Diagnosis of atrial fibrillation in young patients with ischemic stroke: A systematic review and meta-analysis.

INTRODUCTION: The recommended cardiac rhythm evaluation to determine the etiology of ischemic stroke (IS) is similar in all patients regardless of their age and includes an electrocardiogram and at least a 24-hour heart rhythm monitoring. However, it is known that the main causes of IS vary according to patients' age. There is a higher preponderance of arterial dissections and patent foramen ovale in younger patients, while atrial fibrillation (AF) is more common in older patients. AIMS: To determine the proportion of AF in young IS reported in the literature and determine if young IS patients found to have AF had known structural cardiac pathology. METHODS: Systematic review of the literature searching PubMed and Embase for articles published since their inception to August 2020. Inclusion criteria were studies including at least 10 patients, aged 14-50 years-old, clinical or radiological diagnosis of IS and quantification of patients found to have AF. We conducted a meta-analysis using a random-effects model and calculated pooled proportions with 95% confidence intervals. RESULTS: 8331 articles were screened, 154 were selected for full-text review. 43 studies were included in our final analysis (902800 patients). The proportion of AF in young IS overall was 3.1% [95%CI 2.4-3.7], I2 93.88%. Sub-analysis revealed a proportion of AF of 3.8% [95% CI 0.3-7.3] in lower-middle-income economies, versus 5.4% [95% CI 3-7.9] in upper-middle-income economies, and 2.2% [95% CI 1.6-2.8] in high-income economies. Only 3 studies mentioned the proportion of patients with AF that had structural cardiac pathology. CONCLUSION: The proportion of AF in young IS was low. More studies are needed to better understand if young IS patients diagnosed with AF had a priori known structural cardiac pathology that could increase the probability of finding AF. This could lead to a reevaluation of the need for 24 hours cardiac rhythm evaluation in young patients without cardiac pathology.

Atypical White Matter Hyperintensities Markedly Impact Plasma Neurofilament Light Chain Variability in GRN Patients.

GRN mutations, causing frontotemporal dementia, can be associated with atypical white matter hyperintensities (WMH). We hypothesized that the presence of WMH may impact neurofilament light chain (NfL) levels, markers of neuroaxonal damage. We analyzed plasma NfL in 20 GRN patients and studied their association to visually-scored WMH burden. The 12 patients displaying atypical WMH had significantly higher NfL levels (98.4±34.9 pg/mL) than those without WMH (47.2±29.4 pg/mL, p = 0.003), independently from age, disease duration and Fazekas-Schmidt grade. NfL correlated with WMH burden (rho = 0.55, p = 0.01). This study prompts considering WMH burden as a variability factor when evaluating NfL levels in GRN patients.

Physical activity in vascular cognitive impairment: Systematic review with meta-analysis.

BACKGROUND: Vascular cognitive impairment (VCI) is the second most common cause of cognitive impairment worldwide and includes a spectrum from vascular cognitive impairment no dementia (VCIND) to vascular dementia (VaD). There is no specific pharmacological treatment approved for VCI. Physical activity has been indicated to be a promising preventive measure for cognition, with direct as indirectly benefits, while improving several modifiable vascular risk factors, so potentially effective when considering VCI. Our aim was to conduct a systematic review with a meta-analysis approaching the potential preventive role of physical activity on VCI. METHODS: A systematic search was conducted in 7 databases. A total of 6786 studies were screened and assessed for eligibility, culminating in the inclusion of 9 observational prospective studies assessing physical activity impact irrespectively the type for quality assessment and qualitative and quantitative synthesis. Quantitative synthesis was performed using the reported adjusted HRs. Physical activity was handled as a dichotomous variable, with two groups created (high versus low physical activity). Subgroup analyses were done for risk of bias, VaD and length of follow-up. RESULTS: There was considerable methodological heterogeneity across studies. Only three studies reported significant associations. The overall effect was statistically significant (HR 0.68, 95%CI 0.54-0.86, I2 6.8%), with higher levels of physical activity associated with a smaller risk of VCI overtime, particularly VaD. CONCLUSIONS: These findings suggest that physical activity is a potential preventive factor for vascular dementia. Insufficient data is available on VCIND. Randomized studies are desired to confirm these results.

Plasma lysosphingolipids in GRN-related diseases: Monitoring lysosomal dysfunction to track disease progression.

GRN mutations are among the main genetic causes of frontotemporal dementia (FTD). Considering the progranulin involvement in lysosomal homeostasis, we aimed to evaluate if plasma lysosphingolipids (lysoSPL) are increased in GRN mutation carriers, and whether they might represent relevant fluid-based biomarkers in GRN-related diseases. We analyzed four lysoSPL levels in plasmas of 131 GRN carriers and 142 non-carriers, including healthy controls and patients with frontotemporal dementias (FTD) carrying a C9orf72 expansion or without any mutation. GRN carriers consisted of 102 heterozygous FTD patients (FTD-GRN), three homozygous patients with neuronal ceroid lipofuscinosis-11 (CLN-11) and 26 presymptomatic carriers (PS-GRN), the latter with longitudinal assessments. Glucosylsphingosin d18:1 (LGL1), lysosphingomyelins d18:1 and isoform 509 (LSM18:1, LSM509) and lysoglobotriaosylceramide (LGB3) were measured by electrospray ionization-tandem mass spectrometry coupled to ultraperformance liquid chromatography. Levels of LGL1, LSM18:1 and LSM509 were increased in GRN carriers compared to non-carriers (p < 0.0001). No lysoSPL increases were detected in FTD patients without GRN mutations. LGL1 and LSM18:1 progressively increased with age at sampling, and LGL1 with disease duration, in FTD-GRN. Among PS-GRN carriers, LSM18:1 and LGL1 significantly increased over 3.4-year follow-up. LGL1 levels were associated with increasing neurofilaments in presymptomatic carriers. This study evidences an age-dependent increase of ß-glucocerebrosidase and acid sphingomyelinase substrates in GRN patients, with progressive changes as early as the presymptomatic phase. Among FTD patients, plasma lysoSPL appear to be uniquely elevated in GRN carriers, and thus might serve as suitable non-invasive disease-tracking biomarkers of progression, specific to the pathophysiological process. Finally, this study might add lysoSPL to the portfolio of fluid-based biomarkers, and pave the way to disease-modifying approaches based on lysosomal function rescue in GRN diseases.

[Evaluation of the Knowledge of Women of Childbearing Age with Epilepsy about the Impact of Their Disease in Contraception, Pregnancy and Breastfeeding: A Multicenter Cross-Sectional Study]. / Avaliação do Conhecimento das Mulheres com Epilepsia em Idade Fértil sobre o Impacto da sua Doença na Contraceção, Gravidez e Amamentação: Um Estudo Transversal Multicêntrico.

INTRODUCTION: The interaction of antiseizure medication with contraceptives, its potential teratogenicity and implications in pregnancy and breastfeeding are aspects to consider in the neurological care of women with epilepsy of childbearing age. To ensure the commitment in therapeutic decisions and the appropriate planning of maternity, it is essential that women are informed about the implications of their disease in these domains. The main aim of this study was to assess the knowledge of women of childbearing age with epilepsy concerning the impact of epilepsy in contraception, pregnancy and breastfeeding. As secondary aims we defined (1) the demographic, clinical and therapeutic characterization of this group of patients, (2) the identification of variables that correlated with the level of knowledge of women with epilepsy, and (3) the identification of preferential methods to acquire new knowledge about epilepsy. MATERIAL AND METHODS: The study was observational, cross-sectional and multicentric, and was carried out in five hospitals of the Lisbon metropolitan area. After identifying all women of childbearing age with epilepsy followed in the epilepsy clinic of each center, we applied an electronic questionnaire based on a non-systematic review of the literature. RESULTS: One hundred and fourteen participants were validated, with a median age of 33 years. Half of the participants were on monotherapy, and the majority had no seizures in the last six months. We identified important gaps in the participants' knowledge. Sections about complications and administration of antiseizure medication during pregnancy were the ones with the worst results. None of the clinical and demographic variables correlated with the final questionnaire score. Having had a previous pregnancy and the desire to breastfeed in a future pregnancy were positively correlated with the performance in breastfeeding section. Face-to-face discussion during medical outpatient visits was selected as the preferential method to learn about epilepsy, and the internet and social media were the least preferred ones. CONCLUSION: The knowledge of women of childbearing age with epilepsy in the Lisbon metropolitan area concerning the impact of epilepsy in contraception, pregnancy and breastfeeding seems to have significant gaps. Medical teams should consider engaging in patient education particularly during outpatient clinics.

Introdução: A interação dos fármacos anticrise epilética com os métodos contracetivos, a sua potencial teratogenicidade e as implicações na gravidez e amamentação são aspetos a considerar no acompanhamento de mulheres com epilepsia em idade fértil. Para o seu desejado envolvimento nas decisões terapêuticas e o adequado planeamento da maternidade, é essencial que as mulheres estejam corretamente informadas acerca das implicações da sua doença. O objetivo principal do presente estudo foi avaliar o conhecimento das mulheres com epilepsia em idade fértil sobre o impacto da epilepsia na contraceção, gravidez e amamentação. Como objetivos secundários definiram-se (1) a caracterização demográfica, clínica e terapêutica deste grupo de doentes, (2) a identificação de variáveis correlacionadas com o nível de conhecimento das mulheres com epilepsia, e (3) a identificação de meios e suportes preferenciais para aquisição de novos conhecimentos sobre epilepsia. Material e Métodos: O estudo foi observacional, transversal e multicêntrico, tendo decorrido em cinco centros hospitalares da região metropolitana de Lisboa. Após identificação das mulheres com epilepsia em idade fértil seguidas na Consulta de Epilepsia de cada centro, aplicou-se um questionário eletrónico construído após revisão não sistemática da literatura. Resultados: Foram validadas 114 participantes, com uma idade mediana de 33 anos. Metade das participantes apresentavam-se sob monoterapia, tendo a maioria a epilepsia controlada há pelo menos seis meses. Identificaram-se importantes lacunas no conhecimento das participantes. Conceitos sobre complicações dos fármacos anticrise epilética e a sua administração durante a gravidez motivaram piores resultados. Não houve correlação entre variáveis clinico-demográficas e o resultado no questionário. A ocorrência de gravidez prévia e o desejo de amamentar numa gravidez futura correlacionaram-se com o desempenho na secção sobre amamentação. A discussão oral na consulta foi a forma preferencial para aquisição de novos conhecimentos sobre epilepsia, tendo a internet e as redes sociais sido os meios menos escolhidos. Conclusão: O conhecimento das mulheres com epilepsia em idade fértil na área metropolitana de Lisboa sobre o impacto da sua doença na contraceção, gravidez e amamentação parece apresentar lacunas importantes. A educação para a saúde deste grupo deverá constituir uma preocupação por parte das equipas médicas, devendo privilegiar-se a consulta como local de ensino.

Opinions, beliefs and knowledge of people with multiple sclerosis on COVID-19 pandemic and vaccine.

BACKGROUND: Considering the potential COVID-19 impact on pwMS health and the importance of vaccination for this population, we decided to assess: (a) pwMS' beliefs and knowledge on COVID-19 pandemic; (b) their acceptance towards COVID-19 vaccination and (c) pwMS' opinions on general vaccination. METHODS: Observational study, based on a cross-sectional (10-20th September 2020) online survey, conducted in a cohort of pwMS' followed at two Portuguese hospitals. The survey included measures to characterize the sample and a questionnaire designed to assess the topics defined for this study. RESULTS: 270 respondents completed the full survey (response rate 58.2%). pwMS greatest concern during the pandemic was an aggravation of MS, especially by patients older than 50 years old. Almost 40% of the patients older than 50 felt that the pandemic negatively affected their MS related medical assistance. Most patients believed they would recover from COVID-19 infection. More than half of the responders feared a MS aggravation if they got COVID-19; this was more pronounced in patients with progressive MS. About 12% of the participants did not want to be vaccinated and almost 40% was unsure. Regarding vaccines in general, almost a third of the participants feared their side effects or MS related complications. CONCLUSION: Having knowledge of pwMS' opinions on COVID-19 pandemic impact and vaccination is useful to better address these issues. Fears and expectations towards vaccination must be discussed with pwMS.