Podcasts about biogen idec

In this exciting episode of Everything is Personal, host Len May welcomes Dr. Shane Johnson, MD, an expert in biotechnology, healthcare, and cannabinoid science. With a career spanning strategic business advisory roles at companies like Biogen Idec, Amgen, and Genentech, Dr. Johnson brings unparalleled expertise to the conversation. Dr. Johnson, now a prominent figure in the cannabis and cannabinoid science space, shares his journey from advising global biotech companies to co-founding one of Nevada's leading cannabis producers. As a board member of several cannabis-related companies, Dr. Johnson dives deep into: The intersection of biotechnology and cannabinoid science. How cannabinoids are shaping the future of personalized medicine. The clinical opportunities in the cannabis sector and the potential health benefits. His work developing innovative cannabis products, including a patented lozenge. Listeners will gain valuable insights into the cutting-edge world of cannabinoids, and how it's transforming healthcare and wellness.

Synthesis, a process that may sound complex, is actually quite common in our daily lives. From the production of everyday items like Advil, organic milk, citric acid, to the creation of vitamins A and D, and multivitamins, synthesis is a key player.Why does this realization often provoke a negative reaction? Perhaps it's because there's a desire for clean, safe, and consistent natural products, especially when they originate from plants.Surprisingly, synthesis enhances our ability to deliver such products.This week, we're joined by Shane Johnson to delve into the following topics: How minors are manufactured, synthetic vs. biosyntheticUpcoming Minors to keep an eye onNovel APIs & AnalogsAbout Dr. Shane JohnsonDr. Shane Johnson's career has focused principally on offering strategic business advisory services to companies in the biotechnology and healthcare sectors. His work has included guiding regulatory strategy, product portfolio assessment and valuations, and product development and launch strategies for companies including Biogen Idec, Amgen, and Genentech.  Shane was a Principal at Hamilton BioVentures (a Life Science venture capital firm), an Engagement Manager at L.E.K. Consulting (an international strategy consulting firm), and held operational roles in several early stage companies. For the past 4 years, Shane's work has been focused on the cannabis and cannabinoid science space, and he has developed a strong working knowledge of clinical opportunities in the sector.  He is currently on the Board of Directors of several cannabis-related companies, and is a co-founder of one of Nevada's leading cultivators and producers of premium cannabis products including a patented lozenge. Shane holds a B.A. in Studio Art and a B.S. in Neuroscience (with honors) from Brown University, an M.D. from the Stanford University School of Medicine, and is a Fulbright Scholar.Guest Links https://www.baymedica.com/https://www.linkedin.com/in/shanejohnson3/https://www.youtube.com/channel/UC-XRZ0FMzcWgFL_mqdAOPRwhttps://twitter.com/BayMedicaFollow us: Our Links.At Eighth Revolution (8th Rev), we provide services from capital to cannabinoid and everything in between in the cannabinoid industry.8th Revolution Cannabinoid Playbook is an Industry-leading report covering the entire cannabis supply chain The Dime is a top 5% most shared  global podcastThe Dime is a top 50 Cannabis PodcastSign up for our playbook here:

Synthesis, a process that may sound complex, is actually quite common in our daily lives. From the production of everyday items like Advil, organic milk, citric acid, to the creation of vitamins A and D, and multivitamins, synthesis is a key player.Why does this realization often provoke a negative reaction? Perhaps it's because there's a desire for clean, safe, and consistent natural products, especially when they originate from plants.Surprisingly, synthesis enhances our ability to deliver such products.This week, we're joined by Shane Johnson to delve into the following topics: How minors are manufactured, synthetic vs. biosynthetic  Upcoming Minors to keep an eye on  Novel APIs & AnalogsAbout Dr. Shane JohnsonDr. Shane Johnson's career has focused principally on offering strategic business advisory services to companies in the biotechnology and healthcare sectors. His work has included guiding regulatory strategy, product portfolio assessment and valuations, and product development and launch strategies for companies including Biogen Idec, Amgen, and Genentech.  Shane was a Principal at Hamilton BioVentures (a Life Science venture capital firm), an Engagement Manager at L.E.K. Consulting (an international strategy consulting firm), and held operational roles in several early stage companies. For the past 4 years, Shane's work has been focused on the cannabis and cannabinoid science space, and he has developed a strong working knowledge of clinical opportunities in the sector.  He is currently on the Board of Directors of several cannabis-related companies, and is a co-founder of one of Nevada's leading cultivators and producers of premium cannabis products including a patented lozenge. Shane holds a B.A. in Studio Art and a B.S. in Neuroscience (with honors) from Brown University, an M.D. from the Stanford University School of Medicine, and is a Fulbright Scholar.Guest Links https://www.baymedica.com/https://www.linkedin.com/in/shanejohnson3/https://www.youtube.com/channel/UC-XRZ0FMzcWgFL_mqdAOPRwhttps://twitter.com/BayMedicaFollow us: Our Links.At Eighth Revolution (8th Rev), we provide services from capital to cannabinoid and everything in between in the cannabinoid industry.8th Revolution Cannabinoid Playbook is an Industry-leading report covering the entire cannabis supply chain The Dime is a top 5% most shared  global podcastThe Dime is a top 50 Cannabis PodcastSign up for our playbook here:

Synthesis, a process that may sound complex, is actually quite common in our daily lives. From the production of everyday items like Advil, organic milk, citric acid, to the creation of vitamins A and D, and multivitamins, synthesis is a key player.Why does this realization often provoke a negative reaction? Perhaps it's because there's a desire for clean, safe, and consistent natural products, especially when they originate from plants.Surprisingly, synthesis enhances our ability to deliver such products.This week, we're joined by Shane Johnson to delve into the following topics: How minors are manufactured, synthetic vs. biosynthetic  Upcoming Minors to keep an eye on  Novel APIs & AnalogsAbout Dr. Shane JohnsonDr. Shane Johnson's career has focused principally on offering strategic business advisory services to companies in the biotechnology and healthcare sectors. His work has included guiding regulatory strategy, product portfolio assessment and valuations, and product development and launch strategies for companies including Biogen Idec, Amgen, and Genentech.  Shane was a Principal at Hamilton BioVentures (a Life Science venture capital firm), an Engagement Manager at L.E.K. Consulting (an international strategy consulting firm), and held operational roles in several early stage companies. For the past 4 years, Shane's work has been focused on the cannabis and cannabinoid science space, and he has developed a strong working knowledge of clinical opportunities in the sector.  He is currently on the Board of Directors of several cannabis-related companies, and is a co-founder of one of Nevada's leading cultivators and producers of premium cannabis products including a patented lozenge. Shane holds a B.A. in Studio Art and a B.S. in Neuroscience (with honors) from Brown University, an M.D. from the Stanford University School of Medicine, and is a Fulbright Scholar.Guest Links https://www.baymedica.com/https://www.linkedin.com/in/shanejohnson3/https://www.youtube.com/channel/UC-XRZ0FMzcWgFL_mqdAOPRwhttps://twitter.com/BayMedicaFollow us: Our Links.At Eighth Revolution (8th Rev), we provide services from capital to cannabinoid and everything in between in the cannabinoid industry.8th Revolution Cannabinoid Playbook is an Industry-leading report covering the entire cannabis supply chain The Dime is a top 5% most shared  global podcastThe Dime is a top 50 Cannabis PodcastSign up for our playbook here:

In this HCI Podcast episode, Dr. Jonathan H. Westover (https://www.linkedin.com/in/jonathanhwestover/) talks with Michael Reidy and Sharon Confessore about anticipating the future of work that relies on interdependence and teamwide accountability for safety standards. See the video here: https://youtu.be/OSmHhPXBFAc. Michael Reidy, a senior consultant at Interaction Associates and former head of the Dublin Institute of Adult Education, has been training teams in safety culture best practices for more than three decades. His expertise has supported companies around the world, including Alkermes, Abt Associates, Baltimore Gas & Electric-Calvert Cliffs Nuclear, Biogen Idec, Bon Secours Health System, Catholic HealthCare Partners, Curtiss Wright Flow Control, Dell (EMEA), GE Capital, GE Crotonville (MDC) (ECLP), International Paper, Medtronic, Nokia, Library of Congress, and Sirtex.  Sharon Confessore is a health system executive experienced in talent development, training, leadership development, executive coaching, change management, innovation adoption, organization culture, and restructuring. She is known for creating people-focused strategies and best practices for implementing corporate-wide learning solutions, which she's applied as the Chief Learning Officer of a regional faith-based health system and as a unit head of a fully integrated national health system. Check out Dr. Westover's new book, 'Bluer than Indigo' Leadership, here: https://www.innovativehumancapital.com/bluerthanindigo.       Check out Dr. Westover's book, The Alchemy of Truly Remarkable Leadership, here: https://www.innovativehumancapital.com/leadershipalchemy.       Check out the latest issue of the Human Capital Leadership magazine, here: https://www.innovativehumancapital.com/hci-magazine.   Ranked #6 Performance Management Podcast: https://blog.feedspot.com/performance_management_podcasts/  Ranked #6 Workplace Podcast: https://blog.feedspot.com/workplace_podcasts/  Ranked #7 HR Podcast: https://blog.feedspot.com/hr_podcasts/  Ranked #12 Talent Management Podcast: https://blog.feedspot.com/talent_management_podcasts/  Ranked in the Top 20 Personal Development and Self-Improvement Podcasts: https://blog.feedspot.com/personal_development_podcasts/  Ranked in the Top 30 Leadership Podcasts: https://blog.feedspot.com/leadership_podcasts/

Thank you for tuning into my podcast, “Snack Sized Sales,” where I focus on sharing three actionable tips on one topic that you can use to transform your sales. Today, my guest is Jeff Behrens, a serial biotech entrepreneur with experience in general management, business development, finance, and operations. Jeff will highlight the one thing that all successful people have in common and tell us why listening more than talking can help us thrive in sales. He is currently the CEO of GelMEDIX, an ophthalmology startup based on work from Mass Eye and Ear and UCLA. He is also the Founder and CEO of LabShares Newton, a biotech incubator for biotech startups run by biotech entrepreneurs. Formerly, Jeff was President and CEO of Siamab Therapeutics, a biotech company focused on developing antibodies targeting glycan targets in cancer that he exited in 2019. Previously, Jeff served as Senior Director, Business Development and Operations at Edimer Pharmaceuticals (funded by Third Rock Ventures) and also worked at Alnylam and Biogen Idec, where co-founded Biogen's Innovation Incubator.  In 2003, Jeff sold his healthcare IT company, The Telluride Group, to mindSHIFT Technologies, a Fidelity-funded rollup. Jeff has a Ph.D. from EPFL (Lausanne, Switzerland), an MS from the Harvard/MIT Division of Health Sciences and Technology (HST), an MBA from MIT Sloan, and graduated from Harvard College. He teaches HST590, a Ph.D. level course at MIT, and lives in Newton and Wellfleet, MA. This is one episode you won't wanna miss so stay tuned. On Today's Episode of Snack Sized Sales: Being in business and healthcare simultaneously (02:24) Success by being in a sales mode most of the time (03:32) A necessary mind shift needed to succeed as a salesperson (05:22) The multi-step sales process of raising funding for a biotech business (06:40) Listening and asking relevant questions versus lecturing (07:00) Building a sales team around getting a product out to market (10:20) One thing that's missing in a lot of sales organizations today (12:47) Connect with Jeff Behrens: https://www.linkedin.com/in/jbehrens/ (Jeff on LinkedIn) Email Jeff at Jeff@LabShares.com Rate, Review, Learn, and Share Thanks for tuning into the Snack Sized Sales podcast! If you enjoyed this episode and want to learn even more about what it takes to simplify and transform your company's back-office and online customer journey. Don't forget to tune into our other shows and share your favorite episodes on social media! Join the community of Snack Sized Sales fans onhttps://www.facebook.com/WesleyneGreerCEO ( Facebook), https://twitter.com/WesleyneGreer (Twitter),https://www.linkedin.com/in/wesleynegreer/ ( LinkedIn) and https://www.transformedsales.com/ (visit my website )for even more content, information, and resources about leveraging the media.

Dr. Parkinson has served as President and Chief Executive Officer of ESSA Pharma Inc. since January 2016, and as a Director of the company since June 2015. Prior to joining ESSA he had been a Venture Partner at New Enterprise Associates, Inc. From 2007 until 2012, Dr. Parkinson served as President and CEO of Nodality, Inc., a biotechnology company focused on the biological characterization of signaling pathways in patients with malignancy. Until October 2007 he was SVP, Oncology Research and Development at Biogen Idec, where he oversaw all oncology discovery research efforts and the development of the oncology pipeline. Previously he had served as VP, Oncology Development, at Amgen and VP, Global Clinical Oncology Development, at Novartis. In those roles he oversaw the successful clinical development of a series of cancer therapeutics, including Gleevec, Zometa, Femara, and Vectibix. Dr. Parkinson worked at the National Cancer Institute from 1990 to 1997, serving as Chief of the Investigational Drug Branch and then as Acting Associate Director of the Cancer Therapy Evaluation Program (CTEP). He is a past Chairman of the Food & Drug Administration (FDA) Biologics Advisory Committee, a past member of the FDA Science Board, and is a recipient of the FDA’s Cody Medal. He is a past editor of the Journal of Immunotherapy and past president of the Society of Biological Therapy. He has served on the National Cancer Policy Forum of the Institute of Medicine and is a past co-chair of the Cancer Steering Committee of the NIH Foundation Biomarkers Consortium. A past Board Director of the Ontario Institute for Cancer Research, he currently serves as a Board Director for the Multiple Myeloma Research Foundation. He served as Chairperson of the American Association of Cancer Research (AACR) Finance and Audit Committee for 15 years and is a previous elected Board Director of AACR. Dr. Parkinson was a Director of Facet Biotech, Inc., until the acquisition by Abbott Pharmaceuticals, and was a Director of Ambit Biosciences until the acquisition by Daiichi Sankyo. He was also previously a Director at Threshold Pharmaceuticals and Cerulean Pharmaceuticals. He currently serves as Director on the Boards of CTI Biopharma, Inc (CTIC), 3SBio Inc (1530.HK) and is a Co-Founder and Director of Refuge Biotech, Inc. He has held academic positions both at Tufts and at the University of Texas MD Anderson Cancer Center, and has authored over 100 peer-reviewed publications.

This episode is sponsored by Davwill Consulting Inc. - Looking to review your team?Rob Greenly is a savvy, experienced executive coach and organizational effectiveness consultant. He draws upon twenty years of corporate experience and ten years as a coach and consultant to help his clients maximize their leadership and organizational potential. He applies expertise in leadership coaching, communications, conflict negotiation, team building, performance management, culture & organization change, and training to achieve consistent success for clients. Clients give Rob rave reviews for coaching them—and facilitating their teams—to navigate successfully in large, complex organizations. He draws upon his own firsthand experience as a senior leader and shares lessons-learned from his tenure as Vice President of Leadership and Organization Development—Boston Scientific, Director of OD and Training—Astra Pharmaceuticals, Director of Leadership at the MIT Sloan School of Management, and Chief Administrative Officer for Human Resources—Putnam Investments. Rob has provided executive coaching and/or has developed and delivered programs in management, leadership, team building, organization development, and competency modeling with pragmatic applications, for a wide-range of biopharma/healthcare/medical device clients, including AstraZeneca, Biogen Idec, Covidien, Genzyme, Harvard-Vanguard Medical Associates/Atrius Health, The Medicines Company, Millennium Pharmaceuticals, Novartis Institutes for Biomedical Research, Schering-Plough, and UMass Memorial Medical Center. Also, Rob has coached or consulted to CVS/Pharmacies, General Electric, Harvard University, IBM, Liberty Mutual, Merrill Lynch, National Institutes of Corrections, Northeastern University, the US Navy, and others.Rob's Website - http://www.greenlygroup.com/--- Send in a voice message: https://anchor.fm/deb-crowe/message This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit debcrowe.substack.com

During this mini episode, You, Me, and Your Top Three host and CGS Advisors CEO, Gregg Garrett, speaks with Dr. Ethan Becker, president of Boston-based communications firm The Speech Improvement Company. He speaks about communication in times of crisis and disruption; specifically, the long-term effects of this pandemic on general communication and best practices for communicating online and through various digital platforms. Dr. Becker also addresses the importance of listening to effectively communicate. About Dr. Ethan Becker Dr. Ethan F. Becker is a second-generation Executive Speech Coach and Trainer with the 56 year old global business, The Speech Improvement, Inc. He is co-author of the international best-selling book Mastering Communication at Work: How to lead, manage, and influence, which is published worldwide by McGraw-Hill.  The book is also an Amazon #1 best seller in 13 categories. Ethan has developed and delivered powerful customized motivational speeches on various topics related to communication worldwide. In addition to group work, Ethan serves as trusted advisor and executive communication coach to many. In addition to helping business partners in nearly all of the United States, Dr. Becker has unique international experience. He has lived in Kuala Lumpur Malaysia where he immersed himself in the Asian culture conducting research, training, and coaching with the ICLIF leadership and governance center. In addition, he has coached and presented in countries such as China, Japan, Australia, Singapore, Korea, Germany, England, Thailand, and many more. This provides him with valuable international and cultural perspectives, which he brings to his clients. Ethan has taught at and helped such organizations such as Harvard University, John’s Hopkins University, Boston Scientific, Petronas, Apple, Tenaga Nasional, Bank Negara, The New York Giants, Bain Capital, Canon USA, Biogen IDEC, Telekom Malaysia, Maybank, Kenanga, AmBank, RAZAK School of Government, FBI, Biogen Idec, Shire, Magenta, Atlas Ventures, Translate Bio, Cadent Therapeutics, Surface Oncology,  Constellation Pharmaceuticals, Northeast Human Resources Association, Kronos, SuriaKLCC, and IBM, as well as countless individual executives, managers, politicians, celebrities and other clients from around the world. Dr. Becker holds 2 doctorates. His latest is a PhD focused on industry and organizational psychology from the Harold Able School of social behavior and sciences at Capella University. A second doctorate in human letters from Fitchburg State University, an MBA from the school of business and technology at Capella University, with a dual focus on International Business Communication and Leadership, and a BS in mass communication.  Show Highlights 1:00        The importance of communication to build relationships in a social distanced, self-isolated way. 2:04        Dr. Ethan Becker – president of The Speech Improvement Company. 5:00        Short-and long-term effects of social distancing and isolation on communication. 9:08        A focus on tools for communicating virtually; how effective are they? 12:30      “How important is listening to make speaking relevant?” 15:40      Quick communication tips for active listening and speaking through digital platforms. Additional Information Contact Dr. Ethan Becker: Becker’s LinkedIn Becker’s email Contact Gregg Garrett: Gregg’s LinkedIn Gregg’s Twitter Gregg’s Bio Contact CGS Advisors: Website LinkedIn Twitter

Can you "teach" consulting?How do the masters learn?What are the universal truths and secrets to success? These are the fundamental question that Dr. Van Latham answers with Dr. Charles Handler in this episode. There has traditionally been no real training for consulting skills. Most of us have learned via experience and many mistakes! There are some central themes that represent tricks of the trade.In this episode, two highly experienced consultants offer words of wisdom to those interested in building consulting careers.Dr. Latham also shares information about the consulting program he teaches at the University of Texas at Dallas.This episode is a must listen for anyone who is looking to up their game when solving problems for clients. Van M. Latham is an Industrial/Organizational psychologist specializing in Human Resources management. Dr. Latham works in all areas of Human Capital, but is known primarily for his work in organizational and leadership development. At PathPoint, he has helped businesses improve organizational capability and performance through effective people practices. He has consulted with some of the world's most recognizable companies and brands, such as American Express, AMD, Ashland, Biogen Idec, CVS/Caremark, Dollar General, Ernst & Young, Foot Locker, Harvard University, Hershey's, Hubbell, Lenovo, McGraw Hill Financial, Marriott, Paychex, PepsiCo, SAP, and Thermo Fisher Scientific.From the launch of his own consulting practice to his work with the University of Texas at Dallas as part of their Organizational Consulting Certificate program, Dr. Latham is the dynamic personality with a wealth of experience to share with listeners, no matter where they are in their own consulting journey.Find more about Dr. Latham and his work at these links:https://pathpointconsulting.com/https://obcc.utdallas.edu/organizational-consulting-certificate/

1. Body mass index, but not vitamin D status, is associated with brain volume change in MS. 2. [What’s Trending]: preventing firearm injury. In the first segment, Dr. Stacey Clardy talks with Dr. Ellen Mowry about her paper on the associations between body mass index and brain volume change in MS. In the second part of the podcast, Dr. Ted Burns focuses his interview with Dr. Christine Laine on preventing firearm injury. Dr. Clardy serves as the Podcast Section Editor for Neurology and has received research support from Western Institute for Biomedical Research (WIBR). Dr. Ellen Mowry has served on a liothyronine study Data and Safety Monitoring Board; serves on the editorial board of Frontiers in Neuroepidemiomology; has received royalties as an UptoDate chapter editor; has received commercial research support from Teva Neuroscience, Biogen Idec, Genzyme, and Sun Pharma; has received governmental research support from the Department of Defense; and has received foundation/society research support from the National Multiple Sclerosis Society and the Patient-Centered Outcomes Research Institute. Dr. Christine Laine serves on the editorial board of Annals of Internal Medicine; has served as the Senior Vice President of American College of Physicians; and has received foundation/society research support from the Robert Wood Johnson Foundation.

Chief Medical Officer at nanoString Technologies, Dr Alessandra Cesano, brings to light the increasingly critical role of predictive biomarkers in cancer immunotherapy, originally presented during the translational science and new technologies session from 2017’s Immuno-Oncology 360° conference. Save the date for the 4th annual IO360° conference, taking place February 7-9, 2018 in New York City. About Dr Cesano: Alessandra Cesano, MD, PhD has served as CMO at nanoString since July 2015. Prior to joining the company, Dr Cesano was Chief Medical Officer at Cleave Biosciences, Inc. From 2008 to 2014, she served as Chief Medical Officer and Chief Operations Officer at Nodality, Inc, where she built and led the R&D groups, while providing the overall clinical vision for the organization. In addition, Dr Cesano has held various management positions at Amgen, Biogen Idec and SmithKline Beecham Pharmaceuticals, where she helped to advance various oncology drugs through late stage development and FDA approvals. Dr Cesano spent 12 years researching tumor immunology, including nine years at the Wistar Institute, an NCI Basic Cancer Center at the University of Pennsylvania. She also holds membership in several professional and scientific societies, and has been an author on over 100 research publications.

Show description/summary:1) Evaluating the safety of beta-interferons in multiple sclerosis 2) Neurology® Today: New Classifications of Seizures and Epilepsies Include New Seizure Types, Simpler TermsThis podcast begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the June 13, 2017 issue of Neurology. In the first segment, Dr. Michael Levy talks with Dr. Helen Tremlett and Dr. Hilda De Jong about their paper on evaluating the safety of beta-interferons in multiple sclerosis. In the next part of the podcast Dr. Nathan Fountain focuses his interview with Dr. Robert Fisher on the new classifications of seizures and epilepsies presented by the International League Against Epilepsy. Disclosures can be found at Neurology.org.DISCLOSURES:Dr. Levy serves on advisory boards for Asterias, Chugai, and Alexion; serves as Editorial Board member of Multiple Sclerosis and Related Disorders; holds patents for an aquaporin-4 sequence that elicits pathogenic T cell response in animal model of neuromyelitis optica, and for use of a peptide for diagnostic and therapeutic developments; has consulted for Guidepoint Global, Gerson Lehrman Group, and Cowen Group; and has received research support from Viropharma/Shire, Acorda, ApoPharma and Sanofi, Genzyme, Alnylam, Alexion, Terumo BCT, National Institute of Neurological Diseases and Stroke, and Guthy-Jackson Charitable Foundation.Dr. Tremlett has served on scientific advisory boards for US National MS Society and the Centers for Disease Control and Prevention; is the Canada Research Chair for Neuroepidemiology and Multiple Sclerosis; has received research support from the National Multiple Sclerosis Society, the Canadian Institutes of Health Research, Canada Foundation for Innovation, the Multiple Sclerosis Society of Canada, US National Multiple Sclerosis Society, Multiple Sclerosis Scientific Research Foundation, Michael Smith Foundation for Health Research, and the UK MS Trust; has received speaker honoraria and/or travel expenses to attend conferences from the Consortium of MS Centres, the National MS Society, ECTRIMS, the Chesapeake Health Education Program, US Veterans Affairs, Novartis Canada, Biogen Idec, American Academy of Neurology.Dr. Fountain is an epileptologist at the University of Virginia Comprehensive Epilepsy Program (100% effort).All other participants report no disclosures.

Show description/summary:1) Epidemiology and Prognosis of Mild Traumatic Brain Injury in Returning Soldiers: A Cohort Study2) What's Trending: Alemtuzumab treatment and multiple sclerosisThis podcast begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the April 18, 2017 issue of Neurology. In the first segment, Dr. Michael Jaffee talks with Dr. Karen Schwab about her paper on mild traumatic brain injury in returning soldiers. For our “What's Trending” feature of the week, Dr. Mark Keegan talks with Dr. Gavin Giovannoni about his paper on alemtuzumab treatment and multiple sclerosis. For more information on traumatic brain injury services for active duty military and veterans, please visit the Defense and Veterans Brain Injury Center website at http://dvbic.dcoe.mil. Disclosures can be found at Neurology.org.DISCLOSURES: Dr. Jaffee serves on the scientific advisory board for Neurohabitation, Inc., and has received research support from the Florida State Department of Elderly Affairs.Dr. Schwab receives research support from Congressionally Directed Medical Research Programs (Grant #W81XWH-08-2-0105).Dr. Keegan serves on the editorial board for Multiple Sclerosis and Related Disorders; served as eMedicine Chief Editor from 2009 to 2015; receives publishing royalties for Common Pitfalls in Multiple Sclerosis and CNS Demyelinating Diseases: Case-Based Learning (Cambridge University Press 2016); consults for Novartis, Bristol Meyers Squibb, and Bionest; and received research support from Biogen for the ARISE study.Dr. Giovannoni consulted and served on scientific advisory boards for Biogen-Idec, Fiveprime, Genzyme, GW Pharma, Ironwood, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Synthon BV, Teva, Vertex Pharmaceuticals, Abbvie, and Canbex; receives speaker honoraria from Biogen-Idec, Genzyme, GW Pharma, Merck-Serono, Novartis, Roche, and Teva Pharmaceuticals; serves as an editor for Multiple Sclerosis and Related Disorders; served on speaker's bureaus for Novartis and Teva; and received research support from Genzyme and Merck.

Show description/summary:1) Practice guideline summary: Sudden unexpected death in epilepsy 2) What's Trending: 21st Century Cures ActThis podcast begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the April 25, 2017 issue of Neurology. In the first segment, Dr. Andrew Schomer interviews Dr. Cynthia Harden about the AAN practice summary guideline on sudden unexpected death in epilepsy (SUDEP). Then, for our “What's Trending” feature of the week, Dr. Jason Crowell talks with Dr. Nicholas Johnson about the 21st Century Cures Act. Disclosures can be found at Neurology.org.DISCLOSURES: Dr. Johnson serves as Associate Editor for Neurology: Genetics; receives research support from Ionis Pharmaceuticals, Biogen Idec, Balerion Therapeutics, Cytokinetics, Acceleron, NINDS (grant 1K23NS091511-01), Muscular Dystrophy Association, and Myotonic Dystrophy Foundation; and consults for AMO Pharma and AveXis. Dr. Schomer, Harden, and Crowell report no disclosures.

Show description/summary:1) Progressive rural-urban disparity in acute stroke care2) What's Trending: Upcoming changes regarding the Neurology® Resident & Fellow section 3) Topic of the Month: Neuromuscular topicsThis podcast begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the January 31, 2017 issue of Neurology. In the first segment, Dr. Andy Southerland talks with Dr. Allison Willis about her paper on disparities in stroke care between rural and urban areas. Dr. Ted Burns talks with Dr. Eric Olsen regarding CRISPR at the 2016 AANEM meeting for our “What's Trending” feature of the week. In the next part of the podcast, Dr. Ted Burns focuses his interview with Dr. Merit Cudkowicz on amyotrophic lateral sclerosis (ALS). Disclosures can be found at Neurology.org.DISCLOSURES: Dr. Southerland serves as Podcast Deputy Editor for Neurology; receives research support from the American Heart Association-American Stroke Association National Clinical Research Program, American Academy of Neurology, American Board of Psychiatry and Neurology, Health Resources Services Administration and the NIH; has a provisional patent application titled: “Method, system and computer readable medium for improving treatment times for rapid evaluation of acute stroke via mobile telemedicine;” and gave legal expert review. Dr. Allison Willis has served on the editorial board of Pharmacoepidemiology and Drug Safety; and has received research support from NIH/NINDS.Dr. Burns serves as Podcast Editor for Neurology®; and has received research support for consulting activities with UCB, CSL Behring, Walgreens and Alexion Pharmaceuticals, Inc. Dr. Eric Olson holds patents describing DMD gene editing.Dr. Merit Cudkowicz has served on the editorial board of DSMB AstraZenica (through Clintrex); has served on the editorial boards of Neurotherapeutics and JAMA Neurology; holds a patent for Metabolomics in ALS; receives publishing royalties from UpToDate; has been a consultant for Cytokinetics, Biogen-Idec, Voyager, Biohaven, Astrazenica, Genentech, Karyopharm, and Neuraltis; has received research support from NINDS, the Muscular Dystrophy Association, the ALS Association, and the ALS Finding a Cure Association; and has provided expert witness for defense (TEVA).All other participants have no disclosures.

1) Progression of brain atrophy in PSP and CBS over six months and one year2) What's Trending: Interview with Mike Amery about Medicare Sustainable Growth Rate repeal and the Medicare Access and CHIP Reauthorization Act 3) Topic of the month: How to examine and approach movement disordersThis podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. John Morgan interviews Dr. Adam Boxer about his paper about on progression of brain atrophy in progressive supranuclear palsy and corticobasal syndrome. Dr. Ted Burns is interviewing Mike Amery for our “What's Trending” feature of the week about Medicare Sustainable Growth Rate repeal and the Medicare Access and CHIP Reauthorization Act. In the next part of the podcast Dr. Alberto Espay interviews Dr. Rodger Elble on the topic of “how to approach” tremor disorders.DISCLOSURES: Dr. Morgan is a consultant for Impax, Lundbeck Inc., National Parkinson Foundation, Teva Pharmaceutical Industries Ltd., and Veloxis; serves on the speakers' bureau of Impax and Teva Pharmaceutical Industries Ltd.; received compensation for review of medical records and expert witness testimony in multiple cases of litigation involving neurologic co; receives research support from National Parkinson Foundation, Parkinson's Outcome Project Grant and the NIH.Dr. Boxer serves on the scientific advisory board for Alector, Asceneuron and Delos; received funding for travel from the International Society for CNS Clinical Trials Methodology, the Movement Disorders Society, the Association for Frontotemporal Degeneration, Fidelity Biosciences Research Institute and the Tau Consortium; is a consultant for Abbvie, Ionis, Janssen and Merck Serono; holds stock options in Alector and Delos; receives research support from Avid, Biogen Idec, BMS, C2N, Cortice, Forum, Genentech, Inc., Janssen, Pfizer Inc, Eli Lilly and Company, Roche, TauRx, The Tau Research Consortium, the Bluefield Project, Corticobasal Degeneration Solutions, the Alzheimer's Association and the NIH.Dr. Ted Burns serves as Podcast Editor for Neurology®; and has received research support for consulting activities with UCB, CSL Behring, Walgreens and Alexion Pharmaceuticals, Inc.Dr. Amery is employed as Legislative Counsel for the American Academy of Neurology.Dr. Espay serves as Associate Editor for the Journal of Clinical Movement Disorders; serves as an editorial board member of Parkinsonism and Related Disorders and The European Neurological Journal; serves on the scientific advisory board for Solvay Pharmaceuticals, Inc. (now Abbvie), Chelsea Therapeutics International, Ltd., Teva Pharmaceutical Industries Ltd., Impax, Merz Pharmaceuticals, Inc., Pfizer Inc, Solstice Neurosciences, Eli Lilly and Company, ACADIA Pharmaceuticals, Inc. and USWorldMeds; is a consultant for Chelsea Therapeutics International, Ltd., Solvay Pharmaceuticals, Inc. (now Abbvie), ACADIA Pharmaceuticals, Inc., Cynapsus and Lundbeck, Inc; receives royalties for publications of books from Lippincott, Williams & Wilkins and Cambridge University Press; serves on the speakers' bureau of UCB, Teva Pharmaceutical Industries Ltd., American Academy of Neurology and Movement Disorders Society; receives research support from the CleveMed/Great Lake Neurotechnilogies, Michael J. Fox Foundation and the NIH.Dr. Elble receives research support from GlaxoSmithKline, Teva Pharmaceutical Industries Ltd., Phytopharm, Pfizer Inc, Ortho-McNeil, Spastic Paralysis Research Foundation of Kiwanis International, Illinois-Eastern Iowa District and the NIH.

1) Reducing costs while enhancing quality of care in MS2) What's Trending: Interview with Lyell Jones about the topic of the Axon Registry and how it interfaces with practice and reimbursement this is part 2 with part 1 appearing last month 3) Topic of the month: Neurology Today story on the AAN Guideline published in Neurology on the topic of recurrent stroke with patent foramen ovaleThis podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Mark Keegan interviews Dr. Ilya Kister about his paper on the various approaches neurologists may contribute to cost containment while maintaining and enhancing the quality of MS care. Dr. Andy Southerland is interviewing Dr. Lyell Jones for our “What's Trending” feature of the week about the topic of the Axon Registry and how it interfaces with practice and reimbursement. This is part 2 with part 1 appearing last month. In the next part of the podcast Dr. Bryan Eckerle interviews Dr. Steven Messe about a Neurology Today story on the AAN Guideline published in Neurology on the topic of recurrent stroke with patent foramen ovale.DISCLOSURES: Dr. Keegan serves as an editorial board member of Multiple Sclerosis and Related Disorders; served as Chief Editor of eMedicine; receives royalties from the publication of the book: Common Pitfalls in Multiple Sclerosis and CNS Demyelinating Diseases: Case-Based Learning; is a consultant for Novartis, Bristol-Meyers Squibb and Bionest; receives research support from Terumo BCT.Dr. Kister serves on the MS Franchise Data Generation advisory board for Biogen Idec and advisory board for Genentech, Inc.; received a one-time consulting fee from Biogen Idec; received research support from Biogen-Idec, Merck Serono, Novartis, Genzyme Corporation; Guthy-Jackson Charitable Foundation and National Multiple Sclerosis Society.Dr. Southerland serves as Podcast Deputy Editor for Neurology; receives research support from the American Heart Association-American Stroke Association National Clinical Research Program, American Academy of Neurology, American Board of Psychiatry and Neurology, Health Resources Services Administration and the NIH; has a provisional patent application titled: “Method, system and computer readable medium for improving treatment times for rapid evaluation of acute stroke via mobile telemedicine;” and gave legal expert review. Dr. Messe received publishing royalties from UpToDate; received compensation from GlaxoSmithKline for consulting on protocol development for a trial of a neuroprotectant in high risk surgery; received research support from GlaxoSmithKline, Bayer Schering Pharma, WL Gore and the NIH.

Full Transcript: [intro music] Host – Dan Keller Hello, and welcome to Episode Seventy-eight of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m Dan Keller. A lot can be learned about pregnancy and MS by tracking pregnant women and their offspring over time. Dr. Dessa Sadovnick, a professor of medical genetics and neurology at the University of British Columbia in Canada, has started such a registry with international colleagues. I spoke with her at the World Congress of Neurology in Santiago, Chile, in November, where she described these efforts and what a very focused registry can tell us. Interviewee – Dessa Sadovnick I'm not talking about a general registry. What I'm talking about is a pregnancy and outcome registry. So this is not just taking people who have MS and trying to keep track of them. This is looking at actual pregnancy outcomes and what happens to the children after. So it's a very specific type of registry. Interviewer – Dan Keller It seems like there's a multitude of variables you can look at. What sorts of things are you going to be tracking if you get this going? Dr. Sadovnick Well, I think the important factor is that just because you have a disease such as multiple sclerosis doesn't mean you're immune from other factors that can affect pregnancy outcome and child development. So in addition to knowing about drug therapies, disease course, other exposures related to your MS, it's also important to know about your previous pregnancy history, your family history, your basic demographics, including your ethnic background, comorbid diseases which you may also have with the MS. All these factors can affect pregnancy outcome and child health. MSDF Will you be looking at the mother's longitudinally? Or only the children? Dr. Sadovnick Ideally, we'd like to be able to look at the mothers up to a year post-partum, and then follow the children longitudinally. Because there are situations where children do not have a certain disease that the mother may have, but over time, they might be found to have some late onset problems, for example, related to learning disabilities or something like that. MSDF Can you separate those out by biological cause or environmental cause? They're in a household with people who have a disease and have to deal with it. Dr. Sadovnick Well, we know for a fact in terms of MS that there is certainly no transmissibility within a household. We have done a lot of work over the years that show very clearly that the excess of MS you find within biological relatives of people who have MS is very clearly due to genetic sharing, not shared family environment. So from that point of view of the child inheriting MS, we're not looking at the family environment. Obviously, there're many psychological issues and many socioeconomic issues related to having a parent who has a chronic disabling disorder. And the impact this could have on child development must, of course, be taken into consideration. But what I'm trying to look at here is more the general factors in terms of, if the mother is exposed to a disease-modifying therapy at the time of conception or in early gestation, and if there is an adverse outcome in the pregnancy, is that necessarily correlated? Or could that have happened for many other reasons? Similarly, if the child develops problems down the road, could that be related, maybe, to the uterine environment because the mother has an autoimmune disease? Which does not mean the child gets an autoimmune disease, but maybe, in some way, it impacts the autoimmunity long-term? MSDF How long would you have to track children? And how many would you have to track to get meaningful numbers? Dr. Sadovnick Well, this is obviously always a concern, and you would have to track a sizable number. But when you consider how many people there are with MS in North America, and if you could do a centralized registry, I think it's realistic that you follow them at least for a few years after delivering. Once they start reaching their developmental milestones, you can get some ideas. But I think the main factor is that we're always saying, therapy is not indicated if you're contemplating a pregnancy. And this causes many issues for many people. But the evidence for this is so scarce. And my big concern is that, are we really being overly cautious? And we won't know this if every adverse outcome is automatically trying to be related to exposures either at conception or in the early parts of gestation. MSDF Pregnancy itself is immunosuppressive, but it seems women have a rebound after delivery. So what goes on with treatment during pregnancy? Is it okay to stop treatment if they're naturally going to be somewhat immunosuppressed? Dr. Sadovnick This is one of the big areas that we really don't have information, and we need good information. Obviously, if you look at a series of women, what seems to happen is especially in the third trimester, they seem to do better. And then, of course, once you deliver and their hormonal changes take place, there's an increase of relapses after delivery within the first three months. That's not to say women can't have relapses while they're pregnant. That is not to say that women are going to have relapses necessarily after delivery. But if you look at large numbers, this is the pattern. The question then comes up, if you have a relapse while you're pregnant, how severe is the relapse? And how should it be treated? There're no set guidelines. The same way as after delivery, a big factor is whether the mother's breastfeeding or not breastfeeding. In today's society, you're really encouraged to breastfeed, but that could have impacts on how you treat a relapse. The other big issue in terms of pregnancy-related relapses is something that we also experience when we look at people who have MS and they're going into menopause. And that is, are the symptoms really an MS relapse? Or could they be pregnancy-related? If you have a symptom, say you have urinary problems, say you have balance problems, say you have fatigue, how do you measure if this is specifically an MS relapse versus just part of either the later stages of pregnancy, the early stages of pregnancy, or living with a newborn child? There is really nothing concrete on how to measure what's a true relapse, what's a pseudo-relapse. And there are no really specific guidelines on how to treat these symptoms during gestation and immediately after delivery. This is an area that we really need to develop. One of the things that we have been able to do is a lot of people are interested in this topic, but it's never been looked at in a formalized manner using experts from many different areas. So about a year and a half ago, I put together a meeting of a group of people who are interested in reproduction and child health. And we received some funding to have a two-day meeting from the Canadian Institute of Health Research, as well as some money from Teva Neurosciences and Biogen Idec. And what we did is we had a two-day workshop basically saying, is there a need to learn more about this area? And if there is, how can all these specialists work together to try to develop knowledge-based information? So we gave our little virtual network, which has no ongoing funding; it's basically people just working voluntarily. We've given it the name of MS CERCH, which is Center of Excellence for Reproduction and Child Health. And we've put together a voluntary working group. And where we're at right now is we've actually just had a paper published in Obstetrics and Gynecology, the American main journal. They also call it a Green Journal, but it's not neurology. Just talking about limitations, guidelines, what we know and what we don't know about reproduction and child health. So this was published the end of 2014. We're currently working with the American College of Obstetrics and Gynecology to try to have our paper turned into some guidelines for people with multiple sclerosis. We've also just recently as a group published a paper talking about why there is a need for a disease-specific registry rather than a treatment-specific registry. We are also just submitted a manuscript looking at all the issues dealing with males with MS in terms of reproduction and child health, because the focus, of course, is on females. But there're still a lot of males out there, and they face many issues that have not been addressed. And we're in the process of trying to get some funding for the first-ever grant to look prospectively at the occurrence of peripartum depression in both mothers and fathers who have multiple sclerosis, a topic that's never been looked at before. So from our two-day meeting, which was quite casual and informal, we have been able to move forward, and as a group, had some concrete outcomes. And we're hoping that we're be able to move forward with this group, hopefully obtain appropriate funding, and we're be able to, maybe, really come up with some knowledge-based information for people with MS who are contemplating reproduction. Another major area of concern is we're more frequently now identifying the pediatric population with multiple sclerosis. The focus on this population has largely been the recognition that MS does occur in the pediatric population. But what's happening is as years are progressing, this pediatric population is evolving into a population who are capable of reproduction. How diagnosis of pediatric MS can impact not only reproductive ideas, but also just behavior in teenagers, and how all this is interrelated is not known as well. So it's a whole other area that we really need to understand. MSDF Are you looking for buy in from clinicians in all of North America? Or restricted to Canada? Or worldwide? Dr. Sadovnick Ideally, we'd like worldwide. Realistically, right now in our group, we're basically clinicians who are in Canada and the US. We have some buy in from some clinicians in Europe, and it's the obvious problem when you don't have resources, the buy in has to be voluntary. So we do have strong connections between Canada and the US, and we're working forward to try to make this a topic that is more at the forefront. MSDF You have a pretty good system of linked databases in Canada. Can that help you with this? I mean, you know diagnoses and pharmacy and death records and hospital visits and everything else. Dr. Sadovnick Linked databases are a very important resource, but they are exactly what they are: linked databases. You're not dealing with the actual people. You're dealing with how the information has been recorded. So while for some purposes linked databases are extremely important, and there's been a lot of work published out of Canada, including with our group in British Columbia using the BC record linkages. They are informative. But it's not the same as actually dealing with the actual people, because record linkage cannot tell you everything you need to know about the person. Just to use an example in terms of pregnancy outcome. You can identify a woman who has MS. You can look at when she had prescriptions filled for her disease-modifying therapy, for example. You can look at if any birth defects were registered for the child. But what you don't know is, did this mother have previous pregnancy losses? Registries only have live births. Does the mother have a family history of some relative with a certain disease? Could the mother have comorbid diseases that for some reason are not linked into her medical history? Maybe she's moved from another country. Maybe she doesn't have the health coverage. So there's a lot of issues with record linkage. And I think it's very important to know that it has strengths and limitations. But it's not the actual end of everything. The other issue with record linkage is it's someone's interpretation. For example, if it's recorded through record linkage that you have a given disease, it's assumed that all the appropriate diagnostic tests have been done. But is that necessarily the case? Could the person who's actually doing the coding reading from the records make that assumption? So you have to be careful. Years ago when I started in clinical genetics, we had a BC health surveillance registry. And the idea was to basically identify any children who had been within the hospital system in the first seven years of their life. And it was a provincial recording system. But the truth of the matter was is when we went back, and I spent a lot of time working with colleagues going back and reviewing the actual forms from which the data was collected, and the amount of errors you would find. Even in something as simple as MS, looking at cause of death. If you look at record linkage, sometimes it doesn't always note the cause of death the person had MS. Sometimes if there's asphyxia, the question is, was it just asphyxia? Is it related to the MS? Is it from something else? Another issue is very often people who have a specific disease like multiple sclerosis and they die, the real cause of death is ignored. Very often we know that cancer, for example, is underdiagnosed in a person with a specific disease like MS. Just because you're having bladder problems, it's often attributed to MS, where in fact, you could actually have bladder cancer, as an example, or bowel cancer. So if you look at all these data, I think it's important to realize that record linkage is a very useful tool, but it is not the only tool that should be used. MSDF Finally, where does this all stand? You mentioned that you have people doing it on a voluntary basis. Do you foresee something more formal? Dr. Sadovnick We're trying to get something more formal in North America. Obviously, funding is the issue. And right now we're trying to get the drug companies to realize that, if they would work together to have a proper pregnancy registry, it might be in everybody's interest, rather than just assuming that the drugs are not advised during pregnancy or when trying to conceive. The problem with all these registries is that where does the money come from? In Canada, we have a very interesting scenario right now where they're trying to put together a registry of people who have multiple sclerosis in Canada. This has nothing to do with pregnancy. This is just, who has multiple sclerosis in Canada? A registry with minimal data sets. And this started with the Canadian Institute of Health Informatics. This has been going on for quite a few years, and I'm on both the technical and the medical advisory committee for this. But the problem is, who's going to fund it? The concept was to enlist the ministries of health to get involved and fund it, but each ministry of health has its own issues in each province, and their interests are different. So even though the concept there was to try to get a cross-Canada registry for people who have MS, funding after many years of trying is still a major obstacle. It's a big issue, but this is why I'm hoping at least if we can focus on the idea of pregnancy, maybe through some research funding or company funding, we'll be able to at least get a pilot started that will start to answer some of these questions. A lot of money is being spent by each drug company looking at their treatment-specific pregnancy registries. And if we could get them to realize that if they all work together, we might get somewhere. It would be nice. [transition music] MSDF Thank you for listening to Episode Seventy-eight of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Carol Cruzan Morton. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations. Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances. [outro music] We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org. For Multiple Sclerosis Discovery, I'm Dan Keller.

1) Transient ischemic attack service provision: A review of available service models2) What's Trending: Mediterranean diet and brain structure in a multiethnic elderly cohort3) Topic of the month: Pediatric multiple sclerosis This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Bryan Eckerle interviews Dr. Anna Ranta about her paper on transient ischemic attacks as predictors of high risk for subsequent strokes. Dr. Ted Burns is interviewing Dr. Yian Gu for our “What's Trending” feature of the week about his paper on the Mediterranean diet and brain structure in a multiethnic elderly cohort. In the next part of the podcast Dr. Nick Brenton interviews Dr. Daniela Pohl about the topic of disease-modifying therapy management in pediatric multiple sclerosis. DISCLOSURES: Dr. Ranta receives research support from the New Zealand Health Research Council.Dr. Ted Burns serves as Podcast Editor for Neurology; and has received research support for consulting activities with UCB, CSL Behring, Walgreens and Alexion Pharmaceuticals, Inc.Dr. Pohl received funding for travel from Teva Pharmaceutical Industries Ltd., Bayer Schering Pharma, ENS, Merck Serono, Consortium of Multiple Sclerosis Center, LACTRIMS and National Multiple Sclerosis Society; received speaker honoraria from Teva Pharmaceutical Industries Ltd., Bayer Schering Pharma, Merck Serono and Consortium of Multiple Sclerosis Center; serves on the scientific advisory board for Biogen Idec and Merck Serono.

1) Neurology® Neuroimmunology & Neuroinflammation: Therapy with natalizumab is associated with high JCV sero-conversion and rising JCV index values 2) What's Trending: Interviews with Sandi Moriarity and Andy Lucas about their positions and responsibilities with the Neurology podcasts3) Topic of the month: Pediatric multiple sclerosis This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Melanie Ward interviews Dr. Nicholas Schwab about his Neurology: Neuroimmunology & Neuroinflammation paper on therapy with natalizumab and how it is associated with high JCV sero-conversion and rising JCV index values. Dr. Ted Burns is interviewing Sandi Moriarity and Andy Lucas for our “What's Trending” feature of the week about their positions and responsibilities with the Neurology podcast. In the next part of the podcast Dr. Ruth Ann Marrie interviews Dr. Brenda Banwell about the topic of diagnosis of pediatric multiple sclerosis and acute disseminated encephalomyelitis.DISCLOSURES: Dr. Schwab received funding for travel expenses from Biogen Idec; received speaking honoraria from Novartis; has a patent for Usage of L-selectin as predictive marker for progressive multifocal leukoencephalopathy; and receives research support from the Deutsche Forschungsgemeinschaft German Research Foundation and University Münster, IMF.Dr. Ted Burns serves as Podcast Editor for Neurology; and has received research support for consulting activities with UCB, CSL Behring, Walgreens and Alexion Pharmaceuticals, Inc.Sandi Moriarity is Senior Production Editor, Neurology.Andy Lucas is Audio-Visual Administrator, American Academy of Neurology.Dr. Marrie serves as an editorial board member of Neurology and Multiple Sclerosis Journal; receives research support for clinical trials from Sanofi-Aventis, from the Canadian Institutes of Health Research, Research Manitoba, from Multiple Sclerosis Society of Canada and the National Multiple Sclerosis Society, from Multiple Sclerosis Scientific Foundation and from Consortium of Multiple Sclerosis Centers; received research support from the Public Health Agency of Canada.Dr. Banwell serves as an editorial board member of Neurology and Multiple Sclerosis and Related Disorders; serves on the scientific advisory board for Biogen Idec, Sanofi-aventis, Eli Lilly and Company, Novartis; served as a consultant to Biogen Idec, Eli Lilly and Company, Sanofi-aventis; spoken at an event supported by the Consortium of MS Centers; receives research support from the Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Research Foundation, and the National Multiple Sclerosis Society.NO CME WILL BE OFFERED THIS WEEK.

1) Mid-life milk consumption and substantia nigra neuron density at death2) What's Trending: Interview with Dr. Ray Dorsey about new Neurology site, which will be called Innovations in Care Delivery3) Topic of the month: Neurology Today story about should there be a moratorium on human germline editingThis podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Binit Shah interviews Dr. Robert Abbott about his paper on mid-life milk consumption and substantia nigra neuro density at death. Dr. Robert Gross is interviewing Dr. Ray Dorsey for our “What's Trending” feature of the week about being the section editor and curator of our new Neurology site, which will be called Innovations in Care Delivery. In the next part of the podcast Dr. Ted Burns interviews Dr. Thomas Bird about a Neurology Today story on the topic of should there be a moratorium on human germline editing. DISCLOSURES: Dr. Abbott serves as an editorial board member of Keio Journal of Medicine Journal of Epidemiology, and receives non-profit research support from Pacific Health Research and Education Institute.Dr. Gross is supported for educational endeavors from the University of Rochester Medical Center's Clinical and Translational Science Award from the NIH; since his appointment as Editor-in-Chief in 2009, he has ceased participation in industry-sponsored clinical trials and speakers' bureaus and receives an honorarium from AAN as Editor-in-Chief of Neurology.Dr. Dorsey serves on the scientific advisory board of Shire Pharmaceuticals, Huntington's Disease Society of America and NINDS; serves as Editor for HD Insights; serves as an editorial board member of the Journal of Huntington's Disease; serves as Section Editor and Curator for Innovations in Care Delivery mini-site Neurology; received travel funding and honoraria from the American Academy of Neurology; has a patent application related to telemedicine; includes telemedicine in his clinical practice as a movement disorder neurologist (20% effort); has received compensation for expert testimony; is a consultant for 23andME, Amgen, Avid radiopharmaceuticals, Clintrex, Lundbeck Inc, MC10, Inc., Shire Pharmaceuticals, MedAvante, Transpanency Life Sciences and NINDS; receives research support from AMC Health, Avid Radiopharmaceuticals, Biogen Idec, Great Lakes Neurotechnologies, Lundbeck Inc, Medtronic, Inc., Prana Biotechnology, Agency for Health Care Research and Quality; NINDS, National Science Foundation, Patient-Centered Outcomes Research Institute; Davis Phinney Foundation, Michael J. Fox Foundation, Sage Bionetworks.Dr. Ted Burns serves as Podcast Editor for Neurology; and has received research support for consulting activities with UCB, CSL Behring, Walgreens and Alexion Pharmaceuticals, Inc.Dr. Bird serves as an editorial board member of GeneReviews.org; has a patent for Genetic testing technology for CMT1C and SCA14 and receives research support from the Department of Veterans' Affairs, Merit Research Grant.

1) Pregnancy outcomes in aquaporin-4 positive neuromyelitis optica2) What's Trending: Safety and tolerability of resveratrol for Alzheimer disease3) Topic of the month: Endovascular Stroke Therapy This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Melanie Ward interviews Dr. Maria Isabel S. Leite about her paper on pregnancy outcomes in aquaporin-4 positive neuromyelitis optica. Dr. Ted Burns is interviewing Dr. R. Scott Turner for our “What's Trending” feature of the week about his paper on a randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. In the next part of the podcast Dr. Prachi Mehndiratta interviews Dr. Pooja Khatri about the topic of broad overview of the new clinical trials in endovascular stroke therapy. DISCLOSURES: Dr. Leite serves as an editorial board member for Neuromuscular Disorders; has received travel grant and speaking honoraria from Biogen Idec and travel grant from Novartis; is supported by NHS National Specialized Commissioning Group for Neuromyelitis Optica, UK and by NIHR Oxford Biomedical Research Centre.Dr. Ted Burns serves as Podcast Editor for Neurology®; and has received research support for consulting activities with UCB, CSL Behring, Walgreens and Alexion Pharmaceuticals, Inc.Dr. Turner serves on the data safety and monitoring board for the National Institute on Aging; serves as an editorial board Member for Frontiers in Neuroscience and Neuropsychology and Cognition; receives research support from the National Institute on Aging.Dr. Khatri provided expert witnessing for stroke cases over last two years; receives research support from Penumbra, Inc, Genentech, Inc. and the NIH.

1) Stroke risk stratification in acute dizziness presentations and 2) Topic of the month: Neuromyelitis optica. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Andy Southerland interviews Dr. Kevin Kerber about his paper on stroke risk stratification in acute dizziness presentations. Dr. Sarah Wesley is reading our e-Pearl of the week about focal cortical dysplasia. In the next part of the podcast Dr. Stacey Clardy interviews Dr. Jacqueline Palace about the topic of aquaporin-4 molecular mimicry/pathogenesis/research developments. The participants had nothing to disclose except Drs. Southerland, Kerber, Wesley, Clardy and Palace.Dr. Southerland serves as Podcast Deputy Editor for Neurology®; serves as Clinical Research Advisor for Totier Technologies, Inc.Dr. Kerber received funding for travel from Elsevier Inc. and the American Academy of Neurology; receives royalties from the publication of the book Clinical Neurophysiology of the Vestibular System, 4th edition; is a consultant for the American Academy of Neurology, University of California San Francisco (including work on a project funded by AstraZeneca), and Best Doctors, Inc.; receives research support from the NIH; received speaker honoraria from American Academy of Neurology and University of California San Francisco and loan repayment award from the NIH; reviewed legal records of Phil Pearsons, MD, JD and National Medical Consultants.Dr. Wesley serves on the editorial team for the Neurology® Resident and Fellow Section.Dr. Clardy receives research support from the Western Institute for Biomedical Research.Dr. Palace serves as on the scientific advisory board for Merck Serono, Bayer Schering Pharma, Biogen Idec, Teva Pharmaceutical Industries Ltd., Novartis Pharmaceuticals UK Ltd., Sanofi-aventis, Alexion; received support for attending ECTRIMS Merck Serono Novartis and Biogen Idec Talks at scientific meetings (majority have CME) Bayer Schering Pharma, Biogen Idec, Merck Serono, Medimmune; is a consultant for Ono Pharmaceuticals Ltd., Chugai Pharma Ltd., CI Consulting, Biogen Idec, GlaxoSmithKline, Alexion; serves on the speakers' bureau of Teva The CMSC, U. S.; receives research support from Bayer Schering Pharma, Merck Serono, Novartis Teva Pharmaceutical Industries Ltd., MS Society UK, Guthy Jackson Foundation and Department of Health Risk Sharing Scheme, Clinical Coordinator since 2002 Department of Health funding for a neuromyelitis optica service and a congenital myasthenia service; receives revenue from a patent from ISIS innovation Limited, a wholly-owned subsidiary of the University of Oxford, has filed a patent application (WO2013/117930 A2) to protect for the use of metabolomics as a method to diagnose and stage disease in multiple sclerosis.

1) Neurology® Genetics: Phenotypic and molecular analyses of primary lateral sclerosis and 2) Topic of the month: Neurology Today: Recent Publications. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Elliot Dimberg interviews Dr. Hitoshi Mitsumoto about his Neurology: Genetics paper on the phenotypic and molecular analyses of primary lateral sclerosis. Dr. Adam Numis is reading our e-Pearl of the week about cerebral amyloid angiopathy-related inflammation. In the next part of the podcast Dr. Ted Burns interviews Dr. Steve Ringel about a Neurology Today story on the topic of systemic exertion intolerance disease. The participants had nothing to disclose except Drs. Dimberg, Mitsumoto, Numis, Burns and Ringel.Dr. Dimberg serves as an editorial board member of Nerve and Muscle Junction Podcast.Dr. Mitsumoto is a consultant for Biogen Idec; receives research support from Avanir Pharmaceuticals, Teva Pharmaceutical Industries Ltd., Sanofi-aventis, Biogen Idec and the NIH.Dr. Numis serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Ted Burns serves as Podcast Editor for Neurology®; and has received research support for consulting activities with UCB, CSL Behring, Walgreens and Alexion Pharmaceuticals, Inc.Dr. Ringel serves as editor of Neurology Today.NO CME WILL BE OFFERED THIS WEEK.

1) CIDP diagnostic pit-falls and perception of treatment benefits and 2) Topic of the month: Plenary sessions AAN Meeting April 2015. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Michelle Mauermann interviews Dr. Jeffrey Allen about his paper on chronic inflammatory demyelinating polyneuropathy diagnostic pit-falls and perception of treatment benefits. Dr. Adam Numis is reading our e-Pearl of the week about exam findings in hemifacial spasms. In the next part of the podcast Dr. Alberto Espay interviews Dr. Howard Weiner about his Frontiers in Neuroscience Lecture at the AAN Meeting about the topic of immune mechanisms in neurologic diseases. The participants had nothing to disclose except Drs. Mauermann, Allen, Numis, Espay and Weiner.Dr. Mauermann receives research support from ISIS Pharmaceuticals, Inc., Alnylam Pharmaceuticals, Inc. and the NIH.Dr. Allen is a consultant for AxelaCare and CSL Behring.Dr. Numis serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Espay serves as an Associate Editor of Movement Disorders, Frontiers in Movement Disorders and Journal of Clinical Movement Disorders; serves as an editorial board member of Parkinsonism and Related Disorders and The European Neurological Journal; receives royalties for publications of books from Lippincott, Williams & Wilkins and from Cambridge University Press; serves on the scientific advisory board for Solvay Pharmaceuticals, Inc. (now Abbvie), Chelsea Therapeutics, Teva Pharmaceutical Industries Ltd., Impax Pharmaceuticals, Merz, Pfizer Inc, Solstice Neurosciences, LLC, Eli Lilly and Company, US WorldMeds; is a consultant for Chelsea Therapeutics, Solvay Pharmaceuticals, Inc. (now Abbvie); serves on the speakers' bureaus of UCB, Teva Pharmaceutical Industries Ltd., American Academy of Neurology, Movement Disorders Society; receives research support from CleveMed/Great Lakes Neurotechnologies, Michael J. Fox Foundation and the NIH.Dr. Weiner is a consultant for Biogen Idec, Novartis, Merck Serono, Sanofi-aventis, Teva Pharmaceutical Industries Ltd. and Therapix Biosciences Ltd.; served on the advisory board for The Guthy Jackson Charitable Foundation, Teva Pharmaceutical Industries Ltd., Biogen Idec, Novartis, Sanofi-aventis; receives research support from EMD, Merck Serono, National Multiple Sclerosis Society, and the NIH.

1) Switching from natalizumab to fingolimod in patients with remitting-relapsing multiple sclerosis and 2) Topic of the month: Plenary sessions AAN Meeting April 2015. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Mark Keegan interviews Dr. Ludwig Kappos about his paper on switching from natalizumab to fingolimod in patients with remitting-relapsing multiple sclerosis. Dr. Sarah Wesley is reading our e-Pearl of the week about dopamine-responsive dystonia. In the next part of the podcast Dr. Alberto Espay interviews Dr. Timothy Pedley about his Presidential Lecture at the AAN Meeting about the topics of neurologists' burnout, cost and quality of healthcare, value of neurology to congress and payers along with maintenance of certification. The participants had nothing to disclose except Drs. Keegan, Kappos, Wesley, Espay and Pedley.Dr. Keegan serves as Chief Editor of eMedicine; serves as an editorial board member of Multiple Sclerosis and Related Disorders; is a consultant for Novartis, Bristol-Meyers Squibb, Bionest Partners and receives research support from Terumo BCT and Caridian BCT.Dr. Kappos serves as an editorial board member of Multiple Sclerosis Journal, Multiple Sclerosis and Related Disorders and Journal of Neurology; receives research support from Actelion Pharmaceuticals Ltd, Addex, Bayer Schering Pharma, Biogen Idec, Biotica, CSL Behring, Genzyme Corporation, Eli Lilly and Company, Merck Serono, Mitsubishi, Novartis, Ono Pharma, Pfizer Inc, Receptos, Roche, Sanofi-aventis, Santhera, Siemens, Teva Pharmaceutical Industries Ltd., UCB, Xenoport, Swiss National Research Foundation and the European Union and The Swiss MS Society; honoraria and other payments for all these activities have been exclusively used for funding of research of his department.Dr. Wesley serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Espay serves as an Associate Editor of Movement Disorders, Frontiers in Movement Disorders and Journal of Clinical Movement Disorders; serves as an editorial board member of Parkinsonism and Related Disorders and The European Neurological Journal; receives royalties for publications of books from Lippincott, Williams & Wilkins and from Cambridge University Press; serves on the scientific advisory board for Solvay Pharmaceuticals, Inc. (now Abbvie), Chelsea Therapeutics, Teva Pharmaceutical Industries Ltd., Impax Pharmaceuticals, Merz, Pfizer Inc, Solstice Neurosciences, LLC, Eli Lilly and Company, US WorldMeds; is a consultant for Chelsea Therapeutics, Solvay Pharmaceuticals, Inc. (now Abbvie); serves on the speakers' bureaus of UCB, Teva Pharmaceutical Industries Ltd., American Academy of Neurology, Movement Disorders Society; receives research support from CleveMed/Great Lakes Neurotechnologies, Michael J. Fox Foundation and the NIH.Dr. Pedley serves as an editorial board member of Journal of Clinical Neurophysiology and Nature Reviews Neurology and as Editor-in-Chief (Neurology) for UpToDate; serves as President for the American Academy of Neurology; receives royalties form the publication of the books Current Practice of Clinical Electroencephalography, Epilepsy: A comprehensive Textbook and Merritt's Neurology.

1) Rising cost of multiple sclerosis drugs in the U. S. and 2) Topic of the month: Immune-mediated necrotizing myopathy. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. David Jones interviews Dr. Daniel Hartung about his paper on the rising cost of multiple sclerosis drugs in the U. S. Dr. Adam Numis is reading our e-Pearl of the week about Walker-Warburg syndrome. In the next part of the podcast Dr. Ted Burns interviews Dr. Andy Mammen about the topic of treatment overview of immunotherapy for the immune-mediated myopathies. The participants had nothing to disclose except Drs. Jones, Hartung, Numis, Burns and Mammen.Dr. Jones has received personal compensation for attending consultant meetings for Biogen Idec, Novartis and Genzyme Corporation.Dr. Hartung serves on the data safety monitoring board for Kaiser Permanente Center for Health Research; is a consultant for Alkermes Inc.; receives research support from Alkermes Inc. and the Center for Disease Control and National Institute on Drug Abuse. Dr. Numis serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Ted Burns serves as Podcast Editor for Neurology®; and has received research support for consulting activities with CSL Behring and Alexion Pharmaceuticals, Inc.Dr. Mammen serves on the scientific advisory boards of aTYR Pharmaceuticals Inc. and Biogen Idec; serves as an editorial board member of Experimental Neurology and Arthritis and Rheumatism; receives license fee payments, royalties and revenue for a patent from INOVA Diagnostics Inc. for licensed test for anti-HMGCR antibodies; and research support from the NIH.

1) Looking ahead by looking back at practicing neurology and 2) Topic of the month: Immune-mediated necrotizing myopathy. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Heather Harle interviews Dr. Steven Ringel about his paper on looking ahead by looking back at practicing neurology. Dr. Adam Numis is reading our e-Pearl of the week about neurologic complications of heroin inhalation. In the next part of the podcast Dr. Ted Burns interviews Dr. Andy Mammen about the topic of inclusion body myositis. The participants had nothing to disclose except Drs. Ringel, Numis, Burns and Mammen.Dr. Ringel serves as Editor of Neurology Today.Dr. Numis serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Ted Burns serves as Podcast Editor for Neurology®; and has received research support for consulting activities with CSL Behring and Alexion Pharmaceuticals, Inc.Dr. Mammen serves on the scientific advisory boards of aTYR Pharmaceuticals Inc. and Biogen Idec; serves as an editorial board member of Experimental Neurology and Arthritis and Rheumatism; receives license fee payments, royalties and revenue for a patent from INOVA Diagnostics Inc. for licensed test for anti-HMGCR antibodies; and research support from the NIH.

[intro music]   Host – Dan Keller Hello, and welcome to Episode Forty-One of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an interview with Diego Cadavid, who discusses trials of anti-LINGO-1 in MS. But first, a few updates on the latest developments at MSDF.   Our Drug-Development Pipeline includes continually updated information on 44 investigational agents for MS. During the past week, we added 3 new trials and 11 other pieces of information.  The drugs with important additions are dalfampridine, fingolimod, glatiramer acetate, interferon beta-1a, interferon beta-1b, naltrexone, and natalizumab. To find information on all 44 compounds, visit msdiscovery.org and click first on Research Resources and then on Drug-Development Pipeline.   According to our curated list of the latest scientific articles related to MS, 54 such articles were published last week. To see last week’s list, go to msdiscovery.org and click on Papers. We selected two of those papers as Editors’ Picks. One is a meta-analysis of mortality studies showing that excess mortality in MS relative to the general population has not changed over the past 50 years. In the other Editor’s Pick, Jagannadha Avasarala points out that 20% of patients who present with a symptom consistent with a diagnosis of clinically isolated syndrome do not meet radiological criteria on brain MRIs. Dr. Avasarala has contributed an essay to MSDF in which he discusses the consequences of this finding. To see his essay, go to msdiscovery.org and click first on News and Future Directions and then on Essays and Opinions.   [transition music]   Now to the interview. Dr. Diego Cadavid works at Biogen Idec, a pharmaceutical company involved in MS therapeutics. Our executive editor, Bob Finn, caught up with him in Washington D.C. at the annual meeting of the American Academy of Neurology, where Dr. Cadavid presented results of a phase 2 trial of an anti-LINGO-1 antibody called BIIB033 in which the antibody appears to promote myelin repair in the human brain.   Interviewer – Robert Finn Dr. Cadavid, welcome.   Interviewee – Diego Cadavid Thank you, Bob, for having us.   MSDF First, what is anti-LINGO-1, and what does it target?   Dr. Cadavid Anti-LINGO-1 is an investigation and treatment for a myelin repair. It targets a protein called LINGO-1 expressed in the myelin forming cells that normally inhibits the production of myelin. By blocking LINGO-1, we believe healthy cells actually make myelin and at the same time help patients with demyelinating diseases like MS.   MSDF Tell me more about LINGO-1. Why this target makes sense in multiple sclerosis.   Dr. Cadavid Yeah, so LINGO-1 is an inhibitor of myelination. So MS is a demyelinating disease, and it's well established that the majority of patients once they lose myelin they actually are not capable of repairing it. And the question in the field has been why? It's becoming clear that it's not because of a lack of cells; the myelin forming cells are there, but they're not making myelin. So one of the leading hypothesis is that there is a blockade of the ability of these cells to make the myelin. Biogen – more than 10 years ago – was looking for a molecules that could mediate that inhibition, and that's when they found LINGO-1. And through a series of experiments in animal models and in vitro, they showed that when you block LINGO-1 these cells actually differentiate and make myelin. Here we are more than 10 years later reporting the first results of an efficacy trial of anti-LINGO in humans. That's the RENEW study in acute optic neuritis.   MSDF So tell me about the use of optic neuritis sort of as a model of MS.   Dr. Cadavid Yes, we chose acute optic neuritis as the first efficacy trial because, first of all, acute optic neuritis is how many of them, as patients, actually initially present. They're healthy, living in the community, and so then they lose vision in one eye due to acute optic neuritis. In fact, during their lifetime, most MS patients will develop acute optic neuritis, so it is very relevant to MS. But also because it's the one part of the brain that is readily accessible. Through the pupil, we can actually image the neurons of the optic nerve. And using electrophysiology and something called visual evoked potentials, we can very accurately measure the function of this neuronal pathway. So it is not only relevant to MS, we have really good tools to investigate not only the disease but what anti-LINGO-1 may be doing to help the patients.   MSDF But are there indications that anti-LINGO-1 has affects more centrally than the optic nerve?   Dr. Cadavid So the optic nerve – we call it a nerve, but it is really not a nerve – it's a part of the brain. So anti-LINGO-1 is actually a central molecule. What we mean? It's really expressed only in neurons and in the myelin forming cells; it's not expressed outside of the central nervous system. So all the effects of anti-LINGO-1 are believed to occur centrally.   MSDF Where is anti-LINGO-1 in the development process?   Dr. Cadavid We are in the middle of drug development process, Bob, I assume you're asking me. We are in the middle of phase 2. We just finished the first of the two phase 2 trials called RENEW. These are results we are communicating at the academy this year. We believe the RENEW trial results showed efficacy on the primary endpoint: recovery of latency of the visually evoked potential. And we believe this is the first evidence that blocking LINGO-1, in fact, is leading to remyelination in the human brain, first episode of acute optic neuritis. So it's only approved for biology. At the same time, we are running a larger study in MS patients both relapsing-remitting and secondary-progressive. It is a longer trial, 22 months. That trial is fully enroll, ongoing, and we are looking forward to the results next year. The results of both trials will inform on the next steps.   MSDF Is that a phase 2 trial, as well?   Dr. Cadavid Correct. It's the MS trial; it's called SYNERGY, and it's a phase 2 trial. It is dose ranging. Unlike RENEW in which we only tested one dose, in the MS trial – SYNERGY – we are testing several doses.   MSDF How is it administered?   Dr. Cadavid It is a monoclonal antibody given every four weeks by an intravenous infusion.   MSDF So you said that the results of this larger phase 2 trial will be available next year. Assuming that those results are favorable, what's the next step after that?   Dr. Cadavid The final phase of drug development is what we call phase 3, which is when we actually run definite trials where the primary endpoint it's some meaningful clinical endpoint. For example, improvement in disability, slowing of disease worsening. So those phase 3 trials are usually longer and larger, and if the primary endpoints are met and the safety and tolerability is adequate, we file hoping for drug approval and to make this therapy available to patients.   MSDF Four or five years?   Dr. Cadavid Phase 3 trials are usually longer, and we don't know until we're there. But yeah, these are a longer part of the drug development process.   MSDF Now assuming that the clinical trials do pan out – and maybe it's a little bit too early to ask this question, but I'm going to ask it anyway – how will anti-LINGO-1 be used? Is it going to be used early in the disease, late in the disease? The way other DMTs are used now continuously or to respond to a remission?   Dr. Cadavid Ultimately, it will come from the results from the trials. But if you think about demyelination, it is a core component of MS. All forms of MS – from very early to very late – have a loss of myelin. So as long as there is ongoing or preexisting loss of myelin, we believe there is a potential for a remyelinating therapy like anti-LINGO to help the patients.   MSDF Now you mentioned not only relapsing-remitting but secondary-progressive, and I'm sure you know there's a long history of things that have not worked well for progressive disease. Do you have a reason to believe that anti-LINGO-1 will be efficacious for progressive disease?   Dr. Cadavid So, Bob, it is true that there really no effective therapies in SPMS right now. It is an area that we are focusing on anti-LINGO because we know there is extensive demyelination in secondary-progressive MS. Interestingly, there is a lot of cortical demyelination with relative preservation of axons and neurons. So we believe that if this drug is capable of repairing the myelin we could actually be able to help patients with SPMS. The phase 2 program includes patients with SPMS, so we obviously are looking forward to the results from the ongoing phase 2 trials to help us make decisions on next steps.   MSDF Why not primary progressive?   Dr. Cadavid Primary progressive MS is also under consideration. Right now we have to focus. Obviously what we learned from secondary-progressive MS will also inform us as to pursue primary progressive MS. We are aware there is a high unmet need, and we keep those patients at heart too.   MSDF Just in terms of procedurally a technique why are you focusing on secondary-progressive before primary progressive?   Dr. Cadavid So there are some practical reasons. One of them is that SPMS is viewed as closer to relapsing-remitting MS relative to primary progressive MS. So in the phase 2 trial, we have to try to keep some focus on the population. If we spread too much, it may become more difficult to actually interpret the data. There is a strategic reason as SPMS is closer to RRMS than PPMS is.   MSDF Well, Dr. Cadavid, I've come to the end of my prepared questions. Is there anything I haven't asked that I should have asked or anything you'd like to add?   Dr. Cadavid I like to finish by saying that the results of the RENEW trial it's really the first time we have seen evidence from the human brain that it appears possible to repair the myelin. This is a very important step in the field. There is a lot of work to do. But it is encouraging news, and we are happy to share this with the community. And Biogen is very committed to MS and to help patients who are living with this chronic disabling condition. So we welcome the news, and we also are ready to embrace the following stages of drug development, which are obviously very challenging.   MSDF Well Dr. Cadavid, thank you very much.   Dr. Cadavid Thank you, Bob, was a pleasure.   [transition music]   MSDF Thank you for listening to Episode Forty-One of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.   [outro music]  

1) Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis and 2) Topic of the month: Immune-mediated necrotizing myopathy. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Jennifer Bickel interviews Dr. Don Gilden about his paper on the prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis. Dr. Adam Numis is reading our e-Pearl of the week about unresponsive CIDP: Is it POEMS? In the next part of the podcast Dr. Ted Burns interviews Dr. Andy Mammen about the topic of dermatomyositis. The participants had nothing to disclose except Drs. Gilden, Numis, Burns and Mammen.Dr. Gilden serves as an Senior Associate Editor for Journal of NeuroVirology; serves as an editorial board member of In Vivo, Journal of Virology, Scientific American Medicine, Virus Genes, Neurology and Journal of the Neurological Sciences; and receives research support from the NIH.Dr. Numis serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Ted Burns serves as Podcast Editor for Neurology®; and has received research support for consulting activities with CSL Behring and Alexion Pharmaceuticals, Inc.Dr. Mammen serves on the scientific advisory boards of aTYR Pharmaceuticals Inc. and Biogen Idec; serves as an editorial board member of Experimental Neurology and Arthritis and Rheumatism; receives license fee payments, royalties and revenue for a patent from INOVA Diagnostics Inc. for licensed test for anti-HMGCR antibodies; and research support from the NIH.

1) Dystonia: Five new things and 2) Topic of the month: Immune-mediated necrotizing myopathy. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Jeff Ratliff interviews Dr. Brian Berman about his paper on five new things about dystonia. Dr. Adam Numis is reading our e-Pearl of the week about hereditary hemorrhagic telangectasia. In the next part of the podcast Dr. Ted Burns interviews Dr. Andy Mammen about the topic of immune-mediated necrotizing myopathy. The participants had nothing to disclose except Drs. Berman, Numis, Burns and Mammen.Dr. Berman serves on the Medical Advisory Boards for the Benign Essential Blepharospasm Research Foundation and the National Spasmodic Torticollis Association; has received funding for travel to conferences from Parkinson Study Group, American Neurological Association, Movement Disorder Society, Dystonia Medical Research Foundation, Benign Essential Blepharospasm Research Foundation; serves on the editorial board of Journal of Neurology and Neurophysiology; receives research support from the NIH, Dystonia Coalition, Dystonia Medical Research Foundation, Colorado Translational Research Imaging Center, University of Colorado Center for Neuroscience, The Dana Foundation, and the Benign Essential Blepharospasm Research Foundation. Dr. Numis serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Ted Burns serves as Podcast Editor for Neurology®; and has received research support for consulting activities with CSL Behring and Alexion Pharmaceuticals, Inc.Dr. Mammen serves on the scientific advisory boards of aTYR Pharmaceuticals Inc. and Biogen Idec; serves as an editorial board member of Experimental Neurology and Arthritis and Rheumatism; receives license fee payments, royalties and revenue for a patent from INOVA Diagnostics Inc. for licensed test for anti-HMGCR antibodies; and research support from the NIH.

1) When a serum test overrides the clinical assessment and 2) Topic of the month: Stroke in systemic disease. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. John Mytinger interviews Dr. Josep Dalmau about his paper on when a serum test overrides the clinical assessment. Dr. James Addington is reading our e-Pearl of the week about lissencephaly. In the next part of the podcast Dr. Michelle Johansen interviews Dr. Mitch Elkind about the topic of stroke in the setting of systemic infection. The participants had nothing to disclose except Drs. Dalmau, Addington, Johansen and Elkind.Dr. Dalmau serves as an editorial board member of Neurology® and UptoDate; serves as Editor-in-Chief of Neurology® Neuroimmunology and Neuroimflammation; is a consultant for Advance Medical; receives royalties for the following patents: Patent Ma2 autoantibody test, Patent NMDAR autoantibody test, patent application for the use of GABA(B) receptor, DPPX and IgLON5 autoantibody tests; received license fee payments for DPPX and IgLON5 autoantibody tests from Euroimmun; receives research support from Euroimmun, ISCIII, and the NIH.Dr. Addington serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Johansen serves as a scientific advisory member of Stroke and as a contributor to Blogging Stroke.Dr. Elkind serves as Section editor for the Neurology® Resident and Fellow Section; serves on the scientific advisory board for Biogen IDEC, Boehringer Ingelheim, BMS-Pfizer Partnership, Janssen Pharmaceutical; is a consultant for Daiichi Sankyo, BMS-Pfizer Partnership and Biotelemetry; participated in legal proceedings for Organon/Merck Serono, NuvaRing and stroke litigation; receives research support from American Heart Association National Board of Directors, American Heart Association Founders Affiliate Board of Directors, American Heart Association NY City Board of Directors and the NIH.

1) Clinical and serological characterization of the antibodies to GABAA receptor a1 and y2 subunits and 2) Topic of the month: Stroke in systemic disease. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Lara Marcuse interviews Dr. Angela Vincent about her paper on the clinical and serological characterization of the antibodies to GABAA receptor a1 and y2 subunits. Dr. James Addington is reading our e-Pearl of the week about navigating painful neuropathies. In the next part of the podcast Dr. Michelle Johansen interviews Dr. Steve Zeiler about the topic of stroke in the setting of CNS vasculitis. The participants had nothing to disclose except Drs. Vincent, Addington, Johansen and Zeiler.Dr. Vincent serves on the advisory editorial board Journal of Neurology; holds patent with Oxford University for LGI1/CASPR2 antibodies, licensed to Euroimmun AG, and for GABAAR antibodies, in negotiation with Euroimmun AG; was a consultant with Athena Diagnostics; occasional small honoraria, travel and speaker honoraria from Baxter International Inc. and Biogen Idec; receives royalties from Athena Diagnostics (MuSK assays), from Euroimmun AG (LGI1 and CASPR2 assays) Clinical Neuroimmunology (Blackwell Publishing, 2005) and Inflammatory and Autoimmune Disorders of the Nervous System in Children (Mac Keith Press 2010); and receives research support from the NIH.Dr. Addington serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Johansen serves as a scientific advisory member of Stroke and as a contributor to Blogging Stroke.Dr. Zeiler receives research support from Johns Hopkins Neurology and NIH; has provided expert legal testimony in 2013 and 2014.

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1) Imaging prodromal Parkinson disease and 2) Topic of the month: Movement disorder emergencies. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Alberto Espay interviews Dr. Danna Jennings about her paper on imaging prodromal Parkinson disease. Dr. Adam Numis is reading our e-Pearl of the week about distal hereditary neuropathies. In the next part of the podcast Dr. David Taplinger interviews Dr. Steven Frucht about the movement disorder emergency: serotonin syndrome. The participants had nothing to disclose except Drs. Espay, Jennings, Numis and Frucht.Dr. Espay serves as an Associate Editor of Movement Disorders, Frontiers in Movement Disorders and Journal of Clinical Movement Disorders; serves as an editorial board member of Parkinsonism and Related Disorders and The European Neurological Journal; receives royalties for publications of books from Lippincott, Williams & Wilkins and from Cambridge University Press; serves on the scientific advisory board for Solvay Pharmaceuticals, Inc. (now Abbvie), Chelsea Therapeutics, Teva Pharmaceutical Industries Ltd., Impax Pharmaceuticals, Merz, Pfizer Inc, Solstice Neurosciences, LLC, Eli Lilly and Company, US WorldMeds; is a consultant for Chelsea Therapeutics, Solvay Pharmaceuticals, Inc. (now Abbvie); serves on the speakers' bureaus of Novartis, UCB, Teva Pharmaceutical Industries Ltd., American Academy of Neurology, Movement Disorders Society; receives research support from CleveMed/Great Lakes Neurotechnologies, Michael J. Fox Foundation and the NIH.Dr. Jennings received speaker honoraria from Novartis; serves on the speaker board of UCB; receives research funding from Michael J. Fox Foundation, FORUM Pharmaceuticals, Concert Pharmaceuticals, Inc.; Omeros, Amgen, Abbvie, Merck Serono, Eli Lilly and Company, Avid Radiopharmaceuticals, Inc.; Navidea Biopharmaceuticals, Inc.; Eisai Inc., TauRx Therapeutics Ltd and Biogen Idec.Dr. Numis serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Frucht is a consultant for Merz Pharmaceuticals, LLC and Impax Pharmaceuticals and receives royalties from the publication of the book Movement Disorders Emergencies.

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1) Why brain death is considered death and 2) Topic of the month: Neuro-infectious diseases. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Mike Brogan interviews Drs. Chris Burkle and Eelco Wijdicks about their paper on why brain death is considered death. Dr. Adam Numis is reading our e-Pearl of the week about equine encephalitides. In the next part of the podcast Dr. Chenjie Xia interviews Dr. David Clifford about progressive multifocal leukoencephalopathy and neurologic care of patients with HIV/AIDS. The participants had nothing to disclose except Drs. Wijdicks, Numis and Clifford.Dr. Wijdicks served as Editor-in-Chief of Neurocritical Care and receives royalties from the publication of several books published by Oxford University Press.Dr. Numis serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Clifford has served/serves on scientific advisory boards for Amgen, Biogen Idec/Quintiles, BMS, Genentech, Inc., Genzyme Corporation, Pfizer Inc, Millennium Pharmaceuticals, Inc. and Sanofi-aventis; received a speaker honorarium from Sun Pharmaceuticals; serves/has served as a consultant for Millennium Pharmaceuticals, Inc., Genzyme Corporation, Biogen Idec, IAS-USA, CMSC/ACTRIMS, ECTRIMS, Drinker, Biddle, Reath, Cytheris and Novartis; receives research support from Lilly, Roche, Alzheimer Association and the NIH (NIMH, NINR); and has provided consultation in medico-legal cases.

[intro music]   Host – Dan Keller Hello, and welcome to Episode Eleven of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an interview with Dr. Jack Antel about remyelination and microglia. But to begin, here is a brief summary of some of the latest developments on the MS Discovery Forum at msdiscovery.org.   Our latest data visualization reveals a mystery in relapsing-remitting MS. It appears that the annualized relapse rates of patients in the placebo arms of clinical trials – the placebo arms – have been decreasing since 1993. What could possibly account for this? We invite your hypotheses. Visit the MSDF website and go to our data visualizations page under “research resources.” From there you can connect to a discussion forum we’re hosting to share your opinions.   Deep brain stimulation is an extreme brain surgery that can lead to dramatic improvements in patients with Parkinson’s disease or obsessive-compulsive disorder. But in MS patients with tremor, the risk-benefit ratio varies a great deal from patient to patient. The surgery involves placing an electrode into the thalamus and stimulating the surrounding neurons to reduce tremor. However, no one is sure why the procedure works in some people with MS tremor and not in others. Last week, we published a news synthesis—including a dramatic video—on the efficacy of this surgery to treat the otherwise untreatable tremor in some MS patients.   We also reported on results from the phase 1 clinical trial of an anti-LINGO-1 remyelination agent. The drug, called BIIB033, is produced by Biogen Idec and proved safe and tolerable in healthy individuals and people with MS. In mouse models, the drug is shown to work by blocking LINGO-1. LINGO-1 prevents oligodendrocyte progenitor cells from differentiating into myelin-producing cells. The company is now conducting a phase 2 study to determine proper dosage in patients with MS.   [transition music]   Now to the interview. Dr. Jack Antel is a neurologist at the Montreal Neurological Institute and Hospital. His team studies remyelination and repair. He spoke with MSDF about how microglia and progenitor cells affect this process.   Interviewer – Dan Keller Welcome, Dr. Antel.   Interviewee – Jack Antel Thank you very much.   MSDF Where do things stand now? What is the thinking of remyelination? Is it a dynamic process? Is it something that happens all at once? Is there a balance between injury and repair?   Dr. Antel From the perspective of multiple sclerosis itself, we look to our pathologists who've examined the actual MS tissue, and they have established criteria by which they identify that remyelination has occurred, and thus this has been a major incentive to see whether one can accelerate that process. One can now somewhat question the certainty that we are distinguishing between actual remyelination and perhaps partial injury of myelin, and maybe part of what we've seen is actual injury rather than actual repair. The other side of the coin is from the experimental biologist who clearly have shown remyelination to occur and have identified progenitor cells as being the basis of remyelination in animal models. Now we have to bring the observation from the clinical pathology in humans together with those observations are we still certain that all of remyelination is dependent on new cells, or can previously myelinating cells still contribute. And in the context of the human disease, the issue is what is the total potential of the cells? Why doesn't everybody remyelinate? This is because there's intrinsic differences in the myelin cells that humans have. Could the myelin cells themselves be subject to injury? And also, the complicating feature is how much injury is there? So that, if the axons have been damaged, maybe they are not receptive to remyelination. And also, the chronic changes in the environment of all the other glial cells and their products in the human situation, which is after all a disease of months and years not of days and weeks, maybe this is an important influence as to why remyelination occurs or doesn't.   MSDF You had mentioned partial myelination or demyelination. When one looks at a path slide, is it possible to tell whether it's going up or down? Can you distinguish one from the other?   Dr. Antel So that active injury of myelin can be identified because in the active MS lesion myelin debris is freed up and picked up by the phagocytic cells – either the microglia or macrophages – so one can see that there is active injury. If one looks just at the myelin sheath itself, the criteria for remyelination is these sheaths have become rather thinned out, and the segment of the myelin sheath is shorter than in the naturally myelinated cell condition. The issue becomes whether are we absolutely sure that this is remyelination, or could one model developing this histologic feature in some way by injury? And I think that would be a very good challenge for the experimentalists to see if they can get an injury model that reproduces some myelin injury without actually killing the myelinating cells.   MSDF Besides being a target for the immune response, how do glia participate in the immune response?   Dr. Antel So the glia – we can refer both to the astrocytes and microglia – and as you mentioned one of the important issues I think with these cells is how they talk to the immune cells that are coming from the outside into the brain and modulating their properties. In addition, these glial cells themselves can influence the myelination process in several ways. One is that they can produce some of the same molecules that the immune cells produce or novel molecules that can either promote or directly inhibit the capacity of myelinating cells to function – so direct signaling effects on the myelinating cells. The other is they are producing molecules that change the environment so that processes either grow out or don't grow out from the myelinating cells. So we have to consider the glia, which are very dynamic and thus become a target for therapeutic manipulation, in terms of both their effects on immune cells but also can they be so, if you will, "good guys" or "bad guys" in terms of the promoting the myelination process.   MSDF We think of some of the present drugs as modulating the immune system and trafficking and its effect on effector cells. But do you think that some of these may be affecting bystander cells, or I suppose maybe they're not bystanders if they're actively involved. Could they have an affect on glia?   Dr. Antel I think that this is an emerging opportunity in the field because we are now having the first generation of drugs that actually access the central nervous system. The initial generation of drugs, many of the monoclonal antibodies, we felt were acting outside of the nervous system – either on immune cells themselves or on the cells that comprised the blood-brain barrier but with some particularly of the small molecule drugs that access the central nervus system – that these drugs have the capacity to interact with the neural cells. If we use as an example the family of agents that we refer to as this sphingosine-1-phosphate receptor modulators, S1P agents, there has long been data that these receptors are expressed on all cells, including all of the neural cells, and there is existing data that S1P modulators can affect the function of glial cells. Now how this translates into effects that are clinically relevant is the challenge that's ongoing now.   MSDF How does all of this relate to progressive MS?   Dr. Antel So progressive MS, I believe, is an entity that we have not totally understood yet, and we have to consider it in its parts, namely is progressive MS reflective of ongoing injury to the myelinating cells or the underlying axons? Is this a reflection of the injured cells no longer able to maintain themselves are they metabolically failing? And that can we distinguish these processes because if it's ongoing immune injury – whether related to the adaptive or innate immune system – then it makes sense to target those process. If it's an injury or metabolic failure, then that would be another approach. I think we have to consider whether progressive MS, again has evolved over many, many years, and whether one of our challenges is reducing the initial injury process can avoid many of these long-term events.   MSDF In secondary progressive MS, do you see that there's sort of a tipping point? Is there something different in secondary progressive once that occurs?   Dr. Antel It's difficult to provide an answer, and I think here is an area particularly where careful clinical studies are guiding us that the initial notion that multiple events triggered a later process would have been a very nice system to have because then stopping a process early would have predicted a beneficial later response. We are struck that the clinical data is suggesting that progression can occur perhaps even in the absence of ongoing inflammation whether the two are dissociated, at least in some cases, is a real concern. And thus, just controlling the initial immune response – because it triggers a later event – may not be sufficient. And the reverse, which I think has received perhaps less attention, is that from the clinical perspective multiple people have multiple disabling acute events and do not develop the progressive process. So it is not clear that the two are absolutely linked; whether there are genetic susceptibility factors that determine this have not yet emerged; whether it's the nature of the injury; or whether we have multiple diseases processes.   MSDF We often think of bench-to-bedside as the pathway for advancements. Now you had told me earlier that you're working with people in the opposite direction; you're finding things in the human condition and then leading to laboratory validation. Can you tell me a little bit about that?   Dr. Antel I think this is a very important aspect and why it is important that the clinical and clinical pathology experts really identify the core issues so that they can be taken to a laboratory and experimentally addressed. That in MS, we're dealing with a disease that develops over months and years making it more difficult to model it precisely. It's a disease where we have not established the initiating event. Whereas in the animal system, we usually use a arbitrary antigen if we were going to model an immune mediated disorder. We model the demyelination/remyelination process usually by acute toxins in the animal systems; whereas this is not the case in MS that specific exposure. And so I think we need to continue to develop our model systems that can induce some type of progressive disorder that is not specifically introduced perhaps by a specific antigen, at least the antigens we use currently.   MSDF Knowing that remyelination is possible, is there an implication that it may be going on in all of us in healthy brain at all times where you actually get turnover? And if so, can you capitalize on this kind of system?   Dr. Antel So the issue of turnover of myelin, I think, has not been emphasized sufficiently until recently both from the perspective if we have continuous turnover whether this may be one of the mechanisms whereby antigens are presented to the immune system. The other in terms of the turnover rate of myelin or oligodendrocytes – whether the health of these cells is damaged by the disease process, and whether a limiting factor over time is that the injury of the cells, which could be quite subtle – so that the cells are not killed, but they've impaired their function either to maintain the interaction with axons or the necessary transport of key molecules down the processes. Whether interruption of this then results in the inability of the cells to maintain their myelination properties and to continue the turnover or what might be a repair activity. And we interpret this as a later progression of the disease.   MSDF On the topics we've been discussing, is there anything important to add?   Dr. Antel I think the importance is that we now are turning our attention to these topics. That it is very timely that we do this – because until we could control the actual disease activity through immunomodulatory therapies – if that aspect was not controlled it would be much more difficult to think of trying to control the overall disease process. And also, as we couple the biology with careful clinical observations and the advances in imaging of the human brain, so that it gives us greater opportunities to bring our theories from the lab to the clinics and see whether we really impact in a positive way on the processes we've been discussing.   MSDF Very good. We appreciate it.   Dr. Antel My pleasure.   [transition music]   MSDF Thank you for listening to Episode Eleven of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie [intro music]     Host – Dan Keller Hello, and welcome to Episode Eleven of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an interview with Dr. Jack Antel about remyelination and microglia. But to begin, here is a brief summary of some of the latest developments on the MS Discovery Forum at msdiscovery.org.   Our latest data visualization reveals a mystery in relapsing-remitting MS. It appears that the annualized relapse rates of patients in the placebo arms of clinical trials – the placebo arms – have been decreasing since 1993. What could possibly account for this? We invite your hypotheses. Visit the MSDF website and go to our data visualizations page under “research resources.” From there you can connect to a discussion forum we’re hosting to share your opinions.   Deep brain stimulation is an extreme brain surgery that can lead to dramatic improvements in patients with Parkinson’s disease or obsessive-compulsive disorder. But in MS patients with tremor, the risk-benefit ratio varies a great deal from patient to patient. The surgery involves placing an electrode into the thalamus and stimulating the surrounding neurons to reduce tremor. However, no one is sure why the procedure works in some people with MS tremor and not in others. Last week, we published a news synthesis—including a dramatic video—on the efficacy of this surgery to treat the otherwise untreatable tremor in some MS patients.   We also reported on results from the phase 1 clinical trial of an anti-LINGO-1 remyelination agent. The drug, called BIIB033, is produced by Biogen Idec and proved safe and tolerable in healthy individuals and people with MS. In mouse models, the drug is shown to work by blocking LINGO-1. LINGO-1 prevents oligodendrocyte progenitor cells from differentiating into myelin-producing cells. The company is now conducting a phase 2 study to determine proper dosage in patients with MS.   [transition music]   Now to the interview. Dr. Jack Antel is a neurologist at the Montreal Neurological Institute and Hospital. His team studies remyelination and repair. He spoke with MSDF about how microglia and progenitor cells affect this process.   Interviewer – Dan Keller Welcome, Dr. Antel.   Interviewee – Jack Antel Thank you very much.   MSDF Where do things stand now? What is the thinking of remyelination? Is it a dynamic process? Is it something that happens all at once? Is there a balance between injury and repair?   Dr. Antel From the perspective of multiple sclerosis itself, we look to our pathologists who've examined the actual MS tissue, and they have established criteria by which they identify that remyelination has occurred, and thus this has been a major incentive to see whether one can accelerate that process. One can now somewhat question the certainty that we are distinguishing between actual remyelination and perhaps partial injury of myelin, and maybe part of what we've seen is actual injury rather than actual repair. The other side of the coin is from the experimental biologist who clearly have shown remyelination to occur and have identified progenitor cells as being the basis of remyelination in animal models. Now we have to bring the observation from the clinical pathology in humans together with those observations are we still certain that all of remyelination is dependent on new cells, or can previously myelinating cells still contribute. And in the context of the human disease, the issue is what is the total potential of the cells? Why doesn't everybody remyelinate? This is because there's intrinsic differences in the myelin cells that humans have. Could the myelin cells themselves be subject to injury? And also, the complicating feature is how much injury is there? So that, if the axons have been damaged, maybe they are not receptive to remyelination. And also, the chronic changes in the environment of all the other glial cells and their products in the human situation, which is after all a disease of months and years not of days and weeks, maybe this is an important influence as to why remyelination occurs or doesn't.   MSDF You had mentioned partial myelination or demyelination. When one looks at a path slide, is it possible to tell whether it's going up or down? Can you distinguish one from the other?   Dr. Antel So that active injury of myelin can be identified because in the active MS lesion myelin debris is freed up and picked up by the phagocytic cells – either the microglia or macrophages – so one can see that there is active injury. If one looks just at the myelin sheath itself, the criteria for remyelination is these sheaths have become rather thinned out, and the segment of the myelin sheath is shorter than in the naturally myelinated cell condition. The issue becomes whether are we absolutely sure that this is remyelination, or could one model developing this histologic feature in some way by injury? And I think that would be a very good challenge for the experimentalists to see if they can get an injury model that reproduces some myelin injury without actually killing the myelinating cells.   MSDF Besides being a target for the immune response, how do glia participate in the immune response?   Dr. Antel So the glia – we can refer both to the astrocytes and microglia – and as you mentioned one of the important issues I think with these cells is how they talk to the immune cells that are coming from the outside into the brain and modulating their properties. In addition, these glial cells themselves can influence the myelination process in several ways. One is that they can produce some of the same molecules that the immune cells produce or novel molecules that can either promote or directly inhibit the capacity of myelinating cells to function – so direct signaling effects on the myelinating cells. The other is they are producing molecules that change the environment so that processes either grow out or don't grow out from the myelinating cells. So we have to consider the glia, which are very dynamic and thus become a target for therapeutic manipulation, in terms of both their effects on immune cells but also can they be so, if you will, "good guys" or "bad guys" in terms of the promoting the myelination process.   MSDF We think of some of the present drugs as modulating the immune system and trafficking and its effect on effector cells. But do you think that some of these may be affecting bystander cells, or I suppose maybe they're not bystanders if they're actively involved. Could they have an affect on glia?   Dr. Antel I think that this is an emerging opportunity in the field because we are now having the first generation of drugs that actually access the central nervous system. The initial generation of drugs, many of the monoclonal antibodies, we felt were acting outside of the nervous system – either on immune cells themselves or on the cells that comprised the blood-brain barrier but with some particularly of the small molecule drugs that access the central nervus system – that these drugs have the capacity to interact with the neural cells. If we use as an example the family of agents that we refer to as this sphingosine-1-phosphate receptor modulators, S1P agents, there has long been data that these receptors are expressed on all cells, including all of the neural cells, and there is existing data that S1P modulators can affect the function of glial cells. Now how this translates into effects that are clinically relevant is the challenge that's ongoing now.   MSDF How does all of this relate to progressive MS?   Dr. Antel So progressive MS, I believe, is an entity that we have not totally understood yet, and we have to consider it in its parts, namely is progressive MS reflective of ongoing injury to the myelinating cells or the underlying axons? Is this a reflection of the injured cells no longer able to maintain themselves are they metabolically failing? And that can we distinguish these processes because if it's ongoing immune injury – whether related to the adaptive or innate immune system – then it makes sense to target those process. If it's an injury or metabolic failure, then that would be another approach. I think we have to consider whether progressive MS, again has evolved over many, many years, and whether one of our challenges is reducing the initial injury process can avoid many of these long-term events.   MSDF In secondary progressive MS, do you see that there's sort of a tipping point? Is there something different in secondary progressive once that occurs?   Dr. Antel It's difficult to provide an answer, and I think here is an area particularly where careful clinical studies are guiding us that the initial notion that multiple events triggered a later process would have been a very nice system to have because then stopping a process early would have predicted a beneficial later response. We are struck that the clinical data is suggesting that progression can occur perhaps even in the absence of ongoing inflammation whether the two are dissociated, at least in some cases, is a real concern. And thus, just controlling the initial immune response – because it triggers a later event – may not be sufficient. And the reverse, which I think has received perhaps less attention, is that from the clinical perspective multiple people have multiple disabling acute events and do not develop the progressive process. So it is not clear that the two are absolutely linked; whether there are genetic susceptibility factors that determine this have not yet emerged; whether it's the nature of the injury; or whether we have multiple diseases processes.   MSDF We often think of bench-to-bedside as the pathway for advancements. Now you had told me earlier that you're working with people in the opposite direction; you're finding things in the human condition and then leading to laboratory validation. Can you tell me a little bit about that?   Dr. Antel I think this is a very important aspect and why it is important that the clinical and clinical pathology experts really identify the core issues so that they can be taken to a laboratory and experimentally addressed. That in MS, we're dealing with a disease that develops over months and years making it more difficult to model it precisely. It's a disease where we have not established the initiating event. Whereas in the animal system, we usually use a arbitrary antigen if we were going to model an immune mediated disorder. We model the demyelination/remyelination process usually by acute toxins in the animal systems; whereas this is not the case in MS that specific exposure. And so I think we need to continue to develop our model systems that can induce some type of progressive disorder that is not specifically introduced perhaps by a specific antigen, at least the antigens we use currently.   MSDF Knowing that remyelination is possible, is there an implication that it may be going on in all of us in healthy brain at all times where you actually get turnover? And if so, can you capitalize on this kind of system?   Dr. Antel So the issue of turnover of myelin, I think, has not been emphasized sufficiently until recently both from the perspective if we have continuous turnover whether this may be one of the mechanisms whereby antigens are presented to the immune system. The other in terms of the turnover rate of myelin or oligodendrocytes – whether the health of these cells is damaged by the disease process, and whether a limiting factor over time is that the injury of the cells, which could be quite subtle – so that the cells are not killed, but they've impaired their function either to maintain the interaction with axons or the necessary transport of key molecules down the processes. Whether interruption of this then results in the inability of the cells to maintain their myelination properties and to continue the turnover or what might be a repair activity. And we interpret this as a later progression of the disease.   MSDF On the topics we've been discussing, is there anything important to add?   Dr. Antel I think the importance is that we now are turning our attention to these topics. That it is very timely that we do this – because until we could control the actual disease activity through immunomodulatory therapies – if that aspect was not controlled it would be much more difficult to think of trying to control the overall disease process. And also, as we couple the biology with careful clinical observations and the advances in imaging of the human brain, so that it gives us greater opportunities to bring our theories from the lab to the clinics and see whether we really impact in a positive way on the processes we've been discussing.   MSDF Very good. We appreciate it.   Dr. Antel My pleasure.   [transition music]   MSDF Thank you for listening to Episode Eleven of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.   [outro music]     Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.   [outro music]    

Today in FirstWord:

1) Evaluation and construction of diagnostic criteria for inclusion body myositis and 2) Topic of the month: Plenary sessions AAN Meeting April 2014. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Ted Burns interviews Dr. Steven A. Greenberg about his paper on evaluation and construction of diagnostic criteria for inclusion body myositis. Dr. James Addington is reading our e-Pearl of the week about Rapid-Onset Dystonia Parkinsonism. In the next part of the podcast Dr. Alberto Espay continues his interview with Dr. Jon Stone including questions about his Contemporary Clinical Issues Lecture about functional (psychogenic) disorders in neurology from the audience at Interview Central and his responses. The participants had nothing to disclose except Drs. Burns, Greenberg, Addington, Espay and Stone.Dr. Burns serves as Podcast Editor for Neurology®; and has received research support for consulting activities with CSL Behring and Alexion Pharmaceuticals, Inc.Dr. Greenberg is a consultant for MedImmune, aTyr Pharma; receives publishing royalties from the publication of the book EMG Pearls; receives license fee payments from Composition and Methods for Diagnosing and Assessing Inflammatory Myopathies, MedImmune; receives revenue for patents for composition and methods for diagnosing and assessing inflammatory myopathies, detecting inclusion body myositis; receives research support from MedImmune, Novartis and the NIH; serves on the scientific advisory board for MedImmune; received funding for travel from Biogen Idec and Genzyme Corporation.Dr. Addington serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Espay serves as an Associate Editor of Movement Disorders, Frontiers in Movement Disorders and Journal of Clinical Movement Disorders; serves as an editorial board member of Parkinsonism and Related Disorders and The European Neurological Journal; receives royalties for publications of books from Lippincott, Williams & Wilkins and from Cambridge University Press; serves on the scientific advisory board for Solvay Pharmaceuticals, Inc. (now Abbvie), Chelsea Therapeutics, Teva Pharmaceutical Industries Ltd., Impax Pharmaceuticals, Merz, Pfizer Inc, Solstice Neurosciences, LLC, Eli Lilly and Company, US WorldMeds; is a consultant for Chelsea Therapeutics, Solvay Pharmaceuticals, Inc. (now Abbvie); serves on the speakers' bureaus of Novartis, UCB, Teva Pharmaceutical Industries Ltd., American Academy of Neurology, Movement Disorders Society; receives research support from CleveMed/Great Lakes Neurotechnologies, Michael J. Fox Foundation and the NIH.Dr. Stone received speaker honoraria from the Movement Disorders Society, British Medical Association, American Academy of Neurology Royal College of Psychiatrists, UCB Pharma, Novartis, Tribunals Judiciary (UK); receives research support from the National Research Strategy Career Fellow with NHS Scotland Research; receives publishing royalties from UptoDate 2014; runs a free self-help website for patients with functional disorders www.neurosymptoms.org; carries out regular expert witness work in relation to personal injury and medical negligence.

Today in FirstWord:

1) Defining the clinical course of multiple sclerosis: The 2013 revisions and 2) Topic of the month: Plenary sessions AAN Meeting April 2014. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Mark Keegan interviews Dr. Fred Lublin about his paper on defining the clinical course of multiple sclerosis: The 2013 revisions. Dr. James Addington is reading our e-Pearl of the week about familial fatal insomnia. In the next part of the podcast Dr. Alberto Espay interviews Dr. David Eidelberg about his Hot Topics Lecture at the AAN Meeting about functional connectivity and functional imaging in movement disorders. The participants had nothing to disclose except Drs. Keegan, Lublin, Addington, Espay and Eidelberg.Dr. Keegan serves as Chief Editor of eMedicine and receives research support from Terumo BCT.Dr. Lublin serves as co-Chief Editor of Multiple Sclerosis and Related Disorders; serves on the scientific advisory boards and as a consultant for Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Teva Pharmaceutical Industries Ltd., Actelion Pharmaceuticals Ltd, Sanofi-aventis, Acorda Therapeutics Inc, Questcor Pharmaceuticals, Roche, Genentech, Inc., Celgene, Johnson & Johnson, Revalesio Corporation, Coronado Bioscience, Genzyme Corporation, MedImmune, Bristol-Myers Squibb, XenoPort, Inc., Receptos Inc, Forward Pharma, to- BBB technologies; receives research support from Biogen Idec, Teva Pharmaceutical Industries Ltd., Acorda Therapeutics Inc, Novartis, Genzyme Corporation, Sanofi-aventis, Celgene, National Multiple Sclerosis Society and the NIH; holds financial interests/stock options in Cognition Pharmaceuticals. Inc. and may discuss unapproved agents that are in the MS developmental pipeline with any recommendations on their use.Dr. Addington serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Espay serves as an Associate Editor of Movement Disorders, Frontiers in Movement Disorders and Journal of Clinical Movement Disorders; serves as an editorial board member of Parkinsonism and Related Disorders and The European Neurological Journal; receives royalties for publications of books from Lippincott, Williams & Wilkins and from Cambridge University Press; serves on the scientific advisory board for Solvay Pharmaceuticals, Inc. (now Abbvie), Chelsea Therapeutics, Teva Pharmaceutical Industries Ltd., Impax Pharmaceuticals, Merz, Pfizer Inc, Solstice Neurosciences, LLC, Eli Lilly and Company, US WorldMeds; is a consultant for Chelsea Therapeutics, Solvay Pharmaceuticals, Inc. (now Abbvie); serves on the speakers' bureaus of Novartis, UCB, Teva Pharmaceutical Industries Ltd., American Academy of Neurology, Movement Disorders Society; receives research support from CleveMed/Great Lakes Neurotechnologies, Michael J. Fox Foundation and the NIH.Dr. Eidelberg serves as an Associate Editor of Journal of Neuroscience; serves as an editorial board member of Journal of Nuclear Medicine, Current Opinion in Neurology, Annals of Neurology and NeuroImage; serves on the scientific advisory board for the Michael J. Fox Foundation, ; co-inventor of United States Patent No. 5, 632,276 and No. 5,873,823 without financial gain; receives research support from the Michael J. Fox Foundation and the NIH.

1) Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease and 2) Topic of the month: Plenary sessions AAN Meeting April 2014. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. John Mytinger interviews Dr. Russell Dale about his paper on utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Dr. James Addington is reading our e-Pearl of the week about pseudo-internuclear ophthalmoplegia. In the next part of the podcast Dr. Alberto Espay interviews Dr. David Holtzman about his Robert Wartenberg Lecture at the AAN Meeting about Alzheimer's disease in 2014: Mapping a road forward. The participants had nothing to disclose except Drs. Dale, Addington, Espay and Holtzman.Dr. Dale serves on the scientific advisory board for Queensland Children's Medical Institute; serves as an editorial advisory board member of Multiple Sclerosis and Related Disorders Journal; received honoraria for lecturing from Biogen Idec; receives research support from the National Health and Medical Research Council. Dr. Addington serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Espay serves as an Associate Editor of Movement Disorders, Frontiers in Movement Disorders and Journal of Clinical Movement Disorders; serves as an editorial board member of Parkinsonism and Related Disorders and The European Neurological Journal; receives royalties for publications of books from Lippincott, Williams & Wilkins and from Cambridge University Press; serves on the scientific advisory board for Solvay Pharmaceuticals, Inc. (now Abbvie), Chelsea Therapeutics, Teva Pharmaceutical Industries Ltd., Impax Pharmaceuticals, Merz, Pfizer Inc, Solstice Neurosciences, LLC, Eli Lilly and Company, US WorldMeds; is a consultant for Chelsea Therapeutics, Solvay Pharmaceuticals, Inc. (now Abbvie); serves on the speakers' bureaus of Novartis, UCB, Teva Pharmaceutical Industries Ltd., American Academy of Neurology, Movement Disorders Society; receives research support from CleveMed/Great Lakes Neurotechnologies, Michael J. Fox Foundation and the NIH.Dr. Holtzman serves as an Associate Editor of Annuals of Neurology; serves as an editorial board member of Neurobiology of Disease, Experimental Neurology, Molecular Neurodegeneration, Science Translational Medicine and Journal of Experimental Medicine; co-founder of C2N Diagnostic LLC; is a consultant for AstraZeneca, Genentech, Inc., Bristol-Myers Squibb and Forum Pharmaceuticals; receives research support AstraZeneca, Eli Lilly and Company, Biogen Idec, C2N Diagnostic LLC, Cure Alzheimer's Disease, Tau Consortium, Ellison Medical Foundation and the NIH.

1) Long-term safety and effectiveness of natalizumab for re-dosing and treatment of multiple sclerosis and 2) Topic of the month: Plenary sessions AAN Meeting April 2014. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Ruth Ann Marrie interviews Dr. Paul O'Connor about his paper on long-term safety and effectiveness of natalizumab for re-dosing and treatment of multiple sclerosis. Dr. James Addington is reading our e-Pearl of the week about inclusion body myositis. In the next part of the podcast Dr. Alberto Espay interviews Dr. James Bernat about his Presidential Lecture at the AAN Meeting about challenges to ethics and professionalism facing the contemporary neurologist. The participants had nothing to disclose except Drs. Marrie, O'Connor, Addington, Espay and Bernat.Dr. Marrie serves on the editorial board for Neurology® and Multiple Sclerosis Journal; receives research support from Sanofi-aventis, Canadian Institutes of Health Research, Public Health Agency of Canada, Multiple Sclerosis Society of Canada, National Multiple Sclerosis Society, Multiple Sclerosis Scientific Foundation and Consortium of Multiple Sclerosis Centers.Dr. O'Connor served on the editorial advisory board of the MS Journal; serves on the scientific advisory board for Novartis, Sanofi-aventis, Bravo Pharmaceuticals, Genentech, Inc., Roche and Actelion Pharmaceuticals Ltd; is a consultant for Biogen Idec, Teva Pharmaceutical Industries Ltd., Sanofi-aventis and Novartis; received funding for travel to advisory board meeting in Toronto; receives research support from Novartis, Sanofi-aventis, Roche, Biogen Idec and as National Scientific and Clinical Advisor to the MS Society of Canada. Dr. Addington serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Espay serves as an Associate Editor of Movement Disorders, Frontiers in Movement Disorders and Journal of Clinical Movement Disorders; serves as an editorial board member of Parkinsonism and Related Disorders and The European Neurological Journal; receives royalties for publications of books from Lippincott, Williams & Wilkins and from Cambridge University Press; serves on the scientific advisory board for Solvay Pharmaceuticals, Inc. (now Abbvie), Chelsea Therapeutics, Teva Pharmaceutical Industries Ltd., Impax Pharmaceuticals, Merz, Pfizer Inc, Solstice Neurosciences, LLC, Eli Lilly and Company, US WorldMeds; is a consultant for Chelsea Therapeutics, Solvay Pharmaceuticals, Inc. (now Abbvie); serves on the speakers' bureaus of Novartis, UCB, Teva Pharmaceutical Industries Ltd., American Academy of Neurology, Movement Disorders Society; receives research support from CleveMed/Great Lakes Neurotechnologies, Michael J. Fox Foundation and the NIH.Dr. Bernat serves as an unpaid editorial board member of Neurocritical Care, Neurology Today, and Multiple Sclerosis and Related Diseases; a paid editorial board member of The Physician's Index for Ethics and Medicine; and receives royalties from the publication of the books Ethical Issues in Neurology, 3rd ed, Palliative Care in Neurology, and Ethical and Legal Issues in Neurology.

Today in FirstWord:

1) Factors associated with recovery from acute optic neuritis in multiple sclerosis and 2) Topic of the month: Neuro-infectious diseases. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Mark Keegan interviews Dr. Tanuja Chitnis about her paper on factors associated with recovery from acute optic neuritis in multiple sclerosis. Dr. Adam Numis is reading our e-Pearl of the week about tanycytic ependymal tumors. In the next part of the podcast Dr. Chenjie Xia interviews Dr. Karen Roos about neurology and infectious diseases: Bacterial meningoencephalitides. The participants had nothing to disclose except Drs. Jen, Tedeschi, Numis and Roos.Dr. Keegan serves as Chief Editor of eMedicine and receives research support from Terumo BCT.Dr. Chitnis is a consultant for Biogen Idec, Teva Pharmaceutical Industries Ltd., Novartis, Sanofi-aventis; receives research support from Merck Serono and Novartis in the form of Independent Investigator Awards, National Multiple Sclerosis Society. the Peabody Foundation and the Guthy-Jackson Charitable Foundation.Dr. Numis serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Roos receives royalties for five published books.