The Agreement between Wearable Sensors and Force Plates for the Analysis of Stride Time Variability.

The variability and regularity of stride time may help identify individuals at a greater risk of injury during military load carriage. Wearable sensors could provide a cost-effective, portable solution for recording these measures, but establishing their validity is necessary. This study aimed to determine the agreement of several measures of stride time variability across five wearable sensors (Opal APDM, Vicon Blue Trident, Axivity, Plantiga, Xsens DOT) and force plates during military load carriage. Nineteen Australian Army trainee soldiers (age: 24.8 ± 5.3 years, height: 1.77 ± 0.09 m, body mass: 79.5 ± 15.2 kg, service: 1.7 ± 1.7 years) completed three 12-min walking trials on an instrumented treadmill at 5.5 km/h, carrying 23 kg of an external load. Simultaneously, 512 stride time intervals were identified from treadmill-embedded force plates and each sensor where linear (standard deviation and coefficient of variation) and non-linear (detrended fluctuation analysis and sample entropy) measures were obtained. Sensor and force plate agreement was evaluated using Pearson's r and intraclass correlation coefficients. All sensors had at least moderate agreement (ICC > 0.5) and a strong positive correlation (r > 0.5). These results suggest wearable devices could be employed to quantify linear and non-linear measures of stride time variability during military load carriage.

Postural behaviour in people with multiple sclerosis: A complexity paradox.

BACKGROUND: Balance deficits are a major concern for people with multiple sclerosis (pwMS). Measuring complexity of motor behaviour can offer an insight into MS-related changes in adaptability of the balance control system when dealing with increasingly complex tasks. QUESTION: Does postural behaviour complexity differ between pwMS at early stages of the disease and healthy controls (HC)? Does postural behaviour complexity change across increasingly complex tasks? METHODS: Forty-eight pwMS and 24 HC performed four increasingly complex postural tasks with eyes open (EO), eyes closed (EC), on firm (FS) and compliant surface (CS). Lumbar and sternum sensors recorded 3D acceleration, from which complexity index (CI) was calculated using multiscale sample entropy (MSE) in the frontal and sagittal planes. RESULTS: We found that only the complexity index in both planes during the eyes closed on compliant surface (EC-CS) task was significantly lower in pwMS compared to HC. We also found that complexity in pwMS was significantly lower during EC-CS compared to the other three tasks when using both lumbar and sternum sensors. SIGNIFICANCE: Increasing the complexity of postural tasks reduces the complexity of postural behaviour in pwMS. This paradox may reflect reduced adaptability of the sensorimotor integration processes at early stages of MS. CI can provide a different perspective on balance deficits and could potentially be a more sensitive biomarker of MS progression and an early indicator of balance deficit.

Sample Entropy Improves Assessment of Postural Control in Early-Stage Multiple Sclerosis.

Postural impairment in people with multiple sclerosis (pwMS) is an early indicator of disease progression. Common measures of disease assessment are not sensitive to early-stage MS. Sample entropy (SE) may better identify early impairments. We compared the sensitivity and specificity of SE with linear measurements, differentiating pwMS (EDSS 0-4) from healthy controls (HC). 58 pwMS (EDSS ≤ 4) and 23 HC performed quiet standing tasks, combining a hard or foam surface with eyes open or eyes closed as a condition. Sway was recorded at the sternum and lumbar spine. Linear measures, mediolateral acceleration range with eyes open, mediolateral jerk with eyes closed, and SE in the anteroposterior and mediolateral directions were calculated. A multivariate ANOVA and AUC-ROC were used to determine between-groups differences and discriminative ability, respectively. Mild MS (EDSS ≤ 2.0) discriminability was secondarily assessed. Significantly lower SE was observed under most conditions in pwMS compared to HC, except for lumbar and sternum SE when on a hard surface with eyes closed and in the anteroposterior direction, which also offered the strongest discriminability (AUC = 0.747), even for mild MS. Overall, between-groups differences were task-dependent, and SE (anteroposterior, hard surface, eyes closed) was the best pwMS classifier. SE may prove a useful tool to detect subtle MS progression and intervention effectiveness.

Optimal sensor location and direction to accurately classify people with early-stage multiple sclerosis using gait stability.

BACKGROUND: The local divergence exponent (LDE) has been used to assess gait stability in people with multiple sclerosis (pwMS). Although previous studies have consistently found that stability is lower in pwMS, inconsistent methodologies have been used to assess patients with a broad range of disability levels. QUESTIONS: What sensor location and movement direction(s) are better able to classify pwMS at early stages of the disease? METHODS: 49 pwMS with EDSS ≤ 2.5 and 24 healthy controls walked overground for 5 min while 3D acceleration data was obtained from sensors placed at the sternum (STR) and lumbar (LUM) areas. Unidirectional (vertical [VT], mediolateral [ML], and anteroposterior [AP]) and 3-dimensional (3D) LDEs were calculated using STR and LUM data over 150 strides. ROC analyses were performed to assess classification models using single and combined LDEs, with and without velocity per lap (VELLAP) as a covariate. RESULTS: Four models performed equally well by using combinations of VELLAP, LUM3D, LUMVT, LUMML, LUMAP, STRML, and STRAP (AUC = 0.879). The best model using single sensor LDEs included VELLAP, STR3D, STRML, and STRAP (AUC = 0.878), whereas using VELLAP + STRVT (AUC = 0.869) or VELLAP + STR3D (AUC=0.858) performed best using a single LDE. SIGNIFICANCE: The LDE offers an alternative to currently insensitive tests of gait impairment in pwMS at early stages, when deterioration is not clinically evident. For clinical purposes, the implementation of this measure can be simplified using a single sensor at the sternum and a single LDE measure, but speed should be considered. Longitudinal studies to determine the predictive power and responsiveness of the LDE to MS progression are still needed.

Can handling a weapon make soldiers more unstable?

Gait stability in soldiers can be affected by task constraints that may lead to injuries. This study determined the effects of weapon handling and speed on gait stability in seventeen soldiers walking on a treadmill with and without a replica weapon at self-selected (SS), 3.5 km·h-1, 5.5 km·h-1, and 6.5 km·h-1 while carrying a 23-kg load. Local dynamic stability was measured using accelerometry at the sacrum (LDESAC) and sternum (LDESTR). No significant weapon and speed interaction were found. A significant effect of speed for the LDESAC, and a significant effect of speed and weapon for the LDESTR were found. Per plane analyses showed that the weapon effect was consistent across all directions for the LDESTR but not for LDESAC. Weapon handling increased trunk but did not affect pelvis stability. Speed decreased stability when walking slower than SS and increased when faster. These findings can inform injury prevention strategies in the military. Practitioner summary: We determined the effects of two constraints in soldier's walking stability, weapon handling and speed, measured at the trunk and sacrum. No constraints interactions were found, however, lower stability when walking slow and greater stability with the weapon at the trunk can inform preventive strategies in military training.

Implementing education: Personal communication with a healthcare professional is a critical step to address vaccine hesitancy for people with multiple sclerosis.

BACKGROUND: People with Multiple Sclerosis (PwMS) were first able to access COVID-19 vaccines in Australia from March 2021, when vaccine hesitancy in the general population was high (14-43%). High uptake of vaccination is important globally and critical to protect this vulnerable population. We conducted an on-line survey to examine factors influencing COVID-19 vaccination willingness among PwMS in Australia. METHODS: 149 PwMS living in Australia completed the on-line survey (April-September 2021) examining demographic, environmental and clinical factors with respect to vaccine willingness, including attitudes towards COVID-19 illness and vaccines. Additional items explored the influence of different information sources on vaccination decisions. Continuous and ordinal data were compared using the Mann-Whitney U test. All tests were two-tailed, with alpha set at 0.5. RESULTS: A majority of the respondents were female (87.2%) with relapsing-remitting MS (77.5%) treated by a neurologist (94.0%). A majority were on high efficacy disease-modifying therapies (DMTs) (64.9%), while 19.9% were on no DMTs. About one third of respondents (32.9%) had had two doses, 20.8% had received their first dose, and 22.1% were unvaccinated, while 24.2% of responses were missing. When asked about vaccine intentions, 60.6% of the unvaccinated indicated they were likely to extremely likely to get vaccinated, while 15.2% were very unlikely or extremely unlikely to do so and 24.2% were undecided. Unvaccinated people were significantly more concerned about vaccine side effects (mean 5.3 versus 3.1/10; p < .001). Only 53.3% of people on DMTs were vaccinated, compared to 75% of those who were not. People on ocrelizumab therapy (n = 35) had a lower vaccination rate (39%) than those on other medications (n = 86, 59%). Vaccine willingness in the unvaccinated was most highly correlated with knowledge regarding the vaccine (rs2=.709), agreement with the statement that COVID-19 vaccination is "too new for me to be confident about getting vaccinated" (rs2= -.709), anticipation of regret due to side effects of vaccination (rs2= -.642), and lack of knowledge regarding interactions between COVID-19 vaccines and DMTs (rs2= -.570). Almost two thirds had read MS-specific information about COVID-19 vaccinations and found it easy to understand (67.6%) and applicable to their situation (53.6%). However, less than half (47.8%) reported the information helped them make a personal vaccination decision. Over two-thirds (64.9%) had discussed vaccinations with their healthcare professional and 31.1% had not. Those who had not, were significantly more uninformed about the interactions of the vaccine with MS medications (mean 3.9 versus 2.9/10; p = .044) and significantly lower intention of vaccine uptake than those who had (mean 5.8 versus 7.9/10; p = .009). CONCLUSION: Our study highlights that vaccination efforts should be delivered by healthcare professionals, focus on educating those who are managed with DMTs, and include individual recommendations related to specific DMTs, how the vaccines work, expectations regarding potential side-effects, potential exacerbation of MS symptoms, likelihood of recovery from any exacerbation, and the relative risks of side effects versus COVID-19 infection. Specific recommendations are provided.

Gait stability reflects motor tracts damage at early stages of multiple sclerosis.

BACKGROUND: Gait in people with multiple sclerosis (PwMS) is affected even when no changes can be observed on clinical examination. A sensitive measure of gait deterioration is stability; however, its correlation with motor tract damage has not yet been established. OBJECTIVE: To compare stability between PwMS and healthy controls (HCs) and determine associations between stability and diffusion magnetic resonance image (MRI) measures of axonal damage in selected sensorimotor tracts. METHODS: Twenty-five PwMS (Expanded Disability Status Scale (EDSS) < 2.5) and 15 HCs walked on a treadmill. Stability from sacrum (LDESAC), shoulder (LDESHO) and cervical (LDECER) was calculated using the local divergence exponent (LDE). Participants underwent a 7T-MRI brain scan to obtain fibre-specific measures of axonal loss within the corticospinal tract (CST), interhemispheric sensorimotor tract (IHST) and cerebellothalamic tract (CTT). Correlation analyses between LDE and fibre density (FD) within tracts, fibre cross-section (FC) and FD modulated by FC (FDC) were conducted. Between-groups LDE differences were analysed using analysis of variance (ANOVA). RESULTS: Correlations between all stability measures with CSTFD, between CSTFDC with LDESAC and LDECER, and LDECER with IHSTFD and IHSTFDC were significant yet moderate (R < -0.4). Stability was significantly different between groups. CONCLUSIONS: Poorer gait stability is associated with corticospinal tract (CST) axonal loss in PwMS with no-to-low disability and is a sensitive indicator of neurodegeneration.

Axonal loss in major sensorimotor tracts is associated with impaired motor performance in minimally disabled multiple sclerosis patients.

Multiple sclerosis is a neuroinflammatory disease of the CNS that is associated with significant irreversible neuro-axonal loss, leading to permanent disability. There is thus an urgent need for in vivo markers of axonal loss for use in patient monitoring or as end-points for trials of neuroprotective agents. Advanced diffusion MRI can provide markers of diffuse loss of axonal fibre density or atrophy within specific white matter pathways. These markers can be interrogated in specific white matter tracts that underpin important functional domains such as sensorimotor function. This study aimed to evaluate advanced diffusion MRI markers of axonal loss within the major sensorimotor tracts of the brain, and to correlate the degree of axonal loss in these tracts to precise kinematic measures of hand and foot motor control and gait in minimally disabled people with multiple sclerosis. Twenty-eight patients (Expanded Disability Status Scale < 4, and Kurtzke Functional System Scores for pyramidal and cerebellar function ≤ 2) and 18 healthy subjects underwent ultra-high field 7 Tesla diffusion MRI for calculation of fibre-specific measures of axonal loss (fibre density, reflecting diffuse axonal loss and fibre cross-section reflecting tract atrophy) within three tracts: cortico-spinal tract, interhemispheric sensorimotor tract and cerebello-thalamic tracts. A visually guided force-matching task involving either the hand or foot was used to assess visuomotor control, and three-dimensional marker-based video tracking was used to assess gait. Fibre-specific axonal markers for each tract were compared between groups and correlated with visuomotor task performance (force error and lag) and gait parameters (stance, stride length, step width, single and double support) in patients. Patients displayed significant regional loss of fibre cross-section with minimal loss of fibre density in all tracts of interest compared to healthy subjects (family-wise error corrected p-value < 0.05), despite relatively few focal lesions within these tracts. In patients, reduced axonal fibre density and cross-section within the corticospinal tracts and interhemispheric sensorimotor tracts were associated with larger force tracking error and gait impairments (shorter stance, smaller step width and longer double support) (family-wise error corrected p-value < 0.05). In conclusion, significant gait and motor control impairments can be detected in minimally disabled people with multiple sclerosis that correlated with axonal loss in major sensorimotor pathways of the brain. Given that axonal loss is irreversible, the combined use of advanced imaging and kinematic markers could be used to identify patients at risk of more severe motor impairments as they emerge for more aggressive therapeutic interventions.

Impaired Weight-Shift Amplitude in People with Parkinson's Disease with Freezing of Gait.

BACKGROUND: People with Parkinson's disease and freezing of gait (FOG; freezers) suffer from pronounced postural instability. However, the relationship between these phenomena remains unclear and has mostly been tested in paradigms requiring step generation. OBJECTIVE: To determine if freezing-related dynamic balance deficits are present during a task without stepping and determine the influence of dopaminergic medication on dynamic balance control. METHODS: Twenty-two freezers, 16 non-freezers, and 20 healthy age-matched controls performed mediolateral weight-shifts at increasing frequencies when following a visual target projected on a screen (MELBA task). The amplitude and phase shift differences between center of mass and target motion were measured. Balance scores (Mini-BESTest), 360° turning speed and the freezing ratio were also measured. Subjects with Parkinson's disease were tested ON and partial OFF (overnight withdrawal) dopaminergic medication. RESULTS: Freezers had comparable turning speed and balance scores to non-freezers and took more levodopa. Freezers produced hypokinetic weight-shift amplitudes throughout the MELBA task compared to non-freezers (p = 0.002), which were already present at task onset (p < 0.001). Freezers also displayed an earlier weight-shift breakdown than controls when OFF-medication (p = 0.008). Medication improved mediolateral weight-shifting in freezers and non-freezers. Freezers decreased their freezing ratio in response to medication. CONCLUSION: Hypokinetic weight-shifting proved a marked postural control deficit in freezers, while balance scores and turning speed were similar to non-freezers. Both weight-shift amplitudes and the freezing ratio were responsive to medication in freezers, suggesting axial motor vigor is levodopa-responsive. Future work needs to test whether weight-shifting and freezing severity can be further ameliorated through training.

Speech metrics, general disability, brain imaging and quality of life in multiple sclerosis.

BACKGROUND AND PURPOSE: Objective measurement of speech has shown promising results to monitor disease state in multiple sclerosis. In this study, we characterize the relationship between disease severity and speech metrics through perceptual (listener based) and objective acoustic analysis. We further look at deviations of acoustic metrics in people with no perceivable dysarthria. METHODS: Correlations and regression were calculated between speech measurements and disability scores, brain volume, lesion load and quality of life. Speech measurements were further compared between three subgroups of increasing overall neurological disability: mild (as rated by the Expanded Disability Status Scale ≤2.5), moderate (≥3 and ≤5.5) and severe (≥6). RESULTS: Clinical speech impairment occurred majorly in people with severe disability. An experimental acoustic composite score differentiated mild from moderate (P < 0.001) and moderate from severe subgroups (P = 0.003), and correlated with overall neurological disability (r = 0.6, P < 0.001), quality of life (r = 0.5, P < 0.001), white matter volume (r = 0.3, P = 0.007) and lesion load (r = 0.3, P = 0.008). Acoustic metrics also correlated with disability scores in people with no perceivable dysarthria. CONCLUSIONS: Acoustic analysis offers a valuable insight into the development of speech impairment in multiple sclerosis. These results highlight the potential of automated analysis of speech to assist in monitoring disease progression and treatment response.

Multidisciplinary rehabilitation in persons with multiple trauma: A systematic review.

OBJECTIVE: To determine the effectiveness of multidisciplinary rehabilitation in improving functional and psychological outcomes in person with multiple trauma. DATE SOURCES: A comprehensive literature review was conducted using medical and health science electronic databases up to February 2019. DATA EXTRACTION: Two independent reviewers selected studies, extracted data and assessed study quality using the Critical Appraisal Skills Programme (CASP) checklists and Grading of Recommendations, Assessment, Development and Evaluations (GRADE). DATA SYNTHESIS: One randomized controlled trial, 1 clinical controlled trial and 4 observational studies (1 with 2 reports) were included. Qualitative analysis was used to synthesize the evidence due to the heterogeneity of included trials. The quality of the studies varied (CASP approach); the majority were of "low quality". The findings suggest "very low to moderate" evidence (GRADE) for the effectiveness of multidisciplinary rehabilitation in improving functional ability and participation. The majority of studies (n = 6) reported functional improvements after multidisciplinary rehabilitation in the short-term. CONCLUSION: The lack of "high-quality" evidence for multidisciplinary rehabilitation in improving outcomes following trauma highlights gaps in the available evidence, signifying the need for more robust studies.

Individual muscle contributions to hip joint-contact forces during walking in unilateral transfemoral amputees with osseointegrated prostheses.

Direct skeletal attachment of prostheses in transfemoral amputees circumvents skin-interface complications associated with conventional sockets; however, joint pain and musculoskeletal disease is known to occur postoperatively. This study quantified hip contact forces and the roles of individual muscles in producing hip contact forces during walking in transfemoral amputees with osseointegrated prostheses. Musculoskeletal models were developed for four transfemoral amputees. Gluteus maximus and gluteus medius were the major contributors to the hip contact forces, and the intact limb hip muscles demonstrated greater contributions to hip contact forces than those of the residual limb. The findings may be useful for mitigating walking asymmetry.

Increased ankle muscle coactivation in the early stages of multiple sclerosis.

BACKGROUND: Neural damage at early stages of multiple sclerosis (MS) can subtly affect gait muscle activation patterns. Detecting these changes using current clinical tools, however, is not possible. We propose using muscle coactivation measures to detect these subtle gait changes. This may also help in identifying people with MS (PwMS) that may benefit from strategies aimed at preventing further mobility impairments. OBJECTIVE: We aimed to determine if coactivation of ankle muscles during gait is greater in PwMS with Expanded Disability Status Scale (EDSS) score <3.5. A secondary aim is to determine whether coactivation increases are speed dependent. METHODS: For this study 30 PwMS and 15 healthy controls (HC) walked on a treadmill at 1.0 m/s, 1.2 m/s and 1.4 m/s. Electromyography was recorded from the tibialis anterior (TA), soleus (SO) and lateral gastrocnemius (LG). The coactivation index was calculated between SO/TA and LG/TA. Ankle kinematics data were also collected. RESULTS: Compared with HC, PwMS exhibited significantly greater SO/TA and LG/TA coactivation, which was greater during early stance and swing phases (p < .01). Speed did not affect coactivation except during early stance. Ankle kinematic changes were also observed. CONCLUSION: PwMS exhibited greater ankle muscles coactivation than controls regardless of the speed of walking. These changes in muscle activation may serve as a biomarker of neurodegeneration occurring at early stages of the disease.

Gait stability at early stages of multiple sclerosis using different data sources.

BACKGROUND: People at early stages of multiple sclerosis have subtle balance problems that may affect gait stability. However, differences in methods of determining stability such as sensor type and placements, may lead to different results and affect their interpretation when comparing to controls and other studies. QUESTIONS: Do people with multiple sclerosis (PwMS) exhibit lower gait stability? Do location and type of data used to calculate stability metrics affect comparisons? METHODS: 30 PwMS with no walking impairments as clinically measured and 15 healthy controls walked on a treadmill at 1.2 ms-1 while 3D acceleration data was obtained from sacrum, shoulder and cervical markers and from an accelerometer placed at the sacrum. The local divergence exponent was calculated for the four data sources. An ANOVA with group (multiple sclerosis and control) and data source as main factors was used to determine the effect of disease, data source and their interaction on stability metrics. RESULTS: PwMS walked with significantly less stability according to all sensors (no interaction). A significant effect of data source on stability was also found, indicating that the local divergence exponent derived from sacrum accelerometer was lower than that derived from the other 3 sensor locations. SIGNIFICANCE: PwMS with no evident gait impairments are less stable than healthy controls when walking on a treadmill. Although different data sources can be used to determine MS-related stability deterioration, a consensus about location and data source is needed. The local divergence exponent can be a useful measure of progression of gait instability at early stages of MS.

Load response of an osseointegrated implant used in the treatment of unilateral transfemoral amputation: An early implant loosening case study.

BACKGROUND: Osseointegrated implants for transfemoral amputees facilitate direct load transfer between the prosthetic limb and femur; however, implant loosening is a common complication, and the associated implant-bone loads remain poorly understood. This case study aimed to use patient-specific computational modeling to evaluate bone-implant interface loading during standing and walking in a transfemoral amputee with an osseointegrated implant prior to prosthesis loosening and revision surgery. METHODS: One male transfemoral amputee with an osseointegrated implant was recruited (age: 59-yrs, weight: 83 kg) and computed tomography (CT) performed on the residual limb approximately 3 months prior to implant failure. Gait analyses were performed, and the CT images used to develop a finite element model of the patient's implant and surrounding bone. Simulations of static weight bearing, and over-ground walking were then performed. FINDINGS: During standing, maximum and minimum principal strains in trabecular bone adjacent to the implant were 0.26% and -0.30%, respectively. Strains generated at the instant of contralateral toe-off and contralateral heel strike during walking were substantially higher and resulted in local trabecular bone yielding. Specifically, the maximum and minimum principal strains in the thin layer of trabecular bone surrounding the distal end of the implant were 1.15% and -0.98%, respectively. INTERPRETATION: Localised yielding of trabecular bone at the interface between the femur and implant in transfemoral amputee osseointegrated prosthesis recipients may present a risk of implant loosening due to periprosthetic bone fracture during walking. Rehabilitation exercises should aim to produce implant-bone loading that stimulates bone remodelling to provide effective bone conditioning prior to ambulation.

Gait compensatory mechanisms in unilateral transfemoral amputees.

Individuals with unilateral transfemoral amputation depend on compensatory muscle and joint function to generate motion of the lower limbs, which can produce gait asymmetry; however, the functional role of the intact and residual limb muscles of transfemoral amputees in generating progression, support, and mediolateral balance of the body during walking is not well understood. The aim of this study was to quantify the contributions of the intact and the residual limb's contralateral muscles to body center of mass (COM) acceleration during walking in transfemoral amputees. Three-dimensional subject-specific musculoskeletal models of 6 transfemoral amputees fitted with a socket-type prosthesis were developed and used to quantify muscle forces and muscle contributions to the fore-aft, vertical, and mediolateral body COM acceleration using a pseudo-inverse ground reaction force decomposition method during over-ground walking. Anterior pelvic tilt and hip range of motion in the sagittal and frontal planes of the intact limb was significantly larger than those in the residual limb (p<0.05). The mean contributions of the intact limb hip muscles to body COM support, forward propulsion and mediolateral balance were significantly greater than those in the residual limb (p<0.05). Gluteus maximus contributed more to propulsion and support, while gluteus medius contributed more to balance than other muscles in the intact limb than the residual limb. The findings demonstrate the role of the intact limb hip musculature in compensating for reduced or absent muscles and joint function in the residual limb of transfemoral amputees during walking. The results may be useful in developing rehabilitation programs and design of prostheses to improve gait symmetry and mitigate post-operative musculoskeletal pathology.

Multidimensional evaluation of changes in limb function following botulinum toxin injection in persons with stroke.

BACKGROUND: There are limited evidence of instrumented measures of gait and balance to determine the functional effects of botulinum toxin injections (BoNT-A) in spasticity after stroke. OBJECTIVE: To evaluate the functional changes in gait and balance following upper limb and lower limb BoNT-A in persons with stroke. METHODS: A pre-post prospective study of 35 stroke patients with upper and/or lower limb spasticity after focal treatment with BoNT-A. Assessments were at baseline (T0), 6-weeks (T1) and 12-weeks (T2), using validated subjective and objective physical activity measures. RESULTS: After BoNT-A injections, significant improvements in most measures of impairments, activity and participation domains were found at T1 (p < 0.05, effect sizes (r) = 0.5-0.9). There was a significant increase in low intensity physical activity (at T1) and sedentary time reductions at both follow-up periods. Instrumented gait/balance measures showed a significant increase in cadence and turn velocity, but no changes in sway measures were found using posturography. Improvements in most outcome measures were maintained at 12-weeks. CONCLUSION: BONT-A improved scores in most clinical measures but only in some of the objective gait/balance and physical activity measures. Further robust studies should utilize a larger sample size to better determine the benefits of BoNT-A for stroke-related spasticity.

Beyond speed: Gait changes after botulinum toxin injections in chronic stroke survivors (a systematic review).

BACKGROUND: The mechanisms by which spasticity reductions after botulinum toxin A (BoNT) affect gait in stroke are not well understood. We systematically reviewed the effects of BoNT on spatiotemporal, kinematic, kinetic and electromyographic (EMG) measures during gait. QUESTION: What are the effects of botulinum toxin on gait mechanics in stroke patients? METHODS: Systematic search using PubMed and Web of Science. We considered all studies that reported laboratory-based and instrumented gait measures as primary or secondary outcomes to determine the effects of BoNT on walking performance in stroke populations only. Selected studies were classified and analysed based on the injection sites. RESULTS: A total of 240 articles were identified of which 22 were selected for analysis. Overall, 91% of the studies reported spatiotemporal, 64% kinematics, 23% kinetics, 32% EMG and 23% other gait measures. All but one study found significant effects of BoNT on gait measures using instrumented assessments even when clinical measures (i.e. speed) did not significantly improve. However, the majority of the studies had a high risk of bias. Overall, BoNT improved: a) dorsiflexion during stance, propulsive forces and timing and activity of more proximal musculature with injections in the plantarflexors; b) hip, knee and ankle angles and velocities, coordination and energetic cost with injections in the rectus femoris; c) segmental coordination and energetic cost when several lower limb muscles were injected; and, d) elbow and trunk angles when upper limb muscles were injected. CONCLUSION: Instrumented and laboratory measures of gait improve after BoNT injections in different muscle groups even in the absence of clinical changes.

Assessing age-related balance deterioration: Visual or mechanical tasks?

BACKGROUND: Mediolateral balance assessment (MELBA) comprises tracking of predictable and unpredictable targets moving at increasing frequencies, using centre-of-mass feedback. The mediolateral-balance-assessment was shown to be sensitive to subtle age-related balance deterioration. However, it has been suggested that performance during ground-level tasks can be more sensitive to balance deterioration. METHODS: we developed a modified mediolateral-balance-assessment using tracking of surface translations with comparable waveforms (mechanical mediolateral-balance-assessment) to compare age sensitivity of the visual and mechanical mediolateral-balance-assessment, 15 older adults (68 SD 5 yr) and 12 young adults (30 SD 4 yr) performed both tasks. Phase-shift and gain between the CoM and either the visual target or the surface displacement for the visual and the mechanical mediolateral-balance-assessment, respectively, were calculated. To identify differences in tracking strategies between the visual and mechanical mediolateral-balance-assessment, phase-shift between trunk and leg angles was calculated. FINDINGS: Overall, older adults performed worse than young across the predictable and unpredictable tracking and visual and mechanical tasks. Of all mediolateral-balance-assessment performance descriptors, a significant interaction between age and task (visual or mechanical) was only found for the mean phase-shift. Post-hoc comparisons revealed significant age differences in the visual but not in the mechanical mediolateral-balance-assessment. Significant differences in tracking strategies were found between visual and mechanical mediolateral-balance-assessment with a greater decoupling of trunk and legs during the mechanical than the visual mediolateral-balance-assessment. INTERPRETATION: the visual mediolateral-balance-assessment was more sensitive to age-related balance deterioration than the mechanical mediolateral-balance-assessment, possibly because visual tracking elicits motor strategies that are more affected by ageing.

Time-course of transcriptome response to respiratory syncytial virus infection in lung epithelium cells.

Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory tract infection in infants. Winter outbreaks in Chile result in 5% of infected children hospitalized, with 0.01% mortality. Increased evidence indicates that viral and host factors modulate the severity of infection. Using DNA microarrays, we characterized the genome-wide transcriptional response of lung mucoepidermoid cells (NCI-H292) at 0, 24, 48, 72 and 96 hours post-infection (hpi) with a single dose of RSV/A. During the whole studied period, a bi-phasic gene expression profile was observed by a total of 330 differentially expressed genes. About 60% of them were up-regulated between 24-72 hpi and then turned-off at 96 hpi. This transient, early gene expression pattern was significantly enriched in biological processes like interferon signaling, antigen processing and presentation, double-stranded RNA binding and chemokine activity. We detected 27 common genes up-regulated between 24-72 hpi, from which IFIT1, IFI44, MX1, CXCL11 and OAS1 had the highest expression. The second pattern comprised over 120 genes, which remained silenced until 72 hpi, but were steeply up-regulated by 96 hpi. Biological processes of this late-response profile included cell cycle division and microtubule cytoskeleton organization. Conversely, the genes belonging to virus response pathway showed a decreased expression at 96 hpi. We conclude that RSV induces an early innate immune activation profile response until 72 hpi. Thereafter, the viral response is inhibited, leading to host cell recovery. The presented cellular model allows to study the specific pathways involved in elimination of infection at prolonged time intervals and their subsequent analysis in severe RSV disease of infants and/or older adults.