2019 Annual Meeting AANextra Wednesday by American Academy of Neurology

THE ANNUAL MEETING NEWS DAILY

Wednesday, May 8, 2019

BASIC, TRANSLATIONAL RESEARCH HIGHLIGHTED IN TODAY'S PLENARY Basic and translational research related to clinical issues of importance will be highlighted when six outstanding researchers provide summaries of their late-breaking findings and describe the clinical implications of the results in this morning’s Frontiers in Neuroscience Plenary Session. Set to take place from 9:15 a.m. to 11:30 a.m. in the Terrace Ballroom, the session will be moderated by Science Committee member Paul M. George, MD, PhD, MSE, of Stanford Hospital in Stanford, CA. Continued on page 14 u

Education Program Slides and Syllabi As we continue to address the issue with availability of some education program slides and syllabi, please note that all slides and syllabi will be fully loaded by the end of the conference and will be available on AAN.com after the Annual Meeting for up to one year.

Inside

7 7

Axon Registry Simplifies Reporting Measures for MIPS Last Chance to Get to the Exhibit Hall Before 4:00 Closing

Morals Is Focus of 16 Social Today’s New Advancing Medicine Talk

Run/Walk for Research Sees Big Turnout More than 600 turned out yesterday morning to take steps—literally—to support research into cures during the annual 5k Run/Walk for Brain Research. A good time was had by all during the family-friendly trek for a good cause with

Lukas Sveikata, MD taking home the trophy in the men’s division with a time of 18:39 and Lisa Thomas topping the women’s division with a time of 19:53. Continued on page 29 u

In Multiple

Sclerosis—

GREY MATTERS, TOO

FIND OUT WHY

Booth 2300

Wednesday, May 8 Cover Basic, Translational Research

16 Social Morals Is Focus of Today’s

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

Run/Walk for Research Sees Big Turnout

18 Improving Work-life Balance Helps

3 4

Daily Reminder

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

22 The Job Interview: Top Mistakes and

Contact Information:

Axon Registry Simplifies Reporting Measures for MIPS

27 Lots of Information and Fun Planned for Tomorrow’s Free Brain Health Fair for the Philly Community

Last Chance to Get to the Exhibit Hall Before 4:00 Closing

29 Run/Walk for Research Sees Big

We’ve Got Your Back: Regulatory Advocacy, Payer Relations, and the AAN

31 The Best of Philly from Those Who

Highlighted in Today's Plenary

Today’s Experiential Learning Area Highlights

10 What Are Your Colleagues Saying? 14 Six Distinguished Scientists Highlight Basic, Translational Research in Today's Plenary

16 Practice Leadership Program

New Advancing Medicine Talk

Diversity Leadership Program Participant Achieve Key Goal How to Avoid Them

Turnout

Know It Best

33 Bedlack Named Winner

of Brainstorm Competition

34 What Excited You Today at #AANAM? 34 Find the Latest Research at Today’s Poster Session

Graduates Develop New Practice Support Network

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

201 Chicago Avenue Minneapolis, MN 55415 USA Phone: (800) 879-1960 (Toll Free) or (612) 928-6100 (International) Fax: (612) 454-2744 Email: memberservices@aan.com Website: AAN.com AAN Chief Executive Officer: Catherine M. Rydell, CAE Managing Editor: Angela M. Babb, CAE, APR Editor: Tim Streeter Writers: Ryan Knoke, Sarah Parsons Designers: Siu Lee, Andrew Imholte Photography: Will Evans Printing: Phoenix Lithographing Corporation Email: aannews@aan.com AANextra is published by the American Academy of Neurology. The American Academy of Neurology’s registered trademarks and service marks are registered in the United States and various other countries around the world. “American Brain Foundation” is a registered service mark of the American Brain Foundation and is registered in the United States.

Complete your evaluations to get your CME hours by using the AAN Conferences Mobile App at AAN.com/view/MobileApp or by visiting AAN.com/view/CME. CME requests may be made until Monday, May 20, 2019. Transcripts will be emailed approximately six weeks after the meeting. AAN members can also access their transcript via NeuroTracker™ at AAN.com/view/NeuroTracker. 

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

Today’s Experiential Learning Area Highlights HeadTalks

Maximize Your Value and Advocacy to Action

The Zoo Called—You Have a Consult � 1:30 p.m.–2:30 p.m.

Succeeding in Small and Solo Practice 5:00 p.m.–5:45 p.m.

AAN Vice President Ann H. Tilton, MD, FAAN, will take a look at a side of medical care we often do not encounter. As “human” doctors we care for Tilton only one species. What a shame…after all, there is a world around us of other fascinating creatures. Each of these creatures can offer additional understanding into our approach to care and more profound insights into issues we have in common. Hear stories of zoo experiences and lessons learned—with some actual (nonhuman) animals joining in to add to the fun!

A panel of neurologists who work in small and solo practice will discuss how they've learned from their setbacks and career wins and how to develop your own strategies for success.

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

José H. Posas, MD, will identify the existence of unconscious/implicit bias and its impact on health care delivery, highlight the neuroscience/ Posas neuroanatomical correlates of implicit bias, and stress the importance of identification and correction of implicit bias to ameliorate its negative effects on health care delivery.

Eating Your Way to Fewer Migraines 11:45 a.m.–12:30 p.m. There is growing evidence to suggest that dietary interventions may offer a promising approach in the treatment of migraines. Belinda A. Savage-Edwards, MD, FAAN, will present the benefits of a primarily plant-based diet in the reduction of migraine pain, with chef Tess Connors demonstrating three recipes aligned with the “migraine diet.”

Daily meditation induces neuroplastic changes detectable on fMRI and alters immune and epigenetic response. Sarah Mulukutla, MD, MPH, explored the innate connection between meditation and the human nervous system, and how this knowledge and practice can help neurologists in this Live Well session.

Wednesday, May 8, 2019 • AANextra

Research Corner Be sure to attend tomorrow’s session:

Neuroscience of Bias Thursday, 8:00 a.m.–8:30 a.m.

Navigating Your Career

Experience the AAN

How to Successfully Incorporate APPs into Your Practice 3:00 p.m.–3:45 p.m.

11:30 a.m.–3:30 p.m.

AAN President Elect James C. Stevens, MD, FAAN, will cover how to successfully train, Stevens supervise, improve patient access, and have a profitable economic model by incorporation of advanced practice providers (APPs) into your neurology practice.

A.B. Baker Award for Lifetime Achievement in Neurologic Education 1:00 p.m.–1:45 p.m. Come listen to Steven L. Lewis, MD, FAAN, the 2019 A.B. Baker Award for Lifetime Achievement Lewis in Neurologic Education Award recipient, as he presents the keynote lecture “Teaching Neurologic Competency Competently Despite the Competencies.” Also featured will be the presentation of the 2019 Frank A. Rubino Award for Excellence in Clinical Neurology Teaching to Allen J. Aksamit, Jr., MD, FAAN.

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

Innovation Hub The Why and How of Getting a Billion Dollar EHR to Make Its System Work Better for Neurologists 12:30 p.m.–1:00 p.m. Learn from Allison L. Weathers, MD, FAAN, Weathers how the AAN helped advocate for improved EHR functionality for neurologists with a major vendor, resulting in formation of a neuroscience physician advisory group, effecting change in the EHR.

Improving Operational Efficiencies Through Clinically Driven KPIs 2:00 p.m.–2:30 p.m. Learn from Emily Swierski about emerging advancements in data analytics and the Swierski opportunity to track operational metrics in real time to enhance the patient experience. This discussion will involve a case study in the process of identifying meaningful operational KPIs, and the development of analytical tools needed to track these quality measures. These cross-cutting KPIs can identify or predict issues involving the patient experience, employee engagement, and workflow inefficiencies before they negatively impact your business. 

Jennifer Bickel, MD, FAAN, reviewed system-level strategies to reduce burnout as well as how attendees, regardless of their role, can influence change in this Navigating Your Career Experiential Learning Area session.

Wednesday, May 8, 2019 • AANextra

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

Visit booth #1729 or AJOVYhcp.com 6

Axon Registry Simplifies Reporting Measures for MIPS As the Merit-based Incentive Payment System (MIPS) under the Quality Payment Program (QPP) is completing its second reporting year, it’s important for your practice to assess your data submission method. There are multiple methods of submission and each can get you different overall point values. Each year, it’s important to assess the method that is best for your practice. The AAN has invested heavily in your success in this program and has established the Axon Registry ®, free to US neurologist AAN members. The registry provides a free submission method that works well for practices with server-based EHR systems and those EHRs that have agreed to send data directly to a registry on a practice’s behalf. The Axon Registry can help your practice efficiently participate in the MIPS program.

your documentation to calculate performance rates. You are then given a user-friendly dashboard to review in real time throughout the year. All of this is provided as a free member benefit for USbased providers with an up-to-date membership. If the Axon Registry sounds right for your practice, contact registry@aan.com or learn more on our website at AAN.com/view/Axon.

Finding a way to submit measures relevant to your practice helps alleviate the need to document information that is irrelevant to the patient visit. The Axon Registry is designated as a qualified clinical data registry (QCDR), meaning it can add neurologyspecific measures that are not a part of the QPP program. In addition to 18 neurology-specific QPP measures, there are 17 measures in Axon that are not eligible for submission through any other method. They include Parkinson’s, neuro-ophthalmology, headache, multiple sclerosis, falls, epilepsy, distal symmetric polyneuropathy, and child neurology measures. All of which may be incredibly important for your patients but have not been approved for submission via claims, EMR, or manual entry. Many other MIPS submission methods will charge anywhere from $300 to $900 per provider to send data to CMS. The Axon Registry extracts data directly from your EHR system and assesses all

AAN Board member and Registry Committee member Sarah M. Benish, MD, FAAN, answered members’ registry questions.

Last Chance to Get to the Exhibit Hall Before 4:00 Closing Be sure to stop by the Exhibit Hall before it closes at 4:00 this afternoon to meet, mingle, and learn from pharmaceutical and medical device industry representatives, publishers and others. This year’s hall is anything but traditional, and in addition to hundreds of chances to network with medical industry representatives, you’ll also find fun and informative happenings at every turn, including opportunities to:

Don’t Miss Today’s Special Events! Bingo

1:00 p.m.–2:00 p.m.

Food Plating Competitions in the picnic area—who will have

the best designed plate? 12:15 p.m.–12:45 p.m.

Connect with other health organizations throughout the

Wine and Paint Session

Discover emerging technologies within the Technology

Medical Improv

Association Neighborhood Pavilion

Keep up-to-date on what’s new at Publishers Row Gather career resources and more during the Career Fair Preview the latest products and services at Vendor Booths Experience an array of dynamic events at the Innovation Hub

12:00 p.m.–1:00 p.m. and 2:00 p.m.–3:00 p.m. 3:00 p.m.–3:30 p.m.

Remember to fill out the last Exhibit Hall Passport for a chance to win prizes, including a grand prize drawing of a 2020 Annual Meeting registration and a three-night stay in an AAN block hotel—compliments of the Academy. Passports are available in the Exhibit Hall or in your On-site Guide.

Grab a cup of joe and mingle at the Exhibit Hall Buzz Cafes Keep your devices charged in the comfort of the Exhibit Hall

Charging Lounges

Take a break and unwind at the Exhibit Hall Picnic Area

Wednesday, May 8, 2019 • AANextra

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

from Columbia University Vagelos College of Physicians and Surgeons and Weill Cornell Medicine to provide care to thousands of neurology and neurosurgery patients. Faculty from both medical schools are at the forefront of conducting research and clinical studies for a wide range of conditions. Recent advances include: Alzheimer’s • A study that uncovered large-scale changes throughout the epigenome of the human Alzheimer’s disease brain, revealing that tau-induced alterations of chromatin structure are more profound than changes attributable to amyloid pathology. • The launch of our new Alzheimer’s Prevention Clinic that combines evidence-based, low-risk interventions with lifestyle modifications that may help to delay, or in some cases possibly prevent, the progression towards dementia. Brain Tumors • The first-ever dose escalation study using convection-enhanced delivery for diffuse intrinsic pontine glioma to bypass the blood-brain barrier and administer a drug directly to the brain stem tumor site. Stroke • Participated in the DEFUSE trial which has shown the benefit of late thrombectomy from 6 to 24 hours past onset of a large vessel occlusive stroke. Because of these innovations and more, our Neurology and Neurosurgery program is ranked #1 in New York and #5 in the nation by U.S. News & World Report.

Learn more at nyp.org/neuroinnovations

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

We’ve Got Your Back: Regulatory Advocacy, Payer Relations, and the AAN The AAN supports neurologists in seeking fair reimbursement and coverage. When we succeed, you should be able to treat your patients and get reimbursed for your time and effort without the process feeling overly burdensome or unfair. While our goal is to make these systems feel seamless, behind the scenes the AAN is working to keep these processes running smoothly through proactive regulatory advocacy and building payer relationships.

Regulatory Advocacy Regulatory advocacy involves agencies within the US Department of Health and Human Services (HHS). This includes the Centers for Medicare & Medicaid Services (CMS), the Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and more. CMS is a major focus of the AAN’s Medical Economics and Management Committee, which guides our regulatory advocacy efforts. The agency sets Medicare reimbursement rates each year and other policies related to the government insurance program. CMS is especially important because private payers often model their own policies upon what Medicare has implemented. The FDA is also important as it helps regulate the medications and devices that neurologists and their patients use every day. The AAN engages in proactive regulatory advocacy. This means advocating in front of federal agencies before they make rules that impact neurologists and their patients. The Academy routinely meets with regulators, such as HHS leadership in Washington, DC, and CMS staff in the agency’s Baltimore, MD, headquarters. Through the first half of 2019, the AAN met with regulators 10 times to discuss priorities such as reducing regulatory hassles and improving cognitive reimbursement. The AAN’s proactive regulatory advocacy recently delivered value to members when our advocacy resulted in HHS reducing penalties related to performance in Medicare quality programs. The AAN estimates that the associated regulatory changes saved neurologists up to $13 million in potential penalties. Additionally, the AAN submits formal comment letters in response to HHS regulations. This usually involves digesting thousands of pages published by the agency and responding to questions posed in a proposed regulation. Generally, the AAN, along with the entire public, is given 60 days to reply to HHS proposals. The agency must review these responses and then submit an updated, final regulation.

Commercial Payer Relations The AAN also supports its members when it comes to commercial payers. The AAN’s Payment Policy Subcommittee exists to build relationships with these payers so that we can quickly and effectively advocate for our members when they encounter an issue. For example, this year one of the largest payers in the country proposed changes to its intraoperative neurophysiological monitoring policy that would have limited both access and reimbursement. The AAN contacted the payer’s medical directors it has worked with over the years and arranged a meeting with the Payment Policy Subcommittee and one of our member experts. After discussions with the Academy, the payer rescinded the policy. By proactively building these relationships and establishing ourselves as reliable experts who are willing to work collaboratively, the AAN can be effectively reactive and advocate for our members when issues arise.

Teamwork Our advocacy efforts do not happen in a vacuum. The AAN’s regulatory efforts in Washington, DC, often involve teamwork with legislative colleagues who lobby members of Congress on behalf of the AAN. For example, during the period of July through September, AAN regulatory staff met five times with HHS staff and leadership, including the deputy secretary of HHS, to discuss the recent proposal changing the structure of Evaluation & Management (E/M) codes. Parallel to our regulatory efforts that produced a 39-page comment letter on the subject, AAN legislative staff pushed our message through Congress by lobbying individual offices on the subject. This resulted in two bipartisan letters signed by 24 senators and 90 representatives that were submitted to CMS in opposition to the proposed E/M proposal. We also collaborate on coverage issues, making sure to coordinate comment letters to Medicare administrative contractors with comment letters to commercial payers.

Resources We also support our members on an individual level through education and resources, including practice management webinars. Members can email practice@aan.com with specific coding and reimbursement questions. In addition to providing guidance, we can put you in touch with local resources such as state neurosocieties that may be able to support your needs. 

Marc Raphaelson, MD, FAAN Marc Raphaelson, MD, FAAN (second from left) with AAN staff at CMS headquarters.

Neil A. Busis, MD, FAAN

Wednesday, May 8, 2019 • AANextra

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

#AANAM Tarek Chedid II, MD / Dbayeh, Lebanon Resident, poster presenter “What sessions have made the most impact for you?” “The dystonia session was very well-illustrated with videos. Dystonia is one of the topics that as residents we don’t get exposed to very often, especially unusual cases.” “What is your poster topic?” “A case of a spinal cord injury from an indirect gunshot that we saw, plus a review of seven similar cases.”

Claudia Gambrah Sampaney / Philadelphia, PA Fourth-year medical student, abstract presenter, third time attending AAN meeting “What do you enjoy about the AAN Annual Meeting?” “With the AAN meeting, you can pick whatever topic you are interested in and there will be posters on it and people speaking about it and people interested in it. You can really explore your interests, no matter what your niche is.” “What is the topic of your abstract?” “Vitamin D and pediatric MS.”

Maria Gaughan, MBBCh / Dublin, Ireland “What brings you to the meeting this year?” “Excellent teaching. And the opportunity to hear up-to-date research. But mainly the excellent teaching. Especially movement disorders where you can see the video analysis. And neuro-ophthalmology. It’s everyone’s opportunity to brush up on your skills, especially not in your own specialty.”

Francisco Inacio, MD / Coimbra, Portugal Poster presenter “What advice do you have for someone who is attending the meeting for the first time?” “Maybe do what I didn’t. Make some homework on AAN’s website and get the whole picture of the meeting and that will help you!” “What is the topic of your poster?” “Eslicarbazepine acetate in post-stroke epilepsy.”

Wednesday, May 8, 2019 • AANextra

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INDICATION Oxtellar XR® is indicated for the treatment of partial-onset seizures in patients 6 years of age and older. CONTRAINDICATIONS Oxtellar XR is contraindicated in patients with a known hypersensitivity to oxcarbazepine, or to any of the components of Oxtellar XR, or to eslicarbazepine acetate. Reactions have included anaphylaxis and angioedema. *Terms and conditions apply. Not actual patient. Fictionalized for illustrative purposes. References: 1. Oxtellar XR [package insert]. Rockville, MD: Supernus Pharmaceuticals, Inc.; December 2018. 2. Glauser TA. Oxcarbazepine in the treatment of epilepsy. Pharmacotherapy. 2001;21(8):904-919. 3. French JA, Baroldi P, Brittain ST, Johnson JK; for PROSPER Investigators Study Group. Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial. Acta Neurol Scand. 2014;129:143-153.

Please refer to the brief summary of full Prescribing Information on adjacent pages, or visit www.OxtellarXR.com. Oxtellar XR is a registered trademark of Supernus Pharmaceuticals, Inc. ©2019 Supernus Pharmaceuticals, Inc. All rights reserved. SPN.OXT.2019-0023

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OXTELLAR XR® (oxcarbazepine) extended-release tablets, for oral use Brief Summary of Prescribing Information For full prescribing information, see Package Insert. CONTRAINDICATIONS Oxtellar XR is contraindicated in patients with a known hypersensitivity to oxcarbazepine, to any of the components of Oxtellar XR, or to eslicarbazepine acetate. Reactions have included anaphylaxis and angioedema. WARNINGS AND PRECAUTIONS Hyponatremia Clinically significant hyponatremia (sodium <125 mmol/L) may develop during Oxtellar XR® use. Serum sodium levels less than 125 mmol/L have occurred in immediate-release oxcarbazepine-treated patients generally in the first three months of treatment. However, clinically significant hyponatremia may develop more than a year after initiating therapy. Most immediate-release oxcarbazepine-treated patients who developed hyponatremia were asymptomatic in clinical trials. However, some of these patients had their dosage reduced, discontinued, or had their fluid intake restricted for hyponatremia. Serum sodium levels returned toward normal when the dosage was reduced or discontinued, or when the patient was treated conservatively (e.g., fluid restriction). Cases of symptomatic hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been reported during post-marketing use of immediate-release oxcarbazepine. Among treated patients in a controlled trial of adjunctive therapy with Oxtellar XR® in 366 adults with complex partial seizures, 1 patient receiving 2400 mg experienced a severe reduction in serum sodium (117 mEq/L), requiring discontinuation from treatment, while 2 other patients receiving 1200 mg experienced serum sodium concentrations low enough (125 and 126 mEq/L) to require discontinuation from treatment. The overall incidence of clinically significant hyponatremia in patients treated with Oxtellar XR® was 1.2%, although slight shifts in serum sodium concentrations from Normal to Low (<135 mEq/L) were observed for the 2400 mg (6.5%) and 1200 mg (9.8%) groups compared to placebo (1.7%). Measure serum sodium concentrations if patients develop symptoms of hyponatremia (e.g., nausea, malaise, headache, lethargy, confusion, obtunded consciousness, or increase in seizure frequency or severity). Consider measurement of serum sodium concentrations during treatment with Oxtellar XR®, particularly if the patient receives concomitant medications known to decrease serum sodium levels (for example, drugs associated with inappropriate ADH secretion). Anaphylactic Reactions and Angioedema Rare cases of anaphylaxis and angioedema involving the larynx, glottis, lips, and eyelids have been reported in patients after taking the first or subsequent doses of immediate-release oxcarbazepine. Angioedema associated with laryngeal edema can be fatal. If a patient develops any of these reactions after treatment with Oxtellar XR®, discontinue the drug and initiate an alternative treatment. Do not rechallenge these patients with Oxtellar XR®. Cross Hypersensitivity Reaction to Carbamazepine Approximately 25% to 30% of patients who have had hypersensitivity reactions to carbamazepine will experience hypersensitivity reactions with Oxtellar XR®. For this reason, patients should be specifically questioned about any prior experience with carbamazepine, and patients with a history of hypersensitivity reactions to carbamazepine should ordinarily be treated with Oxtellar XR® only if the potential benefit justifies the potential risk. Discontinue Oxtellar XR® immediately if signs or symptoms of hypersensitivity develop. Serious Dermatological Reactions Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have occurred in both children and adults treated with immediate-release oxcarbazepine use. The median time of onset for reported cases was 19 days. Such serious skin reactions may be life threatening, and some patients have required hospitalization with very rare reports of fatal outcome. Recurrence of the serious skin reactions following rechallenge with immediate-release oxcarbazepine has also been reported. The reporting rate of TEN and SJS associated with immediaterelease oxcarbazepine use, which is generally accepted to be an underestimate due to underreporting, exceeds the background incidence rate estimates by a factor of 3- to 10-fold. Estimates of the background incidence rate for these serious skin reactions in the general population range between 0.5 to 6 cases per million-person years. Therefore, if a patient develops a skin reaction while taking Oxtellar XR®, consider discontinuing Oxtellar XR® use and prescribing another AED. Association with HLA-B*1502 Patients carrying the HLA-B*1502 allele may be at increased risk for SJS/TEN with Oxtellar XR® treatment. Human Leukocyte Antigen (HLA) allele B*1502 increases the risk for developing SJS/TEN in patients treated with carbamazepine. The chemical structures of immediate-release oxcarbazepine and Oxtellar XR® are similar to that of carbamazepine. Available clinical evidence, and data from nonclinical studies showing a direct interaction between immediate-release oxcarbazepine and HLA-B*1502 protein, suggest that the HLA-B*1502 allele may also increase the risk for SJS/TEN with Oxtellar XR®. The frequency of HLA-B*1502 allele ranges from 2 to 12% in Han Chinese populations, is about 8% in Thai populations, and above 15% in the Philippines and in some Malaysian populations. Allele frequencies up to about 2% and 6% have been reported in Korea and India, respectively. The frequency of the HLA-B*1502 allele is negligible in people from European descent, several African populations, indigenous peoples of the Americas, Hispanic populations, and in Japanese (<1%). Testing for the presence of the HLA-B*1502 allele should be considered in patients with ancestry in genetically at-risk populations, prior to initiating treatment with Oxtellar XR®. The use of Oxtellar XR® should be avoided in patients positive for HLA-B*1502 unless the benefits clearly outweigh the risks. Consideration should also be given to avoid the use of other drugs associated with SJS/TEN in HLA-B*1502 positive patients, when alternative therapies are otherwise equally acceptable. Screening is not generally recommended in patients from populations in which the prevalence of HLA-B*1502 is low, or in current Oxtellar XR® users, as the risk of SJS/TEN is largely confined to the first few months of therapy, regardless of HLA-B*1502 status. The use of HLA-B*1502 genotyping has important limitations and must never substitute for appropriate clinical vigilance and patient management. The role of other possible factors in the development of, and morbidity from, SJS/TEN, such as antiepileptic drug (AED) dosage, compliance, concomitant medications, comorbidities, and the level of

dermatologic monitoring have not been well characterized. Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including Oxtellar XR®, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed. Risk by Indication for Antiepileptic Drugs in the Pooled Analysis Epilepsy: Placebo Patients with Events per 1000 Patients 1.0. Drug Patients with Events per 1000 patients 3.4. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 3.5. Risk Difference: Additional Drug Patients with Events per 1000 Patients 2.4. Psychiatric: Placebo Patients with Events per 1000 Patients 5.7. Drug Patients with Events per 1000 patients 8.5. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 1.5. Risk Difference: Additional Drug Patients with Events per 1000 Patients 2.9. Other: Placebo Patients with Events per 1000 Patients 1.0. Drug Patients with Events per 1000 patients 1.8. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 1.9. Risk Difference: Additional Drug Patients with Events per 1000 Patients 0.9. Total: Placebo Patients with Events per 1000 Patients 2.4. Drug Patients with Events per 1000 patients 4.3. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 1.8. Risk Difference: Additional Drug Patients with Events per 1000 Patients 1.9. The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Anyone considering prescribing Oxtellar XR® or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during Oxtellar XR® treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Withdrawal of AEDs As with most AEDs, Oxtellar XR® should be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. But if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/ Multi-Organ Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi-organ hypersensitivity, has occurred with immediate-release oxcarbazepine. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocaraditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. Oxtellar XR® should be discontinued if an alternative etiology for the signs and symptoms cannot be established. Hematologic Reactions Rare reports of pancytopenia, agranulocytosis, and leukopenia have been seen in patients treated with immediate-release oxcarbazepine during post-marketing experience. Discontinuation of Oxtellar XR® should be considered if any evidence of these hematologic reactions develops. Risk of Seizures in the Pregnant Patient Due to physiological changes during pregnancy, plasma concentrations of the active metabolite of oxcarbazepine, the 10-monohydroxy derivative (MHD), may gradually decrease throughout pregnancy. Monitor patients carefully during pregnancy and through the postpartum period because MHD concentrations may increase after delivery. Risk of Seizure Aggravation Exacerbation of or new onset primary generalized seizures has been reported with immediate-release oxcarbazepine. The risk of aggravation of primary generalized seizures is seen especially in children but may also occur in adults. In case of seizure aggravation, Oxtellar XR® should be discontinued. ADVERSE REACTIONS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety data presented below are from 384 patients with partial-onset seizures who received Oxtellar XR® (366 adults and 18 pediatric patients) with concomitant AEDs. In addition, safety data presented below are from a total of 2288 patients with seizure disorders treated with immediate-release oxcarbazepine; 1832 were adults and 456 were pediatric patients.

Most Common Adverse Reactions Reported by Adult Patients Receiving Concomitant AEDs in Oxtellar XR® Clinical Studies Table 3 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy treated with Oxtellar XR® or placebo and concomitant AEDs and that were numerically more common in the patients treated with any dosage of Oxtellar XR® than in patients receiving placebo. The overall incidence of adverse reactions appeared to be dose related, particularly during the titration period. The most commonly observed (≥5%) adverse reactions seen in association with Oxtellar XR® and more frequent than in placebo-treated patients were: dizziness, somnolence, headache, balance disorder, tremor, vomiting, diplopia, and asthenia. Table 3: Adverse Reaction Incidence in a Controlled Clinical Study of Oxtellar XR® with Concomitant AEDs in Adults* Oxtellar XR® 2400 mg/day (N=123); Oxtellar XR® 1200 mg/day (N=122). Placebo (N=121). Any System/Any Term: 69%, 57%, 55%. Nervous System Disorders: Dizziness: 41%, 20%, 15%; Somnolence: 14%, 12% 9%; Headache: 15% 8%, 7%; Balance Disorder: 7%, 5% 5%; Tremor: 1%, 5%, 2%; Nystagmus: 3%, 3%, 1%; Ataxia 1%, 3%, 1%. Gastrointestinal Disorders: Vomiting: 15% 6%, 9%; Abdominal Pain Upper: 0%, 3% 1%; Dyspepsia: 0% 3% 1%; Gastritis: 0%, 3% 2%. Eye Disorders: Diplopia: 13%, 10% 4%; Vision Blurred: 1%, 4%, 3%; Visual Impairment: 1%, 3%, 0%. General Disorders and Administration Site Conditions: Asthenia: 7% 3%, 1%; Fatigue: 3%, 6%, 1%; Gait Disturbance: 0%, 3%, 1%; Drug Intolerance: 2%, 0%, 0%. Infections and Infestations: Nasopharyngitis: 0% 3%, 0%; Sinusitis: 0%, 3%, 2%. *Reported by ≥2% of patients treated with Oxtellar XR® and numerically more frequent than in the placebo group. Adverse Reactions Associated with Discontinuation of Oxtellar XR® Treatment: Approximately 23.3% of the 366 adult patients receiving Oxtellar XR® in clinical studies discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation of Oxtellar XR® (reported by ≥2%) were: dizziness (9.8%), vomiting (5.3%), nausea (3.7%), diplopia (3.2%), and somnolence (2.4%). Adjunctive Therapy with Oxtellar XR® in Pediatric Patients 6 to Less Than 17 Years of Age Previously Treated with Other AEDs In a pharmacokinetic study in 18 pediatric patients (including patients 6 to less than 17 years of age) with partial-onset seizures treated with different dosages of Oxtellar XR®, the observed adverse reactions seen in association with Oxtellar XR® were similar to those seen in adults. Most Common Adverse Reactions in Immediate-Release Oxcarbazepine Controlled Clinical Studies Controlled Clinical Studies of Adjunctive Therapy with Immediate-Release Oxcarbazepine in Adults Previously Treated with Other AEDs: Table 4 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy treated with immediate-release oxcarbazepine or placebo with concomitant AEDs and that were numerically more common in the patients treated with any dosage of immediate-release oxcarbazepine than in placebo. As immediate-release oxcarbazepine and Oxtellar XR® were not examined in the same trial, adverse event frequencies cannot be directly compared between the two formulations. Table 4: Adverse Reaction Incidence in a Controlled Clinical Study of Immediate Release Oxcarbazepine with Concomitant AEDs in Adults* Immediate-Release Oxcarbazepine Dosage (mg/day): OXC 600 (N=163); OXC1200 (N=171); OXC2400 (N=126); Placebo (N=166). Body as a Whole: Fatigue: 15%, 12%, 15%, 7%; Asthenia: 6% 3%, 6%, 5%; Edema Legs: 2%, 1%, 2%, 1%; Weight Increase: 1%, 2%, 2%, 1%; Feeling Abnormal: 0%, 1%, 2%, 0%. Cardiovascular System: Hypotension: 0%, 1%, 2%, 0%. Digestive System: Nausea: 15%, 25%, 29% 10%; Vomiting: 13%, 25%, 36%, 5%; Pain Abdominal: 10%, 13%, 11%, 5%; Diarrhea: 5%, 6%, 7%, 6%; Dyspepsia: 5%, 5%, 6%, 2%; Constipation: 2%, 2%, 6%, 4%; Gastritis: 2%, 1%,2%,1%. Metabolic and Nutritional Disorders: Hyponatremia: 3%, 1%, 2%,1%. Musculoskeletal System: Muscle Weakness: 1%, 2%, 2%, 0%; Sprains and Strains: 0%, 2%, 2%, 1%. Nervous System: Headache: 32%, 28% 26%, 23%; Dizziness: 36%, 32%, 49%, 13%; Somnolence: 20%, 28%, 36%, 12%; Ataxia: 9%, 17%, 31%, 5%; Nystagmus: 7% 20%, 26% 5%; Gait Abnormal: 5%, 10%, 17%, 1%; Insomnia: 4%, 2%, 3%, 1%; Tremor: 3% 8%, 16%, 5%; Nervousness: 2%, 4%, 2%, 1%; Agitation: 1%,1%, 2%, 1%; Coordination Abnormal: 1%, 3%, 2%, 1%; EEG Abnormal: 0%, 0%, 2%, 0%; Speech Disorder: 1%, 1%, 3%, 0%; Confusion: 1%, 1%, 2%, 1%; Cranial Injury NOS: 1%, 0%, 2% 1%; Dysmetria: 1%, 2%, 3%, 0%; Thinking Abnormal: 0%, 2%, 4%, 0%. Respiratory System: Rhinitis: 2%, 4%, 5%, 4%; Skin and Appendages: Acne: 1%, 2%, 2%, 0%; Special Senses: Diplopia: 14%, 30%, 40%, 5%; Vertigo: 6%, 12%, 15%, 2%; Vision Abnormal: 6%, 14%, 13%, 4%; Accommodation Abnormal: 0%, 0%, 2%, 0%. *Events in at least 2% of patients treated with 2400 mg/day of immediate-release oxcarbazepine and numerically more frequent than in the placebo group. Other Reactions Observed in Association with the Administration of Immediate-Release Oxcarbazepine In the paragraphs that follow, the adverse reactions, other than those in the preceding tables or text, that occurred in a total of 565 children and 1574 adults exposed to immediate-release oxcarbazepine and that are reasonably likely to be related to drug use are presented. Events common in the population, events reflecting chronic illness and events likely to reflect concomitant illness are omitted particularly if minor. They are listed in order of decreasing frequency. Because the reports cite reactions observed in open-label and uncontrolled trials, the role of immediate-release oxcarbazepine in their causation cannot be reliably determined. Body as a Whole: fever, malaise, pain chest precordial, rigors, weight decrease. Cardiovascular System: bradycardia, cardiac failure, cerebral hemorrhage, hypertension, hypotension postural, palpitation, syncope, tachycardia. Digestive System: appetite increased, blood in stool, cholelithiasis, colitis, duodenal ulcer, dysphagia, enteritis, eructation, esophagitis, flatulence, gastric ulcer, gingival bleeding, gum hyperplasia, hematemesis, hemorrhage rectum, hemorrhoids, hiccup, mouth dry, pain biliary, pain right hypochondrium, retching, sialoadenitis, stomatitis, stomatitis ulcerative. Hematologic and Lymphatic System: thrombocytopenia. Laboratory Abnormality: gamma-GT increased, hyperglycemia, hypocalcemia, hypoglycemia, hypokalemia, liver enzymes elevated, serum transaminase increased. Musculoskeletal System: hypertonia muscle. Nervous System: aggressive reaction, amnesia, anguish, anxiety, apathy, aphasia, aura, convulsions aggravated, delirium, delusion, depressed level of consciousness, dysphonia, dystonia, emotional lability, euphoria,

extrapyramidal disorder, feeling drunk, hemiplegia, hyperkinesia, hyperreflexia, hypoesthesia, hypokinesia, hyporeflexia, hypotonia, hysteria, libido decreased, libido increased, manic reaction, migraine, muscle contractions involuntary, nervousness, neuralgia, oculogyric crisis, panic disorder, paralysis, paroniria, personality disorder, psychosis, ptosis, stupor, tetany. Respiratory System: asthma, bronchitis, coughing, dyspnea, epistaxis, laryngismus, pleurisy. Skin and Appendages: acne, alopecia, angioedema, bruising, dermatitis contact, eczema, facial rash, flushing, folliculitis, heat rash, hot flushes, photosensitivity reaction, pruritus genital, psoriasis, purpura, rash erythematous, rash maculopapular, vitiligo, urticaria. Special Senses: accommodation abnormal, cataract, conjunctival hemorrhage, edema eye, hemianopia, mydriasis, otitis externa, photophobia, scotoma, taste perversion, tinnitus, xerophthalmia. Urogenital and Reproductive System: dysuria, hematuria, intermenstrual bleeding, leukorrhea, menorrhagia, micturition frequency, pain renal, pain urinary tract, polyuria, priapism, renal calculus, urinary tract infection. Other: Systemic lupus erythematosus. Laboratory Tests Serum sodium levels below 125 mmol/L have been observed in patients treated with immediate-release oxcarbazepine. Experience from clinical trials with immediate-release oxcarbazepine indicates that serum sodium levels return toward normal when the dosage is reduced or discontinued, or when the patient was treated conservatively (e.g., fluid restriction). Laboratory data from clinical trials suggest that immediate-release oxcarbazepine use was associated with decreases in T4, without changes in T3 or TSH. Postmarketing and Other Experience The following adverse reactions have been observed in named patient programs or post-marketing experience with immediate-release oxcarbazepine or Oxtellar XR®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Body as a Whole: multi-organ hypersensitivity disorders characterized by features such as rash, fever, lymphadenopathy, abnormal liver function tests, eosinophilia, and arthralgia Cardiovascular System: atrioventricular block Digestive System: pancreatitis and/or lipase and/or amylase increase Hematologic and Lymphatic Systems: aplastic anemia Immune System Disorders: anaphylaxis Metabolism and Nutrition Disorders: hypothyroidism and syndrome of inappropriate antidiuretic hormone secretion (SIADH) Skin and Subcutaneous Tissue Disorders: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, Acute Generalized Exanthematous Pustulosis (AGEP) Musculoskeletal, Connective Tissue and Bone Disorders: There have been reports of decreased bone mineral density, osteoporosis and fractures in patients on long-term therapy with immediate-release oxcarbazepine. DRUG INTERACTIONS Effect of Oxtellar XR on Other Drugs It is recommended that the plasma levels of phenytoin be monitored during the period of Oxtellar XR titration and dosage modification. A decrease in the dosage of phenytoin may be required. Effect of Other Drugs on Oxtellar XR If Oxtellar XR and strong CYP3A4 inducers or UGT inducers (e.g., rifampin, carbamazepine, phenytoin, and phenobarbital) are administered concurrently, it is recommended that the plasma levels of MHD be monitored during the period of Oxtellar XR titration. Dosage adjustment of Oxtellar XR may be required after initiation, dosage modification, or discontinuation of such inducers. Hormonal Contraceptives Concurrent use of immediate-release oxcarbazepine with hormonal contraceptives may render these contraceptives less effective. Studies with other oral or implant contraceptives have not been conducted. USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as Oxtellar XR, during pregnancy. Encourage women who are taking Oxtellar XR during pregnancy to enroll in the North American Antiepileptic Drug (NAAED Pregnancy Registry) by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. Risk Summary There are no adequate data on the developmental risks associated with the use of Oxtellar XR® in pregnant women; however, Oxtellar XR® is closely related structurally to carbamazepine, which is considered to be teratogenic in humans. Data on a limited number of pregnancies from pregnancy registries suggest that oxcarbazepine monotherapy use is associated with congenital malformations (e.g., craniofacial defects such as oral clefts, and cardiac malformations such as ventricular septal defects). Increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity (embryolethality, growth retardation) were observed in the offspring of animals treated with either oxcarbazepine or its active 10-hydroxy metabolite (MHD) during pregnancy at doses similar to the maximum recommended human dose (MRHD). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Clinical Considerations An increase in seizure frequency may occur during pregnancy because of altered levels of the active metabolite of oxcarbazepine. Monitor patients carefully during pregnancy and through the postpartum period. Data Human Data Data from published registries have reported craniofacial defects such as oral clefts and cardiac malformations such as ventricular septal defects in children with prenatal oxcarbazepine exposure. Animal Data When pregnant rats were given oxcarbazepine (30, 300, or 1000 mg/kg/day) orally throughout the period of organogenesis, increased incidences of fetal malformations (craniofacial, cardiovascular, and skeletal) and variations were observed at the intermediate and high doses (approximately 1.2 and 4 times, respectively, the MRHD on a mg/m2 basis). Increased embryofetal death and decreased fetal body weights were seen at the high dose. Doses ≥300 mg/kg were also maternally toxic (decreased body weight gain, clinical signs), but there is no evidence to suggest that teratogenicity was secondary to the maternal effects. In a study in which pregnant rabbits were orally administered MHD (20,

100, or 200 mg/kg/day) during organogenesis, embryofetal mortality was increased at the highest dose (1.5 times the MRHD on a mg/m2 basis). This dose produced only minimal maternal toxicity. In a study in which female rats were dosed orally with oxcarbazepine (25, 50, or 150 mg/kg/day) during the latter part of gestation and throughout the lactation period, a persistent reduction in body weights and altered behavior (decreased activity) were observed in offspring exposed to the highest dose (0.6 times the MRHD on a mg/m2 basis). Oral administration of MHD (25, 75, or 250 mg/kg/day) to rats during gestation and lactation resulted in a persistent reduction in offspring weights at the highest dose (equivalent to the MRHD on a mg/m2 basis). Lactation Risk Summary Oxcarbazepine and its active metabolite (MHD) are present in human milk after oxcarbazepine administration. The effects of oxcarbazepine and its active metabolite (MHD) on the breastfed infant or on milk production are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Oxtellar XR and any potential adverse effects on the breastfed infant from Oxtellar XR or from the underlying maternal condition. Females and Males of Reproductive Potential Contraception Use of Oxtellar XR with hormonal contraceptives containing ethinylestradiol or levonorgestrel is associated with decreased plasma concentrations of these hormones and may result in a failure of the therapeutic effect of the oral contraceptive drug. Advise women of reproductive potential taking Oxtellar XR who are using a contraceptive containing ethinylestradiol or levonorgestrel to use additional or alternative non-hormonal birth control. Pediatric Use The safety and effectiveness of Oxtellar XR® in pediatric patients 6 years of age and older for the treatment of partial-onset seizures is supported by: 1) An adequate and well-controlled safety and efficacy study of Oxtellar XR® in adults that included pharmacokinetic sampling, 2) A pharmacokinetic study of Oxtellar XR® in pediatric patients, which included patients 6 to less than 17 years of age, 3) Safety and efficacy studies with the immediate-release formulation in adults and pediatric patients. Oxtellar XR® is not approved for pediatric patients less than 6 years of age because the size of the tablets are inappropriate for younger children. Geriatric Use Following administration of single (300 mg) and multiple (600 mg/day) doses of immediate-release oxcarbazepine to elderly volunteers (60-82 years of age), the maximum plasma concentrations and AUC values of MHD were 30%-60% higher than in younger volunteers (18-32 years of age). Comparisons of creatinine clearance in young and elderly volunteers indicate that the difference was due to age-related reductions in creatinine clearance. Consider starting at a lower dosage and lower titration. Close monitoring of sodium levels is required in elderly patients at risk for hyponatremia. Renal Impairment There is a linear correlation between creatinine clearance and the renal clearance of MHD. The pharmacokinetics of Oxtellar XR® has not been evaluated in patients with renal impairment. In patients with severe renal impairment (creatinine clearance <30 mL/min) given immediate-release oxcarbazepine, the elimination half-life of MHD was prolonged with a corresponding two-fold increase in AUC. In these patients initiate Oxtellar XR® at a lower starting dosage and increase, if necessary, at a slower than usual rate until the desired clinical response is achieved. In patients with end-stage renal disease on dialysis, it is recommended that immediate-release oxcarbazepine be used instead of Oxtellar XR®. Hepatic Impairment The pharmacokinetics of oxcarbazepine and MHD has not been evaluated in severe hepatic impairment, and therefore is not recommended in these patients. DRUG ABUSE AND DEPENDENCE Abuse The abuse potential of Oxtellar XR® has not been evaluated in human studies. Oxtellar XR® is not habit forming, and is not expected to encourage abuse. Dependence Intragastric injections of oxcarbazepine to four cynomolgus monkeys demonstrated no signs of physical dependence as measured by the desire to self-administer oxcarbazepine by lever pressing activity. OVERDOSAGE Human Overdose Experience Isolated cases of overdose with immediate-release oxcarbazepine have been reported. The maximum dose taken was approximately 48,000 mg. All patients recovered with symptomatic treatment. Nausea, vomiting, somnolence, aggression, agitation, hypotension, and tremor each occurred in more than one patient. Coma, confusional state, convulsion, dyscoordination, depressed level of consciousness, diplopia, dizziness, dyskinesia, dyspnea, QT prolongation, headache, miosis, nystagmus, overdose, decreased urine output, and blurred vision also occurred. Treatment and Management There is no specific antidote for Oxtellar XR® overdose. Administer symptomatic and supportive treatment as appropriate. Options include removal of the drug by gastric lavage and/or inactivation by administering activated charcoal. CLINICAL PHARMACOLOGY Patients with Renal or Hepatic Impairment The effects of renal or hepatic impairment have not been studied for Oxtellar XR®. Based on investigations with immediate-release oxcarbazepine, there is a linear correlation between creatinine clearance and the renal clearance of MHD. When immediate-release oxcarbazepine is administered as a single 300 mg dose in renally-impaired patients (creatinine clearance <30 mL/min), the elimination half-life of MHD is prolonged to 19 hours, with a two-fold increase in AUC. Dosage adjustment is recommended in these patients. The pharmacokinetics and metabolism of immediate-release oxcarbazepine and MHD were evaluated in healthy volunteers and hepatically impaired subjects after a single 900 mg oral dose. Mild-to-moderate hepatic impairment did not affect the pharmacokinetics of immediate-release oxcarbazepine and MHD. The pharmacokinetics of oxcarbazepine and MHD have not been evaluated in severe hepatic impairment, and therefore it is not recommended in these patients. Pregnant Women Due to physiological changes during pregnancy, MHD plasma levels may gradually decrease throughout pregnancy. Drug Interaction Studies

In Vitro: Oxcarbazepine can inhibit CYP2C19 and induce CYP3A4/5 with potentially important effects on plasma concentrations of other drugs. In addition, several AEDs that are cytochrome P450 inducers can decrease plasma concentrations of oxcarbazepine and MHD. Oxcarbazepine was evaluated in human liver microsomes to determine its capacity to inhibit the major cytochrome P450 enzymes responsible for the metabolism of other drugs. Results demonstrate that oxcarbazepine and its pharmacologically active 10-monohydroxy metabolite (MHD) have little or no capacity to function as inhibitors for most of the human cytochrome P450 enzymes evaluated (CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, CYP4A9, and CYP4A11) with the exception of CYP2C19 and CYP3A4/5. Although inhibition of CYP3A4/5 by oxcarbazepine and MHD did occur at high concentrations, it is not likely to be of clinical significance. The inhibition of CYP2C19 by oxcarbazepine and MHD, is clinically relevant. In vitro, the UDP-glucuronyl transferase level was increased, indicating induction of this enzyme. Increases of 22% with MHD and 47% with oxcarbazepine were observed. As MHD, the predominant plasma substrate, is only a weak inducer of UDP-glucuronyl transferase, it is unlikely to have an effect on drugs that are mainly eliminated by conjugation through UDP-glucuronyl transferase (e.g., valproic acid, lamotrigine). In addition, oxcarbazepine and MHD induce a subgroup of the cytochrome P450 3A family (CYP3A4 and CYP3A5) responsible for the metabolism of dihydropyridine calcium antagonists, oral contraceptives and cyclosporine resulting in a lower plasma concentration of these drugs. Several AEDs that are cytochrome P450 inducers can decrease plasma concentrations of oxcarbazepine and MHD. No autoinduction has been observed with immediate-release oxcarbazepine. As binding of MHD to plasma proteins is low (40%), clinically significant interactions with other drugs through competition for protein binding sites are unlikely. In Vivo: Other Antiepileptic Drugs Potential interactions between immediate-release oxcarbazepine and other AEDs were assessed in clinical studies. The effect of these interactions on mean AUCs and Cmin are summarized in Table 5. Table 5: AED Drug Interactions with Immediate-Release (IR) Oxcarbazepine AED Coadministered (daily dosage); IR-Oxcarbazepine (daily dosage); Influence of IR-Oxcarbazepine on AED Concentration Mean Change (90% Confidence Interval); Influence of AED on MHD Concentration (Mean Change, 90% Confidence Interval). Carbamazepine (400-2000 mg): 900 mg, nc1, 40 % decrease [Cl: 17% decrease, 57% decrease]; Phenobarbital (100-150 mg): 600-1800 mg, 14% increase [Cl: 2% increase, 24% increase]; 25% decrease [Cl: 12% decrease, 51% decrease]. Phenytoin (250-500 mg): 600-1800 >1200-2400, nc1,2 up to 40% increase3 [Cl: 12% increase, 60% increase], 30% decrease [Cl: 3% decrease, 48% decrease]. Valproic Acid (400-2800 mg): 600-1800, nc1, 18% decrease [Cl: 13% decrease, 40% decrease]. Lamotrigine (200 mg): 1200, nc1, nc1. 1 nc denotes a mean change of less than 10%; 2Pediatrics; 3 Mean increase in adults at high doses of immediate-release oxcarbazepine Hormonal Contraceptives Coadministration of immediate-release oxcarbazepine with an oral contraceptive has been shown to influence the plasma concentrations of two components of hormonal contraceptives, ethinylestradiol (EE) and levonorgestrel (LNG). The mean AUC values of EE were decreased by 48% [90% CI: 22-65] in one study and 52% [90% CI: 38-52] in another study. The mean AUC values of LNG were decreased by 32% [90% CI: 20-45] in one study and 52% [90% CI: 42-52] in another study. Other Drug Interactions Calcium Antagonists: After repeated coadministration of immediate-release oxcarbazepine, the AUC of felodipine was lowered by 28% [90% CI: 20-33]. Verapamil produced a decrease of 20% [90% CI: 18-27] of the plasma levels of MHD after coadministration with immediate-release oxcarbazepine. Cimetidine, erythromycin and dextropropoxyphene had no effect on the pharmacokinetics of MHD after coadministration with immediate-release oxcarbazepine. Results with warfarin show no evidence of interaction with either single or repeated doses of immediate-release oxcarbazepine. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis In two-year carcinogenicity studies, oxcarbazepine was administered in the diet at doses of up to 100 mg/kg/day to mice and by gavage at doses of up to 250 mg/kg/day to rats, and the pharmacologically active 10-hydroxy metabolite (MHD) was administered orally at doses of up to 600 mg/kg/day to rats. In mice, a dose-related increase in the incidence of hepatocellular adenomas was observed at oxcarbazepine doses ≥70 mg/kg/day or approximately 0.1 times the maximum recommended human dose (MRHD) on a mg/m2 basis. In rats, the incidence of hepatocellular carcinomas was increased in females treated with oxcarbazepine at doses ≥25 mg/kg/day (0.1 times the MRHD on a mg/m2 basis), and incidences of hepatocellular adenomas and/or carcinomas were increased in males and females treated with MHD at doses of 600 mg/kg/day (2.4 times the MRHD on a mg/m2 basis) and ≥250 mg/kg/day (equivalent to the MRHD on a mg/m2 basis), respectively. There was an increase in the incidence of benign testicular interstitial cell tumors in rats at 250 mg oxcarbazepine/kg/day and at ≥250 mg MHD/kg/day, and an increase in the incidence of granular cell tumors in the cervix and vagina in rats at 600 mg MHD/kg/day. Mutagenesis Oxcarbazepine increased mutation frequencies in the Ames test in vitro in the absence of metabolic activation in one of five bacterial strains. Both oxcarbazepine and MHD produced increases in chromosomal aberrations and polyploidy in the Chinese hamster ovary assay in vitro in the absence of metabolic activation. MHD was negative in the Ames test, and no mutagenic or clastogenic activity was found with either oxcarbazepine or MHD in V79 Chinese hamster cells in vitro. Oxcarbazepine and MHD were both negative for clastogenic or aneugenic effects (micronucleus formation) in an in vivo rat bone marrow assay. Impairment of Fertility In a fertility study in which rats were administered MHD (50, 150, or 450 mg/kg) orally prior to and during mating and early gestation, estrous cyclicity was disrupted and numbers of corpora lutea, implantations, and live embryos were reduced in females receiving the highest dose (approximately two times the MRHD on a mg/m2 basis). RA-OXT-BS-PV2

Six Distinguished Scientists Highlight Basic, Translational Research in Today's Plenary Continued from cover

Single Cell Analysis to Capture Disease Signatures in Neurological Disease Burkhard Becher, PhD University of Zurich, Zurich, Switzerland

Emerging Therapies for Neurogenetic Diseases Beverly L. Davidson, PhD The Children’s Hospital of Philadelphia, Philadelphia, PA

Prion-like Propagation of Alpha-synuclein Assemblies and the Molecular Basis of Distinct Synucleinopathies Ronald Melki, PhD Paris-Saclay Institute of Neuroscience, Paris, France

Bridging Biophysics and Neurology: The Role of Phase Transitions in Neurodegeneration J. Paul Taylor, MD, PhD St. Jude Children’s Research Hospital, Memphis, TN

The Silent Culprit in Neurocritical Care of Acute Brain Injury: Spreading Depolarizations Jed Hartings, PhD University of Cincinnati, Cincinnati, OH

The Gut Microbiota and Pediatric Multiple Sclerosis Helen Tremlett, PhD, BPharm University of British Columbia, Vancouver, Canada What is your "aha" moment from the Frontiers in Neuroscience Plenary Session? Join the conversation at #AANAM. 

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Practice Leadership Program Graduates Develop New Practice Support Network The group of AAN members who graduated from the Practice Leadership Program in 2018 decided they wanted to give back to the AAN. Out of this desire, they worked with Academy to create the new Practice Support Network to better facilitate answering member questions directed to the practice@aan.com inbox. The practice @aan.com inbox was a concept generated by the Markowski Small and Solo Task Force in 2016. Members direct their questions regarding practice issues—such as payers, MIPS/MACRA, coding, and practice management— to this email address, and staff members respond within one business day. Now, staff has the additional assistance from a group of practicing neurologists comprising the Practice Support Network. “The 10 Practice Leadership Program graduates met at the Annual Meeting in Los Angeles and brainstormed how we could ‘give back’ to the AAN,” said participant Michael E. Markowski, DO, FAAN. “We proposed a system to assist our fellow neurologists in practice, in particular those who may be

geographically isolated or unable to take advantage of some of the AAN resources through Annual Meetings or leadership programs. We felt this would be the best way for neurologists to support each other, in particular our colleagues struggling with practice-related issues. Over the course of the meeting, we met with multiple AAN staff members and learned that neurologists contact the AAN regularly with a variety of practice-related questions, many of which may be best answered by a practicing neurologist. I have seen firsthand over many years that the AAN has incredible staff throughout the organization, however, many member questions could be best addressed by a neurologist who has encountered that same issue and is better able to provide advice based on shared experiences. These discussions ultimately led to the creation of the AAN’s new Practice Support Network.” Questions submitted by members to the practice @aan.com inbox are stripped of identifying information for anonymity and forwarded to members of the Practice Support Network. Their insights are then returned, anonymously, by staff to the questioner. In this way, members are free to ask potentially sensitive questions regarding fees, compensation, or legal issues (which is not possible with our other popular collaborative resource, the Synapse™ online communities). 

Social Morals Is Focus of Today’s New Advancing Medicine Talk Patricia Churchland, BPhil, will lead a compelling discussion on "The Origin of Moral Intuitions" beginning at 1:00 p.m. today in Ballroom A. This session is the final in the new series of Annual Meeting talks called Advancing Medicine: Inspiration and Innovation that this week have been exploring where neuroscience intersects with various timely, powerful, and global themes.

Wednesday, May 8, 2019 • AANextra

Throughout her successful career, Churchland has contributed to the fields of neurophilosophy, philosophy of the mind, and neuroethics. Her research has centered on the interface between neuroscience and philosophy with a current focus on the association of morality and the social brain. She is a professor emeritus of philosophy at the University of California, San Diego and adjunct professor at the Salk Institute. 

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Neurodiem is a service from Biogen. Biogen-09301 03/19

Improving Work-life Balance Helps Diversity Leadership Program Participant Achieve Key Goal As a Native American neurologist working in rural Arizona, Michael Stitzer, MD, had a goal he wanted to attain to broaden his impact on his community. But he also knew that job burnout— which affects neurologists at the highest rate within the medical field—could be a threat to reaching this goal. Stitzer is the sole neurologist at the multi-specialty Winslow Indian Health Care Center in rural Arizona, working primarily with family practice and urgent care providers, “two other groups also at high risk of burnout,” he said. Then Stitzer applied for and was accepted into the AAN’s Diversity Leadership Program, and things began to fall into place for him. “Part of the assessments we went over and the readings we discussed in the program were about working on personal goals,” said Stitzer. “For me, a chief one was maintaining work-life balance as my leadership roles grow. I’ve got an amazing, supportive wife Stitzer and two wonderful young children, and making sure I’m being efficient in working toward my professional goals and also putting my personal goals on equal footing has been an effective way in keeping that balance.” According to Stitzer, the program taught him a new framework for mapping out both the tactics and strategy needed for a goal well in advance, making sure to periodically block out time to revise the tactics, as needed, and periodically assessing shortand long-term goals in both professional and personal life to ensure they are in balance. “I’ve been sure to take the time every four to six months to apply the framework from the Diversity Leadership Program, and I feel that helps ensure I’m maximizing my time and energy in a smart way,” he said.

Wednesday, May 8, 2019 • AANextra

Stitzer’s improved understanding in how to strike work-life balance was key in his ability to effectively expand his role within his institution—a goal he’s had since joining in 2012. He was recently appointed to the Indian Health Service’s National Council of Chief Clinical Consultants and credits the training and mentoring he received from the Diversity Leadership Program with helping him achieve the initial goal of role creation right up to appointment. “I’ve taken those same skills to start building the plan to improve care for patients with neurologic diseases across the institution over the next several years,” he explained, “and one of the first steps will be restarting a multi-specialty conference next year, geared towards primary providers within Indian Health Services, where I’ll give several courses on common neurologic diseases and the current standards of care.” In addition, Stitzer’s interest in the topic of work-life balance led to his participation in the ABPN’s Physician Burnout Crucial Issues Forum, a role in which he represented the AAN. “This was a great experience and gave me knowledge and tools I continue to use today,” said Stitzer. He has shared what he’s learned about burnout and balance at the forum with others at his clinic. A portion of his HeadTalks presentations on rural neurology at the 2017 and 2018 AAN Annual Meetings also addressed this important topic. “Helping my wife as she leads our local chapter of Healthy Kids Running Series, making time to get to some of my daughter’s after-school dance classes, and enjoying the wonders my preschool-age son sees in the everyday world have all been as rewarding as anything I've done professionally in the last few years,” he added. Since graduating from the Diversity Leadership Program, Stitzer has also increased his work on diversity issues within the AAN by participating in the AAN's Health Care Disparities Task Force and on the Diversity Leadership Subcommittee.

Applications Now Open for Four AAN Leadership Program Opportunities AAN members can apply until June 17 for four empowering opportunities designed specifically to equip participants with the skills, tools, and confidence to successfully tackle the challenges that lie ahead. Perhaps more than any specific skill, Stitzer is quick to point out the most important thing he took away from the Diversity Leadership Program was the invaluable connections to his mentor, coach, peers, and others in the AAN. “I work in a rural area and am the sole neurologist in my multi-specialty practice, so the interactions and collaborations started in 2016 and since have been invaluable. These connections remain active through formal and informal gatherings at the past two AAN Annual Meetings, and via the Academy’s Synapse community for Leadership Alumni. And I've reached out to both my tribe in California and the Indian Health Center’s Indians Into Medicine Program grant recipient at the University of Arizona about mentoring any students interested in neuroscience, neurology, or the medical field in general.” The AAN wants to help members like Stitzer—and like you— achieve their fullest potential and have the greatest possible positive impact on their patients and communities. Learn more about the AAN’s multiple leadership training opportunities at AAN.com/view/LEAD. The Diversity Leadership Program has been supported in part by ACADIA Pharmaceuticals, Inc., Allergan, Inc., Eli Lilly & Company, Neurocrine Biosciences, Sanofi Genzyme, Supernus Pharmaceuticals, Inc. and UCB, Inc.

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

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

Women Leading in Neurology - An empowering and

inspirational leadership development opportunity designed to tackle gender disparities head-on and help women leaders advance to the top levels of leadership in their fields and within the AAN.

Emerging Leaders - Designed to identify, engage, and

mentor talent among early-career members interested in future leadership roles within the AAN and the field of neurology.

Practice Leadership - Designed to identify and engage solo

and small practitioners interested in helping to shape the future of neurology within the AAN and/or their communities. The program’s flexible schedule easily accommodates the restricted schedules of busy practitioners.

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

2313

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

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

Not actual size

• INGREZZA 80 mg provided rapid and significant reductions in TD severity by 6 weeks1,2 —with continued reductions in TD severity through 48 weeks1,3 • Generally well tolerated in clinical trials across a broad range of adult TD patients1,2 • Selectively inhibits VMAT2, with no appreciable binding affinity for serotonergic or dopaminergic receptors1 • Offers convenient, once-daily dosing without complex titration1 VMAT2, vesicular monoamine transporter 2.

Not an actual patient

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

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

Important Information INDICATION & USAGE

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

IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS

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

WARNINGS & PRECAUTIONS Somnolence

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

QT Prolongation

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

ADVERSE REACTIONS

The most common adverse reaction (≥5% and twice the rate of placebo) is somnolence. Other adverse reactions (≥2% and >placebo) include: anticholinergic effects, balance disorders/falls, headache, akathisia, vomiting, nausea, and arthralgia. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088.

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

for oral use

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

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

Postmarketing Experience

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

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS Somnolence

QT Prolongation INGREZZA may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. In patients taking a strong CYP2D6 or CYP3A4 inhibitor, or who are CYP2D6 poor metabolizers, INGREZZA concentrations may be higher and QT prolongation clinically significant. For patients who are CYP2D6 poor metabolizers or are taking a strong CYP2D6 inhibitor, dose reduction may be necessary. For patients taking a strong CYP3A4 inhibitor, reduce the dose of INGREZZA to 40 mg once daily. INGREZZA should be avoided in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage.

The following adverse reactions have been identified during post-approval use of INGREZZA that are not included in other sections of labeling. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders: hypersensitivity reactions (including allergic dermatitis, angioedema, pruritis, and urticaria) Skin and Subcutaneous Tissue Disorders: rash

DRUG INTERACTIONS

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

ADVERSE REACTIONS

Examples: isocarboxazid, phenelzine, selegiline Strong CYP3A4 Inhibitors Clinical Implication: Concomitant use of INGREZZA with strong CYP3A4 inhibitors increased the exposure (Cmax and AUC) to valbenazine and its active metabolite compared with the use of INGREZZA alone. Increased exposure of valbenazine and its active metabolite may increase the risk of exposure-related adverse reactions. Prevention or Reduce INGREZZA dose when INGREZZA is coadministered with a strong CYP3A4 inhibitor. Management:

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

Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Variable and Fixed Dose Placebo-Controlled Trial Experience The safety of INGREZZA was evaluated in 3 placebo-controlled studies, each 6 weeks in duration (fixed dose, dose escalation, dose reduction), including 445 patients. Patients were 26 to 84 years of age with moderate to severe tardive dyskinesia and had concurrent diagnoses of mood disorder (27%) or schizophrenia/ schizoaffective disorder (72%). The mean age was 56 years. Patients were 57% Caucasian, 39% African-American, and 4% other. With respect to ethnicity, 28% were Hispanic or Latino. All subjects continued previous stable regimens of antipsychotics; 85% and 27% of subjects, respectively, were taking atypical and typical antipsychotic medications at study entry. Adverse Reactions Leading to Discontinuation of Treatment A total of 3% of INGREZZA treated patients and 2% of placebo-treated patients discontinued because of adverse reactions. Common Adverse Reactions Adverse reactions that occurred in the 3 placebo-controlled studies at an incidence of ≥2% and greater than placebo are presented in Table 1.

Table 1:

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

Adverse Reaction1

Examples: Strong CYP3A4 Inducers Clinical Implication:

paroxetine, fluoxetine, quinidine

Prevention or Management:

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

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

INGREZZA (n=262) (%)

Placebo (n=183) (%)

General Disorders Somnolence (somnolence, fatigue, sedation)

10.9%

4.2%

Examples: Digoxin Clinical Implication:

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

5.4%

4.9%

Prevention or Management:

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

4.1%

2.2%

Headache Akathisia (akathisia, restlessness)

3.4% 2.7%

Gastrointestinal Disorders Vomiting Nausea Musculoskeletal Disorders Arthralgia 1

Examples: itraconazole, ketoconazole, clarithromycin Strong CYP2D6 Inhibitors Clinical Implication: Concomitant use of INGREZZA with strong CYP2D6 inhibitors may increase the exposure (Cmax and AUC) to valbenazine’s active metabolite compared with the use of INGREZZA alone. Increased exposure of active metabolite may increase the risk of exposurerelated adverse reactions. Prevention or Consider reducing INGREZZA dose based on tolerability when INGREZZA is coadministered with a strong CYP2D6 inhibitor. Management:

2.7% 0.5%

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

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

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

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

OVERDOSAGE

Human Experience 2.6% 2.3%

0.6% 2.1%

2.3%

0.5%

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

Other Adverse Reactions Observed During the Premarketing Evaluation of INGREZZA

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

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

Management of Overdosage No specific antidotes for INGREZZA are known. In managing overdose, provide supportive care, including close medical supervision and monitoring, and consider the possibility of multiple drug involvement. If an overdose occurs, consult a Certified Poison Control Center (1-800-222-1222 or www.poison.org). For further information on INGREZZA, call 84-INGREZZA (844-647-3992). Distributed by: Neurocrine Biosciences, Inc. San Diego, CA 92130 INGREZZA is a registered trademark of Neurocrine Biosciences, Inc. CP-VBZ-US-0203v3 08/18

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

Mistake #1: Reticent to Be Yourself Bottom-line: Interviewees “try to look good” and come off with a false sense of self that the interviewer actually senses because of a conflict between your persona and your language. When you feel like your light switch is "off" or you feel constricted “flat as a pancake”—inside you come from fear, doubt and judgment. You act over composed and you come across stiff, unmotivated, and robotic. That is not going to get you hired. Preparing for an interview is like writing the first draft of a paper, you practice your possible answers and become more confident with each description of what you’ve done. In contrast, when your light switch is “on” you come from authenticity, fulfillment, and joy; thus, things flow better! When you are awake and aware trusting the answer will come from you and the energetic space of you and the interviewers together—creating a dynamic, you breathe, think, feel, speak, and portray who you really are. Keeping a brain-heart connection is essential to revealing your true self, full of intelligence, passion, skills, talents, and aptitude in a meaningful, memorable way to the interviewers. Remember, interviewers want to get to know you because you will be an integral member of their respected physician team. Furthermore, you are also interviewing them, consider, what would be the best part of work with them?

“I learned to describe things crystal clear and improve phrases for greater impact. You made my day; now, I can talk to the program director in an interview!” —Rakesh, AAN Neurology Career Center participant

Mistake #2: Showing up Unprepared Come to an interview prepared by knowing your top 10 values, top 10 accomplishments along with three situations of conflict, stress, or mistakes, and an up-to-date curriculum vitae. Practice makes perfect or at least the more familiar with your macroscopic and microscopic views of your experience, education, and vivid twominute stories. A simple format: What was the situation, What you did to make it better, and The outcome. Or another story-telling format: Start with the climax, and grip them as you describe the remainder of your captivating or life-changing story. Being prepared can bring a sense of confidence, an organized structure, and primed to talk about yourself. The paradox is to be prepared and yet when things don’t go as planned or as you decided ahead of time, you may fumble and shut down getting stuck or even lost. So, put your attention on your intentions—what

Wednesday, May 8, 2019 • AANextra

you want to convey with your achievements, values, learning situations, etc. Be open to interpersonal dynamics that transpire in real time in an interview and speak up. Be prepared and ready to think on your feet. The form of the interview may throw you a curve ball, let go of the attachment to way you think it should look and go with the question-answer conversation in the moment. Another paradox, you must be prepared and open to seize every opportunity!

“The best part of our coaching appointment was answering your questions and then getting feedback! Going through this mock interview reminded me of my plethora of experiences and how to apply them in future interviews.” —Annise, AAN Neurology Career Center participant

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

Mistake #3: Not Taking Credit Where Credit Is Due Speak up! You’ve earned your accomplishments, skills, and abilities. Now, is the time to portray and describe who you are and what you’ve achieved through your education, clinical experience, team approach, and leadership. Remember, nothing you’ve accomplished is too small or insignificant as long as it has relevant implications. This interview is your platform to portray your mastery of all you’ve become thus far in the medical profession. Describe what you know, what you’ve done, and the rewarding experience you treasure. In general, most people want to, what makes you tick, how you became a doctor, and what your vision is for better health care.

“You put the spotlight on my strengths and my weaknesses. I will keep my confidence and stop trailing off at the end of sentences.” —Mirza, AAN Neurology Career Center participant

Mistake #4: Acting Like You Have No Weaknesses or No Mistakes We all have strengths and weakness. We are human, both in our human-ness and our human-mess. Actually, interviewers want to know your areas of learning. That is why there are so many behavior and personality assessments, to make a great match. Interviewers are assessing you for their

neurology team—and they need to know how they can count on you. Don’t be ashamed or feel “less than” with your weaknesses. Weakness can be a disadvantage, such as procrastination, perfectionism, avoidance, failure to prioritize your energy and your time, etc. The best thing you can do is turn your weaknesses into a positive, such as perfectionism or a superior standard of excellence for a neurologist is a great fit—right on. Be honest with yourself. If you know of your weaknesses, hot buttons, or self-limiting beliefs that hold you back from success and don’t like them, get out of your own way. I invite you to face up to them and get resolution! In the resolution process, you will allow yourself to grow, be more compassionate, and move to the next level. Do you want that kind of freedom? 

“I had a big 'Aha!' I took notes on the steps I need and want to take!” —Ryan, AAN Neurology Career Center participant

“Don’t look up at the ceiling; instead, pay attention to the interviewer. Be more eloquent in wording my goals and weaknesses. I appreciated that!” CESC 19AM AMOD Ad—Half Page Horizontal> AANExtra

Placed in AANExtra —Nina, AAN Neurology Career Center participant 8.25 x 5.4375 +0.125 bleed, 4C

NEVER MISS A SESSION! PRE-ORDER AND SAVE $150 • Watch 500+ hours* of presentations with slides and synchronized audio • Access 200+ programs and syllabi within 24 hours of the completion of the live presentation** • Learn at home, the office, or on the go • Earn credits with integrated CME testing

Order by May 10, 2019, to secure your savings and receive a complimentary pair of wireless ear buds. Supplies are limited! Visit our booth in the Pennsylvania Convention Center: eLearning Networking and Innovation Space, Level 100 (Street)

AAN.com/view/19AMOD *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. **With the move to an online offering, hard drives will not be provided.

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

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

Important Safety Information Infusion-Related Reactions (IRRs) In a controlled clinical study, 19% of ONPATTROtreated patients experienced IRRs, compared to 9% of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache. To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.

Reduced Serum Vitamin A Levels and Recommended Supplementation ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking ONPATTRO. Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g. night blindness). Adverse Reactions The most common adverse reactions that occurred in patients treated with ONPATTRO were upper respiratory tract infections (29%) and infusion-related reactions (19%). Please see brief summary of full Prescribing Information following this ad.

References: 1. Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis. 2013; 8:31. 2. Coutinho P, Martins da Silva A, Lopes Lima JL, et al. Excerpta Medica; 1980:88-98. 3. Vinik EJ, Vinik AI, Paulson JF, et al. J Peripher Nerv Syst. 2014;19:104-119. 4. ONPATTRO [package insert]. Cambridge, MA: Alnylam Pharmaceuticals, Inc; 2018. 5. Adams D, Coelho T, Obici L, et al. Neurology. 2015;85(8):675-682. 6. Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. N Engl J Med. 2018;379(1):11-21. 7. Center for Drug Evaluation and Research. NDA 210922—patisiran—cross-discipline team leader review. U.S. Department of Health and Human Services, Food and Drug Administration; 2018. ONPATTRO is a registered trademark of Alnylam Pharmaceuticals, Inc. © 2019 Alnylam Pharmaceuticals, Inc. All rights reserved. TTR02-USA-00023-012019

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

At 18 months, ONPATTRO demonstrated: Reversal in neuropathy impairment4

Study Design The efficacy of ONPATTRO was demonstrated in a randomized, double-blind, placebo-controlled, multicenter clinical trial in adults with hATTR amyloidosis with polyneuropathy. Patients were randomized to receive ONPATTRO 0.3 mg/kg (N=148) or placebo (N=77) via intravenous infusion once every 3 weeks for 18 months. Primary endpoint: The modified Neuropathy Impairment Score + 7 (mNIS+7) is an objective 304-point assessment of neuropathy that measures cranial nerve function, muscle strength, reflexes, postural blood pressure, quantitative sensory testing, and peripheral nerve electrophysiology. Key secondary endpoint: The Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) scale is a patient-reported assessment that evaluates neuropathy in the following domains: physical functioning/large fiber neuropathy, activities of daily living, symptoms, small fiber neuropathy, and autonomic neuropathy (score range -4 to 136). Select secondary endpoint: The Composite Autonomic Symptom Score 31 (COMPASS 31) is a patient-reported questionnaire that evaluates 6 autonomic domains: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor (score range 0 to 100).

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

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

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

Visit Booth #2401 to find out more.

Lots of Information and Fun Planned for Tomorrow’s Free Brain Health Fair for the Philly Community Each year, the AAN presents the Brain Health Fair, a free event for the local community in which the Annual Meeting is held. Beginning at 10:00 a.m. tomorrow, patients, caregivers, families, and students will gather in Exhibit Hall A to hear from top neurologists about multiple sclerosis, epilepsy, autism, stroke, Alzheimer’s disease, dementia, movement disorders, neuromuscular disease, headache, concussion, traumatic brain injury, pediatric neurology, and more. A number of fun and interactive activities will take place throughout the day that will highlight the wonders of the brain, the latest research advances and new treatments in brain disease, and tips and resources on how attendees can keep their brains healthy. Participants will be able to:

May 9, 2019 • Philadelphia

Learn about the latest neurology news and research from

top neurologists

Hear ABC News Anchor Gray Hall talk about his on-air scare

with a colloid-cyst on his brain

Experience the BrainDome—state-of-the-art audio-visual

show exploring the inner workings of the brain

See presentations about specific neurologic diseases Hold an actual human brain View real animal brains, including mouse and dolphin Meet service dogs Pick up a free bike helmet and other giveaways Explore healthy lifestyle tips and home modifications Tour a Mobile Stroke Unit Español: Get free resources, presentations, and neurologists

to answer questions

Annual Meeting attendees who are interested in volunteering at the Brain Health Fair are encouraged to email wvokaty@aan.com to sign up. The 2019 Brain Health Fair Platinum Sponsor is Celgene; Gold Sponsors are Amgen and Novartis; and Silver Sponsors are Avanir Pharmaceuticals, Eisai, Freeman, Greenwich Biosciences, PSAV Presentation Services, Sanofi Genzyme, Sunovion Pharmaceuticals Inc., Supernus Pharmaceuticals, and Wolters Kluwer. Thank you to Phoenix Lithographing Corporation for their printing donation. 

Wednesday, May 8, 2019 • AANextra

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

Faculty:

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

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

Presentation Title

Faculty Member

7:00 – 7:30 PM

Dinner reception

7:30 – 7:35 PM

Welcome and introduction

Perry Shieh, MD, PhD (Chair)

7:35 – 7:55 PM

Gene therapies: a new frontier for neuromuscular disorders

Meredith Schultz, MD

7:55 – 8:15 PM

A focus on adeno-associated virus (AAV) antibodies

Christopher Walker, PhD

8:15 – 8:35 PM

Biosafety considerations for the clinical use of AAVs

Chris Jenkins, PhD

8:35 – 8:45 PM

Panel discussion

All Speakers Facilitated by Chair

8:45 – 8:55 PM

Questions and answers

All Speakers Facilitated by Chair

8:55 – 9:00 PM

Closing remarks

Perry Shieh, MD, PhD (Chair)

In accordance with Federal Law, all food and beverage are reportable. You will have the opportunity to opt-out of food and beverage upon arrival at the Liberty Ballroom, Philadelphia Marriott Downtown This meeting is not part of the AAN Annual Meeting official programming and no CME is given for attendance. This Industry Therapeutic Update is sponsored and organized by AveXis. ©2019 AveXis, Inc. All Rights Reserved.

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

Run/Walk for Research Sees Big Turnout Continued from cover

Winners Lukas Sveikata, MD and Lisa Thomas

Wednesday, May 8, 2019 • AANextra

MAKE A

S â&#x20AC;&#x2122; N O S N I K PAR L L A C E S U HO AT

9 2 7 # H T BOO

The Best of Philly from Those Who Know It Best As America’s birthplace, Philadelphia is the nation’s first World Heritage City, not to mention the home of the first medical school and first neurology program. Where else can you walk from the sites where political luminaries debated standing up to a king to the home of one of the largest collections of Rodin sculptures outside of Paris before making your way to grab an authentic hoagie? Visit the Philadelphia visitors booths (Broad Street Atrium, spiral staircase on the 200 Level Bridge, or 12 and Arch Street-West Concourse) for more local information, including brochures and help making restaurant reservations. 

Need some ideas? Here you go! Welcome to Philadelphia. In addition to enjoying the spectacular AAN Annual Meeting, make sure you take time to explore. Take a stroll thru Olde City where our nation was founded. Also make sure to walk down the beautiful Benjamin Franklin Parkway to the Art Museum with a soft pretzel or cheesesteak in hand. Enjoy the city I call home. —Jonathan P. Hosey, MD, FAAN

St. Luke’s University Health Network, Bethlehem, PA Chair, Industry Relations Subcommittee Member, AAN Board of Directors

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

Wednesday, May 8, 2019 • AANextra

JO I N US

C OMMIT MENT T O

CU RE S MAY 8 , 2019 | P H I L ADE L P H I A

Support the important work to cure brain diseases and disorders while enjoying an evening at one of Philadelphiaâ&#x20AC;&#x2122;s historical treasures. Join us at The Union League of Philadelphia to celebrate a community driven to find a cure. For tickets and more information, please visit AmericanBrainFoundation.org/C2C

Bedlack Named Winner of Brainstorm Competition

Wednesday's AAN Section Meetings 8:00 a.m.–9:00 a.m. Consortium of Neurology Advanced Practice Providers Meeting / 117

8:15 a.m.–9:15 a.m. Neural Repair and Rehabilitation Section / 103 A

12:00 p.m.–1:00 p.m. Endovascular and Interventional Neurology Section / 103 A The innovative idea of Richard Bedlack, MD, PhD, FAAN, for ALSUntangled led to the grand prize at Brainstorm: A Competition for the Innovator in All of Us. From left, competition judges Brad C. Klein, MD, MBA, FAAN, Pearce Korb, MD, FAAN, and Daniel Ackerman, MD, and Bedlack. The exciting competition had contestants vying for the $1,500 grand prize through presentation of their inventive solutions to challenges related to neurology-related issues in front of a panel of judges. The judges provided constructive feedback before turning it back to the contestants who had to think quickly before presenting refinements and improvements. Bedlack will also receive a consultation with the AAN Business Innovation team.

Women’s Issues in Neurology Section / 103 B

2:00 p.m.–3:00 p.m. Ethics Section / 103 A LGBTQI Section / 103 B

4:00 p.m.–5:00 p.m. Multiple Sclerosis Section / 103 A

5:00 p.m.–6:00 p.m. Section Member Reception / Exhibit Hall E

5:30 p.m.–6:00 p.m. Behavioral Neurology Section / 103 A

5:45 p.m.–6:45 p.m.

WEDNESDAY, MAY 8 11:30 A.M. TO 1:00 P.M. Locations: Exhibit Hall E (limited quantities available at Broad Street Atrium)

Option I:

Chilled Herb Seared Chicken

Quinoa, Broccolini, and Roasted Tomatoes with Banyuls Vinaigrette

Mediterranean Veggie Salad with Baby Arugula and Lemon Oregano Vinaigrette

Sugar Cookie

Option II: Vegan/Vegetarian/Gluten Free

Chilled Herb Seared Tofu

Quinoa, Broccolini, and Roasted Tomatoes with Banyuls Vinaigrette

Mediterranean Veggie Salad with Baby Arugula and Lemon Oregano Vinaigrette

Sugar Cookie

Autoimmune Neurology Section / 103 B

New! Enjoy Networking Time with Fellow Section Members Meet your fellow section members and network at the new Section Member Reception tonight from 5:00 p.m. to 6:00 p.m. in the Poster Hall (Exhibit Hall E). Drink tickets and light refreshments will be available for all section members.

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

Hailey Orgass @HaileyOrgass Future neurologists #AANAM #AANadvocacy

Eric Anderson MD PhD @Teleneurology Fascinating historical artifacts up near the wellness nook at #AANAM

Neha Dangayach @drdangayach @AANMember #AANAM being an AAN member means to grow in respect & awe of all the amazing things that #neurology and #neurologists all over the world are doing. It means to push boundaries and to stand on the shoulder of giants to provide the best possible #patientcenteredcare

Find the Latest Research at Today’s Poster Session Today’s poster session runs from 11:30 a.m. to 6:30 p.m., with author standby taking place daily between 5:30 p.m. and 6:30 p.m. To help you navigate your way to the breakthrough research of most interest to you, each of the five sessions in this year’s hall are arranged in 10 topicrelated “neighborhoods.” The example below shows how making your way to your favorite poster is now as easy as 1-2-3. In addition, tours of similar-themed posters will occur daily during the poster hall’s open hours to help visitors focus in on their areas of interest.  Publication Code Example: P4.2-003 • P4 = Poster Session Number • 2 = Neighborhood • 003 = Poster Board Number

Check out what’s in each neighborhood during today’s poster session:

Poster Session 4 1. Aging, Dementia, Cognitive, and Behavioral Neurology: 1-001 to 1-029 2. MS and CNS Inflammatory Disease: 2-001 to 2-106 3. Cerebrovascular Disease and Interventional Neurology: 3-001 to 3-071 4. Neuromuscular Disease and Clinical Neurophysiology (EMG): 4-001 to 4-041 5. Epilepsy/Clinical Neurophysiology (EEG): 5-001 to 5-036 6. Neuroepidemiology; Child Neurology and Developmental Neurology: 6-001 to 6-072 7. Movement Disorders ePosters: 7-001 to 7-010 8. Movement Disorders: 8-001 to 8-052 9. Infectious Disease; Research Methodology, Education, and History; Practice, Policy, and Ethics: 9-001 to 9-081 10. Headache: 10-001 to 10-025

1 2 3

1-001-1-029

Wednesday, May 8, 2019 • AANextra

3-001-3-071

4 5 6

4-001-4-041

5-001-5-036

6-001-6-072

7-001-7-010

ePosters

8 9 10

8-001-8-052

2-001-2-106

9-001-9-081

10-001-10-025

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

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

Genentech Pipeline Presentation

Neuromyelitis Optica Spectrum Disorder Presentation

Dr Susan Begelman, MD, FACC

Dr Adil Javed, MD, PhD

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

Associate Professor of Neurology The University of Chicago Chicago, Illinois

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

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

Spinal Muscular Atrophy Presentation Dr Claudia A. Chiriboga, MD, MPH

Multiple Sclerosis Presentation

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

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

Monday, May 6th 11:30 am and 3:30 pm Huntington’s Disease Presentation Dr Victor Sung, MD Associate Professor, UAB Department of Neurology, Division of Movement Disorders Director, UAB/HDSA Huntington’s Disease Center of Excellence Birmingham, Alabama

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

At Biogen our MISSION is clear

WE ARE PIONEERS IN NEUROSCIENCE

Since our founding in 1978, Biogen has led innovative scientific research with the goal of defeating devastating neurological diseases. Today, our focus on neuroscience, our deep scientific expertise, and our courage to take risks continue to make us leaders in the research and development of medicines to transform neuroscience and benefit society.