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Several neurological manifestations are part of the post-COVID condition. We aimed to: (1) evaluate the 6-month outcome in the cohort of patients with neurological manifestations during the COVID-19 acute phase and surviving the infection, and find outcome predictors; (2) define the prevalence and type of neurological symptoms persistent at six months after the infection. Data source was an international registry of patients with COVID-19 infection and neurological symptoms, signs or diagnoses established by the European Academy of Neurology. Functional status at six-month follow-up was measured with the modified Rankin scale (mRS), and defined as: "stable/improved" if the mRS at six months was equal as or lower than the baseline score; "worse" if it was higher than the baseline score. By October 30, 2022, 1,003 lab-confirmed COVID-19 patients were followed up for a median of 6.5 months. Compared to their pre-morbid status, 522 patients (52%) were stable/improved, whereas 465 (46%) were worse (functional status missing for 16). Age, hospitalization, several pre-COVID-19 comorbidities, and COVID-19 general complications were predictors of a worse status. Amongst neurological manifestations, stroke carried the highest risk for worse outcome (OR 5.96), followed by hyperactive delirium (2.8), and peripheral neuropathies (2.37). On the other hand, hyposmia/hypogeusia (0.38), headache (0.40), myalgia (0.45), and COVID-19 vaccination (0.52) were predictors of a favourable prognosis. Persisting neurological symptoms or signs were reported by 316/1003 patients (31.5%), the commonest being fatigue (n = 133), and impaired memory or concentration (n = 103). Our study identified significant long-term prognostic predictors in patients with COVID-19 and neurological manifestations.
Assuntos
COVID-19 , Doenças do Sistema Nervoso , Sistema de Registros , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Europa (Continente)/epidemiologia , Adulto , Prognóstico , Idoso de 80 Anos ou mais , Comorbidade , Neurologia/estatística & dados numéricos , SeguimentosRESUMO
Little is known about changes in the brain associated with frailty, in particular, which brain areas could be related to frailty in older people without cognitive impairment. This scoping review mapped evidence on functional and/or structural brain changes in frail older adults without cognitive impairment. The methodology proposed by the JBI® was used in this study. The search in PubMed, PubMed PMC, BVS/BIREME, EBSCOHOST, Scopus, Web of Science, Embase, and PROQUEST was conducted up to January 2023. Studies included following the population, concepts, context and the screening and data extraction were performed by two independent reviewers. A total of 9,912 records were identified, 5,676 were duplicates and were excluded. The remaining articles were screened; 31 were read in full and 17 articles were included. The results showed that lesions in white matter hyperintensities, reduced volume of the hippocampus, cerebellum, middle frontal gyrus, low gray matter volume, cortical atrophy, decreased connectivity of the supplementary motor area, presence of amyloid-beta peptide (aß) in the anterior and posterior putamen and precuneus regions were more frequently observed in frail older adults, compared with non-frail individuals. Studies have suggested that such findings may be of neurodegenerative or cerebrovascular origin. The identification of these brain alterations in frail older adults through neuroimaging studies contributes to our understanding of the underlying mechanisms of frailty. Such findings may have implications for the early detection of frailty and implementation of intervention strategies.
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Encéfalo , Fragilidade , Humanos , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Idoso Fragilizado , Disfunção Cognitiva/diagnóstico por imagem , Neuroimagem/métodos , Idoso de 80 Anos ou maisRESUMO
Objectives: Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments. Methods: We studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves. Results: In TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions. Conclusions: This study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients.
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The treatment of epilepsy has advanced over the past 30 years through the development of new antiseizure medications (ASMs). Unfortunately, not all of them have been approved yet in Brazil, and many are still underused. When comparing new ASMs to older ones, they are generally not more effective in treating epilepsy. However, they offer better tolerability, with fewer interactions and long-term side effects, especially for patients with comorbidities or those requiring polytherapy. Enzyme induction caused by older ASMs is associated with increased cholesterol levels, drug interactions with decreased effects of statins and other cardiovascular medications, anticoagulants, chemotherapy, immunosuppressors, anti-infective agents (including HIV treatment), antidepressants, and contraceptives. Additionally, they can reduce levels of vitamin D and sex hormones, as well as decrease bone density. The increasing concern about these effects during life, especially after prolonged exposure, has led most developed countries to change prescription patterns in favor of new ASMs, particularly levetiracetam and lamotrigine. Both are also considered the safest options for women of childbearing age. Regrettably, the prescription trends in Brazil have remained largely unchanged over time. This can be partially attributed to the slower approval process of ASM and the reluctance of general physicians and neurologists to embrace these new concepts. In this concise review, we highlight the various advantages linked to the new ASM, aiming to promote a shift in the prescription pattern for ASM. The selection of ASM should be customized according to individual characteristics, and practical suggestions for choosing ASMs are provided in this paper.
O tratamento da epilepsia avançou nos últimos 30 anos com o desenvolvimento de novos medicamentos anticrise (MAC). Infelizmente, nem todos estão aprovados no Brasil e muitos ainda são subutilizados. Os novos MAC não são mais eficazes que os antigos, mas apresentam melhor tolerabilidade, menos interações e efeitos colaterais a longo prazo, especialmente para pacientes com comorbidades ou que necessitam de politerapia. A indução enzimática causada pelos MAC antigos está associada ao aumento dos níveis de colesterol, interações medicamentosas com redução do efeito das estatinas e outros medicamentos cardiovasculares, anticoagulantes, quimioterapia, imunossupressores, agentes anti-infecciosos (incluindo tratamento do HIV), antidepressivos e contraceptivos. Além disso, podem reduzir os níveis de vitamina D e hormônios sexuais, podendo afetar a massa óssea. A crescente preocupação sobre estes efeitos ao longo da vida, com a exposição prolongada, levou a maioria dos países desenvolvidos a modificar o padrão de prescrição com maior uso dos novos MAC, especialmente levetiracetam e lamotrigina. Ambos são considerados as opções mais seguras para mulheres em idade fértil. Infelizmente, as tendências de prescrição no Brasil permaneceram praticamente inalteradas ao longo do tempo. Isto pode ser parcialmente explicado pela lentidão no processo de aprovação dos MAC e à resistência dos médicos generalistas e neurologistas em adotar estes novos conceitos. Nesta revisão, destacamos as vantagens dos novos MAC e a necessidade da mudança no padrão de prescrição também no Brasil. A escolha do MAC deve ser feita de acordo com as características individuais dos pacientes e sugestões práticas são apresentadas.
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Epilepsia , Vitaminas , Humanos , Feminino , Anticoagulantes , Densidade Óssea , Brasil , AnticonvulsivantesRESUMO
BACKGROUND: Neuropsychiatric sequelae of COVID-19 have been widely documented in patients with severe neurological symptoms during the chronic or subacute phase of the disease. However, it remains unclear whether subclinical changes in brain metabolism can occur early in the acute phase of the disease. The aim of this study was to identify and quantify changes in brain metabolism in patients hospitalized for acute respiratory syndrome due to COVID-19 with no or mild neurological symptoms. RESULTS: Twenty-three non-intubated patients (13 women; mean age 55.5 ± 12.1 years) hospitalized with positive nasopharyngeal swab test (RT-PCR) for COVID-19, requiring supplemental oxygen and no or mild neurological symptoms were studied. Serum C-reactive protein measured at admission ranged from 6.43 to 189.0 mg/L (mean: 96.9 ± 54.2 mg/L). The mean supplemental oxygen demand was 2.9 ± 1.4 L/min. [18F]FDG PET/CT images were acquired with a median of 12 (4-20) days of symptoms. After visual interpretation of the images, semiquantitative analysis of [18F]FDG uptake in multiple brain regions was evaluated using dedicated software and the standard deviation (SD) of brain uptake in each region was automatically calculated in comparison with reference values of a normal database. Evolutionarily ancient structures showed positive SD mean values of [18F]FDG uptake. Lenticular nuclei were bilaterally hypermetabolic (> 2 SD) in 21/23 (91.3%) patients, and thalamus in 16/23 (69.6%), bilaterally in 11/23 (47.8%). About half of patients showed hypermetabolism in brainstems, 40% in hippocampi, and 30% in cerebellums. In contrast, neocortical regions (frontal, parietal, temporal and occipital lobes) presented negative SD mean values of [18F]FDG uptake and hypometabolism (< 2 SD) was observed in up to a third of patients. Associations were found between hypoxia, inflammation, coagulation markers, and [18F]FDG uptake in various brain structures. CONCLUSIONS: Brain metabolism is clearly affected during the acute phase of COVID-19 respiratory syndrome in neurologically asymptomatic or oligosymptomatic patients. The most frequent finding is marked hypermetabolism in evolutionary ancient structures such as lenticular nucleus and thalami. Neocortical metabolism was reduced in up to one third of patients, suggesting a redistribution of brain metabolism from the neocortex to evolutionary ancient brain structures in these patients.
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OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.
Assuntos
Benchmarking , Epilepsia do Lobo Temporal , Humanos , Epilepsia do Lobo Temporal/cirurgia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Criança , Pré-Escolar , Lactente , Complicações Pós-Operatórias/epidemiologia , Procedimentos Neurocirúrgicos/normas , Procedimentos Neurocirúrgicos/métodos , Epilepsia Resistente a Medicamentos/cirurgia , Lobectomia Temporal Anterior/métodosRESUMO
Few resting-state functional magnetic resonance imaging (RS-fMRI) studies evaluated the impact of acute ischemic changes on cerebral functional connectivity (FC) and its relationship with functional outcomes after acute ischemic stroke (AIS), considering the side of lesions. To characterize alterations of FC of patients with AIS by analyzing 12 large-scale brain networks (NWs) with RS-fMRI. Additionally, we evaluated the impact of the side (right (RH) or left (LH) hemisphere) of insult on the disruption of brain NWs. 38 patients diagnosed with AIS (17 RH and 21 LH) who performed 3T MRI scans up to 72 h after stroke were compared to 44 healthy controls. Images were processed and analyzed with the software toolbox UF2C with SPM12. For the first level, we generated individual matrices based on the time series extraction from 70 regions of interest (ROIs) from 12 functional NWs, constructing Pearson's cross-correlation; the second-level analysis included an analysis of covariance (ANCOVA) to investigate differences between groups. The statistical significance was determined with p < 0.05, after correction for multiple comparisons with false discovery rate (FDR) correction. Overall, individuals with LH insults developed poorer clinical outcomes after six months. A widespread pattern of lower FC was observed in the presence of LH insults, while a contralateral pattern of increased FC was identified in the group with RH insults. Our findings suggest that LH stroke causes a severe and widespread pattern of reduction of brain networks' FC, presumably related to the impairment in their long-term recovery.
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Although some studies have shown neuroimaging and neuropsychological alterations in post-COVID-19 patients, fewer combined neuroimaging and neuropsychology evaluations of individuals who presented a mild acute infection. Here we investigated cognitive dysfunction and brain changes in a group of mildly infected individuals. We conducted a cross-sectional study of 97 consecutive subjects (median age of 41 years) without current or history of psychiatric symptoms (including anxiety and depression) after a mild infection, with a median of 79 days (and mean of 97 days) after diagnosis of COVID-19. We performed semi-structured interviews, neurological examinations, 3T-MRI scans, and neuropsychological assessments. For MRI analyses, we included a group of non-infected 77 controls. The MRI study included white matter (WM) investigation with diffusion tensor images (DTI) and functional connectivity with resting-state functional MRI (RS-fMRI). The patients reported memory loss (36%), fatigue (31%) and headache (29%). The quantitative analyses confirmed symptoms of fatigue (83% of participants), excessive somnolence (35%), impaired phonemic verbal fluency (21%), impaired verbal categorical fluency (13%) and impaired logical memory immediate recall (16%). The WM analyses with DTI revealed higher axial diffusivity values in post-infected patients compared to controls. Compared to controls, there were no significant differences in the functional connectivity of the posterior cingulum cortex. There were no significant correlations between neuropsychological scores and neuroimaging features (including DTI and RS-fMRI). Our results suggest persistent cognitive impairment and subtle white matter abnormalities in individuals mildly infected without anxiety or depression symptoms. The longitudinal analyses will clarify whether these alterations are temporary or permanent.
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Encefalopatias , COVID-19 , Disfunção Cognitiva , Substância Branca , Humanos , Adulto , Imagem de Tensor de Difusão/métodos , Estudos Transversais , COVID-19/complicações , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Encéfalo/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Transtornos da Memória , Fadiga/etiologiaRESUMO
Stroke is one of the most common causes of acquired epilepsy, which can also result in disability and increased mortality rates particularly in elderly patients. No preventive treatment for post-stroke epilepsy is currently available. Development of such treatments has been greatly limited by the lack of biomarkers to reliably identify high-risk patients. The glymphatic system, including perivascular spaces (PVS), is the brain's waste clearance system, and enlargement or asymmetry of PVS (ePVS) is hypothesized to play a significant role in the pathogenesis of several neurological conditions. In this article, we discuss potential mechanisms for the role of perivascular spaces in the development of post-stroke epilepsy. Using advanced MR-imaging techniques, it has been shown that there is asymmetry and impairment of glymphatic function in the setting of ischemic stroke. Furthermore, studies have described a dysfunction of PVS in patients with different focal and generalized epilepsy syndromes. It is thought that inflammatory processes involving PVS and the blood-brain barrier, impairment of waste clearance, and sustained hypertension affecting the glymphatic system during a seizure may play a crucial role in epileptogenesis post-stroke. We hypothesize that impairment of the glymphatic system and asymmetry and dynamics of ePVS in the course of a stroke contribute to the development of PSE. Automated ePVS detection in stroke patients might thus assist in the identification of high-risk patients for post-stroke epilepsy trials. PLAIN LANGUAGE SUMMARY: Stroke often leads to epilepsy and is one of the main causes of epilepsy in elderly patients, with no preventative treatment available. The brain's waste removal system, called the glymphatic system which consists of perivascular spaces, may be involved. Enlargement or asymmetry of perivascular spaces could play a role in this and can be visualised with advanced brain imaging after a stroke. Detecting enlarged perivascular spaces in stroke patients could help identify those at risk for post-stroke epilepsy.
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Epilepsia , Sistema Glinfático , Acidente Vascular Cerebral , Humanos , Idoso , Sistema Glinfático/patologia , Encéfalo , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologia , Epilepsia/etiologia , BiomarcadoresRESUMO
Abstract The treatment of epilepsy has advanced over the past 30 years through the development of new antiseizure medications (ASMs). Unfortunately, not all of them have been approved yet in Brazil, and many are still underused. When comparing new ASMs to older ones, they are generally not more effective in treating epilepsy. However, they offer better tolerability, with fewer interactions and long-term side effects, especially for patients with comorbidities or those requiring polytherapy. Enzyme induction caused by older ASMs is associated with increased cholesterol levels, drug interactions with decreased effects of statins and other cardiovascular medications, anticoagulants, chemotherapy, immunosuppressors, anti-infective agents (including HIV treatment), antidepressants, and contraceptives. Additionally, they can reduce levels of vitamin D and sex hormones, as well as decrease bone density. The increasing concern about these effects during life, especially after prolonged exposure, has led most developed countries to change prescription patterns in favor of new ASMs, particularly levetiracetam and lamotrigine. Both are also considered the safest options for women of childbearing age. Regrettably, the prescription trends in Brazil have remained largely unchanged over time. This can be partially attributed to the slower approval process of ASM and the reluctance of general physicians and neurologists to embrace these new concepts. In this concise review, we highlight the various advantages linked to the new ASM, aiming to promote a shift in the prescription pattern for ASM. The selection of ASM should be customized according to individual characteristics, and practical suggestions for choosing ASMs are provided in this paper.
Resumo O tratamento da epilepsia avançou nos últimos 30 anos com o desenvolvimento de novos medicamentos anticrise (MAC). Infelizmente, nem todos estão aprovados no Brasil e muitos ainda são subutilizados. Os novos MAC não são mais eficazes que os antigos, mas apresentam melhor tolerabilidade, menos interações e efeitos colaterais a longo prazo, especialmente para pacientes com comorbidades ou que necessitam de politerapia. A indução enzimática causada pelos MAC antigos está associada ao aumento dos níveis de colesterol, interações medicamentosas com redução do efeito das estatinas e outros medicamentos cardiovasculares, anticoagulantes, quimioterapia, imunossupressores, agentes anti-infecciosos (incluindo tratamento do HIV), antidepressivos e contraceptivos. Além disso, podem reduzir os níveis de vitamina D e hormônios sexuais, podendo afetar a massa óssea. A crescente preocupação sobre estes efeitos ao longo da vida, com a exposição prolongada, levou a maioria dos países desenvolvidos a modificar o padrão de prescrição com maior uso dos novos MAC, especialmente levetiracetam e lamotrigina. Ambos são considerados as opções mais seguras para mulheres em idade fértil. Infelizmente, as tendências de prescrição no Brasil permaneceram praticamente inalteradas ao longo do tempo. Isto pode ser parcialmente explicado pela lentidão no processo de aprovação dos MAC e à resistência dos médicos generalistas e neurologistas em adotar estes novos conceitos. Nesta revisão, destacamos as vantagens dos novos MAC e a necessidade da mudança no padrão de prescrição também no Brasil. A escolha do MAC deve ser feita de acordo com as características individuais dos pacientes e sugestões práticas são apresentadas.
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Abstract Emerging studies indicate the persistence of symptoms beyond the acute phase of COVID-19. Cognitive impairment has been observed in certain individuals for months following infection. Currently, there is limited knowledge about the specific cognitive domains that undergo alterations during the post-acute COVID-19 syndrome and the potential impact of disease severity on cognition. The aim of this review is to examine studies that have reported cognitive impairment in post-acute COVID-19, categorizing them into subacute and chronic phases. The methodology proposed by JBI was followed in this study. The included studies were published between December 2019 and December 2022. The search was conducted in PubMed, PubMed PMC, BVS - BIREME, Embase, SCOPUS, Cochrane, Web of Science, Proquest, PsycInfo, and EBSCOHost. Data extraction included specific details about the population, concepts, context, and key findings or recommendations relevant to the review objectives. A total of 7,540 records were identified and examined, and 47 articles were included. The cognitive domains most frequently reported as altered 4 to 12 weeks after acute COVID-19 were language, episodic memory, and executive function, and after 12 weeks, the domains most affected were attention, episodic memory, and executive function. The results of this scoping review highlight that adults with post-acute COVID-19 syndrome may have impairment in specific cognitive domains.
Resumo Estudos emergentes indicam a persistência dos sintomas além da fase aguda da COVID-19. O comprometimento cognitivo foi observado em alguns indivíduos durante meses após a infecção. Atualmente, há pouco conhecimento sobre os domínios cognitivos específicos que sofrem alterações durante a síndrome pós-aguda da COVID-19 e o possível impacto da gravidade da doença na cognição. O objetivo desta revisão é examinar estudos que relataram comprometimento cognitivo na COVID-19 pós-aguda, categorizando-os em fases subaguda e crônica. A metodologia proposta pela Joanna Briggs Institute foi seguida neste estudo. Os estudos incluídos foram publicados entre dezembro de 2019 e dezembro de 2022. A busca foi realizada no PubMed, PubMed PMC, BVS - BIREME, Embase, SCOPUS, Cochrane, Web of Science, Proquest, PsycInfo e EBSCOHost. A extração de dados incluiu detalhes específicos sobre a população, os conceitos, o contexto e as principais descobertas ou recomendações relevantes para os objetivos da revisão. Um total de 7.540 registros foi identificado e examinado, e 47 artigos foram incluídos. Os domínios cognitivos mais frequentemente relatados como alterados de 4 a 12 semanas após a COVID-19 aguda foram linguagem, memória episódica e função executiva e, após 12 semanas, os domínios mais afetados foram atenção, memória episódica e função executiva. Os resultados dessa revisão de escopo destacam que adultos com síndrome pós-aguda da COVID-19 podem apresentar comprometimento em domínios cognitivos específicos.
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Emerging studies indicate the persistence of symptoms beyond the acute phase of COVID-19. Cognitive impairment has been observed in certain individuals for months following infection. Currently, there is limited knowledge about the specific cognitive domains that undergo alterations during the post-acute COVID-19 syndrome and the potential impact of disease severity on cognition. The aim of this review is to examine studies that have reported cognitive impairment in post-acute COVID-19, categorizing them into subacute and chronic phases. The methodology proposed by JBI was followed in this study. The included studies were published between December 2019 and December 2022. The search was conducted in PubMed, PubMed PMC, BVS - BIREME, Embase, SCOPUS, Cochrane, Web of Science, Proquest, PsycInfo, and EBSCOHost. Data extraction included specific details about the population, concepts, context, and key findings or recommendations relevant to the review objectives. A total of 7,540 records were identified and examined, and 47 articles were included. The cognitive domains most frequently reported as altered 4 to 12 weeks after acute COVID-19 were language, episodic memory, and executive function, and after 12 weeks, the domains most affected were attention, episodic memory, and executive function. The results of this scoping review highlight that adults with post-acute COVID-19 syndrome may have impairment in specific cognitive domains.
Estudos emergentes indicam a persistência dos sintomas além da fase aguda da COVID-19. O comprometimento cognitivo foi observado em alguns indivíduos durante meses após a infecção. Atualmente, há pouco conhecimento sobre os domínios cognitivos específicos que sofrem alterações durante a síndrome pós-aguda da COVID-19 e o possível impacto da gravidade da doença na cognição. O objetivo desta revisão é examinar estudos que relataram comprometimento cognitivo na COVID-19 pós-aguda, categorizando-os em fases subaguda e crônica. A metodologia proposta pela Joanna Briggs Institute foi seguida neste estudo. Os estudos incluídos foram publicados entre dezembro de 2019 e dezembro de 2022. A busca foi realizada no PubMed, PubMed PMC, BVS BIREME, Embase, SCOPUS, Cochrane, Web of Science, Proquest, PsycInfo e EBSCOHost. A extração de dados incluiu detalhes específicos sobre a população, os conceitos, o contexto e as principais descobertas ou recomendações relevantes para os objetivos da revisão. Um total de 7.540 registros foi identificado e examinado, e 47 artigos foram incluídos. Os domínios cognitivos mais frequentemente relatados como alterados de 4 a 12 semanas após a COVID-19 aguda foram linguagem, memória episódica e função executiva e, após 12 semanas, os domínios mais afetados foram atenção, memória episódica e função executiva. Os resultados dessa revisão de escopo destacam que adultos com síndrome pós-aguda da COVID-19 podem apresentar comprometimento em domínios cognitivos específicos.
Assuntos
COVID-19 , Disfunção Cognitiva , Adulto , Humanos , Síndrome de COVID-19 Pós-Aguda , COVID-19/complicações , Disfunção Cognitiva/etiologia , Cognição , Função ExecutivaRESUMO
INTRODUCTION: Despite significant advances in managing acute stroke and reducing stroke mortality, preventing complications like post-stroke epilepsy (PSE) has seen limited progress. PSE research has been scattered worldwide with varying methodologies and data reporting. To address this, we established the International Post-stroke Epilepsy Research Consortium (IPSERC) to integrate global PSE research efforts. This protocol outlines an individual patient data meta-analysis (IPD-MA) to determine outcomes in patients with post-stroke seizures (PSS) and develop/validate PSE prediction models, comparing them with existing models. This protocol informs about creating the International Post-stroke Epilepsy Research Repository (IPSERR) to support future collaborative research. METHODS AND ANALYSIS: We utilised a comprehensive search strategy and searched MEDLINE, Embase, PsycInfo, Cochrane, and Web of Science databases until 30 January 2023. We extracted observational studies of stroke patients aged ≥18 years, presenting early or late PSS with data on patient outcome measures, and conducted the risk of bias assessment. We did not apply any restriction based on the date or language of publication. We will invite these study authors and the IPSERC collaborators to contribute IPD to IPSERR. We will review the IPD lodged within IPSERR to identify patients who developed epileptic seizures and those who did not. We will merge the IPD files of individual data and standardise the variables where possible for consistency. We will conduct an IPD-MA to estimate the prognostic value of clinical characteristics in predicting PSE. ETHICS AND DISSEMINATION: Ethics approval is not required for this study. The results will be published in peer-reviewed journals. This study will contribute to IPSERR, which will be available to researchers for future PSE research projects. It will also serve as a platform to anchor future clinical trials. TRIAL REGISTRATION NUMBER: NCT06108102.
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Epilepsia , Acidente Vascular Cerebral , Humanos , Adolescente , Adulto , Epilepsia/etiologia , Convulsões/etiologia , Prognóstico , Projetos de Pesquisa , Acidente Vascular Cerebral/complicações , Metanálise como AssuntoRESUMO
RESUMO A Covid-19 é uma doença multissistêmica e consequências funcionais e tardias estão em estudo. Sequelas psicológicas e neurocognitivas podem comprometer a Capacidade para o Trabalho (CT) dos trabalhadores. Objetivou-se investigar a CT de pessoas previamente infectadas pelo Sars-CoV-2, correlacionando-a com avaliação da sonolência, ansiedade, depressão e fadiga. Estudo transversal, com trabalhadores diagnosticados com Covid-19 e em acompanhamento no Serviço de Neurologia da Universidade Estadual de Campinas (Unicamp). Aplicou-se o instrumento Índice de Capacidade para o Trabalho (ICT), um formulário com dados sociodemográficos e ocupacionais, bem como escalas de sonolência, ansiedade, depressão e fadiga. Dos 119 trabalhadores que participaram do estudo, mais da metade apresentaram comprometimento da CT (52,9%). Distúrbio emocional foi o agravo relatado mais frequente (31,9%). A regressão logística múltipla mostrou que a interação entre ansiedade e sonolência esteve associada ao comprometimento da CT (OR=4,50 com p=0,002). Ansiedade e sonolência foram alterações tardias da Covid-19 e associadas ao comprometimento da CT dos trabalhadores avaliados. Este estudo demonstra a necessidade de que todos os trabalhadores com teste positivo por Covid-19 tenham sua CT avaliada por ocasião do retorno ao trabalho. Ações de promoção à saúde, reabilitação funcional e adaptação do trabalho de acordo com as sequelas apresentadas pelos trabalhadores.
ABSTRACT COVID-19 is a multisystemic disease, with functional and late consequences still under study. Psychological and neurocognitive sequelae impact workers' quality of life and may compromise the Work Ability (WA). The objective was to investigate the WA of people infected with SARS-CoV-2, correlating it with the assessment of sleepiness, anxiety, depression and fatigue. Cross-sectional study, involving workers diagnosed with COVID-19 under follow-up at the Department of Neurology of Universidade Estadual de Campinas (UNICAMP). Application of the Work Ability Index (WAI) analyzed with sociodemographic and occupational variables, as well the sleepiness, anxiety, depression and fatigue scales. Multiple logistic regression analysis was performed. 119 workers participated in the study and, among them, more than half had WA impairment (52.9%). Emotional disorders were the most frequent reported problem (31.9%). Multiple logistic regression showed that the interaction between anxiety and sleepiness was associated with WA impairment (OR=4.50, p=0.002). Anxiety and sleepiness were associated with previous COVID-19 and they were associated with WA impairment among workers. This study shows the WA evaluation should be provided for all workers with a previous history of COVID-19, when they return to work. This assessment can guide health promotion actions, functional rehabilitation and work adaptation to the sequelae presented by workers, singularly.
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Background: The expression of serine protease granzyme-B (GzmB) by circulating CD8+ T lymphocytes has been recently suggested as a biomarker for poor immunotherapy response and severe disability in patients with Neuromyelitis Optica spectrum disorders (NMOSD). In parallel, venous thromboembolism (VTE) has been reported mainly in NMOSD patients exhibiting transverse myelitis. Case presentation: Here, we describe an Aquaporin-4 positive (AQP4-positive) NMOSD patient who showed short myelitis (SM) and experienced a fatal pulmonary thromboembolism/lower extremity deep vein thrombosis during anti-CD20 treatment. Flow cytometry analyses from the peripheral blood revealed an enhanced cytotoxic behavior through circulating CD8+GzmB+ T, CD4+GzmB+ T lymphocytes, and residual CD19+GzmB+ B cells. Conclusions: Fatal VTE may be a rare outcome, particularly in patients exhibiting SM, and may share poorly understood immunological mechanisms with AQP4-positive NMOSD severity.
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Importance: Published data about the impact of poststroke seizures (PSSs) on the outcomes of patients with stroke are inconsistent and have not been systematically evaluated, to the authors' knowledge. Objective: To investigate outcomes in people with PSS compared with people without PSS. Data Sources: MEDLINE, Embase, PsycInfo, Cochrane, LILACS, LIPECS, and Web of Science, with years searched from 1951 to January 30, 2023. Study Selection: Observational studies that reported PSS outcomes. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was used for abstracting data, and the Joanna Briggs Institute tool was used for risk-of-bias assessment. Data were reported as odds ratio (OR) and standardized mean difference (SMD) with a 95% CI using a random-effects meta-analysis. Publication bias was assessed using funnel plots and the Egger test. Outlier and meta-regression analyses were performed to explore the source of heterogeneity. Data were analyzed from November 2022 to January 2023. Main Outcomes and Measures: Measured outcomes were mortality, poor functional outcome (modified Rankin scale [mRS] score 3-6), disability (mean mRS score), recurrent stroke, and dementia at patient follow-up. Results: The search yielded 71 eligible articles, including 20â¯110 patients with PSS and 1â¯166â¯085 patients without PSS. Of the participants with PSS, 1967 (9.8%) had early seizures, and 10â¯605 (52.7%) had late seizures. The risk of bias was high in 5 studies (7.0%), moderate in 35 (49.3%), and low in 31 (43.7%). PSSs were associated with mortality risk (OR, 2.1; 95% CI, 1.8-2.4), poor functional outcome (OR, 2.2; 95% CI, 1.8-2.8), greater disability (SMD, 0.6; 95% CI, 0.4-0.7), and increased dementia risk (OR, 3.1; 95% CI, 1.3-7.7) compared with patients without PSS. In subgroup analyses, early seizures but not late seizures were associated with mortality (OR, 2.4; 95% CI, 1.9-2.9 vs OR, 1.2; 95% CI, 0.8-2.0) and both ischemic and hemorrhagic stroke subtypes were associated with mortality (OR, 2.2; 95% CI, 1.8-2.7 vs OR, 1.4; 95% CI, 1.0-1.8). In addition, early and late seizures (OR, 2.4; 95% CI, 1.6-3.4 vs OR, 2.7; 95% CI, 1.8-4.1) and stroke subtypes were associated with poor outcomes (OR, 2.6; 95% CI, 1.9-3.7 vs OR, 1.9; 95% CI, 1.0-3.6). Conclusions and Relevance: Results of this systematic review and meta-analysis suggest that PSSs were associated with significantly increased mortality and severe disability in patients with history of stroke. Unraveling these associations is a high clinical and research priority. Trials of interventions to prevent seizures may be warranted.
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Demência , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/complicações , Convulsões/etiologia , Avaliação de Resultados em Cuidados de SaúdeRESUMO
Focal cortical dysplasia (FCD) is a brain malformation that causes medically refractory epilepsy. FCD is classified into three categories based on structural and cellular abnormalities, with FCD type II being the most common and characterized by disrupted organization of the cortex and abnormal neuronal development. In this study, we employed cell-type deconvolution and single-cell signatures to analyze bulk RNA-seq from multiple transcriptomic studies, aiming to characterize the cellular composition of brain lesions in patients with FCD IIa and IIb subtypes. Our deconvolution analyses revealed specific cellular changes in FCD IIb, including neuronal loss and an increase in reactive astrocytes (astrogliosis) when compared to FCD IIa. Astrogliosis in FCD IIb was further supported by a gene signature analysis and histologically confirmed by glial fibrillary acidic protein (GFAP) immunostaining. Overall, our findings demonstrate that FCD II subtypes exhibit differential neuronal and glial compositions, with astrogliosis emerging as a hallmark of FCD IIb. These observations, validated in independent patient cohorts and confirmed using immunohistochemistry, offer novel insights into the involvement of glial cells in FCD type II pathophysiology and may contribute to the development of targeted therapies for this condition.
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Displasia Cortical Focal , Malformações do Desenvolvimento Cortical do Grupo I , Humanos , Gliose , NeurogliaRESUMO
OBJECTIVE: Typical aging is associated with gradual cognitive decline and changes in brain structure. The observation that cognitive performance in mesial temporal lobe epilepsy (TLE) patients diverges from controls early in life with subsequent decline running in parallel would suggest an initial insult but does not support accelerated decline secondary to seizures. Whether TLE patients demonstrate similar trajectories of age-related gray (GM) and white matter (WM) changes as compared to healthy controls remains uncertain. METHODS: 3D T1-weighted and diffusion tensor images were acquired at a single site in 170 TLE patients (aged 23-74 years) with MRI signs of unilateral hippocampal sclerosis (HS, 77 right) and 111 healthy controls (aged 26-80 years). Global brain (GM, WM, total brain, and cerebrospinal fluid) and regional volumes (ipsi- and contralateral hippocampi), and fractional anisotropy (FA) of 10 tracts (three portions of corpus callosum, inferior longitudinal, inferior fronto-occipital and uncinate fasciculi, body of fornix, dorsal and parahippocampal-cingulum, and corticospinal tract) were compared between groups as a function of age. RESULTS: There were significant reductions of global brain and hippocampi volumes (greatest ipsilateral to HS), and FA of all 10 tracts in TLE versus controls. For TLE patients, regression lines run in parallel to those from controls for brain volumes and FA (for all tracts except the parahippocampal-cingulum and corticospinal tract) versus age across the adult lifespan. INTERPRETATION: These results imply a developmental hindrance occurring earlier in life (likely in childhood/neurodevelopmental stages) rather than accelerated atrophy/degeneration of most brain structures herein analyzed in patients with TLE.
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Epilepsia do Lobo Temporal , Substância Branca , Adulto , Humanos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Longevidade , Imagem de Tensor de Difusão/métodos , Encéfalo/diagnóstico por imagemRESUMO
Introduction: Focal cortical dysplasia (FCD) is a common cause of pharmacoresistant epilepsy. According to the 2022 International League Against Epilepsy classification, FCD type II is characterized by dysmorphic neurons (IIa and IIb) and may be associated with balloon cells (IIb). We present a multicentric study to evaluate the transcriptomes of the gray and white matters of surgical FCD type II specimens. We aimed to contribute to pathophysiology and tissue characterization. Methods: We investigated FCD II (a and b) and control samples by performing RNA-sequencing followed by immunohistochemical validation employing digital analyses. Results: We found 342 and 399 transcripts differentially expressed in the gray matter of IIa and IIb lesions compared to controls, respectively. Cholesterol biosynthesis was among the main enriched cellular pathways in both IIa and IIb gray matter. Particularly, the genes HMGCS1, HMGCR, and SQLE were upregulated in both type II groups. We also found 12 differentially expressed genes when comparing transcriptomes of IIa and IIb lesions. Only 1 transcript (MTRNR2L12) was significantly upregulated in FCD IIa. The white matter in IIa and IIb lesions showed 2 and 24 transcripts differentially expressed, respectively, compared to controls. No enriched cellular pathways were detected. GPNMB, not previously described in FCD samples, was upregulated in IIb compared to IIa and control groups. Upregulations of cholesterol biosynthesis enzymes and GPNMB genes in FCD groups were immunohistochemically validated. Such enzymes were mainly detected in both dysmorphic and normal neurons, whereas GPNMB was observed only in balloon cells. Discussion: Overall, our study contributed to identifying cortical enrichment of cholesterol biosynthesis in FCD type II, which may correspond to a neuroprotective response to seizures. Moreover, specific analyses in either the gray or the white matter revealed upregulations of MTRNR2L12 and GPNMB, which might be potential neuropathological biomarkers of a cortex chronically exposed to seizures and of balloon cells, respectively.
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BACKGROUND AND PURPOSE: The genetics of late seizure or epilepsy secondary to traumatic brain injury (TBI) or stroke are poorly understood. We undertook a systematic review to test the association of single-nucleotide polymorphisms (SNPs) with the risk of post-traumatic epilepsy (PTE) and post-stroke epilepsy (PSE). METHODS: We followed methods from our prespecified protocol on PROSPERO to identify indexed articles for this systematic review. We collated the association statistics from the included articles to assess the association of SNPs with the risk of epilepsy amongst TBI or stroke patients. We assessed study quality using the Q-Genie tool. We report odds ratios (OR) and hazard ratios with 95% confidence intervals (CIs). RESULTS: The literature search yielded 420 articles. We included 16 studies in our systematic review, of which seven were of poor quality. We examined published data on 127 SNPs from 32 genes identified in PTE and PSE patients. Eleven SNPs were associated with a significantly increased risk of PTE. Three SNPs, TRMP6 rs2274924, ALDH2 rs671, and CD40 -1C/T, were significantly associated with an increased risk of PSE, while two, AT1R rs12721273 and rs55707609, were significantly associated with reduced risk. The meta-analysis for the association of the APOE É4 with PTE was nonsignificant (OR 1.8, CI 0.6-5.6). CONCLUSIONS: The current evidence on the association of genetic polymorphisms in epilepsy secondary to TBI or stroke is of low quality and lacks validation. A collaborative effort to pool genetic data linked to epileptogenesis in stroke and TBI patients is warranted.