2018 Annual Meeting AAN Extra — Monday, Apr 23 by American Academy of Neurology

THE ANNUAL MEETING NEWS DAILY

Monday, April 23, 2018

INSIDE

ANNUAL MEETING ATTENDEES ENJOY THE MAGIC OF UNIVERSAL STUDIOS AT THE AAN 70TH ANNIVERSARY PARTY

4 5

Some 5,000 neurology professionals on hand for the Annual Meeting explored Continued on page 18 u

New Leadership Course Focuses on Leading in Era of Burnout Epilepsy/Clinical Neurophysiology Highlighted in This Morning’s “Best of” Session

Your Colleagues 20 Watch Present Their Most Inventive Solutions at Today’s Brainstorm “Game Show” Steps to Cure Brain 21 Take Disease at Tomorrow’s Run/Walk

Don’t Miss This Morning’s Contemporary Clinical Issues Plenary Session Highlighting issues most critical to practicing neurologists, this morning's Contemporary Clinical Issues Plenary Session includes abstracts related to new therapeutic Continued on page 10 u

Trainees: Network, Find Opportunities at Tonight’s Faculty and Trainee Reception A premier networking event for those in undergraduate and graduate medical education will take place tonight at the JW Marriott Diamond Ballroom from 6:00 p.m. to 9:00 p.m. Don’t miss this unique opportunity to meet and network with nearly 500 academic personnel. Trainees will have the opportunity to

view residency, fellowship, academic/ research positions, or private and group practice positions. The event kicks off with award presentations and recognition of scholarship recipients. Jaffar Khan, MD, FAAN, chair of the AAN Graduate Continued on page 20 u

In Multiple Sclerosis, when it comes to Brain Preservation

Grey Matters, Too JOIN US AT

Booth 932

Monday, April 23 Cover Annual Meeting Attendees Enjoy the Magic of Universal Studios At the AAN 70th Anniversary Party

3 4 4 5 6 8

Trainees: Network, Find Opportunities at Tonight’s Faculty and Trainee Reception Don’t Miss This Morning’s Contemporary Clinical Issues Plenary Session

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Daily Reminders Check out New ePoster Areas at Poster Sessions

12 Today’s Experiential Learning Area Highlights

17 Quotable Quotes 20 Watch Your Colleagues Present Their Most Inventive Solutions at Today’s Brainstorm “Game Show”

Monday’s AAN Section Meetings

21 Take Steps to Cure Brain Disease at

New Leadership Course Focuses on Leading in Era of Burnout

24 Thank You 2018 Annual Meeting

Reminder: ‘Continue the Conversation’ on Tremor Today at 3:00

32 Through Their Eyes: Recollections of

Epilepsy/Clinical Neurophysiology Highlighted in This Morning’s “Best of” Session Congratulate Safety and Quality Award Recipients

Tomorrow’s Run/Walk Abstract Reviewers!

Past AAN Presidents

37 Visit Foundation Booth for

Crowdfunding Site Demonstration

37 Today’s Boxed Lunch Menu 38 Tweets of the Day

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

Contact Information: American Academy of Neurology 201 Chicago Avenue Minneapolis, MN 55415 USA Phone: (800) 879-1960 (Toll Free) or (612) 928-6100 (International) Fax: (612) 454-2744 Email: memberservices@aan.com Website: AAN.com AAN Executive Director/CEO: Catherine M. Rydell, CAE

Managing Editor: Angela Babb, CAE Editor: Tim Streeter Writers: Ryan Knoke, Sarah Parsons Designer: Jim Hopwood Photography: Will Evans Printing: Lithographix, Inc. Email: aannews@aan.com AANextra is published by the American Academy of Neurology.

Reminder: Today’s Hot Topics Program to Examine Impacts of Dramatic Changes in Stroke Care

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.

Monday’s AAN Section Meetings 7:00 a.m.–8:00 a.m.

1:30 p.m.–2:30 p.m.

Clinical Neurophysiology Section LACC Petree Hall C

Government Service Section LACC Petree Hall D

Spine Section | LACC Petree Hall D

3:30 p.m.–4:30 p.m.

8:00 a.m.–9:00 a.m.

Critical Care & Emergency Neurology Section | LACC Petree Hall D

Consortium of Neurology Advanced Practice Providers | LACC 308AB

8:15 a.m.–9:15 a.m. General Neurology Section LACC Petree Hall D Headache & Facial Pain Section LACC Petree Hall C

12:00 p.m.–1:00 p.m.

Neurohospitalist Section LACC Petree Hall C

5:30 p.m.–6:30 p.m. Business Administration Section LACC Petree Hall D Sports Neurology Section LACC Petree Hall C

History Section | LACC Petree Hall C

5:45 p.m.–6:45 p.m.

Movement Disorders Section LACC Petree Hall D

Multiple Sclerosis Section LACC West Exhibit Hall B 

The American Academy of Neurology sincerely thanks Lithographix, Inc. for its outstanding service, steadfast professionalism, and high quality standards, as well as its generous donation of the 2018 Brain Health Fair program guide.

New Leadership Course Focuses on Leading in Era of Burnout AAN Past President Terrence L. Cascino, MD, FAAN, who spearheaded the AAN’s efforts to research the issue of physician burnout and develop resources to mitigate it, will lead a new Leadership University course tomorrow on “Leadership in the Era of Burnout: A Practical Approach to Becoming a True Physician Leader.” Cascino

Cascino said the course will examine how to lead effectively and at the same time promote wellness. “The challenge of being a leader is complicated by a high rate of burnout,” he said. “This course will offer practical ideas for meeting this challenge and ways to cultivate well-being and resiliency in your practice or institution.” No registration is needed for the course, C118, which will be located in Room 409AB. 

Reminder: ‘Continue the Conversation’ on Tremor Today at 3:00 Be sure to stick around following C70 Evaluating Tremor in the Office course this afternoon from 3:00 p.m. to 3:30 p.m. in 403B to join program director Vicki Shanker, MD, for a small-group conversation and Q & A over wine and cheese as part of the new pilot program, “Continuing the Conversation.”  18: AAN.com Launch Ad—Half Page Horizontal> AN Placed in AANnews 8.25 x 5.25 +0.125 bleed, 4C

Your life is personalized...

now AAN.com is too. Log in today AAN.com/memberprofile

Epilepsy/Clinical Neurophysiology Highlighted in This Morning’s “Best of” Session The top four abstracts on epilepsy/clinical neurophysiology (EEG) will be presented in this morning’s “Best of” Scientific Platform Session. The session is a perfect lead-in to the Contemporary Clinical Issues Plenary Session that immediately follows.

“Best of” Session: Epilepsy/Clinical Neurophysiology (EEG) 8:00 a.m.–9:00 a.m. 408B

8:00 a.m. Maintaining Seizure Freedom During Pregnancy and Postpartum: Findings from the MONEAD Study —Page Pennell, Jacqueline French, Ryan May, Elizabeth Gerard, Laura Kalayjian, Evan Gedzelman, Patricia Penovich, Jennifer Cavitt, Sean Hwang, Alison Pack, Maria Sam, Eugene Moore, Dominic Ippolito, Kimford Meador 8:08 a.m. A Practical Risk Score for EEG Seizures in Hospitalized Patients —Aaron Struck, Berk Ustun, Andres Rodriguez-Ruiz, Jong Lee, Suzette LaRoche, Lawrence Hirsch, Emily Gilmore, Jan Vlachy, Hiba Haider, Cynthia Rudin, M. Westover

8:24 a.m. Interictal Spike Rates Are Correlated with Verbal Memory in Patients with Mesial Temporal Lobe Epilepsy —Kimford Meador, David Loring, Tara Crowder Skarpaas, Martha Morrell 8:35 a.m. Panel Discussion Meet the Investigators 

8:16 a.m. Seizure Semiologies and Effects of Anti-epileptic Drugs in Patients with Leucine-rich gliomainactivated-1 ligand antibody (LGI1-Ab) Autoimmune Epilepsy — Christopher Lamb, Jeffrey Britton, Sean Pittock, Avi Gadoth, Andrew McKeon, Christopher Klein, Anteneh Feyissa

INDUSTRY THERAPEUTIC UPDATE FROM AKCEA THERAPEUTICS*: CHARTING THE COURSE

in Diagnosis of Rare Peripheral Neuropathies Monday, April 23, 2018 7:00 pm | Doors Open 6:30 pm

Westin Bonaventure | Beaudry B | Lobby Level 404 S Figueroa Street | Los Angeles, CA

Please visit register.chartingthecoursepn.com to register for this event. Join Sami Khella, MD, Chair, and our expert faculty panel at this industry therapeutic update where we will discuss rare peripheral neuropathies, including chronic inflammatory demyelinating polyneuropathy, hereditary ATTR amyloidosis, and Charcot-Marie-Tooth disease. This interactive session will illustrate diagnostic challenges and provide guidance toward making a differential diagnosis among these rare neuropathies. Stop by Akcea booth #707 for more information!

Moderator: Sami Khella, MD Professor of Clinical Neurology Chief Department of Neurology Penn Presbyterian Medical Center Philadelphia, PA

*Pursuant to a potential transaction involving a collaboration with Ionis Pharmaceuticals, Inc., which remains subject to stockholder approval and customary closing conditions. Please note that this is a promotional, non-CME program, and no CME credits will be given for attendance. This event is not sponsored or endorsed by AAN. ©2018 Akcea Therapeutics, Inc. All rights reserved. TTR-084 04/18

Monday, April 23, 2018 • AANextra

Congratulate Safety and Quality Award Recipients Recipients of the Safety and Quality Awards, sponsored by the AAN, are being recognized at this week’s meeting. The honorees are: Lily Grossmann, MD, Boston, MA Continuous Anesthesia Protocol for MRI and LP in Children Grossmann is being recognized for her work to improve patient experience for children requiring a lumbar puncture (LP) and MRI for evaluation of their pediatric neurological condition. Through a partnership of the neurology and anesthesia departments, a protocol was developed for continuous anesthesia for MRI and LP tests to be done sequentially. Over the course of Grossmann the project, the protocol was found to be feasible, cost-effective, safe, and less burdensome for patients and their families. Yi Li, MD, PhD, Worcester, MA Utilization of Ultrasound Guided Lumbar Puncture to Improve the Efficacy and Outcome in an Overweight Patient Population Li is being recognized for her project implementing an ultrasound guided lumbar puncture learning module for neurology residents that includes a one-hour didactic presentation with a 30-minute practice session. Residents who have completed the module have shown to have a higher success rate, shorter procedure duration, and lower CHP: 18 Advocacy Awareness Ad, AANextra, Half Page Horizontal patient complaints ofplaced pain. in AANnews USAGE: High Resolution PDF to be SPECS: Trim Size 8.25"x4.4375", Full Bleed +0.125", 4C

Read Capitol Hill Report We’re fighting to make sure the future of your patients and profession isn’t decided without your input. Read Capitol Hill Report to learn what we’re doing and how you can help. Stay informed at AAN.com/view/HillReport. Join the conversation using #AANAdvocacy.

Michael Robers, MD, Phoenix, AZ Improving the Time for Physician Acknowledgement of Send out Labs

Robers

Robers is accepting on behalf of the senior members of his resident class at Barrow Neurological Institute. Their efforts to improve physician acknowledgement of lab results in a timely manner were successful. By leveraging the electronic medical record, physician response rate went from 36 percent to 93 percent and the average time between a reported result and physician acknowledgement went down by 66 percent.

Mauricio Villamar, MD, Lexington, KY Improvement in Time to Administration of Second-line Antiseizure Medications After Implementation of an Inpatient Status Epilepticus Alert Protocol Villamar is being recognized for his work on improving the rapid identification and treatment of patients with status epilepticus (SE). A novel SE alert protocol resulted in rapid notification of key team members including the general neurology resident, the pharmacist, the neurointensivist on call, as well as the rapid response team.  Villamar

VISIT US AT BOOTH #1202

TO LEARN MORE ABOUT GRT

GENE REPLACEMENT THERAPY:

A GENETIC EVOLUTION from Mendel’s work based in nature to notable advancements in medicine

We’ve come a long way since Mendel first laid the foundation of genetics— today, gene replacement therapy (GRT) is being investigated as a therapeutic approach that may have the potential to treat monogenic diseases at their source.1,2

References:1. Gayon J. From Mendel to epigenetics: history of genetics. C R Biol. 2016;339(7-8):225-230. 2. Naldini L. Gene therapy returns to centre stage. Nature. 2015;526(7573):351-360. © 2018 AveXis, Inc. All Rights Reserved. US-UNB-18-0039 04/18

Reminder: Today’s Hot Topics Program to Examine Impacts of Dramatic Changes in Stroke Care Recent changes in the management of acute ischemic stroke (AIS), based on the 2017 DAWN study, 2018 DEFUSE-3 study, and American Heart Association and the American Stroke Association’s new guidelines for early management of AIS, will have significant impacts on workforce, residency, staffing, and other aspects of the neurology profession and practice. Come hear about these dramatic changes and their implications at today’s Hot Topics in Stroke Education and Practice course from 3:30 p.m. to 5:30 p.m. in Concourse Hall 151. Additionally, tomorrow’s Clinical Trials Plenary Session from 9:15 a.m. to 11:30 a.m. in South Exhibit Hall K will discuss the DEFUSE-3 trial. 

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.

Log into the New AAN.com for Chance to Win! Log in on the Academy’s freshly redesigned AAN.com and you could win an Apple HomePod or Alexa Echo Plus. The drawing is open to any AAN member who logs in to AAN.com from Sunday to Thursday or stops by the AAN.com booth. The drawing will be held at noon on Thursday, and you must be present at the AAN.com booth to win.

May 7 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 7, 2018. 

Monday, April 23, 2018 • AANextra

Check out New ePoster Areas at Poster Sessions New this year for the poster sessions, we’ve added semi-private viewing areas for ePosters, allowing for a more interactive and dynamic engagement and discussion with presenters. Look for 12 ePosters each day, where you can delve into the data through touchscreen displays. Today’s Poster Session II will run from 11:30 a.m. to 7:00 p.m. in West Exhibit Hall A of the convention center, with presenter standby from 5:30 p.m. to 7:00 p.m. Once again, we’ve clustered all topic-related posters together into “neighborhoods” to enhance your discussions and make the posters easier to navigate.

Neuromuscular and Clinical Neurophysiology (EMG) Lunchtime Poster Discussion Session Join today’s lunchtime Poster Discussion Session at the poster discussion stage between 11:45 a.m. and 12:35 p.m., where a group of 10 abstracts will be presented by their authors in a five-minute data blitz with a moderator leading stimulating discussion on the content.

Today’s ePoster Sessions: Child Neurology and Developmental Neurology and Epilepsy/Clinical Neurophysiology (EEG) Be sure and check out the center of the poster hall for today’s interactive, touchscreen ePosters. 

Remaining Poster Session Schedule Poster Session III Tuesday: 11:30 a.m.–7:00 p.m. author standby from 5:30 p.m.–7:00 p.m. Poster Session IV Wednesday: 11:30 a.m.–7:00 p.m. author standby from 5:30 p.m.–7:00 p.m. Poster Session V Thursday: 11:30 a.m.–7:00 p.m. author standby from 5:30 p.m.–7:00 p.m. Poster Session VI Friday: 11:30 a.m.–5:30 p.m. author standby from 4:00 p.m.–5:30 p.m.

091–172

173–200

ePosters

085–090

037–084

201–258

b1 g1 339–344 a1 ePosters

Poster Discussion

027–036

001–026

259–294

295–338

345–428

429–480

Poster Session II A. Research Methodology, Education, and History: 001 – 026

a1. Neuromuscular/Clinical Neurophysiology (EMG) Poster Discussion Session: 027 – 036 B. Movement Disorders: 037 – 084

b1. Child Neurology and Developmental Neurology ePoster Session: 085 – 090 C. Pain and Palliative Care; Autonomic Disorders; Neuroophthalmology/Neuro-otology: 091 – 172 D. Aging, Dementia, Cognitive, and Behavioral Neurology: 173 – 200 E. Cerebrovascular Disease and Interventional Neurology: 201 – 258 F. Epilepsy/Clinical Neurophysiology (EEG): 259 – 294 G. Child Neurology and Developmental Neurology: 295 – 338

g1. Epilepsy/Clinical Neurophysiology (EEG) ePoster Session: 339 – 344 H. MS and CNS Inflammatory Disease: 345 – 428 I. Neuromuscular/Clinical Neurophysiology (EMG): 429 – 480

Monday, April 23, 2018 • AANextra

Don’t Miss This Morning’s Contemporary Clinical Issues Plenary Session Continued from cover

developments, clinical applications of basic and translational research, and innovative technical developments. Commentary and discussion follow each presentation. Randolph S. Marshall, MD, FAAN, vice chair of the AAN Science Committee, will moderate the session, which runs from 9:15 a.m. to 11:30 a.m. in South Exhibit Hall K. The topics and speakers are: Retinal Microvasculature in Predicting Risk of Stroke Subtypes

Neuropalliative Care Maisha T. Robinson, MD, MS Mayo Clinic, Jacksonville, FL

Presenter: Michelle P. Lin, MD Johns Hopkins University School of Medicine, Baltimore, MD Discussant: Valerie Biousse, MD Emory University School of Medicine, Atlanta, GA

Robinson

Biosimilars and Non-biologic Complex Drugs Lin

Jeffrey Allan Cohen, MD Cleveland Clinic, Cleveland, OH

Biousse

Predictors of Neurodegeneration in Idiopathic REM Sleep Behavior Disorder: A Multicenter Cohort Study Presenter: Ronald Postuma, MD Montreal General Hospital, Montreal, Quebec, Canada Discussant: Aleksandar Videnovic, MD, MSc, FAAN, MGH Neurological Clinical Research Institute, Boston, MA

Cohen

Non-invasive Neuromodulation Deborah I. Friedman, MD, MPH, FAAN University of Texas Southwestern Medical Center, Dallas, TX 

Postuma

Videnovic

Pediatric Brainstem Encephalitis Outbreak Investigation with Metagenomic Next-generation Sequencing Presenter: Kristoffer Edgar Leon University of California San Francisco, San Francisco, CA Discussant: Shibani Mukerji, MD Massachusetts General Hospital, Boston, MA

Leon

Mukerji

Monday, April 23, 2018 • AANextra

Friedman

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Test your knowledge with The Migraine Prevention Challenge at Booth 1261.

TODAY’S EXPERIENTIAL LEARNING AREA HIGHLIGHTS Live Well: Taking Care of Your Patients Starts with Taking Care of You Perception Is Reality: Are Neurologists Helping Patients Live Well with Dementia? 12:25 p.m.–1:45 p.m. Many persons living with dementia report the negative impact of their interactions with neurologists— especially when receiving their diagnosis—that are often characterized as lacking empathy and compassion, with poor communication of available resources, and a general lack of effort or concern to help patients live well with their diagnosis. These interactions may have far-reaching consequences, including negatively impacting patients’ perceived self-worth and caregiver wellbeing, undermining trust in the physician-patient relationship, and adversely impacting treatment compliance.

HeadTalks Is There a Neurologist on This Flight? 12:00 p.m.–1:00 p.m. With the ever-increasing number of packed planes loaded with passengers of various ages and with various conditions, neurologists are often called to serve when a passenger has a medical condition on a flight. Given that neurologic issues are one of the most common conditions that a physician will encounter on a flight, the frequently asked question is “How does a neurologist address such a situation?” Joseph I. Sirven, MD, FAAN, will lead a lively talk and demonstration aboard a mock plane that explores various scenarios and examines what on-board resources may be available to assist neurologists in these situations. Eminence-based Medicine vs Evidence-based Medicine 1:30 p.m.–2:30 p.m. Evidence-based medicine has become a zeitgeist (spirit of the times) and experience has become derided with the term (eminence-based medicine), implying that the two are not compatible. Martin A. Samuels, MD, MACP, FAAN, will use real case examples of how evidence and experience complement each other in making neurological diagnoses.

Samuels

Contributing factors may include physician burnout, challenges in breaking bad news, implicit bias against people with dementia, failure to support the highest quality care, etc. Daniel C. Potts, MD, FAAN, and Neelum T. Aggarwal, MD, will lead a panel discussion with persons living with dementia; a virtual dementia simulation; a discussion of the changing demographics, genetics, and neuroethics of Alzheimer’s and other dementias; and audience Q&A.

Maximize Your Value and Advocacy to Action

Research Corner: Moving Neurology Forward

Kenneth M. Viste, Jr., MD, Patient Advocate of the Year Award 2:30 p.m.–3:00 p.m.

Awards Day 7:30 a.m.–4:45 p.m.

Stop by to congratulate 2018 recipient Oleg Chernyshev, MD, PhD, for his tireless advocacy efforts!

Stop by throughout the day to recognize the achievements of your fellow colleagues: the 2018 AAN Award program recipients. Celebrate research that has generated paradigmchanging discoveries in epilepsy, fundamental insights in multiple sclerosis, and pioneering breakthroughs in pain, to name a few of the transformative advances conceived by the luminaries that will be honored.

Safety and Quality Awards 3:00 p.m.–3:30 p.m. Join us in recognizing this year’s welldeserved winners: Lily Grossmann, MD Continuous Anesthesia Protocol for MRI and LP in Children Yi Li, MD, PhD Utilization of Ultrasound Guided Lumbar Puncture to Improve the Efficacy and Outcome in an Overweight Patient Population Michael Robers, MD Improving the Time for Physician Acknowledgement of Send out Labs Mauricio Villamar, MD Improvement in Time to Administration of Second-line Antiseizure Medications After Implementation of an Inpatient Status Epilepticus Alert Protocol

The Member Experience: Personalize Your Journey Recognition Wall Check out our recognition wall—up all week long—and congratulate your deserving colleagues for their achievements in the field.

Navigating Your Career Teaching Communication Skills: From Good to Great 3:45 p.m.–4:30 p.m. Tara Cook, MD The ACGME requires neurology residents to show competence in certain palliative care skills, such as communication. Even though a key communication skill is discussing goals of care, many neurologists who teach residents have never received formal training in this skill. Tara Cook, MD, will demonstrate a structured framework—known as REMAP—for teaching neurology trainees that bases the discussion on patient values and responding to emotion that works to improve the quality of the physician-patient interaction. 

INDUSTRY THERAPEUTIC UPDATE FROM ADAMAS PHARMACEUTICALS, INC. HOW CAN WE

FIGHT DYSKINESIA IN

PARKINSON’S DISEASE? Join us for personal and professional perspectives on Parkinson’s disease, with a focus on dyskinesia. This dynamic program features a roundtable discussion among leading experts in the treatment of dyskinesia in Parkinson’s disease, as well as a heartfelt keynote presentation by the daughter of the late, great Muhammad Ali, who lived with Parkinson’s disease for years before he was diagnosed. Don’t miss this opportunity to hear engaging personal and professional perspectives on the impact and management of Parkinson’s disease, with a focus on dyskinesia.

TUESDAY, APRIL 24TH 2018

7:00 PM–10:00 PM REGISTRATION BEGINS AT 6:30 PM

San Diego Ballroom • Westin Bonaventure Hotel • Los Angeles, CA COMPLIMENTARY DINNER WILL BE SERVED

GOCOVRI (amantadine) extended release capsules is the first and only medicine approved by the FDA for the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications.

IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS

GOCOVRI is contraindicated in patients with creatinine clearance below 15 mL/min/1.73 m2. WARNINGS AND PRECAUTIONS Falling Asleep During Activities of Daily Living and Somnolence: Patients treated with Parkinson’s disease medications have reported falling asleep during activities of daily living. If a patient develops daytime sleepiness during activities that require full attention (eg, driving a motor vehicle, conversations, eating), GOCOVRI should ordinarily be discontinued or the patient should be advised to avoid potentially dangerous activities. Suicidality and Depression: Monitor patients for depression, including suicidal ideation or behavior. Prescribers should consider whether the benefits outweigh the risks of treatment with GOCOVRI in patients with a history of suicidality or depression.

PRESENTERS

KEYNOTE SPEAKER

Rajesh Pahwa, MD

Laverne & Joyce Rider Professor of Neurology Kansas Medical Center Chief, Parkinson Disease & Movement Disorder Division Director, Parkinson Foundation Center of Excellence Kansas City, KS

Daniel E. Kremens, MD, JD Associate Professor of Neurology Department of Neurology Sidney Kimmel Medical College at Thomas Jefferson University Philadelphia, PA

Stuart Isaacson, MD

Associate Professor of Neurology Herbert Wertheim College of Medicine Florida International University Miami, FL Director, Institute for Neurodegenerative Diseases of Florida Parkinson’s Disease and Movement Disorders Center of Boca Raton Alzheimer’s and Memory Disorders Center of South Florida Boca Raton, FL

MARYUM ALI Daughter of Muhammad Ali “My Father’s Journey, and What It Means to Me”

IMPORTANT SAFETY INFORMATION (cont.) WARNINGS AND PRECAUTIONS (cont.) Hallucinations/Psychotic Behavior: Patients with a major psychotic disorder should ordinarily not be treated with GOCOVRI because of the risk of exacerbating psychosis. Observe patients for the occurrence of hallucinations throughout treatment, especially at initiation and after dose increases. Dizziness and Orthostatic Hypotension: Monitor patients for dizziness and orthostatic hypotension, especially after starting GOCOVRI or increasing the dose. Withdrawal-Emergent Hyperpyrexia and Confusion: Rapid dose reduction or abrupt discontinuation of GOCOVRI, may cause an increase in the symptoms of Parkinson’s disease or cause delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression, or slurred speech. Avoid sudden discontinuation of GOCOVRI. Impulse Control/Compulsive Behaviors: Patients may experience urges (eg, gambling, sexual, money spending, binge eating) and the inability to control them. It is important for prescribers to ask patients or their caregivers about the development of new or increased urges. Consider dose reduction or stopping medications. ADVERSE REACTIONS The most common adverse reactions (>10%) were hallucination, dizziness, dry mouth, peripheral edema, constipation, fall, and orthostatic hypotension. DRUG INTERACTIONS Other Anticholinergic Drugs: The dose of GOCOVRI should be reduced if atropine-like effects are observed. Drugs Affecting Urinary pH: The pH of the urine has been reported to influence the excretion rate of amantadine. Monitor for efficacy or adverse reactions under conditions that alter the urine pH. Alcohol: Concomitant use with alcohol is not recommended, as it may increase the potential for CNS effects such as dizziness, confusion, lightheadedness, and orthostatic hypotension. Please see Brief Summary of full Prescribing Information on the next page.

Please visit us at Booth 703 For more information and to preregister for this program, please visit

www.fightdyskinesia.com Seating is limited, so preregistration is recommended. This promotional, non-CME program is intended only for healthcare professionals involved in the treatment of people with Parkinson’s disease. This is not an AAN-endorsed event.

GOCOVRI™ (amantadine) extended release capsules Brief Summary of full Prescribing Information. See full Prescribing Information. Rx Only. INDICATIONS AND USAGE: GOCOVRI is indicated for the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications. CONTRAINDICATIONS: Contraindicated in patients with creatinine clearance below 15 mL/min/1.73 m2 WARNINGS AND PRECAUTIONS: Falling Asleep During Activities of Daily Living and Somnolence: Patients treated with Parkinson’s disease medications have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes has resulted in accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. In controlled clinical trials, somnolence and fatigue were reported in 4% vs. 1% of patients treated with GOCOVRI or placebo, respectively. Before initiating treatment with GOCOVRI, advise patients of the potential to develop drowsiness and specifically ask about factors that may increase the risk for somnolence with GOCOVRI, such as concomitant sedating medications or the presence of a sleep disorder. If a patient develops daytime sleepiness or episodes of falling asleep during activities that require full attention (e.g., driving a motor vehicle, conversations, eating), GOCOVRI should ordinarily be discontinued. If a decision is made to continue GOCOVRI, patients should be advised not to drive and to avoid other potentially dangerous activities. There is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living or daytime somnolence. Suicidality and Depression: In controlled clinical trials, suicidal ideation or suicide attempt was reported in 2% vs. 0%; depression or depressed mood 6% vs. 1%; confusional state 3% vs. 2%; apathy 2% vs. 0%, in patients treated with GOCOVRI or placebo, respectively. Monitor patients for depression, including suicidal ideation or behavior. Prescribers should consider whether the benefits outweigh the risks of treatment with GOCOVRI in patients with a history of suicidality or depression. Hallucinations/Psychotic Behavior: Patients with a major psychotic disorder should ordinarily not be treated with GOCOVRI because of the risk of exacerbating psychosis. In controlled trials, the incidence of patients who experienced visual hallucination, auditory hallucination, delusions, illusions, or paranoia was 25% vs 3%; hallucinations caused discontinuation of treatment in 8% vs.0%; in patients treated with GOCOVRI or placebo, respectively. Observe patients for the occurrence of hallucinations throughout treatment, especially at initiation and after dose increases. Dizziness and Orthostatic Hypotension: In controlled clinical trials, 29% vs. 2% experienced dizziness, syncope, orthostatic hypotension, presyncope, postural dizziness or hypotension; and 3% vs. 0% discontinued study treatment because of dizziness, postural dizziness, or syncope; in patients receiving GOCOVRI or placebo, respectively. Monitor patients for dizziness and orthostatic hypotension, especially after starting GOCOVRI or increasing the dose. Concomitant use of alcohol with GOCOVRI is not recommended. Withdrawal-Emergent Hyperpyrexia and Confusion: A symptom complex resembling neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in drugs that increase central dopaminergic tone. Abrupt discontinuation of GOCOVRI may cause an increase in the symptoms of Parkinson’s disease or cause delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression, or slurred speech. If possible, avoid sudden discontinuation of GOCOVRI. Impulse Control/Compulsive Behaviors: Patients can experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and the inability to control these urges while taking one or more of the medications, including GOCOVRI, that increase central dopaminergic tone. In some cases, these urges were reported to have stopped when the dose was reduced or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or their caregivers about the development of such urges, and to consider dose reduction or stopping GOCOVRI treatment. ADVERSE REACTIONS: 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. GOCOVRI was evaluated in two double-blind, placebo-controlled efficacy trials of similar design and population: Study 1 (123 patients) and Study 2 (75 patients). The study population was approximately 56% male and 94% white, with a mean age of 65 years (age range from 34 years to 82 years). The mean duration of levodopa-induced dyskinesia was 4 years (range 0.1 to 14 years). Active treatment started at 137 mg once daily for one week, followed by a dose increase to 274 mg once daily. The treatment duration was 25 weeks for Study 1 and 13 weeks for Study 2. Study 1 was stopped prematurely unrelated to safety, with 39/100 patients (safety population) treated with GOCOVRI for 24 weeks. The most common adverse reactions reported in >10% of GOCOVRI-treated patients and more frequently than on placebo were: hallucination, dizziness, dry mouth, peripheral edema, constipation, falls, and orthostatic hypotension. The overall rate of discontinuation because of adverse reactions was 20% vs. 8% for patients treated with GOCOVRI or placebo, respectively. Adverse reactions that led to treatment discontinuation in at least 2% of patients were hallucination (8% GOCOVRI vs. 0% placebo), dry mouth (3% GOCOVRI vs. 0% placebo), peripheral edema (3% GOCOVRI vs. 0% placebo), blurred vision (GOCOVRI 3% vs.0% placebo), postural dizziness and syncope (GOCOVRI 2% vs. 0% placebo), abnormal dreams (GOCOVRI 2% vs. 1% placebo), dysphagia (GOCOVRI 2% vs. 0% placebo), and gait disturbance (GOCOVRI 2% vs. 0% placebo). Pooled Analysis of Adverse Reactions Reported for ≥ 3% of Patients Treated with GOCOVRI 274 mg (N=100) or placebo (N=98), respectively: Psychiatric disorders: visual and/or auditory hallucination (21%, 3%); anxiety and/or generalized anxiety (7%, 3%); insomnia (7%, 2%); depression/depressed mood (6%, 1%); abnormal dreams (4%, 2%); confusional state (3%, 2%). Nervous system disorders: dizziness (16%, 1%); headache (6%, 4%); dystonia (3%, 1%). Gastrointestinal disorders: dry mouth (16%, 1%); constipation (13%, 3%); nausea (8%, 3%); vomiting (3%, 0%). General disorders and administration site conditions: peripheral edema (16%, 1%); gait disturbance (3%, 0%). Injury, poisoning and procedural complications: fall (13%, 7%); contusion (6%, 1%) Infection and infestations: urinary tract infection (10%, 5%). Skin and

subcutaneous tissue disorders: livedo reticularis (6%, 0%); pigmentation disorder (3%, 0%). Metabolism and nutrition disorders: decreased appetite (6%, 1%). Vascular disorders: orthostatic hypotension, including postural dizziness, syncope, presyncope, and hypotension (13%, 1%). Eye disorders: blurred vision (4%, 1%); cataract (3%, 1%); dry eye (3%, 0%). Musculoskeletal and connective tissue disorders: joint swelling (3%, 0%), muscle spasm (3%, 0%). Reproductive system and breast disorders: benign prostatic hyperplasia—all male (6%, 2%). Respiratory, thoracic and mediastinal disorders: cough (3%, 0%). Other clinically relevant adverse reactions observed at <3% included somnolence, fatigue, suicide ideation or attempt, apathy, delusions, illusions, and paranoia. Difference in the Frequency of Adverse Reactions by Gender in Patients Treated with GOCOVRI. Adverse reactions reported more frequently in women (n=46) vs. men (n=54), were: dry mouth (22% vs.11%), nausea (13% vs. 4%), livedo reticularis (13% vs. 0%), abnormal dreams (9% vs. 0%) and cataracts (7% vs. 0%), respectively. Men vs. women reported the following adverse reactions more frequently: dizziness (20% vs. 11%), peripheral edema (19% vs. 11%), anxiety (11% vs. 2%), orthostatic hypotension in (7% vs. 2%) and gait disturbance (6% vs. 0%), respectively. Difference in the Frequency of Adverse Reactions by Age in Patients Treated with GOCOVRI. Hallucinations (visual or auditory) were reported in 31% of patients age 65 years and over (n=52), vs.10 % in patients below the age of 65 years (n=48). Falls were reported in 17% of patients age 65 and over, vs. 8% of patients below age 65. Orthostatic hypotension was reported in 8% of patients age 65 and over, compared to 2% of patients below age 65. DRUG INTERACTIONS: Other Anticholinergic Drugs: Products with anticholinergic properties may potentiate the anticholinergic-like side effects of amantadine. The dose of anticholinergic drugs or of GOCOVRI should be reduced if atropine-like effects appear when these drugs are used concurrently. Drugs Affecting Urinary pH: The pH of the urine has been reported to influence the excretion rate of amantadine. Urine pH is altered by diet, drugs (e.g., carbonic anhydrase inhibitors, sodium bicarbonate), and clinical state of the patient (e.g., renal tubular acidosis or severe infections of the urinary tract). Since the excretion rate of amantadine increases rapidly when the urine is acidic, the administration of urine acidifying drugs may increase the elimination of the drug from the body. Alterations of urine pH towards the alkaline condition may lead to an accumulation of the drug with a possible increase in adverse reactions. Monitor for efficacy or adverse reactions under conditions that alter the urine pH to more acidic or alkaline, respectively. Live Attenuated Influenza Vaccines: Due to its antiviral properties, amantadine may interfere with the efficacy of live attenuated influenza vaccines. Therefore, live vaccines are not recommended during treatment with GOCOVRI. Inactivated influenza vaccines may be used, as appropriate. Alcohol: Concomitant use with alcohol is not recommended, as it may increase the potential for CNS effects such as dizziness, confusion, lightheadedness, and orthostatic hypotension, and may result in dose-dumping. USE IN SPECIFIC POPULATIONS: Pregnancy: There are no adequate data on the developmental risk associated with use of amantadine in pregnant women. Based on animal data, may cause fetal harm. Lactation: Amantadine is excreted into human milk, but amounts have not been quantified. There is no information on the risk to a breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for GOCOVRI and any potential adverse effects on the breastfed infant from GOCOVRI or from the underlying maternal condition. Pediatric Use: Safety and effectiveness of GOCOVRI in pediatric patients have not been established. Geriatric Use: In Phase 3 clinical trials, the mean age of patients at study entry was 65 years. Of the total number of patients in clinical studies of GOCOVRI, 46% were less than 65 years of age, 39% were 65-74 years of age, and 15% were 75 years of age or older. Hallucinations and falls occurred more frequently in patients 65 years of age or older, compared to those less than 65 years of age. No dose adjustment is recommended on the basis of age. GOCOVRI is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Renal Impairment: GOCOVRI is contraindicated for use in patients with end-stage renal disease (creatinine clearance values lower than 15 mL/min/1.73 m2). A 50% dose reduction of GOCOVRI dosage to a starting daily dose of 68.5 mg daily for a week, followed by a daily maintenance dose of 137 mg is recommended in patients with moderate renal impairment (creatinine clearance between 30 and 59 mL/min/1.73 m2). For patients with severe renal impairment (creatinine clearance between 15 and 29 mL/min/m2), a daily dose of 68.5 mg is recommended. Overdosage: Deaths have been reported from overdose with amantadine immediaterelease. The lowest reported acute lethal dose was 1 gram of amantadine hydrochloride (equivalent to 0.8 g amantadine). Acute toxicity may be attributable to the anticholinergic effects of amantadine. Drug overdose has resulted in cardiac, respiratory, renal, or central nervous system toxicity. Pulmonary edema and respiratory distress (including adult respiratory distress syndrome, ARDS) have been reported with amantadine; renal dysfunction, including increased BUN and decreased creatinine clearance, can occur. Central nervous system effects that have been reported with overdose include agitation, aggressive behavior, hypertonia, hyperkinesia, ataxia, tremor, disorientation, depersonalization, fear, delirium, psychotic reactions, lethargy, and coma. Seizures may be exacerbated in patients with prior history of seizure disorders. Hyperthermia has occurred with amantadine overdose. For acute overdosing, general supportive measures should be employed along with immediate gastric decontamination if appropriate. Give intravenous fluids if necessary. The excretion rate of amantadine increases with acidification of urine, which may increase the elimination of the drug. Monitor patients for arrhythmias and hypotension. Electrocardiographic monitoring may be needed after ingestion because arrhythmias have been reported after overdose, including arrhythmias with fatal outcomes. Adrenergic agents, such as isoproterenol, in patients with an amantadine overdose has been reported to induce arrhythmias. Monitor blood electrolytes, urine pH, and urinary output. Although amantadine is not efficiently removed by hemodialysis, this procedure may be useful in the treatment of amantadine toxicity in patients with renal failure. Gocovri, the Gocovri logo, Adamas, and the Adamas logo are trademarks of Adamas Pharmaceuticals, Inc. or its related companies. © 2018 Adamas Pharmaceuticals, Inc. or its related companies. All rights reserved. GOC-0202 03/18

QUOTABLE QUOTES Meenakshi Raj, MBBS, FRACP Southport, Australia How does this compare to past Annual Meetings you’ve attended?

So far, so good. I've attended a couple meetings, including Vancouver a couple of years ago. I find it very exciting. There’s lots to take in no matter what lecture I choose. It's hard to choose from so many exciting courses. I always end up taking something back to my practice, though, which is really good.

Giovanni Meola, MD, FAAN Milan, Italy How is this different from other AAN Annual Meetings you have attended?

What advice would you give to first-time attendees this year?

I came several times because I'm a member of the Academy and I attended at least for 40 years. I think that the fees are much better, and what I like very much is this is more patient oriented and also very clinically oriented. So, I think it is very helpful. I am a professor of neurology and I do both research and practice because I'm chairman of the neurology department at the University of Milan in Italy.

Plan your meeting, because you’ll come here and you will think ‘I will download the app there’ and, no, there is a lot! Have definite ideas for lectures. And try to attend every year—it’s really good!

Howard Moses, MD, MS, FAAN, FANA Eastville, VA What are your impressions of this meeting?

I’m a clinician, semiretired, and this is probably one of the best organized Academy meetings I have ever been to—and I've never missed one since I joined. And also, the support staff; I'll meet somebody who can tell me where to go and if they don't know the answer they know where to find it. The poster sessions are well laid out with plenty of room. It’s a very well-organized meeting and as a senior neurologist I find it very helpful. Even though that I'm not computer savvy, I've had tremendous help. I always love the poster sessions, they are far superior in terms of improving my fund of knowledge about neurology than some of the platform sessions—and most of these are very good. What will you take back with you that you'll be able to apply in your work?

I do a great deal of teaching in neurology and I learned the newest developments in neuro diagnosis as well as therapy in all phases of neurology. I can't point out any one particular phase which is superior to others—oncology, immunology, heredity. All of those things are very helpful.

Dharampreet Singh, MD Stony Brook, NY What are you hoping to get out of your Annual Meeting experience?

I only caught the tail end of the one in Boston, so this is actually my first full Annual Meeting and it’s very nice. The program agendas are great and the speakers are terrific. I've been here since 7:00 a.m. yesterday and I’ve loved every single minute of it. I have three projects to present, so hopefully I'm able to present those well and get some good feedback. If I can establish some professional connections, that will be an added bonus. But the primary reason is basically education, because I am a resident in my last year and the next steps will be starting to work the real life. So, I feel like this is where, with the AAN, we fill in the gaps that are in any residency program just because it’s all inclusive. If you want to go into a fellowship next or if you want to start working, this is a great opportunity to fill in those gaps.

Fatemeh Touserkani, MD Boston, MA What are you enjoying about this Annual Meeting?

It’s my first time and I think this is an amazing opportunity for everyone like me, as a young researcher, to see other people working in the field and just exploring and learning.

Monday, April 23, 2018 • AANextra

Annual Meeting Attendees Enjoy the Magic of Universal Studios Anniversary Party Continued from cover

the magic of filmmaking at the 70 th Anniversary Party at Universal Studios Hollywood. From exploring the spellbinding Hogwartâ&#x20AC;&#x2122;s Castle to having the bejeebers scared out of them by classic film monsters, the attendees had a chance to connect with some of their favorite cinematic heroes and villains throughout an exhilarating evening of fun and celebration. Platinum Event sponsor was AveXis, Inc. ď&#x201A;˘

VISIT OUR BOOTH #509 The Mount Sinai Hospital is ranked No. 16 in Neurology & Neurosurgery by U.S. News & World Report, 2017-18. Our world-class specialists are commi ed to the discovery of new treatments for neurological conditions and hold faculty appointments at the Icahn School of Medicine at Mount Sinai, ranked among the nation’s top medical schools by U.S. News & World Report. • Comprehensive Stroke Center • Bendheim Parkinson and Movement Disorders Center • Corinne Goldsmith Dickinson Center for Multiple Sclerosis • Center for Headache and Facial Pain • Center for Cognitive Health and Alzheimer’s Disease Research • Parkinson’s Foundation Center of Excellence • Neuromuscular Disease Division • Neuro-Otology and Neurogenetics Division • Neuro-Infectious Diseases and NeuroAIDS Program • Epilepsy Program • Pediatric Neurology Division • Neuro-Oncology Program • Neuro-Ophthalmology Program • Health Outcomes and Knowledge Translation Research Division

1-800-MD-SINAI • mountsinai.org/neurology

Trainees: Network, Find Opportunities at Tonight’s Faculty and Trainee Reception Continued from cover

writing and reviewing opportunities, and AAN Career Center representatives will be available with job search resources. Clerkship directors and program directors will also have a chance to connect with their peers and share innovative practices at their institutions through poster displays on education tools, resources, or works in progress. 

Trainees: Check out Talks at Experiential Learning Area Education Subcommittee and member of the AAN Education Committee, will serve as the master of ceremonies. Medical students, residents, and fellows looking for answers to general questions can stop by the Career Networking Lounge, where clerkship and program directors will be available to answer questions and provide insight on what resources are available at the reception. “Residents and fellows who need help navigating the fellowship application

process and medical students wondering about what to expect in their neurology clerkship should stop in at the Career Networking Lounge, where clerkship, program, and fellowship directors will be happy to talk with them and direct them to other resources that are all concentrated together at this valuable reception,” said Khan. Neurology ® Resident & Fellow Section editors and editorial team members will be on hand to answer questions about the journal and provide details about

Watch Your Colleagues Present Their Most Inventive Solutions at Today’s Brainstorm “Game Show” 4:30 p.m.–6:00 p.m. in the Innovation Hub Does one of your colleagues have an idea so innovative that it could transform the face of neurology through business, technology, education, or public health? Find out today between 4:30 p.m. and 6:00 p.m. at the exciting “Shark Tank”-style Brainstorm: A Competition for the Innovator in All of Us at the Innovation Hub in the Exhibit Hall. Watch as contestants share their highly original, inventive solutions to challenges related to patients, practice, or any other neurologyrelated issues for a chance to win a grand prize of $1,500. A panel of judges will provide feedback and contestants will have to think quickly to present refinements and improvements. 

Monday, April 23, 2018 • AANextra

Medical students and residents should check out the Navigating Your Career Experiential Learning Area for talks on topics such as “Why Choose a Career in Neurology?” “Being a Great Chief Resident,” “Navigating Fellowship in Neurology,” and “Interviewing Skills: Negotiation.” The Navigating Your Career Experiential Learning Area is in the South Lobby of the convention center.

Take Steps to Cure Brain Disease at Tomorrow’s Run/Walk Join your colleagues, friends—and even 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 the AAN’s popular Run/Walk for Brain Research. The family-friendly event is a perfect way to kick off your day of Annual Meeting programming while raising money for a great cause. The run/walk will begin promptly at 6:30 a.m. at Griffith Park, and continue throughout the Crystal Springs area. Bus service to and from the event will be provided from designated hotels. All proceeds will go to support research. Water and refreshments will be available following the race. Be sure to stop by the Live Well Experiential Learning Area in the Los Angeles Convention Center to pick up your t-shirt and to see the run/walk results. Thank you to the following sponsors: Adamas Pharmaceuticals, AveXis, Inc., Biogen, Celgene Corporation, Eisai Inc., EMD Serono, Genentech, a Member of the Roche Group; Lundbeck, Novartis Pharmaceuticals, Sunovion Pharmaceuticals, and Supernus Pharmaceuticals Inc. 

I’M AFRAID TO FAINT AGAIN Look carefully. This may be the face of neurogenic orthostatic hypotension (nOH). If your patients with a pre-existing neurodegenerative disorder are suffering from dizziness or other symptoms that improve upon sitting, they could have nOH.1-3 Patients with nOH may experience symptoms that can make daily tasks a challenge.3,4 Understanding the symptoms commonly associated with nOH may help in diagnosis and may provide a path for appropriate symptom management.4 Access information about identifying and managing nOH in your patients and register for updates at NOHmore.com—your online resource for understanding why nOH matters. References: 1. Freeman R. Neurogenic orthostatic hypotension. N Engl J Med. 2008;358(6):615-624. 2. Kaufmann H, Malamut R, Norcliffe-Kaufmann L, et al. The Orthostatic Hypotension Questionnaire (OHQ): validation of a novel symptom assessment scale. Clin Auton Res. 2012;22(2):79-90. 3. Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011;21(2):69-72. 4. Low PA. Neurogenic orthostatic hypotension: pathophysiology and diagnosis. Am J Manag Care. 2015;21(suppl 13):s248-s257.

Thank You 2018 Annual Meeting Abstract Reviewers! Please join us in thanking these members who reviewed the abstract submissions you are enjoying at the 2018 Annual Meeting. Nicholas Scott Abend, MD

Andrew E. Budson, MD

Michael N. Diringer, MD

Edip M. Gurol, MD

Roy Alcalay, MD

Rebecca C. Burch, MD

Bruce H. Dobkin, MD, FAAN

Ali Habib, MD

Enrique Alvarez, MD, PhD

David B. Burkholder, MD

Megan Donohue, MD

Deborah Hall, MD, PhD, FAAN

Amy W. Amara, MD, PhD

Jeffrey M. Burns, MD

Cynthia L. Harden, MD

Beau M. Ances, MD, PhD, MS, FAAN

Minerva Carrasquillo

Joseph F. Drazkowski, MD, FAAN

Pablo R. Castillo, MD, FAAN

Frank W. Drislane, MD, FAAN

Judith U. Harrer-Haag, MD

Diana Castro, MD

Brian Edlow, MD

John Hart, MD

Tiffany Chang, MD

Eric R. Eggenberger, DO, FAAN

Sheryl R. Haut, MD

Sherita Chapman, MD

Mitchell S.V. Elkind, MD, MS, FAAN

Laura Heitsch

Christopher D. Anderson, MD, PhD Angela Applebee, MD Charles E. Argoff, MD Melissa Armstrong, MD, MSc, FAAN Susan Arnold, MD

Andrew Charles, MD William P. Cheshire, Jr., MD, FAAN

Zoe Arvanitakis, MD, MS, FAAN

Jennifer Chester, FNP

Erika Fullwood Augustine, MD, FAAN

Tanuja Chitnis, MD, FAAN Tracey Cho, MD, FAAN

Christina Azevedo, MD

Kelvin L. Chou, MD, FAAN

Christine B. Baca, MD

Felicia Chow, MD

Laura J. Balcer, MD, MSCE, FAAN

Tiffany W. Chow, MD, FAAN

Brenda Banwell, MD, FAAN

Jeffrey M. Chung, MD, FAAN

A.M. Barrett, MD, FAAN

Jeffrey L. Elliott, MD Deniz Erten-Lyons, MD, FAAN Alberto J. Espay, MD, FAAN Stewart A. Factor, DO, FAAN Guido Jose Falcone, MD Alfonso Fasano, MD, PhD Paolo Federico, MD, PhD J. Americo M. Fernandes, Jr., MD

Claude Hemphill III, MD, FAAN Barry A. Hendin, MD, FAAN Susan T. Herman, MD, FAAN Carrie Michelle Hersh, DO Holly E. Hinson, MD, MCR Sarah Jane Hon, DO, FAAN Maria K. Houtchens, MD Richard L. Hughes, MD, FAAN David Y. Hwang, MD Hyacinth Idu Hyacinth

Emma Ciafaloni, MD, FAAN

Anteneh Mekonnen Feyissa, MD

David Bearden, MD

Daniel O. Claassen, MD

Kathryn Fitzgerald

Richard S. Isaacson, MD

Kyra J. Becker, MD

David B. Clifford, MD, FAAN

Danny Bega, MD

Gary M. Franklin, MD, MPH, FAAN

Fabio Massaiti Iwamoto, MD

Jeffrey Allan Cohen, MD

Elinor Ben-Menachem, MD, FAAN

John Cole, MD

Elliot M. Frohman, MD, FAAN

Cheryl Ann Jay, MD, FAAN

Glen A. Cook, Jr., MD

Jennifer A. Frontera, MD

Robert A. Bermel, MD

Elizabeth A. Coon, MD

Steven Frucht, MD

Nathalie Jette, MD, MSc, FRCPC

Charles Bernick, MD

Irene C.M. Cortese, MD

Erin Furr-Stimming, MD

Gregory A. Jicha, MD, PhD

Suur Biliciler, MD

Fiona Evann Costello, MD

William D. Gaillard, MD

H.A. Jinnah, MD, PhD

Gretchen L. Birbeck, MD, MPH, DTMH, FAAN

James R. Couch, Jr., MD, PhD, FAAN

Neeta Garg, MD

Thomas J. Kaley, MD

Elizabeth R. Gerstner, MD

Padmaja N. Kandula, MD

Riley Bove, MD

Steven C. Cramer, MD, FAAN

Anne-Katrin Giese, MD

Chafic Y. Karam, MD

Adam L. Boxer, MD, PhD

Carlos Cruchaga

Emily Jean Gilmore, MD

Hans D. Katzberg, MD

Tiffany Braley, MD

Kirk R. Daffner, MD, FAAN

Christopher Giza, MD

Daniel Kaufer, MD, FAAN

Ethan Brandler

Nabila Dahodwala, MD

Christopher Glisson, DO

Adam Kelly, MD

K.C. Brennan, MD, FAAN

Marie Ynez Davis, MD, PhD

M. Maria Glymour, PhD

Kevin A. Kerber, MD

James Nick Brenton, MD

Adam De Havenon, MD

Peter Goadsby, MD, PhD

Shaida Khan, DO

Adam Brickman, PhD

Lindsey Blake DeLott, MD

David S. Goldstein, MD, PhD

Pravin Khemani, MD, FAAN

Jeffrey W. Britton, MD, FAAN

Mary Carter Denny, MD

Namita Goyal, MD

Howard S. Kirshner, MD, FAAN

Amy Brodtmann

Rajat Dhar, MD

Jonathan Graff-Radford, MD

Mariko Kita, MD

Devin L. Brown, MD

Bradford Dickerson, MD

Jennifer Graves, MD, PhD

Steven J. Kittner, MD, MPH

Meredith Anne Bryarly, MD

Jorg Dietrich, MD, PhD

David M. Greer, MD, FAAN

Dawn O. Kleindorfer, MD

Jeffrey R. Buchhalter, MD, FAAN

Mazen M. Dimachkie, MD, FAAN

Zachary Grinspan, MD

Peter J. Koehler, MD, PhD, FAAN

Aaron L. Berkowitz, MD, PhD

Kevin E. Chapman, MD

Matthew Harms, MD

Monday, April 23, 2018 • AANextra

David Irwin, MD

Adil Javed, MD, PhD

Jeff Kraakevik, MD

Glenn Lopate, MD

John M. Olichney, MD

Svetlana Lorenzano, MD

Jonathan W. Mink, MD, PhD, FAAN

Stephen Krieger, MD, FAAN

Brendan P. Lucey, MD

Scott Mintzer, MD

Jeffrey S. Kutcher, MD, FAAN

Matthew W. Luedke, MD

Jennifer Lauren Orthmann Murphy, MD, PhD

Justin Y. Kwan, MD, FAAN

Jennifer Lyons, MD

Augusto A. Miravalle, MD, FAAN

James J. Lah, MD, PhD

Kasra Maasumi, MD

Annette M. Langer-Gould, MD, PhD

Irene Malaty, MD

Sandeep Kumar, MD

Douglas J. Lanska, MD, FAAN

Robert Mallery, MD

Daniel Ontaneda, MD

Jill L. Ostrem, MD

Bradley Molyneaux, MD, PhD

Jose-Alberto Palma, MD, PhD

Michelle Monje, MD, PhD

Mamatha Pasnoor, MD

Brian Darryl Moseley, MD

Daniel Pastula, MD, MHS

Ellen M. Mowry, MD, FAAN Shibani Sharon Mukerji, MD

Marc C. Patterson, MD, FAAN, FRACP

Douglas P. Larsen, MD

David E. Mandelbaum, MD, PhD, FAAN

Andrew Bruce Lassman, MD

Edward M. Manno, MD, FAAN

Kathleen Munger, MD

Eric T. Payne, MD

Heather Lau, MD

Ruth-Ann Marrie, MD

Srikanth Muppidi, MD

Phillip L. Pearl, MD, FAAN

Enrique C. Leira, MD, MS, FAAN

Farrah J. Mateen, MD, PhD, FAAN

Abirami Muthukumaran, MD

Guerry Marie Peavy, PhD

Abraham J. Nagy, MD

Daniel Pelletier, MD

James B. Leverenz, MD, FAAN

Eric M. McDade, DO

Fatta Basil Nahab, MD, FAAN

Marta Penas-Prados

Joshua Levine, MD

Robert T. Naismith, MD

Joanna Pera, MD

Daniel J. Licht, MD

Nikolaus McFarland, MD, PhD, FAAN

Avindra Nath, MD, MBBS, FAAN

B. Lee Peterlin, DO

Irene Litvan, MD, FAAN

Raja Mehanna, MD

Sharon P. Nations, MD

Katherine B. Peters, MD, PhD

Warren D. Lo, MD

Daniel L. Menkes, MD, FAAN

Lauren Phillips, MD

Giancarlo Logroscino, MD, PhD, FAAN

Ryan T. Merrell, MD

Scott Douglas Newsome, DO, FAAN

Ana-Claire L. Meyer, MD

Margaret O’Connor

Scott L. Pomeroy, MD, PhD

Zachary N. London, MD, FAAN

Michelle M. Mielke, PhD

Jiwon Oh, MD

Alyx B. Porter, MD

Erin Longbrake, MD, PhD

Mitchell G. Miglis, MD

Darin T. Okuda, MD, FAAN

Douglas G. Postels, MD Continued on page 27 u

Sharon Poisson, MD

A N INDU S T RY THERAPEU T I C UPDAT E FROM G E H E A LT H CA R E “ Why aim for earlier diagnosis of neurodegenerative disorders?” We’ve all heard it. Now we’re talking about it. Catch this lively discussion on the impact of early diagnosis.

The great diagnosis debate View video of the debate online at: gehealthcare.com/talkingtime

#TalkingTime Saturday, April 21, 2018, 8:00 PM PT. Platinum Ballroom, JW Marriott Hotel

This event is not part of the 2018 American Academy of Neurology Annual Meeting. CME credits will not be given by any accredited organizations for attending this event. March 2018 JB56403US

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 TD patients1,2 • Selectively inhibits VMAT2, with no appreciable binding affinity for dopaminergic (including D2) or serotonergic receptors1

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 O T H # 1 0 2 2 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 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 for full Prescribing Information. REFERENCES: 1. INGREZZA [package insert]. San Diego, CA: Neurocrine Biosciences, Inc; 2017. 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.

Thank You 2018 Annual Meeting Abstract Reviewers! Continued from page 25

Ronald Postuma, MD

Marta San Luciano, MD

Jeffrey Statland, MD

Leo Hong-Li Wang, MD, PhD

John Pula, MD, FAAN

Stefano Sandrone, PhD

Olaf Stuve, MD, PhD, FAAN

James C. Watson, MD

Svetlana Pundik, MD

Navdeep Sangha, MD

Victor W. Sung, MD

Kevin David Weber, MD

Mark S. Quigg, MD

Nerses Sanossian, MD Lumy Sawaki, MD, PhD

Jerzy P. Szaflarski, MD, PhD, FAAN

Michael D. Weiss, MD, FAAN

Francisco J. Quintana, PhD

Julie A. Schneider, MD, MS

Nicholas Szumski, MD

Timothy W. West, MD

Alejandro A. Rabinstein, MD, FAAN

Ronald Schondorf, MD

Fernando Testai, MD, PhD

Stephan Schuele, MD, FAAN

Gretchen E. Tietjen, MD

Matthew P. Wicklund, MD, FAAN

Annemarei Ranta, MD

Gil Dan Rabinovici, MD

Michael Weller, MD

Erica A. Schuyler, MD

David L. Tirschwell, MD, FAAN

Joshua Z. Willey, MD

Ana Recober-Montilla, MD

Sunil Sheth, MD

Helen Tremlett, PhD, BPharm

Sibyl E. Wray, MD

Robert Reddig, MD

Hyungsub Shim

Kenneth L. Tyler, MD, FAAN

Allison Wright Willis, MD

Anthony Reder, MD

Scott M. Shorten, MD

Joon H. Uhm, MD, FRCP(C)

Zbigniew K. Wszolek, MD, FAAN

Stephen G. Reich, MD, FAAN

Joshua M. Shulman, MD

Paul C. Van Ness, MD, FAAN

Yvonne W. Wu, MD, MPH

Pavle Repovic, MD, PhD

Nancy L. Sicotte, MD, FAAN

Vijayshree Yadav, MD

Lucas Restrepo, MD

Nicholas Joseph Silvestri, MD, FAAN

Gregory P. Van Stavern, MD, FAAN Bert B. Vargas, MD, FAAN

Laurice T. Yang, MD, MHA

A. Gordon Smith, MD, FAAN

Bradley V. Vaughn, MD, FAAN

Marcy E. Yonker, MD

Matthew S. Robbins, MD, FAAN

Ariane Soldatos, MD

Steven Vernino, MD, PhD, FAAN

Sarah Youssof, MD

Carrie E. Robertson, MD

Guillermo Eduardo Solorzano, MD

Gloria Von Geldern, MD

Cindy Zadikoff, MD

Andrew Mebane Southerland, MD

Aparna Wagle-Shukla, MD

Theresa A. Zesiewicz, MD, FAAN

Rebecca Spain, MD

Mark Wainwright, MD, PhD

Lan Zhou, MD, PhD

Andrew Russman, DO

Luciano A. Sposato, MD

Tobias Walbert, MD, PhD

Wendy C. Ziai, MD

Shiv Saidha, MD

Amaal J. Starling, MD

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Claire Riley, MD Eva K. Ritzl, MD, FAAN

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Kristine Yaffe, MD

For patients with epilepsy 12 years of age and older for the treatment of partial-onset seizures (POS) with or without secondarily generalized seizures and adjunctive therapy in the treatment of primary generalized tonic-clonic (PGTC) seizures

RETHINK CO N V U L S I V E S E I Z U R E CO NTRO L AT B O OTH 17 15

HELP QUIET THE NOISE OF CONVULSIVE SEIZURES

Prescribed for

100,000 PATIENTS1*†

Approved in

Available in

COUNTRIES1†

FORMULATIONS2

TO LEARN MORE, VISIT FYCOMPA .COM/HCP Please see Important Safety Information, including a Boxed WARNING for Serious Psychiatric and Behavioral Reactions, on adjacent page. Please see Brief Summary of Prescribing Information on following pages.

* Worldwide figure for FYCOMPA® from 2012 through July 2017. Nearly 20,000 patients prescribed FYCOMPA in the United States. †Across different indications.

IMPORTANT SAFETY INFORMATION WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS • Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats have been reported in patients taking FYCOMPA® • These reactions occurred in patients with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression • Advise patients and caregivers to contact a healthcare provider immediately if any of these reactions or changes in mood, behavior, or personality that are not typical for the patient are observed while taking FYCOMPA or after discontinuing FYCOMPA • Closely monitor patients particularly during the titration period and at higher doses • FYCOMPA should be reduced if these symptoms occur and should be discontinued immediately if symptoms are severe or are worsening

SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS

SOMNOLENCE AND FATIGUE FYCOMPA caused dose-dependent increases in somnolence and fatigue-related events. Somnolence was reported in 16% and 18% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 7% of placebo-treated patients. Fatigue-related events were reported in 12% and 15% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 5% of placebo-treated patients. These adverse reactions occurred mostly during the titration phase. These adverse reactions were also observed in the PGTC seizure clinical trial. Patients should be advised against engaging in hazardous activities requiring mental alertness, such as operating motor vehicles or dangerous machinery, until the effect of FYCOMPA is known.

FALLS Falls were reported in 5% and 10% of patients in the partial-onset seizure clinical trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 3% of placebo-treated patients.

DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS)

In the partial-onset seizures clinical trials, hostility- and aggression-related adverse reactions occurred in 12% and 20% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 6% of patients in the placebo group. These effects were dose-related and generally appeared within the first 6 weeks of treatment, although new events continued to be observed through more than 37 weeks. These effects in FYCOMPA-treated patients led to dose reduction, interruption, and discontinuation more frequently than placebo-treated patients. Homicidal ideation and/or threat have also been reported postmarketing in patients treated with FYCOMPA. The combination of alcohol and FYCOMPA significantly worsened mood and increased anger. Patients taking FYCOMPA should avoid the use of alcohol. Patients, their caregivers, and families should be informed that FYCOMPA may increase the risk of psychiatric events. Patients should be monitored during treatment and for at least one month after the last dose of FYCOMPA, and especially when taking higher doses and during the initial few weeks of drug therapy (titration period) or at other times of dose increases. Similar serious psychiatric and behavioral events were observed in the primary generalized tonic-clonic (PGTC) seizure clinical trial.

DRESS, also known as multiorgan hypersensitivity, has been reported in patients taking AEDs, including FYCOMPA. DRESS may be 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. If signs or symptoms are present, immediately evaluate the patient and discontinue FYCOMPA if an alternative etiology for signs or symptoms cannot be established.

SUICIDAL BEHAVIOR AND IDEATION

FYCOMPA may decrease the efficacy of contraceptives containing levonorgestrel. Plasma levels of FYCOMPA were decreased when administered with moderate and strong CYP3A4 inducers, including, carbamazepine, phenytoin, or oxcarbazepine. Multiple dosing of FYCOMPA 12 mg per day enhanced the effects of alcohol on vigilance and alertness, and increased levels of anger, confusion, and depression. These effects may also be seen when FYCOMPA is used in combination with other CNS depressants.

Antiepileptic drugs (AEDs), including FYCOMPA, increase the risk of suicidal thoughts or behavior in patients. Anyone considering prescribing FYCOMPA 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. Patients, their caregivers, and families should be informed of the risk and advised to monitor and immediately report the emergence or worsening of depression, suicidal thoughts or behavior, thoughts about self-harm and/or any unusual changes in mood or behavior. Should suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

DIZZINESS AND GAIT DISTURBANCE FYCOMPA caused dose-related increases in events related to dizziness and disturbance in gait or coordination. Dizziness and vertigo were reported in 35% and 47% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 10% of placebo-treated patients. Gait disturbance related events were reported in 12% and 16% of patients in the partial-onset seizure clinical trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 2% of placebo-treated patients. These adverse reactions occurred mostly during the titration phase. These adverse reactions were also observed in the PGTC seizure clinical trial.

WITHDRAWAL OF AEDs A gradual withdrawal is generally recommended with AEDs to minimize the potential of increased seizure frequency, but if withdrawal is a response to adverse events, prompt withdrawal can be considered.

MOST COMMON ADVERSE REACTIONS The most common adverse reactions in patients receiving FYCOMPA (≥5% and ≥1% higher than placebo) include dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo, ataxia, headache, vomiting, contusion, abdominal pain, and anxiety.

DRUG INTERACTIONS

PREGNANCY AND LACTATION Physicians are advised to recommend that pregnant patients taking FYCOMPA enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. Caution should be exercised when FYCOMPA is administered to pregnant or nursing women as there are no adequate data on the developmental risk associated with use in pregnant women, and no data on the presence of perampanel in human milk, the effects on the breastfed child, or the effects of the drug on milk production.

HEPATIC AND RENAL IMPAIRMENT Use in patients with severe hepatic or severe renal impairment is not recommended. Dosage adjustments are recommended in patients with mild or moderate hepatic impairment. Use with caution in patients with moderate renal impairment.

DRUG ABUSE AND DEPENDENCE FYCOMPA is a Schedule III controlled substance and has the potential to be abused and lead to drug dependence.

REFERENCES: 1. Data on file. Eisai Inc. Woodcliff Lake, NJ. 2. FYCOMPA US Prescribing Information. Woodcliff Lake, NJ: Eisai Inc.

Please see Brief Summary of Prescribing Information on following pages. FYCOMPA® is a registered trademark of Eisai R&D Management Co., Ltd., licensed to Eisai Inc. ©2018 Eisai Inc. FYCO-US2026 March 2018

FYCOMPA® (perampanel) tablets, for oral use, CIII FYCOMPA® (perampanel) oral suspension, CIII Initial U.S. Approval: 2012 Brief Summary of Full Prescribing Information dated July 2017 WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS • Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats have been reported in patients taking FYCOMPA. • These reactions occurred in patients with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression. • Advise patients and caregivers to contact a healthcare provider immediately if any of these reactions or changes in mood, behavior, or personality that are not typical for the patient are observed while taking FYCOMPA or after discontinuing FYCOMPA. • Closely monitor patients particularly during the titration period and at higher doses • FYCOMPA should be reduced if these symptoms occur and should be discontinued immediately if symptoms are severe or are worsening. WARNINGS AND PRECAUTIONS Serious Psychiatric and Behavioral Reactions In the controlled partial-onset seizure clinical trials, hostilityand aggression-related adverse reactions occurred in 12% and 20% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 6% of patients in the placebo group. These effects were dose-related and generally appeared within the first 6 weeks of treatment, although new events continued to be observed through more than 37 weeks. FYCOMPA-treated patients experienced more hostility- and aggression-related adverse reactions that were serious, severe, and led to dose reduction, interruption, and discontinuation more frequently than placebo-treated patients. In general, in placebo-controlled partial-onset seizure clinical trials, neuropsychiatric events were reported more frequently in patients being treated with FYCOMPA than in patients taking placebo. These events included irritability, aggression, anger, and anxiety, which occurred in 2% or greater of FYCOMPA-treated patients and twice as frequently as in placebo-treated patients. Other symptoms that occurred with FYCOMPA and were more common than with placebo included belligerence, affect lability, agitation, and physical assault. Some of these events were reported as serious and life-threatening. Homicidal ideation and/or threat were exhibited in 0.1% of 4,368 FYCOMPA-treated patients in controlled and open label trials, including non-epilepsy trials. Homicidal ideation and/or threat have also been reported postmarketing in patients treated with FYCOMPA. In the partial-onset seizure clinical trials, these events occurred in patients with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression. Some patients experienced worsening of their pre-existing psychiatric conditions. Patients with active psychotic disorders and unstable recurrent affective disorders were excluded from the clinical trials. The combination of alcohol and FYCOMPA significantly worsened mood and increased anger. Patients taking FYCOMPA should avoid the use of alcohol. Similar serious psychiatric and behavioral events were observed in the primary generalized tonic-clonic seizure clinical trial. In healthy volunteers taking FYCOMPA, observed psychiatric events included paranoia, euphoric mood, agitation, anger, mental status changes, and disorientation/confusional state. In the non-epilepsy trials, psychiatric events that occurred in perampanel-treated patients more often than placebo-treated patients included disorientation, delusion, and paranoia. Patients, their caregivers, and families should be informed that FYCOMPA may increase the risk of psychiatric events. Patients should be monitored during treatment and for at least 1 month after the last dose of FYCOMPA, and especially when taking higher doses and during the initial few weeks of drug therapy (titration period) or at other times of dose increases. Dose of FYCOMPA should be reduced if these symptoms occur. Permanently discontinue FYCOMPA for persistent severe or worsening psychiatric symptoms or behaviors and refer for psychiatric evaluation. Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including FYCOMPA, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored 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 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 1 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. Table 1 shows absolute and relative risk by indication for all evaluated AEDs. Table 1. Risk by indication for antiepileptic drugs in the pooled analysis Indication

Placebo Patients with Events per 1000 Patients

Drug Patients with Events per 1000 Patients

Epilepsy Psychiatric Other Total

1.0 5.7 1.0 2.4

3.4 8.5 1.8 4.3

Relative Risk: Incidence of Events in Drug Patients/ Incidence in Placebo Patients 3.5 1.5 1.9 1.8

Risk Difference: Additional Drug Patients with Events per 1000 Patients 2.4 2.9 0.9 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 FYCOMPA 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 treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Neurologic Effects Dizziness and Gait Disturbance FYCOMPA caused dose-related increases in events related to dizziness and disturbance in gait or coordination. In the controlled partial-onset seizure clinical trials, dizziness and vertigo were reported in 35% and 47% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 10% of placebo-treated patients. The gait disturbance related events (including ataxia, gait disturbance, balance disorder, and abnormal coordination) were reported in 12% and 16% of patients randomized to

receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 2% of placebo-treated patients. Elderly patients had an increased risk of these adverse reactions compared to younger adults and pediatric patients. These adverse reactions occurred mostly during the titration phase and led to discontinuation in 3% of FYCOMPA-treated patients compared to 1% of placebo-treated patients. These adverse reactions were also observed in the primary generalized tonic-clonic seizure clinical trial. Somnolence and Fatigue FYCOMPA caused dose-dependent increases in somnolence and fatigue-related events (including fatigue, asthenia, and lethargy). In the controlled partial-onset seizure clinical trials, 16% and 18% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, reported somnolence compared to 7% of placebo patients. In the controlled partial-onset seizure clinical trials, 12% and 15% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, reported fatigue-related events compared to 5% of placebo patients. Somnolence or fatigue-related events led to discontinuation in 2% of FYCOMPA-treated patients and 0.5% of placebo-treated patients. Elderly patients had an increased risk of these adverse reactions compared to younger adults and pediatric patients. In the controlled partial-onset seizure clinical trials, these adverse reactions occurred mostly during the titration phase. These adverse reactions were also observed in the primary generalized tonic-clonic seizure clinical trial. Risk Amelioration Prescribers should advise patients against engaging in hazardous activities requiring mental alertness, such as operating motor vehicles or dangerous machinery, until the effect of FYCOMPA is known. Falls An increased risk of falls, in some cases leading to serious injuries including head injuries and bone fracture, occurred in patients being treated with FYCOMPA (with and without concurrent seizures). In the controlled partial-onset seizure clinical trials, falls were reported in 5% and 10% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 3% of placebo-treated patients. Falls were reported as serious and led to discontinuation more frequently in FYCOMPA-treated patients than placebo-treated patients. Elderly patients had an increased risk of falls compared to younger adults and pediatric patients. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as Multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including FYCOMPA. DRESS may be 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, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its expression, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. FYCOMPA should be discontinued if an alternative etiology for the signs or symptoms cannot be established. Withdrawal of Antiepileptic Drugs There is the potential of increased seizure frequency in patients with seizure disorders when antiepileptic drugs are withdrawn abruptly. FYCOMPA has a half-life of approximately 105 hours so that even after abrupt cessation, blood levels fall gradually. In epilepsy clinical trials FYCOMPA was withdrawn without down-titration. Although a small number of patients exhibited seizures following discontinuation, the data were not sufficient to allow any recommendations regarding appropriate withdrawal regimens. A gradual withdrawal is generally recommended with antiepileptic drugs, but if withdrawal is a response to adverse events, prompt withdrawal can be considered. 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. Partial-Onset Seizures A total of 1,038 patients receiving FYCOMPA (2, 4, 8, or 12 mg once daily) constituted the safety population in the pooled analysis of the placebo-controlled trials (Studies 1, 2, and 3) in patients with partial-onset seizures. Approximately 51% of patients were female, and the mean age was 35 years. Adverse Reactions Leading to Discontinuation In controlled clinical trials (Studies 1, 2, and 3), the rate of discontinuation as a result of an adverse reaction was 3%, 8%, and 19% in patients randomized to receive FYCOMPA at the recommended doses of 4 mg, 8 mg, and 12 mg per day, respectively, and 5% in patients randomized to receive placebo. The adverse reactions most commonly leading to discontinuation (≥1% in the 8 mg or 12 mg FYCOMPA group and greater than placebo) were dizziness, somnolence, vertigo, aggression, anger, ataxia, blurred vision, irritability, and dysarthria. Most Common Adverse Reactions Table 2 gives the incidence in the controlled clinical trials (Studies 1, 2, and 3) of the adverse reactions that occurred in ≥2% of patients with partial-onset seizures in the FYCOMPA 12 mg dose group and more frequent than placebo (in order of decreasing frequency for the 12 mg dose group). The most common dose-related adverse reactions in patients receiving FYCOMPA at doses of 8 mg or 12 mg (≥4% and occurring at least 1% higher than the placebo group) included dizziness (36%), somnolence (16%), fatigue (10%), irritability (9%), falls (7%), nausea (7%), ataxia (5%), balance disorder (4%), gait disturbance (4%), vertigo (4%), and weight gain (4%). For almost every adverse reaction, rates were higher on 12 mg and more often led to dose reduction or discontinuation. Table 2. Adverse Reactions in Pooled Placebo-Controlled Trials in Patients with Partial-Onset Seizures (Studies 1, 2, and 3) (Reactions ≥ 2% of Patients in Highest FYCOMPA Dose (12 mg) Group and More Frequent than Placebo) Placebo n=442 % Dizziness Somnolence Headache Irritability Fatigue Falls Ataxia Nausea Vertigo Back pain Dysarthria Anxiety Blurred vision Gait disturbance Weight gain Cough Upper respiratory tract infection Vomiting Hypersomnia Anger Aggression Balance disorder Diplopia Head injury Hypoaesthesia Pain in extremity Constipation

9 7 11 3 5 3 0 5 1 2 0 1 1 1 1 3 3 3 0 <1 1 1 1 1 1 1 2

4 mg n=172 % 16 9 11 4 8 2 1 3 4 2 1 2 1 1 4 1 3 2 1 0 1 0 1 1 0 0 2

FYCOMPA 8 mg n=431 % 32 16 11 7 8 5 3 6 3 2 3 3 3 4 4 1 3 3 2 1 2 5 1 1 0 2 2

12 mg n=255 % 43 18 13 12 12 10 8 8 5 5 4 4 4 4 4 4 4 4 3 3 3 3 3 3 3 3 3

Table 2. Adverse Reactions in Pooled Placebo-Controlled Trials in Patients with Partial-Onset Seizures (Studies 1, 2, and 3) (Reactions ≥ 2% of Patients in Highest FYCOMPA Dose (12 mg) Group and More Frequent than Placebo) (cont.) Myalgia Coordination abnormal Euphoric mood Confusional state Hyponatremia Limb injury Mood altered Arthralgia Asthenia Contusion Memory impairment Musculoskeletal pain Oropharyngeal pain Paraesthesia Peripheral edema Skin laceration

2 0 0 <1 <1 <1 <1 1 1 1 1 1 1 1 1 1

1 1 0 1 0 1 1 0 1 0 0 1 2 0 1 0

1 <1 <1 1 0 1 <1 3 2 2 1 1 2 1 1 2

3 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2

Primary Generalized Tonic-Clonic Seizures A total of 81 patients receiving FYCOMPA 8 mg once daily constituted the safety population in the placebo-controlled trial in patients with primary generalized tonic-clonic seizures (Study 4). Approximately 57% of patients were female, and the mean age was 27 years. In the controlled primary generalized tonic-clonic seizure clinical trial (Study 4), the adverse reaction profile was similar to that noted for the controlled partial-onset seizure clinical trials (Studies 1, 2, and 3). Table 3 gives the incidence of adverse reactions in patients receiving FYCOMPA 8 mg (≥4% and higher than in the placebo group) in Study 4. The most common adverse reactions in patients receiving FYCOMPA (≥10% and greater than placebo) were dizziness (32%), fatigue (15%), headache (12%), somnolence (11%), and irritability (11%). The adverse reactions most commonly leading to discontinuation in patients receiving FYCOMPA 8 mg (≥2% and greater than placebo) were vomiting (2%) and dizziness (2%). Table 3. Adverse Reactions in a Placebo-Controlled Trial in Patients with Primary Generalized Tonic-Clonic Seizures (Study 4) (Reactions ≥ 4% of Patients in FYCOMPA Group and More Frequent than Placebo)

Dizziness Fatigue Headache Somnolence Irritability Vertigo Vomiting Weight gain Contusion Nausea Abdominal pain Anxiety Urinary tract infection Ligament sprain Balance disorder Rash

Placebo n=82 % 6 6 10 4 2 2 2 4 4 5 1 4 1 0 1 1

FYCOMPA 8 mg n=81 % 32 15 12 11 11 9 9 7 6 6 5 5 4 4 4 4

Weight Gain Weight gain has occurred with FYCOMPA. In controlled partial-onset seizure clinical trials, FYCOMPA-treated adults gained an average of 1.1 kg (2.5 lbs) compared to an average of 0.3 kg (0.7 lbs) in placebo-treated adults with a median exposure of 19 weeks. The percentages of adults who gained at least 7% and 15% of their baseline body weight in FYCOMPA-treated patients were 9.1% and 0.9%, respectively, as compared to 4.5% and 0.2% of placebo-treated patients, respectively. Clinical monitoring of weight is recommended. Similar increases in weight were also observed in adult and pediatric patients treated with FYCOMPA in the primary generalized tonic-clonic seizure clinical trial. Elevated triglycerides Increases in triglycerides have occurred with FYCOMPA use. Comparison of Sex and Race No significant sex differences were noted in the incidence of adverse reactions. Although there were few non-Caucasian patients, no differences in the incidence of adverse reactions compared to Caucasian patients were observed. Postmarketing Experience The following adverse reactions have been identified during post approval use of FYCOMPA. 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. Dermatologic: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Psychiatric: Acute psychosis, hallucinations, delusions, paranoia, delirium, confusional state, disorientation, memory impairment. DRUG INTERACTIONS Contraceptives With concomitant use, FYCOMPA at a dose of 12 mg per day reduced levonorgestrel exposure by approximately 40%. Use of FYCOMPA with contraceptives containing levonorgestrel may render them less effective. Additional non-hormonal forms of contraception are recommended. Moderate and Strong CYP3A4 Inducers The concomitant use of known moderate and strong CYP3A4 inducers including carbamazepine, phenytoin, or oxcarbazepine with FYCOMPA decreased the plasma levels of perampanel by approximately 50-67%. The starting doses for FYCOMPA should be increased in the presence of moderate or strong CYP3A4 inducers. When these moderate or strong CYP3A4 inducers are introduced or withdrawn from a patient’s treatment regimen, the patient should be closely monitored for clinical response and tolerability. Dose adjustment of FYCOMPA may be necessary. Alcohol and Other CNS Depressants The concomitant use of FYCOMPA and CNS depressants including alcohol may increase CNS depression. A pharmacodynamic interaction study in healthy subjects found that the effects of FYCOMPA on complex tasks such as driving ability were additive or supra-additive to the impairment effects of alcohol. Multiple dosing of FYCOMPA 12 mg per day also enhanced the effects of alcohol to interfere with vigilance and alertness, and increased levels of anger, confusion, and depression. These effects may also be seen when FYCOMPA is used in combination with other CNS depressants. Care should be taken when administering FYCOMPA with these agents. Patients should limit activity until they have experience with concomitant use of CNS depressants (e.g., benzodiazepines, narcotics, barbiturates, sedating antihistamines). Advise patients not to drive or operate machinery until they have gained sufficient experience on FYCOMPA to gauge whether it adversely affects these activities. USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as FYCOMPA, during pregnancy. Encourage women who are taking FYCOMPA 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 risk associated with use in pregnant women. In animal studies, perampanel induced developmental toxicity in pregnant rat and rabbit at clinically relevant doses. 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. Oral administration of perampanel (1, 3, or 10 mg/kg/day) to pregnant rats throughout organogenesis resulted in an increase in visceral abnormalities (diverticulum of the intestine) at all doses tested; maternal toxicity was observed at the mid and high doses. In a dose-ranging study at higher oral doses (10, 30, or 60 mg/kg/day), embryo lethality and reduced fetal body weight were observed at the mid and high doses tested. The lowest dose tested (1 mg/kg/day) is similar to a human dose of 8 mg per day based on body surface area (mg/m2). Upon oral administration of perampanel (1, 3, or 10 mg/kg per day) to pregnant rabbits throughout organogenesis, embryo lethality was observed at the mid and high doses tested; the no-effect dose for embryo-fetal developmental toxicity in rabbit (1 mg/kg/day) is approximately 2 times a human dose of 8 mg per day based on body surface area (mg/m2). Oral administration of perampanel (1, 3, or 10 mg/kg per day) to rats throughout gestation and lactation resulted in fetal and pup deaths at the mid and high doses (associated with maternal toxicity) and delayed sexual maturation in males and females at the highest dose tested. No effects were observed on measures of neurobehavioral or reproductive function in the offspring. The no-effect dose for pre- and postnatal developmental toxicity in rat (1 mg/kg/day) is similar to a human dose of 8 mg per day based on body surface area (mg/m2). Lactation Risk summary There are no data on the presence of perampanel in human milk, the effects on the breastfed child, or the effects of the drug on milk production. Perampanel and/or its metabolites are excreted in rat milk, and are detected at concentrations higher than that in maternal plasma. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for FYCOMPA and any potential adverse effects on the breastfed child from FYCOMPA or from the underlying maternal condition. Females and Males of Reproductive Potential Contraception Use of FYCOMPA may reduce the efficacy of hormonal contraceptives containing levonorgestrel. Advise women taking FYCOMPA who are using a levonorgestrel-containing contraceptive to use an additional non-hormonal form of contraception while using FYCOMPA and for a month after discontinuation. Pediatric Use The safety and efficacy of FYCOMPA for the treatment of partial-onset seizures in pediatric patients 12 years of age and older was established by three randomized double-blind, placebo-controlled, multicenter studies, which included 72 pediatric patients between 12 and 16 years of age exposed to FYCOMPA. The safety and efficacy of FYCOMPA for the adjunctive therapy of primary generalized tonic-clonic seizures in pediatric patients 12 years of age and older was established in a single randomized double-blind, placebo-controlled, multicenter trial (n=164), which included 11 pediatric patients 12 to 16 years of age exposed to FYCOMPA; an additional 6 patients were treated with FYCOMPA in the open label extension of the study. The safety and effectiveness of FYCOMPA in pediatric patients less than 12 years of age have not been established. Juvenile Animal Data Oral administration of perampanel (1, 3, 3/10/30 mg/kg/day; high dose increased on postnatal days [PND] 28 and 56) to young rats for 12 weeks starting on PND 7 resulted in reduced body weight, reduced growth, neurobehavioral impairment (water maze performance and auditory startle habituation) at the mid and high doses, and delayed sexual maturation at the high doses. CNS signs (reduced activity, incoordination, excessive grooming/scratching), pup death, decreased hindlimb splay, and decreased hindlimb grip strength were observed at all doses. Effects on pup body weight, pup growth, hindlimb splay, impairment in the water maze performance, and auditory startle persisted after dosing was stopped. A no-effect dose for postnatal developmental toxicity was not identified in this study. Oral administration of perampanel (1, 5,5/10 mg/kg/day; high dose increased on PND 56) to juvenile dogs for 33 weeks, starting on PND 42, resulted in CNS signs (incoordination, excessive grooming/licking/scratching, spatial disorientation, and/or ataxic gait) at all doses tested. Geriatric Use Clinical studies of FYCOMPA did not include sufficient numbers of patients aged 65 and over to determine the safety and efficacy of FYCOMPA in the elderly population. Because of increased likelihood for adverse reactions in the elderly, dosing titration should proceed slowly in patients aged 65 years and older. Hepatic Impairment Use of FYCOMPA in patients with severe hepatic impairment is not recommended, and dosage adjustments are recommended in patients with mild or moderate hepatic impairment. Renal Impairment Dose adjustment is not required in patients with mild renal impairment. FYCOMPA should be used with caution in patients with moderate renal impairment, and slower titration may be considered. Use in patients with severe renal impairment or patients undergoing hemodialysis is not recommended. DRUG ABUSE AND DEPENDENCE Controlled Substance FYCOMPA contains perampanel and is listed as a Schedule III controlled substance. Abuse Prescription drug abuse is the intentional non-therapeutic use of a drug, even once, for its rewarding psychological or physiological effects. Drug addiction, which develops after repeated drug abuse, is characterized by a strong desire to take a drug despite harmful consequences, difficulty in controlling its use, giving a higher priority to drug use than to obligations, increased tolerance, and sometimes physical withdrawal. Drug abuse and drug addiction are separate and distinct from physical dependence (for example, abuse may not be accompanied by physical dependence). Studies of human abuse potential were performed to evaluate the abuse potential of FYCOMPA (8 mg, 24 mg, and 36 mg) as compared to alprazolam C-IV (1.5 mg and 3 mg), and oral ketamine C-III (100 mg) in recreational polydrug users. Supra-therapeutic doses of FYCOMPA 24 and 36 mg produced responses for “Euphoria” that were similar to ketamine 100 mg and alprazolam 3 mg. For “High,” FYCOMPA 24 mg and 36 mg produced responses comparable to ketamine 100 mg and significantly higher than both doses of alprazolam on a visual analog scale (VAS). “Drug Liking,” “Overall Drug Liking,” and “Take Drug Again” for FYCOMPA were each statistically lower than ketamine 100 mg. In addition, for “Bad Drug Effects,” FYCOMPA 24 mg and 36 mg produced responses significantly higher than ketamine 100 mg. For “Sedation,” FYCOMPA 24 and 36 mg produced responses similar to alprazolam 3 mg and higher than ketamine 100 mg. Additionally, on VAS measures related to dissociative phenomena such as “Floating,” “Spaced Out,” and “Detached,” FYCOMPA at supra-therapeutic doses produced responses similar to ketamine 100 mg and greater than both doses of alprazolam tested. Of note, due to somnolence a number of subjects had missing data around Tmax of FYCOMPA. The above described data might represent an underestimate of FYCOMPA’s effects. The duration of effects of higher doses of FYCOMPA on the majority of measures was much greater than alprazolam 3 mg and ketamine 100 mg. In this study, the incidence of euphoria following FYCOMPA administration 8 mg, 24 mg, and 36 mg was 37%, 46%, 46%, respectively, which was higher than alprazolam 3 mg (13%) but lower than ketamine 100 mg (89%). Dependence Physical dependence is characterized by withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug. The potential for FYCOMPA to produce withdrawal symptoms has not been adequately evaluated. OVERDOSAGE There is limited clinical experience with FYCOMPA overdose. The highest reported overdose (approximately 264 mg) was intentional. This patient experienced serious adverse reactions of altered mental status, agitation, and aggressive behavior and recovered without sequelae. In general, the adverse reactions associated with overdoses were similar to the reactions at therapeutic doses with dizziness reported most frequently. There were no reported sequelae. There is no available specific antidote to the overdose reactions of FYCOMPA. In the event of overdose, standard medical practice for the management of any overdose should be used. An adequate airway, oxygenation, and ventilation should be ensured; monitoring of cardiac rhythm and vital sign measurement is recommended. A certified poison control center should be contacted for updated information on the management of overdose with FYCOMPA. Due to its long half-life, the reactions caused by FYCOMPA could be prolonged.

Through Their Eyes: Recollections of Past AAN Presidents Maynard M. Cohen, MD, FAAN; Lewis P. Rowland, MD, FAAN; and Stanley Fahn, MD, FAAN; former editor-in-chief of Neurology Robert B. Daroff, MD, FAAN; Sami I. Harik, MD, FAAN; William M. Landau, MD, FAAN; M. Marsel Mesulam, MD, FAAN; Brenda Milner, PhD, ScD; Jerome B. Posner, MD; and H. Richard Tyler, MD, FAAN.

Joseph M. Foley, MD, FAAN President 1963–1965

1973: Front row, Drs. Paul Yakovlev, Russell N. DeJong, Adolph Sahs, A.B. Baker; Standing, Joe Brown, Joe Foley

This year, the AAN celebrates its 70 th anniversary serving neurology professionals in the United States and worldwide. The AAN will publish a series of interviews conducted in recent years with Academy presidents. The interviews were conducted by Douglas J. Lanska, MD, MS, MSPH, FAAN, chair of the recently formed AAN History and Archives Committee, members of the AAN History Section, and Academy staff. “The Academy has a rich history serving the needs of neurology,” said Lanska, “and we want to make it more accessible to our members. We have refurbished the Academy’s history web page at AAN.com/membership/history. New interviews of past presidents will be posted monthly. We invite members to acquaint or reacquaint themselves with how the AAN grew from a conversation between the legendary Dr. A.B. Baker and his University of Minnesota resident Dr. Joseph Resch, its humble beginnings in 1948 with 50 charter members, and how it has responded with increasing sophistication to a widening array of needs by neurologists. We The new AAN History and Archives Committee have much to be includes Douglas J. Lanska, MD, FAAN, chair; Sandra F. Olson, MD, FAAN; Stephen G. Reich, MD, proud of, and much to look forward to.” FAAN; and Christopher J. Boes, MD, FAAN. Not pictured is Peter J. Koehler MD, PhD, FAAN.

The History webpage also includes transcripts of interviews conducted by the Oral History Work Group with neurology leaders, including former past presidents Joseph M. Foley, MD, FAAN;

Monday, April 23, 2018 • AANextra

This is an excerpt from an interview conducted in 2011 with Foley, former chair of the Division of Neurology at Case Western University Medical School and a past president of the American Neurological Association. The interviewers were Lanska (DL) and Barbara W. Sommer (BS). Foley passed away in 2012.

BS: Was there a need for the Academy? Would you talk about that a little bit? JF: I think there was. I think neurology had been growing in numbers and influence. I think they needed some pressure group to put them before the [ United States] Congress and all the rest. That was really the origins of founding of the Academy. BS: To come before the Congress? JF:

In part, yes.

BS: What do you mean by that?

Drs. Joseph M. Foley and Douglas J. Lanska at the 2011 interview.

JF: We appeared before congressional committees to advance the causes of neurology.

DL: There are stories that Forster and Baker actually flew to Washington to champion support for academic program development. JF: That’s right. And I think they did a good job of it. They would sometimes sound somewhat aggressive. Sometimes very unpleasant in their dealings with other people but, on the whole, I think they did marvelous work. DL: They helped get NIH funding as well. JF: Yes, indeed. They were very active in that. And Adolph Sahs, who was in that group as well. DL: They facilitated development of NIH funding for academic programs. JF: Exactly. DL: Do you think that changed how neurology functioned around the country? JF: Oh, I think, no question. But I think also the recognition of some of the—particularly dementia and particularly epilepsy—I think these programs needed a big boost. As a result of the

Academy, I think they got that boost. DL: Do you think it would ultimately have come as well from the ANA [ American Neurological Association] or do you think it needed the Academy to accomplish that? JF: I think it needed the Academy to accomplish it. The ANA was a pretty set organization. They didn’t move forward very much. BS: It was more selective in its membership too, so it had a smaller base. JF: Yes, selective. DL: The political role that the Academy had earlier on and, to a degree continues today, I think, was largely the brainchild of Baker, was it not?

Maynard M. Cohen, MD, FAAN President 1981–1983 Cohen came to the University of Minnesota—and A.B. Baker— after WWII. He worked with Baker for 20 years before going to Rush University. He was interviewed in 2012 by Christopher G. Goetz, MD, FAAN, (CG) and Barbara W. Sommer (BS). Cohen passed away in 2014. CG: How did you get involved with the AAN? How did you start in this? MC: Abe told me. [ laughs] BS: How did he tell you?

JF: Oh, yes. Abe Baker was a very aggressive political animal.

MC: You see, I was working with him before this whole thing happened. I just kind of got drawn in.

BS: Do you think he saw the future or began to think about how neurology could develop?

CG: Did you have any early duties that you remember? Any specific assignments related to the American Academy [ of Neurology]?

JF: I did. I think he knew it when he was a medical student. He was always passionate about the development of neurology….

MC: Oh, sure… I, and three other people, started all this whole thing of these courses and everything. That was the beginning. Abe started the courses…and he [ served as chair of the Special Courses Committee] for 20 years and then I did it. That’s how we did it.… We kept adding all these things that are present today…. I remember Nelson [ Nelson G. Richards] who was the president right after me and was particularly an advocate for practitioners. This was a fellow who was picking at me all the time, of all the years that we were there….

DL: Not only was Baker supportive of a political role, but he also had some strong views on how neurology should be involved in rehabilitation of patients with neurological diseases. JF: That’s right, exactly right. DL: In fact, at one point, you said that his view was that neurologists “must never relinquish to anyone the final responsibility for rehabilitation of the patient.” JF: Did I really? DL: Yes. JF: My God, every so often I said something sensible, didn’t I? [ laughs]…. DL: There are several different versions of how the “Four Horsemen” came to be for the Academy. Do you recall any of that? JF: Who were they? DL: The “Four Horsemen” are considered to be Baker, Forster, Sahs, and DeJong.

CG: Nelson? MC: Yeah, Nelson. When we first got together, I said, “Look, you have been picking at me through all of this. What I want is uniformity. I want you and I to accept—to work out everything in which we are doing and it comes out as one thing.” He was ecstatic. He was absolutely ecstatic. His help with the people who were the doctors, not the researchers—they realized that [ the AAN] had something for the doctors too. He went everywhere with me. He never missed anything. His final word was, “Anybody who tries to get between us will hear about it.” [ laughs] Continued on page 34 u

JF: I know that Baker and Sahs especially were very energetic, very aggressive, sometimes objectionably so in the minds of some people. DeJong settled very quickly into the editorship of the journal. BS: What about Forster as one of the “Four Horsemen?” JF: I knew Forster when I was a medical student. BS: Why was he considered one of the “Four Horsemen” of the AAN? JF: Because I think he had the political awareness to organize things, get things before the Congress, and create something that had not been there before. Foley talks about his associations with neurology pioneers Derek Denny-Brown, Houston Merritt, and Raymond Adams, and his harrowing experience serving as a medic with the first wave of soldiers landing on D-Day. Read the complete interview at bit.ly/2zHSRLD.

1985: AAN Presidents Nelson G. Richards (1983-1985), Maynard M. Cohen (19811983), Melvin Greer (1985-1987).

Monday, April 23, 2018 • AANextra

CG: Maybe Abe said the same thing about you. [ laughs] Being included is an important part of advancing. BS: As you think about the Academy and the education, it seems that the education program really made a difference. MC: You see, what I was trying to do was to unify. Not only him, but unification of the whole thing [ AAN educational effort]. And I wanted the whole thing to be close. It could be large, but it could be close…. Read the complete interview with Cohen, where he shares more about working with Baker, his views on mentorship, and his unique connection with Norwegian neurology at bit.ly/2j9wOqX.  Drs. Maynard M. Cohen and Christopher Goetz at the 2012 interview.

CG: That is a wonderful story. It shows how you faced a challenge, how you faced that dichotomy of spirits. And you’re right, when you sit down and talk, you can come up with a unified—maybe not always uniform—but unified presentation. And that builds and, of course, leaves a future legacy because, then, your tenure is all the longer. It is his tenure plus your tenure and then you pass the baton. MC: I ADS—HALF never thought that he would come to it. But he jumped at it. 18 QPP PRINT PAGE HORIZONTAL> NJ, NCP PLACED IN NEUROLOGY OR NEUROLOGY CLINICAL PRACTICE He wantedJOURNAL, to be loved. 8.25 X 5.4375 +0.125 BLEED, 4C

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for oral use

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

INGREZZA is a vesicular monoamine transporter 2 (VMAT2) inhibitor indicated for the treatment of adults with tardive dyskinesia.

WARNINGS AND 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. 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.

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.

DRUG INTERACTIONS

Drugs Having Clinically Important Interactions with INGREZZA Table 2: Clinically Significant Drug Interactions with INGREZZA Monoamine Oxidase Inhibitors (MAOIs) Clinical Implication:

Prevention or Management: Examples: isocarboxazid, phenelzine, selegiline Strong CYP3A4 Inhibitors Clinical Implication:

ADVERSE REACTIONS

The following adverse reactions are discussed in more detail in other sections of the labeling: • 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.

Prevention or Management: Examples: Strong CYP2D6 Inhibitors

The safety of INGREZZA was evaluated in 3 placebo-controlled studies, each 6 weeks in duration (fixed dose, dose escalation, dose reduction), including 445 patients. Patients were 26 to 84 years of age with moderate to severe tardive dyskinesia and had concurrent diagnoses of mood disorder (27%) or schizophrenia/schizoaffective disorder (72%). The mean age was 56 years. Patients were 57% Caucasian, 39% African-American, and 4% other. With respect to ethnicity, 28% were Hispanic or Latino. All subjects continued previous stable regimens of antipsychotics; 85% and 27% of subjects, respectively, were taking atypical and typical antipsychotic medications at study entry. Adverse Reactions Leading to Discontinuation of Treatment A total of 3% of INGREZZA treated patients and 2% of placebo-treated patients discontinued because of adverse reactions. Common Adverse Reactions Adverse reactions that occurred in the 3 placebo-controlled studies at an incidence of ≥2% and greater than placebo are presented in Table 1. Table 1: Adverse Reactions in 3 Placebo-Controlled Studies of 6-week Treatment Duration Reported at ≥2% and >Placebo INGREZZA (n=262) (%)

Placebo (n=183) (%)

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 exposure-related adverse reactions.

Prevention or Management:

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

Examples:

paroxetine, fluoxetine, quinidine

10.9%

4.2%

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

5.4%

4.9%

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

4.1%

2.2%

Headache Akathisia (akathisia, restlessness)

3.4% 2.7%

2.7% 0.5%

Vomiting Nausea Musculoskeletal Disorders

2.6% 2.3%

0.6% 2.1%

Arthralgia

2.3%

0.5%

Strong CYP3A4 Inducers Clinical Implication:

Prevention or Management: Examples: Digoxin

General Disorders Somnolence (somnolence, fatigue, sedation) Nervous System Disorders 1

Gastrointestinal Disorders

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.

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. Reduce INGREZZA dose when INGREZZA is coadministered with a strong CYP3A4 inhibitor. itraconazole, ketoconazole, clarithromycin

Clinical Implication:

Variable and Fixed Dose Placebo-Controlled Trial Experience

Adverse Reaction1

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. Avoid concomitant use of INGREZZA with MAOIs.

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 strong CYP3A4 inducers with INGREZZA is not recommended. rifampin, carbamazepine, phenytoin, St. John’s wort1

Clinical Implication:

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

Prevention or Management:

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.

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 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 trademark of Neurocrine Biosciences, Inc. CP-VBZ-US-0203v2 09/17

Visit Foundation Booth for Crowdfunding Site Demonstration The American Brain Foundation’s crowdfunding platform at AmericanBrainFoundation.org marks its one-year anniversary this month. Launched as part of the Foundation’s five-year strategic plan to better engage and build public support, the site is the first multi-disorder neuroscience crowdfunding website, offering a unique opportunity for visitors to search for and learn about current research in many areas of brain disease and either support a specific research project that compels them, or make a general donation to support all efforts. Fundamental to the crowdfunding’s success is presenting the right projects to the right audiences at the right time. Having devoted 2017 to building and testing the platform, this year the Foundation is focusing its efforts on educating the public about and promoting each individual research project, as well as the platform itself. The new crowdfunding marketing strategy is grounded in the Foundation’s ‘Cure One, Cure Many’ philosophy—one that envisions how a cure for one brain disease will lead to cures for others. This philosophy sets the Foundation apart from other organizations raising money for a single brain disease. Stop by the American Brain Foundation booth in the West Lobby of the Los Angeles Convention Center throughout the week to meet Foundation staff, learn more about the Foundation’s important mission, and see for yourself how crowdfunding is an innovative way to support the mission to bring researchers and donors together. The booth will be open each day of the meeting from 7:00 a.m. and 5:00 p.m. You can also follow the American Brain Foundation’s Facebook page, Twitter @ABFBrain, and visit AmericanBrainFoundation.org/Crowdfund-for-cures to join the giving and follow the projects that matter most to you. 

Today’s Boxed Lunch Menu Hot Lunch Option: Location: Exhibit Hall G Enjoy lunch while exploring the hundreds of neurology products and services throughout the Exhibit Hall. HHChicken, sun dried tomato, and penne pasta with basil cream sauce HHTraditional Caesar salad (V) HHRice Krispy treat

Cold Lunch Options: Locations: South Lobby, West Hall A, and Exhibit Hall G Choose from three convenient locations, each featuring two box lunch options. Grab your lunch and check out the talks on the Experiential Learning Area stages near the South Lobby; pick up your lunch and head to the Poster Discussion Sessions in West Hall A; or explore the hundreds of neurology products and services throughout the Exhibit Hall. Option I: HHTurkey and Swiss on pretzel roll with honey Dijon mustard HHTurkey and Swiss on GF pretzel roll with honey Dijon mustard (GF) HHPotato salad (V, GF) HHRice Krispy treat HHWhole fresh fruit (V, VG, DF, GF) Option II: HHGrilled zucchini and squash, tomato pesto, and greens on GF flatbread (V, VG, DF, GF) HHMarinated feta and tomato salad (GF, V) HHRice Krispy treat HHWhole fresh fruit (V, VG, DF, GF) V = Vegetarian GF = Gluten free VG = Vegan DF =Dairy free 

Monday, April 23, 2018 • AANextra

TWEETS OF THE DAY Jaime Martin MD PhD @DrJaimeMartin

Follow Follow @DrJaimeMartin Join us at the @AANMember #AANAM Innovation Hub in the Wxhibition Hall for great talks and experiences including Paint and Wine sipping!

Vineeta Singh @DrVineetaSingh5

@DrVineetaSingh5 #AANAM “distracted parenting affects development” Dr Baram

Michele Matarazzo @matarazzomd

Follow Follow @matarazzomd #Stroke drops from the 3rd to the 5th cause of death in just 20 years, prof. Koroshetz says. Advances in prevention and treatment are getting from research to general population. #AANAM

Dr Jeff Ratliff @DrJeffRatliff

Two passengers on a flight to LAX.

Chris Boes @ChrisBoesMD

Hey @AANMember, come take a #selfiewithAB & brush up on your cerebral circulation knowledge at the AAN 70th Anniversary Exhibit. #AANAM

Monday, April 23, 2018 • AANextra

illennial: What takes you to L.A.? M eurologist: The #AANAM! I’m a neurologist. N Millennial: Neurologist: How about you? What’s in L.A.? Millennial: I’m going to #Coachella ! Neurologist: End scene.

Are your patients asking about cannabis? How does cannabis work? What are the differences between the products out there?

Find answers and explore the science at the

CannabinoidClinical.com Booth #435

CannabinoidClinical.com is sponsored by Greenwich Biosciences, Inc., a GW Pharmaceuticals plc company. This site is not intended to provide medical advice or to suggest that any product mentioned is safe or efficacious for any disease or condition. This website is intended for a US audience. ÂŠ2018 Greenwich Biosciences, Inc. All rights reserved.

Industry Therapeutic Update from Biogen

Navigating an Early Diagnosis of Alzheimer’s Disease: A Call for Action

Chair: Ron Petersen Faculty: Mary Sano, James Galvin, and Marwan Sabbagh Tuesday 24 April 2018, 19:00–21:15 JW Marriott Diamond Ballroom (1–4), Los Angeles, USA Join our esteemed faculty for an engaging discussion that will explore an interactive patient case study to support the ongoing effort to increase early diagnosis of Alzheimer’s Disease and improve the management and care of patients affected.

Optional dinner provided upon arrival M-AD-US-01031

Date of preparation: March 2018

This is a non-CME event and is not a part of the AAN Official Programming Artwork acknowledgement: The Hilgos Foundation and I remember better when I paint. Further information can be found at www.hilgos.org and www.irememberbetterwhenipaint.com