the a merican academy of neurology | neurology today.com january 24, 2019 | Volume 19 | issue 2

susan fitzgerald

rophylactic hypothermia for patients with severe traumatic brain injury (TBI) does not improve neurologic outcomes at six months, according to a large randomized, controlled trial that may finally help settle the debate over the therapy. Animal models of TBI had suggested that hypothermia provides neuroprotection in the aftermath of brain injury, but several clinical trials have failed to

show any benefits. Researchers were hoping that this latest trial, in which hypothermia was used prophylactically, would turn in favorable results because it was reasoned from animal studies that early cooling might prevent further brain damage from occurring. The so-called Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury–Randomized Clinical Trial (POLAR-RCT) study did not show benefit from prophylactic hypothermia, and also found that patients who received the therapy were more likely to develop pneumonia or intracranial bleeding than those who did not.

An editorial that accompanied the December 4 report in JAMA noted that “the findings of this trial, along with other data, demonstrate that there is no role for initiation of hypothermia during the acute phases of TBI management.” “This important finding should now be incorporated into relevant guidelines and adopted in emergency departments and intensive care units,” said the lead author of the editorial, Peter J.D. Andrews, MD, MBChB, of Western General Hospital in Edinburgh, and his colleagues. Dr. Andrews co-authored a previous trial called Eurotherm3235 that found hypothermia for elevated intracranial pressure resulted in Continued on page 31

reuTerS

Patients with Traumatic Brain Injury Do Not Benefit from Prophylactic hypothermia, large study finds

Questions remain as to whether the findings will find their way into practice.

lasmiditan delivers migraine relief after two hours without high Volume 91, Number 8, August 21, 2018 cardiovascular risk Neurology.org/N lizette borreli

phase 3 SAMURAI trial of lasmiditan, a serotonin receptor agonist that targets 5-HT1F receptors without vasoconstriction, found the drug was effective and well tolerated for acute migraine among

patients at high risk for cardiovascular disease. The study found that significantly more patients who took lasmiditan (at 100 and 200 mg) were free from headache pain and such symptoms as nausea, phonophobia, and photophobia at two hours after treating a migraine attack. Lasmiditan selectively targets 5-HT1F receptors, including those expressed at

the trigeminal pathway, and it has been designed for the acute treatment of migraine without the vasoconstrictor activity associated with some migraine therapies, explained Kraig Kinchen, MD, senior medical director of migraine and related therapeutics at Eli Lilly and Company. The study was sponsored by CoLucid Pharmaceuticals, Inc., a wholly owned subsidiary of Lilly.

Volume 9, Number 1, February 2019

Neurology.org/CP

Volume 5, Number 1, February 2019

Volume 6, Number 2, March 2019

Neurology.org/NG

Neurology.org/NN

Dr. Kinchen noted that the investigational, oral, selective serotonin 5-HT1F agonist is “structurally and mechanistically” distinct from other approved migraine therapies, such as triptans, which can have vasoconstrictive effects resulting from activity at the 5-HT1B receptors. Triptans are contraindicated in patients with cardiovascular disease, Dr. Continued on page 22 Kinchen said.

The most widely read and highly cited peer-reviewed neurology journal

A peer-reviewed clinical neurology journal for the practicing neurologist

A peer-reviewed clinical and translational neurology open access journal

the Best advances of 2018: Neurology Today editorial Board Picks Page 9

PerIODICAlS

NeurologyToday (ISSN 1533-7006), an official publication of the American Academy of Neurology, is published twice a month for the Academy by Wolters Kluwer, at 14700 Citicorp Drive, Bldg. 3, Hagerstown, MD 21742. POSTMASTER: Send address changes to Neurology Today, PO Box 1610, Hagerstown, MD 21740. Periodicals Postage Paid at Hagerstown, MD and at additional mailing offices.

LWW_NTY_January 24_19_Layout.indd 1

09/01/19 10:44 PM

THE HELIX

CLINICAL/SCIENTIFIC NOTE

2018: Year in Review and Message from the Editors to Our Reviewers e309

Balint syndrome in anti-NMDA receptor encephalitis e532

ARTICLE

RESEARCH

Time-dependent decline of body-specific attention to the paretic limb in chronic stroke patients 346

Quality of life outcomes in patients presenting for evaluation of CNS tumors 32

ARTICLE

Recent advancements in lateral trunk flexion in Parkinson disease 74

Gene variants of adhesion molecules predispose to MS: A case-control study e304

Real-world validation of the 2017 McDonald criteria for pediatric MS e528

RESEARCH

ARTICLE

Genomic deletions upstream of lamin B1 lead to atypical autosomal dominant leukodystrophy e305

HIV is associated with endothelial activation despite ART, in a sub-Saharan African setting e531

Association of orthostatic hypotension with incident dementia, stroke, and cognitive decline 347 ARTICLE

Determinants and outcome of multiple and early recurrent cervical artery dissections 348 ARTICLE

Silent infarct is a risk factor for infarct recurrence in adults with sickle cell anemia 349

REVIEW

Devastating neurologic injuries in the Syrian war 9 COMMENTARY

Using EHRs to advance epilepsy care 83

CLINICAL/SCIENTIFIC NOTE

ARTICLE

Variable reporting of C9orf72 and high rate of uncertain results in ALS genetic testing e301

Mouse model of anti-NMDA receptor post–herpes simplex encephalitis e529

Through it AAN Headquarters, our home since 2012 all, the board has balanced the financial health of the Academy with the need to do increasingly more for our members. I’m very proud that, in 2018, 87 cents out of every dollar of member dues was returned to members in the form of benefits, Continued on page 6

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AANnews • June 2019 5

From Solid to Exceptional: 20 Years of AAN Growth continued from page 5 programs, and services, from discounts on the Annual Meeting and conferences to free education tools for maintenance of certification. Very few associations can make that claim. Since 1999, the AAN’s operating budget has increased from $11M to $61M and its long-term reserves have grown from $7M to $65M. The financial oversight of the board and the acumen of our staff as stewards of Academy resources meant— unlike many national medical associations—we did not have Olson and Rydell in 2004 to reduce member services or lay off staff during the Great Recession of a decade ago. Indeed, our finances were such that we were able to take advantage of depressed land values to secure our location on prime real estate in the growing Mill District of Minneapolis just two blocks away from US Bank Stadium, host of the 2018 Super Bowl and 2019 NCAA Final Four. Our presence is a daily reminder to the community of the need and purpose of neurology. We are a much more diverse organization than we were 20 years ago. Shortly after I began, members elected Dr. Sandra Olson as the first woman to hold the office of president. At this year's Annual Meeting in Philadelphia, members voted to elect Dr. Orly Avitzur as president elect, meaning the AAN will have a second woman to serve as president beginning in 2021. And, as of last month, four of the six officers in the Academy

on the Hill over the years. We have a well-trained army of advocates who join us to lobby in Washington and all 50 states as well as create positive change in their own institutions and communities. I’ve personally met many of these members and am constantly impressed with their passion and determination. Thousands more have participated in grassroots level advocacy by contacting their lawmakers when we’ve asked for their help. These members recognize the power of speaking truth, with one strong united voice, to those in power. And through our many successes, we have gained strength and influence as the trusted organization for neurology. The AAN’s membership has grown from 16,000 in 1999 to 36,000 today. Part of that growth is in our international membership from 141 countries. We have strengthened our relationships with such global bodies as the World Federation of Neurology and the European Academy of Neurology and national associations like the Israeli Neurologic Association, Mexican Academy of Neurology, and Japanese Society of Neurology. At the same time, we are diligently working to increase the number of US medical students who choose neurology and child neurology as their specialty to meet the needs of neurologic patients. To augment the innumerable learning opportunities during our week-long Annual Meetings in the spring, the AAN began to offer a Fall Conference in 2002. An ongoing Winter Conference was eventually replaced with specialized conferences as deemed necessary. With growing focus on the problems of sport concussion, we inaugurated our annual Sport Concussion Conference in 2015. My first Annual Meeting, in Toronto in 1999, was attended by 10,000 neurology professionals. Our most recent one in Philadelphia drew more than 15,000 attendees.

AAN Women and Minority Growth 35% Neurology on the Hill has given a voice to hundreds of impassioned AAN advocates.

are women. The number of women and minority members on the board also has increased, better reflecting demographic changes in our membership. We have helped ensure we will have experienced and skilled governance in the future, thanks in large part to our Leadership Programs. These programs also nurture leaders in diversity, wellness, clinical practice, advocacy, and other key areas. Speaking of advocacy, we’ve had more than 400 members graduate from our flagship Palatucci Advocacy Leadership Forum, and over 1,000 more have participated in Neurology

AANnews • June 2019

2019 33.7%

% Women % Minority

2014 31.1%

30% 2009 24.7%

25%

2014 22.5%

2004 22.3% 2009 19.7%

1999 20% 17.6%

15%

1999 15.8% 2000

2019 30.6%

2004 18.9% 2005

2010

2015

AAN Membership Growth The popularity and evolution of these meetings is a testament to helpful attendee feedback as well as the fantastic planning by volunteer committee members and staff experts. Their willingness to try new things to keep the meeting fresh and exciting for attendees has made it the largest gathering of neurologists and neurology professionals in the world. The AAN’s support for neurologic research has multiplied even as we rebranded and spun off the AAN Foundation as the independent American Brain Foundation in 2012. Last year, we awarded $3.1M in grants. Our public education activities, best demonstrated by our free Brain Health Fairs in conjunction with the Annual Meeting and our public-facing magazine Brain & Life® and the BrainandLife.org website, have expanded our reach to patients, caregivers, and the public. Public awareness has continued with extensive media coverage of breaking research published in Neurology, our Neurology Now ®

Books series, as well as free disease-specific videos and public service announcements. We have close to 400,000 member and public followers on our numerous social media channels. There was no social media 20 years ago, of course. We still relied heavily on snail mail to communicate to members. But the Academy harnessed technology that allows us to be more available and productive. Usually, we made the right technology bets (whatever happened to the Palm Pilot?), and email and the internet reduced our paper footprint. Members now can access Humor is something convenient online we’ve always found useful for coping.” education programs, El

40,000 2018 36,000 35,000

30,000

2015 30,000

25,000

20,000

15,000

2010 24,000 1999 16,000

2005 19,500

2000

2005

2010

2015

read a long-form article in one of our journals, take the RITE® exam, and pay their dues—all online. As I said, these and countless other accomplishments of the AAN are the result of the efforts of our members and staff. It’s often said that being a good boss means hiring talented people and then getting out of their way. But to make that happen, you must trust your instincts, and you must trust those you have hired to successfully do their work. I could not wish for a better team of senior executives and nearly 200 people who come to work each day at the AAN not just for a paycheck, but to promote the highest quality patient-centered neurologic care and enhance member career satisfaction. My trust in them reflects the trust the board has put in me over these 20 years. Together, our vision is—and will continue to be—the same: to be indispensable to our members. Thank you for allowing me to be part of this fantastic organization! 

D E C E M B E R 2 0 1 8/JA N UA RY 2 0 1 9

Cannabidiol Medical Marijuana for Epilepsy and Other Disorders Nutrition What Kind of Fish Is Good for the Brain?

Physical Therapy How High-Tech Tools Are Advancing Recovery

N E U R O LO G Í A PA R A L A V I DA D I A R I A P R I M AV E R A 2 0 1 9

Neuropatía diabética Consejos de un experto para aliviar el dolor Por qué los vegetales de hoja verde son buenos para el cerebro

Catherine M. Rydell, CAE Chief Executive Officer, AAN

— C O M E DY D U O J E A N N I E A N D J I M G A F F I G A N A B O U T J E A N N I E ’S B R A I N T U M O R

Alzheimer puede afectar a los jóvenes que aún tienen mucho por vivir”. —MARIA SHRIVER

AANnews • June 2019

Tools & Resources

Members Love New Practice Management Webinar Format A new format to allow for a deeper dive into subject matter and invite more questions from participants has made the AAN’s Practice Management Webinar series more popular than ever, with 97 percent of participants surveyed saying that the new format offered “quality information that they can incorporate into their practice.” The same percentage said that the webinars provided them strategies to implement these new techniques into their practice. And 98 percent said that they “acquired useful knowledge from this webinar” format. Overall, 60 percent of webinar participants have rated the new format as “Excellent,” with another 37 percent rating it as “Good.” The cumulative rating of 97 percent of respondents saying the new webinars are good or excellent eclipses last year’s 80 approval along similar lines. Each webinar begins with a live, 30to 45-minute webinar where faculty introduces the topic and registrants are able to ask questions. In the weeks following the webinar, several shorter recorded webinars are then posted on AAN.com that explore the topic in greater depth, and participants can access

these at their convenience. Finally, each topic concludes with a 30-minute webchat, so participants can ask further questions. Participants can earn 2 AMA PRA Category 1 Credits™ per webinar for physicians, or a certificate of completion for non-physicians.

November 19 at 12:00 p.m. ET Seeing the Future Clearly: How to Succeed in 2020 Joel M. Kaufman, MD, FAAN

You can purchase a single webinar for $99 or subscribe to the complete series of 2019 webinars for only $189—less than $32 per webinar! Visit AAN.com/view/ pmw19 to learn more and register or contact Jessica Nickrand at jnickrand@aan.com.

Boss, MD: Managing a Better Practice J. Todd Barnes, MBA, CMPE Seth Lefberg

Register for These Upcoming Live Webinars August 13 at 12:00 p.m. ET Increasing Revenue in Your Practice: Care Models, Ancillary Services, and Other Strategies David Evans, MBA October 1 at 12:00 p.m. ET Using Technology for Better Practice Management of Stroke Mark J. Alberts, MD, FAHA Elaine C. Jones, MD, FAAN Lawrence R. Wechsler, MD, FAAN

Understanding How You Get Paid Bruce H. Cohen, MD, FAAN Raissa Villanueva, MD, MPH, FAAN Jeffrey Waugh, MD, PhD Korwyn Williams, MD, PhD Everything You Wanted to Know About Your Patients but Were Afraid to Ask: Having Difficult Conversations with Patients from Vulnerable Populations Farrah N. Daly, MD, MPH Christopher T. Doughty, MD Justin P. Martello, MD Allan D. Wu, MD, PhD 

Accident Motivated Estefan’s Support for Paralysis Research The Brain & Life® June/July 2019 cover story features singer Gloria Estefan, who injured her back in a bus accident in 1990. Her brush with paralysis inspired her to get involved with the Miami Project to Cure Paralysis, a research institute dedicated to improving the lives of those with paralysis. Fatigue Over the years, she has donated time, money, Expert Ways to Manage Tiredness and encouragement. Stroke Recovery Another feature chronicles the recovery journeys of five stroke survivors, who learned important lessons about knowing the signs of stroke, getting immediate help, and accessing ongoing rehabilitation. The story demonstrates that stroke doesn’t discriminate, affecting young and old, rich and poor, men and women, and black, white, and Hispanic alike.

AANnews • June 2019

5 Survivors: What Helped Them Get Through

Cluster Headache New Treatments to Curb the Pain

I try to inspire people who have been paralyzed.”

— S I N G E R G LO R I A E S TE FA N

The issue also offers a deep dive into cluster headache, exploring the causes and risk factors as well as how it’s diagnosed and treated―and promising treatments in the pipeline. J U N E/J U LY 2 0 1 9

Brain & Life magazine is free for AAN members in the United States to distribute to patients, who also can subscribe for free. If you would like to adjust the number of copies you receive for your patients or update your clinic address, email BeGreen@ WasteFreeMail.com. All members have online access to the magazine articles and additional resources at BrainandLife.org. Please share the website with your patients! 

Brain & Life and Neurology Today Recognized with Awards The AAN’s publications Brain & Life® and Neurology Today ® won top awards recently from the editorial competition sponsored by the American Society of Healthcare Publication Editors. Submissions had to have been published in 2018.

Enjoy New Look and Enhanced Convenience of Neurology Today Website

Brain & Life won three Silver Medals for: Best Feature Article: “The Road to Surgery,” June/July 2018 (BrainLifemag.org/RoadToSurgery)

A redesigned Neurology Today ® website launched in April and now more closely resembles the new print design of the AAN’s twice-monthly news source focusing on breaking news, issues, and trends in the practice and science of neurology. New features include:

Best Profile: “Supporting Role,” June/July 2018 (BrainLifemag.org/CourtneyBVance) Best Single News Article: “Early Clues,” October/November 2018 (BrainLifemag.org/EarlyClues) The October 8, 2018, Neurology Today won the Bronze Award for Best Single Issue (AAN.com/view/NeurologyTodayOct2018)

why seizures can recur after surgery Page 23

Easier navigation for viewing articles on major neurologic topics and sections of the magazine

is the thalamus really the Key to the arousal Pathway? Page 28

the official ne ws source of the a merican academy of neurology | neurology today.com january 24, 2019 | Volume 19 | issue 2

Redesigned pages for At the Meetings, featuring coverage of 10 specialty meetings throughout the year

Patients with Traumatic Brain Injury Do Not Benefit from Prophylactic hypothermia, large study finds susan fitzgerald

J U N E/J U LY 2 0 1 8

Surgery What to Expect and How to Prepare Caregiving How to Make It a Family Affair

Whatever journey ALS took my mother on, we had to go on it together.” —AC TO R C O U R T N E Y B . VA N C E

MEM: 17 Membership Continuum Ad—Half Page Horizontal> AN Placed in AANnews 8.25 x 5.25 +0.125 bleed, 4C

Neuro Film Festival Meet the Winners

I’m using my visibility to encourage girls to be interested in science.”

An editorial that accompanied the show any benefits. Researchers were O C TO R /N OV E MinB which E R 2 0 1 8December 4 report in JAMA noted that hoping that thisB Elatest trial, hypothermia was used prophylacti- “the findings of this trial, along with cally, would turn in favorable results other data, demonstrate that there is no because it was reasoned from animal role for initiation of hypothermia during studies that early cooling might pre- the acute phases of TBI management.” “This important finding should now be vent further brain damage from occurring. The so-called Prophylactic incorporated into relevant guidelines and Hypothermia Trial to Lessen Traumatic adopted in emergency departments and Brain Injury–Randomized Clinical intensive care units,” said the lead author of the Trial (POLAR-RCT) study did not editorial, Peter J.D. Andrews, MD, MBChB, of show benefit from prophylactic hypo- Western General Hospital in Edinburgh, and thermia, and also found that patients his colleagues. Dr. Andrews co-authored a prewho received the therapy were more vious trial called Eurotherm3235 that found likely to develop pneumonia or intra- hypothermia for elevated intracranial prescranial bleeding than those who did not. sure resulted in Continued on page 31

Low Back Pain 3 Treatments Experts Recommend

Nutrition Why Leafy Greens Are Good for the Brain

reuTerS

The competition is well-respected within the publishing industry, draws nearly 3,000 entries each year, and is judged by a panel of editors and graphics professionals in the publishing field. 

Homepage that features most current and most popular content, updated daily

Questions remain as to whether the findings will find their way into practice.

lasmiditan delivers migraine relief after two hours without high Research cardiovascular risk lizette borreli

phase 3 SAMURAI trial of lasmiditan, a serotonin receptor agonist that targets 5-HT1F receptors without vasoconstriction, found the drug was effective and well tolerated for acute migraine among

What Scientists the trigeminal pathway, and it has been Are Learning designed for the acute treatment of from Young-onsetmigraine without the vasoconstrictor activity associated with some migraine Alzheimer’s

therapies, explained Kraig Kinchen, MD, senior medical director of migraine and related therapeutics at Eli Lilly and Company. The study was sponsored by CoLucid Pharmaceuticals, Inc., a wholly owned subsidiary of Lilly.

the Best advances of 2018: Neurology Today editorial Board Picks

—AC T R E S S M AY I M B I A L I K

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Order Now: AAN.com/view/19AMOD *Specific presentations within a session may not be available or may be audio only if the presenter has confidential patient information or otherwise declines to be recorded. **With the move to an online offering, hard drives will not be provided.

Tools & Resources

Axon Registry Helps User Increase Measure Performance Scores The Axon Registry ®, a free product for US-based AAN members, gives participants the power to take assessing their quality data into their own hands. It is an easy-to-use platform that provides quality measure data to clinicians and practice managers to implement quality improvement and work flow changes. It provides a solution for reporting data to CMS for the Merit-based Incentive Payment System (MIPS), and participants can receive credit for the ABPN’s Maintenance of Certification (MOC) Part IV PIP clinical module activity and waive eight credits of Part II Self-assessment. In addition to the many benefits of the registry, practices also have used it to improve their documentation workflow. Especially for larger organizations, doctors often document in a variety of ways, which can make it difficult to track the quality of care being provided. Registry data can be used to assess performance rates on each measure in the registry for each individual clinician in the practice. This data can then be compared to find documentation gaps where improvements can be made.

Want to learn more about this valuable resource provided by the AAN? Visit AAN.com/view/Axon. 

Reporting on Registry Neurology Measures Provides MIPS Credit

DENT Neurologic Institute in New York used Axon Registry data to educate its providers about ways to document to receive proper credit for the work they were doing. Being able to drill down to the patient level and find areas for improvement drastically helped increase their measure performance scores.

AAN staff are available to provide insight into how documentation can be used to meet the measure. There is a wide variety of ways to document; so, this process is not required for all practices in the Axon Registry. However, it is one way to help move your practice toward a more efficient way of tracking patient encounter information.

Emily Swierski, Quality and Revenue Cycle coordinator for DENT, explained, “We used the Axon keyword dictionary to create structured templates for providers to use within our EMR, eClinicalWorks. We started small with a few templates for the most popular measures and plan to grow that Swierski number over time. This process update has greatly improved adherence to documentation of measure information.”

The Axon Registry is an efficient way to receive credit for three components of the MIPS program: Quality, Promoting Interoperability, and Improvement Activities. In the 2018 MIPS reporting, participants in the Axon Registry, on average, received a score in the exceptional category. This means that, on average, Axon Registry clinicians scored above 70 points and will be eligible for an exceptional bonus on their Medicare payments in 2020. The quality measures available in the Axon Registry are neurology-specific and can help boost your MIPS score as many have benchmark data. Learn more about QPP/MIPS at AAN.com/view/QPP.

SAVE THE DATE! October 18-20, 2019 The Cosmopolitan of Las Vegas

AAN.com/view/19FC

AANnews • June 2019

Policy & Guidelines

New AAN Guideline on Tourette and Chronic Tics Shared at Annual Meeting Press Conference The AAN presented the new “Practice Guideline: The Treatment of Tics in People with Tourette Syndrome and Chronic Tic Disorders,” during a press conference with media covering the Annual Meeting. The press conference gave an opportunity for journalists to pose questions to lead author Tamara Pringsheim, MD, MSc, FAAN , and guideline senor author John Piacentini, PhD, ABPP. The guideline was published online in Neurology ® on May 6, 2019.

treatments for people with tics, as well as for the assessment of and counseling for these patients. There are approximately 46 recommendations in the clinician summary. Treatment decisions should be individualized to achieve the best balance for Pringsheim each patient.

Evidence reviewed by the guideline shows there is a variety of treatments available for tics. The guideline provides evidence-based recommendations on the efficacy and safety of the medical, behavioral, and neurostimulation

Choosing among the many treatment options should be done through shared decision-making between clinicians and patients. Comprehensive behavioral intervention for tics has high-quality evidence supporting its efficacy for

the treatment of tics, without major adverse effects. It should be made routinely available for individuals with Tourette syndrome. For nondisabling tics in children, watchful waiting also is appropriate. Medical interventions for tics are available but should be periodically reassessed because of the high rate of natural remission of tics in late adolescence. Visit AAN.com to read the guideline and access summaries for clinicians and families/caregivers and a slide presentation set. For more information, email guidelines@aan.com or call (612) 928-6069. 

Members Acknowledged for Work on AAN Guidelines Recently, the Guideline Development, Dissemination, and Implementation Subcommittee (GDDI) honored four subcommittee members for their outstanding work and contributions to the AAN’s guidelines program. The GDDI oversees the development and dissemination of systematic reviews and evidence-based guidelines to assist members in clinical decision-making. The members cited were: Gary S. Gronseth, MD, FAAN John J. Halperin, MD, FAAN Maryam Oskoui, MD, MSc, FAAN, FRCPC Gronseth

Halperin

Oskoui

Narayanaswami

Pushpa Narayanaswami, MBBS, MD, FAAN

AANnews • June 2019 11

Policy & Guidelines

Passion for Advocacy Is Springboard to Leadership Role

Stavros

Kara Stavros, MD, a neurologist at Rhode Island Hospital and assistant professor of neurology at The Warren Alpert Medical School of Brown University, has been an AAN member only since 2012. But after finishing her residency, she knew she had to channel some of her energy for her profession into a higher calling.

“I'm passionate about advocacy because our patients with neurological diseases face so many different challenges,” Stavros shared. “As neurologists, there are many ways we can try to help them and using our voices to advocate is one of them. I've seen AAN advocacy successes that have made a big difference in patients' lives, and this inspires me to do more.” This passion led Stavros to applying for and being accepted to the 2018 class of the Palatucci Advocacy Leadership Forum (PALF). She had a mission, and the AAN provided her with the means to bring it to fruition. “My PALF action plan was to develop an advocacy curriculum for neurology residents and to promote awareness of advocacy education,” she said. “Neurologists have a unique voice and perspective that we can use to advocate for our patients, but most neurology residents don't learn about advocacy skills while in training. My project addresses the need to teach residents the importance of advocacy and the basics of public policy so they will have the tools to advocate in their future careers.” “My project would not have succeeded without PALF, which gave me the skills to organize my goals into concrete steps through action planning. At PALF, I learned how to effectively communicate my message in a cogent sound bite, and I built confidence in public speaking. I also benefitted greatly from the advice of my PALF classmates and advisors, especially my advisor, Dr. Matthew Robbins.” Recently, Stavros and her colleague Jonathan Cahill, MD, introduced a pilot advocacy curriculum for residents at Brown comprised of an interactive lecture series and culminating in a local advocacy day at the State House. “Since introducing the curriculum, some of our residents have participated in Neurology on the Hill, Neurology off the Hill, Brain Week RI, and advocacy-related research. As part of the project, Dr. Cahill and I surveyed US neurology residency program directors using the AAN online community Synapse to gain a

AANnews • June 2019

sense of how many residency programs offer formal advocacy education. We shared those results in a poster at the AAN Annual Meeting.” Stavros, whose dedication to education was honored with a 2018 A.B. Baker Teacher Recognition award, attended Neurology on the Hill (NOH) in 2017, 2018, and 2019—and has participated in Neurology off the Hill. “At NOH, we visit legislators and their staff at their DC offices with several specific legislative ‘asks.’ In the case of an off the Hill visit, we visit the legislators in their local office or another local venue. Often the visit is a bit more comfortable and there may be less time constrictions.” Her NOH experience and connections enabled Stavros to invite Rhode Island Senators Jack Reed and Sheldon Whitehouse to come and give opening remarks at a Brain Week RI advocacythemed event that took place at Rhode Island Hospital. “Hosting an off the Hill visit on our ‘home turf’ was a very rewarding experience. We gave them a brief tour of some of our neurology facilities and discussed the unique services offered by our practice and the importance of access to neurological care for the patients in our state. Both senators were very generous with their time and not only gave opening remarks at the Brain Week RI advocacy event, but also stayed to answer questions from the audience about how to be effective advocates. After they left, my colleague Dr. Anelyssa D’Abreu moderated a panel on effective advocacy skills, which included a physician, a neuroscience researcher, and a representative from the Brain Injury Association of RI.” Getting two senators to the same event is quite a feat. But this is where her NOH experience came into play. “I am so grateful that both Sen. Reed and Sen. Whitehouse agreed to attend the event! Both are very strong supporters of issues related to health care and neurology, but it helped that I got to know members of their staff who were kind enough to consider my invitation. I met their staff in person by participating in Neurology on the Hill and stayed in touch periodically by reaching out to them in response to AAN Advocacy Action Alerts.” Stavros’ successes have not gone unnoticed. She was selected as a member of the new Advocacy Committee, beginning her two-year term last month. Just as she benefitted from the AAN’s advocacy programs, the AAN will undoubtedly continue to benefit from her passion for advocacy. 

Capitol Hill Report Capitol Hill Report presents regular updates on legislative and regulatory actions and how the Academy ensures that the voice of neurology is heard on Capitol Hill. It is emailed to US members twice monthly and is posted at AAN.com/view/HillReport. Below are some recent highlights.

AAN Urges Congress to Reauthorize PCORI by September

New AAN Study Examines Increases in Out-of-pocket Drug Costs

The Patient-Centered Outcomes Research Institute (PCORI) (PCORI.org) was established in 2010 and focuses on comparative clinical effectiveness research, guided by input from patients. The bulk of PCORI’s funding comes from a fee assessed on private insurance and self-insured health plans, about $2 per covered individual. PCORI currently funds a wide range of neurology-related research, studying the patient impact of innovative interventions such as video house calls for Parkinson’s patients and mobile stroke treatment. In fact, neurology is one of the top three conditions funded by PCORI research.

A new study was published in Neurology ® at Neurology.org titled “Out-of-pocket Costs Are on the Rise for Commonly Prescribed Neurological Medications.” The study examined out-of-pocket drug costs for more than 912,000 people with multiple sclerosis (MS), peripheral neuropathy, epilepsy, dementia, or Parkinson's disease using a large health care claims database. Study participants were privately insured and took at least one neurologic medication. Researchers investigated the top five most commonly prescribed medications for each condition as well as any other known high-cost drugs.

Without congressional action, PCORI will no longer be able to fund new research starting September 30, 2019. Due to this, the AAN has made reauthorization a priority in 2019.

The study found that out-of-pocket costs for MS drugs showed the steepest monthly increase. People taking these medications paid an average out-of-pocket cost of $15 a month in 2004 compared to an average of $309 a month in 2016, meaning their out-of-pocket costs were 20 times higher over the 12-year period.

Several AAN members have participated in PCORI grants, including Benzi Kluger, MD, FAAN, of Colorado. He received a PCORI grant in 2015 to compare the effectiveness of an outpatient model of palliative care for Parkinson’s patients. “This study would not have been funded by traditional sources and there are limited avenues for doing the most pragmatic and practical comparative effectiveness trials,” said Kluger. “With the support of PCORI, we have optimized our intervention (which is now serving as a model for other outpatient palliative clinics), completed this trial (will be submitting manuscript of very positive results this month), received additional NIH grant funding to implement this model in community settings, and already are partnering with the Parkinson’s Foundation to make this clinic model the new standard for all of their centers of excellence. PCORI’s interest in palliative care, patient-centered care, and measuring what matters were essential elements in the success of this trial.”

These findings, highlighted in a recent CNN article, will help draw attention to the unique drug pricing burdens that face neurology as the AAN continues to advocate for drug pricing reform. 

AANnews • June 2019 13

IN PATIENTS WITH RELAPSING FORMS OF MULTIPLE SCLEROSIS (RMS)

START WITH THE POWER AND EXPERIENCE OF TYSABRI

IN THE FIGHT AGAINST RMS In the 2-year AFFIRM pivotal trial:

83% placebo (primary endpoint: percentage with sustained increase in disability was 17% vs 29%; p<0.001) of patients taking TYSABRI had no sustained physical disability progression for 12 weeks vs 71% with

1,2

INDICATION TYSABRI® (natalizumab) is indicated as monotherapy for the treatment of patients with relapsing forms of multiple sclerosis. TYSABRI increases the risk of PML. When initiating and continuing treatment with TYSABRI, physicians should consider whether the expected benefit of TYSABRI is sufficient to offset this risk. See Important Safety Information regarding the risk of PML with TYSABRI. IMPORTANT SAFETY INFORMATION WARNING: Progressive Multifocal Leukoencephalopathy (PML) TYSABRI® (natalizumab) increases the risk of PML, an opportunistic viral infection of the brain that usually leads to death or severe disability. Risk factors for the development of PML include duration of therapy, prior use of immunosuppressants, and presence of anti-JCV antibodies. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI. Healthcare professionals should monitor patients on TYSABRI for any new sign or symptom that may be suggestive of PML. TYSABRI dosing should be withheld immediately at the first sign or symptom suggestive of PML. For diagnosis, an evaluation including a gadoliniumenhanced MRI scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended. Because of the risk of PML, TYSABRI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the TOUCH Prescribing Program.  Infection by the JC Virus (JCV) is required for the development of PML.  There are no known interventions that can reliably prevent PML or that can adequately treat PML if it occurs.  Postmarketing data suggest that the risk of developing PML may be associated with relative levels of serum anti-JCV antibody compared to a calibrator as measured by ELISA (often described as an anti-JCV antibody index value).  MRI findings may be apparent before clinical signs or symptoms suggestive of PML. Monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. Consider monitoring patients at high risk for PML more frequently. Lower PML-related mortality and morbidity have been reported following TYSABRI discontinuation in patients with PML who were initially asymptomatic compared to patients with PML who had characteristic clinical signs and symptoms at diagnosis. Important Safety Information continues on the following pages. Please see accompanying brief summary of full Prescribing Information, including Boxed Warning.

T R U S T I N T H E E X P E R I E N C E O F T Y S A B R I ® (n at a l iz u m a b) Choose the power of an established therapy

NEARLY

ALWAYS

APPROXIMATELY

200,000

COMMITTED TO SAFETY

NEW PATIENTS

for relapsing MS with the established therapy of TYSABRI, and counting3,a

The TOUCH® Prescribing Program helps you support patients throughout their treatment on TYSABRI

in the US who start TYSABRI have received no previous DMT4,b

PATIENTS TREATED

1 IN 5

OVER A DECADE OF REAL-WORLD EXPERIENCE VISIT TimeForTYSABRI.com OR TALK TO YOUR BIOGEN REPRESENTATIVE TO LEARN MORE DMT=disease-modifying therapy; a190,800 patients as of August 20183; bAs of July 2017. 4

IMPORTANT SAFETY INFORMATION WARNING: Progressive Multifocal Leukoencephalopathy (PML) (cont’d)  PML has been reported after discontinuation of TYSABRI in patients who did not have findings suggestive of PML at the time of discontinuation. Patients should continue to be monitored for any new signs or symptoms that may be suggestive of PML for approximately 6 months after discontinuation of TYSABRI.  Adverse events that may occur during plasma exchange include clearance of other medications and volume shifts, which have the potential to lead to hypotension or pulmonary edema. Although plasma exchange has not been studied in TYSABRI-treated patients with PML, it has been used in such patients in the postmarketing setting to remove TYSABRI more quickly from the circulation.  JCV infection of granule cell neurons in the cerebellum, i.e., JCV granule cell neuronopathy (GCN), with symptoms similar to PML, has been reported in patients treated with TYSABRI. JCV GCN can occur with or without concomitant PML and can cause cerebellar dysfunction. Diagnosis and management of JCV GCN should follow guidance provided for PML.  Immune reconstitution inflammatory syndrome (IRIS) has been reported in the majority of TYSABRI-treated patients who developed PML and subsequently discontinued TYSABRI. In almost all cases, IRIS occurred after plasma exchange was used to eliminate circulating TYSABRI. It presents as a clinical decline in the patient’s condition after TYSABRI removal (and, in some cases, after apparent clinical improvement) that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes in the MRI. TYSABRI has not been associated with IRIS in patients discontinuing treatment with TYSABRI for reasons unrelated to PML. In TYSABRI-treated patients with PML, IRIS has been reported within days to several weeks after plasma exchange. Monitoring for development of IRIS and appropriate treatment of the associated inflammation should be undertaken. Contraindications  TYSABRI is contraindicated in patients who have or have had PML.  TYSABRI is contraindicated in patients who have had a hypersensitivity reaction to TYSABRI. TYSABRI TOUCH Prescribing Program  Because of the risk of PML, TYSABRI is available only through a restricted distribution program under a REMS called the TOUCH® Prescribing Program.  Patients must be enrolled in the TOUCH Prescribing Program, read the Medication Guide, understand the risks associated with TYSABRI, and complete and sign the Patient-Prescriber Enrollment Form. Herpes Infections – Encephalitis, Meningitis and Acute Retinal Necrosis  TYSABRI increases the risk of developing encephalitis and meningitis caused by herpes simplex and varicella zoster viruses.  Serious, life-threatening, and sometimes fatal cases have been reported in the postmarketing setting in multiple sclerosis patients receiving TYSABRI.  The duration of treatment with TYSABRI prior to onset ranged from a few months to several years.  Monitor patients receiving TYSABRI for signs and symptoms of meningitis and encephalitis. If herpes encephalitis or meningitis occurs, TYSABRI should be discontinued, and appropriate treatment for herpes encephalitis/meningitis should be administered. Important Safety Information continues on the following pages. Please see accompanying brief summary of full Prescribing Information, including Boxed Warning.

IMPORTANT SAFETY INFORMATION (cont’d) Herpes Infections – Encephalitis, Meningitis and Acute Retinal Necrosis (cont’d)  Patients being administered TYSABRI are at a higher risk of acute retinal necrosis (ARN), a fulminant viral infection of the retina caused by the family of herpes viruses. Patients with eye symptoms such as decreased visual acuity, redness or eye pain should be referred for retinal screening as serious cases of ARN can lead to blindness of one or both eyes.  Following clinical diagnosis of ARN, consider discontinuation of TYSABRI. Hepatotoxicity  Clinically significant liver injury, including acute liver failure requiring transplant, has been reported in patients treated with TYSABRI in the postmarketing setting.  Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, occurred as early as six days after the first dose; signs of liver injury have also been reported for the first time after multiple doses.  TYSABRI should be discontinued in patients with jaundice or other evidence of significant liver injury (e.g., laboratory evidence). Hypersensitivity/Antibody Formation  Hypersensitivity reactions have occurred in patients receiving TYSABRI, including serious systemic reactions (e.g., anaphylaxis) which occurred at an incidence of <1%.  Reactions usually occur within 2 hours of the start of the infusion. Symptoms associated with these reactions can include urticaria, dizziness, fever, rash, rigors, pruritus, nausea, flushing, hypotension, dyspnea, and chest pain.  If a hypersensitivity reaction occurs, discontinue administration of TYSABRI and initiate appropriate therapy. Patients who experience a hypersensitivity reaction should not be re-treated with TYSABRI.  Hypersensitivity reactions were more frequent in patients with antibodies to TYSABRI compared with patients who did not develop antibodies to TYSABRI in both MS and CD studies.  Patients who receive TYSABRI for a short exposure (1 to 2 infusions) followed by an extended period without treatment are at higher risk of developing anti-natalizumab antibodies and/or hypersensitivity reactions on re-exposure, compared to patients who received regularly scheduled treatment. Immunosuppression/Infections  The immune system effects of TYSABRI may increase the risk for infections.  In Study MS1, certain types of infections—including pneumonias and urinary tract infections (including serious cases), gastroenteritis, vaginal infections, tooth infections, tonsillitis, and herpes infections—occurred more often in TYSABRI-treated patients than in placebotreated patients. One opportunistic infection, a cryptosporidial gastroenteritis with a prolonged course, was observed in a patient who received TYSABRI in Study MS1.  In Studies MS1 and MS2, an increase in infections was seen in patients concurrently receiving short courses of corticosteroids. However, the increase in infections in TYSABRI-treated patients who received steroids was similar to the increase in placebo-treated patients who received steroids.  In a long-term safety study of patients, opportunistic infections (pulmonary mycobacterium avium intracellulare, aspergilloma, cryptococcal fungemia and meningitis, and Candida pneumonia) have been observed in <1% of TYSABRI-treated patients.  Concurrent use of antineoplastic, immunosuppressant, or immunomodulating agents may further increase the risk of infections over the risk observed with use of TYSABRI alone.  In Studies MS1 and MS2, the rate of any type of infection was approximately 1.5 per patient-year in both TYSABRI-treated patients and placebo-treated patients.  In Study MS1, the incidence of serious infections was approximately 3% in TYSABRI-treated patients and in placebo-treated patients. Most patients did not interrupt treatment with TYSABRI during infections. Laboratory Test Abnormalities  In clinical trials, TYSABRI was observed to induce increases in circulating lymphocytes, monocytes, eosinophils, basophils, and nucleated red blood cells. Observed changes persisted during TYSABRI exposure, but were reversible, returning to baseline levels usually within 16 weeks after the last dose. Elevations of neutrophils were not observed. TYSABRI induces mild decreases in hemoglobin levels (mean decrease of 0.6 g/dL) that are frequently transient. Adverse Reactions  The most common adverse reactions reported at an incidence of ≥10% with TYSABRI and ≥2% difference with placebo were headache (38% vs 33%), fatigue (27% vs 21%), infusion reactions (24% vs 18%), urinary tract infections (21% vs 17%), arthralgia (19% vs 14%), depression (19% vs 16%), pain in extremity (16% vs 14%), rash (12% vs 9%), gastroenteritis (11% vs 9%), and vaginitis (10% vs 6%).  The most frequently reported serious adverse reactions in Study MS1 were infections (3.2% vs 2.6% placebo), including urinary tract infection (0.8% vs 0.3%) and pneumonia (0.6% vs 0%), acute hypersensitivity reactions (1.1% vs 0.3%, including anaphylaxis/anaphylactoid reaction [0.8% vs 0%]), depression (1.0% vs 1.0%, including suicidal ideation or attempt [0.6% vs 0.3%]), and cholelithiasis (1.0% vs 0.3%).  Based on animal data, TYSABRI may cause fetal harm. TYSABRI should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Please see accompanying brief summary of full Prescribing Information, including Boxed Warning. STUDY DESCRIPTION: The AFFIRM (NAtalizumab Safety and EFFIcacy in Relapsing-Remitting MS) study was a pivotal 2-year, double-blind, randomized, controlled trial with 942 relapsing MS patients who received either TYSABRI therapy (300 mg by intravenous infusion [n=627]) or placebo (n=315) every 4 weeks for up to 28 months (30 infusions).1,2 References: 1. TYSABRI Prescribing Information, Cambridge, MA: Biogen Inc. 2. Polman CH, O’Connor PW, Havrdova E, et al; for the AFFIRM investigators. A randomized, placebocontrolled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):899-910. 3. Data on file as of August 2018, Biogen Inc. 4. Data on file as of July 2017, Biogen Inc.

TYSABRI (natalizumab) injection, for intravenous use

Table 1:

Estimated United States Incidence of PML Stratified by Risk Factor

Brief Summary of Full Prescribing Information

WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability. Risk factors for the development of PML include duration of therapy, prior use of immunosuppressants, and presence of anti-JCV antibodies. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI [see Warnings and Precautions (5.1)]. • Healthcare professionals should monitor patients on TYSABRI for any new sign or symptom that may be suggestive of PML. TYSABRI dosing shouldbe withheld immediately at the first sign or symptom suggestive of PML. For diagnosis, an evaluation that includes a gadoliniumenhancedmagnetic enhanced magnetic resonance resonance imaging imaging (MRI) (MRI) scan scan ofof the the brain brain and, and, when when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended [see Contraindications (4), Warnings and Precautions (5.1)]. • Because of the risk of PML, TYSABRI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the TOUCH® Prescribing Program [see Warnings and Precautions (5.2)]. 1.

INDICATIONS AND USAGE

1.1. Multiple Sclerosis (MS) TYSABRI is indicated as monotherapy for the treatment of patients with relapsing forms of multiple sclerosis. TYSABRI increases the risk of PML. When initiating and continuing treatment with TYSABRI, physicians should consider whether the expected benefit of TYSABRI is sufficient to offset this risk. See important information regarding the risk of PML with TYSABRI [see Warnings and Precautions (5.1)]. 2.

DOSAGE AND ADMINISTRATION

2.1. Multiple Sclerosis (MS) Only prescribers registered in the MS TOUCH® Prescribing Program may prescribe TYSABRI for multiple sclerosis [see Warnings and Precautions (5.2)]. The recommended dose of TYSABRI for multiple sclerosis is 300 mg intravenous infusion over one hour every four weeks. 2.3. Dilution Instructions 1. Use aseptic technique when preparing TYSABRI solution for intravenous infusion. Each vial is intended for single use only. Discard any unused portion. 2. TYSABRI is a colorless, clear to slightly opalescent solution. Inspect the TYSABRI vial for particulate material and discoloration prior to dilution and administration. If visible particulates are observed and/or the liquid in the vial is discolored, the vial must not be used. 3. To prepare the diluted solution, withdraw 15 mL of TYSABRI from the vial using a sterile needle and syringe. Inject TYSABRI into 100 mL of 0.9% Sodium Chloride Injection, USP. No other intravenous diluents may be used to prepare the TYSABRI diluted solution. 4. Gently invert the TYSABRI diluted solution to mix completely. Do not shake. Inspect the solution visually for particulate material prior to administration. 5. The final dosage diluted solution has a concentration of 2.6 mg/mL. 6. Following dilution, infuse TYSABRI solution immediately, or refrigerate the diluted solution at 2°C to 8°C, and use within 8 hours. If stored at 2°C to 8°C, allow the diluted solution to warm to room temperature prior to infusion. DO NOT FREEZE. 2.4. Administration Instructions • Infuse TYSABRI 300 mg in 100 mL 0.9% Sodium Chloride Injection, USP, over approximately one hour (infusion rate approximately 5 mg per minute). Do not administer TYSABRI as an intravenous push or bolus injection. After the infusion is complete, flush with 0.9% Sodium Chloride Injection, USP. • Observe patients during the infusion and for one hour after the infusion is complete. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity-type reaction [see Warnings and Precautions (5.5)]. • Use of filtration devices during administration has not been evaluated. Other medications should not be injected into infusion set side ports or mixed with TYSABRI. 3. DOSAGE FORMS AND STRENGTHS Injection: 300 mg/15 mL (20 mg/mL) colorless and clear to slightly opalescent solution in a single-dose vial for dilution prior to infusion. 4.

CONTRAINDICATIONS

• TYSABRI is contraindicated in patients who have or have had progressive multifocal leukoencephalopathy (PML) [see Warnings and Precautions (5.1)].

• TYSABRI is contraindicated in patients who have had a hypersensitivity reaction to TYSABRI. Observed reactions range from urticaria to anaphylaxis [see Warnings and Precautions (5.5)].

WARNINGS AND PRECAUTIONS

5.1. Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability, has occurred in patients who have received TYSABRI. Three factors that are known to increase the risk of PML in TYSABRI-treated patients have been identified: • Longer treatment duration, especially beyond 2 years. There is limited experience in patients who have received more than 6 years of TYSABRI treatment. • Prior treatment with an immunosuppressant (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate mofetil). • The presence of anti-JCV antibodies. Patients who are anti-JCV antibody positive have a higher risk for developing PML. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI.

Anti-JCV Antibody Positive Anti-JCV Antibody Negative

TYSABRI Exposure†

No Prior Immunosuppressant Use

1-24 months

<1/1,000

1/1,000

<1/1,000

25-48 months

3/1,000

12/1,000

49-72 months

6/1,000

13/1,000

Prior Immunosuppressant Use

Notes: The risk estimates are based on postmarketing data in the United States from approximately 69,000 TYSABRI exposed patients. †Data beyond 6 years of treatment are limited. The anti-JCV antibody status was determined using an anti-JCV antibody test (ELISA)that has been analytically and clinically validated and is configured with detection and inhibition steps to confirm the presence of JCV-specific antibodies with an analytical false negative rate of 3%.

Retrospective analyses of postmarketing data from various sources, including observational studies and spontaneous reports obtained worldwide, suggest that the risk of developing PML may be associated with relative levels of serum anti-JCV antibody compared to a calibrator as measured by ELISA (often described as an anti-JCV antibody index value). Ordinarily, patients receiving chronic immunosuppressant or immunomodulatory therapy or who have systemic medical conditions resulting in significantly compromised immune system function should not be treated with TYSABRI. Infection by the JC virus is required for the development of PML. Anti-JCV antibody testing should not be used to diagnose PML. Anti-JCV antibody negative status indicates that antibodies to the JC virus have not been detected. Patients who are anti-JCV antibody negative have a lower risk of PML than those who are positive. Patients who are anti-JCV antibody negative are still at risk for the development of PML due to the potential for a new JCV infection or a false negative test result. The reported rate of seroconversion in patients with MS (changing from anti-JCV antibody negative to positive and remaining positive in subsequent testing) is 3 to 8 percent annually. In addition, some patients’ serostatus may change intermittently. Therefore, patients with a negative anti-JCV antibody test result should be retested periodically. For purposes of risk assessment, a patient with a positive anti-JCV antibody test at any time is considered anti-JCV antibody positive regardless of the results of any prior or subsequent anti-JCV antibody testing. When assessed, anti-JCV antibody status should be determined using an analytically and clinically validated immunoassay. After plasma exchange, wait at least two weeks to test for anti-JCV antibodies to avoid false negative test results caused by the removal of serum antibodies. After infusion of intravenous immunoglobulin (IVIg), wait at least 6 months (5 half-lives) for the IVIg to clear in order to avoid false positive anti-JCV antibody test results. Healthcare professionals should monitor patients on TYSABRI for any new sign or symptom suggestive of PML. Symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. The progression of deficits usually leads to death or severe disability over weeks or months. Withhold TYSABRI dosing immediately and perform an appropriate diagnostic evaluation at the first sign or symptom suggestive of PML. MRI findings may be apparent before clinical signs or symptoms. Cases of PML, diagnosed based on MRI findings and the detection of JCV DNA in the cerebrospinal fluid in the absence of clinical signs or symptoms specific to PML, have been reported. Many of these patients subsequently became symptomatic with PML. Therefore, monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. Consider monitoring patients at high risk for PML more frequently. Lower PML-related mortality and morbidity have been reported following TYSABRI discontinuation in patients with PML who were initially asymptomatic compared to patients with PML who had characteristic clinical signs and symptoms at diagnosis. It is not known whether these differences are due to early detection and discontinuation of TYSABRI or due to differences in disease in these patients. There are no known interventions that can reliably prevent PML or that can adequately treat PML if it occurs. PML has been reported following discontinuation of TYSABRI in patients who did not have findings suggestive of PML at the time of discontinuation. Patients should continue to be monitored for any new signs or symptoms that may be suggestive of PML for at least six months following discontinuation of TYSABRI. Because of the risk of PML, TYSABRI is available only under a restricted distribution program, the TOUCH® Prescribing Program. In multiple sclerosis patients, an MRI scan should be obtained prior to initiating therapy with TYSABRI. This MRI may be helpful in differentiating subsequent multiple sclerosis symptoms from PML. For diagnosis of PML, an evaluation including a gadolinium-enhanced MRI scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended. If the initial evaluations for PML are negative but clinical suspicion for PML remains, continue to withhold TYSABRI dosing, and repeat the evaluations. There are no known interventions that can adequately treat PML if it occurs. Three sessions of plasma exchange over 5 to 8 days were shown to accelerate TYSABRI clearance in a study of 12 patients with MS who did not have PML, although in the majority of patients, alpha-4 integrin receptor binding remained high. Adverse events which may occur during plasma exchange include clearance of other medications and volume shifts, which have the potential to lead to hypotension or pulmonary edema. Although plasma exchange has not been studied in TYSABRI treated patients with PML, it has been used in such patients in the postmarketing setting to remove TYSABRI more quickly from the circulation. JC virus infection of granule cell neurons in the cerebellum (i.e., JC virus granule cell neuronopathy [JCV GCN]) has been reported in patients treated with TYSABRI. JCV GCN can occur with or without concomitant PML. JCV GCN can cause cerebellar dysfunction (e.g., ataxia, incoordination, apraxia, visual disorders), and neuroimaging can show cerebellar atrophy. For diagnosis of JCV GCN, an evaluation that includes a gadolinium-enhanced MRI scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA, is recommended. JCV GCN should be managed similarly to PML. Immune reconstitution inflammatory syndrome (IRIS) has been reported in the majority of TYSABRI treated patients who developed PML and subsequently discontinued TYSABRI. In almost all cases, IRIS occurred after plasma exchange was used to eliminate circulating TYSABRI. It presents as a clinical decline in the patient’s condition after TYSABRI removal (and in some cases after apparent clinical improvement) that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes in the MRI. TYSABRI has not been associated with IRIS in patients discontinuing

treatment with TYSABRI for reasons unrelated to PML. In TYSABRI treated patients with PML, IRIS has been reported within days to several weeks after plasma exchange. Monitoring for development of IRIS and appropriate treatment of the associated inflammation should be undertaken. 5.2. TYSABRI TOUCH® Prescribing Program TYSABRI is available only through a restricted program under a REMS called the TOUCH® Prescribing Program because of the risk of PML [see Warnings and Precautions (5.1)]. For prescribers and patients, the TOUCH® Prescribing Program has two components: MS TOUCH® (for patients with multiple sclerosis) and CD TOUCH® (for patients with Crohn’s disease). Selected requirements of the TOUCH® Prescribing Program include the following: • Prescribers must be certified and comply with the following: – Review the TOUCH® Prescribing Program prescriber educational materials, including the full prescribing information. – Educate patients on the benefits and risks of treatment with TYSABRI, ensure that patients receive the Medication Guide, and encourage them to ask questions. – Review, complete, and sign the Patient-Prescriber Enrollment Form. – Evaluate patients three months after the first infusion, six months after the first infusion, every six months thereafter, and for at least six months after discontinuing TYSABRI. – Determine every six months whether patients should continue on treatment and, if so, authorize treatment for another six months. – Submit to Biogen the “TYSABRI Patient Status Report and Reauthorization Questionnaire” six months after initiating treatment and every six months thereafter. – Complete an “Initial Discontinuation Questionnaire” when TYSABRI is discontinued, and a “6-Month Discontinuation Questionnaire” following discontinuation of TYSABRI. – Report cases of PML, hospitalizations due to opportunistic infections, and deaths to Biogen at 1-800-456-2255 as soon as possible. • Patients must be enrolled in the TOUCH® Prescribing Program, read the Medication Guide, understand the risks associated with TYSABRI, and complete and sign the Patient-Prescriber Enrollment Form. • Pharmacies and infusion centers must be specially certified to dispense or infuse TYSABRI. 5.3. Herpes Infections Herpes Encephalitis and Meningitis TYSABRI increases the risk of developing encephalitis and meningitis caused by herpes simplex and varicella zoster viruses. Serious, life-threatening, and sometimes fatal cases have been reported in the postmarketing setting in multiple sclerosis patients receiving TYSABRI. Laboratory confirmation in those cases was based on positive PCR for viral DNA in the cerebrospinal fluid. The duration of treatment with TYSABRI prior to onset ranged from a few months to several years. Monitor patients receiving TYSABRI for signs and symptoms of meningitis and encephalitis. If herpes encephalitis or meningitis occurs, TYSABRI should be discontinued, and appropriate treatment for herpes encephalitis/meningitis should be administered. Acute Retinal Necrosis Acute retinal necrosis (ARN) is a fulminant viral infection of the retina caused by the family of herpes viruses (e.g., varicella zoster, herpes simplex virus). A higher risk of ARN has been observed in patients being administered TYSABRI. Patients presenting with eye symptoms, including decreased visual acuity, redness, or eye pain, should be referred for retinal screening for ARN. Some ARN cases occurred in patients with central nervous system (CNS) herpes infections (e.g., herpes meningitis or encephalitis). Serious cases of ARN led to blindness of one or both eyes in some patients. Following clinical diagnosis of ARN, consider discontinuation of TYSABRI. The treatment reported in ARN cases included anti-viral therapy and, in some cases, surgery. 5.4. Hepatotoxicity Clinically significant liver injury, including acute liver failure requiring transplant, has been reported in patients treated with TYSABRI in the postmarketing setting. Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, occurred as early as six days after the first dose; signs of liver injury have also been reported for the first time after multiple doses. In some patients, liver injury recurred upon rechallenge, providing evidence that TYSABRI caused the injury. The combination of transaminase elevations and elevated bilirubin without evidence of obstruction is generally recognized as an important predictor of severe liver injury that may lead to death or the need for a liver transplant in some patients. TYSABRI should be discontinued in patients with jaundice or other evidence of significant liver injury (e.g., laboratory evidence). 5.5. Hypersensitivity/Antibody Formation Hypersensitivity reactions have occurred in patients receiving TYSABRI, including serious systemic reactions (e.g., anaphylaxis), which occurred at an incidence of <1%. These reactions usually occur within two hours of the start of the infusion. Symptoms associated with these reactions can include urticaria, dizziness, fever, rash, rigors, pruritus, nausea, flushing, hypotension, dyspnea, and chest pain. Generally, these reactions are associated with antibodies to TYSABRI. If a hypersensitivity reaction occurs, discontinue administration of TYSABRI, and initiate appropriate therapy. Patients who experience a hypersensitivity reaction should not be re-treated with TYSABRI. Hypersensitivity reactions were more frequent in patients with antibodies to TYSABRI compared to patients who did not develop antibodies to TYSABRI in both MS and CD studies. Therefore, the possibility of antibodies to TYSABRI should be considered in patients who have hypersensitivity reactions [see Adverse Reactions (6.2)]. Antibody testing: If the presence of persistent antibodies is suspected, antibody testing should be performed. Antibodies may be detected and confirmed with sequential serum antibody tests. Antibodies detected early in the treatment course (e.g., within the first six months) may be transient and may disappear with continued dosing. It is recommended that testing be repeated three months after an initial positive result to confirm that antibodies are persistent. Prescribers should consider the overall benefits and risks of TYSABRI in a patient with persistent antibodies. Patients who receive TYSABRI for a short exposure (1 to 2 infusions) followed by an extended period without treatment are at higher risk of developing anti-natalizumab antibodies and/or hypersensitivity reactions on re-exposure, compared to patients who received regularly scheduled treatment. Given that patients with persistent antibodies to TYSABRI experience reduced efficacy, and that hypersensitivity reactions are more common in such patients, consideration should be given to testing for the presence of antibodies in patients who wish to recommence therapy following a dose interruption. Following a period of dose interruption, patients testing negative for antibodies prior to re-dosing have a risk of antibody development with re-treatment that is similar to TYSABRI naïve patients [see Adverse Reactions (6.2)].

5.6. Immunosuppression/Infections The immune system effects of TYSABRI may increase the risk for infections. In Study MS1 [see Clinical Studies (14.1)], certain types of infections, including pneumonias and urinary tract infections (including serious cases), gastroenteritis, vaginal infections, tooth infections, tonsillitis, and herpes infections, occurred more often in TYSABRI-treated patients than in placebo-treated patients [see Warnings and Precautions (5.1), Adverse Reactions (6.1)]. One opportunistic infection, a cryptosporidial gastroenteritis with a prolonged course, was observed in a patient who received TYSABRI in Study MS1. In Studies MS1 and MS2, an increase in infections was seen in patients concurrently receiving short courses of corticosteroids. However, the increase in infections in TYSABRI-treated patients who received steroids was similar to the increase in placebo-treated patients who received steroids. In a long-term safety study of patients treated with TYSABRI for multiple sclerosis, opportunistic infections (pulmonary mycobacterium avium intracellulare, aspergilloma, cryptococcal fungemia and meningitis, and Candida pneumonia) have been observed in <1% of TYSABRI-treated patients. In CD clinical studies, opportunistic infections (pneumocystis carinii pneumonia, pulmonary mycobacterium avium intracellulare, bronchopulmonary aspergillosis, and burkholderia cepacia) have been observed in <1% of TYSABRI-treated patients; some of these patients were receiving concurrent immunosuppressants [see Warnings and Precautions (5.1), Adverse Reactions (6.1)]. In Studies CD1 and CD2, an increase in infections was seen in patients concurrently receiving corticosteroids. However, the increase in infections was similar in placebo-treated and TYSABRI-treated patients who received steroids. Concurrent use of antineoplastic, immunosuppressant, or immunomodulating agents may further increase the risk of infections, including PML and other opportunistic infections, over the risk observed with use of TYSABRI alone [see Warnings and Precautions (5.1), Adverse Reactions (6.1)]. The safety and efficacy of TYSABRI in combination with antineoplastic, immunosuppressant, or immunomodulating agents have not been established. Patients receiving chronic immunosuppressant or immunomodulatory therapy or who have systemic medical conditions resulting in significantly compromised immune system function should not ordinarily be treated with TYSABRI. The risk of PML is also increased in patients who have been treated with an immunosuppressant prior to receiving TYSABRI [see Warnings and Precautions (5.1)]. 5.7. Laboratory Test Abnormalities In clinical trials, TYSABRI was observed to induce increases in circulating lymphocytes, monocytes, eosinophils, basophils, and nucleated red blood cells. Observed changes persisted during TYSABRI exposure, but were reversible, returning to baseline levels usually within 16 weeks after the last dose. Elevations of neutrophils were not observed. TYSABRI induces mild decreases in hemoglobin levels (mean decrease of 0.6 g/dL) that are frequently transient. 5.8. Immunizations No data are available on the effects of vaccination in patients receiving TYSABRI. No data are available on the secondary transmission of infection by live vaccines in patients receiving TYSABRI. 6. ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: • Progressive Multifocal Leukoencephalopathy (PML) [see Warnings and Precautions (5.1)] • Herpes Infections [see Warnings and Precautions (5.3)] • Hepatotoxicity [see Warnings and Precautions (5.4)] • Hypersensitivity/Antibody Formation [see Warnings and Precautions (5.5)] • Immunosuppression/Infections [see Warnings and Precautions (5.6)] 6.1. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions (incidence ≥ 10%) were headache and fatigue in both the multiple sclerosis (MS) and Crohn’s disease (CD) studies. Other common adverse reactions (incidence ≥ 10%) in the MS population were arthralgia, urinary tract infection, lower respiratory tract infection, gastroenteritis, vaginitis, depression, pain in extremity, abdominal discomfort, diarrhea NOS, and rash. Other common adverse reactions (incidence ≥ 10%) in the CD population were upper respiratory tract infections and nausea. The most frequently reported adverse reactions resulting in clinical intervention (i.e., discontinuation of TYSABRI) in the MS studies were urticaria (1%) and other hypersensitivity reactions (1%), and in the CD studies (Studies CD1 and CD2) were the exacerbation of Crohn’s disease (4.2%) and acute hypersensitivity reactions (1.5%) [see Warnings and Precautions (5.5)]. A total of 1617 multiple sclerosis patients in controlled studies received TYSABRI, with a median duration of exposure of 28 months. A total of 1563 patients received TYSABRI in all CD studies for a median exposure of 5 months; of these patients, 33% (n=518) received at least one year of treatment and 19% (n=297) received at least two years of treatment. Multiple Sclerosis Clinical Studies The most common serious adverse reactions in Study MS1 [see Clinical Studies (14.1)] with TYSABRI were infections (3.2% versus 2.6% in placebo, including urinary tract infection [0.8% versus 0.3%] and pneumonia [0.6% versus 0%]), acute hypersensitivity reactions (1.1% versus 0.3%, including anaphylaxis/anaphylactoid reaction [0.8% versus 0%]), depression (1.0% versus 1.0%, including suicidal ideation or attempt [0.6% versus 0.3%]), and cholelithiasis (1.0% versus 0.3%). In Study MS2, serious adverse reactions of appendicitis were also more common in patients who received TYSABRI (0.8% versus 0.2% in placebo). Table 2 enumerates adverse reactions and selected laboratory abnormalities that occurred in Study MS1 at an incidence of at least 1 percentage point higher in TYSABRI-treated patients than was observed in placebo-treated patients.

Table 2:

Table 3:

Adverse Reactions in Study MS1 (Monotherapy Study) Adverse Reactions (Preferred Term)

TYSABRI n=627 %

Placebo n=312 %

General Headache Fatigue Arthralgia Chest discomfort Other hypersensitivity reactions** Acute hypersensitivity reactions** Seasonal allergy Rigors Weight increased Weight decreased

38 27 19 5 5 4 3 3 2 2

33 21 14 3 2 <1 2 <1 <1 <1

Infection Urinary tract infection Lower respiratory tract infection Gastroenteritis Vaginitis* Tooth infections Herpes Tonsillitis

21 17 11 10 9 8 7

17 16 9 6 7 7 5

Psychiatric Depression

Musculoskeletal/Connective Tissue Disorders Pain in extremity Muscle cramp Joint swelling

16 5 2

14 3 1

Gastrointestinal Abdominal discomfort Diarrhea NOS Abnormal liver function test

11 10 5

10 9 4

Skin Rash Dermatitis Pruritus Night sweats

12 7 4 1

9 4 2 0

Menstrual Disorders* Irregular menstruation Dysmenorrhea Amenorrhea Ovarian cyst

5 3 2 2

4 <1 1 <1

Neurologic Disorders Vertigo Somnolence

6 2

5 <1

Renal and Urinary Disorders Urinary urgency/frequency Urinary incontinence

9 4

7 3

Injury Limb injury NOS Skin laceration Thermal burn

3 2 1

2 <1 <1

* Percentage based on female patients only. ** Acute versus other hypersensitivity reactions are defined as occurring within 2 hours post-infusion versus more than 2 hours. In Study MS2, peripheral edema was more common in patients who received TYSABRI (5% versus 1% in placebo).

Infections Progressive Multifocal Leukoencephalopathy (PML) occurred in three patients who received TYSABRI in clinical trials [see Warnings and Precautions (5.1)]. Two cases of PML were observed in the 1869 patients with multiple sclerosis who were treated for a median of 120 weeks. These two patients had received TYSABRI in addition to interferon beta-1a [see Warnings and Precautions (5.1)]. The third case occurred after eight doses in one of the 1043 patients with Crohnâ&#x20AC;&#x2122;s disease who were evaluated for PML. In the postmarketing setting, additional cases of PML have been reported in TYSABRI-treated multiple sclerosis and Crohnâ&#x20AC;&#x2122;s disease patients who were not receiving concomitant immunomodulatory therapy. In Studies MS1 and MS2 [see Clinical Studies (14.1)], the rate of any type of infection was approximately 1.5 per patient-year in both TYSABRI-treated patients and placebo-treated patients. The infections were predominately upper respiratory tract infections, influenza, and urinary tract infections. In Study MS1, the incidence of serious infection was approximately 3% in TYSABRI-treated patients and placebo-treated patients. Most patients did not interrupt treatment with TYSABRI during infections. The only opportunistic infection in the multiple sclerosis clinical trials was a case of cryptosporidial gastroenteritis with a prolonged course. In Studies CD1 and CD2 [see Clinical Studies (14.2)], the rate of any type of infection was 1.7 per patient-year in TYSABRI-treated patients and 1.4 per patient-year in placebo-treated patients. In Study CD3, the incidence of any type of infection was 1.7 per patient-year in TYSABRI-treated patients and was similar in placebo-treated patients. The most common infections were nasopharyngitis, upper respiratory tract infection, and influenza. The majority of patients did not interrupt TYSABRI therapy during infections, and recovery occurred with appropriate treatment. Concurrent use of TYSABRI in CD clinical trials with chronic steroids and/or methotrexate, 6-MP, and azathioprine did not result in an increase in overall

Adverse Reactions in Studies CD1 and CD2 (Induction Studies)

Adverse Reactions*

TYSABRI n=983 %

Placebo n=431 %

General Headache Fatigue Arthralgia Influenza-like illness Acute hypersensitivity reactions Tremor

32 10 8 5 2 1

23 8 6 4 <1 <1

Infection Upper respiratory tract infection Vaginal infections** Viral infection Urinary tract infection

22 4 3 3

16 2 2 1

6 3

4 <1

17 5 4 3 2

15 3 2 2 <1

Skin Rash Dry skin

6 1

4 0

Menstrual Disorder Dysmenorrhea**

Respiratory Pharyngolaryngeal pain Cough Gastrointestinal Nausea Dyspepsia Constipation Flatulence Aphthous stomatitis

* Occurred at an incidence of at least 1% higher in TYSABRI-treated patients than placebo-treated patients. ** Percentage based on female patients only. Table 4:

Adverse Reactions in Study CD3 (Maintenance Study)

Adverse Reactions*

TYSABRI n=214 %

Placebo n=214 %

General Headache Influenza-like illness Peripheral edema Toothache

37 11 6 4

31 6 3 <1

Infection Influenza Sinusitis Vaginal infections** Viral infection

12 8 8 7

5 4 <1 3

Respiratory Cough

Gastrointestinal Lower abdominal pain

Musculoskeletal and Connective Tissue Back pain Menstrual Disorder Dysmenorrhea**

* Occurred at an incidence of at least 2% higher in TYSABRI-treated patients than placebo-treated patients. ** Percentage based on female patients only. infections compared to TYSABRI alone; however, the concomitant use of such agents could lead to an increased risk of serious infections. In Studies CD1 and CD2, the incidence of serious infection was approximately 2.1% in both TYSABRItreated patients and placebo-treated patients. In Study CD3, the incidence of serious infection was approximately 3.3% in TYSABRI-treated patients and approximately 2.8% in placebo-treated patients. In clinical studies for CD, opportunistic infections (pneumocystis carinii pneumonia, pulmonary mycobacterium avium intracellulare, bronchopulmonary aspergillosis, and burkholderia cepacia) have been observed in <1% of TYSABRI-treated patients; some of these patients were receiving concurrent immunosuppressants [see Warnings and Precautions (5.6)]. Two serious non-bacterial meningitides occurred in TYSABRI-treated patients compared to none in placebo-treated patients. Infusion-related Reactions An infusion-related reaction was defined in clinical trials as any adverse event occurring within two hours of the start of an infusion. In MS clinical trials, approximately 24% of TYSABRI-treated multiple sclerosis patients experienced an infusion-related reaction, compared to 18% of placebo-treated patients. In the controlled CD clinical trials, infusion-related reactions occurred in approximately 11% of patients treated with TYSABRI compared to 7% of placebo-treated patients. Reactions more common in the TYSABRI-treated MS patients compared to the placebo-treated MS patients included headache, dizziness, fatigue, urticaria, pruritus, and rigors. Acute urticaria was observed in approximately 2% of patients. Other hypersensitivity reactions were observed in 1% of patients receiving TYSABRI. Serious systemic hypersensitivity infusion reactions occurred in <1% of patients [see Warnings and Precautions (5.5)]. All patients recovered with treatment and/or discontinuation of the infusion.

Infusion-related reactions that were more common in CD patients receiving TYSABRI than those receiving placebo included headache, nausea, urticaria, pruritus, and flushing. Serious infusion reactions occurred in Studies CD1, CD2, and CD3 at an incidence of <1% in TYSABRI-treated patients. MS and CD patients who became persistently positive for antibodies to TYSABRI were more likely to have an infusion-related reaction than those who were antibody-negative. 6.2. Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to natalizumab in the studies described below with the incidence of antibodies in other studies or to other products may be misleading. Patients in Study MS1 [see Clinical Studies (14.1)] were tested for antibodies to natalizumab every 12 weeks. The assays used were unable to detect low to moderate levels of antibodies to natalizumab. Approximately 9% of patients receiving TYSABRI developed detectable antibodies at least once during treatment. Approximately 6% of patients had positive antibodies on more than one occasion. Approximately 82% of patients who became persistently antibody-positive developed detectable antibodies by 12 weeks. Anti-natalizumab antibodies were neutralizing in vitro. The presence of anti-natalizumab antibodies was correlated with a reduction in serum natalizumab levels. In Study MS1, the Week 12 pre-infusion mean natalizumab serum concentration in antibody-negative patients was 15 mcg/mL compared to 1.3 mcg/mL in antibody-positive patients. Persistent antibodypositivity resulted in a substantial decrease in the effectiveness of TYSABRI. The risk of increased disability and the annualized relapse rate were similar in persistently antibody-positive TYSABRI-treated patients and patients who received placebo. A similar phenomenon was also observed in Study MS2. Infusion-related reactions that were most often associated with persistent antibody-positivity included urticaria, rigors, nausea, vomiting, headache, flushing, dizziness, pruritus, tremor, feeling cold, and pyrexia. Additional adverse reactions more common in persistently antibody-positive patients included myalgia, hypertension, dyspnea, anxiety, and tachycardia. Patients in CD studies [see Clinical Studies (14.2)] were first tested for antibodies at Week 12, and in a substantial proportion of patients, this was the only test performed given the 12-week duration of placebocontrolled studies. Approximately 10% of patients were found to have anti-natalizumab antibodies on at least one occasion. Five percent (5%) of patients had positive antibodies on more than one occasion. Persistent antibodies resulted in reduced efficacy and an increase in infusion-related reactions with symptoms that include urticaria, pruritus, nausea, flushing, and dyspnea. The long-term immunogenicity of TYSABRI and the effects of low to moderate levels of antibody to natalizumab are unknown [see Warnings and Precautions (5.5), Adverse Reactions (6.1)]. 6.3. Postmarketing Experience The following adverse reactions have been identified during post approval use of TYSABRI. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood disorders: hemolytic anemia 8.

USE IN SPECIFIC POPULATIONS

8.1.

Pregnancy

Risk Summary There are no adequate data on the developmental risk associated with the use of TYSABRI in pregnant women. In animal studies, administration of natalizumab during pregnancy produced fetal immunologic and hematologic effects in monkeys at doses similar to the human dose and reduced offspring survival in guinea pigs at doses greater than the human dose. These doses were not maternally toxic but produced the expected pharmacological effects in maternal animals [see Data]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data In developmental toxicity studies conducted in guinea pigs and monkeys, at natalizumab doses up to 30 mg/kg (7 times the recommended human dose based on body weight [mg/kg]), transplacental transfer and in utero exposure of the embryo/fetus was demonstrated in both species. In a study in which pregnant guinea pigs were administered natalizumab (0, 3, 10, or 30 mg/kg) by intravenous (IV) infusion on alternate days throughout organogenesis (gestation days [GD] 4-30), no effects on embryofetal development were observed. When pregnant monkeys were administered natalizumab (0, 3, 10, or 30 mg/kg) by IV infusion on alternative days throughout organogenesis (GDs 20-70), serum levels in fetuses at delivery were approximately 35% of maternal serum natalizumab levels. There were no effects on embryofetal development; however, natalizumabrelated immunological and hematologic changes were observed in the fetuses at the two highest doses. These changes included decreases in lymphocytes (CD3+ and CD20+), changes in lymphocyte subpopulation percentages, mild anemia, reduced platelet count, increased spleen weights, and reduced liver and thymus weights associated with increased splenic extramedullary hematopoiesis, thymic atrophy, and decreased hepatic hematopoiesis. In a study in which monkeys were exposed to natalizumab during pregnancy (IV infusion of 30 mg/kg) on alternate days from GD20 to GD70 or GD20 to term, abortions were increased approximately 2-fold compared to controls. In offspring born to mothers administered natalizumab on alternate days from GD20 until delivery, hematologic effects (decreased lymphocyte and platelet counts) were also observed. These effects were reversed upon clearance of natalizumab. There was no evidence of anemia in these offspring. Offspring exposed in utero and during lactation had a normal immune response to challenge with a T-cell dependent antigen. In a study in which pregnant guinea pigs were exposed to natalizumab (30 mg/kg IV) on alternate dates during GDs 30-64, a reduction in pup survival was observed.

8.2.

Lactation

Risk Summary Natalizumab has been detected in human milk. There are no data on the effects of this exposure on the breastfed infant or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TYSABRI and any potential adverse effects on the breastfed infant from TYSABRI or from the underlying maternal condition. 8.4. Pediatric Use Safety and effectiveness in pediatric patients with multiple sclerosis or Crohn’s disease below the age of 18 years have not been established. TYSABRI is not indicated for use in pediatric patients. 8.5. Geriatric Use Clinical studies of TYSABRI did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently than younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. 17. PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). General Counseling Information Counsel patients to understand the risks and benefits of TYSABRI before an initial prescription is written. The patient may be educated by either the enrolled prescriber or a healthcare provider under that prescriber’s direction. INSTRUCT PATIENTS USING TYSABRI TO: • Read the Medication Guide before starting TYSABRI and before each TYSABRI infusion. • Promptly report any new or continuously worsening symptoms that persist over several days to their prescriber [see Warnings and Precautions (5.1)]. • Inform all of their physicians that they are receiving TYSABRI. • Plan to see their prescriber three months after the first infusion, six months after the first infusion, every six months thereafter, and for at least six months after discontinuing TYSABRI. Progressive Multifocal Leukoencephalopathy Inform patients that Progressive Multifocal Leukoencephalopathy (PML) has occurred in patients who received TYSABRI. Instruct the patient of the importance of contacting their doctor if they develop any symptoms suggestive of PML. Instruct the patient that typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. Instruct the patient that the progression of deficits usually leads to death or severe disability over weeks or months. Instruct patients to continue to look for new signs and symptoms suggestive of PML for approximately 6 months following discontinuation of TYSABRI [see Warnings and Precautions (5.1)]. TYSABRI TOUCH® Prescribing Program Advise the patient that TYSABRI is only available through a restricted program called the TOUCH® Prescribing Program. Inform the patient of the following requirements: Patients must read the Medication Guide and sign the Patient Prescriber Enrollment Form. Advise patients that TYSABRI is available only from certified pharmacies and infusion centers participating in the program [see Warnings and Precautions (5.2)]. Herpes Infections Inform patients that TYSABRI increases the risk of developing encephalitis, and meningitis, which could be fatal, and acute retinal necrosis, which could lead to blindness, caused by the family of herpes viruses (e.g., herpes simplex and varicella zoster viruses). Instruct patients to immediately report any possible symptoms of encephalitis and meningitis (such as fever, headache, and confusion) or acute retinal necrosis (such as decreased visual acuity, eye redness, or eye pain) [see Warnings and Precautions (5.3)]. Hepatotoxicity Inform patients that TYSABRI may cause liver injury. Instruct patients treated with TYSABRI to report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice [see Warnings and Precautions (5.4)]. Hypersensitivity Reactions Instruct patients to report immediately if they experience symptoms consistent with a hypersensitivity reaction (e.g., urticaria with or without associated symptoms) during or following an infusion of TYSABRI [see Warnings and Precautions (5.5)]. Immunosuppression/Infections Inform patients that TYSABRI may lower the ability of their immune system to fight infections. Instruct the patient of the importance of contacting their doctor if they develop any symptoms of infection [see Warnings and Precautions (5.6)]. Full Prescribing Information is available at TYSABRIhcp.com. TYSABRI (natalizumab) Manufactured by: Biogen Inc. Cambridge, MA 02142 USA US License No. 1697 1-800-456-2255 © 2015-2018 Biogen Inc. All rights reserved. 09/2018 U.S. Patent Numbers: 5,840,299; 6,602,503

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Meet Your New President and Board of Directors continued from cover review of more than 100 clinical practice guidelines submitted by the AAN. He has held many leadership positions within the Academy, serving as the chair of the Practice Committee, chair of the AAN Board Planning Committee, member of the Quality Standards Subcommittee and the Therapeutics and Technology Subcommittee, as well as serving on numerous work groups and task forces, including the Health Reform Task Force, the Solo and Small Group Task Force, and previously served as AAN president elect. Stevens is a graduate of the Palatucci Advocacy Leadership Forum, has been a special advisor to the NINDS clinical research consortium, and is a past president of the Indiana Neurological Society. He also served on the executive committee for the Lutheran Hospital of Indiana and serves as chair of the board of directors for Physicians Health Plan of Indiana. He has been recognized annually as one the “Best Doctors in America,” and has been a recipient of the “Patients Choice Award” since 2008 as one of the outstanding physicians in the United States. Stevens has received multi-year recognition as the “Top Doc” in neurology by the Fort Wayne Journal Gazette. Immediate Past President— Ralph L. Sacco, MD, MS, FAHA, FAAN Ralph L. Sacco, MD, MS, FAHA, FAAN, is the chairman of neurology; Olemberg Family Chair in Neurological Disorders; Miller Professor of Neurology Public Health Sciences, Human Genetics, and Neurosurgery; executive director of the Evelyn McKnight Brain Institute; Senior Associate Dean for Clinical and Translational Science, University of Miami, Miller School of Medicine; and chief of the neurology service at Jackson Memorial Hospital. A graduate of Cornell University and a cum laude graduate of Boston University School of Medicine, he also holds a master's in epidemiology from Columbia University, School of Public Health. Sacco completed his neurology residency training and postdoctoral training in stroke and epidemiology at Columbia

Presbyterian in New York. He was previously professor of neurology, chief of Stroke and Critical Care Division, and associate chairman at Columbia University before taking his current position in 2007.

medical economics, medical practice management, and leadership, and has been the recipient of several APEX writing awards and the 2009 AAN Journalism Fellowship award.

Sacco is an international expert in stroke epidemiology and health disparities. He is the principal investigator of the Northern Manhattan Study, the Florida Puerto Rico Collaboration to Reduce Stroke Disparities, AHA/ASA Bugher Center of Excellence, as well as co-investigator of multiple other NIH grants. Sacco has published extensively with over 600 peer-reviewed articles (h-index 101) in the areas of stroke prevention, treatment, epidemiology, risk factors, vascular cognitive impairment, human genetics, and outcomes.

A graduate of Pennsylvania State University School of Medicine, Avitzur is a clinical instructor at Yale University School of Medicine in New Haven, CT, where she completed her neurology residency, and a clinical assistant professor at New York Medical College in Valhalla, NY. She is a practicing neurologist in Tarrytown, NY, and a medical consultant to the New York Rangers. Vice President—Ann H. Tilton, MD, FAAN Ann H. Tilton, MD, FAAN, is a professor of neurology and pediatrics and section chair of child neurology at Louisiana State Health Science Center in New Orleans, LA. She is director of the Rehabilitation Center at Children’s Hospital of New Orleans and director of the Comprehensive Spasticity Program. Special interests include neurorehabilitation, neuromuscular disorders, and clinical applications and research in novel uses of botulinum toxin and intrathecal baclofen in the care of children and young adults with abnormal tone.

He has been the recipient of numerous awards, including the AAN Wartenberg Lecture, AHA Feinberg Award of Excellence in Clinical Stroke, the WSO Global Stroke Leadership Award, AHA Gold Heart Award, the NINDS Javits Award in neuroscience, and numerous named lectures. Sacco is a fellow of both the Stroke and Epidemiology Councils of the American Heart Association, a Fellow of the ANA, and an elected member of the American Association of Physicians. He was the first neurologist to serve as the president of the American Heart Association from 2010 to 2011.

Tilton has been involved on the executive committee of the Professors of Child Neurology and active in the national Child Neurology Society as a councilor, secretary/treasurer, and served as president of the organization. She is currently the president of the Child Neurology Foundation. She is actively involved in the AAN Board of Directors, where she is serving her second term as the vice president of the AAN. She also chairs the Child Neurology Workgroup.

Officers President Elect— Orly Avitzur, MD, MBA, FAAN Orly Avitzur, MD, MBA, FAAN, previously was the chair of the AAN's Medical Economics and Management Committee. She is a medical writer and the editor-in-chief of Brain & Life®, the AAN’s patient magazine. Since 2001, she has been a writer for Neurology Today ®, reporting on trends in the practice of neurology, and was an associate editor for the publication.

Residency education is one of her priorities, and she served as a member and vice chair of the ACGME Neurology Residency Review Committee. She recently completed her role as the chair of the American Board of Psychiatry and Neurology.

Avitzur was the former medical director at Consumer Reports and has been a frequent contributor to the Washington Post. She writes and frequently speaks about consumer health and wellness,

Tilton's interest in children with disabilities extends to the American Academy of Pediatrics where she served on the national Council Continued on page 22

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Meet Your New President and Board of Directors continued from page 21 for Children with Developmental Disabilities. Tilton has been board certified by the American Board of Pediatrics, the American Board of Psychiatry and Neurology with special qualifications in child neurology, and the American Board of Psychiatry and Neurology in clinical neurophysiology. She has published on numerous topics and has spoken nationally and internationally on child neurology, rehabilitation, and spasticity management. Secretary—Carlayne E. Jackson, MD, FAAN Carlayne E. Jackson, MD, FAAN, is currently professor of neurology and otolaryngology at the University of Texas Health Science Center San Antonio (UTHSCSA). She also serves as chief of the neuromuscular section and vice chair of Faculty Development and Wellness. Jackson is a graduate of Texas A&M University, where she received a Bachelor of Science degree in Chemical Engineering. She obtained her medical degree at UTHSCSA, where she subsequently completed her neurology residency training and clinical neurophysiology fellowship. She has obtained board subspecialty certification in both clinical neurophysiology and neuromuscular medicine. She is a graduate of the Executive Leadership in Academic Medicine (ELAM) program sponsored by Drexel University College of Medicine. Jackson serves as medical director for the South Texas ALSA Center of Excellence and the MDA ALS Research Center. She is a member of the Western ALS Study Group, Northeast ALS Research Group, and the Muscle Study Group. She has participated in over 60 multi-center clinical trials in the areas of ALS, muscular dystrophy, and myasthenia gravis and has published over 200 abstracts, journal articles, and book chapters. Jackson has served the AAN as a member of the Science Committee, Meeting Management Committee, Leadership Development Committee, and the Board of Directors. She currently chairs the Meeting Management Committee and is in her second term as secretary for the Board of Directors. She

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has been a member of the Continuum® editorial board, co-chaired the ALS Measurement Development Panel, and co-authored the ALS Practice Parameters. She has actively participated on the Education Subcommittee and the Neuromuscular Topic Work Group. Jackson participated in the Palatucci Advocacy Leadership Forum in 2013 and has been a delegate to Neurology on the Hill. She has served as a mentor in the Emerging Leaders, the Diversity Leaders, the Transforming Leaders, and the Women Leading in Neurology programs. She was awarded the AAN Leading in Excellence Mentorship Award in 2017. Treasurer—Janis M. Miyasaki, MD, MEd, FRCPC, FAAN Janis M. Miyasaki, MD, MEd, FRCPC, FAAN, is a graduate of the University of Toronto Medical Faculty, neurology residency program, and a movement disorders fellowship. From 1994 to 1998, she was a community neurologist seeing general neurology patients and providing in-hospital care at a regional cancer and dialysis hospital. In 1999, she joined the faculty of medicine at the University of Toronto as full-time faculty, assuming the roles for various periods of director of education for neurology for four hospitals, ward chief, member of the Board of Trustees for the University Health Network, president of the Medical Staff Association, president of the Canadian Movement Disorders Group, deputy physician-in-chief at Toronto Western Hospital, and associate clinical director of the Movement Disorders Centre at Toronto Western Hospital from 2001 to 2013. Her practice consisted of movement disorders, clinical trials, and the development of an interdisciplinary Palliative Care Program for Parkinson's Disease and Related Disorders, the first of its kind in the world. Since 2014, Miyasaki has been a member of the division of neurology at the University of Alberta and active in local and provincial initiatives in palliative care for neurologic patients. Her AAN activities began in 2000 with writing a guideline on Parkinson's disease. Since that time, she has worked

on many AAN committees, including the Practice Committee, Therapeutics and Technology Subcommittee, Practice Improvement Subcommittee, Patient Safety Subcommittee, and co-chaired the Therapeutics and Technology Subcommittee (now the Guideline Development Subcommittee) and Education Committee. Between producing educational content, committees, working groups, and meetings, she estimates since 2000 spending one day per month to a half-day per week on AAN work. It has been rewarding and energizing work.

Directors Brenda Banwell, MD, FAAN Brenda Banwell, MD, FAAN, currently serves as the chief of child neurology and professor of neurology and pediatrics at The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania. Banwell’s clinical and research focus is in the area of pediatric multiple sclerosis, and she leads a 24-site North American prospective study of clinical outcomes, genetics, immunology, and neuroimaging features of MS in children. Banwell also serves as the chair of the International Pediatric Multiple Sclerosis Study Group. Banwell studied medicine at the University of Western Ontario, followed by residencies in pediatrics at the University of Western Ontario and Child Neurology at the University of Toronto. She then pursued a Neuromuscular Fellowship at the Mayo Clinic in Rochester, MN. In 1999 Banwell was appointed assistant professor of pediatrics and neurology at The Hospital for Sick Children at the University of Toronto, and rose to the rank of full professor prior to relocating to The Children's Hospital of Philadelphia in 2012. She remains as adjunct senior scientist in the Research Institute at The Hospital for Sick Children. Banwell has been a member of the AAN since 1996 and has since attended every Annual Meeting. She served on the

Science Committee from 2005 to 2011 and is an active member of the AAN Meeting Management Committee. Banwell was a selected attendee at the Leadership Development Program in 2007 and 2008 and has more recently served as a mentor in the AAN Emerging Leaders Program. She served on the Brain Health Fair Committee where she has been an active annual participant in Brain Health Fair activities. Sarah M. Benish, MD, FAAN Sarah M. Benish, MD, FAAN, is currently the physician co-chief for M Health/Fairview Neuroscience service line. She works for University of Minnesota Physicians and is also section head for general neurology at the University of Minnesota. She enjoys her clinic time as a general neurologist. Over her career she has developed an interest in treating headache patients but continues to enjoy caring for all MEM: 19 FAAN Ad—Half Page Horizontal> AN neurologic diseases. Placed in AANnews joining 8.25 x 5.25Prior +0.125to bleed, 4C the University of

Minnesota, she was a physician owner/ partner at Minneapolis Clinic of

Neurology (MCN), one of the largest physician-owned, single-specialty neurology clinics in the country. She spent seven years on its board of directors and was treasurer for one year. During her decade with this clinic, she learned a lot about the business of medicine and what it takes to survive in the days of modern medicine and payment reform. Benish began her involvement with the AAN as a member of the inaugural class of the Emerging Leaders Forum. At the end of the forum, she joined the Practice Committee, where she led a work group investigating whether the AAN should invest in a registry. When the Axon Registry ® was started, she joined the Registry Committee and chaired the Registry Analytics Subcommittee. In 2019, she is looking forward to starting her third term on the AAN Board of Directors, and serving as the chair of the Registry Subcommittee and member of the newly formed Quality Committee. She has found her involvement in the AAN to be the antidote to burnout. She views herself as a clinician first and tries hard to represent the views of all neurologists in her roles at the AAN.

Charlene Gamaldo, MD, FAAN Charlene Gamaldo, MD, FAAN, has been a faculty member of the Johns Hopkins School of Medicine neurology department since 2004, with joint appointments in the department of psychiatry, nursing, anesthesiology, and schools of public health. She is currently the medical director of the Johns Hopkins Center for Sleep and the vice chair for faculty development for the neurology department. Gamaldo's research interest is studying the impact of sleep on manifestation and progression of neurologic diseases. Her research activities have relied heavily on the interdisciplinary and inter-professional collaborative model for conducting sleep research using the efforts of a diverse group of collaborators and, as a result, have led to ongoing and evolving research projects that now include a growing list of collaborators at Johns Hopkins in neurology, psychiatry, urology, biomedical engineering, Schools of Nursing and Public Health, along with the National Institute on Aging. In Continued on page 24

Shine a light on your achievements Apply for a prestigious Fellow of the American Academy of Neurology (FAAN) designation.

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Meet Your New President and Board of Directors continued from page 23 addition, upon considering the projected shortage of sleep practitioners, she has developed programs to involve and expose undergraduates (sleep learning module), medical students (sleep learning module), graduate students, post-docs, and residents to the sleep medicine field in order to attract the best and the brightest early on in their career. Gamaldo has served as co-chair for the AAN Sleep Section presentations, served as the Johns Hopkins School of Medicine neurology clerkship co-director for six years, and is currently a member of the AAN's Leadership Development Committee, Medical Student Pipeline Work Group, and Joint Coordinating Council on Equity, Diversity, Inclusion, and Disparities. James N. Goldenberg, MD, CPI, FAPCR, FAAN James N. Goldenberg, MD, FAAN, is a boardcertified neurologist who practiced in Palm Beach County for 25 years. He currently serves as medical director for Atlantic Coast Health Network, a regional super clinically integrated network representing over 1,700 physicians and 170,000 lives in South Florida. In this role, he is responsible for strategy, value-based care initiatives, population health, and patient safety. His undergraduate training is in psychology from the University of Florida, and he received his medical degree from the University of South Florida. His neurology training and fellowship in neuromuscular disease were completed at the University of Miami. Goldenberg has served JFK Hospital in Atlantis Florida in multiple leadership roles including chair of the Board of Trustees, chair of the Credentials Committee, chair of the Bylaws Committee, and chief of the department of psychiatry and neurology. He was the founding medical director of JFK Hospital’s stroke program and has helped develop their Comprehensive Stroke Center. Goldenberg founded the JEM Research Institute, a clinical research organization that performs predominantly industry sponsored phase II–IV clinical trials to help develop new treatments in the area

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of neurology. Goldenberg has also served The Joint Commission as a diseasespecific surveyor in stroke―the first physician to hold that position nationally.

served on numerous AAN subcommittees and committees. He is most proud of being in the inaugural class of the Palatucci Advocacy Leadership Forum.

Goldenberg is an affiliated assistant professor of neurology at the Leonard M. Miller School of Medicine at the University of Miami. He has coordinated the neurology rotation for second-year residents at JFK Hospital’s University of Miami-sponsored internal medicine residency program. He has also coordinated the neurology medical student rotation for fourth-year medical students at the University of Miami’s Palm Beach Regional Campus.

Hosey is active in his community, having served as a past president of the American Heart Association/American Stroke Association (AHA/ASA) of Pennsylvania/ Delaware chapter. He has served on many boards, including the Three Rivers Affiliate of the AHA/ASA, Geisinger Health Plan, Pennsylvania Rural Stroke Institute, and was a long-serving trustee of Wyoming Seminary Preparatory School of Pennsylvania, where he was awarded the Joseph Donchess Lifetime Achievement Award for his service. He currently serves on the Board of King's College in WilkesBarre, PA, of which he is an alumnus. He is married to Linda M. Famiglio, MD, FAAP, a pediatric neurologist, and has two children.

Goldenberg is an advocate for patients and physicians at the local, regional, and national levels. He is a past president of the Palm Beach County Medical Society and currently serves on the Board of Trustees. He is responsible for the development of the Physician Leadership Academy of South Florida. He is serving the Florida Medical Association on the Board of Governors and the Council on Medical Economics and Practice Innovation. Goldenberg is an alternate delegate to the American Medical Association through June 2019. He is serving the AAN on the Board of Directors, and Advocacy Committee and chairs the Business Innovation Subcommittee. Through advocacy, education, and the promotion of physician leadership training, he would like to help physicians prepare for the changing health care landscape. Jonathan P. Hosey, MD, FAAN Jonathan P. Hosey, MD, FAAN, is currently the chair of Neurobehavioral Science Service Line for the St. Luke’s University Health Network in Bethlehem, PA, which is composed of 11 hospitals in two states. In 1990, he was involved with the development of neurology residency programs at the Madigan Army Medical Center in Tacoma, and as the founding director of the Geisinger Health System program in 2010. He is a professor of neurology at the Lewis Katz School of Medicine at Temple University and has

Elaine C. Jones, MD, FAAN Elaine C. Jones, MD, FAAN, received her MD from the Medical University of South Carolina in 1994 before completing her neurology residency at Brown University and Rhode Island Hospital in 1998. After her residency, she returned to Brown to complete her fellowship in neurophysiology in 1999. Jones is board certified with the American Board of Psychiatry and Neurology. She is a former president of the Rhode Island Neurological Society, former president of the Rhode Island Medical Society, and is currently a member of the AAN Board of Directors and chairs the Coding and Payment Policy Subcommittee. She previously chaired the AAN’s Gender Disparity Task Force. She is an honored Fellow of the AAN. Jones has worked in a variety of positions including chief of the division of neurology for Roger Williams Medical Center. She worked for 11 years in her own solo private practice, Southern New England Neurology, LLC. Named one of Rhode Island Monthly’s Top Doctors for five years straight, Jones currently works doing teleneurology for SOC Telemed, LLC.

She has also contributed several articles examining the politics of health care and the methods, guidelines, and future of clinical neurology practices. Shannon M. Kilgore, MD, FAAN* Shannon M. Kilgore, MD, FAAN, practices neurology within the Veterans Affairs Health Care System in Palo Alto, CA. She works as both the director of stroke services, and the Palo Alto representative of the National VA Parkinson’s Disease Consortium. Kilgore cares greatly about pharmaceutical pricing and medication safety, leading Palo Alto’s Medical Management Committee and co-leading the regional VA Pharmacy Benefits Committee. Additionally, she represents neurology on the Medical Advisory Panel to Pharmacy Benefits Management, which determines the formulary for the entire Department of Veterans Affairs. Raised in the Texas Hill Country, Kilgore obtained her Bachelor of Arts in psychology from the University of Texas at Austin, and her Doctor of Medicine from the University of Texas Health Science Center at Houston. She then completed her neurology residency and fellowships in both cerebrovascular disease and movement disorders at Stanford. In 2003, she brought this unique combination expertise to the VA, where she has taught medical students, neurology residents, and geriatrics fellows in both outpatient and inpatient settings, as a member of Stanford’s clinical faculty. Kilgore has maintained a long-held interest in combining both education and advocacy. She has joined the Neurology Review Committee for the Accreditation Council for Graduate Medical Education twice, first as a resident/fellow, and then again as a regular member, ultimately serving as chair, before rotating off in 2017. During her time on the committee, she participated in revision of all the programs requirements, development of the milestones, and recognition of child neurology on equal footing with adult neurology within the ACGME. She first became involved with the Academy when she joined the AAN’s delegation to the American Medical Association in 2004,

Thomas R. Vidic, MD, FAAN

bringing her knowledge of advocacy and AMA proceedings gained as an AMA resident and student delegate. Now chair of the delegation, she has sought to broaden the influence of neurology within the greater medical community.

Thomas R. Vidic, MD, FAAN, has dedicated his professional life to patient care, advocacy, teaching, and clinical research. He is a practicing general neurologist at the Elkhart Clinic in Indiana, the director of the regional MDA clinic, and co-director of the rehabilitation unit at Elkhart General Hospital. Vidic established Indiana Medical Research and is its medical director. He is past chair of the Elkhart Clinic, past chief of staff of Elkhart General Hospital, and chair of the bylaws committee.

Kilgore also serves the Academy on the Advocacy Committee, the Education Committee, the Editorial Board of Continuum: Lifelong Learning in Neurology®, and on the recent Drug Pricing Task Force. A member of the 2014–2015 Emerging Leaders Forum class, she now enjoys giving back as a mentor within the various AAN leadership programs. *New to the Board of Directors

Advocacy has been a passion for Vidic. He is a member of the Indiana Neurological Society and has served many roles, including president. He has worked with the Indiana State Medical Association on legislative advocacy and has served as speaker, president, and current chair of the PAC. He currently represents Indiana as an alternate delegate to the AMA.

Brett M. Kissela, MD, MS, FAAN Brett M. Kissela, MD, MS, FAAN, is professor and chair of the department of neurology and rehabilitation medicine at the University of Cincinnati College of Medicine. He has been a member of the University of Cincinnati Stroke team since 2000, and co-director of the Stroke Recovery Center at Drake since 2008. Since November 2017, Kissela has served as the senior associate dean for clinical research at the University of Cincinnati College of Medicine, as well as chief of research services at UC Health. He is fellowship-trained in vascular neurology and has extensive clinical trial experience in acute stroke treatment, prevention, and recovery trials. He is an internationally recognized expert on causes, outcomes, and recovery of stroke, with a special interest in the impact of diabetes on stroke and factors that influence stroke outcomes. He also participates in a variety of stroke recovery projects which look to improve recovery with the use of innovative techniques and devices.

Vidic is a clinical associate professor at the Indiana School of Medicine/South Bend and co-teaches the third-year clerkship in neurology. He is on the Medical Foundation Board, which has helped develop and finance the transition of a regional campus to a four-year program. Vidic was introduced to AAN leadership through the Palatucci Advocacy Leadership Forum and has been active in both advocacy and member issues. He has been a member of AAN committees such as State Affairs, Legislative Affairs, BrainPAC, and as an alternate delegate to the AMA. He has chaired the Membership Committee and currently chairs the Member Research Subcommittee. He was co-author of “Supply and Demand Analysis of the Current and Future US Neurology Work Force” and is a co-author of the Neurology ® article on neurologist burnout. Vidic believes in the importance of neurologists in the medical community and the need to support neurologists through the AAN. He has developed an interdisciplinary skillset to analyze medical/political issues and the interpersonal skills Continued on page 26

Kissela’s honors and awards include the Cincinnati Business Courier's Forty Under 40 Award, Michael S. Pessin Stroke Leadership Prize from the American Academy of Neurology, Alpha Omega Alpha membership, National Medical Honor Society, Phi Beta Kappa, and a UC Faculty Senate Award.

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Meet Your New President and Board of Directors continued from page 25 to implement effective strategies. He is excited about continuing to serve the AAN on its board.

Ex officio (voting) Nicholas E. Johnson, MD, MS-CI, FAAN, Chair, Advocacy Committee Nicholas E. Johnson, MD, MS-CI, FAAN, is an associate professor and vice chair of research in the department of neurology at Virginia Commonwealth University with a focus in inherited neuromuscular disorders. He received his undergraduate degree in molecular and cellular biology and psychology at the University of Arizona. He then obtained his medical degree at the University of Arizona. He completed his neurology residency and combined fellowship in neuromuscular medicine and experimental therapeutics at the University of Rochester. His laboratory is focused on identifying the pathogenesis of myotonic dystrophy and facioscapulohumeral muscular dystrophy and identifying appropriate clinical endpoints for these conditions. Johnson conducts therapeutic trials in many other inherited nerve and muscle disorders. Johnson serves as chair of the AAN Advocacy Committee. He is also a member of the Academy’s delegation to the American Medical Association. In these roles, Johnson advocates for improving the practice of neurology for neurologists and their patients. Brad C. Klein, MD, MBA, FAAN, Chair, Medical Economics and Practice Committee Brad C. Klein, MD, MBA, FAAN, is a full-time practicing neurologist with additional certifications in headache medicine and electromyography in his private practice at Abington Neurological Associates, Ltd., in Willow Grove, PA. He has been a participant and/or principal investigator in more than 20 clinical trials and further serves as the practice’s chief operating

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officer. He is also the director of the Abington Headache Center, AbingtonJefferson Health and a clinical associate professor of neurology at Thomas Jefferson University (TJU). He received his medical degree from Sidney Kimmel Medical College, previously known as Jefferson Medical College, at TJU in Philadelphia, concurrently with his Master of Business Administration degree at Widener University. He completed his neurology residency and headache fellowship at Thomas Jefferson University Hospital. During Klein’s residency, he graduated from the Palatucci Advocacy Leadership Forum and founded the Pennsylvania Neurological Society, serving as its first president. Through his tenure, he provided multiple testimonies to the state legislature and was an advisor on many legislative bills. Thereafter, he served in a number of other state and national leadership roles, including treasurer of the Alliance for Headache Disorders Advocacy, chair of the Practice Committee of the American Headache Society, and as a member of the Pennsylvania Health Care Cost Containment Council. Within the AAN, Klein has served as a member of the Practice Management and Technology Subcommittee, Health Services Research Subcommittee, Benchmark Survey Work Group, Solo and Small Practice Work Group, Meeting Management Committee, multiple education topic work groups, and vice chair of the Medical Economics and Management Committee. He has been the recipient of numerous local, regional, and national awards, including “Patient’s Choice Award,” and Castle Connolly’s “Top Doctor.” Gregory D. Cascino, MD, FAAN, Chair, Member Engagement Committee Gregory D. Cascino, MD, FAAN, is the Whitney MacMillan, Jr. Professor of Neuroscience at the Mayo Clinic College of Medicine and the Enterprise Director of Epilepsy at Mayo

Clinic, Rochester, MN. He attended Northwestern University and received his degree in medicine from Rush Medical College in Chicago, IL. Cascino completed an internal medicine residency at Duke University in Durham, NC, and a neurology residency and clinical neurophysiology fellowship at the Massachusetts General Hospital in Boston, MA. In 1988, Cascino joined the staff of the Mayo Clinic. His interests have included the identification of surgically remediable epileptic syndromes and advanced neuroimaging in patients with drug-resistant focal epilepsy. He has published over 200 peer-reviewed articles and presented approximately 400 invited lectures. Cascino has participated in the training of over 75 epilepsy-EEG fellows. He is currently an associate editor of Neurology ®, chair of the AAN Member Engagement Committee, and an ex officio member of the AAN Board of Directors. He previously served on the American Epilepsy Society (AES) Board of Directors, the Council of the American Clinical Neurophysiology Society, and the Professional Advisory Board Executive Committee of the Epilepsy Foundation of America, and is past-chair of the AAN's Epilepsy Section. Cascino was the recipient of the J. Kiffin Penry Excellence in Epilepsy Care Award presented by the AES in 2013. He is married to Teresa Griffin Cascino and has two sons (Dr. Matthew and Dr. Gregory Joseph), one daughter (Mary), two daughters-in-law (Dr. Missy Haehn and Sarah), and two terrific grandkids (Ira and Charles). Robert A. Gross, MD, PhD, FANA, FAAN, Editor-in-Chief of Neurology ® Robert A. Gross, MD, PhD, FANA, FAAN, graduated from Harvard College in 1975 with an AB in biology, summa cum laude, and from Washington University, MD and PhD (pharmacology) in 1981. After his internship at the Jewish Hospital in St. Louis, he completed his neurology residency at the Massachusetts General Hospital, where he served as chief resident. Faculty positions followed at the University of Michigan and the University

of Minnesota, followed by the University of Rochester Medical Center (1994). Research interests have centered on various aspects of cellular neuropharmacology and, collaboratively, on mechanisms of excitotoxicity and chemobrain. He participated in clinical trials of novel anticonvulsants and served on a multi-center task force to design trials to compare brand to generic AEDs. He was the recipient of the S. Weir Mitchell Award of the American Academy of Neurology in 1988. He sees patients in the Strong Epilepsy Center and is the associate chair for academic affairs in neurology. Gross' educational efforts are diverse. He founded and directs the Academic Research Track; funded by URMC's Clinical and Translational Science Award, this supports medical students for a year-out mentored experience in medical research. He helps direct and lectures (neuropharmacology) in the medical student course “Mind, Brain and Behavior.” He directs a novel basic science course for fourth-year medical students, “Process of Discovery,” in which students design cutting-edge research programs to address gaps in clinical care. He also teaches in AAN Annual Meeting courses, including the Career Development symposium. He served as an associate editor of Neurology® for 10 years, two of which were as deputy editor, and is the current editor-in-chief of the Neurology journals. Gross is a fellow of the AAN and American Neurological Association, and a member of the American Epilepsy Society. He has appeared on the PBS program “Second Opinion” and on local radio shows on the topic of epilepsy. Catherine M. Rydell, CAE, Chief Executive Officer (non-voting) Catherine M. Rydell, CAE, has been the American Academy of Neurology's executive director and chief executive officer since 1999. Along with her executive team, she oversees 198 staff. Under Rydell's leadership, AAN membership has grown from 16,000 to over 36,000 members.

2019–2021 AAN Institute Board of Directors

Since joining the AAN, Rydell has focused on strengthening advocacy and coalitionbuilding efforts, increasing staff development, improving communication with members, and implementing its strategic plan. Under her leadership, the Academy increased educational offerings and established a companion organization to help support new member services and advocacy. Rydell also has been instrumental in expanding the influence and reach of the AAN by creating entities and initiatives to promote and advance the specialty of neurology. Rydell is a Certified Association Executive (CAE), the highest professional credential in the association industry. Less than five percent of all association professionals have earned a CAE designation.

The AAN Institute Board of Directors includes the following additional members.

Officer Charles C. Flippen II, MD, FAAN, AAN Institute Secretary-Treasurer Charles C. Flippen II, MD, FAAN, is a faculty member of the Headache Research and Treatment Program at the Ronald Reagan UCLA Medical Center, attending neurologist at the Olive View-UCLA Medical Center, and professor of neurology and director of the residency program in clinical neurology at the Geffen School of Medicine at UCLA.

Rydell serves on the Board of Directors of the American Brain Foundation and is a member of the American Board of Medical Specialties (ABMS) Continuing Board Certification: Vision for the Future Initiative Commission. She is a member and past chair of the Specialty Society CEO Coalition, and an ex officio member of the Neurology Residency Review Committee and the United Council of Neurologic Subspecialties. She also serves on the Board of the University of North Dakota Foundation and Alumni Association.

Flippen is a diplomate of adult neurology of the American Board of Psychiatry Neurology (ABPN) and of headache medicine of the United Council of Neurologic Subspecialties. He is a member of the American Headache Society, International Headache Society, Fellow of the American Neurological Association, and Fellow of the American Academy of Neurology, where he is active in headache education, having directed several courses, and was chair of the Headache Topic Work Group of the Education Committee. He also served on the Quality and Safety Subcommittee, the AAN Institute Minority Scholars Subcommittee, and the AAN Nomination Committee. He currently is a member of the Diversity Leadership Subcommittee.

Prior to joining the AAN, Rydell served as executive director of the North Dakota Medical Association. From 1984 through 1996, Rydell served as a state representative in the North Dakota State Legislature, where she chaired the House Human Services Committee and the House Education Committee. She was also the director of Women's and Children's Services as well as Surgical Services for St. Alexius Medical Center, a tertiary care center in Bismarck, ND. Rydell has served on numerous national, regional, and state boards and commissions including Robert Wood Johnson North Dakota Single Payer Study Commission, Blue Cross Blue Shield of North Dakota, American Medical Association CEO Advisory Committee, Council of Medical Specialty Societies, the American Brain Coalition, the Theodore Roosevelt Medora Foundation, and the American Society of Association Executives.

Flippen represents the ABPN on the Neurology Residency Review Committee of the Accreditation Council of Graduate Medical Education, is conducting education research funded by the ABPN Faculty Fellowship award, and serves on several intramural committees charged with curricular innovation in the Geffen School of Medicine. Flippen is also active within the general Los Angeles community through his service as a former trustee of the Carlthorp School, board member of 100 Black Men of Los Angeles, assistant scoutmaster and Merit Badge counselor for Troop 223 Continued on page 28

›

AANnews • June 2019 27

Conferences & Community

Meet Your New President and Board of Directors continued from page 27 (Pacific Palisades) of the Boy Scouts of America, West Region Health and Wellness committee member for Alpha Phi Alpha Fraternity Inc., and member of Sigma Pi Phi Fraternity, Inc.

Ex Officio Directors (voting) Lyell K. Jones, Jr., MD, FAAN, Chair, Quality Committee Lyell K. Jones, Jr., MD, FAAN, is a consultant and associate professor of neurology at the Mayo Clinic in Rochester, MN. Jones received his undergraduate and medical degrees from Wake Forest University before completing his neurology residency and neurophysiology fellowship at the Mayo Clinic, where he has been a member of the consulting staff since 2009. Jones’s clinical and research focus is in neuromuscular medicine, particularly neurodegenerative, infectious, and autoimmune neuromuscular disorders. Jones has additional interests in health care policy and economics, specifically value-based care systems. He is a former medical director for the Mayo Clinic Office of Patient Experience and chair of Payment Model Operations at Mayo. He has served on several national society committees including the AAN Medical Economics and Management Committee, the AAN Payment Alternatives Team, the AANEM Quality Committee, and as chair of the AAN Registry Committee, all which are devoted to improving quality of care for patients and providing neurologists with the tools they need to thrive in an era of evolving value-based care models. Prior to joining the staff at the Mayo Clinic, Jones served on active duty in the US Air Force at Wilford Hall Medical Center in San Antonio, TX. Since 2013, Jones has been the program director of the Mayo Clinic–Rochester Adult Neurology Residency Program. Alongside his interest in resident education, Jones has developed with his colleagues a competencybased neurology assessment system and co-edited the two-volume Mayo

AANnews • June 2019

Clinic Neurology Board Review. He has been recognized with the AAN Program Director Award, the ACGME Parker J. Palmer Courage to Teach Award, and has been inducted into the Mayo Clinic Teacher of the Year Hall of Fame. Natalia S. Rost, MD, MPH, FAHA, FAAN, Chair, Science Committee Natalia S. Rost, MD, MPH, FAHA, FAAN, is chief of the stroke division in the department of neurology at Massachusetts General Hospital, associate director of the MGH Comprehensive Stroke Center, and associate professor of neurology at Harvard Medical School. A cum laude graduate of Boston University School of Medicine, she also holds a master's degree from Harvard School of Public Health. Rost trained in neurology and vascular neurology at Massachusetts General Hospital and Brigham and Women's Hospital (Partners) residency and fellowship programs. Rost is a clinician-scientist and international expert on neuroimaging markers of cerebrovascular disease, stroke genetics, and outcome prediction in patients with acute stroke. Her line of research on the role of white matter disease burden in ischemic stroke has been continuously funded since 2007, and she is currently the PI of two NIH R01 awards, and co-investigator of numerous multi-disciplinary, multicenter collaborations involving the NINDS StrokeNET clinical trials network and the International Stroke Genetics Consortium, where she serves as chair of the Neuroimaging Working Group. Rost is a recipient of the AAN’s Michael S. Pessin Stroke Leadership Award. Rost is an author of numerous peerreviewed publications, book chapters, a co-author of the MGH Handbook of Neurology, and medical editor of the HMS Special Health Report on stroke. She is an accomplished mentor, clinical educator, and recipient of the 2017 MGH Neurology Department’s Ray Adams Clinical Mentor Award. She serves as assistant editor of the journal STROKE, and she is past

president of the Boston Board of the American Heart Association (2014–2016). Rost is a Fellow of the American Academy of Neurology, the Stroke Council of the American Heart Association, and the European Stroke Organization. Among her professional accomplishments, Rost is particularly proud of her career-long involvement with the AAN, where she currently serves as chair of the Science Committee. A. Gordon Smith, MD, FAAN, Chair, Education Committee A. Gordon Smith, MD, FAAN, is professor and chair of neurology and Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research (Neurology) at VCU Health at the Virginia Commonwealth University. Prior to that, he was professor of neurology and vice chair for research at the University of Utah, where he also served as chief of the division of neuromuscular medicine and director of the Jack H. Petajan EMG Laboratory. Smith is a graduate of the University of Virginia and the Mayo Medical School. He completed his neurology residency and a neuromuscular fellowship at the University of Michigan. Smith's research team focuses on peripheral neuropathy in diabetes and obesity. He has a particular interest in biomarker development and novel clinical trial design in peripheral neuropathy and longstanding and ongoing NIH and major foundation funding. He is principal investigator of the Utah Regional site in the NINDS-funded Network for Excellence in Neuroscience Clinical Trials. He has led or participated in numerous clinical trials in neuromuscular disorders. He serves as chair of the Education Committee and is a member of the American Brain Foundation Board of Trustees. Smith chaired the Distance Learning Subcommittee and was the Education Editor of AAN.com. He also serves as editor for NeuroLearnSM. He is active in the Peripheral Nerve Society, where he is a former member of the board of directors. 

the

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AANnews • June 2019 29

FOR THE TREATMENT OF RELAPSING FORMS OF MS

START STRONG. STAY STRONG.

In the 2-year DEFINE and CONFIRM pivotal trials, Tecfidera® (dimethyl fumarate) demonstrated a 53% and 44% relative reduction in annualized relapse rate (ARR) vs placebo, respectively (0.172 vs 0.364; P<0.0001), (0.224 vs 0.401; P<0.0001)2

INDICATION Tecfidera (dimethyl fumarate) is indicated for the treatment of patients with relapsing forms of multiple sclerosis. ®

IMPORTANT SAFETY INFORMATION TECFIDERA is contraindicated in patients with known hypersensitivity to dimethyl fumarate or any of the excipients of TECFIDERA. TECFIDERA can cause anaphylaxis and angioedema after the first dose or at any time during treatment. Patients experiencing signs and symptoms of anaphylaxis and angioedema (which have included difficulty breathing, urticaria, and swelling of the throat and tongue) should discontinue TECFIDERA and seek immediate medical care. Progressive multifocal leukoencephalopathy (PML) has occurred in patients with MS treated with TECFIDERA. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. A fatal case of PML occurred in a patient who received TECFIDERA in a clinical trial. PML has also occurred in the postmarketing setting in the presence of lymphopenia (<0.8x109/L) persisting for more than 6 months. While the role of lymphopenia in these cases is uncertain, the majority of cases occurred in patients with lymphocyte counts <0.5x109/L. The symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to

confusion and personality changes. At the first sign or symptom suggestive of PML, withhold TECFIDERA and perform an appropriate diagnostic evaluation. MRI findings may be apparent before clinical signs or symptoms. TECFIDERA may decrease lymphocyte counts; in clinical trials there was a mean decrease of ~30% in lymphocyte counts during the first year which then remained stable. Four weeks after stopping TECFIDERA, mean lymphocyte counts increased but not to baseline. Six percent of TECFIDERA patients and <1% of placebo patients had lymphocyte counts <0.5x109/L. TECFIDERA has not been studied in patients with pre-existing low lymphocyte counts. There was no increased incidence of serious infections observed in patients with lymphocyte counts <0.8x109/L or ≤0.5x109/L in controlled trials, although one patient in an extension study developed PML in the setting of prolonged lymphopenia (lymphocyte counts predominantly <0.5x109/L for 3.5 years). In controlled and uncontrolled clinical trials, 2% of patients experienced lymphocyte counts <0.5x109/L for at least six months. In these patients, the majority of lymphocyte counts remained <0.5x109/L with continued therapy. A complete blood count including lymphocyte count should be obtained before initiating treatment, 6 months after starting, every 6 to 12 months thereafter and as clinically indicated. Consider treatment interruption if lymphocyte counts <0.5x109/L persist for more than six months and follow lymphocyte counts until lymphopenia is resolved. Consider withholding treatment in patients with serious infections

THE #1 PRESCRIBED oral RMS therapy in the US since September 2013 Based on number of prescriptions from IMS NPA™ Weekly Data (September 27, 2013–December 14, 2018).

>340,000

people have been treated with TECFIDERA worldwide1

This includes clinical trial use and patients prescribed TECFIDERA

>625,000

global patient-years of treatment1

This includes clinical trial use and patients prescribed TECFIDERA

Over 10 Years until resolved. Decisions about whether or not to restart TECFIDERA should be based on clinical circumstances. Clinically significant cases of liver injury have been reported in patients treated with TECFIDERA in the postmarketing setting. The onset has ranged from a few days to several months after initiation of treatment. Signs and symptoms of liver injury, including elevation of serum aminotransferases to greater than 5-fold the upper limit of normal and elevation of total bilirubin to greater than 2-fold the upper limit of normal have been observed. These abnormalities resolved upon treatment discontinuation. Some cases required hospitalization. None of the reported cases resulted in liver failure, liver transplant, or death. However, the combination of new serum aminotransferase elevations with increased levels of bilirubin caused by drug-induced hepatocellular injury is an important predictor of serious liver injury that may lead to acute liver failure, liver transplant, or death in some patients. Elevations of hepatic transaminases (most no greater than 3 times the upper limit of normal) were observed during controlled trials. Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels before initiating TECFIDERA and during treatment, as clinically indicated. Discontinue TECFIDERA if clinically significant liver injury induced by TECFIDERA is suspected. TECFIDERA may cause flushing (e.g. warmth, redness, itching, and/or burning sensation). 40% of patients taking TECFIDERA reported flushing, which was mostly mild to moderate in severity. Three percent of patients discontinued TECFIDERA for flushing and <1% had serious flushing events that led to hospitalization. Taking TECFIDERA with food may reduce flushing. Alternatively, administration of non-enteric coated aspirin prior to dosing may reduce the incidence or severity of flushing.

of combined clinical trial and real-world experience1,2

TECFIDERA may cause gastrointestinal (GI) events (e.g., nausea, vomiting, diarrhea, abdominal pain, and dyspepsia). Four percent of TECFIDERA patients and <1% of placebo patients discontinued due to GI events. The incidence of serious GI events was 1%. The most common adverse reactions associated with TECFIDERA versus placebo are flushing (40% vs 6%) and GI events: abdominal pain (18% vs 10%), diarrhea (14% vs 11%), nausea (12% vs 9%). A transient increase in mean eosinophil counts was seen during the first two months. TECFIDERA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Encourage patients who become pregnant while taking TECFIDERA to enroll in the TECFIDERA pregnancy registry by calling 1-866-810-1462 or visiting www.TECFIDERApregnancyregistry.com.

Please see following pages for Brief Summary of Full Prescribing Information. Study Designs2 DEFINE: A 2-year, randomized, double-blind, placebocontrolled study in 1234 patients with RRMS. Secondary endpoint: ARR. CONFIRM: A 2-year, multicenter, randomized, double-blind, placebo-controlled study in 1417 patients with RRMS. Primary endpoint: ARR. RMS=relapsing multiple sclerosis; DEFINE=Determination of Efficacy and Safety of Oral Fumarate in Relapsing-Remitting Multiple Sclerosis; CONFIRM=Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis; RRMS=relapsing-remitting multiple sclerosis. References: 1. Data on file, Biogen. 2. TECFIDERA Prescribing Information, Biogen, Cambridge, MA.

To get started, simply fill out a Start Form at

www.tecfiderahcp.com

Tecfidera® (dimethyl fumarate) delayed-release capsules, for oral use Brief Summary of Full Prescribing Information 1 INDICATIONS AND USAGE TECFIDERA is indicated for the treatment of patients with relapsing forms of multiple sclerosis. 2 DOSAGE AND ADMINISTRATION 2.1 Dosing Information The starting dose for TECFIDERA is 120 mg twice a day orally. After 7 days, the dose should be increased to the maintenance dose of 240 mg twice a day orally. Temporary dose reductions to 120 mg twice a day may be considered for individuals who do not tolerate the maintenance dose. Within 4 weeks, the recommended dose of 240 mg twice a day should be resumed. Discontinuation of TECFIDERA should be considered for patients unable to tolerate return to the maintenance dose. The incidence of flushing may be reduced by administration of TECFIDERA with food. Alternatively, administration of non-enteric coated aspirin (up to a dose of 325 mg) 30 minutes prior to TECFIDERA dosing may reduce the incidence or severity of flushing [see Clinical Pharmacology (12.3)]. TECFIDERA should be swallowed whole and intact. TECFIDERA should not be crushed or chewed and the capsule contents should not be sprinkled on food. TECFIDERA can be taken with or without food. 2.2 Blood Tests Prior to Initiation of Therapy Obtain a complete blood cell count (CBC) including lymphocyte count before initiation of therapy [see Warnings and Precautions (5.3)]. Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels prior to treatment with TECFIDERA [see Warnings and Precautions (5.4)]. 3 DOSAGE FORMS AND STRENGTHS TECFIDERA is available as hard gelatin delayed-release capsules containing 120 mg or 240 mg of dimethyl fumarate. The 120 mg capsules have a green cap and white body, printed with “BG-12 120 mg” in black ink on the body. The 240 mg capsules have a green cap and a green body, printed with “BG-12 240 mg” in black ink on the body. 4 CONTRAINDICATIONS TECFIDERA is contraindicated in patients with known hypersensitivity to dimethyl fumarate or to any of the excipients of TECFIDERA. Reactions have included anaphylaxis and angioedema [see Warnings and Precautions (5.1)]. 5 WARNINGS AND PRECAUTIONS 5.1 Anaphylaxis and Angioedema TECFIDERA can cause anaphylaxis and angioedema after the first dose or at any time during treatment. Signs and symptoms have included difficulty breathing, urticaria, and swelling of the throat and tongue. Patients should be instructed to discontinue TECFIDERA and seek immediate medical care should they experience signs and symptoms of anaphylaxis or angioedema. 5.2 Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy (PML) has occurred in patients with MS treated with TECFIDERA. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. A fatal case of PML occurred in a patient who received TECFIDERA for 4 years while enrolled in a clinical trial. During the clinical trial, the patient experienced prolonged lymphopenia (lymphocyte counts predominantly <0.5x109/L for 3.5 years) while taking TECFIDERA [see Warnings and Precautions (5.3)]. The patient had no other identified systemic medical conditions resulting in compromised immune system function and had not previously been treated with natalizumab, which has a known association with PML. The patient was also not taking any immunosuppressive or immunomodulatory medications concomitantly. PML has also occurred in the postmarketing setting in the presence of lymphopenia (<0.8x109/L) persisting for more than 6 months. While the role of lymphopenia in these cases is uncertain, the majority of cases occurred in patients with lymphocyte counts <0.5x109/L. At the first sign or symptom suggestive of PML, withhold TECFIDERA and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. MRI findings may be apparent before clinical signs or symptoms. Cases of PML, diagnosed based on MRI findings and the detection of JCV DNA in the cerebrospinal fluid in the absence of clinical signs or symptoms specific to PML, have been reported in patients treated with

other MS medications associated with PML. Many of these patients subsequently became symptomatic with PML. Therefore, monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. Lower PML-related mortality and morbidity have been reported following discontinuation of another MS medication associated with PML in patients with PML who were initially asymptomatic compared to patients with PML who had characteristic clinical signs and symptoms at diagnosis. It is not known whether these differences are due to early detection and discontinuation of MS treatment or due to differences in disease in these patients. 5.3 Lymphopenia TECFIDERA may decrease lymphocyte counts. In the MS placebo controlled trials, mean lymphocyte counts decreased by approximately 30% during the first year of treatment with TECFIDERA and then remained stable. Four weeks after stopping TECFIDERA, mean lymphocyte counts increased but did not return to baseline. Six percent (6%) of TECFIDERA patients and <1% of placebo patients experienced lymphocyte counts <0.5x109/L (lower limit of normal 0.91x109/L). The incidence of infections (60% vs 58%) and serious infections (2% vs 2%) was similar in patients treated with TECFIDERA or placebo, respectively. There was no increased incidence of serious infections observed in patients with lymphocyte counts <0.8x109/L or ≤0.5x109/L in controlled trials, although one patient in an extension study developed PML in the setting of prolonged lymphopenia (lymphocyte counts predominantly <0.5x109/L for 3.5 years) [see Warnings and Precautions (5.2)]. In controlled and uncontrolled clinical trials, 2% of patients experienced lymphocyte counts <0.5x109/L for at least six months, and in this group the majority of lymphocyte counts remained <0.5x109/L with continued therapy. TECFIDERA has not been studied in patients with pre-existing low lymphocyte counts. Obtain a CBC, including lymphocyte count, before initiating treatment with TECFIDERA, 6 months after starting treatment, and then every 6 to 12 months thereafter, and as clinically indicated. Consider interruption of TECFIDERA in patients with lymphocyte counts less than 0.5x109/L persisting for more than six months. Given the potential for delayed recovery of lymphocyte counts, continue to obtain lymphocyte counts until their recovery if TECFIDERA is discontinued or interrupted due to lymphopenia. Consider withholding treatment from patients with serious infections until resolution. Decisions about whether or not to restart TECFIDERA should be individualized based on clinical circumstances. 5.4 Liver Injury Clinically significant cases of liver injury have been reported in patients treated with TECFIDERA in the postmarketing setting. The onset has ranged from a few days to several months after initiation of treatment with TECFIDERA. Signs and symptoms of liver injury, including elevation of serum aminotransferases to greater than 5-fold the upper limit of normal and elevation of total bilirubin to greater than 2-fold the upper limit of normal have been observed. These abnormalities resolved upon treatment discontinuation. Some cases required hospitalization. None of the reported cases resulted in liver failure, liver transplant, or death. However, the combination of new serum aminotransferase elevations with increased levels of bilirubin caused by drug-induced hepatocellular injury is an important predictor of serious liver injury that may lead to acute liver failure, liver transplant, or death in some patients. Elevations of hepatic transaminases (most no greater than 3 times the upper limit of normal) were observed during controlled trials [see Adverse Reactions (6.1)]. Obtain serum aminotransferase, alkaline phosphatase (ALP), and total bilirubin levels prior to treatment with TECFIDERA and during treatment, as clinically indicated. Discontinue TECFIDERA if clinically significant liver injury induced by TECFIDERA is suspected. 5.5 Flushing TECFIDERA may cause flushing (e.g., warmth, redness, itching, and/or burning sensation). In clinical trials, 40% of TECFIDERA treated patients experienced flushing. Flushing symptoms generally began soon after initiating TECFIDERA and usually improved or resolved over time. In the majority of patients who experienced flushing, it was mild or moderate in severity. Three percent (3%) of patients discontinued TECFIDERA for flushing and <1% had serious flushing symptoms that were not lifethreatening but led to hospitalization. Administration of TECFIDERA with food may reduce the incidence of flushing. Alternatively, administration of non-enteric coated aspirin (up to a dose of 325 mg) 30 minutes prior to TECFIDERA dosing may reduce the incidence or severity of flushing [see Dosing and Administration (2.1) and Clinical Pharmacology (12.3)]. 6 ADVERSE REACTIONS The following important adverse reactions are described elsewhere in labeling: Anaphylaxis and Angioedema (5.1), Progressive multifocal leukoencephalopathy (5.2), Lymphopenia (5.3), Liver Injury (5.4), Flushing (5.5) [see Warnings and Precautions].

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The most common adverse reactions (incidence ≥10% and ≥2% more than placebo) for TECFIDERA were flushing, abdominal pain, diarrhea, and nausea. Adverse Reactions in Placebo-Controlled Trials In the two well-controlled studies demonstrating effectiveness, 1529 patients received TECFIDERA with an overall exposure of 2244 person-years [see Clinical Studies (14)]. The adverse reactions presented in the table below are based on safety information from 769 patients treated with TECFIDERA 240 mg twice a day and 771 placebo-treated patients. Table 1: Adverse Reactions in Study 1 and 2 reported for TECFIDERA 240 mg BID at ≥2% higher incidence than placebo

Flushing Abdominal pain Diarrhea Nausea Vomiting Pruritus Rash Albumin urine present Erythema Dyspepsia Aspartate aminotransferase increased Lymphopenia

TECFIDERA N=769 %

Placebo N=771 %

40 18 14 12 9 8 8 6 5 5 4 2

6 10 11 9 5 4 3 4 1 3 2 <1

Gastrointestinal TECFIDERA caused GI events (e.g., nausea, vomiting, diarrhea, abdominal pain, and dyspepsia). The incidence of GI events was higher early in the course of treatment (primarily in month 1) and usually decreased over time in patients treated with TECFIDERA compared with placebo. Four percent (4%) of patients treated with TECFIDERA and less than 1% of placebo patients discontinued due to gastrointestinal events. The incidence of serious GI events was 1% in patients treated with TECFIDERA. Hepatic Transaminases An increased incidence of elevations of hepatic transaminases in patients treated with TECFIDERA was seen primarily during the first six months of treatment, and most patients with elevations had levels <3 times the upper limit of normal (ULN) during controlled trials. Elevations of alanine aminotransferase and aspartate aminotransferase to ≥3 times the ULN occurred in a small number of patients treated with both TECFIDERA and placebo and were balanced between groups. There were no elevations in transaminases ≥3 times the ULN with concomitant elevations in total bilirubin >2 times the ULN. Discontinuations due to elevated hepatic transaminases were <1% and were similar in patients treated with TECFIDERA or placebo. Eosinophilia A transient increase in mean eosinophil counts was seen during the first 2 months of therapy. Adverse Reactions in Placebo-Controlled and Uncontrolled Studies In placebo-controlled and uncontrolled clinical studies, a total of 2513 patients have received TECFIDERA and been followed for periods up to 4 years with an overall exposure of 4603 person-years. Approximately 1162 patients have received more than 2 years of treatment with TECFIDERA. The adverse reaction profile of TECFIDERA in the uncontrolled clinical studies was consistent with the experience in the placebo-controlled clinical trials. 6.2 Post Marketing Experience The following adverse reaction has been identified during post approval use of TECFIDERA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Liver function abnormalities (elevations in transaminases ≥3 times ULN with concomitant elevations in total bilirubin >2 times ULN) have been reported following TECFIDERA administration in post marketing experience [See Warnings and Precautions (5.4)].

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to TECFIDERA during pregnancy. Encourage patients to enroll by calling 1-866-810-1462 or visiting www.tecfiderapregnancyregistry.com. Risk Summary There are no adequate data on the developmental risk associated with the use of TECFIDERA in pregnant women. In animals, adverse effects on offspring survival, growth, sexual maturation, and neurobehavioral function were observed when dimethyl fumarate (DMF) was administered during pregnancy and lactation at clinically relevant doses. [see data]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data In rats administered DMF orally (25, 100, 250 mg/kg/day) throughout organogenesis, embryofetal toxicity (reduced fetal body weight and delayed ossification) were observed at the highest dose tested. This dose also produced evidence of maternal toxicity (reduced body weight). Plasma exposure (AUC) for monomethyl fumarate (MMF), the major circulating metabolite, at the no-effect dose is approximately three times that in humans at the recommended human dose (RHD) of 480 mg/day. In rabbits administered DMF orally (25, 75, and 150 mg/kg/day) throughout organogenesis, embryolethality and decreased maternal body weight were observed at the highest dose tested. The plasma AUC for MMF at the no-effect dose is approximately 5 times that in humans at the RHD. Oral administration of DMF (25, 100, and 250 mg/kg/day) to rats throughout organogenesis and lactation resulted in increased lethality, persistent reductions in body weight, delayed sexual maturation (male and female pups), and reduced testicular weight at the highest dose tested. Neurobehavioral impairment was observed at all doses. A no-effect dose for developmental toxicity was not identified. The lowest dose tested was associated with plasma AUC for MMF lower than that in humans at the RHD. 8.2 Lactation Risk Summary There are no data on the presence of DMF or MMF in human milk. The effects on the breastfed infant and on milk production are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TECFIDERA and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Clinical studies of TECFIDERA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. 10 OVERDOSE Cases of overdose with TECFIDERA have been reported. The symptoms described in these cases were consistent with the known adverse event profile of TECFIDERA. There are no known therapeutic interventions to enhance elimination of TECFIDERA nor is there a known antidote. In the event of overdose, initiate symptomatic supportive treatment as clinically indicated. 17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information) Dosage Inform patients that they will be provided two strengths of TECFIDERA when starting treatment: 120 mg capsules for the 7 day starter dose and 240 mg capsules for the maintenance dose, both to be taken twice daily. Inform patients to swallow TECFIDERA capsules whole and intact. Inform patients to not crush, chew, or sprinkle capsule contents on food. Inform patients that TECFIDERA can be taken with or without food [see Dosage and Administration (2.1)].

Anaphylaxis and Angioedema Advise patients to discontinue TECFIDERA and seek medical care if they develop signs and symptoms of anaphylaxis or angioedema [see Warnings and Precautions (5.1)]. Progressive Multifocal Leukoencephalopathy Inform patients that progressive multifocal leukoencephalopathy (PML) has occurred in patients who received TECFIDERA. Inform the patient that PML is characterized by a progression of deficits and usually leads to death or severe disability over weeks or months. Instruct the patient of the importance of contacting their doctor if they develop any symptoms suggestive of PML. Inform the patient that typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes [see Warnings and Precautions (5.2)]. Lymphocyte Counts Inform patients that TECFIDERA may decrease lymphocyte counts. A blood test should be obtained before they start therapy. Blood tests are also recommended after 6 months of treatment, every 6 to 12 months thereafter, and as clinically indicated [see Warnings and Precautions (5.3), Adverse Reactions (6.1)]. Liver Injury Inform patients that TECFIDERA may cause liver injury. Instruct patients treated with TECFIDERA to report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. A blood test should be obtained before patients start therapy and during treatment, as clinically indicated [see Warnings and Precautions (5.4)]. Flushing and Gastrointestinal (GI) Reactions Flushing and GI reactions (abdominal pain, diarrhea, and nausea) are the most common reactions, especially at the initiation of therapy, and may decrease over time. Advise patients to contact their healthcare provider if they experience persistent and/or severe flushing or GI reactions. Advise patients experiencing flushing that taking TECFIDERA with food or taking a non-enteric coated aspirin prior to taking TECFIDERA may help [see Adverse Reactions (6.1)]. Pregnancy and Pregnancy Registry Instruct patients that if they are pregnant or plan to become pregnant while taking TECFIDERA they should inform their physician. Encourage patients to enroll in the TECFIDERA Pregnancy Registry if they become pregnant while taking TECFIDERA. [see Use in Specific Populations (8.1)].

Conferences & Community

Philly Full of Neurology During 2019 Annual Meeting The city of Philadelphia, steeped in American history, helped make history for the AAN as nearly 15,000 attendees came together at the 71st Annual Meeting. Members voted in the slate of board nominees, including President Elect Orly Avitzur, MD, MBA, FAAN, who will rise to the presidency in 2021. Avitzur will follow James C. Stevens, MD, FAAN, who accepted the ceremonial gavel from outgoing President Ralph L. Sacco, MD, MS, FAHA, FAAN, who steps into the role of past president. And, for the first time in the Academy’s history, four of the six officers on the Board of Directors are women: Vice President Ann H. Tilton, MD, FAAN; Secretary Carlayne E. Jackson, MD, FAAN; and Treasurer Janis M. Miyasaki, MD, MEd, FRCPC, FAAN, along with Avitzur. Apart from the momentous election during the business meeting, there was excitement throughout the Pennsylvania Convention Center as new brain research findings were reported, packed education courses stimulated eager minds, a new guideline was published, and a wide range of interactive learning opportunities were shared. From talks on innovation to the walk-through BrainDome to swinging with Jellyroll at the Philly Spectacular opening party, this Annual Meeting was unique and memorable in every way! 

Robert W. Baloh, MD, FAAN / Los Angeles, CA Faculty, Neuro-otology courses “How has the meeting changed over the years?” “It’s gotten so big. There are so many things that it’s impossible to go to everything. Certainly, the plenary sessions are always very good and it’s still the best clinical neurology meeting there is.”

Angelique Manasseh / Garden City, MI Fourth-year medical student “What have you experienced so far?” “I went to two sessions for medical students this morning about what to look for in a residency and what they are looking for. Those two alone were worth the trip! They really gave me the most valuable advice I’ve gotten to date on career issues in medical school!”

Claudia Gambrah Sampaney / Philadelphia, PA Fourth-year medical student, abstract presenter, third time attending AAN meeting “What do you enjoy about the AAN Annual Meeting?” “With the AAN meeting, you can pick whatever topic you are interested in and there will be posters on it and people speaking about it and people interested in it. You can really explore your interests, no matter what your niche is.”

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Conferences & Community

Women’s Leadership Program Graduate Rises to New Heights in Medical Career, Military In only 11 months since Renee Pazdan, MD, FAAN, completed the AAN’s inaugural Women Leading in Neurology program (WLN), she has risen to new heights in her military medical career. During her previous position as commander in the United States Public Health Service, Pazdan Pazdan served time across the globe as a neurologist. Recently, she was appointed as the medical director for the Tricare Overseas Program. In this new role, she is responsible for health care oversight for nearly 500,000 service members and families stationed overseas. Diversity Leadership Program and Transforming Leaders Program graduate Rachel Marie E. Salas, MD, MEdHP, FAAN, recently caught up with Pazdan to learn more about the journey to her new role, and how the WLN program gave her the motivation, skills, and confidence to take the chance on herself.

Salas: Right. I totally agree—I have been there too. Now that you have gone through the program, what was one of the biggest take-homes from the WLN? What's the biggest lesson learned?

Salas

Salas: What prompted you to apply to the WLN? Pazdan: My first exposure to the AAN promoting women leaders was the one-day course at the conference in Washington, DC. I think it was in 2015. I actually wasn't planning on attending that meeting, but then I saw that course. I said, “You know what—I need to apply for this.” I had been literally holding myself back—kind of the quintessential imposter syndrome—I literally was not sitting at the table as the lead on traumatic brain injury—as the subject matter expert at Fort Carson. I went to a meeting where we were developing some program, and I literally did not sit at the command table, where it was clearly the right place for me to be. And so, I did this “Like wait a second, what am I doing? I clearly have the training, the expertise, the knowledge. I'm holding myself back. I'm doubting myself.” Attending that one-day course was eye-opening for me to see the panel of women who were one or two generations ahead of me, to hear their challenges and struggles and how they overcame those, and how they really paved the way for us to continue that work. It was really eye-opening. So, when this sevenmonth program for women leading in neurology opened up, I said, “This is the thing that I need to do to improve myself and my skills and also to help promote women leadership in medicine in general.” Salas: That's fantastic! You mentioned before when you didn't feel that you could sit at the table. Reflecting back now, do you feel like there were probably other occurrences where you just didn't give yourself that credit? Do you feel like there were other times that you should have been sitting at the table, but kept yourself from doing so?

AANnews • June 2019

Pazdan: 100 percent. I think it's just an ongoing struggle even today. Even after going through that course and the WLP. I remember I was eligible for promotion a couple of years ago and I didn't put myself forward in the best way possible. However, a year later I did. Just learning how to present myself and promote myself made a huge impact. Learning how to recognize my accomplishments and feeling comfortable acknowledging them and promoting them. Also, recognizing that there are plenty of people that have helped me do what I do and to get where I am. Now when people say, "Hey, you've done a lot," I can say “Thank you” comfortably as opposed to "Oh, no, it's not that much" or downplay it. It is honestly not an easy thing to do.

Pazdan: There's a lot of lessons learned. One is that I'm not alone—that there are these amazing women from all across the country that are doing phenomenal, groundbreaking things and that have also faced the same struggles as me. To have this community now is really powerful. We reach out to each other. We support each other even though the program is over. The other thing is recognizing that my skills are broader than just my profession as a neurologist. I've trained in neurology. I'm good at what I do. I'm good at patient care. But I have these other skills that I didn't really recognize as skills. Such as being able to support and mentor other women or being able to speak to senior leaders and promote my program, for example. To promote neurology. Honestly, even to be able to do something like this interview and promote the programs that the AAN is doing. This is what made me apply for my new position as medical director for the Tricare Overseas Program. You know, this same position came across my desk about two years ago and I said, “Oh huh, that's interesting—global health.” I put it aside. This time when it came across my desk, I said, “You know what, I'm going to look into this more.” And when I did, I thought, “I don’t exactly have the skill set for this, but I can learn it, and these are the things that I have done in my career— particularly as a public health services officer where I have deployed and learned new practices and built new teams in very quick fashion.” Those were the things that I highlighted in my application and in my interview in order to secure this position. I don't think I could have done this new position two years ago before the WLN. Salas: What do you think the biggest factor was in preventing you from actually applying two years ago? Pazdan: Honestly, I think it’s kind of cliché but you know the studies show that women don't apply for positions unless they are like 110 percent qualified. We say, “Oh, I don't have

those skills,” right? When I just took a step back, I said, “You know what—I don't have that experience but that doesn't mean I don't have those skills.” It was a brain shift in terms of how I thought about myself and what I bring to the table. I think as soon as I presented myself differently, I was accepted differently, and I was looked at differently. Salas: I love that. I think it's very powerful that you can say that now. Pazdan: I honestly do credit the WLN with helping me identify my strengths, my skills, my story to feel that I could take that chance and apply. The WLN allowed me to not be afraid of failing or falling. It gave me that sense that if you never get rejected and never fail at anything, you really haven't put yourself out there. Salas: What would you say if someone asked you, “Say, hey I'm thinking about applying for the WLP. What do you think? Is it worth it? I'm busy, I’m full time, I’ve got my family, I'm trying to get promoted, etc., and just don't know if I have time for this. Is it worth it? Pazdan: 110 percent. I have absolutely encouraged other women neurologists to apply for the WLN—because I think it is life changing. It gives you the paths to make all those successes a reality and opens your eyes to different possibilities. One of the things I wanted to go back on and mention is that during that first one-day conference that I attended in 2015, one of the things that they talked about was the difference in mentorship versus sponsorship. And suddenly my eyes were open, because I had a boss

at the time who I thought was literally crazy because he wanted me to take on more. I was running the traumatic brain injury and concussion clinic at the time and one day he was like, "Renee, you need to come up here. I want you take charge of the pain clinic and merge these two programs and you can be in charge." I was like, “What are you talking about? This makes no sense. I don't know pain.” He was trying to sponsor me, and I didn't have the confidence in myself and, looking back now, I really gave up an opportunity because I could have done that. I would have done a good job. But I didn't believe in myself and I didn't know what he was doing for me. It didn't make sense to me at the time. And so even understanding that there can be mentors who help kind of guide you and support you, but then there are sponsors who kind of put you forward and promote you for things that they understand to be strategically important you may not even see from your viewpoint. That, in and of itself, was a piece of knowledge that will help me for the next time I have the opportunity to be sponsored like that. Salas: Before we wrap up, would you tell me a little bit more about your new position? How many people are you managing and leading? Pazdan: At my new role I do not have any direct reports, but I am responsible for health care delivery oversight to over half a million beneficiaries that are overseas. So, either active duty service members or their families and some of the retirees who are living overseas who are eligible for health care through Tricare. Essentially, the government contracts for these services and as the medical director I am responsible to make sure that the health care delivery is done appropriately with high-quality standards, and that patients get the right care at the right place, and at the right time. I will be involved in developing standards and things like that. It's Continued on page 38

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Conferences & Community

Women’s Leadership Program Graduate Rises to New Heights in Medical Career, Military continued from page 38 really a huge scope of responsibility in terms of how many people I am affecting in policies and procedures. Just a very different side of health care. I am really excited about that opportunity. Salas: Is there anything else that you would like to share, either about the program or just about your work as a neurologist? Pazdan: I just want to say thank you to the AAN for putting their money where their mouth is. I feel like there is a lot of talk out there about promoting women in the workplace and promoting diversity. There are programs out there that don't really have an impact like the WLN. From what I

have seen with the AAN is that it's not just like a one-hour lecture to say, “Oh, this is important and let’s move on.” They have truly developed a framework for increasing diversity in leadership, and there's solace around that. So, to me as a woman neurologist, I think that is really powerful and it propels me to want to be a part of it and to continue to support women in our field. I feel like I am part of a team and part of a community. Women Leading in Neurology is supported in part by ACADIA Pharmaceuticals, Inc; Allergan, Inc.; Sanofi Genzyme, and UCB Inc. 

June 17 Is Last Chance to Apply for These Career-changing Leadership Programs!

Don’t miss your chance to experience the career-changing benefits of these all-expenses-paid opportunities. Visit AAN.com/view/lead today! Emerging Leaders Designed to identify, engage, and mentor talent among early-career members interested in future leadership roles within the AAN and the field of neurology. Transforming Leaders Designed to help innovative leaders with aspirations to transform their communities, institutions, or the field of neurology realize their goals through executive-level coaching and a fully customized intensive leadership development training program.

AANnews • June 2019

Women Leading in Neurology An empowering and inspirational leadership development opportunity designed to tackle gender disparities head-on and help women leaders advance to the top levels of leadership in their fields and within the AAN. Practice Leadership Designed to identify and engage solo and small practitioners interested in helping to shape the future of neurology within the AAN and/or their communities. The program’s flexible schedule easily accommodates the restricted schedules of busy practitioners.

Congratulations New Fellows of the American Academy of Neurology! The AAN congratulates the following members who were named prestigious Fellows of the American Academy of Neurology (FAAN) between January 1 and April 30, 2019. Lilyana M. Amezcua, MD, FAAN Darwin Amir, MD, FAAN Yury Nikolaevitch Bykov, MD, FAAN David P. Chesak, MD, FAAN Bradford Dickerson, MD, FAAN Erika Driver-Dunckley, MD, FAAN Roland Etti, MD, FRCP, FAAN Nada Ghanime Abou Fayssal, MD, FAAN Peter C. Gates, MD, MBBS, FR, FAAN Munish Goyal, MD, FAAN Namita Goyal, MD, FAAN Amy Hessler, DO, FAAN Sara E. Hocker, MD, FAAN Jyh-Gong G. Hou, MD, PhD, FAAN Haitham Hussein, MD, FAAN Sachin Kedar, MD, FAAN Lance Y. Kim, DO, FAAN Robert G. Kohn, DO, FAAN Rebecca K. Lehman, MD, FAAN Emilio M. Melchionna, MD, FAAN Randhi Venkata Narayana, MD, FAAN

Anil Neelakantan, MD, FAAN Eddie L. Patton, MD, MS, FAAN Ladislav Pazdera, MD, FAAN Michael Phipps, MD, MHS, FAAN Sandeep S. Rana, MD, FAAN Andrew Russman, DO, FAAN Rana R. Said, MD, FAAN Susan L. Scarberry, MD, FAAN Xin Ming Shen, PhD, FAAN Jeremy D. Slater, MD, FAAN James Stark, MD, FAAN Robert W. Stein, MD, FAAN Bjorn Tackenberg, MD, FAAN Rama Tharaknath Vemuri, MD, FAAN Pablo Villoslada, MD, PhD, FAAN Scott Vota, DO, FAAN Yunxia Wang, MD, FAAN Benjamin J. Williams, MD, PhD, FAAN Michael R. Wilson, MD, FAAN Clinton B. Wright, MD, FAAN Michael L. Wynn, DO, FAAN 

Interested in Elevating Your Membership Status to FAAN? Visit AAN.com/view/FAANReq to see if you’re eligible for the FAAN designation—or encourage a qualifying colleague to apply. FAAN status acknowledges exemplary work and achievements in the neurosciences, the clinical practice of neurology, or academic/ administrative neurology; helps set you apart both within the Academy and throughout your professional career; and offers eligibility to serve on the AAN Board of Directors.

Missed the Annual Meeting? There’s Still Time to Order Annual Meeting On Demand Even if you missed the 2019 Annual Meeting in Philadelphia, you can still watch 500+ hours* of presentations like you’re there in person with slides and synchronized audio, access 200+ programs and syllabi**, and earn up to 242.75 AMA PRA Category 1 CreditsTM with Annual Meeting On Demand. The convenient online format allows you to learn at your desk or on the go. Accessing Annual Meeting On Demand’s comprehensive collection of 2019 Annual Meeting education and science is quick and easy from the AAN’s Online Learning Center. Learn more or order today at AAN.com/view/19AMOD.  *With the move to an online offering, hard drives will not be provided. **Specific presentations within a session may not be available or may be audio only if the presenter has confidential patient information or otherwise declines to be recorded.

AANnews • June 2019 39

Conferences & Community

June 20 Is Advance Registration and Hotel Deadlines for Sports Concussion Conference continued from cover athletic trainers, and coaches at the high school, college, and professional levels, offering up the very latest scientific advances and best practices via a variety of formats. Attendees will leave feeling confident in their abilities to help prevent, diagnose, and manage sports-related concussion safely and efficiently. Highlights

The session will focus on practical strategies for how to incorporate ancillary services into practice with solutions that attendees can implement immediately. The Fall Conference program includes: NEW! Practice Management programming for neurologists and business administrators NEW! Full-day pre-conference for APPs (additional fee required)

A report from the CDC, including an overview of the CDC’s role in sports concussion prevention

Neurology Updates on the most relevant topics in the world of neurology

A keynote address by Paul Pasquina, MD, Colonel, US Army (ret), Department of Defense, on The Science of Concussion: Perspectives from the Department of Defense

The most popular programs from the 2019 Annual Meeting, including MS, headache, neuro rheumatology, autoimmune neurology, brain death, and concussion

A special reception at the NCAA Hall of Champions

Continuum® Self-assessment

A revamped boot camp offering more hands-on training than ever before

Neuroscience in the Clinic sessions

More robust science programming with an expanded offering of clinical updates

Special Workshop on Saturday (additional fee required)

Two Friday programs:

A session specifically for athletic trainers that will focus on sideline evaluation and management of concussion A session focused on neurology and science

Visit AAN.com/view/SCC to learn more, book your hotel, and secure your best registration savings before June 20. 

Fall Conference Registration Opens This Month continued from cover

AANnews • June 2019

Plenary sessions The Fall Conference’s all-inclusive registration rate offers maximum value, flexibility, and customization so attendees can easily tailor a personalized schedule to their specific interests and needs. The all-inclusive registration does not include the Saturday workshop or the advanced practice provider preconference, but discounts are available to registrants who attend both the pre- and main conference. Be sure to register by August 15 for the biggest early registration savings. 

Careers Careers

AAN.com/careers

Visit the AAN’s Neurology Career Center to view hundreds of additional jobs and sign up for customized, confidential notifications when positions of interest are added.

Neurologist—CapeCod,Massachusetts—CapeCodHealthcare—Live and Work Oceanside. New General Neurology opportunity with Cape Cod Healthcare in beautiful Cape Cod, Massachusetts. When you can, take some time to look at the Cape Cod Healthcare website at www.capecodhealth.org/recruitment. Looking for a Neurologist to join our outstanding Neurology team of 5 Neurologists and an NP with Cape Cod Healthcare. The ideal would be a neurologist with either Parkinson’s / Movement disorder fellowship, Multiple Sclerosis or dementia fellowships who is also willing to see general neurology patients. Responsibilities include: providing Hospital rounds and coverage, treating nervous systems disorders including stroke, pain, headache, epilepsy, tremor, sleep disorders, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, brain and spinal cord injuries, brain tumors and amyotrophic lateral sclerosis (ALS and Lou Gehrig's Disease); documenting all patient interactions including, patient medical history and physical examinations, clinical treatments, prescription renewals, phone conversations with patients, their family; conduct patient appointments, initial and follow-up examinations and ongoing care; reviewing documentation and appropriate action upon all test results/ reports (labs, radiology, EKG, etc.); and providing back-up call coverage in Neurology for the Hospital’s Emergency Center in accordance with Hospital privileges and Hospital Medical Staff requirements. Minimum requirements: MD (foreign equivalent accepted) in Medicine or a related field. Must be eligible for Massachusetts Medical Licensure & BC/BE in Neurology. Enjoy coastal living at its best with miles of sandy beaches, quaint villages and beautiful sunsets over Cape Cod Bay. This is truly a great place to practice medicine and enjoy the amenities the Cape has to offer. If you are interested in speaking further about our position, please email me your CV and the best day/time you are available to talk. Take care, Jolia Georges. Job Requirements are a BC/BE in Neurology and must be a team player. To apply for this job, contact Jolia Georges at jgeorges@capecodhealth.org or 508-862-5481. West Virginia Neurophysiology Opening. Medical school affiliated Academic Medical Center. Opportunity to join growing Neurology department of 8 Neurologists. Faculty members including General, Pediatric, Neuromuscular, Movement and Vascular. New Neurology Residency Program with an accredited Neurophysiology Center on site. Multidisciplinary team includes Radiologists, Pharmacists, Nursing, Dietitians and Physical, Occupational and Speech Therapists. Excellent Salary plus Full Benefits and Academic Appointment. An outdoor enthusiast´s haven: enjoy the scenic shores of an historic river, take in the four-season views while mountain hiking. The region´s best skiing at your doorstep. Year-round family fun. A down-to-earth place to live combined with amazing cultural sensations. NCAA Division One Intercollegiate Sports Teams. Excellent Public and Private Schools. Short Distance to 4 Major Metro Areas. Grand prize winner America´s Best Communities Competition. MENTION CODE 180316 – CN. Minimum Requirements: MD or DO Medical Degree. Eligible to be state licensed in the United States. United States Residency and / or Fellowship training. To apply for this position, contact Rob Rector at rrectorweb@phg.com Phone: 404-591-4218 Fax: 404-816-7853. Cognitive/Behavioral Neurologist. Inova Neuroscience and Spine Institute is part of the Inova Health System and a regional leader in the diagnosis, treatment and research of complex neurological conditions involving the brain, spine and nervous system. From its hub at Inova Fairfax Hospital, the Institute also encompasses specialized programs at Inova Alexandria Hospital, Inova Fair Oaks Hospital, Inova Loudoun Hospital and Inova Mount Vernon Hospital. With a network of five hospitals and more than 14,000 neuroscience patients treated annually, Inova Neuroscience and Spine Institute is the largest program of its kind in Northern Virginia and one of the most comprehensive within the midAtlantic region. Led by highly trained, nationally recognized physicians, the Institute diagnoses and treats adult and pediatric patients with neurotrauma, concussions, stroke and cerebrovascular disease, memory disorders, spine conditions, brain and spinal tumors. Its comprehensive sub-specialty offerings, multidisciplinary approach and seamless interactions within the health system ensure

that every patient receives the appropriate level of leadingedge care in the most convenient and appropriate setting. Inova Neuroscience and Spine Institute includes experts from multiple disciplines including emergency medicine, radiology, neurology, pharmacy, critical care, nursing and rehabilitation working closely together to give each patient the best chance at recovery. We offer sophisticated, minimally invasive technology and advanced imaging by interventional neuroradiologists, and cerebrovascular and endovascular surgeons. Our comprehensive research program is committed to the advancement of treatment protocols. We are seeking an experienced Cognitive/Behavioral Neurologist to serve as Medical Director of the new Inova Brain Health and Performance Enhancement Center in Northern Virginia. Partnering with the established Center for Brain Health at the University of Texas at Dallas, the Inova Brain Health and Performance Enhancement Center will offer a variety of specialized services for individuals with disease and recovering from surgery, as well as healthy adults and adolescents wanting to improve their overall brain performance. In addition to administrative responsibilities, the successful candidate will provide outpatient services as a member of Inova Medical Group—Neurology. IMG provides patients with the highest level of care relating to diagnostic, treatment and research services for neurological and related disorders. Our physicians are board certified in neurology, clinical neurophysiology, sleep medicine, internal medicine, electroencephalography, vascular neurology and electrodiagnostic medicine. Our practice also offers in-office testing for a wide range of neurological and sleep disorders. Inova is a not-for-profit healthcare system based in Northern Virginia that serves more than 2 million people each year from throughout the Washington, DC, metro area and beyond. Inova is a comprehensive network of hospitals, outpatient services and facilities, primary and specialty care practices, and health and wellness initiatives. Full time position with compensation package that includes medical, dental, vision and life insurance, paid time off, CME reimbursement, as well as defined contribution retirement plans. Job Requirements: The ideal candidate will have a minimum of five years of relevant experience. Must be able to obtain a Virginia state medical license and obtain the required privileges with Inova. To apply for this position, contact Allison Spindle at allison.spindle@inova.org or reach her at 703-205-2324. Also, visit the application URL for more information jobs. brassring.com/TGnewUI/Search/home/HomeWithPreLoad? PageType=JobDetails&partnerid=25649&siteid=5465&jobid= 3335435.

injections for migraine and Epilepsy Monitoring Unit for long-term monitoring. Neurology department specializes in the following conditions Autism, Cerebral palsy, Dementia, Epilepsy, Multiple sclerosis (MS), Neuropathy, Stroke, Seizures, Migraine, Nerve and muscle disorders and Tremors. "Hip, Historic and Almost Heaven"—Tourism Board. The cultural, recreational, and business capital of the Appalachian Mountains. There are excellent public and private schools, NCAA Division I Intercollegiate Sports Teams. Driving distance for skiing, water sports, hiking, etc. Bike friendly community with a network of trails. Art walks, downtown street festivals and brown bag concert series. Come play—multiple family friendly venues and activities. MENTION CODE 180802 – CHN. Minimum Requirements: MD or DO Medical Degree. Eligible to be state licensed in the United States. United States Residency and / or Fellowship training. To apply for this position, contact Timothy Stanley Direct: 404-591-4224. 800-492-7771. tstanleyweb@phg. com. Fax: 404-591-4237. Cell / Text: 770-265-2001. AANnews® Classified Advertising The AAN offers a complete package of print, online, and in-person recruitment advertising opportunities. Visit careers.AAN.com for all AAN options, rates, and deadlines.

d copy for the August 2019 print edition of AANnews A must be submitted by July 1, 2019. The same deadline applies to changes/cancellations. he American Academy of Neurology reserves the T right to decline, withdraw, or edit advertisements at its discretion. Every care is taken to avoid mistakes, but the responsibility for clerical or printer errors does not exceed the cost of the ad.

Neurologist -Outpatient. Central Vermont Medical Center (CVMC), a partner in The University of Vermont Health Network is recruiting for a neurologist to join our practice. Located in the heart of the Green Mountain state, CVMC has a reputation for clinical excellence with a staff deeply rooted in our community. We have attracted and retained a very talented staff due to our focus on lifestyle and professional growth. Our Neurology practice specializes in epilepsy/seizure disorders, stroke, chronic headaches/ migraines, multiple sclerosis, Parkinson’s and Alzheimer disease, as well as movement and neuromuscular disorders. Candidates interested in reading EEG’s and/or conducting/ interpreting EMG’s welcomed. Ideal candidate will have an interest in teaching third year medical students. We are looking for a physician who wants to work in an area where you can have a long, sustainable career and enjoy the special lifestyle that comes with living in Vermont. The financial package includes a market based, competitive salary plus quality and productivity bonuses. Full benefit package includes moving expenses and assistance with student loans. To apply for this position, contact Sarah Child at sarah.child@cvmc.org or at 802-225-1739. http://cvmc.org. West Virginia Pediatric Neurology. Join one of the best health care providers and teaching hospital in the state. This is an employed position with competitive salary with full benefit package, $50K sign-on bonus, with more than 30 specialties are represented. Procedures performed: Advanced MS infusion therapies, Electromyography (EMG), Electroencephalogram (EEG), Evoked potentials studies, Lumbar puncture, Nerve conduction studies, Therapeutic

AANnews • June 2019 41

NOW APPROVED

Proven efficacy in RMS with a maximum of

20 days

of oral treatment

over 2 years

1,2

INDICATION MAVENCLAD is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults. Because of its safety profile, use of MAVENCLAD is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS. Limitations of Use: MAVENCLAD is not recommended for use in patients with clinically isolated syndrome (CIS) because of its safety profile. RMS: relapsing forms of multiple sclerosis.

IMPORTANT SAFETY INFORMATION WARNING: MALIGNANCIES and RISK OF TERATOGENICITY ° Treatment with MAVENCLAD may increase the risk of malignancy. MAVENCLAD is contraindicated in patients with current malignancy. In patients with prior malignancy or with increased risk of malignancy, evaluate the benefits and risks of the use of MAVENCLAD on an individual patient basis. Follow standard cancer screening guidelines in patients treated with MAVENCLAD ° MAVENCLAD is contraindicated for use in pregnant women and in women and men of reproductive potential who do not plan to use effective contraception because of the potential for fetal harm. Malformations and embryolethality occurred in animals. Exclude pregnancy before the start of treatment with MAVENCLAD in females of reproductive potential. Advise females and males of reproductive potential to use effective contraception during MAVENCLAD dosing and for 6 months after the last dose in each treatment course. Stop MAVENCLAD if the patient becomes pregnant CONTRAINDICATIONS ° Patients with current malignancy. ° Pregnant women, and women and men of reproductive potential who do not plan to use effective contraception during and for 6 months after the last dose in each treatment course. May cause fetal harm. ° Patients with human immunodeficiency virus (HIV). ° Patients with active chronic infections (e.g., hepatitis or tuberculosis). ° Patients with a history of hypersensitivity to cladribine. ° Women intending to breastfeed while taking MAVENCLAD tablets and for 10 days after the last dose.

In the pivotal Phase III, randomized, placebo-controlled CLARITY trial, MAVENCLAD demonstrated1-3: ARR (primary endpoint)1

EDSS1-3

ACTIVE T1-Gd+1

ACTIVE T21

RELATIVE REDUCTION IN ARR AT 2 YEARS

REDUCTION IN RISK OF 3-MONTH CONFIRMED EDSS PROGRESSION

REDUCTION IN MEDIAN NUMBER OF ACTIVE T1-Gd+ LESIONS

REDUCTION IN MEDIAN NUMBER OF ACTIVE T2 LESIONS

33% VS PLACEBO

58% VS PLACEBO P<0.001

0.14

MAVENCLAD (n=433)

P<0.05*

MAVENCLAD (n=433)

0.33

placebo (n=437)

0 MAVENCLAD vs

(n=433)

0.33 placebo

(n=437)

0 MAVENCLAD vs

0.67 placebo

P<0.001

HR: 0.67

(n=433)

(n=437)

P<0.001

*Nominal P value.

SIGNIFICANT REDUCTION IN MEAN NUMBER OF ACTIVE T1-Gd+ AND T2 LESIONS Relative reduction in mean number of % active T1-Gd+ lesions MAVENCLAD 0.12 vs placebo (n=433) vs 0.91 placebo (n=437); P<0.0012,3

ACTIVE T1-Gd+

ACTIVE T2

Relative reduction in mean number of active % T2 lesions MAVENCLAD 0.38 (n=433) vs 1.43 vs placebo placebo (n=437); P<0.0012,3

Patients were eligible if they met certain criteria, including at least 1 MS relapse within the past 12 months, EDSS scores ≤5.5, and <2 prior DMT failures.2 MOST COMMON (>20%) ADVERSE REACTIONS IN CLARITY1 MAVENCLAD (N=440)

Placebo (N=435)

Upper respiratory tract infection

38%

32%

Headache

25%

19%

Lymphopenia

24%

Other adverse reactions reported in ≤10% of patients included nausea, back pain, arthralgia and arthritis, insomnia, bronchitis, hypertension, fever, and depression.

Learn more at MAVENCLAD.com/hcp ARR: annualized relapse rate; CLARITY: CLAdRIbine Tablets treating multiple sclerosis orallY; DMT: disease-modifying therapy; EDSS: Expanded Disability Status Scale; HR: hazard ratio; T1-Gd+: T1 gadolinium-enhanced.

WARNINGS AND PRECAUTIONS

Malignancies: Treatment with MAVENCLAD may increase the risk of malignancy. After the completion of 2 treatment courses, do not administer additional MAVENCLAD treatment during the next 2 years. The risk of malignancy with reinitiating MAVENCLAD more than 2 years after the completion of 2 treatment courses has not been studied. Follow standard cancer screening guidelines in patients treated with MAVENCLAD.

Risk of Teratogenicity: MAVENCLAD may cause fetal harm when administered to pregnant women. In females of reproductive potential, exclude pregnancy before initiation of each treatment course of MAVENCLAD and prevent by the use of effective contraception during MAVENCLAD dosing and for at least 6 months after the last dose of each treatment course. Women who become pregnant during treatment with MAVENCLAD should discontinue treatment.

Please see additional Important Safety Information and Brief Summary of full Prescribing Information, including boxed WARNING on the following pages.

IMPORTANT SAFETY INFORMATION

Lymphopenia: MAVENCLAD causes a dose-dependent reduction in lymphocyte count. In clinical studies, 87% of MAVENCLAD-treated patients experienced lymphopenia. The lowest absolute lymphocyte counts occurred approximately 2 to 3 months after the start of each treatment course and were lower with each additional treatment course. Concomitant use of MAVENCLAD with hematotoxic drugs may increase the risk of adverse reactions because of the additive hematological effects. Monitor lymphocyte counts before and during treatment, periodically thereafter, and when clinically indicated.

Infections: MAVENCLAD can reduce the body’s immune defense and may increase the likelihood of infections. Infections occurred in 49% of MAVENCLAD-treated patients compared to 44% of patients treated with placebo in clinical studies. The most frequent serious infections included herpes zoster and pyelonephritis. Single fatal cases of tuberculosis and fulminant hepatitis B were reported in the clinical program. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting MAVENCLAD. Screen patients for latent infections; consider delaying treatment until infection is fully controlled. Vaccinate patients antibody-negative to varicella zoster virus prior to treatment. Administer anti-herpes prophylaxis in patients with lymphocyte counts less than 200 cells per microliter. Monitor for infections. In patients treated with parenteral cladribine for oncologic indications, cases of progressive multifocal leukoencephalopathy (PML) have been reported. No case of PML has been reported in clinical studies of cladribine in patients with MS.

Hematologic Toxicity: In addition to lymphopenia, decreases in other blood cells and hematological parameters have been reported with MAVENCLAD in clinical studies. In general, mild to moderate decreases in neutrophil counts, hemoglobin levels, and platelet counts were observed. Severe decreases in neutrophil counts were observed in 3.6% of MAVENCLAD-treated patients, compared to 2.8% of placebo patients. Obtain complete blood count (CBC) with differential including lymphocyte count before and during treatment, periodically thereafter, and when clinically indicated.

Risk of Graft-versus-Host Disease With Blood Transfusions: Transfusion-associated graft-versus-host disease has been observed rarely after transfusion of nonirradiated blood in patients treated with cladribine for non-MS treatment indications.

Liver Injury: In clinical studies, 0.3% of MAVENCLAD-treated patients had liver injury (serious or causing treatment discontinuation) compared to 0 placebo patients. Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels prior to treatment. Discontinue if clinically significant injury is suspected.

Hypersensitivity: In clinical studies, 11% of MAVENCLAD-treated patients had hypersensitivity reactions, compared to 7% of placebo patients. Hypersensitivity reactions that were serious and/or led to discontinuation of MAVENCLAD, occurred in 0.5% of MAVENCLAD-treated patients, compared to 0.1% of placebo patients. If a hypersensitivity reaction is suspected, discontinue MAVENCLAD therapy. Do not use MAVENCLAD in patients with a history of hypersensitivity to cladribine.

Adverse Reactions: The most common adverse reactions with an incidence of >20% for MAVENCLAD are upper respiratory tract infection, headache, and lymphopenia. Drug Interactions/Concomitant Medication: Concomitant use of MAVENCLAD with immunosuppressive or myelosuppressive drugs and some immunomodulatory drugs (e.g., interferon beta) is not recommended and may increase the risk of adverse reactions. Acute short-term therapy with corticosteroids can be administered. Avoid concomitant use of certain antiviral and antiretroviral drugs. Avoid concomitant use of BCRP or ENT/CNT inhibitors as they may alter bioavailability of MAVENCLAD. Use in Specific Populations: Studies have not been performed in pediatric or elderly patients, pregnant or breastfeeding women. Use in patients with moderate to severe renal or hepatic impairment is not recommended. Please see Brief Summary of full Prescribing Information, including boxed WARNING on the following pages.

Visit MAVENCLAD.com/hcp to learn more about this new treatment REFERENCES: 1. MAVENCLAD [prescribing information]. Rockland, MA: EMD Serono, Inc; 2019. 2. Giovannoni G, Comi G, Cook S, et al; for the CLARITY Study Group. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):416-426. 3. Data on file. Merck KGaA, Darmstadt, Germany. ©2019 EMD Serono, Inc. All rights reserved. EMD Serono, Inc., One Technology Place, Rockland, MA 02370 Printed in USA US/CLA/0219/0044 04/19

MAVENCLAD® (cladribine) tablets, for oral use Brief Summary of Full Prescribing Information WARNING: MALIGNANCIES AND RISK OF TERATOGENICITY Malignancies Treatment with MAVENCLAD may increase the risk of malignancy. MAVENCLAD is contraindicated in patients with current malignancy. In patients with prior malignancy or with increased risk of malignancy, evaluate the benefits and risks of the use of MAVENCLAD on an individual patient basis. Follow standard cancer screening guidelines in patients treated with MAVENCLAD [see Contraindications (4) and Warnings and Precautions (5.1)]. Risk of Teratogenicity MAVENCLAD is contraindicated for use in pregnant women and in women and men of reproductive potential who do not plan to use effective contraception because of the potential for fetal harm. Malformations and embryolethality occurred in animals. Exclude pregnancy before the start of treatment with MAVENCLAD in females of reproductive potential. Advise females and males of reproductive potential to use effective contraception during MAVENCLAD dosing and for 6 months after the last dose in each treatment course. Stop MAVENCLAD if the patient becomes pregnant [see Contraindications (4), Warnings and Precautions (5.2), and Use in Specific Populations (8.1, 8.3)] 1 INDICATIONS AND USAGE MAVENCLAD is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include relapsingremitting disease and active secondary progressive disease, in adults. Because of its safety profile, use of MAVENCLAD is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS. MAVENCLAD is not recommended for use in patients with clinically isolated syndrome (CIS) because of its safety profile. 4 CONTRAINDICATIONS MAVENCLAD is contraindicated: • in patients with current malignancy [see Warnings and Precautions (5.1)]. • in pregnant women and in women and men of reproductive potential who do not plan to use effective contraception during MAVENCLAD dosing and for 6 months after the last dose in each treatment course. May cause fetal harm [see Warnings and Precautions (5.2) and Use in Specific Populations (8.1, 8.3)]. • in patients infected with the human immunodeficiency virus (HIV) [see Warnings and Precautions (5.4)]. • in patients with active chronic infections (e.g., hepatitis or tuberculosis) [see Warnings and Precautions (5.4)]. • in patients with a history of hypersensitivity to cladribine [see Warnings and Precautions (5.8)]. 5 WARNINGS AND PRECAUTIONS 5.1 Malignancies Treatment with MAVENCLAD may increase the risk of malignancy. In controlled and extension clinical studies worldwide, malignancies occurred more frequently in MAVENCLAD-treated patients (10 events in 3,754 patient-years [0.27 events per 100 patient-years]), compared to placebo patients (3 events in 2,275 patientyears [0.13 events per 100 patient-years]). Malignancy cases in MAVENCLAD patients included metastatic pancreatic carcinoma, malignant melanoma (2 cases), ovarian cancer, compared to malignancy cases in placebo patients, all of which were curable by surgical resection (basal cell carcinoma, cervical carcinoma in situ [2 cases]). The incidence of malignancies in United States MAVENCLAD clinical study patients was higher than the rest of the world (4 events in 189 patient-years [2.21 events per 100 patient-years] compared to 0 events in United States placebo patients; however, the United States results were based on a limited amount of patient data. After the completion of 2 treatment courses, do not administer additional MAVENCLAD treatment during the next 2 years [see Dosage and Administration (2.2)]. In clinical studies, patients who received additional MAVENCLAD treatment within 2 years after the first 2 treatment courses had an increased incidence of malignancy (7 events in 790 patient-years [0.91 events per 100 patientyears] calculated from the start of cladribine treatment in Year 3). The risk of malignancy with reinitiating MAVENCLAD more than 2 years after the completion of 2 treatment courses has not been studied.

MAVENCLAD is contraindicated in patients with current malignancy. In patients with prior malignancy or with increased risk of malignancy, evaluate the benefits and risks of the use of MAVENCLAD on an individual patient basis. Follow standard cancer screening guidelines in patients treated with MAVENCLAD. 5.2 Risk of Teratogenicity MAVENCLAD may cause fetal harm when administered to pregnant women. Malformations and embryolethality occurred in animals [see Use in Specific Populations (8.1)]. Advise women of the potential risk to a fetus during MAVENCLAD dosing and for 6 months after the last dose in each treatment course. In females of reproductive potential, pregnancy should be excluded before initiation of each treatment course of MAVENCLAD and prevented by the use of effective contraception during MAVENCLAD dosing and for at least 6 months after the last dose of each treatment course. Women who become pregnant during treatment with MAVENCLAD should discontinue treatment [see Use in Specific Populations (8.1, 8.3)]. MAVENCLAD is contraindicated for use in pregnant women and in women and men of reproductive potential who do not plan to use effective contraception. 5.3 Lymphopenia MAVENCLAD causes a dose-dependent reduction in lymphocyte count. In clinical studies, 87% of MAVENCLAD-treated patients experienced lymphopenia. The lowest absolute lymphocyte counts occurred approximately 2 to 3 months after the start of each treatment course and were lower with each additional treatment course. In patients treated with a cumulative dose of MAVENCLAD 3.5 mg per kg over 2 courses as monotherapy, 26% and 1% had nadir absolute lymphocyte counts less than 500 and less than 200 cells per microliter, respectively. At the end of the second treatment course, 2% of clinical study patients had lymphocyte counts less than 500 cells per microliter; median time to recovery to at least 800 cells per microliter was approximately 28 weeks. Additive hematological adverse reactions may be expected if MAVENCLAD is administered prior to or concomitantly with other drugs that affect the hematological profile [see Drug Interactions (7.3)]. The incidence of lymphopenia less than 500 cells per microliter was higher in patients who had used drugs to treat relapsing forms of MS prior to study entry (32.1%), compared to those with no prior use of these drugs (23.8%). Obtain complete blood count (CBC) with differential including lymphocyte count prior to, during, and after treatment with MAVENCLAD. [see Dosage and Administration (2.1, 2.5) and Warnings and Precautions (5.4) for timing of CBC measurements and additional instructions based on the patient’s lymphocyte counts and clinical status (e.g., infections)]. 5.4 Infections MAVENCLAD can reduce the body’s immune defense and may increase the likelihood of infections. Infections occurred in 49% of MAVENCLAD-treated patients compared to 44% of placebo patients in clinical studies. The most frequent serious infections in MAVENCLAD-treated patients included herpes zoster and pyelonephritis [see Herpes Virus Infections]. Fungal infections were observed, including cases of coccidioidomycosis. HIV infection, active tuberculosis, and active hepatitis must be excluded before initiation of each treatment course of MAVENCLAD [see Contraindications (4)]. Consider a delay in initiation of MAVENCLAD in patients with an acute infection until the infection is fully controlled. Initiation of MAVENCLAD in patients currently receiving immunosuppressive or myelosuppressive therapy is not recommended [see Drug Interactions (7.1)]. Concomitant use of MAVENCLAD with these therapies could increase the risk of immunosuppression. Tuberculosis Three of 1,976 (0.2%) cladribine-treated patients in the clinical program developed tuberculosis. All 3 cases occurred in regions where tuberculosis is endemic. One case of tuberculosis was fatal, and 2 cases resolved with treatment. Perform tuberculosis screening prior to initiation of the first and second treatment course of MAVENCLAD. Latent tuberculosis infections may be

activated with use of MAVENCLAD. In patients with tuberculosis infection, delay initiation of MAVENCLAD until the infection has been adequately treated. Hepatitis One clinical study patient died from fulminant hepatitis B infection. Perform screening for hepatitis B and C prior to initiation of the first and second treatment course of MAVENCLAD. Latent hepatitis infections may be activated with use of MAVENCLAD. Patients who are carriers of hepatitis B or C virus may be at risk of irreversible liver damage caused by virus reactivation. In patients with hepatitis infection, delay initiation of MAVENCLAD until the infection has been adequately treated. Herpes Virus Infections In controlled clinical studies, 6% of MAVENCLADtreated patients developed a herpes viral infection compared to 2% of placebo patients. The most frequent types of herpes viral infections were herpes zoster infections (2.0% vs. 0.2%) and oral herpes (2.6% vs. 1.2%). Serious herpes zoster infections occurred in 0.2% of MAVENCLAD-treated patients. Vaccination of patients who are antibody-negative for varicella zoster virus is recommended prior to initiation of MAVENCLAD. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting MAVENCLAD. The incidence of herpes zoster was higher during the period of absolute lymphocyte count less than 500 cells per microliter, compared to the time when the patients were not experiencing this degree of lymphopenia. Administer anti-herpes prophylaxis in patients with lymphocyte counts less than 200 cells per microliter. Patients with lymphocyte counts below 500 cells per microliter should be monitored for signs and symptoms suggestive of infections, including herpes infections. If such signs and symptoms occur, initiate treatment as clinically indicated. Consider interruption or delay of MAVENCLAD until resolution of the infection. Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. No case of PML has been reported in clinical studies of cladribine in patients with multiple sclerosis. In patients treated with parenteral cladribine for oncologic indications, cases of PML have been reported in the postmarketing setting. Obtain a baseline (within 3 months) magnetic resonance imaging (MRI) before initiating the first treatment course of MAVENCLAD. At the first sign or symptom suggestive of PML, withhold MAVENCLAD and perform an appropriate diagnostic evaluation. MRI findings may be apparent before clinical signs or symptoms. Vaccinations Administer all immunizations according to immunization guidelines prior to starting MAVENCLAD. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting MAVENCLAD, because of a risk of active vaccine infection [see Herpes Virus Infections]. Avoid vaccination with live-attenuated or live vaccines during and after MAVENCLAD treatment while the patient’s white blood cell counts are not within normal limits. 5.5 Hematologic Toxicity In addition to lymphopenia [see Warnings and Precautions (5.3)], decreases in other blood cells and hematological parameters have been reported with MAVENCLAD in clinical studies. Mild to moderate decreases in neutrophil counts (cell count between 1,000 cells per microliter and < lower limit of normal [LLN]) were observed in 27% of MAVENCLAD-treated patients, compared to 13% of placebo patients whereas severe decreases in neutrophil counts (cell count below 1,000 cells per microliter) were observed in 3.6% of MAVENCLAD-treated patients, compared to 2.8% of placebo patients. Decreases in hemoglobin levels, in general mild to moderate (hemoglobin

8.0 g per dL to < LLN), were observed in 26% of MAVENCLAD-treated patients, compared to 19% of placebo patients. Decreases in platelet counts were generally mild (cell count 75,000 cells per microliter to < LLN) and were observed in 11% of MAVENCLADtreated patients, compared to 4% of placebo patients. In clinical studies at dosages similar to or higher than the approved MAVENCLAD dosage, serious cases of thrombocytopenia, neutropenia, and pancytopenia (some with documented bone marrow hypoplasia) requiring transfusion and granulocyte-colony stimulating factor treatment have been reported [see Warnings and Precautions (5.6) for information regarding graft-versus-host disease with blood transfusion]. Obtain complete blood count (CBC) with differential prior to, during, and after treatment with MAVENCLAD [see Dosage and Administration (2.1, 2.5)]. 5.6 Graft-Versus-Host Disease With Blood Transfusion Transfusion-associated graft-versus-host disease has been observed rarely after transfusion of nonirradiated blood in patients treated with cladribine for non-MS treatment indications. In patients who require blood transfusion, irradiation of cellular blood components is recommended prior to administration to decrease the risk of transfusionrelated graft-versus-host disease. Consultation with a hematologist is advised. 5.7 Liver Injury In clinical studies, 0.3% of MAVENCLAD-treated patients had liver injury (serious or causing treatment discontinuation) considered related to treatment, compared to 0 placebo patients. Onset has ranged from a few weeks to several months after initiation of treatment with MAVENCLAD. Signs and symptoms of liver injury, including elevation of serum aminotransferases to greater than 20-fold the upper limit of normal, have been observed. These abnormalities resolved upon treatment discontinuation. Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels prior to the first and second treatment course [see Dosage and Administration (2.1)]. If a patient develops clinical signs, including unexplained liver enzyme elevations or symptoms suggestive of hepatic dysfunction (e.g., unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine), promptly measure serum transaminases and total bilirubin and interrupt or discontinue treatment with MAVENCLAD, as appropriate. 5.8 Hypersensitivity In clinical studies, 11% of MAVENCLAD-treated patients had hypersensitivity reactions, compared to 7% of placebo patients. Hypersensitivity reactions that were serious and/or led to discontinuation of MAVENCLAD (e.g., dermatitis, pruritus) occurred in 0.5% of MAVENCLAD-treated patients, compared to 0.1% of placebo patients. One patient had a serious hypersensitivity reaction with rash, mucous membrane ulceration, throat swelling, vertigo, diplopia, and headache after the first dose of MAVENCLAD. If a hypersensitivity reaction is suspected, discontinue MAVENCLAD therapy. Do not use MAVENCLAD in patients with a history of hypersensitivity to cladribine [see Contraindications (4)]. 5.9 Cardiac Failure In clinical studies, one MAVENCLAD-treated patient experienced life-threatening acute cardiac failure with myocarditis, which improved after approximately 1 week. Cases of cardiac failure have also been reported with parenteral cladribine used for treatment indications other than multiple sclerosis. Instruct patients to seek medical advice if they experience symptoms of cardiac failure (e.g., shortness of breath, rapid or irregular heartbeat, swelling). 6 Adverse Reactions The following serious adverse reactions and potential risks are discussed, or discussed in greater detail, in other sections: Malignancies [see Warnings and Precautions (5.1)], Risk of Teratogenicity [see Warnings and Precautions (5.2)], Lymphopenia [see Warnings and Precautions (5.3)], Infections [see Warnings and Precautions (5.4)], Hematologic Toxicity [see Warnings and Precautions (5.5)], Graft-Versus-Host Disease With Blood Transfusion [see Warnings and Precautions (5.6)], Liver Injury [see Warnings and Precautions (5.7)], Hypersensitivity

[see Warnings and Precautions (5.8)], Cardiac Failure [see Warnings and Precautions (5.9)] 6.1 Clinical Trials Experience

Drug Interactions With MAVENCLAD (continued) 7.2 Interferon Beta

MAVENCLAD (N=440) %

Placebo (N=435) %

Clinical Impact

Upper respiratory tract infection

Concomitant use of MAVENCLAD with interferon beta did not change the exposure of cladribine to a clinically significant effect; however, lymphopenia risk may be increased [see Warnings and Precautions (5.3)].

Prevention or Management

Concomitant use is not recommended.

Headache

7.3 Hematotoxic Drugs

Lymphopenia

Nausea

Back pain

Arthralgia and arthritis

Insomnia

Bronchitis

Hypertension

Fever

Depression

Adverse Reactions in Study 1 With an Incidence of at Least 5% for MAVENCLAD and Higher Than Placebo

Hypersensitivity In clinical studies, 11% of MAVENCLAD patients had hypersensitivity adverse reactions, compared to 7% of placebo patients [see Warnings and Precautions (5.8)]. Alopecia Alopecia occurred in 3% of MAVENCLAD-treated patients compared to 1% of placebo patients. Myelodysplastic Syndrome Cases of myelodysplastic syndrome have been reported in patients that had received parenteral cladribine at a higher dosage than that approved for MAVENCLAD. These cases occurred several years after treatment. Herpes Meningoencephalitis Fatal herpes meningoencephalitis occurred in 1 MAVENCLAD-treated patient, at a higher dosage and longer duration of therapy than the approved MAVENCLAD dosage and in combination with interferon beta-1a treatment. Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) SJS and TEN are identified risks of parenteral cladribine for the treatment of oncologic indications. Seizures In clinical studies, serious events of seizure occurred in 0.3% of MAVENCLAD-treated patients compared to 0 placebo patients. Serious events included generalized tonic-clonic seizures and status epilepticus. It is unknown whether these events were related to the effects of multiple sclerosis alone, to MAVENCLAD, or to a combination of both.

Clinical Impact

Concomitant use of MAVENCLAD with hematotoxic drugs may increase the risk of adverse reactions because of the additive hematological effects [see Warnings and Precautions (5.5)].

Prevention or Management

Monitor hematological parameters.

7.4 Antiviral and Antiretroviral Drugs

Clinical Impact

Compounds that require intracellular phosphorylation to become active (e.g., lamivudine, zalcitabine, ribavirin, stavudine, and zidovudine) could interfere with the intracellular phosphorylation and activity of cladribine.

Prevention or Management

Avoid concomitant use.

7.5 Potent ENT, CNT, and BCRP Transporter Inhibitors

Clinical Impact

Cladribine is a substrate of breast cancer resistance protein (BCRP), equilibrative nucleoside (ENT1), and concentrative nucleoside (CNT3) transport proteins. The bioavailability, intracellular distribution, and renal elimination of cladribine may be altered by potent ENT1, CNT3, and BCRP transporter inhibitors.

Prevention or Management

Avoid co-administration of potent ENT1, CNT3, or BCRP transporter inhibitors (e.g., ritonavir, eltrombopag, curcumin, cyclosporine, dilazep, nifedipine, nimodipine, cilostazol, sulindac, dipyridamole, or reserpine) during the 4- to 5-day MAVENCLAD treatment cycles. If this is not possible, consider selection of alternative concomitant drugs with no or minimal ENT1, CNT3, or BCRP transporter inhibiting properties. If this is not possible, dose reduction to the minimum mandatory dose of drugs containing these compounds, separation in the timing of administration, and careful patient monitoring is recommended.

Drug Interactions With MAVENCLAD 7.1 Immunomodulatory, Immunosuppressive, or Myelosuppressive Drugs

Clinical Impact

Prevention or Management

Concomitant use of MAVENCLAD with immunomodulatory, immunosuppressive, or myelosuppressive drugs may increase the risk of adverse reactions because of the additive effects on the immune system [see Warnings and Precautions (5.4)]. Concomitant use with myelosuppressive or other immunosuppressive drugs is not recommended. Acute short-term therapy with corticosteroids can be administered. In patients who have previously been treated with immunomodulatory or immunosuppressive drugs, consider potential additive effect, the mode of action, and duration of effect of the other drugs prior to initiation of MAVENCLAD.

7.6 Potent BCRP and P-gp Transporter Inducers Clinical Impact

Possible decrease in cladribine exposure if potent BCRP or P-gp transporter inducers are co-administered.

Prevention or Management

Consider a possible decrease in cladribine efficacy if potent BCRP (e.g., corticosteroids) or P-gp (e.g., rifampicin, St. Johnâ&#x20AC;&#x2122;s Wort) transporter inducers are co-administered.

7.7 Hormonal Contraceptives Clinical Impact

It is currently unknown whether MAVENCLAD may reduce the effectiveness of systemically acting hormonal contraceptives.

Prevention or Management

Women using systemically acting hormonal contraceptives should add a barrier method during MAVENCLAD dosing and for at least 4 weeks after the last dose in each treatment course.

8 Use in Specific Populations 8.1 Pregnancy Risk Summary MAVENCLAD is contraindicated in pregnant women and in females and males of reproductive potential who do not plan to use effective contraception. There are no adequate data on the developmental risk associated with use of MAVENCLAD in pregnant women. Cladribine was embryolethal when administered to pregnant mice and produced malformations in mice and rabbits [see Data]. The observed developmental effects are consistent with the effects of cladribine on DNA [see Contraindications (4) and Warnings and Precautions (5.2)]. Data Animal Data When cladribine was administered intravenously (0, 0.5, 1.5, or 3 mg/kg/day) to pregnant mice during the period of organogenesis, fetal growth retardation and malformations (including exencephaly and cleft palate) and embryofetal death were observed at the highest dose tested. An increase in skeletal variations was observed at all but the lowest dose tested. There was no evidence of maternal toxicity. When cladribine was administered intravenously (0, 0.3, 1, and 3 mg/kg/day) to pregnant rabbits during the period of organogenesis, fetal growth retardation and a high incidence of craniofacial and limb malformations were observed at the highest dose tested, in the absence of maternal toxicity. When cladribine was administered intravenously (0, 0.5, 1.5, or 3.0 mg/kg/day) to mice throughout pregnancy and lactation, skeletal anomalies and embryolethality were observed at all but the lowest dose tested. 8.2 Lactation MAVENCLAD is contraindicated in breastfeeding women because of the potential for serious adverse reactions in breastfed infants [see Contraindications (4) and Warnings and Precautions (5)]. Advise women not to breastfeed during dosing with MAVENCLAD and for 10 days after the last dose. 8.3 Females and Males of Reproductive Potential Pregnancy Testing In females of reproductive potential, pregnancy should be excluded before the initiation of each treatment course of MAVENCLAD [see Use in Specific Populations (8.1)]. Contraception Females Females of reproductive potential should prevent pregnancy by use of effective contraception during MAVENCLAD dosing and for at least 6 months after the last dose in each treatment course. It is unknown if MAVENCLAD may reduce the effectiveness of the systemically acting hormonal contraceptives. Women using systemically acting hormonal contraceptives should add a barrier method during MAVENCLAD dosing and for at least 4 weeks after the last dose in each treatment course. Women who become pregnant during MAVENCLAD therapy should discontinue treatment [see Warnings and Precautions (5.2) and Drug Interactions (7.7)]. Males As cladribine interferes with DNA synthesis, adverse effects on human gametogenesis could be expected. Therefore, male patients of reproductive potential should take precautions to prevent pregnancy of their partner during MAVENCLAD dosing and for at least 6 months after the last dose in each treatment course [see Warnings and Precautions (5.2) and Nonclinical Toxicology (13.1)]. 8.4 Pediatric Use The safety and effectiveness in pediatric patients (below 18 years of age) have not been established. Use of MAVENCLAD is not recommended in pediatric patients because of the risk of malignancies [see Warnings and Precautions (5.1)]. 8.5 Geriatric Use Clinical studies with MAVENCLAD did not include sufficient numbers of patients aged 65 or over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the

elderly and younger patients. Caution is recommended when MAVENCLAD is used in elderly patients, taking into account the potential greater frequency of decreased hepatic, renal, or cardiac function, concomitant diseases, and other drug therapy. 8.6 Patients With Renal Impairment The concentration of cladribine is predicted to increase in patients with renal impairment [see Clinical Pharmacology (12.3)]. No dosage adjustment is recommended in patients with mild renal impairment (creatinine clearance 60 to 89 mL per minute). MAVENCLAD is not recommended in patients with moderate to severe renal impairment (creatinine clearance below 60 mL per minute) [see Clinical Pharmacology (12.3)]. 8.7 Patients With Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics of cladribine is unknown [see Clinical Pharmacology (12.3)]. No dosage adjustment is recommended in patients with mild hepatic impairment. MAVENCLAD is not recommended in patients with moderate to severe hepatic impairment (Child-Pugh score greater than 6) [see Clinical Pharmacology (12.3)]. 17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Inform patients of the possible risk of malignancies, teratogenicity, lymphopenia, and other hematologic toxicity, infections, liver injury, hypersensitivity, and cardiac failure. Inform women that they cannot breastfeed on a MAVENCLAD treatment day and for 10 days after the last dose. Instruct patients that MAVENCLAD is a cytotoxic drug and to use care when handling MAVENCLAD tablets.

MAVENCLADÂŽ (cladribine) tablets, for oral use Distributed by: EMD SERONO, Inc. MAVENCLAD is a One Technology Place registered trademark of Rockland, MA 02370 Merck KGaA, Darmstadt, Germany US/CLA/0419/0220 04/19 ÂŠ2019 EMD Serono, Inc.

Education & Research

June Continuum Examines Latest Information on MS Diagnosis and Treatment

New Letter of Intent Requirement for Education Research Grants and Medical Education Research Training Fellowship Program

Continuum

The latest updates in multiple sclerosis and other CNS Multiple Scleros is inflammatory diseases are the focus of the June issue of Continuum: Lifelong Learning in Neurology ®. LIFEL ONG LEAR NING IN NEUR OLOG Y ®

GUEST EDITORS:

CYNTHIA L. HARDEN,

MD; ERIK K. ST.

LOUIS, MD, MS,

APRIL June

VOL. 25

NO. 3

FA AN

“This issue contains new information on MS diagnosis, mimics, disease classification, pediatric disease, pregnancy and family planning, and how to start, monitor, and switch disease-modifying therapies,” said Dean M. Wingerchuk, MD, MSc, FRCPC, FAAN, guest editor of this issue. “Our MS experts have compiled information that covers diagnosis, counseling, and treatment in all phases of MS, from incidentally discovered disease to later progressive MS.” CONTINU UMJOURN

AL.COM

Chapter topics include: Multiple Sclerosis Risk Factors and Pathogenesis Diagnosis, Differential Diagnosis, and Misdiagnosis of Multiple Sclerosis Phases and Phenotypes of Multiple Sclerosis Management of Multiple Sclerosis Relapses Clinically Isolated Syndrome and Early Relapsing Multiple Sclerosis Highly Aggressive Multiple Sclerosis Monitoring, Switching, and Stopping Multiple Sclerosis Disease-m odifying Therapies Progressive Multiple Sclerosis Management of Multiple Sclerosis Symptoms and Comorbidities Pregnancy and Family Planning in Multiple Sclerosis Pediatric Central Nervous System Demyelinating Diseases Neuromyelitis Optica Spectrum Disorder and Other Non– Multiple Sclerosis Central Nervous System Inflammatory Diseases AAN members pay only $349 per year for a subscription to Continuum® and Continuum® Audio. Subscribe now by contacting Wolters Kluwer at (800) 361-0633, (301) 223-2300 (international); or visit Shop.LWW.com/continuum. AAN Junior members who are transitioning to neurologist memberships can receive a 50-percent discount on the already low member rate for the Continuum and Continuum Audio subscription. 

AANnews • June 2019

Each year, the AAN awards up to three Education Research Grants of up to $10,000 and one Medical Education Research Training Fellowship up to $65,000 for recipients to study the effectiveness of neurologic educational programs to ensure they are meeting the lifelong needs of their constituents (e.g., medical students, residents, fellows, and practicing neurologists or advanced practice providers), to strengthen the educational programs of the AAN for quality improvement and credentialing purposes (i.e., ACCME accreditation), and to train neurology educators to perform and publish education research as one component of career development for clinician educators. Letters of intent are now required as part of the application process and are currently being accepted until 11:59 p.m. ET on August 31, 2019. Applications will not be considered without letters of intent, which are intended to provide a brief and compelling summary of the proposed course of study and impacts on both neurologic education and the applicant’s career. Those submitting letters of intent will receive feedback on how to strengthen their application before receiving invitations for full application submissions in October. Letters of intent should be submitted to Bridget McDonald at BMcDonald@aan.com. Applicants must be current AAN members, and clinician educators are encouraged. For complete eligibility and letter of intent and application requirements for the Education Research Grant, visit AAN.com/view/EducationResearch, and for the Medical Education Research Training Fellowship Program visit AAN.com/view/MedEdResearch. 

Fisher Succeeds Józefowicz as New UCNS Chair Paul G. Fisher, MD, has been elected the new chair of the UCNS Board of Directors. The two-year term began May 7, 2019. Fisher, who is chief of the Division of Child Neurology at Stanford University School of Medicine in Stanford, CA, served on the UCNS Board of Directors Fisher since 2015, where he represented the Child Neurology Society. Thank you to outgoing chair Ralph F. Józefowicz, MD, FAAN, for his service from 2015 to 2019. Józefowicz will continue to serve as a director on the UCNS Board of Directors until 2021, representing the American Academy of Neurology. 

UCNS Releases Details on New Continuous Certification Model

With the changing landscape of maintenance of certification (MOC), alternative models for recertification are emerging. After Józefowicz over a year of careful evaluation and development, the UCNS is now beginning the transition to a new continuous-certification (C-cert) model designed to provide a more timely, relevant, and convenient means for physicians to maintain UCNS certification. “The field of medicine is advancing at a fast pace,” said Ralph F. Józefowicz, MD, FAAN, immediate past chair of the UCNS Board of Directors. “The objective of MOC is to ensure that physicians are keeping up with the advances in their subspecialty field to provide the best possible patient care. We believe this can be achieved through a process that actively facilitates lifelong learning and the knowledge assessed by a means that is not burdensome for the physician.”

The new continuous certification process includes:

The transition to C-cert will begin in 2019 with full implementation in 2020. All 2019 initial certification examinations will take place as scheduled. Additional information will be released as the new C-cert process begins.

Certification requirements that are delivered and completed on a manageable and continuous basis to replace the current 10-year process/high-stakes examination

Added UCNS Certification Council Chair Matthew E. Fink, MD, “We listened carefully to what our UCNS diplomates had to say, and working with other professional organizations, UCNS has developed a C-cert plan consistent with the way most physicians prefer to accomplish lifelong learning— continuous, ongoing, and based on current needs.”

Involvement of sponsoring organizations and their subspecialty experts in identifying the topics and information that is relevant to lifelong learning for their field Identification of resources that are credible, accessible, and affordable and reflect the fundamental knowledge needed to stay up-todate in the subspecialty field

Visit UCNS.org/go/home for more details on the UCNS and its new C-cert process. 

Development of a process and identification of an online platform to assess knowledge related to the relevant topic content through short online “quizzes”

AANnews • June 2019 49

Dates & Deadlines

MONTH JUNE 2019 2018

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JULY 2019

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18 25

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23 30

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JULY 1

AUGUST 13

Deadline: Event Name UCNS Subspecialty Location Training Program Fellowship AAN.com Accreditation Applications UCNS.org

Deadline: Early Deadline to Apply for UCNS Neurocritical Care Certification Examination Apply by July 1 and save $500 UCNS.org/go/subspecialty/neurocritical/ certification

Webinar: Increasing Revenue in Your Practice: Care Models, Ancillary Services, and Other Strategies Register by August 12 AAN.com/view/pmw19

JUNE 17 Deadline: Leadership Program Applications (Transforming Leaders, Emerging Leaders, Practice Leadership, and Women Leading in Neurology) AAN.com/view/lead

JUNE 20 Deadline: Sports Concussion EDU 19SCC General Ad—Half Page Horizontal> AN Conference Advance Registration Placed in AANnews AAN.com/view/SCC 8.25 x 5.25 +0.125 bleed, 4C

JULY 18–21 AAN Palatucci Advocacy Leadership Forum AAN.com/view/PALF

AUGUST 15 Deadline: Fall Conference Early Registration AAN.com/view/Fall

JUlY 26–28 Sports Concussion Conference Indianapolis, IN AAN.com/view/SCC

We are returning to the home of the NCAA to offer the most cutting-edge concussion management and evolving science available. Programming in conjunction with