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The field of transcranial electrical stimulation (tES) has experienced significant growth in the past 15 years. One of the tES techniques leading this increased interest is transcranial direct current stimulation (tDCS). Significant research efforts have been devoted to determining the clinical potential of tDCS in humans. Despite the promising results obtained with tDCS in basic and clinical neuroscience, further progress has been impeded by a lack of clarity on international regulatory pathways. Therefore, a group of research and clinician experts on tDCS were convened to review the research and clinical use of tDCS. This report reviews the regulatory status of tDCS and summarizes the results according to research, off-label, and compassionate use of tDCS in the following countries: Australia, Brazil, France, Germany, India, Iran, Italy, Portugal, South Korea, Taiwan, and the US. Research use, off label treatment, and compassionate use of tDCS are employed in most of the countries reviewed in this study. It is critical that a global or local effort is organized to pursue definite evidence to either approve and regulate or restrict the use of tDCS in clinical practice on the basis of adequate randomized controlled treatment trials. [ABSTRACT FROM AUTHOR]

Abstract: Transcranial magnetic stimulation (TMS) is used for therapeutic and research purposes, but it is still important to establish safety guidelines and recommendations mainly related to serious adverse effect (SAE). As part of this, safety reports need to be published. Our report highlights a case of a male patient who was a 30-year-old with a history of hemorrhagic stroke following an accidental seizure episode during a single-pulse TMS., Competing Interests: The researchers received support from the São Paulo Research Foundation (FAPESP-SPEC, grant no. 2017/12943-8). Specifically, L.M.M. was supported by a postdoctoral research grant no. 2021/05897-5, São Paulo Research Foundation (FAPESP), and S.P.B. is supported by a postdoctoral research grant no. 2020/08512-4, São Paulo Research Foundation (FAPESP). The rest of the authors have no conflicts of interest or financial disclosures to report., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Event-related desynchronisation (ERD) and event-related synchronisation (ERS) reflect pain perception and integration of the nociceptive sensory inputs. This may contribute to the understanding of how neurophysiological markers of Knee Osteoarthritis (KOA) patients can differ from control individuals, which would improve aspects such as prediction and prognosis. We performed a cross-sectional analysis of our cohort study (DEFINE cohort), KOA arm, with 71 patients, compared with 65 control participants. The study aimed to examine possible differences between ERD and ERS in control participants compared to Knee Osteoarthritis (KOA) patients when adjusting for important covariates., Materials and Methods: We performed independent multivariate regression models considering as dependent variables the power value related to ERD and ERS for four different sensorimotor tasks (Motor Execution, Motor Imagery, Active Observation and Passive Observation) and four sensorimotor oscillations (Alpha, Beta, Low Beta, and High Beta), each model, controlled by age and sex., Results: We demonstrate that the differences between KOA and healthy subjects are frequency specific, as most differences are in the beta bandwidth range. Also, we observed that subjects in the KOA group had significantly higher ERD and ERS. This may be correlated to the amount of lack of brain organisation and a subsequent attempt at compensation induced by KOA., Conclusions: Our findings strengthen the notion that subjects with KOA have a higher degree of brain plasticity changes that are also likely correlated to the degree of compensation and behavioural dysfunction.

Background: Chronic pain is highly burdening and multifactorial in etiology. The endogenous-pain-healing system restores body tissue to a non-painful state after an injury leading to pain, and its disruption could represent a relevant mechanism, especially for nursing interventions., Aim: To review the literature and summarize the results that support this hypothesis., Methods: We hypothesized that the mechanism behind this system mainly depends on the endogenous pain modulatory system (EPMS), which is responsible for inhibiting pain after tissue healing is complete and facilitating it when tissue damage is still present. Different biomarkers can quantify EPMS functioning. We reviewed the literature and included relevant information regarding this hypothesis., Results: First, conditioned pain modulation (CPM) measures pain inhibition and is a possible predictor for pain chronification. Second, motor cortex excitability measures the cortical control of the EPMS, which can be assessed through transcranial magnetic stimulation (using intracortical inhibition) or electroencephalography. Modifiable factors disrupt its functioning, such as sleep deprivation, medication overuse, and mental health status, but could be protective, such as exercise, certain medications, mind-body techniques, and non-invasive neuromodulation therapies. The acquisition of neurophysiological knowledge of how the chronicity of pain occurs and the EPMS involvement in this process may allow for better management of these patients., Conclusions: We raised the hypothesis that the impairment of the EPMS (altered cortical excitability and descendent pain modulation pathways) seems to be related to the disruption of the pain healing process and its chronicity. Further longitudinal studies evaluating the relationship between these biomarkers and chronic pain development are necessary., Competing Interests: Conflicts of InterestAll the authors declare no conflict of interest regarding this work., (© 2024 by the authors.)

Objective: Investigate the relationship between resting-state EEG-measured brain oscillations and clinical and demographic measures in Stroke patients. Methods: We performed a cross-sectional analysis of a cohort study (DEFINE cohort), Stroke arm, with 85 patients, considering demographic, clinical, and stroke characteristics. Resting-state EEG relative power from delta, theta, alpha, and beta oscillations were measured from the central region. Multivariate regression models were used for both affected and non-affected hemispheres. Results: Motor function was negatively associated with Delta and Theta oscillations, while positively associated with Alpha oscillations (both hemispheres). Similarly, cognition levels measured were negatively associated with Delta activity. Depression levels were negatively associated with Alpha activity specifically in the affected hemisphere, while positively associated with Beta activity in both hemispheres. Regarding pain measures, no significant association was observed, while CPM measure showed a positive association with Alpha activity in the non-affected hemisphere. Finally, we found that theta/alpha ratio was negatively associated with motor function and CPM scores. Conclusion: The results lead us to propose a framework for brain oscillations in stroke, whereas Delta and Beta would represent disrupted mal-adaptive brain plasticity and Theta and Alpha would represent compensatory and functional brain oscillations for motor and sensory deficits in stroke, respectively., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Estimates of the worldwide increase in amputees raises the awareness to solve long-standing problems. Understanding the functional brain modifications after a lower limb amputation (LLA) is one of the first steps towards proposing new rehabilitation approaches. Functional modifications in the central nervous system due the amputation could be involved in prosthesis use failures and Phantom Limb Pain (PLP), increasing costs and overwhelming the health services., Objective: This study analyses orphan primary motor area (M1-Orphan) hemodynamic and metabolic behaviour, which previously controlled the limb that was amputated, in comparison with the M1-Preserved, responsible for the intact limb (IL) during phantom limb imagery moving during Mirror Therapy (MT), compared to Isolated Intact Limb Movement Task (I-ILMT)., Methodology: A case-control study with unilateral traumatic LLA with moderate PLP who measured [oxy-Hb] and [deoxy-Hb] in the M1 area by Functional Near InfraredSpectroscopy (fNIRS) during the real (I-ILMT) and MT task., Results: Sixty-five patients, with 67.69% of men, young (40.32 ± 12.91), 65.63% amputated due motorcycle accidents, 4.71 ± 7.38 years ago, predominantly above the knee (57.14%). The M1 activation in the orphan cortex did not differ from the activation in the intact cortex during MT ( P  > .05)., Conclusion: The perception of the Phantom limb moving or intact limb moving is metabolically equivalent in M1, even in the absence of a limb. In other words, the amputation does not alter the brain metabolism in control of phantom movement., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. This research received a grant from the National Institute of Health (NIH), United States. At the time of analysis and writing, AT Sugawara, M Simis and LR Battistella were affiliated with the Instituto de Medicina Fisica e Reabilitacao, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil. De Pretto was affiliated to Center for Lasers and Applications, Nuclear and Energy Research Institute IPEN-CNEN/SP, São Paulo, São Paulo, Brazil and Fregni, F was affliated to Spaulding Neuromodulation Centre, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA., (© The Author(s) 2024.)

Study Design: Using a cross-sectional design, we extracted sociodemographic and clinical data from 488 Spinal Cord Injury (SCI) patients during their initial assessment before receiving intensive rehabilitation treatment., Objectives: The primary objectives of this study were to ascertain the prevalence of cognitive impairment in the study sample and specify the key clinical and demographic predictors of cognitive functioning in SCI patients., Setting: Lucy Montoro Rehabilitation Institute (LMRI), University of Sao Paulo, Sao Paulo, Brazil., Methods: We utilized independent univariate and multivariate regression models with the Montreal Cognitive Assessment (MoCA) scale, adapted for individuals with visual impairment. Moreover, we consider scores from the execution tasks (visuospatial/executive) as the dependent variable., Results: Our findings demonstrate that approximately 80% of the evaluated study sample exhibited cognitive impairment. Through the multivariate regression models, we show that several factors, including age, education, depression levels, and the use of analgesics and/or opioids, are significant predictors of total cognitive scores. These factors are independent of the clinical features associated with SCI, such as age, sex, education, and time since the injury., Conclusions: The results indicate a high prevalence of significant cognitive impairment within the sample, with age, education, depression levels, and the use of analgesics and/or opioids emerging as the primary predictors of total cognitive scores, independent of the clinical features correlated to SCI. These findings hold significant implications for both clinical research and practice, offering valuable guidance for comprehensive management throughout hospitalization and rehabilitation., (© 2024. The Author(s), under exclusive licence to International Spinal Cord Society.)

Background: Knee osteoarthritis (KOA) is a prevalent condition, and its most frequent symptom is pain that often leads to disability. Pain sensitization is a core feature of KOA, and it can be measured through quantitative sensory testing protocols such as pain pressure threshold (PPT). However, there is a lack of understanding about the factors that may influence changes in PPTs in the KOA population., Objective: To explore the clinical and functional factors associated with PPTs in a sample of people with chronic KOA pain and to compare models of local (knees) and remote (thenar regions) sites., Design: Cross-sectional analysis of a prospective cohort., Setting: Primary care in public institution., Participants: 113 adults with KOA., Intervention: N/A., Main Outcome Measures: Multivariable regression analyses evaluating demographic, clinical, and functional variables that could be associated with local and remote PPTs (main outcomes) were performed., Results: Both thenar region (adjusted-R 2 : 0.29) and knee (adjusted-R 2 : 0.45) models had the same significant negative association with being a female, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain levels (thenar: β: -0.15, p = .002; knee: β: -0.2, p < .001), and the 10-Meter Walking Test (thenar: β: -0.05, p = .038; knee: β: -0.08, p = .004). A small significant positive association with depressive symptoms was identified in both models, which acted as a confounder for WOMAC pain and was likely affected by unmeasured confounders., Conclusions: PPTs in KOA pain are associated with functional outcomes such as the 10-Meter Walking Test and activity-related pain intensity; thus more disability is associated with smaller pain thresholds. Similarity between models may suggest central sensitization., (© 2023 American Academy of Physical Medicine and Rehabilitation.)

Background: Phantom pain limb (PLP) has gained more attention due to the large number of people with amputations around the world and growing knowledge of the pain process, although its mechanisms are not completely understood., Objectives: The aim of this study was to understand, in patients with amputations, the association between PLP and residual limb pain (RLP), and the brain metabolic response in cortical motor circuits, using functional near-infrared spectroscopy (fNIRS)., Methods: Sixty participants were recruited from the rehabilitation program in São Paulo, Brazil. Included patients were aged over 18 years, with traumatic unilateral lower-limb amputation, with PLP for at least 3 months after full recovery from amputation surgery. PLP and RLP levels were measured using visual analogue scales. fNIRS was performed during motor execution and motor mirror tasks for 20 s. In order to highlight possible variables related to variation in pain measures, univariate linear regression analyses were performed for both experimental conditions, resulting in four fNIRS variables (two hemispheres x two experimental conditions). Later, in order to test the topographic specificity of the models, eight multivariate regression analyses were performed (two pain scales x two experimental conditions x two hemispheres), including the primary motor cortex (PMC) related channel as an independent variable as well as five other channels related to the premotor area, supplementary area, and somatosensory cortex. All models were controlled for age, sex, ethnicity, and education., Results: We found that: i) there is an asymmetric metabolic activation during motor execution and mirror task between hemispheres (with a predominance that is ipsilateral to the amputated limb), ii) increased metabolic response in the PMC ipsilateral to the amputation is associated with increased PLP (during both experimental tasks), while increased metabolic response in the contralateral PMC is associated with increased RLP (during the mirror motor task only); ii) increased metabolic activity of the ipsilateral premotor region is associated with increased PLP during the motor mirror task; iii) RLP was only associated with higher metabolic activity in the contralateral PMC and lower metabolic activity in the ipsilateral inferior frontal region during motor mirror task, but PLP was associated with higher metabolic activity during both tasks., Conclusion: These results suggest there is both task and region specificity for the association between the brain metabolic response and the two different types of post-amputation pain. The metabolic predominance that is ipsilateral to the amputated limb during both tasks was associated with higher levels of PLP, suggesting a cortical motor network activity imbalance due to potential interhemispheric compensatory mechanisms. The present work contributes to the understanding of the underlying topographical patterns in the motor-related circuits associated with pain after amputations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023. Published by Elsevier Masson SAS.)

Objective: The present study investigated the relationship between three genetic polymorphisms of OPRM1 (rs1799971 - A118G and rs1799972 - C17T) and BDNF (rs6265 - C196T) and EEG-measured brain oscillations in Knee Osteoarthritis (KOA) patients., Materials and Methods: We performed a cross-sectional analysis of a cohort study (DEFINE cohort), KOA arm, with 66 patients, considering demographic (age, sex, and education), clinical (pain intensity and duration), OPRM1 (rs1799971 - A118G and rs1799972 - C17T) and BDNF (rs6265 - C196T) genotypes, and electrophysiological measures. Brain oscillations relative power from Delta, Theta, Alpha, Low Alpha, High Alpha, Beta, Low Beta and High Beta oscillations were measured during resting state EEG. Multivariate regression models were used to explore the main brain oscillation predictors of the three genetic polymorphisms., Results: Our findings demonstrate that Theta and Low Beta oscillations are associated with the variant allele of OPRM1-rs1799971 (A118G) on left frontal and left central regions, respectively, while Alpha brain oscillation is associated with variant genotypes (CT/TT) of BDNF-rs6265 on frontal (decrease of oscillation power) and left central (increase of oscillation power) regions. No significant model was found for OPRM1-rs1799972 (C17T) in addition to the inclusion of pain intensity as a significant predictor of this last model., Conclusion: One potential interpretation for these findings is that polymorphisms of OPRM1 - that is involved with endogenous pain control - lead to increased compensatory oscillatory mechanisms, characterized by increased theta oscillations. Along the same line, polymorphisms of the BDNF lead to decreased alpha oscillations in the frontal area, likely also reflecting the disruption of resting states to also compensate for the increased injury associated with knee OA. It is possible that these polymorphisms require additional brain adaption to the knee OA related injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Masson SAS.)

Background: The mechanism of stroke recovery is related to the reorganization of cerebral activity that can be enhanced by rehabilitation therapy. Two well established treatments are Robot-Assisted Therapy (RT) and Constraint-Induced Movement Therapy (CIMT), however, it is unknown whether there is a difference in the neuroplastic changes induced by these therapies, and if the modifications are related to motor improvement. Therefore, this study aims to identify neurophysiological biomarkers related to motor improvement of participants with chronic stroke that received RT or CIMT, and to test whether there is a difference in neuronal changes induced by these two therapies., Methods: This study included participants with chronic stroke that took part in a pilot experiment to compare CIMT vs. RT. Neurophysiological evaluations were performed with electroencephalography (EEG) and transcranial magnetic stimulation (TMS), pre and post rehabilitation therapy. Motor function was measured by the Wolf Motor Function Test (WMFT) and Fugl-Meyer Assessment Upper Limb (FMA-UL)., Results: Twenty-seven participants with chronic stroke completed the present study [mean age of 58.8 years (SD ± 13.6), mean time since stroke of 18.2 months (SD ± 9.6)]. We found that changes in motor threshold (MT) and motor evoked potential (MEP) in the lesioned hemisphere have a positive and negative correlation with WMFT improvement, respectively. The absolute change in alpha peak in the unlesioned hemisphere and the absolute change of the alpha ratio (unlesioned/lesioned hemisphere) is negatively correlated with WMFT improvement. The decrease of EEG power ratio (increase in the lesioned hemisphere and decrease in the unlesioned hemisphere) for high alpha bandwidths is correlated with better improvement in WMFT. The variable "type of treatment (RT or CIMT)" was not significant in the models., Conclusion: Our results suggest that distinct treatments (RT and CIMT) have similar neuroplastic mechanisms of recovery. Moreover, motor improvements in participants with chronic stroke are related to decreases of cortical excitability in the lesioned hemisphere measured with TMS. Furthermore, the balance of both EEG power and EEG alpha peak frequency in the lesioned hemisphere is related to motor improvement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Simis, Thibaut, Imamura, Battistella and Fregni.)

Competing Interests: CONFLICT OF INTEREST The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: In this study, we aimed to assess the factors that predict a dysfunctional conditioned pain modulation (CPM) in chronic knee OA. Methods: This is a cross-sectional analysis of patients with chronic knee OA from a prospective cohort study in Brazil (n = 85). We performed linear and logistic multivariate regression models using the purposeful selection approach to test the relationship between the CPM in both knees (average) as a dependent variable and demographics, clinical, and neurophysiological as independent variables. Results: A significant negative association between WOMAC pain scores and CPM (β: -0.13) was found. This association was modified by the subjects' race, being stronger in the non-white subjects. In our logistic regression models, pain intensity indexed with the WOMAC pain scale remained a significant association with dichotomized CPM. Furthermore, a significant CPM association with balance, indexed with the Berg Balance score, was evidenced (β: 0.04). Neurophysiological variables showed a significant negative relationship with CPM, such as the relative power of delta oscillations in the frontal area (β: -3.11) and central area (β: -3.23). There was no significant relationship between CPM and the following domains: cognitive, emotion, sleep, opioid receptor polymorphisms, and intrinsic variables of OA disease. There was no association of CPM with TMS-indexed inhibitory markers. Conclusions: These results may indicate that less function of the pain descending inhibitory system in patients with OA is correlated with higher activity-related pain (WOMAC), less balance, and cortical plasticity especially with increased low-frequency (delta) brain oscillations. These associations seem modified by race.

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., (© 2023. The Author(s).)

Objective: To compare the effects of 2 types of robotic-assisted gait training (RAGT) devices that have been used in stroke rehabilitation., Design: Retrospective cohort., Setting: Rehabilitation hospital., Participants: 24 community dwelling people with stroke (N=24)., Interventions: RAGT with either an exoskeleton ( Lokomat ) (mean age=53.8 years; 30% men; mean duration of stroke =17.8 months) or an end-effector ( G-EO ) (mean age=50.5 years; 77.8% men; mean duration of stroke =13.11) delivered 3 times per week (36 sessions total)., Main Outcome Measures: The following tests/scales were employed before and after RAGT: Functional Ambulation Categories (FACs), timed Up and Go (TUG), 10-Meter Walk Test (10MWT), 6-Minute Walk Test (6MWT), Trunk Impairment Scale, Dynamic Gait Index (DGI), Berg Balance Scale (BBS), and ability to climb stairs (time to climb 6 steps of 15 cm each; ability to climb stairs)., Results: There were 5 dropouts, all from the G-EO group. At the end, 10 participants in the Lokomat and 9 in the G-EO group completed the intervention. From pre- to post-RAGT, G-EO patients improved on all functional tests/scales, whereas Lokomat patients improved only on the TUG, DGI, and BBS. Most patients showed improvements above the relative smallest real difference in the TUG, 10MWT, and 6MWT., Conclusions: Both end-effectors and exoskeletons may improve clinically relevant aspects of walking function. However, this study had a small sample, was retrospective, non-randomized, and had a significant number of drop-outs, therefore its findings should be interpreted carefully. Future studies are needed for investigating potential differences in clinical results, side effects, contraindications, and cost effectiveness between these 2 different types of RAGT., (© 2023 The Authors.)

Background/objective: 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., Method: 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., Results: 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., Conclusions: These results underscore the promising role of combining genetic and neurophysiological markers to endotype the treatment response in this population., Competing Interests: No conflict of interest to declare. This study was developed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 The Authors.)

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., Study Design: 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., Objectives: Identify the predictive and multivariate relationship between different sociodemographic and clinical variables of Depression and Anxiety symptoms in SCI patients., Setting: Lucy Montoro Rehabilitation Institute (LMRI), University of Sao Paulo, Sao Paulo, Brazil., Methods: We performed independent univariate and multivariate regression models using the Hospital Anxiety and Depression Scale (HADS) as dependent variable., Results: 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., Conclusions: These findings can potentially be used to guide clinical practices to identify patients at higher risk of experiencing symptoms of Depression and Anxiety., (© 2022. The Author(s), under exclusive licence to International Spinal Cord Society.)

Background: Knee osteoarthritis (OA) is a leading cause of disability in the elderly population. Chronic disabling pain is associated with maladaptive neuroplastic changes in brain networks, commonly associated with central sensitization. The main clinical features of nociplastic pain conditions include combined peripheral and central sensitization, and it is crucial to recognize this type of pain, as it responds to different therapies than nociceptive and neuropathic pain., Objective: To report the effect of the Institute of Physical Medicine and Rehabilitation (IMREA) comprehensive rehabilitation program to reduce pain and to improve functioning in elderly people with knee OA, under the DEFINE cohort., Methods: This is a retrospective observational cohort of 96 patients with knee OA, recruited from October 2018 to December 2019. All patients were evaluated by a trained multidisciplinary team using the Kellgren Lawrence classification, bilateral knee ultrasonography, the visual analog scale (VAS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain, rigidity and difficulty scores, the Timed Up and Go Test (TUG), 10-m and 6-min walking test (10 and 6 MWT), Berg Balance Scale, isokinetic dynamometry for knee extension and flexion strength, and pain pressure thresholds. The rehabilitation program included paraspinous lidocaine blocks, focal extracorporeal shockwaves combined with radial pressure waves and functional electrical stimulation according to individual needs. The baseline was compred with the treatment results with a paired t -test., Results: The study sample is composed of 96 participants, mostly females ( n = 81, 84.38%), with bilateral osteoarthritis ( n = 91, 94.79%), and a mean age of 68.89 (SD 9.73) years. Functional improvement was observed in TUG ( p = 0.019), 6-mwt ( p = 0.033), right knee flexion strength ( p < 0.0001), WOMAC rigidity and difficulty domains ( p < 0.0001). Pain was reduced from baseline as measured by WOMAC pain domain ( p < 0.0001), VAS for both knees ( p < 0.0001), and SF-36 pain domain ( p < 0.0001). Pressure pain threshold was modified above the patella ( p = 0.005 and p = 0.002 for right and left knees, respectively), at the patellar tendons ( p = 0.015 and p = 0.010 for right and left patellar tendons, respectively), left S2 dermatome ( p = 0.017), and L1-L2 ( p = 0.008)., Conclusions: The IMREA comprehensive rehabilitation program improved functioning and reduced disabling pain in elderly people with knee OA. We highlight the relevance and discuss the implementation of our intervention protocol. Although this is an open cohort study, it is important to note the significant improvement with this clinical protocol., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Imamura, Shinzato, Sugawara, Uchiyama, Matheus, Simis, Ayres, dos Santos, Assone, Ramos, Fregni and Battistella.)

Objective: 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)., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Masson SAS.)

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., (Copyright © 2022 International Federation of Clinical Neurophysiology. All rights reserved.)

Introduction: 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., Objective: 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., Methodology: 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., Results: 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., Conclusions: 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., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Pinto Barbosa et al.)

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.

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study aims to investigate the multivariate relationship between different sociodemographic, clinical, and neurophysiological variables with resting-state, high-definition, EEG spectral power in subjects with chronic knee osteoarthritis (OA) pain. This was a cross-sectional study. Sociodemographic and clinical data were collected from 66 knee OA subjects. To identify associated factors, we performed independent univariate and multivariate regression models by frequency bands (delta, theta, alpha, beta, low-beta, and high-beta) and by pre-defined regions (frontal, central, and parietal). From adjusted multivariate models, we found that: (1) increased frontocentral high-beta power and reduced central theta activity are positively correlated with pain intensity (β = 0.012, 95% CI 0.004-0.020; and β = - 0.008; 95% CI 0.014 to - 0.003; respectively); (2) delta and alpha oscillations have a direct relationship with higher cortical inhibition; (3) diffuse increased power at low frequencies (delta and theta) are associated with poor cognition, aging, and depressive symptoms; and (4) higher alpha and beta power over sensorimotor areas seem to be a maladaptive compensatory mechanism to poor motor function and severe joint degeneration. Subjects with higher pain intensity and higher OA severity (likely subjects with maladaptive compensatory mechanisms to severe OA) have higher frontocentral beta power and lower theta activity. On the other hand, subjects with less OA severity and less pain have higher theta oscillations power. These associations showed the potential role of brain oscillations as a marker of pain intensity and clinical phenotypes in chronic knee OA patients. Besides, they suggest a potential compensatory mechanism of these two brain oscillators according to OA severity., (© 2022. The Author(s).)

This study aims to investigate the associative and multivariate relationship between different sociodemographic and clinical variables with cortical excitability as indexed by transcranial magnetic stimulation (TMS) markers in subjects with chronic pain caused by knee osteoarthritis (OA). This was a cross-sectional study. Sociodemographic and clinical data were extracted from 107 knee OA subjects. To identify associated factors, we performed independent univariate and multivariate regression models per TMS markers: motor threshold (MT), motor evoked potential (MEP), short intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). In our multivariate models, the two markers of intracortical inhibition, SICI and CSP, had a similar signature. SICI was associated with age (β: 0.01), WOMAC pain (β: 0.023), OA severity (as indexed by Kellgren-Lawrence Classification) (β: - 0.07), and anxiety (β: - 0.015). Similarly, CSP was associated with age (β: - 0.929), OA severity (β: 6.755), and cognition (as indexed by the Montreal Cognitive Assessment) (β: - 2.106). ICF and MT showed distinct signatures from SICI and CSP. ICF was associated with pain measured through the Visual Analogue Scale (β: - 0.094) and WOMAC (β: 0.062), and anxiety (β: - 0.039). Likewise, MT was associated with WOMAC (β: 1.029) and VAS (β: - 2.003) pain scales, anxiety (β: - 0.813), and age (β: - 0.306). These associations showed the fundamental role of intracortical inhibition as a marker of adaptation to chronic pain. Subjects with higher intracortical inhibition (likely subjects with more compensation) are younger, have greater cartilage degeneration (as seen by radiographic severity), and have less pain in WOMAC scale. While it does seem that ICF and MT may indicate a more acute marker of adaptation, such as that higher ICF and MT in the motor cortex is associated with lesser pain and anxiety., (© 2021. The Author(s).)

Introduction: There is no diagnosis for phantom limb pain (PLP), and its investigation is based on anamnesis, which is subject to several biases. Therefore, it is important to describe and standardize the diagnostic methodology for PLP., Objective: To characterise PLP and, secondarily, to determine predictors for its diagnosis. Methodology . This is a cross-sectional study involving patients with unilateral traumatic lower-limb amputation aged over 18 years. Those with clinical decompensation or evidence of disease, trauma, or surgery in the central or peripheral nervous system were excluded. Sociodemographic and rehabilitative data were collected; PLP was characterised using the visual analogue scale (VAS), pain descriptors, and weekly frequency., Results: A total of 55 eligible patients participated in the study; most were male, young, above-knee amputees in the preprosthetic phase of the rehabilitation. The median PLP VAS was 60 (50-79.3) mm characterised by 13 (6-20) different descriptors in the same patient, which coexist, alternate, and add up to a frequency of 3.94 (2.5-4.38) times per week. The most frequent descriptor was movement of the phantom limb (70.91%). Tingling, numbness, flushing, itchiness, spasm, tremor, and throbbing are statistically significant PLP descriptor numbers per patient predicted by above-knee amputation, prosthetic phase, higher education level, and greater PLP intensity by VAS ( p < 0.05)., Conclusion: PLP is not a single symptom, but a set with different sensations and perceptions that need directed and guided anamnesis for proper diagnosis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 André Tadeu Sugawara et al.)

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., (© 2021. The Author(s), under exclusive licence to International Spinal Cord Society.)

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: 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Simis, Imamura, Sampaio de Melo, Marduy, Battistella and Fregni.)

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.

Background: Stroke is one of the leading causes of adult disability, and up to 80% of stroke survivors undergo upper extremity motor dysfunction. Constraint-Induced Movement Therapy (CIMT) and Robot-Assisted Therapy (RT) are used for upper limb stroke rehabilitation. Although CIMT and RT are different techniques, both are beneficial; however, their results must be compared. The objective is to establish the difference between RT and CIMT after a rehabilitation program for chronic stroke patients. Method: This is a randomized clinical trial, registered at ClinicalTrials.gov (ID number NCT02700061), in which patients with stroke received sessions of RT or CIMT protocol, combined with a conventional rehabilitation program for 12 weeks. The primary outcome was measured by Wolf Motor Function Test (WMFT) and Fugl-Meyer Assessment-Upper Limb (FMA-UL). Activities of daily living were also assessed. Results: Fifty one patients with mild to moderate upper limb impairment were enrolled in this trial, 25 women and 26 men, mean age of 60,02 years old (SD 14,48), with 6 to 36 months after stroke onset. Function significantly improved regardless of the treatment group. However, no statistical difference was found between both groups as p -values of the median change of function measured by WMFT and FMA were 0.293 and 0.187, respectively. Conclusion: This study showed that Robotic Therapy (RT) was not different from Constraint-Induced Movement Therapy (CIMT) regardless of the analyzed variables. There was an overall upper limb function, motor recovery, functionality, and activities of daily living improvement regardless of the interventions. At last, the combination of both techniques should be considered in future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Terranova, Simis, Santos, Alfieri, Imamura, Fregni and Battistella.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of CINP.)

Background: Functional 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., Method: In 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., Results: Fifteen 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- R 2 : 0.23) and balance ( p = 0.043; β coefficient: -0.158; and adj- R 2 :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- R 2 : 0.23; Balance: p = 0.043; β coefficient: -0.158; and adj- R 2 : 0.24)., Conclusion: In 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Simis, Doruk Camsari, Imamura, Filippo, Rubio De Souza, Battistella and Fregni.)

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: 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., Competing Interests: Declaration of Competing Interest None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Introduction: The exact mechanisms underlying the development and maintenance of phantom limb pain (PLP) are still unclear. This study aimed to identify the factors affecting pain intensity in patients with chronic, lower limb, traumatic PLP., Methods: This is a cross-sectional analysis of patients with PLP. We assessed amputation-related and pain-related clinical and demographic variables. We used univariate and multivariate models to evaluate the associated factors modulating PLP and residual limb pain (RLP) intensity., Results: We included 71 unilateral traumatic lower limb amputees. Results showed that (1) amputation-related perceptions were experienced by a large majority of the patients with chronic PLP (sensations: 90.1%, n = 64; residual pain: 81.7%, n = 58); (2) PLP intensity has 2 significant protective factors (phantom limb movement and having effective treatment for PLP previously) and 2 significant risk factors (phantom limb sensation intensity and age); and (3) on the other hand, for RLP, 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 PLP and RLP intensity. While PLP risk factors seem to be related to maladaptive plasticity, since phantom sensation and older age are associated with more pain, RLP risk factors seem to have components 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., (© 2020 World Institute of Pain.)