Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial.

Cervical spinal cord injury (SCI) leads to permanent impairment of arm and hand functions. Here we conducted a prospective, single-arm, multicenter, open-label, non-significant risk trial that evaluated the safety and efficacy of ARCEX Therapy to improve arm and hand functions in people with chronic SCI. ARCEX Therapy involves the delivery of externally applied electrical stimulation over the cervical spinal cord during structured rehabilitation. The primary endpoints were safety and efficacy as measured by whether the majority of participants exhibited significant improvement in both strength and functional performance in response to ARCEX Therapy compared to the end of an equivalent period of rehabilitation alone. Sixty participants completed the protocol. No serious adverse events related to ARCEX Therapy were reported, and the primary effectiveness endpoint was met. Seventy-two percent of participants demonstrated improvements greater than the minimally important difference criteria for both strength and functional domains. Secondary endpoint analysis revealed significant improvements in fingertip pinch force, hand prehension and strength, upper extremity motor and sensory abilities and self-reported increases in quality of life. These results demonstrate the safety and efficacy of ARCEX Therapy to improve hand and arm functions in people living with cervical SCI. ClinicalTrials.gov identifier: NCT04697472 .

Effects of Perturbation-Based Treadmill Training on Balance Performance, Daily Life Gait, and Falls in Older Adults: REACT Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to evaluate the effect of perturbation-based treadmill training on gait quality in daily life, a predictor of fall risk that was used as the primary outcome. An additional aim was to evaluate the effects on secondary outcomes, including balance, gait performance, self-efficacy, daily life physical activity, and falls. METHODS: Seventy community-dwelling older adults (mean age = 74.73 [SD = 5.69] years; 46 women) at risk of falling were randomized and received 4 weeks of dual-task treadmill training, either with or without treadmill perturbations. Balance, gait performance, self-efficacy, and daily life trunk accelerometry at baseline, after intervention, and at a 6-month follow-up were assessed and compared within group over time and between groups for each time point, and their change rates between groups over time were also assessed. RESULTS: Both groups improved in their balance, gait performance, and self-efficacy; the experimental group showed a significantly larger decrease in concern of falling and an increase in physical performance than the controls. These training effects did not translate into significant improvements in daily life gait quality or physical activity. However, the number of daily life falls and the percentage of fallers decreased significantly more in the experimental group. CONCLUSION: A 4-week perturbation-based dual-task treadmill training program can improve self-efficacy, balance, and gait performance in a controlled setting and reduce daily life falls, although not through changes in quantity or quality of daily life gait. IMPACT: Perturbation-based treadmill training is a safe and efficient way to train older adults' balance recovery and gait performance, increase self-efficacy, and prevent falls.

Development of a Balance Recovery Performance Measure for Gait Perturbation Training Based on the Center of Pressure.

Background: The availability of instrumented treadmills that can apply unexpected perturbations during walking has made gait perturbation training more popular in clinical practice. To quantify and monitor balance recovery while training, easy to use measures are needed and may be based on integrated force plate data. Therefore, we aimed to quantify and evaluate different implementations of the recovery performance measure based on center of pressure data. Methods: Recovery performance was calculated based on differences in center of pressure trajectories between unperturbed walking and balance recovery after a perturbation. Five methodological choices leading to 36 different implementations were evaluated. Test-retest reliability, effect sizes, and concurrent validity were evaluated against trunk velocity measures. Results: Differences in measures of (dis-)similarity, time normalization and reference data affected reliability, sensitivity and validity and none of the performance measure implementations based on center of pressure trajectories was superior on all criteria. Measures assessing perturbation effects on trunk velocities provided more reliable and sensitive recovery outcomes. Discussion: Different implementations of the recovery performance measure can be chosen dependent on constraints imposed in the clinical setting. Conclusion: Quantifying recovery performance based on center of pressure data is possible and may be suitable to monitor improvement in recovery performance after gait perturbations in specific clinical setups. Validity of performance measures in general requires further attention.

Perturbation-based gait training to improve daily life gait stability in older adults at risk of falling: protocol for the REACT randomized controlled trial.

BACKGROUND: The European population is rapidly ageing. There is an urgent need for innovative solutions to reduce fall risk in older adults. Perturbation-based gait training is a promising new method to improve reactive balance responses. Whereas positive effects on task-specific dynamic balance recovery during gait have been shown in clinical or laboratory settings, translation of these effects to daily life gait function and fall risk is limited. We aim to evaluate the effect of a 4-week perturbation-based treadmill training on daily-life dynamic gait stability, assessed with inertial sensor data. Secondary outcomes are balance recovery performance, clinical balance and gait assessment scores, the amount of physical activity in daily life and falls incidence during 6 months follow-up. METHODS: The study is a monocenter assessor-blinded randomized controlled trial. The target study sample consists of 70 older adults of 65 years and older, living in the community and with an elevated risk of falling. A block-randomization to avoid seasonal effects will be used to allocate the participants into two groups. The experimental group receives a 4-week, two times per week perturbation-based gait training programme on a treadmill, with simulated slips and trips, in combination with cognitive dual tasks. The control group receives a 4-week, two times per week treadmill training programme under cognitive dual-task conditions without perturbations. Participants will be assessed at baseline and after the 4-weeks intervention period on their daily-life gait stability by wearing an inertial sensor on the lower back for seven consecutive days. In addition, clinical balance and gait assessments as well as questionnaires on falls- and gait-efficacy will be taken. Daily life falls will be followed up over 6 months by a fall calendar. DISCUSSION: Whereas perturbation-based training has shown positive effects in improving balance recovery strategies and in reducing laboratory falls, this study will contribute to investigate the translation of perturbation-based treadmill training effects in a clinical setting towards improving daily life gait stability and reducing fall risk and falls. TRIAL REGISTRATION: NTR7703 / NL66322.028.18, Registered: January 8, 2019; Enrolment of the first participant April 8, 2019.

Gap junction remodeling and altered connexin43 expression in the failing human heart.

Gap junctions (GJ) are important determinants of cardiac conduction and the evidence has recently emerged that altered distribution of these junctions and changes in the expression of their constituent connexins (Cx) may lead to abnormal coupling between cardiomyocytes and likely contribute to arrhythmogenesis. However, it is largely unknown whether changes in the expression and distribution of the major cardiac GJ protein, Cx43, is a general feature of diverse chronic myocardial diseases or is confined to some particular pathophysiological settings. In the present study, we therefore set out to investigate qualitatively and quantitatively the distribution and expression of Cx43 in normal human myocardium and in patients with dilated (DCM), ischemic (ICM), and inflammatory cardiomyopathies (MYO). Left ventricular tissue samples were obtained at the time of cardiac transplantation and investigated with immunoconfocal and electron microscopy. As compared with the control group, Cx43 labeling in myocytes bordering regions of healed myocardial infarction (ICM), small areas of replacement fibrosis (DCM) and myocardial inflammation (MYO) was found to be highly disrupted instead of being confined to the intercalated discs. In all groups, myocardium distant from these regions showed an apparently normal Cx43 distribution at the intercalated discs. Quantitative immunoconfocal analysis of Cx43 in the latter myocytes revealed that the Cx43 area per myocyte area or per myocyte volume is significantly decreased by respectively 30 and 55% in DCM, 23 and 48% in ICM, and by 21 and 40% in MYO as compared with normal human myocardium. In conclusion, focal disorganization of GJ distribution and down-regulation of Cx43 are typical features of myocardial remodeling that may play an important role in the development of an arrhythmogenic substrate in human cardiomyopathies.