Multiple sclerosis: meeting unmet needs throughscientific discoveries and clinical practice9-10 April 2016 - Berlin, Germany

INTERNATIONAL CONFERENCEFINAL PROGRAMME AND ABSTRACT BOOK

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OverviewSeveral advances have been made from the clinico-diagnostic, scientific andtherapeutic points of view in the multiple sclerosis (MS) field over the past fewyears. Although new opportunities have been offered to MS patients, new issuesare concerning the MS community. Among them, the need to better definetherapeutic algorithms and to balance risks and benefits related to the newdisease modifying drugs (DMDs) are still of pivotal importance. If the relapsing-remitting phase of MS can benefit from the new DMDs, an effective treatment forthe progressive forms is still lacking. Therefore, basic scientists and clinicianshave put great effort into trying to better understand the pathogenic mechanismsunderlying progressive MS and discover new potential therapeutic targets.The programme will offer a comprehensive overview of MS pathophysiology,diagnosis and treatment as well as give participants the most up-to-dateinformation in basic science, diagnostic workout, clinical management and riskstratification in order to globally improve the lives and health care of MS patients.

Learning objectivesBy attending this live educational conference, participants will be able to: • Describe the main advances in MS pathogenesis• Discuss the role of different tools in MS diagnosis, monitoring and treatmentchoices

• Review the mechanisms of neurodegeneration and repair

Target audienceNeurologists involved in the management of MS patients.

ChairsDavid BatesDepartment of NeurologyRoyal Victoria InfirmaryNewcastle upon Tyne, UK

Giancarlo ComiDepartment of NeurologyInstitute of Experimental NeurologyVita-Salute San Raffaele UniversityMilan, Italy

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CME ProviderEXCEMED is a non profit foundation dedicated, since the last four decades, to thedevelopment of high-quality medical education programme all over the world.

EXCEMED adheres to the guidelines and standards of the European AccreditationCouncil for Continuing Medical Education (EACCME®) which states thatcontinuing medical education must be balanced, independent, objective, andscientifically rigorous.

Continuing medical educationEXCEMED (www.excemed.org) is accredited by the European AccreditationCouncil for Continuing Medical Education (EACCME®) to provide the followingCME activity for medical specialists. The EACCME® is an institution of theEuropean Union of Medical Specialists (UEMS), www.uems.net

The CME conference “Multiple sclerosis: meeting unmet needs throughscientific discoveries and clinical practice” held on 9-10 April 2016 in Berlin,Germany, is designated for a maximum of 9 (nine) hours of European CMEcredits (ECMEC). Each medical specialist should claim only those credits thathe/she actually spent in the educational activity. EACCME® credits are recognizedby the American Medical Association (AMA) towards the Physician's RecognitionAward (PRA). To convert EACCME® credit to AMA PRA category 1 credit, pleasecontact the AMA.

The Medical Association Berlin (Ärztekammer Berlin) granted 6 (six) CMEpoints for the first day and 3 (three) CME points for the second day of theconference.

EXCEMED adheres to the principles of the Good CME Practice group (gCMEp).

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LanguageThe official language of this live educational conference is English.

CME ProviderEXCEMED - Excellence in Medical Education

Senior Programme Manager: Alessia AddessiT +39 06 420413 591 - F +39 06 420413 677alessia.addessi@excemed.org

Medical Advisors: Federica Cerri | cerri.federica@hsr.itMedical Advisors: Doriana Landi | doriana.landi@gmail.com

For any logistic support please contact: Meridiano Congress InternationalCongress Manager: David H. SlangenT +39 06 88 595 250 - F +39 06 88595 234david.slangen@meridiano.it

FormatThis live educational event is accompanied by innovative technological toolsallowing participants to express their own views and opinions through real-timesurveys, discussion, a voting system, interactive workshops, Q&A sessions,questions cards, a dedicated website and mobile application.

Dedicated website Access http://www.excemedms.org to: - View the agenda - Fill in the post-event surveys - Get your certificate of attendance - Get your EACCME certificate

Mobile application Download the conference application:“2016ExcemedMS” and enjoy easy

access to: - Scientific programme - Faculty - Ask a question section - Tweets and extra content - Note-taking feature - Meeting rooms map

GENERAL INFORMATION

PROGRAMME

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9 April

Legend

L : Lecture Real-time survey Discussion S : Snapshot WS : Workshop

08.45 Opening and introduction D. Bates (UK) - G. Comi (Italy) Real-time survey

UPDATE ON PATHOGENESIS Chairs: D. Bates (UK) - G. Comi (Italy)

09.00 L1: Revisiting the role of T and B cells in MS A. Bar-Or (Canada) 09.20 L2: Variability of MS evolution: the role of genetics and environment D.A. Hafler (USA)

09.40 L3: Basic mechanisms of underlying disease “progression” H. Lassmann (Austria)

10.00 Discussion

10.20 Coffee break

Expert meet up

MS TREATMENT Chairs: D. Bates (UK) - G. Comi (Italy)

10.50 L4: Risk minimization P.S. Sørensen (Denmark)

11.10 L5: MRI as a guide for treatment decisions N. De Stefano (Italy)

11.30 L6: Visual platforms in clinical trials and patient monitoring P. Villoslada (USA)

11.50 L7: How the lab could burden CD4 and CD5 M. Comabella (Spain)

12.10 Discussion

Revisiting real-time survey

12.30 Lunch

SESSION I

SESSION II

Plenary room Red group Yellow group Blue group Green group

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9 April

08.45 MS TREATMENT Chairs: D. Bates (UK) - G. Comi (Italy)

Real-time survey

13.30 L8: Methodological aspects in comparing treatment efficacy L. Kappos (Switzerland) 13.50 L9: How to assess treatment response M. Tintorè (Spain)

14.10 L10: Revisited induction G. Comi (Italy)

14.30 Discussion

14.50 Snapshots

S1: Current and emerging treatments A. Chan (Switzerland)

S2: Emerging MRI techniques and their relationship to clinical outcomes J. Oh (Canada)

S3: Managing immunosuppression S. Schippling (Switzerland)

15.20 Coffee break

Expert meet up

RECOVERY AND REHABILITATION Chairs: D. Bates (UK) - G. Comi (Italy)

15.50 L11: Myelin repair S. Bittner (Germany)

16.10 L12: Pharmacology for enhanced recovery D. Centonze (Italy)

16.30 L13: New basis for rehabilitation J. Kesselring (Switzerland)

16.50 Discussion

Revisiting real-time survey

17.10 End of the first day

SESSION III

SESSION IV

PROGRAMME

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10 April

From 08.30 to10.30 *

WS1: Instrumental techniques MRI - N. De Stefano (Italy) Functional tests (VEP) - L. Leocani (Italy)

WS2: Decision making process G. Comi (Italy) M. Tintorè (Spain)

WS3: Symptomatic treatments J. Kesselring (Switzerland) P.S. Sørensen (Denmark)

WS4: Fluids biomarkers A. Bar-Or (Canada) L. Kappos (Switzerland)

10.30 Coffee break

Expert meet up

Back to plenary

11.00 Gauging your knowledge and views Be the first to correctly answer and win!

D. Bates (UK)

11.30 Closing plenary lecture New challenges and new frontiers: the PMSA experience A.J. Thompson (UK)

12.00 Wrap up

12.10 End of the conference

Lunch

WORKSHOPS

* This session includes four different workshops running in parallel, each one lasting two hours. Participants will have the chance to attendone of the workshops. Each workshop has a limited number of available places, registrations have been collected on a first come first servedbasis and places have been assigned accordingly.

DISCLOSURE OF FACULTY RELATIONSHIPS

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EXCEMED adheres to guidelines of the European Accreditation Council for Continuing Medical Education (EACCME®) andall other professional organizations, as applicable, which state that programmes awarding continuing education creditsmust be balanced, independent, objective, and scientifically rigorous. Investigative and other uses for pharmaceuticalagents, medical devices, and other products (other than those uses indicated in approved product labeling/package insertfor the product) may be presented in the programme (which may reflect clinical experience, the professional literature orother clinical sources known to the presenter). We ask all presenters to provide participants with information aboutrelationships with pharmaceutical or medical equipment companies that may have relevance to their lectures. This policyis not intended to exclude faculty who have relationships with such companies; it is only intended to inform participants ofany potential conflicts so that participants may form their own judgements, based on full disclosure of the facts. Further,all opinions and recommendations presented during the programme and all programme-related materials neither implyan endorsement nor a recommendation on the part of EXCEMED. All presentations represent solely the independent viewsof the presenters/authors.

The following faculty provided information regarding significant commercial relationships and/or discussions ofinvestigational or non-EMEA/FDA approved (off-label) uses of drugs:

Amit Bar-Or Declared receipt of honoraria or consultation fees or grant support from Amplimmune, BayhillTherapeutics, Berlex/Bayer, Biogen Idec, Diogenix, Eli-Lilly, Genentech, GlaxoSmithKline,Guthy-Jackson/GGF, Merck/EMD Serono, Medimmune, Mitsubishi Pharma, Novartis, OnoPharma, Receptos, Roche, Sanofi-Genzyme, Teva Neuroscience, Wyeth.

David Bates Declared no potential conflict of interest.

Stefan Bittner Declared receipt of honoraria or consultation fees from Genzyme, Biogen Idec, Teva.

Diego Centonze Declared receipt of grants and contracts from Bayer Schering, Biogen Idec, Merck, Mitshubishi,Novartis, Roche, Sanofi-Aventis, Teva. He declared receipt of honoraria or consultation feesfrom Almirall, Bayer Schering, Biogen Idec, Genzyme, Gw Pharmaceuticals, Merck, Novartis,Sanofi-Aventis, Teva. He declared to be member of a company advisor board, board of directorsor other similar group: Almirall, Bayer Schering, Biogen, Genzyme, Gw Pharmaceutivals,Merck, Novartis, Teva.

Andrew Chan Declared receipt of grants and contracts from Genzyme, Biogen, Novartis. He declared receiptof honoraria or consultation fees from Bayer, Biogen, Genzyme, Merck, Novartis, Roche, Teva.

Manuel Comabella Declared no potential conflict of interest.

Giancarlo Comi Declared receipt of honoraria or consultation fees from Novartis, Teva, Sanofi, Genzyme, Merck,Biogen, Bayer, Roche, Almirall, Chugai, Receptos, Forward Pharma.

Nicola De Stefano Declared receipt of honoraria or consultation fees from Novartis, Merck, Biogen Idec, Roche. Hedeclared to be member of a company advisor board, board of directors or other similar group:Novartis, Merck, Biogen Idec, Roche. He declared participation in a company sponsoredspeaker’s bureau: Novartis, Merck, Genzyme.

David A. Hafler Declared to be member of a company advisor board, board of directors or other similar group:Bristol Myers Squibb, EMD Serono, Genzyme, Sanofi Aventis, Juno Therapeutics, MedImmune,Mylan Phamaceuticals, NKT Therapeutics.

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Ludwig Kappos Declared to have served as member or chair of planning and steering committees oradvisory boards as well as independent safety boards, in most cases in conjunction withcorporate-sponsored clinical trials in multiple sclerosis and other neurological diseases.The sponsoring pharmaceutical companies for these activities include Actelion, Alkermes,Almirall, Bayer, Biogen, GeNeuro SA, Genzyme, Merck, Mitsubishi Pharma, Novartis,Receptos, Toche, Sanofi-Aventis, Santhera, Teva and royalties from Neurostatus SystemAG. For educational activities he received honoraria from Allergan, Almirall, Bayer, Biogen,Genzyme, Merck, Novartis, Pfizer, Sanofi-Aventis, Teva and UCB. The research of the MSCenter in Basel has been supported by grants from Bayes, Biogen, Novartis, the Swiss MSSociety, the Swiss National Research Foundation, the European Union and Roche ResearchFoundations. He received grants from patients services from Bayer, Merck and Teva.

Jürg Kesselring Declared receipt of honoraria or consultation fee from DMC Fingolimod studies. Hedeclared to be member of a company advisor board, board of directors or other similargroup: DMC Fingolimod studies.

Hans Lassmann Declared receipt of honoraria or consultation fees from Novartis, Teva, Biogen.

Letizia Leocani Declared receipt of grants and contracts from Merck. Declared receipt of honoraria orconsultation fee from Biogen Idec and participation to Advisory Board: Biogen.

Jiwon Oh Declared receipt of grants and contracts from MS Society of Canada, Biogen Idec,Genzyme. She declared receipt of honoraria or consultation fee from EMD Serono, Biogen,Genzyme, Novartis, Teva.

Sven Schippling Declared receipt of grants and contracts from from Bayer Healthcare, Biogen, Novartis,Sanofi Genzyme. He declaed receipt of consultation fees from Bayer Healthcare, Biogen,Merck Serono, Novartis, Sanofi, Genzyme and Teva.

Per Soelberg Sørensen Declared receipt personal compensation for serving on scientific advisory boards, steeringcommittees or independent data monitoring boards for Biogen Idec, Merck, Novartis,Genzyme, Teva Pharmaceutical Industries Ltd., Glaxo SmithKlime, medDayPharmaceuticals and Forward Pharma. He declared receipt of honoraria from Biogen Idec,Merck, Teva Pharmaceutical Industries Ltd., Genzyme and Novartis. His departmentreceived support from Biogen Idec, Merck, Teva, Sanofi-Aventis, Genzyme, Novartis, Bayer,RoFAR, Roche, the Danish Multiple Sclerosis Society, the Danish Medical Research Counciland the European Union Sixth Framework Programme.

Alan J. Thompson Declared receipt of honoraria or consultation fees from Biogen, Eisai, MedDay, Novartis.

Mar Tintorè Declared receipt of honoraria or consultation fees from Bayer, Biogen, Merck, Genzyme,Novartis, Sanofi-Aventis, Teva, Roche, Almirall. She declared to be member of a companyadvisor board: Roche, Biogen.

Pablo Villoslada Declared receipt of grants and contracts from Roche, Biogen, Genzyme, ISCII, EC-Horyzon2020, Fundation Marato TV3, GAEM. Declared receipt of honoraria or consultationfee from Roche, Novartis, Health Engineering, Araclon. He is takeholder in Bionure Inc,Spire Bioventures, MintLabs.

BIOGRAPHIES

Amit Bar-Or is a neurologist and neuroimmunologist, Professor of Neuroimmunology and Associate Director TranslationalResearch, at the Montreal Neurological Institute, McGill University, where he also serves as Director of the ExperimentalTherapeutics Program which integrates “mode of action” studies of novel therapies, with studies of human disease mechanism.Prof. Bar-Or’s clinical focus is in the area of multiple sclerosis and related CNS inflammatory disorders, and he currently servesas President of the Canadian Consortium of MS Clinics (CNMSC). His lab examines basic principles of immune regulation andimmune-neural interaction in the context of CNS inflammation, injury and repair. Immune system studies include elucidation ofeffector and regulatory properties of distinct immune cell (principally B cell, myeloid cell and T cell) subsets; their interactions;and how these may contribute to inflammatory neurological diseases such as multiple sclerosis, in both children and adults.Studies of immune-neural interaction consider both relapsing and progressive disease biology, including mechanisms by whichneural cells respond to, as well as contribute to, CNS inflammation and degeneration. An overarching theme is translation ofbasic lab discoveries towards understanding and development of novel experimental therapies. This includes human in vivobiological proof-of-principle studies of therapeutic mode-of-action and immune reconstitution; development and application ofbiological assays to monitor disease activity and evaluate response to treatments; and the development of clinically meaningfulbiomarkers for patients with autoimmune and neurological disease supported.

Amit Bar-OrClinical Research UnitMontreal Neurological InstituteMontreal, Canada

David Bates trained in Medicine at Downing College, Cambridge and the Middlesex Hospital, London and in Neurologyat the University of Newcastle upon Tyne, UK, and the Mayo Clinic, Rochester, Minnesota, USA. He is EmeritusProfessor of Clinical Neurology at the University of Newcastle upon Tyne, Former Editor of the International MS Journaland past Chairman of both the MS Forum and the Medical Research Advisory Committee of the MS Society of GreatBritain and Northern Ireland. He is Chairman of the Joint Colleges Working Party on the Vegetative State and Criteriafor Brain Stem Death and Chairman of the Consensus Conference on the Epilepsies for the Royal College of Physicians,Edinburgh. His research interests are in vascular disease, coma and the unconscious patient, and in MS. ProfessorBates has published more than 150 peer-reviewed papers, edited three textbooks and contributed chapters to morethan 20. His current research involvement is predominantly in clinical trials of novel therapy in MS and in the role ofmitochondria in protecting and repairing axons in the more chronic phases of that disease.

David BatesDepartment of NeurologyRoyal Victoria InfirmaryNewcastle upon Tyne, UK

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BIOGRAPHIES

Stefan Bittner, MD is a professor of neuroimmunology at the Department of Neurology of the Johannes Gutenberg-University in Mainz, Germany. Following studies in medicine and biomedicine in Würzburg, he received his clinical andscientific education as a junior research group leader and resident in the Department of Neurology (Prof. Wiendl andMeuth) at the University of Münster. His main research interest is the understanding of pathophysiological mechanismsunderlying the crosstalk between the immune and central nervous systems. A special focus is the role of ion channelsas regulators of immune cell and CNS functions. Ion channels are ubiquitous signal integrators regulating basiccellular functions mandatory for key pathways in autoinflammatory conditions, such as immune cell activation, effectorfunctions, demyelination and neuronal cell death. Furthermore, he has recently identified that ion channels regulatethe inflammatory phenotype of endothelial cells opening up novel research direction on the blood-brain barrier. Hisresearch group is part of the focus program translational neuroscience, the research center for immunotherapy andthe rhine-main neuroscience network.

Stefan BittnerDepartment of Neurology University of Muenster Muenster, Germany

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Diego Centonze is Full Professor of Neurology at Tor Vergata University, Rome, Italy and Director of the Neurology Unitat the IRCSS Istituto Neurologico Mediterraneo Neuromed, Pozzilli (IS), Italy. He also leads the Experimental NeurologyLaboratory at Tor Vergata University. His major clinical interest involves the evaluation of new drugs for the treatmentof MS. His research interests are related to the role of synaptic transmission and plasticity in the pathophysiology of MSand its experimental model, as well as to the physiology of the endocannabinoid system and its involvement ininflammatory neurodegenerative diseases. Prof. Centonze graduated in Medicine at the University of Rome LaSapienza in 1994, specialised in Neurology in 1999 and in Psychiatry in 2006 at the University of Rome Tor Vergata. Heobtained his PhD in Rehabilitation Medicine in 2012. He is Principal Investigator of many phase II, III and IV national andinternational trials with new therapeutic agents for MS and is a member of the Society for Neuroscience, the ItalianNeurological Society (SIN) and the Italian Neuroscience Society (SINS). Prof. Centonze is author of around 300 peer-reviewed papers published in international journals of Neuroscience, Neurology and Psychiatry.

Diego CentonzeNeurology UnitIRCSS Istituto Neurologico Mediterraneo NeuromedPozzilli (IS), ItalyandTor Vergata UniversityRome, Italy

Manuel Comabella holds a senior research position and is the head of the lab of the Clinical Neuroimmunology Unit -Multiple Sclerosis Center of Catalonia (Cemcat), a leading multiple sclerosis group in Spain directed by Prof. XavierMontalban. Dr. Comabella’s main research interests are the search of biomarkers related with different aspects ofmultiple sclerosis such as genetic susceptibility, conversion to multiple sclerosis in patients with a first attacksuggestive of demyelinating disorder, disease course and prognosis, and response to therapies; and the search of newtherapies for multiple sclerosis.

Manuel ComabellaMultiple Sclerosis Centre of Catalonia (Cemcat)Neurology-Neuroimmunology DepartmentVall d’Hebron University HospitalBarcelona, Spain

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Andrew Chan is Head of Ambulantes Neurozentrum Inselspital, Bern University Hospital, Bern (Switzerland) andProfessor of Neurology at the Ruhr-University Bochum. He is also Deputy Head of department, Clinical consultant,Dept. Neurology, University of Bochum, St. Josef-Hospital, Germany. He is an ECTRIMS council board member until2015, Advisory Board of the German Multiple Sclerosis Society and member of the Ethics Committee, Ruhr-UniversityBochum, Germany until 2015. He is also a reviewer for the European Union FP7, national research boards, and forinternational neurological and neuroimmunological journals. He has received the Award for the best “Habilitation”(postdoctoral lecturer qualification) of Georg-August University, Göttingen, Germany: (2005/2006) and LangheinrichPrize for Multiple Sclerosis research (2002).

Andrew ChanNeurocenter InselspitalUniversity Hospital BernBern, Switzerland

BIOGRAPHIES

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Nicola De Stefano is Associate Professor of Neurology at the Department of Medicine, Surgery and Neuroscience,University of Siena, Italy. He is also Head of the NeuroImaging Laboratory in the same Department; Adjunct Professor,Montreal Neurological Institute, McGill University, Canada; and Honorary Visiting Professor, Imperial College London, UK.Prof. De Stefano graduated with his MD degree from the University of Siena, Italy, and went on to undertake his internship.After successfully completing his residency in neurology, he went on to pursue postgraduate training overseas in Canadabefore returning to his alma mater where he obtained his PhD. Prof. De Stefano’s current research interests lie in multiplesclerosis and other neurological diseases involving the brain white matter. In particular, he is a world renowned expert onthe clinical application of new neuroimaging techniques in brain and muscle of patients with neurological disease. Prof.De Stefano is a member of several prestigious professional societies and organisations including the American Academyof Neurology, the European Neurological Society, the Italian Society of Neurology, and the International Society forMagnetic Resonance in Medicine. Since 2009, he has been co-chairing the MAGNIMS European network for the study ofmagnetic resonance in multiple sclerosis.

Nicola De StefanoNeurology and Neurometabolic UnitDepartment of Neurological and Behavioral SciencesUniversity of SienaSiena, Italy

Giancarlo Comi is Professor of Neurology, Chairman of the Department of Neurology and Director of the Institute ofExperimental Neurology at the Vita-Salute San Raffaele University, Milan. He is also the President of the EuropeanCharcot Foundation (ECF), member of the Board of Administration of the Italian Multiple Sclerosis (MS) Foundation andthe Scientific Committee of Associazione Italiana Sclerosi Multipla and Co-chair of the Scientific Steering Committeeof the Progressive MS Alliance. He joined the Department of Neurology, Scientific Institute San Raffaele, Vita-SaluteSan Raffaele University, Milan, as a Clinical Assistant in 1974 and was appointed Assistant Professor in ClinicalNeurophysiology in 1988. Professor Comi has served as President of the European Neurology Society, the ItalianSociety of Clinical Neurophysiology and the Italian Society of Neurology. In 2015 Prof. Comi has obtained, as the firstItalian, the “Charcot Award for MS research” by the MS International Federation (MSIF) and also granted both honorarymembership of the European Neurological Society (ENS) and fellow of the European Academy of Neurology (FEAN).Recently he has been awarded the Gold medal of Benemeranza Civica from the City of Milan.

Giancarlo ComiDepartment of NeurologyInstitute of Experimental NeurologyVita-Salute San Raffaele UniversityMilan, Italy

David A. Hafler is the William S. and Lois Stiles Edgerly Professor and Chairman Department of Neurology andProfessor or Immunobiology, Yale School of Medicine, and is the Neurologist-in-Chief of the Yale-New Haven Hospital.He graduated magna cum laude in 1974 from Emory University with combined B.S. and M.Sc. degrees in biochemistry,and the University of Miami School of Medicine in 1978. He then completed his internship in internal medicine at JohnsHopkins followed by a neurology residency at Cornell Medical Center-New York Hospital in New York. Dr. Hafler wastrained in immunology at the Rockefeller University and then at Harvard where he joined the faculty in 1984 and laterbecame the Breakstone Professorship of Neurology at Harvard and was a founding Associated Member of the BroadInstitute at MIT. In 2009 he move to Yale as the Chair of the Department of Neurology. Dr. Hafler is a clinical scientistwith a research interest in the mechanism of multiple sclerosis with over 370 publications in the field of MS,autoimmunity and immunology. He is a co-founder of the International MS Genetic Consortium a group that identifiedthe genes causing MS. Dr. Hafler has been elected to membership in the American Society of Clinical Investigation, theAlpha Omega Society, and was a Weaver Scholar of the NMSS.

David A. HaflerWilliam S. and Lois Stiles Edgerly Department of NeurologyYale School of MedicineYale New Haven Hospital New Haven, CT, USA

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Ludwig Kappos is Chair of the Department of Neurology at the University Hospital in Basel (Switzerland) and Professorof Neurology and Clinical Neuroimmunology at the University of Basel, Medical Faculty, where he is Academic HeadDepartments of Medicine and Neurology. Ludwig Kappos serves as chair or as a member of several steeringcommittees and advisory boards for clinical trials and in organizations active in the field of MS and general neurology.He has received the “Kuratorium der Unterfränkischen” and “Langheinrich Stiftung” prizes for Research in the field ofmultiple sclerosis. He was also awarded an Honorary Doctorate from the Medical Science Faculty, Aristotle University,Thessaloniki, Greece 2014/2015. He was published more than 640 original papers, chapters and reviews in scientificjournals and books; more than 950 published abstracts and more than 600 invited lectures and seminars.

Ludwig KapposDepartment of Biomedicine University Hospital BaselBasel, Switzerland

Hans Lassmann is professor and head of Division of Neuroimmunology at the Centre for Brain Research in Vienna(Austria) and Honorary Professor at the University College of London (UK). He is Member of the Deutsche Akademieder Naturforscher Leopoldina and Full Member of the Austrian Academy of Sciences. He was Founding Director of theCenter for Brain Research at the University of Vienna / Medical University of Vienna (till 2007) and Member of the Senateof the Medical University of Vienna (till 2013). Furthermore, he was Vice Director of the Center for Brain Research ofthe Medical University of Vienna (till 2012). Among several others recognitions, he has received First Prize in Neurologyin the 2006 BMA Medical and the Wagner Jauregg Medaillie der Öst. Ges. f. Biologische Psychiatrie Book Competition(2015); he was awarded by the American Association of Neuropathologists with the TEVA / Parisi Neuroscience Award(2009) and by the British Neuropathological Society with the Alfred Maier Award (2011). Nominated Highly CitedResearcher in ISI Highly Cited Researchers Project (2014), he is Distinguished Member of the Japanese Society ofNeurology.

Hans LassmannDivision of NeuroimmunologyCenter for Brain ResearchMedical University of ViennaVienna, Austria

BIOGRAPHIES

Jürg Kesselring is head of the department of Neurology & Neurorehabilitation at the Rehabilitation Centre in Valens(Switzerland) and Professor of Clinical Neurology and Neurorehabilitation at the University of Bern. He is formerchairman of the International Medical and Scientific Board and honorary lifetime member of Directors of the MultipleSclerosis International Federation (MSIF). He has received a Golden Needle of Honour for International Achievementsand was awarded by the German Multiple Sclerosis Society for which he also presided. In 2015 he became FirstHonorary President of the Swiss Multiple Sclerosis Society; that same year, he also won the Margrit Egnér Prize 2015for outstanding achievements in anthropologichal philosophy and psychology. Furthermore he was chairman of theWHO working group on Multiple Sclerosis, former ICRC medical delegate to Lebanon, Pakistan and Zaire, president ofthe European Committee on Treatment and Research in Multiple Sclerosis (ECTRIMS) in 1990/91 and 1995–1999,president of the group of experts of the National Research Programme NFP 38 “Diseases of the Nervous System“ (till2001), founding member and vice-president of the Swiss Society for Neurorehabilitation (till 2002) and honorary seniorresearch fellow at the Institute of Neurology, National Hospital of London.

Jürg KesselringDepartment of NeurorehabilitationValens Clinic Rehabilitation CenterValens, Switzerland

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Jiwon Oh is Assistant Professor of Medicine in the Division of Neurology at the University of Toronto. After obtaining herMD from the Faculty of Medicine at Queen’s University in 2005, she completed a neurology residency at the Universityof Toronto in 2010. She subsequently pursed a clinical and research fellowship in neuroimmunology and neurologicalinfections at the Johns Hopkins School of Medicine, and concurrently completed a PhD in the Graduate TrainingProgram in Clinical Investigation at the Johns Hopkins School of Public Health. Dr. Oh is currently on staff at St.Michael’s Hospital (Toronto, Canada), and specializes in the care of patients with neuroimmunological disorders, withspecific interest in patients with multiple sclerosis. Dr. Oh’s research focuses on the development of advanced magneticresonance imaging (MRI) techniques in the spinal cord of MS patients. Using advanced techniques such as diffusion-tensor and magnetization-transfer imaging, she hopes to clarify how microstructural changes in the spinal cord causesensorimotor deficits in MS patients and develop these markers as surrogate outcome measures in clinical trialsettings.

Jiwon OhDivision of Neurology University of TorontoToronto, Canada

Letizia Leocani, after obtaining her medical degree at the State University of Milan, took a PhD in Human Physiologyand specialized in Neurology at the same university. She was also a Research Fellow at the Human Motor ControlSection of the National Institutes of Health in Bethesda (USA). She is currently Associate Professor of Neurology at Vita-Salute University of Milan, and a Group Leader of the Experimental Neurophysiology Unit and of MAGICS-IntraCerebralStimulation Center at INSPE-Institute of Experimental Neurology of OSR. Her main focus is on thedevelopment and validation of neurophysiological and OCT markers of assessment and monitoring of central nervoussystem diseases.

Letizia LeocaniInstitute of Experimental NeurologyUniversity Vita-Salute IRCCSSan Raffaele HospitalMilan, Italy

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Sven Schippling is currently Deputy Head of the Department of Neuroimmunology and Clinical Multiple SclerosisResearch (nims) at the University Hospital Zürich, Switzerland. He is also the Co-Director of the Clinical ResearchPriority Program MS (CRPPMS) and Consultant Neurologist at the Department of Neurology at University HospitalZürich. He is a Senior Group Leader at the Neuroscience Center Zurich of the Federal Technical Highschool Zurich andthe University of Zurich. Priorto this, he was Head of the first MS Day Clinic in Germany at the University Medical Centerof Hamburg University, Germany. From 2005 to 2006 he was a Postdoctoral Research Fellow at the Institute ofNeurology, University College London, UK and the National Hospital for Neurology and Neurosurgery, London.Schippling’s areas of special interest are clinical neuroimmunology, mainly within the fields of multiple sclerosis (MS)and neuromyelitis optica. His research focuses include multimodal imaging methods in MS, such as magneticresonance imaging and optical coherence tomography, transcranial magnetic stimulation and clinical trials includingstem cell therapies in MS (haematopoietic and mesenchymal). He is also a member of the steering group for the “MSin the 21st Century” initiative, the multinational OCTIMS and BENEFIT11 trials and has authored numerous peer-reviewed publications.

Sven SchipplingCRPP Multiple SclerosisUniversity of ZurichZurich, Switzerland

BIOGRAPHIES

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Per Soelberg Sørensen is Professor of Neurology at the University of Copenhagen and senior consultant at Departmentof Neurology, Rigshospitalet, Copenhagen. He is the founder of the Danish Multiple Sclerosis Center, Rigshospitalet.Core elements in his research include development of new MS therapies, translational and biomarker research, andhe has initiated and conducted several large international trials. Professor Sorensen has held several honorary officesincluding: President of the Danish Neurological Society (1991–1994) and the Danish Society for Research in MultipleSclerosis (1995–2001); Executive Member of the European Committee for Treatment and Research in Multiple Sclerosis(1996–2000); and Chairman of the EFNS Scientist Panel of Demyelinating Diseases (2003–2009). Currently ProfessorSorensen’s appointments include Secretary General of ECTRIMS; Executive Board member of the European Academyof Neurology; Executive Board member of the European Charcot Foundation for Research in Multiple Sclerosis;Member of the Medical Advisory Board of the International Federation of Multiple Sclerosis Societies (IFMSS); Memberof the International Advisory Committee on Clinical Trials in MS, under the sponsorship of the US National MS Societyand ECTRIMS; and Chairman of the Danish Multiple Sclerosis Group; and Board member of the Danish Committee forResearch in Multiple Sclerosis.

Per Soelberg SørensenDanish Multiple Sclerosis CenterDepartment of NeurologyRigshospitalet, University of CopenhagenCopenhagen, Denmark

Mar Tintorè MD, PhD is Senior Consultant at the Multiple Sclerosis Centre of Catalonia (Cemcat) and clinical chief ofthe Neurology/Neuroimmunology Department at Vall d’Hebron University Hospital in Barcelona, Spain. The Cemcatconducts clinical and basic research on MS and neuroimmunology to aid people living with MS. Dr Tintorè’s mainresearch interests are the initial presentation of demyelinating events, prognostic factors, paediatric MS, advances inMRI techniques, the immunological aspects of MS, and treatment of the disease. Dr Tintorè has authored or co-authored more than 165 articles in peer-reviewed journals and is Editor for Multiple Sclerosis Journal – Experimental,Translational and Clinical. She also acts as a reviewer for several national and international journals, as well asnational research support and funding agencies.

Mar TintorèMultiple Sclerosis Centre of Catalonia (Cemcat)Neurology-Neuroimmunology DepartmentVall d’Hebron University HospitalBarcelona, Spain

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Alan J. Thompson is Dean of the Faculty of Brain Sciences at University College London, Garfield Weston Professor ofClinical Neurology and Neurorehabilitation at the UCL Institute of Neurology, a consultant neurologist at the NationalHospital for Neurology and Neurosurgery, Queen Square, and Chair of the Neuroscience Programme at the UCLPAcademic Health Sciences Centre. His main area of expertise is in demyelinating disease, particularly the diagnosis,evaluation, and management of multiple sclerosis (MS), focusing on the pathological mechanisms that underpinneurological disability and recovery using structural and functional imaging. He has published extensively in theseareas in high-impact journals. A further focus is neurorehabilitation, and as Dean, he leads comprehensiveprogrammes of research in dementia and mental health within the Faculty. Professor Thompson is chair of theScientific Committee of the International Progressive MS Alliance, a Senior Investigator for the National Institute forHealth Research, Editor-in-Chief for Multiple Sclerosis Journal, and a Guarantor of Brain. He received hisundergraduate and postgraduate degrees from Trinity College Dublin, and an honorary doctorate from HasseltUniversity, Belgium.

Alan J. ThompsonDepartment of Brain Repair and Rehabilitation Institute of Neurology, University College London National Hospital for Neurology and NeurosurgeryLondon, UK

Pablo Villoslada received his MD at the University of Santiago de Compostela (Spain) in 1990. He completed his specialityin Neurology in 1995 at the Hospital Vall d’Hebron (Spain) and his PhD in Neuroimmunology in 1996 at the AutonomousUniversity of Barcelona (Spain). He moved to the University of California, San Fracisco (USA) as a postdoctoral fellowreturning to Barcelona in 1998 and he worked as Assistant and Asociate Professor of the University of Navarra from 2001to 2008. He is currently Professor and Group Leader at the Center of Neuroimmunology, Institute of BiomedicalResearch August Pi Sunyer (IDIBAPS), University of Barcelona and Adjunct Professor at the University of California, SanFrancisco. He is founder and scientific advisor in Bionure Inc, Menlo Park, dedicated to the development ofneuroprotective therapies for brain diseases. He was Director of the Multiple Sclerosis Center at the University ofNavarra Medical Center (till 2008). He was awarded by the AEGACA Galicia-Catalonia Entrepreneur Association forMedical and Science Achivements (2014) and by the Spanish Neurology Society for research in the field of demyelinatingdiseases. Dr. Pablo Villoslada has been active in neurosciences and translational research for more than 15 yearscontributing to the application of systems biology to neurological diseases, development of new therapies or biomarkersfor Multiple Sclerosis, and clinical research assessment of the retinal nerve fiber layer with optic coherence tomographyand cognition in brain diseases. He has published more than 120 papers in top journals in the field of neurology (AnnNeurol, Neurology, Arch Neurol, Brain, etc) and 9 patents in biomarkers and new therapies for brain diseases.

Pablo VillosladaDepartment of NeurologyUniversity of California, San Francisco (UCSF)San Francisco, CA, USA

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ABSTRACTS

While MS has traditionally been thought of as principally a T cell-mediated disease, the substantial impact of selectiveB-cell targeting on disease activity underscores key roles for B cells, at least in the relapsing biology of MS.1,2 Of note,the contribution of B cells invokes important antibody-independent functions of these cells, including their potential toact as either pro- or anti-inflammatory mediators, thereby influencing disease-relevant T-cell responses. Contrastingresults of different treatments targeting B cells in patients (despite predictions of therapeutic benefits from animalmodels) call for a better understanding of the multiple roles that distinct human B-cell responses likely play in MS.Most recently, the implication of a GM–CSF-expressing subset of B cells in MS patients points to a role of B cells in theactivation of myeloid cells which, in turn, can induce pro-inflammatory T cell responses.2 The implications of suchcascades of cellular immune interactions (B cell : Myeloid : T cell) in MS relapses are coming to the fore, with growinginterest also in their potential relevance to the CNS-compartmentalized processes influencing progressive (non-relapsing) disease.

References:1. Michel L, Touil H, Pikor NB, et al. B Cells in the Multiple Sclerosis Central Nervous System: Trafficking and Contribution to CNS-

Compartmentalized Inflammation. Front Immunol. 2015;6:636.2. Li R, Rezk A, Miyazaki Y, Hilgenberg E, et al. Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy.

Sci Transl Med. 2015; 21;7:310ra166.

L1. Revisiting the role of T and B cells in MS

Amit Bar-OrClinical Research Unit, Montreal Neurological InstituteMontreal, Canada

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Genome-wide association studies (GWAS) have identified genetic loci underlying human diseases and traits. However,the precise nucleotide changes and the mechanisms that cause heritable differences among individuals remain largelyunknown. To identify and characterize the causal variants driving autoimmune disease risk, we leveraged a newgeneration of dense genotyping data and a novel algorithm for fine mapping single nucleotide polymorphisms (SNPs).1,2

This work enabled us to explicitly predict, for each individual SNP associated with 21 autoimmune diseases, thelikelihood that it represents a causal mutation.3 We then integrated these data with transcription and cis-regulatoryelement annotations, which we derived by mapping RNA and chromatin state in key immune cell types. These cell typesincluded CD4+ T-cell subsets in resting and activated states, FoxP3+ regulatory cells, CD8+ T-cells, B-cells andmonocytes. We found that the causal variants in 88% of GWAS loci are non-coding, with a majority mapping to immune-cell specific enhancers, many of which transcribe enhancer-associated eRNAs and increase histone acetylation uponimmune activation.3 Candidate causal variants tend to coincide with nucleosome-depleted regions bound by masterregulators of immune differentiation and stimulus-dependent gene activation, including IRF4, PU.1, NFκB and AP-1family transcription factors. However, our analysis suggests that only a minority of causal variants directly alter cognatetranscription factor binding motifs. Rather, most variants that confer disease risk, including those that alter geneexpression, instead alter adjacent, non-canonical sequence determinants.3 Finally, autoimmune disease develops as aresult of untoward interactions between genetics and the environment. We showed that increased salt concentrationsfound locally under physiological conditions in vivo dramatically boost the induction of Th17 cells mediated by SGK1.4

Th17 cells generated under high-salt conditions display a highly pathogenic and stable phenotype, characterized by up-regulation of the pro-inflammatory cytokines GM–CSF, TNF-α and IL-2. Mice fed a high-salt diet develop a more severeform of EAE compared with those fed a standard diet. It was of interest to observe that RNA array analyses of genesinduced by sodium chloride were markedly enhanced among GWAS hits. Identifying specific sites where a single, non-coding nucleotide variant is responsible for disease risk may pinpoint specific disruptions of consensus transcriptionfactor binding sites that ultimately define disease risk as related to environmental factors.

L2. Variability of MS evolution: the role of genetics andenvironment

David A. Hafler William S. and Lois Stiles Edgerly, Department of Neurology, Yale School of MedicineYale New Haven Hospital , New Haven, CT, USA

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References:1. International Multiple Sclerosis Genetics Consortium (IMSGC), Beecham AH, Patsopoulos NA, et al. Analysis of immune-related loci

identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013;45:1353-60. 2. Patsopoulos NA, Barcellos LF, Hintzen RQ, et al. Fine-mapping the genetic association of the major histocompatibility complex in multiple

sclerosis: HLA and non-HLA effects. PLoS Genet. 2013;9:e1003926. 3. Farh KK, Marson A, Zhu J, et al. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature 2015;518:337-43.4. Kleinewietfeld M, Manzel A, Titze J, et al. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature

2013;496:518-22.

Although in the early stages of disease MS leads to focal inflammatory demyelinating lesions, predominantly in thewhite matter of the brain and spinal cord, MS pathology changes with disease duration and, in particular, when patientsenter the progressive phase.1,2 In this phase the formation of new focal white matter lesions is sparse, but pre-existinglesions tend to expand slowly.2 In addition extensive (subpial) demyelination is seen in the cerebral and cerebellarcortex. Diffuse demyelination and axonal or neuronal degeneration take place in normal appearing white and greymatter; the combination of these changes results in profound tissue loss, and atrophy of the brain and spinal cord.1

Active demyelination and neurodegeneration in progressive MS correlate significantly with the degree of inflammationby T-cells, B-cells and plasma cells. However, inflammation is at least in part trapped behind a closed blood–brainbarrier, and gives rise to lymphocytic follicle-like aggregates in the meninges and the large perivascular spaces.Demyelination and tissue damage is in part mediated by soluble factors produced by the inflammatory cells, but thenature of these soluble factors remains undefined. Oxidative injury plays a major role in tissue degeneration, which maylead to mitochondrial injury and a state of energy deficiency.1 Mitochondrial damage, however, also augments oxidativeinjury by the liberation of electrons from the respiratory chain.3 Age-related iron accumulation and its liberation in thelesions may further amplify oxidative injury of the brain.3,4 Thus, in progressive MS, tissue injury appears to be drivenby an inflammatory process, largely compartmentalized within the central nervous system, and mediated throughmicroglia activation and oxidative stress. This process is further amplified by factors related to brain ageing and theaccumulation of structural damage in the nervous system.1,2

L3. Basic mechanisms of underlying disease“progression”

Hans LassmannDivision of Neuroimmunology, Center for Brain Research, Medical University of ViennaVienna, Austria

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References:1. Lassmann H. Pathology and disease mechanisms in different stages of multiple sclerosis. J Neurol Sci. 2013;333:1-4.2. Frischer JM, Weigand SD, Guo Y, et al. Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis

plaque. Ann Neurol. 2015;78:710-21.3. Witte ME, Mahad DJ, Lassmann H, et al. Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis. Trends Mol Med.

2014;20:179-87.4. Hametner S, Wimmer I, Haider L, et al. Iron and neurodegeneration in the multiple sclerosis brain. Ann Neurol. 2013;74:848-61.

The original first-line injectable disease-modifying treatments for MS, interferon (IFN)-beta and glatiramer acetate,have been used for decades and are widely regarded as having favourable safety profiles. However, the occurrence ofneutralising antibodies (NAb) against IFN-beta can hamper its disease modifying effects; hence, regular NAbmeasurement is recommended during the first 2 years of IFN-beta therapy.1

Some of the newer, more effective, therapies for MS carry the risk of severe or even life-threatening adverse effects.Consequently, the possibility of identifying patients at risk of adverse events – and having the ability to minimize suchrisk – is of paramount importance for the utility of these therapies.

The new first-line oral treatments, teriflunomide and dimethyl fumarate, appear to have good safety profiles, althoughprogressive multifocal leukoencephalopathy (PML) can be a rare complication associated with dimethyl fumaratetreatment. In particular, PML may occur in patients with low lymphocyte counts. Therefore, the regular measurementof blood lymphocyte levels is recommended as a risk minimizing measure in patients receiving dimethyl fumarate.2

Treatment with natalizumab can be associated with development of anti-natalizumab antibodies that abrogate itstherapeutic effects. Occurrence of these antibodies is related to both so-called acute infusion-related reactions and, inparticular, hypersensitivity reactions. Antibodies are measured after 6, 12 and 18 months’ natalizumab therapy and inpatients with hypersensitivity reactions; persistency of antibodies can be predicted from antibody titres.3

The most severe adverse event associated with natalizumab treatment is the occurrence of PML; established riskfactors for PML development are latent infection with JC virus, duration of natalizumab therapy, and prior use ofimmunosuppressive therapy. With the development of reliable and validated assays for the detection of antibodiesdirected against JC virus (JCV Ab), it is now possible to identify persons who are carriers of JC virus. Recently,measuring JCV Ab concentrations provide an additional option for risk stratification of PML in patients using orconsidering natalizumab therapy.3 To minimize the risk of PML development, patients with MS who also have JCV Ab,in particular those with high titres, should not be treated with natalizumab.

Fingolimod therapy can be associated with herpesvirus infections, in particular primary infections with varicella zostervirus (VZV). Hence VZV antibody titres should be measured before commencing fingolimod treatment; patients with lowor absent antibody titres should be vaccinated against VZV before start of therapy.4 After the first administration offingolimod, some patients develop severe bradycardia or heart block;5 concomitant use of drugs that lower heart rateor could influence conduction – such as antiarrhythmic drugs (quinidine, disopyramide, amiodarone, sotalol), Ca++-channel blockers (e.g. verapamil, digoxin), β-blockers (e.g. atenolol), or pilocarpine – should be avoided.Alemtuzumab causes immune mediated thyroid diseases in over 30 % of patients on treatment and idiopathicthrombocytopenic purpura (ITP) in a small percentage (although in one clinical trial, ITP resulted in a fatal intracranialhaemorrhage).6 Risk-minimization procedures include monthly measurement of thrombocyte levels and urinalysis,and 3-monthly thyroid function tests until 4 years after the last alemtuzumab infusion.

References:1. Sørensen PS, Deisenhammer F, Duda P, et al. Guidelines on use of anti-IFN-beta antibody measurements in multiple sclerosis: report of

an EFNS Task Force on IFN-beta antibodies in multiple sclerosis. Eur J Neurol. 2005;12:817-27.2. Faulkner M. Risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis. Expert Opin Drug Saf. 2015;14:1737-48.3. Fernández O. Best practice in the use of natalizumab in multiple sclerosis. Ther Adv Neurol Disord. 2013;6:69-79.4. Arvin AM, Wolinsky JS, Kappos L, et al. Varicella-zoster virus infections in patients treated with fingolimod: risk assessment and consensus

recommendations for management. JAMA Neurol. 2015;72:31-9. 5. DiMarco JP, O'Connor P, Cohen JA, et al. First-dose effects of fingolimod: Pooled safety data from three phase 3 studies. Mult Scler Relat

Disord. 2014;3:629-38.6. Minagar A, Alexander JS, Sahraian MA, et al. Alemtuzumab and multiple sclerosis: therapeutic application. Expert Opin Biol Ther.

2010;10:421-9.

L4. Risk minimization

Per Soelberg SørensenDanish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of CopenhagenCopenhagen, Denmark

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The advent of a large number of new MS therapies warrants the development of tools that enable the best treatmentoptions to be selected for each new MS patient. Evidence from clinical trials clearly supports the efficacy of severaldrugs for treating MS, but only a small number of factors that predict treatment response on an individual patient basishave emerged.1,2 This might be due, at least in part, to the lack of a standardized definition of the clinical outcome usedto assess improvement/worsening of MS. MRI markers and clinical relapses have been the most widely studied short-term factors for predicting long-term therapeutic response in patients with MS, although results are conflicting.Recently, integrated strategies combining MRI and clinical markers in scoring systems have provided a potentiallyuseful approach for the management of MS patients. This presentation reviews the many definitions of response totherapy and explore the MRI markers able to predict such response. Also, the presentation highlights advantages andlimitations of existing scoring systems to predict the response to interferon, in the light of a future expansion of thesemodels to biological markers and to other classes of new emerging therapies for MS.

References:1. Sormani MP, Rio J, Tintorè M, Signori A, et al. Scoring treatment response in patients with relapsing multiple sclerosis. Mult Scler.

2013;19:605-12. 2. Pravica V, Markovic M, Cupic M, et al. Multiple sclerosis: individualized disease susceptibility and therapy response. Biomark Med.

2013;7:59-71.

L5. MRI as a guide for treatment decisions

Nicola De StefanoNeurology and Neurometabolic Unit, Department of Neurological and Behavioral SciencesUniversity of Siena, Siena, Italy

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MS is a very heterogeneous disease and for this reason predicting the clinical course, future disability burden andresponse to therapy represent substantial challenges. Studying the visual pathway is beneficial: accurate technologiesare now available to quantify nervous tissue damage, the close relationship between morphology, function and visualscales, and to illustrate the fact that visual pathway damage is common in people with MS.1 Optical coherencetomography (OCT) is a laser technology commonly used in ophthalmology that quantifies, with exquisite accuracy,retinal thickness.2 OCT has been validated as a tool for monitoring optic neuritis, having defined the dynamics of retinalatrophy as a consequence of acute damage and identified biomarkers of permanent disability.1 Recent studies havealso shown that atrophy of the retinal nerve fibre layer in eyes without previous optic neuritis is predictive of disabilityworsening in the subsequent 2–5 years.2 In addition, retinal atrophy parallels brain atrophy and has been shown toreflect both acute damage (due to optic neuritis) and diffuse damage (due to retrograde and transynaptic axonaldegeneration). These results offer the opportunity of using OCT in clinical practice for identifying individuals at risk ofmore active and/or severe disease, supporting therapeutic decisions based on these biomarkers.2 In addition, OCT-based biomarkers can be used for therapeutic clinical studies that aim to develop neuroprotective or remyelinatingtherapies. OCT can be used for recruiting the most informative patients to a clinical trial, as a sensitive surrogate end-point and for patient monitoring during the trial. In addition, techniques such as electrophysiology (e.g. visual evokedpotentials, electroretinography) or molecular imaging (e.g. Raman spectroscopy of the retina) can complement OCT invisual pathway analysis. Moreover, a combination of different modalities including brain MRI, cerebrospinal fluidbiomarkers or genetic markers, offer the promise of having new diagnostic tools for personalized monitoring ofpatients with MS, in the near future.

L6. Visual platforms in clinical trials and patientmonitoring

Pablo VillosladaDepartment of Neurology, University of California, San Francisco (UCSF)San Francisco, CA, USA

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References:1. Martínez-Lapiscina EH, Sanchez-Dalmau B, Fraga-Pumar E, et al. The visual pathway as a model to understand brain damage in multiple

sclerosis. Mult Scler. 2014;20:1678-85.2. Bennett JL, de Seze J, Lana-Peixoto M, Palace J, et al. Neuromyelitis optica and multiple sclerosis: Seeing differences through optical

coherence tomography. Mult Scler. 2015;21:678-88.

T cells, especially CD4 positive T helper cells, were traditionally considered the main immune drivers in multiplesclerosis (MS). This was based on considerable research, including the discovery that the major genetic risk factor isin the major histocompatibility complex (MHC) class II region which has a central role in the development of T celltolerance. [1. Distanto] However, a substantial amount of evidence accumulated in the last few decades has indicatedthat B cells play a central role in the pathology of MS. [2. Blauth] Antigen presentation by B cells appears to be anecessary step for triggering autoimmunity against central nervous system (CNS) demyelination. [3. von Büdingen]Furthermore, B cells can have pro-inflammatory, anti-inflammatory and/or regulatory roles and provide activation andeffector mechanisms. Elevated levels of B cells occur in the CNS tissue and are significantly increased in thecerebrospinal fluid (CSF) of MS patients. Thus it is now generally accepted that both T and B lymphocytes have a rolein MS pathology.

This presentation will comment on the use of changes observed in particular cellular populations secondary to diseaseactivity or by the effect of therapies as potential disease activity or treatment response cell-based biomarkers inpatients with MS.

References:1. Distanto G, Morahan JM, Barnett MH, et al. The evidence for a role of B cells in multiple sclerosis. Neurol 2012;78:823–32.2. Blauth K, Owens GP, Bennett JL. The ins and outs of B cells in multiple sclerosis. Front Immunol 2015;6:565.Doi:10.3389/

fimmu.2015.00565.3. von Büdingen H-C, Palanichamy A, Lehmann-Horn, et al. Update on the autoimmune pathology of multiple sclerosis: B-cells as disease-

drivers and therapeutic targets. Eur Nerol 2015;73:238–46.

L7. How the lab could burden CD4 and CD5

Manuel ComabellaMultiple Sclerosis Centre of Catalonia (Cemcat), Neurology-Neuroimmunology DepartmentVall d’Hebron University Hospital, Barcelona, Spain

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With the increasing number of approved treatment choices for multiple sclerosis the issue of selection criteria gainsmore and more importance. In the context of considerations about mode of action and safety / convenience theassessment of comparative efficacy takes a central role.

Across Study comparison of controlled trials comparing with placebo is prone to bias by different methodologies andselection criteria but also by less easy to understand factors like epoch and regulatory environment.

Therefore assessment of treatment efficacy ideally should rely on the results of head to head controlled trials but it isquestionable if we would ever have enough resources to conduct such trials. Up to now only 9 of 90 such trials for 10currently approved compounds have been conducted and most are not free from methodological flaws.

Limitations of controlled Clinical studies include:

- Relatively short follow-up and therefore limited information about long-term effectiveness and delayed AEs.

- Limited number of exposed subjects and therefore high probability of missing potential rare AEs of a drug (< 0.1%).

- Highly selected target population and highly structured protocol with limited ability to iform about the impact of age,ethnicity, comorbidities and co-medications.

In addition to selected head to head controlled comparative trials we need prospectively planned, thoroughly conductedcomprehensive observational and cohort studies. Such studies cannot anymore be primarily corporate sponsored andmust be investigator initiated and publicly funded.

Possible advantages of such observational studies including possible remedies against some of the important sourcesof bias will be discussed.

References:- Sormani, M. P. & Bruzzi, P. Can we measure long-term treatment effects in multiple sclerosis? Nat. Rev. Neurol. 11, 176–182 (2015).

L8. Methodological aspects in comparing treatmentefficacy

Ludwig KapposDepartment of Biomedicine, University Hospital BaselBasel, Switzerland

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From the clinical perspective, different criteria for response to MS therapy have been established, based on presenceof relapse or increase in disability. However, follow-up MRI analyses have become essential for the early identificationof non-responders to MS therapy.1 Combined scores (incorporating clinical and MRI parameters) allow integration ofdisease activity data into therapeutic decision making for people with MS.2 The arrival of new therapeutic options in theMS armamentarium is introducing new concepts, such as patients with “no evidence of disease activity” (NEDA), whichis defined as the absence of clinical relapses, disease progression and MRI activity. The definition of NEDA may evolve,however, as new metrics (such as timed 25-foot walk [T25FW] test, symbol digit modalities test [SDMT], MRI measuresof brain atrophy) are adopted into clinical practice. NEDA may become an important therapeutic goal for MS care,however, in clinical settings, NEDA is difficult to sustain in the long term.3 Minimal clinical or MRI activity is notnecessarily associated with a poor long-term response. Should we aim for “minimal evidence of disease activity”(MEDA) rather than NEDA? Certainly, real-world data, with long-term follow-up, are needed for each MS therapy.

L9. How to assess treatment response

Mar TintorèMultiple Sclerosis Centre of Catalonia (Cemcat), Neurology-Neuroimmunology DepartmentVall d’Hebron University Hospital, Barcelona, Spain

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References:1. Wattjes MP, Rovira À, Miller D, et al. (MAGNIMS study group). Evidence-based guidelines: MAGNIMS consensus guidelines on the use of

MRI in multiple sclerosis--establishing disease prognosis and monitoring patients. Nat Rev Neurol. 2015;11:597-606.2. Río J, Rovira A, Tintorè M, et al. Evaluating the response to glatiramer acetate in relapsing-remitting multiple sclerosis (RRMS) patients.

Mult Scler. 2014;20:1602-8.3. Rotstein DL, Healy BC, Malik MT, et al. Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort. JAMA

Neurol. 2015;72:152-8.

The objective of early treatment is to control the disease activity since the early phase of the disease in order todecrease the risk to enter the progressive phase of MS[1]. This objective is quite relevant because so far there are noavailable treatments to influence the progression of disability after the patient enters the progressive phase of thedisease. Unfortunately post-marketing studies[2] have shown that about 85% of the patients treated with a first-linetherapy have a sub-optimal response to therapy, requiring a shift to second-line therapy. This escalating approachwhich is widely used until now has major limitations because a real contrast to the disease tend to be late in most ofthe cases, determining a large proportion of patients with increased disability. An alternative approach is the so-calledinduction strategy where patients are early treated with immunosuppressive agent targeting T- and B-cells in order todestroy auto-reactive cells and reset the autoimmune system. The therapeutic advantage of such an approach is toobtain a long-lasting control of disease activity with an increase of the prevention of disability progression. Then in thisapproach there should be no evidence of disease activity (NEDA). Some recent clinical trials have shown thatalemtuzumab is able to achieve NEDA condition in a high proportion of patients and the persistence of such a conditionin more than one third of patients even a year after treatment discontinuation. Moreover a previous study [3]demonstrated that patients treated with an induction approach have a significantly decrease of risk of disabilityprogression compared to patients treated with an escalation approach after a 3 year follow-up. The advantage of theinduction strategy has to be confronted with more risk of adverse effects of this strategy compared with the use of first-line therapy that are typically characterized by a better safety profile. At present the choice of an induction or anescalation approach should be based on the estimation of the individual prognosis and on the a priori probability of agood response to various treatments[4-6]. Unfortunately our knowledge of the value of prognostic factors is incompleteand further studies are mandatory in order to optimize the individual treatment in multiple sclerosis.

References:1. Freedman MS. Induction vs. escalation of therapy for relapsing multiple sclerosis: the evidence. Neurol Sci 2008;29 Suppl 2:S250-2522. Romeo et al. Validation of 1-year predictive score of long-term response to interferon in every day clinical practice multiple sclerosis

patients. Eur J Neurol 2015;22:973-980 3. Edan et al. Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomized trial. J Neurol

Neurosurg Psychiatry 2011;82(12):1344-1350.4. Romeo et al. Clinical and MRI predictors of response to interferon-beta and glatiramer acetate in relapsing remitting multiple sclerosis

patients. Eur J Neurol 2013;20:1060-10675. Rio et al. Predicting responders to therapies for multiple sclerosis. Nat Rev Neurol 2009;5:553-5606. Sormani et al. Assessing response to interferon-beta in a large multicenter dataset of multiple sclerosis patients. Neurology 2016 [in press]

L10. Revisited induction

Giancarlo ComiDepartment of Neurology, Institute of Experimental Neurology, Vita-Salute San Raffaele UniversityMilan, Italy

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A number of immunomodulatory agents are licensed by the European Medicine Agency and the Food and DrugAdministration to treat patients with multiple sclerosis (MS). These include the older injectable disease-modifyingdrugs (DMDs) (interferons and glatiramer acetate) and the more recently approved oral agents (fingolimod,teriflunomide, dimethyl fumarate) and those administered by infusion (natalizumab and alemtuzumab). All these DMDsact by modulating and/or suppressing the immune system at different levels and have a variety of mechanisms ofaction. [1. Gajofatto, 2. Carrithers] Although they all have a beneficial effect in relapsing-remitting MS they areassociated with different degrees of efficacy and safety.

Many monoclonal antibodies have been evaluated in clinical trials of MS although only natalizumab and alemtuzumabare currently licensed. [3. Rommer] Both have high efficacy but with potentially severe side effects. They tend to be usedin patients with more aggressive disease or as a second-line therapy.

Abnormalities in mitochondria including DNA defects, abnormal gene expression, defective enzyme activities, deficientDNA repair activity and mitochondrial dysfunction may have a role in the development and progression of MS [4. Mao].In addition, a study of mitochondria sequence variation in MS has suggested that certain genetic variants wereassociated with MS and primary progressive MS which may represent a target for future therapies. [5. Tranah]

This presentation will review the immunomodulatory and monoclonal antibody treatments for MS and the importanceof the cytokine profile of the surviving peripheral blood mononuclear cells with respect to specific DMDs.

References:1. Gajofatto A, Benedetti MD. Treatment strategies for multiple sclerosis: When to start, when to change, when to stop. World J Clin Cases

2015;3:545–55.2. Carrithers MD. Update on disease-modifying treatments for multiple sclerosis. Clin Ther 2014;36:1938–45.3. Rommer PS, Dudesek A, Stüve O, et al. Monoclonal antibodies in treatment of multiple sclerosis. Clinical and Experimental Immunology

2014;175:373–84.4. Mao P, Hemachandra Reddy P. Is multiple sclerosis a mitochondrial disease? Biochimica et Biophysica 2010;1802:66–79.5. Tranah GJ, Santaniello A, Caillier SJ, et al. Mitochondrial DNA sequence variation in multiple sclerosis. Neurol 2015;85:325–30.

S1. Current and emerging treatments

Andrew ChanNeurocenter Inselspital, University Hospital BernBern, Switzerland

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MRI has revolutionized the diagnosis and clinical monitoring of patients with MS. However, conventional MRItechniques are susceptible to a phenomenon known as the “clinicoradiological paradox”, due to deficiencies insensitivity and specificity to underlying pathological processes relevant to MS. As such, conventional MRI techniquesgenerally demonstrate weak correlations with clinical disability in MS patients.1

A number of advanced, quantitative MRI measures have demonstrated moderate to strong correlations with clinicaldisability and longitudinal disability progression, which is an improvement compared with conventional, lesion-basedmeasures.2 These measures include whole-brain atrophy, deep grey matter atrophy, cortical atrophy and spinal cordatrophy. In addition, novel sequences have enabled improved detection of lesions in the spinal cord.3 Furthermore, anumber of emerging quantitative techniques (such as diffusion-tensor imaging, magnetization-transfer imaging, andfunctional imaging) are promising to improve clinical correlations, and to shed insight into MS disease mechanisms.4

Before any of these emerging quantitative MRI techniques can be applied routinely in clinical practice, however, anecessary prerequisite is optimization, standardization, and validation of MRI sequences and post-acquisition imageprocessing algorithms.

References:1. Barkhof F. The clinico-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol. 2002;15:239-45.2. West J, Aalto A, Tisell A, et al. Normal appearing and diffusely abnormal white matter in patients with multiple sclerosis assessed with

quantitative MR. PLoS One. 2014;9:e95161.3. Traboulsee A, Simon JH, Stone L, et al. Revised Recommendations of the Consortium of MS Centers Task Force for a Standardized MRI

Protocol and Clinical Guidelines for the Diagnosis and Follow-Up of Multiple Sclerosis. AJNR Am J Neuroradiol. 2016;37:394-401. 4. Absinta M, Reich DS, Filippi M. Spring cleaning: time to rethink imaging research lines in MS? J Neurol. 2016; Feb 17 (e-pub ahead of print).

S2. Emerging MRI techniques and their relationship toclinical outcomes

Jiwon OhDivision of Neurology, University of TorontoToronto, Canada

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Currently 11 disease modifying drugs (DMDs) are approved in most countries for relapsing-remitting multiple sclerosis(MS). All DMDs reduce the number of relapses and have a variety of other beneficial effects although their efficacyvaries from moderate to high. Furthermore, they are all associated with side effects ranging from minor to potentiallyserious and life threatening. Generally, the more potent DMDs are associated with more severe side effects. [1. Bridel]In addition to immunomodulatory agents, immunosuppressive drugs such as mitoxantrone are still being used to treatrapidly worsening or secondary progressive MS. [2. Tanasescu] Mitoxantrone is associated with a number of side effectsincluding increased risk of infections, cardiotoxicity and secondary leukemia.

Progressive multifocal leukoencephalopathy (PML) is a potentially severe side effect that may occur in patients treatedwith DMDs especially natalizumab. Recently, PML cases have also been reported with fingolimod and dimethylfumarate. [3. Bloomgren, 4. Faulkner] However, risk stratification has been developed for natalizumab as a number offactors have been identified including positivity for anti-JC virus antibodies, that are associated with an increased riskof PML. As of 2015, PML is rare with fingolimod (3 cases) and dimethyl fumarate (4 cases), and it is unlikely to occur inthe first year of treatment but thereafter neurologists need to be vigilant if symptoms suggesting a non-typicalMSrelapse are seen. [5. Van Schependom, 6. Fitzgerald]. Herpes-virus reactivation has also been observed in MS patientstreated with some DMDs. [7. Kohlmann, 8. Pfender] Furthermore, an association with some DMDs and cancer hasbeen suggested but convincing evidence is lacking.

This presentation will review the management of immunosuppression in MS patients treated with DMDs and the risksassociated with these therapies.

References:1. Bridel C, Lalive PH. Update on multiple sclerosis treatments. Swiss Med Wkly 2014;144:w14012.2. Tanasescu R, Ionete C, Chou IJ, Constantinescu CS. Advances in the treatment of relapsing-remitting multiple sclerosis. Biomed J

2014;37:41–49.3. Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med

2012;366:1870–80. 4. Faulkner M. Risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis. Expert Opin Drug Saf 2015;14:1737–48.5. Van Schependom J, Gielen J, Laton J, Nagels G. Assessing PML risk under immunotherapy: if all you have is a hammer, everything looks

like a nail. Mult Scler 2016;22:389–92.6. Fitzgerald S. Third PML case associated with fingolimod: How to distinguish PML from MS relapse. Neurol Today, October 8, 2015. 7. Kohlmann R, Salmen A, Chan A, et al. Serological evidence of increased susceptibility to varicella-zoster virus reactivation or reinfection

in natalizumab-treated patients with multiple sclerosis. Mult Scler 20156;21:1823-32.8. Pfender N, Jelcic I, Linnebank M, Schwarz U, Martin R. Reactivation of herpesvirus under fingolimod: A case of severe herpes simplex

encephalitis. Neurology. 2015 Jun 9;84(23):2377-8..

S3. Managing immunosuppression

Sven SchipplingCRPP Multiple Sclerosis, University of ZurichZurich, Switzerland

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MS is characterized by infiltration of immune cells and progressive damage to myelin sheaths and neurons. ViewingMS as both an inflammatory and neurodegenerative disease has substantial implications for future treatmentstrategies;1,2 it is not sufficient to address merely the inflammatory components of the disease in order to prevent (oreven reduce) cumulative neurological deficits in affected patients.2,3 Several lines of evidence link axonal loss to thefailure of remyelination, which occurs as MS progresses.2–5 For example, areas of remyelination exhibit reduced axonalloss compared with areas of chronic demyelination in brain tissue from MS patients.2

Remyelination is a spontaneous regenerative process that can occur in animal models following demyelination andalso in MS patients.5 Differentiation of oligodendrocyte precursor cells (OPCs) to pre-oligodendrocytes and functionaloligodendrocytes includes multiple steps of cellular differentiation, influenced by intrinsic and extrinsic signals.2,3

However, spontaneous repair is limited due to an inhibitory microenvironment.2 All currently available MS therapiesprimarily target ongoing inflammation. However, it has been speculated that some of these agents may additionally acton the CNS via promotion of myelin repair to prevent chronic disability. We will discuss existing data on these potentialeffects. Remyelination-enhancing therapies for MS patients are not yet reality, but the combined use of genetics,transcriptome analysis and in vivo models has identified multiple novel target structures interfering with remyelination.Anti-LINGO-1, a monoclonal antibody that results in enhanced myelin repair in animal models of MS, is the mostadvanced concept with clinical trials being conducted in patients with optic neuritis, relapsing remitting MS andsecondary progressive MS.6 We will discuss preliminary experiences from clinical trials, but also look at novel emergingconcepts including (but not limited to) semaphorins, BMP4, RXRg, GPR17 and Notch or Wnt signaling pathways.2,3,6

Finally, we will discuss the complexity of clinical assessment and limitations of remyelination approaches. In vivoquantification of remyelination in the human CNS by a robust marker will be a challenge in MS research. At present,combining currently available MRI techniques with measurements of brain atrophy and retinal nerve fibre layerthickness seems to be the best available strategy to assess the efficacy of novel treatments on myelination in MSpatients. However, it might be not sufficient to simply promote myelin repair as neuronal functions on a cellular andmost importantly network level are integral steps towards a systemic approach of CNS functions.

References:1. Fakhoury M. Immune-mediated processes in neurodegeneration: where do we stand? J Neurol. 2016; e-pub ahead of print.2. Münzel EJ, Williams A. Promoting remyelination in multiple sclerosis-recent advances. Drugs. 2013;73:2017-29. doi: 10.1007/s40265-013-

0146-8.3. Kremer D, Küry P, Dutta R. Promoting remyelination in multiple sclerosis: current drugs and future prospects. Mult Scler. 2015;21:541-9. 4. Manrique-Hoyos N, Jürgens T, Grønborg M, et al. Late motor decline after accomplished remyelination: impact for progressive multiple

sclerosis. Ann Neurol. 2012;71:227-44.5. Hagemeier K, Brück W, Kuhlmann T. Multiple sclerosis – remyelination failure as a cause of disease progression. Histol Histopathol.

2012;27:277-87.6. Harlow DE, Honce JM, Miravalle AA. Remyelination Therapy in Multiple Sclerosis. Front Neurol. 2015;6:257.

L11. Myelin repair

Stefan BittnerDepartment of Neurology, University of Muenster Muenster, Germany

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Recent evidence shows that clinical disability in MS and in other neurological disorders develops when the synapticplasticity reserve of surviving neurons is exhausted.1,2 Long-term potentiation (LTP) is a form of synaptic plasticity thatmay be able to minimize the effects of neuronal damage by restoring the excitability of neurons that have lost part oftheir synaptic inputs.1 In addition, rehabilitation might exert clinical benefits though the preservation or enhancementof the LTP brain reserve. LTP requires the activation of NMDA, cannabinoid, dopamine receptors and neurotrophins,and can be impaired by acute inflammation. This raises the possibility that effective MS treatment with disease-modifying drugs impacts favourably on rehabilitation.3 Pharmacological interventions aimed at favouring NMDAreceptor signalling with D-aspartate, cannabinoid receptor stimulation with phytocannabinoids, dopamine receptoractivation with L-dopa, or BDNF release with SSRI could enhance the beneficial effects of rehabilitation treatment byfavouring synaptic plasticity.

L12. Pharmacology for enhanced recovery

Diego CentonzeNeurology Unit, IRCSS Istituto Neurologico Mediterraneo Neuromed, Pozzilli (IS), Italy andTor Vergata University, Rome, Italy

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References:1. Weiss S, Mori F, Rossi S, Centonze D. Disability in multiple sclerosis: when synaptic long-term potentiation fails. Neurosci Biobehav Rev.

2014 Jun;43:88-99.2. Mori F, Kusayanagi H, Nicoletti CG, et al. Cortical plasticity predicts recovery from relapse in multiple sclerosis. Mult Scler. 2014;20:451-7.3. Tomassini V, Matthews PM, Thompson AJ, et al. Neuroplasticity and functional recovery in multiple sclerosis. Nat Rev Neurol. 2012;8:635-46.

Multiple sclerosis is the most prevalent neurological disease in young adults; it is associated with a variety of symptomsand functional deficits that result in a range of progressive impairments and handicap. The symptoms of MS, whichcontribute to loss of independence and restrictions to participating in social activities, are often responsible for acontinuing decline in health-related quality-of-life (HRQoL). Compensation of functional deficits, adaptation andreconditioning, together with the management of symptoms, impairment, emotional coping and self-estimation, areimportant long-term objectives. Recent studies indicate that rehabilitation improves personal activities andparticipation in social activities, thereby improving HRQoL, which is determined more by disability and handicap thanby functional deficit and disease progression.1

L13. New basis for rehabilitation

Jürg KesselringDepartment of Neurorehabilitation, Valens Clinic Rehabilitation CenterValens, Switzerland

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References:1. Beer S, Kesselring J. Multiple sclerosis: rehabilitation and long-term course. Ophthalmologe. 2014;111:715-21.

WS1. Instrumental techniques MRI Functional tests (VEP)

This workshop will be conducted by N. De Stefano (Italy) and L. Leocani (Italy)

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Several diagnostic tools may help neurologists to diagnose multiple sclerosis and monitor the disease evolution. TheMS diagnosis is not always obvious and many others MS mimickers should be ruled out. Moreover, predicting thedisease course is challenging and, as a consequence, physicians should face with treatment decision making processand risk stratification. Among the diagnostic tools, magnetic resonance imaging (MRI) still plays a crucial role, both inthe early phase of the diagnostic workup, and in disease monitoring. Together with structural analysis, functional datamight help to predict MS evolution and recovery. In this workshop, the role of MRI and functional tests will be reviewedand their role in the evolving MS scenario will be elucidated.

WS2. Decision making process

This workshop will be conducted by G. Comi (Italy) and M. Tintorè (Spain)

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The advent of new disease modifying drugs (DMDs) together with the interferons, have ameliorated the disease controlwhile increasing the complexity of the decision making process. Even though effective, the new DMDs show a limitedsafety profile, thus requiring a careful overview of patients clinical situation in order to avoid DMDs related side effects.The decision making process is even more complicated when a switch of therapy is needed. A great effort has been putin predicting response to treatment and, on the other hand, the risk of relapses. This workshop will help neurologiststo move among new treatments and side effects in order to simplify treatment choices in the daily practice.

WS3. Symptomatic treatments

This workshop will be conducted by J. Kesselring ( Switzerland) and P.S. Sørensen ( Denmark)

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Even though the MS therapeutic armamentarium has been consistently evolved in the last few years, the DMDs havelimited impact on the majority of MS related symptoms. Fatigue, spasticity and genitor-urinary problems are frequentlyreferred to MS patients and might interfere with daily life with negative impact on the patient’s quality of life. Thus, acomprehensive patient’s view is needed in order to ameliorate the MS patient management. This workshop will reviewthe most appropriate rehabilitative approach and the available treatments for the main MS related symptoms.

WS4. Fluids biomarkers

This workshop will be conducted by A. Bar-Or (Canada) and L. Kappos (Switzerland)

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T lymphocytes, in particular CD4, have been traditionally considered key players in MS pathogenesis. More recently,also B cells have gained importance as pathogenic agents in multiple sclerosis, exerting both pro and anti-inflammatory effects. Even though several scientific advances have been made, there is still strong unmet clinical needfor objective body fluid biomarkers to assist early diagnosis and estimate long-term prognosis, monitor treatmentresponse and predict potential adverse effects in multiple sclerosis. Both cerebrospinal fluid (CSF) and serum markersmight help to predict conversion from clinically isolated syndrome to definite MS or might be modified by theinflammatory phase or the effect of treatment. Even though the clinical application as faithful biomarkers should beimplemented, several molecules are of interest. The data available on putative CSF and serum biomarkers of diseaseprogression, MS type and prognosis will be reviewed and their role discuss in this workshop.

There are few neurological conditions that have seen such a transformation in public perception as Multiple Sclerosis(MS). Over the last twenty years, it has moved from being an untreatable condition, with few management options to aposition active management underpinned by over a dozen oral and injectable treatments for patients with therelapsing/remitting form of MS (RRMS). These encouraging advances are overshadowed by a less palatable fact - thatfor those patients with progressive MS, there are few treatment options. These patients constitute over 50% of the 2.3million people with MS worldwide and, not surprisingly, they harbour sentiments of frustration and a sense of neglect.Addressing their needs is all the more important as progression is the main determinant of disability in MS and carriesthe greatest economic burden for society.

The rationale behind this therapeutic vacuum and the challenges standing in the way of developing an effectivetreatment for progressive MS are not inconsiderable (1). They include difficulty defining progression, incompleteunderstanding of the underlying pathological mechanisms (2) and thereby difficulty in identifying potential targets,developing an appropriate trial design with effective biomarkers and clinical outcomes (3) and improving symptommanagement and rehabilitation (4).

This overwhelming need is the main driver of the International Progressive MS Alliance (PMSA). With the mission todevelop effective treatments both for progression and symptom management, PMSA has united MS Societies andclinical academics worldwide and encouraged them to focus on and work together to overcome the blocks delayingachievement of this ambitious but critical goal (5). PMSA has worked to raise the profile of progressive MS and hasprovided funding to stimulate research into the blocks to treatment. This research activity complements the notinconsiderable body of activity already taking place in progressive MS, which has been further strengthened by therecent presentation of the first positive phase III trial in primary progressive MS, involving a monoclonal antibodytargeting B lymphocytes - Ocrelizumab. PMSA hosts regular scientific meetings which bring together all the relevantscientific and clinical interests including industry (6) and is currently in the middle of a major network grant awardround.

Although this is a very challenging vision, it is very encouraging to see what has been achieved in a relatively shortperiod of time. However, there is still very much to be done!

References:1. Thompson AJ. A much-needed focus on progression in multiple sclerosis (Commentary, Reflection and Reaction). Lancet Neurology 2015;14:133-135

2. Mahad D, Trapp B, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurology 2015; 14(2):183-1933. Ontaneda D, Fox R, Chataway J. Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives Lancet Neurology

2015; 14(2); 208-223.4. Feinstein A, Freeman J, Lo A. Treatment of progressive multiple sclerosis: what works, what does not, and what is needed. Lancet

Neurology 2015; 14(2); 194-2075. Fox R, Thompson A, Baker D, et al. Setting a research agenda for Progressive Multiple Sclerosis. The International Collaborative on

Progressive MS. MSJ 2012; 18:1534-15406. Salvetti M, Landsman D, Schwarz-Lam P, Comi G, Thompson AJ, Fox R. Progressive MS – from pathophysiology to drug discovery. A

meeting review (Boston, 2-4 March 2015) MSJ 2015; 21:1376-1384

New challenges and new frontiers: the PMSA experience

Alan J. ThompsonDepartment of Brain Repair and Rehabilitation, Institute of Neurology, University College London National Hospital for Neurology and Neurosurgery, London, UK

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NOTES

All EXCEMED programmes are organized solely to promote the exchange and dissemination of scientific and medical information. No forms of promotionalactivities are permitted. There may be presentations discussing investigational uses of various products. These views are the responsibility of the namedspeakers, and do not represent an endorsement or recommendation on the part of EXCEMED. This programme is made possible thanks to an educational grantreceived from Merck KGaA, Darmstadt, Germany

All EXCEMED programmes are organized solely to promote the exchange and dissemination of scientific and medical information. No forms of promotionalactivities are permitted. There may be presentations discussing investigational uses of various products. These views are the responsibility of the namedspeakers, and do not represent an endorsement or recommendation on the part of EXCEMED. This programme is made possible thanks to an educational grantreceived from Merck KGaA, Darmstadt, Germany

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