Comparing a Novel Neuroanimation Experience to Conventional Therapy for High-Dose Intensive Upper-Limb Training in Subacute Stroke: The SMARTS2 Randomized Trial

BACKGROUND Evidence from animal studies suggests that greater reductions in poststroke motor impairment can be attained with significantly higher doses and intensities of therapy focused on movement quality. These studies also indicate a dose-timing interaction, with more pronounced effects if high-intensity therapy is delivered in the acute/subacute, rather than chronic, poststroke period. OBJECTIVE To compare 2 approaches of delivering high-intensity, high-dose upper-limb therapy in patients with subacute stroke: a novel exploratory neuroanimation therapy (NAT) and modified conventional occupational therapy (COT). METHODS A total of 24 patients were randomized to NAT or COT and underwent 30 sessions of 60 minutes time-on-task in addition to standard care. The primary outcome was the Fugl-Meyer Upper Extremity motor score (FM-UE). Secondary outcomes included Action Research Arm Test (ARAT), grip strength, Stroke Impact Scale hand domain, and upper-limb kinematics. Outcomes were assessed at baseline, and days 3, 90, and 180 posttraining. Both groups were compared to a matched historical cohort (HC), which received only 30 minutes of upper-limb therapy per day. RESULTS There were no significant between-group differences in FM-UE change or any of the secondary outcomes at any timepoint. Both high-dose groups showed greater recovery on the ARAT (7.3 ± 2.9 points; P = .011) but not the FM-UE (1.4 ± 2.6 points; P = .564) when compared with the HC. CONCLUSIONS Neuroanimation may offer a new, enjoyable, efficient, and scalable way to deliver high-dose and intensive upper-limb therapy

Corticospinal and intracortical responses from both motor cortices following unilateral concentric versus eccentric contractions

Cross-education is the phenomenon where training of one limb can cause neuromuscular adaptations in the opposite untrained limb. This effect has been reported to be greater after eccentric (ECC) than concentric (CON) strength training; however, the underpinning neurophysiological mechanisms remain unclear. Thus, we compared responses to transcranial magnetic stimulation (TMS) in both motor cortices following single sessions of unilateral ECC and CON exercise of the elbow flexors. Fourteen healthy adults performed three sets of 10 ECC and CON right elbow flexor contractions at 75 % of respective maximum on separate days. Elbow flexor maximal voluntary isometric contraction (MVIC) torques were measured before and after exercise, and responses to single- and paired-pulse TMS were recorded from the non-exercised left and exercised right biceps brachii. Pre-exercise and post-exercise responses for ECC and CON were compared by repeated measures analyses of variance (ANOVAs). MVIC torque of the exercised arm decreased (p \u3c 0.01) after CON ( − 30 ± 14 %) and ECC ( − 39 ± 13 %) similarly. For the non-exercised left biceps brachii, resting motor threshold (RMT) decreased after CON only ( − 4.2 ± 3.9 % of maximum stimulator output [MSO], p \u3c 0.01), and intracortical facilitation (ICF) decreased (−15.2 ± 20.0 %, p = 0.038) after ECC only. For the exercised right biceps, RMT increased after ECC (8.6 ± 6.2 % MSO, p = 0.014) but not after CON (6.4 ± 8.1% MSO, p = 0.066). Thus, unilateral ECC and CON elbow flexor exercise modulated excitability differently for the non-exercised hemisphere. These findings suggest that responses after a single bout of exercise may not reflect longer term adaptations

Gait training with haptic feedback assistance

Aquest treball serveix com a prova de concepte per desenvolupar un cinturó basat en retroalimentació hàptica per fomentar l'exploració de la marxa humana. La rehabilitació actual i l'entrenament de dispositius assistits depèn de la repetició de moviments invariables. Contràriament, es troben estudis que demostren que entrenar amb una major variabilitat pot millorar l'adquisició d'aprenentatge motor i l'actuació de l'individu durant la realització de noves tasques. En conseqüència, és probable que entrenar l'habilitat de l'usuari per explorar nous moviments sigui beneficiós per poder aprofitar al màxim la tecnologia assistida. El dispositiu presentat en aquest treball de fi de grau fa un seguiment de la seva pròpia posició i, depenent de la seva localització, vibra un dels dos motors vibrotàctils que té instal·lats per tal de notificar a l'usuari. Aquesta investigació serveix com a base per futurament crear un dispositiu que guiarà als usuaris a explorar un rang de moviment més divers i, per tant, executar moviments més variables. La versió futura del dispositiu podria ajudar a persones amb discapacitat a explorar les seves vies de control motor aconseguint així que es puguin adaptar més fàcilment a noves tasques, com per exemple, adaptar-se a portar un exoesquelet.Este trabajo sirve como prueba de concepto para desarrollar un cinturón basado en retroalimentación háptica para fomentar la exploración de la marcha humana. La rehabilitación actual y el entrenamiento de dispositivos asistidos depende de la repetición de movimientos invariables. Por el contrario, existen estudios que demuestran que entrenar con una mayor variabilidad puede mejorar la adquisición de aprendizaje motor y la actuación del individuo durante la realización de nuevas tareas. En consecuencia, es probable que entrenar la habilidad del usuario para explorar nuevos movimientos sea beneficioso para poder aprovechar al máximo la tecnología asistida. El dispositivo presentado en este trabajo de final de grado hace un rastreo de su propia posición y, dependiendo de su localización, vibra uno de los dos motores vibrotáctiles que incorpora con la finalidad de notificar al usuario. Esta investigación sirve como base para futuramente crear un dispositivo que guiará a los usuarios a explorar un rango de movimiento más diverso y, por tanto, ejecutar movimientos más variables. La versión futura del dispositivo podría ayudar a personas con discapacidad a explorar sus vías de control motor, consiguiendo así que se puedan adaptar más fácilmente a nuevas tareas, como por ejemplo, adaptarse al uso de un exoesqueleto.This work serves as a proof of concept for developing a haptic feedback hip belt to encourage gait exploration. Current rehabilitation and assistive device training relies on repeating consistent movements. In contrast, past work has shown that training with increased variability can improve motor learning and performance of new tasks. Consequently, it is likely that training user ability to explore new movements is beneficial to taking full advantage of assistive technology. The device presented in this thesis tracks its own position and, depending on its location, vibrates one of two vibrotactile motors to give instructions to the user. This work serves as a basis for further development of a device that will guide users to explore a more diverse range of motion and to perform variable movements. The future device could help people with disabilities explore their motor control pathways and more easily adapt to novel tasks (such as adapting to an exoskeleton).Outgoin

Time to reconcile research findings and clinical practice on upper limb neurorehabilitation

In the field of upper limb neurorehabilitation, the translation from research findings to clinical practice remains troublesome. Patients are not receiving treatments based on the best available evidence. There are certainly multiple reasons to account for this issue, including the power of habit over innovation, subjective beliefs over objective results. We need to take a step forward, by looking at most important results from randomized controlled trials, and then identify key active ingredients that determined the success of interventions. On the other hand, we need to recognize those specific categories of patients having the greatest benefit from each intervention, and why. The aim is to reach the ability to design a neurorehabilitation program based on motor learning principles with established clinical efficacy and tailored for specific patient's needs. The objective of the present manuscript is to facilitate the translation of research findings to clinical practice. Starting from a literature review of selected neurorehabilitation approaches, for each intervention the following elements were highlighted: definition of active ingredients; identification of underlying motor learning principles and neural mechanisms of recovery; inferences from research findings; and recommendations for clinical practice. Furthermore, we included a dedicated chapter on the importance of a comprehensive assessment (objective impairments and patient's perspective) to design personalized and effective neurorehabilitation interventions. It's time to reconcile research findings with clinical practice. Evidence from literature is consistently showing that neurological patients improve upper limb function, when core strategies based on motor learning principles are applied. To this end, practical take-home messages in the concluding section are provided, focusing on the importance of graded task practice, high number of repetitions, interventions tailored to patient's goals and expectations, solutions to increase and distribute therapy beyond the formal patient-therapist session, and how to integrate different interventions to maximize upper limb motor outcomes. We hope that this manuscript will serve as starting point to fill the gap between theory and practice in upper limb neurorehabilitation, and as a practical tool to leverage the positive impact of clinicians on patients' recovery

Time to reconcile research findings and clinical practice on upper limb neurorehabilitation

The problemIn the field of upper limb neurorehabilitation, the translation from research findings to clinical practice remains troublesome. Patients are not receiving treatments based on the best available evidence. There are certainly multiple reasons to account for this issue, including the power of habit over innovation, subjective beliefs over objective results. We need to take a step forward, by looking at most important results from randomized controlled trials, and then identify key active ingredients that determined the success of interventions. On the other hand, we need to recognize those specific categories of patients having the greatest benefit from each intervention, and why. The aim is to reach the ability to design a neurorehabilitation program based on motor learning principles with established clinical efficacy and tailored for specific patient's needs. Proposed solutionsThe objective of the present manuscript is to facilitate the translation of research findings to clinical practice. Starting from a literature review of selected neurorehabilitation approaches, for each intervention the following elements were highlighted: definition of active ingredients; identification of underlying motor learning principles and neural mechanisms of recovery; inferences from research findings; and recommendations for clinical practice. Furthermore, we included a dedicated chapter on the importance of a comprehensive assessment (objective impairments and patient's perspective) to design personalized and effective neurorehabilitation interventions. ConclusionsIt's time to reconcile research findings with clinical practice. Evidence from literature is consistently showing that neurological patients improve upper limb function, when core strategies based on motor learning principles are applied. To this end, practical take-home messages in the concluding section are provided, focusing on the importance of graded task practice, high number of repetitions, interventions tailored to patient's goals and expectations, solutions to increase and distribute therapy beyond the formal patient-therapist session, and how to integrate different interventions to maximize upper limb motor outcomes. We hope that this manuscript will serve as starting point to fill the gap between theory and practice in upper limb neurorehabilitation, and as a practical tool to leverage the positive impact of clinicians on patients' recovery

Wearable Robotics for Impaired Upper-Limb Assistance and Rehabilitation: State of the Art and Future Perspectives

Despite more than thirty-five years of research on wearable technologies to assist the upper-limb and a multitude of promising preliminary results, the goal of restoring pre-impairment quality of life of people with physical disabilities has not been fully reached yet. Whether it is for rehabilitation or for assistance, nowadays robotics is still only used in a few high-tech clinics and hospitals, limiting the access to a small amount of people. This work provides a description of the three major 'revolutions' occurred in the field (end-effector robots, rigid exoskeletons, and soft exosuits), reviewing forty-eight systems for the upper-limb (excluding hand-only devices) used in eighty-nine studies enrolling a clinical population before June 2022. The review critically discusses the state of the art, analyzes the different technologies, and compares the clinical outcomes, with the goal of determine new potential directions to follow

Time to reconcile research findings and clinical practice on upper limb neurorehabilitation

The problemIn the field of upper limb neurorehabilitation, the translation from research findings to clinical practice remains troublesome. Patients are not receiving treatments based on the best available evidence. There are certainly multiple reasons to account for this issue, including the power of habit over innovation, subjective beliefs over objective results. We need to take a step forward, by looking at most important results from randomized controlled trials, and then identify key active ingredients that determined the success of interventions. On the other hand, we need to recognize those specific categories of patients having the greatest benefit from each intervention, and why. The aim is to reach the ability to design a neurorehabilitation program based on motor learning principles with established clinical efficacy and tailored for specific patient's needs.Proposed solutionsThe objective of the present manuscript is to facilitate the translation of research findings to clinical practice. Starting from a literature review of selected neurorehabilitation approaches, for each intervention the following elements were highlighted: definition of active ingredients; identification of underlying motor learning principles and neural mechanisms of recovery; inferences from research findings; and recommendations for clinical practice. Furthermore, we included a dedicated chapter on the importance of a comprehensive assessment (objective impairments and patient's perspective) to design personalized and effective neurorehabilitation interventions.ConclusionsIt's time to reconcile research findings with clinical practice. Evidence from literature is consistently showing that neurological patients improve upper limb function, when core strategies based on motor learning principles are applied. To this end, practical take-home messages in the concluding section are provided, focusing on the importance of graded task practice, high number of repetitions, interventions tailored to patient's goals and expectations, solutions to increase and distribute therapy beyond the formal patient-therapist session, and how to integrate different interventions to maximize upper limb motor outcomes. We hope that this manuscript will serve as starting point to fill the gap between theory and practice in upper limb neurorehabilitation, and as a practical tool to leverage the positive impact of clinicians on patients' recovery

Contribution of SMN Deficient Skeletal Muscle to Spinal Muscular Atrophy

The autosomal recessively inherited motor neuron disease spinal muscular atrophy (SMA) is caused by reduced expression of survival motor neuron (SMN) protein. Although SMN is ubiquitously expressed, it remains unresolved whether SMA disease manifestations are caused by SMN deficiency only in motor neurons, or whether SMN deficiency in other cell types contributes to disease. This has particular relevance for SMA therapeutics as the splice switching antisense oligonucleotide (ASO) nusinersen, delivered by lumbar intrathecal injection, targets only the CNS, whereas the splice-switching small molecule risdiplam has widespread distribution. Our laboratory previously demonstrated that increased SMN expression in both motor neurons and skeletal muscle improved but did not completely rescue the SMA phenotype in severe SMA mice. Previous studies showed that SMN deficiency restricted to skeletal muscle caused muscle pathologies, weakness, and early lethality. Together these data suggest that cell autonomous defects of SMN-deficient skeletal muscle contribute to SMA disease manifestations. Nonetheless, the specific functional abnormalities of SMN-deficient muscle remain poorly characterized. We show that in a mouse model with skeletal muscle-specific knockdown of SMN, muscles exhibit reduced function in motor behavior assays and in physiological measurements of force production. These functional abnormalities are associated with a reduction in myofiber size and a reduced number of mitochondria, as well as a downregulation of mitochondrial genes that are involved in the electron transport chain. However, oxygen respiration assays reveal intact respiratory chain function and in more affected muscles an increase in oxygen consumption. These studies suggest that SMN deficiency in muscle alone leads to cell autonomous defects that contribute to disease manifestations, and SMN therapeutics that target both motor neurons and muscle may have enhanced benefit