Traumatic brain injury (TBI) is a major risk factor for several neurodegenerative disorders, including Parkinson’s disease (PD) and Alzheimer’s disease (AD). Neuroinflammation is a cause of later secondary cell death following TBI, has the potential to aggravate the initial impact, and provides a therapeutic target, albeit that has failed to translate into clinical trial success. Thalidomide-like compounds have neuroinflammation reduction properties across cellular and animal models of TBI and neurodegenerative disorders. They lower the generation of proinflammatory cytokines, particularly TNF-α which is pivotal in microglial cell activation. Unfortunately, thalidomide-like drugs possess adverse effects in humans before achieving anti-inflammatory drug levels. We developed F-3,6′-dithiopomalidomide (F-3,6′-DP) as a novel thalidomide-like compound to ameliorate inflammation. F-3,6′-DP binds to cereblon but does not efficiently trigger the degradation of the transcription factors (SALL4, Ikaros, and Aiolos) associated with the teratogenic and anti-proliferative responses of thalidomide-like drugs. We utilized a phenotypic drug discovery approach that employed cellular and animal models in the selection and development of F-3,6’-DP. F-3,6′-DP significantly mitigated LPS-induced inflammatory markers in RAW 264.7 cells, and lowered proinflammatory cytokine/chemokine levels in the plasma and brain of rats challenged with systemic LPS. We subsequently examined immunohistochemical, biochemical, and behavioral measures following controlled cortical impact (CCI) in mice, a model of moderate TBI known to induce inflammation. F-3,6′-DP decreased CCI-induced neuroinflammation, neuronal loss, and behavioral deficits when administered after TBI. F-3,6′-DP represents a novel class of thalidomide-like drugs that do not lower classical cereblon-associated transcription factors but retain anti-inflammatory actions and possess efficacy in the treatment of TBI and potentially longer-term neurodegenerative disorders.

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Activity of a Novel Anti-Inflammatory Agent F-3,6′-dithiopomalidomide as a Treatment for Traumatic Brain Injury

The purpose of this study was to examine vestibular and balance function in individuals with chronic dizziness associated with mTBI/blast. A prospective case-control study design was used to examine ocular motor, vestibular function, and postural stability in veterans with symptoms of dizziness and/or imbalance following an mTBI or blast exposure (n = 77) and a healthy control group (n = 32). Significant group differences were observed for saccadic accuracy, VOR gain during slow harmonic acceleration at 0.01 Hz, cervical vestibular evoked myogenic potentials asymmetry ratio, composite equilibrium score on the sensory organization test, total Dynamic Gait Index score, and gait. The frequency of test abnormalities in participants with mTBI/blast ranged from 0 to 70% across vestibular, ocular motor, and balance/gait testing, with the most frequent abnormalities occurring on tests of balance and gait function. Seventy-two percent of the mTBI/blast participants had abnormal findings on one or more of the balance and gait tests. Vestibular test abnormalities occurred in ~34% of the individuals with chronic dizziness and mTBI/blast, and abnormalities occurred more frequently for measures of otolith organ function (25% for cVEMP and 18% for oVEMP) than for measures of hSCC function (8% for SHA and 6% for caloric test). Abnormal ocular motor function occurred in 18% of the mTBI/blast group. These findings support the need for comprehensive vestibular and balance assessment in individuals with dizziness following mTBI/blast-related injury.

Vestibular and balance function in veterans with chronic dizziness associated with mild traumatic brain injury and blast exposure

Simple Summary Physical therapy and rehabilitation are emerging in veterinary medicine, and more research is needed to understand the effect of various exercises on kinematics and kinetics in animals. This will allow the animal physiotherapist to best utilize these exercises as a therapeutic and even diagnostic tool. Walking over obstacles is a typical canine physiotherapy exercise; however, no studies investigating the kinetics have been conducted. The present study showed significant changes in ground reaction forces and center of pressure in dogs walking over obstacles compared to normal walking. This can reflect a challenge that the animals have to overcome in order to perform this exercise. The data can be used for further studies in diseased animals or in the future as a diagnostic tool. Abstract Walking over obstacles is a widely used physiotherapy exercise in dogs. Current research is limited to the effect of this exercise in kinematics and muscle activation in dogs. The present study assessed the influence of walking over obstacles on the ground reaction forces (GRFs) and center of pressure (COP) in dogs. Data of dogs walking over one and two obstacles over a pressure platform were retrospectively analyzed and compared to normal walking. Walking over one obstacle did not affect the GRFs and COP of the forelimbs; however, significant changes were observed for the hindlimbs, especially the leading hindlimb. Walking over two obstacles caused significant changes to only one value at the forelimbs, whereas multiple significant changes in the GRFs and COP values were observed at the hindlimbs. Walking over obstacles seems to be challenging even for healthy adult dogs. Further studies are needed to investigate how different heights of obstacles and distances between them can further challenge the animals. The combination of kinetics and kinematics during walking over obstacles may be used in future as a diagnostic tool in geriatric and neurological patients in order to assess their proprioception awareness or to assess the improvement after an intervention, e.g., physiotherapy treatment.

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Ground Reaction Forces and Center of Pressure within the Paws When Stepping over Obstacles in Dogs

Falls are common in patients with neurological diseases and can be very problematic. Recently, there has been an increase in fall prevention research in people with neurological diseases; however, these studies are usually condition-specific (e.g., only MS, PD or stroke). Here, our aim was to evaluate and compare the efficacy of an advanced and innovative dual-task, motor-cognitive rehabilitation program in individuals with different neurological diseases who are at risk of falling. We recruited 95 consecutive adults with neurological diseases who are at risk of falling and divided them into four groups: 31 with cerebrovascular disease (CVD), 20 with Parkinson’s disease (PD), 23 with traumatic brain injury (TBI) and 21 with other neurological diseases (OND). Each patient completed a dual-task, motor-cognitive training program and underwent two test evaluations to assess balance, gait, fear of falling and walking performance at the pre-and post-intervention. We found that our experimental motor-cognitive, dual-task rehabilitation program was an effective method for improving walking balance, gait, walking endurance and speed, and fear of falling, and that it reduced the risk of falls in patients with different neurological diseases. This study presents an alternative approach for people with chronic neurological diseases and provides innovative data for managing this population.

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The Effect of Dual-Task Motor-Cognitive Training in Adults with Neurological Diseases Who Are at Risk of Falling

This study characterized the absolute pressure measurement error and reliability of a new fully integrated (Kinetyx, SI) plantar-pressure measurement system (PPMS) versus an industry-standard PPMS (F-Scan, Tekscan) during an established benchtop testing protocol as well as via a research-grade, instrumented treadmill (Bertec) during a running protocol. Benchtop testing results showed that both SI and F-Scan had strong positive linearity (Pearson’s correlation coefficient, PCC = 0.86–0.97, PCC = 0.87–0.92; RMSE = 15.96 ± 9.49) and mean root mean squared error RMSE (9.17 ± 2.02) compared to the F-Scan on a progressive loading step test. The SI and F-Scan had comparable results for linearity and hysteresis on a sinusoidal loading test (PCC = 0.92–0.99; 5.04 ± 1.41; PCC = 0.94–0.99; 6.15 ± 1.39, respectively). SI had less mean RMSE (6.19 ± 1.38) than the F-Scan (8.66 ±2.31) on the sinusoidal test and less absolute error (4.08 ± 3.26) than the F-Scan (16.38 ± 12.43) on a static test. Both the SI and F-Scan had near-perfect between-day reliability interclass correlation coefficient, ICC = 0.97–1.00) to the F-Scan (ICC = 0.96–1.00). During running, the SI pressure output had a near-perfect linearity and low RMSE compared to the force measurement from the Bertec treadmill. However, the SI pressure output had a mean hysteresis of 7.67% with a 28.47% maximum hysteresis, which may have implications for the accurate quantification of kinetic gait measures during running.

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Characterization of the Kinetyx SI Wireless Pressure-Measuring Insole during Benchtop Testing and Running Gait

Introduction: Gait impairment occurs across the spectrum of traumatic brain injury (TBI); from mild (mTBI) to moderate (modTBI), to severe (sevTBI). Recent evidence suggests that objective gait assessment may be a surrogate marker for neurological impairment such as TBI. However, the most optimal method of objective gait assessment is still not well understood due to previous reliance on subjective assessment approaches. The purpose of this review was to examine objective assessment of gait impairments across the spectrum of TBI. Methods: PubMed, AMED, OVID and CINAHL databases were searched with a search strategy containing key search terms for TBI and gait. Original research articles reporting gait outcomes in adults with TBI (mTBI, modTBI, sevTBI) were included. Results: 156 citations were identified from the search, of these, 13 studies met the initial criteria and were included into the review. The findings from the reviewed studies suggest that gait is impaired in mTBI, modTBI and sevTBI (in acute and chronic stages), but methodological limitations were evident within all studies. Inertial measurement units were most used to assess gait, with single-task, dual-task and obstacle crossing conditions used. No studies examined gait across the full spectrum of TBI and all studies differed in their gait assessment protocols. Recommendations for future studies are provided. Conclusion: Gait was found to be impaired in TBI within the reviewed studies regardless of severity level (mTBI, modTBI, sevTBI), but methodological limitations of studies (transparency and reproducibility) limit clinical application. Further research is required to establish a standardised gait assessment procedure to fully determine gait impairment across the spectrum of TBI with comprehensive outcomes and consistent protocols.

https://www.mdpi.com/1424-8220/22/4/1480/pdf?version=1645062356

Gait Impairment in Traumatic Brain Injury: A Systematic Review

Running gait assessment has traditionally been performed using subjective observation or expensive laboratory-based objective technologies, such as three-dimensional motion capture or force plates. However, recent developments in wearable devices allow for continuous monitoring and analysis of running mechanics in any environment. Objective measurement of running gait is an important (clinical) tool for injury assessment and provides measures that can be used to enhance performance.We aimed to systematically review the available literature investigating how wearable technology is being used for running gait analysis in adults.A systematic search of the literature was conducted in the following scientific databases: PubMed, Scopus, Web of Science and SPORTDiscus. Information was extracted from each included article regarding the type of study, participants, protocol, wearable device(s), main outcomes/measures, analysis and key findings.A total of 131 articles were reviewed: 56 investigated the validity of wearable technology, 22 examined the reliability and 77 focused on applied use. Most studies used inertial measurement units (n = 62) [i.e. a combination of accelerometers, gyroscopes and magnetometers in a single unit] or solely accelerometers (n = 40), with one using gyroscopes alone and 31 using pressure sensors. On average, studies used one wearable device to examine running gait. Wearable locations were distributed among the shank, shoe and waist. The mean number of participants was 26 (± 27), with an average age of 28.3 (± 7.0) years. Most studies took place indoors (n = 93), using a treadmill (n = 62), with the main aims seeking to identify running gait outcomes or investigate the effects of injury, fatigue, intrinsic factors (e.g. age, sex, morphology) or footwear on running gait outcomes. Generally, wearables were found to be valid and reliable tools for assessing running gait compared to reference standards.This comprehensive review highlighted that most studies that have examined running gait using wearable sensors have done so with young adult recreational runners, using one inertial measurement unit sensor, with participants running on a treadmill and reporting outcomes of ground contact time, stride length, stride frequency and tibial acceleration. Future studies are required to obtain consensus regarding terminology, protocols for testing validity and the reliability of devices and suitability of gait outcomes.CRD42021235527. 

https://link.springer.com/content/pdf/10.1007/s40279-022-01760-6.pdf

Wearables for Running Gait Analysis: A Systematic Review

Running gait assessment is essential for the development of technical optimization strategies as well as to inform injury prevention and rehabilitation. Currently, running gait assessment relies on (i) visual assessment, exhibiting subjectivity and limited reliability, or (ii) use of instrumented approaches, which often carry high costs and can be intrusive due to the attachment of equipment to the body. Here, the use of an IoT-enabled markerless computer vision smartphone application based upon Google’s pose estimation model BlazePose was evaluated for running gait assessment for use in low-resource settings. That human pose estimation architecture was used to extract contact time, swing time, step time, knee flexion angle, and foot strike location from a large cohort of runners. The gold-standard Vicon 3D motion capture system was used as a reference. The proposed approach performs robustly, demonstrating good (ICC(2,1) > 0.75) to excellent (ICC(2,1) > 0.90) agreement in all running gait outcomes. Additionally, temporal outcomes exhibit low mean error (0.01–0.014 s) in left foot outcomes. However, there are some discrepancies in right foot outcomes, due to occlusion. This study demonstrates that the proposed low-cost and markerless system provides accurate running gait assessment outcomes. The approach may help routine running gait assessment in low-resource environments.

https://www.mdpi.com/1424-8220/23/2/696/pdf?version=1674008164

Internet-of-Things-Enabled Markerless Running Gait Assessment from a Single Smartphone Camera

Running gait assessment is critical in performance optimization and injury prevention. Traditional approaches to running gait assessment are inhibited by unnatural running environments (e.g., indoor lab), varied assessor (i.e., subjective experience) and high costs with traditional reference standard equipment. Thus, development of valid, reproduceable and low-cost approaches are key. Use of wearables such as inertial measurement units have shown promise but despite their flexible use in any environment and reduced cost, they often retain complexities such as connectivity to mobile platforms and stringent attachment protocols. Here, we propose a non-wearable camera-based approach to running gait assessment, focusing on identification of initial contact events within a runner's stride. We investigated different artificial intelligence and object tracking approaches to determine the optimal methodology. A cohort of 40 healthy runners were video recorded (240FPS, multi-angle) during 2-minute running bouts on a treadmill. Validation of the proposed approach is obtained from comparison to manually labelled videos. The computing vision approach can accurately identify initial contact events (ICC(2,1) = 0.902).

A proposed computer vision model for running gait assessment

Following mild traumatic brain injury (mTBI), patients are often advised to restrict physical activity until full symptom resolution followed by gradual return to activity. However, extended rest periods may prolong recovery and contribute to persistent symptoms. Emerging evidence suggests early active rehabilitation that increases heart rate without exacerbating symptoms may improve mTBI patient recovery. This review aims to: (1) appraise evidence on active rehabilitation intervention for mTBI recovery within one-month of injury (i.e., exercise type, duration, intensity, etc.); and (2) recommend evidence-based rehabilitation protocols. Pubmed, CINAHL, PsychARTICLES, SportDISCUS, and AMED databases were searched using key terms “mild Traumatic Brain Injury”, “Rehabilitation”, “Acute”, and their synonyms. Evidence was appraised using Cochrane RoB-2 and ROBINS-I. 434 citations were initially identified with seven papers systematically reviewed. Within the reviewed articles, only three were randomized controlled trials with low risk of bias, and four were non-randomized trials with low to moderate risk of bias. Findings highlighted that a range of active rehabilitation protocols were used with different exercise modalities (primarily treadmills and static cycling), durations (9–20 min, or until symptomatic, for 30–50 days or symptoms resolved), and intensities (low, moderate or high). Active rehabilitation did not cause any serious adverse events (i.e., death, hospitalisation etc.), and six studies reported that it did not exacerbate mTBI symptoms in any participants (with one participant having symptom worsening in one study). Overall, the majority of reviewed studies ( n = 4) showed that active rehabilitation decreased time to mTBI symptom resolution compared to controls (strict rest/stretching exercises). Individualized active rehabilitation prescribed within one-month post-mTBI appears to be safe and effective at decreasing recovery time to symptom resolution in mTBI. However, there is a lack of consensus regarding specific intervention protocols that needs to be addressed before adoption within clinical practice.

R. Mason

Papers

Gait Impairment in Traumatic Brain Injury: A Systematic Review

Wearables for Running Gait Analysis: A Systematic Review

Internet-of-Things-Enabled Markerless Running Gait Assessment from a Single Smartphone Camera

A proposed computer vision model for running gait assessment

Active Rehabilitation Following Acute Mild Traumatic Brain Injury: A Systematic Review