Cognitive impairment in multiple sclerosis: diagnosis and monitoring

Multiple sclerosis; Neurophysiological monitoring; Neuropsychological testsEsclerosi múltiple; Monitorització neurofisiològica; Proves neuropsicològiquesEsclerosis múltiple; Monitoreo neurofisiológico; Pruebas neuropsicológicasIntroduction Cognitive impairment (CI) has a prevalence of 45–70% in people with multiple sclerosis (MS), producing a negative impact on their quality of life, personal life, and work. Early detection of CI has become an important aspect to be considered for an adequate follow-up, to optimize social adaptation and to implement specific cognitive rehabilitation strategies. The aim of this work is to propose a suitable cognitive evaluation of patients with MS based on available and efficient tools for diagnosis and monitoring purposes well supported by literature review and clinical experience. Methods A multidisciplinary panel of professionals from the field of neurology, neuropsychology, and neuroimaging performed a literature review of the topic of cognitive impairment assessment. This was combined and completed with their clinical experience to produce a set of recommendations. Results Some limitations to cognitive evaluation are described: shortage of time and resources during the neurology consultation, scarceness or absence of specialized professionals’ availability, importance of tests adaptation, and doubts about its use to define therapeutic efficiency. We recommend a baseline and annual screening evaluation, and we suggest a baseline and periodic neuropsychological assessment. The latter ought to change to a recommendation with the presence of either positive screening test, or subjective to cognitive complaints, screening-test results and patient or family report mismatch, or in specific social/work situations. Conclusions Cognitive evaluation should be performed on all patients diagnosed with MS and throughout follow-up. It is necessary to support the creation of multidisciplinary MS teams to optimize the evaluation and follow-up of MS patients

Therapeutic inertia in the management of neuromyelitis optica spectrum disorder

Introduction and objectiveLimited information is available on how neurologists make therapeutic decisions in neuromyelitis optica spectrum disorder (NMOSD), especially when new treatments with different mechanisms of action, administration, and safety profile are being approved. Decision-making can be complex under this uncertainty and may lead to therapeutic inertia (TI), which refers to lack of treatment initiation or intensification when therapeutic goals are not met. The study aim was to assess neurologists’ TI in NMOSD.MethodsAn online, cross-sectional study was conducted in collaboration with the Spanish Society of Neurology. Neurologists answered a survey composed of demographic characteristics, professional background, and behavioral traits. TI was defined as the lack of initiation or intensification with high-efficacy treatments when there is evidence of disease activity and was assessed through five NMOSD aquaporin-4 positive (AQP4+) simulated case scenarios. A multivariate logistic regression analysis was used to determine the association between neurologists’ characteristics and TI.ResultsA total of 78 neurologists were included (median interquartile range [IQR] age: 36.0 [29.0–46.0] years, 55.1% male, median [IQR] experience managing demyelinating conditions was 5.2 [3.0–11.1] years). The majority of participants were general neurologists (59.0%) attending a median (IQR) of 5.0 NMOSD patients (3.0–12.0) annually. Thirty participants (38.5%) were classified as having TI. Working in a low complexity hospital and giving high importance to patient’s tolerability/safety when choosing a treatment were predictors of TI.ConclusionTI is a common phenomenon among neurologists managing NMOSD AQP4+. Identifying TI and implementing specific intervention strategies may be critical to improving therapeutic decisions and patient care

SARS-CoV-2 Infection in Multiple Sclerosis

To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments. Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome. Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome. This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal diseas

XIII Reunión Post-ECTRIMS: Revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (II)

Introducción: Desde hace más de una década, tras el Congreso ECTRIMS, se celebra en España la reunión post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) se reúnen para revisar las novedades presentadas en el ECTRIMS. Objetivo: En el presente artículo, publicado en dos partes, se resumen las ponencias de la reunión post-ECTRIMS, celebrada los días 16 y 17 de octubre de 2020 virtualmente. Desarrollo: En esta segunda parte se destaca la importancia del género y la edad en la compresión de la patología de la enfermedad y la optimización de su manejo. Se exponen los avances realizados en la EM pediátrica desde un punto de vista neuropsicológico y de neuroimagen. Por su parte, cobran especial protagonismo los hallazgos que contribuyen a realizar un enfoque del tratamiento más personalizado y a elegir la mejor estrategia de tratamiento (farmacológica y no farmacológica) para cada paciente. De igual forma, se abordan los resultados relacionados con las estrategias posibles que promuevan la remielinización. Aunque no hay grandes avances en el tratamiento de formas progresivas, se destacan algunos métodos cuantitativos para la clasificación de estos pacientes. Además, se incluyen los resultados sobre herramientas potenciales de evaluación y tratamiento de los déficits cognitivos, y algunos aspectos relevantes observados en el espectro de los trastornos de la neuromielitis óptica. Por último, se detallan los resultados de las ponencias consideradas como noticias de última hora en el ECTRIMS-ACTRIMS. Conclusiones: Se presentaron avances principalmente sobre el conocimiento de la EM pediátrica, las estrategias de remielinización y la evaluación cognitiva en la EM.Introduction. For more than a decade, after the ECTRIMS Congress, Spain has hosted the Post-ECTRIMS meeting, where neurologists with expertise in multiple sclerosis (MS) meet to review the new developments presented at the ECTRIMS. Aim. This article, published in two parts, summarises the presentations of the post-ECTRIMS meeting, held online on 16 and 17 October 2020. Development. This second part highlights the importance of gender and age in understanding the pathology of the disease and optimising its management. The advances made in paediatric MS, from a neuropsychological and neuroimaging point of view, are presented. In turn, special attention is paid to the findings that contribute to a more personalised approach to therapy and to choosing the best treatment strategy (pharmacological and non-pharmacological) for each patient. Similarly, results related to possible strategies to promote remyelination are addressed. Although there are no major advances in the treatment of progressive forms, some quantitative methods for the classification of these patients are highlighted. In addition, the study also includes results on potential tools for assessment and treatment of cognitive deficits, and some relevant aspects observed in the spectrum of neuromyelitis optica disorders. Finally, the results of the papers considered as breaking news at the ECTRIMS-ACTRIMS are detailed. Conclusions. Most of the advances presented were related to the knowledge of paediatric MS, remyelination strategies and cognitive assessment in MS

Fatiga en esclerosis múltiple : aspectos clínicos, biológicos y radiológicos /

Consultable des del TDXTítol obtingut de la portada digitalitzadaLa esclerosis múltiple (EM) es una enfermedad inmunomediada del sistema nervioso central. Más del 50% de pacientes presenta fatiga relacionada con la EM, y este síntoma puede llegar a ser el más discapacitante. En los últimos años se ha publicado una enorme cantidad de trabajos que intenta aclarar datos sobre la etiología y el tratamiento de la fatiga en EM, pero las conclusiones nos ayudan poco en el día a día. La presente tesis recoge cuatro trabajos destinados a conocer mejor aspectos relacionados con el origen de la fatiga, su cuantificación y su historia natural. En el primer trabajo concluimos que la fatiga en pacientes con EM se relaciona de forma muy estrecha con determinados aspectos clínicos como la depresión y en menor grado la discapacidad. Adicionalmente se comparan dos escalas de medición del síntoma (la escala modificada del impacto de la fatiga y la escala de gravedad de fatiga) y se concluye que la primera ofrece una aproximación más amplia y multidimensional que la segunda. En el segundo trabajo analizamos la historia natural del síntoma fatiga en una cohorte de pacientes seguidos longitudinalmente y concluimos que la fatiga es un síntoma que persiste o se agrava durante el tiempo en la mayoría de los pacientes con EM, pero no disminuye. En el tercer trabajo analizamos de forma longitudinal la relación entre determinados parámetros hormonales y fatiga y observamos que el grado de fatiga en pacientes con EM primariamente progresiva se relaciona con concentraciones bajas de dihidroepiandrosterona sérica de forma persistente en el tiempo, indicando un posible papel de esta hormona en la patogenia del síntoma en este subgrupo de pacientes. En el cuarto trabajo estudiamos la relación entre el daño axonal en determinadas regiones cerebrales y el grado de fatiga en una muestra de pacientes con EM remitente-recurrente mediante espectroscopia por resonancia magnética de protón. Concluimos que podría existir una relación entre el grado de daño axonal a nivel de ganglios de la base y la presencia de fatiga señalando esta localización como potencialmente responsable en el origen del síntoma fatiga en determinados pacientes. En resumen, podemos decir que la fatiga en EM es un síntoma probablemente con un origen multifactorial, que persiste a lo largo del tiempo y que las herramientas que mejor nos ayudan a cuantificarla son aquellas que proporcionan información multidimensionalMultiple sclerosis (MS) is a central nervous sytem immunomediated disease. More than 50% of patients refer MS related fatigue, and in a high proportion of them, fatigue could be the most disabling symptom. Despite the large number of studies, the origin and treatment of MS related fatigue is not known. In this thesis we collect four works conducted with the objective to study the origin, the natural history and the ideal system to measure the symptom fatigue in MS. In the first study we concluded that MS-fatigue is strongly related to other clinical aspects such as mood disorders, and disability to a lesser degree. In addition we compare two measure scales for assessing fatigue (the Fatigue Severity Scale and the Modified Fatigue Impact Scale) and found the second as the more appropriate to quantify the symptom due to their multidimensional approach. In the second study we longitudinally analyse the evolution of fatigue over one year period of time and observed that fatigue persist or even worse, but did not improve during this follow up period. The third study demonstrated the relationship between the degree of MS-fatigue and low serum levels of dehydroepiandrosterone in a selected cohort of patients with primary progressive MS, followed for a two years period of time. In the last study we analyse the relationship between fatigue and axonal damage in certain brain areas, using magnetic resonance spectroscopy. We observed in a selected sample of relapsing remitting MS patients that fatigue could be partially related to a focal axonal damage in the basal ganglia. Summarizing, we suggest that the symptom fatigue in MS has a multifactorial origin, persist over time, and the best tools to assess it are the multidimensional scales

Fatiga en esclerosis múltiple: aspectos clínicos, biológicos y radiológicos

La esclerosis múltiple (EM) es una enfermedad inmunomediada del sistema nervioso central. Más del 50% de pacientes presenta fatiga relacionada con la EM, y este síntoma puede llegar a ser el más discapacitante. En los últimos años se ha publicado una enorme cantidad de trabajos que intenta aclarar datos sobre la etiología y el tratamiento de la fatiga en EM, pero las conclusiones nos ayudan poco en el día a día. La presente tesis recoge cuatro trabajos destinados a conocer mejor aspectos relacionados con el origen de la fatiga, su cuantificación y su historia natural. En el primer trabajo concluimos que la fatiga en pacientes con EM se relaciona de forma muy estrecha con determinados aspectos clínicos como la depresión y en menor grado la discapacidad. Adicionalmente se comparan dos escalas de medición del síntoma (la escala modificada del impacto de la fatiga y la escala de gravedad de fatiga) y se concluye que la primera ofrece una aproximación más amplia y multidimensional que la segunda.En el segundo trabajo analizamos la historia natural del síntoma fatiga en una cohorte de pacientes seguidos longitudinalmente y concluimos que la fatiga es un síntoma que persiste o se agrava durante el tiempo en la mayoría de los pacientes con EM, pero no disminuye. En el tercer trabajo analizamos de forma longitudinal la relación entre determinados parámetros hormonales y fatiga y observamos que el grado de fatiga en pacientes con EM primariamente progresiva se relaciona con concentraciones bajas de dihidroepiandrosterona sérica de forma persistente en el tiempo, indicando un posible papel de esta hormona en la patogenia del síntoma en este subgrupo de pacientes.En el cuarto trabajo estudiamos la relación entre el daño axonal en determinadas regiones cerebrales y el grado de fatiga en una muestra de pacientes con EM remitente-recurrente mediante espectroscopia por resonancia magnética de protón. Concluimos que podría existir una relación entre el grado de daño axonal a nivel de ganglios de la base y la presencia de fatiga señalando esta localización como potencialmente responsable en el origen del síntoma fatiga en determinados pacientes. En resumen, podemos decir que la fatiga en EM es un síntoma probablemente con un origen multifactorial, que persiste a lo largo del tiempo y que las herramientas que mejor nos ayudan a cuantificarla son aquellas que proporcionan información multidimensionalMultiple sclerosis (MS) is a central nervous sytem immunomediated disease. More than 50% of patients refer MS related fatigue, and in a high proportion of them, fatigue could be the most disabling symptom. Despite the large number of studies, the origin and treatment of MS related fatigue is not known. In this thesis we collect four works conducted with the objective to study the origin, the natural history and the ideal system to measure the symptom fatigue in MS. In the first study we concluded that MS-fatigue is strongly related to other clinical aspects such as mood disorders, and disability to a lesser degree. In addition we compare two measure scales for assessing fatigue (the Fatigue Severity Scale and the Modified Fatigue Impact Scale) and found the second as the more appropriate to quantify the symptom due to their multidimensional approach. In the second study we longitudinally analyse the evolution of fatigue over one year period of time and observed that fatigue persist or even worse, but did not improve during this follow up period. The third study demonstrated the relationship between the degree of MS-fatigue and low serum levels of dehydroepiandrosterone in a selected cohort of patients with primary progressive MS, followed for a two years period of time. In the last study we analyse the relationship between fatigue and axonal damage in certain brain areas, using magnetic resonance spectroscopy. We observed in a selected sample of relapsing remitting MS patients that fatigue could be partially related to a focal axonal damage in the basal ganglia.Summarizing, we suggest that the symptom fatigue in MS has a multifactorial origin, persist over time, and the best tools to assess it are the multidimensional scales

Deciphering Multiple Sclerosis Progression.

Multiple sclerosis (MS) is primarily an inflammatory and degenerative disease of the central nervous system, triggered by unknown environmental factors in patients with predisposing genetic risk profiles. The prevention of neurological disability is one of the essential goals to be achieved in a patient with MS. However, the pathogenic mechanisms driving the progressive phase of the disease remain unknown. It was described that the pathophysiological mechanisms associated with disease progression are present from disease onset. In daily practice, there is a lack of clinical, radiological, or biological markers that favor an early detection of the disease's progression. Different definitions of disability progression were used in clinical trials. According to the most descriptive, progression was defined as a minimum increase in the Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 from a baseline level of 0, 1.0-5.0, and 5.5, respectively. Nevertheless, the EDSS is not the most sensitive scale to assess progression, and there is no consensus regarding any specific diagnostic criteria for disability progression. This review document discusses the current pathophysiological concepts associated with MS progression, the different measurement strategies, the biomarkers associated with disability progression, and the available pharmacologic therapeutic approaches

Cognitive impairment in multiple sclerosis: diagnosis and monitoring.

Cognitive impairment (CI) has a prevalence of 45-70% in people with multiple sclerosis (MS), producing a negative impact on their quality of life, personal life, and work. Early detection of CI has become an important aspect to be considered for an adequate follow-up, to optimize social adaptation and to implement specific cognitive rehabilitation strategies. The aim of this work is to propose a suitable cognitive evaluation of patients with MS based on available and efficient tools for diagnosis and monitoring purposes well supported by literature review and clinical experience. A multidisciplinary panel of professionals from the field of neurology, neuropsychology, and neuroimaging performed a literature review of the topic of cognitive impairment assessment. This was combined and completed with their clinical experience to produce a set of recommendations. Some limitations to cognitive evaluation are described: shortage of time and resources during the neurology consultation, scarceness or absence of specialized professionals' availability, importance of tests adaptation, and doubts about its use to define therapeutic efficiency. We recommend a baseline and annual screening evaluation, and we suggest a baseline and periodic neuropsychological assessment. The latter ought to change to a recommendation with the presence of either positive screening test, or subjective to cognitive complaints, screening-test results and patient or family report mismatch, or in specific social/work situations. Cognitive evaluation should be performed on all patients diagnosed with MS and throughout follow-up. It is necessary to support the creation of multidisciplinary MS teams to optimize the evaluation and follow-up of MS patients

The Need for the Closer Monitoring of Novel Drugs in MS: A Siponimod Retrospective Cohort Study (Realhes Study)

Background: Severe cases of lymphopenia have been reported during siponimod clinical trials, which may negatively impact its benefit/risk profile. Objective: We aimed to evaluate the incidence of lymphopenia following the initiation of siponimod treatment in clinical practice. The secondary objectives included the analysis of factors predisposing to and the clinical relevance of lymphopenia events. Methods: In this multicenter retrospective cohort study, information collected from the medical records of 129 patients with MS from 15 tertiary hospitals in Spain who initiated treatment with Siponimod were followed-up for at least 3 months, including at least one lymphocyte count evaluation per patient. Results: Of the 129 patients, 121 (93.6%) reported lymphopenia events, including 110 (85.3%) with grade <= 3 and 11 (8.5%) with grade 4 lymphopenia, higher than those reported in the pivotal clinical trial (73.3% and 3.3% for grade <= 3 and grade 4 lymphopenia, respectively). The study included an unexpectedly high proportion of male subjects (72.9%), which might have led to an underestimation of the actual magnitude of the risk. Conclusions: In this study, the incidence and severity of lymphopenia after starting siponimod treatment were higher than those reported in previous clinical trials. Therefore, our results reinforce the need for the closer monitoring of novel MS drugs in clinical practice, as well as larger and longer follow-up studies to properly characterize this risk