RESUMO
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.
Assuntos
Epilepsia , Vitaminas , Humanos , Feminino , Anticoagulantes , Densidade Óssea , Brasil , AnticonvulsivantesRESUMO
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.
Assuntos
Encéfalo , AVC Isquêmico , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , AVC Isquêmico/fisiopatologia , AVC Isquêmico/diagnóstico por imagem , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Idoso , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Lateralidade Funcional/fisiologia , Descanso/fisiologia , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Adulto , Mapeamento Encefálico/métodosRESUMO
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.
RESUMO
Background: Fatigue and cognitive complaints are the most frequent persistent symptoms in patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to assess fatigue and neuropsychological performance and investigate changes in the thickness and volume of gray matter (GM) and microstructural abnormalities in the white matter (WM) in a group of patients with mild-to-moderate coronavirus disease 2019 (COVID-19). Methods: We studied 56 COVID-19 patients and 37 matched controls using magnetic resonance imaging (MRI). Cognition was assessed using Montreal Cognitive Assessment and Cambridge Neuropsychological Test Automated Battery, and fatigue was assessed using Chalder Fatigue Scale (CFQ-11). T1-weighted MRI was used to assess GM thickness and volume. Fiber-specific apparent fiber density (FD), free water index, and diffusion tensor imaging data were extracted using diffusion-weighted MRI (d-MRI). d-MRI data were correlated with clinical and cognitive measures using partial correlations and general linear modeling. Results: COVID-19 patients had mild-to-moderate acute illness (95% non-hospitalized). The average period between real-time quantitative reverse transcription polymerase chain reaction-based diagnosis and clinical/MRI assessments was 93.3 (±26.4) days. The COVID-19 group had higher total CFQ-11 scores than the control group (p < 0.001). There were no differences in neuropsychological performance between groups. The COVID-19 group had lower FD in the association, projection, and commissural tracts, but no change in GM. The corona radiata, corticospinal tract, corpus callosum, arcuate fasciculus, cingulate, fornix, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus were involved. CFQ-11 scores, performance in reaction time, and visual memory tests correlated with microstructural changes in patients with COVID-19. Conclusions: Quantitative d-MRI detected changes in the WM microstructure of patients recovering from COVID-19. This study suggests a possible brain substrate underlying the symptoms caused by SARS-CoV-2 during medium- to long-term recovery.
RESUMO
BACKGROUND: Neuropsychiatric disorders are a significant cause of death and disability worldwide. The mechanisms underlying these disorders include a constellation of structural, infectious, immunological, metabolic, and genetic etiologies. Advances in next-generation sequencing techniques have demonstrated that the composition of the enteric microbiome is dynamic and plays a pivotal role in host homeostasis and several diseases. The enteric microbiome acts as a key mediator in neuronal signaling via metabolic, neuroimmune, and neuroendocrine pathways. OBJECTIVE: In this review, we aim to present and discuss the most current knowledge regarding the putative influence of the gut microbiome in neuropsychiatric disorders. METHODS: We examined some of the preclinical and clinical evidence and therapeutic strategies associated with the manipulation of the gut microbiome. RESULTS: targeted taxa were described and grouped from major studies to each disease. CONCLUSIONS: Understanding the complexity of these ecological interactions and their association with susceptibility and progression of acute and chronic disorders could lead to novel diagnostic biomarkers based on molecular targets. Moreover, research on the microbiome can also improve some emerging treatment choices, such as fecal transplantation, personalized probiotics, and dietary interventions, which could be used to reduce the impact of specific neuropsychiatric disorders. We expect that this knowledge will help physicians caring for patients with neuropsychiatric disorders.
Assuntos
Microbioma Gastrointestinal , Microbioma Gastrointestinal/fisiologia , HumanosRESUMO
ABSTRACT Background: Neuropsychiatric disorders are a significant cause of death and disability worldwide. The mechanisms underlying these disorders include a constellation of structural, infectious, immunological, metabolic, and genetic etiologies. Advances in next-generation sequencing techniques have demonstrated that the composition of the enteric microbiome is dynamic and plays a pivotal role in host homeostasis and several diseases. The enteric microbiome acts as a key mediator in neuronal signaling via metabolic, neuroimmune, and neuroendocrine pathways. Objective: In this review, we aim to present and discuss the most current knowledge regarding the putative influence of the gut microbiome in neuropsychiatric disorders. Methods: We examined some of the preclinical and clinical evidence and therapeutic strategies associated with the manipulation of the gut microbiome. Results: targeted taxa were described and grouped from major studies to each disease. Conclusions: Understanding the complexity of these ecological interactions and their association with susceptibility and progression of acute and chronic disorders could lead to novel diagnostic biomarkers based on molecular targets. Moreover, research on the microbiome can also improve some emerging treatment choices, such as fecal transplantation, personalized probiotics, and dietary interventions, which could be used to reduce the impact of specific neuropsychiatric disorders. We expect that this knowledge will help physicians caring for patients with neuropsychiatric disorders.
RESUMO Antecedentes: Os transtornos neuropsiquiátricos são uma importante causa de morte e invalidez no mundo. Os mecanismos subjacentes a esses transtornos incluem uma constelação de etiologias estruturais, infecciosas, imunológicas, metabólicas e genéticas. Avanços nas técnicas de sequenciamento do DNA têm demonstrado que a composição do microbioma entérico é dinâmica e desempenha um papel fundamental não apenas na homeostase do hospedeiro, mas também em várias doenças. O microbioma entérico atua como mediador na sinalização das vias metabólica, neuroimune e neuroendócrina. Objetivo: Apresentar os estudos mais recentes sobre a possível influência do microbioma intestinal nas diversas doenças neuropsiquiátricas e discutir tanto os resultados quanto a eficácia dos tratamentos que envolvem a manipulação do microbioma intestinal. Métodos: foram examinadas algumas das evidências pré-clínicas e clínicas e estratégias terapêuticas associadas à manipulação do microbioma intestinal. Resultados: os táxons-alvo foram descritos e agrupados a partir dos principais estudos para cada doença. Conclusões: Entender a fundo a complexidade das interações ecológicas no intestino e sua associação com a suscetibilidade a certas doenças agudas e crônicas pode levar ao desenvolvimento de novos biomarcadores diagnósticos com base em alvos moleculares. Além disso, o estudo do microbioma intestinal pode auxiliar na otimização de tratamentos não farmacológicos emergentes, tais como o transplante de microbiota fecal, o uso de probióticos e intervenções nutricionais personalizadas. Dessa forma, terapias alternativas poderiam ser usadas para reduzir o impacto dos transtornos neuropsiquiátricos na saúde pública. Esperamos que esse conhecimento seja útil para médicos que cuidam de pacientes com diversos transtornos neuropsiquiátricos.