Weight-bearing Asymmetry Research Articles

Exoskeleton-assisted training to enhance lower limb motor recovery in subacute stroke: does timing matter? A pilot randomized trial

BackgroundLower limb motor recovery, including abnormal muscle synergies, occurs mainly within the first 5–8 weeks after a stroke. This suggests the importance of delivering impairment-focused therapies, such as therapeutic robots that promote symmetric gait, during this time-sensitive period, following the principle of “the earlier, the better.”ObjectiveFirst, to compare early robotic training (ERT) with usual care (UC) against UC alone on restoring intralimb muscle synergies and interlimb symmetry during functional tasks; Second, to investigate whether ERT is superior to delayed robotic training (DRT) starting after the proposed time-sensitive period.MethodsThis observer-blinded, randomized pilot trial with crossover design involved 19 nonambulatory adults included within 14 days poststroke. Those allocated to ERT (N = 10) received immediately 4 weeks of training (16 sessions, 4× /week) with the Ekso GT® above UC and were compared with the DRT group (N = 9) who received UC alone at this point. Thereafter a 3-week UC period followed to investigate sustainability of ERT and the interventional roles were exchanged; at about week 8 poststroke DRT subjects started the same experimental robotic protocol and ERT subjects continued UC as controls. Outcomes included changes in Fugl-Meyer lower extremity scores (FM-LE) reflecting muscle synergies, weight-bearing asymmetry (WBA), and dynamic control asymmetry (DCA) during quiet standing. Functional ambulation category (FAC) was used to classify walking independence (cut-off ≥4).ResultsA trend toward earlier reacquisition of walking independence favoring ERT with UC over UC was not accompanied by differences in FM-LE, WBA, or DCA (first objective). Thereafter, DRT with UC did not yield any significant changes relative to UC, such that no between-group differences were found favoring restorative effects of ERT over DRT (second objective).ConclusionThis pilot trial shows the feasibility of investigating a wearable exoskeleton as an adjunct therapy in subacute stroke. Nevertheless, our preliminary findings suggest that motor recovery of lower limb muscle synergies was not enhanced by 4 weeks of robotic training to reduce compensations with the less-affected side, irrespective of the timing of application.Trial registrationClinicalTrials.gov, identifier: NCT03727919.

Sustained morphine exposure alters spinal NMDA receptor and astrocyte expression and exacerbates chronic pain behavior in female rats.

Sustained opioid use has long-term negative impacts on future pain experience, particularly in women. This study aimed to investigate the underlying spinal neurobiology of this clinical observation in an experimental model of joint pain. In this study, we tested the hypothesis that sustained opioid treatment exacerbates chronic pain responses and alters spinal cord dorsal horn astrogliosis and the expression of GluN2B-containing N-methyl-d-aspartate receptors in female rats. Subcutaneous morphine (3 mg/kg) or saline was administered twice daily for 1 week before inducing a model of joint knee pain (intra-articular injection of 2 mg of monosodium iodoacetate [MIA]) in adult female Sprague-Dawley rats, with pain-free controls receiving 50 µL of saline. Pain behavior (weight-bearing and mechanical paw withdrawal thresholds) was measured at baseline and at intervals thereafter. Twice-daily morphine/saline treatment was continued for up to 3 weeks after intra-articular injections, and spinal cord tissue was collected for Western blot analyses. Area under the curve analysis of weight-bearing asymmetry confirmed a significant exacerbation of pain behavior in the morphine/MIA group, compared with the saline/MIA group (F(3,18) = 46.3, P < 0.0001), despite comparable joint damage in both groups. Sustained morphine treatment was associated with significant elevations in dorsal horn expression of astrocytic glial fibrillary acidic protein (27 ± 5% increase) and neuronal GluN2B (80 ± 30% increase), but not microglial IBA1, irrespective of the model of joint pain. These data suggest that sustained morphine treatment in female rats drives spinal cord plasticity, including spinal astrogliosis and the expression of GluN2B-containing N-methyl-d-aspartate receptors, priming the dorsal horn to incoming sensory inputs and producing exacerbated pain responses.

Application of the participatory design in the testing of a baropodometric insole prototype for weight-bearing asymmetry after a stroke: A qualitative study.

Currently studies indicate the need to incorporate the user`s perspective in the testing of new assistive technologies. The objective of this paper is to test a baropodometric insole prototype for monitoring and treatment weight-bearing asymmetry, according to the Participatory Design. We used a qualitative case study approach during the testing phase of the baropodometric insole prototype. The focus group approach addressed topics related to the experience and accessibility of the potential user in conjunction with professionals, researchers, and physiotherapy students. Facilitators, barriers, and requirements for the device were collected through audio recordings of the discussions during and after prototype testing. Key steps in the prototype testing process were divided into (1) Test of the prototype according to the Participatory Design, divided into Who, When, How, and Why the potential user was involved in the study; and (2) Facilitators, barriers and requirements to improve the prototype. The baropodometric insole prototype can be seen as a promising device for monitoring and treating weight-bearing asymmetry.

Does visuospatial neglect contribute to standing balance within the first 12 weeks post-stroke? A prospective longitudinal cohort study.

Visuospatial neglect (VSN) has been suggested to limit standing balance improvement post-stroke. However, studies investigating this association longitudinally by means of repeated within-subject measurements early post-stroke are lacking. This prospective longitudinal cohort study evaluates the longitudinal association of egocentric and allocentric VSN severity with 1) standing balance independence and 2) postural control and weight-bearing asymmetry (WBA) during quiet standing, in the first 12 weeks post-stroke. Thirty-six hemiplegic individuals after a first-ever unilateral stroke were evaluated at weeks 3, 5, 8 and 12 post-stroke. Egocentric and allocentric VSN severity were evaluated using the Broken Hearts Test. The standing unperturbed item of the Berg Balance Scale (BBS-s) was used to clinically evaluate standing independence. Posturographic measures included measures of postural control (mediolateral (ML)/anteroposterior (AP) net center-of-pressure velocities (COPvel)) and WBA during quiet standing. A linear mixed model was used to examine longitudinal associations between egocentric and allocentric VSN, and BBS-s, COPvel-ML, COPvel-AP and WBA within the first 12 weeks post-stroke. Egocentric (β = -0.08, 95%CI[-0.15;-0.01], P = .029) and allocentric VSN severity (β = -0.09, 95%CI[-0.15; -0.04], P = .002) were significant independent factors for BBS-s scores in the first 12 weeks post-stroke. Egocentric and allocentric VSN were no significant independent factors for COPvel-ML, COPvel-AP and WBA in the first 12 weeks post-stroke. Allocentric and egocentric VSN severity were significantly associated with decreased standing independence, but not impaired postural control or greater asymmetric weight-bearing, in the early subacute post-stroke phase. This may involve traditional VSN measures being not sensitive enough to detect fine-grained VSN deficits due to a ceiling effect between 5 and 8 weeks post-stroke, once the individual regains standing ability. Future studies may require more sensitive VSN measurements to detect such deficits. Trial registration Clinicaltrials.gov. unique identifier NCT05060458.

Ab. No. 59 Reliability of Dual Weighing Scale Biofeedback System (DWSBS), a New Apparatus for Assessment and Training of Weight Bearing Asymmetry (WBA)

Introduction: Weight bearing asymmetry leads to major impact on gait execution strategies post neurological conditions. A cheap and cost-effective apparatus which can be incorporated in routine use with less costs per session, will help treat asymmetry and enhance a near normal gait pattern with reduction in compensatory strategies. Introduction of new, cost effective and reliable apparatus against costly and cumbersome apparatus which is portable and needs less clinical expertise to use. Secondary objective is to target, population with neurological issues where weight bearing asymmetry leads to major gait disturbances. Methods: 56 Normal Healthy individuals (45-65 years) Instrumentation of DWSBS, by using 2 platforms for standing, measuring 12 x 12 inches each, embedded on a single platform, placed at a distance of 2 centimetres between them. A common display with digital output for both weighing scale was used. Reliability testing - 56 healthy individuals without any balance issues recruited and asked to stand bipedally, with eyes open on each of 2 weighing scales separately;post 3 trials, average of reading were documented. Data collected by 2 raters (Rater 1- reading on day 1 and 3; Rater 2 - reading on day 2) were analyzed using Cronbach’s alfa test in SPSS version 23 software. Result: Excellent reliability for Intrarater and interrater testing as per ICC values 0.9. neck ROM. Conclusion: The new apparatus has proven to be reliable and is fit to be tested for validity. Implications: DWSBS will help reduce to cost and execution-based burden for weight bearing asymmetry training.

Ab. No. 87 Comparative Efficacy of Modified Constraint-Induced Movement Therapy (M-CIMT) Technique With or Without Restraint Device on Gait and Balance of Hemiplegic Patients With Stroke: A Pilot Study

Introduction: The purpose was to compare the effect of Modified Constraint-induced movement therapy (m-CIMT) with or without the restraint device on static balance, dynamic balance and gait of patients with hemiplegia. Using m-CIMT as a rehabilitative approach in Physiotherapy practice may improve the weight-bearing asymmetries, static balance, dynamic balance and gait. Patients with hemiplegia (n=16) of both genders aged 40-65 years with MMSE score≥ 24, Brunnstrom recovery stages≥ III were randomly divided into two groups. Methodology: Group 1(n=8) underwent m-CIMT therapy with a weight cuff on the unaffected ankle during exercises, while Group 2(n=8) performed the same exercises without any restraint device keeping their non-paretic hip and knee extended and feet flat. Gait quality and balance were assessed using the Dynamic Gait Index (DGI) and Berg Balance Scale (BBS) respectively. Doses were 5 days per week for 2 weeks. Paired T-test was used for within groups and independent sample T-test was used to compare between groups. The probability of error was accepted at P&lt;0.05. SPSS 26.0 was used for analysis. Result: Significant (P&lt;0.05) improvement was observed in DGI in both groups and the BBS improved only in group 1. Between groups, the analysis showed significant (P&lt;0.05) differences in DGI score and insignificant (P&gt;0.05) differences with BBS. Conclusion: m-CIMT with restraint device improves gait and balance. m-CIMT without restraint device improves gait only and not balance. m-CIMT using a restraint device is more effective in improving gait. There was no difference between the two groups in terms of balance. Implication: m-CIMT using a restraining device can improve dynamic gait and balance in patients with hemiplegia.

Analysis and Mechanism(s) of Hemophilia a Pain in Factor VIII Knockout Mice

Hemophilia A (HA) is characterized by spontaneous bleeding and pain. To understand mechanisms underlying HA pain, we developed models of chronic &amp; acute pain in FVIII knock-out (F8KO; B6;129S-F8tm1Kaz/J) male mice using innovative translatable measures to assess pain-related behaviors &amp; gait. We tested for: [i] mechanical hyperalgesia using von-Frey monofilaments; [ii] physical activity using weight-bearing with incapacitance meter and video recordings of free moving mice for locomotion (walking/running), grooming (licking/rubbing body) &amp; rearing (standing); and [iii] gait analysis during normal walking using in-house assembled MouseWalker with high-speed camera &amp; artificial intelligence (AI)-based algorithms. We observed significant increase in behavioral features of pain starting at ~8wks which continues to 20wks in F8KO Vs age matched B6 (p&amp;lt;0.05), including mechanical hyperalgesia, weight-bearing asymmetry, less time in locomotion, rearing &amp; grooming. Gait analysis of ~10wks F8KO showed lowered all-stance, increased body instability, single-swing &amp; posterior extreme position indices to compensate for body instability. This suggests that joint pain may interfere with weight-bearing &amp; locomotion in F8KO, consistent with joint pain, and affect daily activities such as walking in HA patients. To simulate bleeding-induced “ acute” pain, we gently inserted 30 G needle into sub patellar position of right hind leg of ~6wks old, anesthetized mice. F8KO showed significantly (p&amp;lt;0.05) reduced locomotion, rearing, grooming, %weight applied and increased mechanical sensitivity on injured limb at 4 days post-injury (4D PI) Vs uninjured (UI) F8KO lasting to 4wks PI for most of behavioral parameters suggesting that nociceptive inputs are induced at injury and pain persists after healing. We observed significant spatiotemporal gait alterations in F8KO PI Vs UI (p&amp;lt;0.05 for all features), including reduced stance duration, step length, swing speed and increased swing duration in the injured right hind limb (IRHL) indicative of avoidance of weight bearing on IRHL. To compensate, UI left hind limb (LHL) showed increased stance &amp; reduced swing duration on LHL &amp; left front limb (LFL). These data suggest that F8KO tends to spend shorter ground time on IRHL and longer airtime, compensated by UI LHL &amp; LFL. These observations are complementary to those of mice with sciatic nerve injury &amp; arthritis and patients with rheumatoid arthritis, ankylosing spondylitis, and gout. We observed significant (&amp;lt;0.05) alterations in interlimb coordination with decreased diagonal swing &amp; compensation with increased bound swing, the simultaneous motion of both FLs. A significant increase in all stance index could be compared to increased double support phase &amp; stance phase in patients with HA. F8KO 4D PI showed significant (p&amp;lt;0.05) increase in plasma serum amyloid P &amp; IL6 Vs UI F8KO &amp; injured B6 (IB6). Knee joint at 4D PI Vs UI F8KO &amp; IB6, showed expansion of synovial membrane with increased cellular infiltrate &amp; significant (p&amp;lt;0.05) increase in myeloperoxidase, neutrophil elastase +ve cells, degranulating mast cells, calcitonin gene related peptide (CGRP) and substance P (SP). H&amp;E and iron-stained sections of the knee joint ~8wks PI showed significant signs of hemarthropathy (p&amp;lt;0.05) Vs UI F8KO &amp; I B6. Interestingly, at ~14wks UI knee joint of F8KO showed significant stromal changes Vs UI B6 demonstrated by increased vasculature, iron stores &amp; mild synovial hyperplasia, indicative of subclinical bleeding that could trigger the transition to chronic pain with age. The underlying mechanisms involve inflammation, mast cell and neutrophil activation, and vascular changes, perhaps triggered by bleeding. Mast cell tryptase &amp; neutrophil elastase activate protease-activated receptor 2, which may cause nociceptor and endothelial activation, leading to vascular dysfunction and pain. SP and CGRP stimulate vascular permeability and arteriolar dilatation, respectively, and are involved in the generation and maintenance of pain. Thus, neuro-immune and neuro-vascular mechanisms underlie HA pain and may interfere with healing. We show features of pain, gait &amp; weight bearing changes in F8KO mice similar to those of HA patients. Sensory and gait tests used by us have the potential to develop objective measures of pain in HA. Gait changes in F8KO mice precede joint arthropathy, thus may be an early assessment tool in patients with HA.

Reliability of force plate-based measures of standing balance in the sub-acute stage of post-stroke recovery

BackgroundDifficulty controlling balance is one of the major contributors to the increased risk of falls among individuals with stroke. It is important to use reliable and objective measures to improve examination of balance impairments post-stroke, and to in turn inform clinical decision-making. The main objective of this study was to examine the relative and absolute reliabilities of force plate-based balance measures in quiet standing, in the sub-acute stage of stroke recovery. MethodsTwenty-four people with sub-acute stroke (mean age = 61 years) performed two trials of quiet standing, each 30 s long. Sixteen force plate-based balance measures in the time, frequency, or nonlinear domains were calculated. Within-session test-retest reliabilities were investigated using intraclass correlation coefficient (ICC), standard error of measurement, and minimal detectable change. ResultsMean speed of displacements of the centre of pressure along the anterior-posterior axis (ICC = 0.91; CI95 % = [0.83, 0.95]), and directional weight-bearing asymmetry (ICC = 0.91; CI95 % = [0.82, 0.95]) demonstrated high relative reliabilities, followed by the speed-based symmetry index and absolute weight-bearing asymmetry (both ICCs = 0.86; CI95 % = [0.74, 0.93]). ConclusionsMean speeds of centre of pressure, directional weight-bearing asymmetry, and speed-based symmetry index are the most reliable force plate-based measures that were evaluated in our study, and can be included in the balance assessments of individuals within the sub-acute stage of post-stroke recovery. These findings can better inform clinicians about the specific balance problems experienced by people in this population.

Sigma-1 receptor agonism exacerbates immune-driven nociception: Role of TRPV1 + nociceptors

The analgesic effects of sigma-1 antagonists are undisputed, but the effects of sigma-1 agonists on pain are not well studied. Here, we used a mouse model to show that the administration of the sigma-1 agonists dextromethorphan (a widely used antitussive drug), PRE-084 (a standard sigma-1 ligand), and pridopidine (a selective drug being investigated in clinical trials for the treatment of neurodegenerative diseases) enhances PGE2-induced mechanical hyperalgesia. Superficial plantar incision induced transient weight-bearing asymmetry at early time points, but the mice appeared to recover at 24 h, despite noticeable edema and infiltration of neutrophils (a well-known cellular source of PGE2) at the injured site. Sigma-1 agonists induced a relapse of weight bearing asymmetry in a manner dependent on the presence of neutrophils. The effects of sigma-1 agonists were all reversed by administration of the sigma-1 antagonist BD-1063 in wild-type mice, and were absent in sigma-1 knockout mice, supporting the selectivity of the effects observed. The proalgesic effects of sigma-1 agonism were also abolished by the TRP antagonist ruthenium red and by in vivo resiniferatoxin ablation of TRPV1 + peripheral sensory neurons. Therefore, sigma-1 agonism exacerbates pain-like responses in mice with a mild inflammatory state through the action of TRPV1 + nociceptors. We also show that sigma-1 receptors are present in most (if not all) mouse and human DRG neurons. If our findings translate to humans, further studies will be needed to investigate potential proalgesic effects induced by sigma-1 agonism in patients treated with sigma-1 agonists.

Inhibition of Brd4 alleviates osteoarthritis pain via suppression of neuroinflammation and activation of Nrf2-mediated antioxidant signalling.

Osteoarthritis (OA) pain remains a major clinical problem. It is urgent to identify novel therapeutic approaches for OA pain states. Bromodomain and extra-terminal (BET) protein inhibitors have robust anti-inflammatory effects in several pain models. However, the underlying mechanisms of these inhibitors in OA pain have not been determined. We, therefore, investigated the effects and the underlying mechanism(s) of BET inhibition on pain-related behaviours in a rat model of OA. The OA model was established by intra-articular injection of monosodium iodoacetate (MIA) in rat knees. Pain behaviours were assessed in rats by hindlimb weight-bearing asymmetry, mechanical allodynia and thermal hyperalgesia. Possible mechanisms underlying BET inhibition were explored in the MIA-induced OA pain model in the spinal cord and dorsal root ganglia (DRG). Inhibiting bromodomain-containing protein 4 (Brd4) with either JQ1 or MS417, or using AAV2/9-shRNA-Brd4-EGFP-mediated knockdown of Brd4 genes, significantly attenuated MIA-induced pain behaviours. Brd4 inhibition suppressed NF-κB and NF-κB-mediated inflammatory cytokines in both the spinal cord and DRG in rats with MIA-induced OA pain. Brd4 inhibition also attenuated the oxidative stress and promoted nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent antioxidant genes in both the spinal cord and DRG in our odel of MIA-induced OA pain. In conclusion, Brd4 inhibition alleviated MIA-induced OA pain in rats, via suppression of neuroinflammation and activation of Nrf2-mediated antioxidant signalling. Although our model does not perfectly represent how OA develops in humans, inhibition of Brd4 may provide novel insights into possible treatments for OA pain.

Recovery of Quiet Standing Balance and Lower Limb Motor Impairment Early Poststroke: How Are They Related?

Background Recovery of quiet standing balance early poststroke has been poorly investigated using repeated measurements. Objective To investigate (1) the time course of steady-state balance in terms of postural stability and inter-limb symmetry, and (2) longitudinal associations with lower limb motor recovery in the first 3 months poststroke. Methods Forty-eight hemiparetic subjects (age: 58.9 ± 16.1 years) were evaluated at weeks 3, 5, 8, and 12 poststroke. Motor impairments concerned the Fugl-Meyer assessment (FM-LE) and Motricity Index total score (MI-LE) or ankle item separately (MI-ankle). Postural stability during quiet 2-legged stance was calculated as the net center-of-pressure area (COPArea) and direction-dependent velocities (COPVel-ML and COPVel-AP). Dynamic control asymmetry (DCA) and weight-bearing asymmetry (WBA) estimated inter-limb symmetries in balance control and loading. Linear mixed models determined (1) time-dependent change and (2) the between- and within-subject associations between motor impairments and postural stability or inter-limb symmetry. Results Time-dependent improvements were significant for FM-LE, MI-LE, MI-ankle, COPArea, COPVel-ML, and COPVel-AP, and tended to plateau by week 8. DCA and WBA did not exhibit significant change. Between-subject analyses yielded significant regression coefficients for FM-LE, MI-LE, and MI-ankle scores with COPArea, COPVel-ML, and COPVel-AP up until week 8, and with WBA until week 12. Within-subject regression coefficients of motor recovery with change in COPArea, COPVel-ML, COPVel-AP, DCA, or WBA were generally non-significant. Conclusions Postural stability improved significantly in the first 8 weeks poststroke, independent of lower limb motor recovery at the most affected side within subjects. Our findings suggest that subjects preferred to compensate with their less affected side, making metrics reflecting inter-limb asymmetries in balance invariant for change early poststroke. Clinical Trial Registration: Clinicaltrials.gov. unique identifier NCT03728036.

Seated postural organization during bilateral upper limb symmetric and asymmetric pushing tasks in individuals after stroke compared to healthy controls

BackgroundAsymmetric weight distribution in sitting has been reported in people after stroke. However, postural strategies used during bilateral symmetric and asymmetric movements performed while seated require more evidence to inform rehabilitation strategies. Research questionsHow do symmetric and asymmetric effort levels exerted during upper limb (UL) pushing movements affect seated postural organization parameters (weight bearing (WB) between hands and hemibody sides, and forward trunk displacement) of stroke compared to healthy individuals? How are these parameters associated? MethodsUsing an instrumented exerciser, 19 post-stroke individuals were compared to 17 healthy individuals when executing four bilateral UL pushing movements in a seated position: symmetrical pushing at 30 % and 15 % of their maximal force (MF) and asymmetrical pushing with 15 % of their MF for one UL vs. 30 % of the MF for the other UL and vice versa. Anterior and vertical forces of the push, as well as vertical forces under each foot and thigh were compared between groups, sides and conditions. Forward trunk displacement was compared between groups and conditions. Correlations were used to determine the association between trunk displacement, hands and hemibody vertical forces. ResultsIncreasing pushing effort caused increased WB on thighs and decreased on WB on feet during the 30 % MF symmetric condition compared to the 15 % MF and asymmetric conditions (p < 0.05). Individuals post-stroke showed WB asymmetry and greater forward trunk displacement when compared to healthy persons (p < 0.05). For both groups, hemibody WB and trunk displacement showed moderate association (r > - 0.5) in the asymmetric condition executed with more resistance on the paretic or non-dominant hand. SignificanceIndividuals post-stroke presented a similar WB pattern to that of healthy persons during symmetric and asymmetric bilateral UL movements with greater forward trunk displacement and asymmetry. Increased effort and asymmetric force between both UL had effects on seated postural organization strategy.

Six-month outcomes and patterns of recovery for people with lateropulsion following stroke

Purpose This study investigated the (1) six-month outcomes of individuals with lateropulsion; (2) the relationship between baseline measures (from in-patient hospitalisation) and six-month functional abilities; and (3) recovery patterns for lateropulsion in stroke survivors. Materials and methods Forty-one individuals with lateropulsion participated in this study. Measures of lateropulsion, postural function, and weight-bearing asymmetry in standing were taken initially and fortnightly over eight weeks. Functional independence and walking abilities were assessed at six months post-stroke. Results Compared to individuals with moderate to severe lateropulsion, those with mild lateropulsion achieved higher levels of functional outcome at six months. However, there were a wide range of scores. Baseline lateropulsion severity explained 26% of the variation in functional outcome. A stronger correlation with functional outcome was observed for lateropulsion (−0.526) than function independence at baseline (0.384). For the task of standing with arm support, patterns of asymmetry were divergent at baseline, favouring either the paretic or non-paretic leg. Over the eight-week period, asymmetry moved towards the non-paretic leg and lateropulsion reduced consistently. Conclusions Individuals with lateropulsion can recover from lateropulsion and make meaningful functional gains, including some individuals with more severe lateropulsion. Lateropulsion severity is a key indicator of functional outcome post-stroke. IMPLICATIONS FOR REHABILITATION Individuals with lateropulsion can make significant gains in terms of mobility and functional abilities by six months post-stroke, learning to compensate for their verticality impairment in standing by loading their non-paretic leg. It is important that stroke survivors with lateropulsion, including those with moderate and severe lateropulsion, are provided with adequate rehabilitation to optimise their longer-term mobility and functional abilities. Routine screening of acute stroke survivors for lateropulsion is recommended, given lateropulsion may negatively impact longer-term functional outcomes in stroke survivors. Therapists should carefully analyse the weight-bearing pattern which an individual with lateropulsion adopts in standing and subsequently tailor treatment to target this.

Determining an optimal posturography dataset to identify standing behaviors in the post-stroke subacute phase. Cross-sectional study.

A key issue for posturography is the expression of robust results, in a simplified way. Most studies of individuals post-stroke concern the chronic phase, with small sample sizes. By reducing the number of posturographic indices, we aimed to determine an optimal dataset and understand typical postural behaviors in the subacute post-stroke phase. In this cross-sectional study ancillary to the DOBRAS cohort, individuals were assessed as soon they could complete a full posturography session (with and without vision) after a first hemispheric stroke. Body-weight distribution on the mediolateral (ML) axis, position of the center of pressure on the antero-posterior (AP) axis, and postural sway on both axes were computed. Balance ability in daily life was quantified with the Postural Assessment Scale for Stroke. Data were analyzed by principal component and hierarchical clustering analyses as well as multiple linear regression. We enrolled 95 individuals (median age: 67.0 years [Q1; Q3 56.0; 72.0]; 68% males). Vision suppression had a marginal effect, only increasing postural sway. Regardless of the visual condition, posturographic behavior was captured by a set of 3 indices that explained almost all the information. One postural sway index (ML or AP) gave more information (48%) than both position indices (ML 26% and AP 15%). These 3 indices identified 3 standing behaviors: 1) stable and symmetric, 2) asymmetric, unstable, and positioned backward, and 3) very unstable and positioned forward. Balance ability in daily life was explained (49% of the information, 95%CI [35; 63]) by weight-bearing asymmetry and postural sway on the ML axis, which played an independent role (both p<10-5), with similar impact. Three typical behaviors allow standing after stroke: described by only 3 posturographic indices. Weight-bearing asymmetry is not the primary parameter and should not be considered in isolation as an outcome. To increase the feasibility of posturography in the early subacute phase and to simplify evaluation sessions, trials could be limited to eyes open. NCT03203109.

No Evidence for Cognitive Impairment in an Experimental Rat Model of Knee Osteoarthritis and Associated Chronic Pain

Although chronic pain states have been associated with impaired cognitive functions, including memory and cognitive flexibility, the cognitive effects of osteoarthritis (OA) pain remain to be clarified. The aim of this study was to measure cognitive function in the mono-iodoacetate (MIA) rat model of chronic OA-like knee pain. We used young adult male Lister hooded rats, which are well-suited for cognitive testing. Rats received either a unilateral knee injection of MIA (3 mg/50 µL) or saline as control. Joint pain at rest was assessed for up to 12 weeks, using weight-bearing asymmetry, and referred pain at a distal site, using determination of hindpaw withdrawal thresholds. The watermaze delayed-matching-to-place test of rapid place learning, novel object recognition memory assay, and an operant response-shift and -reversal task were used to measure memory and behavioral flexibility. Open-field locomotor activity, startle response, and prepulse inhibition were also measured for comparison. MIA-injected rats showed markedly reduced weight-bearing on the injured limb, as well as pronounced cartilage damage and synovitis, but interestingly no changes in paw withdrawal threshold. Rearing was reduced, but otherwise, locomotor activity was normal and no changes in startle and prepulse inhibition were detected. MIA-injected rats had intact watermaze delayed-matching-to-place performance, suggesting no substantial change in hippocampal function, and there were no changes in novel object recognition memory or performance on the operant task of behavioral flexibility. Our finding that OA-like pain does not alter hippocampal function, unlike other chronic pain conditions, is consistent with human neuroimaging findings. PerspectiveYoung adult rats with OA-like knee pain showed no impairments in hippocampal memory function and behavioral flexibility, suggesting that OA pain impacts cognitive functions less than other chronic pain conditions. In patients, OA pain may interact with other factors (e.g., age, socio-economic factors, and medication) to impair cognition.

An Experimental Study to Analyze the Efficacy of Backwards Gait Training on Balance and Weight Bearing Asymmetry on Sub-Acute Stroke Patient

Background: Stroke is the leading cause of long-term disability and death, and the second leading cause of deathworldwide. The first month after a stroke is a vital period since the brain goes through major plastic changes duringthis time. Motor learning studies emphasize the significance of experience and learning in functional rehabilitation.Because training is a potent stimulator of neuroplasticity, the addition of a focused rehabilitation strategy canimprove recovery by maximizing brain reconfiguration. Backward Walking Training (BWT) is an adjuvanttherapeutic and rehabilitation method to improve proprioception, muscle strength, intra-limb coordination, andbalance. Studies examining its effects on balance and weight bearing asymmetry are lacking.Objective: To determine the effect of BWT on balance and weight bearing asymmetry in sub acute stroke subjects.Results: The difference between the pre- and post-test results within the group for balance on Berg Balance Scale(BBS) as well as the weight on the affected and unaffected Lower Limb (LL) on the Body Weighing Machine(BWM) are both deemed to be significant for paired T-Test. According to conventional standards, when comparingpre- and post-test results for balance and the difference in weight between the two groups for the affected andunaffected Lower Limb (LL) on the BWM for the experimental and control groups using Unpaired T-Test, it canbe inferred that the difference is statistically significant.Conclusions: When combined with conventional physiotherapy as opposed to conventional physiotherapyalone, backwards gait training has a modestly greater impact on balance and weight bearing asymmetry. Bergbalance score and weight bearing asymmetry can both be improved in stroke patients using BWT as an additionto standard care (moderate evidence).

Effect of Increasing Assistance From a Powered Prosthesis on Weight-Bearing Symmetry, Effort, and Speed During Stand-Up in Individuals With Above-Knee Amputation.

After above-knee amputation, the missing biological knee and ankle are commonly replaced with a passive prosthesis, which cannot provide net-positive energy to assist the user. During activities such as sit-to-stand, above-knee amputees must compensate for this lack of power using their upper body, intact limb, and residual limb, resulting in slower, less symmetric, and higher effort movements. Previous studies have shown that powered prostheses can improve symmetry and speed by providing positive assistive power. However, we still lack a systematic investigation of the effect of powered prosthesis assistance. Without this knowledge, researchers and clinicians have no framework for tuning powered prostheses to optimally assist users. Here we show that varying the assistive knee torque significantly affected weight-bearing symmetry, effort, and speed during the stand-up movement in eight above-knee amputees. Specifically, we observed improvements in the index of asymmetry of the vertical ground reaction force at the point approximating maximum vertical center of mass acceleration, the integral of the intact vastus medialis activation measured using electromyography, and the stand-up duration compared to the passive prosthesis. We saw significant improvements in all three metrics when subjects used the powered prosthesis compared to the passive prosthesis. We saw improvements in all three metrics with increasing assistive torque levels commanded by the powered prosthesis. We also observed increased weight-bearing asymmetry at the end of movement, and increased kinematic asymmetry with increasing assistance from the powered prosthesis. These results show that powered prostheses can improve functional mobility, potentially increasing quality of life for millions of people living with above-knee amputations.

Pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat (Rattus norvegicus).

Relatively little work has evaluated both the disease of osteoarthritis (OA) and clinically-relevant pain outcome measures across different OA models in rats. The objective of this study was to compare sensitivity, pain, and histological disease severity across chemical and surgical models of OA in the rat. Stifle OA was induced in Sprague-Dawley rats via intraarticular injection of monoiodoacetate (MIA) or surgical transection of anterior cruciate ligament and/or destabilization of medial meniscus (ACL+DMM or DMM alone). Reflexive (e.g., mechanical and thermal stimuli) measures of sensitivity and non-reflexive assays (e.g., lameness, static hindlimb weight-bearing asymmetry, dynamic gait analysis) of pain were measured over time. Joint degeneration was assessed histologically. Six-weeks post OA-induction, the ACL+DMM animals had significantly greater visually observed lameness than MIA animals; however, both ACL+DMM and MIA animals showed equal pain as measured by limb use during ambulation and standing. The MIA animals showed increased thermal, but not mechanical, sensitivity compared to ACL+DMM animals. Joint degeneration was significantly more severe in the MIA model at 6 weeks. Our pilot data suggest both the ACL+DMM and MIA models are equal in terms of clinically relevant pain behaviors, but the MIA model is associated with more severe histological changes over time potentially making it more suitable for screening disease modifying agents. Future work should further characterize each model in terms of complex pain behaviors and biochemical, molecular, and imaging analysis of the sensory system and joint tissues, which will allow for more informed decisions associated with model selection and investigative outcomes.

Osteoarthritis Pain in Old Mice Aggravates Neuroinflammation and Frailty: The Positive Effect of Morphine Treatment.

Knee osteoarthritis is a common cause of pain and disability in old subjects. Pain may predispose to the development of frailty. Studies on mechanisms underlying pain in osteoarthritis models during aging are lacking. In this work, we used the monosodium iodoacetate model of osteoarthritis in adult (11-week-old) and old (20-month-old) C57BL/6J mice to compare hypersensitivity, locomotion, neuroinflammation, and the effects of morphine treatment. After osteoarthritis induction in adult and old mice, weight-bearing asymmetry, mechanical allodynia, and thermal hyperalgesia similarly developed, while locomotion and frailty were more affected in old than in adult animals. When behavioral deficits were present, the animals were treated for 7 days with morphine. This opioid counteracts the behavioral alterations and the frailty index worsening both in adult and old mice. To address the mechanisms that underlie pain, we evaluated neuroinflammatory markers and proinflammatory cytokine expression in the sciatic nerve, DRGs, and spinal cord. Overexpression of cytokines and glia markers were present in osteoarthritis adult and old mice, but the activation was qualitatively and quantitatively more evident in aged mice. Morphine was able to counteract neuroinflammation in both age groups. We demonstrate that old mice are more vulnerable to pain's detrimental effects, but prompt treatment is successful at mitigating these effects.

Therapeutic Effects of Live Lactobacillus plantarum GKD7 in a Rat Model of Knee Osteoarthritis

Osteoarthritis (OA) is a painful, progressive chronic inflammatory disease marked by cartilage destruction. Certain synovial inflammatory cytokines, such as IL-1β and TNF-α, promote OA inflammation and pain. Lactobacillus spp. is a well-known probiotic with anti-inflammatory, analgesic, antioxidant, and antiosteoporotic properties. This study evaluated the therapeutic effects of a live L. plantarum strain (GKD7) in the anterior cruciate ligament transection (ACLT)-induced OA rat model. The results show that oral administration of live L. plantarum GKD7 improved weight-bearing asymmetry after ACLT surgery. Moreover, micro-computed tomography images and histopathological analysis show that oral live L. plantarum GKD7 improved subchondral bone architecture, protected articular cartilage against ACLT-induced damage, and reduced synovial inflammation. L. plantarum GKD7 also reduced IL-1β and TNF-α production in OA cartilage and synovium. Thus, orally administered live L. plantarum GKD7 appears to effectively slow the progression of OA.