Navrag B. Singh

Kinematic measures for assessing gait stability in elderly individuals: a systematic review

Falls not only present a considerable health threat, but the resulting treatment and loss of working days also place a heavy economic burden on society. Gait instability is a major fall risk factor, particularly in geriatric patients, and walking is one of the most frequent dynamic activities of daily living. To allow preventive strategies to become effective, it is therefore imperative to identify individuals with an unstable gait. Assessment of dynamic stability and gait variability via biomechanical measures of foot kinematics provides a viable option for quantitative evaluation of gait stability, but the ability of these methods to predict falls has generally not been assessed. Although various methods for assessing gait stability exist, their sensitivity and applicability in a clinical setting, as well as their cost-effectiveness, need verification. The objective of this systematic review was therefore to evaluate the sensitivity of biomechanical measures that quantify gait stability among elderly individuals and to evaluate the cost of measurement instrumentation required for application in a clinical setting. To assess gait stability, a comparative effect size (Cohens d) analysis of variability and dynamic stability of foot trajectories during level walking was performed on 29 of an initial yield of 9889 articles from four electronic databases. The results of this survey demonstrate that linear variability of temporal measures of swing and stance was most capable of distinguishing between fallers and non-fallers, whereas step width and stride velocity prove more capable of discriminating between old versus young (OY) adults. In addition, while orbital stability measures (Floquet multipliers) applied to gait have been shown to distinguish between both elderly fallers and non-fallers as well as between young and old adults, local stability measures (λs) have been able to distinguish between young and old adults. Both linear and nonlinear measures of foot time series during gait seem to hold predictive ability in distinguishing healthy from fall-prone elderly adults. In conclusion, biomechanical measurements offer promise for identifying individuals at risk of falling and can be obtained with relatively low-cost tools. Incorporation of the most promising measures in combined retrospective and prospective studies for understanding fall risk and designing preventive strategies is warranted.

Terminally Differentiated CD8+ T Cells Negatively Affect Bone Regeneration in Humans

A subset of T cells inhibits bone regeneration in humans. No Bones About It Sticks and stones may break your bones, but immune cells will not hurt you, at least if Reinke et al. have anything to say about it. The immune system seems to have a hand in everything these days, and bone repair is no exception. T cells have been implicated in modulating bone fracture repair, even in the absence of infection. Reinke et al. take these studies into patients and find that delayed fracture healing correlated with a subset of T cells—terminally differentiated effector memory CD8+ T (TEMRA) cells. The authors examined the number of CD8+ TEMRA cells over time and found that the difference in CD8+ TEMRA cell number in patients with delayed healing reflected the individual’s immune profile, or lifelong response to infection, rather than a more acute, fracture-related event. They specifically found these cells in fracture hematoma, one of the earliest stages of fracture healing. They then took these studies into mice and found that the absence of CD8+ T cells improved bone regeneration, whereas adding CD8+ T cells impaired fracture healing. This mechanistic link supported their association in patients and suggests that these CD8+ TEMRA cells may be targeted or serve as markers for intervention in patients with delayed bone fracture healing. There is growing evidence that adaptive immunity contributes to endogenous regeneration processes: For example, endogenous bone fracture repair is modulated by T cells even in the absence of infection. Because delayed or incomplete fracture healing is associated with poor long-term outcomes and high socioeconomic costs, we investigated the relationship between an individual’s immune reactivity and healing outcome. Our study revealed that delayed fracture healing significantly correlated with enhanced levels of terminally differentiated CD8+ effector memory T (TEMRA) cells (CD3+CD8+CD11a++CD28−CD57+ T cells) in peripheral blood. This difference was long lasting, reflecting rather the individual’s immune profile in response to lifelong antigen exposure than a post-fracture reaction. Moreover, CD8+ TEMRA cells were enriched in fracture hematoma; these cells were the major producers of interferon-γ/tumor necrosis factor–α, which inhibit osteogenic differentiation and survival of human mesenchymal stromal cells. Accordingly, depletion of CD8+ T cells in a mouse osteotomy model resulted in enhanced endogenous fracture regeneration, whereas a transfer of CD8+ T cells impaired the healing process. Our data demonstrate the high impact of the individual adaptive immune profile on endogenous bone regeneration. Quantification of CD8+ TEMRA cells represents a potential marker for the prognosis of the healing outcome and opens new opportunities for early and targeted intervention strategies.

The spectral content of postural sway during quiet stance: Influences of age, vision and somatosensory inputs

Maintenance of human upright stance requires the acquisition and integration of sensory inputs. Conventional measures of sway have had success in identifying age- and some disease-related changes, but remain unable to address the complexities and dynamics associated with postural control. We investigated the effects of vision, surface compliance, age, and gender on the spectral content of center of pressure (COP) time series. Sixteen healthy young (age 18-24) and older participants (age 55-65) performed trials of quiet, upright stance under different vision (eyes open vs. closed) and surface (hard vs. compliant) conditions. Spectral analyses were conducted to describe COP mean normalized power in discretized bands. Effects of the two sensory modalities and age were distinct in the antero-posterior and medio-lateral directions, and a reorganization of spectral content was evident with increasing task difficulty (eyes open vs. closed and hard vs. compliant surface) and among older adults. These results indicate that vision and surface compliance are predominantly associated with responses from musculature associated with antero-posterior and medio-lateral directions of sway, respectively. Finally, distinguishing between the contributions of different afferent systems to the postural control system using the spectral content of sway bi-directionally may help in diagnosing individuals with balance impairments.

Stair climbing results in more challenging patellofemoral contact mechanics and kinematics than walking at early knee flexion under physiological-like quadriceps loading

The mechanical environment during stair climbing has been associated with patellofemoral pain, but the contribution of loading to this condition is not clearly understood. It was hypothesized that the loading conditions during stair climbing induce higher patellofemoral pressures, a more lateral force distribution on the trochlea and a more lateral shift and tilt of the patella compared to walking at early knee flexion. Optical markers for kinematic measurements were attached to eight cadaveric knees, which were loaded with muscle forces at instances of walking and stair climbing cycles at 12 degrees and 30 degrees knee flexion. Contact mechanics were determined using a pressure sensitive film. At 12 degrees knee flexion, stair climbing loads resulted in higher peak pressure (p=0.012) than walking, more lateral force distribution (p=0.012) and more lateral tilt (p=0.012), whilst mean pressure (p=0.069) and contact area (p=0.123) were not significantly different. At 30 degrees knee flexion, although stair climbing compared to walking loads resulted in significantly higher patellofemoral mean (p=0.012) and peak pressures (p=0.012), contact area (p=0.025), as well as tilt (p=0.017), the medial-lateral force distribution (p=0.674) was not significantly different. No significant differences were observed in patellar shift between walking and stair climbing at either 12 degrees (p=0.093) or 30 degrees (p=0.575) knee flexion. Stair climbing thus leads to more challenging patellofemoral contact mechanics and kinematics than level walking at early knee flexion. The increase in patellofemoral pressure, lateral force distribution and lateral tilt during stair climbing provides a possible biomechanical explanation for the patellofemoral pain frequently experienced during this activity.

Towards clinical application: Repetitive sensor position re-calibration for improved reliability of gait parameters

While camera-based motion tracking systems are considered to be the gold standard for kinematic analysis, these systems are not practical in clinical practice. However, the collection of gait parameters using inertial sensors is feasible in clinical settings and less expensive, but suffers from drift error that excludes accurate analyses. The goal of this study was to apply a combination of repetitive sensor position re-calibration techniques in order to improve the intra-day and inter-day reliability of gait parameters using inertial sensors. Kinematic data of nineteen healthy elderly individuals were captured twice within the first day and once on a second day after one week using inertial sensors fixed on the subjects forefoot during gait. Parameters of walking speed, minimum foot clearance (MFC), minimum toe clearance (MTC), stride length, stance time and swing time, as well as their corresponding measures of variability were calculated. Intra-day and inter-day differences were rated using intra-class correlation coefficients (ICC(3,1)), as well as the bias and limits of agreement. The results indicate excellent reliability for all intra-day and inter-day mean parameters (ICC: MFC 0.83-stride length 0.99). While good to excellent reliability was observed during intra-day parameters of variability (ICC: walking speed 0.71-MTC 0.98), corresponding inter-day reliability ranged from poor to excellent (ICC: walking speed 0.32-MTC 0.95). In conclusion, the system is suitable for reliable measurement of mean temporo-spatial parameters and the variability of MFC and MTC. However, the systems accuracy needs to be improved before remaining parameters of variability can reliably be collected.

Effect of fatigue on force fluctuations in knee extensors in young adults

This study investigated the hypothesis that fatiguing exercises led to increased force fluctuations during submaximal isometric knee extensions and to decreased accuracy and steadiness in the time and frequency domains. Sixteen young adults (eight males, eight females) were tested, in a seated posture with 90° knee flexion, to assess their ability to reproduce target extensor torques set at 15 per cent and 20 per cent of their maximum voluntary isometric contraction, both before and after fatiguing exercises. Normalized mean (NMAE) and peak (NPAE) of the absolute error were both used to quantify accuracy, whereas normalized standard deviation of the absolute error (NSAE) was used to quantify steadiness of the torque trials in the time domain. Mean and median power frequencies (MnPF, MdPF) and normalized peak power (NPkP) were used to assess the spectral structure of the torque signals. NMAE, NSAE and NPAE all showed excellent intra- as well as intersession reliabilities (intraclass correlation values greater than 0.75 and low standard error of measurement values), demonstrating repeatability of the test set-up. NMAE, NSAE and NPAE increased significantly post-fatigue (greater than 42%), together with a shift towards higher frequency (MnPF and MdPF) components, indicating that the set-up was sensitive enough to detect the decreased force accuracy and steadiness of the musculature after fatigue. Increased force variability in both the time and frequency domains could therefore explain decreased steadiness after fatigue.

Extreme Levels of Noise Constitute a Key Neuromuscular Deficit in the Elderly

Fluctuations during isometric force production tasks occur due to the inability of musculature to generate purely constant submaximal forces and are considered to be an estimation of neuromuscular noise. The human sensori-motor system regulates complex interactions between multiple afferent and efferent systems, which results in variability during functional task performance. Since muscles are the only active component of the motor system, it therefore seems reasonable that neuromuscular noise plays a key role in governing variability during both standing and walking. Seventy elderly women (including 34 fallers) performed multiple repetitions of isometric force production, quiet standing and walking tasks. No relationship between neuromuscular noise and functional task performance was observed in either the faller or the non-faller cohorts. When classified into groups with either nominal (group NOM, 25th –75th percentile) or extreme (either too high or too low, group EXT) levels of neuromuscular noise, group NOM demonstrated a clear association (r2>0.23, p<0.05) between neuromuscular noise and variability during task performance. On the other hand, group EXT demonstrated no such relationship, but also tended to walk slower, and had lower stride lengths, as well as lower isometric strength. These results suggest that neuromuscular noise is related to the quality of both static and dynamic functional task performance, but also that extreme levels of neuromuscular noise constitute a key neuromuscular deficit in the elderly.

Towards the assessment of local dynamic stability of level-grounded walking in an older population.

Local dynamic stability is a critical aspect of stable gait but its assessment for use in clinical settings has not yet been sufficiently evaluated, particularly with respect to inertial sensors applied on the feet and/or trunk. Furthermore, key questions remain as to which state-space reconstruction is most reliable and valid. In this study, we evaluated the reliability as well as the ability of different sensor placement and state-spaces to distinguish between local dynamic stability in young and older adults. Gait data of 19 older and 20 young subjects were captured with inertial sensors twice within the first day as well as after seven days. 21 different signals (and combinations of signals) were used to span the systems state-space to calculate different measures of local dynamic stability. Our data revealed moderate or high effect sizes in 12 of the 21 old vs. young comparisons. We also observed considerable differences in the reliability of these 12 results, with intra-class correlation coefficients ranging from 0.09 to 0.81. Our results demonstrate that in order to obtain reliable and valid estimates of gait stability λ of walking time series is best evaluated using trunk data or 1-dimensional data from foot sensors.

Regulation of the patellofemoral contact area: An essential mechanism in patellofemoral joint mechanics?

Although the relationship between contact area and pressure under physiological loading has been described in the feline patellofemoral joint, this interaction has only been examined under simplified loading conditions and/or considerably lower forces than those occurring during demanding activities in humans. We hypothesized that patellofemoral contact area increases non-linearly under an increasing joint reaction force to regulate patellofemoral pressure. Eight human cadaveric knees were ramp loaded with muscle forces representative of the stance phase of stair climbing at 30° knee flexion. Continuous pressure data were acquired with a pressure sensitive film that was positioned within the patellofemoral joint. While pressure was linearly dependent upon the resulting joint reaction force, contact area asymptotically approached a maximum value and reached 95% of this maximum at patellofemoral forces of 349-723N (95% CI). Our findings indicate that the regulatory influence of increasing contact area to protect against high patellofemoral pressure is exhausted at relatively low loads.

Revealing the quality of movement: A meta-analysis review to quantify the thresholds to pathological variability during standing and walking

Neuromotor processes are inherently noisy, which results in variability during movement and fluctuations in motor control. Although controversial, low levels of variability are traditionally considered healthy, while increased levels are thought to be pathological. This systematic review and meta-analysis of the literature investigates the thresholds between healthy and pathological task variability. After examining 13,195 publications, 109 studies were included. Results from over 3000 healthy subjects and 2775 patients revealed an overall positive effect size of pathology on variability of 0.59 for walking and 0.80 for sway. For the coefficient of variation of stride time (ST) and sway area (SA), upper thresholds of 2.6% and 265mm(2) discriminated pathological from asymptomatic performance, while 1.1% and 62mm(2) identified the lower thresholds for pathological variability. This window of healthy performance now provides science based evidence for the discrimination of both extremely low and extremely high levels of variability in the identification as well as standardised monitoring of functional status in neurological cases.