Comparison of two high doses of oral methylprednisolone for multiple sclerosis relapses: a pilot, multicentre, randomized, double-blind, non-inferiority trial.

BACKGROUND AND PURPOSE: Oral or intravenous methylprednisolone (≥500 mg/day for 5 days) is recommended for multiple sclerosis (MS) relapses. Nonetheless, the optimal dose remains uncertain. We compared clinical and radiological effectiveness, safety and quality of life (QoL) of oral methylprednisolone [1250 mg/day (standard high dose)] versus 625 mg/day (lesser high dose), both for 3 days] in MS relapses. METHODS: A total of 49 patients with moderate to severe MS relapse within the previous 15 days were randomized in a pilot, double-blind, multicentre, non-inferiority trial (ClinicalTrial.gov, NCT01986998). The primary endpoint was non-inferiority of the lesser high dose by Expanded Disability Status Scale (EDSS) score improvement on day 30 (non-inferiority margin, 1 point). The secondary endpoints were EDSS score change on days 7 and 90, changes in T1 gadolinium-enhanced and new/enlarged T2 lesions on days 7 and 30, and safety and QoL results. RESULTS: The primary outcome was achieved [mean (95% confidence interval) EDSS score difference, -0.26 (-0.7 to 0.18) at 30 days (P = 0.246)]. The standard high dose yielded a superior EDSS score improvement on day 7 (P = 0.028). No differences were observed in EDSS score on day 90 (P = 0.352) or in the number of T1 gadolinium-enhanced or new/enlarged T2 lesions on day 7 (P = 0.401, 0.347) or day 30 (P = 0.349, 0.529). Safety and QoL were good at both doses. CONCLUSIONS: A lesser high-dose oral methylprednisolone regimen may not be inferior to the standard high dose in terms of clinical and radiological response.

Genitourinary syndrome of menopause. Prevalence and quality of life in Spanish postmenopausal women. The GENISSE study.

OBJECTIVE: To determine the prevalence of genitourinary syndrome of menopause (GSM) and urogynecological conditions associated with menopause, and to evaluate the impact of GSM on quality of life in a cohort of Spanish postmenopausal women. METHODS: Multicenter, cross-sectional, and observational study involving 430 women. RESULTS: The prevalence of GSM was 70%. GSM was diagnosed in 60.2% of women with no known diagnosis of vulvovaginal atrophy or GSM. Most prevalent symptoms were vaginal dryness (93.3%) and reduced lubrication with sexual activity (90.0%). Most prevalent signs were decreased moisture (93.7%) and loss of vaginal rugae (78.4%). GSM was significantly associated with stress or mixed urinary incontinence, overactive bladder, and vaginal prolapse. Symptoms showed a low-moderate impact on quality of life, mainly in sexual functioning and self-concept and body image. CONCLUSIONS: The GSM is very prevalent in Spanish postmenopausal women, affecting up to 70% of those consulting the gynecologist. Despite the high prevalence of symptoms and signs and its impact on the women's well-being, GSM remains underdiagnosed and undertreated. Given its relationship with urogynecological conditions, it seems necessary to provide an adequate evaluation of postmenopausal women for identifying potential co-morbidities and providing most adequate treatments. An adequate management of GSM will contribute to an improvement in the quality of life of these women.

Spanish consensus on the use of natalizumab (Tysabri®)-2013.

INTRODUCTION: Natalizumab treatment has been shown to be very efficacious in clinical trials and very effective in clinical practice in patients with relapsing-remitting multiple sclerosis, by reducing relapses, slowing disease progression, and improving magnetic resonance imaging patterns. However, the drug has also been associated with a risk of progressive multifocal leukoencephalopathy (PML). The first consensus statement on natalizumab use, published in 2011, has been updated to include new data on diagnostic procedures, monitoring for patients undergoing treatment, PML management, and other topics of interest including the management of patients discontinuing natalizumab. MATERIAL AND METHODS: This updated version followed the method used in the first consensus. A group of Spanish experts in multiple sclerosis (the authors of the present document) reviewed all currently available literature on natalizumab and identified the relevant topics would need updating based on their clinical experience. The initial draft passed through review cycles until the final version was completed. RESULTS AND CONCLUSIONS: Studies in clinical practice have demonstrated that changing to natalizumab is more effective than switching between immunomodulators. They favour early treatment with natalizumab rather than using natalizumab in a later stage as a rescue therapy. Although the drug is very effective, its potential adverse effects need to be considered, with particular attention to the patient's likelihood of developing PML. The neurologist should carefully explain the risks and benefits of the treatment, comparing them to the risks of multiple sclerosis in terms the patient can understand. Before treatment is started, laboratory tests and magnetic resonance images should be available to permit proper follow-up. The risk of PML should be stratified as high, medium, or low according to presence or absence of anti-JC virus antibodies, history of immunosuppressive therapy, and treatment duration. Although the presence of anti-JC virus antibodies is a significant finding, it should not be considered an absolute contraindication for natalizumab. This update provides general recommendations, but neurologists must use their clinical expertise to provide personalised follow-up for each patient.

[XVI Post-ECTRIMS Meeting: review of the new developments presented at the 2023 ECTRIMS Congress (I)]. / XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (I).

The XVI Post-ECTRIMS meeting took place in Seville on 20 and 21 October 2023. This meeting was attended by neurologists specialising in multiple sclerosis (MS) from Spain, who shared a summary of the most interesting innovations at the ECTRIMS congress, which had taken place in Milan the previous week. The aim of this article is to summarise new developments related to the pathogenesis, diagnosis and prognosis of MS. The contributions of innate immunity and central nervous system resident cells, including macrophages and microglia in MS pathophysiology and as therapeutic targets were discussed. Compartmentalised intrathecal inflammation was recognised as central to understanding the progression of MS, and the relationship between inflammatory infiltrates and disease progression was highlighted. Perspectives in demyelinating pathologies were reviewed, focusing on neuromyelitis optica and myelin oligodendrocyte glycoprotein antibody-associated disease, highlighting their pathophysiological and diagnostic differences compared to MS. Advances in neuroimaging were also discussed, and especially the analysis of active chronic lesions, such as paramagnetic rim lesions. In the absence of clinical improvements in trials of remyelinating treatments, methodological strategies to optimise the design of future studies were proposed. Breakthroughs in detecting the prodromal phase of MS, the use of biomarkers in body fluids to assess activity, progression and treatment response, and research on progression independent of flares were addressed. The need to define criteria for radiologically isolated syndrome and to clarify the concept was also discussed.

TITLE: XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (I).La XVI edición de la reunión Post-ECTRIMS se celebró los días 20 y 21 de octubre de 2023 en Sevilla. Este encuentro reunió a neurólogos especialistas en esclerosis múltiple (EM) de España, quienes compartieron un resumen de las innovaciones más destacables del congreso ECTRIMS, acontecido en Milán la semana anterior. El objetivo de este artículo es sintetizar las novedades relativas a la patogenia, el diagnóstico y el pronóstico de la EM. Se destacaron las contribuciones de la inmunidad innata y las células residentes del sistema nervioso central, incluyendo macrófagos y microglía, en la patofisiología de la EM y como objetivos terapéuticos. La inflamación intratecal compartimentada se reconoció como fundamental para entender la progresión de la EM, y destaca la relación entre infiltrados inflamatorios y la evolución de la enfermedad. Se revisaron perspectivas en patologías desmielinizantes, enfocadas en la neuromielitis óptica y la enfermedad asociada a anticuerpos contra la glucoproteína de mielina de oligodendrocitos, subrayando sus distinciones patofisiológicas y diagnósticas con la EM. También se abordaron los avances en neuroimagen, especialmente en el análisis de las lesiones crónicas activas, como las lesiones con borde paramagnético. Ante la ausencia de mejoras clínicas en ensayos de tratamientos remielinizantes, se propusieron estrategias metodológicas para optimizar el diseño de futuros estudios. Se abordaron los avances en la detección de la fase prodrómica de la EM, el uso de biomarcadores en fluidos corporales para evaluar la actividad, la progresión y la respuesta al tratamiento, y la investigación sobre la progresión independiente de la actividad de brote. Además, se debatió sobre la necesidad de definir criterios para el síndrome radiológico aislado o precisar su concepto.

[XVI Post-ECTRIMS Meeting: review of the new developments presented at the 2023 ECTRIMS Congress (II)]. / XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (II).

The XVI Post-ECTRIMS meeting was held in Seville on 20 and 21 October 2023, where expert neurologists in multiple sclerosis (MS) summarised the main new developments presented at the ECTRIMS 2023 congress, which took place in Milan from 11 to 13 October. The aim of this article is to summarise the content presented at the Post-ECTRIMS Meeting, in an article in two parts. This second part covers the health of women and elderly MS patients, new trends in the treatment of cognitive impairment, focusing particularly on meditation, neuroeducation and cognitive rehabilitation, and introduces the concept of fatigability, which has been used to a limited extent in MS. The key role of digitalization and artificial intelligence in the theoretically near future is subject to debate, along with the potential these technologies can offer. The most recent research on the various treatment algorithms and their efficacy and safety in the management of the disease is reviewed. Finally, the most relevant data for cladribine and evobrutinib are presented, as well as future therapeutic strategies currently being investigated.

TITLE: XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (II).Los días 20 y 21 de octubre se celebró en Sevilla la XVI edición de la reunión Post-ECTRIMS, en la que neurólogos expertos en esclerosis múltiple (EM) resumieron las principales novedades presentadas en el congreso del ECTRIMS 2023, celebrado en Milán del 11 al 13 de octubre. El objetivo de este artículo es sintetizar las ponencias que tuvieron lugar en la reunión Post-ECTRIMS en un artículo desglosado en dos partes. En esta segunda parte se abordan la salud de la mujer y del paciente mayor con EM, las nuevas tendencias en el tratamiento del deterioro cognitivo, con especial mención a la meditación, la neuroeducación y la rehabilitación cognitiva, y se introduce el concepto de fatigabilidad, poco utilizado en la EM. El papel clave de la digitalización y la inteligencia artificial en un futuro teóricamente cercano es objeto de debate, junto con las expectativas que pueden ofrecer. Se repasa la investigación más reciente sobre los distintos algoritmos de tratamiento, y su eficacia y seguridad en el manejo de la enfermedad. Por último, se exponen los datos más relevantes sobre la cladribina y el evobrutinib, y se presentan las futuras estrategias terapéuticas actualmente en investigación.

Partial recovery of SARS-CoV-2 immunity after booster vaccination in renal transplant recipients.

The pandemic caused by the SARS-CoV-2 coronavirus has been especially detrimental to patients with end-stage renal disease. History with other vaccines suggests that patients with renal disease may not respond adequately to the SARS-CoV-2 vaccine. The aim of this study is to evaluate the immunity to SARS-CoV-2 mRNA vaccines in renal patients. Post SARS-CoV-2 vaccination first, and after the booster dose, antibodies and cellular immunity were studied in patients on hemodialysis (N = 20), peritoneal dialysis (N = 10) and renal transplantation (N = 10). After the two doses of vaccine, there was an effective immunity in dialysis patients, with 100% seroconversion and 87% detection of cellular immunity (85% in hemodialysis and 90% in peritoneal dialysis). In contrast, in renal transplant recipients there was only 50% seroconversion and cellular immunity was detected in 30% of patients. After the booster dose, all dialysis patients achieved a cellular and antibody immunity, whereas in transplant patients, despite improvement, 20% did not produce antibodies and in 37.5% cellular immunity could not be detected. The mRNA vaccine plus booster performs excellently in dialysis patients, whereas in kidney transplant recipients, despite the booster, complete immunization is not achieved.

Recommendations for the coordination of Neurology and Neuroradiology Departments in the management of patients with multiple sclerosis.

INTRODUCTION: Magnetic resonance imaging (MRI) is widely used for the diagnosis and follow-up of patients with multiple sclerosis (MS). Coordination between neurology and neuroradiology departments is crucial for performing and interpreting radiological studies as efficiently and as accurately as possible. However, improvements can be made in the communication between these departments in many Spanish hospitals. METHODS: A panel of 17 neurologists and neuroradiologists from 8 Spanish hospitals held in-person and online meetings to draft a series of good practice guidelines for the coordinated management of MS. The drafting process included 4 phases: 1) establishing the scope of the guidelines and the methodology of the study; 2) literature review on good practices or recommendations on the use of MRI in MS; 3) discussion and consensus between experts; and 4) validation of the contents. RESULTS: The expert panel agreed a total of 9 recommendations for improving coordination between neurology and neuroradiology departments. The recommendations revolve around 4 main pillars: 1) standardising the process for requesting and scheduling MRI studies and reports; 2) designing common protocols for MRI studies; 3) establishing multidisciplinary committees and coordination meetings; and 4) creating formal communication channels between both departments. CONCLUSIONS: These consensus recommendations are intended to optimise coordination between neurologists and neuroradiologists, with the ultimate goal of improving the diagnosis and follow-up of patients with MS.

Evaluating factors influencing customers' intention to eat Korean cuisine "Samgyeopsal" in the Philippines: A structural equation model forest classifier approach.

Samgyeopsal has become a widely popular cuisine in the Philippines since 2014. The rise of Samgyeopsal is evident worldwide as it is available in countries such as the United States, Northern, and Southern Asia. This study aimed to explore the intention to eat Samgyeopsal during the COVID-19 pandemic utilizing structural equation modeling and random forest classifier. With a total of 1014 responses collected online, the result showed that utilitarian and hedonic motivation, Korean influence, and attitude led to very high actual behavior in east Samgyeopsal in the Philippines. Moreover, subjective norm, perceived behavioral control, and intention led to significant results influencing intention to actual behavior. Lastly, the COVID-19 safety protocol showed the least significant result. This study is the first study that evaluated the intention of consumers to eat Samgyeopsal in the Philippines during the COVID-19 pandemic. The results of this study would be beneficial to Korean BBQ restaurateurs and the further development of their marketing strategies even in other countries. Finally, the model construct of this study can be extended and applied in evaluating the consumers' eating intention toward other varieties of food or cuisines worldwide.

[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part II)]. / XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).

INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis outlined the latest developments presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: This second part describes the new developments in terms of therapeutic strategies for escalation and de-escalation of disease-modifying therapies (DMT), when and in whom to initiate or switch to highly effective DMT, the definition of therapeutic failure, the possibility of treating radiologically isolated syndrome and the future of personalised treatment and precision medicine. It also considers the efficacy and safety of autologous haematopoietic stem cell transplantation, different approaches in clinical trial design and outcome measures to assess DMT in progressive stages, challenges in the diagnosis and treatment of cognitive impairment, and treatment in special situations (pregnancy, comorbidity and the elderly). In addition, results from some of the latest studies with oral cladribine and evobrutinib presented at ECTRIMS 2022 are shown.

TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la Reunión Post-ECTRIMS, en la que neurólogos expertos en esclerosis múltiple resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado entre el 26 y el 28 de octubre en Ámsterdam. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta segunda parte, se presentan las novedades sobre las estrategias terapéuticas de escalado y desescalado de los tratamientos modificadores de la enfermedad (TME), cuándo y a quién iniciar o cambiar a TME de alta eficacia, la definición de fracaso terapéutico, la posibilidad de tratar el síndrome radiológico asilado, el futuro del tratamiento personalizado y la medicina de precisión, la eficacia y seguridad del autotrasplante de células madre hematopoyéticas, diferentes aproximaciones en el diseño de ensayos clínicos y en las medidas de resultados para evaluar TME en fases progresivas, retos en el diagnóstico y tratamiento del deterioro cognitivo, y tratamiento en situaciones especiales (embarazo, comorbilidad y personas mayores). Además, se muestran los resultados de algunos de los últimos estudios realizados con cladribina oral y evobrutinib presentados en el ECTRIMS 2022.

[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part I)]. / XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (I).

INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis (MS) outlined the most relevant novelties presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: In this first part, the initial events involved in the onset of MS, the role played by lymphocytes and the migration of immune system cells into the central nervous system are presented. It describes emerging biomarkers in body fluids and imaging findings that are predictive of disease progression and useful in the differential diagnosis of MS. It also discusses advances in imaging techniques which, together with a better understanding of the agents involved in demyelination and remyelination processes, provide a basis for dealing with remyelination in the clinical setting. Finally, the mechanisms triggering the inflammatory reaction and neurodegeneration involved in MS pathology are reviewed.

TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (I).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la XV edición de la Reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado en Ámsterdam entre el 26 y el 28 de octubre. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta primera parte se presentan los primeros eventos involucrados en el inicio de la EM, la implicación de los linfocitos y la migración de células del sistema inmunitario hacia el sistema nervioso central. Se describen los biomarcadores emergentes en fluidos corporales y los hallazgos de imagen que permiten predecir la evolución de la enfermedad, y que resultan útiles en el diagnóstico diferencial de la EM. También se exponen los avances en las técnicas de imagen que, junto con un mayor conocimiento de los agentes involucrados en los procesos de desmielinización y remielinización, proporcionan una base para abordar la remielinización en el entorno clínico. Por último, se repasan los mecanismos desencadenantes de la reacción inflamatoria y la neurodegeneración implicados en la patología de la EM.

Gadolinium-enhanced brain lesions in multiple sclerosis relapse.

OBJECTIVE: To study the clinico-radiological paradox in multiple sclerosis (MS) relapse by analyzing the number and location of gadolinium-enhanced (Gd+) lesions on brain MRI before methylprednisolone (MP) treatment. METHODS: We analyzed brain MRI from 90 relapsed MS patients in two Phase IV multicenter double-blind randomized clinical trials that showed the noninferiority of different routes and doses of MP administration. A 1.5- or 3-T brain MRI was performed at baseline before MP treatment and within 15 days of symptom onset. The number and location of Gd+ lesions were analyzed. Associations were studied using univariate analysis. RESULTS: Sixty-two percent of patients had at least 1 Gd+ brain lesion; the median number was 1 (interquartile range 0-4), and 41% of patients had 2 or more lesions. The most frequent location of Gd+ lesions was subcortical (41.4%). Gd+ brain lesions were found in 71.4% of patients with brainstem-cerebellum symptoms, 57.1% with spinal cord symptoms and 55.5% with optic neuritis (ON). Thirty percent of patients with brain symptoms did not have Gd+ lesions, and only 43.6% of patients had symptomatic Gd+ lesions. The univariate analysis showed a negative correlation between age and the number of Gd+ lesions (p=0.002). CONCLUSION: Most patients with relapse showed several Gd+ lesions on brain MRI, even when the clinical manifestation was outside of the brain. Our findings illustrate the clinico-radiological paradox in MS relapse and support the value of brain MRI in this scenario.

Multiple sclerosis and cognitive decline: is ApoE-4 a surrogate marker?

BACKGROUND - The role of the apolipoprotein E (ApoE) polymorphism has been well demonstrated in neurodegenerative disorders such as Alzheimer. However, its role in multiple sclerosis (MS) remains unclear. AIMS - The aims of our study were as follows: (i) to assess whether ApoE-4 might be a surrogate marker of cognitive decline in MS; (ii) to confirm the presence of cognitive impairment in mildly disabled patients treated with interferon-beta; and (iii) to analyse the correlation between cognitive disturbances and clinical variables. MATERIAL AND METHODS - Fifty relapsing-remitting MS patients underwent a battery of neuropsychological tests and were genotyped for ApoE. Their scores were compared with those of 35 controls. RESULTS - No association was found between ApoE-4 and cognitive impairment. Significant differences in most domains were observed between MS and the control group. Cognitive decline was not related to disability progression. CONCLUSION - No association between cognitive impairment and ApoE-4 or clinical markers was detected in our MS patients.

Recommendations for the coordination of Neurology and Neuroradiology Departments in the management of patients with multiple sclerosis. / Recomendaciones para la coordinación de los servicios de Neurología y Neurorradiología en la atención a pacientes con esclerosis múltiple.

INTRODUCTION: Magnetic resonance imaging (MRI) is widely used for the diagnosis and follow-up of patients with multiple sclerosis (MS). Coordination between Neurology and Neuroradiology departments is crucial for performing and interpreting radiological studies as efficiently and as accurately as possible. However, improvements can be made in the communication between these departments in many Spanish hospitals. METHODS: A panel of 17 neurologists and neuroradiologists from 8 Spanish hospitals held in-person and online meetings to draft a series of good practice guidelines for the coordinated management of MS. The drafting process included 4 phases: 1) establishing the scope of the guidelines and the methodology of the study; 2) literature review on good practices or recommendations on the use of MRI in MS; 3) discussion and consensus between experts; and 4) validation of the contents. RESULTS: The expert panel agreed a total of 9 recommendations for improving coordination between neurology and neuroradiology departments. The recommendations revolve around 4 main pillars: 1) standardising the process for requesting and scheduling MRI studies and reports; 2) designing common protocols for MRI studies; 3) establishing multidisciplinary committees and coordination meetings; and 4) creating formal communication channels between both departments. CONCLUSIONS: These consensus recommendations are intended to optimise coordination between neurologists and neuroradiologists, with the ultimate goal of improving the diagnosis and follow-up of patients with MS.

Recommendations for vaccination in patients with multiple sclerosis who are eligible for immunosuppressive therapies: Spanish consensus statement. / Recomendaciones para la vacunación en pacientes con esclerosis múltiple candidatos a terapias inmunosupresoras: documento de consenso español.

BACKGROUND: The recent development of highly effective treatments for multiple sclerosis (MS) and the potential risk of infectious complications require the development of prevention and risk minimisation strategies. Vaccination is an essential element of the management of these patients. This consensus statement includes a series of recommendations and practical scenarios for the vaccination of adult patients with MS who are eligible for highly effective immunosuppressive treatments. METHODOLOGY: A formal consensus procedure was followed. Having defined the scope of the statement, we conducted a literature search on recommendations for the vaccination of patients with MS and specific vaccination guidelines for immunosuppressed patients receiving biological therapy for other conditions. The modified nominal group technique methodology was used to formulate the recommendations. DEVELOPMENT: Vaccination in patients who are candidates for immunosuppressive therapy should be considered before starting immunosuppressive treatment providing the patient's clinical situation allows. Vaccines included in the routine adult vaccination schedule, as well as some specific ones, are recommended depending on the pre-existing immunity status. If immunosuppressive treatment is already established, live attenuated vaccines are contraindicated. For vaccines with a correlate of protection, it is recommended to monitor the serological response in an optimal interval of 1-2 months from the last dose.

Anticipation of age at onset in multiple sclerosis: methodologic pitfalls.

BACKGROUND/AIM: There are several reports that claim anticipation in complex or polygenic diseases such as multiple sclerosis (MS), Crohn disease or schizophrenia. The aim of the present study was to assess age at onset of MS during the last 60 years in the region of Costa de Ponent (Barcelona, Spain) showing how apparent changes in age at onset between generations can be an artefact of analysis based on cohorts that have not been followed enough time. METHODS: The study comprised 1100 patients diagnosed of MS. The method used to correct for follow-up time bias involves constructing comparison cohorts that had been observed for the same amount of time. To ensure equal follow-up times, we restricted our analysis to patients whose onset was by 37 years of age (percentile 75) and were at least 37 years old. We analysed differences in age at onset using log-rank test to compare survival curves estimated by Kaplan-Meier method. RESULTS: Age at onset decreases progressively from older to younger generations. However, when adjustment to equal follow-up time was done, anticipation in age at onset was not found. CONCLUSION: Anticipation of age at onset is undetectable when adjusted for follow-up time.

Will neurological care change over the next 5 years due to the COVID-19 pandemic? Key informant consensus survey. / ¿Va a cambiar la neurología tras la pandemia de COVID-19 en los próximos 5 años? Estudio de enfoque mediante informadores clave.

INTRODUCTION: The COVID-19 pandemic will give rise to long-term changes in neurological care, which are not easily predictable. MATERIAL AND METHODS: A key informant survey was used to enquire about the changes expected in the specialty over the next 5 years. The survey was completed by heads of neurology departments with broad knowledge of the situation, having been active during the pandemic. RESULTS: Despite a low level of consensus between participants, there was strong (85%) and moderate consensus (70%) about certain subjects, mainly the increase in precautions to be taken, the use of telemedicine and teleconsultations, the reduction of care provided in in-person consultations to avoid the presence of large numbers of people in waiting rooms, the development of remote training solutions, and the changes in monitoring visits during clinical trials. There was consensus that there would be no changes to the indication of complementary testing or neurological examination. CONCLUSION: The key informant survey identified the foreseeable changes in neurological care after the pandemic.

Recomendaciones para la coordinación de los servicios de Neurología y Neurorradiología en la atención a pacientes con esclerosis múltiple / Recommendations for the coordination of Neurology and Neuroradiology Departments in the management of patients with multiple sclerosis

Introducción: El uso de la resonancia magnética (RM) está ampliamente extendido en el diagnóstico y el seguimiento de los pacientes con esclerosis múltiple (EM). La coordinación entre los servicios de Neurología y Neurorradiología es clave para la realización e interpretación de estudios radiológicos de la manera más eficaz posible. Sin embargo, esta coordinación es susceptible de mejoras en una gran parte de los hospitales nacionales. Métodos: Un panel de 17 neurólogos y neurorradiólogos de 8 hospitales españoles, presencialmente y a través de comunicación online, consensuaron una guía de buenas prácticas en la coordinación en EM. La guía se estableció en 4 fases: 1) definición del alcance de la guía y metodología del estudio; 2) revisión bibliográfica sobre buenas prácticas o recomendaciones en el uso de la RM en EM; 3) discusión y búsqueda de consenso entre los expertos; y 4) formalización y validación de los contenidos para elaborar el documento de consenso. Resultados: Se consensuaron un total de 9 recomendaciones dirigidas a la mejora de la coordinación entre los servicios de Neurología y Neurorradiología, que se pueden resumir en: 1) estandarizar las solicitudes de RM, informes y planificación; 2) crear protocolos compartidos para los estudios de RM; 3) establecer comités multidisciplinares y sesiones de coordinación, y 4) generar canales de comunicación formales entre los profesionales de ambos departamentos. Conclusiones: Se espera que las recomendaciones consensuadas sirvan de guía para optimizar la coordinación entre neurólogos y neurorradiólogos y que repercutan en la mejora del diagnóstico y seguimiento de los pacientes con EM.(AU)

Introduction: Magnetic resonance imaging (MRI) is widely used for the diagnosis and follow-up of patients with multiple sclerosis (MS). Coordination between Neurology and Neuroradiology departments is crucial for performing and interpreting radiological studies as efficiently and as accurately as possible. However, improvements can be made in the communication between these departments in many Spanish hospitals. Methods: A panel of 17 neurologists and neuroradiologists from 8 Spanish hospitals held in-person and online meetings to draft a series of good practice guidelines for the coordinated management of MS. The drafting process included 4 phases: 1) establishing the scope of the guidelines and the methodology of the study; 2) literature review on good practices or recommendations on the use of MRI in MS; 3) discussion and consensus between experts; and 4) validation of the contents. Results: The expert panel agreed a total of 9 recommendations for improving coordination between neurology and neuroradiology departments. The recommendations revolve around 4 main pillars: 1) standardising the process for requesting and scheduling MRI studies and reports; 2) designing common protocols for MRI studies; 3) establishing multidisciplinary committees and coordination meetings; and 4) creating formal communication channels between both departments. Conclusions: These consensus recommendations are intended to optimise coordination between neurologists and neuroradiologists, with the ultimate goal of improving the diagnosis and follow-up of patients with MS.(AU)

A guide to treating gait impairment with prolonged-release fampridine (Fampyra®) in patients with multiple sclerosis. / Guía de tratamiento del deterioro de la marcha con fampridina de liberación prolongada (Fampyra®) en pacientes con esclerosis múltiple.

INTRODUCTION: Gait impairment, a frequent sign in multiple sclerosis (MS), places a major burden on patients since it results in progressive loss of personal and social autonomy, along with work productivity. This guide aims to provide recommendations on how to evaluate gait impairment and use prolonged-release fampridine (PR-fampridine) as treatment for MS patients with gait impairment in Spain. DEVELOPMENT: PR-fampridine dosed at 10mg every 12hours is currently the only drug approved to treat gait impairment in adults with MS. Additionally, PR-fampridine has been shown in clinical practice to significantly improve quality of life (QoL) in patients who respond to treatment. Treatment response can be assessed with the Timed 25-Foot Walk (T25FW) or the 12-item MS Walking Scale (MSWS-12); tests should be completed before and after starting treatment. The minimum time recommended for evaluating treatment response is 2 weeks after treatment onset. Patients are considered responders and permitted to continue the treatment when they demonstrate a decrease in their T25FW time or an increase in MSWS-12 scores. A re-evaluation is recommended at least every 6 months. The SF-36 (Short Form-36) and the MSIS-29 (MS Impact Scale-29) tests are recommended for clinicians interested in performing a detailed QoL assessment. This drug is generally well-tolerated and has a good safety profile. It should be taken on an empty stomach and renal function must be monitored regularly. CONCLUSIONS: These recommendations will help ensure safer and more efficient prescription practices and easier management of PR-fampridine as treatment for gait impairment in Spanish adults with MS.

Gadolinium-enhanced brain lesions in multiple sclerosis relapse / Lesiones cerebrales captantes de gadolinio en el brote de los pacientes con esclerosis múltiple

Objective: To study the clinico-radiological paradox in multiple sclerosis (MS) relapse by analyzing the number and location of gadolinium-enhanced (Gd+) lesions on brain MRI before methylprednisolone (MP) treatment. Methods: We analyzed brain MRI from 90 relapsed MS patients in two Phase IV multicenter double-blind randomized clinical trials that showed the noninferiority of different routes and doses of MP administration. A 1.5- or 3-T brain MRI was performed at baseline before MP treatment and within 15 days of symptom onset. The number and location of Gd+ lesions were analyzed. Associations were studied using univariate analysis. Results: Sixty-two percent of patients had at least 1 Gd+ brain lesion; the median number was 1 (interquartile range 0–4), and 41% of patients had 2 or more lesions. The most frequent location of Gd+ lesions was subcortical (41.4%). Gd+ brain lesions were found in 71.4% of patients with brainstem-cerebellum symptoms, 57.1% with spinal cord symptoms and 55.5% with optic neuritis (ON). Thirty percent of patients with brain symptoms did not have Gd+ lesions, and only 43.6% of patients had symptomatic Gd+ lesions. The univariate analysis showed a negative correlation between age and the number of Gd+ lesions (p = 0.002). Conclusion: Most patients with relapse showed several Gd+ lesions on brain MRI, even when the clinical manifestation was outside of the brain. Our findings illustrate the clinico-radiological paradox in MS relapse and support the value of brain MRI in this scenario. (AU)

Objetivo: Estudiar la paradoja clínico-radiológica en el brote de la esclerosis múltiple (EM) mediante el análisis de lesiones captantes de gadolinio (Gd+) en la RM cerebral antes del tratamiento con metilprednisolona (MP). Métodos: Analizamos la RM cerebral basal de 90 pacientes con EM en brote de 2 ensayos clínicos aleatorizados multicéntricos fase IV que demostraron la no inferioridad de diferentes vías y dosis de MP, realizadas antes del tratamiento con MP y en los 15 días siguientes a la aparición de los síntomas. Se analizaron el número y la localización de las lesiones Gd+. Se estudiaron las asociaciones mediante análisis univariado. Resultados: El 62% de los pacientes tenía al menos una lesión Gd+ cerebral y el 41% de los pacientes tenía 2 o más lesiones. La localización más frecuente fue la subcortical (41,4%). Se encontraron lesiones Gd+ cerebrales en el 71,4% de los pacientes con síntomas de tronco cerebral o cerebelo, en el 57,1% con síntomas medulares y en el 55,5% con neuritis óptica. El 30% de los pacientes con síntomas cerebrales no tenían lesiones Gd+ y sólo el 4,.6% de los pacientes tenían lesiones Gd+ sintomáticas. El análisis univariante mostró una correlación negativa entre la edad y el número de lesiones Gd+ (p = 0,002). Conclusiones: La mayoría de los pacientes en brote mostraron varias lesiones Gd+ en la RM cerebral, incluso cuando la manifestación clínica fue medular u óptica. Nuestros hallazgos ilustran la paradoja clínico-radiológica en el brote de la EM y apoyan el valor de la RM cerebral en este escenario. (AU)

Effect of glatiramer acetate (Copaxone) on the immunophenotypic and cytokine profile and BDNF production in multiple sclerosis: a longitudinal study.

We assessed the effect of glatiramer acetate (GA) on the immunophenotypic and cytokine profile and the BDNF production by peripheral blood mononuclear cells, and their association with the clinical response in 19 naïve-treated MS patients prospectively followed-up after GA therapy. Two patients withdrew the therapy. After a median follow-up of 21 months, twelve were considered responders and five as non-responders. Non-responder patients had significant longer disease duration and a higher EDSS score at baseline. In the responder group, a significant decrease in the percentage of INF-gamma producing total lymphocytes, CD4+ and CD8+ T cells, and reduced percentage of IL-2 producing CD4+ and CD8+ T cells were observed at 12, 18 and 24 months. These changes were associated with a significant increase in the percentage of CD3+, CD4+ and CD4(+) CD45RA(+) T cells, and BDNF production from month 6 that remained significant throughout the study. We did not observe significant changes in the nonresponder group for any of the parameters studied. Our data suggest that GA treatment induces a downmodulation of proinflammatory cytokines associated with the regulation of the peripheral T cell compartment and with increased production of BDNF that might be related to the clinical response.