Feasibility of performing a multi-arm clinical trial examining the novel combination of repetitive transcranial magnetic stimulation and aerobic exercise for post-stroke depression.

BACKGROUND: Post-stroke depression (PSD) occurs in approximately one-third of chronic stroke survivors. Although pharmacotherapy reduces depressive symptoms, side effects are common and stroke survivors have increased likelihood of multimorbidity and subsequent polypharmacy. Thus, alternative non-pharmacological treatments are needed. Combining two non-pharmacological anti-depressant treatments, aerobic exercise (AEx) and repetitive transcranial magnetic stimulation (rTMS), has been demonstrated to be feasible and well-tolerated in chronic stroke survivors. OBJECTIVES: The purpose of this trial was to determine the feasibility of conducting a multi-arm combinatorial trial of rTMS and AEx and to provide an estimate of effect size of rTMS+AEx on PSD symptoms. METHODS: Twenty-four participants were allocated to one of four treatment arms AEx, rTMS, rTMS+AEx, or non-depressed Control receiving AEx. All participants received a total of 24 treatment sessions. Participant adherence was the primary outcome measure for feasibility and within group effect sizes in Patient Health Questionnaire-9 (PHQ-9) score was the primary outcome for preliminary efficacy. RESULTS: Mean adherence rates to the exercise intervention for AEx, rTMS+AEx, and Control subjects were 83%, 98%, and 95%, respectively. Mean adherence rates for rTMS and rTMS+AEx subjects were 97% and 99%, respectively. The rTMS and rTMS+AEx treatment groups demonstrated clinically significant reductions of 10.5 and 6.2 points in PHQ-9 scores, respectively. CONCLUSION: Performing a multi-arm combinatorial trial examining the effect of rTMS+AEx on PSD appears feasible. All treatment arms demonstrated strong adherence to their respective interventions and were well received. rTMS and the combination of AEx with rTMS may be alternative treatments for PSD.

Effect of functional electrical stimulation-based mirror therapy using gesture recognition biofeedback on upper extremity function in patients with chronic stroke: A randomized controlled trial.

BACKGROUND: Mirror therapy (MT) is an intervention used for upper extremity rehabilitation in stroke patients and has been studied in various fields. Recently, effective MT methods have been introduced in combination with neuromuscular electrical stimulation or with electromyography (EMG)-triggered biofeedback. The purpose of this study was to investigate the effects of functional electrical stimulation (FES)-based MT incorporating a motion recognition biofeedback device on upper extremity motor recovery to chronic stroke patients. METHODS: Twenty-six chronic stroke patients with onset of more than 6 months were randomly assigned into experimental group (n = 13) and control group (n = 13). Both groups participated in conventional rehabilitation program, while the control group received conventional MT intervention and the experimental group received FES-based MT with motion recognition biofeedback device. All interventions were conducted for 30 min/d, 5 d/wk, for 4 weeks. Upper limb motor recovery, upper limb function, active-range of motion (ROM), and activities of daily living independence were measured before and after the intervention and compared between the 2 groups. RESULTS: The Fugl-Meyer assessment (FMA), manual function test (MFT), K-MBI, and active-ROM (excluding deviation) were significantly improved in both groups (P < .05). Only the experimental group showed significant improvement in upper extremity recovery, ulnar and radial deviation (P < .05). There was a significant difference of change in Brunstrom's recovery level, FMA, MFT, and active-ROM in the experimental group compared to the control group (P < .05). CONCLUSION: FES-based MT using gesture recognition biofeedback is an effective intervention method for improving upper extremity motor recovery and function, active-ROM in patients with chronic stroke. This study suggests that incorporating gesture-recognition biofeedback into FES-based MT can provide additional benefits to patients with chronic stroke.

Effects of myofascial release with tennis ball on spasticity and motor functions of upper limb in patients with chronic stroke: A randomized controlled trial.

BACKGROUND: Impaired motor function and upper extremity spasticity are common concerns in patients after stroke. It is essential to plan therapeutic techniques to recover from the stroke. The objective of this study was to investigate the effects of myofascial release with the tennis ball on spasticity and motor functions of the upper extremity in patients with chronic stroke. METHODS: Twenty-two chronic stroke patients (male-16, female-6) were selected to conduct this study. Two groups were formed: the control group (n=11) which included conventional physiotherapy only and the experimental group (n=11) which included conventional physiotherapy along with tennis ball myofascial release - in both groups interventions were performed for 6 sessions (35 minutes/session) per week for a total of 4 weeks. The conventional physiotherapy program consisted of active and passive ROM exercises, positional stretch exercises, resistance strength training, postural control exercises, and exercises to improve lower limb functions. All patients were evaluated with a modified Ashworth scale for spasticity of upper limb muscles (biceps brachii, pronator teres, and the long finger flexors) and a Fugl-Meyer assessment scale for upper limb motor functions before and after 4 weeks. Nonparametric (Mann-Whitney U test and Wilcoxon signed-rank test) tests were used to analyze data statistically. This study has been registered on clinicaltrial.gov (ID: NCT05242679). RESULTS: A significant improvement (P < .05) was observed in the spasticity of all 3 muscles in both groups. For upper limb motor functions, significant improvement (P < .05) was observed in the experimental group only. When both groups were compared, greater improvement (P < .05) was observed in the experimental group in comparison to the control group for both spasticity of muscles and upper limb motor functions. CONCLUSION: Myofascial release performed with a tennis ball in conjunction with conventional physiotherapy has more beneficial effects on spasticity and motor functions of the upper extremity in patients with chronic stroke compared to conventional therapy alone.

O uso da estimulação transcraniana como tratamento na reabilitação motora de criança com paralisia cerebral - projeto de estudo de caso / El uso de la estimulación transcraneal como tratamiento en la rehabilitación motora de un niño con parálisis cerebral -un proyecto de estudio de caso / The use of transcranial stimulation as a treatment in the motor rehabilitation of a child with cerebral palsy -a case study projec

RESUMO A Paralisia Cerebral (PC) também denominada como encefalopatia crônica não-progressiva da infância é consequência de lesões não progressivas que aconteceram no cérebro imaturo no período pré, peri ou pós-natal, afetando o sistema nervoso central em fase de maturação estrutural e funcional. O presente trabalho trata-se de um estudo de caso com características de Pesquisa Experimental, Intervencional, onde foi realizado um protocolo de duas sessões semanais, com tempo de atendimento de 40 minutos, num total de 20 (vinte) sessões. O protocolo terapêutico consistiu de estimulação transcraniana e teve como objetivo geral investigar os efeitos da ETCC, associada à cinesioterapia e ativação dos neurônios espelhos, na reabilitação de uma criança com paralisia cerebral, sexo masculino, 54 meses de idade cronológica, grau moderado de hipotonia muscular em membros inferiores, movimentos voluntários com debilidade de força muscular; escoliose dorso-lombar e pontuação zero na Escala de Mobilidade Funcional e Asworth Modificada. O Sistema de Classificação da Função Motora Grossa (GMFCS) apresentou-se com classificação nível V, limitação na habilidade de manter as posturas anti-gravitacionais da cabeça e tronco e de controlar os movimentos de braços e pernas. Índice de Barthel Modificado com pontuação 11- classificação de dependência severa. A escala Denver II com prejuízos significativos nos domínios: pessoal-social, motor fino adaptativo, linguagem e motor grosso.

RESUMEN La parálisis cerebral (PC) también denominada como encefalopatía crónica no progresiva de la infancia es consecuencia de lesiones no progresivas que ocurrieron en el cerebro inmaduro en el periodo pre, peri o post-natal, afectando el sistema nervioso central en la fase de maduración estructural y funcional. El presente trabajo trata de un estudio de caso con características de investigación experimental, intervencional, donde fue realizado un protocolo de dos sesiones semanales de cuarenta minutos, con un total de veinte (20) sesiones. El protocolo terapéutico consistió en una estimulación transcraniana y tuvo como objetivo general, investigar los efectos de la ETCC, asociada a la cinesioterapia y activación de las neuronas espejo, en la rehabilitación de un niño con parálisis cerebral de 54 meses de edad cronológica, grado moderado de hipertonía muscular en miembros inferiores, movimientos voluntarios con debilidad de fuerza muscular; escoliosis dorsolumbar y puntuación cero en la escala de Movilidad Fun.

ABSTRACT Cerebral Palsy (CP) also known as chronic non-progressive encephalopathy of childhood is a consequence of non-progressive lesions that occurred in the immature brain in the pre, peri or postnatal period, affecting the central nervous system in a phase of structural maturation and functional. The present work is a case study with characteristics of Experimental, Interventional Research, where a protocol of two weekly sessions was carried out, with a service time of 40 minutes, in a total of 20 (twenty) sessions. The therapeutic protocol consisted of transcranial stimulation and aimed to investigate the effects of tDCS, associated with kinesiotherapy and activation of mirror neurons, in the rehabilitation of a 54-month-old male child with cerebral palsy, moderate degree of muscular hypotonia in the lower limbs, voluntary movements with weak muscular strength; dorsolumbar scoliosis and zero score on the Functional Mobility and Modified Asworth Scale. The Gross Motor Function Classification System (GMFCS) has a level V classification, limiting the ability to maintain antigravity postures of the head and trunk and to control arm and leg movements. Modified Barthel Index with score 11- severe dependency rating. The Denver II scale with significant impairments in the following domains: personal-social, adaptive fine motor, language and gross motor.

Neferine Protects against Hypoxic-Ischemic Brain Damage in Neonatal Rats by Suppressing NLRP3-Mediated Inflammasome Activation.

Hypoxic-ischemic encephalopathy (HIE) is recognized as the main cause of neonatal death, and efficient treatment strategies remain limited. Given the prevalence of HIE and the associated fatality, further studies on its pathogenesis are warranted. Oxidative stress and neuroinflammatory injury are two important factors leading to brain tissue injury and nerve cell loss in HIE. Neferine, an alkaloid extracted from lotus seed embryo, exerts considerable effects against several diseases such as cancers and myocardial injury. In this study, we demonstrated the neuroprotective effect of neferine on HIE and hypothesized that it involves the inhibition of neuronal pyroptosis, thereby ameliorating neurological inflammation and oxidative stress. We demonstrated that the mRNA levels of proteins associated with pyroptosis including caspase-1, the caspase adaptor ASC, gasdermin D, interleukin- (IL-) 18, IL-1ß, and some inflammatory factors were significantly increased in neonatal HIBD model rats compared to those in the control group. The increase in these factors was significantly suppressed by treatment with neferine. We stimulated PC12 cells with CoCl2 to induce neuronal HIBD in vitro and investigated the relationship between neferine and pyroptosis by altering the expression of the NLRP3 inflammasome. The overexpression of NLRP3 partially reversed the neuroprotective effect of neferine on HIBD, whereas NLRP3 knockdown further inhibited caspase-1 activation and IL-1ß and IL18 expression. In addition, simultaneous alteration of NLRP3 expression induced changes in intracellular oxidative stress levels after HIBD. These findings indicate that neferine ameliorates neuroinflammation and oxidative stress injury by inhibiting pyroptosis after HIBD. Our study provides valuable information for future studies on neferine with respect to neuroinflammation and pyroptosis.

Nutritional interventions to improve neurophysiological impairments following traumatic brain injury: A systematic review.

Traumatic brain injury (TBI) accounts for significant global health burden. Effects of TBI can become chronic even following mild injury. There is a need to develop effective therapies to attenuate the damaging effects of TBI and improve recovery outcomes. This literature review using a priori criteria (PROSPERO; CRD42018100623) summarized 43 studies between January 1998 and July 2019 that investigated nutritional interventions (NUT) delivered with the objective of altering neurophysiological (NP) outcomes following TBI. Risk of bias was assessed for included studies, and NP outcomes recorded. The systematic search resulted in 43 of 3,748 identified studies met inclusion criteria. No studies evaluated the effect of a NUT on NP outcomes of TBI in humans. Biomarkers of morphological changes and apoptosis, oxidative stress, and plasticity, neurogenesis, and neurotransmission were the most evaluated NP outcomes across the 43 studies that used 2,897 animals. The risk of bias was unclear in all reviewed studies due to poorly detailed methodology sections. Taking these limitations into account, anti-oxidants, branched chain amino acids, and ω-3 polyunsaturated fatty acids have shown the most promising pre-clinical results for altering NP outcomes following TBI. Refinement of pre-clinical methodologies used to evaluate effects of interventions on secondary damage of TBI would improve the likelihood of translation to clinical populations.

Sphingosine 1-Phosphate Receptors in Cerebral Ischemia.

Sphingosine 1-phosphate (S1P) is an important lipid biomolecule that exerts pleiotropic cellular actions as it binds to and activates its five G-protein-coupled receptors, S1P1-5. Through these receptors, S1P can mediate diverse biological activities in both healthy and diseased conditions. S1P is produced by S1P-producing enzymes, sphingosine kinases (SphK1 and SphK2), and is abundantly present in different organs, including the brain. The medically important roles of receptor-mediated S1P signaling are well characterized in multiple sclerosis because FTY720 (Gilenya™, Novartis), a non-selective S1P receptor modulator, is currently used as a treatment for this disease. In cerebral ischemia, its role is also notable because of FTY720's efficacy in both rodent models and human patients with cerebral ischemia. In particular, some of the S1P receptors, including S1P1, S1P2, and S1P3, have been identified as pathogenic players in cerebral ischemia. Other than these receptors, S1P itself and S1P-producing enzymes have been shown to play certain roles in cerebral ischemia. This review aims to compile the current updates and overviews about the roles of S1P signaling, along with a focus on S1P receptors in cerebral ischemia, based on recent studies that used in vivo rodent models of cerebral ischemia.

Dietary docosahexaenoic acid inhibits neurodegeneration and prevents stroke.

Stroke severely impairs quality of life and has a high mortality rate. On the other hand, dietary docosahexaenoic acid (DHA) prevents neuronal damage. In this review, we describe the effects of dietary DHA on ischemic stroke-associated neuronal damage and its role in stroke prevention. Recent epidemiological studies have been conducted to analyze stroke prevention through DHA intake. The effects of dietary intake and supply of DHA to neuronal cells, DHA-mediated inhibition of neuronal damage, and its mechanism, including the effects of the DHA metabolite, neuroprotectin D1 (NPD1), were investigated. These studies revealed that DHA intake was associated with a reduced risk of stroke. Moreover, studies have shown that DHA intake may reduce stroke mortality rates. DHA, which is abundant in fish oil, passes through the blood-brain barrier to accumulate as a constituent of phospholipids in the cell membranes of neuronal cells and astrocytes. Astrocytes supply DHA to neuronal cells, and neuronal DHA, in turn, activates Akt and Raf-1 to prevent neuronal death or damage. Therefore, DHA indirectly prevents neuronal damage. Furthermore, NDP1 blocks neuronal apoptosis. DHA, together with NPD1, may block neuronal damage and prevent stroke. The inhibitory effect on neuronal damage is achieved through the antioxidant (via inducing the Nrf2/HO-1 system) and anti-inflammatory effects (via promoting JNK/AP-1 signaling) of DHA.

Inhaled H2 or CO2 Do Not Augment the Neuroprotective Effect of Therapeutic Hypothermia in a Severe Neonatal Hypoxic-Ischemic Encephalopathy Piglet Model.

Hypoxic-ischemic encephalopathy (HIE) is still a major cause of neonatal death and disability as therapeutic hypothermia (TH) alone cannot afford sufficient neuroprotection. The present study investigated whether ventilation with molecular hydrogen (2.1% H2) or graded restoration of normocapnia with CO2 for 4 h after asphyxia would augment the neuroprotective effect of TH in a subacute (48 h) HIE piglet model. Piglets were randomized to untreated naïve, control-normothermia, asphyxia-normothermia (20-min 4%O2-20%CO2 ventilation; Tcore = 38.5 °C), asphyxia-hypothermia (A-HT, Tcore = 33.5 °C, 2-36 h post-asphyxia), A-HT + H2, or A-HT + CO2 treatment groups. Asphyxia elicited severe hypoxia (pO2 = 19 ± 5 mmHg) and mixed acidosis (pH = 6.79 ± 0.10). HIE development was confirmed by altered cerebral electrical activity and neuropathology. TH was significantly neuroprotective in the caudate nucleus but demonstrated virtually no such effect in the hippocampus. The mRNA levels of apoptosis-inducing factor and caspase-3 showed a ~10-fold increase in the A-HT group compared to naïve animals in the hippocampus but not in the caudate nucleus coinciding with the region-specific neuroprotective effect of TH. H2 or CO2 did not augment TH-induced neuroprotection in any brain areas; rather, CO2 even abolished the neuroprotective effect of TH in the caudate nucleus. In conclusion, the present findings do not support the use of these medical gases to supplement TH in HIE management.

Increased Functional Connectivity Within Intrinsic Neural Networks in Chronic Stroke Following Treatment with Red/Near-Infrared Transcranial Photobiomodulation: Case Series with Improved Naming in Aphasia.

Objective: To examine effects of four different transcranial, red/near-infrared (NIR), light-emitting diode (tLED) protocols on naming ability in persons with aphasia (PWA) due to left hemisphere (LH) stroke. This is the first study to report beneficial effects from tLED therapy in chronic stroke, and parallel changes on functional magnetic resonance imaging (fMRI). Materials and methods: Six PWA, 2-18 years poststroke, in whom 18 tLED treatments were applied (3 × /week, 6 weeks) using LED cluster heads: 500 mW, red (633 nm) and NIR (870 nm), 22.48 cm2, 22.2 mW/cm2. Results: After Protocol A with bilateral LED placements, including midline, at scalp vertex over left and right supplementary motor areas (L and R SMAs), picture naming was not improved. P1 underwent pre-/postovert, picture-naming task-fMRI scans; P2 could not. After Protocol A, P1 showed increased activation in LH and right hemisphere, including L and R SMAs. After Protocol B with LEDs only on ipsilesional, LH side, naming ability significantly improved for P1 and P2; the fMRI scans for P1 then showed activation only on the ipsilesional LH side. After Protocol C with LED placements on ipsilesional LH side, plus one midline placement over mesial prefrontal cortex (mPFC) at front hairline, a cortical node of the default mode network (DMN), P3 and P4 had only moderate/poor response, and no increase in functional connectivity on resting-state functional-connectivity MRI. After Protocol D, however, with LED placements on ipsilesional LH side, plus over two midline nodes of DMN, mPFC, and precuneus (high parietal) simultaneously, P5 and P6 each had good response with significant increase in functional connectivity within DMN, p < 0.0005; salience network, p < 0.0005; and central executive network, p < 0.05. Conclusions: NIR photons can affect surface brain cortex areas subjacent to where LEDs are applied on the scalp. Improved naming ability was present with optimal Protocol D. Transcranial photobiomodulation may be an additional noninvasive therapy for stroke.

Effect of horse riding equipment in activity of trunk and lower limb muscles in equine-assisted therapy

Equine-assisted therapy uses the horse in rehabilitation and/or education of people, such as Down syndrome(SD), cerebral palsy(PC)and intellectual disability(DI). In context, the rehabilitation program and horse riding equipment should be usedaccording to the specific characteristics of each individual, becoming an ally in the quest for excellence in equine-assisted therapy programs. The aim was to evaluate the effect of riding equipment used in equine-assisted therapy on the muscular activityof trunk and lower limb of individuals with SD, PC and DI. The study included 15 individuals equally assigned to each group: SD, PC and DIwith a mean age of 16.2 (±1.10), 16 (±1.22)e 16 (±0) years,respectively. The analysis of muscle activity was performed through surface electromyography, using four variations of horse riding equipment: saddle with and without feet supported on the stirrups and blanket with and without feet supported on the stirrups. Sigma Stat 3.5®software was used for statistical analysis.The Shapiro Wilk's test was used for normality of the data, the Bartlett test for homogeneity of the variances and the Kruskal-Wallis test for repeated measures with no normal distribution.Statistically significant differences were observed forp<0.05.The SDgroup presented a greater muscular activity of trunk and lower limbs with blanket equipment without the feet supported in the stirrups (H = 15.078, p = 0.002), as in the DI group (H=8.302, p = 0.040), while inPCgroup was the saddle with feet supported in the stirrups (H=11.137,p = 0.011). The choice of riding equipment used in equine-assisted therapy interferes differently in the pattern of muscular activation of the trunk and the lower limbs, according to the pathological processes of the practitioners. It should be an important aspect to consider when planninga treatment.

Amiloride Alleviates Neurological Deficits Following Transient Global Ischemia and Engagement of Central IL-6 and TNF-α Signal.

BACKGROUND: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine if blocking acid sensing ion channels (ASICs) using amiloride in the Central Nervous System can alleviate neurological deficits after the induction of CA and further examine the participation of PIC signal in the hippocampus for the effects of amiloride. METHODS: CA was induced by asphyxia and then cardiopulmonary resuscitation was performed in rats. Western blot analysis and ELISA were used to determine the protein expression of ASIC subunit ASIC1 in the hippocampus, and the levels of PICs. As noted, it is unlikely that this procedure is clinically used although amiloride and other pharmacological agents were given into the brain in this study. RESULTS: CA increased ASIC1 in the hippocampus of rats in comparison with control animals. This was associated with the increase in IL-1ß, IL-6 and TNF-α together with Caspase-3 and Caspase-9. The administration of amiloride into the lateral ventricle attenuated the upregulation of Caspase-3/Caspase-9 and this further alleviated neurological severity score and brain edema. Inhibition of central IL-6 and TNF-α also decreased ASIC1 in the hippocampus of CA rats. CONCLUSION: Transient global ischemia induced by CA amplifies ASIC1a in the hippocampus likely via PIC signal. Amiloride administered into the Central Nervous System plays a neuroprotective role in the process of global ischemia. Thus, targeting ASICs (i.e., ASIC1a) is suggested for the treatment and improvement of CA-evoked global cerebral ischemia.

Desenvolvimento de um protótipo lúdico para reabilitação motora de crianças com encefalopatia crônica não progressiva da infância / Development of a playful prototype for motor rehabilitation of children with Childhood Chronic Non-progressive Encephalopathy

NTRODUÇÃO: A Encefalopatia Crônica Não Progressiva da Infância - ECNPI é um transtorno complexo de grande impacto na vida da pessoa acometida, na dinâmica familiar, na sociedade e interfere nas políticas públicas, por representar uma condição clínica crônica complexa e que gera custos elevados para seu tratamento. As demandas de cuidados de crianças com ECNPI requerem a articulação de vários atores e cenários e impõem constantes desafios às famílias e aos profissionais de saúde, em particular para os fisioterapeutas, dada a necessidade de buscar um equilíbrio entre as atividades desempenhadas, a motivação das crianças e a eficácia da terapia estabelecida. Uma das tendências que vem revolucionando o campo da neuropediatria é a intervenção através de ambientes de Realidade Virtual (RV), utilizando-se o videogame como abordagem terapêutica. OBJETIVO: Desenvolver um protótipo lúdico, do tipo serious game, para o suporte no tratamento reabilitatório motor de crianças com ECNPI. MÉTODO: Estudo metodológico, que descreve os passos para o desenvolvimento desse protótipo lúdico, fundamentado na abordagem centrada no usuário. O recrutamento foi realizado em dois centros de reabilitação especializados em crianças neurotípicas e a etapa de desenvolvimento computacional foi realizada em uma instituição federal de ensino superior, com coleta de dados no período de janeiro de 2018 a abril de 2019, totalizando 32 participantes. A primeira etapa da pesquisa objetivou identificar as necessidades de reabilitação motora das crianças. Conduziram-se dois grupos focais, com a participação de oito mães de crianças com diagnóstico de ECNPI, para identificar as necessidades motoras de seus filhos. Realizou-se análise de contéudo do tipo dedutiva desses dados e elaboraram-se as categorias: o cuidado cotidiano das crianças com ECNPI; desafios motores das crianças com ECNPI; a importância da reabilitação e dificuldades no desenvolvimento de atividades lúdicas. A avaliação motora clínica foi realizada com 12 crianças com ECNPI, utilizando-se o instrumento Gross Motor Function Measure. Uma equipe multiprofissional, composta por quatro profissionais de saúde, também contribuiu para traçar o perfil das necessidades de reabilitação motora dessas crianças. Ao término dessa primeira etapa, foi possível delimitar os conteúdos específicos da tecnologia com profissionais da área computacional que mapearam essas solicitações em requisitos funcionais e não funcionais presentes no protótipo. A terceira etapa constou de um pré-teste utilizando o protótipo lúdico, na qual participaram quatro crianças com diagnóstico de ECNPI e suas mães, bem como profissionais da equipe multidisciplinar. Esta fase objetivou validar a viabilidade do protótipo como ferramenta auxiliar para potencializar a reabilitação motora das crianças em sessões de fisioterapia. RESULTADOS: O protótipo apresenta um ambiente tridimensional, utilizando o sensor Kinect para a captura dos movimentos corporais, visando auxiliar no controle motor dessas crianças. Foram desenvolvidos três módulos: balões, figuras geométricas e corrida, ou seja, jogos com enfoque na estimulação motora ampla e fina, direcionados especificamente para as necessidades das crianças com ECNPI. O pré-teste mostrou o protótipo lúdico como altamente promissor. CONCLUSÃO: Os resultados desta pesquisa contribuem para apoiar o processo reabilitatório em fisioterapia neurológica infantil, proporcionando motivação e ludicidade nos atendimentos e, em conjunto, potencial para aprimorar as habilidades motoras das crianças em seguimento e fortalecer o cuidado integral dessa clientela

INTRODUCTION: Childhood Chronic Non-progressive Encephalopathy - CCNPE is a complex disorder that has a great impact on the life of the person affected by family dynamics and in society and interferes in public policies because it represents a complex chronicle clinical condition that generates high costs for its treatment. The demands of childcare with CCNPE require the articulation of several actors and scenarios and impose constant challenges on families and health professionals, in particular on physical therapists, given the need to strike a balance between the activities performed, the motivation of the children, and the efficacy of the established therapy. One of the trends that has revolutionized the field of neuropediatrics is the intervention through Virtual Reality (VR) environments, using videogame as a therapeutic approach. OBJECTIVE: To develop a playful prototype, serious game type, for support in the motor rehabilitation treatment of children with CCNPE. METHOD: Methodological study, which describes the steps for the development of this prototype ludic, based on the user-centered design approach. Recruitment was carried out at two rehabilitation centers specialized in neurotypical children and the step of computational development ocurred at a federal institution of higher education, with data collection from January 2018 to April 2019, totaling 32 participants. The first stage of the research aimed to identify the needs of children's motor rehabilitation. Two focus groups were conducted, with the participation of eight mothers of children diagnosed with CCNPE, to identify the motor needs of their children. Deductive data analysis was performed and the categories were elaborated: the daily care of children with CCNPE; motor challenges of children with CCNPE; the importance of rehabilitation and difficulties in the development of play activities. Clinical motor assessment was performed with 12 children with CCNPE, using the Gross Motor Function Measure instrument. A multiprofessional team, composed of four health professionals, also contributed to the profile of the motor rehabilitation needs of these children. At the end of this first stage, it was possible to delimit the specific contents of the technology with professionals of the computational area that mapped these requests of the functional and non-functional requirements present in the prototype. The third stage consisted of a pre-test using the play prototype, in which four children with a diagnosis of CCNPE and their mothers, as well as professionals from the multidisciplinary team participated. This phase aimed to validate the viability of the prototype as an auxiliary tool to enhance the motor rehabilitation of children in physiotherapy sessions. RESULTS: The prototype presents a three-dimensional environment, using the Kinect sensor to capture body movements, aiming to assist in the motor control of these children. Three modules were developed: balloons, geometric figures, and running, that is, games focused on gross and fine motor stimulation, specifically targeted to the needs of children with CCNPE. The pre-test showed the playful prototype as highly promising. CONCLUSION: The results of this research contribute to support the rehabilitation process in children's neurological physiotherapy, promoting motivation and playfulness in their assistance. The results also contributes to improve the motor skills of the children in follow-up and strengthening the comprehensive care of this clientele

Comparison of neuroprotective efficacy of poly-arginine R18 and R18D (D-enantiomer) peptides following permanent middle cerebral artery occlusion in the Wistar rat and in vitro toxicity studies.

We have previously demonstrated that arginine-rich and poly-arginine peptides possess potent neuroprotective properties, with poly-arginine peptide R18 identified as being highly effective at reducing infarct volume following middle cerebral artery occlusion (MCAO) in the Sprague Dawley rat. Since peptides synthesised using D-isoform amino acids have greater stability than L-isoform peptides due to increased resistance to proteolytic degradation, they represent potentially more effective peptide therapeutics. Therefore we compared the neuroprotective efficacy of R18 and its D-enantiomer R18D following permanent MCAO in the Wistar rat. Furthermore, as increased peptide stability may also increase peptide toxicity, we examined the effects of R18 and R18D on cultured cortical neurons, astrocytes, brain endothelial cells (bEND.3), and embryonic kidney cells (HEK293) following a 10-minute or 24-hour peptide exposure duration. The in vivo studies demonstrated that R18D resulted in a greater reduction in mean infarct volume compared to R18 (33%, p = 0.004 vs 12%, p = 0.27) after intravenous administration at 300 nmol/kg 30 minutes after MCAO. Both R18D and R18 reduced cerebral hemisphere swelling to a comparable degree (27%, p = 0.03 and 30%, p = 0.02), and improved neurological assessment scores (1.5, p = 0.02 and 2, p = 0.058 vs 3 for vehicle). No abnormal histological findings specific to peptide treatments were observed in hematoxylin and eosin stained sections of kidney, liver, spleen, lung and heart. In vitro studies demonstrated that R18 and R18D were most toxic to neurons, followed by astrocytes, HEK293 and bEND.3 cells, but only at high concentrations and/or following 24-hour exposure. These findings further highlight the neuroprotective properties of poly-arginine peptides, and indicate that R18D at the dose examined is more potent than R18 in Wistar rats, and justify continued investigation of the R18 peptide as a novel neuroprotective agent for stroke.

Ethanol Iris tenuifolia extract reduces brain damage in a mouse model of cerebral ischaemia.

In the previous experiments, the neuroprotective role of Iris tenuifolia Pall. (IT) in the model of middle cerebral artery occlusion (MCAO) was investigated. In addition, the concentrations of the cytokines tumour necrosis factor-alpha and interleukin-6 in blood plasma were measured. It was found that IT administered 1 hr prior to MCAO or immediately after MCAO reduced infarct volume significantly. IT application 1 and 4 hr after MCAO, respectively, was without any effect on infarct volume. There were no significant changes as regards tumour necrosis factor-alpha, whereas interleukin-6 concentrations were increased in blood plasma. This is the first evidence that flavonoids from Iris tenuifolia exert protective effects in the in vivo MCAO model. Our results suggest that these flavonoids are likely to be beneficial to humans by virtue of their ability to reduce infarct volume.

Epigallocatechin-3-Gallate Protects against Homocysteine-Induced Brain Damage in Rats.

High levels of homocysteine are implicated in many neurovascular and neurodegeneration diseases. Epigallocatechin 3-gallate (EGCG), one of green tea polyphenols, has potential anti-oxidative and anti-inflammatory activities. However, it has not been explored whether EGCG has an effect on homocysteine-induced neuro-inflammation and neurodegeneration. In this study, we investigated the effects of EGCG on memory deficit, oxidative stress, neuro-inflammation, and neurodegeneration in hyper-homocysteinemic rats after a 2 wk homocysteine injection by vena caudalis. We found that supplementation of EGCG could rescue deficit of spatial memory induced by homocysteine. Treatment of EGCG significantly reduced the expression of malondialdehyde, glial fibrillary acidic protein, tumor necrosis factor-α, and interleukin-1ß and increased glutathione level in the homocysteine-treated group. In TdT-mediated dUTP nick end labeling (TUNEL) assay and Fluoro-Jade B staining, supplementation of EGCG could attenuate the apoptotic neurons and neurodegeneration. Interestingly, EGCG significantly ameliorated homocysteine-induced cerebrovascular injury. Our data suggest that EGCG could be a promising candidate for arresting homocysteine-induced neurodegeneration and neuro-inflammation in the brain.

[Infantile acquired brain injury, a personal experience. Demands from the socio-familial point of view]. / Daño cerebral sobrevenido infantil, una experiencia personal. Reclamaciones desde el punto de vista sociofamiliar.

We report on the experience of a family in which the youngest child has acquired brain injury and the struggle undertaken by the family to improve the neurorehabilitation resources in the public health service. The article outlines the main demands, from the socio-familial point of view, as regards the improvement of neurological rehabilitation and the resources needed to deliver it.

TITLE: Daño cerebral sobrevenido infantil, una experiencia personal. Reclamaciones desde el punto de vista sociofamiliar.Se describe la experiencia de una familia en la que el hijo menor tiene daño cerebral sobrevenido y la lucha emprendida por la familia para mejorar los recursos neurorrehabilitadores de la sanidad publica. Se recogen las principales reclamaciones, desde el punto de vista sociofamiliar, en cuanto a la mejora en la atencion neurorrehabilitadora y los recursos necesarios.

Music interventions for acquired brain injury.

BACKGROUND: Acquired brain injury (ABI) can result in impairments in motor function, language, cognition, and sensory processing, and in emotional disturbances, which can severely reduce a survivor's quality of life. Music interventions have been used in rehabilitation to stimulate brain functions involved in movement, cognition, speech, emotions, and sensory perceptions. An update of the systematic review published in 2010 was needed to gauge the efficacy of music interventions in rehabilitation for people with ABI. OBJECTIVES: To assess the effects of music interventions for functional outcomes in people with ABI. We expanded the criteria of our existing review to: 1) examine the efficacy of music interventions in addressing recovery in people with ABI including gait, upper extremity function, communication, mood and emotions, cognitive functioning, social skills, pain, behavioural outcomes, activities of daily living, and adverse events; 2) compare the efficacy of music interventions and standard care with a) standard care alone, b) standard care and placebo treatments, or c) standard care and other therapies; 3) compare the efficacy of different types of music interventions (music therapy delivered by trained music therapists versus music interventions delivered by other professionals). SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (January 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 6), MEDLINE (1946 to June 2015), Embase (1980 to June 2015), CINAHL (1982 to June 2015), PsycINFO (1806 to June 2015), LILACS (1982 to January 2016), and AMED (1985 to June 2015). We handsearched music therapy journals and conference proceedings, searched dissertation and specialist music databases, trials and research registers, reference lists, and contacted relevant experts and music therapy associations to identify unpublished research. We imposed no language restriction. We performed the original search in 2009. SELECTION CRITERIA: We included all randomised controlled trials and controlled clinical trials that compared music interventions and standard care with standard care alone or combined with other therapies. We examined studies that included people older than 16 years of age who had ABI of a non-degenerative nature and were participating in treatment programmes offered in hospital, outpatient, or community settings. We included studies in any language, published and unpublished. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias of the included studies. We contacted trial researchers to obtain missing data or for additional information when necessary. Where possible, we presented results for continuous outcomes in meta-analyses using mean differences (MDs) and standardised mean differences (SMDs). We used post-test scores. In cases of significant baseline difference, we used change scores. We conducted a sensitivity analysis to assess the impact of the randomisation method. MAIN RESULTS: We identified 22 new studies for this update. The evidence for this update is based on 29 trials involving 775 participants. A music intervention known as rhythmic auditory stimulation may be beneficial for improving the following gait parameters after stroke. We found a reported increase in gait velocity of 11.34 metres per minute (95% confidence interval (CI) 8.40 to 14.28; 9 trials; 268 participants; P < 0.00001; moderate-quality evidence). Stride length of the affected side may also benefit, with a reported average of 0.12 metres more (95% CI 0.04 to 0.20; 5 trials; 129 participants; P = 0.003; moderate-quality evidence). We found a reported average improvement for general gait of 7.67 units on the Dynamic Gait Index (95% CI 5.67 to 9.67; 2 trials; 48 participants; P < 0.00001). There may also be an improvement in gait cadence, with a reported average increase of 10.77 steps per minute (95% CI 4.36 to 17.18; 7 trials; 223 participants; P = 0.001; low-quality evidence).Music interventions may be beneficial for improving the timing of upper extremity function after stroke as scored by a reduction of 1.08 seconds on the Wolf Motor Function Test (95% CI -1.69 to -0.47; 2 trials; 122 participants; very low-quality evidence).Music interventions may be beneficial for communication outcomes in people with aphasia following stroke. Overall, communication improved by 0.75 standard deviations in the intervention group, a moderate effect (95% CI 0.11 to 1.39; 3 trials; 67 participants; P = 0.02; very low-quality evidence). Naming was reported as improving by 9.79 units on the Aachen Aphasia Test (95% CI 1.37 to 18.21; 2 trials; 35 participants; P = 0.02). Music interventions may have a beneficial effect on speech repetition, reported as an average increase of 8.90 score on the Aachen Aphasia Test (95% CI 3.25 to 14.55; 2 trials; 35 participants; P = 0.002).There may be an improvement in quality of life following stroke using rhythmic auditory stimulation, reported at 0.89 standard deviations improvement on the Stroke Specific Quality of Life Scale, which is considered to be a large effect (95% CI 0.32 to 1.46; 2 trials; 53 participants; P = 0.002; low-quality evidence). We found no strong evidence for effects on memory and attention. Data were insufficient to examine the effect of music interventions on other outcomes.The majority of studies included in this review update presented a high risk of bias, therefore the quality of the evidence is low. AUTHORS' CONCLUSIONS: Music interventions may be beneficial for gait, the timing of upper extremity function, communication outcomes, and quality of life after stroke. These results are encouraging, but more high-quality randomised controlled trials are needed on all outcomes before recommendations can be made for clinical practice.

Caso: negativa de los padres al tratamiento en un menor de edad. Nutrición enteral a una paciente con déficit neurológico severo / Case: parental refusal to treatment in a minor enteral nutrition to a patient with severe neurologial deficit

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Comentario al caso: negativa de los padres al tratamiento en un menor de edad. Nutrición enteral a una paciente con déficit neurológico severo / Commentary o the case: parental refusal to treatment in a minor. Enteral nutrition to a patient with severe neurological deficit

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