Effectiveness and Safety of Teriflunomide in Relapsing-Remitting Multiple Sclerosis and Improvements in Quality of Life: Results from the Real-World TERICARE Study.

INTRODUCTION: Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on the local label), based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2 years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression. METHODS: This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4 weeks. The following patient-reported outcomes (PROs) were collected at baseline and every 6 months for 2 years: the 29-item Multiple Sclerosis Impact Scale version 2 (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the Beck Depression Inventory (BDI-II), the Short Form (SF)-Qualiveen and the Treatment Satisfaction Questionnaire for Medication v1.4 (TSQM). Annualised relapse rate (ARR), disability progression according to the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA-3) were also assessed. RESULTS: A total of 325 patients were analysed. Patients had a mean (SD) age of 43.2 years (10.4), a mean baseline EDSS score of 1.75 (1.5), a mean number of relapses in the past 2 years of 1.5 (0.7), and 64% had received prior disease-modifying therapy (DMT). Patients showed significant improvements in the psychological domain of MSIS-29 from 35.9 (26.6) at baseline to 29.4 (25.5) at 18 months (p = 0.004) and 29.0 (24.6) at 24 months (p = 0.002). Levels of fatigue and depression were also reduced. After 2 years of treatment with teriflunomide, ARR was reduced to 0.17 (95% CI 0.14-0.21) from the baseline of 0.42 (95% CI 0.38-0.48), representing a 60.1% reduction. Mean EDSS scores remained stable during the study, and 79.9% of patients showed no disability progression. 54.7% of patients achieved NEDA-3 in the first 12 months, which increased to 61.4% during months 12-24. Patients reported increased satisfaction with treatment over the course of the study, regardless of whether they were DMT naive or not. CONCLUSION: Teriflunomide improves psychological aspects of HRQoL and maintains low levels of fatigue and depression. Treatment with teriflunomide over 2 years is effective in reducing ARR and disability progression.

Treatment of multiple sclerosis with rituximab: A Spanish multicenter experience.

Introduction: Rituximab (RTX) is considered a potential therapeutic option for relapsing-remitting (RRMS) and progressive forms (PMS) of multiple sclerosis (MS). The main objective of this work was to investigate the effectiveness and safety of rituximab in MS. Patients and methods: Observational multicenter study of clinical and radiological effectiveness and safety of rituximab in RRMS and PMS. Results: A total of 479 rituximab-treated patients were included in 12 Spanish centers, 188 RRMS (39.3%) and 291 (60.7%) PMS. Despite standard treatment, the annualized relapse rate (ARR) the year before RTX was 0.63 (SD: 0.8) and 156 patients (41%) had at least one gadolinium-enhanced lesion (GEL) on baseline MRI. Mean EDSS had increased from 4.3 (SD: 1.9) to 4.8 (SD: 1.7) and almost half of the patients (41%) had worsened at least one point. After a median follow-up of 14.2 months (IQR: 6.5-27.2), ARR decreased by 85.7% (p < 0.001) and GEL by 82.9%, from 0.41 to 0.07 (p < 0.001). A significant decrease in EDSS to 4.7 (p = 0.046) was observed after 1 year of treatment and this variable remained stable during the second year of therapy. There was no evidence of disease activity in 68% of patients. Infusion-related symptoms were the most frequent side effect (19.6%) and most were mild. Relevant infections were reported only in 18 patients (including one case of probable progressive multifocal leukoencephalopathy). Conclusion: Rituximab could be an effective and safe treatment in RRMS, including aggressive forms of the disease. Some selected PMS patients could also benefit from this treatment.

MAB-MIG: registry of the spanish neurological society of erenumab for migraine prevention.

BACKGROUND: Erenumab was approved in Europe for migraine prevention in patients with ≥ 4 monthly migraine days (MMDs). In Spain, Novartis started a personalized managed access program, which allowed free access to erenumab before official reimbursement. The Spanish Neurological Society started a prospective registry to evaluate real-world effectiveness and tolerability, and all Spanish headache experts were invited to participate. We present their first results. METHODS: Patients fulfilled the ICHD-3 criteria for migraine and had ≥ 4 MMDs. Sociodemographic and clinical data were registered as well as MMDs, monthly headache days, MHDs, prior and concomitant preventive treatment, medication overuse headache (MOH), migraine evolution, adverse events, and patient-reported outcomes (PROs): headache impact test (HIT-6), migraine disability assessment questionnaire (MIDAS), and patient global improvement change (PGIC). A > 50% reduction of MMDs after 12 weeks was considered as a response. RESULTS: We included 210 patients (female 86.7%, mean age 46.4 years old) from 22 Spanish hospitals from February 2019 to June 2020. Most patients (89.5%) suffered from chronic migraine with a mean evolution of 8.6 years. MOH was present in 70% of patients, and 17.1% had migraine with aura. Patients had failed a mean of 7.8 preventive treatments at baseline (botulinum toxin type A-BoNT/A-had been used by 95.2% of patients). Most patients (67.6%) started with erenumab 70 mg. Sixty-one percent of patients were also simultaneously taking oral preventive drugs and 27.6% were getting simultaneous BoNT/A. Responder rate was 37.1% and the mean reduction of MMDs and MHDs was -6.28 and -8.6, respectively. Changes in PROs were: MIDAS: -35 points, HIT-6: -11.6 points, PIGC: 4.7 points. Predictors of good response were prior HIT-6 score < 80 points (p = 0.01), ≤ 5 prior preventive treatment failures (p = 0.026), absence of MOH (p = 0.039), and simultaneous BoNT/A treatment (p < 0.001). Twenty percent of patients had an adverse event, but only two of them were severe (0.9%), which led to treatment discontinuation. Mild constipation was the most frequent adverse event (8.1%). CONCLUSIONS: In real-life, in a personalized managed access program, erenumab shows a good effectiveness profile and an excellent tolerability in migraine prevention in our cohort of refractory patients.

Serum CGRP, VIP, and PACAP usefulness in migraine: a case-control study in chronic migraine patients in real clinical practice.

Calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypetide-38 (PACAP-38) have relevant roles in migraine pathophysiology. Their serum levels have been proposed as biomarkers for migraine. Our aim was to assess their diagnostic value in real clinical practice in a cohort of chronic migraine (CM), episodic migraine (EM) and healthy controls (HC). We recruited subjects with CM, EM and HC at two medical centers. Blood samples were drawn under fasting conditions in the interictal period, immediately centrifuged and stored at - 80 ºC. Serum levels were determined by ELISA. Neuropeptide levels, the effect of preventatives, correlations with clinical and demographic variables, and their diagnostic value were studied among clinical categories. 296 age- and sex-matched subjects (101 CM, 98 EM and 97 HC) were included. All three neuropeptide serum levels were higher in CM [median and IQ for CGRP = 18.023 pg/ml (14.4-24.7); VIP = 121.732 pg/ml (48.72-186.72) and PACAP = 204.931 pg/ml (101.08-597.64)] vs EM [CGRP = 14.659 pg/ml (10.29-17.45); VIP = 75.603 pg/ml (28.722-107.10); and PACAP = 94.992 pg/ml (65.77-128.48)] and vs HC [CGRP = 13.988 pg/ml (10.095-17.87); VIP = 84.685 pg/ml (35.32-99.79), and PACAP = 103.142 pg/ml (59.42-123.97)]. Using multinomial modeling, only VIP (OR 1.011, 95% CI 1.003-1.018, p = 0.005) and PACAP (OR 1.003, 95% CI 1.001-1.005, p = 0.002) increased the risk for CM, but not for EM. CGRP did not predict CM or EM. This model could correctly classify only 62/101 (61.38%) of CM, 75/98 (76.53%) of EM, and 5/97 (4.12%) of HC [globally 147/296 (49.8%)]. Individually, PACAP performed the best for classifying clinical categories [global accuracy 150/296 (50.67%)]. In CM, neuropeptide levels were higher in those OnaBT-treated than in no-treated patients. Although interictal serum CGRP and VIP were higher in CM than both EM or HC, their utility to discriminate migraine categories was low. Contrary to other studies, PACAP serum levels were also higher in CM than in EM or HC and had more discriminative capability to distinguish CM from EM and HC. Further investigation is needed for determination technique standardization.

XII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2019 (II) / 12th Post-ECTRIMS Meeting: review of the novelties from the 2019 ECTRIMS Congress (II)

INTRODUCCIÓN: Como cada año, tras la celebración del Congreso del ECTRIMS, reconocidos neurólogos españoles expertos en esclerosis múltiple expusieron en la Reunión Post-ECTRIMS las principales novedades en investigación en este ámbito. OBJETIVO: Sintetizar el contenido presentado en la XII edición de la Reunión Post-ECTRIMS, que tuvo lugar en septiembre de 2019 en Sevilla y que se presenta en dos partes. DESARROLLO: En esta segunda parte, se exponen las evidencias más recientes sobre el uso de tratamientos modificadores de la enfermedad durante el embarazo. Se detallan los resultados de ensayos clínicos en fase 3 en los que se ha evaluado la eficacia y la seguridad de dos potenciales tratamientos modificadores de la enfermedad para la esclerosis múltiple remitente recurrente: ponesimod y ofatumumab. Para las formas progresivas, se revisan los tratamientos modificadores de la enfermedad disponibles y en investigación. En el ámbito de las terapias con células madre, se incluyen los resultados del único ensayo clínico hasta la fecha que compara a pacientes con esclerosis múltiple remitente recurrente tratados con trasplante autólogo de células madre hematopoyéticas y a los tratados con tratamientos modificadores de la enfermedad. No hay grandes novedades sobre tratamientos sintomáticos, aunque la Academia Europea de Neurología ha publicado una guía sobre cuidados paliativos. Se revisan las distintas fuentes de información que recogen datos de farmacovigilancia en el entorno poscomercialización. CONCLUSIONES: Los pacientes diagnosticados en los últimos años tienden a tener una menor gravedad de la esclerosis múltiple, probablemente debido al diagnóstico desde sus estadios más leves y al continuo aumento de tratamientos disponibles

INTRODUCTION: Like every year, after the ECTRIMS Congress, renowned Spanish neurologists who are experts in multiple sclerosis presented the main novelties in research in this field at the Post-ECTRIMS Meeting. AIM: To summarise the content presented at the 12th edition of the Post-ECTRIMS Meeting, which took place in September 2019 in Sevilla and is presented in two parts. DEVELOPMENT. In this second part, the most recent evidence on the use of disease-modifying treatments during pregnancy is presented. Details are provided concerning the results of phase 3 clinical trials conducted to evaluate the efficacy and safety of two potential disease-modifying treatments for relapsing-remitting multiple sclerosis: ponesimod and ofatumumab. For the progressive forms, both available disease modifying treatments and others still in the research phase are reviewed. In the field of stem cell therapies, the article includes the results of the only clinical trial carried out to date comparing patients with relapsing-remitting multiple sclerosis treated with autologous haematopoietic stem cell transplantation and those treated with disease-modifying therapies. There are no important developments as regards symptomatic treatments, although the European Academy of Neurology has published a guide on palliative care. The various sources of information that collect pharmacovigilance data in the post-marketing setting are reviewed. CONCLUSIONS:l Patients diagnosed in recent years tend to have less severe multiple sclerosis, probably due to the fact that it is diagnosed in its milder stages together with the steady increase in the number of treatments available

XII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2019 (I) / 12th Post-ECTRIMS Meeting: review of the novelties from the 2019 ECTRIMS Congress (I)

INTRODUCCIÓN: Como cada año, tras la celebración del Congreso ECTRIMS, reconocidos neurólogos españoles expertos en esclerosis múltiple expusieron en la Reunión Post-ECTRIMS las principales novedades en investigación en este ámbito. OBJETIVO: Sintetizar el contenido presentado en la XII edición de la Reunión Post-ECTRIMS, que tuvo lugar en septiembre de 2019 en Sevilla y que se presenta en dos partes. DESARROLLO: Esta primera parte aborda los últimos estudios sobre el déficit de vitamina D y las discrepancias existentes acerca de su tratamiento. Los avances en epigenética realizados permiten presentar esta aproximación como un posible biomarcador de la esclerosis múltiple. Se explica el creciente protagonismo de las técnicas de imagen para detectar la atrofia y otros fenómenos que acontecen durante la enfermedad, como los cambios en la concentración de hierro o los procesos de remielinización, que nos permiten ganar comprensión sobre los mecanismos de la patología cortical, y sobre la dimensionalidad de la neurodegeneración durante su evolución. Se discuten los hallazgos relacionados con los mecanismos inmunológicos y los avances realizados en las potenciales terapias específicas del antígeno. Se presentan los últimos estudios sobre la evaluación del deterioro cognitivo y su rehabilitación, que cobran cada vez más importancia por la alta prevalencia de estas alteraciones y por la ausencia de su evaluación sistemática en la práctica clínica. Por último, se exponen las necesidades sociosanitarias no cubiertas de los pacientes de esclerosis múltiple en nuestro país, poniendo el acento en los déficits actuales del sistema de protección social

INTRODUCTION. Like every year, after the ECTRIMS Congress, renowned Spanish neurologists who are experts in multiple sclerosis presented the main novelties in research in this field at the Post-ECTRIMS Meeting. AIM. To summarise the content presented at the 12th edition of the Post-ECTRIMS Meeting, which took place in September 2019 in Sevilla and is presented in two parts. DEVELOPMENT. This first part addresses the latest studies on vitamin D deficiency and the discrepancies that currently exist regarding its treatment. The advances made in epigenetics allow us to present this approach as a possible biomarker of multiple sclerosis. An account is provided to explain the growing importance of imaging techniques to detect atrophy and other phenomena that occur during the disease, such as changes in iron concentration or remyelination processes, which allow us to further our understanding of the mechanisms of cortical pathology, and the dimensionality of neurodegeneration during its course. Findings related to immunological mechanisms and advances in potential antigen-specific therapies are discussed. The contribution presents the latest studies on the assessment of cognitive impairment and its rehabilitation, which are becoming increasingly important due to the high prevalence of these disorders and the absence of their systematic assessment in clinical practice. Finally, the unmet social and health needs of multiple sclerosis patients in our country are presented, with emphasis on the current deficits in the system of social protection

New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab.

Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression. Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from <1/3,300 in patients with anti-John Cunninghan virus antibody indices <0.9 and relapse rate >0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from <1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices <0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case. Conclusions: In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopathy.

Necesidad real y consumo de recursos en las unidades de cefalea: estudio observacional retrospectivo sobre una cohorte en Cantabria / Real need for headache services and their resource consumption: a retrospective observational study on a cohort in Cantabria

Introducción. Las unidades de cefalea surgen por una necesidad de mejorar la asistencia a los pacientes con cefalea; no obstante, se desconocen aspectos importantes de gestión clínica que demuestren su eficiencia. Objetivo. Estimar la necesidad de unidades de cefalea en nuestro medio. Pacientes y métodos. Estudio retrospectivo realizado en dos fases: identificación de las primeras consultas por cefalea durante tres meses consecutivos y recogida de datos asistenciales ocurridos durante un año. Criterios de asistencia en unidades de cefalea: migraña crónica, cefaleas raras, necesidad de técnicas especiales y cefaleas con mala respuesta terapéutica. Resultados. De las 1.418 primeras consultas, en 298 (20,38%) la cefalea fue el motivo asistencial. El 82,9% procedía de atención primaria. La distribución de diagnósticos fue: 54% migraña, 11% cefalea tensional y 35% otras cefaleas. Un total de 108 pacientes cumplía los criterios de derivación a unidades de cefalea: 63 por migraña crónica, 13 por bloqueos nerviosos, 9 por migraña frecuente, 8 por cefaleas trigeminoautonómicas, 5 por necesidad de toxina botulínica y 10 por otros motivos. Los pacientes atendidos por unidades de cefalea acudieron menos veces a urgencias que los de consulta general, se les realizaron menos tomografías cerebrales y se les indicó más toxina botulínica. Conclusión. Las unidades de cefalea están justificadas por gestionar mejor los pacientes con las variantes más graves de cefalea. En nuestro medio se justifican al menos dos consultas semanales para atender un área de 350.000 usuarios del Sistema Nacional de Salud

Introduction. Headache services arise out of a need to improve care for patients with different types of headache; however, some important aspects of clinical management that demonstrate their efficiency remain unknown. Aim. To estimate the need for headache services in our area. Patients and methods. We conducted a retrospective study in two phases: identification of the first visits due to headache during three consecutive months and collection of care data during one year. The care criteria in headache services considered were: chronic migraine, rare headaches, need for special techniques and headaches with poor therapeutic response. Results. Of the 1,418 first visits, in 298 cases (20.38%) the reason for seeking medical attention was headache. Of these, 82.9% were from primary care. The distribution of the diagnoses was: 54%, migraine; 11%, tension-type headache; and 35%, other headaches. Altogether 108 patients met the criteria for referral to headache services: 63 for chronic migraine; 13 for nerve blocks; 9 for frequent migraine; 8 for trigeminal-autonomic cephalgias; 5 due to a need for botulinum toxin; and 10 for other reasons. The patients attended by headache services went to the emergency department less often than those who visited the general outpatient department, had fewer brain scans and more botulinum toxin was indicated. CONCLUSION. Headache services are justified because they offer better management of patients with the most severe variants of headache. In our country, at least two visits a week are needed to cover an area of 350,000 users of the Spanish National Health System

Revisión de las novedades presentadas en el Congreso ECTRIMS 2018: XI Reunión Post-ECTRIMS (II) / Review of the novelties presented at the 2018 ECTRIMS Congress: 11th Post-ECTRIMS Meeting (II)

La reunión Post-ECTRIMS se celebró por undécimo año consecutivo el pasado octubre de 2018 en Madrid, con el objetivo de analizar los avances en esclerosis múltiple destacados en el último congreso anual ECTRIMS. Fruto de esta reunión, formada por los líderes de opinión en esclerosis múltiple de ámbito nacional, se presentan dos artículos de revisión. En esta segunda parte, se incluye el creciente número de evidencias que confirman la seguridad de la exposición a los tratamientos modificadores de la enfermedad en mujeres que planifican un embarazo, y el efecto beneficioso de la lactancia, siempre y cuando la enfermedad no esté muy activa. Se abordan los datos que muestran cómo la aplicación de los criterios de McDonald de 2017 en población pediátrica ha mejorado considerablemente el diagnóstico en comparación con los criterios anteriores. En cuanto a la esclerosis múltiple progresiva, los resultados de los fármacos neuroprotectores son poco concluyentes, pero se proponen biomarcadores para mejorar la evaluación de la respuesta terapéutica. Los estudios sobre tratamientos de reparación de la mielina sugieren que la remielinización en la esclerosis múltiple es posible. De igual manera, se exponen indicios favorables sobre el trasplante de células madre hematopoyéticas, siempre que se seleccione adecuadamente a los pacientes. Por otro lado, se revisan las similitudes y diferencias de las recomendaciones de las nuevas guías de práctica clínica publicadas. Por último, los resultados positivos de la rehabilitación cognitiva y motora con el uso de las nuevas tecnologías vaticinan la incorporación sistemática de estas herramientas en el tratamiento de la enfermedad en un futuro próximo

The Post-ECTRIMS Meeting was held for the eleventh consecutive year in October 2018 in Madrid, with the aim of analysing the advances made in multiple sclerosis that were highlighted at the latest ECTRIMS annual congress. Based on the issues discussed at this meeting, attended by the nation’s foremost opinion leaders on multiple sclerosis, two review articles are presented. This second part includes the growing body of evidence confirming the safety of exposure to disease-modifying treatments in women planning a pregnancy, and the beneficial effect of breastfeeding, provided that the disease is not very active. It addresses data showing how the application of the 2017 McDonald criteria in the paediatric population has significantly improved diagnosis compared to the previous criteria. With regard to progressive multiple sclerosis, the results of neuroprotective drugs are inconclusive, but biomarkers are proposed to improve the evaluation of the therapeutic response. Studies on myelin repair treatments suggest that remyelination in multiple sclerosis is possible. Likewise, there are favourable indications for haematopoietic stem cell transplantation, provided that patients are selected appropriately. On the other hand, we also conduct a review of the similarities and differences of the recommendations in the new clinical practice guidelines. Finally, the positive results of cognitive and motor rehabilitation with the use of new technologies point to the systematic incorporation of these tools in the treatment of the disease in the near future

Revisión de las novedades presentadas en el congreso ECTRIMS 2018: XI Reunión Post-ECTRIMS (I) / Review of the novelties presented at the 2018 ECTRIMS Congress: 11th Post-ECTRIMS Meeting (I)

La reunión Post-ECTRIMS es un encuentro emblemático en España que persigue revisar y difundir los principales avances en esclerosis múltiple presentados en el congreso anual ECTRIMS. En octubre de 2018, la reunión Post-ECTRIMS celebró en Madrid su undécima edición, contando con los mayores expertos de ámbito nacional en esclerosis múltiple. Como resultado de esta reunión, se presentan dos artículos donde se recogen las novedades más destacadas en la misma. En esta primera parte se incluyen los últimos resultados sobre la influencia de los factores de riesgo modificables y no modificables en la esclerosis múltiple, destacando los progresos realizados en el ámbito genético, donde el descubrimiento de genes asociados a la esclerosis múltiple ha aumentado exponencialmente. Se aborda la complejidad del sistema inmune y se realizan algunas aportaciones sobre los mecanismos de autoinmunidad, en los que se observan relaciones bidireccionales entre las células inmunes y las células residentes del sistema nervioso central, como la microglía y los astrocitos. Los biomarcadores, tanto en suero y líquido cefalorraquídeo como de imagen, ganan cada vez más atención por su papel actual, y sobre todo potencial, en el diagnóstico y pronóstico de la enfermedad y en la evaluación de la eficacia de los tratamientos. Por último, se presentan las observaciones realizadas respecto a los cambios en la conectividad estructural y funcional en los pacientes y su relación con las alteraciones clínicas

The Post-ECTRIMS Meeting is an emblematic event in Spain which seeks to review and disseminate the main advances in multiple sclerosis presented at the ECTRIMS annual congress. In October 2018, the eleventh Post-ECTRIMS meeting was held in Madrid and was attended by the country’s leading experts in multiple sclerosis. As a result of this meeting, we present two articles which outline the most interesting novelties discussed there. This first part includes the latest results obtained regarding the influence of modifiable and non-modifiable risk factors in multiple sclerosis, with emphasis on the progress made in the field of genetics, where the discovery of genes associated with multiple sclerosis has increased exponentially. The complexity of the immune system is addressed and some contributions are made on autoimmunity mechanisms, in which bidirectional relations are observed between immune cells and cells residing in the central nervous system, such as microglial cells and astrocytes. Biomarkers, both in serum and cerebrospinal fluid as well as in imaging, are gaining more and more attention due to their current and, above all, potential role in the diagnosis and prognosis of the disease and in the evaluation of the efficacy of treatments. Finally, the observations made regarding changes in structural and functional connectivity in patients and their relationship with clinical alterations are presented

Multi-centre validation of a flow cytometry method to identify optimal responders to interferon-beta in multiple sclerosis.

BACKGROUND AND OBJECTIVES: Percentages of blood CD19+CD5+ B cells and CD8+perforin+ T lymphocytes can predict response to Interferon (IFN)-beta treatment in relapsing-remitting multiple sclerosis (RRMS) patients. We aimed to standardize their detection in a multicenter study, prior to their implementation in clinical practice. METHODS: Fourteen hospitals participated in the study. A reference centre was established for comparison studies. Peripheral blood cells of 105 untreated RRMS patients were studied. Every sample was analyzed in duplicate in the participating centre and in the reference one by flow cytometry. When needed, participating centres corrected fluorescence compensations and negative cut-off position following reference centre suggestions. Concordance between results obtained by participating centres and by reference one was evaluated by intraclass correlation coefficients (ICC) and Spearman correlation test. Centre performance was measured by using z-scores values. RESULTS: After results review and corrective actions implementation, overall ICC was 0.86 (CI: 0.81-0.91) for CD19+CD5+ B cell and 0.89 (CI: 0.85-0.93) for CD8+ perforin+ T cell quantification; Spearman r was 0.92 (0.89-0.95; p <0.0001) and 0.92 (0.88-0.95; p <0.0001) respectively. All centres obtained z-scores≤0.5 for both biomarkers. CONCLUSION: Homogenous percentages of CD19+CD5+ B cells and CD8 perforin+ T lymphocytes can be obtained if suitable compensation values and negative cut-off are pre-established.

Revisión de las novedades del Congreso ECTRIMS 2017, presentadas en la X Reunión Post-ECTRIMS (II) / Review of the novelties from the 2017 ECTRIMS Congress, presented at the 10th Post-ECTRIMS Meeting (II)

La reunión Post-ECTRIMS es una reunión emblemática en el ámbito de la esclerosis múltiple en España, con el claro objetivo de analizar, de la mano de reconocidos neurólogos especialistas nacionales, los principales avances en esclerosis múltiple y revisar los temas más importantes del congreso ECTRIMS. En noviembre de 2017, la reunión Post-ECTRIMS celebro su décima edición, y se ha consolidado como un importante foro de encuentro de expertos en nuestro país para favorecer la comunicación, establecer sinergias, y promover y potenciar la investigación para mejorar, en última instancia, el pronóstico y la calidad de vida de los pacientes con esclerosis múltiple. En esta segunda parte se abordan las diferentes estrategias para el manejo de los pacientes con enfermedad avanzada y la seguridad de la terapia en esclerosis múltiple, y se resaltan las áreas que requieren una mayor evidencia científica y clínica. La esclerosis múltiple en la población pediátrica y el envejecimiento en la enfermedad cobran especial importancia en esta edición, remarcando la necesidad del desarrollo de estudios colaborativos y de una mayor concienciación de los especialistas en la detección y el manejo de las comorbilidades en la esclerosis múltiple

The Post-ECTRIMS Meeting is an emblematic event in the field of multiple sclerosis in Spain. Its chief aim is bring together the country’s leading specialist neurologists to analyse the main advances made in multiple sclerosis and to review the most important topics addressed at the ECTRIMS Congress. The tenth Post-ECTRIMS Meeting was held in November 2017. Over the years this event has firmly established itself as an important meeting point where experts from all over the country get together to foster communication, establish synergies and promote and enhance research ultimately aimed at improving the prognosis and quality of life of patients with multiple sclerosis. This second part addresses the different strategies for the management of patients in advanced stages of the disease and the safety of therapy in multiple sclerosis. Likewise, attention is also drawn to the areas that require further scientific and clinical evidence. In this edition, particular importance is given to multiple sclerosis in the paediatric population and ageing in the disease. At the same time emphasis is placed on the need to conduct collaborative studies and to foster greater awareness among specialists regarding the detection and management of the comorbidities in multiple sclerosis

Revisión de las novedades del Congreso ECTRIMS 2017, presentadas en la X Reunión Post-ECTRIMS (I) / Review of the novelties from the 2017 ECTRIMS Congress, presented at the 10th Post-ECTRIMS Meeting (I)

La reunión Post-ECTRIMS es una reunión emblemática en el ámbito de la esclerosis múltiple en España, con el claro objetivo de analizar, de la mano de reconocidos neurólogos especialistas nacionales, los principales avances en esclerosis múltiple y revisar los temas más importantes del congreso ECTRIMS. En noviembre de 2017, la reunión Post-ECTRIMS celebró su décima edición, y se ha consolidado como un importante foro de encuentro de expertos en nuestro país para favorecer la comunicación, establecer sinergias, y promover y potenciar la investigación para mejorar, en última instancia, el pronóstico y la calidad de vida de los pacientes con esclerosis múltiple. En esta primera parte se avanza la publicación de las nuevas guías clínicas europea y americana para el uso de los tratamientos modificadores de la enfermedad, y los nuevos criterios diagnósticos. Se discuten las estrategias para el seguimiento de los pacientes tratados con terapias modificadoras de la enfermedad, se revisan la atrofia cerebral y los biomarcadores de neurodegeneración y neuroinflamación, y se analiza el papel de la neuroglía en la patogenia y el tratamiento. Se hace un recorrido por la historia natural de la enfermedad, con la evidencia que aportan los registros, y nos adelantamos al futuro gracias a los avances en genética e inmunología

The Post-ECTRIMS Meeting is an emblematic event in the field of multiple sclerosis in Spain. Its chief aim is bring together the country’s leading specialist neurologists to analyse the main advances made in multiple sclerosis and to review the most important topics addressed at the ECTRIMS Congress. The tenth Post-ECTRIMS Meeting was held in November 2017. Over the years this event has firmly established itself as an important meeting point where experts from all over the country get together to foster communication, establish synergies and promote and enhance research ultimately aimed at improving the prognosis and quality of life of patients with multiple sclerosis. This first part reports on the publication of the new European and American clinical guidelines on the use of disease-modifying treatments and the new diagnostic criteria. It also discusses the strategies for following up patients treated with disease-modifying therapies, reviews cerebral atrophy and biomarkers of neurodegeneration and neuroinflammation, and analyses the role of neuroglia in pathogenesis and treatment. The study examines the natural history of the disease, with the evidence provided by registers, and we anticipate the future thanks to the progress being made in genetics and immunology

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)

Utilidad del tratamiento con atorvastatina 40 mg más ezetimiba 10 mg frente a atorvastatina 80 mg en la reducción de los niveles de colesterol LDL en pacientes con ictus isquémico o ataque isquémico transitorio / Utility of treatment with atorvastatin 40 mg plus ezetimibe 10 mg versus atorvastatin 80 mg in reducing the levels of LDL cholesterol in patients with ischaemic stroke or transient ischaemic attack

Introducción. Tras un ictus isquémico, reducir los niveles de colesterol LDL (LDLc) disminuye el riesgo de recurrencia. El riesgo de recurrencia es menor con reducciones más intensas de las cifras de LDLc. Objetivo. Evaluar la eficacia y seguridad del tratamiento hipolipemiante combinado con atorvastatina 40 mg más ezetimiba 10 mg tras un ictus isquémico o ataque isquémico transitorio (AIT). Pacientes y métodos. Evaluación de la eficacia del tratamiento con atorvastatina 40 mg más ezetimiba 10 mg (n = 34) frente a atorvastatina 80 mg (n = 52) en la modificación de parámetros lipídicos tras un ictus isquémico o AIT. Se estableció como objetivo primario la obtención de niveles de LDLc ≤ 70 mg/dL o la reducción de las cifras de LDLc ≥ 50%. Adicionalmente se evaluó la presencia de efectos secundarios en ambos grupos. Resultados. Se observó un incremento significativo de las probabilidades de alcanzar el objetivo primario en el grupo tratado con atorvastatina 40 mg más ezetimiba 10 mg (odds ratio: 11,94; intervalo de confianza al 95%: 2,82-50,64; p = 0,001) y en los varones (odds ratio: 4,76; intervalo de confianza al 95%: 1,35-16,67; p = 0,02). El tratamiento con atorvastatina 40 mg más ezetimiba 10 mg obtuvo reducciones superiores de LDLc (p < 0,001), colesterol total (p = 0,001) y no HDLc (p < 0,001). Ambos tratamientos fueron seguros, con escaso número de efectos secundarios. Conclusiones. En comparación con atorvastatina 80 mg, el tratamiento con atorvastatina 40 mg más ezetimiba 10 mg incrementa la probabilidad de alcanzar los objetivos de LDLc. Ambos tratamientos son seguros y bien tolerados (AU)

Introduction. After an ischaemic stroke, to reduce LDL cholesterol (LDLc) levels decreases the risk of recurrence. The risk of recurrence is lower with more intense reductions in LDLc levels. Aim. To evaluate the efficacy and security of atorvastatin 40 mg plus ezetimibe 10 mg after ischaemic stroke or transient ischaemic attack (TIA). Patients and methods. We retrospectively evaluated stroke or TIA patients admitted to our hospital who received atorvastatin 40 mg plus ezetimibe 10 mg (n = 34) or atorvastatin 80 mg (n = 52) at discharge. We analyzed changes in lipid parameters and established as a primary outcome LDLc ≤ 70 mg/dL and/or reduction in LDLc ≥ 50%. Furthermore, safety parameters were assessed. Results. Predictors associated with primary outcome achievement were treatment with atorvastatin 40 mg plus ezetimibe 10 mg (odds ratio: 11.94; 95% CI: 2.82-50.64; p = 0.001) and male (odds ratio: 4.76; 95% CI: 1.35-16.67; p = 0.02). Treatment with atorvastatin 40 mg plus ezetimibe 10 mg achieved significantly greater reductions in LDLc (p < 0.001), total cholesterol (p < 0.001) and non-HDLc (p < 0.001). Both treatments were safe and well tolerated, with a low number of secondary effects. Conclusions. Compared with atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe 10 mg increases the likelihood of achieving LDLc goals after ischaemic stroke or transient ischaemic attack. Both treatments were safe and well tolerated (AU)

[Utility of treatment with atorvastatin 40 mg plus ezetimibe 10 mg versus atorvastatin 80 mg in reducing the levels of LDL cholesterol in patients with ischaemic stroke or transient ischaemic attack]. / Utilidad del tratamiento con atorvastatina 40 mg más ezetimiba 10 mg frente a atorvastatina 80 mg en la reducción de los niveles de colesterol LDL en pacientes con ictus isquémico o ataque isquémico transitorio.

INTRODUCTION: After an ischaemic stroke, to reduce LDL cholesterol (LDLc) levels decreases the risk of recurrence. The risk of recurrence is lower with more intense reductions in LDLc levels. AIM: To evaluate the efficacy and security of atorvastatin 40 mg plus ezetimibe 10 mg after ischaemic stroke or transient ischaemic attack (TIA). PATIENTS AND METHODS: We retrospectively evaluated stroke or TIA patients admitted to our hospital who received atorvastatin 40 mg plus ezetimibe 10 mg (n = 34) or atorvastatin 80 mg (n = 52) at discharge. We analyzed changes in lipid parameters and established as a primary outcome LDLc <= 70 mg/dL and/or reduction in LDLc >= 50%. Furthermore, safety parameters were assessed. RESULTS: Predictors associated with primary outcome achievement were treatment with atorvastatin 40 mg plus ezetimibe 10 mg (odds ratio: 11.94; 95% CI: 2.82-50.64; p = 0.001) and male (odds ratio: 4.76; 95% CI: 1.35-16.67; p = 0.02). Treatment with atorvastatin 40 mg plus ezetimibe 10 mg achieved significantly greater reductions in LDLc (p < 0.001), total cholesterol (p < 0.001) and non-HDLc (p < 0.001). Both treatments were safe and well tolerated, with a low number of secondary effects. CONCLUSIONS: Compared with atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe 10 mg increases the likelihood of achieving LDLc goals after ischaemic stroke or transient ischaemic attack. Both treatments were safe and well tolerated.

TITLE: Utilidad del tratamiento con atorvastatina 40 mg mas ezetimiba 10 mg frente a atorvastatina 80 mg en la reduccion de los niveles de colesterol LDL en pacientes con ictus isquemico o ataque isquemico transitorio.Introduccion. Tras un ictus isquemico, reducir los niveles de colesterol LDL (LDLc) disminuye el riesgo de recurrencia. El riesgo de recurrencia es menor con reducciones mas intensas de las cifras de LDLc. Objetivo. Evaluar la eficacia y seguridad del tratamiento hipolipemiante combinado con atorvastatina 40 mg mas ezetimiba 10 mg tras un ictus isquemico o ataque isquemico transitorio (AIT). Pacientes y metodos. Evaluacion de la eficacia del tratamiento con atorvastatina 40 mg mas ezetimiba 10 mg (n = 34) frente a atorvastatina 80 mg (n = 52) en la modificacion de parametros lipidicos tras un ictus isquemico o AIT. Se establecio como objetivo primario la obtencion de niveles de LDLc <= 70 mg/dL o la reduccion de las cifras de LDLc >= 50%. Adicionalmente se evaluo la presencia de efectos secundarios en ambos grupos. Resultados. Se observo un incremento significativo de las probabilidades de alcanzar el objetivo primario en el grupo tratado con atorvastatina 40 mg mas ezetimiba 10 mg (odds ratio: 11,94; intervalo de confianza al 95%: 2,82-50,64; p = 0,001) y en los varones (odds ratio: 4,76; intervalo de confianza al 95%: 1,35-16,67; p = 0,02). El tratamiento con atorvastatina 40 mg mas ezetimiba 10 mg obtuvo reducciones superiores de LDLc (p < 0,001), colesterol total (p = 0,001) y no HDLc (p < 0,001). Ambos tratamientos fueron seguros, con escaso numero de efectos secundarios. Conclusiones. En comparacion con atorvastatina 80 mg, el tratamiento con atorvastatina 40 mg mas ezetimiba 10 mg incrementa la probabilidad de alcanzar los objetivos de LDLc. Ambos tratamientos son seguros y bien tolerados.

Systemic and cerebral endothelial dysfunction in chronic migraine. A case-control study with an active comparator.

BACKGROUND AND OBJECTIVE: Unlike migraine and migraine with aura, little information exists regarding chronic migraine (CM) as a risk factor for cardiovascular disease. In this study we aim to determine whether an association between CM and endothelial dysfunction exists. METHODS: Individuals 18 years and older diagnosed with episodic migraine (EM) and CM according to ICHD criteria were studied. After an overnight fast and abstinence from vasoactive drugs, ultrasound studies were performed and blood samples taken from patients and matched controls according to internationally agreed on protocols. RESULTS: A total of 113 individuals were enrolled (35 CM, 37 EM, 41 controls). CM patients had a lower percentage of flow-mediated vasodilation (FMD; difference of means = 5.03%; p = 1.0E-6) and breath-holding index (BHI; difference of means 0.754; p = 2.0E-6), as well as increased carotid intima media thickness (cIMT; difference of means = 0.128 mm; p = 7.0E-5) than controls. The EM patients and controls comparison found similar, but less pronounced, differences: decreased BHI (p = 0.031), and increased cIMT (p = 0.028). Fibrinogen (r = 0.277; p = 0.006), C-reactive protein (r = 0.288; p = 0.003), and erythrocyte rate sedimentation (r = 0.298; p = 0.002) also correlated with cIMT, and inversely with BHImV and FMD. CONCLUSIONS: Migraine is associated with systemic and cerebral endothelial dysfunction demonstrated by ultrasound studies and biological markers. The degree of these changes was strongly associated with the severity of migraine. Our data indicate that migraine may be a cerebral disorder with systemic endothelial damage.

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

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

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

Lipid-specific immunoglobulin M bands in cerebrospinal fluid are associated with a reduced risk of developing progressive multifocal leukoencephalopathy during treatment with natalizumab.

OBJECTIVE: Progressive multifocal leukoencephalopathy (PML) is a serious side effect associated with natalizumab treatment in multiple sclerosis (MS). PML risk increases in individuals seropositive for anti-John Cunningham virus (JC) antibodies, with prolonged duration of natalizumab treatment, and with prior exposure to immunosuppressants. We explored whether the presence of lipid-specific immunoglobulin M oligoclonal bands in cerebrospinal fluid (CSF; IgM bands), a recognized marker of highly inflammatory MS, may identify individuals better able to counteract the potential immunosuppressive effect of natalizumab and hence be associated with a reduced risk of developing PML. METHODS: We studied 24 MS patients who developed PML and another 343 who did not suffer this opportunistic infection during natalizumab treatment. Patients were recruited at 25 university hospitals. IgM bands were studied by isoelectric focusing and immunodetection. CSF lymphocyte counts were explored in 151 MS patients recruited at Ramon y Cajal Hospital in Madrid, Spain. RESULTS: IgM bands were independently associated with decreased PML risk (odds ratio [OR] = 45.9, 95% confidence interval [CI] = 5.9-339.3, p < 0.0001) in patients treated with natalizumab. They were also associated with significantly higher CSF CD4, CD8, and B-cell numbers. Patients positive for IgM bands and anti-JC antibodies had similar levels of reduced PML risk to those who were anti-JC negative (OR = 1.55, 95% CI = 0.09-25.2, p = 1.0). Higher risk was observed in patients positive for anti-JC antibodies and negative for IgM bands (19% of the total cohort, OR = 59.71, 95% CI = 13.6-262.2). INTERPRETATION: The presence of IgM bands reflects a process that may diminish the risk of PML by counteracting the excess of immunosuppression that may occur during natalizumab therapy.