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regional conferencefinal programme and abstract book

2016 pre-lactrims conference16 November, 2016 - Buenos Aires, Argentina

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2016 Pre-LACTRIMS Conference

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OverviewMultiple Sclerosis (MS) is the most common demyelinating disorder of the central nervous system in Western Countries. However, as research evolves, new variants of demyelinating disorders emerge characterized by clinical phenotypes resembling MS. Spinal cord and visual pathway damage have a crucial role in orienting the differential diagnosis, as well as in providing prognostic elements in traditional MS. Therefore, dedicated sessions have been planned in this meeting to review these topics and help clinicians to address the ‘no better clinical explanation’ criterium. Additionally, updates on the main novelties in MS, from pathogenesis to treatment, will be provided. Finally, the role of rehabilitation in counteracting disability accrual will be explored and discussed.

Learning objectivesBy attending this conference the participants will be able to:

•Summarize the key elements of differential diagnosis of non traumatic myelopathy•Illustrate the main diagnostic tool to estimate optic nerve damage•Discuss novel biomarkers for treatment monitoring•Describe the biological basis of neurorehabilitation

Target audienceNeurologists involved in MS patient management and physicians with a particular interest in MS, mainly from Latin America.

Chairsedgardo cristiano MS Center, Department of Neurology Hospital Italiano de Buenos Aires Buenos Aires, Argentina

celia oreja-guevaraDepartment of Neurology Hospital Clínico San Carlos. San Carlos Institute for Health Research (IdISSC) Universidad Complutense de Madrid Madrid, Spain

This live educational course is endorsed by LACTRIMS Latin American Committee for the treatment and research in Multiple Sclerosis

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

EXCEMED adheres to the guidelines and standards of the European Accreditation Council for Continuing Medical Education (EACCME®) which states that continuing medical education must be balanced, independent, objective, and scientifically rigorous.

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

Continuing medical educationEXCEMED (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 CME conference “2016 pre lactrims” being held on 16 November 2016 in Buenos Aires, Argentina, is designated for a maximum of 6 (six) 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 (AMA) towards the Physician’s Recognition Award (PRA). To convert EACCME® credit to AMA PRA category 1 credit, please contact the AMA.

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general information

VenueThis educational conference will take place at the:Hilton Hotel buenos airesMacacha Güemes 351, C1106BKG CABABuenos Aires, Argentina

LanguageThe official language of this live educational conference is Spanish and English.

CME ProviderEXCEMED - Excellence in Medical EducationProgramme and Relations Manager: Serena Dell’AricciaT +39 06 420413 251 - F +39 06 420413 677serena.dellariccia@excemed.org Medical Advisor: Doriana Landidoriana.landi@gmail.com

for any logistic support please contact:Meridiano Congress International (Italy) Senior Project Manager: Federica RussettiT +39 06 88 595 209 - F +39 06 88595 234federica.russetti@meridiano.it

Visitwww.excemed.org

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faculty

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faculty

Jorge barahona strauch Universidad Católica de Chile, Universidad des Desarrollo Clinica AlemanaSantiago, Chile

fernando caceresINEBANeuro Sciences Institute of Buenos Aires Buenos Aires, Argentina

giancarlo comiInstitute of Experimental NeurologyUniversity Vita-Salute - IRCCS San Raffaele HospitalMilan, Italy

Jorge correale Department of NeurologyInstitute for Neurological Research Dr. Raúl Carrea, FLENIBuenos Aires, Argentina

edgardo cristiano MS Center, Department of NeurologyHospital Italiano de Buenos AiresBuenos Aires, Argentina

Hans peter Hartung Department of Neurology, Heinrich-Heine University Düsseldorf Düsseldorf, Germany

letizia leocaniInstitute of Experimental NeurologyUniversity Vita-Salute - IRCCS San Raffaele HospitalMilan, Italy

carlos navasDemyelinating disease Unit and Multiple Sclerosis ClinicUniversity Hospital of ColombiaBogotà, Colombia

enedina oliveiraNeuroimmunology Center, MS clinic Neurology & Neurosurgery Department Federal University of São Paulo São Paulo, Brazil

celia oreja-guevaraDepartment of Neurology, Hospital Clínico San Carlos San Carlos Institute for Health Research (IdISSC) Universidad Complutense de MadridMadrid, Spain

marcos papais alvarengaDepartment of Neurology,Federal University of the State of Rio de Janeiro-UNIRIO Department of Neurology, Hospital da Lagoa Ministry of HealthRio de Janeiro, Brazil

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faculty

liliana patrucco MS Center, Department of Neurology Hospital Italiano de Buenos AiresBuenos Aires, Argentina

Victor rivera The Department of Neurology (V.M.R.) Baylor College of MedicineHouston, Texas, USA

Juan ignacio rojasMS Center, Department of NeurologyHospital Italiano de Buenos AiresBuenos Aires, Argentina

darwin VizcarraUniversidad Peruana Cayetano Heredia Hypnos Instituto del Sueño Clinica San FelipeLima, Peru

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programme

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Wednesday, 16 november 2016

08.30 opening and introduction G. Comi (Italy); E. Cristiano (Argentina); C. Oreja-Guevara (Spain)

session i optic nerve chairs: G. Comi (Italy) - E. Oliveira (Brazil)

09.00 l1: eye and visual pathway involvement in ms H.P. Hartung (Germany)

09.30 l2: functional and structural investigations L. Leocani (Italy)

10.00 differential diagnosis of visual impairment – case based approach M. Papais Alvarenga (Brazil)

10.35 coffee break

session ii spinal cord chairs: E. Cristiano (Argentina) - J. Barahona Strauch (Chile) 11.10 l3: animal models and pathology of spinal cord damage H.P. Hartung (Germany)

11.40 l4: acute myelitis: from ms to nmo and more G. Comi (Italy)

12.10 l5: the prognostic value of spinal cord damage L. Patrucco (Argentina)

12.40 differential diagnosis of non-traumatic myelopathy – case based approach D. Vizcarra (Perù)

13.15 lunch

session iii ms at a glance

chairs: C. Navas (Colombia) - C. Oreja Guevara (Spain)

14.20 l6: expanding epidemiology E. Cristiano (Argentina)

14.40 l7: b and t cells in ms pathogenesis and monitoring J. Correale (Argentina)

15.10 l8: conventional mri: is it time for standardization? C. Oreja Guevara (Spain)

15.40 l9: brain atrophy: is it time for clinical use? J. Rojas (Argentina)

16.15 coffee break

session iV disability assessment and rehabilitation

chair: V. Rivera (USA)

16.50 l10: neurophysiology to assess ms related damage L. Leocani (Italy)

17.20 l11: rehabilitation and pharmacological enhancers of motor impairment F. Caceres (Argentina)

17.50 Video session on rehabilitation F. Caceres (Argentina)

18.20 Q&a: let’s talk

18.30 closing remarks

end of the live educational conference

legend

l: Lecture :Clinical cases : Video session

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disclosure of faculty relationships

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

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

fernando caceres Declared no potential conflict of interest.

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

Jorge correale Declared the receipt of grants and contracts from Novartis Argentina. He declared the receipt of honoraria and consultation fees from Novartis Argentina and Latin America, Merck Argentina and Genzyme Argentina. Declared to be member of Genzyme, Merck Argentina, Genzyme Argentina and Novartis Latin America advisory boards, board of directors or similar groups. He also declared to be member of speakers bureau sponsored by Genzyme Argentina, Novartis Argentina and Latin America, Biogen Argentina and Merck Argentina.

edgardo cristiano Declared the receipt of grants and contracts from Merck. He declared the receipt of honoraria and consultation fees from Biogen, Novartis and Merck. Declared to be member of Novartis, Merck and Roche advisory boards and of speakers bureau sponsored by Merck, Biogen, Novartis and Genzyme.

Hans peter Hartung Declared receipt of honoraria or consultation fees from Biogen, Bayer, Geneuro, Genzyme, Merck, Receptos, Novartis, Teva, Roche and Opexa.

letizia leocani Declared the receipt of a research support from Merck, Novartis.

carlos navas Declared the receipt of grants and contracts from Novartis, Merck, Stendhal, Sanofi. He declared the receipt of honoraria and consultation fees from Novartis and declared to be member of speakers bureau sponsored by Novartis and Merck.

enedina maria oliveira Has received financial compensations for participating in scientific and advisory board meetings, as well as traveling grants and speaker fees sponsored by Bayer Health Care, Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme and Teva.

liliana patrucco Declared no potential conflict of interest.

Victor rivera Declared receipt of honoraria or consultation fees from Mallinkrodt, Genzyme and Teva and declared to be member of speakers bureau sponsored by Bayer, EMD Serono, Genzyme and Stendhal.

Juan ignacio rojas Declared the receipt of grant and contract from Merck and Novartis and the receipt of honoraria and consultation fees from Merck, Novartis and Genzyme.

darwin Vizcarra Declared the receipt of a research support from Novartis, to be member of a Genzyme Medical Advisory board and to be member of speakers bureau sponsored by Genzyme, Novartis and Stendhal.

The following faculty have provided no information regarding significant relationship with commercial supporters and/or discussion of investigational or non-EMEA/FDA approved (off-label) uses of drugs as of 7 November 2016.

Jorge barahona strauchcelia oreja-guevaramarcos papais alvarenga

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abstracts

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l2. functional and structural investigations

letizia leocaniInstitute of Experimental Neurology - University Vita-Salute - IRCCS San Raffaele Hospital - Milan, Italy

In Multiple Sclerosis (MS), functional deficits derive from the balance between demyelination and neurodegeneration on one side, together with compensatory functional reorganization and some level of remyelination and neuroregeneration. Although the pathogenesis of demyelination has been well described, the cellular and molecular mechanisms of neurodegeneration are not fully understood. While neurophysiological methods, namely evoked potentials (EP), are currently used for the assessment of functional consequences of demyelination and remyelination, they present limitations in the quantification of axonal and neuronal loss. In the visual pathways, the combination of visual evoked potentials (VEPs) with OCT provides a complete evaluation of structural and functional damage, potentially representing a surrogate measure of neurodegeneration e demyelination. The early detection of VEPs slowing may also provide some prediction on the future evolution of disability, consistently with the hypothesis that demyelination may prompt future neuronal loss. If further validated, neurophysiological methods and OCT 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 demyelination, while OCT may be more suitable for assessing neuroprotection strategies.

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cc. differential diagnosis of non-traumatic myelopathy – case based approach

darwin Vizcarra escobarUniversidad Peruana Cayetano Heredia, Hypnos Instituto del Sueño, Clinica San Felipe, Lima, Peru.

Several clinical cases will be presented where the decision framework will be challenged to obtain the correct diagnosis. Clinical information and auxiliary tests will be supplied for each case. Cases can include infectious diseases, neoplasms, metabolic diseases, vascular diseases and other immunological diseases. Objectives: 1. To discuss the different disorders of the spinal cord that can be considered in the differential diagnosis of multiple sclerosis (MS). 2. To enlight red flags in the medical history or in the medical images that should be recognized in order to avoid MS misdiagnosis. Conclusions: the clinical keypoints useful in order to make a correct differential diagnosis will be stressed.

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l5. the prognostic value of spinal cord damage

liliana patrucco MS Center, Department of Neurology - Hospital Italiano de Buenos Aires - Buenos Aires, Argentina

Conventional spinal cord MRI is a valuable resource for assessing patients with multiple sclerosis because of its high sensitivity for depicting demyelinating lesions in this structure.Focal spinal cord lesions are commonly seen in patients with multiple sclerosis, and tissue abnormalities are reported in 80–90% of patients on conventional MRI. In patients with clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS), asymptomatic spinal cord lesions have been described in 30–40% of patients. In CIS patients, asymptomatic spinal cord lesions, predict not only the time to development of clinically definite multiple sclerosis, but also the degree of future disability. In RIS patients, asymptomatic spinal cord lesions increase the risk of progression to a CIS or to primary progressive multiple sclerosis in a short time, regardless of the brain imaging findings. In most other neurologic diseases, especially in cerebrovascular disorders, autoimmune inflammatory disorders, and also in healthy aging, SC lesions are rather rare, whereas cerebral white matter changes are common.Advanced quantitative techniques, in particular spinal cord atrophy, can measure the degree of tissue damage, providing a reliable assessment of the true burden of the disease.In summary, spinal cord MRI provides additional useful information to brain MRI to establish a prompt and accurate diagnosis of MS, to provide valuable prognostic information, and in certain cases for monitoring disease course and treatment response.

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l6. expanding epidemiology

edgardo cristianoMS Center, Department of Neurology - Hospital Italiano de Buenos Aires - Buenos Aires, Argentina

Epidemiology of MS cannot be explained by any single environmental or genetic factor in isolation. A combination of a heterogeneous distribution of both genetic and environmental factors appear to be required to explain the available data on MS.MS is about tenfold more common in caucasians of northern Europe, North America and Canada than in Latin America (LA), specially between indian populations and in tropical zones. Nevertheless, MS prevalence and incidence seem to increase over time all around the world including latinamerican countries. The increase in prevalence is presumed to be due to prolonged survival of patients, while for incidence it may be due to a number of factors, in particular, the increasing in the ratio of disease in women to men. It may be due to changes in cigarette smoking, sodium intake, UV radiation exposure, vitamin D deficit, birth control, obesity and later childbirth or other factors probably related to industrialisation. For LA, awareness of disease, availability of MRI and more access to healthcare may also contribute. Regarding phenotypes, recent reports didn´t show differencies for clinical behavior of the disease between Latin American and European or North American countries.

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l7. b and t cells in ms pathogenesis and monitoring

Jorge correale, mdDepartment of Neurology - Institute for Neurological Research Dr. Raúl Carrea, FLENI - Buenos Aires, Argentina

Early MS is primarily mediated by adaptive immune responses and involves autoreactive T cells, B cells and antibodies, while chronic stages of MS are characterized by a compartmentalized immune response in the CNS with activated microglia and macrophages. The objective of the following presentation is to summarize the role of T and B cells in the pathogenesis of MS, as well as to describe recent methods designed to monitor the evolution of the disease by tracking different lymphocyte populations.The most accepted hypothesis is that MS starts with activation of CNS-antigens-specific CD4+ T cells in the periphery. This hypothesis is mainly stems from the similarities between MS and experimental autoimmune encephalomyelitis (EAE). However, little is known about the antigens responsible for activating of autoreactive CD4+ T cells in the periphery. It is possible that CD4+ T cells might be activated by the same CNS –derived antigens, which they recognize later in the target tissue, or alternative by cross-reactive antigens. Although evidence supports an important role of CD4+ T cells in initiating MS, data indicate that CNS antigen-specific CD8+ T cells are involved in a second step causing CNS damage during relapses and in the chronic phase. The activation of CNS-specific autoreactive T cells in the periphery might be influenced by dysregulation of both the innate and the adaptive arms of the immune system.Besides CD4+ and CD8+ T cells, nonconventional lymphocytes have been described. These include invariant NKT cells, γδ T cells, and mucosal associated invariant T (MAIT) cells, and represent either intermediates between adaptive and innate lymphocytes, or are considered only part of the innate system like NK cells. Recent data on MAIT cells indicate that this population may play an important role as effector cell-types in MS. They have been found to be expanded in the brain of MS patients and reduced in peripheral blood particularly during exacerbations.Finally, several studies identified B cells and plasma cells/plasmablasts in the immune infiltrate of the CNS in tissue from MS patients. Indeed the fact that MS patients characteristically show oligoclonal production of immunoglobulin in the CSF is probably the first evidence that MS is an immunomediated disorder. Paradoxically the specificity of these immunoglobulins after seven decades is still unknown. Furthermore, strong support for a role of B cells in MS stems from therapeutic studies using anti-CD20 monoclonal antibodies.Our knowledge about the antigen specificity of autoreactive T cells and autoantibodies in MS has advanced relatively little in the last decades, limiting the development of antigen specific therapies for MS. On the other hand the antigen receptors for T and B cells are highly polymorphic due to recombination or mutation of the encoding genes, which can be therefore be used as fingerprints to track individual T- and B cell clones. Such studies can shed light on mechanisms driving the immune responses and providing insights into the pathogenesis of the disease. Furthermore, studies of dominant clones could represent potential biomarkers or targets for selective therapies.

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l9. brain atrophy: is it time for clinical use?

Juan ignacio rojasMS Center, Department of Neurology - Hospital Italiano de Buenos Aires - Buenos Aires, Argentina

The assessment of brain atrophy in patients with multiple sclerosis (MS) has become one of the most important correlates and predictors for the development of physical and cognitive disability in short-mid- and long-term. Nowadays, the interpretation of brain atrophy results from MS clinical trials has important implications for individual treatment choice selection both in academic- and in community-based MS centers, hence there is an imminent need for incorporating brain atrophy assessments at the individual patient level for treatment monitoring. Despite the previous, several limitations currently exists to disseminate brain atrophy measurement in clinical practice. In fact, several challenges must be overcome before brain atrophy is recommended for treatment monitoring at the individual patient level.

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l10. neurophysiology to assess ms related damage

letizia leocaniInstitute of Experimental Neurology - University Vita-Salute - IRCCS San Raffaele Hospital - Milan, Italy

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 identified 1 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 lesions 2,3 . 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 studies 3 . If further validated, neurophysiological methods may have a role in the early identification of patients whoare 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.

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notes

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notes

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All EXCEMED programmes 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 the responsibility of the named speakers, and do not represent an endorsement or recommendation on the part of EXCEMED. This programme is made possible thanks to an educational grant received from Merck KGaA, Darmstadt, Germany

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