Lesiones cerebrales captantes de gadolinio en el brote de los pacientes con esclerosis múltiple

Esclerosis múltiple; Brote; Resonancia magnéticaEsclerosi múltiple; Brot; Imatge per ressonància magnèticaMultiple sclerosis; Outbreak; Magnetic resonance imagingObjective 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

Mielitis. Diferencias entre esclerosis múltiple y otras etiologías

Resumen: Introducción: Un primer brote de mielitis puede ocurrir en el contexto de enfermedades desmielinizantes, inflamatorias sistémicas o infecciosas. Nuestro objetivo fue analizar las diferencias entre mielitis asociadas a esclerosis múltiple (EM) y mielitis por otras etiologías. Métodos: Análisis retrospectivo, unicéntrico, de pacientes con primer brote de mielitis (2000-2013). Se analizaron variables demográficas, etiológicas, clínicas, radiológicas y pronósticas, y se compararon entre mielitis por EM y mielitis por otras etiologías. Resultados: Se incluyó un total de 91 pacientes. Tiempo medio de seguimiento: 7 años. Diagnósticos: EM 57 (63%), mielitis transversa idiopática 22 (24%), asociada a enfermedades sistémicas 6 (7%), otros diagnósticos (6%). Mielitis por EM: menor edad de inicio (35 ± 11 vs .41 ± 13; p = 0,02), mayor afectación esfinteriana (40,4 vs. 27,3%; p = 0,05), mayor afectación multifocal en la RM medular (77,2 vs. 26,5%; p = 0,001), menor extensión de la lesión (segmentos vertebrales 2,4 vs. 1,4; p = 0,001), localización cervical (82,5 vs. 64,7%; p = 0,05) y localización posterior (89,5 vs. 41,2%; p = 0,001). Mielitis por otras etiologías: mayor localización anterior (47,1 vs. 24,6%; p = 0,02) y centromedular (47,1 vs. 14,1%; p = 0,001) y mejor recuperación al año (EDSS 2,0 vs. 1,5; p = 0,01). Análisis multivariante: la afectación multifocal medular (OR 9,38; IC 95%: 2,04-43,1) y del cordón posterior (OR 2,16; IC 95%: 2,04-2,67) se asociaron de forma independiente al diagnóstico de EM. Conclusiones: Un alto porcentaje de pacientes con un primer brote de mielitis serán diagnosticados de EM. La presencia de lesiones medulares multifocales y en el cordón posterior se asocian de forma significativa a este diagnóstico. Abstract: Background: Myelitis can appear as an initial symptom in the context of demyelinating diseases, systemic inflammatory diseases, and infectious diseases. We aim to analyse the differences between myelitis associated with multiple sclerosis (MS) and myelitis resulting from other aetiologies. Methods: Single-centre, retrospective analysis of patients with initial myelitis (2000-2013). Demographic, aetiological, clinical, radiological and prognostic variables were analysed and compared between patients with myelitis from MS and those with myelitis due to other aetiologies. Results: We included 91 patients; mean follow-up was 7 years. Diagnoses were as follows: MS 57 (63%), idiopathic transverse myelitis 22 (24%), associated systemic diseases 6 (7%), and other diagnoses (6%). Myelitis due to MS was associated with younger age of onset (35 ± 11 vs. 41 ± 13; P  =  .02), more pronounced sphincter involvement (40.4 vs. 27.3%; P=.05), greater multifocal involvement in spinal MRI (77.2 vs. 26.5%; P=.001), shorter lesion extension (2.4 vs. 1.4 vertebral segments; P=.001), cervical location (82.5 vs. 64.7%; P=.05) and posterior location (89.5 vs. 41.2%; P=.001). Myelitis due to other aetiologies more frequently showed anterior location (47.1 vs. 24.6%; P=.02), and central cord involvement (47.1 vs. 14.1%; P=.001), with better recovery at one year of follow up (EDSS 2.0 vs. 1.5; P=.01). Multivariate analysis showed that multifocal spinal cord involvement (OR 9.38, 95% CI: 2.04-43.1) and posterior cord involvement (OR 2.16, 95% CI: 2.04-2.67) were independently associated with the diagnosis of MS. Conclusions: A high percentage of patients with an initial myelitis event will be diagnosed with MS. The presence of multifocal and posterior spinal cord lesions was significantly associated with the diagnosis of MS. Palabras clave: Mielitis, Esclerosis múltiple, Mielitis idiopáticas, Enfermedades sistémicas, Keywords: Myelitis, Multiple sclerosis, Idiopathic myelitis, Systemic disease

Myelitis: Differences between multiple sclerosis and other aetiologies

Background: Myelitis can appear as an initial symptom in the context of demyelinating diseases, systemic inflammatory diseases, and infectious diseases. We aim to analyse the differences between myelitis associated with multiple sclerosis (MS) and myelitis resulting from other aetiologies. Methods: Single-centre, retrospective analysis of patients with initial myelitis (2000-2013). Demographic, aetiological, clinical, radiological and prognostic variables were analysed and compared between patients with myelitis from MS and those with myelitis due to other aetiologies. Results: We included 91 patients; mean follow-up was 7 years. Diagnoses were as follows: MS 57 (63%), idiopathic transverse myelitis 22 (24%), associated systemic diseases 6 (7%), and other diagnoses (6%). Myelitis due to MS was associated with younger age of onset (35 ± 11 vs 41 ± 13; P = .02), more pronounced sphincter involvement (40.4% vs 27.3%; P = .05), greater multifocal involvement in spinal MRI (77.2% vs 26.5%; P = .001), shorter lesion extension (2.4 vs. 1.4 vertebral segments; P = .001), cervical location (82.5% vs 64.7%; P = .05) and posterior location (89.5% vs 41.2%; P = .001). Myelitis due to other aetiologies more frequently showed anterior location (47.1% vs 24.6%; P = .02), and central cord involvement (47.1% vs 14.1%; P = .001), with better recovery at one year of follow up (EDSS 2.0 vs 1.5; P = .01). Multivariate analysis showed that multifocal spinal cord involvement (OR 9.38, 95% CI: 2.04-43.1) and posterior cord involvement (OR 2.16, 95% CI: 2.04-2.67) were independently associated with the diagnosis of MS. Conclusions: A high percentage of patients with an initial myelitis event will be diagnosed with MS. The presence of multifocal and posterior spinal cord lesions was significantly associated with the diagnosis of MS. Resumen: Introducción: Un primer brote de mielitis puede ocurrir en el contexto de enfermedades desmielinizantes, inflamatorias sistémicas o infecciosas. Nuestro objetivo fue analizar las diferencias entre mielitis asociadas a esclerosis múltiple (EM) y mielitis por otras etiologías. Métodos: Análisis retrospectivo, unicéntrico, de pacientes con primer brote de mielitis (2000-2013). Se analizaron variables demográficas, etiológicas, clínicas, radiológicas y pronósticas, y se compararon entre mielitis por EM y mielitis por otras etiologías. Resultados: Se incluyó un total de 91 pacientes. Tiempo medio de seguimiento: 7 años. Diagnósticos: EM 57 (63%), mielitis transversa idiopática 22 (24%), asociada a enfermedades sistémicas 6 (7%), otros diagnósticos (6%). Mielitis por EM: menor edad de inicio (35 ± 11 vs .41 ± 13; p = 0,02), mayor afectación esfinteriana (40,4 vs 27,3%; p = 0,05), mayor afectación multifocal en la RM medular (77,2 vs 26,5%; p = 0,001), menor extensión de la lesión (segmentos vertebrales 2,4 vs 1,4; p = 0,001), localización cervical (82,5 vs 64,7%; p = 0,05) y localización posterior (89,5 vs 41,2%; p = 0,001). Mielitis por otras etiologías: mayor localización anterior (47,1 vs 24,6%; p = 0,02) y centromedular (47,1 vs 14,1%; p = 0,001) y mejor recuperación al año (EDSS 2,0 vs 1,5; p = 0,01). Análisis multivariante: la afectación multifocal medular (OR 9,38; IC 95%: 2,04-43,1) y del cordón posterior (OR 2,16; IC 95%: 2,04-2,67) se asociaron de forma independiente al diagnóstico de EM. Conclusiones: Un alto porcentaje de pacientes con un primer brote de mielitis serán diagnosticados de EM. La presencia de lesiones medulares multifocales y en el cordón posterior se asocian de forma significativa a este diagnóstico. Keywords: Myelitis, Multiple sclerosis, Idiopathic myelitis, Systemic diseases, Palabras clave: Mielitis, Esclerosis múltiple, Mielitis idiopáticas, Enfermedades sistémica

Gadolinium-enhanced brain lesions in multiple sclerosis relapse Lesiones cerebrales captantes de gadolinio en el brote de los pacientes con esclerosis múltiple

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

Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration

Introductio: Based on the advances in the treatment of multiple sclerosis (MS), currently available disease-modifying treatments (DMT) have positively influenced the disease course of MS. However, the efficacy of DMT is highly variable and increasing treatment efficacy comes with a more severe risk profile. Hence, the unmet need for safer and more selective treatments remains. Specifically restoring immune tolerance towards myelin antigens may provide an attractive alternative. In this respect, antigen-specific tolerisation with autologous tolerogenic dendritic cells (tolDC) is a promising approach. Methods and analysis: Here, we will evaluate the clinical use of tolDC in a well-defined population of MS patients in two phase I clinical trials. In doing so, we aim to compare two ways of tolDC administration, namely intradermal and intranodal. The cells will be injected at consecutive intervals in three cohorts receiving incremental doses of tolDC, according to a best-of-five design. The primary objective is to assess the safety and feasibility of tolDC administration. For safety, the number of adverse events including MRI and clinical outcomes will be assessed. For feasibility, successful production of tolDC will be determined. Secondary endpoints include clinical and MRI outcome measures. The patients’ immune profile will be assessed to find presumptive evidence for a tolerogenic effect in vivo. Ethics and dissemination: Ethics approval was obtained for the two phase I clinical trials. The results of the trials will be disseminated in a peer-reviewed journal, at scientific conferences and to patient associations

Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration

Introductio: Based on the advances in the treatment of multiple sclerosis (MS), currently available disease-modifying treatments (DMT) have positively influenced the disease course of MS. However, the efficacy of DMT is highly variable and increasing treatment efficacy comes with a more severe risk profile. Hence, the unmet need for safer and more selective treatments remains. Specifically restoring immune tolerance towards myelin antigens may provide an attractive alternative. In this respect, antigen-specific tolerisation with autologous tolerogenic dendritic cells (tolDC) is a promising approach. Methods and analysis: Here, we will evaluate the clinical use of tolDC in a well-defined population of MS patients in two phase I clinical trials. In doing so, we aim to compare two ways of tolDC administration, namely intradermal and intranodal. The cells will be injected at consecutive intervals in three cohorts receiving incremental doses of tolDC, according to a best-of-five design. The primary objective is to assess the safety and feasibility of tolDC administration. For safety, the number of adverse events including MRI and clinical outcomes will be assessed. For feasibility, successful production of tolDC will be determined. Secondary endpoints include clinical and MRI outcome measures. The patients’ immune profile will be assessed to find presumptive evidence for a tolerogenic effect in vivo. Ethics and dissemination: Ethics approval was obtained for the two phase I clinical trials. The results of the trials will be disseminated in a peer-reviewed journal, at scientific conferences and to patient associations