Efeito da estimulação elétrica transcutânea do nervo vago na inflamação, modulação autonômica cardíaca e evolução clínica dos pacientes com COVID-19: estudo de protocolo para um ensaio clínico, controlado, randomizado e cego / Efecto de la estimulación eléctrica transcutánea del nervio vago sobre la inflamación, la modulación autonómica cardiac y la evolución clínica de pacientes con COVID-19: estudio de protocolo para un ensayo clínico, controlado, aleatorizado y ciego / Effects of transcutaneous auricular vagus nerve stimulation on inflammation, cardiac autonomic modulation, and clinical evolution of patients with COVID-19: protocol for a clinical, controlled, randomized, and blind trial

RESUMO O objetivo deste estudo é avaliar o efeito da estimulação elétrica transcutânea do nervo vago (EETNV) na inflamação, modulação autonômica cardíaca e evolução clínica dos pacientes com COVID-19. Trata-se de um ensaio clínico, controlado por sham, randomizado e cego, no qual participarão 52 indivíduos hospitalizados com diagnóstico de COVID-19, que serão randomizados em dois grupos de tratamento: grupo experimental (tratamento médico usual associado à EETNV ativa) ou grupo-controle (tratamento médico usual associado à EETNV sham). A EETNV será realizada por meio de um estimulador elétrico neuromuscular (modelo Dualpex 071 da Quark Medical Products), com o eletrodo de estimulação posicionado sobre o tragus esquerdo, com corrente alternada, frequência de 30Hz e variação de 50%, intensidade ajustada para o limiar sensorial do paciente, com duração de 90 minutos cada sessão de estimulação, duas vezes ao dia, durante sete dias consecutivos, totalizando 14 sessões. Serão avaliados pré e pós-intervenção o nível de interleucina-6 (IL-6) e interleucina-10 (IL-10), cortisol e proteína C reativa (PCR), pressão arterial, variabilidade da frequência cardíaca pelos parâmetros de baixa frequência (BF), alta frequência (AF) e pela razão da baixa e alta frequência (BF/AF), além de evolução clínica dos pacientes, incluindo o nível de ansiedade e depressão, cujos dados serão obtidos por meio de prontuários e questionários. Será realizado também um acompanhamento 7 e 14 dias após o término das intervenções para verificar a evolução clínica, incluindo nível de ansiedade e depressão, e durante seis meses serão avaliadas memória e atenção.

RESUMEN El objetivo de este estudio es evaluar el efecto de la estimulación eléctrica transcutánea del nervio vago (EETNV) sobre la inflamación, la modulación autonómica cardíaca y la evolución clínica de pacientes con COVID-19. Se trata de un ensayo clínico, controlado por simulado, aleatorizado y ciego, en el que participarán 52 individuos hospitalizados diagnosticados de COVID-19, que serán aleatorizados en dos grupos de tratamiento: grupo experimental (tratamiento médico habitual asociado a la EETNV activa) o grupo control (tratamiento médico habitual asociado a la EETNV simulada). La EETNV se realizará mediante un estimulador eléctrico neuromuscular (modelo Dualpex 071 de Quark Medical Products), con el electrodo de estimulación colocado en el trago izquierdo, con corriente alterna, frecuencia de 30Hz y 50% de variación, intensidad ajustada al umbral sensorial del paciente, con una duración de 90 minutos cada sesión de estimulación, dos veces al día, durante siete días consecutivos, lo que totaliza 14 sesiones. Se evaluarán antes y después de la intervención la interleucina-6 (IL-6) y la interleucina-10 (IL-10), el cortisol y la proteína C reactiva (PCR), la presión arterial, la variabilidad de la frecuencia cardíaca por los parámetros de baja frecuencia (BF), alta frecuencia (AF) y razón de baja y alta frecuencia (BF/AF), así como la evolución clínica de los pacientes, incluidos los parámetros de ansiedad y depresión cuyos datos se obtendrán de historias clínicas y cuestionarios. También se realizará un seguimiento de 7 y 14 días tras finalizadas las intervenciones para verificar la evolución clínica, incluidos el nivel de ansiedad y de depresión, y durante seis meses se evaluará la memoria y la atención.

ABSTRACT This study aims to evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on inflammation, cardiac autonomic modulation, and clinical evolution of patients with COVID-19. This is a clinical, sham-controlled, randomized, and blind trial, in which 52 hospitalized individuals diagnosed with COVID-19 will participate. They will be randomized into: experimental group (usual medical treatment associated with active taVNS) and control group (usual medical treatment associated with sham taVNS). The taVNS will be performed by a neuromuscular electric stimulator (Dualpex model 071 of Quark Medical Products), with the stimulation electrode positioned on the left tragus, with alternating current, at a 30Hz frequency with 50% variation. Intensity will be adjusted to the patient's sensory threshold, with 90-minutes-long stimulation sessions, happening twice per day for seven consecutive days, totaling 14 sessions. Interleukin-6 (IL-6) and interleukin-10 (IL-10), cortisol and C-reactive protein (CRP), blood pressure, heart rate variability (HRV) by low frequency (LF), high frequency (HF) and low and high frequency ratio (LF/HF) parameters will be evaluated before and after the intervention, as well as patients' clinical evolution-including anxiety and depression levels-whose data will be obtained through medical records and questionnaires. A follow-up will also be performed seven and 14 days after the end of the interventions to verify the clinical evolution, including anxiety and depression levels. Memory and attention levels will be evaluated for six months.

Appraising the effectiveness of electrical and magnetic brain stimulation techniques in acute major depressive episodes: an umbrella review of meta-analyses of randomized controlled trials

Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.

Transcranial direct-current stimulation in combination with exercise: a systematic review / Estimulação transcraniana por corrente contínua em combinação com o exercício: uma revisão sistemática / Estimulación transcraneana por corriente continua en combinación con el ejercicio: una revisión sistemática

ABSTRACT Introduction Transcranial direct-current stimulation (tDCS) is a noninvasive technique that allows the modulation of cortical excitability and can produce changes in neuronal plasticity. The application of tDCS has recently been associated with physical activity. Objectives To verify the effect of Transcranial Direct-Current Stimulation (tDCS) in combination with physical exercise, characterizing methodological aspects of the technique. Methods In the database search, studies with animals, other neuromodulation techniques and opinion and review articles were excluded. Publications up to 2016 were selected and the methodological quality of the articles was verified through the PEDro scale. Results The majority of studies (86%) used tDCS on the motor cortex area, with anodal current and the allocation of monocephalic electrodes (46.5%). The prevalent current intensity was 2mA (72%), with duration of 20min (55.8%). The profile of the research participants was predominantly of subjects aged up to 60 years (72.1%). The outcomes were favorable for the use of anodal tDCS in combination with physical exercise. Conclusion Transcranial Direct-Current Stimulation is a promising technique when used in combination with aerobic and anaerobic exercises; however, it is necessary to investigate concurrent exercise. Level of Evidence II; Therapeutic Studies Investigating the Results of Treatment (systematic review of Level II studies or Level I studies with inconsistent results).

RESUMO Introdução A estimulação transcraniana por corrente contínua (ETCC) é uma técnica não invasiva que permite a modulação da excitabilidade cortical e pode produzir alterações na plasticidade neuronal. A aplicação da ETCC tem sido recentemente associada à atividade física. Objetivos Verificar o efeito da Estimulação Transcraniana por Corrente Contínua (ETCC) em combinação com o exercício físico, caracterizando os aspectos metodológicos da técnica. Métodos Na busca em base de dados, excluíram-se estudos com animais e outras técnicas de neuromodulação, além de artigos de revisão e opinião. Foram selecionadas publicações até 2016 e a qualidade metodológica dos artigos foi verificada através da escala PEDRo. Resultados A maioria dos estudos (86%) utilizou a ETCC na área do córtex motor, com corrente anódica e montagem monocefálica (unipolar) (46,5%). A intensidade da corrente dominante foi 2mA (72%) com duração de 20 min (55,8%). O perfil dos participantes da pesquisa foi predominantemente de indivíduos com até 60 anos de idade (72,1%). Os desfechos foram favoráveis ao uso da ETCC anódica em combinação com o exercício físico. Conclusão A Estimulação Transcraniana por Corrente Contínua é uma técnica promissora quando utilizada em combinação com os os exercícios aeróbicos e anaeróbicos; entretanto, é necessário investigar o exercício concomitante. Nível de evidência II; Estudos terapêuticos investigando os resultados do tratamento (revisão sistemática dos estudos de nível II ou estudos de nível I com resultados inconsistentes).

RESUMEN Introducción La estimulación transcraneana por corriente continua (ETCC) es una técnica no invasiva que permite la modulación de la excitabilidad cortical y puede producir alteraciones en la plasticidad neuronal. La aplicación de la ETCC ha sido recientemente asociada a la actividad física. Objetivos Verificar el efecto de la Estimulación Transcraneana por Corriente Continua (ETCC) en combinación con el ejercicio físico, caracterizando los aspectos metodológicos de la técnica. Métodos En la búsqueda en base de datos, se excluyeron estudios con animales y otras técnicas de neuromodulación, además de artículos de revisión y opinión. Fueron seleccionadas publicaciones hasta 2016 y la calidad metodológica de los artículos fue verificada a través de la escala PEDRo. Resultados La mayoría de los estudios (86%) utilizó la ETCC en el área del córtex motor, con corriente anódica y montaje monocefálico (unipolar) (46,5%). La intensidad de la corriente dominante fue 2mA (72%) con duración de 20 min (55,8%). El perfil de los participantes de la investigación fue predominantemente de individuos con hasta 60 años de edad (72,1%). Los desenlaces fueron favorables al uso de la ETCC anódica en combinación con el ejercicio físico. Conclusión La Estimulación Transcraneana por Corriente Continua es una técnica alentadora cuando utilizada en combinación con los ejercicios aeróbicos y anaeróbicos; entretanto, es necesario investigar el ejercicio concomitante. Nivel de evidencia II; Estudios terapéuticos investigando los resultados del tratamiento (revisión sistemática de los estudios de nivel II o estudios de nivel I con resultados inconsistentes).

Non-invasive brain stimulation and computational models in post-stroke aphasic patients: single session of transcranial magnetic stimulation and transcranial direct current stimulation. A randomized clinical trial

ABSTRACT CONTEXT AND OBJECTIVE: Patients undergoing the same neuromodulation protocol may present different responses. Computational models may help in understanding such differences. The aims of this study were, firstly, to compare the performance of aphasic patients in naming tasks before and after one session of transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS) and sham, and analyze the results between these neuromodulation techniques; and secondly, through computational model on the cortex and surrounding tissues, to assess current flow distribution and responses among patients who received tDCS and presented different levels of results from naming tasks. DESIGN AND SETTING: Prospective, descriptive, qualitative and quantitative, double blind, randomized and placebo-controlled study conducted at Faculdade de Ciências Médicas da Santa Casa de São Paulo. METHODS: Patients with aphasia received one session of tDCS, TMS or sham stimulation. The time taken to name pictures and the response time were evaluated before and after neuromodulation. Selected patients from the first intervention underwent a computational model stimulation procedure that simulated tDCS. RESULTS: The results did not indicate any statistically significant differences from before to after the stimulation.The computational models showed different current flow distributions. CONCLUSIONS: The present study did not show any statistically significant difference between tDCS, TMS and sham stimulation regarding naming tasks. The patients'responses to the computational model showed different patterns of current distribution.

Assessment of the accuracy of portable monitors for halitosis evaluation in subjects without malodor complaint. Are they reliable for clinical practice?

Abstract Halitosis is defined as a foul odor emanated from the oral cavity, with great impact in quality of life and social restraints. Recently, the use of Breath Alert™ in research increased significantly. Halimeter™, another portable device, is often used in clinical practice. Nevertheless, not many studies have verified the accuracy and compared the results of both devices simultaneously. Objective: To verify the accuracy of Breath Alert™ and Halimeter™ in patients without chief complaint of halitosis, using the organoleptic test (OT) as "gold standard." The second aim was to verify whether their concomitant use could enhance the diagnostic accuracy of halitosis. Material and Methods: A cross-sectional analytical study was performed. The quality of expired air of 34 subjects without chief complaint of halitosis was assessed. Two experienced examiners carried out the OT. Afterward, a third blinded examiner performed Halimeter™ (HT) and Breath Alert™ (BA) tests. Results: The OT identified halitosis in 21 subjects (62%). The area under the ROC curve (95% confidence interval) was 0.67 (0.48-0.85) and 0.54 (0.34-0.75) for HT and BA, respectively. The accuracy for HT and BA was 59% and 47%, respectively. The combined usage of HT and BA provided 11 positive results, being 9 subjects (43%) out of the total of 21 positive cases. Conclusions: Halimeter™ and Breath Alert™ were not able to diagnose halitosis in non-complainer subjects at the same level as the organoleptic examination, since their accuracy were low. Our results suggest that such portable devices are not reliable tools to assess halitosis and may neglect or misdiagnose a considerable number of patients in clinical practice.

Clinical research in Latin America: scientific production in high impact clinical research journals from 2000 to 2010.

Background: Scientific production has long been dominated by a few countries such as the United States, Europe and Japan. Historically Latin American countries have contributed marginally to the world’s scientific production, however important changes are now taking place in the geography of scientific research. Methods: In order to determine the current contribution of Latin America to global clinical research and whether the region has been participating in the growth of internationally collaborative research we reviewed the literature in 10 high-impact medical journals between 2000 and 2010. We manually searched original articles in 10 journals that have a strong focus on clinical research and had the highest impact factors in their fields during the study period. We identified a total of 1047 original articles published. Results: Our results show that Latin America was a minor contributor of research published in high impact journals with only 4 (0.38%) of the articles citing a corresponding author affiliated with a Latin American institution. Furthermore, only 23 articles (2.2%) cited non-corresponding authors from Latin America in contrast to 358 articles (34.2%) in which all the authors were affiliated with US institutions. Conclusions: Although these results show limited contribution from Latin America to the production of health and clinical research, it also shows that Latin America is represented in the most competitive journals given the relative lack of research infra-structure, training and challenges with language. Factors such as GDP and investment in research may play a significant role, but may not be the only contributing factors for this scenario.

Effect of a single session of transcranial direct-current stimulation on balance and spatiotemporal gait variables in children with cerebral palsy: A randomized sham-controlled study

Background: Transcranial direct-current stimulation (tDCS) has been widely studied with the aim of enhancing local synaptic efficacy and modulating the electrical activity of the cortex in patients with neurological disorders. Objective: The purpose of the present study was to determine the effect of a single session of tDCS regarding immediate changes in spatiotemporal gait and oscillations of the center of pressure (30 seconds) in children with cerebral palsy (CP). Method: A randomized controlled trial with a blinded evaluator was conducted involving 20 children with CP between six and ten years of age. Gait and balance were evaluated three times: Evaluation 1 (before the stimulation), Evaluation 2 (immediately after stimulation), and Evaluation 3 (20 minutes after the stimulation). The protocol consisted of a 20-minute session of tDCS applied to the primary motor cortex at an intensity of 1 mA. The participants were randomly allocated to two groups: experimental group - anodal stimulation of the primary motor cortex; and control group - placebo transcranial stimulation. Results: Significant reductions were found in the experimental group regarding oscillations during standing in the anteroposterior and mediolateral directions with eyes open and eyes closed in comparison with the control group (p<0.05). In the intra-group analysis, the experimental group exhibited significant improvements in gait velocity, cadence, and oscillation in the center of pressure during standing (p<0.05). No significant differences were found in the control group among the different evaluations. Conclusion: A single session of tDCS applied to the primary motor cortex promotes positive changes in static balance and gait velocity in children with cerebral palsy. .

Transcutaneous vagus and trigeminal nerve stimulation for neuropsychiatric disorders: a systematic review / Estimulação transcutânea do nervo vago e do nervo trigêmeo para o tratamento de distúrbios neuropsiquiátricos: revisão sistemática

We reviewed trigeminal nerve stimulation (TNS) and transcutaneous vagus nerve stimulation (tVNS). All techniques have shown preliminary promising results, although the results are mixed. Method: We performed a systematic review of the Medline and Embase databases, with no constraint to dates, through June 2013. The keywords were [(1) trigeminal nerve stimulation OR (2) cranial nerve OR (3) trigemin* OR (4) transcutaneous VNS OR (5) transcutaneous cranial nerve stimulation] and (6) mental disorders. Results: We included four preclinical and clinical five studies on TNS. All clinical data were based on open-label studies with small samples, which diminished the external validity of the results, thus reflecting the modest impact of TNS in current clinical practice. Of the tVNS clinical trials, three assessed physiological features in healthy volunteers, and one examined patients with epilepsy. Conclusion: TNS and tVNS improve treatment of particular neuropsychiatric disorders such as depression. .

O uso de estimulação de nervos cranianos de maneira transcutânea tem sido uma estratégia em desenvolvimento recente. Diferentes estudos apontam para resultados clínicos favoráveis no tratamento de diferentes quadros neuropsiquiátricos. Método: Revisão sistemática da literatura com base nas bibliotecas eletrônicas Medline e Embase, sem restrição de data inicial, até agosto de 2013. Os termos de busca utilizados foram [(1) trigeminal nerve stimulation OR (2) cranial nerve OR (3) trigemin* OR (4) transcutaneous VNS OR (5) transcutaneous cranial nerve stimulation] and (6) mental disorders. Resultados: Incluímos quatro estudos pré-clinicos e cinco estudos clínicos abordando estimulação do nervo trigêmeo. Todos os estudos foram abertos, com pequenas amostras, o que reduz a validade externa dos dados, refletindo a ainda incipiente atuação da técnica, apesar de promissora. Considerando-se a estimulação do nervo vago, três artigos avaliaram aspectos fisiológicos em voluntários saudáveis e um artigo estudou pacientes com epilepsia. Conclusão: As estratégias de estimulação transcutânea de nervos cranianos, apesar de incipiente, tem demonstrado resultados clínicos favoráveis no tratamento de distúrbios neuropsiquiátricos. .

Clinical research in pediatric organ transplantation

Solid organ transplantation has greatly improved survival in children with end-stage disease, becoming one of the main treatment options in this population. Nonetheless, there are significant challenges associated with validating and optimizing the effects of these interventions in clinical trials. Therefore, we reviewed the main issues related to conducting clinical transplantation research in children. We divided these challenges into three different categories: (i) challenges related to surgical techniques and anesthetic procedures, (ii) challenges related to post-transplant care and (iii) challenges specific to a particular population group and disease type. Some of the observed burdens for clinical research in this field are related to the limitations of conducting studies with a placebo or sham procedure, determining the standard of care for a control group, low prevalence of cases, ethical concerns related to use of a placebo control group and lack of generalizability from animal studies and clinical trials conducted in adult populations. To overcome some of these barriers, it is necessary to utilize alternative clinical trial designs, such as observational studies or non-inferiority trials, and to develop multicenter collaborations to increase the recruitment rate. In conclusion, the lack of robust data related to pediatric transplantation remains problematic, and further clinical trials are needed to develop more efficacious and safer treatments.

O que é estimulação magnética transcraniana? / What is transcranial magnetic stimulation?

Estimulação magnética transcraniana (EMT) é uma técnica capaz de induzir correntes elétricas em regiões corticais de forma não invasiva que apresenta um grande potencial tanto como uma ferramenta diagnóstica quanto terapêutica nos transtornos neuropsiquiátricos, como na depressão, esquizofrenia e neurológicos como no AVC e epilepsia. Este artigo aborda sinteticamente a EMT: fundamentos, tipos, aplicações, efeitos adversos e medidas de segurança...

Transcranial magnetic stimulation (TMS) is a non-invasive technique that can induce electrical currents in cortical areas, having thus a significant potential both as an investigational and as a therapeutic tool in neuropsychiatric disorders, such as depression and schizophrenia, and neurological, such as stroke and epilepsy. This article synthetically summarizes the applications of transcranial magnetic stimulation: fundamentals, type of stimulation, applications, adverse effects e safety...

Limits to clinical trials in surgical areas

Randomized clinical trials are considered to be the gold standard of evidence-based medicine nowadays. However, it is important that we point out some limitations of randomized clinical trials relating to surgical interventions. There are limitations that affect the external and internal validity of many surgical study designs. Some limitations can be bypassed, but can make it more difficult for the study to be carried out. Other limitations cannot be bypassed. When it is intended to extrapolate the result of a randomized clinical trial, the premise is that the performed or to be performed intervention will be similar wherever applied and/or for every doctor using it. However, no matter how standardized the technique may be, the results are not similar for all surgeons, which implies a significant limitation to surgical randomized clinical trials concerning external validity. When considering the various limitations presented for performing surgical trials capable of generating scientific evidence within the patterns currently proposed in the evidence level classifications of medical publications, it is necessary to rethink whether those scientific evidence levels are similarly applicable to surgical works and to nonsurgical trials. We currently live in a time of supposed ''inferiority'' of surgical scientific works under the optics of the current quality criteria for a ''suitable'' clinical trial.

Ensaios clínicos controlados e randomizados na ortopedia: dificuldades e limitações / Randomized controlled clinical trials in orthopedics: difficulties and limitations

Os ensaios clínicos controlados e randomizados (ECCR) são considerados o padrão ouro da medicina baseada em evidências na atualidade, sendo importantes para direcionar a conduta médica através de observações científicas consistentes. Passos como seleção dos pacientes, randomização e cegamento são fundamentais na realização de um ECCR e apresentam algumas dificuldades extras nos ensaios que envolvem procedimentos cirúrgicos, como é comum na Ortopedia. O objetivo deste artigo é destacar e discutir algumas dificuldades e eventuais limitações dos ECCR na área cirúrgica.

Randomized controlled clinical trials (RCTs) are considered to be the gold standard for evidence-based medicine nowadays, and are important for directing medical practice through consistent scientific observations. Steps such as patient selection, randomization and blinding are fundamental for conducting an RCT, but some additional difficulties are presented in trials that involve surgical procedures, as in common in orthopedics. The aim of this article was to highlight and discuss some difficulties and possible limitations on RCTs within the field of surgery.

Modulation of inhibitory systems to enhance motor rehabilitation: insights for the use of noninvasive brain stimulation

Motor impairment following stroke is a leading cause of disability in adults. Despite advances in motor rehabilitation techniques, many adult stroke survivors never approach full functional recovery. Intriguingly, children exhibit better rehabilitation outcomes when compared to adults suffering from comparable brain injuries, yet the reasons for this remain unclear. A common explanation is that neuroplasticity in adults is substantially limited following stroke, thus constraining the brain's ability to reorganize in response to neurological insult. This explanation, however, does not suffice for there is much evidence suggesting that neuroplasticity in adults is not limited following stroke. We hypothesize that diminished functional recovery in adults is in part due to inhibitory neuronal interactions, such as transcallosal inhibition, that serve to optimize motor performance as the brain matures. Following stroke, these inhibitory interactions pose rigid barriers to recovery by inhibiting activity in the affected regions and hindering recruitment of compensatory pathways. In contrast, children exhibit better rehabilitation outcomes in part because they have not fully developed the inhibitory interactions that impede functional recovery in adults. We suggest that noninvasive brain stimulation can be used in the context of motor rehabilitation following stroke to reduce the effects of existing inhibitory connections, effectively returning the brain to a state that is more amenable to rehabilitation. We conclude by discussing further research to explore this hypothesis and its implications

Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting / Estratégias de neuromodulação para o tratamento da depressão maior: desafios e recomendações de uma força-tarefa

The use of neuromodulation as a treatment for major depressive disorder (MDD) has recently attracted renewed interest due to development of other non-pharmacological therapies besides electroconvulsive therapy (ECT) such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). METHOD: We convened a working group of researchers to discuss the updates and key challenges of neuromodulation use for the treatment of MDD. RESULTS: The state-of-art of neuromodulation techniques was reviewed and discussed in four sections: [1] epidemiology and pathophysiology of MDD; [2] a comprehensive overview of the neuromodulation techniques; [3] using neuromodulation techniques in MDD associated with non-psychiatric conditions; [4] the main challenges of neuromodulation research and alternatives to overcome them. DISCUSSION: ECT is the first-line treatment for severe depression. TMS and tDCS are strategies with a relative benign profile of side effects; however, while TMS effects are comparable to antidepressant drugs for treating MDD; further research is needed to establish the role of tDCS. DBS and VNS are invasive strategies with a possible role in treatment-resistant depression. In summary, MDD is a chronic and incapacitating condition with a high prevalence; therefore clinicians should consider all the treatment options including invasive and non-invasive neuromodulation approaches.

O uso de técnicas de neuromodulação para o tratamento do transtorno depressivo maior (TDM) tem despertado um renovado interesse nos últimos anos com o desenvolvimento de outras intervenções não-farmacólogicas além da eletroconvulsoterapia (ECT), como a estimulação magnética transcraniana (EMT), a estimulação transcraniana por corrente continua (ETCC), a estimulação cerebral profunda (DBS) e a estimulação de nervo vago (VNS). MÉTODO: Nós organizamos um grupo de trabalho com vários pesquisadores para discutir os avanços recentes e os principais desafios para o uso da neuromodulação no tratamento do TDM. RESULTADOS: O estado-da-arte da neuromodulação foi revisado e discutido em quatro seções: [1] epidemiologia e fisiopatologia do TDM; [2] uma revisão das técnicas de neuromodulação; [3] o uso das técnicas de neuromodulação na depressão que ocorre associada ou em virtude de condições não-psiquiátricas; [4] os principais desafios da pesquisa na neuromodulação e alternativas para superá-los. DISCUSSÃO: ECT é o tratamento de primeira linha para depressão grave. EMT e ETCC são estratégias com um perfil benigno de efeitos adversos; contudo, enquanto os efeitos da EMT são comparáveis ao das drogas antidepressivas para o tratamento da TDM, a eficácia da ETCC ainda precisa ser estabelecida por mais pesquisas clínicas. DBS e VNS são intervenções invasivas com um papel possível para a depressão refratária. Em resumo, TDM é uma condição crônica, incapacitante e de alta prevalência; portanto na prática clínica todas as opções de tratamento possíveis, incluindo as farmacológicas e não-farmacológicas, devem ser consideradas.

Recovery after ECT: comparison of propofol, etomidate and thiopental / Recuperação pós-eletroconvulsoterapia: comparação entre propofol, etomidato e tiopental

OBJECTIVES: To compare post anesthetic time for patient recovery after electroconvulsive therapy, as measured by the post anesthetic Recovery Score of Aldrete and Kroulik, using three different types of hypnotic drugs (propofol, etomidate and thiopental). METHOD: Thirty patients were randomized to receive one of the three drugs (n = 10 in each group), during a course of electroconvulsive therapy treatment. Patients and raters were blinded to which drug was received. Main treatment characteristics were recorded (as total electric charge received seizure threshold, number of treatments, and the mean time for recovery) along the whole treatment. RESULTS: Thiopental and propofol were associated with a significance increase in charge needed to induce a seizure (p < 0.0001) when compared to etomidate, as well as a significant decrease of time for recovery (p = 0.042). CONCLUSIONS: These findings suggest that, although there seems to be no difference in the clinical outcome across these three drugs, propofol offers the best recovery profile. However, it makes a higher mean electric charge necessary.

OBJETIVOS: Comparar o tempo de recuperação dos pacientes após eletroconvulsoterapia avaliada com a escala de recuperação pós-anestésica de Aldrete e Kroulik, utilizando três tipos de medicações anestésicas (propofol, etomidato and tiopental). MÉTODO: Trinta pacientes foram randomizados para receber uma das medicações (n = 10 em cada grupo) durante uma série de tratamentos com eletroconvulsoterapia. Os pacientes e o examinador ficaram cegos para o tipo de anestésico utilizado. As principais características do tratamento foram avaliadas (como carga total de eletricidade recebida, limiar convulsivo, número de sessões e o tempo médio para recuperação) ao longo de toda a série de tratamentos. RESULTADOS: Tiopental e propofol se associaram a um aumento significativo na carga elétrica total utilizada (p < 0,0001) quando comparados com etomidato, bem como uma diminuição significativa no tempo de recuperação pós-anestésica (p = 0,042). CONCLUSÕES: Estes achados sugerem que, apesar de não haver diferença na evolução clínica entre os três grupos estudados, a droga propofol oferece o melhor perfil de recuperação apesar de requerer uma carga elétrica média maior.

Estimulação cerebral para o tratamento de dor neuropática / Estimulacion cerebral para el tratamiento del dolor neuropatico / Brain stimulation for the neuropathic pain’s treatment

As alternativas terapêuticas para o tratamento da dor neuropática ainda são insatisfatórias apesar de a terapia farmacológica ter avançado muito nas últimas décadas. O completo restabelecimento do paciente em suas atividades diárias ainda é um desafio e tem como base uma abordagem interdisciplinar e o uso de outras intervenções além dos fármacos. Um dos desafios no tratamento de dor crônica é que esse distúrbio leva a modificações plásticas no cérebro que sustentam o quadro. O desenvolvimento das técnicas de estimulação cerebral demonstra que esses métodos podem ser uma opção importante no manejo da dor. Estudos recentes têm mostrado que essas técnicas revertem modificações plásticas por um longo período de tempo. Uma técnica de estimulação cerebral simples, de baixo custo e segura é a estimulação transcraniana por corrente contínua de baixa intensidade. Trata-se de procedimento não-invasivo e indolor capaz de modular a atividade cerebral localmente, apresentando efeitos terapêuticos. Pelo fato de a dor crônica ser um sintoma debilitante, contribuir com a diminuição da qualidade de vida e estar associada a uma disfunção do sistema nervoso central, a estimulação cerebral pode ter um resultado benéfico nesse grupo de pacientes.

Despite of the advance of pharmacological therapies in the last decades, therapeutic approaches to the treatment of neuropathic pain are still non-satisfactory. The patient full recovery in their daily activities is still a challenge and is based on an interdisciplinary approach involving others interventions than pharmacological one. One of the challenges in treating chronic pain is that the disorder leads to plastic changes in the brain that support this condition. The development of brain stimulation techniques shows that these methods can be an important option in pain management. Recent studies have shown that these techniques revert plastic alterations for a long period of time. One simple, low-cost and secure technique of brain stimulation is the transcranial direct current stimulation. It is a non-invasive and painless procedure able to modulate locally the brain activity, providing therapeutic effects. Because of chronic pain is a debilitating symptom, one of the most important in the quality of life and is associated with a dysfunction of the central nervous system, brain stimulation may have a beneficial effect in this group of patients.

Aunque la terapia farmacológica haya avanzado mucho em las últimas décadas, las alternativas terapéuticas para el tratamiento del dolor neuropático todavia son insatisfatorias. El completo reestablecimiento del paciente en sus actividades diarias todavia es un desafio y tiene como base un abordaje interdisciplinario y el uso de otras intervenciones además de los fármacos. Uno de los desafíos en el tratamiento del dolor crónico es que ese trastorno lleva a modificaciones plásticas en el cerebro que sustentan el cuadro. El desarrollo de las técnicas de estimulación cerebral demuestra que esos métodos pueden ser una opción importante en el manejo del dolor. Estudios recientes han mostrado que esas técnicas se revierten en modificaciones plásticas por un largo período de tiempo. Una técnica de estimulación cerebral simple, de bajo costo y segura es la estimulación transcraneana por corriente contínua de baja intensidad. Se trata de un procedimiento no invasivo e indoloro capaz de modular la actividad cerebral localmente, apresentando efectos terapéuticos. Debido al hecho del dolor crónica ser un síntoma debilitante, contribuir con la disminución de la calidad de vida y estar asociado a una disfunción del sistema nervioso central, la estimulación cerebral puede tener un resultado benéfico en ese grupo de pacientes.

Avaliação de fatores associados à duração do tratamento com a estimulação magnéticatranscraniana repetitiva na depressão / An evaluation of factors affecting duration of treatment with repetitive transcranial magnetic stimulation for depression

Objetivo: Investigar os efeitos da estimulação magnética transcranianarepetitiva em pacientes com depressão maior que se submeteram aesse tratamento durante o período de 2000 a 2006. Métodos: Realizouseum estudo retrospectivo com 204 pacientes, que se submeteramao tratamento com a estimulação magnética transcraniana repetitiva,coletando os dados daqueles que tiveram remissão do quadro(definido como escore da HAM-D menor ou igual a 7). Os pacientesforam seguidos até seis meses após o tratamento. A duração médiada remissão para essa coorte de pacientes foi 70,2 dias (± 58,4).Resultados: A única variável que foi associada com a duração daremissão no modelo de regressão linear foi o número de sessões com a estimulação magnética transcraniana repetitiva. Conclusão: Nossosachados sugerem que, quanto maior o número de sessões, maislonga a duração dos efeitos da estimulação magnética transcranianarepetitiva. Conseqüentemente, pesquisas futuras que investiguem osefeitos da estimulação magnética transcraniana de repetição precisamexplorar essa variável para maximizar os efeitos terapêuticos dessanova técnica de estimulação cerebral.

Afasia global sem hemiparesia: AVC ou transtorno conversivo? / Global aphasia without hemiparesis: stroke or conversion disorder?

CONTEXTO: A realização de diagnóstico neurológico e psiquiátrico em ambiente de emergência hospitalar com freqüência é uma tarefa complexa e exige colaboração interdisciplinar. Um dos diagnósticos diferenciais de doenças neurológicas é o transtorno conversivo, cuja característica principal é a presença de sintomas afetando funções motoras ou sensoriais, que sugerem desordem clínica ou neurológica, porém sem doença orgânica subjacente que explique o quadro. RELATO DE CASO: Os autores relatam o caso de uma paciente de 23 anos com apresentação clínica atípica de acidente vascular cerebral, afasia global sem hemiparesia, que foi inicialmente diagnosticada como transtorno psiquiátrico pelo serviço de clínica médica de emergência. CONCLUSÃO: Certas apresentações neurológicas podem ser interpretadas como transtorno conversivo pelas similaridades clínicas entre as duas desordens, raridade do quadro clínico, pela presença de sintomatologia psiquiátrica e fatores psicossociais nos pacientes neurológicos. Mesmo com apresentações neurológicas atípicas e sintomas psiquiátricos, pacientes com quadro sugestivo de transtorno conversivo devem ser sempre investigados de forma interdisciplinar.

BACKGROUND: The neurologic and psychiatric diagnosis in emergency settings are difficult tasks and require interdisciplinary effort. Conversion disorder is one of the differential diagnosis for certain neurologic disorders. The main characteristic is motor or sensory deficits suggesting neurologic or medical condition, but without organic disease that explains the symptoms. CASE REPORT: We present a 23 year-old-woman with an atypical clinical presentation of stroke: global aphasia without hemiparesis. This patient was initially diagnosed with conversion disorder by the internal medicine service in the emergency room. CONCLUSION: Some rare neurologic diseases can be interpreted as conversive disorders due to some reasons: clinical similarities between the two disorders, unusual clinical presentations, comorbidity of neurologic and psychiatric disorders and psychological features of the neurological patients. Patients presenting with atypical neurological or psychiatric symptoms, in which a diagnosis of conversion disorder is suspected, should always be investigated in an interdisciplinary setting.