testing

LEARN ABOUT A NEW ORAL TREATMENT FOR MULTIPLE SCLEROSIS

Visit Booth ©2019 EMD Serono, Inc. All rights reserved.

Printed in the USA US/NPR/0319/0198 03/19

2313

THE ANNUAL MEETING NEWS DAILY

Thursday, May 9, 2019

EXPERTS DEBATE MOST CURRENT, CONTROVERSIAL ISSUES IN THIS MORNING’S PLENARY SESSION

Brooks-Kayal

Videnovic

Humans Versus Machines is the membersuggested topic that will be explored during today’s lively Controversies in Neurology Plenary Session, which runs this morning from 9:15 to 11:30 in the Terrace Ballroom. The session will showcase six experts discussing the most current and controversial issues in neuroscience. In debate-style format, two speakers will argue one side of a topic, followed by a rebuttal. The session will be moderated by AAN Science Committee members Amy R. Brooks-Kayal, MD, FAAN, from Children’s Hospital Colorado, Aurora, CO, and Aleksandar Videnovic, MD, MSc, FAAN, from MGH Neurological Clinical Research Institute, Boston, MA. Continued on page 4 u

Continued on page 4 u

Tomorrow’s Grand Finale to Offer Robust Lineup of Learning, Fun You won’t want to miss the Friday Grand Finale, an enhanced daylong experience offering engaging events, fun activities, and insightful presentations, capped off by a special Closing Party in celebration of May Day! Schedule: 9:15 a.m.–11:30 a.m.

Neurology Year in Review Plenary Session highlighting the latest research from the past year within a specific subspecialty topic Continued on page 5 u

Celebrate May Day at Tomorrow’s Closing Party!

Join your friends and colleagues in Ballroom B of the Pennsylvania Convention Center tomorrow between 5:00 p.m. and 7:00 p.m. to celebrate a triumphant week of the best science, education, and networking in the world of Continued on page 4 u

Inside

9

Tomorrow’s Plenary to Showcase Top Research over the Past Year

and Dementia 10 Aging Highlighted in Today’s

Invited Science Session

Evidenced12 Understand based Medicine with EBM Online

In Multiple

Sclerosis—

GREY MATTERS, TOO

Thursday, May 9 Cover Experts Debate Most Current,

13 Understand Evidenced-based

The Vision of the AAN is to be indispensable to our members.

Controversial Issues in This Morning’s Plenary Session

15 Commitment to Cures Celebrates

Tomorrow’s Grand Finale to Offer Robust Lineup of Learning, Fun

16 Today’s Experiential Learning Area

The Mission of the AAN is to promote the highest quality patient-centered neurologic care and enhance member career satisfaction.

Celebrate May Day at Tomorrow’s Closing Party!

5

Advancing Medicine Series Explores Interface Between Neuroscience and Philosophy

9

Tomorrow’s Plenary to Showcase Top Research over the Past Year

19 What excited you today at #AANAM? 20 Boxed Lunch Menu 21 What Are Your Colleagues Saying?

24 Participant Credits Diversity

9

Before You Go: Don’t Forget to Complete Your Evaluations to Claim Your Annual Meeting CME!

10 Aging and Dementia Highlighted in Today’s Invited Science Session 12 Upcoming AAN Conference Opportunities

Medicine with EBM Online

Brain Research and Public Leaders Highlights

Leadership Program with Reducing Burnout, More

25 The Best of Philly from Those Who Know It Best

26 Friday’s Experiential Learning Area Highlights

28 Find the Latest Research at Today’s Poster Session

13 New AAN Leadership Program

Provides Guidance for New Directors

B:11.125” T:10.875” S:9.875”

Daily Reminders Education Program Syllabi and Slides Available Online Only Education Program syllabi and slides are available online only at AAN.com/view/syllabi or through the AAN Conferences Mobile App at AAN.com/view/MobileApp.

May 20 Is Deadline to Submit Online Evaluations for Annual Meeting CME

FIND OUT WHY

Booth 2300

Complete your evaluations to get your CME hours by using the AAN Conferences Mobile App at AAN.com/view/MobileApp or by visiting AAN.com/view/CME. CME requests may be made until Monday, May 20, 2019. © 2019 Celgene Corporation All rights reserved.

03/19 US-CLG-19-0291

Transcripts will be emailed approximately six weeks after the meeting. AAN members can also access their transcript via NeuroTracker™ at AAN.com/view/NeuroTracker. 

Contact Information: 201 Chicago Avenue Minneapolis, MN 55415 USA Phone: (800) 879-1960 (Toll Free) or

(612) 928-6100 (International) Fax: (612) 454-2744 Email: memberservices@aan.com Website: AAN.com AAN Chief Executive Officer:

Catherine M. Rydell, CAE Managing Editor: Angela M. Babb, CAE, APR Editor: Tim Streeter Writers: Ryan Knoke, Sarah Parsons Designers: Siu Lee, Andrew Imholte Photography: Will Evans Printing: Phoenix Lithographing Corporation Email: aannews@aan.com AANextra is published by the American Academy of Neurology.

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.

Thursday AANextra cover

Philadelphia

ÑOL EN ESPA SO AL DOR

EVENT PROGRAM

Thursday, May 9, 2019 • 10:00 a.m.–4:00 p.m.

Pennsylvania Convention Center

The American Academy of Neurology sincerely thanks Phoenix Lithographing Corporation for its outstanding service, steadfast professionalism, and high quality standards, as well as its generous donation of the 2019 Brain Health Fair program guide.

Celebrate May Day at Tomorrow’s Closing Party! continued from cover neurology. The floral-themed May Day extravaganza will feature live music by the Philadelphia String Quartet, tasty refreshments and libations, a fun floral selfie wall, special botanical appearances, and more. All registered meeting attendees receive one free ticket and additional tickets may be purchased for $50 each at Registration. 

Experts Debate Most Current, Controversial Issues in This Morning’s Plenary Session continued from cover

Speakers and topics include: Should Ambulances Bypass Primary Stroke Centers for Comprehensive Stroke Centers?

Yes: Lee H. Schwamm, MD Massachusetts General Hospital, Boston, MA No: Johanna Therese Fifi, MD Mount Sinai Hospital, New York, NY

Schwamm

Fifi

Advancing Medicine Series Explores Interface Between Neuroscience and Philosophy The Advancing Medicine: Inspiration and Innovation series concluded Wednesday with Patricia Churchland, BPhil, leading a compelling discussion on The Origin of Moral Intuitions. Churchland, a professor emeritus of philosophy at the University of California, San Diego, and adjunct professor at the Salk Institute, has contributed to the fields of neurophilosophy, philosophy of the mind, and neuroethics. Her research has centered on the interface between neuroscience and —Xxxxxxxxxxxx, MD philosophy with a current Xxxxxxxxx, xxxxxxxx,xxxxxxxxxxxxxxxxxxxx focus on the association xxxxxxxxx of morality and the social brain. 

“Annual Meeting attendees found the talk enlightening.

XXXXXXXXXXX XXXXX, XXXXXXXXXXXXXXXXX XXXXXXXXX.”

“Annual Meeting attendees found the talk enlightening.

XXXXXXXXXXX XXXXX, XXXXXXXXXXXXXXXXX XXXXXXXXX.” —Xxxxxxxxxxxx, MD

Xxxxxxxxx, xxxxxxxx,xxxxxxxxxxxxxxxxxxxx xxxxxxxxx

Saving the Clinical Art of Neurology: Human Versus Machine?

Yes: Joseph R. Berger, MD, FAAN University of Pennsylvania, Philadelphia, PA No: David E. Newman-Toker, MD, PhD, FAAN Johns Hopkins University, Baltimore, MD

Tomorrow’s Grand Finale to Offer Robust Lineup of Learning, Fun continued from cover

11:30 a.m.–1:00 p.m.

Berger

Newman-Toker

Continuous EEG in the ICU: Does It Really Matter?

Yes: Emily Jean Gilmore, MD Yale University School of Medicine, New Haven, CT No: Brandon P. Foreman, MD University of Cincinnati, Cincinnati, OH

Innovation Lunch, with a special neuroimaging session, featuring posters and invited talks.

1:00 p.m.–3:00 p.m.

Four major scientific sessions

selected to appeal to a wide variety of attendees: Multiple sclerosis Neuromuscular Stroke Headache

3:30 p.m.–4:30 p.m.

4:30 p.m–5:30 p.m.

Education Blitz Programs featuring quick-fire learning on the following:

NeuroZone—Gear up for the Closing Party with this madcap series of game show challenges.

Child concussion Normal pressure

5:00 p.m–7:00 p.m.

hydrocephalus Emerging infectious diseases Evolution of autoimmune neurology Multiple sclerosis Sleep

Closing Party celebrating May Day! 

Four Neurology Update

Gilmore

Foreman

programs: Movement disorders Aging/dementia Epilepsy Neuro-ophthalmology/ neuro-otology

What is your "aha" moment from the Controversies in Neurology Plenary Session? Join the conversation at #AANAM. 

4

Thursday, May 9, 2019 • AANextra

Thursday, May 9, 2019 • AANextra

5

With hereditary transthyretin-mediated (hATTR) amyloidosis...

Patients and their families face a future of functional decline1-3

ONPATTRO® (patisiran) can reverse polyneuropathy manifestations of the disease4 A novel RNAi-based approach that may transform the future for your patients1,4-6 ONPATTRO is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

At 18 months, ONPATTRO demonstrated: Reversal in neuropathy impairment4

Study Design Important Safety Information Infusion-Related Reactions (IRRs) In a controlled clinical study, 19% of ONPATTROtreated patients experienced IRRs, compared to 9% of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache.

To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.

Reduced Serum Vitamin A Levels and Recommended Supplementation ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking ONPATTRO. Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g. night blindness).

Adverse Reactions The most common adverse reactions that occurred in patients treated with ONPATTRO were upper respiratory tract infections (29%) and infusion-related reactions (19%).

Please see brief summary of full Prescribing Information following this ad.

References: 1. Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis. 2013; 8:31. 2. Coutinho P, Martins da Silva A, Lopes Lima JL, et al. Excerpta Medica; 1980:88-98.

3. Vinik EJ, Vinik AI, Paulson JF, et al. J Peripher Nerv Syst. 2014;19:104-119. 4. ONPATTRO [package insert]. Cambridge, MA: Alnylam Pharmaceuticals, Inc; 2018.

5. Adams D, Coelho T, Obici L, et al. Neurology. 2015;85(8):675-682. 6. Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. N Engl J Med. 2018;379(1):11-21. 7. Center for Drug Evaluation and Research. NDA 210922—patisiran—cross-discipline team leader review. U.S. Department of Health and Human Services, Food and Drug Administration; 2018.

ONPATTRO is a registered trademark of Alnylam Pharmaceuticals, Inc. © 2019 Alnylam Pharmaceuticals, Inc. All rights reserved. TTR02-USA-00023-012019

The efficacy of ONPATTRO was demonstrated in a randomized, double-blind, placebo-controlled, multicenter clinical trial in adults with hATTR amyloidosis with polyneuropathy. Patients were randomized to receive ONPATTRO 0.3 mg/kg (N=148) or placebo (N=77) via intravenous infusion once every 3 weeks for 18 months.

Primary endpoint: The modified Neuropathy Impairment Score + 7 (mNIS+7) is an objective 304-point assessment of neuropathy that measures cranial nerve function, muscle strength, reflexes, postural blood pressure, quantitative sensory testing, and peripheral nerve electrophysiology.

Key secondary endpoint: The Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) scale is a patient-reported assessment that evaluates neuropathy in the following domains: physical functioning/large fiber neuropathy, activities of daily living, symptoms, small fiber neuropathy, and autonomic neuropathy (score range -4 to 136).

Select secondary endpoint: The Composite Autonomic Symptom Score 31 (COMPASS 31) is a patient-reported questionnaire that evaluates 6 autonomic domains: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor (score range 0 to 100).

• Mean change from baseline in mNIS+7 of -6.0 points vs 28.0 with placebo, a treatment difference of -34 points (95% CI: -39.9, -28.1; p<0.001)

Improvement in quality of life4 • Mean change from baseline in Norfolk QoL-DN score of -6.7 points vs 14.4 with placebo, a treatment difference of -21.1 points (95% CI: -27.2, -15.0; p<0.001)

Reduction in autonomic symptoms6,7 • Mean change from baseline in COMPASS 31 of -5.3 points vs 2.2 with placebo, a treatment difference of -7.5 points (95% CI: -11.9, -3.2; p<0.001) CI=confidence interval; RNA=ribonucleic acid; RNAi=RNA interference.

Visit Booth #2401 to find out more.

Tomorrow’s Plenary to Showcase Top Research over the Past Year Tomorrow’s daylong Grand Finale lineup will kick off at 9:15 a.m. in the Terrace Ballroom with the Neurology Year in Review Plenary Session. AAN Science Committee member Martinson K. Arnan, MD, of Bronson Neuroscience Center/Western Michigan University, Kalamazoo, MI, will moderate and be joined by six expert speakers who will focus on the latest research that has happened in the last year within a specific subspecialty topic.

Arnan The Evolving Landscape of

Amyotrophic Lateral Sclerosis Jinsy Andrews, MD, FAAN Columbia University Medical Center, New York, NY

Neurology of Pregnancy

Sleep

Annette M. Langer-Gould, MD, PhD Kaiser Permanente Southern California, Pasadena, CA

Alberto Ramos, MD Miller School of Medicine, Miami, FL

Langer-Gould

Ramos

Andrews Non-Alzheimer’s Dementia

B:11.125” T:10.875” S:9.875”

and Cognitive Neurology Lauren R. Moo, MD Massachusetts General Hospital, Boston, MA

Moo

Emerging Neuromodulation

Neuromyelitis Optica Spectrum

Strategies for Traumatic Myelopathies Leif A. Havton, MD, PhD UCLA School of Medicine, Los Angeles, CA

Disorders: What a Difference a Few Years Makes Stacey Clardy, MD, PhD University of Utah, Salt Lake City, UT

Clardy

Havton

Share your "aha" moment from tomorrow’s plenary session at #AANAM. 

BEFORE YOU GO:

Don’t Forget to Complete Your Evaluations to Claim Your Annual Meeting CME!

May 20 is the deadline to complete your evaluations to get your CME credits for the courses you attended this week. You can complete your evaluations quickly and easily using the AAN Conferences App available at AAN.com/view/MobileApp or by visiting AAN.com/view/CME. 

Thursday, May 9, 2019 • AANextra

9

Aging and Dementia Highlighted in Today’s Invited Science Session Cutting-edge science in Alzheimer’s disease and related dementias will be highlighted in today’s Invited Science Session from 3:30 p.m. to 5:30 p.m. in Room 203 AB. The session, in collaboration with the Alzheimer’s Association and the Alzheimer’s Association International Congress, will focus on basic, translational, and clinical sciences related to genetics, pathophysiology, and therapeutic approaches as they evolve toward a more complete understanding of dementia, emerging trends, and impact on global health.

Abstracts and authors include: 3:30 p.m.–3:35 p.m.

Thursday's AAN Section Meetings

12:00 p.m.–1:00 p.m.

Pain and Palliative Care Section 103 A

Introduction Karen S. Marder, MD, MPH, FAAN, New York, NY, and Heather M. Snyder, PhD, Chicago, IL

History Section 103 B

A Randomized Trial of Intensive Versus Standard Systolic Blood Pressure Control on Brain Structure: Results from SPRINT MIND MRI Ilya Nasrallah, MD, PhD, Philadelphia, PA

4:00 p.m.–5:00 p.m.

3:35 p.m.–3:55 p.m.

US Perspective on Clinical Amyloid Imaging Ronald C. Petersen, PhD, MD, FAAN, Rochester, MN

3:55 p.m.–4:15 p.m.

Challenges in Using CSF Biomarkers for Operationalizing the NIA-AA AD Research Framework Michelle M. Mielke, PhD, Rochester, MN

4:15 p.m.–4:35 p.m.

Medical Management—Recommendations from the Dementia Care Practice Recommendations Mary Guerriero Austrom, PhD, Indianapolis, IN

4:35 p.m.–4:55 p.m.

The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) Study—Report of Screening Data Results Rema Raman, PhD, San Diego, CA 4:55 p.m.–5:15 p.m.

US Perspective on Clinical Amyloid Imaging Ronald C. Petersen, PhD, MD, FAAN, Rochester, MN

Neuroimaging Section 103 A

INDUSTRY THERAPEUTIC UPDATE FROM AVEXIS A NEW FRONTIER FOR NEUROMUSCULAR DISORDERS: SPOTLIGHT ON GENE THERAPY Wednesday May 8 2019, 7:00 PM for 7:30 PM start* Room: Liberty Ballroom, Philadelphia Marriott Downtown

Faculty:

Perry Shieh, MD, PhD (Chair) Meredith Schultz, MD Christopher Walker, PhD Chris Jenkins, PhD *Dinner to be served at 7:00 PM

The Faculty of experts will explore the latest advances in gene therapy (GT) research and the use of GT in the clinical treatment of neuromuscular diseases, taking the treatment from bench to bedside.

Time

Presentation Title

7:00 – 7:30 PM

Dinner reception

7:30 – 7:35 PM

Welcome and introduction

Perry Shieh, MD, PhD (Chair)

7:35 – 7:55 PM

Gene therapies: a new frontier for neuromuscular disorders

Meredith Schultz, MD

7:55 – 8:15 PM

A focus on adeno-associated virus (AAV) antibodies

Christopher Walker, PhD

8:15 – 8:35 PM

Biosafety considerations for the clinical use of AAVs

Chris Jenkins, PhD

8:35 – 8:45 PM

Panel discussion

All Speakers Facilitated by Chair

8:45 – 8:55 PM

Questions and answers

All Speakers Facilitated by Chair

8:55 – 9:00 PM

Closing remarks

Perry Shieh, MD, PhD (Chair)

5:15 p.m.–5:30 p.m.

Questions and Answers Faculty 

Faculty Member

In accordance with Federal Law, all food and beverage are reportable. You will have the opportunity to opt-out of food and beverage upon arrival at the Liberty Ballroom, Philadelphia Marriott Downtown This meeting is not part of the AAN Annual Meeting official programming and no CME is given for attendance.

This Industry Therapeutic Update is sponsored and organized by AveXis. ©2019 AveXis, Inc. All Rights Reserved.

10

Thursday, May 9, 2019 • AANextra

MED-CON-UNB-00019-US 04/2019

Upcoming AAN Conference Opportunities 2019 SPORTS CONCUSSION CONFERENCE

2019 FALL CONFERENCE

July 26–28, 2019

The Cosmopolitan of Las Vegas

JW Marriott, Indianapolis, IN

SPORTS CONCUSSION JULY 26–28, 2019 INDIANAPOLIS, IN

CONFERENCE

Discover the latest scientific advances and best practices for the prevention, diagnosis, and treatment of sports-related concussion from youth on up to professional levels. Look for an updated bootcamp offering more hands-on training than ever before; a session specifically for athletic trainers that will focus on sideline evaluation and management of concussion; a report from the CDC, including an overview of the CDC’s role in sports concussion prevention; a keynote address on The Science of Concussion: Perspectives from the Department of Defense; and a special reception at the NCAA Hall of Champions. Learn more and register at AAN.com/view/SCC.

Seeking Concussion-related Abstracts May 16 is the deadline to submit scientific abstracts for the 2019 Sports Concussion Conference. Previously presented work is encouraged if it is of interest to the field.

Visit AAN.com/view/SCC for more on submission guidelines and to submit.

October 18-20, 2019 Get the latest updates in neurology and practice management from expert faculty—plus valuable end-of-year CME. The Fall Conference’s all-inclusive registration rate provides maximum value, flexibility, and customization, allowing you to tailor a personal schedule to your specific interests and needs. New this year will be a oneday pre-conference designed specifically for advanced practice providers. Registration will open in June. Visit AAN.com/view/19FC for more information.

“We’re excited to introduce this new opportunity to help emerging directors as they learn how to be most effective in these crucial roles.”

—Jaffar Khan, MD, FAAN

Chair of the AAN Graduate Education Subcommittee and member of the Education Committee

Toronto, ON, Canada

Be sure to stop by the 2020 Toronto Booth in Exhibit Hall E to preview all the fun Toronto attractions. Sign up at AAN.com/view/AM20Interest to be notified when call for abstracts and registration opens 

EBM Online is available in the Academy’s new Online Learning Center. The program: Contains five hours of on-demand

Smith

courses in 10 modules

Allows learners to review core concepts and diagnostic and

statistical tools at their own pace and convenience

New AAN Leadership Program Provides Guidance for New Directors The AAN is expanding its Leadership Programs to include mentorship for new clerkship directors, program directors, and fellowship directors.

The 12-month program will provide new directors, defined as those within their role for less than two years, with practical advice and guidance from seasoned directors, defined as those who have served in the role for more than three years. Both mentors and mentees were selected through an application process. The program is designed to encourage directors’ personal growth, enhance their career development, and increase their engagement with the AAN.

LEARN ABOUT A NEW ORAL TREATMENT FOR MULTIPLE SCLEROSIS

The AAN has converted and refined its popular classroom evidence-based medicine training into a convenient ondemand, self-paced online program that is free to all AAN members.

Uses common, real-life neurologic clinical examples

2020 ANNUAL MEETING IN TORONTO April 25–May 1, 2020

Understand Evidenced-based Medicine with EBM Online

“The AAN's online evidence-based medicine course is comprehensive and user-paced,” said Don B. Smith, MD, FAAN, member of the eLearning Subcommittee and AAN EBM methodologist. “It covers topics ranging from formulating evidence-answerable questions to conducting a meta-analysis.

It teaches how to search for relevant evidence, how to assess for bias, how to calculate and evaluate effect sizes, and how to assess the generalizability of evidence. It also explores weighting the risks and benefits of a proposed treatment according to a patient's values. AAN members have found the course to be a great value. Check it out!”

For a number of years, the Academy’s EBM training was available only to residents and program directors. The latter have found the program useful to teach EBM concepts in an easy-to-understand manner, supplement/replace EBM instruction in journal club or clinical rounds, and monitor residents' progress and track their scores. And course completion statistics can be a barometer for meeting ACGME core competencies.

Learn more and sign up (or sign your residents up) for this free AAN member benefit at AAN.com/view/EBMOnline. 

Mentorship pairs will take part in an orientation at the Annual Meeting and then touch base with quarterly phone calls based on the academic calendar, reviewing what is coming up in the next quarter and discussing any challenges from the previous quarter.

y l n o re b Memnefit Be

E E FR

“We’re excited to introduce this new opportunity to help emerging directors as they learn how to be most effective in these crucial roles,” said Jaffar Khan, MD, FAAN, chair of the AAN Graduate Education Subcommittee and member of the Education Committee. “The Annual Meeting is the perfect time to bring people together to share their questions and the skills and knowledge they have learned over the years.” 

Visit Booth ©2019 EMD Serono, Inc. All rights reserved.

Printed in the USA US/NPR/0319/0198 03/19

2313

Thursday, May 9, 2019 • AANextra

13

Commitment to Cures Celebrates Brain Research and Public Leaders The American Brain Foundation held its annual Commitment to Cures event last evening at the historic Union League of Philadelphia. The dinner and fundraiser supports the Foundation’s research mission by offering an opportunity for leaders in neurology to honor prestigious members of the public for their contributions to finding cures for brain diseases through advocacy, public awareness, and fundraising.

What’s the key to breakthrough Neuro research and treatments?

Collaboration. At NewYork-Presbyterian Hospital, we partner with specialists

Former Pennsylvania Governor Ed Rendell joined Romney and Lurie for an informal discussion about the urgent need to discover cures and treatments for brain diseases. Rendell spoke of this

Photo of the event T:10.875”

Brain Tumors • The first-ever dose escalation study using convection-enhanced delivery for diffuse intrinsic pontine glioma to bypass the blood-brain barrier and administer a drug directly to the brain stem tumor site.

Philadelphia Eagles owner and movie producer Jeffrey Lurie was honored with the Foundation’s Commitment to Cures Award.

recent diagnosis of Parkinson’s disease and the impact that has had on his life and family. 

Former first lady of Massachusetts Ann Romney received the Public Leadership in Neurology Award for her tireless advocacy in raising awareness of and research for multiple sclerosis, as well as her collaboration in the Ann

from Columbia University Vagelos College of Physicians and Surgeons and Weill Cornell Medicine to provide care to thousands of neurology and neurosurgery patients. Faculty from both medical schools are at the forefront of conducting research and clinical studies for a wide range of conditions. Recent advances include: Alzheimer’s • A study that uncovered large-scale changes throughout the epigenome of the human Alzheimer’s disease brain, revealing that tau-induced alterations of chromatin structure are more profound than changes attributable to amyloid pathology.

• The launch of our new Alzheimer’s Prevention Clinic that combines evidence-based, low-risk interventions with lifestyle modifications that may help to delay, or in some cases possibly prevent, the progression towards dementia.

Romney Center for Neurologic Diseases at Brigham and Women’s Hospital.

Stroke • Participated in the DEFUSE trial which has shown the benefit of late thrombectomy from 6 to 24 hours past onset of a large vessel occlusive stroke.

Because of these innovations and more, our Neurology and Neurosurgery program is ranked #1 in New York and #5 in the nation by U.S. News & World Report.

Photo of the event

Learn more at nyp.org/neuroinnovations

Photo of the event New York’s #1 hospital for a reason.

Source: New York’s #1 hospital as ranked by U.S. News & World Report 2018-19

Thursday, May 9, 2019 • AANextra

15

Today’s Experiential Learning Area Highlights HeadTalks Rocky’s Legacy: Historical Controversies of Boxing-related Concussions 1:30 p.m.–2:30 p.m.

Don’t miss this engaging discussion as concussion experts Tad Dean Seifert, MD; Barry D. Jordan, MD; and Anthony G. Alessi, MD, FAAN, review the history and controversies surrounding the sport of boxing.

Live Well: Taking Care of Your Patients Starts with Taking Care of You How Your Social Life Might Be Helping (or Harming) Your Brain 11:45 a.m.–12:30 p.m.

Evidence implicating social and behavioral influences, such as social isolation, with higher risk of stroke, cognitive dysfunction, and accumulation of Alzheimer's disease pathology suggests that healthy cognitive aging may be heavily influenced by social relationships, a largely unexplained modifiable risk factor that represents the combined effect of distinct functional

(social support) and structural (social network) elements. Joel Armando Salinas, MD, will examine the existing evidence supporting this association and discuss challenges and opportunities in its study.

Maximize Your Value and Advocacy to Action Innovative Ways to Decrease Wait Times in Your Practice 2:00 p.m.–2:45 p.m.

Explore technology and practice management tools to decrease wait times and improve patient satisfaction with Jason J. Sico, MD, FAAN.

Research Corner

Navigating Your Career

Experience the AAN

Don't miss this tomorrow

Neurohospitalist Career Choices: A Growing Landscape

Connect with more than 20,000 professionals in your subspecialty area of interest on Synapse Online Communities. 

Grant Writing 101: Getting Started Friday, 7:00 a.m.–7:30 a.m.

In tomorrow’s session, Logan D. Schneider, MD, will touch upon the many facets of grant writing, many of which are known, but the aspects of which may be overlooked and the subtleties of which often lack formal discussion. In sharing some fundamentals of grant writing, a framework for getting started on the first or next grant can benefit most individuals but is meant for inexperienced grant writers.

2:00 p.m.–2:45 p.m.

Neurohospitalist careers have exploded in popularity in the last decade. S. Andrew Josephson, MD, FAAN, will explore the options for this exciting career choice.

Caption: Gkfjksdk kjhgdsfg oiudfgiorejtiodfg oij lfghfg jkbcjfbkhfncbk

Need new caption Wednesday HeadTalks / The Zoo Called—You Have a Consult / 1:30 p.m.–2:30 p.m.

Wednesday Research Corner / Recruiting Underrepresented Populations into Trials / 8:00 a.m.–8:30 a.m.

Investigators frequently note that there can be difficulty in recruiting underrepresented populations. Temitayo Oyegbile, MD, PhD, addressed reasons for this difficulty in recruiting these populations and potential solutions and strategies to address the problem in this Research Corner session.

AAN Vice President Ann H. Tilton, MD, FAAN, shared her stories of zoo experiences and lessons learned—with some actual [nonhuman] animals joining in to add to the fun!

16

Thursday, May 9, 2019 • AANextra

Thursday, May 9, 2019 • AANextra

17

What excited you today at #AANAM? Join the conversation at #AANAM

+

RELENTLESS IN OUR PURSUIT

of INNOVATIVE neuroscience

Our focus on neuroscience, our deep scientific expertise, and our courage to take risks continue to make us leaders in the research and development of medicines to transform neuroscience and benefit society.

Our mission is strengthened by engaging the scientists, researchers, and medical professionals attending the 2019 AAN Annual Meeting. We know that, working with you, we can continue to bring patients the treatments and hope they deserve.

Discover more at Biogen.com ©2019 Biogen. All rights reserved. 04/19 FCH-US-4749

Thursday, May 9, 2019 • AANextra

19

What Are Your Colleagues Saying?

Share your thoughts at #AANAM. Join the conversation!

THURSDAY, MAY 9 11:30 A.M. TO 1:00 P.M.

#AANAM

Locations: Exhibit Hall E (limited quantities available at Broad Street Atrium)

Boxed Lunch Menu Lunch Options Option I: Smoked Turkey Wrap with Brie and Cranberry Mayo Chips Fruit

Option II Vegan/Vegetarian/Gluten Free: Grilled Eggplant and Hummus Wrap Chips Fruit

FRIDAY, MAY 10 11:30 A.M. TO 1:00 P.M. Location: Exhibit Hall E Friday’s lunch will be available in Exhibit Hall E as the poster hall transforms to highlight abstracts and talks as they relate to the neuroimaging community.

20

Thursday, May 9, 2019 • AANextra

Thursday, May 9, 2019 • AANextra

21

THE FIRST FDA-APPROVED TREATMENT INDICATED FOR ADULTS WITH TARDIVE DYSKINESIA (TD)1

for oral use

Brief Summary: for full Prescribing Information and Patient Information, refer to package insert.

INDICATIONS AND USAGE

Postmarketing Experience

INGREZZA® is indicated for the treatment of adults with tardive dyskinesia.

ONE CAPSULE, ONCE DAILY

CONTRAINDICATIONS

INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.

1

WARNINGS AND PRECAUTIONS

Convenient, once-daily dosing without complex titration1

Somnolence

INGREZZA can cause somnolence. Patients should not perform activities requiring mental alertness such as operating a motor vehicle or operating hazardous machinery until they know how they will be affected by INGREZZA.

Not actual size

QT Prolongation

• INGREZZA 80 mg provided rapid and significant reductions in TD severity by 6 weeks1,2 —with continued reductions in TD severity through 48 weeks1,3

INGREZZA may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. In patients taking a strong CYP2D6 or CYP3A4 inhibitor, or who are CYP2D6 poor metabolizers, INGREZZA concentrations may be higher and QT prolongation clinically significant. For patients who are CYP2D6 poor metabolizers or are taking a strong CYP2D6 inhibitor, dose reduction may be necessary. For patients taking a strong CYP3A4 inhibitor, reduce the dose of INGREZZA to 40 mg once daily.

INGREZZA should be avoided in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage.

• Generally well tolerated in clinical trials across a broad range of adult TD patients1,2 • Selectively inhibits VMAT2, with no appreciable binding affinity for serotonergic or dopaminergic receptors1

Endocrine Disorders: blood glucose increased General Disorders: weight increased Infectious Disorders: respiratory infections Neurologic Disorders: drooling, dyskinesia, extrapyramidal symptoms (non-akathisia) Psychiatric Disorders: anxiety, insomnia During controlled trials, there was a dose-related increase in prolactin. Additionally, there was a dose-related increase in alkaline phosphatase and bilirubin, suggesting a potential risk for cholestasis.

The following adverse reactions have been identified during post-approval use of INGREZZA that are not included in other sections of labeling. 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.

Immune System Disorders: hypersensitivity reactions (including allergic dermatitis, angioedema, pruritis, and urticaria) Skin and Subcutaneous Tissue Disorders: rash

DRUG INTERACTIONS

Drugs Having Clinically Important Interactions with INGREZZA Table 2: Clinically Significant Drug Interactions with INGREZZA Monoamine Oxidase Inhibitors (MAOIs) Clinical Implication: Concomitant use of INGREZZA with MAOIs may increase the concentration of monoamine neurotransmitters in synapses, potentially leading to increased risk of adverse reactions such as serotonin syndrome, or attenuated treatment effect of INGREZZA. Prevention or Avoid concomitant use of INGREZZA with MAOIs. Management:

ADVERSE REACTIONS

Examples: isocarboxazid, phenelzine, selegiline Strong CYP3A4 Inhibitors Clinical Implication: Concomitant use of INGREZZA with strong CYP3A4 inhibitors increased the exposure (Cmax and AUC) to valbenazine and its active metabolite compared with the use of INGREZZA alone.

Increased exposure of valbenazine and its active metabolite may increase the risk of exposure-related adverse reactions.

Prevention or Reduce INGREZZA dose when INGREZZA is coadministered with a strong CYP3A4 inhibitor.

Management:

The following adverse reactions are discussed in more detail in other sections of the labeling: • Hypersensitivity • Somnolence • QT Prolongation

• Offers convenient, once-daily dosing without complex titration1

Clinical Trials Experience VMAT2, vesicular monoamine transporter 2.

Not an actual patient

I S I T T D O R A C U T E E P S ? | TA K E T H E T D C H A L L E N G E AT B O OT H # 9 0 0 EPS, extrapyramidal symptoms.

W W W. I N G R E Z Z A H C P. C O M

Important Information INDICATION & USAGE

INGREZZA® (valbenazine) capsules is indicated for the treatment of adults with tardive dyskinesia.

IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS

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.

Variable and Fixed Dose Placebo-Controlled Trial Experience The safety of INGREZZA was evaluated in 3 placebo-controlled studies, each 6 weeks in duration (fixed dose, dose escalation, dose reduction), including 445 patients. Patients were 26 to 84 years of age with moderate to severe tardive dyskinesia and had concurrent diagnoses of mood disorder (27%) or schizophrenia/ schizoaffective disorder (72%). The mean age was 56 years.

Patients were 57% Caucasian, 39% African-American, and 4% other. With respect to ethnicity, 28% were Hispanic or Latino. All subjects continued previous stable regimens of antipsychotics; 85% and 27% of subjects, respectively, were taking atypical and typical antipsychotic medications at study entry.

Adverse Reactions Leading to Discontinuation of Treatment A total of 3% of INGREZZA treated patients and 2% of placebo-treated patients discontinued because of adverse reactions.

Common Adverse Reactions Adverse reactions that occurred in the 3 placebo-controlled studies at an incidence of ≥2% and greater than placebo are presented in Table 1.

Table 1:

Adverse Reactions in 3 Placebo-Controlled Studies of 6-week Treatment Duration Reported at ≥2% and >Placebo

INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.

Adverse Reaction1

WARNINGS & PRECAUTIONS Somnolence

INGREZZA can cause somnolence. Patients should not perform activities requiring mental alertness such as operating a motor vehicle or operating hazardous machinery until they know how they will be affected by INGREZZA.

QT Prolongation

rifampin, carbamazepine, phenytoin, St. John’s wort1

Digoxin concentrations should be monitored when co-administering INGREZZA with digoxin. Increased digoxin exposure may increase the risk of exposure related adverse reactions. Dosage adjustment of digoxin may be necessary.

10.9%

4.2%

Nervous System Disorders Anticholinergic effects (dry mouth, constipation, disturbance in attention, vision blurred, urinary retention)

5.4%

4.9%

Prevention or Management:

2.2%

3.4% 2.7%

ADVERSE REACTIONS

Gastrointestinal Disorders Vomiting Nausea Musculoskeletal Disorders Arthralgia

©2019 Neurocrine Biosciences, Inc. All Rights Reserved. CP-VBZ-US-0525v2 5/19

Concomitant use of strong CYP3A4 inducers with INGREZZA is not recommended.

Examples: Digoxin Clinical Implication:

Headache Akathisia (akathisia, restlessness)

REFERENCES: 1. INGREZZA [package insert]. San Diego, CA: Neurocrine Biosciences, Inc; 2018. 2. Hauser RA, Factor SA, Marder SR, et al. KINECT 3: a phase 3 randomized, double-blind, placebo-controlled trial of valbenazine for tardive dyskinesia. Am J Psychiatry. 2017;174(5):476-484. 3. Factor SA, Remington G, Comella CL, et al. The effects of valbenazine in participants with tardive dyskinesia: results of the 1-Year KINECT 3 extension study. J Clin Psychiatry. 2017;78(9):1344-1350.

Prevention or Management:

General Disorders Somnolence (somnolence, fatigue, sedation)

4.1%

Please see the adjacent page for brief summary of Prescribing Information and visit www.INGREZZAHCP.com/PI for full Prescribing Information.

paroxetine, fluoxetine, quinidine

Placebo (n=183) (%)

Balance disorders/fall (fall, gait disturbance, dizziness, balance disorder)

1

Examples: Strong CYP3A4 Inducers Clinical Implication:

INGREZZA (n=262) (%)

INGREZZA may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. INGREZZA should be avoided in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage.

The most common adverse reaction (≥5% and twice the rate of placebo) is somnolence. Other adverse reactions (≥2% and >placebo) include: anticholinergic effects, balance disorders/falls, headache, akathisia, vomiting, nausea, and arthralgia.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088.

Examples: itraconazole, ketoconazole, clarithromycin Strong CYP2D6 Inhibitors Clinical Implication: Concomitant use of INGREZZA with strong CYP2D6 inhibitors may increase the exposure (Cmax and AUC) to valbenazine’s active metabolite compared with the use of INGREZZA alone. Increased exposure of active metabolite may increase the risk of exposurerelated adverse reactions.

Prevention or Consider reducing INGREZZA dose based on tolerability when INGREZZA is coadministered with a strong CYP2D6 inhibitor.

Management:

2.7% 0.5%

1

Concomitant use of INGREZZA with a strong CYP3A4 inducer decreased the exposure of valbenazine and its active metabolite compared to the use of INGREZZA alone. Reduced exposure of valbenazine and its active metabolite may reduce efficacy.

Concomitant use of INGREZZA with digoxin increased digoxin levels because of inhibition of intestinal P-glycoprotein (P-gp).

The induction potency of St. John’s wort may vary widely based on preparation.

Drugs Having No Clinically Important Interactions with INGREZZA Dosage adjustment for INGREZZA is not necessary when used in combination with substrates of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2E1, or CYP3A4/5 based on in vitro study results.

OVERDOSAGE

Human Experience 2.6% 2.3%

0.6% 2.1%

2.3%

0.5%

Within each adverse reaction category, the observed adverse reactions are listed in order of decreasing frequency.

Other Adverse Reactions Observed During the Premarketing Evaluation of INGREZZA

Other adverse reactions of ≥1% incidence and greater than placebo are shown below. The following list does not include adverse reactions: 1) already listed in previous tables or elsewhere in the labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have clinically significant implications, or 5) which occurred at a rate equal to or less than placebo.

The pre-marketing clinical trials involving INGREZZA in approximately 850 subjects do not provide information regarding symptoms with overdose.

Management of Overdosage No specific antidotes for INGREZZA are known. In managing overdose, provide supportive care, including close medical supervision and monitoring, and consider the possibility of multiple drug involvement. If an overdose occurs, consult a Certified Poison Control Center (1-800-222-1222 or www.poison.org).

For further information on INGREZZA, call 84-INGREZZA (844-647-3992).

Distributed by: Neurocrine Biosciences, Inc. San Diego, CA 92130 INGREZZA is a registered trademark of Neurocrine Biosciences, Inc. CP-VBZ-US-0203v3 08/18

Participant Credits Diversity Leadership Program with Reducing Burnout, More Burnout. It’s a word—a feeling—that is increasingly prevalent in the medical field, with neurologists experiencing among the highest rates. While many factors contribute to it, one AAN Leadership Program participant specifically credits the critical thinking, skills, and knowledge he gained from the Diversity Leadership Program with helping him combat this serious issue.

“I feel participation in the Diversity Leadership Program and my subsequent involvement in the Academy have helped decrease my burnout,” said 2015 graduate Roderick C. Spears, MD, FAAN, “which is ironic, I think, because it has actually required more energy and time.”

But the added time has come with great payoff, according to Spears, who is a neurologist at the University of Pennsylvania specializing in headache medicine. “It has been encouraging to participate in the process of changes occurring in the field and practice of neurology. I have been more proactive in my practice dealing with change and growth, such as recently adding an advanced practice provider. And I was selected to be on the Clinical and Professional Services Committee, which meets quarterly with the executive director and medical directors to discuss important matters affecting our division here at Penn.”

Discovering his own strengths—and weaknesses—and learning how to assess others through the program’s Insight Training was one of the highlights for Spears, and it provided important principles that he applies on a daily basis. “My single greatest accomplishment has been being selected to act as a liaison between the two departments I am a part of and report to the executive director and chair of my department on overlapping concerns.”

Spears also feels his Diversity Leadership Program experience primed him for his role on the AAN Practice Committee. “[I got an] excellent education about the AAN and the different opportunities available to serve the Academy and contribute to neurology as a field. It was also great to meet new people in the Academy motivated to contribute to the well-being of members, patients, and others involved in neurology. This has flowed well with my position on the AAN Practice Committee where similar issues are discussed and action plans are developed.”

Added Spears, “I would recommend the program to anyone interested in learning more about the Academy, being a leader, and getting more involved with AAN and in their local practice.”

The Diversity Leadership Program is a prestigious and interactive program designed to develop and engage a more diverse membership and demonstrate to participants the long-term benefits of AAN involvement. The program is designed for talented and highly motivated individuals at any stage in their post-residency

career who are committed to the profession of neurology and to providing high-quality patient-centered care, and are US AAN Spears members from one of the following underrepresented minority groups: African American/Black, Hispanic/Latino, American Indian, Native Hawaiian, or Alaska Native ethnicity. Visit AAN.com/view/ DiversityLeadership to learn more.

The Diversity Leadership Program has been supported in part

by ACADIA Pharmaceuticals, Inc., Allergan, Inc., Eli Lilly & Company, Neurocrine Biosciences, Sanofi Genzyme, Supernus Pharmaceuticals, Inc. and UCB, Inc.

The Best of Philly from Those Who Know It Best As America’s birthplace, Philadelphia is the nation’s first World Heritage City, not to mention the home of the first medical school and first neurology program. Where else can you walk from the sites where political luminaries debated standing up to a king to the home of one of the largest collections of Rodin sculptures outside of Paris before making your way to grab an authentic hoagie?

Philadelphia’s top-tier attractions are part of why it’s consistently ranked as one of the top places to visit in the United States, and we hope you'll enjoy exploring the city while you're in town for the Annual Meeting.

Visit the Philadelphia visitors booths (Broad Street Atrium, spiral staircase on the 200 Level Bridge, or 12 and Arch Street- West Concourse) for more local information, including brochures and help making restaurant reservations. 

Need some ideas? Here you go!

Applications Now Open for Four AAN Leadership Program Opportunities

Applications are open until June 17 for four empowering opportunities for AAN members designed specifically to equip participants with the skills, tools, and confidence to successfully tackle the challenges that lie ahead.

Past participants of these all-expenses-paid programs have found them to be incredibly valuable, citing the personalized coaching with industry leading consultants, mentorship by neurology leaders, and expansion of professional network as particularly impactful.

Transforming Leaders - Designed to help innovative leaders

realize their goals through executive-level coaching and a fully customized intensive leadership development training program.

Cheesesteaks galore!

So many cheesesteaks, so little time! The debate over who makes the best cheesesteak is one that has lasted for decades. From which cheese (provolone, American, or the legendary gooey, artificially flavored Cheez Whiz), to the frying of the onions—Chopped? Caramelized? Sliced?—ight down to who has the best bread, or as we Philadelphians call it, “the roll.” Philly cheesesteaks are more than a local phenomenon and clearly something to be taken very seriously.

The Philly cheesesteak choices are endless. Consider the "Wiz Wit," a Philly term that any true cheesesteak connoisseur should be familiar with. This is a cheesesteak with whiz (MUST be artfully blended with the meat and NEVER just slopped on top!) and fried onions.

Judge for yourself by giving these Philly cheesesteak hotspots a try: Jim’s Steaks, Tony Luke’s, Pat’s King of Steaks, Geno’s Steaks, Steve’s Prince of Steaks, or Dalessandro's!

—Brad C. Klein, MD, MBA, FAAN Abington Neurological Associates, Willow Grove, PA Chair, Medical Economics and Practice Committee Ex officio voting member, AAN Institute Board of Directors

What are your Philly recommendations?

Join the conversation at #AANAM

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.

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.

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.

Visit AAN.com/view/LEAD to learn more or apply by the June 17 deadline. 

24

Thursday, May 9, 2019 • AANextra

Thursday, May 9, 2019 • AANextra

25

NOW

Friday’s Experiential Learning Area Highlights HeadTalks

Maximize Your Value and Advocacy to Action

NeuroZone 4:30 p.m.–5:30 p.m.

in The Grand Experience

Growing Research in Medical Marijuana

Gear up for the Closing Party with this madcap series of game show challenges.

Will your fellow attendees survive these tests and trials? Who will emerge victorious? Don’t miss this zany finish to a week of fun with Bert B. Vargas, MD, FAAN; Jennifer Bickel, MD, FAAN; Mark Milstein, MD, FAAN; and Wayne E. Anderson, MD, FAAN.

1:00 p.m.–1:45 p.m.

Live Well: Taking Care of Your Patients Starts with Taking Care of You

8:00 a.m.–8:30 a.m.

Acupuncture Demonstration —Auriculotherapy 1:00 p.m.–1:45 p.m.

Receive an introduction to auriculotherapy from a neurologist also certified in acupuncture—Jennifer Bickel, MD, FAAN. Auriculotherapy is a form of acupuncture focused on the external ear, which is widely used throughout the US military and VA systems. Treatments are tailored for general pain relief and relaxation.

Waiver required.

Anup Patel, MD, FAAN, will discuss updates on research in medical marijuana.

Research Corner How to Put Together an Effective Research Presentation Grand Hall, Grand Experience / Stage 1 Learn tips and tricks from Enrique C. Leira, MD, MS, FAAN, to improve your research proposals.

Navigating Your Career How to Give Effective Feedback 8:00 a.m.–8:45 a.m.

Room 202 AB

Effective feedback must be individualized; expectations must be appropriate for the level of the recipient. Feedback should include reflection, ample sincere praise, and constructive criticism. Most feedback,

AVA I LA B LE

especially praise, can be delivered in a group setting. In-person feedback should be followed by written narrative comments.

In this interactive session presented by Diana M. Barratt, MD, MPH, FAAN; Farah Yolanda Fourcand, MD; Jill S. Liebman, DO; Adnan Subei, DO; and Maryam Shakir, MPH, trainees, clerkship and program directors will reenact common scenarios, and audience members will assess the participants and provide feedback.

Finally, there’s a whole new path to explore

Choosing a Career in Neuro-oncology 2:00 p.m.–2:45 p.m.

Room 202 AB

Booth 2129

Sylvia C. Kurz, MD, PhD, discusses neurooncology, a rapidly expanding field to which many trainees have little exposure during their training. A rewarding and exciting field, it also offers broad research opportunities.

Follow the footprints in the exhibit hall and discover EPIDIOLEX® (cannabidiol) Cv

Experience the AAN Learn how to make AAN.com work for you and your specific professional needs.  Caption

Greenwich Biosciences is growing innovation Photo of the event day

Photo of the event day

Step into the growing and manufacturing process with a virtual reality experience at the booth.

Visit EPIDIOLEXhcp.com for more information

Caption

©2019 Greenwich Biosciences Inc. All rights reserved. EPX-04965-0319

26

Thursday, May 9, 2019 • AANextra

Find the Latest Research at Today’s Poster Session Today’s poster session runs from 11:30 a.m. to 6:30 p.m., with author standby taking place daily between 5:30 p.m. and 6:30 p.m.

To help you navigate your way to the breakthrough research of most interest to you, each of the five sessions in this year’s hall are arranged in 10 topic-related “neighborhoods.” The example below shows how making your way to your favorite poster is now as easy as 1-2-3. In addition, tours of similar-themed posters will occur daily during the poster hall’s open hours to help visitors focus in on their areas of interest.

Publication Code Example: P5.2-003 P5 = Poster Session Number 2 = Neighborhood 003 = Poster Board Number 

Poster Session 5 1. Aging, Dementia, Cognitive, and Behavioral Neurology: 1-001 to 1-032 2. MS and CNS Inflammatory Disease: 2-001 to 2-111 3. Cerebrovascular Disease and Interventional Neurology: 3-001 to 3-069 4. Neuromuscular Disease and Clinical Neurophysiology (EMG): 4-001 to 4-041 5. Epilepsy/Clinical Neurophysiology (EEG): 5-001 to 5-034 6. Neuro-rehabilitation; General Neurology; Child Neurology and Developmental Neurology: 6-001 to 6-070 7. Aging, Dementia, Cognitive, and Behavioral Neurology ePosters: 7-001 to 7-010 8. Movement Disorders: 8-001 to 8-050 9. Infectious Disease; Neurocritical Care; Practice, Policy, and Ethics: 9-001 to 9-078 10. Headache: 10-001 to 10-028

1 2 3

1-001-1-032

Thursday, May 9, 2019 • AANextra

3-001-3-069

4 5 6

4-001-4-041

5-001-5-034

6-001-6-070

7

7-001-7-010

ePosters

8 9 10

8-001-8-050

28

2-001-2-111

9-001-9-078

10-001-10-028

Thursday, May 9, 2019 • AANextra

29

VISIT US AT BOOTH #1413 I N P A R T I A L - O N S E T S E I Z U R E S 1…

The mountains of evidence support one powerful MONOTHERAPY choice2,3

11 POSITIVE

CLINICAL TRIALS FOR THE TREATMENT OF PARTIAL-ONSET SEIZURES2,3

guaranteed, for a minimum of 12 months* www.OxtellarXRhcp.com

SEE YOU NEXT YEAR TORONTO, CANADA

APRIL 25 –MAY 1, 2O2O

Visit AAN.com/view/AM20Interest

INDICATION Oxtellar XR® is indicated for the treatment of partial-onset seizures in patients 6 years of age and older.

CONTRAINDICATIONS Oxtellar XR is contraindicated in patients with a known hypersensitivity to oxcarbazepine, or to any of the components of Oxtellar XR, or to eslicarbazepine acetate. Reactions have included anaphylaxis and angioedema. *Terms and conditions apply.

Not actual patient. Fictionalized for illustrative purposes.

References: 1. Oxtellar XR [package insert]. Rockville, MD: Supernus Pharmaceuticals, Inc.; December 2018. 2. Glauser TA. Oxcarbazepine in the treatment of epilepsy. Pharmacotherapy. 2001;21(8):904-919. 3. French JA, Baroldi P, Brittain ST, Johnson JK; for PROSPER Investigators Study Group. Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial. Acta Neurol Scand. 2014;129:143-153.

Please refer to the brief summary of full Prescribing Information on adjacent pages, or visit www.OxtellarXR.com.

Oxtellar XR is a registered trademark of Supernus Pharmaceuticals, Inc. ©2019 Supernus Pharmaceuticals, Inc. All rights reserved. SPN.OXT.2019-0023

Powerfully evident choice

OXTELLAR XR® (oxcarbazepine) extended-release tablets, for oral use Brief Summary of Prescribing Information For full prescribing information, see Package Insert.

CONTRAINDICATIONS Oxtellar XR is contraindicated in patients with a known hypersensitivity to oxcarbazepine, to any of the components of Oxtellar XR, or to eslicarbazepine acetate. Reactions have included anaphylaxis and angioedema.

WARNINGS AND PRECAUTIONS Hyponatremia Clinically significant hyponatremia (sodium <125 mmol/L) may develop during Oxtellar XR® use. Serum sodium levels less than 125 mmol/L have occurred in immediate-release oxcarbazepine-treated patients generally in the first three months of treatment. However, clinically significant hyponatremia may develop more than a year after initiating therapy.

Most immediate-release oxcarbazepine-treated patients who developed hyponatremia were asymptomatic in clinical trials. However, some of these patients had their dosage reduced, discontinued, or had their fluid intake restricted for hyponatremia. Serum sodium levels returned toward normal when the dosage was reduced or discontinued, or when the patient was treated conservatively (e.g., fluid restriction).

Cases of symptomatic hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been reported during post-marketing use of immediate-release oxcarbazepine.

Among treated patients in a controlled trial of adjunctive therapy with Oxtellar XR® in 366 adults with complex partial seizures, 1 patient receiving 2400 mg experienced a severe reduction in serum sodium (117 mEq/L), requiring discontinuation from treatment, while 2 other patients receiving 1200 mg experienced serum sodium concentrations low enough (125 and 126 mEq/L) to require discontinuation from treatment. The overall incidence of clinically significant hyponatremia in patients treated with Oxtellar XR® was 1.2%, although slight shifts in serum sodium concentrations from Normal to Low (<135 mEq/L) were observed for the 2400 mg (6.5%) and 1200 mg (9.8%) groups compared to placebo (1.7%).

Measure serum sodium concentrations if patients develop symptoms of hyponatremia (e.g., nausea, malaise, headache, lethargy, confusion, obtunded consciousness, or increase in seizure frequency or severity). Consider measurement of serum sodium concentrations during treatment with Oxtellar XR®, particularly if the patient receives concomitant medications known to decrease serum sodium levels (for example, drugs associated with inappropriate ADH secretion).

Anaphylactic Reactions and Angioedema Rare cases of anaphylaxis and angioedema involving the larynx, glottis, lips, and eyelids have been reported in patients after taking the first or subsequent doses of immediate-release oxcarbazepine. Angioedema associated with laryngeal edema can be fatal. If a patient develops any of these reactions after treatment with Oxtellar XR®, discontinue the drug and initiate an alternative treatment. Do not rechallenge these patients with Oxtellar XR®.

Cross Hypersensitivity Reaction to Carbamazepine Approximately 25% to 30% of patients who have had hypersensitivity reactions to carbamazepine will experience hypersensitivity reactions with Oxtellar XR®. For this reason, patients should be specifically questioned about any prior experience with carbamazepine, and patients with a history of hypersensitivity reactions to carbamazepine should ordinarily be treated with Oxtellar XR® only if the potential benefit justifies the potential risk. Discontinue Oxtellar XR® immediately if signs or symptoms of hypersensitivity develop.

Serious Dermatological Reactions Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have occurred in both children and adults treated with immediate-release oxcarbazepine use.

The median time of onset for reported cases was 19 days. Such serious skin reactions may be life threatening, and some patients have required hospitalization with very rare reports of fatal outcome. Recurrence of the serious skin reactions following rechallenge with immediate-release oxcarbazepine has also been reported.

The reporting rate of TEN and SJS associated with immediaterelease oxcarbazepine use, which is generally accepted to be an underestimate due to underreporting, exceeds the background incidence rate estimates by a factor of 3- to 10-fold. Estimates of the background incidence rate for these serious skin reactions in the general population range between 0.5 to 6 cases per million-person years. Therefore, if a patient develops a skin reaction while taking Oxtellar XR®, consider discontinuing Oxtellar XR® use and prescribing another AED. Association with HLA-B*1502 Patients carrying the HLA-B*1502 allele may be at increased risk for SJS/TEN with Oxtellar XR® treatment.

Human Leukocyte Antigen (HLA) allele B*1502 increases the risk for developing SJS/TEN in patients treated with carbamazepine. The chemical structures of immediate-release oxcarbazepine and Oxtellar XR® are similar to that of carbamazepine. Available clinical evidence, and data from nonclinical studies showing a direct interaction between immediate-release oxcarbazepine and HLA-B*1502 protein, suggest that the HLA-B*1502 allele may also increase the risk for SJS/TEN with Oxtellar XR®.

The frequency of HLA-B*1502 allele ranges from 2 to 12% in Han Chinese populations, is about 8% in Thai populations, and above 15% in the Philippines and in some Malaysian populations. Allele frequencies up to about 2% and 6% have been reported in Korea and India, respectively.

The frequency of the HLA-B*1502 allele is negligible in people from European descent, several African populations, indigenous peoples of the Americas, Hispanic populations, and in Japanese (<1%).

Testing for the presence of the HLA-B*1502 allele should be considered in patients with ancestry in genetically at-risk populations, prior to initiating treatment with Oxtellar XR®. The use of Oxtellar XR® should be avoided in patients positive for HLA-B*1502 unless the benefits clearly outweigh the risks. Consideration should also be given to avoid the use of other drugs associated with SJS/TEN in HLA-B*1502 positive patients, when alternative therapies are otherwise equally acceptable. Screening is not generally recommended in patients from populations in which the prevalence of HLA-B*1502 is low, or in current Oxtellar XR® users, as the risk of SJS/TEN is largely confined to the first few months of therapy, regardless of HLA-B*1502 status.

The use of HLA-B*1502 genotyping has important limitations and must never substitute for appropriate clinical vigilance and patient management. The role of other possible factors in the development of, and morbidity from, SJS/TEN, such as antiepileptic drug (AED) dosage, compliance, concomitant medications, comorbidities, and the level of

dermatologic monitoring have not been well characterized.

Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including Oxtellar XR®, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed.

Risk by Indication for Antiepileptic Drugs in the Pooled Analysis Epilepsy: Placebo Patients with Events per 1000 Patients 1.0. Drug Patients with Events per 1000 patients 3.4. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 3.5. Risk Difference: Additional Drug Patients with Events per 1000 Patients 2.4.

Psychiatric: Placebo Patients with Events per 1000 Patients 5.7. Drug Patients with Events per 1000 patients 8.5. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 1.5. Risk Difference: Additional Drug Patients with Events per 1000 Patients 2.9.

Other: Placebo Patients with Events per 1000 Patients 1.0. Drug Patients with Events per 1000 patients 1.8. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 1.9. Risk Difference: Additional Drug Patients with Events per 1000 Patients 0.9. Total: Placebo Patients with Events per 1000 Patients 2.4. Drug Patients with Events per 1000 patients 4.3. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 1.8. Risk Difference: Additional Drug Patients with Events per 1000 Patients 1.9.

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

Anyone considering prescribing Oxtellar XR® or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during Oxtellar XR® treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

Withdrawal of AEDs As with most AEDs, Oxtellar XR® should be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. But if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/ Multi-Organ Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi-organ hypersensitivity, has occurred with immediate-release oxcarbazepine. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocaraditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. Oxtellar XR® should be discontinued if an alternative etiology for the signs and symptoms cannot be established.

Hematologic Reactions Rare reports of pancytopenia, agranulocytosis, and leukopenia have been seen in patients treated with immediate-release oxcarbazepine during post-marketing experience. Discontinuation of Oxtellar XR® should be considered if any evidence of these hematologic reactions develops.

Risk of Seizures in the Pregnant Patient Due to physiological changes during pregnancy, plasma concentrations of the active metabolite of oxcarbazepine, the 10-monohydroxy derivative (MHD), may gradually decrease throughout pregnancy. Monitor patients carefully during pregnancy and through the postpartum period because MHD concentrations may increase after delivery.

Risk of Seizure Aggravation Exacerbation of or new onset primary generalized seizures has been reported with immediate-release oxcarbazepine. The risk of aggravation of primary generalized seizures is seen especially in children but may also occur in adults. In case of seizure aggravation, Oxtellar XR® should be discontinued.

ADVERSE REACTIONS 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 clinical practice.

The safety data presented below are from 384 patients with partial-onset seizures who received Oxtellar XR® (366 adults and 18 pediatric patients) with concomitant AEDs. In addition, safety data presented below are from a total of 2288 patients with seizure disorders treated with immediate-release oxcarbazepine; 1832 were adults and 456 were pediatric patients.

Most Common Adverse Reactions Reported by Adult Patients Receiving Concomitant AEDs in Oxtellar XR® Clinical Studies Table 3 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy treated with Oxtellar XR® or placebo and concomitant AEDs and that were numerically more common in the patients treated with any dosage of Oxtellar XR® than in patients receiving placebo.

The overall incidence of adverse reactions appeared to be dose related, particularly during the titration period. The most commonly observed (≥5%) adverse reactions seen in association with Oxtellar XR® and more frequent than in placebo-treated patients were: dizziness, somnolence, headache, balance disorder, tremor, vomiting, diplopia, and asthenia.

Table 3: Adverse Reaction Incidence in a Controlled Clinical Study of Oxtellar XR® with Concomitant AEDs in Adults* Oxtellar XR® 2400 mg/day (N=123); Oxtellar XR® 1200 mg/day (N=122).

Placebo (N=121). Any System/Any Term: 69%, 57%, 55%. Nervous System Disorders: Dizziness: 41%, 20%, 15%; Somnolence: 14%, 12% 9%; Headache: 15% 8%, 7%; Balance Disorder: 7%, 5% 5%; Tremor: 1%, 5%, 2%; Nystagmus: 3%, 3%, 1%; Ataxia 1%, 3%, 1%. Gastrointestinal Disorders: Vomiting: 15% 6%, 9%; Abdominal Pain Upper: 0%, 3% 1%; Dyspepsia: 0% 3% 1%; Gastritis: 0%, 3% 2%. Eye Disorders: Diplopia: 13%, 10% 4%; Vision Blurred: 1%, 4%, 3%; Visual Impairment: 1%, 3%, 0%.

General Disorders and Administration Site Conditions: Asthenia: 7% 3%, 1%; Fatigue: 3%, 6%, 1%; Gait Disturbance: 0%, 3%, 1%; Drug Intolerance: 2%, 0%, 0%. Infections and Infestations: Nasopharyngitis: 0% 3%, 0%; Sinusitis: 0%, 3%, 2%. *Reported by ≥2% of patients treated with Oxtellar XR® and numerically more frequent than in the placebo group.

Adverse Reactions Associated with Discontinuation of Oxtellar XR® Treatment: Approximately 23.3% of the 366 adult patients receiving Oxtellar XR® in clinical studies discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation of Oxtellar XR® (reported by ≥2%) were: dizziness (9.8%), vomiting (5.3%), nausea (3.7%), diplopia (3.2%), and somnolence (2.4%).

Adjunctive Therapy with Oxtellar XR® in Pediatric Patients 6 to Less Than 17 Years of Age Previously Treated with Other AEDs In a pharmacokinetic study in 18 pediatric patients (including patients 6 to less than 17 years of age) with partial-onset seizures treated with different dosages of Oxtellar XR®, the observed adverse reactions seen in association with Oxtellar XR® were similar to those seen in adults.

Most Common Adverse Reactions in Immediate-Release Oxcarbazepine Controlled Clinical Studies Controlled Clinical Studies of Adjunctive Therapy with Immediate-Release Oxcarbazepine in Adults Previously Treated with Other AEDs: Table 4 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy treated with immediate-release oxcarbazepine or placebo with concomitant AEDs and that were numerically more common in the patients treated with any dosage of immediate-release oxcarbazepine than in placebo. As immediate-release oxcarbazepine and Oxtellar XR® were not examined in the same trial, adverse event frequencies cannot be directly compared between the two formulations.

Table 4: Adverse Reaction Incidence in a Controlled Clinical Study of Immediate Release Oxcarbazepine with Concomitant AEDs in Adults* Immediate-Release Oxcarbazepine Dosage (mg/day): OXC 600 (N=163); OXC1200 (N=171); OXC2400 (N=126); Placebo (N=166). Body as a Whole: Fatigue: 15%, 12%, 15%, 7%; Asthenia: 6% 3%, 6%, 5%; Edema Legs: 2%, 1%, 2%, 1%; Weight Increase: 1%, 2%, 2%, 1%; Feeling Abnormal: 0%, 1%, 2%, 0%. Cardiovascular System: Hypotension: 0%, 1%, 2%, 0%.

Digestive System: Nausea: 15%, 25%, 29% 10%; Vomiting: 13%, 25%, 36%, 5%; Pain Abdominal: 10%, 13%, 11%, 5%; Diarrhea: 5%, 6%, 7%, 6%; Dyspepsia: 5%, 5%, 6%, 2%; Constipation: 2%, 2%, 6%, 4%; Gastritis: 2%, 1%,2%,1%. Metabolic and Nutritional Disorders: Hyponatremia: 3%, 1%, 2%,1%. Musculoskeletal System: Muscle Weakness: 1%, 2%, 2%, 0%; Sprains and Strains: 0%, 2%, 2%, 1%. Nervous System: Headache: 32%, 28% 26%, 23%; Dizziness: 36%, 32%, 49%, 13%; Somnolence: 20%, 28%, 36%, 12%; Ataxia: 9%, 17%, 31%, 5%; Nystagmus: 7% 20%, 26% 5%; Gait Abnormal: 5%, 10%, 17%, 1%; Insomnia: 4%, 2%, 3%, 1%; Tremor: 3% 8%, 16%, 5%; Nervousness: 2%, 4%, 2%, 1%; Agitation: 1%,1%, 2%, 1%; Coordination Abnormal: 1%, 3%, 2%, 1%; EEG Abnormal: 0%, 0%, 2%, 0%; Speech Disorder: 1%, 1%, 3%, 0%; Confusion: 1%, 1%, 2%, 1%; Cranial Injury NOS: 1%, 0%, 2% 1%; Dysmetria: 1%, 2%, 3%, 0%; Thinking Abnormal: 0%, 2%, 4%, 0%. Respiratory System: Rhinitis: 2%, 4%, 5%, 4%; Skin and Appendages: Acne: 1%, 2%, 2%, 0%; Special Senses: Diplopia: 14%, 30%, 40%, 5%; Vertigo: 6%, 12%, 15%, 2%; Vision Abnormal: 6%, 14%, 13%, 4%; Accommodation Abnormal: 0%, 0%, 2%, 0%. *Events in at least 2% of patients treated with 2400 mg/day of immediate-release oxcarbazepine and numerically more frequent than in the placebo group.

Other Reactions Observed in Association with the Administration of Immediate-Release Oxcarbazepine In the paragraphs that follow, the adverse reactions, other than those in the preceding tables or text, that occurred in a total of 565 children and 1574 adults exposed to immediate-release oxcarbazepine and that are reasonably likely to be related to drug use are presented. Events common in the population, events reflecting chronic illness and events likely to reflect concomitant illness are omitted particularly if minor.

They are listed in order of decreasing frequency. Because the reports cite reactions observed in open-label and uncontrolled trials, the role of immediate-release oxcarbazepine in their causation cannot be reliably determined.

Body as a Whole: fever, malaise, pain chest precordial, rigors, weight decrease.

Cardiovascular System: bradycardia, cardiac failure, cerebral hemorrhage, hypertension, hypotension postural, palpitation, syncope, tachycardia.

Digestive System: appetite increased, blood in stool, cholelithiasis, colitis, duodenal ulcer, dysphagia, enteritis, eructation, esophagitis, flatulence, gastric ulcer, gingival bleeding, gum hyperplasia, hematemesis, hemorrhage rectum, hemorrhoids, hiccup, mouth dry, pain biliary, pain right hypochondrium, retching, sialoadenitis, stomatitis, stomatitis ulcerative.

Hematologic and Lymphatic System: thrombocytopenia.

Laboratory Abnormality: gamma-GT increased, hyperglycemia, hypocalcemia, hypoglycemia, hypokalemia, liver enzymes elevated, serum transaminase increased.

Musculoskeletal System: hypertonia muscle.

Nervous System: aggressive reaction, amnesia, anguish, anxiety, apathy, aphasia, aura, convulsions aggravated, delirium, delusion, depressed level of consciousness, dysphonia, dystonia, emotional lability, euphoria,

extrapyramidal disorder, feeling drunk, hemiplegia, hyperkinesia, hyperreflexia, hypoesthesia, hypokinesia, hyporeflexia, hypotonia, hysteria, libido decreased, libido increased, manic reaction, migraine, muscle contractions involuntary, nervousness, neuralgia, oculogyric crisis, panic disorder, paralysis, paroniria, personality disorder, psychosis, ptosis, stupor, tetany.

Respiratory System: asthma, bronchitis, coughing, dyspnea, epistaxis, laryngismus, pleurisy.

Skin and Appendages: acne, alopecia, angioedema, bruising, dermatitis contact, eczema, facial rash, flushing, folliculitis, heat rash, hot flushes, photosensitivity reaction, pruritus genital, psoriasis, purpura, rash erythematous, rash maculopapular, vitiligo, urticaria.

Special Senses: accommodation abnormal, cataract, conjunctival hemorrhage, edema eye, hemianopia, mydriasis, otitis externa, photophobia, scotoma, taste perversion, tinnitus, xerophthalmia.

Urogenital and Reproductive System: dysuria, hematuria, intermenstrual bleeding, leukorrhea, menorrhagia, micturition frequency, pain renal, pain urinary tract, polyuria, priapism, renal calculus, urinary tract infection.

Other: Systemic lupus erythematosus.

Laboratory Tests Serum sodium levels below 125 mmol/L have been observed in patients treated with immediate-release oxcarbazepine. Experience from clinical trials with immediate-release oxcarbazepine indicates that serum sodium levels return toward normal when the dosage is reduced or discontinued, or when the patient was treated conservatively (e.g., fluid restriction).

Laboratory data from clinical trials suggest that immediate-release oxcarbazepine use was associated with decreases in T4, without changes in T3 or TSH. Postmarketing and Other Experience The following adverse reactions have been observed in named patient programs or post-marketing experience with immediate-release oxcarbazepine or Oxtellar XR®. 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.

Body as a Whole: multi-organ hypersensitivity disorders characterized by features such as rash, fever, lymphadenopathy, abnormal liver function tests, eosinophilia, and arthralgia Cardiovascular System: atrioventricular block Digestive System: pancreatitis and/or lipase and/or amylase increase Hematologic and Lymphatic Systems: aplastic anemia Immune System Disorders: anaphylaxis Metabolism and Nutrition Disorders: hypothyroidism and syndrome of inappropriate antidiuretic hormone secretion (SIADH) Skin and Subcutaneous Tissue Disorders: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, Acute Generalized Exanthematous Pustulosis (AGEP) Musculoskeletal, Connective Tissue and Bone Disorders: There have been reports of decreased bone mineral density, osteoporosis and fractures in patients on long-term therapy with immediate-release oxcarbazepine.

DRUG INTERACTIONS Effect of Oxtellar XR on Other Drugs It is recommended that the plasma levels of phenytoin be monitored during the period of Oxtellar XR titration and dosage modification. A decrease in the dosage of phenytoin may be required.

Effect of Other Drugs on Oxtellar XR If Oxtellar XR and strong CYP3A4 inducers or UGT inducers (e.g., rifampin, carbamazepine, phenytoin, and phenobarbital) are administered concurrently, it is recommended that the plasma levels of MHD be monitored during the period of Oxtellar XR titration. Dosage adjustment of Oxtellar XR may be required after initiation, dosage modification, or discontinuation of such inducers.

Hormonal Contraceptives Concurrent use of immediate-release oxcarbazepine with hormonal contraceptives may render these contraceptives less effective. Studies with other oral or implant contraceptives have not been conducted.

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as Oxtellar XR, during pregnancy.

Encourage women who are taking Oxtellar XR during pregnancy to enroll in the North American Antiepileptic Drug (NAAED Pregnancy Registry) by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/.

Risk Summary There are no adequate data on the developmental risks associated with the use of Oxtellar XR® in pregnant women; however, Oxtellar XR® is closely related structurally to carbamazepine, which is considered to be teratogenic in humans. Data on a limited number of pregnancies from pregnancy registries suggest that oxcarbazepine monotherapy use is associated with congenital malformations (e.g., craniofacial defects such as oral clefts, and cardiac malformations such as ventricular septal defects). Increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity (embryolethality, growth retardation) were observed in the offspring of animals treated with either oxcarbazepine or its active 10-hydroxy metabolite (MHD) during pregnancy at doses similar to the maximum recommended human dose (MRHD).

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.

Clinical Considerations An increase in seizure frequency may occur during pregnancy because of altered levels of the active metabolite of oxcarbazepine. Monitor patients carefully during pregnancy and through the postpartum period.

Data Human Data Data from published registries have reported craniofacial defects such as oral clefts and cardiac malformations such as ventricular septal defects in children with prenatal oxcarbazepine exposure.

Animal Data When pregnant rats were given oxcarbazepine (30, 300, or 1000 mg/kg/day) orally throughout the period of organogenesis, increased incidences of fetal malformations (craniofacial, cardiovascular, and skeletal) and variations were observed at the intermediate and high doses (approximately 1.2 and 4 times, respectively, the MRHD on a mg/m2 basis).

Increased embryofetal death and decreased fetal body weights were seen at the high dose. Doses ≥300 mg/kg were also maternally toxic (decreased body weight gain, clinical signs), but there is no evidence to suggest that teratogenicity was secondary to the maternal effects.

In a study in which pregnant rabbits were orally administered MHD (20,

100, or 200 mg/kg/day) during organogenesis, embryofetal mortality was increased at the highest dose (1.5 times the MRHD on a mg/m2 basis). This dose produced only minimal maternal toxicity.

In a study in which female rats were dosed orally with oxcarbazepine (25, 50, or 150 mg/kg/day) during the latter part of gestation and throughout the lactation period, a persistent reduction in body weights and altered behavior (decreased activity) were observed in offspring exposed to the highest dose (0.6 times the MRHD on a mg/m2 basis). Oral administration of MHD (25, 75, or 250 mg/kg/day) to rats during gestation and lactation resulted in a persistent reduction in offspring weights at the highest dose (equivalent to the MRHD on a mg/m2 basis).

Lactation Risk Summary Oxcarbazepine and its active metabolite (MHD) are present in human milk after oxcarbazepine administration. The effects of oxcarbazepine and its active metabolite (MHD) on the breastfed infant or on milk production are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Oxtellar XR and any potential adverse effects on the breastfed infant from Oxtellar XR or from the underlying maternal condition.

Females and Males of Reproductive Potential Contraception Use of Oxtellar XR with hormonal contraceptives containing ethinylestradiol or levonorgestrel is associated with decreased plasma concentrations of these hormones and may result in a failure of the therapeutic effect of the oral contraceptive drug. Advise women of reproductive potential taking Oxtellar XR who are using a contraceptive containing ethinylestradiol or levonorgestrel to use additional or alternative non-hormonal birth control.

Pediatric Use The safety and effectiveness of Oxtellar XR® in pediatric patients 6 years of age and older for the treatment of partial-onset seizures is supported by: 1) An adequate and well-controlled safety and efficacy study of Oxtellar XR® in adults that included pharmacokinetic sampling, 2) A pharmacokinetic study of Oxtellar XR® in pediatric patients, which included patients 6 to less than 17 years of age, 3) Safety and efficacy studies with the immediate-release formulation in adults and pediatric patients.

Oxtellar XR® is not approved for pediatric patients less than 6 years of age because the size of the tablets are inappropriate for younger children.

Geriatric Use Following administration of single (300 mg) and multiple (600 mg/day) doses of immediate-release oxcarbazepine to elderly volunteers (60-82 years of age), the maximum plasma concentrations and AUC values of MHD were 30%-60% higher than in younger volunteers (18-32 years of age). Comparisons of creatinine clearance in young and elderly volunteers indicate that the difference was due to age-related reductions in creatinine clearance. Consider starting at a lower dosage and lower titration. Close monitoring of sodium levels is required in elderly patients at risk for hyponatremia.

Renal Impairment There is a linear correlation between creatinine clearance and the renal clearance of MHD. The pharmacokinetics of Oxtellar XR® has not been evaluated in patients with renal impairment. In patients with severe renal impairment (creatinine clearance <30 mL/min) given immediate-release oxcarbazepine, the elimination half-life of MHD was prolonged with a corresponding two-fold increase in AUC. In these patients initiate Oxtellar XR® at a lower starting dosage and increase, if necessary, at a slower than usual rate until the desired clinical response is achieved.

In patients with end-stage renal disease on dialysis, it is recommended that immediate-release oxcarbazepine be used instead of Oxtellar XR®.

Hepatic Impairment The pharmacokinetics of oxcarbazepine and MHD has not been evaluated in severe hepatic impairment, and therefore is not recommended in these patients.

DRUG ABUSE AND DEPENDENCE Abuse The abuse potential of Oxtellar XR® has not been evaluated in human studies.

Oxtellar XR® is not habit forming, and is not expected to encourage abuse.

Dependence Intragastric injections of oxcarbazepine to four cynomolgus monkeys demonstrated no signs of physical dependence as measured by the desire to self-administer oxcarbazepine by lever pressing activity.

OVERDOSAGE Human Overdose Experience Isolated cases of overdose with immediate-release oxcarbazepine have been reported. The maximum dose taken was approximately 48,000 mg.

All patients recovered with symptomatic treatment. Nausea, vomiting, somnolence, aggression, agitation, hypotension, and tremor each occurred in more than one patient. Coma, confusional state, convulsion, dyscoordination, depressed level of consciousness, diplopia, dizziness, dyskinesia, dyspnea, QT prolongation, headache, miosis, nystagmus, overdose, decreased urine output, and blurred vision also occurred.

Treatment and Management There is no specific antidote for Oxtellar XR® overdose. Administer symptomatic and supportive treatment as appropriate. Options include removal of the drug by gastric lavage and/or inactivation by administering activated charcoal.

CLINICAL PHARMACOLOGY Patients with Renal or Hepatic Impairment The effects of renal or hepatic impairment have not been studied for Oxtellar XR®.

Based on investigations with immediate-release oxcarbazepine, there is a linear correlation between creatinine clearance and the renal clearance of MHD. When immediate-release oxcarbazepine is administered as a single 300 mg dose in renally-impaired patients (creatinine clearance <30 mL/min), the elimination half-life of MHD is prolonged to 19 hours, with a two-fold increase in AUC. Dosage adjustment is recommended in these patients.

The pharmacokinetics and metabolism of immediate-release oxcarbazepine and MHD were evaluated in healthy volunteers and hepatically impaired subjects after a single 900 mg oral dose. Mild-to-moderate hepatic impairment did not affect the pharmacokinetics of immediate-release oxcarbazepine and MHD. The pharmacokinetics of oxcarbazepine and MHD have not been evaluated in severe hepatic impairment, and therefore it is not recommended in these patients.

Pregnant Women Due to physiological changes during pregnancy, MHD plasma levels may gradually decrease throughout pregnancy.

Drug Interaction Studies

In Vitro: Oxcarbazepine can inhibit CYP2C19 and induce CYP3A4/5 with potentially important effects on plasma concentrations of other drugs. In addition, several AEDs that are cytochrome P450 inducers can decrease plasma concentrations of oxcarbazepine and MHD. Oxcarbazepine was evaluated in human liver microsomes to determine its capacity to inhibit the major cytochrome P450 enzymes responsible for the metabolism of other drugs. Results demonstrate that oxcarbazepine and its pharmacologically active 10-monohydroxy metabolite (MHD) have little or no capacity to function as inhibitors for most of the human cytochrome P450 enzymes evaluated (CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, CYP4A9, and CYP4A11) with the exception of CYP2C19 and CYP3A4/5.

Although inhibition of CYP3A4/5 by oxcarbazepine and MHD did occur at high concentrations, it is not likely to be of clinical significance. The inhibition of CYP2C19 by oxcarbazepine and MHD, is clinically relevant.

In vitro, the UDP-glucuronyl transferase level was increased, indicating induction of this enzyme. Increases of 22% with MHD and 47% with oxcarbazepine were observed. As MHD, the predominant plasma substrate, is only a weak inducer of UDP-glucuronyl transferase, it is unlikely to have an effect on drugs that are mainly eliminated by conjugation through UDP-glucuronyl transferase (e.g., valproic acid, lamotrigine).

In addition, oxcarbazepine and MHD induce a subgroup of the cytochrome P450 3A family (CYP3A4 and CYP3A5) responsible for the metabolism of dihydropyridine calcium antagonists, oral contraceptives and cyclosporine resulting in a lower plasma concentration of these drugs.

Several AEDs that are cytochrome P450 inducers can decrease plasma concentrations of oxcarbazepine and MHD. No autoinduction has been observed with immediate-release oxcarbazepine.

As binding of MHD to plasma proteins is low (40%), clinically significant interactions with other drugs through competition for protein binding sites are unlikely.

In Vivo: Other Antiepileptic Drugs Potential interactions between immediate-release oxcarbazepine and other AEDs were assessed in clinical studies. The effect of these interactions on mean AUCs and Cmin are summarized in Table 5.

Table 5: AED Drug Interactions with Immediate-Release (IR) Oxcarbazepine AED Coadministered (daily dosage); IR-Oxcarbazepine (daily dosage); Influence of IR-Oxcarbazepine on AED Concentration Mean Change (90% Confidence Interval); Influence of AED on MHD Concentration (Mean Change, 90% Confidence Interval). Carbamazepine (400-2000 mg): 900 mg, nc1, 40 % decrease [Cl: 17% decrease, 57% decrease]; Phenobarbital (100-150 mg): 600-1800 mg, 14% increase [Cl: 2% increase, 24% increase]; 25% decrease [Cl: 12% decrease, 51% decrease]. Phenytoin (250-500 mg): 600-1800 >1200-2400, nc1,2 up to 40% increase3 [Cl: 12% increase, 60% increase], 30% decrease [Cl: 3% decrease, 48% decrease]. Valproic Acid (400-2800 mg): 600-1800, nc1, 18% decrease [Cl: 13% decrease, 40% decrease]. Lamotrigine (200 mg): 1200, nc1, nc1.

1 nc denotes a mean change of less than 10%; 2Pediatrics; 3 Mean increase in adults at high doses of immediate-release oxcarbazepine Hormonal Contraceptives Coadministration of immediate-release oxcarbazepine with an oral contraceptive has been shown to influence the plasma concentrations of two components of hormonal contraceptives, ethinylestradiol (EE) and levonorgestrel (LNG). The mean AUC values of EE were decreased by 48% [90% CI: 22-65] in one study and 52% [90% CI: 38-52] in another study. The mean AUC values of LNG were decreased by 32% [90% CI: 20-45] in one study and 52% [90% CI: 42-52] in another study.

Other Drug Interactions Calcium Antagonists: After repeated coadministration of immediate-release oxcarbazepine, the AUC of felodipine was lowered by 28% [90% CI: 20-33]. Verapamil produced a decrease of 20% [90% CI: 18-27] of the plasma levels of MHD after coadministration with immediate-release oxcarbazepine.

Cimetidine, erythromycin and dextropropoxyphene had no effect on the pharmacokinetics of MHD after coadministration with immediate-release oxcarbazepine. Results with warfarin show no evidence of interaction with either single or repeated doses of immediate-release oxcarbazepine.

NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis In two-year carcinogenicity studies, oxcarbazepine was administered in the diet at doses of up to 100 mg/kg/day to mice and by gavage at doses of up to 250 mg/kg/day to rats, and the pharmacologically active 10-hydroxy metabolite (MHD) was administered orally at doses of up to 600 mg/kg/day to rats. In mice, a dose-related increase in the incidence of hepatocellular adenomas was observed at oxcarbazepine doses ≥70 mg/kg/day or approximately 0.1 times the maximum recommended human dose (MRHD) on a mg/m2 basis. In rats, the incidence of hepatocellular carcinomas was increased in females treated with oxcarbazepine at doses ≥25 mg/kg/day (0.1 times the MRHD on a mg/m2 basis), and incidences of hepatocellular adenomas and/or carcinomas were increased in males and females treated with MHD at doses of 600 mg/kg/day (2.4 times the MRHD on a mg/m2 basis) and ≥250 mg/kg/day (equivalent to the MRHD on a mg/m2 basis), respectively. There was an increase in the incidence of benign testicular interstitial cell tumors in rats at 250 mg oxcarbazepine/kg/day and at ≥250 mg MHD/kg/day, and an increase in the incidence of granular cell tumors in the cervix and vagina in rats at 600 mg MHD/kg/day.

Mutagenesis Oxcarbazepine increased mutation frequencies in the Ames test in vitro in the absence of metabolic activation in one of five bacterial strains. Both oxcarbazepine and MHD produced increases in chromosomal aberrations and polyploidy in the Chinese hamster ovary assay in vitro in the absence of metabolic activation. MHD was negative in the Ames test, and no mutagenic or clastogenic activity was found with either oxcarbazepine or MHD in V79 Chinese hamster cells in vitro. Oxcarbazepine and MHD were both negative for clastogenic or aneugenic effects (micronucleus formation) in an in vivo rat bone marrow assay.

Impairment of Fertility In a fertility study in which rats were administered MHD (50, 150, or 450 mg/kg) orally prior to and during mating and early gestation, estrous cyclicity was disrupted and numbers of corpora lutea, implantations, and live embryos were reduced in females receiving the highest dose (approximately two times the MRHD on a mg/m2 basis).

RA-OXT-BS-PV2

Enhance Your Annual Meeting Experience with Annual Meeting On Demand This comprehensive, CME-accredited digital library offers: • 500+ hours* of presentations—watch like you’re there in person with slides and synchronized audio with PDF and mp3 files available for download • 200+ programs and syllabi available** • Convenience—learn from your desk or on the go • Integrated CME testing with over 240 hours of CME eligible content (earn up to 242.75 AMA PRA Category 1 Credits™)

New for 2019!

DISCOVER EMERGING SCIENCE IN NEUROLOGY FROM GENENTECH Sunday, May 5th 12:15 pm and 3:15 pm

Tuesday, May 7th 12:00 pm | 1:00 pm | 2:00 pm | 3:00 pm

Genentech Pipeline Presentation

Neuromyelitis Optica Spectrum Disorder Presentation

Dr Susan Begelman, MD, FACC

• Lower Price—By moving Annual Meeting On Demand to the AAN’s Online Learning Center, we’ve been able to lower the purchase price.

Monday, May 6th 12:30 pm and 2:30 pm

• Simplified, Convenient Access—Access through the Online Learning Center, along with other AAN learning content.

Spinal Muscular Atrophy Presentation

• Complimentary Earbuds—Pre-order by May 10, 2019, and receive free wireless earbuds, while supplies last.

Pre-order by May 10, 2019, and Save $150 on 2019 Annual Meeting On Demand!

Dr Adil Javed, MD, PhD

Vice President, Spectrum Medical Unit | US Medical Affairs | Genentech Inc. San Francisco, California

Associate Professor of Neurology The University of Chicago Chicago, Illinois

Wednesday, May 8th 12:00 pm | 1:00 pm | 2:00 pm | 3:00 pm

Dr Claudia A. Chiriboga, MD, MPH

Multiple Sclerosis Presentation

Professor of Neurology and Pediatrics Division of Pediatric Neurology Columbia University Medical Center New York, New York

Dr Mark Cascione, MD Tampa Neurology Associates South Tampa Multiple Sclerosis Center Tampa, Florida

Monday, May 6th 11:30 am and 3:30 pm

Onsite: Visit the eLearning Networking and Innovation Space at the Annual Meeting for any Annual Meeting On Demand or other online learning questions.

Huntington’s Disease Presentation

Order Online: AAN.com/view/AMOD2019

Associate Professor, UAB Department of Neurology, Division of Movement Disorders Director, UAB/HDSA Huntington’s Disease Center of Excellence Birmingham, Alabama

* Specific presentations within a session may not be available based on permissions granted by the presenter.

Come to booth 2329 to learn about Genentech Neurology or visit us at roche.com/neuroscience

Dr Victor Sung, MD

** With the move to an online offering, hard drives will not be provided. © 2019 Genentech USA, Inc. All rights reserved. OCR/021919/0046a 04/19

Discover more at

BOOTH 1329 ©2019 Biogen. All rights reserved. 04/19 TEC-US-3363