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The study aimed to examine the clinical and neurophysiological predictors of motor event-related desynchronization (ERD) and synchronization (ERS) in patients with chronic pain due to knee osteoarthritis (KOA).We performed a cross-sectional analysis of our cohort study (DEFINE cohort), KOA arm, with 71 patients, including demographic, functionality, genetic and neurophysiological measures. ERD/ERS was evaluated during hand motor tasks (motor execution, active and passive observation, and imagery). Multivariate regression models were used to explore predictors of ERD/ERS.Although we found an altered ERD/ERS pattern during motor execution and active observation, the ERS pattern could only be clearly differentiated after passive observation.`. We found no predictors of ERD (excitatory biomarker). For ERS (inhibitory biomarker), our results showed that the main predictors differ across EEG frequency bands. Considering pain measures, we found that visual analogue scale (VAS, right knee) and chronicity of pain negatively predict low beta and high beta ERS, respectively. Pain threshold was positively correlated with alpha ERS, while 36-Item Short Form Survey (SF-36) emotional domain positively predicted beta ERS. Regarding transcranial magnetic stimulation (TMS) markers, intracortical inhibition (ICF) negatively predicted beta and low beta ERS, and left hemisphere cortical silent period (CSP) negatively predicted low beta ERS.Considering that higher power of ERS indicates a stronger cortical organization and inhibitory drive, our results show that limitation of activities due to emotional factors, lower pain threshold, higher VAS pain, and longer duration of pain are associated with lower ERS power (in alpha and beta frequencies), thus indicating a lower inhibitory drive. In the same direction, a lower inhibitory drive as indicated by higher ERS power is associated with higher ICF amplitude. Although there was a negative association between ERS and CSP, this may indicate that ICF values are adjusting CSP results. Our findings support the idea that a less organized cortical response as indicated by changes to the ERS is associated with higher pain correlates in subjects with KOA.

Episodic memory decline is a major signature of both normal and pathological aging. Many neural regions have been implicated in the processes subserving both episodic memory and typical aging decline. Here, we demonstrate that the cerebellum is causally involved episodic memory under aging. We show that a 12-day neurostimulation program delivered to the right cerebellum led to improvements in episodic memory performance under healthy aging that long outlast the stimulation period — healthy elderly individuals show episodic memory improvement both immediately after the intervention program and in a 4-month follow-up. These results demonstrate the causal relevance of the cerebellum in processes associated with long-term episodic memory, potentially highlighting its role in regulating and maintaining cognitive processing. Moreover, they point to the importance of non-pharmacological interventions that prevent or diminish cognitive decline in healthy aging.

Purpose The study aimed to examine associations between the 36-item short form health survey (SF-36) in clinical and neurophysiological measures to identify its predictors in patients with knee osteoarthritis (KOA) in a rehabilitation program. Methods We analyzed data from our cohort study (DEFINE cohort). We analyzed data from our KOA arm, with 107 patients, including clinical assessments, demographic data, pain scales, motor function (Timed Up and Go Test (TUG), 10 meters walk test, and 6-minute walk), balance (BBS), sleepiness (ESS), and Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG). Results Our results showed 83.19% of patients were female with an average age of 68.6 years and an average number of days of pain was 96 days; around 31.86% were using more than five medications per day. Regarding the multimodal model to explain SF-36, the main variables relevant to the quality of life (QoL) were related to emotional aspects, such as anxiety and depression. Moreover, our study added findings with polymorphism (OPRM1/rs1799971) predicting mental aspects. Cognitive variables were important in predicting the mental health, emotional, and social support dimensions of the SF-36. In the physical domain, pain-related variables predominantly predicted QoL in these relationships. The domain of vitality significantly predicted all dimensions studied, except for mental and general health. Conclusion The results help in understanding the aspects that contribute to QoL and are discussed considering the general literature on physical rehabilitation and specific to this clinical group. Furthermore, the statistical methods allowed us to explore and effectively understand the dimensions related to QoL.

Chronic pain due to osteoarthritis (OA) is a prevalent cause of global disability. New biomarkers are needed to improve treatment allocation, and genetic polymorphisms are promising candidates.We aimed to assess the association of OPRM1 (A118G and C17T) and brain-derived neurotrophic factor (BDNF [G196A]) polymorphisms with pain-related outcomes and motor cortex excitability metrics (measured by transcranial magnetic stimulation) in 113 knee OA patients with chronic pain. We performed adjusted multivariate regression analyses to compare carriers versus non-carriers in terms of clinical and neurophysiological characteristics at baseline, and treatment response (pain reduction and increased cortical inhibitory tonus) after rehabilitation.Compared to non-carriers, participants with polymorphisms on both OPRM1 (A118G) and BDNF (G196A) genes were less likely to improve pain after rehabilitation (85 and 72% fewer odds of improvement, respectively). Likewise, both carriers of OPRM1 polymorphisms (A118G and C17T) were also less likely to improve cortical inhibition (short intracortical inhibition [SICI], and intracortical facilitation [ICF], respectively). While pain and cortical inhibition improvement did not correlate in the total sample, the presence of OPRM1 (A118G) and BDNF (G196A) polymorphisms moderated this relationship.These results underscore the promising role of combining genetic and neurophysiological markers to endotype the treatment response in this population.

Objectives The pain related to spinal cord injury (SCI) is difficult to treat, and it is associated with significant morbidity. One aspect to improve therapeutics is to explore markers of pain and its correlates in SCI. Methods In this cross-sectional neurophysiological analysis of a randomized, double-blind controlled trial, 39 patients with SCI were included. We analyzed conditioned pain modulation (CPM) efficiency as the index of the descending pain inhibitory system, EEG variables, and clinical pain levels as measured by the Visual Analogue Scale. Regression analyses were performed to assess the relationship among EEG variables, pain levels, and CPM. Results We included 39 SCI patients, 74% reported SCI-related pain. We found that (1) less alpha and beta power are related to pain presence, (2) less alpha and beta power are associated with higher pain levels among patients with pain, (3) patients with pain have decreased peak alpha-theta frequency compared to no-pain group, (4) more relative theta power are related to the presence of low CPM efficiency, (5) higher relative theta power is associated with lower CPM efficiency. Conclusions Our results confirm and provide additional data on the relationship between decreased alpha and beta frequencies and higher pain levels. One important finding, though, was a specific and different EEG signature for the descending inhibitory pain system, as we showed that increased theta EEG power is related to decreased CPM efficiency; suggesting that, although low CPM efficiency plays a major role in pain in these participants, it does seem to be associated with a specific oscillatory brain rhythm different from clinical pain. These findings have significant implications for future research on EEG-based biomarkers of pain in post-SCI and new interventions as neurofeedback to manage pain in this population.

BACKGROUND: Stroke is the second leading cause of death in Brazil and the main cause of disability. Inability to identify alarm signals causes delays in seeking emergency services, thereby leading to a worse prognosis. OBJECTIVES: To assess the population's knowledge of how to recognize and prevent stroke. DESIGN AND SETTING: Prospective cross-sectional study on data derived from a questionnaire that was administered during the 2016 World Stroke Campaign, launched in the city of São Paulo, Brazil. METHODS: Data on 806 interviewees were evaluated using descriptive statistics and univariate and multivariate analyses. RESULTS: Among all the interviewees, 52.1% knew how to conceptualize stroke; 70.07% knew someone who had suffered a stroke; and 29.03% listed three or more risk factors. Only 27.5% mentioned controlling high blood pressure as a preventive measure. In the event of witnessing a stroke, 57.8% would call the emergency service and 2.9% would check the timing. Less educated individuals were 5.6 times more likely (95% confidence interval, CI 3.45-9.02) to have poor knowledge of stroke, compared with the more educated group. Knowing someone who had had a stroke reduced the chances of not knowing the terms relating to the disease (odds ratio, OR = 0.56; 95% CI 0.4-0.78). CONCLUSIONS: Despite the severity and prevalence of stroke, the population still has little information on this disease. In this context, the importance of mounting campaigns to improve prevention and treatment and to contribute to healthcare policies becomes evident.

Objective: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES.Methods: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided.Results: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity.Conclusions: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases. Significance: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials. (C) 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. Device appraisal showed moderate digitalization readiness, with high safety and the possibility of trial implementation, but low connectivity. Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; although they reached no consensus about aspects regarding methodological biases. We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.Graphical Abstract. Consensus Roadmap(A) Recruitment process. The study procedure started with defining the components of the research problem by the core research team. After defining the problems, two different sets of participants (the steering committee (SC) including key leaders of the field identified by the core team and the expert panel (EP) as a more diverse group of experts identified based on the number of publications based on a systematic review) were identified and were invited to participate in a Delphi study. The study facilitators (first and last authors) led the communications with the SC to design the initial questionnaire through an iterative approach. (B) Evidence synthesis: To collect the available evidence, companies producing portable tES (ptES) devices were contacted, based on the companies suggested by the SC and EP to provide details about the available devices. For mapping methodological processes of digitizing tES trials, two distinct strategies were performed and embedded into the questionnaire, namely SIPOC (Suppliers, Inputs, Process, Outputs, and Customer) and SWOT (Strengths, Weaknesses, Opportunities, and Threats) assessment were performed and embedded into the questionnaire. (C) Consensus development: In the next phase, the questionnaire was validated and finalized via collecting and summarizing opinions. Afterward, the SC and EP responded to the final questionnaire, and results were analyzed providing a list of recommendations for running tES digital trials based on a pre-registered consensus threshold.

Objective The role of motor cortex reorganization in the development and maintenance of phantom limb pain (PLP) is still unclear. This study aims to evaluate neurophysiological and structural motor cortex asymmetry in patients with PLP and its relationship with pain intensity. Methods Cross-sectional analysis of an ongoing randomized-controlled trial. We evaluated the motor cortex asymmetry through two techniques: i) changes in cortical excitability indexed by transcranial magnetic stimulation (motor evoked potential, paired-pulse paradigms and cortical mapping), and ii) voxel-wise grey matter asymmetry analysis by brain magnetic resonance imaging. Results We included 62 unilateral traumatic lower limb amputees with a mean PLP of 5.9 (SD = 1.79). We found, in the affected hemisphere, an anterior shift of the hand area center of gravity (23 mm, 95% CI 6 to 38, p = 0.005) and a disorganized and widespread representation. Regarding voxel-wise grey matter asymmetry analysis, data from 21 participants show a loss of grey matter volume in the motor area of the affected hemisphere. This asymmetry seems negatively associated with time since amputation. For TMS data, only the ICF ratio is negatively correlated with PLP intensity (r = −0.25, p = 0.04). Conclusion There is an asymmetrical reorganization of the motor cortex in patients with PLP, characterized by a disorganized, widespread, and shifted hand cortical representation and a loss in grey matter volume in the affected hemisphere. This reorganization seems to reduce across time since amputation. However, it is not associated with pain intensity. Significance These findings are significant to understand the role of the motor cortex reorganization in patients with PLP, showing that the pain intensity may be related with other neurophysiological factors, not just cortical reorganization.

Objective: To evaluate the effect of abdominal electrical stimulation (EE) on bowel movement frequency and feces consistency and expelled amount in people with constipation due to spinal cord injuries (SCI). Method: This is an experimental, crossover, randomized pilot study with two treatment groups: conventional intestinal rehabilitation and conventional rehabilitation associated with EE via 8- and 20-Hz Functional Electrical Stimulation (FES) of the abdominal muscles. Both groups were followed for two weeks with daily 30-minute EE sessions. Participants were hospitalized in a rehabilitation institute in the municipality of São Paulo. Data were analyzed using descriptive and inferential statistics. Results: This study included 10 people with SCI, of which most were male (70%), with a mean age of 39 years (SD = 16.37). EE, associated with conventional treatment, was more effective in increasing defecation frequency (p = 0.029) and amount of feces expelled (p = 0.031). Conclusion: Abdominal EE, associated with conventional treatment, helped to increase defecation frequency and amount of feces expelled in people with constipation due to SCI. This pilot study will serve as the basis for a future clinical trial with greater sampling and statistical evidence. RESUMEN Objetivo: Evaluar el efecto de la electroestimulación abdominal (EE) sobre la frecuencia de las evacuaciones, la consistencia y la cantidad de heces en personas con estreñimiento debido a una lesión de la médula espinal (LME). Método: Estudio piloto experimental de tipo crossover-aleatorizado en dos grupos de tratamiento: convencional rehabilitación intestinal y convencional asociado a EE con Functional Electrical Stimulation (FES) de 8 y 20 Hz aplicados a los músculos abdominales. Se realizó un seguimiento de ambos grupos durante dos semanas con 30 minutos de sesión diaria de EE. Los participantes estaban hospitalizados en un instituto de rehabilitación de la ciudad de São Paulo. Los datos se analizaron mediante estadística descriptiva e inferencial. Resultados: Diez personas con LME participaron en el estudio, la mayoría hombres (70%) con una edad media de 39 años (DE = 16,37). La EE asociada al tratamiento convencional demostró ser más eficaz en el aumento de la frecuencia de evacuación (p = 0,029) y la cantidad de heces (p = 0,031). Conclusión: La EE abdominal asociada al tratamiento convencional ayudó a aumentar la frecuencia de evacuación y la cantidad de heces en el contexto de estreñimiento en personas con LME. Este estudio piloto servirá de base para futuros ensayos clínicos con mayor muestreo y evidencia estadística. RESUMO Objetivo: Avaliar o efeito da eletroestimulação (EE) abdominal sobre a frequência de evacuações, a consistência e a quantidade de fezes em pessoas com constipação decorrente da lesão medular (LM). Método: Estudo piloto experimental do tipo crossover-randomizado em dois grupos de tratamento: convencional de reabilitação intestinal e convencional associado à EE com Functional Electrical Stimulation (FES) de 8 e 20 Hz aplicados na musculatura abdominal. Ambos os grupos em seguimento por duas semanas, com 30 minutos de sessão diária de EE. Os participantes estavam internados em um instituto de reabilitação da cidade de São Paulo. Os dados foram analisados por meio de estatística descritiva e inferencial. Resultados: Participaram do estudo 10 pessoas com LM, a maioria do sexo masculino (70%), com média de idade de 39 anos (DP = 16,37). A EE, associada ao tratamento convencional, mostrou-se mais eficaz no aumento da frequência evacuatória (p = 0,029) e na quantidade de fezes (p = 0,031). Conclusão: A EE abdominal associada ao tratamento convencional auxiliou no aumento da frequência evacuatória e na quantidade de fezes no quadro de constipação em pessoas com LM. Este estudo piloto servirá como base para um futuro ensaio clínico com maior amostragem e comprovação estatística.

There is evidence that brain plasticity is the central mechanism involved in the functional recovery process of patients with knee osteoarthritis. Studies involving the analysis of central nervous system mechanisms of pain control and recovery could provide more data on future therapeutic approaches.The aim of the study was to explore possible functional changes in cortical activity of patients submitted to knee osteoarthritis standardized pain treatment using electroencephalography.Ten patients with clinical and radiological diagnosis of painful knee unilateral or bilateral osteoarthritis were recruited to participate in clinical (Pain's Visual Analog Scale), radiological (Kellgren-Lawrence Scale), and neurophysiological (electroencephalography) assessments to evaluate cortical activity during cortical pain modulation activity. The clinical and neurophysiological analyses were performed before and after standardized pain treatment.Eight patients participated in this study. A significant improvement in pain perception and relative increase in interhemispheric connectivity after therapies was observed. In electroencephalography analysis, tests with real movement showed a relative increase in density directed at Graph's analysis.Relative increase density directed measures at connectivity analysis in electroencephalography after pain treatment can be possible parameters to be explored in future research with a larger number of patients.

STUDY DESIGN: A randomized, sham-controlled clinical trial. OBJECTIVE: To test the effects of tDCS, combined with robotic training, on gait disability in SCI. Our hypothesis was that participants who received active tDCS would experience greater walking gains, as indexed by the WISCI-II, than those who received sham tDCS. SETTING: University of São Paulo, Brazil. METHODS: This randomized, double-blind study comprised 43 participants with incomplete SCI who underwent 30 sessions of active (n = 21) or sham (n = 22) tDCS (20 min, 2 mA) before every Lokomat session of 30 min (3 times a week over 12 weeks or 5 times a week over 6 weeks). The main outcome was the improvement in WISCI-II. Participants were assessed at baseline, after 15 and 30 sessions of Lokomat, and after three months of treatment. RESULTS: There was a significant difference in the percentage of participants that improved in WISCI-II at the 30-session, compared with baseline: 33.3% in the sham group and 70.0% in the active group (p = 0.046; OR: 3.7; 95% CI: 1.0–13.5). At the follow-up, the improvement compared with baseline in the sham group was 35.0% vs. 68.4% for the active group (p = 0.046; OR: 3.7; 95% CI: 1.0–13.5). There was no significant difference at the 15-session. CONCLUSION: Thirty sessions of active tDCS is associated with a significant improvement in walking, compared to sham. Moreover, 15 sessions had no significant effect. The improvement in WISCI-II can be related to different aspects of motor learning, including motor recovery and compensation.

Background: Brain plasticity is an intrinsic property of the nervous system, which is modified during its lifetime. This is one mechanism of recuperation after injuries with an important role in rehabilitation. Evidence suggests that injuries in the nervous system disturb the stability between inhibition and excitability essential for the recuperation process of neuroplasticity. However, the mechanisms involved in this balance are not completely understood and, besides the advancement in the field, the knowledge has had a low impact on the rehabilitation practice. Therefore, the understanding of the relationship between biomarkers and functional disability may help to optimize and individualize treatments and build consistent studies in the future.Methods: This cohort study, the deficit of inhibition as a marker of neuroplasticity study, will follow four groups (stroke, spinal cord injury, limb amputation, and osteoarthritis) to understand the neuroplasticity mechanisms involved in motor rehabilitation. We will recruit 500 subjects (including 100 age- and sex-matched controls). A battery of neurophysiological assessments, transcranial magnetic stimulation, electroencephalography, functional near-infrared spectroscopy, and magnetic resonance imaging, is going to be used to assess plasticity on the motor cortex before and after rehabilitation. One of the main hypotheses in this cohort is that the level of intracortical inhibition is related to functional deficits. We expect to develop a better understanding of the neuroplasticity mechanisms involved in the rehabilitation, and we expect to build neurophysiological “transdiagnostic” biomarkers, especially the markers of inhibition, which will have great relevance in the scientific and therapeutic improvement in rehabilitation. The relationship between neurophysiological and clinical outcomes will be analyzed using linear and logistic regression models.Discussion: By evaluating the reliability of electroencephalography, functional near-infrared spectroscopy, transcranial magnetic stimulation, and magnetic resonance imaging measures as possible biomarkers for neurologic rehabilitation in different neurologic disorders, this study will aid in the understanding of brain plasticity mechanisms in rehabilitation, allowing more effective approaches and screening methods to take place.

Spinal Cord Injury (SCI) is a condition whose consequences can impact the physical, emotional, and social aspects of patient's life, including Depression and Anxiety disorders.Using a cross-sectional design, sociodemographic and clinical data were extracted from 556 SCI patients at the time of initial assessment, prior to intensive rehabilitation treatment at the local rehabilitation institute.Identify the predictive and multivariate relationship between different sociodemographic and clinical variables of Depression and Anxiety symptoms in SCI patients.Lucy Montoro Rehabilitation Institute (LMRI), University of Sao Paulo, Sao Paulo, Brazil.We performed independent univariate and multivariate regression models using the Hospital Anxiety and Depression Scale (HADS) as dependent variable.Symptoms of depression and anxiety present in SCI patients negatively correlate with the level of independence for locomotion, personal hygiene, bowel control, social interaction measured by the Functional Independence Scale (FIM), type of medication in use and the Language subtest of the MoCA Scale. Unlike previous studies, we did not find a relationship with the use of alcohol and illicit drugs, injury levels, etiological diagnosis or duration of injury. For the anxiety models, the main predictor was Depression symptoms, with SCI-related aspects not being significant. It was found that characteristics of the FIM Scale and cognitive aspects of the MoCA Scale were the main predictors of symptoms of Depression. Characteristics of the injury and motor deficit were not statistically significant.These findings can potentially be used to guide clinical practices to identify patients at higher risk of experiencing symptoms of Depression and Anxiety.

Phantom limb pain (PLP) is a frequent complication in amputees, which is often refractory to treatments. We aim to assess in a factorial trial the effects of transcranial direct current stimulation (tDCS) and mirror therapy (MT) in patients with traumatic lower limb amputation; and whether the motor cortex plasticity changes drive these results. In this large randomized, blinded, 2-site, sham-controlled, 2 × 2 factorial trial, 112 participants with traumatic lower limb amputation were randomized into treatment groups. The interventions were active or covered MT for 4 weeks (20 sessions, 15 minutes each) combined with 2 weeks of either active or sham tDCS (10 sessions, 20 minutes each) applied to the contralateral primary motor cortex. The primary outcome was PLP changes on the visual analogue scale at the end of interventions (4 weeks). Motor cortex excitability and cortical mapping were assessed by transcranial magnetic stimulation (TMS). We found no interaction between tDCS and MT groups ( F = 1.90, P = .13). In the adjusted models, there was a main effect of active tDCS compared to sham tDCS (beta coefficient = −0.99, P = .04) on phantom pain. The overall effect size was 1.19 (95% confidence interval: 0.90, 1.47). No changes in depression and anxiety were found. TDCS intervention was associated with increased intracortical inhibition (coefficient = 0.96, P = .02) and facilitation (coefficient = 2.03, P = .03) as well as a posterolateral shift of the center of gravity in the affected hemisphere. MT induced no motor cortex plasticity changes assessed by TMS. These findings indicate that transcranial motor cortex stimulation might be an affordable and beneficial PLP treatment modality.

Rehabilitation is a widely used term, with many definitions. According to the World Health Organization, “Rehabilitation is a set of interventions needed when a person is experiencing or is likely to experience limitations in everyday functioning due to aging or a health condition, including chronic diseases or disorders, injuries or traumas.” In the context of tDCS, it is commonly used to improve/maintain function (motor, sensorial, autonomic, and cognitive), decrease the impact of symptoms (such as pain), with the ultimate goal of improving the quality of life of the patient and the caregiver. tDCS is being studied in the context of rehabilitation for several applications. This investigation has been associated with exponential growth. The growing understanding of the biological mechanisms of the effects of tDCS applied in rehabilitation is contributing to this growth. It is currently understood that tDCS can alter and strengthen spontaneous synaptic activity and inflect plasticity interceded by neurotransmitters on a structural level. Thus, tDCS’s ability to promote broad neuroplasticity emphasizes its promise in the framework of rehabilitation [1].

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.

Background Transcranial direct current stimulation has shown promising clinical results, leading to increased demand for an evidence-based review on its clinical effects. Objective We convened a team of transcranial direct current stimulation experts to conduct a systematic review of clinical trials with more than 1 session of stimulation testing: pain, Parkinson’s disease motor function and cognition, stroke motor function and language, epilepsy, major depressive disorder, obsessive compulsive disorder, Tourette syndrome, schizophrenia, and drug addiction. Methods Experts were asked to conduct this systematic review according to the search methodology from PRISMA guidelines. Recommendations on efficacy were categorized into Levels A (definitely effective), B (probably effective), C (possibly effective), or no recommendation. We assessed risk of bias for all included studies to confirm whether results were driven by potentially biased studies. Results Although most of the clinical trials have been designed as proof-of-concept trials, some of the indications analyzed in this review can be considered as definitely effective (Level A), such as depression, and probably effective (Level B), such as neuropathic pain, fibromyalgia, migraine, post-operative patient-controlled analgesia and pain, Parkinson’s disease (motor and cognition), stroke (motor), epilepsy, schizophrenia, and alcohol addiction. Assessment of bias showed that most of the studies had low risk of biases, and sensitivity analysis for bias did not change these results. Effect sizes vary from 0.01 to 0.70 and were significant in about 8 conditions, with the largest effect size being in postoperative acute pain and smaller in stroke motor recovery (nonsignificant when combined with robotic therapy). Conclusion All recommendations listed here are based on current published PubMed-indexed data. Despite high levels of evidence in some conditions, it must be underscored that effect sizes and duration of effects are often limited; thus, real clinical impact needs to be further determined with different study designs.

BackgroundFunctional changes after spinal cord injury (SCI) are related to changes in cortical plasticity. These changes can be measured with electroencephalography (EEG) and has potential to be used as a clinical biomarker.MethodIn this longitudinal study participants underwent a total of 30 sessions of robotic-assisted gait training (RAGT) over a course of 6 weeks. The duration of each session was 30 min. Resting state EEG was recorded before and after 30-session rehabilitation therapy. To measure gait, we used the Walking Index for Spinal Cord Injury Scale, 10-Meter- Walking Test, Timed-Up-and-Go, and 6-Min-Walking Test. Balance was measured using Berg Balance Scale.ResultsFifteen participants with incomplete SCI who had AIS C or D injuries based on American Spinal Cord Injury Association Impairment Scale classification were included in this study. Mean age was 35.7 years (range 17–51) and the mean time since injury was 17.08 (range 4–37) months. All participants showed clinical improvement with the rehabilitation program. EEG data revealed that high beta EEG activity in the central area had a negative correlation with gait (p = 0.049; β coefficient: −0.351; and adj-R2: 0.23) and balance (p = 0.043; β coefficient: −0.158; and adj-R2:0.24) measured at baseline, in a way that greater high beta EEG power was related to worse clinical function at baseline. Moreover, improvement in gait and balance had negative correlations with the change in alpha/theta ratio in the parietal area (Gait: p = 0.049; β coefficient: −0.351; adj-R2: 0.23; Balance: p = 0.043; β coefficient: −0.158; and adj-R2: 0.24).ConclusionIn SCI, functional impairment and subsequent improvement following rehabilitation therapy with RAGT correlated with the change in cortical activity measured by EEG. Our results suggest that EEG alpha/theta ratio may be a potential surrogate marker of functional improvement during rehabilitation. Future studies are necessary to improve and validate these findings as a neurophysiological biomarker for SCI rehabilitation.

Stroke is currently the second leading cause of death in Brazil. Neurologists’ reports on the absence of adequate resources for stroke care are frequent; however, there are no objective data on this perception. Objective To assess the perception of neurologists of stroke care conditions in Brazil. Methods Neurologists from all over Brazil were surveyed by means of an anonymous questionnaire about the main shortcomings in stroke care, focusing particularly on physical structure and infrastructure (diagnostic methods, patient transport, availability of beds, multi-professional team). Results The main shortcomings are indicated: the worst conditions, among all items surveyed, were found in the public sector. In the private sector, conditions were better. Conclusions Care conditions are worse in the public sector with regard to both infrastructure and human resources. Future public health policies for the prevention and treatment of stroke should be formulated, taking into consideration neurologists’ perceptions. RESUMO O acidente vascular cerebral é atualmente a segunda causa de morte no Brasil. São frequentes os relatos de médicos neurologistas sobre a ausência de recursos adequados para o atendimento do AVC, no entanto, não existem dados objetivos sobre essa percepção. Objetivo Analisar a percepção de médicos neurologistas sobre as condições para o atendimento de AVC no Brasil. Métodos Neste estudo foi realizada pesquisa por questionário anônimo com médicos neurologistas de todo o Brasil, perguntando-se as principais deficiências para o atendimento, com foco na estrutura física, infraestrutura (métodos diagnósticos, transporte do doente, disponibilidade de leitos, equipe multiprofissional). Resultados As principais deficiências são apontadas; no setor público notou-se as piores condições, em todos os itens pesquisados. No setor privado, as condições são melhores. Conclusões As condições de atendimento são piores no setor público, tanto de infraestrutura quanto de recursos humanos. Futuras políticas de saúde pública para prevenção e tratamento do AVC deveriam ser elaboradas levando em consideração a percepção do neurologista.

Rotator cuff tear is a common disease affecting patients after stroke. It's a cause of pain and dysfunction that may compromise normal stroke rehabilitation. For many cases there is still controversy between whether to use surgical or conservative intervention. Treatment for cuff tears range from physical therapy to surgery. This paper describes for the first time the effect of Fascial Manipulation® (FM®) on rotator cuff tear in a post stroke patient. A 69 year old female stroke patient with full absence of distal components of the tendons of the rotator cuff, functional limitations on active movement of shoulder flexion and abduction of the left arm and perceived pain scored 10/10 on the Visual Analogic Scale, was assessed and treat with one session of FM® A basic theory that explains the healing results of FM® is that mechanoreceptors, such as spindle cells and other receptors, are located in the deep fascia and activated when movement are performed. Increased viscosity of the deep fascia and muscles due to increased viscosity of hyaluronic acid (HA) molecules prevents the normal gliding of fascia during movement inhibiting normal proprioception and muscle function.

Objective The gait recovery in spinal cord injury (SCI) seems to be partially related to the reorganization of cerebral function; however, the neural mechanisms and the respective biomarkers are not well known. This study tested the hypothesis that enhanced beta-band oscillations may be a marker of compensatory neural plasticity during the recovery period in SCI. We tested this hypothesis at baseline in SCI subjects and also in response to cortical stimulation with transcranial direct current stimulation (tDCS) combined with robotic-assisted gait training (RAGT). Methods In this neurophysiological analysis of a randomized controlled trial, thirty-nine patients with incomplete SCI were included. They received 30 sessions of either active or sham anodal tDCS over the primary motor area for 20 min combined with RAGT. We analyzed the Electroencephalography (EEG) power spectrum and task-related power modulation of EEG oscillations, and their association with gait function indexed by Walk Index for Spinal Cord Injury (WISCI-II). Univariate and multivariate linear/logistic regression analyses were performed to identify the predictors of gait function and recovery. Results Consistent with our hypothesis, we found that in the sensorimotor area: (1) Anodal tDCS combined with RAGT can modulate high-beta EEG oscillations power and enhance gait recovery; (2) higher high-beta EEG oscillations power at baseline can predict baseline gait function; (3) high-beta EEG oscillations power at baseline can predict gait recovery – the higher power at baseline, the better gait recovery; (4) decreases in relative high-beta power and increases in beta power decrease during walking are associated with gait recovery. Conclusions Enhanced EEG beta oscillations in the sensorimotor area in SCI subjects may be part of a compensatory mechanism to enhance local plasticity. Our results point to the direction that interventions enhancing local plasticity such as tDCS combined with robotic training also lead to an immediate increase in sensorimotor cortex activation, improvement in gait recovery, and subsequent decrease in high-beta power. These findings suggest that beta-band oscillations may be potential biomarkers of gait function and recovery in SCI. Significance These findings are significant for rehabilitation in SCI patients, and as EEG is a portable, inexpensive, and easy-to-apply system, the clinical translation is feasible to follow better the recovery process and to help to individualize rehabilitation therapies of SCI patients.

INTRODUCTION: The exact mechanisms underlying the development and maintenance of phantom limb pain are still unclear. This study aimed to identify the factors affecting pain intensity in chronic, lower limb, traumatic phantom limb pain patients. METHODS: This is a cross-sectional analysis of patients with phantom limb pain. We assessed amputation-related, pain-related clinical and demographic variables. We performed univariate and multivariate models to evaluate the associated factors modulating phantom limb pain and residual limb pain intensity. RESULTS: We included 71 unilateral traumatic lower limb amputees. Results showed that (i) amputation related perceptions were experienced by a large majority of the chronic phantom limb pain patients (sensations: 90.1%, N=64; residual pain: 81.7%, N=58); (ii) phantom limb pain intensity has two significant protective factors: phantom limb movement and having effective treatment for phantom limb pain previously and two significant risk factors: phantom limb sensation intensity and age; (iii) on the other hand, for residual limb pain, risk factors are different: presence of pain before amputation and level of amputation (in addition to the same protective factors). CONCLUSION: These results suggest different neurobiological mechanisms to explain phantom limb and residual limb pain intensity. While phantom limb pain risk factors seem to be related to maladaptive plasticity as phantom sensation and older age are associated with more pain, residual limb pain risk factors seem to have factors leading to neuropathic pain such as the amount of neural lesion and previous history of chronic pain. Interestingly, the phantom movement appears to be protective for both phenomena.

During the 2nd Semester of 2018, at the Brazilian Aeronautics Institute of Technology (Instituto Tecnologico de Aeronautica – ITA), a successful Collaborative Interdisciplinary Problem-Based Learning (Co-IPBL) experience took place. At that time, more than 20 undergrad and graduate students from 3 different courses, within just 17 academic weeks, had the opportunity of conceptualizing, modeling, developing, and testing a Computer System involving multiple actors (Patients, Doctors, Hospitals, and Suppliers) for real-time decision making in the rehabilitation with Exoskeletons of patients suffering from Lower Limb Impairment after motorcycle accidents. Differently from other existing products from universities, research centers, governmental agencies, and other public and/or private companies, this product was developed, using the best practices of the Agile Scrum Method, along with emerging Information Technologies (ITs) such as Blockchain Hyperledger, Internet of Things (IoT), among others. This Co-IPBL was performed with the participation of a rehabilitation medical team from the Hospital of Clinics at the Faculty of Medicine of the University of Sao Paulo (HC-FMUSP). The experience described in this paper illustrates a way of dealing with the multiple challenges involved in teaching, learning, designing, and implementing complex intelligent systems to address health care issues with collaborative work involving multidisciplinary teams facing real-life problems such as exoskeletons applied to clinical recover of Patients.

Summary Objectives Transcranial magnetic stimulation (TMS) has been used to measure cortical excitability as a functional measurement of corticomotor pathways. Given its potential application as an assessment tool in stroke, we aimed to analyze the correlation of TMS parameters with clinical features in stroke using data from 10 different centers. Methods Data of 341 patients with a clinical diagnosis of stroke were collected from studies assessing cortical excitability using TMS. We used a multivariate regression model in which the baseline cortical excitability parameter “resting Motor Threshold (rMT)” was the main outcome and the demographic, anatomic and clinical characteristics were included as independent variables. Results The variable “severity of motor deficit” consistently remained significant in predicting rMT in the affected hemisphere, with a positive β coefficient, in the multivariate models after sensitive analyses and adjusting for important confounders such as site center. Additionally, we found that the correlations between “age” or “time since stroke” and the rMT in the affected hemisphere were significant, as well as the interaction between “time since stroke” and “severity of motor deficit”. Conclusions We have shown that severity of motor deficit is an important predictor for rMT in the affected hemisphere. Additionally, time since stroke seems to be an effect modifier for the correlation between motor deficit and rMT. In the unaffected motor cortex, these correlations were not significant. We discuss these findings in the context of stroke rehabilitation.

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of daily activities due to lower and upper limb impairments. Intensive physical and occupational therapy are still considered main treatments, but new adjunct therapies to standard rehabilitation that may optimize functional outcomes are being studied. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that polarizes underlying brain regions through the application of weak direct currents through electrodes on the scalp, modulating cortical excitability. Increased interest in this technique can be attributed to its low cost, ease of use, and effects on human neural plasticity. Recent research has been performed to determine the clinical potential of tDCS in diverse conditions such as depression, Parkinson's disease, and motor rehabilitation after stroke. tDCS helps enhance brain plasticity and seems to be a promising technique in rehabilitation programs. A number of robotic devices have been developed to assist in the rehabilitation of upper limb function after stroke. The rehabilitation of motor deficits is often a long process requiring multidisciplinary approaches for a patient to achieve maximum independence. These devices do not intend to replace manual rehabilitation therapy; instead, they were designed as an additional tool to rehabilitation programs, allowing immediate perception of results and tracking of improvements, thus helping patients to stay motivated. Both tDSC and robot-assisted therapy are promising add-ons to stroke rehabilitation and target the modulation of brain plasticity, with several reports describing their use to be associated with conventional therapy and the improvement of therapeutic outcomes. However, more recently, some small clinical trials have been developed that describe the associated use of tDCS and robot-assisted therapy in stroke rehabilitation. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

More than 30 years have already passed since the seminal article of Baker et al., in which a transcranial magnetic stimulation (TMS) pulse over the motor cortex (MC) was successfully used to painlessly elicit a recordable electromyography response. Since then, multiple studies have been conducted exploring the underlying physiology of TMS effects, its potential uses in clinical settings, as well as safety. In this chapter, we provide an overview regarding the basic mechanisms of TMS, how it can be used as a tool to investigate human brain cortex physiology, how it can be used to alter cortical excitability, its safety concerns, and its use in clinical settings.