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Esclerosis múltiple; Brote; Resonancia magnética Esclerosi múltiple; Brot; Imatge per ressonància magnètica Multiple sclerosis; Outbreak; Magnetic resonance imaging Objective To study the clinico-radiological paradox in multiple sclerosis (MS) relapse by analyzing the number and location of gadolinium-enhanced (Gd+) lesions on brain MRI before methylprednisolone (MP) treatment. Methods We analyzed brain MRI from 90 relapsed MS patients in two Phase IV multicenter double-blind randomized clinical trials that showed the noninferiority of different routes and doses of MP administration. A 1.5- or 3-T brain MRI was performed at baseline before MP treatment and within 15 days of symptom onset. The number and location of Gd+ lesions were analyzed. Associations were studied using univariate analysis. Results Sixty-two percent of patients had at least 1 Gd+ brain lesion; the median number was 1 (interquartile range 0–4), and 41% of patients had 2 or more lesions. The most frequent location of Gd+ lesions was subcortical (41.4%). Gd+ brain lesions were found in 71.4% of patients with brainstem-cerebellum symptoms, 57.1% with spinal cord symptoms and 55.5% with optic neuritis (ON). Thirty percent of patients with brain symptoms did not have Gd+ lesions, and only 43.6% of patients had symptomatic Gd+ lesions. The univariate analysis showed a negative correlation between age and the number of Gd+ lesions (p = 0.002). Conclusion Most patients with relapse showed several Gd+ lesions on brain MRI, even when the clinical manifestation was outside of the brain. Our findings illustrate the clinico-radiological paradox in MS relapse and support the value of brain MRI in this scenario. Objetivo Estudiar la paradoja clínico-radiológica en el brote de la esclerosis múltiple (EM) mediante el análisis de lesiones captantes de gadolinio (Gd+) en la RM cerebral antes del tratamiento con metilprednisolona (MP). Métodos Analizamos la RM cerebral basal de 90 pacientes con EM en brote de 2 ensayos clínicos aleatorizados multicéntricos fase IV que demostraron la no inferioridad de diferentes vías y dosis de MP, realizadas antes del tratamiento con MP y en los 15 días siguientes a la aparición de los síntomas. Se analizaron el número y la localización de las lesiones Gd+. Se estudiaron las asociaciones mediante análisis univariado. Resultados El 62% de los pacientes tenía al menos una lesión Gd+ cerebral y el 41% de los pacientes tenía 2 o más lesiones. La localización más frecuente fue la subcortical (41,4%). Se encontraron lesiones Gd+ cerebrales en el 71,4% de los pacientes con síntomas de tronco cerebral o cerebelo, en el 57,1% con síntomas medulares y en el 55,5% con neuritis óptica. El 30% de los pacientes con síntomas cerebrales no tenían lesiones Gd+ y sólo el 4,.6% de los pacientes tenían lesiones Gd+ sintomáticas. El análisis univariante mostró una correlación negativa entre la edad y el número de lesiones Gd+ (p = 0,002). Conclusiones La mayoría de los pacientes en brote mostraron varias lesiones Gd+ en la RM cerebral, incluso cuando la manifestación clínica fue medular u óptica. Nuestros hallazgos ilustran la paradoja clínico-radiológica en el brote de la EM y apoyan el valor de la RM cerebral en este escenario. This work was supported in part by the Ministry of Health of Spain (grant numbers EC07/90278 and EC11/132) and personal grant Rio Hortega CM19/00042 to LMA.

IMPORTANCE Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressiveMS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition. OBJECTIVE To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition. DESIGN, SETTING, AND PARTICIPANTS Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remittingMS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up. EXPOSURES The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017). MAIN OUTCOME AND MEASURE Conversion to objectively defined secondary progressiveMS. RESULTS Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressiveMS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; P

BackgroundIn natalizumab-treated relapsing-remitting MS (RRMS) patients, various extended interval dosing strategies are under evaluation to minimize severe treatment-associated side effects, mainly progressive multifocal leukoencephalopathy development. Up to now, it has not been presented any approach, even in form of assay design, to determine the optimal percentage of CD49d receptor occupancy (RO) associated with a favorable clinical, radiological, and immunological response. MethodsA multiparametric quantitative flow cytometry method was settled to measure CD49d RO on peripheral blood lymphocytes. The analytical protocol was tested in a 6-month follow-up from 19 RRMS patients treated with the natalizumab standard dosing of every 4 weeks or an extended-interval dosing of every 6 weeks. ResultsExtended natalizumab dose schedule promoted an increase of CD49d molecules per cell surface and a reduction of CD49d RO levels. The reduction observed on CD49d RO was not only depending on dose schedule but also on individual parameters such as body mass. Interestingly, individual clinical outcome was apparently the same between the different dose schedules or even better with the extended interval dosing. ConclusionsFollowing up CD49d RO levels with a well-regulated monitoring work scheme is crucial to further identify over-/under-treated patients and to define a safe, personalized natalizumab regimen. (c) 2017 International Clinical Cytometry Society

32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) -- SEP 14-17, 2016 -- London, ENGLAND Ramo-Tello, Cristina M/0000-0001-8643-5053; Lugaresi, Alessandra/0000-0003-2902-5589; Havrdova, Eva Kubala/0000-0002-9543-4359; Horakova, Dana/0000-0003-1915-0036; Oreja-Guevara, Celia/0000-0002-9221-5716; WOS: 000383267201481 … European Comm Treatment & Res Multiple Sclerosis BiogenBiogen; Bayer ScheringBayer AG; Biogen IdecBiogen; Merck SeronoMerck SeronoMerck & Company; NovartisNovartis; SanofiSanofi-Aventis; Teva; Associazione Italiana Sclerosi MultiplaFondazione Italiana Sclerosi Multipla (FISM); Fondazione Italiana Sclerosi MultiplaFondazione Italiana Sclerosi Multipla (FISM); MerckMerck & Company; GenzymeGenzyme Corporation; Czech Ministry of EducationMinistry of Education, Youth & Sports - Czech Republic [NT13237-4/2012, PRVOUK-P26/LF1/4]; Czech Ministry of HealthMinistry of Health, Czech Republic [NT13237-4/2012, PRVOUK-P26/LF1/4]; Merck Teva; Biogen-IdecBiogen; Merck-SeronoMerck SeronoMerck & Company; CIHRCanadian Institutes of Health Research (CIHR); MS Society of Canada; Teva Neurosciences; Mitsubishi; ONO Pharmaceuticals; Teva-Neuroscience; Canadian Multiple sclerosis society; Bayer-ScheringBayer AG; Sanofi AventisSanofi-Aventis; Sanofi-Genzyme; Novartis Pharma; Sanofi-AventisSanofi-Aventis; Almirall; Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche Johannes Lorscheider has accepted conference travel support from Novartis and has received research support from Biogen.; Tim Spelman received compensation for travel from Biogen Idec.; Alessandra Lugaresi is a Bayer Schering, Biogen Idec, Genzyme, Merck Serono Advisory Board Member. She received travel grants and honoraria from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi, Teva, and Associazione Italiana Sclerosi Multipla and her institution received research grants from Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi, Teva, and Fondazione Italiana Sclerosi Multipla.; Eva Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck, Novartis, Genzyme and Teva, as well as support for research activities from the Czech Ministries of Education and Health (NT13237-4/2012, PRVOUK-P26/LF1/4) and Biogen Idec and Merck Serono.; Dana Horakova received speaker honoraria and consulting fees from Biogen Idec, Merck Teva, Genzyme, and Novartis, as well as support for research activities from the Czech Ministries of Education and Health (NT13237-4/2012, PRVOUK-P26/LF1/4) and Biogen Idec.; Maria Troiano received speaking honoraria from Biogen-Idec, Bayer-Schering, Sanofi Aventis, Merck-Serono, Teva and Novartis; has received research grants from Biogen-Idec, Merck-Serono, and Novartis.; Pierre Duquette has served on editorial boards and has been supported to attend meetings by EMDSerono, Biogen-Idec, Novartis, Genzyme, and TEVA Neuroscience. Dr Duquette holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen-Idec, Novartis, and Genzyme.; Francois Grand'Maison received honoraria or research funding from Biogen Idec, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.; Pierre Grammond is a Novartis, Teva-neuroscience, Biogen Idec and Genzyme advisory board member, consultant for Merck Serono, received payments for lectures by Merck Serono, Teva-Neuroscience and Canadian Multiple sclerosis society, and received grants for travel from Teva-Neuroscience and Novartis.; Eugenio Pucci served on scientific advisory boards for Genzyme, Merck-Serono and Biogen-Idec; he received honoraria and/or congress and travel/accommodation expense compensations from Sanofi Aventis, Novartis, Biogen-Idec, Merck-Serono, Genzyme, Teva and Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche.; Daniele Spitaleri received honoraria as a consultant on scientific advisory boards by Bayer-Schering, Novartis and Sanofi-Aventis and compensation for travel from Novartis, Biogen Idec, Sanofi Aventis, Teva and Merck-Serono.; Jeanette Lechner-Scott has accepted travel compensation from Novartis, Biogen and Merck Serono. Her institution receives the honoraria for talks and advisory board commitment and also clinic support from Bayer Health Care, Biogen Idec, CSL, Genzyme Sanofi, Merck Serono and Novartis.; Murat Terzi received travel grants from Merck Serono, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.; Vincent van Pesch has served on advisory boards for Biogen Idec, Novartis Pharma and Sanofi-Genzyme; has received travel grants and consultancy fees from Biogen Idec, Bayer Schering, Sanofi Aventis, Merck Serono, Sanofi-Genzyme and Novartis Pharma; has received research grants from Bayer Schering.; Robert Bergamaschi has served on scientific advisory boards for Biogen Idec and Almirall; has received funding for travel and speaker honoraria from Sanofi-Aventis, Genzyme, Biogen Idec, Bayer Schering, Teva Neurosciences, Merck Serono, Almirall, and Novartis; received research support from Merck Serono, Biogen Idec, Teva Neurosciences, Bayer Schering, Novartis, Sanofi-Aventis.; Cristina Ramo-Tello received research funding, consulting/advisory fees or compensation for travel from Biogen-Idec, Novartis, Genzyme and Almirall.