Neuromyelitis optica associated with the use of Atezolizumab in a patient with advanced lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) are a pharmacological group increasingly used in Oncology and Hematology. These treatments can lead to autoimmune complications, with neurological conditions, especially central nervous system (CNS) involvement, being rare. We describe a case of seropositive neuromyelitis optica in a patient with locally advanced lung adenocarcinoma treated with Atezolizumab.

Early Alzheimer's Disease Screening Approach Using Plasma Biomarkers.

Alzheimer's disease (AD) is the most prevalent dementia, but it shows similar initial symptoms to other neurocognitive diseases (Lewy body disease (LBD) and frontotemporal dementia (FTD)). Thus, the identification of reliable AD plasma biomarkers is required. The aim of this work is to evaluate the use of a few plasma biomarkers to develop an early and specific AD screening method. Plasma p-Tau181, neurofilament light (NfL), and glial fibrillary acid protein (GFAP) were determined by Single Molecule Assay (SIMOA® Quanterix, Billerica, MA, USA) in patients with mild cognitive impairment due to AD (MCI-AD, n = 50), AD dementia (n = 10), FTD (n = 20), LBD (n = 5), and subjective cognitive impairment (SCI (n = 21)). Plasma p-Tau181 and GFAP showed the highest levels in AD dementia, and significant correlations with clinical AD characteristics; meanwhile, NfL showed the highest levels in FTD, but no significant correlations with AD. The partial least squares (PLS) diagnosis model developed between the AD and SCI groups showed good accuracy with a receiver operating characteristic (ROC) area under curve (AUC) of 0.935 (CI 95% 0.87-0.98), sensitivity of 86%, and specificity of 88%. In a first screen, NfL plasma levels could identify FTD patients among subjects with cognitive impairment. Then, the developed PLS model including p-Tau181 and GFAP levels could identify AD patients, constituting a simple, early, and specific diagnosis approach.

Assessment of Plasma and Cerebrospinal Fluid Biomarkers in Different Stages of Alzheimer's Disease and Frontotemporal Dementia.

Alzheimer's disease (AD) is the primary type of dementia, followed by frontotemporal lobar degeneration (FTLD). They share some clinical characteristics, mainly at the early stages. So, the identification of early, specific, and minimally invasive biomarkers is required. In this study, some plasma biomarkers (Amyloid ß42, p-Tau181, t-Tau, neurofilament light (NfL), TAR DNA-binding protein 43 (TDP-43)) were determined by single molecule array technology (SIMOA®) in control subjects (n = 22), mild cognitive impairment due to AD (MCI-AD, n = 33), mild dementia due to AD (n = 12), and FTLD (n = 11) patients. The correlations between plasma and cerebrospinal fluid (CSF) levels and the accuracy of plasma biomarkers for AD early diagnosis and discriminating from FTLD were analyzed. As result, plasma p-Tau181 and NfL levels correlated with the corresponding CSF levels. Additionally, plasma p-Tau181 showed good accuracy for distinguishing between the controls and AD, as well as discriminating between AD and FTLD. Moreover, plasma NfL could discriminate dementia-AD vs. controls, FTLD vs. controls, and MCI-AD vs. dementia-AD. Therefore, the determination of these biomarkers in plasma is potentially helpful in AD spectrum diagnosis, but also discriminating from FTLD. In addition, the accessibility of these potential early and specific biomarkers may be useful for AD screening protocols in the future.

Prognostic utility of the IgM oligoclonal bands against myelin lipids in multiple sclerosis.

IgM oligoclonal bands (OCMBs) against myelin-specific lipids have been identified as a marker for poor prognosis in multiple sclerosis (MS). The aim is to examine the relation between lipid-specific OCMBs (LS-OCMBs) and the evolution of MS. An analytical, ambispective and individual-based study was conducted. We selected 116 patients, out of whom 95 had LS-OCMBs. The predominant lipid recognized was phosphatidylcholine. The positive gangliosides OCMB group reached better scores in the 9HPT, and the phosphatidylcholine, sphingolipids and phosphatidylethanolamine OCMB groups showed statistical differences in the magnetic resonance parameters. In conclusion: some LS-OCMBs showed statistically significant differences with functional or imaging tests.

Brain Atrophy in Relapsing Optic Neuritis Is Associated With Crion Phenotype.

Background and objective: Chronic relapsing inflammatory optic neuritis (CRION) is one of the more common phenotypes related to myelin oligodendrocyte glycoprotein antibodies (MOG-Abs). The absence of specific biomarkers makes distinguishing between CRION and relapsing inflammatory ON (RION) difficult. A recent work has suggested a widespread affectation of the central nervous system in CRION patients. In order to search for a potential CRION marker we have measured brain atrophy in a cohort of patients, stratified by phenotypes: CRION, RION, multiple sclerosis with a history of optic neuritis (MS-ON), and MOG-Abs status. Methods: A cross-sectional study was conducted in 31 patients (seven CRION, 11 RION, and 13 MS-ON). All patients were tested for MOG and aquaporin-4 antibodies (AQ4-Abs). Clinical data were collected. Brain atrophy was calculated by measuring the brain parenchyma fraction (BPF) with Neuroquant® software. Results: Four of seven CRION patients and one of 11 RION patients were positive for MOG-Abs (p = 0.046) and no MS-ON patients tested positive to MOG-Abs. All patients were negative to AQ4-Abs. The BPF was lower in patients with CRION than patients with RION (70.6 vs. 75.3%, p = 0.019) and similar to that in MS-ON patients. Conclusions: Brain atrophy in idiopathic inflammatory relapsing ON is present in patients with the CRION phenotype. Data from this study reflect that the optic nerve is a main target involved in these patients but not the only one. Our results should be further investigated in comprehensive and prospective studies.

Perception of stigma in patients with primary progressive multiple sclerosis.

Stigma associated with neurological disorders may contribute to a poor health-related quality of life. However, limited information is available in primary progressive multiple sclerosis. We investigated the presence and impact of stigma in patients with primary progressive multiple sclerosis. A non-interventional, cross-sectional study was conducted. A total of 55 primary progressive multiple sclerosis patients were studied (mean age 55.8±9.5 years, 56.4% male). The median Expanded Disability Status Scale score was 5.5 (4.0-6.5). Stigma prevalence was 78.2% (n=43). Twenty-four patients (43.6%) were classified as depressed. Scores on the eight-item Stigma Scale for Chronic Illness correlated with physical (rho=0.464, p<0.001) and psychological (rho=0.358, p=0.007) 29-item Multiple Sclerosis Impact Scale subscores. Stigma predicted concurrent depression (odds ratio=1.13; p=0.046). Stigma was highly prevalent with a detrimental effect on quality of life and mood in primary progressive multiple sclerosis.

Progressive Demyelination in the Presence of Serum Myelin Oligodendrocyte Glycoprotein-IgG: A Case Report.

The clinical diagnosis of patients with autoantibodies directed to conformational myelin oligodendrocyte glycoprotein MOG-IgG, can be challenging because of atypical clinical presentation. MOG-IgG seropositivity has been reported in several demyelinating diseases, including relapsing opticospinal syndromes [in the neuromyelitis optica spectrum disorders (NMOSD) and less frequently, in multiple sclerosis (MS)], but it has rarely been associated with the progressive course of disease. To contribute to the characterization of MOG-related demyelination, we describe the case of a patient with progressive demyelinating opticospinal disease, IgG-oligoclonal bands (OCB), and serum MOG-IgG.

Atypical periodic alternating nystagmus responding to high-dose intravenous immunoglobulins: a case report.

BACKGROUND: Acquired periodic alternating nystagmus (PAN) is a rare but well-defined syndrome that consists of a horizontal nystagmus that cyclically reverses its direction. PAN can be caused by degenerative, neoplastic, or toxic diseases of the cerebellum and, in a few cases, by subacute cerebellar ataxia of immune origin. CASE PRESENTATION: A 44-year-old man came to our attention because of rapidly progressive gait instability and blurred vision. Clinical examination showed PAN and a mild pancerebellar syndrome. Eye movement recordings disclosed a short cycle PAN with significant slow-phase velocity only in darkness. Under the effect of a γ-aminobutyric acid type B (GABAB) agonist, PAN was not modified. Right after treatment with intravenous immunoglobulin (IVIg) was started, PAN was essentially eliminated. Three months after last dose of IVIg, this nystagmus reappeared. CONCLUSIONS: IVIg resolved PAN in this patient. This finding may point to an autoimmune mechanism underlying this patient's nystagmus. This case suggests that the usefulness of IVIg at treating PAN might be worth a consideration in similar clinical settings.

Impact of adherence on subcutaneous interferon beta-1a effectiveness administered by Rebismart® in patients with multiple sclerosis.

BACKGROUND: Adherence to disease-modifying drugs (DMDs) is one of the key factors for achieving optimal clinical outcomes. Rebismart® is an injection device for subcutaneous administration of interferon beta-1a (INF ß-1a) that is also able to monitor adherence objectively. The aim of this study was to describe adherence to INF ß-1a using the said electronic autoinjection device and to explore the relationship between adherence and relapses in a Spanish cohort. METHODS: This is a retrospective observational study in which 110 Spanish patients self-administered INF ß-1a subcutaneously using an electronic autoinjection device between June 2010 and June 2015. The primary end point was the percentage of adherence measured by Rebismart® to subcutaneous INF ß-1a injections calculated as number of injections received in time period versus number of injections scheduled in time period. Other variables recorded were demographic and clinical data. Statistical analysis was performed using SPSS 19.0 software. RESULTS: Median adherence for the total study period was 96.5% (interquartile range [IQR]: 91.1-99.1). Similar values were observed during the first 6 months: 98.7% (IQR: 91.3-100), and the last 6 months: 97.6% (IQR: 91.1-99.8). Median duration of treatment was 979 days (IQR: 613.8-1,266.8). During the entire treatment period, 77.3% of patients were relapse free and mean annualized relapse rate was 0.14 (standard deviation: 0.33). Increased adherence was associated with better clinical outcomes, leading to lower relapse risk (odds ratio: 0.953; 95% confidence interval: 0.912-0.995). Specifically, every percentage unit increase in adherence resulted in a 4.7% decrease in relapse. CONCLUSION: Patients with multiple sclerosis who self-injected INF ß-1a with Rebismart® had excellent adherence, correlating with a high proportion of relapse-free patients and very low annualized relapse rate.

Description of the Characteristics of Multiple Sclerosis Patients in the Region of Valencia (Spain) Who Requested Treatment with Disease-Modifying Drugs during the 2005-2014 Decade.

BACKGROUND: More than 3,000 multiple sclerosis (MS) patients were treated with disease-modifying drugs (DMDs) in the Region of Valencia during 2005-2014. We aimed at describing the demographic and clinical characteristics of MS patients who requested treatment with DMDs, variations in their use, and the factors associated with change to second-line therapies during this decade. METHODS: A retrospective cohort study with information from Subcomité Especializado de Medicamentos de Alto Impacto Sanitario y/o Económico registers. A statistical analysis was run in 2 phases: descriptive analysis of the sample using classical statistical methods, and of DMD trend by a chi-square test for linear trends; analytic analysis to examine the factors associated with change to second-line treatment (logistic regression model). RESULTS: We selected 2,205 patients (mean age 32.12, SD 9.64; 70% females, and 86.6% remising-remitting MS (RRMS)); 1,012 patients were attended to in highly specialized MS units (45.8%); 525 in monographic units (23.8%); and 668 in general units (30.2%). DMD prescriptions increased, and glatiramer acetate was more widespread at the end of the period (35.4%). CONCLUSION: Variability in access to different treatments was slight. The younger the patient, the higher the risk of first-line RRMS treatment failing in female gender and first treatment with interferon.

[Therapeutic plasma exchange: applications in neurology]. / Recambio plasmático terapéutico: aplicaciones en neurología.

INTRODUCTION: Plasma exchange is a technique used in the treatment of some neurological autoimmune disorders since the 80s, especially in acute conditions. In recent years new data about it use has been published in many diseases with autoimmune basis, expanding the range of use of this technique. AIM: To update the current indications of this technique in the treatment of neurological diseases. DEVELOPMENT: We conducted a thorough review of all articles about the efficacy of plasma exchange in the treatment of different neurological diseases published since the 80s. We have also carried out a detailed analysis of recommendations and evidence of the use of this procedure by analyzing the guidelines of different scientific societies. CONCLUSIONS: Plasma exchange has proven to be an effective alternative treatment with high grade scientific evidence in diseases such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy and myasthenia gravis. It has been effective in treating acute demyelinating episodes unresponsive to other therapies, neuromyelitis optica relapses and other central nervous system diseases induced by antibodies. In comparative studies with intravenous immunoglobulin efficacy of both therapies is similar. Comparative studies should continue to be conducted in order to better understand the mechanisms of action, prioritize indications and compare the cost-effectiveness ratio of both procedures.

TITLE: Recambio plasmatico terapeutico: aplicaciones en neurologia.Introduccion. El recambio plasmatico es una tecnica utilizada en el tratamiento de algunas enfermedades neurologicas de base autoinmune desde los años ochenta, especialmente en situaciones agudas. En los ultimos años se han publicado nuevos datos sobre su empleo en numerosas entidades con base autoinmune, ampliando, con ello, el espectro de utilizacion. Objetivo. Actualizar las indicaciones de esta tecnica en el tratamiento de las enfermedades neurologicas. Desarrollo. Se ha realizado una revision exhaustiva de todos los articulos publicados desde los años ochenta sobre la eficacia del recambio plasmatico en el tratamiento de las diferentes enfermedades neurologicas. Tambien se ha efectuado un analisis detallado de las recomendaciones y evidencias de la utilizacion de este procedimiento por parte de las diferentes sociedades cientificas. Conclusiones. El recambio plasmatico ha demostrado ser una alternativa eficaz con evidencia cientifica de primer nivel en enfermedades como el sindrome de Guillain-Barre, la polineuropatia desmielinizante inflamatoria cronica o la miastenia grave. Ha mostrado ser eficaz en el tratamiento de episodios desmielinizantes agudos sin respuesta a otras terapias, en los brotes de neuromielitis optica y en otras enfermedades del sistema nervioso central producidas por anticuerpos. En los estudios comparativos con inmunoglobulinas intravenosas, la eficacia de ambas terapias es similar. Es preciso seguir realizando estudios comparativos para conocer mejor los mecanismos y establecer indicaciones prioritarias y comparar la relacion coste-eficacia de ambos procedimientos.

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.

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

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 second part of the Post-ECTRIMS review focuses on diagnostic imaging and differential diagnosis, the clinical and paraclinical monitoring of neurodegeneration, progression and disability, and functional imaging and neural connectivity. It is clear that conventional multiple sclerosis sequences remain essential for the diagnosis, differential diagnosis and disease monitoring, that new MRI techniques help to assess the neurodegenerative process, and that some of the new sequences are more specific to neuroaxonal injury. Very high field magnetic resonance imaging allows better understanding of the lesion load, distribution and heterogeneity of the lesions, and positron emission tomography studies offer new insight into the patho-physiology of the disease. Functional imaging and neural connectivity studies show that there is cortical reorganisation in multiple sclerosis, whose equilibrium with structural damage is responsible for the impairment.

TITLE: Revision de las novedades presentadas en el XXIX Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (II).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 segunda parte de la revision Post-ECTRIMS se centra en la imagen del diagnostico y diagnostico diferencial, en la monitorizacion clinica y paraclinica de la neurodegeneracion, progresion y discapacidad, y en la imagen funcional y conectividad neural. Queda patente que las secuencias convencionales de esclerosis multiple siguen siendo basicas para el diagnostico, el diagnostico diferencial y el seguimiento de la enfermedad, que las nuevas tecnicas de resonancia magnetica ayudan a evaluar el proceso de neurodegeneracion, y algunas de las nuevas secuencias son mas especificas del daño neuronal-axonal. La resonancia magnetica de campo muy alto permite un mejor conocimiento de la carga lesional, distribucion y heterogeneidad de las lesiones, y los estudios con tomografia por emision de positrones ofrecen una nueva vision de la fisiopatologia de la enfermedad. Los estudios de imagen funcional y conectividad neural muestran que en la esclerosis multiple existe una reorganizacion cortical cuyo equilibrio con el daño estructural es responsable de la discapacidad.

Biomarkers in multiple sclerosis: an update for 2014.

Multiple sclerosis is a chronic, demyelinating and inflammatory disease of the central nervous system that mainly affects young adults. It is characterised by processes involving inflammation, demyelination and axonal destruction, and as a result the pathogenic aspects and response to treatment of the disease vary widely. It is therefore difficult to establish a prognosis for these patients or to determine the effectiveness of the different drugs that are employed. Current clinical research into the development of new biomarkers has advanced a great deal in recent years, especially in the early stages of the disease. Yet, it is essential to further our knowledge about novel markers of the disease, and not only in the more advanced stages, so as to be able to stop disability from progressing and to establish new therapy regimens in these patients. This review presents an update on the information available about the biomarkers that are currently validated and used in multiple sclerosis, together with the possible candidates for utilisation in routine clinical practice.

TITLE: Biomarcadores en la esclerosis multiple: puesta al dia 2014.La esclerosis multiple es una enfermedad cronica, desmielinizante e inflamatoria del sistema nervioso central, que afecta principalmente a adultos jovenes. Se caracteriza por procesos de inflamacion, desmielinizacion y destruccion axonal, que confieren a esta enfermedad una gran variabilidad en los aspectos patogenicos y de respuesta al tratamiento. Por ello es muy dificil establecer el pronostico de estos pacientes, asi como la eficacia de los diferentes farmacos. La investigacion clinica actual en el desarrollo de nuevos biomarcadores ha experimentado un gran avance en los ultimos años, especialmente al inicio de la enfermedad. Sin embargo, es prioritario avanzar en el conocimiento de nuevos marcadores de la enfermedad, no solo en la fase mas avanzada, con el objetivo de prevenir la progresion de la discapacidad y establecer nuevas pautas terapeuticas en estos pacientes. Esta revision presenta una actualizacion de la informacion acerca de los biomarcadores actualmente validados y utilizados en la esclerosis multiple, asi como de los posibles candidatos de utilizacion en la practica clinica habitual.

[Consensus document on spasticity in patients with multiple sclerosis. Grupo de Enfermedades Desmielinizantes de la Sociedad Española de Neurología]. / Documento de consenso sobre la espasticidad en pacientes con esclerosis multiple.

INTRODUCTION: Multiple sclerosis is a chronic neurological inflammatory demyelinating disease. Specialists involved in the symptomatic treatment of this disease tend to apply heterogeneous diagnostic and treatment criteria. AIM: To establish homogeneous criteria for treating spasticity based on available scientific knowledge, facilitating decision-making in regular clinical practice. DEVELOPMENT: A group of multiple sclerosis specialists from the Spanish Neurological Society demyelinating diseases working group met to review aspects related to spasticity in this disease and draw up the consensus. After an exhaustive bibliographic search and following a metaplan technique, a number of preliminary recommendations were established to incorporate into the document. Finally, each argument was classified depending on the degree of recommendation according to the SIGN (Scottish Intercollegiate Guidelines Network) system. The resulting text was submitted for review by the demyelinating disease group. An experts' consensus was reached regarding spasticity triggering factors, related symptoms, diagnostic criteria, assessment methods, quality of life and therapeutic management (drug and non-drug) criteria. CONCLUSION: The recommendations included in this consensus can be a useful tool for improving the quality of life of multiple sclerosis patients, as they enable improved diagnosis and treatment of spasticity.

TITLE: Documento de consenso sobre la espasticidad en pacientes con esclerosis multiple.Introduccion. La esclerosis multiple es una enfermedad neurologica cronica, desmielinizante e inflamatoria. Los neurologos implicados en el tratamiento sintomatico de esta enfermedad tienden a aplicar criterios diagnosticos y de tratamiento heterogeneos. Objetivo. Elaborar un documento de consenso para establecer criterios homogeneos para el tratamiento de la espasticidad, basados en el conocimiento cientifico disponible que faciliten la toma de decisiones en la practica clinica habitual. Desarrollo. Un grupo de expertos españoles en esclerosis multiple del Grupo de Enfermedades Desmielinizantes de la Sociedad Española de Neurologia (SEN) se reunieron para revisar los aspectos relacionados con la espasticidad en esta enfermedad y elaborar el consenso. Tras una busqueda bibliografica exhaustiva y siguiendo la metodologia metaplan se establecieron unas recomendaciones preliminares para incorporar al documento. Finalmente, cada argumento se clasifico segun su grado de recomendacion, atendiendo a las categorias del sistema SIGN (Scottish Intercollegiate Guidelines Network). El texto resultante fue sometido a la revision de los miembros del Grupo de Enfermedades Desmielinizantes de la SEN. Se ha alcanzado un consenso de expertos respecto a los factores desencadenantes de la espasticidad, la sintomatologia relacionada, los criterios diagnosticos, los metodos de valoracion de la espasticidad, la calidad de vida y los criterios en el manejo terapeutico (farmacologicos y no farmacologicos). Conclusion. Las recomendaciones contenidas en este consenso pueden ser una herramienta util para el neurologo para la practica clinica del dia a dia y para mejorar la calidad de vida del paciente, ya que permiten un mejor diagnostico y tratamiento de la espasticidad.

Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (III).

The most significant data presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in France in October 2012, have been summarised in the fifth edition of the Post-ECTRIMS Experts Meeting, held in Madrid in October 2012. This led to the drafting of this review, which has been published in three parts. This third part of the Post-ECTRIMS review presents the findings from the latest studies conducted with disease-modifying treatments, more specifically with glatiramer acetate, laquinimod, ponesimod, BG-12, teriflunomide, daclizumab, natalizumab and secukinumab (AIN457). Likewise, we also address the reasons that justify the search for innovative treatments for multiple sclerosis, with antigen-specific therapy, cell therapy and therapy aimed at promoting remyelination being highlighted among other future therapeutic strategies. Access to new pharmacological agents and the complexity of the therapy of multiple sclerosis in the future will require new design strategies and directions in clinical trials, including the use of surrogate markers, new statistical applications, superiority, inferiority or equivalence clinical trials and adaptable designs.

TITLE: Revision de las novedades presentadas en el XXVIII Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (III).Los datos mas relevantes presentados en la XXVIII edicion del Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS), celebrado en octubre de 2012 en Francia, han sido resumidos en la quinta edicion de la Reunion de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2012, fruto de la cual nace esta revision que se publica en tres partes. Esta tercera parte de la revision Post-ECTRIMS expone los resultados de los ultimos estudios realizados con los tratamientos modificadores de la enfermedad, concretamente con acetato de glatiramero, laquinimod, ponesimod, BG-12, teriflunomida, daclizumab, natalizumab y secukinumab (AIN457). Asimismo, se abordan las razones que justifican la busqueda de tratamientos innovadores para la esclerosis multiple, destacando la terapia antigenoespecifica, la terapia celular y la terapia dirigida a promover la remielinizacion entre las futuras estrategias terapeuticas. La disponibilidad de nuevos farmacos y la complejidad de la futura terapia de la esclerosis multiple necesitan nuevas direcciones y estrategias de diseño en los ensayos clinicos, entre ellas el uso de marcadores subrogados, nuevas aplicaciones estadisticas, ensayos clinicos de superioridad, inferioridad o equivalencia, y diseños adaptables.

Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I).

The most relevant data presented at the 28th edition of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2012 in France, have been summarized in the fifth edition of the Post-ECTRIMS Expert Meeting held in Madrid in October 2012. The present review summarizes the views and results of the meeting and is being published in three parts. This first part of the Post-ECTRIMS review addresses the incidence and prevalence of multiple sclerosis (MS), which has increased at the global level, largely due to the increased incidence in women because the risk of developing the disease is increased in females, with minimal concurrent effect on the progression of MS. Sexual dimorphism is evident in MS, and all evidence points to an interaction between hormonal, genetic, and environmental factors. The paediatric population represents an ideal group to study susceptibility factors to the disease, which is why collaborative studies designed to increase the patient samples are being considered, given its low prevalence. In this review, inflammatory and neurodegenerative phenomena involved in the pathogenesis of the disease and that have a cause-and-effect or shared relationship with the disease are being discussed. Current hypotheses suggest a phenomenon of compartmentalization, presumably inaccessible to current immunomodulatory therapy. Among the possible mechanisms involved in these processes of inflammation and demyelination, the role of Th17 cells, mitochondrial dysfunction, early disruption of astrocytic processes, and chronic hypoxia are discussed.

TITLE: Revision de las novedades presentadas en el XXVIII Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (I).Los datos mas relevantes presentados en la XXVIII edicion del Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS), celebrado en octubre de 2012 en Francia, se han resumido en la quinta edicion de la Reunion de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2012, fruto de la cual nace esta revision, que se publica en tres partes. Esta primera parte de la revision Post-ECTRIMS aborda la incidencia y prevalencia de la esclerosis multiple (EM), que, en el ambito mundial, ha aumentado a expensas de las mujeres, ya que el sexo femenino aumenta el riesgo de desarrollar la enfermedad, aunque no afecta de forma negativa a su evolucion. El dimorfismo sexual en la EM es evidente, y todo apunta a una interaccion entre factores hormonales, geneticos y medioambientales. La poblacion pediatrica representa un grupo idoneo para el estudio de factores de susceptibilidad a la enfermedad, razon por la que se estan planteando estudios colaborativos ideados para aumentar la muestra de pacientes, dada su baja prevalencia. En esta revision se discute sobre los fenomenos inflamatorios y de neurodegeneracion que intervienen en la patogenia de la enfermedad, y que probablemente esten relacionados, bien de forma compartida o como causa efecto. Las hipotesis actuales apuntan a un fenomeno de compartimentacion presumiblemente inaccesible a la terapia inmunomoduladora actual. Entre los posibles mecanismos involucrados en estos procesos de inflamacion y desmielinizacion se discute el papel de las celulas Th17, disfuncion mitocondrial, disrupcion precoz de procesos astrocitarios e hipoxia cronica.

Review of the novelties presented at the 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (II).

The new insights presented at the 5th Joint Triennial Congress of the European and Americas Committees on Treatment and Research in Multiple Sclerosis (ECTRIMS and ACTRIMS) held in Amsterdam, the Netherlands, 19-22 October 2011, have been summarized at the fourth edition of Post-ECTRIMS meeting held in Madrid in November 2011. Regional grey-matter atrophy is more sensitive to cognitive impairment than global grey-matter atrophy measures. In patients with clinically isolated syndrome cognitive impairment does not predict conversion to multiple sclerosis (MS) after 5-years of follow-up. Focusing on central nervous system plasticity and functional reorganization in MS, an early intervention can improve clinical aspects and enhances brain plasticity. Preservation of a potential for plasticity provides a rationale for rehabilitation interventions even in later stages of disease. Therapeutical strategies have focused on stem cell-mediated remyelination and immunomodulation functions, on cellular infiltration into the brain, and on new ways for immuno-modulation for the development of future therapies in MS. Encouraging findings from clinical trials with current and emerging disease-modifying therapy being developed was also a key theme at this edition. Positive results have been reported for rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab, teriflunomide, BG-12, and laquinimod, including a favorable safety profile. Since armamentarium for the treatment of MS is fast increasing, concerns exist about the risk of severe adverse events with their use. This aspect reinforces the importance of disease registries as a proactive tool for monitoring drug safety in the post-approval setting.

Review of the novelties presented at the 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I).

The new insights presented at the 5th Joint Triennial Congress of the European and Americas Committees on Treatment and Research in Multiple Sclerosis (ECTRIMS and ACTRIMS) held in Amsterdam, the Netherlands, 19-22 October 2011, have been summarized at the fourth edition of Post-ECTRIMS meeting held in Madrid in November 2011. Further evidence from epidemiological studies yield a possible relationship between nutrition and alterations of the microbiota that may result in the development of multiple sclerosis (MS) and that may trigger the exacerbation of disease symptoms. Also show the magnitude of impact of comorbidities in multiple sclerosis course as well as the impact of early identification and management. Review of current data on chronic cerebrospinal venous insufficiency and MS sclerosis concludes that there is no role of chronic cerebrospinal venous insufficiency in either multiple sclerosis risk or MS severity. New diagnostic criteria for MS have simplified requirements for demonstrating dissemination of lesions in time. High-field magnetic resonance imaging improves cortical visualization and become a promising tool to detect remyelinization and cortical and medullary lesions, and optical coherence tomography is established as a powerful tool for neuroprotection trials. Diffuse meningeal inflammation through B-cell follicle-like structures is associated with cortical pathology and an accelerated clinical course in secondary progressive MS sclerosis. Systemic inflammation may contribute to neurodegeneration processes in MS, and with regard to grey matter damage recent findings conclude that occurs early in disease course, and correlates with future MS-related disability.

[Review of the novelties presented at the 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I)]. / Revision de las novedades presentadas en el XXVI Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (I).

The new insights presented at European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in the city of Gothenburg, Sweden, in October 2010, have been summarized at the third edition of Post-ECTRIMS meeting held in Madrid in November 2010. The age is an important factor related to the course and prognosis of multiple sclerosis (MS). The evolution to progressive disease persists more than 50 years after diagnosis of MS and a reduction in the delay of diagnosis has been detected. Several strategies have been proposed in order to improve the efficacy of magnetic resonance regarding prognosis and course of disease. The studies presented at the Congress reflect the influence of gender on course and severity of disease symptoms, showing an increase of worldwide prevalence of MS in women. Neuroprotective action of estrogen receptor beta has been reported. The genome wide association studies have allowed investigators to identify numerous susceptible alleles. In this regard, HLA class II genes, seems to contribute to genetic risk for developing neutralizing antibodies against beta-interferon. Vitamin D deficiency and Epstein-Barr virus have been highlighted as risk factors for MS in the reported findings. On the subject of the ongoing controversy regarding the role of inflammation and degeneration in MS, several arguments have been found to support the role of CNS autoimmunity to explain the presence of inflammatory phenomenon. The available data hold the potential therapeutic role of mesenchymal cells given the involvement of these stem cells in CNS repair.