Systematic Reviews of Clinical Benefits of Exoskeleton Use for Gait and Mobility in Neurologic Disorders: A Tertiary Study.

OBJECTIVE: To describe systematic reviews (SRs) of the use of exoskeletons for gait and mobility by persons with neurologic disorders and to evaluate their quality as guidance for research and clinical practice. DATA SOURCES: PubMed, EMBASE, Web of Science, CINAHL Complete, PsycINFO, Cochrane Database of Systematic Reviews, PEDro, and Google Scholar were searched from database inception to January 23, 2018. STUDY SELECTION: A total of 331 deduplicated abstracts from bibliographic database and ancestor searching were independently screened by 2 reviewers, resulting in 109 articles for which full text was obtained. Independent screening of those 109 articles by 2 reviewers resulted in a final selection of 17 SRs. DATA EXTRACTION: Data were extracted by 1 reviewer using a pretested Excel form with 158 fields and checked by a second reviewer. Key data included the purpose of the SR, methods used, outcome measures presented, and conclusions. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses and A MeaSurement Tool to Assess Systematic Reviews version 2 were used to evaluate reporting and methodological quality, respectively, of the SRs. DATA SYNTHESIS: The SRs generally were of poor methodological and reporting quality. They failed to report some information on patients (eg, height, weight, baseline ambulatory status) and interventions (eg, treatment hours or sessions planned and delivered) that clinicians and other stakeholders might want to have, and often failed to notice that the primary studies duplicated subjects. CONCLUSIONS: Published SRs on exoskeletons have many weaknesses in design and execution; clinicians, researchers, and other stakeholders should be cautious in relying on them to make decisions on the use of this technology. Future primary and secondary studies need to address the multiple methodological limitations.

The effects of concentric and eccentric training in murine models of dysferlin-associated muscular dystrophy.

INTRODUCTION: Dysferlin-deficient murine muscle sustains severe damage after repeated eccentric contractions. METHODS: With a robotic dynamometer, we studied the response of dysferlin-sufficient and dysferlin-deficient mice to 12 weeks of concentrically or eccentrically biased contractions. We also studied whether concentric contractions before or after eccentric contractions reduced muscle damage in dysferlin-deficient mice. RESULTS: After 12 weeks of concentric training, there was no net gain in contractile force in dysferlin-sufficient or dysferlin-deficient mice, whereas eccentric training produced a net gain in force in both mouse strains. However, eccentric training induced more muscle damage in dysferlin-deficient vs dysferlin-sufficient mice. Although concentric training produced minimal muscle damage in dysferlin-deficient mice, it still led to a prominent increase in centrally nucleated fibers. Previous exposure to concentric contractions conferred slight protection on dysferlin-deficient muscle against damage from subsequent injurious eccentric contractions. DISCUSSION: Concentric contractions may help dysferlin-deficient muscle derive the benefits of exercise without inducing damage.

Aerobic Exercise Preconception and During Pregnancy Enhances Oxidative Capacity in the Hindlimb Muscles of Mice Offspring.

Liu, J, Lee, I, Feng, H-Z, Galen, SS, Hüttemann, PP, Perkins, GA, Jin, J-P, Hüttemann, M, and Malek, MH. Aerobic exercise preconception and during pregnancy enhances oxidative capacity in the hindlimb muscles of mice offspring. J Strength Cond Res 32(5): 1391-1403, 2018-Little is known about the effect of maternal exercise on offspring skeletal muscle health. The purpose of this study, therefore, was to determine whether maternal exercise (preconception and during pregnancy) alters offspring skeletal muscle capillarity and mitochondrial biogenesis. We hypothesized that offspring from exercised dams would have higher capillarity and mitochondrial density in the hindlimb muscles compared with offspring from sedentary dams. Female mice in the exercise condition had access to a running wheel in their individual cage 30 days before mating and throughout pregnancy, whereas the sedentary group did not have access to the running wheel before mating and during pregnancy. Male offspring from both groups were killed when they were 2 months old, and their tissues were analyzed. The results indicated no significant (p > 0.05) mean differences for capillarity density, capillarity-to-fiber ratio, or regulators of angiogenesis such as VEGF-A and TSP-1. Compared with offspring from sedentary dams, however, offspring from exercised dams had an increase in protein expression of myosin heavy chain type I (MHC I) (∼134%; p = 0.009), but no change in MHC II. For mitochondrial morphology, we found significant (all p-values ≤ 0.0124) increases in mitochondrial volume density (∼55%) and length (∼18%) as well as mitochondria per unit area (∼19%). For mitochondrial enzymes, there were also significant (all p-values ≤ 0.0058) increases in basal citrate synthase (∼79%) and cytochrome c oxidase activity (∼67%) in the nonoxidative muscle fibers as well as increases in basal (ATP) (∼52%). Last, there were also significant mean differences in protein expression for regulators (FIS1, Lon protease, and TFAM) of mitochondrial biogenesis. These findings suggest that maternal exercise before and during pregnancy enhances offspring skeletal muscle mitochondria functionality, but not capillarity.

Test-retest reliability of the electromyographic fatigue threshold for cycle ergometry.

INTRODUCTION: The purpose of this study was to determine the intersession reliability of the electromyographic fatigue threshold (EMGFT ) for cycle ergometry. METHODS: On separate occasions, 10 healthy, college-aged men performed an incremental test to voluntary exhaustion on a cycle ergometer. The EMG amplitude vs. time relationships for each power output from the quadriceps femoris muscles were analyzed using linear regression. EMGFT was defined operationally as the average of the highest power output that resulted in a non-significant slope coefficient (P > 0.05) and the lowest power output that resulted in a significant (P < 0.05) positive slope coefficient. The EMGFT values for trials 1 and 2 were used to calculate the intraclass correlation coefficient (ICC). RESULTS: Overall, the reliability of the EMGFT (ICC2,1 = 0.85; 95% confidence interval 0.49-0.96) was in the "excellent" category. CONCLUSIONS: The EMGFT for cycle ergometry is a reliable measure for assessing muscular fatigue.

Acute Low-Dose Caffeine Supplementation Increases Electromyographic Fatigue Threshold in Healthy Men.

Morse, JJ, Pallaska, G, Pierce, PR, Fields, TM, Galen, SS, and Malek, MH. Acute low-dose caffeine supplementation increases electromyographic fatigue threshold in healthy men. J Strength Cond Res 30(11): 3236-3241, 2016-The purpose of this study is to determine whether consumption of a single low-dose caffeine drink will delay the onset of the electromyographic fatigue threshold (EMGFT) in the superficial quadriceps femoris muscles. We hypothesize that the EMGFT values for the caffeine condition will be significantly higher than the EMGFT values for the placebo condition. On separate occasions, 10 physically active men performed incremental single-leg knee-extensor ergometry 1 hour after caffeine (200 mg) or placebo consumption. The EMGFT was determined for each participant for both conditions. The results indicated a significant increase for maximal power output (16%; p = 0.004) and EMGFT (45%; p = 0.004) in the caffeine condition compared with placebo. These findings suggest that acute low-dose caffeine supplementation delays neuromuscular fatigue in the quadriceps femoris muscles.

Reliability of the log-transformed EMG amplitude-power output relationship for incremental knee-extensor ergometry.

INTRODUCTION: The purpose of this investigation was to determine the reproducibility of the log-transformed model for electromyography (EMG) amplitude during incremental single-leg knee-extensor exercise. METHODS: Eight healthy college-aged men performed 3 incremental tests on separate occasions on a knee-extensor ergometer. EMG amplitude was analyzed for each participant on each occasion for the rectus femoris and vastus medialis muscles at 4 different exercise power outputs (30%, 50%, 70%, and 90%) corresponding to each participant's maximal power output. Intraclass correlation coefficients (ICC) were determined for the slope and y-intercept terms derived from the log-transformed EMG amplitude-power output relationship for each muscle. RESULTS: The ICC values for the rectus femoris (slope = 0.779; y-intercept = 0.787) and vastus medialis (slope = 0.756; y-intercept = 0.763) muscles were high. CONCLUSIONS: The log-transformed EMG amplitude-power output relationship is a reliable index for measuring motor unit activation.

A single electromyographic testing point is valid to monitor neuromuscular fatigue during continuous exercise.

Two different protocols for estimating the electromyographic fatigue threshold (EMGFT) have been proposed in the literature. These protocols are distinguished by the number of visits required to determine the EMGFT. The purpose of this study, therefore, was to statistically compare the estimated EMGFT from the single-visit incremental test and the multiple-visit constant workload tests for single-leg knee-extensor exercise. Seven healthy college-aged men [mean ± SEM; age = 25.0 ± 0.7 years] performed the incremental test and on separate occasions also performed 4 constant workload tests to voluntary exhaustion. The EMG amplitude was recorded from the rectus femoris muscle during all the testing sessions. For the single-visit test, the EMG amplitude vs. time relationship for each power output was examined using linear regression. For the multiple-visit tests, the EMG amplitude vs. time relationship was calculated for each constant power output. Thereafter, the power outputs were plotted as a function of the slope coefficient for the EMG amplitude vs. time relationships, and linear regression was performed. The EMGFT was defined as the intersection of the regression line with the y-intercept of the power output vs. slope coefficient plot. The results indicated that the estimated EMGFT from the single-visit test was significantly (p = 0.012) lower than the estimate from the multiple-visit tests. Because this test is performed during a single visit and concludes within 20 minutes, it may also have application in clinical rehabilitation settings and not merely for an athletic population.

Minimally Invasive Muscle Embedding Generates Donor-Cell-Derived Muscle Fibers that Express Desmin and Dystrophin.

INTRODUCTION: The aim of this study was to quantify the extent of donor-cell-derived myogenesis achieved by a novel surgical technique known as Minimally Invasive Muscle Embedding (MIME). MATERIALS AND METHODS: Through MIME, we implanted a single extensor digitorum longus muscle from donor mice (N = 2) that expressed a red fluorescent protein (RFP), into the left tibialis anterior (TA) muscle of immunodeficient host mice (N = 4) that expressed a green fluorescent protein (GFP). Soon after MIME, we injected a myotoxin (barium chloride), into the host TA muscle, to trigger concerted muscle degeneration and regeneration. In lieu of MIME, we performed a SHAM procedure on the right TA muscle of the same set of animals. RESULTS: In MIME-treated muscles, 22% ± 7% and 78% ± 7% muscle fibers were RFP+ and GFP+, respectively (mean ± standard deviation); and all RFP+ fibers were positive for desmin and dystrophin. Conclusion. We conclude that MIME helps generate muscle fibers of donor origin, in host muscle.

Robotic exoskeletons for reengaging in everyday activities: promises, pitfalls, and opportunities.

PURPOSE: Media images and marketing materials suggest a future in which individuals with spinal cord injury (SCI) can utilize robotic exoskeletons to reengage in everyday activities, yet these narratives may not align with the current technological realities. The purpose of this paper is to present and describe the current use of robotic exoskeletons in rehabilitation and home settings and discuss the benefits and limitations of the devices. MATERIALS AND METHODS: We provide an overview of the features and limitations of the four robotic exoskeleton products (EKSO Bionics, ReWalk, Rex Bionics, and Indego) that are currently being used in in the United States in rehabilitation settings. We follow by suggesting ways that these devices fall short of fulfilling the promise of reengage in everyday activities in real-world life contexts. RESULTS AND DISCUSSION: Available devices appear to be better suited for rehabilitation settings than for home use. Device weight, the need for upper extremity supports, supervision requirements, and a limited range of movements are all issues that limit functionality and restrict opportunities for using such devices in real-world contexts. Designing the next generation of exoskeletons to be more useful in everyday life will require further collaboration among engineers, clinicians, and patients. Implications for Rehabilitation Exoskeletons offer the promise of allowing individuals with neurological injury to reengage in everyday activities from a standing position. Several exoskeleton devices are currently available for use in the United States. Weight of exoskeleton devices, the need for upper extremity supports, supervision requirements of hone units, and a limited range of movements are issues that restrict opportunities for using such devices in real-world contexts. Further development of exoskeleton technologies is warranted to improve the devices for real-world use.

Diltiazem improves contractile properties of skeletal muscle in dysferlin-deficient BLAJ mice, but does not reduce contraction-induced muscle damage.

B6.A-Dysfprmd /GeneJ (BLAJ) mice model human limb-girdle muscular dystrophy 2B (LGMD2B), which is linked to mutations in the dysferlin (DYSF) gene. We tested the hypothesis that, the calcium ion (Ca2+ ) channel blocker diltiazem (DTZ), reduces contraction-induced skeletal muscle damage, in BLAJ mice. We randomly assigned mice (N = 12; 3-4 month old males) to one of two groups - DTZ (N = 6) or vehicle (VEH, distilled water, N = 6). We conditioned mice with either DTZ or VEH for 1 week, after which, their tibialis anterior (TA) muscles were tested for contractile torque and susceptibility to injury from forced eccentric contractions. We continued dosing with DTZ or VEH for 3 days following eccentric contractions, and then studied torque recovery and muscle damage. We analyzed contractile torque before eccentric contractions, immediately after eccentric contractions, and at 3 days after eccentric contractions; and counted damaged fibers in the injured and uninjured TA muscles. We found that DTZ improved contractile torque before and immediately after forced eccentric contractions, but did not reduce delayed-onset muscle damage that was observed at 3 days after eccentric contractions.

Minimally Invasive Muscle Embedding (MIME) - A Novel Experimental Technique to Facilitate Donor-Cell-Mediated Myogenesis.

Skeletal muscle possesses regenerative capacity due to tissue-resident, muscle-fiber-generating (myogenic) satellite cells (SCs), which can form new muscle fibers under the right conditions. Although SCs can be harvested from muscle tissue and cultured in vitro, the resulting myoblast cells are not very effective in promoting myogenesis when transplanted into host muscle. Surgically exposing the host muscle and grafting segments of donor muscle tissue, or the isolated muscle fibers with their SCs onto host muscle, promotes better myogenesis compared to myoblast transplantation. We have developed a novel technique that we call Minimally Invasive Muscle Embedding (MIME). MIME involves passing a surgical needle through the host muscle, drawing a piece of donor muscle tissue through the needle track, and then leaving the donor tissue embedded in the host muscle so that it may act as a source of SCs for the host muscle. Here we describe in detail the steps involved in performing MIME in an immunodeficient mouse model that expresses a green fluorescent protein (GFP) in all of its cells. Immunodeficiency in the host mouse reduces the risk of immune rejection of the donor tissue, and GFP expression enables easy identification of the host muscle fibers (GFP+) and donor-cell-derived muscle fibers (GFP-). Our pilot data suggest that MIME can be used to implant an extensor digitorum longus (EDL) muscle from a donor mouse into the tibialis anterior (TA) muscle of a host mouse. Our data also suggest that when a myotoxin (barium chloride, BaCl2) is injected into the host muscle after MIME, there is evidence of donor-cell-derived myogenesis in the host muscle, with approximately 5%, 26%, 26% and 43% of the fibers in a single host TA muscle showing no host contribution, minimal host contribution, moderate host contribution, and maximal host contribution, respectively.

Video Movement Analysis Using Smartphones (ViMAS): A Pilot Study.

The use of smartphones in clinical practice is steadily increasing with the availability of low cost/freely available "apps" that could be used to assess human gait. The primary aim of this manuscript is to test the concurrent validity of kinematic measures recorded by a smartphone application in comparison to a 3D motion capture system in the sagittal plane. The secondary aim was to develop a protocol for clinicians on the set up of the smartphone camera for video movement analysis. The sagittal plane knee angle was measured during heel strike and toe off events using the smart phone app and a 3D motion-capture system in 32 healthy subjects. Three trials were performed at near (2-m) and far (4-m) smartphone camera distances. The order of the distances was randomized. Regression analysis was performed to estimate the height of the camera based on either the subject's height or leg length. Absolute measurement errors were least during toe off (3.12 ± 5.44 degrees) compared to heel strike (5.81 ± 5.26 degrees). There were significant (p < 0.05) but moderate agreements between the application and 3D motion capture measures of knee angles. There were also no significant (p > 0.05) differences between the absolute measurement errors between the two camera positions. The measurement errors averaged between 3 - 5 degrees during toe off and heel strike events of the gait cycle. The use of smartphone apps can be a useful tool in the clinic for performing gait or human movement analysis. Further studies are needed to establish the accuracy in measuring movements of the upper extremity and trunk.

Validity of a Wireless Gait Analysis Tool (Wi-GAT) in assessing spatio-temporal gait parameters at slow, preferred and fast walking speeds.

BACKGROUND: The wireless gait assessment tool (Wi-GAT) measures have been shown to have good to excellent concurrent validity with preferred walking speeds, however, the validity of the Wi-GAT measures at slow and fast walking speeds is unknown. OBJECTIVE: To establish validity of the Wi-GAT spatio-temporal gait measures at slow, fast, and preferred walking speeds. METHODS: Twenty two healthy adult volunteers, with a mean age of 25.7 (± 5.3) participated in this study. The spatio-temporal gait variables of each participant were concurrently recorded using the GAITrite and the Wi-GAT system, while the participants performed 3 trials for each walking speed in a randomized order. Intraclass correlation analyses were performed to establish the agreement between the measures recorded by the GAITrite and Wi-GAT systems. RESULTS: Walking speed measured both by the Wi-GAT and the GAITrite systems showed excellent agreement for preferred (ICC = 0.979 p< 0.001), slow (ICC = 0.989 p< 0.001) and fast (ICC = 0.967 p< 0.001) walking speeds. Most gait parameters recorded at slow walking speed showed good (ICC > 0.70) to excellent (ICC > 0.85) agreement. CONCLUSIONS: Gait parameters recorded by the Wi-GAT system showed fair to excellent validity for preferred and slow walking speeds.

Determining The Electromyographic Fatigue Threshold Following a Single Visit Exercise Test.

Theoretically, the electromyographic (EMG) fatigue threshold is the exercise intensity an individual can maintain indefinitely without the need to recruit more motor units which is associated with an increase in the EMG amplitude. Although different protocols have been used to estimate the EMG fatigue threshold they require multiple visits which are impractical for a clinical setting. Here, we present a protocol for estimating the EMG fatigue threshold for cycle ergometry which requires a single visit. This protocol is simple, convenient, and completed within 15-20 min, therefore, has the potential to be translated into a tool that clinicians can use in exercise prescription.

Validity of an Interactive Functional Reach Test.

INTRODUCTION: Videogaming platforms such as the Microsoft (Redmond, WA) Kinect(®) are increasingly being used in rehabilitation to improve balance performance and mobility. These gaming platforms do not have built-in clinical measures that offer clinically meaningful data. We have now developed software that will enable the Kinect sensor to assess a patient's balance using an interactive functional reach test (I-FRT). The aim of the study was to test the concurrent validity of the I-FRT and to establish the feasibility of implementing the I-FRT in a clinical setting. SUBJECTS AND METHODS: The concurrent validity of the I-FRT was tested among 20 healthy adults (mean age, 25.8±3.4 years; 14 women). The Functional Reach Test (FRT) was measured simultaneously by both the Kinect sensor using the I-FRT software and the Optotrak Certus(®) 3D motion-capture system (Northern Digital Inc., Waterloo, ON, Canada). The feasibility of implementing the I-FRT in a clinical setting was assessed by performing the I-FRT in 10 participants with mild balance impairments recruited from the outpatient physical therapy clinic (mean age, 55.8±13.5 years; four women) and obtaining their feedback using a NASA Task Load Index (NASA-TLX) questionnaire. RESULTS: There was moderate to good agreement between FRT measures made by the two measurement systems. The greatest agreement between the two measurement system was found with the Kinect sensor placed at a distance of 2.5 m [intraclass correlation coefficient (2,k)=0.786; P<0.001] from the participant. Participants with mild balance impairments whose balance was assessed using the I-FRT software scored their experience favorably by assigning lower scores for the Frustration, Mental Demand, and Temporal Demand subscales on the NASA/TLX questionnaire. CONCLUSIONS: FRT measures made using the Kinect sensor I-FRT software provides a valid clinical measure that can be used with the gaming platforms.

Development and validation of a low-cost, portable and wireless gait assessment tool.

BACKGROUND: Performing gait analysis in a clinical setting can often be challenging due to time, cost and the availability of sophisticated three-dimensional (3D) gait analysis systems. This study has developed and tested a portable wireless gait assessment tool (wi-GAT) to address these challenges. AIM: To investigate the concurrent validity of the wi-GAT in measuring spatio-temporal gait parameters such as stride length, stride duration, cadence, double support time (DST), stance and swing time compared to a 3D Vicon motion analysis system. METHODS: Ten healthy volunteers participated in the study (age range 23-30 years). Spatio-temporal gait parameters were recorded simultaneously by the Vicon and the wi-GAT systems as each subject walked at their self-selected speed. RESULTS: The stride length and duration, cadence, stance duration and walking speed recorded using the wi-GAT showed strong agreement with those same parameters recorded by the Vicon (ICC of 0.94-0.996). A difference between the systems in registering "toe off" resulted in less agreement (ICC of 0.299-0.847) in gait parameters such as %stance and %swing and DST. DISCUSSION AND CONCLUSION: The study demonstrated good concurrent validity for the wi-GAT system. The wi-GAT has the potential to be a useful assessment tool for clinicians.

Isometric hip and knee torque measurements as an outcome measure in robot assisted gait training.

BACKGROUND: Strength changes in lower limb muscles following robot assisted gait training (RAGT) in subjects with incomplete spinal cord injury (ISCI) has not been quantified using objective outcome measures. OBJECTIVE: To record changes in the force generating capacity of lower limb muscles (recorded as peak voluntary isometric torque at the knee and hip), before, during and after RAGT in both acute and subacute/chronic ISCI subjects using a repeated measures study design. METHODS: Eighteen subjects with ISCI participated in this study (Age range: 26-63 years mean age = 49.3 ± 11 years). Each subject participated in the study for a total period of eight weeks, including 6 weeks of RAGT using the Lokomat system (Hocoma AG, Switzerland). Peak torques were recorded in hip flexors, extensors, knee flexors and extensors using torque sensors that are incorporated within the Lokomat. RESULTS: All the tested lower limb muscle groups showed statistically significant (p < 0.001) increases in peak torques in the acute subjects. Comparison between the change in peak torque generated by a muscle and its motor score over time showed a non-linear relationship. CONCLUSIONS: The peak torque recorded during isometric contractions provided an objective outcome measure to record changes in muscle strength following RAGT.