The Blood-Cerebrospinal Fluid Barrier Dysfunction in Brain Disorders and Stroke: Why, How, What For?

Ischemic stroke (IS) results in the interruption of blood flow to the brain, which can cause significant damage. The pathophysiological mechanisms of IS include ionic imbalances, oxidative stress, neuroinflammation, and impairment of brain barriers. Brain barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (B-CSF), protect the brain from harmful substances by regulating the neurochemical environment. Although the BBB is widely recognized for its crucial role in protecting the brain and its involvement in conditions such as stroke, the B-CSF requires further study. The B-CSF plays a fundamental role in regulating the CSF environment and maintaining the homeostasis of the central nervous system (CNS). However, the impact of B-CSF impairment during pathological events such as IS is not yet fully understood. In conditions like IS and other neurological disorders, the B-CSF can become compromised, allowing the entry of inflammatory substances and increasing neuronal damage. Understanding and preserving the integrity of the B-CSF are crucial for mitigating damage and facilitating recovery after ischemic stroke, highlighting its fundamental role in regulating the CNS during adverse neurological conditions.

Pharyngeal phase of swallowing in post-stroke dysphagia: videoendoscopy and speech-language-hearing assessment. / Fase faríngea da deglutição na disfagia pós-AVE: achados videoendoscópios e da avaliação fonoaudiológica.

PURPOSE: To investigate the outcomes of fiberoptic endoscopic evaluation of pharyngeal swallowing phase and clinical evaluation of swallowing among dysphagic individuals with and without chronic stroke in different food consistencies. METHODS: This is a cross-sectional and retrospective study based on data collection from medical records. 134 swallowing video endoscopy exams of dysphagic patients were analyzed, in which they were divided into two groups according to the diagnosis of stroke, in which data were collected regarding mobility and strength of the tongue, phonation and cough efficiency, and the pharyngeal signs of dysphagia with four food consistencies from the International Dysphagia Diet Standardization Initiative (IDDSI), for comparison between groups. To analyze and classify the severity of pharyngeal residues, the Yale Pharyngeal Residue Severity Rating Scale (YPRSRS) was used by two independent professionals. RESULTS: There was a significant difference in the presence of pharyngeal residue, laryngeal penetration and laryngotracheal aspiration in all consistencies evaluated (level 0, 2, 4 and 7) (p= <0.001), in addition to the association with multiple swallowing in thin liquid, slightly thickened liquid and solid (level 0, 2 and 7) (p= 0.026). CONCLUSION: Dysphagic individuals diagnosed with stroke showed differences in videoendoscope signs of pharyngeal residue, laryngeal penetration and laryngotracheal aspiration, regardless of the food consistency assessed, compared to dysphagic individuals without the diagnosis. Just as there was a difference in the finding of multiple swallowing only in the consistencies of thin liquid, extremely thickened liquid and solid.

OBJETIVO: Investigar os achados videoendoscópios da fase faríngea da deglutição e da avaliação clínica da deglutição, entre indivíduos disfágicos com e sem AVE crônico em diferentes consistências alimentares. MÉTODO: Trata-se de um estudo transversal e retrospectivo com base na coleta de dados dos prontuários. Foram analisados 134 exames da videoendoscopia da deglutição de pacientes disfágicos, em que foram divididos em dois grupos de acordo com o diagnóstico de AVE, na qual, foram coletados dados com relação à mobilidade e força de língua, fonação e eficiência da tosse, e os sinais faríngeos de disfagia com quatro consistências alimentares do International Dysphagia Diet Standartisation Initiative (IDDSI), para comparação entre os grupos. Para análise e classificação da gravidade dos resíduos faríngeos, foi utilizado o Yale Pharyngeal Residue Severity Rating Scale (YPRSRS) por dois profissionais independentes. RESULTADOS: Houve diferença significativa com a presença de resíduos faríngeos, penetração laríngea e aspiração laringotraqueal em todas as consistências avaliadas (nível 0, 2, 4 e 7) (p= <0,001), além da associação com deglutições múltiplas em líquido ralo, líquido levemente espessado e sólido (nível 0, 2 e 7) (p= 0,026). CONCLUSÃO: Os indivíduos disfágicos com diagnóstico de acidente vascular encefálico apresentaram diferença nos sinais videoendoscópios de resíduos faríngeos, penetração laríngea e aspiração laringotraqueal independentemente da consistência alimentar avaliada, em comparação aos indivíduos disfágicos sem o diagnóstico. Assim como houve diferença no achado da deglutição múltipla apenas nas consistências de líquido ralo, líquido extremamente espessado e sólido.

Respiratory muscle strength in stroke: a case-control study.

AIM: The aim of the study was to determine the respiratory muscle strength of stroke patients and compare them with healthy individuals. METHOD: The study was conducted with 171 patients who had a stroke between 2017 and 2021 and 32 healthy controls. Respiratory muscle strength and inspiratory and expiratory mouth pressure (MIP and MEP) were measured using the portable MicroRPM device (Micro Medical, Basingstoke, UK). RESULTS: The stroke group exhibited significantly lower values in both MIP for men (p<0.001) and women (p=0.013) and maximal expiratory pressure for men (p<0.001) and women (p=0.042), compared with the healthy control group. Notably, there was a significant difference in the MIPmen (p=0.026) and MEPmen (p=0.026) values when comparing the reference values, which were calculated based on age and sex, with those of the healthy group. The baseline values calculated according to age for stroke patients were as follows: MIPmen 31.68%, MIPwomen 63.58%, MEPmen 22.54%, and MEPwomen 42.30%. CONCLUSION: This study highlights the significant respiratory muscle weakness experienced by stroke patients, with gender-specific differences. It highlights the importance of incorporating respiratory assessments and interventions into stroke rehabilitation protocols to improve the overall health and well-being of stroke patients.

Teriparatida para o tratamento de osteoporose secundária a glicocorticoides, pacientes do sexo masculino e pacientes que apresentaram infarto do miocárdio ou acidente vascular cerebral no ano anterior / Teriparatide for the treatment of osteoporosis secondary to glucocorticoids in male patients and patients who have had myocardial infarction or stroke in the previous year

INTRODUÇÃO: A osteoporose é uma enfermidade que aumenta a fragilidade óssea e suscetibilidade à fratura. No mundo, afeta aproximadamente 200 milhões de pessoas. Sua prevalência no Brasil varia de 6% a 33%. O tratamento indicado inclui estratégias não medicamentosas e medicamentosas, entre as quais encontram-se o carbonato de cálcio e a vitamina D como parte de todos os esquemas terapêuticos; os agentes anti reabsortivos (bifosfonatos - alendronato, risedronato, pamidronato e ácido zoledrônico); o modulador seletivo dos receptores de estrogênio (raloxifeno); os estrógenos conjugados; calcitonina e o agente anabólico (teriparatida). Estas são opções disponíveis no Protocolo Clínico de Diretrizes Terapêuticas (PCDT) de Osteoporose do Sistema Único de Saúde (SUS). Em caso de falha terapêutica, que pode acompanhar 25% dos pacientes, as diretrizes clínicas nacionais e internacionais de sociedades médicas recomendam o uso de denosumabe, teriparatida ou romosozumabe, dependendo da população. O objetivo do presente relatório é analisar as evidências econômicas do uso da teriparatida para o tratamento da falha terapêutica em: (a) homens; (b) pacientes com osteoporose severa por uso de glicocorticoides (GC); (c) pacientes com acidente vascular cerebral (AVC); e d) pacientes com infarto agudo do miocárdio (IAM) no ano anterior. PERGUNTA: A teriparatida é custo-efetiva no tratamento de: (a) homens com osteoporose, (b) pacientes com osteoporose severa por uso de GC, (c) pacientes com AVC ou IAM no ano anterior, como alternativa aos bifosfonatos? AVALIAÇÃO ECONÔMICA: A avaliação de custo-efetividade não demonstrou a superioridade da teriparatida quando comparada ao alendronato e ao risedronato no tratamento de homens ou pacientes utilizando ou com AVC ou IAM. Para pacientes com uso de glicocorticoides, a razão de custo-efetividade incremental se situou em torno do limiar de R$ 40.000,00/QALY. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: O impacto orçamentário, dependendo do market share, foi de 117 milhões para a população masculina, 17 milhões para pacientes usando glicocorticoides, 9,3 milhões com AVC e 10,3 milhões com IAM. O uso integral da teriparatida elevaria esse gasto para 187 milhões, 71 milhões, 37 milhões e 41 milhões, respectivamente. Deve-se observar que nesses valores pode haver dupla contagem, uma vez que as estimativas feitas para os homens não excluíram as comorbidades. EXPERIÊNCIAS INTERNACIONAIS/RECOMENDAÇÕES DE OUTRAS AGÊNCIAS DE ATS: Quanto ao uso da teriparatida em homens, o National Health System (NHS) a recomenda como alternativa de tratamento para a osteoporose secundária e prevenção de fraturas por fragilidade osteoporótica em homens intolerantes ao alendronato e risedronato ou com "resposta insatisfatória. É financiada pelo NHS England Specialized Commissioning. Na Nova Zelândia, a Pharmaceutical Management Agency (PHARMAC) sugere o financiamento da teriparatida como tratamento de última linha para a osteoporose, restringindo-a aos pacientes com evidência de fraturas contínuas e/ou T-escore <-3, após tentarem todos os tratamentos financiados para a osteoporose. Este uso está condicionado a uma redução significativa dos preços. A Austrália, por meio do The Pharmaceutical Benefits Scheme (PBS), incorporou a teriparatida para o tratamento de osteoporose grave em pacientes com risco alto de fratura com critérios muito bem estabelecidos. Deve ser a única terapia subsidiada pela PBS para esta condição, não excedendo um máximo de 18 meses. O informe de posicionamento terapêutico da teriparatida junto a Agência Espanhola de Medicamentos e Produtos Sanitários (AEMPS) indica seu uso para o tratamento de osteoporose em homens com aumento do risco de fratura. A Canadian Agency for Drugs and Technologies in Health (CADTH) não recomenda seu uso. A Pharmaceuticals and Medical Devices Agency (PMDA) do Japão não se posiciona quanto ao uso deste medicamento em homens com alto risco de fratura. O informe de posicionamento terapêutico para a teriparatida junto à AEMPS e à PMDA indicam seu uso para o tratamento de osteoporose associada à terapia sistêmica com GC, em homens e mulheres com incremento de risco de fratura. Não se encontrou posicionamento relacionado o seu uso em pacientes em uso de GC no sítio do NICE. O CADTH recomendou, em julho de 2009, a não incorporação do Forteo® para pessoas em uso de GC. Não se encontrou informe de posicionamento terapêutico para a teriparatida no tratamento de indivíduos com AVC ou IAM prévios, na PMDA, NICE, NHS, AEMPS ou PMDA. CONSIDERAÇÕES FINAIS: Na maioria dos cenários analisados, o uso dos bifosfonatos produz economia de recursos em relação à teriparatida no tratamento de homens ou com AVC ou IAM no ano anterior. A teriparatida não se mostrou custo-efetiva em nenhuma situação. A única alternativa em que ela mostrou possibilidades de ser custo efetiva foi em pacientes utilizando glicocorticóides. O impacto orçamentário de acordo com o market share variou de 9 milhões com AVC e 117 milhões para homens com ostorporose e falha terapêutica. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Embora a teriparatida só se mostre custo-efetiva para pacientes usando glicocorticóides e não haja economia de recursos, os membros do Comitê de Medicamentos, na 129ª reunião ordinária da Conitec, realizada no dia 8 de maio de 2024, deliberaram, por unanimidade, que a matéria fosse disponibilizada em consulta pública com recomendação preliminar favorável à restrição do uso da teriparatida para o tratamento no SUS da osteoporose em falha terapêutica para: (a) homens; (b) pacientes com osteoporose severa por uso de glicocorticoides (GC); (c) pacientes com acidente vascular cerebral (AVC) no ano anterior; e d) pacientes com infarto agudo do miocárdio (IAM) no ano anterior, haja vista que esses pacientes não são atendidos com as opções terapêuticas disponíveis no SUS. CONSULTA PÚBLICA: A Consulta Pública nº 040 foi realizada entre os dias 26/06/2024 e 15/07/2024. Foram recebidas 6 contribuições, todas de cunho técnico-científico. No total, 1 não concordou e não discordou da recomendação inicial da Conitec, 1 concordou e 4 discordaram. Embora as evidências clínicas não fossem objeto da análise do relatório da consulta pública, todos os participantes que discordaram da restrição do uso da teriparatida relataram a necessidade do uso do medicamento em pacientes com osteoporose grave. Nenhuma das contribuições sobre avaliação econômica apresentou argumentos, indicando apenas uma bibliografia genérica sobre a eficácia do teriparatida. A empresa argumentou que existe evidências da segurança, eficácia e efetividade nos ensaios clínicos e que houve uma autorização de aumento de 4,5% pela CMED que não foi repassado aos preços. Confirmou o preço da última proposta de R$ 12.282,06 para o fornecimento da teriparatida se as restrições fossem aprovadas As das contribuições recebidas na Consulta Pública não trouxeram novos fundamentos na parte econômica que justificassem a alteração da decisão preliminar. As evidências clínicas não estavam em avaliação e não foram objeto de análise. RECOMENDAÇÃO FINAL DA CONITEC: Através do registro de deliberação nº 918/2024, os membros do Comitê de Medicamentos, presentes na 132ª Reunião ordinária da Conitec, realizada no dia 07 de agosto de 2024, deliberaram por maioria pela recomendação FAVORÁVEL pela exclusão da teriparatida para o tratamento de osteoporose grave. O Comitê considerou que a terapia não era custo-efetiva nos cenários apresentados e uma alternativa mais econômica e conveniente estaria disponível em um horizonte tecnológico curto. DECISÃO: excluir, no âmbito do Sistema Único de Saúde - SUS, a teriparatida para o tratamento da osteoporose grave e falha terapêutica aos medicamentos disponíveis no SUS, publicada no Diário Oficial da União, número 183, Seção 1, página 147, em 20 de setembro de 2024.

Social rhythm and implications on functionality of patients after stroke.

The study aimed to assess the regularity, intensity, frequency, and period of activities comprising social rhythm and associate them with the functionality of stroke patients. The sample consisted of 73 patients (41 men and 32 women) with a mean age of 60 years (±10). Social rhythm was assessed by Social Rhythm Metric (SRM) and Activity Level Index (ALI). The functionality was evaluated using the International Classification of Functioning, Disability, and Health (ICF). Data were analyzed using Student's t-test, ANOVA, and Chi-square test. The mean SRM was 5.1 ± 0.9, and ALI was 58.3 ± 14.9. Notably, 40% of the patients exhibited both low regularity and low intensity of activities. Six SRM activities, performed with low frequency (going outside, starting work, exercising, snacking, watching other TV programs, and going home), exhibited a tendency to have periods that deviated from the expected 24-hour daily cycle. ICF domains most associated with SRM were: d2-General tasks and demands, d3-Communication, d4-Mobility, d5-Self care, d8-Major life areas, and d9-Community, social and civic life. The results indicated changes in social rhythm with implications for patient functionality. Screening for disruptions in social rhythm could be part of the functional assessment during the rehabilitation process for post-stroke patients.

Effect of transcranial direct current stimulation in the initial weeks post-stroke: a pilot randomized study.

OBJECTIVE: This study aimed at assessing the alterations in upper limb motor impairment and connectivity between motor areas following the post-stroke delivery of cathodal transcranial direct current stimulation sessions. METHODS: Modifications in the Fugl-Meyer Assessment scores, connectivity between the primary motor cortex of the unaffected and affected hemispheres, and between the primary motor and premotor cortices of the unaffected hemisphere were compared prior to and following six sessions of cathodal transcranial direct current stimulation application in 13 patients (active = 6; sham = 7); this modality targets the primary motor cortex of the unaffected hemisphere early after a stroke. RESULTS: Clinically relevant distinctions in Fugl-Meyer Assessment scores (≥9 points) were observed more frequently in the Sham Group than in the Active Group. Between-group differences in the alterations in Fugl-Meyer Assessment scores were not statistically significant (Mann-Whitney test, p=0.133). ROI-to-ROI correlations between the primary motor cortices of the affected and unaffected hemispheres post-therapeutically increased in 5/6 and 2/7 participants in the Active and Sham Groups, respectively. Between-group differences in modifications in connectivity between the aforementioned areas were not statistically significant. Motor performance enhancements were more frequent in the Sham Group compared to the Active Group. CONCLUSION: The results of this hypothesis-generating investigation suggest that heightened connectivity may not translate into early clinical benefits following a stroke and will be crucial in designing larger cohort studies to explore mechanisms underlying the impacts of this intervention. ClinicalTrials.gov Identifier: NCT02455427.

Muscle quality and major adverse cardiovascular events in post-acute myocardial infarction: A prospective cohort study.

BACKGROUND & AIMS: Functional muscle quality, as assessed through the muscle quality index (MQI), represents a contemporary method to measure the capacity to generate force. Despite its potential, the prognostic significance of MQI remains uncertain in various clinical conditions, particularly among patients following acute myocardial infarction (AMI). In light of this, our study sought to evaluate the prognostic relevance of MQI concerning major adverse cardiovascular events (MACE) in patients following AMI. METHODS AND RESULTS: This is a secondary analysis of a prospective cohort study that included subjects aged ≥20 years from a Cardiovascular Unit Hospital. Functional muscle quality was estimated using MQI, defined as the ratio of handgrip strength (HGS) to muscle mass (MM) derived from bioelectrical impedance analysis. The outcomes included prolonged length of hospital stay, new adverse cardiovascular events (AMI, stroke and hospital readmission for unstable angina), and cardiovascular mortality. A composite score comprising all adverse events over the 1-year follow-up was calculated and defined as MACE. This study included 163 patients, with a median age of 61 years (IQ: 54-69 years), and the majority consisted of males (76.1%). Individual components of the functional muscle quality (HGS and MM) were not associated with any of the adverse outcomes. Only MQI was associated mortality over the 1-year follow-up. For each increase in MQI, the hazard of mortality decreases: adjusted HR: 0.08 (95% CI 0.01-0.84). CONCLUSION: Functional muscle quality assessed by the MQI may be a valuable clinical predictor of 1-year cardiovascular mortality in patients hospitalized post-AMI.

Acute predictors of self-rated health in individuals with stroke at 3 and 12 months after hospital discharge.

BACKGROUND: Self-rated health (SRH) is the perception of an individual regarding their health and an indicator of health status. Identifying predictors of SRH allows the selection of evidence-based interventions that mitigate factors leading to poor SRH and the identification of individuals at risk of worse SRH. OBJECTIVE: To determine the acute predictors of general and time-comparative SRH of individuals with stroke at 3 and 12 months after hospital discharge, considering personal, physical, and mental functions. METHODS: A prospective study was developed to assess general and time-comparative SRH at 3 and 12 months after hospital discharge according to 2 questions ("In general, how would you say your health is?" and "Compared to a year ago, how would you rate your general health now?"). Potential acute predictors analyzed were personal (age, sex, comorbidities, socioeconomic status, and family arrangement), physical (stroke severity, motor impairment, and independence for basic activities of daily living [ADLs]), and mental (cognitive) functions. RESULTS: Age (adjusted odds ratio [aOR]=2.10) and independence in basic ADLs (aOR=0.29) were significant predictors of SRH at 3 months; at 12 months, no significant predictor was found. Motor impairment (aOR=3.90) was a significant predictor of time-comparative SRH at 3 months; at 12 months, sex (aOR=0.36) and independence in basic ADLs (aOR=0.32) were significant predictors. CONCLUSIONS: At 3 months, individuals with stroke who were ≥65 years old and dependent on basic ADLs were more likely to have worse general SRH, while those with higher motor impairments were more likely to have worse time-comparative SRH. At 12 months, women and individuals dependent on basic ADLs were more likely to have worse time-comparative SRH.

Acute clinical outcomes predict both generic and specific health-related quality of life six and 12 months after stroke: A one-year prospective study developed in a middle-income country.

OBJECTIVE: To identify acute predictors of generic and specific health-related quality of life (HRQoL) six and 12 months after stroke in individuals from a middle-income country. MATERIAL AND METHODS: This was a prospective study. The dependent outcomes assessed during six and 12 months after stroke included both generic and specific HRQoL (Short Form Health Survey-36 [SF-36] and stroke-specific quality of life [SSQOL]). The predictors were age, sex, education level, length of hospital stay, current living arrangement, stroke severity, functional independence, and motor impairment. RESULTS: 122 (59.9±14 years) and 103 (59.8±14.71 years) individuals were evaluated six and 12 months after stroke, respectively. Functional independence and sex were significant acute predictors of both generic and specific HRQoL. Functional independence was the strongest predictor (0.149≤R2≤0.262; 20.01≤F≤43.96, p<0.001), except for generic HRQoL at 12 months, where sex was the strongest predictor (R2=0.14; F=17.97, p<0.001). CONCLUSION: Generic and specific HRQoL in chronic individuals six and 12 months after stroke, from a middle-income country, can be predicted based on functional independence, the strongest predictor, assessed in the acute phase, except for generic HRQoL at 12 months. Functional independence can be modified by rehabilitation strategies and thus should be considered for HRQoL prognoses at chronic phase.

Presence of Self-Reported Sleep Alterations After Stroke and Their Relationship With Disability: A Longitudinal Study.

BACKGROUND: Sleep disorders have a prevalence of 30% to 70% in post-stroke individuals. The presence of sleep disorders and poor sleep quality after stroke can affect important functions and lead to worse outcomes. However, most studies are restricted to the acute post-stroke stage only. OBJECTIVE: To investigate the frequency of self-reported sleep alterations in a sample of chronic stroke individuals and to identify which self-reported sleep alterations were associated with disability. METHODS: Prospective exploratory study. Self-reported sleep alterations were measured by the Pittsburgh Sleep Quality Index, Insomnia Severity Index, Epworth Sleepiness Scale, and STOP-Bang Questionnaire. The dependent variable was measured 3 years after the first contact by the Modified Rankin Scale (mRS). Step-wise multiple linear regression analysis was employed to identify which sleep alterations were associated with disability. RESULTS: Sixty-five individuals with stroke participated. About 67.7% of participants had poor sleep quality, 52.4% reported insomnia symptoms, 33.9% reported excessive daytime sleepiness, and 80.0% were classified as intermediate or high risk for obstructive sleep apnea. Only risk for obstructive sleep apnea was significantly associated with disability and explained 5% of the variance in the mRS scores. CONCLUSION: Self-reported sleep alterations had a considerable frequency in a sample of chronic stroke individuals. The risk of obstructive sleep apnea was associated with disability in the chronic stage of stroke. Sleep alterations must be considered and evaluated in the rehabilitation process even after a long period since the stroke onset.

Repetitive peripheral sensory stimulation for motor recovery after stroke: a scoping review.

BACKGROUND AND PURPOSE: Enhancing afferent information from the paretic limb can improve post-stroke motor recovery. However, uncertainties exist regarding varied sensory peripheral neuromodulation protocols and their specific impacts. This study outlines the use of repetitive peripheral sensory stimulation (RPSS) and repetitive magnetic stimulation (rPMS) in individuals with stroke. METHODS: This scoping review was conducted according to the JBI Evidence Synthesis guidelines. We searched studies published until June 2023 on several databases using a three-step analysis and categorization of the studies: pre-analysis, exploration of the material, and data processing. RESULTS: We identified 916 studies, 52 of which were included (N = 1,125 participants). Approximately 53.84% of the participants were in the chronic phase, displaying moderate-to-severe functional impairment. Thirty-two studies used RPSS often combining it with task-oriented training, while 20 used rPMS as a standalone intervention. The RPSS primarily targeted the median and ulnar nerves, stimulating for an average of 92.78 min at an intensity that induced paresthesia. RPMS targeted the upper and lower limb paretic muscles, employing a 20 Hz frequency in most studies. The mean stimulation time was 12.74 min, with an intensity of 70% of the maximal stimulator output. Among the 114 variables analyzed in the 52 studies, 88 (77.20%) were in the "s,b" domain, with 26 (22.8%) falling under the "d" domain of the ICF. DISCUSSION AND CONCLUSION: Sensory peripheral neuromodulation protocols hold the potential for enhancing post-stroke motor recovery, yet optimal outcomes were obtained when integrated with intensive or task-oriented motor training.

Effects of eccentric strength training on motor function in individuals with stroke: a scoping review.

BACKGROUND: Preliminary evidence suggests that eccentric strength training (ECC) improves muscle strength and postural control in individuals with stroke; however, the evidence about the effects of ECC in people living with stroke has not been systematically analyzed. OBJECTIVE: To determine the effects of ECC, compared to other exercise modalities (i.e., concentric training), on motor function in individuals with stroke. METHODS: This scoping review was performed according to PRISMA extension for scoping reviews. Until March 2023, a comprehensive search of studies using ECC intervention to improve motor functions in individuals with stroke was performed. Study designs included were randomized and non-randomized controlled trials and quasi-experimental studies using MEDLINE, Web of Science, Rehabilitation & Sports Medicine, PEDro, and OTSeeker databases. Two independent reviewers selected articles based on title and abstract and extracted relevant information from the eligible studies. The results were qualitatively synthesized, and the critical appraisal was performed using the Rob 2.0 and Robins-I tools. RESULTS: Ten studies, with 257 individuals, were analyzed. ECC revealed positive effects on muscle strength, muscular activity, balance, gait speed, and functionality, mainly compared with concentric training, physical therapy, and daily routine. No significant adverse events were reported during ECC. The critical appraisal of individual articles ranged from some to high concern. CONCLUSION: ECC had a greater and positive effect on motor function in individuals with stroke than other exercise modalities. However, the limited number of studies, variability of outcomes, and the risk of bias produced a low certainty of evidence.

Improvement of gait and balance function in chronic post-stroke patients induced by Lower Extremity - Constraint Induced Movement Therapy: a randomized controlled clinical trial.

OBJECTIVE: To evaluate the effects of Lower Extremity - Constraint Induced Movement Therapy on gait function and balance in chronic hemiparetic patients. METHODS: Randomized, controlled, single-blinded study. We recruited chronic post stroke patients and allocated them to Lower Extremity - Constraint Induced Movement Tharapy (LE-CIMT) or Control Group. The LE-CIMT group received this protocol 2.5 hour/day for 15 followed days, including: 1) intensive supervised training, 2) use of shaping as a strategy for motor training, and 3) application of a transfer package. The control group received conventional physiotherapy for 2.5 hours/day for 15 followed days. Outcomes were assessed at baseline, after the interventions, and after 6 months, through 6-minute walk test and Mini-Balance Evaluation Systems Test; 10-meter walk test, Timed Up and Go, 3-D gait analysis, and Lower Extremity - Motor Activity Log. RESULTS: LE-CIMT was superior on the Assistance and confidence subscale of Lower Extremity - Motor Activity Log, Mini-BESTest and 6-minute walk test. The effect size for all outcomes was small when comparing both groups. LE-CIMT showed clinically significant differences in daily activities, balance, and gait capacity, with no clinically significant difference for spatiotemporal parameters. CONCLUSION: The LE-CIMT protocol had positive outcomes on balance, performance, and confidence perception.

Resting-state EEG as Biomarker of Maladaptive Motor Function and Depressive Profile in Stroke Patients.

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.

R3-Walk and R6-Walk, Simple Clinical Equations to Accurately Predict Independent Walking at 3 and 6 Months After Stroke: A Prospective, Cohort Study.

OBJECTIVE: To investigate if independent walking at 3 and 6 months poststroke can be accurately predicted within the first 72 hours, based on simple clinical bedside tests. DESIGN: Prospective observational cohort study with 3-time measurements: immediately after stroke, and 3 and 6 months poststroke. SETTING: Public hospital. PARTICIPANTS: Adults with first-ever stroke evaluated at 3 (N=263) and 6 (N=212) months poststroke. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: The outcome of interest was independent walking at 3 and 6 months after stroke. Predictors were age, walking ability, lower limb strength, motor recovery, spatial neglect, continence, and independence in activities of daily living. RESULTS: The equation for predicting walking 3 months poststroke was 3.040 + (0.283 × FAC baseline) + (0.021 × Modified Barthel Index), and for predicting walking 6 months poststroke was 3.644 + (-0.014 × age) + (0.014 × Modified Barthel Index). For walking ability 3 months after stroke, sensitivity was classified as high (91%; 95% CI: 81-96), specificity was moderate (57%; 95% CI: 45-69), positive predictive value was high (76%; 95% CI: 64-86), and negative predictive value was high (80%; 95% CI: 60-93). For walking ability 6 months after stroke, sensitivity was classified as moderate (54%; 95% CI: 47-61), specificity was high (81%; 95% CI: 61-92), positive predictive value was high (87%; 95% CI: 70-96), and negative predictive value was low (42%; 95% CI: 50-73). CONCLUSIONS: This study provided 2 simple equations that predict walking ability 3 and 6 months after stroke. This represents an important step to accurately identify individuals, who are at high risk of walking dependence early after stroke.

Exoesqueletos para la recuperación funcional de la marcha en pacientes con patologías del sistema nervioso central como la esclerosis múltiple, ictus y/o lesiones medulares post-traumatismo / Exoskeletons for the functional recovery of walking ability in patients with central nervous system disorders such as multiple sclerosis, stroke, and traumatic spinal injury

INTRODUCCIÓN: La rehabilitación robótica de la marcha, conocida como Robot-Assisted Gait Therapy, ha surgido como una alternativa innovadora a la rehabilitación convencional de la marcha. Esta terapia ofrece un enfoque de rehabilitación controlada, repetitiva e intensiva, permitiendo una evaluación objetiva del progreso de los pacientes. La rehabilitación de la marcha es especialmente relevante en pacientes con trastornos del sistema nervioso central, como la esclerosis múltiple, ictus o lesión medular. Estas condiciones pueden provocar una pérdida significativa de la capacidad motora y afectar la calidad de vida de los pacientes. Los exoesqueletos pueden ser utilizados en la rehabilitación de estos pacientes, buscando mejorar los patrones de marcha y mitigar los síntomas asociados. En resumen, la rehabilitación robótica de la marcha mediante exoesqueletos para las extremidades inferiores ofrece una opción terapéutica innovadora para mejorar la funcionalidad y la independencia en la marcha de los pacientes con trastornos del sistema nervioso central. Este informe busca proporcionar una evaluación completa de estos dispositivos en la rehabilitación de la marcha, centrándose en pacientes con esclerosis múltiple, ictus y lesión medular. OBJETIVOS: 1) Identificar, sintetizar, analizar y evaluar la evidencia científica disponible sobre la efectividad y seguridad de los exoesqueletos para la recuperación

INTRODUCTION: Robot-assisted gait training has emerged as an innovative alternative to conventional gait rehabilitation. The focus of this type of training is highly-controlled intensive repetitive rehabilitation, enabling objective evaluation of patient progress. Gait rehabilitation is key in patients with central nervous system damage such as that associated with multiple sclerosis, stroke, and spinal injury. These conditions can cause significant loss of motor function, and hence, impair patient quality of life. Exoskeletons may be used in the rehabilitation of these patients, seeking to improve gait patterns and ameliorate associated symptoms. In brief, robot-assisted gait rehabilitation using lower-extremity exoskeletons is an innovative treatment option for improving gait function and independence in patients with central nervous system damage. This report aims to provide a complete assessment of these gait rehabilitation devices, with a focus on patients with multiple sclerosis, stroke, or spinal injury. AIMS: 1) To identify, synthetise, analyse and evaluate the scientific evidence available concerning the efficacy/effectiveness and safety of exoskeletons for functional gait recovery in adult patients with central nervous system damage associated with multiple scl

Effects of central intermittent theta-burst stimulation combined with repetitive peripheral magnetic stimulation on upper limb function in stroke patients.

Background: Intermittent theta-burst stimulation and repetitive peripheral magnetic stimulation can improve motor function in poststroke patients, but the therapeutic effect of this combination remains unclear. Objective: To determine the effects of central intermittent theta-burst stimulation and repetitive peripheral magnetic stimulation on upper limb function. Methods: Fifty-six subacute stroke patients were randomly assigned to three groups: the CMS (n = 18), peripheral magnetic stimulation (PMS) (n = 19) and CPS (n = 19) groups. The CMS group received intermittent theta-burst stimulation and peripheral false stimulation, while the PMS group received repetitive peripheral magnetic stimulation and central false stimulation once a day for five days a week over four weeks. The CPS group received intermittent theta-burst stimulation and repetitive peripheral magnetic stimulation simultaneously once daily for four weeks. The Fugl-Meyer Assessment, Action Research Arm Test, Modified Barthel Index and Modified Ashworth Scale evaluated outcomes before and after four weeks of treatment. Results: The motor function scores of all groups were significantly increased after treatment compared with before treatment, while the Modified Ashworth Scale score showed no significant change. There was a significant difference in the motor function score of the CPS group compared with that of the CMS and PMS groups, but there was no significant improvement in the Modified Ashworth Scale score. Conclusion: Combining the two treatment methods can improve patients' motor function and daily living abilities but cannot improve muscle tone.

Antecedentes: La estimulación intermitente de theta-burst y la estimulación magnética periférica repetitiva pueden mejorar la función motora en pacientes postictus, pero el efecto terapéutico de esta combinación sigue sin estar claro. Objetivo: Determinar el efecto de la estimulacion central intermitente theta-burst y la estimulación magnética repetitiva periférica en la función del miembro superior. Métodos: Se asignaron aleatoriamente a tres grupos 56 pacientes con ictus subagudo: CMS (n = 18), estimulación magnética periferica (PMS) (n = 19) y CPS(Cm1) (n = 19). El grupo CMS recibió estimulación intermitente de theta-burst y falsa estimulación periférica, el grupo PMS recibió estimulación magnética periférica repetitiva y falsa estimulación central una vez al día durante cinco días a la semana a lo largo de cuatro semanas. El grupo SPC recibió estimulación intermitente theta-burst y estimulación magnética periférica repetitiva simultáneamente una vez al día durante cuatro semanas. Se utilizaron la Fugl-Meyer Assessment, Action Research Arm Test, Modified Barthel Index and Modified Ashworth Scale para evaluar losresultados antes y después de cuatro semanas de tratamiento. Resultados: Las puntuaciones de la función motora de todos los grupos aumentaron significativamente después del tratamiento en comparación con antes del tratamiento, mientras que la puntuación de la Escala de Ashworth Modificada no mostró cambios significativos. Hubo una diferencia significativa en la puntuación de la función motora del grupo CPS en comparación con la de los grupos CMS y PMS, pero no hubo una mejora significativa en la puntuación de la Escala de Ashworth Modificada. Conclusiones: La combinación de los dos métodos de tratamiento puede mejorar la función motora y las capacidades de la vida diaria de los pacientes, pero no puede mejorar el tono muscular.

Association of Proinflammatory Cytokine Levels with Stroke Severity, Infarct Size, and Muscle Strength in the Acute Phase of Stroke.

OBJECTIVE: Patterns of cytokine levels and their association with stroke severity, infarct size, and muscle strength are obscure. We aimed to analyze the immune mediators linked to T helper (Th)1, Th2, Th17, and regulatory T cell patterns and their association with stroke severity, infarct size, and muscle strength. MATERIALS AND METHODS: We included patients with acute stroke (n = 15) and healthy non-disabled individuals (n = 20) aged > 18 years. The dependent variables were stroke severity according to the National Institute of Health Stroke Scale (NIHSS), infarct size on computed tomography, handgrip strength by dynamometry, and global muscle strength according to the Medical Research Council (MRC) scale. The independent variables were the circulating cytokine levels. The cytokine levels were compared between the groups, and correlations between the clinical data were verified. RESULTS: The stroke group had higher interleukin (IL)-6 (p < 0.0001) and IL-10 (p < 0.0001) levels, but lower tumor necrosis factor (TNF)-α (p = 0.036) levels than the control group. IL-10 and soluble tumor necrosis factor receptor (sTNF-RII) levels were correlated with each other (r = 0.533; p = 0.042) and infarct size (r = 0.653; p = 0.033 and r = 0.689; p = 0.018, respectively). MRC scores were positively and negatively correlated with handgrip strength of the affected side (r = 0.78; p = 0.001) and NIHSS scores (r = -0.87; p < 0.0001), respectively. CONCLUSIONS: Plasma levels of some cytokines were associated with changes in the acute phase of stroke, and IL-10 and sTNF-RII levels are potential biomarkers of infarct size.

Review of studies on dynamic cerebral autoregulation in the acute phase of stroke and the relationship with clinical outcome.

Acute stroke is associated with high morbidity and mortality. In the last decades, new therapies have been investigated with the aim of improving clinical outcomes in the acute phase post stroke onset. However, despite such advances, a large number of patients do not demonstrate improvement, furthermore, some unfortunately deteriorate. Thus, there is a need for additional treatments targeted to the individual patient. A potential therapeutic target is interventions to optimize cerebral perfusion guided by cerebral hemodynamic parameters such as dynamic cerebral autoregulation (dCA). This narrative led to the development of the INFOMATAS (Identifying New targets FOr Management And Therapy in Acute Stroke) project, designed to foster interventions directed towards understanding and improving hemodynamic aspects of the cerebral circulation in acute cerebrovascular disease states. This comprehensive review aims to summarize relevant studies on assessing dCA in patients suffering acute ischemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage. The review will provide to the reader the most consistent findings, the inconsistent findings which still need to be explored further and discuss the main limitations of these studies. This will allow for the creation of a research agenda for the use of bedside dCA information for prognostication and targeted perfusion interventions.

Gait, balance, and functional independence level in stroke patients

Introduction: Most stroke patients present limited movement, which alters gait speed and balance. This study aimed to correlate balance and gait speed, and weight distribution and balance in post-stroke patients.Methods: In total, 36 participants were included. Data collection occurred as follows: filling out the assessment form; assessment with the Berg Balance Scale (BBS); assessment with the baropodometric platform; performing the 10 Meter Walk Test (10mWT) with accelerometer; measurements with the modified Rankin Scale (mRS); the Functional Ambulation Classification (FAC); and the Barthel Index (BI).Results: A negative correlation between FAC and mRS (r = −0.708; p < 0.05) and between BI and mRS (r = −0.716; p < 0.05) was found. The correlation between BI and FAC was positive (r = 0.591). There was a strong positive correlation between the 10mWT values and the BBS score (r = 0.708; p < 0.05). Moreover, a weak negative correlation was observed between BBS values and lower limb weight distribution (r = −0.378; p < 0.05).Conclusion: We found a correlation between the functional ambulation and the degree of independence.This study showed that the better the balance, the greater the gait speed, and the lower the difference on lower limbs weight distribution, the better the balance in post-stroke patients.