Multiple sclerosis, disease-modifying therapies and COVID-19: A systematic review on immune response and vaccination recommendations

Understanding the risks of COVID-19 in patients with Multiple Sclerosis (MS) receiving disease-modifying therapies (DMTs) and their immune reactions is vital to analyze vaccine response dynamics. A systematic review on COVID-19 course and outcomes in patients receiving different DMTs was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Emerging data on SARS-CoV-2 vaccines was used to elaborate recommendations. Data from 4417 patients suggest that MS per se do not portend a higher risk of severe COVID-19. As for the general population, advanced age, comorbidities, and higher disability significantly impact COVID-19 outcomes. Most DMTs have a negligible influence on COVID-19 incidence and outcome, while for those causing severe lymphopenia and hypogammaglobulinemia, such as anti-CD20 therapies, there might be a tendency of increased hospitalization, worse outcomes and a higher risk of re-infection. Blunted immune responses have been reported for many DMTs, with vaccination implications. Clinical evidence does not support an increased risk of MS relapse or vaccination failure, but vaccination timing needs to be individually tailored. For cladribine and alemtuzumab, it is recommended to wait 3–6 months after the last cycle until vaccination. For the general anti-CD20 therapies, vaccination must be deferred toward the end of the cycle and the next dose administered at least 4–6 weeks after completing vaccination. Serological status after vaccination is highly encouraged. Growing clinical evidence and continuous surveillance are extremely important to continue guiding future treatment strategies and vaccination protocols

Consenso Português para a Identificação Precoce de Esclerose Múltipla Secundária Progressiva: Painel Delphi

Introduction: Multiple sclerosis is a disease with a heterogeneous evolution. The early identification of secondary progressive multiple sclerosis is a clinical challenge, which would benefit from the definition of biomarkers and diagnostic tools applicable in the transition phase from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis. We aimed to reach a Portuguese national consensus on the monitoring of patients with multiple sclerosis and on the more relevant clinical variables for the early identification of its progression. Material and methods: A Delphi panel which included eleven Portuguese Neurologists participated in two rounds of questions between July and August of 2021. In the first round, 39 questions which belonged to the functional, cognitive, imaging, biomarkers and additional evaluations were included. Questions for which no consensus was obtained in the first round (less than 80% of agreement), were appraised by the panel during the second round. Results: The response rate was 100% in both rounds and consensus was reached for a total of 33 questions (84.6%). Consensus was reached for monitoring time, evaluation scales and clinical variables such as the degree of brain atrophy and mobility reduction, changes suggestive of secondary progressive multiple sclerosis. Additionally, digital devices were considered tools with potential to identify disease progression. Most questions for which no consensus was obtained referred to the cognitive assessment and the remaining referred to both functional and imaging domains. Conclusion: Consensus was obtained for the determination of the monitorization interval and for most of the clinical variables. Most questions that did not reach consensus were related with the confirmation of progression taking into account only one test/domain, reinforcing the multifactorial nature of multiple sclerosis.Introdução: A esclerose múltipla é uma doença de evolução heterogénea. A identificação precoce da forma secundária progressiva é um desafio clínico, carecendo da definição de biomarcadores e ferramentas de diagnóstico aplicáveis na fase de transição da forma surto-remissão para a forma secundária progressiva. Este trabalho teve como objetivo estabelecer um consenso nacional português sobre a monitorização dos doentes e das variáveis clínicas mais relevantes para a identificação precoce da progressão da esclerose múltipla. Material e Métodos: Um painel Delphi constituído por 11 neurologistas portugueses respondeu a duas rondas de perguntas entre julho e agosto de 2021. Na primeira ronda foram incluídas 39 questões relacionadas com a avaliação funcional, cognitiva, imagiológica, de biomarcadores e outras, e na segunda, as questões para as quais não foi atingido consenso (menos de 80% de concordância) na primeira ronda voltaram a ser submetidas a avaliação pelo painel. Resultados: A taxa de resposta foi de 100% em ambas as rondas e 33 das 39 questões (84,6%) atingiram concordância. Foi atingido consenso relativamente ao tempo de monitorização dos doentes, às escalas de avaliação a empregar e a variáveis clínicas tais como o grau de atrofia cerebral ou redução da mobilidade, cuja alteração é sugestiva de esclerose múltipla secundária progressiva. Adicionalmente, os dispositivos digitais foram considerados ferramentas com potencial para identificar a progressão da doença. A maioria das questões para as quais não foi obtido consenso dizem respeito à avaliação cognitiva, estando as restantes inseridas nos domínios funcional e imagiológico. Conclusão: Foi obtido consenso para a determinação do intervalo de monitorização e para a maioria das variáveis clínicas. A maioria das questões sem consenso estavam relacionadas com a confirmação do diagnóstico de progressão tendo em conta apenas um teste/domínio, realçando a natureza multifatorial da esclerose múltipla.info:eu-repo/semantics/publishedVersio

Consensus Recommendations of the Multiple Sclerosis Study Group and Portuguese Neuroradiological Society for the Use of the Magnetic Resonance Imaging in Multiple Sclerosis in Clinical Practice: Part 1

INTRODUCTION: Magnetic resonance imaging is established as a recognizable tool in the diagnosis and monitoring of multiple sclerosis patients. In the present, among multiple sclerosis centers, there are different magnetic resonance imaging sequences and protocols used to study multiple sclerosis that may hamper the optimal use of magnetic resonance imaging in multiple sclerosis. In this context, the Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after a joint discussion, appointed a committee of experts to create recommendations adapted to the national reality on the use of magnetic resonance imaging in multiple sclerosis. The purpose of this document is to publish the first Portuguese consensus recommendations on the use of magnetic resonance imaging in multiple sclerosis in clinical practice. MATERIAL AND METHODS: The Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after discussion of the topic in national meetings and after a working group meeting held in Figueira da Foz on May 2017, have appointed a committee of experts that have developed by consensus several standard protocols on the use of magnetic resonance imaging in the diagnosis and follow-up of multiple sclerosis. The document obtained was based on the best scientific evidence and expert opinion. Subsequently, the majority of Portuguese multiple sclerosis consultants and departments of neuroradiology scrutinized and reviewed the consensus paper; comments and suggestions were considered. Technical magnetic resonance imaging protocols regarding diagnostic, monitoring and the recommended information to be included in the magnetic resonance imaging report will be published in a separate paper. RESULTS: We provide some practical guidelines to promote standardized strategies to be applied in the clinical practice setting of Portuguese healthcare professionals regarding the use of magnetic resonance imaging in multiple sclerosis. CONCLUSION: We hope that these first Portuguese magnetic resonance imaging guidelines, based in the best available clinical evidence and practices, will serve to optimize multiple sclerosis management and improve multiple sclerosis patient care across Portugal.info:eu-repo/semantics/publishedVersio

Cognitive Impairment and Magnetic Resonance Imaging Correlates in Primary Progressive Multiple Sclerosis

Objectives: To characterize cognitive impairment in primary progressive multiple sclerosis (PPMS) and to correlate the pattern of cognitive deficits with brain magnetic resonance imaging (MRI) volumetric data. Materials and methods: In a multicenter cross-sectional study, we recruited consecutive patients with PPMS as well as age, sex, and education level-matched healthy controls (HC). All participants underwent neuropsychological (NP) assessment, and brain MRI was performed in patients with PPMS for analysis of lesion load, subcortical GM volumes, and regional cortical volumes. Results: We recruited 55 patients with PPMS and 36 HC. Thirty-six patients were included in the MRI analysis. Patients with PPMS performed significantly worse than HC in all NP tests. Subcortical GM volume was significantly correlated with all NP tests, except for Stroop Test, with the largest effect for the thalamus (r=-.516 [BVMT-R DR, P=.016 FDR-corrected] to r=.664 [SDMT, P<.001 FDR-corrected]). In the stepwise linear regression model, thalamic volume was the only predictor of performance in all NP tests. Conclusion: Cognitive impairment is common in PPMS and affects all evaluated cognitive domains. Subcortical GM volume, particularly of the thalamus, is a strong predictor of cognitive performance, suggesting it has a central role in the pathophysiology of PPMS-related cognitive dysfunction.info:eu-repo/semantics/publishedVersio

A Multicenter, Non-Interventional Study to Evaluate the Disease Activity in Multiple Sclerosis after Withdrawal of Natalizumab in Portugal

Objectives: Natalizumab (NTZ) is very effective for treatment of relapsing-remitting multiple sclerosis (RRMS), its use is mainly limited by safety issues. Discontinuation of NTZ is associated with recurrence of disease activity (reactivation and rebound). The best strategy for subsequent therapy and the predictive factors for recurrence in such patients are areas of active research. We aimed to evaluate predictors of reactivation in a multicentric study. Patients and methods: Multicentric retrospective observational study in five portuguese MS referral centers. Demographic, clinical and imagiological data were collected in the year prior, during and in the year following NTZ discontinuation. Predictors of reactivation and rebound after NTZ suspension were studied using a multivariate Cox model. Results: Sixty-nine patients were included. They were mainly non-naïve patients (97%), with a mean age of 29.1 ± 8.3 years at diagnosis, and a mean age of 37.2 ± 10.3 years at NTZ initiation. The mean annualized relapse rate (ARR) previous, during and after NTZ was 1.6 ± 1.2, 0.2 ± 0.5 and 0.6 ± 1.0, respectively. The median EDSS before, during and after NTZ was 3.5 (IQR 3.3), 3.5 (IQR 3.5) and 4.0 (IQR 3.8), respectively. The median number of infusions was 26.0 (IQR 12.5) and the main reason to NTZ discontinuation was progressive multifocal leukoencephalopathy (PML) risk (70%). After NTZ suspension, reactivation was observed in 25 (36%) patients after a median time of 20.0 (IQR 29.0) weeks. Reactivation predictors in our sample included NTZ suspension for reasons other than PML (adjusted HR = 0.228, 95% CI [0.084- 0.616], p = 0.004), ARR before NTZ (adjusted HR = 1.914 95% [CI 1.330-2.754], p < 0.001) and a longer disease duration at time of NTZ initiation (adjusted HR = 1.154, 95% CI [1.020-1.306], p = 0.023). Rebound occurred in 5 (7%) patients after a median time of 20 (IQR 34.5) weeks. Conclusion: Significant predictors of disease reactivation in our cohort were discontinuation of NTZ for reasons other than PML risk, higher disease activity before NTZ treatment, and longer disease duration. Our study provides valuable data of portuguese patients after NTZ withdrawal.info:eu-repo/semantics/publishedVersio

Esclerosis múltiple y decisión de la maternidad: estudio observacional en pacientes portuguesas

Introducción. La esclerosis múltiple (EM) es una enfermedad incapacitante que afecta mayoritariamente a mujeres en edad fértil. La EM puede alterar el deseo de crear una familia y concebir hijos. Objetivo. Estudiar la influencia del diagnóstico de la EM y de su evolución sobre la decisión de ser madre. Pacientes y métodos. Se seleccionó una cohorte integrada por pacientes de 35-45 años diagnosticadas de EM desde hacía por lo menos 10 años que eran atendidas en seis centros portugueses. Las participantes respondieron a un cuestionario estructurado en días de consulta consecutivos. Se revisaron las historias clínicas para caracterizar y recabar información sobre la enfermedad y los embarazos. Resultados. Participaron 100 mujeres; la media de edad en el momento del diagnóstico de la EM era de 26,3 ± 5,0 años; el 90% de las participantes presentaba la forma remitente recurrente; el 57% de las pacientes no se habían quedado embarazadas después del diagnóstico. El tipo de EM y el número de recidivas no difirieron de manera significativa entre las mujeres que habían concebido después del diagnóstico y las que no (p = 0,39 y p = 0,50, respectivamente). El 77% no había tenido el número de hijos deseado. Los principales motivos aducidos fueron el temor a la incapacidad futura y la posibilidad de sufrir recidivas. Cuarenta y tres mujeres creían que el embarazo podía agravar la EM. Conclusión. En la población del estudio, la decisión de ser o no ser madre no guardó relación con el tipo de EM ni con el número de recidivas. No obstante, un número relevante de mujeres tuvieron menos embarazos de los que habían desea- do antes de ser diagnosticadas y pensaban que la gestación podía empeorar la enfermedad. Sería conveniente mejorar la información que reciben estas pacientes a fin de minimizar el impacto del diagnóstico de la EM en la decisión de ser madre

Consensus Document on Coding of Cardiac Magnetic Resonance Examinations in Portugal

Um dos obstáculos a uma utilização mais frequente e apropriada da ressonância magnética cardíaca (RMC) em Portugal tem sido a ausência de códigos específicos que descrevam adequadamente os exames tal como são efetuados actualmente. Este documento de consenso fornece recomendações para a atualização e uniformização dos códigos empregues na RMC. São igualmente feitas recomendações quanto às técnicas e códigos a utilizar nas indicações clínicas mais frequentes

State of the Art and Future Challenges in Multiple Sclerosis Research and Medical Management: An Insight into the 5th International Porto Congress of Multiple Sclerosis

The 5th International Porto Congress of Multiple Sclerosis took place between the 14th and 16th of February 2019 in Porto, Portugal. Its intensive programme covered a wide-range of themes—including many of the hot topics, challenges, pitfalls and yet unmet needs in the field of multiple sclerosis (MS)—led by a number of well-acknowledged world experts. This meeting review summarizes the talks that took place during the congress, which focussed on issues in MS as diverse as the development and challenges of progressive MS, epidemiology, differential diagnosis, medical management, molecular research and imaging tools

Impairment of Adenosinergic System in Rett syndrome: Novel Therapeutic Target to Boost BDNF Signalling

Rett syndrome (RTT; OMIM#312750) is mainly caused by mutations in the X-linked MECP2 gene (methyl-CpG-binding protein 2 gene; OMIM*300005), which leads to impairments in the brain-derived neurotrophic factor (BDNF) signalling. The boost of BDNF mediated effects would be a significant breakthrough but it has been hampered by the difficulty to administer BDNF to the central nervous system. Adenosine, an endogenous neuromodulator, may accomplish that role since through A2AR it potentiates BDNF synaptic actions in healthy animals. We thus characterized several hallmarks of the adenosinergic and BDNF signalling in RTT and explored whether A2AR activation could boost BDNF actions. For this study, the RTT animal model, the Mecp2 knockout (Mecp2-/y) (B6.129P2 (C)-Mecp2tm1.1Bird/J) mouse was used. Whenever possible, parallel data was also obtained from post-mortem brain samples from one RTT patient. Ex vivo extracellular recordings of field excitatory post-synaptic potentials in CA1 hippocampal area were performed to evaluate synaptic transmission and long-term potentiation (LTP). RT-PCR was used to assess mRNA levels and Western Blot or radioligand binding assays were performed to evaluate protein levels. Changes in cortical and hippocampal adenosine content were assessed by liquid chromatography with diode array detection (LC/DAD). Hippocampal ex vivo experiments revealed that the facilitatory actions of BDNF upon LTP is absent in Mecp2-/y mice and that TrkB full-length (TrkB-FL) receptor levels are significantly decreased. Extracts of the hippocampus and cortex of Mecp2-/y mice revealed less adenosine amount as well as less A2AR protein levels when compared to WT littermates, which may partially explain the deficits in adenosinergic tonus in these animals. Remarkably, the lack of BDNF effect on hippocampal LTP in Mecp2-/y mice was overcome by selective activation of A2AR with CGS21680. Overall, in Mecp2-/y mice there is an impairment on adenosinergic system and BDNF signalling. These findings set the stage for adenosine-based pharmacological therapeutic strategies for RTT, highlighting A2AR as a therapeutic target in this devastating pathology.info:eu-repo/semantics/publishedVersio

Profound and Sustained Reduction in Chlamydia trachomatis in The Gambia: A Five-Year Longitudinal Study of Trachoma Endemic Communities

Trachoma is the most common infectious cause of blindness worldwide. Mass antibiotic treatment with azithromycin is used to control ocular Chlamydia trachomatis infection. There is uncertainty over how frequently and for how long treatment is needed, particularly in low prevalence settings. This study examines the effect of a single round of treatment on clinical disease and infection in a cluster of trachoma endemic Gambian villages over a five-year period. These villages had good water supplies and sanitation improved part way through the study. We found treatment was followed by a marked decline in infection prevalence (by PCR) to less than 1%. The decline in prevalence of active disease in children was less marked. Several villages had a prevalence of active trachoma in 1 to 9 year old children of greater than 10% during the follow-up period, mostly in the absence of detectable infection. The implication of this study is that a single, high coverage mass treatment may be sufficient to control C. trachomatis infection in a low prevalence setting, particularly when combined with environmental measures to limit transmission. However, relying on clinical signs to guide treatment decisions is likely to lead to significant amounts of over treatment where current guidelines are implemented