2018 Annual Meeting AAN Extra — Wednesday, Apr 25 by American Academy of Neurology

THE ANNUAL MEETING NEWS DAILY

Wednesday, April 25, 2018

TRANSLATIONAL RESEARCH HIGHLIGHTED IN THIS MORNING’S PLENARY SESSION Experts will look to the future of neurology at this morning’s Frontiers in Neuroscience Plenary Session, with presentations on connectomics, BigBrain, the 3D digital atlas of the brain, as well as how the brain works while under anesthesia and understanding the circadian rhythm. Attendees can also learn about what pediatric Continued on page 13 u

More Than 550 Turned Out to Take Steps to Support Brain Research A cool, foggy morning in LA greeted more than 550 Annual Meeting attendees who turned out to move us one step closer to cures for brain disease during yesterday morning’s 5k Run/1k Walk in Griffith Park.

The American Heart Association and American Stroke Association are partnering with the AAN to host a two-hour program in 515B from 3:30 p.m. to 5:30 p.m. today that will examine disparities in stroke care.

A good time was had by all in this familyfriendly trek for a good cause, with Continued on page 24 u

INSIDE

Disorders Is 10 Movement Focus of This Morning’s “Best of” Session Is Highlighted in 20 Sleep Today’s Invited Science Platform Session

Don’t Miss Today’s Session on Disparities in Stroke Care

Bridging Racial and Ethnic Disparities in the Management of Stroke

Invited Science 29 Thursday’s Examines Latest NIH BRAIN Initiative Findings Your Way to the 31 Make Exhibit Hall Before Today’s 3:00 Closing

3:30 p.m.–3:45 p.m. State of Racial and Ethnic Disparities in Stroke Salvador Cruz-Flores, MD, FAAN 3:45 p.m.–4:00 p.m. What More Can be Done to Address Racial and Ethnic Disparities in Stroke? Faculty 4:00 p.m.–4:15 p.m. Avenues to Engage in Stroke Disparities Research Faculty

Continued on page 21 u

In Multiple Sclerosis, when it comes to Brain Preservation

Grey Matters, Too JOIN US AT

Booth 932

Wednesday, April 25 Cover Translational Research Highlighted in 4 5 5 5 7

14 Recollections of Past AAN Presidents

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

This Morning’s Plenary Session

20 Sleep Is Highlighted in Today’s

More Than 550 Turned Out to Take Steps to Support Brain Research

22 Check out New ePoster Areas at

Don’t Miss Today’s Session on Disparities in Stroke Care

29 Thursday’s Invited Science Examines

Tonight’s Commitment to Cures Poised to Raise Critical Support for Research

American Academy of Neurology 201 Chicago Avenue Minneapolis, MN 55415 USA

30 Improve Your Patients’ Experience

Celebrate the End of a Great Meeting at Friday’s Closing Party Happy Hour

31 Make Your Way to the Exhibit Hall

Phone: (800) 879-1960 (Toll Free) or (612) 928-6100 (International) Fax: (612) 454-2744 Email: memberservices@aan.com Website: AAN.com

Today’s ‘What Do I Do Now?’ Sessions Offer Unique Opportunities to Compare Your Approach to Others

34 Quotable Quotes

Rare Books Draw Eager Eyes Today’s Experiential Learning Area Highlights

10 Movement Disorders Is Focus of This

Invited Science Platform Session Poster Sessions

Latest NIH BRAIN Initiative Findings with Interactive Electronic Exam Room Posters Before Today’s 3:00 Closing

36 Real World Job Search: A 12-Month Timeline to Stay on Track

39 Tweets of the Day 39 Today’s Boxed Lunch Menu

Morning’s “Best of” Session

Contact Information:

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.

Wednesday’s AAN Section Meetings 8:15 a.m.–9:15 a.m. Neural Repair & Rehabilitation Section LACC Petree Hall C

3:30 p.m.–4:30 p.m. Behavioral Neurology Section LACC Petree Hall D

Neuroendocrinology Section LACC Petree Hall D

Neuro-infectious Disease Section LACC Petree Hall C

12:00 p.m.–1:00 p.m. Endovascular & Interventional Neurology Section | LACC Petree Hall C

5:30 p.m.–6:30 p.m. Child Neurology Section LACC Petree Hall D

Neurohealth and Integrative Neurology Section | LACC Petree Hall D

7:00 p.m.–8:00 p.m. Neuro-oncology Section Meeting LACC Petree Hall C 

1:30 p.m.–2:30 p.m. Stroke & Vascular Neurology Section LACC Petree Hall C

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.

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.

Tonight’s Commitment to Cures Poised to Raise Critical Support for Research LIMITED Tickets Still Available! The American Brain Foundation’s popular annual Commitment to Cures fundraiser is poised to highlight the work of the American Brain Foundation. The event begins at 6:00 p.m. tonight at the JW Marriott Los Angeles. Comedian Michael Pritchard will serve as the program emcee, entertaining attendees with his unique comedic style while underscoring the importance of finding cures and treatments for brain disease. He will help recognize 2018 Public Leadership in Neurology Award recipient Temple Grandin, PhD, who will appear via video. Grandin is a professor of animal science at Colorado State University, consultant to the livestock industry on animal behavior, and well-known autism spokesperson. DeMaurice Smith, executive director of the NFL Players’ Association, will receive the 2018 Commitment to Cures Award, and acoustic guitarist, singer, composer, and American Brain Foundation Honorary Board Member Billy McLaughlin will provide a memorable live performance. McLaughlin was diagnosed with focal dystonia in 2001, but his passion and drive sent him on an unlikely journey of teaching himself to play in what has now become his own signature left-handed style. Tickets are still available for $125. Stop by the Foundation booth in the West Lobby of the Los Angeles Convention Center to get yours! 

Grandin

McLaughlin

Pritchard

Smith

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Wednesday, April 25, 2018 • AANextra

Celebrate the End of a Great Meeting at Friday’s Closing Party Happy Hour All Annual Meeting attendees are invited to join 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 at a special happy hour. Enjoy drinks, games, socializing, and a toe-tapping live performance of your favorite jazz standards by NEURO JAZZ, a five-piece ensemble led by AAN member Phillip Pearl, MD, FAAN.

Rare Books Draw Eager Eyes Members of the AAN History Section enjoyed a Monday tour of rare books in the collection of the Louise M. Darling Biomedical Library at the University of California-Los Angeles. This is the second annual excursion to a local repository of exceptional tomes related to neurology, which began at last year’s Annual Meeting in Boston. 

Each registered meeting attendee receives one free ticket to this event, and additional guest tickets are available through registration for $50. 

Today’s ‘What Do I Do Now?’ Sessions Offer Unique Opportunities to Compare Your Approach to Others Don’t miss today’s interactive and engaging new “What Do I Do Now?” sessions. Faculty will share a challenging real-life case before asking audience members, “What do I do now?” Attendees will be given the opportunity to weigh in on what they would do in a similar scenario before the panel explains how they actually handled the situation. 7:00 a.m.–9:00 a.m. 408A C137 What Do I Do Now? Emergency and Inpatient Management of Migraine and Other Headache Disorders

3:30 p.m.–5:30 p.m. 403B C164 What Do I Do Now? Neurologic Consultations in Cancer Patients II 

1:00 p.m.–3:00 p.m. 403B C149 What Do I Do Now? Neurologic Consultations in Cancer Patients I

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TODAY’S EXPERIENTIAL LEARNING AREA HIGHLIGHTS HeadTalks Neuro-Jeopardy: Telencephalon Twisters 12:00 p.m.–1:00 p.m. Looking to take a break from the scientific programs? Want to show what you know? Test your neurologic fortitude against top neurologists or simply sit back and watch the action as Laurice T. Yang, MD, MHA, and Veronica E. Santini, MD, host this exciting game show-style event. The Neurology of Voodoo 4:15 p.m.–5:00 p.m. Join Ann H. Tilton, MD, FAAN, as she looks through the lens of voodoo to gain increased awareness of nontraditional cultural rituals in our own medical practices. The underlying principles of illness, pain, possession, and death in voodoo raise our understanding and increase the mystery of our own perceptions of what constitutes western medicine. Neurology, Illustrated: The Neurology of Art 5:15 p.m.–6:15 p.m. From its initial conception as a way to brighten a neurology waiting room, "Neurology, Illustrated" became a journey to describe neurology by examples in art, and to understand art by its neurologic influence. It is now an installed art exhibit that spans millennia and is meant to educate and please patients, families, medical students, nurses, doctors, administrators, and anyone else who wanders through the department of neurology at Tufts Medical Center in Boston. David Thaler, MD, PhD, will explain the journey using examples from the exhibit that connect an Egyptian stele with FDR, Charcot with melting Antarctic ice, and Wilde’s incision with homophobia.

A panel of renowned women shared their leadership journeys and discussed their career challenges and successes at the Women in Neurology presentation on the HeadTalks stage.

AAN President Elect James C. Stevens, MD, FAAN, provided valuable insight from his 30 years as a clinical private practicing neurologist on the important considerations when choosing a career opportunity in clinical practice during his Navigating Your Career Experiential Learning Area talk.

Live Well: Taking Care of Your Patients Starts with Taking Care of You Acupuncture Demonstration: Auriculotherapy 8:00 a.m.–8:45 a.m. Certified acupuncturist and neurologist Jennifer Bickel, MD, FAAN, will provide an introduction to auriculotherapy. Auriculotherapy is a form of acupuncture focused on the external ear that is widely used throughout the US military and VA systems. Treatments are tailored for general pain relief and relaxation. Waiver required. Introduction to Acupuncture II: Evidence-based Applications for Acupuncture in the Treatment of Neurologic Conditions 3:00 p.m. to 3:45 p.m. Attendees of the Research Corner talk with Deborah A growing body of Hall, MD, PhD, FAAN, discovered tips on how to choose acupuncture research the right mentor, or mentor team, and how to get the over the last two decades most out of the mentor-mentee relationship. has yielded new evidence in the treatment of various neurologic conditions including migraine, tension headache, cervical and lumbar radiculopathy, peripheral neuropathy, fibromyalgia, spasticity, and stroke rehabilitation. Acupuncture research and practice present unique challenges including proper blinding, standardized regimens, and dosing. Alexandra Dimitrova, MD, will present a critical overview of the evidence that will address indications for acupuncture referral and the role of acupuncture as an adjunct therapy in various Continued on page 8 u neurologic conditions.

TODAY’S EXPERIENTIAL LEARNING AREA HIGHLIGHTS Continued from page 7

During “Is There a Neurologist on This Flight?” at the HeadTalks stage, Joseph I. Sirven, MD, FAAN, reenacted scenarios aboard an airplane to demonstrate how to approach different medical conditions during a flight and what resources are available to help.

Maximize Your Value and Advocacy to Action Ask Anything about Telemedicine 12:00 p.m.-12:30 p.m. What do you want to know about teleneurology? Do you want to know how to incorporate it into your practice? Come ask Eric R. Anderson, MD, PhD, anything you’ve wanted to know about telemedicine.

Research Corner: Moving Neurology Forward Diversity in Science Day 8:00 a.m.–5:30 p.m. Look for programming throughout the day that focuses on underrepresented female and minority populations: 12:00 p.m.–12:30 p.m.: Office Hours: Recruiting Difficult and Underrepresented Populations in Research 12:40 p.m.–1:10 p.m.: Neuroscience of Bias 1:00 p.m.–1:50 p.m.: Community Education in Minority Populations 2:00 p.m.–2:30 p.m.: Women in Neuroscience

Attendees got a preview of NIH funding and NINDS opportunities by NINDS Director Walter J. Koroshetz, MD, FAAN, and Deputy Director Nina F. Schor, MD, PhD, FAAN, during NINDS Day at the Research Corner Experiential Learning Area.

Wednesday, April 25, 2018 • AANextra

Charles C. Flippen II, MD, FAAN, along with Jeffrey C. McClean, MD, FAAN; and Laraine Kaminsky; led a highly interactive presentation about the impact of conscious and unconscious bias, and made some recommendations on mitigation during a HeadTalks presentation.

Navigating Your Career How to Give Effective Feedback 8:15 a.m.–9:00 a.m. Never underestimate the importance of giving effective feedback. Laurice T. Yang, MD, MHA, and Veronica E. Santini, MD, will review the techniques to incorporate effective feedback into your daily interactions, and a smallgroup activity will allow you to apply learned concepts. Jennifer Bickel, MD, FAAN, along with Bert B. Vargas, MD, FAAN; Joseph I. Sirven, MD, FAAN; and Constantine Moschonas, MD, FAAN, performed “live examinations” of “zombie patients” to demonstrate the various manifestations of the gravely serious epidemic of neurologist safety and quality of life during the Zombie Apocalypse HeadTalks presentation. US Representative Judy Chu (D-CA) provided a update and Q&A on the status of various pieces of health care legislation under consideration by Congress, including leading AAN advocacy issues.

The Member Experience: Personalize Your Journey Synapse Demonstrations Synapse™ Online Communities is the official, free online communication platform for AAN members, sections, and consortia, offering endless opportunities to engage with others in your area of interest. Stop by to see how it works and if you’re not already a Synapse member—there’s no better chance to join! 

Wednesday, April 25, 2018 • AANextra

Movement Disorders Is Focus of This Morning’s “Best of” Session The four top-rated abstracts in movement disorders will be the focus of this morning’s “Best of” Scientific Platform Session, which will be immediately followed by the Frontiers in Neuroscience Plenary Session.

“Best of” Session: Movement Disorders 8:00 a.m.–9:00 a.m. 408B 8:00 a.m.—Unified Staging System for Lewy Body Disorders: Clinicopathologic Correlations Charles Adler, Thomas Beach, Nan Zhang, Holly Shill, Erika Driver-Dunckley, John Caviness, Shyamal Mehta, Marwan Sabbagh, Geidy Serrano, Lucia Sue, Christine Belden, Jessica Powell, Sandra Jacobson, Edward Zamrini, David Shprecher, Kathryn Davis, Brittany Dugger, Joseph Hentz 8:08 a.m.—Exenatide Modulates Neuronal Insulin Signaling in Parkinson’s Disease Dilan Athauda, Seema Gulyani, Hanuma Karnati, Yazhou Li, David Tweedie, Simon Skene, Kashfia Chowdhury, Nigel Greig, Dimitrios Kapogiannis, Thomas Foltynie 8:16 a.m.—Sensitivity and Specificity of Clinical Criteria for 4-Repeat Tauopathies in Autopsy-confirmed Cases Jessica Weinstein, David Irwin, John Trojanowski, Pouya Khankhanian, Murray Grossman, Corey McMillan

Wednesday, April 25, 2018 • AANextra

8:24 a.m.—Multiple Ascending Dose Study of the Taudirected Monoclonal Antibody BIIB092 in Patients with Progressive Supranuclear Palsy Adam Boxer, Irfan Qureshi, Michael Grundman, Giridhar S. Tirucherai, Clifford Bechtold, Michael Ahlijanian, Gerry Kolaitis, Lawrence Golbe, Lawrence Honig, Stuart Isaacson, Murray Grossman, Nikolaus McFarland, Irene Litvan, David Geldmacher, Tao Xie, Yvette Bordelon, Paul Tuite, Padraig O’Suilleabhain, Theresa Zesiewicz 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

Translational Research Highlighted in This Morning’s Plenary Session Continued from cover

MS can tell us about the environmental and genetic risk factors for MS in general and how patient-derived cell and animal models can help us understand mechanisms in epilepsy and develop precision therapies. The session runs from 9:15 a.m. to 11:30 a.m. in South Exhibit Hall K. Moderator: Paul M. George, MD, PhD, MSE, Member, Science Committee

Topics and speakers: The Dynamics of the Unconscious Brain Under General Anesthesia Emery N. Brown, MD, PhD Massachusetts Institute of Technology, Cambridge, MA

BigBrain: A High-resolution 3D Digital Human Brain Atlas Alan Evans, PhD McGill University, Montreal, Quebec, Canada

Does Connectomics Make Sense? Jeff Lichtman, MD, PhD Harvard University, Boston, MA

Pediatric MS: A Unique Window into Environmental and Genetic Risk Factors for MS Emmanuelle Waubant, MD, FAAN University of California San Francisco, San Francisco, CA 

Biology of Bedtime: Understanding Circadian Rhythms and Sleep Amita Sehgal, PhD University of Pennsylvania, Philadelphia, PA

Combining Patient-derived Cell and Animal Models to Uncover Epilepsy Mechanisms and Precision Therapies Jack M. Parent, MD University of Michigan, Ann Arbor, MI

Wednesday, April 25, 2018 • AANextra

Recollections of Past AAN Presidents 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 2012 Oral History Project interview between Lewis P. (Bud) Rowland, MD, FAAN, and Steven Frucht, MD. Rowland served the AAN in numerous capacities, including AAN president (1989–1991), president of the AAN Education and Research Foundation (now American Brain Foundation; 1995–1997), and as editor-in-chief of the flagship journal Neurology ® (1977–1986) and Neurology Today ® (2001–2009). He passed away in March 2017. presentations. LR: And the courses. Don’t forget the courses. I’ve been involved in the courses from way back. I developed a course called “The Scientific Basis of Neurology.” I really relished doing it because it was just fun and it was effective as determined by questionnaires and by requests to do it again for another year. I’ve forgotten how many years I did it—at least 10. That kind of thing still goes on. The courses are the main attraction of the Annual Meeting. And Continuum. I didn’t have much to do with that but that’s another important contribution to lifelong education. LR: I’ll tell you how the training grants started. It affected me and Fishman [Robert A. Fishman, AAN president 1975–1977]. The director of NINDB was Pearce Bailey [AAN president 1951–1953]. He was a friend of Merritt’s [Merritt Houston]. The story went something like this—this is an approximation of what happened 60 years ago. Houston and Pearce Bailey, they knew each other from being on committees together. Merritt probably had something to do with Bailey being picked as the director. Merritt was on the NINDB or DS council three times, the only one in history who was appointed three times. Bailey said to him, “Houston, we’re trying to set up some training programs to train clinical investigators. We think you ought to have one. Don’t you think so?” Houston said, “Of course I ought to have one. We ought to have one.” Then he said, “Do you have any SF: Maybe I can ask you about your activities with the Academy—with the journal and with the institution. LR: I was at one time president of the Academy. I was president of the foundation—the Academy foundation. I was made the president of the Academy by Steve [Steven P.] Ringel, who was a kingmaker. It was his idea. I enjoyed that and I thought it was important. Some people don’t like that kind of bureaucratic assignment but I relished it. The people who get into that are such, themselves, remarkable people. A guy like Fran [Francis I.] Kittredge—a big wheel in the organization. He had a private practice in Portland, Maine; we ended up having a pattern of having a clinician for one term [as AAN president] and then an academic for another term. I thought it worked great. We all learned a different field and I don’t think there was ever any friction between the two that “you’re taking my territory” or something like that. I just admired the whole bunch of them. SF: The Academy is certainly—it went through an explosive period of growth in the ’70s and in the ’80s in terms of the meeting and the size of the meeting, the

Wednesday, April 25, 2018 • AANextra

Rowland with past editors-in-chief of Neurology John H. Noseworthy, MD, FAAN; Robert C. “Berch” Griggs, MD, FAAN; and Robert B. Daroff, MD, FAAN.

candidates for it?” He said, “Well, I’ve got these two guys here that I call the Gold Dust Twins. Fishman and Rowland.” So, Bailey said, “Send down the information about them.” Well, he did and the next thing we knew, Houston said, “What are we going to do now that we have a clinical research grant?” Or maybe he had to put a program up that they could approve it down there. So that is how it started. Both Fishman and I got good training…. It was Darryl De Vivo. He and I were on a committee, might have been an Academy committee that was advising NIH. It was Darryl’s idea was that what we needed was a fellowship that would be sponsored by the Academy, funded half by the Academy and half by an academic center. We would call it Training in Research Clinical Investigation or Clinical. That is still going. I think at one time there were 30 of them. That was what we were asking. It still exists. It has been so successful compared to the number of outstanding people who were trained. I think it was all Darryl’s fault, not mine. He is very imaginative when it comes to organization. Former President Steven P. Ringel, MD, FAAN, (SR) spoke about Rowland’s contributions to the AAN’s publications in a 2017 interview with AAN staff writer Tim Streeter (TS). TS: You mentioned Neurology Today. You and Dr. Rowland worked to launch that. SR: Yes. When I was chairing AAN Enterprises, or involved in AAN Enterprises, I really felt that the newspapers which were gaining prominence in the neurology newspapers weren’t doing a great job in the sense that they would have a reporter go out and report something, but they

weren’t interviewing people to say, “Is this good stuff or not good stuff?” I felt we could really do a better job. Bud Rowland was a star. He was admired by everyone. He had been editor of Neurology, had been president of the American Academy of Neurology, had been president of the American Neurological Association, and on and on and on. Twenty-five years as chair at Columbia. He trained most of the many, many famous academic neurologists, so it was an easy choice picking him to edit this. I was his associate editor. The happy triad with Fay Ellis, who as it turned out was a wonderful journalist who came at that time from I think it was Lippincott before it was Wolters Kluwer. It turned out to be a very happy marriage for the three of us and the newspaper has just grown over the years. Really, Bud brought it credibility. He was a tireless editor. He loved making sure that things were accurate. He really made sure the quality was outstanding. TS: He had a red pen, didn’t he? SR: Yeah, he had a big red pen. That was what he was known for. When I started, my first paper submitted to Neurology, I got it back from Bud. We didn’t have track changes and computers, and Bud had redlined everything, but that was because he really was a journalist and understood, say it clearly, don’t use all these words, get rid of all this excess language. He was wonderful. Visit AAN.com/view/AANhistory to read the complete transcript of Rowland’s interview and learn about his pioneering work in movement disorders and run-in with 1950s McCarthyism. Ringel’s interview will be posted later this summer. 

Wednesday, April 25, 2018 • AANextra

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.

Sleep Is Highlighted in Today’s Invited Science Platform Session Authors of “best of” abstracts previously presented at the Sleep Medicine/Sleep Research Society Annual Meeting will take to the stage beginning at 1:00 p.m. today in 402AB for encore presentations of their work. Presenters will emphasize basic, clinical, and translational science as they evolve toward a more complete understanding of sleep with the overall goal of developing more effective prevention and treatment. Abstracts and authors include: 3:30 p.m.–3:50 p.m. Recurrent Circuitry for Balancing Sleep Need Jeffrey Donlea, PhD, UCLA, David Geffen School of Medicine, Los Angeles, CA 3:50 p.m.–4:10 p.m. A Circuit for the Circadian Control of Aggression William D. Todd, PhD, Beth Israel Deaconess Medical Center, Boston, MA 4:10 p.m.–4:30 p.m. Direct Electrical Stimulation to the Human Amygdala Enhances Recognition Memory Following Sleep Jon T. Willie, MD, PhD, Emory University, Atlanta, GA 4:30 p.m.–4:50 p.m. Sleep Loading Improves Visual Search Response Time and Reduces Fatigue in Professional Baseball Players Cheri D. Mah, MS, University of California San Francisco Human Performance Center, San Francisco, CA

Wednesday, April 25, 2018 • AANextra

4:50 p.m.–5:10 p.m. Sleep While On-Call Overnight Does Not Restore Performance Among First-Year Resident Physicians Melissa A. St. Hilaire, PhD, Brigham and Women’s Hospital, Boston, MA 5:10 p.m.–5:30 p.m. The Role of Nightly Zopiclone on Obstructive Sleep Apnea Severity and Symptoms in People with Low to Moderate Respiratory Arousal Thresholds: A Randomized, DoubleBlind, Placebo-Controlled Trial Sophie Carter, NeuRA, Randwick, Australia 

Don’t Miss Today’s Session on Disparities in Stroke Care Continued from cover

4:15 p.m.–4:30 p.m. Obstacles and Opportunities in Stroke Care Access Among Racial and Ethnic Minorities Enrique C. Leira, MD, MS, FAAN

Breakthroughs in Engaging Minority and Rural Communities in Stroke Studies 4:30 p.m.–4:45 p.m. Learning About Your Community (and Establishing a Community Advisory Board) Faculty 4:45 p.m.–5:00 p.m. Captivating the Community and Sustaining Ties Bernadette Boden-Albala, MPH 5:00 p.m.–5:15 p.m. Building Trust with Your Community Through Communication Brett M. Kissela, MD, FAAN, MS 5:15 p.m.–5:30 p.m. Dissemination of Results and Presenting Information Faculty 

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 IV 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.

Remaining Poster Session Schedule Poster Session IV

Wednesday: 11:30 a.m.–7:00 p.m. author standby from 5:30 p.m.–7:00 p.m.

Poster Session V

Thursday: 11:30 a.m.–7:00 p.m. author standby from 5:30 p.m.–7:00 p.m.

Poster Session VI

Friday: 11:30 a.m.–5:30 p.m. author standby from 4:00 p.m.–5:30 p.m.

Cerebrovascular disease and interventional neurology is the focus of the poster discussion session as well as both ePoster sessions today, covering topics ranging from safety outcomes and seizures in acute stroke patients to care of stroke patients with language barriers.

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

Today’s ePoster Sessions: Cerebrovascular Disease and Interventional Neurology Be sure and check out the center of the poster hall for today’s interactive, touchscreen ePosters. 

091–172

173–200

ePosters

085–090

037–084

259–294

201–258

b1 g1 339–344 a1 ePosters

Poster Discussion

027–036

001–026

295–338

345–428

429–480

Poster Session IV A. General Neurology: 001 – 026

a1. Cerebrovascular Disease and Interventional Neurology Poster Discussion Session: 027 – 036 B. Movement Disorders: 037 – 084

b1. Cerebrovascular Disease and Interventional Neurology I ePoster Session: 085 – 090 C. Headache; Neuro-oncology; Practice, Policy, and Ethics: 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. Cerebrovascular Disease and Interventional Neurology II ePoster Session: 339 – 344 H. MS and CNS Inflammatory Disease: 345 – 428 I. Neuromuscular/Clinical Neurophysiology (EMG): 429 – 480

Wednesday, April 25, 2018 • AANextra

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

More Than 550 Turned Out to Take Steps to Support Brain Research Continued from cover

Collin Anderson, PhD, of Salt Lake City, UT, taking home the trophy in the men’s division with a time of 16:25. Topping the women’s division with a winning time 19:46 was Lisa Thomas, of Alexandria, VA.

Wednesday, April 25, 2018 • AANextra

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

Thursday’s Invited Science Examines Latest NIH BRAIN Initiative Findings Stop by 403A from 1:00 p.m. to 2:30 p.m. tomorrow to hear about the latest findings from the NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, a large-scale effort aimed at revolutionizing our understanding of the human brain. Launched in 2013 by President Obama as a “moonshot to explore the frontiers of the mind,” the BRAIN Initiative seeks development of the technologies and insights to facilitate preventions, treatments, and cures of brain disorders. This session will be presented in partnership with the National Institutes of Health. Topics and presenters include: Full-scale Neuronal Network Modeling of Spatial Learning and Memory in Hippocampus Ivan Soltesz, PhD, Stanford University School of Medicine, Stanford, CA

Non-degenerate Multiphoton Microscopy for Deep Brain Imaging Anna Devor, PhD, University of California, San Diego, San Diego, CA Defining Cell Types, Lineage, and Connectivity in Developing Human Cortex Faculty Using Tissue Clearing and Optogenetics to Dissect the Circuitry Underlying Neurological Disorders Viviana Gradinaru, PhD, California Institute of Technology, Pasadena, CA 

Improve Your Patients’ Experience with Interactive Electronic Exam Room Posters The AAN has partnered with Health Monitor Network, a patient education company, to offer free electronic touchscreen posters for US members’ exam rooms. The AAN will review content for the digital posters for medical accuracy. “The feedback from physicians who have the digital posters in their exam rooms has been very positive,” said Bert B. Vargas, MD, FAAN, chair of the Digital Strategy Subcommittee. “They especially like the graphics and high-yield informational content which can be used for patient education. Vargas

Wednesday, April 25, 2018 • AANextra

These posters may also be an effective way to increase patient satisfaction and decrease their perceived wait time.” Each digital poster features educational charts, diagrams, and tips on managing neurologic conditions. They remain free to all members as they are industry advertiser supported. The 21.5” screen silently rotates panels every 25 seconds, with no interaction needed from health care professionals, office staff, or patients. Clear, engaging videos play only when activated, with a suite of controls, including an easy-to-find pause button. Installation of the posters is free, and they do not require WiFi. They plug into the wall, and any maintenance is conducted by Health Monitor Network. Content is updated quarterly. The posters are available for all member practices in the US, excluding Alaska,

Hawaii, and Puerto Rico. Health Monitor Network has partnerships with other medical organizations, such as the American Gastroenterological Association, as well as patient advocacy groups. To learn more about the electronic posters, visit Health Monitor Network in the Exhibit Hall at booth #2129, or visit Healthmonitor.com/products/aan-dep to sign up to receive your free electronic poster(s). 

Make Your Way to the Exhibit Hall Before Today’s 3:00 Closing Be sure to stop by the Exhibit Hall before it closes at 3:00 this afternoon to join your fellow colleagues and more than 250 exhibiting organizations offering the latest products, services, and therapies in the neurology industry to help you excel in your career and provide the best possible care for your patients. Exhibitors include pharmaceutical companies, medical device vendors, equipment, and technology companies; and scores of voluntary health associations dedicated to helping people live with neurologic disease. While there, don’t forget to visit these exciting areas: AAN’s Innovation Hub Stretch your brain in new directions at this creative and interactive area featuring unique physicianlead presentations, teleneurology demonstrations, daily paint and wine sessions, and more!

Technology Pavilion Experience cutting-edge technology that can change the way you care for patients.

Career Fair Neighborhood Learn about career opportunities available nationwide.

Association Neighborhood Visit with our association partners who are fighting to further disease awareness and help raise funds to find cures.

Buzz Café This new area is a great spot to reconnect with colleagues while enjoying a complimentary caffeinated beverage.

Charging Hubs Charge your devices while you check in with your office, catch up on emails, or just relax in these comfortable areas.

Visit AAN.com/conferences-community/ annual-meeting/exhibits-advertisingindustry for today’s schedule of events. 

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

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

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

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

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.

QUOTABLE QUOTES Diana M. Cejas, MD Carrboro, NC What brings you to the meeting this year?

I haven't had the chance to go to the Annual Meeting before. While I was in training, I just never seemed to be able to go. So, now that I'm in my first year of a faculty position, I tried to see if I could make time and here I am! What things are you most interested attending?

I'm a child neurologist, so I definitely have more of a peds focus, but I love that I've been able to get to some of the adult lectures that have had more of an approach that goes across the lifespan, so I'm not just learning about peds issues, I’m learning about how those same issues will present in my patients when they're older. So, I’m able to give a little bit better anticipatory guidance for some of these things. What advice would you have to people who were going to be attending for their first year?

Just come early, stay late. It's been great. I've been trying to show up at 7:00 every day. I learn something new—even though I'm exhausted!

Mary Genevieve, MD San Luis Obispo, CA Are you finding information that you'll be able to put to use in your practice?

This year I’ve changed my approach a little bit because my needs have changed. I'm transitioning my solo practice, so I’m looking at more practice needs as opposed to being in more classes like I had been in the past. That's been a helpful resource to have. I’ve attended some advocacy activities and I participated in the talk yesterday with the California Neurology Society. And I’m a supporter of BrainPAC. Is there any advice that you would give to practicing neurologists who are attending the meeting?

I'm 58 years old and last year in Boston I attended the new wellness sessions they had, like taking care of yourself, being well-balanced, and those programs changed my life. Changed my life! I'm not kidding. I went back and cut down the number of hours I was working. I live in San Luis Obispo and I have ocean access and yet I've been too busy over the last 20 years to be in the ocean. So, I went home and I took scuba diving lessons—I'm now a scuba diver! I go to yoga three to five times a week now, and ride my bike to work twice a week. Because when I was in those Annual Meeting sessions, I asked ‘What am I happiest doing?’ I'm happiest on my bike and in the water. I love being in the office, too. I love neurology but I didn't have a balance. And that really changed my life.

Wednesday, April 25, 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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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.

Real World Job Search: A 12-Month Timeline to Stay on Track As their training winds down, neurology residents and fellows begin one more process in the midst of further sharpening their practice skills: the real world job search. Some residents and fellows already have job offers—or contracts signed—soon after their training begins, or even before. For those in search phase, some good news: the job search can be relatively straightforward. And adhering to a process can help to ensure that you land the coveted position for which you’ve spent years preparing. Below is a simple timeline to help you structure a job search that runs its course during the 12 months of your fellowship. If you have special circumstances—for instance, if you need a J-1 Visa—start your search process earlier and adjust accordingly.

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

12 to 9 Months Out July, August, September): Pinpoint the kind of work you want. “The first thing you have to do is figure out what kind of job you want: A traditional academic research position? A primarily clinical position, seeing patients in a university or hospital? A group practice position?” says Ralph Józefowicz, MD, FAAN. He is professor of neurology and medicine and associate chair for education at the department of neurology at the University of Rochester School of Medicine and Dentistry. His advice to residents and fellows includes deciding what geographic area they want to live in, a decision which might depend on family or personal circumstances. For those who plan to live in popular areas, such as San Francisco or Boston, the earlier the search process begins, the better. Perfect your CV and LinkedIn profile. Recruiters will be in touch, so now’s the time to update and complete your “marketing materials.”

9 to 6 Months Out (October, November, December): Identify specific organizations where you want to work. Resist the urge to limit too narrowly, as you may not have any basis of comparison. You may, for instance, be drawn to a particular facility due to its salary, but another employer could offer you perks like more flexibility or less call, which you may not take into account if you are too closely focused. Aim for a list of perhaps 20 to 25 organizations; then hone it down by researching and talking to people. For the top 5 or 10, do a deeper dive: If you’re looking at hospitals, for example, discover who would hire you, and who would be your department chief. If you’re investigating private practice, learn about the partners, the patient numbers, the conditions the practice treats, etc. At this stage, many residents and fellows may already be interviewing, considering offers, or signing contracts, which can be an advantage. “As they go into the new year, residents and fellows can concentrate, and not fly around the country doing interviews,” says Beth Brackenridge, FASPR, senior recruiter with Grand Rapids, Michigan-based Spectrum Health. Recruiters, too, she adds, prefer to have offers buttoned up by December or January, because of the paperwork and the credentialing process involved.

Prepare for the phone interview. “Be knowledgeable,” says Brackenridge. “Search websites. Understand employer goals or missions. Would their systems be good fits? Looking at a website and what a system has done can give you some ideas of where they’ve been, and their growth.”

Most positions involve 70-hour work weeks but offer very high salaries, he adds. While this can be a grueling start to your professional life, there are some up sides: You will hone your skills quickly while also earning enough to help pay down student debt you may have accumulated during training.

6 to 3 Months Out (January, February, March):

Throughout Your Training:

Visit potential employers, if you don’t yet have an offer. Visits, which are typically scheduled between October and March, are necessary so you can understand job elements, communicate your strengths, and negotiate well. To arrange visits to hospitals, contact hospital physician recruiters: “I’m interested. How do I arrange a visit?” For private practice and academic positions, refer to the list you’ve developed, and contact practice managers, partners, or department chairs. “There’s such a great need for neurologists in all fields; I don’t think people will be struggling to find positions,” says Józefowicz. Still, if there is a particular place you want to work, you’re going to need to strategize to lock it in. Anticipate offers and contracts. By now you may be fielding offers and peering at employment contracts. Józefowicz advises retaining an attorney to review the 2 of 2 contract, for a number of reasons. For example, while some employers offer big money, signing bonuses, or incentive plans, “They may be so unrealistic you may burn out,” Józefowicz explains. It’s wise to have an attorney ensure that if you need to, you can get out of the contract before it ends.

3 Months Out to End of Fellowship (April, May, June): Still awaiting offers? Shift action plans if necessary. Send letters directly to department chiefs or chairs, or practice managers or partners and make reference to former visits. If you’re not close to an offer by 30 days out, something needs to shift: You may need to push harder on employers who are close to extending an offer, or accept that you may not be working when your fellowship ends. In this case, consider temporary positions. Józefowicz says he routinely hears from facilities with needs for a range of locum tenens practitioners, from stroke doctors to neurologists who can take in-house calls to those who can commit to working for just one month.

Prepare for business. Heading into private practice? If you can, set aside time during your residency or fellowship to learn medicine’s business operations side. Consider taking an online class; the American Academy of Neurology has a wide range of inexpensive online practice management webinars that can help prepare you at AAN.com/view/pmw16. You also may want to sign up for relevant newsletters, or even volunteer at a nonprofit clinic to experience real-world practice conditions. Plan for academics. Is teaching one of your professional goals? Mastering the subject matter is one aspect; mastering the art of teaching is another. Can you enroll in a short course on adult learning styles, or another class to help maximize your teaching methods? You may not need these extra steps to win over a future employer, but they can increase your confidence in the classroom or lecture hall. Don’t miss conferences. Attend or present at as many meetings as you can fit into your schedule. In addition to raising your professional profile, you’ll be positioning yourself to meet potential employers and future colleagues. “It’s never too early to start looking,” states Brackenridge. For more ideas and advice on specific aspects of the job search process, visit the American Academy of Neurology’s online Neurology Career Center. The Neurology Career Center features nearly 500 open neurology positions in a variety of practice settings nationwide. Save time and stay on top of your job search by creating a Job Seeker profile and create a Job Alert to be notified only when new positions of interest have been posted.

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.

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TWEETS OF THE DAY Walter J. Koroshetz @NINDSdirector

Today is #NINDS Day at #AANAM! Come see us & learn about our #training programs, @NIH grant review process, @NINDSNews clinical trials and networks, & #pain research funding opportunities! Sessions located in the “Research Corner” in the South Hall

Today’s Boxed Lunch Menu Hot Lunch Option:

Özlem Yıldız @ozlemyildiz1881 #NeurologyHills #AANAM

Location: Exhibit Hall G Enjoy lunch while exploring the hundreds of neurology products and services throughout the Exhibit Hall. HHBurrito bowl, grilled chicken, cilantro lime rice, black beans, and corn salsa HHCesar Chavez salad HHBlondie bar HHWhole fresh fruit (V, VG, DF, GF)

Cold Lunch Options:

MaryJo VanDeHey Pugh @alamomanatee

Two new Fellows of the American Academy of Neurology #AANAM #CENC

Locations: South Lobby, West Hall A, and Exhibit Hall G Choose from three convenient locations, each featuring two box lunch options. Grab your lunch and check out the talks on the Experiential Learning Area stages near the South Lobby; pick up your lunch and head to the Poster Discussion Sessions in West Hall A; or explore the hundreds of neurology products and services throughout the Exhibit Hall. Option I: HHGlass noodle salad with chicken (DF, GF) HHNapa cabbage, wonton crisps on side, shredded carrots, glass noodles, edamame, and Asian vinaigrette (GF, DF) HHBlondie bar HHWhole fresh fruit (V, VG, DF, GF) Option II: HHGrilled vegetables and garlic hummus wrap (DF, GF, V, VG) HHThree bean and basil salad with white balsamic dressing (DF, GF, V, VG) HHVegan lemon bars HHWhole fresh fruit (V, VG, DF, GF) V = Vegetarian GF = Gluten free VG = Vegan DF =Dairy free 

VISIT US AT BOOTH #1315