ms preceptorship updating knowledge in multiple sclerosis … · updating knowledge in multiple...

FINAL PROGRAM AND ABSTRACT BOOK

MS PreceptorshipUpdating knowledge in Multiple sclerosisFall editionBarcelona, Spain - November 7-9, 2011

General information

VenueThe workshop takes place at the:

Alimara HotelBerrugete 126 - 08035 BarcelonaT (34) 935 040 440 - F (34) 934 279 292www.alimarahotel.com

and

Vall d’Hebron University Hospital Unitat de Neuroimmunologia ClínicaEUI 2ª Pl. Ps. Vall d’Hebron, 119-12908035 Barcelona, Spain

LanguageThe official language of the workshop is English.

LocationBarcelona was founded on the mediterranean coast between two rivers more than two thousand years ago. It is located in the northeast of the iberian peninsula, just a short distance from France. Romans, arabs and christians all influenced Barcelona throughout thecenturies. Traces of this diverse history with contrasting cultures can be found all over the city. From the gothic quarter built on romanruins to its art noveau district dominated by Gaudí's exuberant architecture: Barcelona surely is a city of contrasts.

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MS PreceptorshipUpdating knowledge in Multiple sclerosisFall edition

Serono Symposia International Foundation workshop on:

MS PreceptorshipUpdating knowledge in Multiple sclerosisFall editionBarcelona, Spain - November 7-9, 2011

Aim of the workshopThe MS Preceptorship offers a balanced mix of comprehensive lectures and interactive sessions that cover all main aspects ofMultiple Sclerosis (MS) scientific background and management. Acquiring the most updated knowledge and sharing theirexperience with top-level experts and highly qualified colleagues, participants will improve competence in patients’ management.

Learning objectivesAt the end of the workshop, attendees will have received comprehensive information on the following aspects of MS:• Epidemiology• Genetics• Pathogenic mechanisms• Diagnosis and differential diagnosis• Treatment

Target audienceThis program is designed mainly for neurologists already involved in Multiple Sclerosis management as well as clinicians interestedin entering this field.

AccreditationSerono Symposia International Foundation (www.seronosymposia.org) is accredited by the European Accreditation Council forContinuing Medical Education (EACCME) to provide the following CME activity for medical specialists. The EACCME is an institutionof the European Union of Medical Specialists (UEMS), www.uems.net

The MS Preceptorship Updating knowledge in Multiple sclerosis - Fall edition (Barcelona, Spain - November 7-9, 2011) isdesignated for a maximum of 11 (eleven) hours of European external CME credits. Each medical specialist should claim only thosecredits that he/she actually spent in the educational activity. EACCME credits are recognized by the American Medical Associationtowards the Physician's Recognition Award (PRA). To convert EACCME credit to AMA PRA category 1 credit, please contact the AMA.

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All Serono Symposia International Foundation programs are organized solely to promote the exchange and dissemination of scientific and medical information.No forms of promotional activities are permitted. There may be presentations discussing investigational uses of various products. These views are theresponsibility of the named speakers, and do not represent an endorsement or recommendation on the part of Serono Symposia International Foundation. Thisprogram is made possible thanks to unrestricted educational grants received from: Centre d’Esclerosi Multiple de Catalunya, ComtecMed, Congrex Sweden,Congrex Switzerland, Cryo-Save, Datanalysis, Esaote, European Society of Endocrinology, Fondazione Humanitas, Fundación IVI, ISFP International Society forFertility Preservation, ISMH International Society of Men’s Health, K.I.T.E., Merck Serono, Sanofi-Aventis, University of Catania, Vall d'Hebron University Hospital.

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Learning effectiveness project

The world of CME is changing with many different live and online formats, and Serono Symposia International Foundation(SSIF) is continually trying to improve its CME activities.

With your participation in a structured series of evaluations, SSIF can provide cutting-edge learning activities designed to giveyou the greatest value from the time you invest.

SSIF is running the learning effectiveness project for this meeting.

You will be involved in four main steps:

• Pre-event: after registering to the conference, you were asked to complete a questionnaire via e-mail to evaluate yourknowledge on the specific topics that will be covered during the conference.

• During the conference: you will be asked to complete a Program evaluation form to assess the program in various domainssuch as whether you were satisfied with the meeting, whether it met the stated learning objectives, whether the contentswere neutral and will be applicable to your daily practice.

• Post-event: three weeks after the event we will email you a short questionnaire which will give you the opportunity to tellus how much of what you learned has had an affect on your know-how and daily practice.

• Follow-up: three-months after the event, we will contact you with the final questionnaire.

We will collate and analyse your responses and use the results to improve and develop our ongoing programs.

Of course, we commit to maintaining the confidentiality of the information you provide and we will inform you about the resultsof the process regarding the activity that you attended.

Thank you very much for participating in this project!

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Scientific organizersXavier Montalban and Jaume Sastre-GarrigaMultiple Sclerosis Centre of Catalonia Unit of Clinical NeuroimmunologyVall d’Hebron University HospitalBarcelona, Spain

Local scientific and organizing coordinationIlaria LaganàTeaching & training managerMultiple Sclerosis Centre of Catalonia E-mail: [email protected]

Scientific secretariatSerono Symposia International FoundationSalita di San Nicola da Tolentino, 1/b00187 Rome, Italy

Project manager: Serena Dell’AricciaT +39 (0)6 420 413 251F +39 (0)6 420 413 677E-mail: [email protected]

Serono Symposia International Foundation is a Swiss Foundation with headquarters in 14, rue du Rhône, 1204 Geneva, Switzerland

Organizing secretariatMeridiano Congress International Via Mentana, 2/B - 00185 Rome, ItalyCongress coordinator: Denise RizzitelliT +39 (0)6 88 595 210 - F +39 (0)6 88595 234E-mail: [email protected]

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List of speakers and chairmen

José Carlos Álvarez-CermeñoService of NeurologyHospital Ramón y CajalMadrid, Spain

Maria Pia AmatoDepartment of Neurological and Psychiatric SciencesUniversity of FlorenceFlorence, Italy

María Jesús ArévaloMultiple Sclerosis Center of Catalonia (CEM-Cat)Unit of Clinical NeuroimmunologyVall d’Hebron University HospitalBarcelona, Spain

Georgina ArrambideMultiple Sclerosis Center of Catalonia (CEM-Cat)Unit of Clinical NeuroimmunologyVall d’Hebron University HospitalBarcelona, Spain

Yolanda BlancoNeuroimmunology UnitMultiple Sclerosis UnitHospital ClínicBarcelona, Spain

Wolfgang BrückInstitute of Neuropathology Universitätsmedizin Göttingen Georg-August-UniversitatGottingen, Germany

Manuel ComabellaMultiple Sclerosis Center of Catalonia (CEM-Cat)Unit of Clinical NeuroimmunologyVall d’Hebron University HospitalBarcelona, Spain

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

Carme Costa RiuMultiple Sclerosis Center of Catalonia (CEM-Cat) Unit of Clinical Neuroimmunology Vall d'Hebron University HospitalBarcelona, Spain

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Herena EixarchMultiple Sclerosis Center of Catalonia (CEM-Cat)Unit of Clinical NeuroimmunologyResearch InstituteVall d'Hebron University HospitalBarcelona, Spain

Oscar FernándezClinical neurosciences InstituteUniversity Regional Hospital “Carlos Haya”Malaga, Spain

Nicolás FissoloMultiple Sclerosis Centre of Catalonia (CEM-Cat)Unit of Clinical NeuroimmunologyInstitut de RecercaVall d’Hebron University HospitalBarcelona, Spain

Angelo GhezziMultiple Sclerosis CentreGallarate HospitalGallarate (VA), Italy

Eva HavrdovàMS Centre and Neurology ClinicCharles University Prague, Czech Republic

Alejandro HorgaMRC Centre for Neuromuscular DiseasesNational Hospital for Neurology and NeurosurgeryQueen Square, London, UK

Rosalia HornoMultiple Sclerosis Center of Catalonia (CEM-Cat) Unit of Clinical NeuroimmunologyVall d’Hebron University HospitalBarcelona, Spain

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

Xavier MontalbanMultiple Sclerosis Center of Catalonia (CEM-Cat)Unit of Clinical Neuroimmunology Vall d’Hebron University HospitalBarcelona, Spain

List of speakers and chairmen

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Mar TintoréMultiple Sclerosis Center of Catalonia (CEM-Cat)Unit of Clinical NeuroimmunologyVall d’Hebron University HospitalBarcelona, Spain

Carmen TurMultiple Sclerosis Center of Catalonia (CEM-Cat) Unit of NeurorehabilitationVall d’Hebron University HospitalBarcelona, Spain

Angela Vidal Multiple Sclerosis Center of Catalonia (CEM-Cat) Unit of Clinical Neuroimmunology Vall d’Hebron University HospitalBarcelona, Spain

Heinz WiendlDepartment of Neurology Inflammatory disorders of the nervous system and neurooncology University of MunsterMunster, Germany

Susana OteroMultiple Sclerosis Center of Catalonia (CEM-Cat) Department of Epidemiology Vall d'Hebron University HospitalBarcelona, Spain

Lluís Ramió i TorrentàDepartment of NeurologyMultiple Sclerosis Unit“Dr. Josep Trueta” Hospital in GironaGirona, Spain

Marta Renom GuiterasMultiple Sclerosis Center of Catalonia (CEM-Cat)Unit of NeurorehabilitationVall d’Hebron University HospitalBarcelona, Spain

Jordi RíoMultiple Sclerosis Center of Catalonia (CEM-Cat)Unit of Clinical NeuroimmunologyVall d’Hebron University HospitalBarcelona, Spain

Lucia RomeroUnit of Multiple Sclerosis University Hospital of BellvitgeBarcelona, Spain

Alex RoviraUnit of Magnetic ResonanceDepartment of RadiologyVall d’Hebron University Hospital-IDIBarcelona, Spain

Carme SantoyoMultiple Sclerosis Center of Catalonia (CEM-Cat)Unit of NeurorehabilitationVall d’Hebron University HospitalBarcelona, Spain

Jaume Sastre-GarrigaMultiple Sclerosis Center of Catalonia (CEM-Cat) Unit of Clinical Neuroimmunology Vall d’Hebron University HospitalBarcelona, Spain

Alan J. ThompsonDepartment of Brain Repair and RehabilitationNational Hospital for Neurology and NeurosurgeryLondon, UK

Scientific programNovember 7-9, 2011

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Chairpersons: Xavier Montalban and Jaume Sastre-Garriga

Monday - November 7

08.30 Registration at Welcome Desk

08.45 Serono Symposia International Foundation (SSIF)OpeningGiancarlo Comi, Italy

09.00 Opening and introduction to MS Centre of Catalonia(CEM-Cat)Xavier Montalban, Spain

09.30 L1: Epidemiology of MSSusana Otero, Spain

10.00 L2: Genetics of MS Manuel Comabella, Spain

10.30 KNS1: Immunopathogenesis of MSHeinz Wiendl, Germany

11.00 L3: Pathology of MSWolfgang Bruc̈k, Germany

11.30 Coffee break

12.00 PD1: Panel Discussion on “New Revision ofMcDonald’s Criteria”

Chairman: Oscar Fernández, Spain

MS diagnosis and differential diagnosisMar Tintoré, Spain

MRI in MS: the radiologist perspectiveAlex Rovira, Spain

Cerebrospinal fluid (CSF) analysis in MSJosé C. Álvarez-Cermeño, Spain

VEPs in MSLetizia Leocani, Italy

Discussion

13.30 Working Lunch

14.30 CS1: Challenging cases in MS

Chairman: Jaume Sastre-Garriga

Clinical case #1Carmen Tur, Spain

Clinical case #2Georgina Arrambide, Spain

15.30 Visit 1: Visit to MS clinic and laboratory, MRI andNRHB Units

Inside the Vall d’Hebron Hospital

Visit “Clinic”Held in the Ambulatories and Psychological officeswith a presentation of patients’ flow within thedifferent premises.

Visit “Laboratory”Held in the Laboratories to have an overview oftechnical equipments and discuss procedures.

Visit “MRI”Held at the MRI unit with a presentation ofequipments and procedures and discussion of clinicalcases.

FEM - Rehabilitation Unit

Session “Rehabilitation”Held at the Day Hospital rehabilitation center with apresentation of approaches targeted to differentlevels of disability.

17.30 End of Day 1

Legend: L : Lecture; KNS : Key Note Speech; CS : Case Study; S : Snapshot; PD : Panel Discussion

Scientific programNovember 7-9, 2011

Tuesday - November 8

08.00 Specific forms of demyelinating diseases

L4: Neuromyelitis Optica – NMOAlejandro Horga, Spain

L5: Primary Progressive MSAlan J. Thompson, UK

L6: Pediatric and Juvenile MSAngelo Ghezzi, Italy

09.30 L7: Overview on symptomatic therapy andrehabilitationJaume Sastre-Garriga, Spain

10.00 S1: Symptomatic Therapy Snapshot #1 on GaitrehabilitationCarme Santoyo, Spain

10.15 S2: Symptomatic Therapy Snapshot #2 onManagement of dysphagia Marta Renom Guiteras, Spain

10.30 Coffee break

11.00 PD2: Panel Discussion on “Cognition Disorders in MS”

Chairman: Alan J. Thompson, UK

Diagnosis Maria Pia Amato, Italy

Treatment María Jesús Arévalo, Spain

Clinical case presentation Angela Vidal, Spain

Discussion

12.30 KNS2: Injectable therapies in MSEva Havrdovà, Czech Republic

13.00 L8: Role of MS nurses in MS patients’managementRosalía Horno, Spain

13.30 Working lunch

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14.30 CS2: Case study session on DMDs

Clinical case: DMDs risk/benefitLluís Ramió i Torrentà, Spain

Clinical case: DMDs and pregnancyLucia Romero, Spain

Clinical case: Controversies in early treatmentYolanda Blanco, Spain

15.30 Visit 2: Visit to MS clinic and laboratory, MRI andNRHB UnitsFor visit description, please see details in Day 1

17.30 End of Day 2

Wednesday - November 9

08.00 PD3: Panel Discussion on “Define treatmentsuccess”

Chairwoman: Mar Tintoré, Spain

Define treatment success in present dailypractice with clinical and MRI surrogatesJordi Río, Spain

Define treatment success in the age ofpharmacogenomicsManuel Comabella, Spain

Discussion

09.30 L9: Fostering treatment adherence andcompliance: a role playMaría Jesús Arévalo, Spain and Jaume Sastre-Garriga, Spain

10.30 KNS3: Oral therapies in MSXavier Montalban, Spain

11.00 Coffee Break

11.30 KNS4: Monoclonal antibodies therapy in MSGiancarlo Comi, Italy

12.15 S3: Snapshot #1 on Gene therapy in MS Herena Eixarch, Spain

12.30 S4: Snapshot #2 on DNA vaccines in MS Nicolás Fissolo, Spain

12.45 S5: Snapshot #3 on Stem cell therapy in MS Carme Costa Riu, Spain

13.00 Course Wrap-up Xavier Montalban, Spain

13.30 End of the workshop and Working lunch

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Disclosure of faculty relationships

Serono Symposia International Foundation adheres to guidelines of the European Accreditation Council for Continuing MedicalEducation (EACCME) and all other professional organizations, as applicable, which state that programs awarding continuingeducation credits must be balanced, independent, objective, and scientifically rigorous. Investigative and other uses forpharmaceutical agents, medical devices, and other products (other than those uses indicated in approved product labeling/packageinsert for the product) may be presented in the program (which may reflect clinical experience, the professional literature or otherclinical sources known to the presenter). We ask all presenters to provide participants with information about relationships withpharmaceutical or medical equipment companies that may have relevance to their lectures. This policy is not intended to excludefaculty who have relationships with such companies; it is only intended to inform participants of any potential conflicts soparticipants may form their own judgments, based on full disclosure of the facts. Further, all opinions and recommendationspresented during the program and all program-related materials neither imply an endorsement, nor a recommendation, on the partof Serono Symposia International Foundation. All presentations solely represent the independent views of the presenters/authors.

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

José C. Álvarez-Cermeño Declared receipt of grants and contracts from: FIS; Teva; Biogen Idec; Merck Serono; Novartis.He declared also receipt of consultation fees from Bayer Schering. He is also member ofcompany advisory board, boad of directors or other similar group: Biogen Idec, Merck Serono;Novartis. He declared benefit from a relationship with commercial enterprises: Biogen Idec;Merck Serono; Novartis; Sanofi: Teva.

Maria Pia Amato Declared to be member of company advisory board, board of directors or other similar group:Biogen Idec BG 12. She declared also benefits from a relationship with commercialenterprises: Biogen Dompè; Merck Serono; Bayer Schering; Novartis.

María Jesús Arévalo Declared no potential conflict of interest.

Georgina Arrambide Declared receipt of grants and contracts from MSIF McDonald Fellowship.

Wolfgang Brück Declared receipt of grants and contracts from: Teva; Novartis; Biogen Idec. He also declaredreceipt of honoraria or consultation fees from: Teva; Sanofi-Aventis; Biogen Idec; MerckSerono; Bayer; Novartis. He is member of company advisory board, board of directors or othersimilar groups: Teva; Sanofi-Aventis; Biogen Idec.

Manuel Comabella Declared receipt of honoraria or consultation fees from: Teva; Bayer Schering; Biogen; MerckSerono.

Giancarlo Comi Declared receipt of honoraria or consultation fees from: Novartis; Teva Pharmaceuticals IndLtd; Sanofi-Aventis; Merck Serono; Bayer Schering; Biogen; SSIF.

Carme Costa Riu Declared no potential conflict of interest.

Herena Eixharch Declared no potential conflict of interest.

Oscar Fernández Declared no potential conflict of interest.

Nicolás Fissolo Declared no potential conflict of interest.

Angelo Ghezzi Declared receipt of honoraria or consultation fees from: Biogen; Teva; Merck Serono. He declared also participation in company sponsored speaker’s bureau: Biogen Dompè;Novartis; Sanofi Aventis.

Eva Havrdovà Declared receipt of grants or contracts from Biogen Idec. She also declared receipt ofhonoraria or consultation fees from: Biogen Idec; Genzyme; Merck; Bayer; Teva; Novartis. She is member of company advisory board, board of directors or other similar group: BiogenIdec; Genzyme; Novartis; Bayer; Merck.

Alejandro Horga Declared no potential conflict of interest.

Letizia Leocani Declared no potential conflict of interest.

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Xavier Montalban Declared receipt of honoraria or consultation fees from: Bayer Schering; Biogen Idec; MerckSerono; Novartis; Teva; Sanofi; Almirall.

Susana Otero Declared no potential conflict of interest.

Jordi Río Declared receipt of honoraria or consultation fees from: Serono; Schering; Biogen; Teva;Novartis; Almirall.

Carme Santoyo Declared no potential conflict of interest.

Marta Renom Guiteras Declared no potential conflict of interest.

Alex Rovira Declared receipt of grants and contracts from Bayer Schering Pharma. He declared to bemember of a company advisory board, board of directors or other similar groups: NeuroTEC;OLEA Medical; Bayer Schering Pharma; BTG International Ltd. He declared also participationin a company sponsored speaker’s bureau: Bayer Schering Pharma; Sanofi-Aventis; Bracco;Merck Serono; Teva Pharmaceutical Industries Ltd; Biogen Idec.

Jaume Sastre-Garriga Declared participation in company sponsored speaker’s bureau: Biogen; Merck Serono; Sanofi-Aventis; Novartis.

Alan J. Thompson Declared receipt of consultation fees from: Biogen Idec; Teva Pharmaceutical; Merck Serono;DIGNA Biotech; Novartis Pharma; EISAI Ltd; GE Healthcare. He declared also receipt ofhonoraria from: Biogen Idec Canada; SSIF; NIHR. He is member of company advisory board,board of directors or other similar groups: MSIF; NMSS. He declared benefits fromrelationships with commercial enterprises: Sage Publication; Elsevier; Remedica.

Mar Tintoré Declared receipt of grants and contracts from: Bayer Schering; Biogen Idec; Merck Serono;Teva; Sanofi-Aventis; Novartis. Declared also receipt of honoraria or consultation fees from:Bayer Schering; Biogen Idec; Merck Serono; Teva; Sanofi Aventis and Novartis. She declared tobe member of company advisory board, board of directors or other similar groups: Teva;Biogen Idec.

Carmen Tur Declared receipt of honoraria or consultation fees from: TEVA; SSIF; Novartis.

Angela Vidal Declared no potential conflict of interest.

Heinz Wiendl Declared receipt of grants and contracts from: Sanofi-Aventis; IZKF Muenster; BMBF; BIIB;Bayer Vital; Novo Nordisk; Merck Serono; Novartis. He declared also receipt of honoraria orconsultation fees from: Bayer Healthcare; Biogen Idec; Sanofi-Aventis; Schering; Serono; TEVA;Medack; Lundbeck; Novo Nordisk. He is member of company advisory board, board ofdirectors or other similar groups: FTY.

The following faculty have provided no information regarding significant relationship with commercial supporters and/or discussionof investigational or non-EMEA/FDA approved (off-label) uses of drugs as of October 28, 2011.

Yolanda Blanco

Rosalia Horno

Lluís Ramió i Torrentà

Lucia Romero

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Abstracts

L1 - Epidemiology of MS

Epidemiology can be defined as the study of the distribution and determinants of disease from a population perspective, usingquantitative methods. Descriptive epidemiology pictures the distribution and time trends, using prevalence and incidence data, andanalytic epidemiology seeks for possible risk factors related to the disease.

The first descriptive epidemiological studies on multiple sclerosis (MS) used prevalence data to map de distribution of MS aroundthe world. They showed that the disease was not evenly distributed and there was a latitudinal gradient with higher prevalence aswe move away from de equator. It should be noted that this studies had certain limitations that have to be considered whencomparing data. There were differences between studies regarding methodological aspects such as case definition, sources ofinformation, population size and there was data lacking in certain parts of the world.

Despite the methodological limitations, the characteristic distribution led to genetic and environmental pathogenic hypothesis.Considering that MS has an important genetic component of susceptibility, the distribution could be due to the variation of geneticand ethnic backgrounds of the world’s population. Nevertheless, there are reasons to believe that genetics can not explain all of it.In regions with homogenous population, this gradient is still present, and according to studies in migrant population, risk of MS canvary when migrating to a different area, particularly when migration occurs early in life. Furthermore, studies conducted inmonozygotic twins, show concordance rates for MS of 24% that would reflect other factors acting in uterine or early lifeenvironments.

There are several environmental factors that have been postulated. The mirror-image gradient of MS points to a sun related factorsuch as Vitamin D. On the other hand, an infectious agent acting directly (as a trigger of the disease) or indirectly (protecting ifacquired early in life -hygiene hypothesis-) has also been postulated. Epstein-Bar virus (EBV), seems one of the strongestcandidates, as MS in unlikely to develop in a EBV negative individual, there is strong evidence that links epidemiology of infectiousmononucleosis with MS, and recent studies have shown an increase in EBV antibodies preceding symptomatic MS.

Recent data from prospective studies performed in Europe, America and Asia show that MS incidence seems to be increasing duringthe past 20 years and the classical prevalence gradient is disappearing in certain areas. This phenomenon could be explained by animproved case ascertainment thanks to better diagnostic techniques, such as MRI, the emergence of data in areas that had not beenstudied previously or changes in population composition due to migration. However, it can not be ruled out a true increase in MSrisk as a result in a change in causal factors.

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Susana OteroMultiple Sclerosis Center of Catalonia (CEM-Cat) and Epidemiology Unit, Vall d'Hebron University Hospital, Barcelona, Spain

References:- Kurtzke JF. Geographic distribution of multiple sclerosis: An update with special reference to Europe and the Mediterranean region. Acta Neurol Scand 1980;62:65-80.- Ebers GC. Environmental factors and multiple sclerosis. Lancet Neurol 2008;7:268-77.- Rosati G. The prevalence of multiple sclerosis in the world: an update. Neurol Sci 2001 Apr;22(2):117-39.- Hammond SR, English DR, McLeod JG. The age-range of risk of developing multiple sclerosis: evidence from a migrant population in Australia. Brain 2000;123:968-74.- Koch-Henriksen N. The Danish Multiple Sclerosis Registry: a 50-year follow-up. Mult Scler 1999;5:293-6.- Grytten N, Glad SB, Aarseth JH, Nyland H, Midgard R, Myhr KM. A 50-year follow-up of the incidence of multiple sclerosis in Hordaland County, Norway. Neurology2006;66:182-6

- Alonso A, Hernan MA. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology 2008;71:129-35.

L2 - Genetics of MS

During the last two decades, many research groups have dedicated important efforts to identify the individual genes that confersusceptibility to multiple sclerosis (MS). The main conclusion derived from this work is that the HLA-class II region on chromosome6p21, specifically the HLA-DRB1*15 haplotype, contributes by far the most to genetic susceptibility in MS, and results from manyMS genetic studies support this association. Unfortunately, despite the evidence that MS is a complex genetic trait with multiplegenes contributing to disease susceptibility, genetic studies aiming to identify additional risk genes for MS have been ratherdisappointing, as many of the candidate genes identified in one study were not confirmed in others. It has not been until recently thatadditional genes located outside the HLA region have been proposed, although with weaker effects, as solid candidates for MSgenetic risk. In particular, three single-nucleotide polymorphisms (SNPs), two located within the interleukin-2 receptor α (IL2RA)and one located within the interleukin-7 receptor α (IL7RA), were strongly associated with MS. Other SNPs positioned in attractivegenes were also found to be associated with the disease. Most of the genes proposed as risk genes for the disease are related withthe immune system. These latest findings have certainly opened new scenarios in MS genetic research.

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Manuel ComabellaMultiple Sclerosis Center of Catalonia (CEM-Cat), Unit of Clinical Neuroimmunology, Vall d’Hebron University Hospital, Barcelona, Spain

References:1 - Chappel SC, Howles C 1991 Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Human Reproduction

6 1206-1212. 2 - Filicori M, Cognigni GE, Pocognoli P et al. 2003 Current concepts and novel applications of LH activity in ovarian stimulation. Trends in Endocrinology and

Metabolism 14, 267-273.

KNS1 - Immunopathogenesis of MS

Abstract not in hand at the time of going to press.

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1. Adapting the ovarian stimulation protocol according to the patient’s individual profile and the experience from her previousstimulation cycles.

2. Reducing FSH and compensating with LH in the stimulation protocol to selectively stimulate the greatest follicles andprevent the growth of smaller ones.

Learning ObjectivesBy the end of the programme participants should appreciate: • International Variation in Assisted Reproduction Practice• Need to collect data to reflect practice• Value of e-Learning to facilitate best practice

IntroductionXxx xxx

MethodsXxx xxx

ResultsXxx xxx

ConclusionsXxx xxx

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Heinz WiendlDepartment of Neurology, Inflammatory disorders of the nervous system and neurooncology, University of Munster, Munster, Germany




L3 - Pathology of MS


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Wolfgang BrückInstitute of Neuropathology, Universitätsmedizin Göttingen Georg-August-Universitat, Gottingen, Germany

References:1 - Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H: Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of

demyelination. Annals of Neurology 2000, 47:707-717.2 - Kutzelnigg A, Lucchinetti CF, Stadelmann C, Bruck W, Rauschka H, Bergmann M, Schmidbauer M, Parisi JE, Lassmann H: Cortical demyelination and diffuse

white matter injury in multiple sclerosis. Brain 2005, 128:2705-2712.3 - Wegner C, Esiri MM, Chance SA, Palace J, Matthews PM: Neocortical neuronal, synaptic, and glial loss in multiple sclerosis. Neurology 2006, 67:960-967.4 - Albert M, Antel J, Bruck W, Stadelmann C: Extensive cortical remyelination in patients with chronic multiple sclerosis. Brain Pathol 2007, 17:129-138.5 - Wegner C, Stadelmann C: Grey matter pathology and multiple sclerosis, Curr Neurol Neurosci Rep 2009, 9: 399-404.

PD1 - Panel Discussion on “New Revision of McDonald’sCriteria”

1 - Multiple Sclerosis Center of Catalonia (CEM-Cat), Unit of Clinical Neuroimmunology, Vall d’Hebron University Hospital, Barcelona, Spain;2 - Unit of Magnetic Resonance, Department of Radiology, Vall d’Hebron University Hospital-IDI, Barcelona, Spain;3 - Service of Neurology, Hospital Ramón y Cajal, Madrid, Spain4 - Institute of Experimental Neurology, University Vita-Salute IRCCS, San Raffaele Hospital, Milan, Italy

Cerebrospinal fluid (CSF) analysis in MSJosé C. Álvarez-Cermeño

In the recent revision of McDonald´s criteria, the study of cerebrospinal fluid (CSF) has been considered important to confirm theunderlying inflammatory demyelinating nature of the underlying condition, to evaluate alternative diagnoses, and to predict CDMSin CIS patients. However, this study has not been included in the criteria for the diagnosis of relapsing-remitting multiple sclerosis(RRMS). Meanwhile, CSF analysis remains to play a role in the diagnosis of primary-progressive MS, since it rules out other non-inflammatory sources of progressive neurological symptoms.We argue that CSF study has also an important role in the diagnosis of RRMS due to the high positive predictive value of CSF studyfor MS conversion in CIS patients, and the other properties acknowledged by the panel.

MRI in MS: the radiologist perspective Alex Rovira

Conventional MR imaging techniques, such as T2-weighted and gadolinium-enhanced T1-weighted sequences are highly sensitivein detecting multiple sclerosis (MS) plaques and provide a quantitative assessment of inflammatory activity and lesion load. However,the changes identified by MR imaging in patients with MS are not disease-specific. Other disorders can cause white matter lesionswith imaging characteristics similar to those seen in MS. Nevertheless, the MR imaging pattern of brain MS is usually relativelyspecific when age, clinical information, and the full range of MR imaging abnormalities (including lesion number, distribution, size,shape, associated volume changes, and contrast enhancement) are taken into consideration. Even when only the number, location,and size of lesions are considered, the sensitivity and specificity for the diagnosis of MS is quite good, particularly after otherdiagnoses have been excluded by appropriate tests. MS lesions tend to affect specific regions of the brain hemispheres, including the periventricular white matter, the calloso-septalinterface along the inferior surface of the corpus callosum, and the juxtacortical white matter (“U” fibers). Posterior fossa lesions preferentially involve the floor of the fourth ventricle, the middle cerebellar peduncles, and the brainstem.Most brainstem lesions are contiguous with the cisternal or ventricular cerebrospinal fluid spaces, and range from large confluentpatches to solitary, well-delineated paramedian lesions or discrete "linings" of the cerebrospinal fluid border zones. These areas area key feature that helps to identify MS plaques and differentiate them from focal areas of ischemic demyelination and infarction,which preferentially involve the central pontine white matter. MS lesions of the spinal cord resemble those in the brain. On sagittal scans, the lesions characteristically have a cigar shape andrarely exceed two vertebral segments in length. On cross-section they typically occupy the lateral and posterior white-mattercolumns, extend to involve the central grey matter, and rarely occupy more than one half the cross-sectional area of the cord. Theprevalence of cord abnormalities is as high as 92% in established MS. MRI identification of subclinical spinal cord lesions in patientswith non-specific brain findings, particularly those >50 years old, can increase the diagnostic certainty because these lesions arerelatively frequent in MS, but rare in other white matter diseases. Longitudinal and cross-sectional MR studies have shown thatformation of new MS plaques is often associated with contrast enhancement. Incomplete ring enhancement on T1-weightedgadolinium-enhanced images, with the open border facing the gray matter of the cortex or basal ganglia is a common finding inactive MS plaques and is a helpful feature for distinguishing between inflammatory-demyelinating lesions and other focal lesionssuch as tumors or abscesses. Knowledge of the full range of MR imaging abnormalities that characterize MS lesions increases the diagnostic specificity of MRI.This is particularly important, as MRI is now integrated in the overall diagnostic scheme of the disease, and in guiding therapeuticdecisions.

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Mar Tintoré, Spain 1

Alex Rovira, Spain 2

José C. Álvarez-Cermeño, Spain 3

Letizia Leocani, Italy 4

CS1 - Challenging cases in MS

1 - Multiple Sclerosis Center of Catalonia (CEM-Cat), Unit of Neurorehabilitation, Vall d’Hebron University Hospital, Barcelona, Spain;2 - Multiple Sclerosis Center of Catalonia (CEM-Cat), Unit of Clinical Neuroimmunology, Vall d’Hebron University Hospital, Barcelona, Spain.

Abstract not in hand at the time of going to press. Clinical case #2Sara Llufriu, Yolanda Blanco and Albert Saiz

A twenty six years old woman was referred to our MS Unit on June 2006 for a second opinion about the management of MS.

Her MS started in 2001, when she was 17 years old, with a multifocal relapse (right optic neuritis and cervical myelitis symptoms).Brain and spinal cord MRI disclosed T2 lesions that fulfilled the Barkhof´s criteria. Three months later she presented with a secondrelapse and was diagnosed with MS. Chronic therapy with interferon beta 1b was started. On treatment she had two relapses in 2002,one in 2003 and another one in October 2005. After this last relapse the EDSS had increased from 2.5 to 4.0, and then the treatmentwas switched to glatiramer acetate. Over the ensuing 6 months she suffered two severe spinal cord relapses and a multifocal relapsewith incomplete recovery despite corticosteroid treatment. On June 2006 the patient was evaluated at our hospital. Her EDSS was6.5 and a brain MRI disclosed more than15 gadolinium-enhancing lesions. The patient was included in the ASTIMS trial (Autologous Stem cell Transplantation International Multiple Sclerosis) which comparedmitoxantrone with autologous haematopoietic stem cell transplantation (AHSCT) in patients with severe MS. She was randomizedto receive AHSCT. The peripheral blood stem cells were mobilised with cyclophosphamide (6.25 g) and granulocyte colony-stimulating factor. Five days later the patient presented motor and sensitive worsening due to a spinal cord relapse. Her EDSSincreased to 7.5 and treatment with methylprednisolone was given. One month after mobilisation, the EDSS had improved (6.5) and the brain MRI still showed gadolinium-enhancing lesions. Theconditioning regimen with BEAM (camustine+etoposide+cytarabine+melphalan) chemotherapy was performed and 7 days later thehaematopoietic stem cells were infused. Six months after AHSCT her EDSS was 5.5 and the MRI did not show any gadolinium-enhancing lesions. A year later the EDSS was4.0, and for 3 years she has been free of relapses and brain MRI disease’s activity.Autologous haematopoietic stem-cell transplantation in multiple sclerosis preceded by intense immunosuppression has beenperformed in more than 400 patients worldwide since 1995. It has been assessed as a possible therapeutic strategy in breakthroughcases of multiple sclerosis that do not respond to conventional treatments. The procedure eradicates the self-reactive immune cellsby intense immunosuppression and achieves a full immune reconstitution on the engraftment of autologous hemato-lymphopoieticstem cells that could become tolerant of self-antigens over an extended period of time1. Although the lack of large prospectivecomparative studies, the available information from small phase I/II studies1,2 demonstrated that after a follow-up period of 3 yearsa median of 60-70% of treated cases did not progress and dramatically decreased the gadolinium-enhancing activity on MRI. Themost important limitations of this treatment are the transplant related mortality, the absence of consensus on the best conditioningregimen and the lack of studies comparing this procedure to the new powerful drugs like the monoclonal antibodies1-4.

References:1 - Mancardi G, Saccardi R. Autologous haematopoietic stem-cell transplantation in multiple sclerosis. Lancet Neurol 2008; 7:626-36. 2 - Blanco Y, Saiz A, Carreras E, Graus F.Autologous haematopoietic-stem-cell transplantation for multiple sclerosis. Lancet Neurol. 2005; 4(1):54-63. 3 - Fassas A., Kimiskidis VK, Sakellari I, et al. Long-term results of stem cell transplantation for MS. Neurology 2002; 22:1066-70.4 - Saccardi R, Kozak T, Bocelli-Tyndall C, et al. Autologous stem cel l transplantation for progressive multiple sclerosis: uptdate of the European Group of Blood

and Marrow Transplantation autoimmune diseases working party database. Mult Scler 2006; 12:814-23.

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Carmen Tur, Spain 1

Georgina Arrambide, Spain 2

L4 - Neuromyelitis Optica – NMO

Neuromyelitis optica (NMO) is an uncommon inflammatory demyelinating disease of the CNS that predominantly involves the opticnerve and spinal cord. Recent clinical, serological, radiological and pathological findings support the hypothesis that NMO is ahumorally mediated autoimmune disease and a distinct entity from classical multiple sclerosis (MS). The aim of this talk is topresent an updated overview on the clinical manifestations, diagnostic evaluation and therapeutic management of NMO.

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Alejandro HorgaMRC Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK




L5 - Primary Progressive MS


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Alan J. ThompsonUCL Institute of Neurology, Queen Square, London, UK




L6 - Pediatric and Juvenile MS

Juvenile Multiple Sclerosis (JMS) is increasingly recognized, raising the question whether it has peculiar aspects compared with theadult form (adult onset MS-AOMS).

JMS is defined by the onset of the disease before 16 years of age in most studies, and occurs in about 3 to 5% of all MS cases, witha clear preponderance of females during the adolescence (f/m ratio about 4) (1,2). The presentation of JMS can be monofocal orpolyfocal, sometimes with symptoms consistent with acute demyelinating encephalomyelitis (ADEM) raising the problem of thedifferential diagnosis from this disease, particularly with respect to the recurrent (new event of ADEM with a recurrence of the initialsymptoms 3 or more months after the 1st event, without clinical/MRI involvement of new areas) or multiphasic variant (ADEMfollowed by new clinical events also meeting the criteria of ADEM but involving new areas) (3).

The evolution of JMS is initially relapsing-remitting in most cases, the primary-progressive course representing less than 4% ofcases (2). Relapses are rather frequent in early phases of the disease, with an annualized relapse rate of about 1-1.9 (1,2,4,5), slightlyhigher than that commonly reported in adults.

Prognosis is in general less severe than AOMS, as the mean time to reach mild (EDSS4) or severe disability (EDSS6 or 7) as well asthe shift to the secondary progressive phase is longer compared to AOMS, however these landmarks are reached at an ageapproximately 10 years younger (6-8). Factors related to a poor prognosis are the number/frequency of relapses in the first stagesof the disease, the early shift to progression, early disability. Recent studies have demonstrated that cognitive impairment can occurprecociously, with a negative impact on school and social activities (9-10).

MRI and CSF examination contribute to the increasing recognition and early diagnosis of JMS, although their sensitivity is lower withrespect to AOMS (1,2).

Treatment is currently based on strategies optimised for AOMS. Immunomodulating agents, namely Interferon-Beta and GlatiramerAcetate, have not been evaluated in children with double-blind, placebo-controlled trials, but in open-label, observational studiesshowing they are safe and well tolerated, meanwhile reducing relapse rate and disease progression (1,2,11).

The overall positive results of IFNB and GA in JMS has led the European Regulatory Agency to modify the label of drugs includingthe following statement: “limited published data suggest that safety profile in adolescents from 12 to 16 years of age receiving IFNBor GA is similar to that seen in adults (…)”, whereas there is not enough information on the use of IFNB or GA in children below 12years of age.

Second-line treatment with cyclophosphamide and now with natalizumab are used off-label and can be proposed in selected caseswith an aggressive evolution.

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Angelo GhezziMultiple Sclerosis Centre, Gallarate Hospital, Gallarate (VA), Italy

References:01 - Ghezzi A. Childhood-juvenile multiple sclerosis: clinical characteristics and treatment. Expert rev Neurotherapeutics 2005, 5:403-41102 - Banwell B, Ghezzi A. A. Bar-Or et al. Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions. Lancet Neurol. 2007, 6:887-

90203 - Krupp LB, Banwell B., Tenembaum S. et al. Consensus definitions proposed for pediatric multiple sclerosis and related disorders. Neurology 2007 (suppl2)

S7-S1204 - Ghezzi A. Pozzilli C., Liguori M. et al. Prospective study of multiple sclerosis with early onset. Multiple Sclerosis 2002, 8:115-11805 - Gusev E., Boiko A., Bikova O. et al. The natural history of early onset multiple sclerosis: comparison of data from Moskow and Vancouver. Clin. Neurology

Neurosurg. 2002, 104:203-20706 - Simone I.L., Carrara D., Tortorella C. et al. Course and prognosis in early onset MS. Comparison with adult-onset forms. Neurology 2002, 59:1922-192807 - Boiko A. Vorobeychik G., Paty D., et al. Early onset multiple sclerosis. A longitudinal study. Neurology 2002, 59:1006-101008 - Renoux C., Vukusic S., Mikaeloff Y et al. Natural History of multiple sclerosis with childhood onset. N Engl. J Med. 2007, 356:2603-1309 - Amato MP, Goretti B, Ghezzi A Cognitive and psychosocial features of childhood and juvenile MS.Neurology. 2008;70(20):1891-7.10 - Ghezzi A, Amato MP, Annovazzi P, et al. Long-term results of immunomodulatory treatment in children and adolescents with multiple sclerosis: the Italian

experience. Neurol Sci. 2009 30(3):193-911 - Ghezzi A. Therapeutic strategies in childhood multiple sclerosis. Ther. Adv. Neurol. Disorders, 2010 in press

L7 - Overview on symptomatic therapy and rehabilitation

Multiple Sclerosis (MS) may cause a variety of symptoms: fatigue, cognitive dysfunction, bladder and bowel problems, sexualproblems, tremor, spasticity, speech and swallowing disorders, sensory symptoms including pain, among others. Motor andcoordination symptoms causing gait problems and upper limb dysfunction also need to be considered. These symptoms, in isolation,or more commonly in association, are the ultimate cause of worsening quality of life and therefore must be treated with the sameemphasis as the condition itself. There is a need for an interdisciplinary management of symptoms in MS; this management is thefocus of neurorehabilitation. Neurorehabilitation approaches emphasize education of patients and self-management of symptoms;this approach is ideally suited to meet the evolving needs of people with MS. Thus, symptom management should be performed ona neurorehabilitation setting using an interdisciplinary approach. According to this, clinical trials evaluating the efficacy and safetyof a drug intervention to treat a given symptom lack the added value of interdisciplinary interventions (e.g. drug A may be useful forspasticity, but its combined efficacy together with physiotherapy and occupational therapy has not been investigated; in combinationthey are likely to have a greater impact on quality of life, the final goal of any symptomatic therapy). Clinical trials evaluating theeffectiveness of neurorehabilitation approaches in people with MS have shown that improvements in activities and participation areto be expected. However, modalities of intervention have been usually ill-defined (rehabilitation black box) and clinical trialmethodologies suboptimal. Therefore, further research is needed to improve clinical trial methodology and our ways of evaluatingthe impact of neurorehabilitation by means of goal achievement frameworks and through the use of clinically appropriate andscientifically sound outcome measure tools. In this lecture I will briefly overview current therapies for symptoms of MultipleSclerosis.

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Jaume Sastre-GarrigaMultiple Sclerosis Center of Catalonia (CEM-Cat), Unit of Clinical Neuroimmunology, Vall d’Hebron University Hospital, Barcelona, Spain

S1 - Symptomatic Therapy Snapshot #1 on Gaitrehabilitation

One of the most pronounced incapacitating manifestations of MS are gait disorders, resulting from the combined effect of decreasein muscle strength, spasticity, gait ataxia, sensory disorders and reduction in aerobic capacity. Pathological gait patterns are lessfunctional, secure, and effective contributing to secondary problems such as increased risk of falls and increased energyexpenditure.

Physical therapy interventions firstly aim to develop motor recovery and secondly to train compensatory strategies in order toimprove or maintain functional independence and efficacy in deambulation.

In this speech we’ll revise the main rehabilitation strategies for gait impairment in MS: from conventional rehabilitation to the latestrobotic biofeedback devices.

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Carme SantoyoMultiple Sclerosis Center of Catalonia (CEM-Cat), Unit of Neurorehabilitation, Vall d’Hebron University Hospital, Barcelona, Spain

References:- Hobart JC et al. Measuring the impact of MS in walking ability: the 12-item MS Walking Scale (MSWS-12). Neurology 2003; 60(1):31-6- Paltamaa J et al. Reliability of physical functioning measures in ambulatory subjects with MS. Physiother Res Int 2005; 10(2): 93:109- Gijbels D et al. Predicting habitual walking performance in multiple sclerosis : relevance of capacity and self-report measures. Mul Scler 2010 Mar 5- Levin MF et al. What do motor recovery and compensation mean in patients following stroke? Neurorehabili Neural Repair 2009; 23; 313 originally publishedonline Dec 31, 2008

S2 - Symptomatic Therapy Snapshot #2 on Managementof dysphagia

The reported prevalence of dysphagia in MS ranges between 33% and 43%. It is clearly more frequent in advanced stages of thedisease but can also appear in early stages. It is associated to brainstem and cerebellar impairment. Dysphagia can lead to seriouscomplications such as bronchopneumonitis, bad nutritional state and decrease of the quality of life. It can affect swallowing of liquidsand/or solids, the later being more frequent in severe dysphagia.

The intervention is interdisciplinary and can involve neurologists, speech and language pathologists, physiotherapists, nurses,radiologists and dieticians among others.

Assessment: the presence of altered feeding habits and of cough and/or choking during, or after, meals are the two most commonlyreported symptoms. A questionnaire is currently available to detect dysphagia (DYMUS). Clinical assessment should includeobservation of the oral anatomy and examination of the cranial nerves involved in swallowing and of the muscular tone, oral reflexesand movement execution pattern. A functional assessment of chewing, swallowing, phonation and articulation should also beperformed. A bedside screening examination has been described, which includes the 50-ml water test, pharyngeal sensationexamination and pulse oximetry.

Referral to instrumental examination should be done in any case in moderate to severe dysphagia. Videofluoroscopy and fiberopticlaryngoscopy are the two most commonly used instrumental procedures.

Treatment of dysphagia should begin soon after appearance of the first symptoms. Its goal is to improve security and efficacy ofswallowing and to improve quality of life and social participation. It can include rehabilitation, pharmacological treatment andeventually implementation of enteral feeding. Rehabilitation includes restorative, compensatory and adaptive approaches and alsoeducation on security manoeuvres. The restorative approach includes different interventions directed to improve the sensorimotorcontrol of the swallowing mechanisms. The compensatory approach consists of general advice, strategies and manoeuvres to betaken into account while eating and drinking. The adaptive approach includes measures involving adaptation of environmentalfactors, including food consistency.

Family and caregivers should be involved in rehabilitation. Pharmacological treatment may help alleviate associated problems suchas hyper-salivation, hiccups or reflux.

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Marta Renom GuiterasMultiple Sclerosis Center of Catalonia (CEM-Cat), Unit of Neurorehabilitation, Vall d’Hebron University Hospital, Barcelona, Spain

References:- Abraham S, Scheinberg LC, Smith ChR, La Rocca, NG (1997) Neurologic impairment and disability status in outpatients with multiple sclerosis reportingdysphagia symptomatology. J Neur Rehab 11:7-13

- De Pauw A, Dejaeger E, D’hooge B, Carton H (2002) Dysphagia in multiple sclerosis. Clin Neurol Neurosurg 104:345-351- Prosiegel M, Schelling A, Wagner-Sonntag E (2004) Dysphagia and multiple sclerosis. Int MS J 11:22-31- Terré-Bolliart R, Orient-López F, Guevara-Espinosa D et al. (2004) Disfagia orofaríngea en pacientes afectados de esclerosis múltiple. Rev Neurol 39:707-710- Giusti A, Giambuzzi M (2008) Management of dysphagia in MS. Neurol Sci 29:364-366- Tassorelli C, Bergamaschi R, Buscone S et al. (2008) Dysphagia in multiple sclerosis: from pathogenesis to diagnosis. Neurol Sci (2008) 29;360-363- Bergamaschi R, Crivelli P, Rezzani C et al. (2008): The DYMUS questionnaire for the assessment of dysphagia in multiple sclerosis. J Neurol Sci 269:49-53- Poorjavad M, Derakhshandeh F, Etemadifar M, et al. (2010): Oropharyngeal dysphagia in multiple sclerosis. Mult Scler. 16(3):362-5- Bogaardt H, van Dam D, Wever NM, et al. (2009): Use of neuromuscular electrostimulation in the treatment of dysphagia in patients with multiple sclerosis. AnnOtol Rhinol Laryngol. Apr;118(4):241-6.

PD2 - Panel Discussion on “Cognition Disorders in MS”

1 - Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy2 - Multiple Sclerosis Center of Catalonia (CEM-Cat), Unit of Clinical Neuroimmunology, Vall d’Hebron University Hospital, Barcelona, Spain

Cognition disorders in MS: DiagnosisMaria Pia Amato

Only during the past 20 years clinicians have become aware of the prevalence and functional impact of MS-related cognitiveimpairment and its profound functional impact. Cognitive dysfunction is highly variable and estimates of its frequency range from43% to 65% of the cases. The domains most commonly impaired are episodic memory, complex attention and informationprocessing speed, executive functions and verbal fluency. Language, semantic memory and attention span are less frequentlyinvolved. Cognitive dysfunction can have a dramatic impact on several aspects of quality of life, independently on degree of physicaldisability and is one of the most important predictors of the patient work status.. Current therapeutic approaches include the use ofdisease-modifying drugs, symptomatic drugs for fatigue and donepezil, as well as different rehabilitative programs. Recent data onthe use of interferon-beta in patients with clinically isolated syndromes and early relapsing-remiting MS have suggested a betterpreservation of cognitive functioning in subjects treated at the very beginning of the disease. Due to the high prevalence and greatfunctional impact of MS-related cognitive imapirment, the search for effective therapeutic strategies is an urgent priority for futureresearch.

Cognition disorders in MS: TreatmentMaría Jesús Arévalo

Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system. The main pathophysiological feature of MS isdemyelination. MS is one of three most common causes of severe disability in youngest people. In patients with MS (PwMS), apartfrom complete psychophysical status and objective neurologic status, a subjective perception of symptoms and signs, known asquality of life, must be considered, too.PwMS have a substantial risk of cognitive dysfunction, even in the earliest stages of the disease, where there is minimum physicaldisability. Despite the high prevalence rates and the significant impact of cognitive dysfunction on quality of life in this population,cognitive functions are not routinely assessed due to the high cost and time consumption. Studies of the cognitive profile of PwMS suggest that some cognitive abilities are more likely to decline than others (e.g. disturbancesin memory, attention, concentration, speed of information processing and executive functions). Although some reduction in self-awareness of cognitive decline occurs, metacognitive skills and awareness of more concrete impairments appear preserved.Cognitive impairments can be extremely disruptive and interfere with PwMS ability to work, engage in social activities, maintain ahousehold and drive. Since the onset and progression of MS typically occurs when PwMS are attempting to establish and maintaincognitively demanding life roles (e.g. parent and worker), their cognitive symptoms can further accentuate the need to successfullymaintain functioning.The available immune-modulating agents may reduce the development of new lesions and therefore prevent or minimize theprogression of cognitive decline. There is currently insufficient evidence concerning the efficiency of symptomatic treatment in MS.Donepezil and rivastigmine (AChEls) have demonstrated some specific benefits in PwMS cognitively impaired, but the studies weresmall. There is also currently no optimal non-pharmacological treatment strategy for cognitive decline in MS, as the studiespublished to date report heterogeneous results. Nevertheless, non-pharmacological treatments such as cognitive rehabilitation maybenefit some MS patients. In the present talk, we will briefly review recent research on non-pharmacological and pharmacological approaches to improvecognitive function in our patients.

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Maria Pia Amato, Italy 1

María Jesús Arévalo, Spain 2

Angela Vidal, Spain 2

KNS2 - Injectable therapies in MS

Disease modifying drugs (DMDs) in MS: First line drugs: Three recombinant interferon beta (IFNb) preparations and glatirameracetate (GA) are currently approved for relapsing-remitting multiple sclerosis (RR MS). Their efficacy is very similar and was proveneven in head-to-head trials conducted recently. IFNb-1a i.m. and IFNb-1b s.c. are approved for patients with clinically isolatedsyndrome (CIS) and high risk for clinically definite MS, IFNb-1a s.c has extended indication for CIS according to McDonald´s criteria,GA was recently also approved for CIS. In some countries there is extended approval for RR MS under age of 18. There is no proveneffect of these drugs for chronic progression of MS without the presence of relapses. There is not enough publications supportingthe idea of combination therapies to start with; and there is not enough publications on sequential therapy. Long-term follow-upsof clinical trials though systematic have many limitations: no control groups any more, no blinding, and selection bias due to drop-outs. They may be useful in trying to define some prognostic markers. Post marketing follow-ups on long-term efficacy of thesedrugs show the importance of early treatment as the only tool to slow down the development of disability in MS. Long-term sideeffect profile and tolerability of above mentioned drugs is very good, the adherence to injectable treatments decreases over time,and seems to be a challenge for both the patient and treating physician.

There may be suboptimal treatment response to each of these drugs defined by the presence of relapses, disability progressionand/or MRI activity (Gd+ lesions or new or enlarging T2 lesions). In such cases therapy escalation should be discussed with thepatient. There are following possibilities:

1. Natalizumab, monoclonal antibody against adhesion molecules on lymphocytes. The efficacy is doubled compared to IFNb andGA. It is approved for RR MS if first-line drugs fail to stabilize the disease, or if there is rapidly evolving severe RR MS defined by 2or more disabling relapses in one year, and with one or more Gd-enhancing lesions on brain MRI or a significant increase in T2 lesionload compared to a previous one. Safety concerns concentrate predominantly on progressive multifocal leukoencefalopathy (PML),a DNA JC virus opportunistic infection of the brain. Risk factors known to increase the probability of PML are the use of natalizumabfor more than 2 years, previous immunosuppression and presence of antibodies against JCV. Patient and physician information isthe basis for sustained pharmaco-surveillance effort.

2. Mitoxantrone which received its marketing approval in 2002 for patiens with secondary progressive (SP) MS or progressingrelapsing MS in case of failure of previous DMDs. It is a cytostatic drug used in haemato-oncology. The activity of the disease maybe temporarily shut down for several months including MRI but the patient must be closely followed for possible side effects whichinclude cardiotoxicity (recommended life-time cumulative dose is 100mg/m2, echocardiography has to be checked regularly not onlybefore and during treatment, but also for several years after treatment) and malignancies (acute myeloid leukaemia being the mostcommon) have been associated to mitoxantrone therapy. Overall risk for cardiomyopathy/leukaemia is 1:250-800. Therefore, the useof mitoxantrone is declining in MS.

3. Fingolimod, sphingosine-1 phosphate (S1P) modulator, is the first oral drug on the market (0.5mg once daily). S1P on lymphocytesregulates homing and egress of lymphocytes in and from lymphoid organs thus preventing their entry to the target organ. Fingolimoddecreases relapses by 54%, and suppresses MRI activity by 82% (number of Gd+ enhancing lesions). The label of fingolimod doesnot differ from label of natalizumab. Adverse effects involve initial bradycardia, slightly increased number of infections, macularoedema, elevation of liver tests, reproductive toxicity, and risk of malignancies. Again, pharmacovigilance must take place in all thepatients. In some countries it is possible to use fingolimod as a first line drug.

New treatment options are available for patients with more severe disability – cannabinoids for spasticity and fampridine for walkingdifficulties (EDSS 4-7).

More options in the treatment of MS represents a great challenge for both the physician and the patient. Shared decisions andprecise follow-up of patients is the only way how to deal with it.

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Eva HavrdovàMS Centre and Neurology Clinic, Charles University, Prague, Czech Republic

L8 - Role of MS nurses in MS patients’ management

The MS nurse has multiple roles within the MS team. We discuss these different roles and explain how they are developed.

Traditionally, nurses have had a cooperative role but during recent decades they have also taken independent roles that areconsistent with a growth of knowledge.

At the end of the 90s, the idea of having a specialist nurse began to take shape, mostly as a result of the introduction ofimmunomodulatory treatment. Part of the role of the MS specialist nurse is to educate the patient not only about the managementof the medication but also the disease itself. These patients need follow-up, and to feel cared for and looked after. If patientsexperience problems or have questions, they can contact the nurse directly by telephone or by visiting the hospital.

This role has been very difficult to initiate in the hospital, and some sites still do not have nurses fully dedicated to MS patients.Furthermore, some countries have no courses aimed at training MS specialized nurses, thus nurses have to participate in self-training in their time off.

MS nurses also take a role in research activities, as an important part of the team. In clinical trials, the MS nurse is a reference pointfor the patient, as a data collector as well as taking care of all the diagnostic steps of the study.

MS nurses are also involved in the administration of all the intravenous therapy patients undergo, both in clinical practice and clinicaltrials. Some of these medications, such as natalizumab, are becoming more and more popular as a second-line treatment, becauseof their easy administration and the short period of time the patients usually have to stay in the day hospital.

Usually, people with MS are treated as outpatients and hospital admission is not required, but attendance at a day hospital allowsMS nurse to observe the patient during the infusion period and also to check vital signs at any time according to the administrationprotocol or whenever the MS Nurse feels it is appropriate.

From the traditional cooperative role, MS nurses assist the neurologist when performing a lumbar puncture, when filling up asubcutaneous reservoir with baclophen for an intrathecal infusion by internal pump.

Oral therapies for MS won’t limit the MS nurse’s role; nurses will continue to be a reference point in the management of people withMS, because a large number of patients will still require parenteral treatment. Moreover, management of new oral drugs will mostprobably require a multidisciplinary team focus.

In our center we have a very low rate of drop-out from therapy, partly because the medical and nursing work, combined with theactivities of the other members of the team, make the patients feel cared for. Nevertheless, MS is still a disease without a cure soit’s a chronic disease, and patients have a high risk of complications together with the possibility of disability.

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Rosalía Horno andGemma RodríguezMultiple Sclerosis Center of Catalonia (CEM-Cat), Unit of Clinical Neuroimmunology, Vall d’Hebron University Hospital, Barcelona, Spain




CS2 - Case study session on DMDs

1 - Department of Neurology, Multiple Sclerosis Unit, “Dr. Josep Trueta” Hospital in Girona, Girona, Spain2 - Unit of Multiple Sclerosis, University Hospital of Bellvitge, Barcelona, Spain3 - Neuroimmunology Unit / Multiple Sclerosis Unit, Hospital Clínic, Barcelona, Spain

Abstracts not in hand at the time of going to press.





IntroductionXxx xxx

MethodsXxx xxx

ResultsXxx xxx

ConclusionsXxx xxx

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Lluís Ramió i Torrentà, Spain 1

Lucia Romero, Spain 2

Yolanda Blanco, Spain 3




PD3 - Panel Discussion on “Define treatment success”

* Multiple Sclerosis Center of Catalonia (CEM-Cat), Unit of Clinical Neuroimmunology, Vall d’Hebron University Hospital, Barcelona, Spain

Define treatment success in present daily practice with clinical and MRI surrogateJordi Río

The objective of the definition of treatment response is to select earlier responders on one hand, and of poor- or non-responders onthe other hand. Patient response outcomes should be measured taking into consideration the interfering factors related to thedisease itself. MRI offers an advantage in the response evaluation as it produces objective data, however the frequency of evaluationis limited and low frequency of MRI evaluations leads to poor perspective data.Several criteria for treatment response to interferon beta have been proposed. Nevertheless, these different criteria have not beenvalidated and there is no consensus among different investigators. Long-term disability data are crucial in order to select the mostclinically meaningful definition. These criteria are based on relapses, disability progression or both. Several factors make difficultthe employment of relapse outcomes to determine therapeutic response (low predictive value, regression to the mean, etc.). Theprogression of neurological impairment is another criterion employed to quantify response, however efficacy fluctuations related todepression, fatigue, spasticity, concurrent illness and prolonged relapse need be excluded. Nevertheless, criteria of response toIFNb therapy using disability progression are more clinically relevant than those based only on relapse rate.On the other hand, there are limited prospective data to validate MRI measures of disease activity as reliable prognostic factors ofsuboptimal response to therapy, but MRI changes which occurred during the first months of IFN may have a prognostic value foridentifying patients with a confirmed increase of disability in the next years of therapy. Moreover, the combination of measures ofclinical and MRI disease activity may have a prognostic value for identifiyng patients with a poor outcome during the next years oftherapy.Several factors are related to response, from MS heterogeneity to genetic load and IFN response genes, to poor healingmechanisms. Other factors related to suboptimal response are: excess disease activity, poor adherence to therapy, misdiagnosis,“pseudo” failure” or loss of drug efficacy.In conclusion, in relation with response to therapy in multiple sclerosis patients, the proportion of non-responders varies dependingon the definition used, criteria based on relapse measures have poor sensitivity and positive diagnostic value, non-responders havea higher clinical activity at baseline, baseline EDSS predicts long-term disability, there are limited prospective MRI data as predictorsof therapeutic response and the combination of clinical and MRI measures of disease activity may have a prognostic value foridentifiyng patients with a poor response.

Define treatment success in the age of pharmacogenomicsManuel Comabella

The mechanisms underlying heterogeneity in the response to treatment in multiple sclerosis (MS) are not completely understood,although genetic factors are most likely to be playing important roles. Moreover, given the complex nature of the disease, thisheterogeneity is probably explained by the contribution of multiple genes. Disease Modifying Therapies (DMTs) are the mainstay oftreatment in relapsing-remitting MS and have demonstrated a beneficial effect on disease activity. However, DMTs are partiallyeffective, and their long-term impact on disease progression remains elusive. In addition, not all patients respond to current DMTs.The increasing number of new therapies for MS and the potential risk for a lack of response and/or serious adverse reactions makeindividualized therapy a high-priority for MS. Pharmacogenomics applies technologies such as gene expression profiling, singlenucleotide polymorphisms (SNP) screens, and proteomics in order to predict response to treatment and toxicity to drugs. Althoughpharmacogenomics holds great promise for individualized therapy in MS, big efforts should first be made to identify markers fortreatment efficacy.This talk will focus on the current status and future directions of pharmacogenomic studies in MS, mainly in relation withnterferonbeta treatment.

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Jordi Río, Spain *Manuel Comabella, Spain *

L9 - Fostering treatment adherence and compliance: a role play

Evidence coming from the pivotal clinical trials and from some other well-performed clinical trials has clearly demonstrated thebenefit of immunomodulatory therapies in MS. It is also clear that present therapies are not without side effects and mode ofadministration is still cumbersome for a number of patients; these factors impact on adherence to treatment, which may render thetherapeutic efforts futile. Several studies have shown that most drop-outs occur in the early phases of therapy so especial careneeds to be taken when patients start their immunomodulating therapy, in order to avoid treatment discontinuation. Availableevidence suggests that individualized care is an important factor to keep drop-out rates low; in this regard, management of sideeffects of therapies is crucial, as it is responsible for almost a half of all discontinuations. Another important factor related totreatment discontinuation seems to be perceived lack of efficacy, as a consequence of wrong expectations about treatment effects;therefore, adequate setting of expectations about therapy is crucial from outset of treatment with disease-modifying drugs. Sideeffects profile of IFNbeta preparations and GA are not entirely overlapping. In the case of IFNbeta preparations, it is especiallyimportant to manage flu-like symptoms at onset of therapy. Several strategies can be implemented to diminish patient discomfort,such as gradual dose increase and anti-inflammatory therapy administration schemes. Other side effects such as injection sitereactions, flushing and laboratory abnormalities also need to be closely monitored. Nurse-led patient education at onset of therapymay be helpful to manage patients’ expectations from therapy and to anticipate and diminish the impact of side effects on adherenceto treatment. Finally, even though results from clinical trials are the keystone to our clinical practice, measuring efficacy of therapyin clinical practice in an appropriate manner is crucial to obtain the most from available therapies. Clinical daily practiceindividualized monitoring of treatment response, treatment adherence, and side effects profile is therefore highly recommended ifclinical trials efficacy results are to be met in our clinics.

In the present talk, we will briefly review these issues and in the role playing that will ensue, we will put into practice ourinterpersonal skills so as to maximize patients’ adherence to treatment in order to make the most of the available therapies.

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María Jesús Arévalo and Jaume Sastre-GarrigaMultiple Sclerosis Center of Catalonia (CEM-Cat), Unit of Clinical Neuroimmunology, Vall d’Hebron University Hospital, Barcelona, Spain




KNS3 - Oral therapies in MS

Abstracts not in hand at the time of going to press.

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Xavier MontalbanMultiple Sclerosis Center of Catalonia (CEM-Cat), Unit of Clinical Neuroimmunology, Vall d’Hebron University Hospital, Barcelona, Spain




KNS4 - Monoclonal antibodies therapy in MS






IntroductionXxx xxx

MethodsXxx xxx

ResultsXxx xxx

ConclusionsXxx xxx

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




S3 - Snapshot #1 on Gene therapy in MS

Gene therapy is a group of techniques that involve an individual's modification of genetic makeup to treat acquired and hereditarydiseases. Among all the different vehicles used to deliver genes into an individual's cells, viral vectors are the most used due to theirinnate capability of viruses to introduce their genetic material into host cells. Gene therapy is a relatively new field in biomedicinesince the first clinical trial was approved in 1989. From then on, the amount of trials increased exponentially, indeed, from the late90’s until now approximately 100 clinical trials are approved each year worldwide.

Although gene therapy is generally understood as a replacement approach directed to treat genetic diseases, several approachesbased on gene therapy have been made in the animal model of multiple sclerosis (experimental autoimmune encephalomyelitis,EAE). These experimental approaches include the delivery of immunomodulatory molecules in the CNS, enhancement ofneuroprotection or induction of antigen-specific immune tolerance. Moreover, our work is being focused in antigen-specificapproaches. In the last years, we have been developing a strategy to induce immune tolerance using retroviral gene transfer into thehematopoietic system. To this end, we used a retroviral vector that expressed a chimeric protein in order to target the autoantigenMOG40-55 into the MHC class II compartment to prevent or reduce susceptibility to the disease, thus restoring the tolerance to theautoantigen. We have shown that this strategy constitutes a powerful tool to induce antigen-specific immune tolerance bothpreventively and therapeutically.

In summary, in the present talk we will review general aspects of gene therapy, how this technology can be applied in the treatmentof MS and the advantages and disadvantages of using viral vectors as gene-delivery systems.

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Herena EixarchMultiple Sclerosis Center of Catalonia (CEM-Cat), Unit of Clinical Neuroimmunology, Research Institute, Vall d'Hebron University Hospital , Barcelona, Spain

S4 - Snapshot #2 on DNA vaccines in MS

Since the discovery, over a decade and a half ago, that genetically engineered DNA can be delivered in vaccine form and elicit animmune response, there has been much progress in understanding the basic biology of this technology.

DNA vaccination is a strategy of immunization based on the injection of a gene encoding a target protein with the goal of eliciting apotentially protective immune response in the host. Classically, DNA vaccines have been successful at generating protective immuneresponses in various cancer models and infectious diseases, due to an activation of the immune system. Although, in the last yearsdifferent studies have shown the potential use of DNA vaccines to modulate autoimmune diseases, like multiple sclerosis (MS),inducing tolerance rather than stimulation of an immune response.

Compared to traditional immunization procedures, DNA vaccination offers several advantages: for instance, expression of nativeantigens in situ, prolonged in vivo antigen production, increased availability of antigenic peptides because of the endogenous andlong-term synthesis of the gene product and the modification of the vaccination protocol that could induce either Th1 or Th2 immuneresponses.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, probably of autoimmune aetiology,in which auto-reactive T cells play an essential role in the pathogenesis of the disease through the attack of myelin components. Atpresent, there is not an effective treatment for the disease. Most of the currently used drugs for the treatment of MS target theimmune response, but are not selective for the auto-reactive T cells.

The application of DNA vaccination to the treatment of the animal model of MS, experimental autoimmune encephalomyelitis (EAE),has demonstrated the great potential of this procedure for therapeutic purposes. The protection appears to be highly influenced bythe capacity of DNA vaccination to modulate immune responses affecting the Th1, Th2 and, importantly, the T cell immunoregulatoryarms.

So far, two clinical trials of DNA vaccines have been reported in MS. From these studies, it can be concluded that the vaccine wassafe, well-tolerated, and caused antigen-specific immune tolerance.

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Nicolás FissoloMultiple Sclerosis Centre of Catalonia (CEM-Cat), Unit of Clinical Neuroimmunology, Institut de Recerca, Vall d’Hebron University Hospital, Barcelona, Spain

S5 - Snapshot #3 on Stem cell therapy in MS

Stem cells are found in all multicellular organisms. They are characterized by the ability to renew themselves trough mitotic celldivision and differentiated into a diverse range of specialized cell types.

There are different kinds of stem cells. The embryonic stem cells are obtained from embryos and can differentiate into whatever cellof the organism, they are pluripotent. The adults also have stem cells, which can only give rise to cells closely related to their organor tissue of origin, they are multipotent. Recently, researchers have created induced stem cells, they are a type of pluripotent stemcells artificially derived from an adult somatic cell by inducing a forced expression of certain genes.

Since the stem cells have the ability to repair and regenerate the damaged tissue, the therapies with stem cells were originallyconceived as replacement therapies. But it has been shown that stem cells affect the recovery by an additional mechanism, theyalso have the ability to regulate the immune system.

Several studies with stem cells have been undertaken in animal models of multiple sclerosis with encouraging results. They haveshown that stem cells can contribute to repair the tissue damage, but they play a more important role in modulating the immunesystem.

Treatments with haematopoietic or mesenchymal stem cells have been used to treat multiple sclerosis patients. The results havebeen apparently positive, but there still are controversies and further studies are necessary.

35

Carme Costa RiuMultiple Sclerosis Center of Catalonia (CEM-Cat), Unit of Clinical Neuroimmunology, Vall d'Hebron University Hospital, Barcelona, Spain




Our future health depends on today’s medical experts minds, therefore, the SeronoSymposia International Foundation (SSIF), in partnership with the European NeurologicalSociety (ENS), has decided to establish a prestigious award to recognize and rewardexcellence in medical education.

The Serono Symposia International Foundation (SSIF) is seeking candidates amongmedical experts who are continuing to drive medical education forward through theirresearch and dedication in the field of neurology.

The criteria for candidate application cover a wide range of skills and attributes that SSIFis looking for in a potential candidate and winner of the SSIF award.

The Award Committee composed of Members of the SSIF Scientific Committee and Boardof Directors Members and ENS Members will assess the candidate’s professionaldedication and leadership to continuining medical education.

If you are a physician and/or scientist from 35 to 50 years old working in:• degenerative dementias and/or• multiple sclerosis and/or• neurodegenerative disease entailing movement disorders and/or• Parkinson’s disease

The SSIF Award will be a great opportunity for you!

Find out more and apply to the SSIF award on www.ssifaward.org

The winner of the SSIF award will receive Euro 10,000, less any taxes deductable, and will become a member of the SSIF advisory committee.

Applications are open for submission from May 28, 2011 until February 20, 2012.

SSIF awardRewarding scientific excellencein medical education

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Your Continuing Medical Education Partnerwww.seronosymposia.org

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