Consensus statement on the use of alemtuzumab in daily clinical practice in Spain.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain. / Consenso de expertos sobre el uso de alemtuzumab en la práctica clínica diaria en España.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

Cuantificación de la atrofia cerebral en esclerosis múltiple mediante medidas bidimensionales / Quantification of brain atrophy in multiple sclerosis using two-dimensional measurements

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[Appraisal of cerebral atrophy in multiple sclerosis by means of the corpus callosum index. Reply]. / Valoracion de la atrofia cerebral en la esclerosis multiple mediante el indice de cuerpo calloso. Replica.

TITLE: Valoracion de la atrofia cerebral en la esclerosis multiple mediante el indice de cuerpo calloso. Replica.

[Appraisal of cerebral atrophy in multiple sclerosis by means of the corpus callosum index]. / Valoracion de la atrofia cerebral en la esclerosis multiple mediante el indice de cuerpo calloso.

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.

TITLE: Valoracion de la atrofia cerebral en la esclerosis multiple mediante el indice de cuerpo calloso.Introduccion. La esclerosis multiple se caracteriza en su evolucion por el desarrollo de atrofia cerebral. Su monitorizacion resulta de interes para evaluar la respuesta al tratamiento, y son de eleccion los analisis volumetricos cerebrales, actualmente confinados al ambito de la investigacion. Objetivo. Analizar el indice de cuerpo calloso (ICC) como una posible alternativa a los metodos basados en la segmentacion cerebral. Sujetos y metodos. Se reune a 109 pacientes con enfermedades desmielinizantes de reciente diagnostico (90 con esclerosis multiple remitente recurrente, 7 con formas primarias progresivas y 12 con sindrome desmielinizante aislado) y se calcula el ICC en su primer estudio de resonancia magnetica cerebral, asi como en 101 controles sanos. Las secuencias de los pacientes se someten a analisis volumetrico 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 estadisticamente significativa (p < 0,001). El ICC muestra una correlacion estadisticamente significativa con el volumen encefalico (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 asociacion con el volumen de la sustancia gris (p = 0,058). Conclusiones. El ICC se relaciona con el volumen encefalico global obtenido mediante tecnicas volumetricas 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 rapido y sencillo calculo.

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

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.

TITLE: Revision de las novedades del XXXII Congreso ECTRIMS 2016, presentadas en la IX Reunion Post-ECTRIMS (II).Por noveno año consecutivo se ha celebrado en Madrid (España) la Reunion Post-ECTRIMS con el objetivo de presentar y discutir los temas mas debatidos en el congreso ECTRIMS de la mano de reconocidos especialistas en esclerosis multiple de nuestro pais. Fruto de esta reunion cientifica, avalada por la Sociedad Española de Neurologia, se genera este articulo de revision que sale publicado en dos partes. En esta segunda parte se pone de manifiesto la controversia actual en el manejo de la esclerosis multiple, especialmente en cuanto a formas progresivas y diagnostico diferencial se refiere. Se presentan los ultimos avances en remielinizacion, donde destaca el uso de la tecnica con micropilares en el laboratorio, y en neuroproteccion, la cual se revisa a traves del estudio del nervio optico. Los anticuerpos anti-CD20 ofrecen grandes expectativas, y estamos ante un nuevo mecanismo de accion y diana terapeutica en unas celulas a las que les habiamos prestado poca atencion hasta la fecha. Otro hecho destacable es la elevada correlacion entre los niveles de neurofilamentos en el liquido cefalorraquideo y el suero, que podria evitar el uso del liquido cefalorraquideo como muestra biologica en futuros estudios de biomarcadores. Tambien se anticipan los avances en investigacion clinica que en el futuro acabaran convergiendo en la practica clinica, condicionando los pasos que se deberan seguir en el abordaje terapeutico de la esclerosis multiple.

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

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.

TITLE: Revision de las novedades del XXXII Congreso ECTRIMS 2016, presentadas en la IX Reunion Post-ECTRIMS (I).Por noveno año consecutivo se ha celebrado en Madrid (España) la Reunion Post-ECTRIMS con el objetivo de presentar y discutir los temas mas debatidos en el congreso ECTRIMS de la mano de reconocidos especialistas en esclerosis multiple de nuestro pais. Fruto de esta actividad cientifica, avalada por la Sociedad Española de Neurologia, se genera este articulo de revision que sale publicado en dos partes. Esta primera parte aborda la planificacion familiar en las mujeres con esclerosis multiple, el manejo del embarazo y el papel de la lactancia. Se dirige la atencion a la poblacion pediatrica, a las caracteristicas de la resonancia magnetica y a los factores de riesgo geneticoambientales para el desarrollo de la enfermedad en niños, sin olvidar los factores de riesgo de progresion en los adultos. Se actualiza la epidemiologia del deterioro cognitivo en los pacientes con esclerosis multiple, las ventajas e inconvenientes de las herramientas de evaluacion disponibles, y los enfoques actuales de manejo, y se insiste en la importancia de la afectacion cognitiva en el curso de la enfermedad. Ademas, se introduce el concepto de medicina individualizada y de precision, desde el diagnostico de la enfermedad hasta el tratamiento, con las polemicas que inevitablemente surgen en el manejo de los pacientes, principalmente en lo relacionado con el cambio de tratamiento y el manejo de riesgos asociados.

[Fingolimod: effectiveness and safety in routine clinical practice. An observational, retrospective, multi-centre study in Asturias and Cantabria]. / Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Asturias y Cantabria.

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 gadolinium-enhancing 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.

TITLE: Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Asturias y Cantabria.Objetivo. Evaluar la efectividad y seguridad del fingolimod en la practica clinica habitual en la region de Asturias y Cantabria (España). Pacientes y metodos. Estudio retrospectivo y multicentrico de pacientes con esclerosis multiple recurrente remitente tratados con fingolimod, segun la ficha tecnica. La efectividad se evaluo en los pacientes con al menos un año de tratamiento. Se calculo 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 puntuacion en la escala expandida del estado de discapacidad (EDSS). Se analizo la poblacion total y segun el tratamiento previo: inmunomodulador (interferon beta-1 o acetato de glatiramero) o natalizumab. Resultados. Un total de 138 pacientes iniciaron tratamiento con fingolimod; el 60% recibio previamente inmunomodulador; el 28%, natalizumab; y el 9%, ningun tratamiento. Noventa y nueve pacientes estuvieron al menos un año en tratamiento con fingolimod. Despues de un año de tratamiento, el fingolimod disminuyo la TAB en un 67% (1,26 a 0,42; p < 0,0001), aumento 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 mejoro/mantuvo la puntuacion 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 practica clinica habitual en las regiones de Asturias y Cantabria muestra que el fingolimod tiene resultados similares a los observados en los ensayos clinicos, al comparar las variables clinicorradiologicas utilizadas en estos ultimos.

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

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.

TITLE: Revision de las novedades del XXXI Congreso ECTRIMS 2015, presentadas en la VIII Reunion Post-ECTRIMS.Reconocidos especialistas nacionales en esclerosis multiple (EM) se han reunido, por octavo año consecutivo, para exponer lo mas novedoso que se presento en la ultima edicion del congreso ECTRIMS 2015 y que recoge esta revision. En esta edicion ha destacado la nueva clasificacion de los fenotipos de la EM. Tambien se revisaron los criterios diagnosticos del espectro de la neuromielitis optica y los problemas en el diagnostico diferencial derivados de la falta de definicion del espectro radiologico. La microbiota adquiere protagonismo como posible factor determinante de la enfermedad, junto con factores extrinsecos como el tabaco, la ingesta de sal o el deficit de vitamina D. Los avances en inmunomodulacion 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 farmaco para la artritis reumatoide, destaca como candidato potencial para el tratamiento de la neuromielitis optica. Ciertos antibioticos y vitaminas tambien podrian tener un papel en el tratamiento de la EM. En esta edicion se presto especial atencion a la terapia personalizada. Actualmente disponemos de 11 farmacos aprobados en Europa. Se necesitan algoritmos terapeuticos 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 terapeuticas, para lo que se precisan biomarcadores moleculares y otras herramientas pronosticas. Los problemas aun existentes en la tecnologia del software en resonancia magnetica dificultan su traslacion a la practica clinica diaria.

Review of the novelties from the 2014 ECTRIMS-ACTRIMS Joint Congress, presented at the 7th Post-ECTRIMS Meeting (II).

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.

TITLE: Revision de las novedades del congreso conjunto ECTRIMS-ACTRIMS 2014, presentadas en la VII Reunion Post-ECTRIMS (II).Por septimo año consecutivo se ha celebrado en Madrid (España) la Reunion Post-ECTRIMS. Reconocidos especialistas en esclerosis multiple y lideres de opinion nacionales se han reunido un año mas para exponer las novedades presentadas en el Congreso Mundial ECTRIMS-ACTRIMS 2014, y fruto de esa reunion se genera esta revision que se publica en dos partes. En esta segunda parte se pone de manifiesto que los fenomenos inmunologicos cada vez estan mas presentes en la patogenia de la enfermedad, y que la interaccion entre inflamacion y neurodegeneracion es mas evidente. Fenomenos metabolicos, de disfuncion mitocondrial y de estres oxidativo tambien se implican en la degeneracion axonal, y los modelos experimentales abren paso a nuevos enfoques terapeuticos con esperanza para las estrategias regenerativas. Aunque resulte ambicioso, los progenitores neurales inducibles se convierten en una prometedora alternativa a los tratamientos convencionales con celulas madre, y la identificacion de nuevas variantes geneticas de susceptibilidad a la esclerosis multiple abre camino al descubrimiento de nuevos farmacos. Replantear el valor de antiguos farmacos y procedimientos seria otra alternativa de desarrollo terapeutico.

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

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 sub-populations 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.

TITLE: Revision de las novedades del congreso conjunto ECTRIMS-ACTRIMS 2014, presentadas en la VII Reunion Post-ECTRIMS (I).Por septimo año consecutivo se ha celebrado en Madrid (España) la Reunion Post-ECTRIMS. Reconocidos especialistas en esclerosis multiple y lideres de opinion nacionales se han reunido un año mas para exponer las novedades presentadas en el Congreso Mundial ECTRIMS-ACTRIMS 2014, y fruto de esa reunion se genera esta revision que sale publicada en dos partes. Como principales conclusiones de esta primera parte se destaca el mayor entendimiento del componente genetico de la esclerosis multiple al que estamos asistiendo, el cual no resulta suficiente si no se considera su interaccion con los factores ambientales de riesgo de la enfermedad, ni el impacto de la comorbilidad y de las conductas saludables en la susceptibilidad y pronostico de los pacientes. Al respecto, los autores insisten en que, en la practica clinica, las alteraciones cognitivas y psiquiatricas estan infradiagnosticadas y son poco consideradas en la investigacion clinica; no obstante, la evidencia, aunque escasa, apunta hacia posibles beneficios de los farmacos modificadores de la enfermedad y alternativas al tratamiento inhibidor selectivo de la recaptacion de serotonina. El abordaje de las subpoblaciones en esclerosis multiple y variantes de la enfermedad refuerza la importancia del diagnostico precoz y preciso para ofrecer a los pacientes un pronostico y un tratamiento mas seguros y personalizados. La esclerosis multiple pediatrica es idonea 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.

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

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, to be published in three parts. This first part of the Post-ECTRIMS review presents an update on gender differences in multiple sclerosis (MS) as well as new evidence on the impact of sex hormones on the disease. We should consider that there is still much to discover with regard to the genetic components of the disease. Similarly, possible infections and lifestyle habits are added as triggers of the known environmental risk factors for MS. The interaction between genetics and the environment has been increasingly implicated as a cause of susceptibility to MS. With regard to the mechanisms of inflammation, axo-glial proteins, instead of myelin proteins, may be the early antigenic targets, and B cells have been implicated in the production of cytokines toxic to oligodendrocytes. Chitinase 3-like 1 (CHI3L1) is validated as a prognostic marker of conversion to MS, and immunoglobulin M oligoclonal bands and L-selectin could be incorporated as possible measures of the risk stratification strategy in patients treated with natalizumab.

TITLE: Revision de las novedades presentadas en el XXIX Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (I).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 primera parte de la revision Post-ECTRIMS presenta una vision actualizada de las diferencias de genero en la esclerosis multiple (EM), asi como las nuevas evidencias sobre el impacto de las hormonas sexuales en la enfermedad. Podemos asumir que aun queda mucho por descubrir con relacion al componente genetico de la enfermedad. De la misma manera, a los ya conocidos factores ambientales de riesgo para la EM se unen posibles infecciones y habitos de vida como desencadenantes. La interaccion entre la genetica y el ambiente cada vez cobra mas fuerza como causa de susceptibilidad a la EM. En cuanto a los mecanismos de inflamacion, las proteinas del complejo axoglial pueden ser las dianas antigenicas iniciales en lugar de las proteinas de mielina, y las celulas B se han visto implicadas en la produccion de citocinas toxicas para los oligodendrocitos. La quitinasa 3-like 1 se valida como marcador pronostico de conversion a EM, y las bandas oligoclonales de inmunoglobulina M y la L-selectina podrian incorporarse como posibles medidas dentro de la estrategia de estratificacion del riesgo en pacientes tratados con natalizumab.

[Rivastigmine in a case of autopsy proved frontotemporal dementia (Pick's disease)]. / Rivastigmina en un caso de demencia frontotemporal, enfermedad de Pick verificada por autopsia.

INTRODUCTION: Cholinesterase inhibitors are useful in the treatment of behavioural and psychological symptoms in Alzheimer's disease. Their effectiveness in frontotemporal dementia has not been proved, since such a claim has only been backed by the publication of one open-label trial in which the behavioural and psychological symptoms of the patients treated with rivastigmine over a 12-month period improved significantly with respect to those belonging to a group that were given a placebo. We report a case of frontotemporal dementia, Pick's disease, which improved with rivastigmine treatment. CASE REPORT: A 61-year-old male who presented a progressive clinical picture of behavioural disorders and executive-cognitive impairment that had begun two years earlier. Magnetic resonance imaging of the head revealed severe frontotemporal atrophy. Neuropsychological Inventory (NPI). Overall score 36/144 (6/12: anxiety, disinhibition and aberrant motor behaviour, 4/12: agitation, irritability and apathy; 3/12: sleep and eating disorders. After three months' treatment with rivastigmine, the overall score on the NPI was 10/144. This improvement remained stable over the months that followed. The patient died eight months later after developing liver cancer with metastasis. The microscopic study of the brain showed tau-positive neuronal inclusions, gliosis and neuronal loss. The inclusions were well-circumscribed Pick bodies, which were present in the frontal and temporal cortices and in the dentate gyrus of the hippocampus. CONCLUSIONS: This case confirms the idea that treatment with cholinesterase inhibitors can be effective in the behavioural and psychological symptoms of frontotemporal dementia.

Rivastigmina en un caso de demencia frontotemporal, enfermedad de Pick verificada por autopsia / Rivastigmine in a case of autopsy proved frontotemporal dementia (pick´s disease)

Introducción. Los inhibidores de la colinesterasa son útiles en el tratamiento de los síntomas conductuales y psicológicos en la enfermedad de Alzheimer. Su eficacia en la demencia frontotemporal no está demostrada, pues sólo la avala la publicación de un estudio abierto en el que los síntomas conductuales y psicológicos de los pacientes tratados con rivastigmina durante 12 meses mejoraron significativamente respecto de los del grupo placebo. Describimos un caso de demencia frontotemporal, enfermedad de Pick, que mejoró con el tratamiento con rivastigmina. Caso clínico. Varón de 61 años de edad que presentaba un cuadro clínico progresivo de alteraciones de conducta y afectación ejecutivocognitiva de dos años de evolución. En la resonancia magnética craneal se observó una atrofia frontotemporal grave. En el inventario neuropsicológico (NPI) alcanzó una puntuación global de 36/144 (6/12: ansiedad, desinhibición y conducta motora aberrante, 4/12: agitación, irritabilidad y apatía; 3/12: alteraciones del sueño y de la conducta alimentaria). Tras tres meses de tratamiento con rivastigmina, la puntuación global en el NPI fue de 10/144. Esta mejoría se mantuvo estable en los siguientes meses. Falleció ocho meses después tras desarrollar un hepatocarcinoma con metástasis. En el estudio microscópico del cerebro se observaron inclusiones neuronales tau positivas, pérdida neuronal y gliosis. Las inclusiones eran cuerpos de Pick, bien circunscritos, presentes en la corteza frontal, temporal y en el giro dentado del hipocampo. Conclusión. Este caso confirma que el tratamiento con inhibidores de la colinesterasa puede ser eficaz en los síntomas conductuales y psicológicos de demencia frontotemporal (AU)

Introduction. Cholinesterase inhibitors are useful in the treatment of behavioural and psychological symptoms in Alzheimer's disease. Their effectiveness in frontotemporal dementia has not been proved, since such a claim has only been backed by the publication of one open-label trial in which the behavioural and psychological symptoms of the patients treated with rivastigmine over a 12-month period improved significantly with respect to those belonging to a group that were given a placebo. We report a case of frontotemporal dementia, Pick’s disease, which improved with rivastigmine treatment. Case report. A 61-year-old male who presented a progressive clinical picture of behavioural disorders and executive-cognitive impairment that had begun two years earlier. Magnetic resonance imaging of the head revealed severe frontotemporal atrophy. Neuropsychological Inventory (NPI). Overall score 36/144 (6/12: anxiety, disinhibition and aberrant motor behaviour, 4/12: agitation, irritability and apathy; 3/12: sleep and eating disorders. After three months’ treatment with rivastigmine, the overall score on the NPI was 10/144. This improvement remained stable over the months that followed. The patient died eight months later after developing liver cancer with metastasis. The microscopic study of the brain showed tau-positive neuronal inclusions, gliosis and neuronal loss. The inclusions were well-circumscribed Pick bodies, which were present in the frontal and temporal cortices and in the dentate gyrus of the hippocampus. Conclusions. This case confirms the idea that treatment with cholinesterase inhibitors can be effective in the behavioural and psychological symptoms of frontotemporal dementia (AU)