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.

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)

Tratamiento de la esclerosis múltiple remitente recurrente con fingolimod en la práctica clínica habitual / Treatment of relapsing-remitting multiple sclerosis with fingolimod in routine clinical practice

Introducción. El fingolimod es un inmunosupresor selectivo dirigido contra el receptor SP-1, indicado en el tratamiento de la esclerosis múltiple remitente recurrente (EMRR) agresiva y tras el fracaso del tratamiento con fármacos de primera línea. Objetivo. Investigar la seguridad y efectividad del fingolimod en condiciones de práctica clínica habitual. Pacientes y métodos. Estudio observacional con seguimiento prospectivo de pacientes con EMRR que recibieron fingolimod desde enero de 2011 hasta febrero de 2014. Se evaluó la tasa anual de brotes (TAB), la discapacidad medida por la escala expandida del estado de discapacidad (EDSS), la actividad en la resonancia magnética y la aparición de efectos adversos. Resultados. Incluimos 122 pacientes, el 79,5% mujeres y con una edad media de 26,8 años. Se clasificaron según el último tratamiento recibido en: naïve (EMRR agresiva; n = 17), fracaso a terapias previas (n = 67) y retirada de natalizumab por riesgo de leucoencefalopatía multifocal progresiva (n = 38). Tras un seguimiento medio de 29,9 ± 15,9 meses, se redujo de forma significativa la TAB y la aparición de nuevas lesiones con realce de gadolinio en el grupo naïve y el de fracaso a terapias previas. No ha habido diferencias en la evolución de la EDSS ni en el tiempo hasta el primer brote o el fracaso terapéutico entre los diferentes subgrupos. El riesgo a fracaso terapéutico es mayor con la EDSS basal > 3 (hazard ratio: 4,24; p = 0,001) y presencia de bandas oligoclonales IgM (hazard ratio: 2,45; p < 0,022). Conclusiones. El fingolimod es un fármaco eficaz y seguro en la EMRR en condiciones de práctica clínica habitual. Tener una EDSS basal > 3 y bandas oligoclonales IgM predice una mala respuesta al fingolimod (AU)

Introduction. Fingolimod is a selective immunosuppressant that targets the S1P receptor, and is indicated in the treatment of aggressive relapsing-remitting multiple sclerosis (RRMS) and following treatment failure with first-order drugs. Aim. To investigate the safety and effectiveness of fingolimod under the conditions of routine clinical practice. Patients and methods. We conducted an observational study with prospective follow-up of patients with RRMS who received fingolimod from January 2011 until February 2014. Data assessed were the annualised relapse rate (ARR), disability measured by the Expanded Disability Status Scale (EDSS), magnetic resonance activity and the appearance of side effects. Results. Our sample consisted of 122 patients, 79.5% of them females and with a mean age of 26.8 years. They were classified, according to the last treatment received, as being: naïve (aggressive RRMS; n = 17), previous treatment failure (n = 67) and withdrawal of natalizumab due to risk of progressive multifocal leukoencephalopathy (n = 38). After a mean follow-up of 29.9 ± 15.9 months, the ARR and the appearance of new lesions with gadolinium enhancement were reduced in both the naïve and the previous treatment failure groups. There were no differences between the various subgroups as regards the progression of EDSS or the time elapsed until the first attack or treatment failure. The risk of treatment failure is higher with a baseline EDSS > 3 (hazard ratio: 4.24; p = 0.001) and presence of IgM oligoclonal bands (hazard ratio: 2.45; p < 0.022). Conclusions: Fingolimod is an effective and well-tolerated drug under conditions of routine clinical practice. Having a baseline EDSS > 3 and IgM oligoclonal bands is predictive of a poor response to fingolimod (AU)

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.

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)

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

Introducción. El recambio plasmático es una técnica utilizada en el tratamiento de algunas enfermedades neurológicas de base autoinmune desde los años ochenta, especialmente en situaciones agudas. En los últimos años se han publicado nuevos datos sobre su empleo en numerosas entidades con base autoinmune, ampliando, con ello, el espectro de utilización. Objetivo. Actualizar las indicaciones de esta técnica en el tratamiento de las enfermedades neurológicas. Desarrollo. Se ha realizado una revisión exhaustiva de todos los artículos publicados desde los años ochenta sobre la eficacia del recambio plasmático en el tratamiento de las diferentes enfermedades neurológicas. También se ha efectuado un análisis detallado de las recomendaciones y evidencias de la utilización de este procedimiento por parte de las diferentes sociedades científicas. Conclusiones. El recambio plasmático ha demostrado ser una alternativa eficaz con evidencia científica de primer nivel en enfermedades como el síndrome de Guillain-Barré, la polineuropatía desmielinizante inflamatoria crónica 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 óptica 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 relación coste-eficacia de ambos procedimientos (AU)

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-Barré 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 (AU)

[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.

Comorbilidad en esclerosis múltiple y su abordaje asistencial / Cormorbidity in multiple sclerosis and its therapeutic approach

La esclerosis múltiple (EM) es una enfermedad crónica de muy larga evolución, donde procesos intercurrentes se van a presentar en las personas con EM con una frecuencia 3 veces mayor que en las personas sin EM. El conocimiento de la comorbilidad, su definición y su medida (índice de Charlson) van a permitir un mejor tratamiento de los pacientes, de forma que actuando sobre los procesos intercurrentes podemos mejorar la progresión de la discapacidad, que está estrechamente relacionada con el número de procesos morbosos concurrentes y con los estados y hábitos de salud. Pero, además, la presencia de procesos concurrentes va a retrasar el diagnóstico de la EM, con lo que supone de retraso en el inicio del tratamiento. La comorbilidad que esperamos encontrar en la EM va a abarcar, sobre todo, a otras enfermedades autoinmunes (tiroiditis, lupus eritematoso o pénfigo), pero también enfermedades generales como asma o alteraciones osteomusculares, y sobre todo alteraciones psiquiátricas. Todas estas situaciones deberemos recogerlas en escalas multidimensionales (Disability Expectancy Table, DET), que nos permitirán conocer mejor la evolución real y la calidad de vida de los pacientes, y saber cómo la EM, los procesos concurrentes e intercurrentes que acompañan la evolución de los pacientes así como los tratamientos que se administran, afectan a los pacientes con EM, para abordar globalmente el estado de salud y poder mejorar su calidad de vida (AU)

Multiple sclerosis (MS) is a long-term chronic disease, in which intercurrent processes develop three times more frequently in affected individuals than in persons without MS. Knowledge of the comorbidity of MS, its definition and measurement (Charlson index) improves patient management. Acting on comorbid conditions delays the progression of disability, which is intimately linked to the number of concurrent processes and with health states and habits. Moreover, the presence of comorbidities delays the diagnosis of MS, which in turn delays the start of treatment. The main comorbidity found in MS includes other autoimmune diseases (thyroiditis, systemic lupus erythematosus, or pemphigus) but can also include general diseases, such as asthma or osteomuscular alterations, and, in particular, psychiatric disturbances. All these alterations should be evaluated with multidimensional scales (Disability Expectancy Table, DET), which allow more accurate determination of the patient's real clinical course and quality of life. These scales also allow identification of how MS, concurrent and intercurrent processes occurring during the clinical course, and the treatment provided affect patients with MS. An overall approach to patients’ health status helps to improve quality of life (AU)

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.

Revisión de las novedades presentadas en el XXIX Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS) (II) / Review of the novelties presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (II)

Los datos más relevantes presentados en la XXIX edición del Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS), celebrado en octubre de 2013 en Dinamarca, se han resumido en la sexta edición de la Reunión de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2013, fruto de la cual nace esta revisión, que se publica en tres partes. Esta segunda parte de la revisión Post-ECTRIMS se centra en la imagen del diagnóstico y diagnóstico diferencial, en la monitorización clínica y paraclínica de la neurodegeneración, progresión y discapacidad, y en la imagen funcional y conectividad neural. Queda patente que las secuencias convencionales de esclerosis múltiple siguen siendo básicas para el diagnóstico, el diagnóstico diferencial y el seguimiento de la enfermedad, que las nuevas técnicas de resonancia magnética ayudan a evaluar el proceso de neurodegeneración, y algunas de las nuevas secuencias son más específicas del daño neuronal-axonal. La resonancia magnética de campo muy alto permite un mejor conocimiento de la carga lesional, distribución y heterogeneidad de las lesiones, y los estudios con tomografía por emisión de positrones ofrecen una nueva visión de la fisiopatología de la enfermedad. Los estudios de imagen funcional y conectividad neural muestran que en la esclerosis múltiple existe una reorganización cortical cuyo equilibrio con el daño estructural es responsable de la discapacidad (AU)

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 pathophysiology 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 (AU)

Revisión de las novedades presentadas en el XXIX Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS) (III) / Review of the novelties presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (III)

Los datos más relevantes presentados en la XXIX edición del Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS), celebrado en octubre de 2013 en Dinamarca, se han resumido en la sexta edición de la Reunión de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2013, fruto de la cual nace esta revisión, que se publica en tres partes. Esta tercera parte de la revisión Post-ECTRIMS aborda los efectos del tratamiento inmunomodulador en la historia natural de la esclerosis múltiple, con especial atención a la valoración del efecto a largo plazo y al uso de controles históricos como alternativa a los estudios aleatorizados comparados con placebo. Este artículo recoge posibles estrategias terapéuticas futuras que pasan por los modelos experimentales, y expone los ensayos clínicos en marcha y futuros tratamientos. Asimismo, resume los resultados de los últimos estudios de los tratamientos modificadores de la enfermedad y las novedades en el manejo sintomático. Brevemente, en el horizonte, hay muchos fármacos con diferentes mecanismos de acción, aunque son necesarias nuevas estrategias y algoritmos terapéuticos, biomarcadores y nuevas medidas de evaluación de la progresión secundaria, y registros a largo plazo para evaluar la seguridad. En cuanto al tratamiento sintomático de la enfermedad, se apuesta por un plan personalizado de tratamiento y una aproximación multidisciplinar, de cara a mejorar la calidad de vida de los pacientes (AU)

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 (AU)