2018 Annual Meeting AAN Extra — Thursday, Apr 26 by American Academy of Neurology

THE ANNUAL MEETING NEWS DAILY

INSIDE

out New ePoster 17 Check Areas at Poster Sessions Experiential 18 Today’s Learning Area Highlights

Thursday, April 26, 2018

CATCH THE DEBATE AT THIS MORNING’S PLENARY SESSION Experts will debate topical issues in neurology at this morning’s Controversies in Neurology Continued on page 11 u

and Donors 27 Researchers Celebrated at Foundation Fundraiser You at Tomorrow 38 See Night’s Closing Party Happy Hour!

Don’t Miss Tonight’s Case Studies Lineup

Today’s Invited Science Platform Session Showcases Key Talks on Neuro Trauma

Tonight’s popular Case Studies cover a wide range of unusual and challenging issues. Each course runs from 6:30 p.m. to 9:30 p.m. and is free and included with Annual Meeting registration.

Key talks previously given at the National Neurotrauma Society Annual Meeting will be reprised today, from 3:30 p.m. to 5:30 p.m. in Theatre 411. Speakers will emphasize basic, clinical, and translational science as they evolve toward a more complete understanding of neurotrauma with the overall goal of developing more effective prevention and treatment.

C210 Case Studies: Unusual Diagnostic and Management of Cases in Neuromuscular Disease Director: Anne M. Connolly, MD, FAAN, St. Louis, MO 409AB

Continued on page 5 u

Topics and speakers include: 3:30 p.m.–4:10 p.m. Operation Brain Trauma Therapy Consortium —Patrick M. Kochanek, MD, MCCM, University of Pittsburgh, Pittsburgh, PA 4:10 p.m.–4:30 p.m. The Glymphatic System: Role in Post-TBI Edema? —Miranda M. Lim, MD, PhD, Oregon Health & Science University, Portland, OR 4:30 p.m.–4:50 p.m. Hormonal Alternations and Sleep Following Brain Injury —Grace Griesbach, PhD, Centre for Neuro Skills, Encino, CA 4:50 p.m.–5:10 p.m. The Invisible Wounds of War: Combat Concussions —Christine MacDonald, PhD, Washington University School of Medicine, St. Louis, MO 5:10 p.m.–5:30 p.m. Traumatic Brain Injury: Lessons from Drosophila —David Wassarman, PhD, University of Wisconsin-Madison, Madison, WI 

In Multiple Sclerosis–

THE ART OF BRAIN PRESERVATION Adding Grey to the Palette Completes the Picture

GREY MATTERS, TOO

Thursday, April 26 Cover Don’t Miss Tonight’s Case Studies Lineup

4 4 5 6

Catch the Debate at This Morning’s Plenary Session Today’s Invited Science Platform Session Showcases Key Talks on Neuro Trauma

14 Remaining “Best of” Sessions

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

17 Check out New ePoster Areas at

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

18 Today’s Experiential Learning Area

Contact Information:

Highlight Neuromuscular Clinical Trials, Inflammatory Diseases Poster Sessions Highlights

24 Recollections of Past AAN Presidents

Omalu, DeKosky Share Their Stories from First Diagnosis to Hollywood Movie

27 Researchers and Donors Celebrated at Foundation Fundraiser

Brain Trauma and Those Who Serve

28 Upcoming AAN Conference

Emerging Therapies Elucidated at Tomorrow’s Plenary Session The Job Interview: Top Mistakes and How to Avoid Them

11 Catch the Debate at This Morning’s Plenary Session

13 Quotable Quotes

Opportunities

34 Tweets of the Day 37 Attend Invited Science:

BRAIN Initiative at 1:00 Today

37 Daily Reminders 38 Today’s Boxed Lunch Menu 38 Friday’s Boxed Lunch Menu 38 See You at Tomorrow Night’s Closing Party Happy Hour!

Thursday’s AAN Section Meeting

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. 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.

8:15 a.m.–9:15 a.m. Epilepsy Section / LACC Petree Hall C

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.

Omalu, DeKosky Share Their Stories from First Diagnosis to Hollywood Movie A rapt audience turned out to hear Bennet Omalu, MBBS, MPH, MBA, and Steven DeKosky, MD, FAAN, FANA, FACP, discuss their work to confirm the first case of dementia pugilistica/chronic encephalopathy in an American football player.

Natalia S. Rost, MD @nsanar

As chronicled in the 2015 film “Concussion,” Omalu and DeKosky together confirmed the first case of dementia pugilistica/chronic encephalopathy. As the first doctors to identify chronic brain damage as a major factor in the deaths of some professional athletes, DeKosky and Omalu withstood dismissals, backlash, and pressure from peers and the National Football League. 

“Truth doesn’t have a point of view. Truth is at the heart of humanity of humanity. Science for the sake of science is what I call “scientificity.” The truth empowers and elevated the humanity of all of us. #AANAM @AANPublic @AANMember

Dr. Casey Farin @

CaseyFarinMD “Parents need to discourage their children from playing contact sports, because it damages the mind.” -@ bennetomalu9168 And my boyfriend wonders why I won’t watch boxing matches with him. #AANAM

Brain Trauma and Those Who Serve The unique insights and perspectives from military neurologists and how they apply to our field as a whole were provided in “Good Neurology in Challenging Conditions: Lessons Learned from Military Neurology.” The session offered insights to neurologic conditions that may impact a servicemember’s ability to remain in the service, traumatic brain injury, traumatic peripheral nerve injuries, and finished with a panel discussing neurology in the deployed setting. 

The course faculty (left to right): Major (Dr.) Jonathan Smith, MD, US Army; Major (Dr.) Michelle Gatheridge, MD, US Air Force; Lieutenant Colonel (Dr.) Brett Theeler, MD, US Army; Commander (Dr.) Rene Pazdan, MD, FAAN, US Public Health Service; and Lieutenant Colonel (Dr.) Jeffrey C. McClean II, MD, FAAN, US Air Force (Course Director).\

Thursday, April 26, 2018 • AANextra

Emerging Therapies Elucidated at Tomorrow’s Plenary Session The latest research in treatment in six subspecialty areas will be detailed at tomorrow morning’s Neurology Year in Review: Emerging Therapies Plenary Session, which runs from 9:15 a.m. to 11:30 a.m. in South Exhibit Hall K and rounds out the week of premier lectures. The session moderator is Antonio M. P. Omuro, MD, member of the AAN Science Committee. The topics and speakers are: A Year in Review of Neuromuscular Diseases: Making Treatments Great Again — Ericka P. Simpson, MD, FAAN Methodist Hospital, Houston, TX

Dementia — Liana Apostolova, MD, FAAN Indiana University School of Medicine, Indianapolis, IN

Headache Medicine 2018: Year in Review — Matthew S. Robbins, MD, FAAN Montefiore Headache Center, Bronx, NY

Finally, Some Closure on PFO Closure — Steven R. Messé, MD, FAAN, FAHA Hospital of the University of Pennsylvania, Philadelphia, PA

Pediatric Epilepsy — Kelly G. Knupp, MD Children’s Hospital Colorado, Aurora, CO

Neuro-oncology Year in Review: Progress, Breakthroughs, and Future Directions — Antonio M. P. Omuro, MD University of Miami Miller School of Medicine, Miami, FL 

Don’t Miss Tonight’s Case Studies Lineup Continued from cover

C211 Case Studies in the ICU Director: Nicholas Joseph Silvestri, MD, FAAN, Buffalo, NY 403B

C214 Case Studies: Challenging Headache Cases Director: Deborah I. Friedman, MD, MPH, FAAN, Dallas, TX 408B

C212 Case Studies: Test Your Knowledge: A Case-based Approach to Neuroimaging Director: Joshua P. Klein, MD, PhD, FANA, FAAN, Boston, MA 502A

C215 Case Studies in Behavioral Neurology: Focus on Frontotemporal Degeneration Director: Daniel Kaufer, MD, FAAN, Chapel Hill, NC 502B 

C213 Case Studies: Unusual Movement Disorders Director: Kailash P. Bhatia, MD, FAAN, London, United Kingdom 403A

Thursday, April 26, 2018 • AANextra

The Job Interview: Top Mistakes and How to Avoid Them Interviewing can be intimidating or scary because you want to be in control of all situations you find yourself in, and interviews throw you into the realm of the unknown. What questions will they ask? What are they looking for? The mistakes we make during the interviewing process often comes from excess pressure to be “perfect” that we put on ourselves. By learning about some common mistakes and being honest with yourself, you can grow and learn.

Mistake #1: Reticent to Be Yourself Bottom-line: Interviewees “try to look good” and come off with a false sense of self that the interviewer actually senses because of a conflict between your persona and your language. When you feel like your light switch is ‘off’ or you feel constricted “flat as a pancake”—inside you come from fear, doubt and judgment. You act over composed and you come across stiff and unmotivated, and robotic. That is not going to get you hired. Preparing for an interview is like writing the first draft of a paper, you practice your possible answers and become more confident with each description of what you’ve done. In contrast, when your light switch is “on” you come from authenticity, fulfillment, and joy; thus, things flow better! When you are awake and aware trusting the answer will come from you and the energetic space of you and the interviewers together—creating a dynamic, you breathe, think, feel, speak and portray who you really are.

Keeping a brain-heart connection is essential to revealing your true self, full of intelligence, passion, skills, talents, and aptitude in a meaningful, memorable way to the interviewers. Remember, interviewers want to get to know you because you will be an integral member of their respected physician team. Furthermore, you are also interviewing them, consider, what would be the best part of work with them? “I learned to describe things crystal clear and improve phrases for greater impact. You made my day; now, I can talk to the Program director in an interview!”—Rakesh, AAN Neurology Career Center

Mistake #2: Showing up Unprepared Come to an interview prepared by knowing your top 10 values, top 10 accomplishments along with three situations of conflict, stress, or mistakes, and an up-todate curriculum vitae. Practice makes perfect or at least the more familiar with your macroscopic and microscopic views of your experience, education, and vivid two-minute stories. A simple format: What was the situation, What you did to make it better, and The outcome. Or another story-telling format: Start with the climax, and grip them as you describe the remainder of your captivating or lifechanging story. Being prepared can bring a sense of confidence, an organized structure, and primed to talk about yourself. The paradox is to be prepared and yet when things don’t go as planned or as you decided ahead of time, you may fumble and shutdown getting stuck or even lost. So, put your attention on your intentions— what you want to convey with your achievements, values, learning situations, etc. Be open to interpersonal dynamics that transpire in real time in an interview and speak up. Be prepared and ready to think on your feet. The form of the interview may throw you curve ball, let go of the attachment to way you think it should look and go with the question-answer conversation in the moment. Another paradox, you must be prepared and open to seize every opportunity! “The best part of our coaching appointment was answering your questions and then getting feedback! Going through this mock interview reminded me of my pletheroa of experiences and how to apply them in future interviews.”—Annise, AAN Neurology Career Center

“You helped me boil it down to what is most important to convey about my experience, stories and presenting myself!”— Petya, AAN Neurology Career Center

Mistake #3: Not Taking Credit Where Credit Is Due Speak up! You’ve earned your accomplishments, skills, and abilities. Now, is the time to portray and describe who you are and what you’ve achieved through your education, clinical experience, team approach, and leadership. Remember, nothing you’ve accomplished is too small or insignificant as long as it has relevant implications. This interview is your platform to portray your mastery of all you’ve become thus far in the medical profession. Describe what you know, what you’ve done, and the rewarding experience you treasure. In general, most people want to know, what makes you tick, how you became a doctor, and what your vision is for better health care. “You put the spotlight on my strengths and my weaknesses. I will keep my confidence and stop trailing off at the end of sentences.” —Mirza, AAN Neurology Career Center

Mistake #4: Acting Like You Have No Weaknesses or No Mistakes We all have strengths and weakness. We are human, both in our human-ness and our human-mess. Actually, interviewers want to know your areas of learning. That is why there are so many behavior and personality assessments, to make a great match. Interviewers are assessing you for their neurology team—and they need to know how they can count on you. Don’t be ashamed or feel “less than” with your weaknesses. Weakness can be a disadvantage, such as procrastination, perfectionism, avoidance, failure to prioritize your energy and your time, etc. The best thing you can do is turn your weaknesses into a positive, such as perfectionism or a superior standard of excellence for a neurosurgeon is a great fit—right on. Be honest with yourself. If you know of your weaknesses, hot buttons, or self-limiting beliefs that hold you back from success and don’t like them, get out of your own way. I invite you to face up to them and get resolution! In the resolution process, you will allow yourself to grow, be more compassionate, and move to the next level. Do you want that kind of freedom? “I had a big “Aha!” I took notes on the steps I need and want to take!”—Ryan, AAN Neurology Career Center “Don’t look up at the ceiling; instead, pay attention to the interviewer. Be more eloquent in wording my goals and weaknesses. I appreciated that!”—Nina, AAN Neurology Career Center

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

THE TROUBLE WITH DYSKINESIA:

GOCOVRI™ (amantadine) extended release capsules is the first and only FDA-approved medication indicated 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 (e.g., 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.

In Parkinson’s disease

THE TREATMENT FOR DYSKINESIA: GOCOVRI 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 (e.g. 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.

In 2 pivotal studies, patients treated with GOCOVRI once daily at bedtime over 12 weeks experienced:

UP TO

LESS OFF TIME

LESS DYSKINESIA (Primary Endpoint)

UP TO

HRS

MORE FUNCTIONAL TIME (defined as ON time without troublesome dyskinesia)

• Study 1: 37% reduction in UDysRS total score from baseline vs 12% with placebo1,2*

• Study 1: 30% placebo-adjusted decrease in OFF time from baseline3†

• Study 1: +3.6 hours of functional time vs +0.8 hours with placebo (P < 0.0001)1

• Study 2: 46% reduction in UDysRS total score from baseline vs 16% with placebo1,2*

• Study 2: 48% placebo-adjusted decrease in OFF time from baseline3†

• Study 2: +4 hours of functional time vs +2.1 hours with placebo (P = 0.0168)1

• The most common adverse reactions (>10%) with GOCOVRI were hallucination, dizziness, dry mouth, peripheral edema, constipation, fall, and orthostatic hypotension1

Study Description: The efficacy and safety of GOCOVRI 274 mg were evaluated in 2 Phase 3, randomized, placebo-controlled trials. Study 1 was conducted in 121 PD patients with dyskinesia (GOCOVRI [n = 63], placebo [n = 58]). Study 2 was conducted in 75 PD patients with dyskinesia (GOCOVRI [n = 37], placebo [n = 38]). The primary efficacy endpoint was change in UDysRS total score from baseline to Week 12. Key secondary endpoints from a PD home diary: changes from baseline to Week 12 in ON time without troublesome dyskinesia and OFF time.1 Unified Dyskinesia Rating Scale (UDysRS) is a 4-part rating scale incorporating patient and clinician evaluation of the presence, duration, and severity of dyskinesia. *GOCOVRI demonstrated reductions in UDysRS total score of -15.9 (vs -8.0 for placebo; P = 0.0009) and -20.7 (vs -6.3 for placebo; P < 0.0001) in Study 1 and Study 2, respectively. †GOCOVRI demonstrated reduction of -0.6 hours of OFF time vs +0.3 hours with placebo (P = 0.0171) and -0.5 hours of OFF time vs +0.6 hours with placebo (P = 0.0199) in Study 1 and Study 2, respectively.1

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 accompanying page. References: 1. GOCOVRI [Prescribing Information]. Emeryville, CA: Adamas Pharma LLC; 2017. 2. Elmer LW, et al. CNS Drugs. 2018 Mar 12. [Epub ahead of print] 3. Data on file. Adamas Pharma LLC, Emeryville, CA.

LEARN MORE AT GOCOVRIHCP.com/experience

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-0273 03/18

Catch the Debate at This Morning’s Plenary Session Continued from cover

Plenary Session, which runs from 9:15 a.m. to 11:30 a.m. in South Exhibit Hall K. This plenary session will feature audience response technology to create an interactive attendee experience.Moderators for the session are Science Committee members Aleksandar Videnovic, MD, MSc, FAAN, and Amy R. Brooks-Kayal, MD, FAAN. The topics and speakers are:

Should We Use Biomarkers Alone for Diagnosis of Alzheimer’s? Yes: Michael W. Weiner, MD University of California, San Francisco San Francisco, CA

No: Maria Glymour, PhD University of California, San Francisco San Francisco, CA

Should the Neurologist Be Primarily Responsible for Taking Care of Patients with Functional Disorders? Yes: David L. Perez, MD Massachusetts General Hospital Boston, MA

No: Andrea Leigh Haller, MD Fort Wayne Neurological Center Fort Wayne, IN

Would You Let Your Child Play Contact Sports? Yes: Jack W. Tsao, MD, DPhil, FAAN The University of Tennessee Health Science Center Memphis, TN

No: Christopher Giza, MD UCLA Los Angeles, CA 

Thursday, April 26, 2018 • AANextra

Can’t Attend Every Session? Enhance your Meeting experience with Annual Meeting On Demand. Maximize your investment in attending the 2018 AAN Annual Meeting with Annual Meeting On Demand. Watch sessions you missed, or revisit your favorite sessions. Get access to approximately 500 hours1 within 24 hours of the live presentation. Features: Watch like you’re there in person! By combining slides with synchronized audio, our technology re-creates the live session experience. Learn at your desk, in your car, or on the go! Start watching on one device, and pick up exactly where you left off on another. Earn credits and satisfy your requirements. Simply watch a CME eligible session and click on the CME Test button. Learn offline and take notes. PDFs of slides can be downloaded onto your computer for easier review and note taking. Listen while you learn. MP3 audio files are easily loaded onto your favorite device, so you can listen to sessions while on-the-go. LIST PRICE

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Visit our On Demand Sales Booth location: West Lobby Online: Orders.OnDemand.org/AAN/losangeles Phone: (800) 501-2303 (US Only) or (818) 844-3299 Monday – Friday 6:00 a.m. and 5:00 p.m. PST 1

Specific presentations within a session may not be available or may be audio only if the presenter has confidential patient information or otherwise declines to be recorded.

QUOTABLE QUOTES Stephanie L. Bissonnette, DO Boston, MA What are some of the highlights of the meeting for you so far?

I just went to the plenary session, and it was really great. I felt there is a lot of excitement about the new trials that are coming. And there are things that affect me as a movement disorders specialist that I'm looking forward to. That was one of the highlights. I'm doing a handful of the updates to kick-start me towards my service that I have coming up in the fall, to just refresh my memory coming out of fellowship but also for some the things that I knew that I may have missed during this year. I'm at Boston Medical Center and I'm staying on in July as faculty. So, I’m trying to get updated on everything that may have changed.

Suresh Kotagal, MD, FAAN Rochester, MN What are you looking forward to at the meeting?

I will be attending the hypersomnia session, and I will chair a session on pediatric hypersomnia sleep disorders. The Annual Meeting has absolutely the best of the science and also good opportunities to interact with colleagues.

Thomas R. Vidic, MD, FAAN Elkhart, IN As an AAN Board member, how is this meeting shaping up in your eyes?

Florence Ching-Fen Chang, FRACP Wentworthville, NSW, Australia What have you come to learn about?

I wanted to get an update on general neurology because I’m mainly a movement disorder neurologist. Because I'm working Huntington's disease, I’d say the plenary session where they mentioned a new gene-silencing treatment for Huntington's disease was quite exciting for me. I think it's a very worthwhile meeting. You can go and attend any sessions you like. You don't have to necessarily sign up for most of them beforehand.

Brian A. Trimble, MD, MPH, FAAN Anchorage, AK How is your experience at the meeting?

Good. This is a very different meeting this year. I really like Ralph Sacco’s plan to have the opening party at Universal Studios. That was amazing! It's a good meeting. I’ve been over to the BrainPAC booth and I'm wearing the green bowtie from Neurology on the Hill because I participated this year for the first time. I had heard for many years that it was a great thing and it is. I did it and it really is a nice way to advocate for neurology. Are you satisfied with the advocacy efforts of the Academy?

Very satisfied, yes. I’m very impressed with the advocacy. The Academy has recognized the need to deal with burnout amongst neurologist very early and have really done a lot to overcome that by early mentoring, making maintenance of certification requirements free—I really appreciate that. And they’re in there working and lobbying Congress.

I think the meeting is incredible. There’s a lot for everybody. I think the educational sessions are amazing, but also the programs on how to be better in practice, how to be better in your research, how to manage your career. There's aspects for everything. We're here looking at the poster sessions and seeing the basic science, and we’ve had the opportunity to see how that grows into practical patient care and the whole arena. It's a great opportunity, as is the format in which we can go to different classes without having to preregister— whatever strikes our fancy, what we get excited about, and fits into our schedule. You’ve been very involved with the Academy 's advocacy activities. Have you had a chance to encourage other members to participate?

Very much so. I'll touch on everything from the BrainPAC booth to some of the different opportunities about how to be active at home, in your community, with your patients. There's something for everyone here and it's almost too much, but that's what makes it fun. And the opportunity to re-energize with old friends, that's a great opportunity also.

Thursday, April 26, 2018 • AANextra

Remaining “Best of” Sessions Highlight Neuromuscular Clinical Trials, Inflammatory Diseases Don’t miss your chance to see authors present the four top-rated abstracts in clinical trials in neuromuscular disorders during this morning’s “Best of” Scientific Platform session immediately preceding the Controversies in Neurology Plenary Session. Then look for top abstracts in MS and CNS inflammatory diseases beginning tomorrow at 8:00 a.m., prior to the Neurology in Review Plenary Session.

“Best of” Session: Clinical Trial Updates in Neuromuscular Disorders

“Best of” Session: MS and CNS Inflammatory Diseases

Thursday, 8:00 a.m.–9:00 a.m. 408B

Friday, 8:00 a.m.–9:00 a.m.

8:00 a.m.—Preliminary Results from a Phase 2 Study to Evaluate ACE-083, a Local Muscle Therapeutic, in Patients with Facioscapulohumeral Muscular Dystrophy Jeffrey Statland, Anthony Amato, Elena Bravver, Craig Campbell, Lauren Elman, Nicholas Johnson, Nanette Joyce, Chafic Karam, John Kissel, Lawrence Korngut, Erin O’Ferrall, Georgios Manousakis, Alan Pestronk, Perry Shieh, Alrabi Tawil, Ashley Leneus, Barry Miller, Matthew Sherman, Chad E Glasser, Kenneth Attie 8:08 a.m.—NurOwn® Phase 2 ALS Trial: ALSFRS-R Improvement is Reflected in Subscale Domains Ralph Kern, Merit Cudkowicz, James Berry, Anthony Windebank, Nathan Staff, Margaret Owegi, Chaim Lebovits, Yael Gothelf, Robert Brown 8:16 a.m.—Long-Term Efficacy and Safety of Bimagrumab in Inclusion Body Myositis: 2 Years Results Anthony Amato, Lixin Zhang-Auberson, Michael Hanna, Umesh Badrising, Merrilee Needham, Hector Chinoy, Masashi Aoki, Barbara Koumaras, Laszlo Tanko, Min Wu, Dimritris Papanicolaou, Olivier Benveniste 8:24 a.m.—Randomized Phase 2B trial of NP001, a Novel Immune Regulator, in ALS Robert Miller, Jonathan Katz, Gilbert Block, NP001-10-003 Study Group 8:35 a.m.—Panel Discussion/Meet the Investigators

West Exhibit Hall B

8:00 a.m.—Longitudinal Changes in Quantitative Spinal Cord MRI in Multiple Sclerosis Patients: Results of a 5-year Study Jiwon Oh, Kateryna Cybulsky, Min Chen, Suradech Suthiphosuwan, Estelle Seyman, Aaron Carass, Marie Diener-West, Peter Van Zijl, Jerry Prince, Daniel Reich, Peter Calabresi 8:08 a.m.—Effect of Age at Puberty on Risk of Multiple Sclerosis: A Mendelian Randomization Study Adil Harroud, John A. Morris, Vincenzo Forgetta, Ruth Mitchell, George Davey Smith, Stephen Sawcer, J. Brent Richards 8:16 a.m.—Longitudinal Assessment of Rates of Brain and Retinal Atrophy in African American Versus Caucasian American Patients with Multiple Sclerosis Natalia Gonzalez Caldito, Shiv Saidha, Elias Sotirchos, Blake Dewey, Norah Cowley, jeffrey Glaister, Kathryn Fitzgerald, James Nguyen, Alissa Rothman, Esther Ogbuokiri, Dorlan Kimbrough, Teresa Frohman, Elliot Frohman, Laura Balcer, Ciprian Crainiceanu, Dzung Pham, Jerry Prince, Peter Calabresi 8:24 a.m.—Meta-analysis of the Age-dependent Efficacy of Multiple Sclerosis Treatments Ann Weideman, Marco Tapia-Maltos, Kory Johnson, Mark Greenwood, Bibiana Bielekova 8:35 a.m.—Panel Discussion/Meet the Investigators 

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.

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

Check out New ePoster Areas at Poster Sessions New this year for the poster sessions, we’ve added semiprivate 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 V 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. Again this year, we’ve clustered all topic-related posters together into “neighborhoods” to enhance your discussions and make the posters easier to navigate. See the map for the neighborhood locations.

MS and CNS Inflammatory Disease Lunchtime Poster Discussion Session

Today’s ePoster Sessions: Two Sessions on Infectious Disease and Global Health Be sure and check out the center of the poster hall for today’s interactive, touchscreen ePosters. 

Tomorrow’s Poster Session Schedule Poster Session VI Friday: 11:30 a.m.–5:30 p.m. author standby from 4:00 p.m.–5:30 p.m. Movement disorders is the focus of the poster discussion session, as well as both ePoster sessions, with abstracts on Huntington’s disease, Guillain-Barré syndrome, Friedreich’s ataxia, dystonia, and more.

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.

091–172

037–084

173–200

b1 g1 085–090 339–344 a1 ePosters

201–258

ePosters

Poster Discussion

027–036

001–026

259–294

295–338

345–428

429–480

Poster Session V

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

Poster Session VI A. General Neurology: 001–026

a1. MS and CNS Inflammatory Disease Poster Discussion Session: 027 – 036

a1. Movement Disorders Poster Discussion Session: 027–036

B. Movement Disorders: 037 – 084

b1. Movement Disorders I ePoster Session: 085–090

C. Infectious Disease; Global Health; Neuroepidemiology: 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. History of Neurology; General Neurology: 295 – 338

g1. Infectious Disease and Global Health II ePoster Session: 339 – 344

345–428

429–480

A. Neuro-rehabilitation: 001 – 026

b1. Infectious Disease and Global Health I ePoster Session: 085 – 090

B. Movement Disorders: 037–084 C. Neuro-oncology: 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. Neuro Trauma, Critical Care, and Sports Neurology: 295–338

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

H. MS and CNS Inflammatory Disease: 345 – 428 I. Neuromuscular/Clinical Neurophysiology (EMG): 429 – 480

Thursday, April 26, 2018 • AANextra

TODAY’S EXPERIENTIAL LEARNING AREA HIGHLIGHTS HeadTalks Who Wants to Be a Millionaire

12:00 p.m.–1:00 p.m. You won’t want to miss this exciting game show-style event! Brenda Banwell, MD, FAAN; Carlayne E. Jackson, MD, FAAN; and Jose H. Posas, MD, will challenge contestants with increasingly difficult neuro-based questions along with lively audience interaction.

Consejos Prácticos para un Buen Examen Neurológico 3:00 p.m.–4:00 p.m. Unirse Jose Biller, MD, FAAN, FACP, FAHA, y Vladimir Hachinski, MD, DSc, FAAN, para a presentación en aspectos útiles del examen neurológico.

Don’t Miss These Friday Highlights

Live Well: Taking Care of Your Patients Starts with Taking Care of You Complimentary Chair Massages 12:00 p.m.-4:00 p.m.

The Purpose Checkup: Find Meaning, Live Longer, Better

12:00 p.m.–12:45 p.m. What makes you want to get out of bed in the morning? At times in our lives, the answer to that question seems more difficult than earlier to answer. Based on his perennial bestselling book, The Power of Purpose: Find Meaning, Live Longer, Better, preeminent executive-life coach Richard Leider will help you unlock your purpose to answer the question. Purpose is not a luxury. It is fundamental to health, healing, and, ultimately, to happiness.

Café Talk: Magnifying Your Life Through Poetry

3:00 p.m.–3:45 p.m. Neurologists have an intimate and unique relationship with language. Poetry is an ideal tool for expressing those frequent moments in a neurologist’s life that deserve intellectual and artistic exploration. Michael L. Wynn, DO, will demonstrate how poetry can augment the neurologist’s life in and away from the clinic and present the anatomy of a successful poem to encourage you to begin or enhance your own experience of reading and writing poetry.

Thursday, April 26, 2018 • AANextra

The Neurology of Creativity at the Keyboard 12:00 p.m.–1:00 p.m. Speaker: Phillip L. Pearl, MD, FAAN Live Intraoperative Monitoring 1:30 p.m.–2:30 p.m. Speaker: Constantine Moschonas, MD, FAAN

Attendees at the HeadTalks stage got to test their neurologic fortitude against top neurologists at the exciting Neuro-Jeopardy: Telencephalon Twisters, led by Laurice T. Yang, MD, MHA, and Veronica E. Santini, MD.

Medical Marijuana: What Do Neurologists Need to Know?

1:00 p.m.–1:45 p.m. As medical marijuana becomes legal in more states, practicing neurologists need to know how to advise their patients about its use. This session will review the evidence for medical marijuana and related products in the treatment of neurologic disorders, and provide practical information about prescribing including dosage forms, side effects, and legal issues.

Join Us Tomorrow for Our Final Yoga Session Be sure and join us Friday morning from 7:00 a.m.–7:45 a.m. for the final yoga session of the meeting. See you there!

Maximize Your Value and Advocacy to Action Enhancing Epilepsy Care in Your Practice: In-person Digital Learning and Emotional for Self-Management, Education, and Community Supports from the National Epilepsy Education and Awareness Collaborative

8:00 a.m.–9:00 a.m. The National Epilepsy Foundation and partners within the National Epilepsy Education and Awareness Collaborative will present time-efficient and validated methods to screen people with epilepsy for depression and anxiety, evidence-based selfmanagement programs and digital resources that patients can access, and examples of community-based resources to assist in referring patients for mental health that can be especially valuable in settings with limited access. Presenters include Barbara C. Jobst, MD, FAAN, and Patricia Shafer, RN, MN.

Friday Session Examines Payment Models Incorporating a Semi-concierge Model into Your Own Neurology Practice 12:00 p.m.–12:30 p.m. Speaker: Teryn M. Clarke, MD

Research Corner: Moving Neurology Forward

American Brain Foundation Crowdfunding Application Process

3:50 p.m.–4:20 p.m. Find out how the Foundation can help you secure more funding for your research. Mark Mehler, MD, FAAN, will walk attendees through the online neuroscience crowdfunding application process.

Friday Research Highlight

How to Put Together an Effective Research Presentation 12:40 p.m.–1:10 p.m. Stop by for presentations throughout the afternoon by Speaker: Enrique C. Leira, MD, MS, FAAN representatives from the American Brain Foundation. Learn more about their mission to bring researchers and donors together to defeat brain disease and hear about their accomplishments over the Navigating Your Career past year implementing the world’s first neuroscience crowdfunding platform and granting over $1 million to 11 early career researchers Teaching History and Exam with Teleneurology 11:45 a.m.–12:30 p.m. and raising $3.9 million for current and future awards. Raghav Govindarajan, MD, FAAN, will discuss the pearls and American Brain Foundation Crowdfunding pitfalls in history and physical exam with teleneurology.

American Brain Foundation Day

Marketing Strategy

2:30 p.m.–3:00 p.m. Joseph Sirven, MD, will discuss how the American Brain Foundation can help you raise funds for your research through social media and other marketing tools.

What Is the American Brain Foundation?

3:10 p.m. – 3:40 p.m. Jane Ransom and Ralph Józefowicz, MD, FAAN, will highlight the Foundation’s accomplishments over the last 25 years and its mission to cure brain disease through investment in research.

The Member Experience: Personalize Your Journey Social Chatup Swing by to network with other social media mavens, ask questions about social channels, set up a new social account, check out the daily social media influencers, and take a new headshot—all while charging your device!

Daniel C. Potts, MD, FAAN, and Neelum T. Aggarwal, MD, led a panel discussion with persons living with dementia, a virtual dementia simulation, and a discussion of the changing demographics, genetics, and neuroethics of Alzheimer’s and other dementias during the LiveWell presentation on Perception Is Reality: Are Neurologists Helping Patients Live Well with Dementia?

Diviya Kaul, MD, explained why dance, specifically, helps improve symptoms for patients with Parkinson's disease before giving a live demonstration with audience participation at the LiveWell area’s Dancing with Parkinson’s presentation.

Lyell K. Jones, MD, FAAN, and Anup D. Patel, MD, FAAN, led an interactive discussion on how attendees can incorporate the Axon Registry® into practice and improve their value at the Maximize Your Value area.

Allison Brashear, MD, MBA, FAAN, gave tips on how to negotiate with peers and supervisors, create the win-win, and talk about compensation and expectations during the Navigating Your Career’s Interviewing Skills: Negotiation.

Ann H. Tilton, MD, FAAN, described how underlying principles of illness, pain, possession, and death in voodoo can help raise our understanding and increase the mystery of our own perceptions of what constitutes western medicine during the Neurology of Voodoo presentation on the HeadTalks stage.

Thursday, April 26, 2018 • AANextra

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.

Recollections of Past AAN Presidents Roger N. Rosenberg, MD, FAAN / President 1991–1993 Francis. I. Kittredge, Jr., MD, JD, FAAN / President 1999–2001

Throughout 2018, the AAN is celebrating the history of the Academy during its 70th anniversary with a series of interviews of past presidents. The following excerpt is from a 2017 joint interview with Roger N. Rosenberg, MD, FAAN (RR), and Francis. I. Kittredge, Jr., MD, JD, FAAN (FK), conducted by AANnews editor Tim Streeter (TS). Rosenberg and Kittredge, along with then-President Lewis P. (Bud) Rowland, MD, FAAN, were instrumental in the launch of what is now known as the American Brain Foundation. TS: I’d like to take you back to the 1990s and The Decade of the Brain. Did the Academy benefit from that? RR: Yes, The Decade of the Brain in the 2000s had an effect. It had a major educational effect. It got people really interested in the brain. It increased the budget of the NIH. Those are very important. It was education not only of our colleagues in medicine and science, but the public. The public has an insatiable interest, as Dr. Kittredge said. We did not have good therapies for multiple sclerosis then; we do now. Parkinson’s then, we didn’t; we do now. Stroke then, we do now. The public is involved in this. They are our advocates with the Congress, the congressional appropriations, which has driven the ability to do more research. That is why we have to preserve the NIH budget now, which is under some concern. An increase in the budget for neurologic disease benefits everybody. No matter what your political persuasion may be. We have to deal with and develop new therapies for stroke and Alzheimer’s disease. These are democratic diseases. They affect everybody of any persuasion. We need to benefit the American people. I think The Decade of the Brain was the start and it had a real effect in terms of increasing the NIH budget of mobilizing the public at large from an education point of view and it just continues. The budget now of the NIH is 32 billion dollars. NINDS and NIH, the mental health institutes are up, and we are getting answers to neurologic disease. Look at what has happened in terms of stroke: tPA and endarterectomy and stents. It has had a practical effect. The Decade of the Brain really focused the public’s education on the brain in a very concerted way for the first time. It had a real benefit. Now we see the dividends from that investment. TS: Dr. Kittredge, you came into the presidency at the end of The Decade of the Brain. Did you see any effects? John Whitaker, MD; Sen. Mark Hatfield (R-OR); Did you have something and Francis J. Kittredge, Jr., MD, JD, FAAN, to build off of during your in Washington, DC, 1992. presidency from that? FK: I thought that The Decade of the Brain, as Roger said, was amazingly exciting. I mean, they expanded funding for NINDS by 100 percent. They doubled the budget over that 10-year period. The unfortunate thing is that after 2001, the budget has

been sort of flatlined. There is an integration that occurs that starts with the basic sciences and NIH is primarily interested in that. If we don’t have the basic science going on at NIH and we don’t have the translational science going on in the university system in the neurology departments, and that kind of thing, then industry does not then follow up with the clinical applications and development of new target drugs. These are so closely linked and industry, as I understand it, has been pulling back from funding research on their part because of the fact that it is so difficult, expensive, and timeconsuming to go ahead and introduce new drug products that are calculated, as Roger was saying, that have identified targets in the genome in the neuropathophysiology, if you will, that could be identified and targeted with new products because of the cost. There is a cost-benefit ratio to the investors and the people in the drug companies that really, I think, is at risk to some extent with that. You can’t really go ahead and cut our basic science research budget and expect that we are going to have new treatments and new cures for brain disease or any other group of diseases. You really need a guarantee or an assurance that you are going to maintain your budget at an inflation-adjusted level so that you don’t have to give up research programs because you don’t have the money. RR: …Dr. Kittredge and I were very active in starting a program which we called the [American Academy of Neurology] Education and Research Foundation, very much so. Dr. Kittredge and I had the view that, as he indicated, in order to get people to want to go in to do research after a residency, they weren’t prepared. They need fellowship support. They needed research grants. To go from a residency into a research program and to write grants and become independent without any formal training was extremely difficult. I do remember in 1991, 1990, going to Jan

Stanley B. Prusiner, MD; AAN President Roger N. Rosenberg, MD, FAAN; Francis H.C. Crick, OM FRS; and William H. Oldendorf, MD, at the 1992 Annual Meeting.

Kolehmainen, who at the time was the executive director, and indicated we need to do something to develop the needs for post-residency fellowship training to get people to go into research. We talked about a development office and I really said, “No, we need to move forward with a foundation of some sort. Something independent and dynamic.” I shared my thoughts with Dr. Kittredge and with Bud Rowland, who was the president at the time. We went forward and we established the AAN Education and Research Foundation. I was delighted to be the president as it began, but Dr. Kittredge was the first chair of the foundation.

TS: More than 20 million dollars it has given away. RR: Dr. Kittredge, Dr. Rowland, and I feel pleased about that; that mission has been accomplished and wonderful people are now in academic medicine and doing science and research to help life for us all. FK: We created, I think in a sense, the seed corn for academic neurology. RR: I think so. FK: Because the interesting thing was these folks came out of their foundation fellowship and were successful at a very high level of getting an RO1 grant from NIH and that was something, at least some years ago, where 95 to 98 percent of them were in academic neurology. As a matter of fact, the chairman at Harvard, here, was one of our first fellows. RR: It’s terrific. It really—it goes on and on and on in terms of what it is—

Rosenberg and Kittredge spoke during the Hall of Presidents presentation at the 2017 Annual Meeting.

FK: It’s just the ripple effect has been phenomenal. Visit AAN.com/view/AANhistory to read the complete transcript of the interview with Rosenberg and Kittredge and learn how they were inspired to become neurologists and champions of brain research. 

FK: I was the first president. RR: First president of the foundation and he moved it forward and established it and was responsible for its success. FK: It is interesting because the conversation started during Bud Rowland’s term and Bud established a committee of the board that was the financial development committee of the board of trustees or the executive board of the Academy and Roger was on the committee and I chaired it and Steve Ringel was on the committee and we came back with two recommendations. The first was that we start a foundation, as Roger says, and the second was to go ahead and start a publishing company to take over the journal and develop other publications for the Academy that would go ahead and provide additional revenue. The foundation was started, I remember it vividly, sitting at a board meeting with Bud Rowland, who was sitting there, and Bud had an interesting comment and we were talking about money and at the time Audrey Penn was the deputy director at NINDS and was in charge of translational research. She was pushing that. But, as we said, “Well, what are we going to do with the money when we raise it?” Bud says, “I think we ought to go ahead and start clinical fellowships,” and that was the genesis of our clinical fellowship program, which is usually a two-year program after residency in a specialty or in a subject that is of interest. RR: It has been a great success. The synergism among all of us a great success. Now it is the American Brain Foundation. TS: Right. RR: It is funding millions of dollars and dozens of wonderful fellowships.

Academy Staff Celebrates Anniversary Many of the AAN’s nearly 200 employees were on hand or dialed into the Minneapolis headquarters on March 13 to celebrate the 70th anniversary of the date of the Academy’s 1948 incorporation. Staff enjoyed a presentation on AAN history incorporating archival photos and insightful quotes from past Academy leaders—and, of course, a cake! Pictured with the cake are executive staff members Chief Business Development Officer Chris Becker; Executive Director and CEO Catherine M. Rydell, CAE; Chief Communications Officer Angela Babb, CAE, APR; General Counsel Bruce Levi, JD; Deputy Executive Director Christine E. Phelps. 

Being a teaching hospital makes us stronger. Being a teaching hospital for two great medical schools makes us NewYork-Presbyterian Hosptial. What happens when two great medical schools bring their highly regarded faculties and groundbreaking research to one hospital? You get more innovation. A wider breadth of expertise. Greater diversity. And most importantly, better outcomes for patients. The physician faculties of Columbia and Weill Cornell have powered NewYork-Presbyterian to U.S. News & World Reportâ&#x20AC;&#x2122;s top ranking for New York hospitals for 17 straight years.

Learn more at nyp.org/amazingadvances

Researchers and Donors Celebrated at Foundation Fundraiser More than 350 people who are passionate about finding cures for brain disease came together last night for the American Brain Foundation’s Commitment to Cures fundraiser. The event honored award recipients and highlighted the Foundation’s important work. The annual Commitment to Cures has grown over the past two years, generating much-needed support for the American Brain Foundation’s mission to bring researchers and donors together to defeat brain disease. Join us next year in Philadelphia for what is sure to be another memorable event! 

Thursday, April 26, 2018 • AANextra

Upcoming AAN Conference Opportunities Sports Concussion Conference July 20–22, 2018

JW Marriott, Indianapolis, IN Stay up-to-date and discover the latest information on the prevention, diagnosis, and treatment—and earn up to 20 CME or CE credits—through interactive hands-on workshops, debates, and other engaging formats led by world-renowned expert faculty and keynote presenters. New this year will be joint programming with the NCAA including a Networking Reception at the NCAA Hall of Champions and talks focusing on the NCAA-DoD CARE Consortium; a Working Lunch with Experts who will address controversial issues in sports; a Year in Review featuring the latest updates in concussion research and clinical guidance; and “What Do I Do Now?” sessions where faculty will share challenging real-life cases and attendees will be invited to weigh in on best practices. Early registration ends June 14. Learn more and register at AAN. com/view/ConcussionConference.

SPORTS CONCUSSION CONFERENCE JULY 20–22, 2018 INDIANAPOLIS, IN

Fall Conference October 26–28, 2018

The Cosmopolitan of Las Vegas Quality CME, expert faculty, and the goal of improved patient care are on the docket for this always-popular conference. The Fall Conference’s all-inclusive registration rate provides maximum value, flexibility, and customization. And the popular Neurology Update and Practice Management programs allow you to tailor a personal schedule to your specific interests and needs. Watch for updated information on AAN.com.

A N INDU ST RY TH ERAPEUT I C UPDAT E FR O M GE 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

How well do you know migraine prevention? Nearly 40% of Americans who suffer from migraine could be appropriate for preventive treatment. Teva is committed to advancing the science and education of migraine. Together, we can reinvent the migraine paradigm.

Visit MoreToMigrainePrevention.com to learn more

ÂŠ2018 Teva Pharmaceuticals USA, Inc. MIG-40601 March 2018

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

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.

TWEETS OF THE DAY Dr Allison Brashear @DrABrashear

#AANAM Leadership Development Committee meets at the annual meeting. Celebrating Neurology future leaders @ cphelps_aan @AANMember @wakehealth

Bert Vargas @BertVargas

Laura Dixon, DNP @ldixon746

Advocating for our patients and for nurse practitioners in neurology. @AANMember @ TaraBillerNP #AANAM

Check out our incredible #Jeopardy set and our awesome hosts Drs #LauriceYang & #VeronicaSantini on the #HeadTalks stage @#AANAM

UMiami Neurology @UMiamiNeuro

Great Alumni Reception so happy to see so many #colleagues, past residents and fellows at @AANMember #AANAM .

Dr. Casey Farin @CaseyFarinMD

I love that @bennetomalu9168 is the big celebrity of #AANAM. There are hundreds of neurologists listening to his life story and his story of how he first described CTE.

Altaf Saadi @AltafSaadiMD

Listening to @ bennetomalu9168 at #AANAM speaking about #science not for the sake of publications & self-promotion, but for the sake of humanity. Great talk! NFL concussion & #CTE whistleblower, he is among long history of doctors & scientists who prioritize truth-telling.

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

Attend Invited Science: BRAIN Initiative at 1:00 Today Don’t miss today’s Invited Science: Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative beginning at 1:00 p.m. until 2:30 p.m. in 403A. Presented in partnership with the National Institutes of Health (NIH), the session will examine this large-scale effort aimed at revolutionizing our understanding of the human brain, which was launched by President Obama in 2013 and seeks development of the technologies and insights to facilitate preventions, treatments, and cures of brain disorders. 

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. 

COME CELEBRATE THE

1-YEAR ANNIVERSARY JOIN US AT BOOTH

1802

Today’s Boxed Lunch Menu Lunch Options Locations: South Lobby and West Hall A Choose from two convenient locations, each featuring two box lunch options. Grab your lunch and enjoy while taking in talks on the Experiential Learning Area stages near the South Lobby, or pick up your lunch and head to the Poster Discussion Sessions in West Hall A.

Option I:

HHBlackened salmon filet (GF, DF) HHWhite bean, chick peas, roasted red pepper with honey Dijon mustard vinaigrette (DF, GF, V, VG) HHChocolate brownie HHWhole fresh fruit (V, VG, DF, GF)

Option II:

HHTuscan marinated and grilled tofu (V, VG, DF, GF) HHFarro, blistered tomatoes, and roasted vegetable salad (V, VG, DF, GF) HHPeanut butter and granola cookie HHWhole fresh fruit (V, VG, DF, GF)

Friday’s Boxed Lunch Menu Lunch Options Locations: South Lobby and West Hall A Choose from two convenient locations, each featuring two box lunch options. Grab your lunch and enjoy while taking in talks on the Experiential Learning Area stages near the South Lobby, or pick up your lunch and head to the Poster Discussion Sessions in West Hall A.

Option I:

HHChicken taco salad HHBlack bean and roasted corn salsa, cilantro lime vinaigrette, queso fresco (V, GF) HHLemon bars 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 

Thursday, April 26, 2018 • AANextra

See You at Tomorrow Night’s Closing Party Happy Hour! Join your friends and colleagues this Friday from 5:30 p.m. to 7:00 p.m. in Concourse Hall of the convention center to cap off a great meeting! Enjoy drinks, games, socializing, and your favorite jazz standards performed live by NEURO JAZZ, a fivepiece ensemble led by AAN member Phillip Pearl, MD, FAAN. Each registered meeting attendee receives one free ticket to this event, and additional guest tickets are available through registration for $50. See you there! 

SEE YOU NEXT YEAR

Philadelphia, PA · May 4–10, 2019

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