165 results on '"Costa-Frossard, L."'
Search Results
2. Documento de consenso de la Sociedad Española de Neurología sobre el tratamiento de la esclerosis múltiple y manejo holístico del paciente 2023
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Meca-Lallana, J.E., Martínez Yélamos, S., Eichau, S., Llaneza, M.A., Martín Martínez, J., Peña Martínez, J., Meca Lallana, V., Alonso Torres, A.M., Moral Torres, E., Río, J., Calles, C., Ares Luque, A., Ramió-Torrentà, L., Marzo Sola, M.E., Prieto, J.M., Martínez Ginés, M.L., Arroyo, R., Otano Martínez, M.Á., Brieva Ruiz, L., Gómez Gutiérrez, M., Rodríguez-Antigüedad Zarranz, A., Sánchez-Seco, V.G., Costa-Frossard, L., Hernández Pérez, M.Á., Landete Pascual, L., González Platas, M., and Oreja-Guevara, C.
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- 2024
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3. Real-life safety and effectiveness outcomes of teriflunomide in patients with relapsing–remitting multiple sclerosis: The TERICAM study
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Martínez-Ginés, M.L., García-Domínguez, J.M., Cuello, J.P., Meca-Lallana, V., Aguirre, C., Costa-Frossard, L., Monreal, E., Sainz de la Maza, S., Salgado-Cámara, P., Labiano-Fontcuberta, A., Fernández-Cabredo, L., Aladro-Benito, Y., Canelo, L.B., Valle, O.Sánchez-del, Blasco, M.R., Sabin-Muñoz, J., Caminero-Rodríguez, A.B., Gracia-Gil, J., Fernandez-Diaz, E., Mendoza-Rodríguez, A., Gómez-Moreno, M., Orviz-García, A., Moreno-Torres, I., Casanova-Peño, L.I., and Lozano-Ros, A.
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- 2023
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4. Recommendations for the coordination of Neurology and Neuroradiology Departments in the management of patients with multiple sclerosis
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Llufriu, S., Agüera, E., Costa-Frossard, L., Galán, V., Landete, L., Lourido, D., Meca-Lallana, J.E., Moral, E., Bravo-Rodríguez, F., Koren, L., Labiano, A., León, A., Martín, P., Monedero, M.D., Requeni, L., Zubizarreta, I., and Rovira, À.
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- 2023
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5. Recomendaciones para la coordinación de los servicios de Neurología y Neurorradiología en la atención a pacientes con esclerosis múltiple
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Llufriu, S., Agüera, E., Costa-Frossard, L., Galán, V., Landete, L., Lourido, D., Meca-Lallana, J.E., Moral, E., Bravo-Rodríguez, F., Koren, L., Labiano, A., León, A., Martín, P., Monedero, M.D., Requeni, L., Zubizarreta, I., and Rovira, À.
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- 2023
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6. Monitoring response to disease-modifying treatment in multiple sclerosis
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Río, J., Peña, J., Brieva, L., García-Domínguez, J.M., Rodríguez-Antigüedad, A., Oreja-Guevara, C., Costa-Frossard, L., and Arroyo, R.
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- 2023
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7. Recommendations for vaccination in patients with multiple sclerosis who are eligible for immunosuppressive therapies: Spanish consensus statement
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Otero-Romero, S., Rodríguez-García, J., Vilella, A., Ara, J.R., Brieva, L., Calles, C., Carmona, O., Casanova, V., Costa-Frossard, L., Eichau, S., García-Merino, J.A., Garcia-Vidal, C., González-Platas, M., Llaneza, M., Martínez-Ginés, M., Meca-Lallana, J.E., Prieto, J.M., Rodríguez-Antigüedad, A., Tintoré, M., Blanco, Y., and Moral, E.
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- 2021
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8. Recomendaciones para la vacunación en pacientes con esclerosis múltiple candidatos a terapias inmunosupresoras: documento de consenso español
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Otero-Romero, S., Rodríguez-García, J., Vilella, A., Ara, J.R., Brieva, L., Calles, C., Carmona, O., Casanova, V., Costa-Frossard, L., Eichau, S., García-Merino, J.A., Garcia-Vidal, C., González-Platas, M., Llaneza, M., Martínez-Ginés, M., Meca-Lallana, J.E., Prieto, J.M., Rodríguez-Antigüedad, A., Tintoré, M., Blanco, Y., and Moral, E.
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- 2021
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9. Perception of Stigma in Patients with Neuromyelitis Optica Spectrum Disorder
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Meca-Lallana JE, Prefasi D, Pérez-Miralles F, Forero L, Sepúlveda M, Calles C, Martínez-Ginés ML, González-Suárez I, Boyero S, Romero-Pinel L, Sempere ÁP, Meca-Lallana V, Querol L, Costa-Frossard L, de Castro-Trapiello H, Canal N, and Maurino J
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neuromyelitis optica spectrum disorder ,stigma ,quality of life ,depression ,patient-reported outcomes ,Medicine (General) ,R5-920 - Abstract
Jose E Meca-Lallana,1 Daniel Prefasi,2 Francisco Pérez-Miralles,3 Lucía Forero,4 María Sepúlveda,5 Carmen Calles,6 María L Martínez-Ginés,7 Inés González-Suárez,8 Sabas Boyero,9 Lucía Romero-Pinel,10 Ángel P Sempere,11 Virginia Meca-Lallana,12 Luis Querol,13 Lucienne Costa-Frossard,14 Hugo de Castro-Trapiello,2 Neus Canal,15 Jorge Maurino2 1Clinical Neuroimmunology Unit and Multiple Sclerosis CSUR. Department of Neurology. Hospital Universitario “Virgen de la Arrixaca”, IMIB-Arrixaca, Murcia, Spain; 2Medical Department, Roche Farma, Madrid, Spain; 3Unit of Neuroimmunology, Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain; 4Department of Neurology, Hospital Universitario Puerta del Mar, Cádiz, Spain; 5Department of Neurology, Hospital Clínic i Provincial de Barcelona, Barcelona, Spain; 6Department of Neurology, Hospital Universitari Son Espases, Palma de Mallorca, Spain; 7Department of Neurology, Hospital Universitario Gregorio Marañón, Madrid, Spain; 8Department of Neurology, Hospital Universitario Álvaro Cunqueiro, Vigo, Spain; 9Department of Neurology, Hospital Universitario Cruces, Bilbao, Spain; 10Department of Neurology, Hospital Universitari de Bellvitge, Barcelona, Spain; 11Department of Neurology, Hospital General Universitario de Alicante, Alicante, Spain; 12Department of Neurology, Hospital Universitario La Princesa, Madrid, Spain; 13Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 14Department of Neurology, Hospital Universitario Ramón y Cajal, Madrid, Spain; 15Department of Statistics, IQVIA, Barcelona, SpainCorrespondence: Jorge MaurinoRoche Farma, Ribera Del Loira, 50, Madrid, 28042, SpainTel +34 913 24 81 00Email jorge.maurino@roche.comBackground: Perception of stigma was associated with low self-esteem, psychological problems, and decreased health-seeking behavior among patients with different neurological disorders. The purpose of this study was to assess stigmatization and its impact in patients with neuromyelitis optica spectrum disorder (NMOSD).Methods: A non-interventional study was conducted at thirteen neuroimmunology clinics in Spain. Patients with a diagnosis of NMOSD (2015 Wingerchuk criteria) were included. The 8-item Stigma Scale for Chronic Illness (SSCI-8), the Expanded Disability Status Scale (EDSS), the 29-item Multiple Sclerosis Impact Scale (MSIS-29), the Beck Depression Inventory-Fast Screen (BDI-FS), the MOS Pain Effects Scale (MOS-PES) and the Fatigue Impact Scale for Daily Use (D-FIS) were used to assess the perception of stigma, disability, quality of life, mood, pain, and fatigue, respectively. Associations between outcome measures were analyzed using Spearman’s rank correlation.Results: Seventy-one patients were studied (mean age: 47.4 years ± 14.9, 81.7% female, mean time since disease onset: 9.9 years ± 8.1). The median EDSS score was 3.0 (interquartile range 1.5, 4.5). Stigma prevalence was 61.4% (n=43). Thirty-one patients (43.6%) had depression. The SSCI-8 score showed a significant correlation with both physical (rho=0.576, p< 0.0001) and psychological (rho=0.608, p< 0.0001) MSIS-29 scales scores, EDSS score (rho=0.349, p=0.0033), BDI-FS score (rho= 0.613, p< 0.0001), MOS-PES score (rho= 0.457, p< 0.0001), and D-FIS score (rho=0.556, p< 0.0001).Conclusion: Stigma is a common phenomenon affecting over 6 out of 10 patients with NMOSD. Understanding stigma may be useful to develop educational strategies improving NMOSD knowledge.Keywords: neuromyelitis optica spectrum disorder, stigma, quality of life, depression, patient-reported outcomes
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- 2021
10. 21131. MICRORNAS Y NIVELES DE CADENA LIGERA DE NEUROFILAMENTOS ASOCIADOS CON VARIABLES CLÍNICAS Y RADIOLÓGICAS EN PACIENTES CON ESCLEROSIS MÚLTIPLE
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Casanova Peño, L., Domínguez Mozo, M., Monreal, E., Costa- Frossard, L., Sainz de la Maza, S., Sainz Amo, R., Aladro Benito, Y., López Ruiz, P., de Torres, L., Abellán Ayuso, S., Herranz de las Heras, S., García Martínez, M., de la Cuesta, D., Lourido, D., Torrado, A., Gómez Barbosa, C., Linares Villavicencio, C., Villar Guimerans, L., Arroyo González, R., and Álvarez Lafuente, R.
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- 2024
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11. 21391. SEGUIMIENTO A 36 MESES DE MAVEN4: ESTUDIO ESPAÑOL, FASE IV, MULTICÉNTRICO, NO INTERVENCIONAL, PARA EVALUAR LA EFECTIVIDAD A LARGO PLAZO DE CLADRIBINA COMPRIMIDOS EN PRÁCTICA CLÍNICA REAL
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Aladro Benito, Y., Saiz, A., Costa-Frossard, L., Sánchez Magro, M., and Rodríguez-Antigüedad, A.
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- 2024
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12. 20486. BÚSQUEDA DE NUEVOS BIOMARCADORES A TRAVÉS DEL ESTUDIO DE LOS NIVELES DE PROTEÍNAS INFLAMATORIAS EN MUESTRAS DE SUERO DE PACIENTES DE ESCLEROSIS MÚLTIPLE NO TRATADOS
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Álvarez Lafuente, R., Domínguez Mozo, M., García Martínez, M., Villar Guimerans, L., Costa Frossard, L., Villarrubia Migallón, N., Aladro Benito, Y., Pilo de la Fuente, B., Montalban Gairín, X., Comabella López, M., González Suárez, I., Casanova Peño, I., Martínez Ginés, M., García Domínguez, J., and Arroyo González, R.
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- 2024
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13. 20485. ÁCIDOS GRASOS DE CADENA CORTA EN PACIENTES DE ESCLEROSIS MÚLTIPLE: ESTUDIO DE SU ASOCIACIÓN CON LA ACTIVIDAD Y LA PROGRESIÓN DE LA ENFERMEDAD
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Álvarez Lafuente, R., Domínguez Mozo, M., García Martínez, M., Villar Guimerans, L., Costa Frossard, L., Villarrubia Migallón, N., Aladro Benito, Y., Pilo de la Fuente, B., Montalban Gairín, X., Comabella López, M., González Suárez, I., Casanova Peño, I., Martínez Ginés, M., García Domínguez, J., García Calvo, E., Machuca Marcos, A., Luque García, J., Abdelhak, A., Tumani, H., Bachhuber, F., and Arroyo González, R.
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- 2024
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14. 20178. LA VELOCIDAD DE TECLEO OBTENIDA DURANTE EL PRIMER MES ES PREDICTIVA DE LA PROGRESIÓN INDEPENDIENTE DE BROTES EN PACIENTES CON ESCLEROSIS MÚLTIPLE
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Chico García, J., Sainz Amo, R., Monreal, E., Sainz de la Maza, S., Rodríguez Jorge, F., Masjuan, J., Costa-Frossard, L., and Villar, L.
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- 2024
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15. 21185. SUSPENSIÓN DE TRATAMIENTO MODIFICADOR DE LA ENFERMEDAD EN PACIENTES CON ESCLEROSIS MÚLTIPLE: ESTUDIO RETROSPECTIVO
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Garay Albízuri, P., Rodríguez Jorge, F., Llanes Ferrer, A., Sainz Amo, R., Pérez Gil, D., Sainz de la Maza, S., Martínez García, B., Monreal, E., García Alcántara, G., Moreno López, C., López Rebolledo, R., Pastor, R., Campos, M., Mena, N., Cabañas, G., Masjuan, J., Villar, L., Costa-Frossard, L., and Chico, J.
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- 2024
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16. 20403. NIVELES SÉRICOS DE NEUROFILAMENTOS DE CADENA LIGERA COMO FACTOR PREDICTOR DE RESPUESTA EN UNA COHORTE MULTICÉNTRICA DE PACIENTES CON ESCLEROSIS MÚLTIPLE TRATADOS CON OCRELIZUMAB
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Rodríguez Jorge, F., Fernández Velasco, J., Villarubia Migallón, N., Gracia Gil, J., Fernández Díaz, E., Bau Vila, L., Martínez Yélamos, S., Díaz Pérez, C., Meca Lallana, V., Sainz de la Maza Cantero, S., Pacheco Cortegana, E., Monreal Laguillo, E., Borrega, L., Chico García, J., López Real, A., Sainz Amo, R., Barrero, F., Martínez Ginés, M., de la Fuente, S., Moreno, I., Caminero, A., Castellanos, F., Ayuso, L., Abreu, R., Meca, J., Quiroga, A., Ramió, L., Masjuan, J., Costa-Frossard, L., and Villar Guimerans, L.
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- 2024
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17. Recommendations for the clinical use of motor evoked potentials in multiple sclerosis
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Fernández, V., Valls-Sole, J., Relova, J.L., Raguer, N., Miralles, F., Dinca, L., Taramundi, S., Costa-Frossard, L., Ferrandiz, M., Ramió-Torrentà, Ll., Villoslada, P., Saiz, A., Calles, C., Antigüedad, A., Alvarez-Cermeño, J.C., Prieto, J.M., Izquierdo, G., Montalbán, X., and Fernández, O.
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- 2013
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18. Recomendaciones para la utilización clínica del estudio de potenciales evocados motores en la esclerosis múltiple
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Fernández, V., Valls-Sole, J., Relova, J.L., Raguer, N., Miralles, F., Dinca, L., Taramundi, S., Costa-Frossard, L., Ferrandiz, M., Ramió-Torrentà, Ll., Villoslada, P., Saiz, A., Calles, C., Antigüedad, A., Alvarez-Cermeño, J.C., Prieto, J.M., Izquierdo, G., Montalbán, X., and Fernández, O.
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- 2013
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19. Spasticity improvement in patients with relapsing–remitting multiple sclerosis switching from interferon-β to glatiramer acetate: The Escala Study
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Meca-Lallana, J.E., Balseiro, J.J., Lacruz, F., Guijarro, C., Sanchez, O., Cano, A., Costa-Frossard, L., Hernández-Clares, R., and Sanchez-de la Rosa, R.
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- 2012
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20. Cerebrospinal fluid immunological biomarkers associated with axonal damage in multiple sclerosis
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Villar, L. M., Picón, C., Costa-Frossard, L., Alenda, R., García-Caldentey, J., Espiño, M., Muriel, A., and Álvarez-Cermeño, J. C.
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- 2015
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21. Natural killer cell subsets in cerebrospinal fluid of patients with multiple sclerosis
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Rodríguez-Martín, E., Picón, C., Costa-Frossard, L., Alenda, R., de la Maza, Sainz S., Roldán, E., Espiño, M., Villar, L. M., and Álvarez-Cermeño, J. C.
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- 2015
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22. Identification of the major HHV-6 antigen recognized by cerebrospinal fluid IgG in multiple sclerosis
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Alenda, R., Álvarez-Lafuente, R., Costa-Frossard, L., Arroyo, R., Mirete, S., Álvarez-Cermeño, J. C., and Villar, L. M.
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- 2014
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23. Brain region volumes and their relationship with disability progression and cognitive function in primary progressive multiple sclerosis
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Perez-Miralles F, Prefasi D, Garcia-Merino A, Ara J, Izquierdo G, Meca-Lallana V, Gascon-Gimenez F, Martinez-Gines M, Ramio-Torrenta L, Costa-Frossard L, Fernandez O, Moreno-Garcia S, Maurino J, Carreres-Polo J, and Casanova B
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disability progression ,primary progressive multiple sclerosis ,magnetic resonance imaging ,brain volume ,cognitive function - Abstract
Background and purpose Evidence on regional changes resulting from neurodegenerative processes underlying primary progressive multiple sclerosis (PPMS) is still limited. We assessed brain region volumes and their relationship with disability progression and cognitive function in PPMS patients. Methods This was an MRI analysis of 43 patients from the prospective Understanding Primary Progressive Multiple Sclerosis (UPPMS) cohort study. MRI scans were performed within 3 months before enrollment and at month 12. Results Gray matter volume of declive and white matter volumes adjacent to left straight gyrus, right calcarine sulcus, and right inferior occipital gyrus significantly decreased from baseline to month 12. Baseline white matter volumes adjacent to right amygdala and left cuneus significantly differed between patients with and without disability progression, as well as baseline gray matter volumes of left cuneus, right parahippocampal gyrus, right insula, left superior frontal gyrus, declive, right inferior temporal gyrus, right superior temporal gyrus (pole), and right calcarine sulcus. Baseline gray matter volumes of right cuneus and right superior temporal gyrus positively correlated with 12-month Selective Reminding Test and Word List Generation performance, respectively. Gray matter changes in right superior semilunar lobe and white matter adjacent to left declive and right cerebellar tonsil also positively correlated with Word List Generation scores, while white matter change in left inferior semilunar lobe positively correlated with Symbol Digit Modalities Test performance after 12 months. Conclusions White and gray matter volumes of specific brain regions could predict disability progression and cognitive performance of PPMS patients after one year.
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- 2021
24. Short-term data on disease activity, cognition, mood, stigma and employment outcomes in a cohort of patients with primary progressive multiple sclerosis (UPPMS study)
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Perez-Miralles F, Prefasi D, Garcia-Merino A, Ara J, Izquierdo G, Meca-Lallana V, Gascon-Gimenez F, Martinez-Gines M, Ramio-Torrenta L, Costa-Frossard L, Fernandez O, Moreno-Garcia S, Medrano N, Maurino J, and Casanova B
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Disability progression, Disease activity, Primary progressive multiple sclerosis - Abstract
BACKGROUND: Primary progressive multiple sclerosis (PPMS) has long been defined by progressive disability accrual in the absence of initial relapses. However, its underlying neurodegenerative process seems to be accompanied by central nervous system inflammation. A new classification defined multiple sclerosis courses according to clinical/radiological activity and progression. We provide further insight into PPMS activity according to this classification and other daily living aspects. METHODS: This was a multicentre, prospective, cohort study including 55 adult patients with PPMS according to 2010 McDonald criteria, within ten years from neurologic symptom onset and not receiving disease-modifying therapies during the past six months, who were followed up for 12 months. The primary study endpoint was the percentage of patients with active disease based on clinical relapses and/or magnetic resonance activity. Disability progression, cognitive function, physical/psychological impact, depression symptoms, stigma and employment were secondary endpoints. RESULTS: Eleven (25.6%) patients exhibited multiple sclerosis activity throughout the 12-month study follow-up. Fourteen showed non-active multiple sclerosis without progression, 11 non-active multiple sclerosis with progression, 6 active multiple sclerosis without progression and 4 active multiple sclerosis with progression; one patient with disease activity was not assessable for progression. Cognitive function scores remained unchanged or increased, disease physical impact was maintained and disease psychological impact significantly decreased. The proportion of patients with depression symptoms or stigma remained without significant changes as well as employment outcomes. CONCLUSION: This study shows that one-fourth of PPMS patients may exhibit disease activity over one year, with disability progression in approximately one-third but without worsening of cognitive function, disease impact, depression, stigma or employment outcomes.
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- 2021
25. 13th Post-ECTRIMS Meeting: review of the new developments presented at the 2020 ECTRIMS Congress (I)
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Fernández O, Montalban X, Aladro Y, Alonso A, Arroyo R, Calles C, Castillo-Triviño T, Comabella M, Costa-Frossard L, Forero L, Ginestal R, Landete L, Llaneza M, Llufriu S, Martínez-Ginés ML, Meca-Lallana J, Mendibe M, Oreja-Guevara C, Oterino A, Prieto JM, Ramió-Torrentà L, Romero-Pinel L, Téllez N, and Rodríguez-Antigüedad A
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ECTRIMS ,Multiple sclerosis ,Post-ECTRIMS ,ACTRIMS ,Congress ,MS - Abstract
Introduction. For more than a decade, following the ECTRIMS Congress, the Post-ECTRIMS Meeting has been held in Spain, where neurologists with expertise in multiple sclerosis (MS) from all over the country meet to review the most relevant latest developments presented at the ECTRIMS congress (on this occasion held together with ACTRIMS). Aim. This article, published in two parts, summarises the presentations that took place at the Post-ECTRIMS Meeting, held online on 16 and 17 October 2020. Development. This first part includes the latest results regarding the impact of the environment and lifestyle on risk of MS and its clinical course, and the role of epigenetics and genetic factors on these processes. Findings from preclinical and clinical research on the lymphocyte subtypes identified and the involvement of lymphoid follicles and meningeal involvement in the disease are discussed. Changes in brain structure are addressed at the microscopic and macroscopic levels, including results from high-resolution imaging techniques. The latest advances on biomarkers for the diagnosis and prognosis of MS, and on the involvement of the microbiome in these patients are also reported. Finally, results from patient registries on the impact of COVID-19 in MS patients are outlined. Conclusions. There have been new data on MS risk factors, the impact of MS at the cellular and structural level, the role of the microbiome in the disease, biomarkers, and the relationship between COVID-19 and MS.
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- 2021
26. Recomendaciones para la vacunación en pacientes con esclerosis múltiple candidatos a terapias inmunosupresoras: documento de consenso español
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Otero-Romero, S, Rodríguez-García, J, Vilella, A, Ara, J R, Brieva, L, Calles, C, Carmona, O, Casanova, V, Costa-Frossard, L, Eichau, S, García-Merino, J A, Garcia-Vidal, C, González-Platas, M, Llaneza, M, Martínez-Ginés, M, Meca-Lallana, J E, Prieto, J M, Rodríguez-Antigüedad, A, Tintoré, M, Blanco, Y, Moral, E, and en nombre del Grupo de enfermedades desmielizantes de la SEN
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Adult ,Immunosuppression Therapy ,Consensus ,Multiple Sclerosis ,Vaccination ,Vacunación ,Recommendations ,Vaccines, Attenuated ,Inmunosupresión ,Consenso ,Esclerosis múltiple ,Recomendaciones ,Humans ,Immunosuppression - Abstract
The recent development of highly effective treatments for multiple sclerosis (MS) and the potential risk of infectious complications require the development of prevention and risk minimisation strategies. Vaccination is an essential element of the management of these patients. This consensus statement includes a series of recommendations and practical scenarios for the vaccination of adult patients with MS who are eligible for highly effective immunosuppressive treatments. A formal consensus procedure was followed. Having defined the scope of the statement, we conducted a literature search on recommendations for the vaccination of patients with MS and specific vaccination guidelines for immunosuppressed patients receiving biological therapy for other conditions. The modified nominal group technique methodology was used to formulate the recommendations. Vaccination in patients who are candidates for immunosuppressive therapy should be considered before starting immunosuppressive treatment providing the patient's clinical situation allows. Vaccines included in the routine adult vaccination schedule, as well as some specific ones, are recommended depending on the pre-existing immunity status. If immunosuppressive treatment is already established, live attenuated vaccines are contraindicated. For vaccines with a correlate of protection, it is recommended to monitor the serological response in an optimal interval of 1-2 months from the last dose.
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- 2020
27. Identification of the Immunological Changes Appearing in the CSF During the Early Immunosenescence Process Occurring in Multiple Sclerosis
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Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), European Commission, Picón, C., Tejeda-Velarde, A., Fernández-Velasco, J.I., Comabella, Manuel, Alvarez-Lafuente, R., Quintana, E., Sainz de la Maza, S., Monreal, E., Villarrubia, N., Álvarez-Cermeño, José Carlos, Dominguez-Mozo, M.I., Ramió-Torrentà, Lluís, Rodríguez-Martín, Eulalia, Roldán, E., Aladro, Yolanda, Medina, S., Espiño, Mercedes, Masjuán, J., Matute-Blanch, Clara, Muñoz-San Martín, M., Espejo, C., Guaza, Carmen, Muriel, Alfonso, Costa-Frossard, L., Villar, L.M., Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), European Commission, Picón, C., Tejeda-Velarde, A., Fernández-Velasco, J.I., Comabella, Manuel, Alvarez-Lafuente, R., Quintana, E., Sainz de la Maza, S., Monreal, E., Villarrubia, N., Álvarez-Cermeño, José Carlos, Dominguez-Mozo, M.I., Ramió-Torrentà, Lluís, Rodríguez-Martín, Eulalia, Roldán, E., Aladro, Yolanda, Medina, S., Espiño, Mercedes, Masjuán, J., Matute-Blanch, Clara, Muñoz-San Martín, M., Espejo, C., Guaza, Carmen, Muriel, Alfonso, Costa-Frossard, L., and Villar, L.M.
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Patients with multiple sclerosis (MS) suffer with age an early immunosenescence process, which influence the treatment response and increase the risk of infections. We explored whether lipid-specific oligoclonal IgM bands (LS-OCMB) associated with highly inflammatory MS modify the immunological profile induced by age in MS. This cross-sectional study included 263 MS patients who were classified according to the presence (M+, n=72) and absence (M-, n=191) of LS-OCMB. CSF cellular subsets and molecules implicated in immunosenescence were explored. In M- patients, aging induced remarkable decreases in absolute CSF counts of CD4+ and CD8+ T lymphocytes, including Th1 and Th17 cells, and of B cells, including those secreting TNF-alpha. It also increased serum anti-CMV IgG antibody titers (indicative of immunosenescence) and CSF CHI3L1 levels (related to astrocyte activation). In contrast, M+ patients showed an age-associated increase of TIM-3 (a biomarker of T cell exhaustion) and increased values of CHI3L1, independently of age. Finally, in both groups, age induced an increase in CSF levels of PD-L1 (an inductor of T cell tolerance) and activin A (part of the senescence-associated secretome and related to inflammaging). These changes were independent of the disease duration. Finally, this resulted in augmented disability. In summary, all MS patients experience with age a modest induction of T-cell tolerance and an activation of the innate immunity, resulting in increased disability. Additionally, M- patients show clear decreases in CSF lymphocyte numbers, which could increase the risk of infections. Thus, age and immunological status are important for tailoring effective therapies in MS.
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- 2021
28. Recomendaciones para la coordinación de los servicios de Neurología y Neurorradiología en la atención a pacientes con esclerosis múltiple
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Llufriu, S., primary, Agüera, E., additional, Costa-Frossard, L., additional, Galán, V., additional, Landete, L., additional, Lourido, D., additional, Meca-Lallana, J.E., additional, Moral, E., additional, Bravo-Rodríguez, F., additional, Koren, L., additional, Labiano, A., additional, León, A., additional, Martín, P., additional, Monedero, M.D., additional, Requeni, L., additional, Zubizarreta, I., additional, and Rovira, À., additional
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- 2021
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29. Predictive factors and early biomarkers of response in multiple sclerosis patients treated with natalizumab
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Dominguez-Mozo, M.I., Pérez-Pérez, S., Villar, L.M., Oliver-Martos, Begoña, Villarrubia, N., Matesanz, F., Costa-Frossard, L., Pinto-Medel, María Jesús, García-Sánchez, María Isabel, Ortega-Madueño, Isabel, Lopez-Lozano, L., García-Martínez, A., Izquierdo, G., Fernández, Óscar, Álvarez-Cermeño, José Carlos, Arroyo, Rafael, Alvarez-Lafuente, R., Dominguez-Mozo, M.I., Pérez-Pérez, S., Villar, L.M., Oliver-Martos, Begoña, Villarrubia, N., Matesanz, F., Costa-Frossard, L., Pinto-Medel, María Jesús, García-Sánchez, María Isabel, Ortega-Madueño, Isabel, Lopez-Lozano, L., García-Martínez, A., Izquierdo, G., Fernández, Óscar, Álvarez-Cermeño, José Carlos, Arroyo, Rafael, and Alvarez-Lafuente, R.
- Abstract
There are an increasing number of treatments available for multiple sclerosis (MS). The early identification of optimal responders to individual treatments is important to achieve individualized therapy. With this aim, we performed a multicenter retrospective longitudinal study including 186 MS patients treated with natalizumab who were followed for 2 years. We analyzed the following variables at recruitment: sex, current age, age at disease onset, disease duration, EDSS, number of T2 and Gd + lesions, IgG and IgM oligoclonal bands, HLA class II (DR, DRB, DQA, DQB, and DRB1*15:01), IgG and IgM antibody titers against human herpesvirus 6 (HHV-6) and the antibody response to Epstein–Barr virus (EBV) through the measurement of the anti-EBNA-1 and anti-VCA IgG titers, in relation to clinical response (no relapses or disability progression), and to NEDA-3 (no evidence of disease activity in terms of clinical response and no changes in MRI scans either) after 2-years follow-up. Baseline EDSS score, baseline EBNA-1 IgG titers and percentage change of HHV6 IgG titers between baseline and 6 month visits were significantly different in clinical responders and in NEDA-3 status (all of them remained significant in the multivariate analysis). We identified three variables for the early identification of natalizumab optimal responders in a rapid and cost-effective approach.
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- 2020
30. Clinical usefulness of prognostic biomarkers in optic neuritis
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Tejeda-Velarde, A., primary, Costa-Frossard, L., additional, Sainz de la Maza, S., additional, Carrasco, Á., additional, Espiño, M., additional, Picón, C., additional, Toboso, I., additional, Walo, P. E., additional, Lourido, D., additional, Muriel, A., additional, Álvarez-Cermeño, J. C., additional, and Villar, L. M., additional
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- 2018
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31. Manejo de los sintomas asociados a la espasticidad en pacientes con esclerosis multiple
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Fernandez-Pablos, MA, Costa-Frossard, L, Garcia-Hernandez, C, Garcia-Montes, I, Escutia-Roig, M, and Grp Enfermeras Expertas Manejo
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Multiple sclerosis ,Neurologia ,Neurology ,Cannabinoids ,Cannabinoides ,Enfermeria ,Symptoms ,Esclerosis multiple ,Sintomas ,Espasticidad ,Muscle spasticity ,Nursing - Abstract
OBJECTIVE: To describe the role of nurses in the management of symptoms related to spasticity in patients with multiple sclerosis (MS). METHOD: A descriptive study was developed based on a questionnaire on spasticity in MS patients. The questionnarie was completed through an anonymous tele-voting system at a national meeting with nurses involved in the management of these patients. RESULTS: Apart from fatigue, according to the opinion of the participants, the spasticity symptom associated with MS most notified by patients was difficulty in walking, followed by spasms and pain. Participants thought that it is important that nursing takes: 1) a role in identifying these symptoms, 2) should focus on the detection of the triggering or aggravating factors, and 3) on providing support in the assessment of the level of spasticity. It is important to inform about the correct use of anti-spasticity drugs, how to adjust the dosage and side effects of treatments, including cannabinoids via an oromucosal spray, titrating its doses according to each patient, and monitoring its tolerability, efficacy and adherence. Although there are usually resources to follow up these patients, there are still important gaps, including the lack of a specific follow-up protocol. CONCLUSIONS: Although all the participants are experts in the management of patients with MS, there is still diversity in the functions they perform, and the available resources they have in their hospitals. Nurses act as a key element in the process of identification of symptoms, training and monitoring of these patients with spasticity in EM.
- Published
- 2016
32. Lipid-specific immunoglobulin M bands in cerebrospinal fluid are associated with a reduced risk of developing progressive multifocal leukoencephalopathy during treatment with natalizumab
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Villar LM, Costa-Frossard L, Masterman T, Fernandez O, Montalban X, Casanova B, Izquierdo G, Coret F, Tumani H, Saiz A, Arroyo R, Fink K, Leyva L, Espejo C, Simó-Castelló M, García-Sánchez MI, Lauda F, Llufriú S, Álvarez-Lafuente R, Olascoaga J, Prada A, Oterino A, de Andrés C, Tintoré M, Ramió-Torrentà L, Rodríguez-Martín E, Picón C, Comabella M, Quintana E, Agüera E, Díaz S, Fernandez-Bolaños R, García-Merino JA, Landete L, Menéndez-González M, Navarro L, Pérez D, Sánchez-López F, Serrano-Castro PJ, Tuñón A, Espiño M, Muriel A, Bar-Or A, Álvarez-Cermeño JC, Instituto de Salud Carlos III, and Ministerio de Economía y Competitividad (España)
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Adult ,Male ,Risk ,Multiple Sclerosis ,Natalizumab ,Oligoclonal Bands ,Leukoencephalopathy, Progressive Multifocal ,Humans ,Female ,Middle Aged ,Antibodies, Monoclonal, Humanized ,JC Virus ,Biomarkers - Abstract
[Objective]: Progressive multifocal leukoencephalopathy (PML) is a serious side effect associated with natalizumab treatment in multiple sclerosis (MS). PML risk increases in individuals seropositive for anti–John Cunningham virus (JC) antibodies, with prolonged duration of natalizumab treatment, and with prior exposure to immunosuppressants. We explored whether the presence of lipid‐specific immunoglobulin M oligoclonal bands in cerebrospinal fluid (CSF; IgM bands), a recognized marker of highly inflammatory MS, may identify individuals better able to counteract the potential immunosuppressive effect of natalizumab and hence be associated with a reduced risk of developing PML. [Methods]: We studied 24 MS patients who developed PML and another 343 who did not suffer this opportunistic infection during natalizumab treatment. Patients were recruited at 25 university hospitals. IgM bands were studied by isoelectric focusing and immunodetection. CSF lymphocyte counts were explored in 151 MS patients recruited at Ramon y Cajal Hospital in Madrid, Spain. [Results]: IgM bands were independently associated with decreased PML risk (odds ratio [OR] = 45.9, 95% confidence interval [CI] = 5.9–339.3, p, This work was supported by grants; PI12–00239 from FIS; Instituto de Salud Carlos III; SAF 2012‐34670, and RD12/0032/0005 from the Spanish Ministry of Economy and Competitiveness; and BMBF grant KKNMS (Competence Net Multiple Sclerosis; H.T.).
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- 2015
33. Anti-lipid oligoclonal IgM bands contribute to progressive multifocal leukoencephalopathy (PML) risk stratification in multiple sclerosis patients treated with natalizumab
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Villar, L., Costa-Frossard, L., Fernandez, O., Montalban, X., Casanova, B., Izquierdo, G., Masterman, T., Coret, F., Tumani, H., Saiz, A., Arroyo, R., Laura Leyva, Espejo, C., Garcia-Sanchez, M. I., Fink, K., Lauda, F., Llufriu, S., Alvarez-Lafuente, R., Olascoaga, J., Oterino, A., Andres, C., Garcia-Merino, J. A., Landete, L., Menendez, M., Navarro, L., Perez, D., Ramio, L., Tunon, A., and Alvarez-Cermeno, J. C.
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- 2013
34. Cerebrospinal fluid immunological biomarkers associated with axonal damage in multiple sclerosis
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Villar, L. M., primary, Picón, C., additional, Costa-Frossard, L., additional, Alenda, R., additional, García-Caldentey, J., additional, Espiño, M., additional, Muriel, A., additional, and Álvarez-Cermeño, J. C., additional
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- 2014
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35. Efectividad de la lacosamida en el tratamiento del dolor neuropático refractario: estudio observacional abierto
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Toribio-Díaz Me, Morin-Martin Mdel M, Almajano J, Colás J, Lara M, J. M. Gomez-Argüelles, M. Blanco, Ceballos Má, Costa-Frossard L, García del Carrizo F, Latorre-González G, Bermejo Pe, Valenzuela-Rojas Fj, Aragón E, and Sánchez-Del Valle O
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Tratamiento farmacologico ,Multicenter study ,business.industry ,Medicine ,Neurology (clinical) ,General Medicine ,business ,Humanities - Abstract
Introduccion. Aunque se dispone de diferentes tratamientos para el dolor neuropatico, en muchas ocasiones estos pacientes son refractarios, lo que hace necesario probar tratamientos que, por su utilidad en otras patologias, podrian ser eficaces en el dolor neuropatico. Pacientes y metodos. Se recogieron las historias clinicas de pacientes que hubieran sido tratados con lacosamida para el dolor neuropatico, en diferentes hospitales de la zona centro peninsular, y que cumplieran unas caracteristicas similares en cuanto a refractariedad a otros tratamientos estandares, en un seguimiento de al menos seis meses, o que hubiesen tenido que suspender el tratamiento con dicho farmaco por cualquier motivo. Se obtuvo una muestra de 114 pacientes, 61 varones y 53 mujeres, con una edad media de 60,5 anos. Resultados. Las causas de dolor neuropatico mas frecuentes fueron: polineuropatia diabetica (31,6%), neuralgia postherpetica (22,8%), neuralgia del trigemino (17,5%), neuralgia suboccipital y lumbociatalgia (un 12,3% en ambas). La eficacia fue buena/muy buena en la mayoria de los pacientes, con un descenso medio en la escala analogica visual tras seis meses de 7,7 a 4,8. No se registraron efectos secundarios graves en ningun paciente, pero en 12 y 10 pacientes no hubo registro mas alla de seis meses, por ineficacia e intolerancia al tratamiento, respectivamente. Conclusiones. El tratamiento con lacosamida en el dolor neuropatico de diferentes causas podria considerarse como una alternativa efectiva y bien tolerada para aquellos pacientes que no respondan a los tratamientos estandares.
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- 2014
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36. Downregulation of Intrathecal IgM Synthesis Associates with Optimal Response to Natalizumab in Multiple Sclerosis (P06.175)
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Villar, L. M., primary, Garcia-Sanchez, M., additional, Costa-Frossard, L., additional, Espino, M., additional, Roldan, E., additional, Paramo, D., additional, Lucas, M., additional, Izquierdo, G., additional, and Alvarez-Cermeno, J., additional
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- 2012
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37. CSF Free Kappa Chains Predict Conversion to Multiple Sclerosis in Clinically Isolated Syndromes (P02.125)
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Alvarez-Cermeno, J., primary, Espino, M., additional, Costa-Frossard, L., additional, Muriel, A., additional, and Villar, L., additional
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- 2012
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38. P1.8 Diagnostic value of vestibular evoked myogenic potentials (VEMP) in multiple sclerosis
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Pedrera-Mazarro, A., primary, Carretero-García, M., additional, Costa-Frossard, L., additional, Alvarez-Cermeño, J.C., additional, and Paradinas-Jiménez, F., additional
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- 2011
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39. Colitis ulcerosa en una paciente con esclerosis múltiple en tratamiento con interferón
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Costa-Frossard L, Corral-Corral I, Zarza B, and Palao-Duarte S
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medicine.medical_specialty ,business.industry ,Multiple sclerosis ,General Medicine ,medicine.disease ,Ulcerative colitis ,Gastroenterology ,Interferon ,Internal medicine ,Female patient ,Medicine ,Neurology (clinical) ,business ,medicine.drug - Published
- 2005
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40. Integrated Management of Multiple Sclerosis Spasticity and Associated Symptoms Using the Spasticity-Plus Syndrome Concept: Results of a Structured Specialists' Discussion Using the Workmat
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Oscar Fernandez, Lucienne Costa-Frossard, Maria Luisa Martínez-Ginés, Paloma Montero, Jose María Prieto-González, Lluís Ramió-Torrentà, Institut Català de la Salut, [Fernandez O] Department of Pharmacology, Biomedical Research Institute of Malaga, University of Málaga, Málaga, Spain. [Costa-Frossard L] Department of Neurology, Hospital Universitario Ramón y Cajal, Madrid, Spain. [ Martínez-Ginés L] Department of Neurology, Hospital Gregorio Marañón, Madrid, Spain. [Montero P] Department of Neurology, Hospital Clínico San Carlos, Madrid, Spain. [Prieto-González JM] Department of Neurology, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain. [Ramió-Torrentà Ll] Departament de Neurologia, Hospital Universitari de Girona Doctor Josep Trueta, Institut Català de la Salut (ICS), Girona, Spain. Neuroimmunology and Multiple Sclerosis Unit, Girona Biomedical Research Institute (IDIBGI), Girona, Spain. Medical Sciences Department, University of Girona, Girona, Spain, and Hospital Universitari de Girona Dr Josep Trueta
- Subjects
medicine.medical_specialty ,Organic Chemicals::Hydrocarbons::Terpenes::Cannabinoids::Cannabidiol [CHEMICALS AND DRUGS] ,compuestos orgánicos::hidrocarburos::terpenos::cannabinoides::cannabidiol [COMPUESTOS QUÍMICOS Y DROGAS] ,symptom management ,Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Neurologic Manifestations::Neuromuscular Manifestations::Muscle Hypertonia::Muscle Spasticity [DISEASES] ,Esclerosi múltiple ,Disease ,multiple sclerosis ,Quality of life ,Espasticitat muscular ,medicine ,In patient ,Spasticity ,RC346-429 ,Depression (differential diagnoses) ,Original Research ,symptomatic treatment ,business.industry ,Symptom management ,Multiple sclerosis ,spasticity ,medicine.disease ,syndrome ,nervous system diseases ,cannabidiol (CBD) ,Immune System Diseases::Autoimmune Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES] ,enfermedades musculoesqueléticas::enfermedades musculares::espasticidad muscular [ENFERMEDADES] ,Sexual dysfunction ,Neurology ,quality of life ,Cannabinoides ,enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES] ,Physical therapy ,tetrahydrocannabinol (THC) ,Neurology (clinical) ,Neurology. Diseases of the nervous system ,medicine.symptom ,business - Abstract
Esclerosi múltiple; Espasticitat; Cannabinoides Múltiple esclerosis; Espasticidad; Cannabidiol Multiple sclerosis; Muscle spasticity; Cannabidiol Background: Multiple sclerosis (MS) treatment has radically improved over the last years; however, MS symptom management is still challenging. The novel Spasticity-Plus syndrome was conceptualized to frame several spasticity-related symptoms that can be addressed together with broad-spectrum medication, such as certain cannabinoid-based drugs. The aim of this project was to gain insight into Spanish neurologists' clinical experience on MS spasticity and associated symptoms, and to assess the acknowledgment and applicability of the Spasticity-Plus syndrome concept in patients with MS. Methods: Ten online meetings were conducted using the Workmat® methodology to allow structured discussions. Fifty-five Spanish neurologists, experts in MS management, completed and discussed a set of predefined exercises comprising MS symptom assessment and its management in clinical practice, MS symptoms clustering in clinical practice, and their perception of the Spasticity-Plus syndrome concept. This document presents the quantitative and qualitative results of these discussions. Results: The specialists considered that polytherapy is a common concern in MS and that simplifying the management of MS spasticity and associated manifestations could be useful. They generally agreed that MS spasticity should be diagnosed before moderate or severe forms appear. According to the neurologists' clinical experience, symptoms commonly associated with MS spasticity included spasms/cramps (100% of the specialists), pain (85%), bladder dysfunction (62%), bowel dysfunction (42%), sleep disorders (42%), and sexual dysfunction (40%). The multiple correspondence analysis revealed two main symptom clusters: spasticity-spasms/cramps-pain, and ataxia-instability-vertigo. Twelve out of 16 symptoms (75%) were scored >7 in a 0-10 QoL impact scale by the specialists, representing a moderate-high impact. The MS specialists considered that pain, spasticity, spasms/cramps, bladder dysfunction, and depression should be a treatment priority given their frequency and chance of therapeutic success. The neurologists agreed on the usefulness of the new Spasticity-Plus syndrome concept to manage spasticity and associated symptoms together, and their experience with treatments targeting the cannabinoid system was satisfactory. Conclusions: The applicability of the new concept of Spasticity-Plus in MS clinical practice seems possible and may lead to an integrated management of several MS symptoms, thus reducing the treatment burden of disease symptoms. The study was funded by an investigational grant from Almirall SA
- Published
- 2021
41. Corrigendum: Biomarkers of response to ocrelizumab in relapsing-remitting multiple sclerosis.
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Rodríguez-Jorge F, Fernández-Velasco JI, Villarrubia N, Gracia-Gil J, Fernández E, Meca-Lallana V, Díaz-Pérez C, Sainz de la Maza S, Pacheco EM, Quiroga A, Ramió-Torrentà L, Martínez-Yélamos S, Bau L, Monreal E, López-Real A, Rodero-Romero A, Borrega L, Díaz S, Eguía P, Espiño M, Chico-García JL, Barrero FJ, Martínez-Ginés ML, García-Domínguez JM, De la Fuente S, Moreno I, Sainz-Amo R, Mañé-Martínez MA, Caminero A, Castellanos-Pinedo F, Gómez López A, Labiano-Fontcuberta A, Ayuso L, Abreu R, Hernández MÁ, Meca-Lallana J, Martín-Aguilar L, Muriel García A, Masjuan J, Costa-Frossard L, and Villar LM
- Abstract
[This corrects the article DOI: 10.3389/fimmu.2024.1480676.]., (Copyright © 2024 Rodríguez-Jorge, Fernández-Velasco, Villarrubia, Gracia-Gil, Fernández, Meca-Lallana, Díaz-Pérez, Sainz de la Maza, Pacheco, Quiroga, Ramió-Torrentà, Martínez-Yélamos, Bau, Monreal, López-Real, Rodero-Romero, Borrega, Díaz, Eguía, Espiño, Chico-García, Barrero, Martínez-Ginés, García-Domínguez, De la Fuente, Moreno, Sainz-Amo, Mañé-Martínez, Caminero, Castellanos-Pinedo, Gómez López, Labiano-Fontcuberta, Ayuso, Abreu, Hernández, Meca-Lallana, Martín-Aguilar, Muriel García, Masjuan, Costa-Frossard and Villar.)
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- 2024
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42. Effect of Natalizumab on sNfL and sGFAP Levels in Multiple Sclerosis Patients.
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Sainz-Amo R, Rodero-Romero A, Monreal E, Chico-García JL, Rodríguez-Jorge F, Fernández-Velasco JI, Villarrubia N, Veiga-González JL, de la Maza SS, Masjuan J, Costa-Frossard L, and Villar LM
- Subjects
- Humans, Female, Adult, Male, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting blood, Multiple Sclerosis drug therapy, Multiple Sclerosis blood, Biomarkers blood, Case-Control Studies, Natalizumab therapeutic use, Neurofilament Proteins blood, Glial Fibrillary Acidic Protein blood
- Abstract
Natalizumab is a highly effective therapy for multiple sclerosis (MS). The aim of this study was to evaluate serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) in patients with relapsing-remitting MS treated with Natalizumab. sNfL and sGFAP were analyzed at baseline, 6 and 12 months post treatment using the single-molecule array (SiMoA) technique. We recruited matched healthy controls for comparison. The study included 54 patients, with a median age of 33 years (Interquartile range (IQR), 29-41), with 32 women (60%) and 76 healthy controls. A decrease in sNfL was observed at 6 (67%, p = 0.005) and 12 (72%, p < 0.0001) months compared to baseline. After two years, six patients experienced evidence of disease activity (EDA-3). The remaining ones had no evidence of disease activity (NEDA-3). NEDA-3 presented a remarkable reduction in sNfL ( p < 0.0001) and sGFAP ( p = 0.01) after 6 months of treatment that continued to be observed after 12 months compared to baseline. EDA-3 only reached a significant decrease in sNfL after 12 months; there were no significant changes in sGFAP values. Natalizumab leads to a decrease in sNfL, which is higher and occurs earlier in NEDA-3 patients. Patients also showed a significant reduction in sGFAP levels, which was not observed in the EDA-3 group.
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- 2024
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43. Serum biomarkers at disease onset for personalized therapy in multiple sclerosis.
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Monreal E, Fernández-Velasco JI, Álvarez-Lafuente R, Sainz de la Maza S, García-Sánchez MI, Llufriu S, Casanova B, Comabella M, Martínez-Yélamos S, Galimberti D, Ramió-Torrentà L, Martínez-Ginés ML, Aladro Y, Ayuso L, Martínez-Rodríguez JE, Brieva L, Villarrubia N, Eichau S, Zamora J, Rodero-Romero A, Espiño M, Blanco Y, Saiz A, Montalbán X, Tintoré M, Domínguez-Mozo MI, Cuello JP, Romero-Pinel L, Ghezzi L, Pilo de la Fuente B, Pérez-Miralles F, Quiroga-Varela A, Rubio L, Rodríguez-Jorge F, Chico-García JL, Sainz-Amo R, Masjuan J, Costa-Frossard L, and Villar LM
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- Humans, Female, Male, Adult, Glial Fibrillary Acidic Protein blood, Disease Progression, Follow-Up Studies, Middle Aged, Biomarkers blood, Neurofilament Proteins blood, Multiple Sclerosis blood, Multiple Sclerosis drug therapy, Precision Medicine methods
- Abstract
The potential for combining serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels to predict worsening disability in multiple sclerosis remains underexplored. We aimed to investigate whether sNfL and sGFAP values identify distinct subgroups of patients according to the risk of disability worsening and their response to disease-modifying treatments (DMTs). This multicentre study, conducted across 13 European hospitals, spanned from 15 July 1994 to 18 August 2022, with follow-up until 26 September 2023. We enrolled patients with multiple sclerosis who had serum samples collected within 12 months from disease onset and before initiating DMTs. Multivariable regression models were used to estimate the risk of relapse-associated worsening (RAW), progression independent of relapse activity (PIRA) and Expanded Disability Status Scale (EDSS) score of 3. Of the 725 patients included, the median age was 34.2 (interquartile range, 27.6-42.4) years, and 509 patients (70.2%) were female. The median follow-up duration was 6.43 (interquartile range, 4.65-9.81) years. Higher sNfL values were associated with an elevated risk of RAW [hazard ratio (HR) of 1.45; 95% confidence interval (CI) 1.19-1.76; P < 0.001], PIRA (HR of 1.43; 95% CI 1.13-1.81; P = 0.003) and reaching an EDSS of 3 (HR of 1.55; 95% CI 1.29-1.85; P < 0.001). Moreover, higher sGFAP levels were linked to a higher risk of achieving an EDSS score of 3 (HR of 1.36; 95% CI 1.06-1.74; P = 0.02) and, in patients with low sNfL values, to PIRA (HR of 1.86; 95% CI 1.01-3.45; P = 0.04). We also examined the combined effect of sNfL and sGFAP levels. Patients with low sNfL and sGFAP values exhibited a low risk of all outcomes and served as a reference. Untreated patients with high sNfL levels showed a higher risk of RAW, PIRA and reaching an EDSS of 3. Injectable or oral DMTs reduced the risk of RAW in these patients but failed to mitigate the risk of PIRA and reaching an EDSS of 3. Conversely, high-efficacy DMTs counteracted the heightened risk of these outcomes, except for the risk of PIRA in patients with high sNfL and sGFAP levels. Patients with low sNfL and high sGFAP values showed an increased risk of PIRA and achieving an EDSS of 3, which remained unchanged with either high-efficacy or other DMTs. In conclusion, evaluating sNfL and sGFAP levels at disease onset in multiple sclerosis might identify distinct phenotypes associated with diverse immunological pathways of disability acquisition and therapeutic response., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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44. A Clinical Care Algorithm for Detecting Progression in Multiple Sclerosis: RetratEMos Project.
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Meca-Lallana JE, Robles R, Landete L, Téllez N, García-Domínguez JM, Garcés P, and Costa-Frossard L
- Abstract
Objective: The diagnosis of secondary progressive multiple sclerosis (SPMS) is often established retrospectively leading to a delay in detection. This work presents a clinical care algorithm that aims to facilitate the recognition of the secondary progressive phase of the disease, analyzing its usefulness and the feasibility of its implementation in routine clinical practice., Methods: The algorithm was developed in four phases: 1) choice of validated diagnostic tools for the detection of progression; 2) assessment of these tools based on experience of use, applicability, time consumed, perceived usefulness and suitability for a profile of a patient in transition to SPMS; 3) framework and final sequence of application; 4) feasibility evaluation through application in clinical practice., Results: A hierarchical algorithm was developed with an initial screening phase to detect warning signs and establish suspicion of progression (which included the tests "Your Multiple Sclerosis (Your MS)," "MSProDiscuss," and "Nomogram") and a second phase conditional on a positive result in the first, including a functional examination with the Symbol Digit Modalities Test (SDMT), 9-Hole Peg Test (9-HPT), and Timed 25-Foot Walk (T25FW) tools. The algorithm was applied to 373 patients with Expanded Disability Status Scale (EDSS) ≥ 2. The mean time spent per patient in the screening was eight minutes and 20.4 minutes for the complete algorithm. The perceived usefulness of the process by the neurologists was 3.1 (range of 1-4, with 4 being the maximum). In 46% of the cases, the algorithm detected the need for additional functional exploration., Conclusions: From our experience, this clinical care algorithm is effective and feasible for detecting progression in MS, although its implementation requires proper organization and can be uneven depending on the resources of each center., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: The RetratEMos project was sponsored by Novartis. Financial relationships: José Eustasio Meca-Lallana declare(s) personal fees from Alexion, Biogen, BMS, Janssen, Merck, Novartis, Roche, and Sanofi. Disclosures have been added in the relevant section of the article. Nieves Téllez declare(s) personal fees from Bayer, Biogen, Merck, Novartis, Sanofi, Teva, Roche, and BMS. Disclosures have been added in the relevant section of the article. Lucienne Costa-Frossard declare(s) personal fees and Support for attending advisory boards/travel from Biogen, Sanofi, Merck, Bayer, Novartis, Roche, Teva, BMS, Janssen, Sandoz, Viatris, and Almirall. Disclosures have been added in the relevant section of the article. René Robles declare(s) personal fees from Biogen, Novartis, Bayer, Merck, Sanofi, Roche, Teva, Almirall, and BMS. Disclosures have been added in the relevant section of the article. Lamberto Landete declare(s) personal fees from Almirall, Bayer, Biogen, BMS, Sanofi, Merck, Novartis, UCB Pharma, Roche, and Teva. Disclosures have been added in the relevant section of the article. Pilar Garcés declare(s) employment from Novartis. Disclosures have been added in the relevant section of the article. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Meca-Lallana et al.)
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- 2024
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45. Biomarkers of response to ocrelizumab in relapsing-remitting multiple sclerosis.
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Rodríguez-Jorge F, Fernández-Velasco JI, Villarrubia N, Gracia-Gil J, Fernández E, Meca-Lallana V, Díaz-Pérez C, Sainz de la Maza S, Pacheco EM, Quiroga A, Ramió-Torrentà L, Martínez-Yélamos S, Bau L, Monreal E, López-Real A, Rodero-Romero A, Borrega L, Díaz S, Eguía P, Espiño M, Chico-García JL, Barrero FJ, Martínez-Ginés ML, García-Domínguez JM, De la Fuente S, Moreno I, Sainz-Amo R, Mañé-Martínez MA, Caminero A, Castellanos F, Gómez López A, Labiano-Fontcuberta A, Ayuso L, Abreu R, Hernández MÁ, Meca-Lallana J, Martín-Aguilar L, Muriel García A, Masjuan J, Costa-Frossard L, and Villar LM
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- Humans, Female, Male, Adult, Prospective Studies, Glial Fibrillary Acidic Protein blood, Middle Aged, Immunologic Factors therapeutic use, Treatment Outcome, Disease Progression, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting blood, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, Biomarkers blood, Neurofilament Proteins blood
- Abstract
Objective: To ascertain the changes of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) values in relapsing-remitting multiple sclerosis (RRMS) patients treated with ocrelizumab and their association with treatment response., Methods: Multicenter prospective study including 115 RRMS patients initiating ocrelizumab treatment between February 2020 and March 2022 followed during a year. Serum samples were collected at baseline and every 3 months to measure sNfL and sGFAP levels using single-molecule array (SIMOA) technology. Based on age and body mass index, sNfL values were standardized using z-score. NEDA (non-evidence of disease activity)-3 status was defined for patients free of disease activity after a year of follow-up. Inflammation (INFL) was considered when new relapses occurred during follow-up or new MRI lesions were found at 1-year exploration. PIRA (progression independent of relapse activity) was defined as disability progression occurring in the absence of relapses or new MRI activity., Results: After a year on ocrelizumab, 85 patients (73.9%) achieved NEDA-3. Thirty patients did not achieve NEDA: 20 (17.4%) because of INFL and 10 (8.7%) because of PIRA. Of INFL patients, 6 (30.0%) had relapses, and 17 (85.0%) had at least one new MRI lesion at the 12-month examination. At baseline, INFL patients had higher sNfL (p = 0.0003) and sGFAP (p = 0.03) than the NEDA-3 group. PIRA patients mostly exhibited low sNfL and heterogeneous sGFAP levels. After a year, NEDA-3 and INFL patients showed similar decreases in sNfL (p < 0.0001) and sGFAP (p < 0.0001 for NEDA-3 and p = 0.001 for INFL ones). However, the decrease occurred earlier in NEDA-3 patients. Accordingly, sNfL > 1.5 z-score 3 months after ocrelizumab initiation indicated a higher risk of inflammation (OR = 13.6; p < 0.0001). Decrease in sGFAP values occurred later in both groups, with significant reductions observed at 12 months for INFL and 6 and 12 months for NEDA-3. No significant changes in sNfL or sGFAP were observed in PIRA patients., Conclusion: Ocrelizumab induced normalization of sNfL and sGFAP in the majority of NEDA-3 and inflammatory patients but did not cause changes in the PIRA group. Our data suggest that normalization of sNfL and sGFAP is associated with the lack of inflammatory-associated disease progression but it may not affect non-inflammatory PIRA., Competing Interests: FR-J received research grants and travel support for speaking engagements from Janssen, Biogen, Novartis, Roche, Sanofi-Genzyme, Bristol-Myers-Squibb and Merck. JG-G received research support, compensation for participating on advisory boards, lecture fees, and/or travel support from Almirall, Bayer, Biogen, Genzyme‐Sanofi, Novartis, Roche, and Teva. EF received research support, compensation for participating on advisory boards, speaking fees, and/or funding for travel from Almirall, Bayer, Biogen, Genzyme‐Sanofi, Merck, Novartis, and Roche. VM-L received consulting and speaking fees from Almirall, Biogen, Genzyme, Janssen, Merck, Novartis, Roche, Terumo, Sanofi, Teva, and Bristol Myers Squibb. CD-P received funding for training and scientific meetings from Sanofi, Merck, Novartis and Roche. SS received research grants, travel support or honoraria for speaking engagements from Almirall, Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. AQ is funded by a grant from the Fundación Francisco Soria y Melguizo and has received funding from Merck, Novartis, and Horizon Therapeutics to attend conferences. LR-T received compensation for consulting services and speaking fees from Biogen, Novartis, Bayer, Merck, Sanofi, Genzyme, Roche, Bristol-Myers-Squibb, TEVA, and Horizon. SM-Y received honoraria for participating on advisory boards and for collaborations as consultant and scientific communications and also received research support as well as funding for travel and congress expenses from Roche, Biogen Idec, Novartis, TEVA, Merck, Genzyme, Sanofi, Bayer, Almirall, and Bristol Myers Squibb. EM received research grants, travel support, or honoraria for speaking engagements from Almirall, Merck, Roche, Sanofi, Bristol Myers Squibbb, Biogen, Janssen, and Novartis. AL-R received speaker and consultation fees from Biogen, Janssen, Novartis, Roche and Sanofi, and congress travel support from Roche. LBo received research grants and travel support from Merck, Roche, Novartis, Sanofi, Horizon and Bristol Myer Squibb. JC-G received speaker fees, travel support, and/or served on advisory boards by Biogen, Sanofi, Bayer, Janssen, BMS, and Bial. FB received compensation for consulting services and speaking honoraria from Almirall, Biogen, Bristol Myer Squibb, Genzyme, Johnson & Johnson, Merck, Novartis, Roche, Sanofi, Teva. MM-G received compensation for consulting services and speaking fees from Merck, Biogen, Novartis, Sanofi-Genzyme, Almirall, BMS, Janssen, Roche, Horizon, and Viatris. JG-D received honoraria as speaker, advisor and researcher from Almirall, Bristol Myers Squibb, Biogen, Janssen, Merck, Novartis, Roche, Teva, and Sanofi. MM-M received research support, funding for travel and congress expenses from Biogen Idec, Teva Pharmaceutical Industries Ltd., Sanofi-Aventis, Merck Serono, Novartis, Bayer Schering Pharma, Bristol Myers Squibb and Roche. JM-L received honoraria as a consultant, lecturer in meetings and has participated in clinical trials and other research projects promoted by Alexion, Almirall, Biogen, Bristol-Meyers-Squibb, Horizon, Johnson & Johnson, Merck, Neuraxpharm, Novartis, Roche, Sandoz, Sanofi and UCB. LC-F received speaker fees, travel support, and/or served on advisory boards by Biogen, Sanofi, Merck, Bayer, Novartis, Roche, Teva, Celgene, Ipsen, Biopas, Almirall. LV received research grants and personal fees from Merck, Roche, Sanofi, Bristol Myers Squibb, Biogen, and Novartis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Rodríguez-Jorge, Fernández-Velasco, Villarrubia, Gracia-Gil, Fernández, Meca-Lallana, Díaz-Pérez, Sainz de la Maza, Pacheco, Quiroga, Ramió-Torrentà, Martínez-Yélamos, Bau, Monreal, López-Real, Rodero-Romero, Borrega, Díaz, Eguía, Espiño, Chico-García, Barrero, Martínez-Ginés, García-Domínguez, De la Fuente, Moreno, Sainz-Amo, Mañé-Martínez, Caminero, Castellanos, Gómez López, Labiano-Fontcuberta, Ayuso, Abreu, Hernández, Meca-Lallana, Martín-Aguilar, Muriel García, Masjuan, Costa-Frossard and Villar.)
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- 2024
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46. Real-World Experience with Diroximel Fumarate in Patients with Multiple Sclerosis: A Prospective Multicenter Study.
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Aguirre C, Alonso-Torres A, Agüera E, García-Domínguez JM, Montero-Escribano P, González-Quintanilla V, Costa-Frossard L, Oreja-Guevara C, Reyes-Garrido V, Caminero-Rodríguez AB, Riancho J, Sánchez O, Forero L, Pérez-Parra F, Ares-Luque A, Téllez N, Arzalluz-Luque J, Iglesias F, Casado-Ruiz V, Castellano-Vicente AJ, Borrega L, Galán V, de Antonio LAR, Romero C, García-Rodríguez R, Cano-Orgaz AT, Sánchez-Menoyo JL, Pérez-Ruiz D, Gutiérrez-Martin F, Hernández-Echevarría L, and Meca-Lallana V
- Subjects
- Humans, Female, Male, Adult, Prospective Studies, Middle Aged, Treatment Outcome, Immunosuppressive Agents therapeutic use, Immunosuppressive Agents adverse effects, Immunosuppressive Agents administration & dosage, Registries, Multiple Sclerosis drug therapy, Dimethyl Fumarate therapeutic use, Dimethyl Fumarate adverse effects
- Abstract
Background: Current literature and a real-world study suggest that diroximel fumarate (DRF) is safer than dimethyl fumarate (DMF) in the treatment of multiple sclerosis (MS). However, no real-world study to date has significantly addressed the efficacy of this treatment., Objectives: This study aims to elucidate the safety, tolerability, and efficacy of DRF in a real-world setting, utilizing data from a Spanish national registry of patients commencing DRF therapy post-market introduction., Methods: In this multicenter, prospective observational study, data were collected from MS patients who initiated DRF treatment. The study monitored demographic and clinical characteristics, safety outcomes (including adverse events, reasons for discontinuation, and lymphocyte counts), and efficacy outcomes (radiological and clinical activity)., Results: A total of 195 MS patients across 26 neurological departments were included, predominantly female (79.5%), with a mean age of 42.17 years, and a mean duration of treatment with DRF of 6.3 months. Most patients (70.3%) reported no adverse events, while gastrointestinal issues and flushing were the most common adverse events observed. The majority of patients (84.6%) continued with DRF treatment, with tolerability issues being the primary reason for discontinuation. Efficacy analysis showed low relapse rates post-DRF initiation, with most patients exhibiting stable or improved Expanded Disability Status Scale scores and radiological assessments demonstrating minimal activity., Conclusion: This comprehensive analysis provides valuable insights into the real-world application of DRF, confirming its safety and tolerability while offering preliminary evidence of its efficacy in managing MS., Competing Interests: Declarations Funding Writing and editorial assistance was provided by Content Ed Net (Madrid, Spain) with funding from Biogen. Conflict of interest C.A. has received lecture honoraria, consultancy fees, and travel expenses from Biogen, Bristol Mayers Squibb, Merck, Novartis, Sanofi-Genzyme and Roche. A.A.T. has received fees as a speaker, consultant or travel support from Biogen, Almirall, Merck, Roche, Sanofi, Sandoz and Janssen. E.A. has no disclosures for financial affiliation, financial support nor grants moneys and has disclosure for speaker honorarium from Novartis, Merck and Biogen. JM.G.D. has received compensation as a consultant, researcher, or speaker from Biogen, Sanofi, Roche, Zenas Biopharma, Almirall, Novartis, Merck, Bristol-Myers-Squidd, and Johnson & Johnson. PM-E has received speaker and consultation fees from Allergan, Almirall, Biogen Idec, Merck, Merz, Novartis and Sanofi-Genzyme. V.G.Q has no conflict of interest related to this work. L.C.F. has received lecture honoraria, consultancy fees, clinical research funding, and travel expenses from Almirall, Amgen, AstraZeneca, Biogen, Bristol Mayers Squibb, Janssen, Merck, Neuraxpharma, Novartis, Sanofi-Genzyme, Roche. C.O.G. has received speaker and consultation fees from Alexion, Biogen Idec, BMS, Horizon, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. V.R.G. has received fees as a speaker, consultant or travel support from Almirall, Merck, Alexion, Roche and Sanofi. AB.C.R. has received honoraria as speaker/meeting moderator/courses/symposium organized by Almirall Prodesfarma S.A, Biogen Idec Inc, Bristol-Myers-Squibb, Janssen Pharmaceutical; Merck-Serono, Mylan, Novartis Pharmaceutical, Roche, Sanofi-Genzyme, Teva Pharmaceuticals; and for congress assistance from Biogen Idec Inc, Bial, Merck-Serono, Novartis Pharmaceutical, Roche, Sanofi-Genzyme, Teva Pharmaceuticals. J.R. has received speaking/consulting fees and/or travel funding from Merck, Sanofi-Genzyme, Roche, Biogen, Novartis, BMS, Jannsen and Teva. O.S. has received fees from Almirall, Biogen, Novartis, Merck, Sanofi, Alter, Bial, Teva, Neuraxfarma, Esteve, Pfizer, Roche and UCB. L.F. has no conflict of interest related to this work. F.P.P has no conflict of interest related to this work. A.A.R. has received fees as a speaker and advisor, and funding for attendance at congresses and other medical meetings, from Bayer, Biogen, Bristol, Janssen, Merck, Novartis, Roche, Sanofi and Teva. J.A.L. received consultant fees from Merck. F.I. has received speaker honoraria and travel reimbursement from Biogen, Merck, Novartis, Roche Spain, and Genzyme-Sanofi. V.C.R has no conflict of interest related to this work. AJ.C.V. has no conflict of interest related to this work. L.B. has no conflict of interest related to this work. V.G. has received speaker fees from Merck, Roche, Biogen, Novartis and Sanofi. L.A.R.A. declares to have received travel aid and financial compensation for talks from BMS and Novartis. R.G.R received payments from Biogen for participating in training conferences. AT.C.O. has received payments from Biogen for participating in training conferences for other professionals. JL.S.M. accepted travel compensation from Novartis, Merck and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer and Teva and has participated in clinical trials by Biogen, Sanofi, Merck and Roche. D.P.R. has received honoraria as a speaker, funding to attend courses and conferences, and consultancies and research grants from Merck, Biogen, Novartis, Sanofi, Teva, Roche and Almirall. F.G.M has received speaker honoraria and travel reimbursement from Biogen, Merck, Novartis, Roche Spain, and Genzyme-Sanofi. L.H.E. has received speaker and consultation fees from Biogen, Merck, Novartis, Roche and Sanofi. Ethics approval The research protocol received approval from the independent ethics committee at the Hospital Universitario de La Princesa (10 November 2022, acta CEIM 5723). Consent to participate This investigation adhered to the principles of the Helsinki Declaration and complied with the EU General Data Protection Regulation (GDPR). All personal identifiers were excluded from the findings. Consent for publication Not applicable. Data availability statement Data are available from the corresponding author upon reasonable request. Author contributions CAH and VML made substantial contributions to the conception and design of the work, interpretation of data and drafting the manuscript. All authors contributed to the acquisition of data and revised the manuscript and approved the version to be published. Code availability Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2024
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47. Beyond lines of treatment: embracing early high-efficacy disease-modifying treatments for multiple sclerosis management.
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Oreja-Guevara C, Martínez-Yélamos S, Eichau S, Llaneza MÁ, Martín-Martínez J, Peña-Martínez J, Meca-Lallana V, Alonso-Torres AM, Moral-Torres E, Río J, Calles C, Ares-Luque A, Ramió-Torrentà L, Marzo-Sola ME, Prieto JM, Martínez-Ginés ML, Arroyo R, Otano-Martínez MÁ, Brieva-Ruiz L, Gómez-Gutiérrez M, Rodríguez-Antigüedad A, Galán Sánchez-Seco V, Costa-Frossard L, Hernández-Pérez MÁ, Landete-Pascual L, González-Platas M, and Meca-Lallana JE
- Abstract
Recent advances in multiple sclerosis (MS) management have shifted perspectives on treatment strategies, advocating for the early initiation of high-efficacy disease-modifying therapies (heDMTs). This perspective review discusses the rationale, benefits, and challenges associated with early heDMT initiation, reflecting on the obsolescence of the traditional "first-line" and "second-line" treatment classifications. The article emerges from the last update of the consensus document of the Spanish Society of Neurology on the treatment of MS. During its development, there was a recognized need to further discuss the concept of treatment lines and the early use of heDMTs. Evidence from randomized controlled trials and real-world studies suggests that early heDMT initiation leads to improved clinical outcomes, including reduced relapse rates, slowed disease progression, and decreased radiological activity, especially in younger patients or those in early disease stages. Despite the historical belief that heDMTs involve more risks and adverse events compared to moderate-efficacy DMTs (meDMTs), some studies have reported comparable safety profiles between early heDMTs and meDMTs, though long-term safety data are still lacking. The review also addresses the need for a personalized approach based on patient characteristics, prognostic factors, and preferences, explores the importance of therapeutic inertia, and highlights the evolving landscape of international and national guidelines that increasingly advocate for early intensive treatment approaches. The article also addresses the challenges of ensuring access to these therapies and the importance of further research to establish long-term safety and effectiveness of DMTs in MS., (© The Author(s), 2024.)
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- 2024
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48. Clinical characteristics and impact on patient-reported outcomes and quality of life of people with ambulatory secondary progressive multiple sclerosis: DISCOVER study.
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Oreja-Guevara C, Meca-Lallana JE, Díaz-Díaz J, Ara JR, Hernández Pérez MÁ, Gracia Gil J, Alonso Torres AM, Pilo de la Fuente B, Ramió-Torrentà L, Eichau Madueño S, Gascón-Giménez F, Casanova B, Martínez-Yélamos S, Aguado Valcárcel M, Martínez Ginés ML, El Berdei Montero Y, López Real AM, González-Quintanilla V, De Torres L, Martínez-Rodríguez JE, Costa-Frossard L, Garcés Redondo M, Labiano Fontcuberta A, Castellanos-Pinedo F, García Merino JA, Muñoz Fernández C, Castillo-Triviño T, Meca-Lallana V, Peña Martínez J, Rodríguez-Antigüedad A, Prieto González JM, Agüera Morales E, Pérez Molina I, Solar Sánchez DM, Herrera Varo N, Romero Sevilla R, Gómez Vicente L, and Río J
- Subjects
- Humans, Female, Male, Middle Aged, Cross-Sectional Studies, Adult, Retrospective Studies, Spain, Quality of Life, Patient Reported Outcome Measures, Multiple Sclerosis, Chronic Progressive physiopathology, Multiple Sclerosis, Chronic Progressive economics, Multiple Sclerosis, Chronic Progressive psychology
- Abstract
Background: People with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population., Methods: DISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected., Results: A total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6-6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score. Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs., Conclusions: PwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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49. Association of MicroRNA Expression and Serum Neurofilament Light Chain Levels with Clinical and Radiological Findings in Multiple Sclerosis.
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Domínguez-Mozo MI, Casanova I, Monreal E, Costa-Frossard L, Sainz-de-la-Maza S, Sainz-Amo R, Aladro-Benito Y, Lopez-Ruiz P, De-Torres L, Abellán S, Garcia-Martinez MA, De-la-Cuesta D, Lourido D, Torrado-Carvajal A, Gomez-Barbosa C, Linares-Villavicencio C, Villar LM, López-De-Silanes C, Arroyo R, and Alvarez-Lafuente R
- Subjects
- Humans, Male, Female, Adult, Middle Aged, Prospective Studies, Longitudinal Studies, Brain diagnostic imaging, Brain pathology, Brain metabolism, Neurofilament Proteins blood, Neurofilament Proteins genetics, MicroRNAs blood, MicroRNAs genetics, Multiple Sclerosis blood, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis genetics, Multiple Sclerosis pathology, Biomarkers blood, Magnetic Resonance Imaging methods
- Abstract
microRNAs (miRNAs) are promising biomarkers for many diseases, including multiple sclerosis (MS). The neurofilament light chain (NfL) is a biomarker that can detect axonal damage in different neurological diseases. The objective of this study was to evaluate the association of the expression profile of pre-selected miRNAs and NfL levels with clinical and radiological variables in MS patients. We conducted a 1-year longitudinal prospective study in MS patients with different clinical forms. We measured clinical disability using the expanded disability status scale (EDSS), the magnetic resonance imaging (MRI) volumetry baseline, and cognitive functioning using the processing speed test (PST) at baseline and 1 year later. Selected serum miRNAs and serum NfL (sNfL) levels were quantified. Seventy-three patients were recruited. MiR-126.3p correlated with EDSS and cognitive status at baseline and miR-126.3p and miR-9p correlated with cognitive deterioration at 1 year. Correlations with regional brain volumes were observed between miR-126.3p and the cortical gray matter, cerebellum, putamen, and pallidum; miR-146a.5p with the cerebellum and pallidum; miR-29b.3p with white matter and the pallidum; miR-138.5p with the pallidum; and miR-9.5p with the thalamus. sNfL was correlated with miR-9.5p. miR-146a.5p was also associated with the MS phenotype. These data justify future studies to further explore the utility of miRNAs (mirR-126.3p, miR-146.5p, and miR.9-5p) and sNfL levels as biomarkers of MS.
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- 2024
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50. Progression independent of relapse activity can be predicted by passively acquired tapping speed through a smartphone for 1 month: A prospective study.
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Chico-Garcia JL, Sainz Amo R, Monreal E, Sainz de la Maza S, Rodriguez Jorge F, Masjuan J, Costa-Frossard L, and Villar LM
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- Humans, Female, Male, Adult, Middle Aged, Prospective Studies, Multiple Sclerosis physiopathology, Recurrence, Mobile Applications, Psychomotor Performance physiology, Smartphone, Disease Progression
- Abstract
Background: Tapping speed (TS) correlates with baseline disability scales in people with multiple sclerosis (pwMS)., Objective: The study aimed to address if progression independent of relapse activity (PIRA) could be predicted by first-month measurement of TS., Methods: Prospective study including pwMS in one referral MS center. Consecutive patients were included and keys/second (Keys/s) were passively measured each day using an in-house smartphone application for 1 month. Median, mean, and maximum keys/s were obtained. Multivariate logistic regression models (including keys/s, age, sex, and baseline disability scores) were obtained for prediction of a PIRA event after 1 year., Results: Overall, 59 patients were included in the final analysis (64.4% women, median age of 44.5 years). However, 10 patients presented a PIRA event, without differences regarding baseline characteristics between PIRA and no-PIRA groups. PIRA group presented lower median keys/s (2 vs 4 keys/s, p = 0.002) and mean keys/s (2.8 vs 4.6, p = 0.008), while maximum keys/s were similar ( p = 0.32). A median ⩽ 3 keys/s was independently associated with PIRA (aOR = 16.8, p = 0.03), as did a mean ⩽ 3.7 keys/s (aOR = 17, p = 0.02). These differences were not detected regarding other variables analyzed., Conclusion: Low median or mean keys/s obtained during initial month of assessment were indicative of a PIRA event within the next year., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.L.C-G. has received honorary for speaking engagements or consulting services from Biogen, Bayer, Bial, Bristol Myers Squibb, Johnson & Johnson, Roche, and Sanofi Genzyme. R.S.A. has received honorary for speaking engagements from Johnson & Johnson. E.M. received research grants, travel support, or honoraria for speaking engagements from Biogen, Merck, Novartis, Roche, Almirall, Janssen, Bristol Myers Squibb, and Sanofi Genzyme. F.R.J. has received honorary for speaking engagements or consulting services from Bial, Biogen, Johnson & Johnson, and Sanofi Genzyme. S.S.d.l.M. received payment for lecturing or travel expenses from Merck Serono, Biogen, Sanofi Genzyme, Roche, Janssen, and Novartis. L.C-F. received speaker fees and travel support, and served on advisory boards by Biogen, Sanofi, Merck, Bayer, Novartis, Roche, Teva, Celgene, Ipsen, Biopas, and Almirall. L.M.V. received research grants, travel support, or honoraria for speaking engagements from Biogen, Merck, Novartis, Roche, Sanofi Genzyme, Celgene, and Bristol Myers Squibb. The remaining authors have no conflicts of interest to declare.
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- 2024
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