Practical tool to identify Spasticity-Plus Syndrome amongst patients with multiple sclerosis. Algorithm development based on a conjoint analysis.

Introduction: The Spasticity-Plus Syndrome (SPS) in multiple sclerosis (MS) refers to a combination of spasticity and other signs/symptoms such as spasms, cramps, bladder dysfunction, tremor, sleep disorder, pain, and fatigue. The main purpose is to develop a user-friendly tool that could help neurologists to detect SPS in MS patients as soon as possible. Methods: A survey research based on a conjoint analysis approach was used. An orthogonal factorial design was employed to form 12 patient profiles combining, at random, the eight principal SPS signs/symptoms. Expert neurologists evaluated in a survey and a logistic regression model determined the weight of each SPS sign/symptom, classifying profiles as SPS or not. Results: 72 neurologists participated in the survey answering the conjoint exercise. Logistic regression results of the survey showed the relative contribution of each sign/symptom to the classification as SPS. Spasticity was the most influential sign, followed by spasms, tremor, cramps, and bladder dysfunction. The goodness of fit of the model was appropriate (AUC = 0.816). Concordance between the experts' evaluation vs. model estimation showed strong Pearson's (r = 0.936) and Spearman's (r = 0.893) correlation coefficients. The application of the algorithm provides with a probability of showing SPS and the following ranges are proposed to interpret the results: high (> 60%), moderate (30-60%), or low (< 30%) probability of SPS. Discussion: This study offers an algorithmic tool to help healthcare professionals to identify SPS in MS patients. The use of this tool could simplify the management of SPS, reducing side effects related with polypharmacotherapy.

Debut de enfermedad de Crohn durante tratamiento con ocrelizumab en paciente con esclerosis múltiple / Crohn's disease induced by ocrelizumab in a patient with multiple sclerosis

La enfermedad inflamatoria intestinal (EII) inducida por fármacos es una entidad clínica en aumento debido al uso frecuente de terapia inmunosupresora y biológica. Presentamos el caso de una paciente diagnosticada de enfermedad de Crohn durante el tratamiento con Ocrelizumab, anticuerpo monoclonal humanizado anti-CD20 aprobado para el tratamiento de la esclerosis múltiple. Se desconoce el mecanismo exacto por el que los fármacos inmunomoduladores pueden desencadenar EII, pero dado que la EII y la esclerosis múltiple son procesos incluidos dentro del espectro de enfermedades inmunomediadas, podríamos postular que el Ocrelizumab, al igual que otros anti-CD20 como el Rituximab o anti-TNF como Etanercept, pueda desencadenar o desenmascarar EII en pacientes genéticamente predispuestos. (AU)

Crohn's disease induced by ocrelizumab in a patient with multiple sclerosis.

Drug-induced inflammatory bowel disease (IBD) is a clinical entity on the rise due to the frequent use of immunomodulatory therapy. Here we report the case of Crohn's disease due to Ocrelizumab, a humanized anti-CD20 monoclonal antibody approved for the treatment of multiple sclerosis. The exact mechanism by which anti-CD20 antibodies can trigger IBD is unknown, but since IBD and multiple sclerosis are processes included within the spectrum of immunomediated diseases, we could suggest that Ocrelizumab could trigger IBD in genetically predisposed patients.

Clinical characterization and outcomes of 85 patients with neurosarcoidosis.

To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confirmation of granulomatous disease was used to subclassify NS into definite (confirmation in neurological tissue), probable (confirmation in extraneurological tissue) and possible (no histopathological confirmation of the disease). Of the 1532 patients included in the cohort, 85 (5.5%) fulfilled the Stern criteria for NS (49 women, mean age at diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In 59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the disease. According to the classification proposed by Stern et al., 11 (13%) were classified as a definite NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with the systemic phenotype of patients without NS, patients with CNS involvement presented a lower frequency of thoracic involvement (82% vs 93%, q = 0.018), a higher frequency of ocular (27% vs 10%, q < 0.001) and salivary gland (15% vs 4%, q = 0.002) WASOG involvements. In contrast, patients with PNS involvement showed a higher frequency of liver involvement (36% vs 12%, p = 0.02) in comparison with patients without NS. Neurosarcoidosis was identified in 5.5% of patients. CNS involvement prevails significantly over PNS involvement, and both conditions do not overlap in any patient. The systemic phenotype associated to each involvement was clearly differentiated, and can be helpful not only in the early identification of neurological involvement, but also in the systemic evaluation of patients diagnosed with neurosarcoidosis.

Réplica: Valoración de la atrofia cerebral en la esclerosis múltiple mediante el índice de cuerpo calloso / Reply: Appraisal of cerebral atrophy in multiple sclerosis by means of the corpus callosum index

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Valoración de la atrofia cerebral en la esclerosis múltiple mediante el índice de cuerpo calloso / Appraisal of cerebral atrophy in multiple sclerosis by means of the corpus callosum index

Introducción. La esclerosis múltiple se caracteriza en su evolución por el desarrollo de atrofia cerebral. Su monitorización resulta de interés para evaluar la respuesta al tratamiento, y son de elección los análisis volumétricos cerebrales, actualmente confinados al ámbito de la investigación. Objetivo. Analizar el índice de cuerpo calloso (ICC) como una posible alternativa a los métodos basados en la segmentación cerebral. Sujetos y métodos. Se reúne a 109 pacientes con enfermedades desmielinizantes de reciente diagnóstico (90 con esclerosis múltiple remitente recurrente, 7 con formas primarias progresivas y 12 con síndrome desmielinizante aislado) y se calcula el ICC en su primer estudio de resonancia magnética cerebral, así como en 101 controles sanos. Las secuencias de los pacientes se someten a análisis volumétrico mediante el programa MSmetrix. Resultados. El valor medio del ICC es de 0,377 en los pacientes y 0,411 en los controles, y la diferencia es estadísticamente significativa (p < 0,001). El ICC muestra una correlación estadísticamente significativa con el volumen encefálico (p < 0,001; r = 0,444) y con el volumen lesional en secuencia FLAIR (p < 0,001; r = -0,521), mientras que no se demuestra asociación con el volumen de la sustancia gris (p = 0,058). Conclusiones. El ICC se relaciona con el volumen encefálico global obtenido mediante técnicas volumétricas y puede reflejar la presencia de atrofia ya en los estadios iniciales de las enfermedades desmielinizantes, por lo que se presenta como una alternativa de rápido y sencillo cálculo

Introduction. The course of multiple sclerosis is characterised by the development of cerebral atrophy. It is of interest to monitor it in order to evaluate the treatment response, and the preferred technique consists in performing brain volume analyses, which are currently restricted to the field of research. Aim. To analyse the corpus callosum index (CCI) as a possible alternative to the methods based on brain segmentation. Subjects and methods. Our sample was made up of 109 patients with recently diagnosed demyelinating diseases (90 relapsing-remitting multiple sclerosis, 7 primary progressive forms and 12 isolated demyelinating syndromes), and the CCI was calculated in their first magnetic resonance brain scan, together with 101 healthy controls. The sequences of the patients were submitted to a volumetric analysis using the software package MSmetrix. Results. The mean value of the CCI was 0.377 in patients and 0.411 in the controls, and the difference was statistically significant (p < 0.001). The CCI also showed a statistically significant correlation with the brain volume (p < 0.001; r = 0.444) and with the lesional volume in the FLAIR sequence (p < 0.001; r = -0.521), while no association was observed with the volume of grey matter (p = 0.058). Conclusions. The CCI is related to the overall brain volume obtained by volumetric techniques and may reflect the presence of atrophy in the initial stages of demyelinating diseases, which makes it a fast and easy to calculate alternative

The impact of rituximab infusion protocol on the long-term outcome in anti-MuSK myasthenia gravis.

Objective: To evaluate whether the clinical benefit and relapse rates in anti-muscle-specific kinase (MuSK) myasthenia gravis (MG) differ depending on the protocol of rituximab followed. Methods: This retrospective multicentre study in patients with MuSK MG compared three rituximab protocols in terms of clinical status, relapse, changes in treatment, and adverse side effects. The primary effectiveness endpoint was clinical relapse requiring a further infusion of rituximab. Survival curves were estimated using Kaplan-Meier methods and survival analyses were undertaken using Cox proportional-hazards models. Results: Twenty-five patients were included: 11 treated with protocol 4 + 2 (375 mg/m2/4 weeks, then monthly for 2 months), five treated with protocol 1 + 1 (two 1 g doses 2 weeks apart), and nine treated with protocol 4 (375 mg/m2/4 weeks). Mean follow-up was 5.0 years (SD 3.3). Relapse occurred in 18.2%, 80%, and 33.3%, and mean time to relapse was 3.5 (SD 1.5), 1.1 (SD 0.4), and 2.5 (SD 1.4) years, respectively. Based on Kaplan-Meier estimates, patients treated with protocol 4 + 2 had fewer and later relapses than patients treated with the other two protocols (log-rank test P = 0.0001). Patients treated with protocol 1 + 1 had a higher risk of relapse than patients treated with protocol 4 + 2 (HR 112.8, 95% CI, 5.7-2250.4, P = 0.002). Patients treated with protocol 4 showed a trend to a higher risk of relapse than those treated with protocol 4 + 2 (HR 9.2, 95% CI 0.9-91.8, P = 0.059). Interpretation: This study provides class IV evidence that the 4 + 2 rituximab protocol has a lower clinical relapse rate and produces a more durable response than the 1 + 1 and 4 protocols in patients with MuSK MG.

Revisión de las novedades del XXXII Congreso ECTRIMS 2016, presentadas en la IX Reunión Post-ECTRIMS (I) / Review of the novelties from the 32nd ECTRIMS Congress, 2016, presented at the 9th Post-ECTRIMS Meeting (I)

Por noveno año consecutivo se ha celebrado en Madrid (España) la Reunión Post-ECTRIMS con el objetivo de presentar y discutir los temas más debatidos en el congreso ECTRIMS de la mano de reconocidos especialistas en esclerosis múltiple de nuestro país. Fruto de esta actividad científica, avalada por la Sociedad Española de Neurología, se genera este artículo de revisión que sale publicado en dos partes. Esta primera parte aborda la planificación familiar en las mujeres con esclerosis múltiple, el manejo del embarazo y el papel de la lactancia. Se dirige la atención a la población pediátrica, a las características de la resonancia magnética y a los factores de riesgo geneticoambientales para el desarrollo de la enfermedad en niños, sin olvidar los factores de riesgo de progresión en los adultos. Se actualiza la epidemiología del deterioro cognitivo en los pacientes con esclerosis múltiple, las ventajas e inconvenientes de las herramientas de evaluación disponibles, y los enfoques actuales de manejo, y se insiste en la importancia de la afectación cognitiva en el curso de la enfermedad. Además, se introduce el concepto de medicina individualizada y de precisión, desde el diagnóstico de la enfermedad hasta el tratamiento, con las polémicas que inevitablemente surgen en el manejo de los pacientes, principalmente en lo relacionado con el cambio de tratamiento y el manejo de riesgos asociados (AU)

For the ninth year in a row the Post-ECTRIMS Meeting has been held in Madrid (Spain) with the aim of presenting and discussing the hottest issues debated at the ECTRIMS Congress by renowned specialists in multiple sclerosis in our country. One outcome of this scientific activity, endorsed by the Spanish Neurology Society, is this review article, which is published in two parts. This first part addresses family planning, pregnancy management and the role of breastfeeding in women with multiple sclerosis. Attention is drawn to the paediatric population, to magnetic resonance imaging features and to the genetic-environmental risk factors for developing the disease in children, without neglecting the risk factors for development in adults. The review updates the epidemiology of cognitive deterioration in patients with multiple sclerosis, the advantages and disadvantages of available assessment tools, and current management approaches, while also insisting on the importance of cognitive involvement during the course of the disease. Furthermore, the concept of individualised, precision medicine is introduced, from the diagnosis of the disease until its treatment, with the controversies that inevitably arise in patient management, above all with regard to the change of treatment and the handling of associated risks (AU)

Revisión de las novedades del XXXII Congreso ECTRIMS 2016, presentadas en la IX Reunión Post-ECTRIMS (II) / Review of the novelties from the 32nd ECTRIMS Congress, 2016, presented at the 9th Post-ECTRIMS Meeting (II)

Por noveno año consecutivo se ha celebrado en Madrid (España) la Reunión Post-ECTRIMS con el objetivo de presentar y discutir los temas más debatidos en el congreso ECTRIMS de la mano de reconocidos especialistas en esclerosis múltiple de nuestro país. Fruto de esta reunión científica, avalada por la Sociedad Española de Neurología, se genera este artículo de revisión que sale publicado en dos partes. En esta segunda parte se pone de manifiesto la controversia actual en el manejo de la esclerosis múltiple, especialmente en cuanto a formas progresivas y diagnóstico diferencial se refiere. Se presentan los últimos avances en remielinización, donde destaca el uso de la técnica con micropilares en el laboratorio, y en neuroprotección, la cual se revisa a través del estudio del nervio óptico. Los anticuerpos anti-CD20 ofrecen grandes expectativas, y estamos ante un nuevo mecanismo de acción y diana terapéutica en unas células a las que les habíamos prestado poca atención hasta la fecha. Otro hecho destacable es la elevada correlación entre los niveles de neurofilamentos en el líquido cefalorraquídeo y el suero, que podría evitar el uso del líquido cefalorraquídeo como muestra biológica en futuros estudios de biomarcadores. También se anticipan los avances en investigación clínica que en el futuro acabarán convergiendo en la práctica clínica, condicionando los pasos que se deberán seguir en el abordaje terapéutico de la esclerosis múltiple (AU)

For the ninth year in a row the Post-ECTRIMS Meeting has been held in Madrid (Spain) with the aim of presenting and discussing the hottest issues debated at the ECTRIMS Congress by renowned specialists in multiple sclerosis in our country. One outcome of this scientific activity, endorsed by the Spanish Neurology Society, is this review article, which is published in two parts. This second part reflects the current controversy over the management of multiple sclerosis, especially as regards the progressive forms and their differential diagnosis. The work presents the latest advances in remyelination, where the use of the micropillar technique in laboratory stands out, and in neuroprotection, which is reviewed through a study of the optic nerve. Anti-CD20 antibodies are a very promising development and we find ourselves before a new mechanism of action and therapeutic target in cells to which little attention has been paid to date. Another notable fact is the high correlation between the levels of neurofilaments in cerebrospinal fluid and in serum, which could make it possible to avoid the use of cerebrospinal fluid as a biological sample in future studies of biomarkers. The review also provides a preview of the advances in clinical research, which will converge in clinical practice in the future, thereby conditioning the steps that should be taken in the therapeutic management of multiple sclerosis (AU)

Involuntary movements of pelvic stump.

Although involuntary movements of stumps are less frequent than phantom sensation or other neurological sequelae of limb amputation, they represent a phenomenon that has been known for many years. The pathophysiology remains unknown, but it seems to be related to damage to the peripheral nervous system. Treatment is not standardized, but antimyoclonic drugs seem to be useful.

Latent orbital pseudotumor secondary to systemic lupus erythematosus.

Orbital inflammatory pseudotumor is a rare complication of systemic lupus erythematosus. It may present a challenge for differential diagnosis, especially in the context of treatment with hydroxychloroquine, although dosage and duration of the treatment may guide us. Although high antibody titers can be found, this is not specific.

Revisión de las novedades del XXXI Congreso ECTRIMS 2015, presentadas en la VIII Reunión Post-ECTRIMS / Review of the novelties from the 31st ECTRIMS Congress, 2015, presented at the 8th Post-ECTRIMS meeting

Reconocidos especialistas nacionales en esclerosis múltiple (EM) se han reunido, por octavo año consecutivo, para exponer lo más novedoso que se presentó en la última edición del congreso ECTRIMS 2015 y que recoge esta revisión. En esta edición ha destacado la nueva clasificación de los fenotipos de la EM. También se revisaron los criterios diagnósticos del espectro de la neuromielitis óptica y los problemas en el diagnóstico diferencial derivados de la falta de definición del espectro radiológico. La microbiota adquiere protagonismo como posible factor determinante de la enfermedad, junto con factores extrínsecos como el tabaco, la ingesta de sal o el déficit de vitamina D. Los avances en inmunomodulación impulsan el progreso en el tratamiento de la EM. El ocrelizumab es el primer tratamiento con resultados positivos en las formas primariamente progresivas, y el tocilizumab, un fármaco para la artritis reumatoide, destaca como candidato potencial para el tratamiento de la neuromielitis óptica. Ciertos antibióticos y vitaminas también podrían tener un papel en el tratamiento de la EM. En esta edición se prestó especial atención a la terapia personalizada. Actualmente disponemos de 11 fármacos aprobados en Europa. Se necesitan algoritmos terapéuticos que nos ayuden a elegir el mejor tratamiento para cada paciente. Asimismo, necesitamos poder identificar en los estadios precoces de la enfermedad el riesgo de desarrollar discapacidad, para diseñar estrategias terapéuticas, para lo que se precisan biomarcadores moleculares y otras herramientas pronósticas. Los problemas aún existentes en la tecnología del software en resonancia magnética dificultan su traslación a la práctica clínica diaria (AU)

Renowned national specialists in multiple sclerosis (MS) met, for the eighth year in a row, to give details of the latest novelties presented at the last ECTRIMS Congress 2015, which are included in this review. One of the highlights at this Congress was the new classification of the phenotypes of MS. Both the diagnostic criteria of the neuromyelitis optica spectrum and the problems involved in the differential diagnosis derived from the lack of definition of the radiological spectrum were reviewed. The microbiota comes to the fore as a possible factor determining the disease, together with extrinsic factors such as tobacco, salt ingestion or vitamin D deficiency. Advances made in immunomodulation are driving the progress being made in the treatment of MS. Ocrelizumab is the first treatment with positive results in the primarily progressive forms and tocilizumab, a drug product for rheumatoid arthritis, stands out as a potential candidate for the treatment of neuromyelitis optica. Certain antibiotics and vitamins could also play a role in the treatment of MS. In this edition of the Congress special attention was paid to personalised therapy. To date, 11 drugs have been approved for use in Europe. There is a need for therapeutic algorithms that help us to choose the best treatment for each patient. Likewise, we need to be able to identify, in the early stages of the disease, the risk of developing disability, so as to be able to design therapeutic strategies. To do so, molecular biomarkers and other predictive tools are required. The problems that still exist in software technology in magnetic resonance hinder its application in daily clinical practice (AU)

IFN beta 1a as Glucocorticoids-Sparing Therapy in a Patient with CLIPPERS.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described inflammatory disease of the central nervous system, distinguished by brainstem- and spinal cord-centered lesions with a characteristic contrast enhancement on MRI, a lymphocytic perivascular infiltrate on pathological exam, and a dramatic response to and dependence on steroids therapy. Since its initial description in 2010, different glucocorticoid-sparing agents, mostly immunosuppressant drugs, have been used to minimize the dosage, but these therapies also carry the risk of important secondary effects. We present the first reported case of CLIPPERS treated with interferon beta 1a as add-on therapy. CASE REPORT: A previously healthy 31-year-old man presented with gait ataxia and dysarthria. MRI showed pons-centered hyperintense patchy lesions on T2-weighted images. Additional tests ruled out other possible diagnoses and symptoms reversed with intravenous methylprednisolone. Over the years the patient presented with several episodes of deterioration each year, which were partly reversed with glucocorticoid therapy, but leaving him with growing sequelae. Four years after the initial event, treatment with interferon-beta-1a was initiated, achieving reduced frequency of the relapses to 1 every 4 years, which were no longer associated to increasing disability. This allowed reducing glucocorticoids to 30 mg of Deflazacort every other day. CONCLUSIONS: Interferon beta-1a could be an alternative to corticosteroid-combined therapy in CLIPPERS and its more benign profile of secondary effects compared to immunosuppressants could make it an attractive choice.

Fingolimod: efectividad y seguridad en la práctica clínica habitual. Estudio observacional, retrospectivo y multicéntrico en Asturias y Cantabria / Fingolimod: effectiveness and safety in routine clinical practice. An observational, retrospective, multi-centre study in Asturias and Cantabria

Objetivo. Evaluar la efectividad y seguridad del fingolimod en la práctica clínica habitual en la región de Asturias y Cantabria (España). Pacientes y métodos. Estudio retrospectivo y multicéntrico de pacientes con esclerosis múltiple recurrente remitente tratados con fingolimod, según la ficha técnica. La efectividad se evaluó en los pacientes con al menos un año de tratamiento. Se calculó la tasa anualizada de brotes (TAB), el porcentaje de pacientes libres de brotes y libres de lesiones captantes de gadolinio, y los que mejoraron/mantuvieron la puntuación en la escala expandida del estado de discapacidad (EDSS). Se analizó la población total y según el tratamiento previo: inmunomodulador (interferón beta-1 o acetato de glatiramero) o natalizumab. Resultados. Un total de 138 pacientes iniciaron tratamiento con fingolimod; el 60% recibió previamente inmunomodulador; el 28%, natalizumab; y el 9%, ningún tratamiento. Noventa y nueve pacientes estuvieron al menos un año en tratamiento con fingolimod. Después de un año de tratamiento, el fingolimod disminuyó la TAB en un 67% (1,26 a 0,42; p < 0,0001), aumentó el porcentaje de pacientes libres de brotes de un 24% a un 69% (p < 0,0001), y el porcentaje de pacientes libres de lesiones captantes de gadolinio de un 70% a un 85% (p < 0,0106). El 77% de los pacientes mejoró/mantuvo la puntuación en la EDSS. Resultados similares se observaron en pacientes tratados previamente con inmunomodulador. La efectividad de los pacientes tratados previamente con natalizumab se mantuvo tras el tratamiento con fingolimod. Conclusiones. La práctica clínica habitual en las regiones de Asturias y Cantabria muestra que el fingolimod tiene resultados similares a los observados en los ensayos clínicos, al comparar las variables clinicorradiológicas utilizadas en estos últimos (AU)

Aim. To evaluate the effectiveness and safety of fingolimod in routine clinical practice in the region of Asturias and Cantabria (Spain). Patients and methods. We conducted a retrospective multicentre study of patients with relapsing-remitting multiple sclerosis treated with fingolimod, in accordance with the product data sheet. Effectiveness was evaluated in patients with at least one year’s treatment. The following were calculated: annualised relapse rate (ARR), the percentage of patients free from relapses and free from gadolinium-enhancing lesions, and those who improved/maintained their score on the Expanded Disability Status Scale (EDSS). Both total population and according to previous treatment: immunomodulator (interferon beta-1 or glatiramer acetate) or natalizumab, were analysed. Results. A total of 138 patients started treatment with fingolimod; 60% previously received an immunomodulator; 28% were given natalizumab; and 9% had no treatment. Ninety-nine patients were treated with fingolimod for at least one year. After one year of treatment, fingolimod decreased the ARR by 67% (1.26 to 0.42; p < 0.0001), increased the percentage of patients free from relapses from 24% to 69% (p < 0.0001) and the percentage of patients free from gadoliniumenhancing lesions from 70% to 85% (p < 0.0106). Altogether, 77% of the patients improved/maintained their score on the EDSS. Similar results were observed in patients previously treated with an immunomodulator. The effectiveness of the patients previously treated with natalizumab remained the same following treatment with fingolimod. Conclusions. Routine clinical practice in the regions of Asturias and Cantabria shows that fingolimod yields similar results to those observed in clinical trials, on comparing the clinicoradiological variables used in them (AU)

Revisión de las novedades del congreso conjunto ECTRIMS-ACTRIMS 2014, presentadas en la VII Reunión Post-ECTRIMS (I) / Review of the novelties from the 2014 ECTRIMS-ACTRIMS Joint Congress, presented at the 7th Post-ECTRIMS meeting (I)

Por séptimo año consecutivo se ha celebrado en Madrid (España) la Reunión Post-ECTRIMS. Reconocidos especialistas en esclerosis múltiple y líderes de opinión nacionales se han reunido un año más para exponer las novedades presentadas en el Congreso Mundial ECTRIMS-ACTRIMS 2014, y fruto de esa reunión se genera esta revisión que sale publicada en dos partes. Como principales conclusiones de esta primera parte se destaca el mayor entendimiento del componente genético de la esclerosis múltiple al que estamos asistiendo, el cual no resulta suficiente si no se considera su interacción con los factores ambientales de riesgo de la enfermedad, ni el impacto de la comorbilidad y de las conductas saludables en la susceptibilidad y pronóstico de los pacientes. Al respecto, los autores insisten en que, en la práctica clínica, las alteraciones cognitivas y psiquiátricas están infradiagnosticadas y son poco consideradas en la investigación clínica; no obstante, la evidencia, aunque escasa, apunta hacia posibles beneficios de los fármacos modificadores de la enfermedad y alternativas al tratamiento inhibidor selectivo de la recaptación de serotonina. El abordaje de las subpoblaciones en esclerosis múltiple y variantes de la enfermedad refuerza la importancia del diagnóstico precoz y preciso para ofrecer a los pacientes un pronóstico y un tratamiento más seguros y personalizados. La esclerosis múltiple pediátrica es idónea para estudiar factores de riesgo de la enfermedad, pero dada su baja prevalencia, se cuestionan los estudios prospectivos y se aboga por los estudios colaborativos (AU)

For the seventh year in a row the Post-ECTRIMS Meeting has been held in Madrid (Spain). Renowned specialists in multiple sclerosis and national leaders in this area have gathered once again to discuss the novelties presented at the 2014 ECTRIM-ACTRIMS World Congress. That meeting gave rise to this review, which will be published in two parts. One of the main conclusions in this first part is the deeper understanding of the genetic component of multiple sclerosis that we are acquiring, although it is still insufficient unless we bear in mind its interaction with the environmental risk factors of the disease or the impact of comorbidity and healthy habits on the patients’ susceptibility and prognosis. In this respect, the authors insist on the fact that, in clinical practice, the cognitive and psychiatric disorders remain under-diagnosed and are rarely taken into account in clinical research. Yet, although scarce, the evidence we have points to the possible benefits of disease-modifying drugs and alternatives to treatment with selective serotonin reuptake inhibitors. Addressing the subpopulations in multiple sclerosis and variants of the disease enhances the importance of an early accurate diagnosis in order to offer patients a safer and more personalised prognosis and treatment. Paediatric multiple sclerosis is ideal for studying the risk factors of the disease but, given its low prevalence, the use of prospective studies raises a number of doubts and there is a preference for conducting collaborative studies (AU)

Revisión de las novedades del congreso conjunto ECTRIMS-ACTRIMS 2014, presentadas en la VII Reunión Post-ECTRIMS (II) / Review of the novelties from the 2014 ECTRIMS-ACTRIMS Joint Congress, presented at the 7th Post-ECTRIMS Meeting (II)

Por séptimo año consecutivo se ha celebrado en Madrid (España) la Reunión Post-ECTRIMS. Reconocidos especialistas en esclerosis múltiple y líderes de opinión nacionales se han reunido un año más para exponer las novedades presentadas en el Congreso Mundial ECTRIMS-ACTRIMS 2014, y fruto de esa reunión se genera esta revisión que se publica en dos partes. En esta segunda parte se pone de manifiesto que los fenómenos inmunológicos cada vez están más presentes en la patogenia de la enfermedad, y que la interacción entre inflamación y neurodegeneración es más evidente. Fenómenos metabólicos, de disfunción mitocondrial y de estrés oxidativo también se implican en la degeneración axonal, y los modelos experimentales abren paso a nuevos enfoques terapéuticos con esperanza para las estrategias regenerativas. Aunque resulte ambicioso, los progenitores neurales inducibles se convierten en una prometedora alternativa a los tratamientos convencionales con células madre, y la identificación de nuevas variantes genéticas de susceptibilidad a la esclerosis múltiple abre camino al descubrimiento de nuevos fármacos. Replantear el valor de antiguos fármacos y procedimientos sería otra alternativa de desarrollo terapéutico (AU)

For the seventh year in a row the Post-ECTRIMS Meeting has been held in Madrid (Spain). Renowned specialists in multiple sclerosis and national leaders in this area have gathered once again to discuss the novelties presented at the 2014 ECTRIM-ACTRIMS World Congress. That meeting gave rise to this review, which is published in two parts. This second part shows that immunological phenomena are increasingly more present in the pathogenesis of the disease, and that the interaction between inflammation and neurodegeneration is becoming more apparent. Metabolic, mitochondrial dysfunction and oxidative stress phenomena are also involved in axonal degeneration and the experimental models open up the way to promising new therapeutic approaches for regenerative strategies. Although ambitious, inducible neural progenitor cells have become a promising alternative to the conventional treatments with stem cells, and the identification of new genetic variants of susceptibility to multiple sclerosis opens up the way to the discovery of new drugs. Reconsidering the value of old drugs and procedures would be another alternative therapeutic development (AU)

Increased natural killer cell chemotaxis to CXCL12 in patients with multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease characterized by leukocyte infiltration into the central nervous system (CNS). Migration of lymphocyte subpopulations towards CXCL12 was analyzed coupled to six-color flow cytometry in untreated patients in the remitting phase, during relapse, in patients with clinically isolated syndrome (CIS), and in healthy volunteers. Significantly higher migration rates of natural killer cells (CD45+CD3-CD16/56+) were observed in patients in remission and CIS patients than in patients during relapse and in controls. Moreover, the frequency of CD3-CD16/56+CXCR4+ cells is higher in patients in remission and in CIS patients, but not during relapse.

Review of the novelties presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (III).

The most relevant data presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2013 in Denmark, were summarised at the sixth edition of the Post-ECTRIMS Expert Meeting held in Madrid in October 2013, resulting in this review, which is being published in three parts. This third part of the Post-ECTRIMS review discusses the effects of immunomodulatory therapy on the natural history of multiple sclerosis, with special attention to the assessment of long-term effects and the use of historical controls as an alternative to randomised trials compared with placebo. This article contains possible future therapeutic strategies to be tested in experimental models and discusses clinical trials that are underway and future treatments. It also summarises the results of recent studies of disease-modifying treatments and developments in symptom management. Briefly, on the horizon are many drugs with different mechanisms of action, although new strategies and treatment algorithms are needed, as are new biomarkers and assessment measures of secondary progression and long-term records to assess safety. As for the symptomatic treatment of the disease, the proposal is a personalised treatment plan and a multidisciplinary approach to improve the quality of life of patients.

TITLE: Revision de las novedades presentadas en el XXIX Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (III).Los datos mas relevantes presentados en la XXIX edicion del Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS), celebrado en octubre de 2013 en Dinamarca, se han resumido en la sexta edicion de la Reunion de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2013, fruto de la cual nace esta revision, que se publica en tres partes. Esta tercera parte de la revision Post-ECTRIMS aborda los efectos del tratamiento inmunomodulador en la historia natural de la esclerosis multiple, con especial atencion a la valoracion del efecto a largo plazo y al uso de controles historicos como alternativa a los estudios aleatorizados comparados con placebo. Este articulo recoge posibles estrategias terapeuticas futuras que pasan por los modelos experimentales, y expone los ensayos clinicos en marcha y futuros tratamientos. Asimismo, resume los resultados de los ultimos estudios de los tratamientos modificadores de la enfermedad y las novedades en el manejo sintomatico. Brevemente, en el horizonte, hay muchos farmacos con diferentes mecanismos de accion, aunque son necesarias nuevas estrategias y algoritmos terapeuticos, biomarcadores y nuevas medidas de evaluacion de la progresion secundaria, y registros a largo plazo para evaluar la seguridad. En cuanto al tratamiento sintomatico de la enfermedad, se apuesta por un plan personalizado de tratamiento y una aproximacion multidisciplinar, de cara a mejorar la calidad de vida de los pacientes.