Segurança da estimulação transcraniana por corrente contínua em uma paciente com implante de eletrodos de estimulação cerebral profunda

Descrição: A estimulação transcraniana por corrente contínua (ETCC) tem sido investigada nos distúrbios de movimento, tornando-a uma alternativa terapêutica no contexto clínico. Contudo, não há consenso quanto aos protocolos mais apropriados na maioria dos casos e a presença de eletrodos de estimulação cerebral profunda (ECP) é geralmente considerada uma contraindicação. Recentemente, estudamos os efeitos da ETCC cerebelar em uma paciente do sexo feminino com implante de eletrodos de estimulação cerebral profunda (ECP) para distonia generalizada. Ela também apresentava dor crônica e depressão. A ETCC foi realizada dois anos após o implante de eletrodos de ECP. Com a ECP houve melhora da distonia e a toxina botulínica reduziu a dor. Contudo, os sintomas depressivos pioraram após a cirurgia de ECP. Métodos: Foi proposta ETCC cerebelar anódica de 2mA, sobre os dois hemisférios em cada sessão de 30min: 15 min de ETCC cerebelar esquerda seguida de 15min de ETCC cerebelar direita. Resultados: Embora o nosso objetivo tenha sido melhorar os movimentos distônicos, após 10 sessões de ETCC houve melhora também do humor da paciente. Não houve nenhuma complicação, apesar da presença de eletrodos de ECP. Conclusão: Nossos resultados apontam para a segurança da tDCS e sua aplicação potencial e efetiva como ferramenta neuromodulatória adicional no tratamento de possíveis sintomas persistentes após a ECP em pacientes com distúrbios de movimento.Background: Transcranial direct current stimulation (tDCS) has been investigated in movement disorders, making it a therapeutic alternative in clinical settings. However, there is still no consensus on the most appropriate treatment protocols in most cases, and the presence of deep brain stimulation (DBS) electrodes has been regarded as a contraindication to the procedure. We recently studied the effects of cerebellar tDCS on a female patient already undergoing subthalamic nucleus deep brain stimulation (STN-DBS) for generalized dystonia. She also presented with chronic pain and depression. With STN-DBS, there was improvement of dystonia, and botulinum toxin significantly reduced pain. However, depressive symptoms were worse after STN-DBS surgery. Methods: Neuromodulation with 2 mA anodal cerebellar tDCS was initiated, targeting both hemispheres in each daily 30 minute session: 15 minutes of left cerebellar stimulation followed by 15 minutes of right cerebellar stimulation. The DBS electrodes were in place and functional, but the current was turned off during tDCS. Results: Although our goal was to improve dystonic movements, after 10 tDCS sessions there was also improvement in mood with normalization of Beck Depression Inventory scores. There were no complications in spite of the implanted STN-DBS leads. Conclusion: Our results indicate that tDCS is safe in patients with DBS electrodes and may be an effective add-on neuromodulatory tool in the treatment of potential DBS partial efficacy in patients with movement disorders

Contribuições ao estudo dos efeitos da neuromodulação não-invasiva sobre parâmetros neuropsicológicos normais e em distúrbios neuropsiquiátricos

Tese (doutorado)—Universidade de Brasília, Instituto de Psicologia, Departamento de Processos Psicológicos Básicos, Programa de Pós-Graduação em Ciências do Comportamento, 2017.Em todo o mundo, em virtude do aumento da prevalência de transtornos neuropsiquiátricos e neurológicos, alto custo dos tratamentos farmacológicos, e aumento do número de pacientes refratários aos tratamentos convencionais, novas técnicas, menos invasivas, com menos efeitos colaterais e com resultados promissores têm surgido com o advento das técnicas de estimulação não-invasiva do cérebro (Non-Invasive Brain Stimulation – NIBS). A partir da introdução da estimulação não-invasiva do córtex motor por Barker et al. (1985), surgiu a Estimulação Magnética Transcraniana (EMT), atualmente voltada também para o tratamento da depressão e, mais recentemente, na última década, dos transtornos neurológicos, como a epilepsia e a Doença de Parkinson (DA). Outras patologias, como os transtornos de ansiedade, doenças do sistema nervoso central (Acidente Vascular Cerebral – AVC), demências e distúrbios cognitivos (Doença de Alzheimer), dor, entre outros, têm se beneficiado com o tratamento da EMT e de técnicas não-invasivas mais recentemente desenvolvidas, como a Estimulação Transcraniana por Corrente Contínua (ETCC). Embora essas técnicas utilizem processos físicos e fisiológicos distintos, ambas utilizam como princípios a estimulação ou inibição de regiões cerebrais, gerando um efeito modulatório da disfunção, em regiões específicas do sistema nervoso envolvidas em certas patologias. Contudo, mesmo com o avanço destas técnicas e, sabendo de suas vantagens e desvantagens, no tratamento de transtornos específicos, novos estudos são necessários a fim de propiciar o desenvolvimento de novos protocolos terapêuticos desses transtornos. Nesta tese apresentamos quatro contribuições originais ao estudo da neuromodulação não invasiva do sistema nervoso: 1 revisão das possíveis aplicações clínicas dessas técnicas nos distúrbios de ansiedade e em outras condições neuropsiquiátricas; 1 estudo experimental dos efeitos da ETCC sobre o córtex pré-frontal dorsolateral esquerdo sobre a memória de trabalho de voluntários idosos; 2 estudos de caso de tratamento de ETCC, respectivamente, de transtorno cognitivo leve e de distonia generalizada. Concluímos que a EMT e a ETCC apresentam potencial terapêutico nos distúrbios neuropsiquiátricos, transtornos cognitivos leves e distonias, além de serem ferramentas interessantes para o estudo da fisiologia normal do sistema nervoso.Throughout the world, due to the increased prevalence of neuropsychiatric and neurological disorders, high cost of pharmacological treatments, and an increase in the number of patients refractory to conventional treatments, new techniques, less invasive, with fewer side effects and with promising results have arisen with the advent of Non-Invasive Brain Stimulation (NIBS) methods. From the introduction of non-invasive motor cortex stimulation by Barker et al. (1985), Transcranial Magnetic Stimulation (TMS), now also focused on the treatment of depression and, even more recently, neurological disorders such as epilepsy and Parkinson's disease (PD). Other pathologies, such as anxiety disorders, central nervous system diseases, dementias and cognitive disorders (Alzheimer's Disease), and pain, among others, have benefited from the treatment by TMS and other non-Invasive techniques such as Transcranial Direct Current Stimulation (tDCS). Although these techniques work through different physical and physiological processes, both use the principle of stimulation or inhibition of brain regions, generating a modulatory effect of the dysfunction, in specific regions of the nervous system involved in certain pathologies. However, even with the advancement of these techniques and, knowing their advantages and disadvantages in the treatment of specific disorders, new studies are necessary in order to foster the development of new therapeutic protocols for these diseases. In this thesis we present four original contributions to the study of noninvasive neuromodulation of the nervous system: 1 review of the possible clinical applications of these techniques in anxiety disorders and other neuropsychiatric conditions; 1 experimental study of the effects of tDCS on the left dorsolateral prefrontal cortex on the working memory of elderly volunteers; 2 case-studies of the treatment of tDCS, respectively, of mild cognitive impairment and generalized dystonia. We conclude that EMT and ETCC present therapeutic potential in neuropsychiatric disorders, mild neurocognitive disorders and dystonias, and are interesting tools for the study of normal nervous system physiology

Investigação longitudinal da influência do uso de antidepressivos sobre os sintomas psiquiátricos e desempenhos neuropsicológicos e funcionais em idosos com e sem Doença de Alzheimer

Dissertação (mestrado)—Universidade de Brasília, Instituto de Psicologia, Departamento de Processos Psicológicos Básicos, Programa de Pós-Graduação em Ciências da Comportamento, 2012.O presente estudo tem como objetivo geral investigar a influência do uso de antidepressivos e estabilizadores de humor sobre os desempenhos neuropsicológicos, funcionais e sintomas psiquiátricos, em pacientes idosos entre 60 e 90 anos de idade. Para tanto, realizou-se avaliação neuropsicológica, por meio de escala cognitiva (Mini Exame do Estado Mental – MEEM), escalas funcionais (Escala de Atividades Básicas de Vida Diária – ABVD; Escala de Atividades Instrumentais de Vida Diária – AIVD) e, escalas psiquiátricas (Escala Cornell de Depressão em Demência - ECDD; Inventário Neuropsiquiátrico - NPI), para análise comparativa quantitativa e longitudinal, entre os dois grupos de pacientes idosos, onde Grupo 1: pacientes com tratamento antidepressivo (grupo experimental), e Grupo 2: pacientes sem tratamento antidepressivo (grupo controle), sendo os subgrupos: pacientes com e sem doença de Alzheimer (DA). A análise longitudinal foi realizada, através de duas etapas, onde os mesmos instrumentos avaliativos foram utilizados, a fim de comparar os resultados obtidos na 1ª e a 2ª etapa, com intervalo médio de 26,2 semanas, e verificar se houve influência do tratamento antidepressivo, nos pacientes do grupo experimental, em relação aos pacientes do grupo controle. Em relação aos efeitos dos antidepressivos, verificou-se, uma redução dos escores na ECDD, após 25,3 semanas de tratamento antidepressivo, no grupo experimental, resultando em diminuição dos sintomas depressivos, em comparação com os escores obtidos antes do início do tratamento. _______________________________________________________________________________________ ABSTRACTThe present study aims at investigating the possible influence of antidepressants and mood stabilizers on neuropsychological performance, functional and psychiatric symptoms in elderly patients between 60 and 90 years of age. To this end, we carried out a neuropsychological evaluation by means of scale cognitive (Mini Mental State Examination - MMEM), functional scales (Scale of Basic Activities of Daily Living - ABVD; Scale Instrumental Activities of Daily Living - IADL), and scales psychiatric (Cornell Scale for Depression in Dementia - ECDD; Neuropsychiatric Inventory - NPI) for quantitative and longitudinal comparative analysis between the two groups of elderly patients, where group 1: patients with antidepressant treatment (clinical group) and group 2: patients without antidepressant treatment (control group), and subgroups: patients with and without Alzheimer's disease (AD). The longitudinal analysis was performed through two steps, where the same evaluative tools were used to compare the results obtained in the 1st and 2nd stage, with a mean interval of 26.2 weeks, and see if there was influence of antidepressant treatment, patients in the clinical group, compared to control patients. Regarding the effect of antidepressants, there was a reduction in scores ECDD, 25.3 weeks after treatment antidepressant, among the patients, resulting in decrease of depressive symptoms, compared with scores obtained before the start of treatment

Uso clínico da estimulação magnética transcraniana e da estimulação transcraniana por corrente direta em transtornos de ansiedade e de transtornos neuropsiquiátricos

A estimulação magnética transcraniana (TMS) foi recentemente proposta como um possível tratamento adjuvante para muitos distúrbios neuropsiquiátricos, e já foi aprovada para o tratamento de depressão fármaco-resistente nos Estados Unidos e no Brasil, entre outros países. Apesar do fato de que seu uso em outros transtornos neuropsiquiátricos ainda é em grande parte experimental, muitos médicos têm utilizado essas técnicas como uma terapia off-label em várias doenças. Mais recentemente, uma outra técnica, a estimulação transcraniana por corrente contínua (ETCC), tornou-se também disponível como uma alternativa muito mais barata e portátil do que a TMS, embora os seus mecanismos de ação sejam diferentes daqueles da TMS. O uso off-label de TMS ou ETCC tende a ocorrer no caso de doenças que são notoriamente resistentes a outras modalidades terapêuticas. Aqui nós discutimos o caso dos transtornos de ansiedade, ou seja, transtorno do pânico e estresse pós-traumático, destacando as incertezas, benefícios e problemas potenciais inerentes ao uso clínico dessas técnicas neuromoduladoras no atual estágio do conhecimento.Transcranial magnetic stimulation (TMS) has recently been investigated as a possible adjuvant treatment for many neuropsychiatric disorders, and has already been approved for the treatment of drug-resistant depression in the United States and in Brazil, among other countries. Although its use in other neuropsychiatric disorders is still largely experimental, many physicians have been using it as an off-label add-on therapy for various disorders. More recently, another technique, transcranial direct current stimulation (tDCS), has also become available as a much cheaper and portable alternative to TMS, although its mechanisms of action are different from those of TMS. The use of off-label therapeutic TMS or tDCS tends to occur in the setting of diseases that are notoriously resistant to other treatment modalities. Here we discuss the case of anxiety disorders, namely panic and post-traumatic stress disorders, highlighting the uncertainties and potential problems and benefits of the clinical use of these neuromodulatory techniques at the current stage of knowledge

Comparing the effects of focal and conventional tDCS on motor skill learning: A proof of principle study

Transcranial direct current stimulation (tDCS) has emerged as a promising intervention in clinical and behavioral neuroscience; however, the response variability to this technique has limited its impact, partly due to the widespread of current flow with conventional methods. Here, we investigate whether a more targeted, focal approach over the primary motor cortex (M1) is advantageous for motor learning and targeting specific neuronal populations. Our preliminary results show that focal stimulation leads to enhanced skill learning and differentially recruits distinct pathways to M1. This finding suggests that focal tDCS approaches may improve the outcomes of future studies aiming to enhance behavior

Adaptation of Topology-Based Routing Protocols for Data Gathering Applications in VANETs

International audienceThe use of VANETs for data gathering applications imply that vehicles are not only able to generate data but also to forward it from others towards an access point (AP). Given the mobility characteristics of vehicles and the difficult propagation conditions of urban scenarios, it is commonly stated that topology-based routing solutions are less efficient than geographic-based routing solutions. However, these statements refer to generic vehicular communications, ignoring specific characteristics of data gathering scenarios. In this work, two existing routing protocols that prior to forwarding data, set a path from each vehicle towards the AP are adapted for data gathering applications. While the existence of a path reduces the number of ineffective retransmissions and the delay, it also increases the overhead, and therefore the presented protocols were adapted to improve the overall performance. Aiming to correctly evaluate the routing protocols, simulations are launched using a realistic trace from the city of Cologne. The results obtained show that it is possible to limit the overhead associated to topology updates, outperforming geographic-based solutions

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

National trends in total cholesterol obscure heterogeneous changes in HDL and non-HDL cholesterol and total-to-HDL cholesterol ratio : a pooled analysis of 458 population-based studies in Asian and Western countries

Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and nonHDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries. Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group. Results: Since similar to 1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at similar to 0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as similar to 0.7 per decade in Swiss men (equivalent to similar to 26% decline in coronary heart disease risk per decade). The ratio increased in China. Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol.Peer reviewe

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups