2019 Annual Meeting AANextra Monday by American Academy of Neurology

THE ANNUAL MEETING NEWS DAILY

Monday, May 6, 2019

MOST CRITICAL PRACTICE ISSUES OUTLINED IN TODAY’S CONTEMPORARY CLINICAL ISSUES PLENARY

Marshall

Those interested in issues most critical to practicing neurologists should make their way to the Terrace Ballroom this morning between 9:15 a.m. and 12:00 p.m. to hear leading researchers discuss abstracts related to new therapeutic developments, clinical applications of basic and translational research, and innovative technical developments during the Contemporary Clinical Issues Plenary Session. The session will be moderated by AAN Science Committee Vice Chair Randolph S. Marshall, MD, FAAN, of Columbia University in New York, and discussion will follow each presentation. Medical Student Essay Award recipients will also be recognized during the session. Continued on page 39 u

Powerful Talk on Flint Water Crisis Set for 1:00 p.m. Today The pediatrician whose research exposed the Flint water crisis, Mona Hanna-Attisha, MD, MPH, will lead a powerful talk today Attisha as part of the Annual Meeting’s new series Advancing Medicine: Inspiration and Innovation talks. The talk is at 1:00 p.m. today in Ballroom A. The new sessions are designed to explore where neuroscience intersects with timely global themes. Continued on page 41 u

Hear from Winners of Prestigious Awards at The Grand Experience Stage Celebrate AAN awards in a new way by joining us at the Grand Experience, Grand Hall, Stage 1 today through Wednesday at 3:30 p.m. for three special award presentations, each followed by a panel Q&A discussion with past award recipients. In addition, the prestigious A.B. Baker Award for Lifetime Achievement in Neurologic Education will be presented on Wednesday at 1:00 p.m. in the Grand Experience, Grand Hall, Stage 3 “These three awards recognize major research contributions in the field of Continued on page 33 u

Inside

Focus on What Matters to You with Curated Program Tracks

Network, Find 16 Trainees: Opportunities at Tonight’s Early Career Reception

Your Colleagues’ 17 Hear Ground-breaking Ideas at Today’s Brainstorm Competition

In Multiple

Sclerosis—

GREY MATTERS, TOO

FIND OUT WHY

Booth 2300

Monday, May 6 Cover Most Critical Practice Issues

Outlined in Today’s Contemporary Clinical Issues Plenary

Powerful Talk on Flint Water Crisis Set for 1:00 p.m. Today

Hear from Winners of Prestigious Awards at The Grand Experience Stage

Attendees Had Spectacular Time at Last Night’s Philly Spectacular

Rost Hosts Press Conference for Media

Focus on What Matters to You with Curated Program Tracks

Make Neuro Center Your Destination for Daily Discovery

AAN Leaders Praise FAANs at Recognition Breakfast

13 Join the Fun at Tomorrow's

Run/Walk for Brain Research

13 Monday's AAN Section Meetings 14 Today’s Experiential Learning Area Highlights

16 Trainees: Network, Find

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

Opportunities at Tonight’s Early Career Reception

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

17 Hear Your Colleagues’ Groundbreaking Ideas at Today’s Brainstorm Competition

Contact Information:

18 Head Over to the BrainDome

201 Chicago Avenue Minneapolis, MN 55415 USA

for an Immersive Exploration

19 MIPS Benchmarking—What to Know and Do to Succeed

23 Colorful Poster of New Continuum

Covers Offered Free with Subscription, Renewal

24 The AAN’s Role in Advancing Coding and Reimbursement for Neurology

26 The Best of Philly from Those Who Know It Best

29 Find the Latest Research at Today’s Poster Session

32 Boxed Lunch Menu 36 Networking for Neurologists: Use a Three-ring Approach to Create Contacts, Friends, and Mentors

42 What Are Your Colleagues Saying?

46 What Excited You Today at #AANAM?

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.

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

Celebrate with Neurology: Neuroimmunology and Neuroinflammation Join the Neurology ® Neuroimmunology and Neuroinflammation journal as it celebrates its fifth anniversary and being awarded an Impact Factor this year with cupcakes at 11:00 a.m. today in the Publications Area located on the second level in the bridge of the Pennsylvania Convention Center. 

MoNDAY, MAY

6, 2019

ES PRACTICE ISSU MOST CRITICAL Y’S CONTEMPORARY OUTLINED IN TODAPLENARY CLINICAL ISSUES

THE ANNUAL

MEETING NEWS

DAILY

Marshall

to in issues most critical Those interested should make their practicing neurologists Ballroom this morning way to the Terrace hear and 12:00 p.m. to between 9:15 a.m. discuss abstracts leading researchers developments, related to new therapeutic and translational of basic clinical applications technical research, and innovative Contemporary the developments during Session. The Clinical Issues Plenary by AAN Science session will be moderated S. Marshall, Chair Randolph Committee Vice University in MD, FAAN, of Columbia will follow each New York, and discussion Student Essay Award presentation. Medical be recognized during recipients will also the session.

Powerful Talk on Flint Water Crisis Today Set for 1:00 p.m.

Hear from Winners of Prestigious Awards at The Grand Experience Stage in a new way by

The pediatrician Celebrate AAN awards Experience, Grand whose research joining us at in the 1 today through exposed the Flint Grand Hall, Stage p.m. for three special water crisis, Mona Wednesday at 3:30 a each followed by Hanna-Attisha, MD, award presentations, with past award MPH, will lead a panel Q&A discussion the prestigious A.B. powerful talk today Attisha in recipients. In addition, Lifetime Achievement as part of the Annual Baker Award for will be presented Meeting’s new series Neurologic Education 1:00 p.m. in the Grand Advancing Medicine: talks. The talk on Wednesday at Hall, Stage 3 Inspiration and Innovation Experience, Grand in Ballroom A. The is at 1:00 p.m. today recognize major designed to explore “These three awards in the field of new sessions are timely with intersects research contributions where neuroscience u 33 global themes. Continued on page Continued on page

Continued on page

u 39

Inside

Focus on What Matters to You with Curated Program Tracks

Network, 16 Trainees: Opportunities at Tonight’s Find

Early Career Reception

Your Colleagues’ 17 Hear Ideas Ground-breaking at Today’s Brainstorm Competition

u 41

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.

Philadelphia

ÑOL EN ESPA SO AL DOR

EVENT PROGRAM

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

Attendees Had Spectacular Time at Last Night’s Philly Spectacular Last night’s Philly Spectacular at Reading Terminal Market drew a large crowd who gathered for great food, drink, and merriment at one of the United States’ largest and oldest public markets. Philly’s popular party dance band, Jellyroll, got attendees on their feet and dancing in the street to a diverse repertoire of toe-tappers, from old-school classics to the latest top 40 hits. 

The family sub sandwich business of Dr. Sacco—Sack o’ Subs of New Jersey—handed out subs to attendees alongside a cardboard cutout of the AAN president. Sacco’s sister, Bess Sacco, and brother-in-law, Peter Varsalona, pose with their cardboard relation!

Monday, May 6, 2019 • AANextra

Subscription includes ContinuumÂŽ Audioâ&#x20AC;&#x201D;AAN members get both products for only $349! Renew or subscribe on-site and receive a limited-edition poster featuring cover art from 2018 while supplies last. ContinuumJournal.com Visit us in the Publications Area on Level 2 across from Registration!

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

Pharma Ad

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

Faculty Member

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)

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.

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

Rost Hosts Press Conference for Media Natalia S. Rost, MD, MPH, FAHA, FAAN, chair of the Science Committee, spoke to reporters during Sunday’s media event on exciting work from researchers Sean J. Pittock, MD, left, Erin Beck, MD, PhD, and Alexander Kolevzon, MD. Pittock’s abstract is titled Efficacy and safety of eculizumab in aquaporin-4 antibody positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD): a phase 3, randomized, double-blind, placebo-controlled, multicenter trial (PREVENT). Beck’s abstract is titled: A pilot study of adoptive cellular immunotherapy for progressive multifocal leukoencephalopathy with ex vivo generated polyomavirus-specific T-cells. Kolevzon’s abstract is titled: STARS: Results from a safety and efficacy study of OV101 (gaboxadol) in adults and adolescents with Angelman syndrome.

Focus on What Matters to You with Curated Program Tracks Don’t miss these specially selected course lineups, designed to help you maximize your time at the meeting based on your personal career path and interests. “We want to be indispensable to AAN members. By creating tracks, our goal is to make it easy for you to find your way around the Disney World of meetings,” said Joseph I. Sirven, MD, FAAN, chair of the AAN Conference Subcommittee. “Branded tracks let us help you find your way and navigate around the meeting so that we can provide the best meeting experience possible.” You can find the full course listings for each track quickly and easily by filtering for tracks within the AAN Conferences App or at AAN.com/view/AMSearchProgram.

Academic Medicine Track Provides a variety of offerings for academic neurologists across career roles and stages. Programming will cover faculty development, leadership, research, team building, career development, improving communication, and more.

Business of Neurology Track Perfect for individuals interested in starting a new practice or learning the fundamentals of neurology business.

Career Essentials Track Whether you are early in your career and seeking help with career development, looking to launch into private practice or academics, or interested in the finer points of financial planning and wellness, this track is for you.

Foundations for Clinical Neurology for APPs Track

Sirven

lineup covers everything from prevention, telestroke, critical care monitoring and consultations, and issues encountered in the ICU.

Created for advanced practice providers who are new to neurology, this track focuses on laying the foundations for success in clinical neurology.

Spanish-language Track Look for education courses, scientific updates, and experiential learning area talks on a wide range of topics including MS, teleneurology, transnational research opportunities, and the challenges and opportunities of different career paths in neurology—all taught entirely in Spanish. Also of special interest to both Spanish and English speakers is a new experiential learning area program on cross-cultural communication that will be taught in English. 

Futures in Neurological Research Track This track offers both formal coursework and learning sessions to round out research-interested trainees’ Annual Meeting experience. Look for popular events such as the Futures in Neurology Boot Camp, Luncheon, and Subspecialty Mentoring Sessions.

Neurohospitalist Track Created specifically for neurohospitalists whose primary focus is inpatient care, or for anyone who would like to learn more about the care of hospitalized patients, this

Monday, May 6, 2019 • AANextra

Make Neuro Center Your Destination for Daily Discovery Be sure to check out the new Neuro Center through Wednesday in Exhibit Halls B–E. It’s only here that you’ll find within a single destination everything from presentations, posters, and exhibits, to an experiential learning area, a café, and even a picnic area! Scientific Poster Presentations

Visit the Poster Neighborhoods and network with colleagues while learning about the latest breakthroughs in neurologic research.

ePoster Presentations

Interactive presentations on digital monitors feature videos, 3D models/graphics, and more.

Alternate Viewing Area

Catch live streams of plenary sessions, education programs, and other unique and encore programming.

Innovation Hub

Enjoy daily Wine and Paint Sessions and innovative physicianled presentations in this experiential learning area.

Charging Areas

Relax and recharge—both yourself and your phone— before your next course.

Buzz Cafes

Take a break with your colleagues with complimentary coffee and comfy seating.

Exhibits

Hear about the latest in the field, learn about career opportunities, find patient resources, and more.

Lunch and Picnic Space

Select from a variety of nutritious lunch options and enjoy music, bingo, and more. 

AAN Leaders Praise FAANs at Recognition Breakfast AAN leadership―including Vice President Ann Tilton, MD, FAAN, and Gregory D. Cascino, MD, FAAN, chair of the Member Engagement Committee, along with other representatives of this committee, the Member Application Review Subcommittee, AAN executive staff, and the Board of Directors―were on hand Sunday morning for a special Fellow Recognition Breakfast honoring all new 2018 Fellow members. These valued FAAN members took advantage of this exclusive opportunity to socialize with leaders and colleagues as they were recognized for their exemplary contributions to neurology.  Gregory D. Cascino, MD, FAAN, chair of the Member Engagement Committee, congratulated the new Fellows.

Monday, May 6, 2019 • AANextra

Discover more at

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

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

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

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 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.

Join the Fun at Tomorrow's Run/Walk for Brain Research Stop by the Live Well Experiential Learning Area in the Pennsylvania Convention Center before 12:00 noon today to sign up to join your colleagues, friends, and family Tuesday morning for a friendly 5k Run/1k Walk to support neurology research. Both occasional and seasoned runners and walkers are invited to take part in this popular annual event for a great cause. The run/walk will begin promptly at 6:30 a.m. at Lloyd Hall in Boathouse Row and continue throughout scenic Kelly Drive in Fairmont Park East. Bus service to and from the event will be provided from designated hotels as communicated to recipients via email. All proceeds will to go support research, and winners will receive prizes. Water and refreshments will be available following the race. After the run/walk, be sure to stop by the Live Well Experiential Learning Area to pick up your t-shirt and to see the run/walk results. Thank you to the following sponsors*: Arbor Pharmaceuticals, Inc.; AveXis, Inc.; Biogen; Celgene; Eisai; EMD Serono, Inc.; Genentech; Greenwich Biosciences; Kyowa Kirin, Inc.; Sunovion Pharmaceuticals, Inc.; and Voyager Therapeutics  *As of March 25, 2019

Monday's AAN Section Meetings

7:00 a.m.–8:00 a.m.

Sleep Medicine Section / 103 A Autonomic Nervous System Section / 103 B

8:15 a.m.–9:15 a.m.

Government Service Section / 103 A Global Health Section / 103 B

12:00 p.m.–1:00 p.m.

Movement Disorders Section / 103 A Neuromuscular Section / 103 B

2:00 p.m.–3:00 p.m.

General Neurology Section / 103 A Neurohospitalist Section / 103 B 4:00 p.m.–5:00 p.m. A.B. Baker Section on Neurological Education / 103 A Business Administration Section / 103 B

5:30 p.m.–6:30 p.m.

Epilepsy Section / 103 A Neuro-oncology Section / 103 B

5:45 p.m.–6:45 p.m.

Headache and Facial Pain Section / 203 AB 

Today’s Experiential Learning Area Highlights HeadTalks Self Reflected: Deeply Fusing Art and Science to Create the World’s Most Complex Artistic Depiction of the Human Brain 2:45 p.m.–3:30 p.m. Self Reflected bridges the visual and conceptual connection between the macroscopic brain and the microscopic behavior of neurons by fusing neuroscientific data, hand drawings, algorithmic manipulation, optical engineering, photolithography, and gilding to etch half a million neurons into large sheets of gold. Self Reflected was created to remind us that the most marvelous machine in the known universe is at the core of our being and is the root of our shared humanity.

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

Research Corner

The Ripple Effect of Positive Psychology 1:00 p.m.–1:45 p.m.

NIH Day 8:00 a.m.–5:00 p.m.

Heidi B. Schwarz, MD, FAAN, will discuss the principles and power of positive psychology and how to apply them to individual and organizational issues.

Maximize Your Value and Advocacy to Action Meet a Member of Congress 12:00 p.m.–1:00 p.m. US Representative Brendan Boyle (D-PA) will deliver short remarks and be available for questions about the role of Congress in the future of neurology.

Contestants tested their guessing skills in all things neurology with Neurology Pictionary host Bert B. Vargas, MD, FAAN.

Monday, May 6, 2019 • AANextra

Don’t miss tomorrow’s National Institutes of Health Day!

Starting with an overview of NIH funding with NINDS Director Walter J. Koroshetz, MD, FAAN, and National Institute on Aging Director, Division of Neuroscience Eliezer Masliah, MD, at 8:00 a.m., and continuing with presentations all afternoon, NIH Day will offer many chances to learn about funding opportunities, the grant review process, clinical trials, and more.

Navigating Your Career A Career in Clinical Practice 2:00 p.m.–2:45 p.m. Hear from a panel of experts on pursuing a career in clinical practice, ranging from community practice to those residing in large academic medical centers.

Experience the AAN

Innovation Hub

11:30 a.m.–3:30 p.m.

Brainstorm: A Competition for the Innovator in All of Us 3:30 p.m.–4:00 p.m.

Get a professional profile picture taken to update your digital presence, including your AAN.com and Synapse profiles.

The 2018 competition winner, Darin T. Okuda, kicks off the event with a presentation on his project on 3D phenotyping and its role in medicine to better understand disease.

And be sure to attend tomorrow’s session:

4:00 p.m.–5:30 p.m.

Turning the Diversity Tax into Currency in Neurology 8:00 a.m.–8:45 a.m. Roy H. Hamilton, MD, MS, FAAN, states: “The objectives of this talk are to: recognize the burden that diversity and inclusion advocacy places on certain populations of practicing neurologists and trainees; discuss strategies for finding the right balance between promoting diversity-related activities and dedicating oneself to traditional career goals; and present practical strategies for translating diversity-related efforts into activities that are considered meritorious for career development in neurology.”

Watch as fellow attendees present their innovative ideas on how to improve neurologic care to a panel of judges to see who takes home the grand prize. 

Anup Patel, MD, FAAN, covered how to publish quality improvement projects in the Research Corner Experiential Learning Area.

In the Advocacy to Action Experiential Learning Area, Nicholas E. Johnson, MD, FAAN, discussed ultra-high cost neurology drugs.

Allison Brashear, MD, MBA, FAAN, reviewed how to negotiate with peers and superiors at the Navigating Your Career Experiential Learning Area.

Relax with daily paint and wine sessions at 12:00 p.m. and 2:00 p.m. through Wednesday.

Monday, May 6, 2019 • AANextra

Trainees: Network, Find Opportunities at Tonight’s Early Career Reception A premier networking and learning event for those in undergraduate and graduate medical education will take place tonight in the Grand Ballroom of the Philadelphia Marriott Downtown from 6:00 p.m. to 9:00 p.m. Don’t miss this unique opportunity to meet and network with chairs of neurology departments and their faculty. Trainees will have the chance to learn about residency, clerkship, fellowship, and careers in neurology. The event has been revamped to provide an even greater focus on trainees to provide them with networking opportunities with peers and leaders with the goal of furthering their career development. Academic departments, governmental organizations, and medical associations will be on hand with information about opportunities and available to answer questions. Three lounge areas will be designated for information and discussions on career track opportunities in clinical practice, research, and teaching, as well as fellowship training opportunities, with leaders available to help answer questions.

“Medical students looking for information about neurology clerkships, residents who need help navigating the fellowship application process, and any trainees wondering what careers are open to them in the field of neurology should attend this event,” said Jaffar Khan, MD, FAAN, chair of the AAN Graduate Education Subcommittee and member of the Education Committee. “Department chairs, clerkship, program, and fellowship directors will be happy to talk with them

and answer their questions and direct them to other resources that are all concentrated together at this valuable reception.” 

In addition, trainees can learn about AAN programs and services that can help them throughout their careers in neurology in the Academy Connection area.

Let’s Talk Cannabinoids

Stop by booth #2011 at the AAN annual meeting in Philadelphia, from May 5–8, and learn about the evidence for and against cannabinoids as medicine.

Talk to your patients about cannabinoids with a deeper understanding of the science behind the medicine.

Visit

Evidence-driven medicine

Hear Your Colleagues’ Ground-breaking Ideas at Today’s Brainstorm Competition Make your way to the Innovation Hub presentation stage in Exhibit Hall B from 4:00 p.m. to 5:30 p.m. today for the lively game-style Brainstorm: A Competition for the Innovator in All of Us. Watch your trailblazing colleagues give it their all presenting their original, innovative solutions to challenges related to patients, practice, or other medical-related issues in front of a panel of AAN judges in the hopes of winning a $1,500 grand prize and consultation with the AAN Business Innovation team.

Awss Zidan, MD DancingEYES

Evan Noch, MD DESTROKE

DancingEyes is a mobile app that tracks subjects' eyes at rest and during different gazes in a manner similar to clinical exam. Then, DancingEyes analyzes the movements to provide useful information regarding the presence and the type of eye movement disorders, such as heterotropias, nystagmus and ocular motor oscillations. DancingEyes will be a useful asset to physicians in all clinical settings where diplopia, vertigo, or other symptoms arising from ocular movements may be encountered.

Stroke is the fifth leading cause of death. The biggest factor in stroke outcome is time to treatment, but there is no existing validated tool for early detection of stroke by patients. DESTROKE is a mobile-based app for early detection of stroke in realtime, based on the validated NIH stroke scale. The app allows immediate communication of test results to emergency contacts and emergency medical services, and uses facial, motion, and speech/language recognition technologies.

Andrew Southerland, MD Artificial intelligence-based software that screens for stroke using video recorded on a mobile device

Richard Bedlack, MD, PhD, FAAN ALSUntangled

Our idea is to improve the diagnosis and triage of stroke in the field by using artificial intelligence to help providers make more accurate decisions about stroke. We are developing software that interprets a video examination of a patient and determines the presence of neurological deficits indicative of stroke. Our software will help EMS providers more accurately identify stroke patients in need of timely treatment.

Patients with ALS often consider alternative treatments (ATs) on the Internet. ATs can be expensive and potentially harmful; accurate information about them is hard to find. ALSUntangled collects ATs from patients via Twitter, allows users to vote for their favorites, systematically reviews the most popular ideas, crowd sources these reviews across an international team of clinicians, then publishes these reviews “free open access,” thereby empowering patients to make more informed decisions.

Benjamin Sanchez, PhD Enhanced muscle diagnostics using needle i-EMG technology

The 2018 Brainstorm competition in Los Angeles drew a crowd to hear the participants' innovative ideas.

The medical community needs improved tools to evaluate neuromuscular disorders. One technology that could be incorporated into needle EMG to overcome its limitations is electrical impedance myography (EIM). Needle impedance-EMG has potential for greatly enhancing the accuracy of EMG, the clinical standard, ultimately yielding a “smarter EMG” diagnostic technology. We believe that needle i-EMG could ultimately become the new standard tool in clinical neuromuscular disease practice.

Monday, May 6, 2019 • AANextra

Head Over to the BrainDome for an Immersive Exploration Make your way to Exhibit Hall A for a completely new Annual Meeting experience when you step inside the one-of-a-kind BrainDome for a 10-minute journey of learning and exploration like no other. Open today through Wednesday from 12:00 p.m. to 5:00 p.m., and again on Friday from 12:00 p.m. to 4:00 p.m., the giant BrainDome will allow you to immerse yourself in the inner workings of the brain via a state-ofthe-art guided audio-visual spectacle. ď&#x201A;˘

ABF-HorizontalAds-2a_Hh.pdf

4/3/19

7:52 AM

Give monthly. Impact brain research all year long. Join a community in relentless pursuit to identify causes, improve treatments, and discover cures. The Brain Squad fuels the next generation of researchers who are building bridges between diseases and breaking new ground in research and application.

Visit our booth near registration to learn more.

MIPS Benchmarking—What to Know and Do to Succeed The requirements for the Quality Payment Program (QPP) Merit-based Incentive Payment System (MIPS) administered by the Centers for Medicare & Medicaid Services (CMS) are complex and can be confusing. AAN members may be unaware of how CMS has benchmarked quality measure performance and the impact these benchmarks can have on individual payment. Adam Webb, MD, and Sarah M. Benish, MD, FAAN, have answered some questions to help members better understand what benchmarking is, how it works, and how AAN members can use this information to succeed.

What is benchmarking? Webb: Benchmarking is a method of evaluating performance between organizations and individual providers. For MIPS, CMS sets benchmarks each year for each quality measure in the program. The benchmarks are specific to each type of submission method. As a result, providers reporting on the same measure will have different benchmarks depending on if they are reporting the measure via claims, their EHR, or a registry such as the Axon Registry ®.

How do these benchmarks impact MIPS scoring? Benish: For the MIPS quality component, providers should be reporting on six measures and one of these measures should be an outcome measure. CMS will award between one to 10 points for each MIPS measure based on your performance compared to their benchmarks. So, if you meet the data completeness requirements and do better on the six measures you report compared to your peers, you could be awarded 60 points. On the other hand, if you don’t do as well as your peers or you pick measures without benchmarks, you could be awarded 6-18 points. The goal is to get as many points as possible so your payment adjustment is positive. In English, that means a bonus rather than a penalty.

What is data completeness? Webb: For quality measures reported via claims, providers must report on 60 percent of the individual MIPS-eligible clinician’s Medicare Part B patients for the performance period. For quality measures reported via a qualified clinical data registry (QCDR), qualified registry, or EHR, eligible clinicians must report on 60 percent of the individual MIPS-eligible clinician’s patients across all payers for the performance period.

Benish

Webb

Benish: It is the minimum cases you need to report to CMS to get full credit for reporting the measure.

What should AAN members do to succeed? Webb: Work with your team to identify measures early in the year and track performance regularly. You should be identifying measures that are meaningful to your patient populations. Report on measures that have benchmarks and measures that don’t have benchmarks. Although CMS requires reporting on six measures, by reporting measures without benchmarks you can help CMS have enough performance data to establish benchmarks in future years. Benish: Don’t get overwhelmed. For a lot of members in academic practices, their administration already is reporting this data for multiple specialties. Measure data on medication reconciliation, blood pressure monitoring, etc., is being collected. Encourage your team to start reporting neurology measure data to help establish benchmarks. For solo and small practices, CMS has MIPS support available to you for free.

Where can members find information on benchmarking and the free MIPS support? Benish: The AAN has this information available at AAN.com/MACRA. CMS has information on their website at QPP.CMS.gov. The AAN is available to answer questions at macra@aan.com. 

UP TO +7% PAYMENT ADJUSTMENT

UP TO -7% PAYMENT ADJUSTMENT

HIGH PERFORMANCE BONUS

Monday, May 6, 2019 • AANextra

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

ONE CAPSULE, ONCE DAILY1 Convenient, once-daily dosing without complex titration1

Not actual size

• 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 • 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 • Offers convenient, once-daily dosing without complex titration1 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

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.

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

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.

ADVERSE REACTIONS

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.

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

for oral use

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

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.

Postmarketing Experience

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

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS Somnolence

QT Prolongation 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.

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

Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. 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

Adverse Reaction1

Examples: Strong CYP3A4 Inducers Clinical Implication:

paroxetine, fluoxetine, quinidine

Prevention or Management:

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

INGREZZA (n=262) (%)

Placebo (n=183) (%)

General Disorders Somnolence (somnolence, fatigue, sedation)

10.9%

4.2%

Examples: Digoxin Clinical Implication:

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

5.4%

4.9%

Prevention or Management:

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

4.1%

2.2%

Headache Akathisia (akathisia, restlessness)

3.4% 2.7%

Gastrointestinal Disorders Vomiting Nausea Musculoskeletal Disorders Arthralgia 1

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%

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

NOW

AVA ILABLE

Finally, there’s a whole new path to explore

Booth 2129 Follow the footprints in the exhibit hall and discover EPIDIOLEX® (cannabidiol) Cv

Greenwich Biosciences is growing innovation Step into the growing and manufacturing process with a virtual reality experience at the booth. Visit EPIDIOLEXhcp.com for more information

Colorful Poster of New Continuum Covers Offered Free with Subscription, Renewal A striking poster of the 2018 Continuum® cover designs by one of the world’s leading information illustrators is available for free to those who order a new Continuum subscription or renew their existing subscription at the Annual Meeting. The British artist Peter Grundy designed the covers for the redesigned Continuum, which launched in February 2018. Grundy has created simple, elegant infographics for clients and institutions around the world, including the Imperial War Museum, Shell International, the World Bank, and the United Nations. In 2013, he illustrated The Human Body, a book for children and adults that gave medical illustration a fresh, new look.

Child Neu rology

FEBR UARY

20 18

VOL . 24

NO. 1

Spinal Cor d Disorder

APRI L

Visit the Publications Area on Level 2 across from Registration to renew or subscribe to Continuum and receive a limited-edition poster while supplies last. A subscription to Continuum includes Continuum Audio, featuring lively conversations with article authors. 

Behavio

ral Neurolo gy and Psyc

hiatry JUNE 20 18

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AUG UST

Neuroin fectious

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The AAN’s Role in Advancing Coding and Reimbursement for Neurology An important component of a successful neurology practice is correct coding and claims submission for the critical services provided by a neurologist. The AAN strives to ensure appropriate reimbursement for neurology and to provide coding resources to support members and answer their questions quickly. This is especially critical given the rapidly changing landscape of health care. Physician volunteers and Academy staff participate in several external processes and strategic discussions that have allowed the AAN to be “at the table” when it comes to proposed payment changes that impact our members. How the AAN Participates in the CPT Process

How Can Members Get Involved?

The Current Procedural Terminology (CPT) code set created by the American Medical Association (AMA) is used to bill outpatient and office procedures. These five-digit codes provide a standard system to report medical procedures and services under public and private health insurance programs. The AMA’s CPT Editorial Panel meets three times each year to discuss and approve any CPT code additions, deletions, and revisions. The AAN has appointed several members as CPT advisors who review all proposed changes and, where appropriate, submit comments or requests for changes on behalf of neurology. The panel considers these written comments. AAN representatives and staff attend panel meetings and speak about any issues of relevance to neurology. The AMA publishes an updated CPT manual on an annual basis. New and revised codes are released in August with the publication of the AMA’s CPT® Professional and go into effect the following January. Because the AMA maintains the rights to the CPT code set, societies are bound by its confidentiality rules until the embargo lifts each year.

The recommendations presented by the AAN are based on survey data on the time and intensity of a given service. The AMA has a standard survey tool that is used by all medical specialties when surveying a CPT code and is distributed to physician members within the organization who are familiar with the service. If you receive a RUC survey from the AAN, please take the time to participate in this important process. The survey is the crucial foundation upon which the AAN develops recommendations to be considered by the RUC. Annually, the AMA submits the RUC recommended values to CMS, which has the final decision on payment rates that are published each year in the CMS Physician Fee Schedule. AAN coding and regulatory staff work as a team when anticipating new CPT codes and determining the need for outreach to CMS officials to raise awareness on the value of services provided by neurologists.

How the AAN Participates in the RUC Process The next phase of the process is an annual update to the physician work relative values. These values are based on recommendations from a committee involving the AMA and national medical specialty societies, known as the AMA/ Specialty Society Relative Value Scale Update Committee (RUC). The RUC acts as an expert panel in developing and delivering relative value recommendations for new or revised CPT codes to the Centers for Medicare & Medicaid Services (CMS). The RUC gives physicians a voice in shaping Medicare relative values. The RUC represents the entire medical profession—including the AAN, which holds a permanent seat on the committee. Academy members and staff attend the RUC meetings (also three times a year) to share recommendations on physician work and practice expense inputs (including staff time, equipment, and supplies) for codes.

Monday, May 6, 2019 • AANextra

Use These AAN Resources! The AAN provides online support to our members, including

Coding FAQs, E/M templates, and Care Management Service coding tables located at AAN.com/view/practicing.

The Practice Management Webinar Series includes several

topics geared toward coding and reimbursement. View the recorded webinar “Understanding How You Get Paid” at AAN.com/view/pmw19.

Members also can email practice@aan.com with coding and

reimbursement questions. 

What’s the key to breakthrough Neuro research and treatments? Collaboration. At NewYork-Presbyterian Hospital, we partner with specialists

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. 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. 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.

Learn more at nyp.org/neuroinnovations

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

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

Need some ideas? Here you go!

If you are in Philadelphia, you have to have a cheesesteak. My favorite place for a quick bite is Woodrow's on 7th and South Street. The truffle cheese is amazing. If you like jazz and southern charm, check out South Kitchen and Jazz Bar. It is easy to get to from the city and has a great vibe. If you get a chance to eat at Zahav, a mix of Israeli and Mediterranean influence, you will not be disappointed. If you are in the mood for Latin fusion and mojitos, Mixto restaurant fits the bill.

For amazing views of the city, grab a cocktail and sit at the bar at R2L.

Sharon Lewis, MD University of Pennsylvania 2019 Diversity Leadership Program participant

What are your Philly recommendations? Join the conversation at #AANAM

Monday, May 6, 2019 • AANextra

INDUSTRY THERAPEUTIC UPDATE FROM GENENTECH, A MEMBER OF THE ROCHE GROUP FROM

Horses to Zebras

New Perspectives in Common and Rare Neurologic Diseases

Monday, May 6, 2019 7:00 pm – 9:15 pm Independence Ballroom Philadelphia Marriott Downtown 1201 Market St, Philadelphia, PA

P R O G R A M FA C U LT Y M O D E R AT O R

Paulo Fontoura, MD, PhD

Global Head Clinical Development, Neuroscience Genentech and Roche Basel, Switzerland ALZHEIMER’S DISEASE

Jeffrey L. Cummings, MD, ScD

Research Professor UNLV School of Allied Health Sciences Director Center for Neurodegeneration and Translational Neuroscience Director Emeritus Cleveland Clinic Lou Ruvo Center for Brain Health Las Vegas, NV HUNTINGTON’S DISEASE

Victor Sung, MD

Clinical Director of UAB Huntington’s Disease Clinic Associate Professor of Neurology UAB Division of Movement Disorders Birmingham, AL S P I N A L M U S C U L A R AT R O P H Y

Although every neuromuscular and neurodegenerative disease is unique, approaches to treating these conditions have clear commonalities. In this program, the faculty will review recent advancements in neurology that may in turn help us advance the management of common and rare neurologic diseases.

John W. Day, MD, PhD

Professor of Neurology, Pediatrics, and Pathology Director Neuromuscular Division and Clinics Stanford University School of Medicine Palo Alto, CA ADVOCACY MEMBER

Mary Dunkle

Senior Advisor National Organization for Rare Disorders (NORD®) Danbury, CT

For more information and to preregister for this program, please visit www.horses2zebras.com Complimentary dinner will be served. Please note that seating is limited and priority admission will be given to preregistrants

Meals may be reportable under country, federal, state, and local jurisdictions. If you are a licensed healthcare professional in NJ, VT, or MN, please separately identify yourself to the registration staff at the symposium. Tables without food service will be available.

Please note: This event is not part of the official AAN Annual Meeting activities or endorsed by the AAN.

Want to learn more about AJOVY® (fremanezumab-vfrm) injection?

Visit booth #1729 or AJOVYhcp.com

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: P2.2-003 P2 = Poster Session Number 2 = Neighborhood 003 = Poster Board Number 

Poster Session 2 1. Aging, Dementia, Cognitive, and Behavioral Neurology: 1-001 to 1-035 2. Autoimmune Neurology; MS and CNS Inflammatory Disease: 2-001 to 2-110 3. Cerebrovascular Disease and Interventional Neurology: 3-001 to 3-069 4. Neuromuscular Disease and Clinical Neurophysiology (EMG): 4-001 to 4-045 5. Epilepsy/Clinical Neurophysiology (EEG): 5-001 to 5-036 6. Neuro-oncology; Global Health; Pain and Palliative Care; TRANSCENDS Scholarship Recipients: 6-001 to 6-079 7. Cerebrovascular Disease ePosters: 7-001 to 7-010 8. Movement Disorders: 8-001 to 8-054 9. Research Methodology, Education, and History; Neuro Trauma and Sports Neurology; Neurocritical Care; Medical Student Essay Award Recipients: 9-001 to 9-085 10. Headache: 10-001 to 10-025

1 2 3

1-001-1-035

2-001-2-110

3-001-3-069

4 5 6

4-001-4-045

5-001-5-036

6-001-6-079

7-001-7-010

ePosters

8 9 10

8-001-8-054

9-001-9-085

10-001-10-025

Monday, May 6, 2019 • AANextra

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! • Lower Price—By moving Annual Meeting On Demand to the AAN’s Online Learning Center, we’ve been able to lower the purchase price. • Simplified, Convenient Access—Access through the Online Learning Center, along with other AAN learning content. • 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! Gold Registration = Best Value! Upgrade to Gold Registration and receive all sessions at the meeting2 as well as access to Annual Meeting On Demand. With so many concurrent sessions, Gold Registration is the best value for attendees who want to experience the full value of the meeting. 2

Some courses require pre-registration, may have a separate registration fee, and are subject to closure due to reaching maximum capacity.

Select Gold Registration when you register for the meeting!

Order Online: AAN.com/view/19AMOD

Order Onsite Be sure to visit the eLearning Networking and Innovation space at the Annual Meeting for any Annual Meeting On Demand or other online learning questions!

Gold RegistrationÂ Student Members and Nonmember Students

$99

Honorary and Senior Members

$279

Intern and Junior Members

$459

Nonphysician Members (Advanced Practice Provider, Business Administrator, Researcher)

$694

Neurologist and Physician Affiliate Members

$1,284

Nonmembers

$2,129

* Specific presentations within a session may not be available based on permissions granted by the presenter. **With the move to an online offering, hard drives will not be provided.

MONDAY, MAY 6 11:30 A.M. TO 1:00 P.M. Locations: Exhibit Hall C (limited quantities available at Broad Street Atrium)

Boxed Lunch Menu Lunch Options Option I:

Rice Noodle Salad

Thai Spiced Chicken

Asian Blend Vegetables with Ginger Lime Vinaigrette

Sliced Apples

Spiced Almond Cookie

Option II Vegan/Vegetarian/Gluten Free:

Rice Noodle Salad

Thai Spiced Tofu

Asian Blend Vegetables with Ginger Lime Vinaigrette

Sliced Apples

Spiced Almond Cookie

Almuerzos con Colegas

12:00 p.m.–12:45 p.m. Exhibit Hall, zona de almuerzo Reunámonos a comer con colegas hispanoparlantes para charlar sobre temas de interés común. Temas de hoy: Neurología general e investigaciones clínicas.

Hear from Winners of Prestigious Awards at The Grand Experience Stage continued from cover neurology, and our hope is always that the recognition and funding from these awards will help these trailblazers continue their important work,” said AAN Science Committee Chair Natalia S. Rost, MD, MPH, FAAN, FAHA. “With that in mind, we’re excited to offer the opportunity at this year’s Annual Meeting to hear from our past recipients of these awards and learn about their research and successes since receiving these awards.” Potamkin Prize for Research

in Pick’s, Alzheimer’s, and Related Diseases

Monday, May 6, 3:30 p.m. Recipient: Randall Bateman, MD Distinguished Panel Members David M. Holtzman, MD, FAAN Virginia Lee, PhD

Bateman

Holtzman

Lee

Sperling

Gitler

Cudkowicz

Przedborski

Shefner

Cross

Raine

Steinman

Antel

Reisa A. Sperling, MD Sheila Essey Award: An Award

for ALS Research

Tuesday, May 7, 3:30 p.m. Recipient: Aaron Gitler, PhD Distinguished Panel Members Merit Cudkowicz, MD, MSc Serge Przedborski, MD, PhD Jeremy Shefner, MD, PhD, FAAN John Dystel Prize for Multiple

Sclerosis Research

Wednesday, May 8, 3:30 p.m. Recipient: Anne Cross, MD Distinguished Panel Members

Cedric S. Raine, PhD, DSc Lawrence Steinman, MD, FAAN Jack P. Antel, MD, FAAN Howard L. Weiner, MD

Weiner

A.B. Baker Award for Lifetime Achievement in Neurologic Education

Stop by the Navigating Your Career Stage between 1:00 p.m. and 1:45 p.m. on Wednesday to hear A.B. Baker Award for Lifetime Achievement in Neurologic Education recipient Steven L. Lewis, MD, FAAN, present his keynote address "Teaching Neurologic Competency Competently Despite the Competencies." The Frank A. Rubino Award for Excellence in Clinical Neurology Teaching will also be presented to Allan J. Aksamit, Jr., MD, FAAN. 

Aksamit

Lewis

Monday, May 6, 2019 • AANextra

Visit us at Booth #2345 at the AAN Annual Meeting

Follow the PATH The next step in CIDP

• Learn about our portfolio of Ig products, including the first and only subcutaneous Ig (SCIg) for CIDP maintenance in adults For adults with CIDP stabilized on IVIg

PROVEN CIDP CONTROL Greater Freedom for Everyday Living

• Watch a video of a CIDP patient demonstrating SCIg self-administration • See results from PATH— the largest study in CIDP

Important Safety Information Hizentra is indicated for: • Treatment of primary immunodeficiency (PI) in adults and pediatric patients 2 years and older. • Maintenance therapy in adults with chronic inflammatory demyelinating polyneuropathy (CIDP) to prevent relapse of neuromuscular disability and impairment. – Limitation of Use: Maintenance therapy in CIDP has been systematically studied for 6 months and for a further 12 months in a follow-up study. Continued maintenance beyond these periods should be individualized based on patient response and need for continued therapy. For subcutaneous infusion only. WARNING: Thrombosis may occur with immune globulin products, including Hizentra. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity, and cardiovascular risk factors. For patients at risk of thrombosis, administer Hizentra at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Hizentra is contraindicated in patients with a history of anaphylactic or severe systemic reaction to human immune globulin (Ig) or components of Hizentra (eg, polysorbate 80), as well as in patients with immunoglobulin A deficiency with

antibodies against IgA and a history of hypersensitivity. Because Hizentra contains L-proline as stabilizer, use in patients with hyperprolinemia is contraindicated. IgA-deficient patients with anti-IgA antibodies are at greater risk of severe hypersensitivity and anaphylactic reactions. Thrombosis may occur following treatment with Ig products, including Hizentra. Monitor patients for aseptic meningitis syndrome (AMS), which may occur following treatment with Ig products, including Hizentra. In patients at risk of acute renal failure, monitor renal function, including blood urea nitrogen, serum creatinine and urine output. In addition, monitor patients for clinical signs of hemolysis or pulmonary adverse reactions (eg, transfusion-related acute lung injury [TRALI]). Hizentra is derived from human blood. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent and its variant (vCJD), cannot be completely eliminated. The most common adverse reactions (observed in ≥5% of study subjects) were local infusion-site reactions, as well as headache, diarrhea, fatigue, back pain, nausea, extremity pain, cough, upper respiratory tract infection, rash, pruritus, vomiting, upper abdominal pain, migraine, arthralgia, pain, fall, and nasopharyngitis. The passive transfer of antibodies can interfere with response to live virus vaccines and lead to misinterpretation of serologic test results. Please see the following brief summary of prescribing information for Hizentra, including boxed warning.

Scan your badge at Booth #2345. We’ll contribute to support people with CIDP.

CSL Behring will contribute to the GBS|CIDP Foundation International with every scanned badge. Help us reach our sponsorship goal of $25,000! CSL Behring does not make products indicated for GBS in the US.

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May is CIDP Awareness Month

Hizentra is manufactured by CSL Behring AG and distributed by CSL Behring LLC. Hizentra® is a registered trademark of CSL Behring AG. Biotherapies for Life® is a registered trademark of CSL Behring LLC. ©2019 CSL Behring LLC 1020 First Avenue, PO Box 61501, King of Prussia, PA 19406-0901 USA www.CSLBehring.com www.Hizentra.com HIZ-0838-MAR19

HIZENTRA®, Immune Globulin Subcutaneous (Human), 20% Liquid Initial U.S. Approval: 2010 BRIEF SUMMARY OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use HIZENTRA safely and effectively. See full prescribing information for HIZENTRA. WARNING: THROMBOSIS

See full prescribing information for complete boxed warning. • Thrombosis may occur with immune globulin products, including HIZENTRA. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity, and cardiovascular risk factors. • For patients at risk of thrombosis, administer HIZENTRA at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. -----------------------------------INDICATIONS AND USAGE----------------------------------HIZENTRA is indicated for: *Treatment of primary immunodeficiency (PI) in adults and pediatric patients 2 years and older. * Maintenance therapy in adults with chronic inflammatory demyelinating polyneuropathy (CIDP) to prevent relapse of neuromuscular disability and impairment. -Limitation of Use: Maintenance therapy in CIDP has been systematically studied for 6 months and for a further 12 months in a follow-up study. Continued maintenance beyond these periods should be individualized based on patient response and need for continued therapy. For subcutaneous infusion only. -------------------------------DOSAGE FORMS AND STRENGTHS---------------------------0.2 g per mL (20%) protein solution for subcutaneous injection

-------------------------------------CONTRAINDICATIONS-------------------------------------• Anaphylactic or severe systemic reaction to human immune globulin or components of HIZENTRA, such as polysorbate 80 • Hyperprolinemia (type I or II) (HIZENTRA contains the stabilizer L-proline) • IgA-deficient patients with antibodies against IgA and a history of hypersensitivity -------------------------------WARNINGS AND PRECAUTIONS-------------------------------• IgA-deficient patients with anti-IgA antibodies are at greater risk of severe hypersensitivity and anaphylactic reactions. • Thrombosis may occur following treatment with immune globulin products, including HIZENTRA. • Aseptic meningitis syndrome has been reported with IGIV or IGSC, including HIZENTRA treatment. • Monitor renal function, including blood urea nitrogen, serum creatinine, and urine output in patients at risk of acute renal failure. • Monitor for clinical signs and symptoms of hemolysis. • Monitor for pulmonary adverse reactions (transfusion-related acute lung injury [TRALI]) • HIZENTRA is made from human plasma and may contain infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the CreutzfeldtJakob disease (CJD) agent. -------------------------------------ADVERSE REACTIONS--------------------------------------The most common adverse reactions observed in ≥5% of study subjects were local infusion site reactions, headache, diarrhea, fatigue, back pain, nausea, pain in extremity, cough, upper respiratory tract infection, rash, pruritus, vomiting, abdominal pain (upper), migraine, arthralgia, pain, fall and nasopharyngitis. To report SUSPECTED ADVERSE REACTIONS, contact CSL Behring Pharmacovigilance at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda. gov/medwatch. ----------------------------------------DRUG INTERACTIONS-----------------------------------The passive transfer of antibodies may interfere with the response to live virus vaccines, and lead to misinterpretation of the results of serological testing. Based on March 2018 revision

Networking for Neurologists: Use a Three-ring Approach to Create Contacts, Friends, and Mentors If you’ve read any career or job search advice lately, then you know how frequently networking is prescribed as the solution to your problems or the pathway to your goals. When you add up all the curative powers of this one process, it’s almost as if networking were the career equivalent of eating your apples and broccoli to stay healthy. (Remember the adage, “An apple a day keeps the doctor away”?) There’s just one problem: Knowing about networking isn’t the same as knowing how to network. Read on. With a few simple steps, you can go from keeping those doctors away to having them accepting your request for help and advice as you progress through your career.

What Networking Is (and Isn’t)

The first thing to know is that networking isn’t a special form of communication or an extra type of outreach. It’s much simpler and more powerful than that. In its purest form, networking is simply the forging of relationships around common bonds or for mutual assistance. If you have a specific need—say, for an introduction to a department chair—networking can be driven by a goal. But in other circumstances, it’s less about reaching objectives and more about creating liaisons that will likely be helpful to both people somewhere down the road. Also, it’s good to know that, while networking isn’t mentoring, it can be a very important part of that process. For example, when you want to develop a mentoring relationship with a more senior neurologist acting as your guide, having networked with that person earlier can lay the groundwork nicely. And, after your formal mentoring relationship has ended, you both may benefit from meeting people in each others’ networks as you move forward in your respective careers.

Understanding the Three Rings

One of the easiest ways to develop networking as a habit is to envision the process as three concentric circles, with you in the center. In this case, the circles each represent a different aspect of your professional life. (Although for other purposes—say if you needed help raising funds for a charity—you might envision your rings differently.) Here’s how the circles might look for a vascular fellow in a medium-sized city hospital who hopes to build strong relationships for future job search assistance, and for more immediate mentoring. RING ONE: Vascular neurology or stroke department of the hospital. If you were a vascular fellow, this would be home territory, so the people in this ring would already be familiar to you. Still, it pays to take a quick inventory, as it can be too easy to focus attention on only those you interact with closely. It’s likely that your department includes any or all of the following: fellows and chief fellow, of course; physicians, attendings, or residents who may rotate through; nurses; NPs and other advanced practice professionals; professors or academic staff; department chair and others in that office; clerical staff…you

Monday, May 6, 2019 • AANextra

get the idea. If you were situated in a hospital as a practitioner rather than as a fellow, this first ring might look the same, but if you were a practitioner in a private practice group, it would probably be much smaller. RING TWO: The hospital as a whole. Given the high workloads for many fellows, it might seem optimistic to imagine connecting with others outside your immediate line of vision. Even so, it probably won’t get easier to make these connections once you’ve finished training. Now’s the time to be more aware of your surroundings and the people in other parts of your organization. There will be too many to list, so the goal is to better understand this ring in general terms. To start, it helps to have an organizational chart of departments, as well as an understanding about where your hospital may fit in a larger corporation or grouping of organizations. People in these other locations may be far-flung, but they’re still “kin,” so to speak, since you share the same employer. Again, if you were out of training but practicing in a hospital, your list would look similar to the list a fellow might build. But it would differ if you were situated elsewhere. For example, for a neurologist employed in a university, this circle could also contain the other academic departments, or the broader administrative staff. A doctor in private practice would envision this ring by identifying people in closely-affiliated organizations, such as the hospital where he or she has privileges. RING THREE: Your profession of neurology. Now things get simple again, even though this circle is vastly larger than the other two. Using the resources

available to you as an AAN member, it’s fairly easy to identify the groupings and individuals who fall under the general concept or specialty areas of neurology. But there may still be a twist: If our vascular fellow in this example were coming from an earlier profession—say, he or she started in internal medicine before returning for specialized neurology training—this circle could include an even larger group of professionals.

Connecting with Others—When’s the Best Time?

Now that you have a sense of how many people you could connect with, and a way to categorize them conceptually, it’s time to dig in. The actual process of networking doesn’t have to be intensive, unless you have a time-sensitive issue that you need help with. The goal is to lay the foundation with a few people in each ring as early as possible so that you can stay connected casually and collegially over the ensuing years. Building a networking mindset while still in training is ideal because it’s usually easier to request brief conversations or advice at this stage. For one thing, if you’re in training now, you’re already in a learning frame of mind. Moreover, others may feel more open to accepting your request for a connection, as they can usually relate to the experience of being in the career stage you’re in now. That said, networking can be initiated or enhanced at any stage of a career. Indeed, the further you get from your training, the more you are likely to value the advice and friendship of others in your field.

How Can You Make the Outreach?

This will be easier than you think, once you resolve any initial discomfort or nervousness you may feel about the process. That’s a very normal feeling, as we often imagine others are too busy to respond or will resent being contacted. In fact, that may be true in a minority of cases, but you can’t control or predict that, so the best way to proceed is to imagine how you’d like to be contacted if the situation were reversed. As a rule, one or more of the following methods will work to reach out to almost anyone: Send a short, polite email introducing yourself and stating that you’d like to connect at a later point to: (choose one) learn more about their department; ask their advice; something else. If the person is someone you see regularly, ask them in person: Would you have time for a cup of coffee in the next week or two? I’d like to: (choose one) feel more connected with people in our department; get to know you better, as I’ve admired your work; ask your advice; something else. If the person is someone you feel intimidated by but would like to connect with, consider asking an intermediary to introduce you. If you’re on LinkedIn or another social media tool designed for professionals, reach out by issuing an invitation to connect. Be sure to word the invitation personally, rather than using the default “I’d like to be connected” option, as this lets them know you’re sincere. If you know that you will both be in the same place at the same time—say at the AAN Annual Meeting, or perhaps a more local gathering— send an email inviting them to join you for a cup of coffee or a brief connection before or after a session.

A Small Investment for a Lifetime of Rewards

Are you ready to add networking to your list of careerbuilding tools? It doesn’t have to take much of your time. Start with just one or two contacts a month—perhaps a total of 20 minutes for reaching out, and an additional hour or two if you schedule conversations. If you create a database or email files to store your contacts, you’ll be able to tell later who might be good to talk with if something time-sensitive arises. You’ll be surprised to see how much easier it is to ask for help when you’ve already got a connection to someone, however casual it may be. And don’t forget the power of a compliment. Even if you don’t have a purpose for building a particular relationship, a short note complimenting someone on their published article or the poster they presented will never go awry. With our electronic tools, this takes only a minute but the positive effects can last a lifetime—for both parties.

Monday, May 6, 2019 • AANextra

Most Critical Practice Issues Outlined in Today’s Contemporary Clinical Issues Plenary continued from cover Topics and presenters include: Implementation and Patient Experience with Outpatient Subspecialty Teleneurology Visits at a Single Academic Institution over Four Years

AFM: Beyond Acute and Flaccid

A Pilot Study of Adoptive Cellular Immunotherapy for Progressive Multifocal Leukoencephalopathy with Ex Vivo Generated Polyomavirusspecific T-cells

Presenter: Lindsay Ross, MD, Cleveland Clinic Foundation, Cleveland, OH

Presenter: Erin Savner Beck, MD, NINDS, NIH, Bethesda, MD

Discussant: Lawrence R. Wechsler, MD, FAAN, University of Pittsburgh School of Medicine, Pittsburgh, PA

Discussant: Carolyn B. Britton, MD, Columbia University Irving Medical Center, New York, NY

Amyloid PET Leads to Frequent Changes in Management of Cognitively Impaired Patients: The Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) Study

Continuous Theta Burst Stimulation over Right Pars Triangularis Facilitates Naming Abilities in Chronic Post-stroke Aphasia by Enhancing Phonological Access

Presenter: Gil Dan Rabinovici, MD, University of California, San Francisco Memory & Aging Center, San Francisco, CA

Presenter: Denise Y. Harvey, PhD, University of Pennsylvania, Philadelphia, PA

Discussant: Eric M. Reiman, MD, Banner Alzheimer’s Institute, Phoenix, AZ

Discussant: Eric M. Wassermann, MD, National Institutes of Health, Bethesda, MD

Teri Schreiner, MD, MPH, Children’s Hospital Colorado, Aurora, CO

Advances in the Acute Treatment of Migraine Jessica Ailani, MD, Medstar Georgetown Neurology, McLean, VA

What is your aha moment from the Contemporary Clinical Issues Plenary Session? Join the conversation at #AANAM. 

Monday, May 6, 2019 • AANextra

SEE YOU NEXT YEAR TORONTO, CANADA

APRIL 25 â&#x20AC;&#x201C;MAY 1, 2O2O

Visit AAN.com/view/AM20Interest

Powerful Talk on Flint Water Crisis Set for 1:00 p.m. Today continued from cover Hanna-Attisha is a pediatrician, professor, and public health advocate whose bestselling book, What the Eyes Don’t See: A Story of Crisis, Resistance, and Hope in an American City, is a fascinating account of a shameful disaster that became a tale of activism and hope. A limited number of free books will be available to attendees, as well as additional copies for purchase. There will be one final Advancing Medicine talk on social morals beginning at 1:00 p.m. in Ballroom A on Wednesday. 

NEW IN

2019

2313

What Are Your Colleagues Saying? Share your thoughts at #AANAM. Join the conversation!

#AANAM Chaitanya Bonda, MD / Bentonville, AK “What brought you to the Annual Meeting?” “I’m especially interested in MS treatment and symptom management. I specialize in neuromuscular, but I see a lot of MS patients, and MS is the most challenging part of my practice. This is my first time attending. So far the plenary sessions have been very good.”

Lisa M. Ford, MD, FAAN / Morristown, NJ “What are the highlights of the meeting for you so far?” “I’m a child neurologist. There are a lot of presentations on SMA and Batten disease, which is quite exciting. We’re really starting to see some progress in areas where there were no treatments. It’s a pleasure to be here.”

Justine Brink, DO, MPH / Reno, NV “What brings you to the Annual Meeting?” “I come for the latest updates in MS. I went to the Clerkship Director meeting, where the take-aways for me were how to write good questions for assessing our students and how to mitigate trainee burnout. Those were engaging. And seeing all my friends from medical school, residency, and fellowship. I also want to talk to my colleagues about the new MS medications that just came on the market.”

Robert W. Baloh, MD, FAAN / Los Angeles, CA Faculty, Neuro-otology courses “How many Annual Meetings have you attended?” “I don’t think I’ve missed one since 1971, when I was a third-year resident. I enjoy seeing friends and former trainees. Probably the social aspect is what I enjoy most. And I go to sessions.” “How has the meeting changed over the years?” “It’s gotten so big. There are so many things that it’s impossible to go to everything. Certainly, the plenary sessions are always very good and it’s still the best clinical neurology meeting there is.”

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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

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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

What Excited You Today at #AANAM? Join the conversation at #AANAM

Jeff Kraakevik MD @ohsuneuro In the neuro pictionary draw of the match, Dr Chad Hales drew something like this. Anybody know the neurological term he was drawing? #AANAM We have a winner! @ivanrf brings it home using the eponym = major bonus points. Hansen disease or leprosy is commonly carried by armadillos. You win a virtual cuppa tea on a rainy day in Philly! #AANAM

Nilay Shah @docnilay

Allison Weathers, MD @AlWeathersMD Phemenonal talk (as always) by @Teleneurology on Telemedicine FAILs at the innovation hub. Informative yet a bit terrifying. Loved the robust audience participation and hearing all the different perspectives. #AANAM

Happy to participate and donate! @ABFbrain #AANAM

Rachael J. Murphy @RachaelJMurphy @AANMember #AANAM Got my shirt

Amy Guzik MD @timeisbrain “Culture is what is expected, reinforced, and rewarded” Re: pushing the culture towards gender equality. #womeninleadership session #AANAM

Monday, May 6, 2019 • AANextra

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

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

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

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

Spinal Muscular Atrophy Presentation 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 Huntington’s Disease Presentation Dr Victor Sung, MD Associate Professor, UAB Department of Neurology, Division of Movement Disorders Director, UAB/HDSA Huntington’s Disease Center of Excellence Birmingham, Alabama

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

Industry Therapeutic Update from Biogen

Spinal muscular atrophy in adults: Natural history and management of disease Dinner* will be provided.

Featuring: Chair: Stephen J. Kolb, MD, PhD Ohio State Wexner Medical Center Columbus, OH Perry Shieh, MD, PhD David Geffen School of Medicine Los Angeles, CA Kathryn J. Swoboda, MD Massachusetts General Hospital Boston, MA

When:

Where:

Tuesday, May 7, 2019 7:00 PM

Marriott Downtown Hotel, Philadelphia, PA Independence Ballroom

* In accordance with the Sunshine Act reporting requirement, meals served at this event may be considered transfers of value and could be reportable. Please review your local state guidelines around promotional programs to ensure compliance.

Not an official event of the 2019 AAN Annual Meeting. Not sponsored, endorsed, or accredited by AAN. This is not a CME program nor will CME credits be given for attendance.

Biogen-10791