The Promotoer, a brain-computer interface-assisted intervention to promote upper limb functional motor recovery after stroke: a statistical analysis plan for a randomized controlled trial

Background: Electroencephalography (EEG)-based brain-computer interfaces (BCIs) allow to modulate the sensorimotor rhythms and are emerging technologies for promoting post-stroke motor function recovery. The Promotoer study aims to assess the short and long-term efficacy of the Promotoer system, an EEG-based BCI assisting motor imagery (MI) practice, in enhancing post-stroke functional hand motor recovery. This paper details the statistical analysis plan of the Promotoer study. Methods: The Promotoer study is a randomized, controlled, assessor-blinded, single-centre, superiority trial, with two parallel groups and a 1:1 allocation ratio. Subacute stroke patients are randomized to EEG-based BCI-assisted MI training or to MI training alone (i.e. no BCI). An internal pilot study for sample size re-assessment is planned. The primary outcome is the effectiveness of the Upper Extremity Fugl-Meyer Assessment (UE-FMA) score. Secondary outcomes include clinical, functional, and user experience scores assessed at the end of intervention and at follow-up. Neurophysiological assessments are also planned. Effectiveness formulas have been specified, and intention-to-treat and per-protocol populations have been defined. Statistical methods for comparisons of groups and for development of a predictive score of significant improvement are described. Explorative subgroup analyses and methodology to handle missing data are considered. Discussion: The Promotoer study will provide robust evidence for the short/long-term efficacy of the Promotoer system in subacute stroke patients undergoing a rehabilitation program. Moreover, the development of a predictive score of response will allow transferring of the Promotoer system to optimal clinical practice. By carefully describing the statistical principles and procedures, the statistical analysis plan provides transparency in the analysis of data. Trial registration: ClinicalTrials.gov NCT04353297 . Registered on April 15, 2020

Feasibility of a second iteration wrist and hand supported training system for self-administered training at home in chronic stroke

Telerehabilitation allows continued rehabilitation at home after discharge. The use of rehabilitation technology supporting wrist and hand movements within a motivational gaming environment could enable patients to train independently and ultimately serve as a way to increase the dosage of practice. This has been previously examined in the European SCRIPT project using a first prototype, showing potential feasibility, although several usability issues needed further attention. The current study examined feasibility and clinical changes of a second iteration training system, involving an updated wrist and hand supporting orthosis and larger variety of games with respect to the first iteration. Nine chronic stroke patients with impaired arm and hand function were recruited to use the training system at home for six weeks. Evaluation of feasibility and arm and hand function were assessed before and after training. Median weekly training duration was 113 minutes. Participants accepted the six weeks of training (median Intrinsic Motivation Inventory = 4.4 points and median System Usability Scale = 73%). After training, significant improvements were found for the Fugl Meyer assessment, Action Research Arm Test and self-perceived amount of arm and hand use in daily life. These findings indicate that technology-supported arm and hand training can be a promising tool for self-administered practice at home after stroke.Final Accepted Versio

Home-based therapy programmes for upper limb functional recovery following stroke

Background: With an increased focus on home-based stroke services and the undertaking of programmes, targeted at upper limb recovery within clinical practice, a systematic review of home-based therapy programmes for individuals with upper limb impairment following stroke was required. Objectives: To determine the effects of home-based therapy programmes for upper limb recovery in patients with upper limb impairment following stroke. Search methods: We searched the Cochrane Stroke Group's Specialised Trials Register (May 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (1950 to May 2011), EMBASE (1980 to May 2011), AMED (1985 to May 2011) and six additional databases. We also searched reference lists and trials registers. Selection criteria: Randomised controlled trials (RCTs) in adults after stroke, where the intervention was a home-based therapy programme targeted at the upper limb, compared with placebo, or no intervention or usual care. Primary outcomes were performance in activities of daily living (ADL) and functional movement of the upper limb. Secondary outcomes were performance in extended ADL and motor impairment of the arm. Data collection and analysis: Two review authors independently screened abstracts, extracted data and appraised trials. We undertook assessment of risk of bias in terms of method of randomisation and allocation concealment (selection bias), blinding of outcome assessment (detection bias), whether all the randomised patients were accounted for in the analysis (attrition bias) and the presence of selective outcome reporting. Main results: We included four studies with 166 participants. No studies compared the effects of home-based upper limb therapy programmes with placebo or no intervention. Three studies compared the effects of home-based upper limb therapy programmes with usual care. Primary outcomes: we found no statistically significant result for performance of ADL (mean difference (MD) 2.85; 95% confidence interval (CI) -1.43 to 7.14) or functional movement of the upper limb (MD 2.25; 95% CI -0.24 to 4.73)). Secondary outcomes: no statistically significant results for extended ADL (MD 0.83; 95% CI -0.51 to 2.17)) or upper limb motor impairment (MD 1.46; 95% CI -0.58 to 3.51). One study compared the effects of a home-based upper limb programme with the same upper limb programme based in hospital, measuring upper limb motor impairment only; we found no statistically significant difference between groups (MD 0.60; 95% CI -8.94 to 10.14). Authors' conclusions: There is insufficient good quality evidence to make recommendations about the relative effect of home-based therapy programmes compared with placebo, no intervention or usual care

Functional Electrical Stimulation mediated by Iterative Learning Control and 3D robotics reduces motor impairment in chronic stroke

Background: Novel stroke rehabilitation techniques that employ electrical stimulation (ES) and robotic technologies are effective in reducing upper limb impairments. ES is most effective when it is applied to support the patients’ voluntary effort; however, current systems fail to fully exploit this connection. This study builds on previous work using advanced ES controllers, and aims to investigate the feasibility of Stimulation Assistance through Iterative Learning (SAIL), a novel upper limb stroke rehabilitation system which utilises robotic support, ES, and voluntary effort. Methods: Five hemiparetic, chronic stroke participants with impaired upper limb function attended 18, 1 hour intervention sessions. Participants completed virtual reality tracking tasks whereby they moved their impaired arm to follow a slowly moving sphere along a specified trajectory. To do this, the participants’ arm was supported by a robot. ES, mediated by advanced iterative learning control (ILC) algorithms, was applied to the triceps and anterior deltoid muscles. Each movement was repeated 6 times and ILC adjusted the amount of stimulation applied on each trial to improve accuracy and maximise voluntary effort. Participants completed clinical assessments (Fugl-Meyer, Action Research Arm Test) at baseline and post-intervention, as well as unassisted tracking tasks at the beginning and end of each intervention session. Data were analysed using t-tests and linear regression. Results: From baseline to post-intervention, Fugl-Meyer scores improved, assisted and unassisted tracking performance improved, and the amount of ES required to assist tracking reduced. Conclusions: The concept of minimising support from ES using ILC algorithms was demonstrated. The positive results are promising with respect to reducing upper limb impairments following stroke, however, a larger study is required to confirm this

Computational neurorehabilitation: modeling plasticity and learning to predict recovery

Despite progress in using computational approaches to inform medicine and neuroscience in the last 30 years, there have been few attempts to model the mechanisms underlying sensorimotor rehabilitation. We argue that a fundamental understanding of neurologic recovery, and as a result accurate predictions at the individual level, will be facilitated by developing computational models of the salient neural processes, including plasticity and learning systems of the brain, and integrating them into a context specific to rehabilitation. Here, we therefore discuss Computational Neurorehabilitation, a newly emerging field aimed at modeling plasticity and motor learning to understand and improve movement recovery of individuals with neurologic impairment. We first explain how the emergence of robotics and wearable sensors for rehabilitation is providing data that make development and testing of such models increasingly feasible. We then review key aspects of plasticity and motor learning that such models will incorporate. We proceed by discussing how computational neurorehabilitation models relate to the current benchmark in rehabilitation modeling – regression-based, prognostic modeling. We then critically discuss the first computational neurorehabilitation models, which have primarily focused on modeling rehabilitation of the upper extremity after stroke, and show how even simple models have produced novel ideas for future investigation. Finally, we conclude with key directions for future research, anticipating that soon we will see the emergence of mechanistic models of motor recovery that are informed by clinical imaging results and driven by the actual movement content of rehabilitation therapy as well as wearable sensor-based records of daily activity

A review of the effectiveness of lower limb orthoses used in cerebral palsy

To produce this review, a systematic literature search was conducted for relevant articles published in the period between the date of the previous ISPO consensus conference report on cerebral palsy (1994) and April 2008. The search terms were 'cerebral and pals* (palsy, palsies), 'hemiplegia', 'diplegia', 'orthos*' (orthoses, orthosis) orthot* (orthotic, orthotics), brace or AFO

Technology-assisted stroke rehabilitation in Mexico: a pilot randomized trial comparing traditional therapy to circuit training in a Robot/technology-assisted therapy gym

Background Stroke rehabilitation in low- and middle-income countries, such as Mexico, is often hampered by lack of clinical resources and funding. To provide a cost-effective solution for comprehensive post-stroke rehabilitation that can alleviate the need for one-on-one physical or occupational therapy, in lower and upper extremities, we proposed and implemented a technology-assisted rehabilitation gymnasium in Chihuahua, Mexico. The Gymnasium for Robotic Rehabilitation (Robot Gym) consisted of low- and high-tech systems for upper and lower limb rehabilitation. Our hypothesis is that the Robot Gym can provide a cost- and labor-efficient alternative for post-stroke rehabilitation, while being more or as effective as traditional physical and occupational therapy approaches. Methods A typical group of stroke patients was randomly allocated to an intervention (n = 10) or a control group (n = 10). The intervention group received rehabilitation using the devices in the Robot Gym, whereas the control group (n = 10) received time-matched standard care. All of the study subjects were subjected to 24 two-hour therapy sessions over a period of 6 to 8 weeks. Several clinical assessments tests for upper and lower extremities were used to evaluate motor function pre- and post-intervention. A cost analysis was done to compare the cost effectiveness for both therapies. Results No significant differences were observed when comparing the results of the pre-intervention Mini-mental, Brunnstrom Test, and Geriatric Depression Scale Test, showing that both groups were functionally similar prior to the intervention. Although, both training groups were functionally equivalent, they had a significant age difference. The results of all of the upper extremity tests showed an improvement in function in both groups with no statistically significant differences between the groups. The Fugl-Meyer and the 10 Meters Walk lower extremity tests showed greater improvement in the intervention group compared to the control group. On the Time Up and Go Test, no statistically significant differences were observed pre- and post-intervention when comparing the control and the intervention groups. For the 6 Minute Walk Test, both groups presented a statistically significant difference pre- and post-intervention, showing progress in their performance. The robot gym therapy was more cost-effective than the traditional one-to-one therapy used during this study in that it enabled therapist to train up to 1.5 to 6 times more patients for the approximately same cost in the long term. Conclusions The results of this study showed that the patients that received therapy using the Robot Gym had enhanced functionality in the upper extremity tests similar to patients in the control group. In the lower extremity tests, the intervention patients showed more improvement than those subjected to traditional therapy. These results support that the Robot Gym can be as effective as traditional therapy for stroke patients, presenting a more cost- and labor-efficient option for countries with scarce clinical resources and funding. Trial registration ISRCTN98578807

Biomechanics

Biomechanics is a vast discipline within the field of Biomedical Engineering. It explores the underlying mechanics of how biological and physiological systems move. It encompasses important clinical applications to address questions related to medicine using engineering mechanics principles. Biomechanics includes interdisciplinary concepts from engineers, physicians, therapists, biologists, physicists, and mathematicians. Through their collaborative efforts, biomechanics research is ever changing and expanding, explaining new mechanisms and principles for dynamic human systems. Biomechanics is used to describe how the human body moves, walks, and breathes, in addition to how it responds to injury and rehabilitation. Advanced biomechanical modeling methods, such as inverse dynamics, finite element analysis, and musculoskeletal modeling are used to simulate and investigate human situations in regard to movement and injury. Biomechanical technologies are progressing to answer contemporary medical questions. The future of biomechanics is dependent on interdisciplinary research efforts and the education of tomorrow’s scientists

Reinforced Feedback in Virtual Environment for Plantar Flexor Poststroke Spasticity Reduction and Gait Function Improvement

Background. Ankle spasticity is a frequent phenomenon that limits functionality in poststroke patients. Objectives. Our aim was to determine if there was decreased spasticity in the ankle plantar flex (PF) muscles in the plegic lower extremity (LE) and improvement of gait function in stroke patients after traditional rehabilitation (TR) in combination with virtual reality with reinforced feedback, which is termed "reinforced feedback virtual environment" (RFVE). Methods. The evaluation, before and after treatment, of 10 hemiparetic patients was performed using the Modified Ashworth Scale (MAS), Functional Ambulatory Category (FAC), and Functional Independence Measure (FIM). The intervention consisted of 1 hour/day of TR plus 1 hour/day of RFVE (5 days/week for 3 weeks; 15 sessions in total). Results. The MAS and FAC reached statistical significance (P<0.05). The changes in the FIM did not reach statistical significance (P=0.066). The analysis between the ischemic and haemorrhagic patients showed significant differences in favour of the haemorrhagic group in the FIM scale. A significant correlation between the FAC and the months after the stroke was established (P=-0.711). Indeed, patients who most increased their score on the FAC at the end of treatment were those who started the treatment earliest after stroke. Conclusions. The combined treatment of TR and RFVE showed encouraging results regarding the reduction of spasticity and improvement of gait function. An early commencement of the treatment seems to be ideal, and future research should increase the sample size and assessment tools