Dear Conference Delegate, - EXCEMEDMedical Advisor: Federica Cerri EXCEMED is a Swiss Foundation with headquarters in 14, Rue du Rhône, 1204 Geneva, Switzerland Organising secretariat

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Dear Conference Delegate,

A warm welcome to all attending the 2014 Annual conference “Multiple sclerosis: improving patient outcomes through scientific and clinical advances.”

I would like to inform you that as of 28 April 2014 the name of our Foundation changed to EXCEMED – Excellence in Medical Education. The name change will not impact your registration status in this or any other Foundation event.

This transition marks an exciting point in the evolution of the Foundation. We are proud to have provided world-class education to thousands of healthcare professionals over the past four decades - as a result, the Foundation has become synonymous with delivery excellence and high-impact CME.

As we further develop our scientific and geographical presence it is important to us that our name accurately reflects the independent nature of the education we provide; EXCEMED symbolises our enduring mission to support the best possible outcomes for patients through the medical education we offer. We take pride in our complete dedication to the provision of CME - it is our sole focus and our passion.

I wish you an inspiring and successful learning experience here in Dubai.

Yours Sincerely,

Rachel ClarkCEO, EXCEMED

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Dear Colleague,

On behalf of EXCEMED, it is our pleasure to welcome you to the 2014 Annual conference: “Multiple sclerosis: impro-ving patient outcomes through scientific and clinical advances”. At this meeting, leading international experts will share cutting-edge research on the roles of genetics and the environment in the pathogenesis of multiple sclerosis (MS), and discuss how best to incorporate our knowledge within a patient-centred approach to clinical management. You will also have the opportunity to earn CME credits.This live educational conference will consist of three plenary sessions, along with three workshop sessions and a round table session. Session I will cover the latest epidemiological and genetic findings, and give an update on our understanding of MS pathogenesis. In Session II you will hear presentations on how patients at risk of poor prognosis can be identified and managed, as well as the importance of defining, predicting and optimizing treatment response. In the third plenary session, experts will debate on the optimal timing of MS treatment initiation, and how we should best monitor and assess treatment response. The workshop sessions will be your opportunity to learn about key aspects of managing the care of people with MS in a more informal setting.

In addition, you will hear a round table discussion on patients’ perception and reported outcomes with a panel of experts. The aims of the 2014 Annual conference are to explain the role of genetic susceptibility and environment in MS pathogenesis, and to enable selection of the most suitable treatment on the basis of the phase of the disease and the need of the individual patient. This highly interactive programme will provide up-to-date information for clinicians on current research as well as practical advice on patient-centred management. We hope that you will be able to join us and take part in what we anticipate will be engaging and lively discussions.

Yours sincerely

David BatesScientific organiserNewcastle upon Tyne, UK

2014 Annual conferenceMultiple sclerosis: improving patient outcomes through scientific and clinical advancesDubai, UAE - 9-10 May 2014

AimMultiple sclerosis is one of the most disabling neurological disorders and has a significant impact on the lives of young adults, the age group that is most affected. Even though the scientific discoveries of recent decades have improved both diagnostic capability and the therapeutic opportunities, there are still open questions. The medical approach has changed from disease-oriented to patient-centred as a result of the patient’s need to be involved in the decision making process and the opportunity to better tailor treatment based on the disease activity. The aim of this live educational conference will be to explore the roles of genetics and environment in the pathogenesis of MS and examine options within the patient-centred approach to clinical management.

Learning objectivesBy attending this live educational conference learners will be able to:• Describe the latest advances in MS pathogenesis• Explain the role of genetic susceptibility and environment in MS pathogenesis• Select the most suitable treatment on the basis of disease phase• Identify the main predictors of disease evolution• Summarize how to assess non responders to treatment and how to change therapies

Target audienceNeurologists involved in the management of MS patients.

AccreditationEXCEMED (www.excemed.org) is accredited by the European Accreditation Council for Continuing Medical Education (EACCME®) to provide the following CME activity for medical specialists. The EACCME is an institution of the European Union of Medical Specialists (UEMS), www.uems.net. The 2014 Annual conference “Multiple sclerosis: improving patient outcomes through scientific and clinical advances” held in Dubai, UAE on 9-10 May 2014, is designated for a maximum of 9 (nine) hours of European CME credits (ECMEC). Each medical specialist should claim only those credits that he/she actually spent in the educational activity. EACCME® credits are recognized by the American Medical Association towards the Physician’s Recognition Award (PRA).To convert EACCME credit to AMA PRA category 1 credit, please contact the AMA.

This programme is awarded 9.75 CPD credit points by Dubai Health Authority.

This live educational conference is endorsed by SIN (Italian Society of Neurology) and EMINS (Emirates Neurology Society)

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

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VenueJW Marriott Marquis HotelSheikh Zayed RoadDubai, UAE

LanguageThe official language of this conference will be English

Scientific organiserDavid BatesDepartment of NeurologyRoyal Victoria InfirmaryNewcastle upon Tyne, UK

Scientific committeeDavid BatesDepartment of NeurologyRoyal Victoria InfirmaryNewcastle upon Tyne, UK

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

Aksel SivaDepartment of NeurologyIstanbul UniversityIstanbul, Turkey

Local scientific organiserJihad InshasiNeurology DepartmentRashid HospitalDubai Health Authority (DHA)Dubai, UAE

Scientific secretariatEXCEMEDSalita di San Nicola da Tolentino, 1/b, 00187 Rome, ItalySenior Programme Manager: Alessia AddessiT +39 (0)6 420 413 591 - F +39 (0)6 420 413 677E-mail: [email protected] Advisor: Federica Cerri

EXCEMED is a Swiss Foundation with headquarters in14, Rue du Rhône, 1204 Geneva, Switzerland

Organising secretariatMeridiano Congress InternationalVia Sapri, 6 - 00185 Rome, ItalySenior project manager and team leader: Sara GuglielminiT +39 (0)6 88 595 211 - F +39 (0)6 88595 234E-mail: [email protected]

General information

We value your opinion!We are continually trying to develop and improve our educational initiative to provide you with cutting-edge learning activities. During this live educational conference you will be asked to answer a real-time survey and after this educational event you will be receiving a post online survey to better tailor our future educational initiatives.

We thank you for participating!

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exCeMeD_Neurology

http://twitter.com/exCeMeD_Neurology#MS2014

Register to exCeMeD website:www.excemed.org

Scientific programme

exCeMeD opening R. Clark (CEO EXCEMED)

Introduction to the conference D. Bates (UK)

Local welcome J. Inshasi (UAE)

Chairs: G. Comi (Italy) - I. Alsharoqi (Bahrain)

Real-time survey

epidemiology S. Bohlega (Saudi Arabia)

Risk factors: the role of infections and environment O. Aktas (Germany)

Genetics of multiple sclerosis: current and emerging candidates F. Martinelli Boneschi (Italy)

Coffee break

Deciphering MS pathogenesis: the role of MRI M. A. Rocca (Italy)

Neurodegeneration: the role of neurophisiology L. Leocani (Italy)

Question time

Revisiting real-time survey

Scientific programmeFriday, 9 May 2014

08.40

08.50

08.30

09.00 L1:

09.20 L2:

09.40 L3:

10.20 L4:

10.40 L5:

11.00

10.00

Session I MS pathogenesis and basic research

13.15

3.

4.

5.

6.

Workshop Session I 11.15 - 13.15

Treatment initiation and therapeutic contract C. Pozzilli (Italy) - A. Siva (Turkey)

How to manage response to first-line therapies O. Aktas (Germany) - G. Edan (France)

Therapeutic options G. Comi (Italy) - P. Rieckmann (Germany)

Role of MRI in monitoring treatment N. De Stefano (Italy) - M. A. Rocca (Italy)

Genes and environment G. Edan (France) - F. Martinelli Boneschi (Italy)

Patient engagement in the decision-making process D. Langdon (UK) - A. Solari (Italy)

Lunch

1.

2.

The workshop sessions will involve attendees in an interactive discussion, giving them the chance to share opinions and understanding of different MS related topics. There will be three sessions including six different workshops, each lasting one hour. The audience will be divided into six groups, at the end of the conference each participant will have attended all the six workshops in rotation.

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3.

4.

5.

6.







end of the first day

1.

2.

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Workshop Session II 16.10 - 18.10

14.15 L6:

14.35 L7:

14.55 L8:

15.15 L9:

15.35

15.50

18.10

Chairs: D. Bates (UK) - A. Siva (Turkey)

Real-time survey

Prognosis from natural history R. Bergamaschi (Italy)

How to define non-responders R. Fox (USA)

Predictivity of response to treatment M. Tintoré (Spain)

How to keep patients on treatment C. Pozzilli (Italy)

Question time


Coffee break

Session II Clinical approach to MS

3.

4.

5.

6.







1.

2.

Scientific programmeSaturday, 10 May 2014

10.30

10.45

11.30

Real-time survey

Introduction B. Yamout (Lebanon)

Patient’s perception and patient’s reported outcomes Chairs: D. Bates (UK) - B. Yamout (Lebanon)

R. Alroughani (Kuwait) D. Langdon (UK) M. A. Sahraian (Iran) I. A. Slassi (Morocco)

Coffee break

Workshop Session III 08.30 - 10.30

Patient’s perception and patient’s reported outcomes - round table

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11.50 D1:

12.35 D2:

Treatment initiation Start immediately vs Wait and see G. Comi (Italy) A. Siva (Turkey)

Audience poll

Discussion

Assessing treatment failure MRI matters vs Clinical response only N. De Stefano (Italy) V. Martinelli (Italy)

Audience poll

Discussion


Conference wrap-up Scientific committee

Lunch

Chairs: R. Alroughani (Kuwait) - D. Bates (UK) - J. Inshasi (UAE)

Experts will debate different topics related to the MS environment. Each debate will be conducted by two speakers presenting two different points of view; at the end attendees will vote for the most convincing position. Attendees will have the chance to discuss the debate outcomes with the experts.

Session III Therapeutic management

13.20

13.30

16.30

14.30 Q&A: let’s talk Messages: let’s recap Scientific committee

end of the conference

MS focus interactive session (optional)

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Biographies

Orhan Aktas Department of Neurology Heinrich-Heine-University Düsseldorf, Germany

Orhan Aktas received his undergraduate training at the universities of Bochum, Germany and Strasbourg, France. After graduation

as MD in 1999, he served a neuroimmunology fellowship at the Charité, Humboldt-University of Berlin, Germany. He started his

career in neurology at the Charité and was appointed Associate Professor and Head of the MS Clinical Research Group at the

Department of Neurology, Heinrich Heine University, Düsseldorf, Germany, in 2008. He is co-ordinator of the recently founded

Düsseldorf Multiple Sclerosis Center at the Department of Neurology, Heinrich-Heine University.

Professor Aktas’ clinical and research interests are in the field of basic and clinical neuroimmunology and in particular Multiple

Sclerosis and neuromyelitis optica. He has authored or co-authored a large series of primary research articles in peer-reviewed

journals such as Nature Medicine, Nature Cell Biology, Cell, Neuron, and contributed to review articles and editorials in Trends in

Neurosciences, Lancet Neurology, Journal of Neurology, and Annals of Neurology. He has been involved as a principal investigator

in international multicentre therapeutic trials in MS and has designed investigator-initiated trials in translational neuroimmunology.

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Raed Alroughani Amiri Hospital Dasman Research Institute Kuwait City, Kuwait

Doctor Alroughani completed his medical degree (MD) from Charles University. He completed his Neurology Residency program

at the University of British Columbia (UBC). He then completed a 2-year fellowship in Demyelinating disorders and neuro-immuno-

logy at UBC. Doctor Alroughani is a Fellow of the Royal College of Physician of Canada and a certified MS specialist by Consortium

of MS Centers (CMSC). He serves as a consultant neurologist at Al-Amiri & Al-Seef Hospitals and as a director of the MS

Clinic in Dasman Research Institute, which serves the cornerstone of MS research in Kuwait. Doctor Alroughani’s main research

interests are MS epidemiology and therapeutics. He is a member in multiple international committees for MS and related demye-

linating disorders.

David Bates Department of Neurology Royal Victoria Infirmary Newcastle upon Tyne, UK

David Bates trained in Medicine at Downing College, Cambridge and the Middlesex Hospital, London and in Neurology at the

University of Newcastle upon Tyne, UK, and the Mayo Clinic, Rochester, Minnesota, USA. He is Emeritus Professor of Clinical

Neurology at the University of Newcastle upon Tyne, Former Editor of the International MS Journal and past Chairman of both the

MS Forum and the Medical Research Advisory Committee of the MS Society of Great Britain and Northern Ireland. He is Chairman

of the Joint Colleges Working Party on the Vegetative State and Criteria for 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. Professor Bates has published more than 150 peer-reviewed papers, edited three textbooks

and contributed chapters to more than 20. His current research involvement is predominantly in clinical trials of novel therapy in

MS and in the role of mitochondria in protecting and repairing axons in the more chronic phases of that disease.

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Biographies

Roberto Bergamaschi National Neurological Institute C. Mondino Pavia, Italy

Roberto Bergamaschi received from the University of Pavia (Italy) his medical degree in 1984, post-graduation in Neurology

in 1988 and in Medical Statistics in 1992. Since 1992 he is Senior Neurologist at the Department of Clinical Neurology of the

IRCCS National Neurological Institute ‘C. Mondino’, Pavia, Italy. Since 2003 he teaches at the post-degree school in Neurology

(course “Demyelinating Diseases”). Since 2009 he acts as the head of the Multiple Sclerosis Center, where about 1,300 patients

are followed. He published more than 200 original articles in the domain of Neurology and Neuroepidemiology. His current research

activity concerns: epidemiological, clinical and instrumental aspects of multiple sclerosis (MS); environmental factors and MS;

relationships between MS and other autoimmune diseases; clinical trials on disease modifying therapies of MS; epidemiological,

clinical and instrumental aspects of Devic’s optic neuromyelitis; Bayesian prognostic models; Bayesian mapping of geographical

disease distribution.

Isa Alsharoqi Department of Clinical Neurosciences Salmaniya medical complex Manama, Bahrain

Isa Abdulla Alsharoqi is Consultant Neurologist at the Department of Clinical Neurosciences at the Salmaniya medical complex

in Manama, Bahrain.

Saeed Bohlega Department of Neurosciences King Faisal Specialist Hospital and Research Centre Riyadh, Saudi Arabia

Doctor Bohlega obtains his basic medical training at King Saud University and graduated in 1980. Then in 1982, he went to Canada

where he did his training in Neurology at University of British Columbia, Vancouver BC. He trained with Professor Don Paty. He

develops specialist interest in Multiple Sclerosis and he did subspecialty training in Neurophysiology.

In 1989, he joined as a Consultant Neurologist in the Department of Neurosciences at King Faisal Specialist Hospital and Research

Centre and worked as a Consultant and then as a Senior Consultant and appointed as Professor of Neurology at Al Faisal University.

In 1998, he was the Founder and the President of the Saudi Multiple Sclerosis Advisory Group and he served in this post for fourteen

years. He is a member of many neurological societies like the American Neurological Association and the British Royal College of

Physicians and Surgeons. He worked as a Section Head of Neurology then as a Chairman of Department of Neurosciences. Also,

he is a founder and a chairperson of the National Saudi Board of Neurology for ten years. Also, he is the President of the Saudi

Neurology Society and the President Elect for the PAN Arab Union of Neurological Societies (PANUS). He received numbers of

national and international award for his clinical and academic contributions. Doctor Bohlega published more than 128 papers in a

peer reviewed journals. He wrote a few book chapters. Also, he presented more than 180 presentations in various conferences.

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Giancarlo Comi Department of Neurology Institute of Experimental Neurology Vita-Salute San Raffaele University Milan, Italy

Giancarlo Comi received a degree in medicine in 1973 and a neurological certification in 1977, both from Milan University. He

joined the Department of Neurology, Scientific Institute San Raffaele, Milan University, in 1974 as a Clinical Assistant and in 1988 was

appointed Assistant Professor in Clinical Neurophysiology of the same University. Currently he is Professor of Neurology, Chairman

of the Department of Neurology, and Director of the Institute of Experimental Neurology, at Vita-Salute San Raffaele University,

Scientific Institute San Raffaele, Milan. His fields of interest are principally directed towards the study of the pathophysiology and

treatment of multiple sclerosis. Professor Comi has authored and co-authored more than 800 articles in peer-reviewed journals, and

edited several books. He has a long-standing involvement as an active member of steering committees and advisory boards of many

international clinical trials, mainly in the field of multiple sclerosis. He is currently the President of the European Charcot Foundation

(ECF) and member of the Board of Administration of the Italian Multiple Sclerosis Foundation and the Scientific Committee of

the Italian Multiple Sclerosis Association. Professor Comi has also served as President of the European Neurology Society and the

Italian Society of Clinical Neurophysiology. He is currently the President of the Italian Society of Neurology for the period of 2012-

2014. In the past year, he has received the Romanian Society of Neurology honorary award “Gh. Marinescu” and been awarded

honorary membership of the Russian Neurological Academic Society. He currently sits on the executive boards of various scientific

associations and in the editorial boards of Clinical Investigation, European Journal of Neurology, Multiple Sclerosis and is the

Associate Editor of the Neurological Sciences.

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Biographies

Gilles edan Centre Hospitalier Universitaire de Rennes Rennes, France

Gilles Edan is Head of Neurosciences at the University of Rennes, France. He gained his MD at the same university in 1981 and

became a Professor of Clinical Neurology in 1990, Head of the Department of Neurology in 1997 and gained his current position in

2012. He has been involved in clinical trials in multiple sclerosis as an investigator since 1992.

Nicola De Stefano Neurology and Neurometabolic Unit Department of Neurological and Behavioral Sciences University of Siena Siena, Italy

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. Professor 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 Canada before returning to his alma mater where

he obtained his PhD. Professor De Stefano’s current research interests lie in multiple sclerosis and other neurological diseases

involving the brain white matter. In particular, he is a world renowned expert on the clinical application of new

neuroimaging techniques in brain and muscle of patients with neurological disease. Professor De Stefano is a member of

several prestigious professional societies and organisations including the American Academy of Neurology, the European Neurological

Society, the Italian Society of Neurology, and the International Society for Magnetic Resonance in Medicine. Since 2009, he has been

co-chairing the MAGNIMS European network for the study of magnetic resonance in multiple sclerosis. He has delivered

numerous invited lectures worldwide, and to date, he has published numerous books and book chapters as well as about 200

papers in prestigious international peer-reviewed publications in the area of neurology and neurometabolic disorders. He is also

currently serving as a reviewer for the most relevant international neurological journals.

Robert J. Fox Mellen Center for MS Cleveland Clinic Cleveland, USA

Doctor Fox is Staff Neurologist at the Mellen Center for Multiple Sclerosis, Cleveland Clinic Foundation and Associate Professor at

the Cleveland Clinic Lerner School of Medicine. He received his medical degree from Johns Hopkins University, neurology training at

the University of Pennsylvania, a master’s degree in Clinical Research from Case Western Reserve University, and multiple sclerosis

fellowship training at Cleveland Clinic. Doctor Fox’s current research interests focus clinical trials in multiple sclerosis, innovative

MRI techniques to evaluate tissue recovery after injury and the effects of MS treatments, as well as MS patient decision-making and

tolerance to risk. He serves as an advisor for many clinical trials, including the principal investigator of the Phase II SPRINT-MS trial

of ibudilast in progressive MS. In addition, he serves as the Managing Director of the NARCOMS MS Patient Registry, which currently

follows over 13,000 MS patients. Doctor Fox serves as a member of various advisory and review committees for the National MS

Society (USA) and National Institutes of Health (USA), the General Advisory Council for the Cleveland Clinic Clinical Research Unit,

the Editorial Board of Neurology and Multiple Sclerosis Journal, and as a consultant to the pharmaceutical industry.

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Jihad Inshasi Neurology Department Rashid Hospital Dubai Health Authority (DHA) Dubai, UAE

Consultant Neurologist, Rashid Hospital, Dubai Health Authority (DHA) Professor in Neurology, Dubai Medical College (DMC/DHA)

Fellow of the American Academy of Neurology (FAAN) Member, American Academy of Neurology (AAN) & European Neurology

Society (ENS) Founding member, board Member and Head of scientific committee, Emirates Neurology Society (EMINS/EMA) &

Founding member and ex-president of the Emirates League against Epilepsy (ILAE) Member and Delegate, World Federation of

Neurology (WFN) and (PAUNS). Participated as principle investigator in many phase 3 drug trials and research projects particularly

in the field of MS. Member in many local and regional advisory boards.

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Letizia Leocani Institute of Experimental Neurology University Vita-Salute IRCCS San Raffaele Hospital Milan, Italy

Letizia Leocani is Supervisor of Experimental Neurophysiology Laboratory at the Scientific Institute Hospital San Raffaele, Milan.

After the Degree in Medicine at the State University of Milan, Letizia Leocani completed a PhD in Human Physiology and specialized

in Neurology at the same University. She was Research Fellow at the National Institutes of Health (Bethesda, USA). She has been

the Secretary and currently is a Board member of the Italian Society of Psychophysiology. She has been a Board member and

International Delegate of the Italian Society of Clinical Neurophysiology and is currently the national representative of UEMS-Clinical

Neurophysiology Section. Her main areas of scientific interest concern the electrophysiological study of central nervous system, with

particular reference to motor and cognitive functions and to neurophysiological and psychophysiological research methods

(functional neuroimaging with advanced analysis of electroencephalography and evoked potentials, transcranial magnetic stimulation).

Biographies

Dawn Langdon Department of Psychology Royal Holloway University of London London, UK

Dawn Langdon completed her clinical training at the University of Oxford and Institute of Psychiatry, London. She worked as a

clinical psychologist at the National Hospital, Queen Square, obtaining accreditation as a health psychologist and neuropsychologist,

and also a PhD from the Institute of Neurology. She is currently Professor of Neuropsychology at Royal Holloway, University of

London. Her research interests include all psychological aspects of MS, especially cognition. She is also interested in mechanisms

of cognitive rehabilitation, the cognitive trajectory through the disease, how cognition and other factors affect MS patients’

understanding of their disease and medication risks, and assessment of cognition. She has been neuropsychology lead on a

number of international trials and served on many international committees. She is a Trustee of the UK MS Trust and author of

their online cognition tool (www.stayingsmart.org). She is co-chair of the BICAMS project (www.BICAMS.net).

Filippo Martinelli Boneschi Neurological Complex Disorders Department of Neuro-rehabilitation INSPE Scientific Institute San Raffaele Milan, Italy

Filippo Martinelli Boneschi is a neurologist, and he is the head of the laboratory of genetics of neurological complex disorders at the

INSPE laboratories at the Scientific Institute San Raffaele in Milan. He is contract professor at the University “Vita e Salute” in Milan.

His research interests include the application of array technology and the development of statistical and bioinformatic approaches to

identify genetic and environmental risk factors of complex neurological diseases including multiple sclerosis and dementia, as well

as the identification of biomarkers implicated in drug response.

He is repository of the Progetto Giovani Ricercatori from the Italian Ministry of Health, and of several grants from private Foundations

(Italian Foundation of Multiple Sclerosis, Cariplo Foundation) and from the European Community (PROPANE).

He coordinates a large consortium of Italian Multiple Sclerosis Centers involved in the study of genetics of Multiple Sclerosis

(PROGRESSO consortium).

He is full member of the International Multiple Sclerosis Genetics Consortium (IMSGC) and of the Immunochip consortium.

He is referee of several journals, and he is author of more than 90 papers on peer-reviewed journals.

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Vittorio Martinelli Neurology Unit San Raffaele Scientific Institute Vita-Salute San Raffaele University Milan, Italy

Vittorio Martinelli is the head of the Neurological Unit, Coordinator of the MS Centre and Head of the Inflammatory CNS Disorders

Unit at San Raffaele Hospital, Milan. He has published over 190 journal articles, most of them focusing on clinical, therapeutic,

neuroradiological, immunological, psychological and neurophysiological MS aspects.

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Peter Rieckmann Bamberg Hospital and University of Erlange Bamberg, Germany

Professor Peter Rieckmann received his medical degree from the University of Göttingen in 1989. After a postdoctoral fellowship

in molecular immunology at the NIH, Bethesda, USA he completed his training in Neurology at the National Institute for Nervous

Disease, London, UK and the University of Göttingen, Germany. Professor Rieckmann received Board certification in Neurology

in 1995. His academic and clinical positions have included Senior (staff) Neurologist and Professor for Neurology, Department of

Neurology, as well as head of the Clinical Research Group for Multiple Sclerosis and Neuroimmunology, at the Julius-Maximilians

University of Würzburg. He holds several positions as visiting professor across the globe. In 2007 Professor Rieckmann became

the MS Society of Canada Research Chair and Director of the MS Program at the University of British Columbia and Vancouver

Hospital, Canada. Under his leadership the Vancouver programme was awarded Western-Pacific Research and Training Center

by the MS Society of Canada. He is founding member of the EndMS campaign in Canada. His major research interests are

disease-modifying factors and regeneration in MS as well as functional aspects of the blood-brain barrier in neuroimmunological

diseases. Professor Rieckmann’s clinical goals include enhancing awareness and education about MS, developing effective and

properly resourced services for MS outpatient care, and providing more customized treatments for patients. As a clinician

scientist he has been actively involved in different efforts to transfer bench results to clinical developments and serves on steering

committees of various international multi-centre MS trials (Phase II and III). In September 2009 he started a new position as

Director of the Neurological Clinic at the Academic Hospital in Bamberg, and Professor of Neurology at the University of Erlangen,

Germany. Professor Rieckmann is a Fellow of the Royal College of Physicians and Surgeons, Canada. He has received numerous

awards and research grants and has over 200 papers to his credit in peer-reviewed medical journals.

Biographies

Carlo Pozzilli Department of Neurology and Psychiatry “La Sapienza” University of Rome Rome, Italy

Carlo Pozzilli is Professor of Clinical Neurology and Chief at the Multiple Sclerosis Center of Ospedale S. Andrea, at the University

of Rome “La Sapienza”. He gained his MD at the University of Rome “La Sapienza” in 1979 and in 2000 became an Associate

Professor, then Professor Clinical Neurology in 2006. He is a member of the European Committee for Treatment and Research in

Multiple Sclerosis, the Italian Neurological Society and the International Federation of Multiple Sclerosis (International Medical

Advisory Board). He has participated as the first investigator in around 120 multicentre clinical trials on patients with MS. Carlo

Pozzilli is the author of 269 papers and editor of several books on MS.

Maria Assunta Rocca Neuroimaging Research Unit Institute of Experimental Neurology Division of Neuroscience San Raffaele Scientific Institute Vita-Salute San Raffaele University Milan, Italy

Maria A. Rocca obtained her Graduation in Medicine in 1996 and her Post-Degree Graduation in Neurology in 2002. Doctor Rocca

is currently Head of the “Neuroimaging of CNS White Matter Unit”, Department of Neurology, Institute of Experimental Neurology,

Scientific Institute Ospedale San Raffaele, Milan, Italy. Her activity is mainly focused on the application of structural and functional

MR-based techniques to improve the understanding of central nervous system function and dysfunction in healthy individuals and

diseased people, particularly patients with MS and other white matter disorders. Doctor Rocca is currently conducting and coordi-

nating several national and international projects in adult and paediatric populations. She is also extensively applying advanced

methods of analysis in an attempt to improve the understanding of the role of brain functional and structural plasticity in the

different phases of MS, and the influence of pharmacological and rehabilitative interventions on brain reorganization.

She is member of various national and international Scientific Societies and, in some of them, she covered or is covering institutional

roles (MAGNIMS, ENS, Neuroimaging Study Group of the Italian Neurological Society, AMPC of the ISMRM). She coordinated the

MRI acquisition and analysis of several large-scale international MRI-monitored trials of MS.

Doctor Rocca is the author or co-author of more than 306 papers published in peer-reviewed journals and of 36 book chapters.

She is also a reviewer for several international scientific journals and for many Governmental Organizations and private Founda-

tions. In her scientific activity she has participated, as a speaker and/or chairman, in more than 250 international congresses and

she received several national and international Awards.

Doctor Rocca is Non-Tenured Professor at University Vita-Salute San Raffaele, Milan.

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Mohammad Ali Sahraian MS research center Tehran University of Medical Sciences Tehran, Iran

Doctor Sahraian graduated from Shiraz University of Medical Sciences (Shiraz-Iran). He joined the board of neurology and

fellowship in medical education from Tehran University of Medical Sciences. Doctor Sahraian followed subspecialty training

in multiple sclerosis at the University Hospital Basel (Switzerland). He is currently an associate professor of neurology and the

head of MS Research Center in Tehran University of Medical Sciences. He has served as an investigator on several clinical trials in

neurology and has published more than 100 articles in peer-reviewed journals and presented abstracts on MS at international

meetings. He has been invited to deliver several lectures on MR evaluations and disability assessment at different meetings on

multiple sclerosis. He has published “MRI atlas of lesions in multiple sclerosis” and has been the author of “Multiple Sclerosis”

chapter in Encyclopedia of Diagnostic Imaging. He is one of the authors of the MRI Training CD-ROM which was translated into

four languages. Doctor Sahraian’s areas of interests are management of multiple sclerosis and MRI in MS.

Aksel Siva Department of Neurology Istanbul University Istanbul, Turkey

Aksel Siva graduated from the Istanbul University, Cerrahpaşa School of Medicine (MD1978), and completed his residency in

neurology in the same institution in 1983. He currently works as Professor of Neurology, at the Department of Neurology of Istanbul

University, Cerrahpaşa School of Medicine, where he was the past-chairman, and continues to head the Clinical Neuroimmunology

Unit & Multiple Sclerosis Clinic and senior advisor of the Headache Clinic. Professor Siva worked as a visiting research fellow in the

Departments of Neurology and Radiology (Neuroradiology), University of Massachusetts Medical School and St Vincent Hospital,

Worchester, Massachusetts, USA (02/1982-11/1982) and spent a sabbatical as a visiting scientist in the Departments of Neurology

and Health Sciences Research (Clinical Neuroepidemiology), at Mayo Clinic, Rochester, Minnesota, USA, between 09/1991-05/1992.

He served as President of The Turkish Neurological Society for 3 consecutive terms between 2003 and 2009. Professor Siva was a

member of The National Advisory Board for Stemcell Research between 2006 and 2012. He is a founding member of the Headache

and Pain Research Society of Turkey, of which he is its current president. He is also a founding member of The Turkish Multiple

Sclerosis Society and Chairman of the National Scientific Committee. Professor Siva served as a Council member between 1995 and

2003; and then as an Executive Committee member between 2003 and 2006 of the European Committee on Treatment and Research

in Multiple Sclerosis (ECTRIMS) and currently is a member of The International Medical and Scientific Board of Multiple Sclerosis

International Federation. Professor Siva has been elected member of The European Neurological Society (ENS) Executive Committee

since 06/2009. He served as a member of the Education Executive Committee of The World Federation of Neurology between 2002

and 2010 and appointed chair of Task Force on Evaluation & Accreditation for endorsement of national and international meetings,

WFN 2010 - 2013. He is also a member of The American Academy of Neurology, American Neurological Association, European

Headache Federation and International Headache Society. He is on the editorial board of the Turkish Pain Journal (1990); Turkish

Neurological Journal (1995); Journal of Neurological Sciences (2006 and re-appointed in 2013), Journal of Headache and Pain (2000)

and Brazilian Journal of Multiple Sclerosis (2012). His areas of interest and work are: Clinical neuro-immunology (mainly “Multiple

Sclerosis” and “Neuro-Behcet’s Syndrome”), headaches and neuro-epidemiology.

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Biographies

23

Ilham Slassi Ibn Rochd Hospital Casablanca, Morocco

Doctor Slassi is Director in Neurogenetics and handicap and Gentic and Molecular Pathology Laboratory at the University of Ain Chok

Hassan II in Casablanca.

Having obtained the title of assistant master in Neurology in 1984 at the Faculty of Medicine and Pharmacy, Rabat, she joined the

University of Montpellier for training in Neuro-immunology. Holder of an CES in Immunology and a Master in Neuro-imminology she

returned to Morocco where she rejoined the neurology department of the UHC Ibn.

With the title of Master of Associate Conference in 1992, she sets on a research laboratory in the Department of Neurology at the

hospital specialties. In 1997, she joined the University Hassan II, and Ibn Rochd and UHC of Casablanca creates the neurology

department, establishes the residency of neurology, structure the teaching of this discipline and builds up a university research team.

She is part of various learned societies, associations, committees. She is also a founding member of the Maghreb Federation of

Neurology, a member of the Francophone Club MS, a member of the Ethics Committee for Biomedical Research at the Faculty of

Medicine and pharmacy of Casablanca.

Her areas of interest are particularly inflammatory diseases, autoimmune and infectious diseases of the nervous and management

of neurological disability system. As such, she has made, framed, participated in numerous works, try and clinical publications. She

also has the associative framework initiated in collaboration with a number of colleagues, the multidisciplinary management of

muscle diseases and neurological disability and the creation of a Moroccan network.

Alessandra Solari Unit of Neuroepidemiology Foundation IRCCS Neurological Institute C. Besta Milan, Italy

Professor Solari’s main area of research is the validation of instruments and outcome measures (chiefly patient-reported outcome

measures) for clinical, epidemiological, and quality of care studies in neurological diseases, particularly multiple sclerosis. Her

other main interest is the design, conduction and analysis of randomised controlled trials on rare diseases and on complex

interventions. She has published in leading medical journals, including Lancet Neurology, Neurology and Brain.

24

Mar Tintoré Multiple Sclerosis Centre of Catalonia (Cemcat) Neurology-Neuroimmunology Department Vall d’Hebron University Hospital Barcelona, Spain

Doctor Mar Tintoré serves a asenior neurologist at the Neurology/Neuroimmunology Department, MS Centre of Catalonia

(Cemcat), Hospital Vall d’Hebron (Barcelona). The Cemcat follows a patient base of over 4000 persons with MS and conducts

clinical and basic research on MS in aid of the persons living with MS. Doctor Tintoré’s main research line is based on first pre-

sentations of demyelinating events, magnetic resonance, immunological aspects and MS treatment. Doctor Tintoré’s publica-

tion record of over 100 publications in national and international peer-reviewed journals. Finally, Doctor Tintoré is a reviewer for

national and international journals and national research support and funding agencies.

Bassem Yamout Multiple Sclerosis Center Clinical Research American University of Beirut Medical Center Beirut, Lebanon

Doctor Yamout is currently Professor of neurology at the American University of Beirut Medical Center. He graduated from

medical school at AUB in 1984, received his training in neurology at the University of Cincinnati-Ohio followed by a fellowship

at the Montreal Neurological Institute-McGill University, and joined the faculty of the American University of Beirut in 1988. He

is currently head of clinical research at the Multiple Sclerosis Center and member of the “Regional Advisory Board for Multiple

Sclerosis in the Middle East” and the “Intercontinental Advisory Board for Multiple Sclerosis” and fellow of the American Academy

of Neurology. Doctor Yamout is one of the leading experts on multiple sclerosis in the Middle East and Arab region with recent

research on epidemiology of the disease in the region, quality of life of patients in the Middle East and novel therapies such as

stem cell transplantation and venous stenosis. In addition he is currently the principal investigator on several ongoing

international multiple sclerosis research trials. Doctor Yamout has authored many research and review papers and is currently

Chief Editor of the MS newsletter “MS today”, and on the editorial board of “Multiple Sclerosis and Related Disorders”.

Biographies

Abstracts

Multiple sclerosis (MS) is reported globally and is the most common cause of neurological disability in young adults. Comparisons of

the incidence and prevalence of disease among different populations and ethnic groups confirm that both genetic and environmental

factors contribute to MS aetiology.

The findings of many meta-analyses suggest that the incidence of MS has increased over time and provide some evidence that this

is due primarily to an increase in rates of MS among women.

When reviewing such epidemiological studies, study duration and diagnostic criteria applied are the two most important factors

to take into account before forming conclusions. Another factor is that, in the past, comparisons between studies have lacked the

appropriate standardization. However, the most recently reported analyses generally had high-quality scores. Such studies have

suggested the following additional factors that might be linked to the increase in MS prevalence: the reporting of cases in the early

stages of disease, access to neurological care centers, the availability of magnetic resonance imaging, and the use of

disease-modifying therapies. Available MS treatments have increased the life expectancy of individual patients and changed the

natural history of the disease worldwide.

The noted increase in the prevalence and incidence of MS in different ethnic groups is likely to be a multifactorial phenomenon.

Several of these factors have been described, including genetic background and environment, infections, status of self-immunity,

travel across continents, and alteration of vitamin D and calcium levels in the different communities and among patients; other

reasons are yet to be elucidated.

Saeed BohlegaDepartment of Neurosciences, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

L1 - epidemiology

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The precise aetiology of multiple sclerosis (MS) remains unclear, but evidence shows that environmental factors probably have a role. This presentation will summarize what is known about these factors, and consider how they may be driving the apparent changes in global epidemiology of MS.

Infectious pathogens associated with the development or exacerbation of MS include bacteria and viruses1. The herpes virus Epstein-Barr virus (EBV) is widely considered to be a risk factor for development of MS,2,3 with MS risk extremely low in individuals who are EBV-negative, but increasing several fold following infection with EBV3. However, the biological mechanisms underlying this epidemiological association are not known.

Other possible risk factors for MS include modifiable lifestyle factors such as childhood obesity and smoking4;both duration and intensity of smoking have been shown to contribute independently to the increased risk of MS5; An association with exposure to sunlight has also been proposed, and recent findings suggest a protective role for vitamin D in MS risk and progression6; Such factors may also underlie the strong latitude gradient in MS prevalence4 that has been reported by studies globally7. References1. Libbey JE, Cusick MF, Fujinami RS. Role of pathogens in multiple sclerosis. Int Rev Immunol 2013;doi:10.3109/08830185.2013.823422.2. Pakpoor J, Disanto G, Gerber JE, Dobson R, Meier UC, Giovannoni G, Ramagopalan SV. The risk of developing multiple sclerosis in individuals seronegative for Epstein–Barr virus: a meta-analysis. Mult Scler 2013;19(2):162-6.3. Ascherio A, Munger KL. Epstein–Barr virus infection and multiple sclerosis: a review. J Neuroimmune Pharmacol 2010;5(3):271-7.4. Ascherio A. Environmental factors in multiple sclerosis. Expert Rev Neurother 2013;13(12 Suppl):3-9.5. Hedström AK, Hillert J, Olsson T, Alfredsson L. Smoking and multiple sclerosis susceptibility. Eur J Epidemiol 2013;28(11):867-74.6. Simon KC, Munger KL, Ascherio A. Vitamin D and multiple sclerosis: epidemiology, immunology, and genetics. Curr Opin Neurol 2012;25(3):246-51.7. Simpson S, Blizzard L, Otahal P, Van der Mei I, Taylor B. Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis. J Neurol Neurosurg Psychiatry 2011;82(10):1132-41.

L2 - Risk factors: the role of infections and environment

Orhan AktasDepartment of Neurology, Heinrich-Heine-University, Düsseldorf, Germany

In the presentation we will discuss the novel and exciting genetics discoveries that have been driven by the application of array technology and the establishment of large international consortia such as the International Multiple Sclerosis Genetics Consortium (IMSGC). Genome-wide association studies and custom arrays (Immunochip) have allowed the identification of different loci in the major histocompatibility complex (MHC) region and 110 multiple sclerosis risk variants at 103 discrete loci outside the MHC region,1,2 expanding our knowledge of the role of the immune system in the mechanisms of the disease. Novel challenges are represented by the identification of the functional variants driving the association, which have been tagged by identified single-nucleotide polymorphisms and by the understanding of the molecular mechanisms linking genes to disease.

Working sessions will be dedicated to the discussion of the role of genetic and non-genetic risk factors in influencing the risk of disease, providing some examples of interactions between genes and the environment such as human leukocyte antigen genetic loci and smoking3, and N-acetyltransferases and smoking4.

References1. International Multiple Sclerosis Genetics Consortium, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011;476:214–9. 2. International Multiple Sclerosis Genetics Consortium, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nature Genetics, 2013;45:1353–60. 3. Hedström AK, Sundqvist E, Bäärnhielm M, et al. Smoking and two human leukocyte antigen genes interact to increase the risk for multiple sclerosis. Brain 2011;134:653–64.4. Briggs FB, Acuna B, Shen L, et al. Smoking and risk of multiple sclerosis: evidence of modification by NAT1 variants. Epidemiology 2014;doi: 10.1097/EDE.0000000000000089.

Filippo Martinelli BoneschiNeurological Complex Disorders, Department of Neuro-rehabilitation, INSPE Scientific Institute San Raffaele, Milan, Italy

L3 - Genetics of multiple sclerosis:current and emerging candidates

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Owing to its exquisite sensitivity to multiple sclerosis (MS) abnormalities, magnetic resonance imaging (MRI) has become an established tool to diagnose the disease and to monitor its evolution. MRI has been formally included in the diagnostic workup of patients at presentation with clinically isolated syndromes suggestive of MS and ad hoc criteria have been proposed and are updated on a regular basis. On the contrary, in patients with established MS, the ability of MR measures in explaining patient clinical status and progression of disability is still suboptimal. This has prompted the extensive application of modern MR-based technologies to estimate overall MS burden in patients at different stages of the disease. The use of these techniques has made it possible to grade in vivo the heterogeneity of MS pathology not only in focal lesions, but also in the normal-appearing white and grey matter. More recently, additional aspects of MS pathology, including macrophage infiltration and abnormal iron deposition have become quantifiable. Functional MRI (either task related or resting state) has provided important insights into cortical reorganization and how this might have an adaptive role in limiting the clinical consequences of structural damage. Furthermore, progress has been made in assessing the spinal cord and the optic nerve. High-field-strength MRI scanners (7.0 Tesla or more) are likely to advance further the understanding of damaging and reparative mechanisms of MS. All of this is improving our understanding of the factors associated with MS progression.

Maria Assunta RoccaNeuroimaging Research Unit, Institute of Experimental Neurology, Division of NeuroscienceSan Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

L4 - Deciphering MS pathogenesis: the role of MRI

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In Multiple Sclerosis (MS), the underlying pathology may precede by years the clinical presentation. Demyelination and neurodegeneration lead to accumulation or progression of disability, although may be countered by functional reorganization, together with some level of remyelination and neuroregeneration. Indeed, early MS disease course is dependent on the balance between demyelination and remyelination, with the clinical manifestation determined by the degree of plasticity offsetting the effect of damage. Although the pathogenesis of demyelination has been well described, the cellular and molecular mechanisms of neurodegeneration are not fully understood. Among the major factors, ion channel expression and redistribution, together with neuroprotective pathways counteracting oxidative stress and mitochondrial dysfunction have been identified1 Neurophysiological methods, mainly evoked potentials, are currently used for the assessment of functional consequences of demyelination, remyelination and axonal loss occurring in the course of the disease, as well as in pre-clinical testing. The functional information provided by evoked potentials accounts for their correlation with disease severity and point to their possible role as paraclinical measure for monitoring disease progression. In particular, they can help assessing the functional impact of the disease on central sensorimotor and cognitive networks affected by MS, and may reveal subclinical lesions2,3. Furthermore, they also provide some prediction on the future evolution of disability, consistently with the hypothesis that early demyelination may prompt future neuronal loss, as shown in longitudinal studies3. If further validated, neurophysiological methods may have a role in the early identification of patients who are more likely to develop future disability and for whom a closer clinical monitoring of treatment response is necessary. Finally, the possibility to demonstrate improved conduction through evoked potentials can represent a key feature in the assessment of efficacy of novel therapeutic approaches targeting remyelination.

References1. Friese MA, Schattling B, Fugger L. Mechanisms of neurodegeneration and axonal dysfunction in multiple sclerosis. Nat Rev Neurol 2014;10:225–38.2. Leocani L, Comi G. Neurophysiological markers. Neurol Sci. 2008;29 Suppl 2:S218–21.3. Leocani L, Comi G. Clinical neurophysiology of multiple sclerosis. Handb Clin Neurol. 2014;122:671–9.

Letizia LeocaniInstitute of Experimental Neurology, University Vita-Salute IRCCS, San Raffaele Hospital, Milan, Italy

L5 - Neurodegeneration: the role of neurophisiology

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Early prediction of long-term evolution is a major challenge in multiple sclerosis (MS), given that MS is classically described as an unpredictable disease and that the outcome of a patient with MS varies greatly, from remaining almost asymptomatic to becoming severely disabled. A reliable prognostic tool for MS is extremely valuable, both in clinical practice and in the evaluation of treatment efficacy. Prognostic factors are important to the patient who wants to be informed about his/her prospects, and to the clinician who needs to individualize the patients who deserve immune treatments at an early stage of the disease and to distinguish between patients requiring aggressive therapies from those who do not. Although several clinical factors (male gender; late age; motor and sphincter involvement; progressive course at onset; short inter-attack interval and high number of early attacks; relevant early residual disability) related to a poor MS prognosis have already been identified, no single factor has been found to satisfactorily predict patient outcome. Thus, concise tools taking into account all negative prognostic factors and the relative importance of their different characteristics are required. Recently, a propensity score was employed to group patients with a similar likelihood of receiving therapy. Similarly, the application of the Bayesian predictive model of the natural history of MS led to the measurement of the risk of experiencing an unfavourable evolution at an individual patient level. Future studies should move to combine clinical aspects of the disease and paraclinical information.

Roberto BergamaschiNational Neurological Institute C. Mondino, Pavia, Italy

L6 - Prognosis from natural history

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There are approximately a dozen multiple sclerosis (MS) disease-modifying therapies with demonstrated efficacy in MS. Typically, treatment efficacy was defined in Phase III clinical trials focused on patients with relapsing MS, where treatment was shown to decrease rates of relapse, new lesions on magnetic resonance imaging (MRI), and/or progression of disability. Those trials also found that not all patients responded to therapy and continued having relapses, disease activity on MRI, and/or progression of disability. An important facet of using MS therapies in daily practice is defining when therapies are not working sufficiently so that alternative treatments can be considered. However, there are no standard, validated guidelines for defining treatment non-response. Several aspects should be considered when defining MS treatment non-responders. First, disease activity should be clearly demonstrated. This may include clearly defined clinical relapses and new lesions on MRI. In practice, this can be difficult, as relapse symptoms are often indistinct, and reference MRIs are not always obtained at the time of changing therapy. Additionally, progressive disability may be from residual symptoms from a relapse or may represent transition into secondary progressive MS, where anti-inflammatory therapies have reduced efficacy in slowing disability progression. Secondly, the magnitude of disease activity needs to be recognized. A clinical relapse that both causes and leaves behind significant functional impairment would be weighed differently from a mild relapse that left behind no symptoms. The number of new lesions on MRI is related to the probability of later disability progression. Third, the timing of assessments is important, as disease-modifying therapies can have a different time course of onset, with some becoming effective within a few months of initiation, while others take up to 6-9 months. Patient adherence to therapy is also an important consideration, as non-compliance can appear as a non-response to therapy. Biologic factors can help define non-responders. For example, neutralizing antibodies to a therapy (i.e. natalizumab) can completely abrogate the effect of the therapy. With the development of many disease-modifying therapies in MS, there is need to develop and validate more formal algorithms for defining non-response to treatment.

Robert FoxMellen Center for MS, Cleveland Clinic, Cleveland, USA

L7 - How to define non-responders

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Patients with multiple sclerosis (MS) who continue to experience clinical or magnetic resonance imaging (MRI) activity despite treatment with disease-modifying drugs are considered non-responders, although individually it is difficult to establish whether a given patient presents a good response to treatment and if so to what degree. From the clinical point of view, different criteria of response to therapy have been established based on the presence of relapses or disability increase. However, to optimize MS therapy, early identification of those patients who will be non-responders is important. To this end it may be necessary to evaluate the contribution of MRI scans performed at disease-modifying therapy onset and during follow-up, toward the identification of such non-responders. The arrival of new therapeutic options in the MS armamentarium is introducing new concepts such as “patients with no evidence of disease activity” that will probably be able to better identify true responders. Tools to better predict response to treatment even before starting a drug would be of more help to choose the right drug for the right patient, to prevent side effects and to achieve cost-effectiveness for our treatments.

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

L8 - Predictivity of response to treatment

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Interferon beta was the first disease-modifying drug (DMD) to be approved for the treatment of multiple sclerosis (MS). Other first line DMDs such as the Glatiramer Acetate and more recently oral compound such as Teriflunomide and BG12 have been introduced in the market. As more treatments have become available, the rate of patients switching between them has increased. Factors related to therapy are to be considered in order to improve treatment adherence, which is essential to maximize treatment benefit and to ensure cost-effectiveness. Patients with MS, particularly those who have already switched from one therapy to another, may benefit from supportive measures to enhance adherence. Adherence is significantly influenced by disease related factors such as disability, illness duration, depression and quality of life. Psychological coping has proved to be crucially important for adjusting to the adaptive demands of chronic diseases, and in the last few years it has received growing interest in MS. However, few studies tried to identify coping strategies during therapy initiation which may allow customized support and improve treatment adherence.On the other hand, several programs have been studied to improve adherence by pharmaceutical company making several services and products available to patients.They include:1) The availability of an experienced specialist nurse from the beginning of therapy and throughout ongoing stages of therapy under the supervision of the treating physician.2) New autoinjectors devices for patients to become familiar with self-administration and to show the potential reduction in the rate of adverse events associated with subcutaneous injection which might contribute to improved treatment adherence.3) Websites which provided MS news services latest developments with treatments or latest news on MS. It also enabled exchange with the MS community and provided resources to manage the condition.

Carlo PozzilliDepartment of Neurology and Psychiatry, “La Sapienza” University of Rome, Rome, Italy

L9 - How to keep patients on treatment

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In the last few years impressive research and development programmes for drug treatments in multiple sclerosis (MS) have been developed. Based on the understanding that MS is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease, therapeutic strategies have been directed at immune modulation and inflammation control. At present, there are several options to treat MS: both licensed first-line disease-modifying drugs (DMDs) and second-line treatments. Currently available first-line MS therapies have shown significant efficacy throughout many trials, but they may produce different side effects. Despite this, DMDs are well known and well tolerated, they require regular and frequent parenteral administration and they are associated with limited long-term treatment adherence. Moreover, DMDs are only partially effective in halting MS relapses and in particular on disability progression if they are not administered in the early stage of the disease – the treatment effect size for DMDs is larger when given to patients with clinically isolated syndrome than to those with relapsing–remitting MS. Given the limitations of current DMD interventions, management of MS has been significantly improved by more recently developed second-line treatments, which include monoclonal antibodies and new oral agents, which show greater efficacy and probably better patient compliance compared with the injectables, but which may also carry novel safety and tolerability concerns. Neurologists are starting to use more powerful but potentially dangerous drugs in the treatment of MS. Safety is likely to become the most important factor in the future development of MS drugs. The most challenging aspect for the neurologist will be helping their patient to understand the need for balancing each case, the pro and cons of a new treatment, and where serious side effects may outweigh benefits in certain individuals. This is particularly important given the lack of long-term safety data with these new treatments versus currently approved DMD therapies. New drugs for MS need to be placed within this evolving marketplace, where ease of delivery together with efficacy and side effects needs to be balanced against the known issues but also the known long-term safety of standard injectables. The final decision to use these new therapies will most likely be based on an overall assessment of efficacy, safety, tolerability and adherence, the potential need for monitoring and cost effectiveness.

Workshop 1 - Treatment initiation and therapeutic contract

This workshop will be conducted by Carlo Pozzilli (Italy) and Aksel Siva (Turkey)

Carlo PozzilliDepartment of Neurology and Psychiatry, “La Sapienza University” of Rome, Rome, Italy

36

For many MS patients, immunomodulatory treatment with interferons remains the first choice, that treatment being effective and well tolerated. The switch from one therapy to another is a critical step in patient management. For that, before changing the treatment or switching to a more aggressive one, the response to treatment should be deeply investigated. The clear definition of non-responders to treatment is still a matter of debate. Both clinical evaluation and MRI studies should help neurologists make the right decision. A key point is the assessment of the individual adherence to treatment that may profoundly influence the response to treatment and should be assessed during the patient follow-up.

Workshop 2 - How to manage response to first-line therapies

This workshop will be conducted by Orhan Akatas (Germany) and Gilles edan (France)

37

With the approval of new oral disease-modifying therapies for relapsing multiple sclerosis, new therapeutic options for baseline treatment have emerged from the plethora of potential immunotherapies. In this workshop four clinical case vignettes will be discussed to better define scenarios in which therapeutic options are key questions at patient’s consultation:1. Initial diagnosis2. Discomfort with injections3. Planned pregnancy4. Breakthrough disease.

Workshop 3 - Therapeutic options

This workshop will be conducted by Giancarlo Comi (Italy) and Peter Rieckmann (Germany)

Peter RieckmannBamberg Hospital and University of Erlange, Bamberg, Germany

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Measures derived from conventional magnetic resonance imaging (MRI), including the number of active lesions, as well as the overall burden of T2-hyperintense and T1-hypointense lesions, and brain volume, have clear advantages over clinical assessment, including that they are more objective and have an increased sensitivity to multiple sclerosis (MS) related changes. For these reasons, conventional MRI has been incorporated into the diagnostic workup of patients with clinically isolated syndromes who are at risk of developing MS, and it is always recommended in patients with definite MS to monitor the course of the disease. Even though no standardised guidelines exist, follow-up brain MRI is advised whenever new diagnostic questions arise or new neurological symptoms develop, especially if suggestive of comorbid conditions. Patients about to start a new treatment or to change treatment should undergo a brain MRI scan. This MRI scan should then be repeated after 6 and 12 months to assess the effectiveness of the treatment regimen. In addition, conventional MRI-derived end-points have been used as primary and secondary outcome measures for monitoring MS clinical trials. The rationale for using conventional MRI scans as surrogates for clinical outcomes is that the efficacy of a treatment in reducing relapses can be predicted at a trial level by its capacity to reduce active MRI lesions. In this context, the most widely used conventional MRI measures are those reflecting disease activity (new or enlarged T2 lesion counts, enhancing and new gadolinium-enhancing lesion counts, enhancing lesion volume measurement) and accumulated disease burden (T2 lesion load assessment). In the near future, it is likely that novel MR markers of MS evolution will be offered by non-conventional techniques and ultra-high field scanners.

Workshop 4 - Role of MRI in monitoring treatment

This workshop will be conducted by Nicola De Stefano (Italy) and Maria Assunta Rocca (Italy)

Maria Assunta RoccaNeuroimaging Research Unit, Institute of Experimental Neurology, Division of NeuroscienceSan Raffaele Scientific Institute Vita-Salute San Raffaele University, Milan, Italy

39

Multiple Sclerosis is a complex disorder that is likely caused by a interaction between multiple genes and environmental factors, leading to inflammatory-mediated central nervous system deterioration. Several studies focused on genetic background of MS patients have discovered key genetic variables linked to the immune system, confirming the central role of immunity in the disease pathogenesis. Together with the individual genetic susceptibility, more recent studies have highlighted the role of environmental exposures acting from gestation to early adulthood. The workshop will review the main findings about genetic susceptibility and the role of environmental factors in disease onset and progression.

Workshop 5 - Genes and environment

This workshop will be conducted by Gilles edan (France) and Filippo Martinelli Boneschi (Italy)

40

The role of the patient is no longer that of a passive recipient of care. A chronic disease that affects a large portion of a patient’s lifetime requires a good relationship between the patient and the healthcare professionals (HCP) for optimal management and outcomes. It is now recognized that this essential partnership needs to be facilitated and nurtured by HCPs. Patient engagement is a key aspect of this partnership. Only by engaging patients can they be involved in decisions relating to their care. An engaged patient is more likely to manage their disease optimally, with good understanding of treatment and identification of symptoms that need attention from the HCP team. Multiple sclerosis poses certain challenges to engagement, with cognition, depression, fatigue and other symptoms requiring skilful communication by HCPs. At points of crisis in health and emotions, patients require empathic consultation to maintain and support their engagement in decision making.

Workshop 6 - Patient engagement in the decision-making process

This workshop will be conducted Dawn Langdon (UK) and Alessandra Solari (Italy)

Dawn LangdonDepartment of Psychology, Royal Holloway University of London, London, UK

Originally developed in family medicine, patient-centred care (PCC) has six dimensions: exploring illness experience as well as the disease; understanding the whole person; finding common ground; incorporating prevention and health promotion; enhancing the patient–physician relationship; and being realistic1. Shared decision making (SDM) is a development of PCC applied to the patient–health provider dialogue. SDM goes beyond informed consent (which implies discussion of risks and benefits of each healthcare option, including the option of doing nothing), providing an opportunity for patients to select options concurrent with their personal values and preferences2,3.For some decisions, there is only one realistic option – a fractured hip needs repair. But most health decisions are preference-sensitive and it is here that SDM is vital4. PCC and SDM have been associated with increased patient satisfaction and empowerment, reduced decisional conflict and treatment non-compliance5 as well as improved health provider satisfaction, strengthened patient-health provider alliance, and reduced medical litigation6.In multiple sclerosis (MS), therapeutic options have expanded significantly in recent years. Such options are not straightforward and patients have to evaluate complex information, and make difficult decisions, shortly after diagnosis. Suboptimal adherence to and withdrawal from long-term injectable immunomodulants are common7. SDM is relevant also for the new drugs, which are more effective and easier to administer, but associated with rare but severe side effects8,9. For rehabilitation in MS, goal-setting and goal attainment are essential for success. Here, too, SDM is important: establishing goals and verifying their attainment jointly helps produce the best outcomes and maximizes patient satisfaction10. The European MS Platform’s Code on Good Practice in MS (http://www.emsp.org/attachments/article/134/1code08.pdf) and the UK National Institute for Health and Clinical Excellence guidelines for MS diagnosis and management (http://www.nice.org.uk/nicemedia/live/10930/29199/29199.pdf) urge the provision of clear, concise, high-quality information from diagnosis onwards, to empower persons with MS to self-manage their disease as much as possible. This contrasts with the current reality of inadequate MS knowledge in patients11 and their relatives12 and limited SDM skills of MS physicians13. Recently, MS information and decision aids have been developed, and some have been evaluated in randomized controlled trials14. Strategies to improve communication and SDM skills of MS health professionals are also needed15.

References1. Crossing the quality chasm. A new health system for the 21st century. Committee on Quality of Health Care in America. Institute of Medicine. National Academy Press, Washington DC; 2001.2. Charles C, Gafni A, Whelan T. Shared decision-making in the medical encounter: What does it mean? (or it takes at least two to tango). Soc Sci Med 1997;44:681–92. 3. Coulter A. Engaging patients in their healthcare. How is the UK doing relative to other countries? Oxford, UK: Picker Institute Europe; 2006.4. Street RL, Makoul G, Arora NK, Epstein RM. How does communication heal? Pathways linking clinician–patient communication to health outcomes. Patient Educ Couns 2009;74:295–301.5. Joosten EAG, DeFuentes-Merilla L, de Weert GH, et al. Systematic review of the effects of shared decision making on patient satisfaction, treatment adherence and health status. Psychother Psychosom 2008;77:219–26. 6. King JS, Moulton BW. Rethinking informed consent: The case for shared medical decision making. Am J Law Med 2006;32:429–501.7. Devonshire V, Lapierre Y, Macdonell R, et al., for the GAP Study Group. The Global Adherence Project (GAP): a multicenter observational study on adherence to disease-modifying therapies in patients with relapsing-remitting multiple sclerosis. Eur J Neurol 2011;18:69–77.8. Yadav V, Bourdette D. New disease-modifying therapies and new challenges for MS. Curr Neurol Neurosci Rep 2012;12:489–91.9. Tur C, Tintoré M, Vidal-Jordana A, et al. Natalizumab discontinuation after PML risk stratification: outcome from a shared and informed decision. Mult Scler 2012;18:1193–6.10. Playford D. Outcome measurement in neurological disease. Curr Opin Neurol 2008;21:649–53.11. Giordano A, Messmer Uccelli M, Pucci E, et al. The Multiple Sclerosis Knowledge Questionnaire: A self-administered instrument for recently diagnosed patients. Mult Scler 2010;16:100–11. 12. Messmer Uccelli M, Traversa S, Trojano M, et al. Lack of information about multiple sclerosis in children can impact parents’ sense of competency and satisfaction within the couple. J Neurol Sci 2013;324:100–5.13. Pietrolongo E, Giordano A, Kleinefeld M, et al., AutoMS group. Decision-making in multiple sclerosis consultations in Italy: third observer and patient assessments. PLoS One 2013;8:e60721.14. Köpke S, Solari A, Khan F, et al. Information provision for persons with multiple sclerosis. Cochrane Database Syst Rev 2010;10:CD008757. 15. Légaré F, Politi MC, Drolet R, et al. Training health professionals in shared decision-making: An international environmental scan. Patient Educ Couns 2012;88:159–69.

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Alessandra Solari

Unit of Neuroepidemiology, Foundation IRCCS Neurological Institute C. Besta, Milan, Italy

Round table: Patient’s perception and patient’s reported outcomes

The role of patients in the decision making process has been recently highlighted. Patients perception about the disease and the treatment response is a key component of the MS management. Traditionally, outcome scales based on clinical perspective have been applied both in clinical practice and in the scientific setting. In order to make the role of patients more relevant, patient-centered outcome measure have been developed and the need to include them in clinical trials highlighted.Key opinion leaders grouped in the round table will discuss these key emerging aspects in the MS management.

R. Alroughani (Kuwait), D. Bates (UK), D. Langdon (UK), M. A. Sahraian (Iran), I. A. Slassi (Morocco), B. Yamout (Lebanon)

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D1: Treatment initiation

Multiple sclerosis (MS) is an immune-mediated, neuro-inflammatory and neurodegenerative disease of the central nervous system, with a highly heterogeneous clinical presentation and unpredictable disease course. Its first manifestations appear most commonly in young adults between the ages of 20–40 years, and then it remains a lifelong disease with differing forms of clinical expression, and progression, in some, in an age-dependent manner. An increase in the incidence of MS has been observed and reported in recent years. However, whether MS is really increasing or just being diagnosed earlier and more commonly owing to several factors, such as increased awareness, more common use of magnetic resonance imaging (MRI) in clinical practice or the development and use of other diagnostic tools, remains controversial. Naturally, earlier diagnosis is also associated with earlier treatment initiation, a result of a number of studies showing that early treatment is better. However, how early and in whom long-term treatment should be initiated are still questions that remain unanswered. Although most MS experts support the concept of early treatment, some believe that such a decision should be on a patient-by-patient basis and that we should be more selective in initiating long-term disease modifying drug (DMD) treatment.

The increasing use of MRI in various neurological problems or for other causes unrelated to MS has also revealed a growing number of cases with incidental preclinical abnormalities suggestive of MS and the term ‘radiologically isolated syndrome’ had gained acceptance to define such individuals in whom MRI studies disclose incidental lesions consistent with the imaging criteria for MS in the absence of any MS symptoms and signs. Such unexpected findings has introduced a number of questions and evoked a discussion on how to interpret these changes and whether or not these individuals should be treated at this stage! Recent studies have revealed that only one-third of these individuals at 5 years and probably about half at 10 years will convert to a clinically isolated syndrome (CIS) and/or MS. Although some demographic and imaging factors are predictive for clinical conversion, none are definite; current evidence does not support DMDs at this stage and in these individuals.

Currently, the common clinical practice is to initiate long-term DMD therapy as soon as an individual is diagnosed with a CIS highly suggestive of MS. Although the most recent diagnostic criteria for MS, the McDonald revised 2010 version, require MS-related symptomatology with supportive MRI findings, the common clinical practice is to start treatment immediately, whether the dissemination in space and time criteria are met or not. Even in those patients with CIS who meet the ‘early MS’ criteria according to the new diagnostic criteria, it has been shown that some of these cases may turn out not to be MS after an extensive differential diagnosis or in the long run. On the other hand, it is also well known that a significant number of the so-called ‘CIS/MS’ cases may either remain as such, without developing any further clinical event for long periods or ever, despite the fact that they may continue to have further MRI activity. Moreover, up to one-third of patients with relapsing–remitting MS may have ‘benign MS’, without developing any significant neurological deficit after 20 years or more of their diagnosis. All these data and observations support the notion that not all people with a diagnosis of ‘MS’ are the same and have the same destiny.

The aim of the present immunomodulatory therapies in MS, whether they have immunosuppressive properties or not, are to minimize inflammation and axonal damage and, therefore, to prevent relapses and slow disability progression. However, as already mentioned, in some individuals these disease mechanisms may not be severe enough to result in long-term disability, and/or the individual’s immunogenetic background may keep the disease process limited without requiring an external – theraupetic – inter-vention. The ongoing molecular biology and genetic studies, along with a large number of clinical, imaging and biologic studies to determine disease course and treatment response on an individual basis may be interpreted that such information, when available, will provide the most appropriate answer with regards who and when one should be treated once diagnosed with CIS/MS – early MS. Until then, I believe that a decision to start early DMD therapy should be made on an individual basis, based on each patient’s initial demographic–clinical presentations, along with initial imaging and biologic predictive features. Such an approach is to reach not only whether early treatment should be initiated or not, but also for the type and what line therapy to start once early treatment is decided.

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Giancarlo Comi (Italy) and Aksel Siva (Turkey) will debate on treatment initiation

Aksel SivaDepartment of Neurology Istanbul University, Istanbul, Turkey

D2: Assessing treatment failure

Nicola De Stefano (Italy) and Vittorio Martinelli (Italy) will debate on assessing treatment failure

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The assessment of treatment response is a key component of the MS patients management. Depending on disease course and disease activity, different therapeutic options should be considered. Up to date, no clear evidences are available to sustain the priority of MRI follow up or clinical evaluation in treatment failure assessment. MRI is an important tool in MS monitoring, but MRI activity without clinical evidence of progression could be not enough to define a failure and to decide to switch among treatments. Moreover, clinical progression could happen without a detectable MRI activity by standard techniques. The pros and cons about MRI and clinical evaluation in the assessment of treatment failure will be highlighted from different perspecitives.

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Declared receipt of honoraria or consultation fees from Bayer, Biogen, Sanofi, Merck Serono.

Declared receipt of grants and contract from Merck Serono, Bayer, Biogen, Genzyme, Novartis, Sanofi, Teva. He declared receipt of honoraria or consultation fees from Merck Serono, Bayer, Biogen, Genzyme, Novartis, Sanofi, Teva. He declared to be member of these company advisory boards, board of directors or other similar boards: Bayer, Biogen.

Declared receipt of grants and contracts from Merck Serono. He declared receipt of honoraria or consultation fees from Biogen and Novartis.

Declared receipt of honoraria or consultation fees from: Novartis, Teva, Genzyme, Merck Serono, Bayer, Biogen, Actelion, Almirall.

Declared receipt of honoraria or consultation fees from Novartis, Merck Serono, Teva, Biogen, Sanofi Aventis. He declared to be member of these company advisory boards, board of directors or other similar boards: Novartis, Merck Serono. He declared participation in a company sponsored speaker’s bureau: Novartis, Merck Serono, Biogen Idec, Teva, Bayer, Sanofi-Aventis.

Declared receipt of grants and fees from Merck Serono,Teva, Biogen Idec, Novartis, Sanofi.

Declared receipt of grants and contract from Biogen Idec, Novartis. He declared receipt of honoraria or consultation fees from: Allozyne, Biogen Idec, Novartis, Teva, Xenoport.

Declared no potential conflicts of interest

Declared receipt of grants and contracts from Bayer, Biogen, Novartis

Documents

Dear Conference Delegate, - EXCEMEDMedical Advisor: Federica Cerri EXCEMED is a Swiss Foundation with headquarters in 14, Rue du Rhône, 1204 Geneva, Switzerland Organising secretariat