Muscle weakness and lack of reflex gain adaptation predominate during post-stroke posture control of the wrist

Instead of hyper-reflexia as sole paradigm, post-stroke movement disorders are currently considered the result of a complex interplay between neuronal and muscular properties, modified by level of activity. We used a closed loop system identification technique to quantify individual contributors to wrist joint stiffness during an active posture task. Continuous random torque perturbations applied to the wrist joint by a haptic manipulator had to be resisted maximally. Reflex provoking conditions were applied i.e. additional viscous loads and reduced perturbation signal bandwidth. Linear system identification and neuromuscular modeling were used to separate joint stiffness into the intrinsic resistance of the muscles including co-contraction and the reflex mediated contribution. Compared to an age and sex matched control group, patients showed an overall 50% drop in intrinsic elasticity while their reflexive contribution did not respond to provoking conditions. Patients showed an increased mechanical stability compared to control subjects. Post stroke, we found active posture tasking to be dominated by: 1) muscle weakness and 2) lack of reflex adaptation. This adds to existing doubts on reflex blocking therapy as the sole paradigm to improve active task performance and draws attention to muscle strength and power recovery and the role of the inability to modulate reflexes in post stroke movement disorders.Mechanical, Maritime and Materials Engineerin

Muscle and reflex changes with varying joint angle in hemiparetic stroke

<p>Abstract</p> <p>Background</p> <p>Despite intensive investigation, the origins of the neuromuscular abnormalities associated with spasticity are not well understood. In particular, the mechanical properties induced by stretch reflex activity have been especially difficult to study because of a lack of accurate tools separating reflex torque from torque generated by musculo-tendinous structures. The present study addresses this deficit by characterizing the contribution of neural and muscular components to the abnormally high stiffness of the spastic joint.</p> <p>Methods</p> <p>Using system identification techniques, we characterized the neuromuscular abnormalities associated with spasticity of ankle muscles in chronic hemiparetic stroke survivors. In particular, we systematically tracked changes in muscle mechanical properties and in stretch reflex activity during changes in ankle joint angle. Modulation of mechanical properties was assessed by applying perturbations at different initial angles, over the entire range of motion (ROM). Experiments were performed on both paretic and non-paretic sides of stroke survivors, and in healthy controls.</p> <p>Results</p> <p>Both reflex and intrinsic muscle stiffnesses were significantly greater in the spastic/paretic ankle than on the non-paretic side, and these changes were strongly position dependent. The major reflex contributions were observed over the central portion of the angular range, while the intrinsic contributions were most pronounced with the ankle in the dorsiflexed position.</p> <p>Conclusion</p> <p>In spastic ankle muscles, the abnormalities in intrinsic and reflex components of joint torque varied systematically with changing position over the full angular range of motion, indicating that clinical perceptions of increased tone may have quite different origins depending upon the angle where the tests are initiated.</p> <p>Furthermore, reflex stiffness was considerably larger in the non-paretic limb of stroke patients than in healthy control subjects, suggesting that the non-paretic limb may not be a suitable control for studying neuromuscular properties of the ankle joint.</p> <p>Our findings will help elucidate the origins of the neuromuscular abnormalities associated with stroke-induced spasticity.</p

Functional Changes in Muscle Afferent Neurones in an Osteoarthritis Model: Implications for Impaired Proprioceptive Performance

Impaired proprioceptive performance is a significant clinical issue for many who suffer osteoarthritis (OA) and is a risk factor for falls and other liabilities. This study was designed to evaluate weight-bearing distribution in a rat model of OA and to determine whether changes also occur in muscle afferent neurones.Intracellular recordings were made in functionally identified dorsal root ganglion neurones in acute electrophysiological experiments on the anaesthetized animal following measurements of hind limb weight bearing in the incapacitance test. OA rats but not naïve control rats stood with less weight on the ipsilateral hind leg (P = 0.02). In the acute electrophysiological experiments that followed weight bearing measurements, action potentials (AP) elicited by electrical stimulation of the dorsal roots differed in OA rats, including longer AP duration (P = 0.006), slower rise time (P = 0.001) and slower maximum rising rate (P = 0.03). Depolarizing intracellular current injection elicited more APs in models than in naïve muscle afferent neurones (P = 0.01) indicating greater excitability. Axonal conduction velocity in model animals was slower (P = 0.04).The present study demonstrates changes in hind limb stance accompanied by changes in the functional properties of muscle afferent neurones in this derangement model of OA. This may provide a possible avenue to explore mechanisms underlying the impaired proprioceptive performance and perhaps other sensory disorders in people with OA

Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage

Controlled intermittent shortening contractions of a muscle-tendon complex: muscle fibre damage and effects on force transmission from a single head of rat EDL

This study was performed to examine effects of prolonged (3 h) intermittent shortening (amplitude 2 mm) contractions (muscles were excited maximally) of head III of rat extensor digitorum longus muscle (EDL III) on indices of muscle damage and on force transmission within the intact anterior crural compartment. Three hours after the EDL III exercise, muscle fibre damage, as assessed by immunohistochemical staining of structural proteins (i.e. dystrophin, desmin, titin, laminin-2), was found in EDL, tibialis anterior (TA) and extensor hallucis longus (EHL) muscles. The damaged muscle fibres were not uniformly distributed throughout the muscle cross-sections, but were located predominantly near the interface of TA and EDL muscles as well as near intra- and extramuscular neurovascular tracts. In addition, changes were observed in desmin, muscle ankyrin repeat protein 1, and muscle LIM protein gene expression: significantly (P < 0.01) higher (1.3, 45.5 and 2.3-fold, respectively) transcript levels compared to the contralateral muscles. Post-EDL III exercise, length-distal force characteristics of EDL III were altered significantly (P < 0.05): at high EDL III lengths, active forces decreased and the length range between active slack length and optimum length increased. For all EDL III lengths tested, proximal passive and active force of EDL decreased. The slope of the EDL III length-TA + EHL force curve decreased, which indicates a decrease of the degree of intermuscular interaction between EDL III and TA + EHL. It is concluded that prolonged intermittent shortening contractions of a single head of multi-tendoned EDL muscle results in structural damage to muscle fibres as well as altered force transmission within the compartment. A possible role of myofascial force transmission is discussed. © Springer 2005

Phase 1 evaluation of a local delivery device releasing silver ions in periodontal pockets: Safety, pharmacokinetics and bioavailability

A new local delivery device (LDD) capable of releasing silver in periodontal pockets has been developed and tested pre-clinically. Silver has potent antimicrobial effects on Gram-negative periodontal pathogens with a mean in vitro minimum bactericidal concentration (MBC) ≤0.5 μg/ml. This phase 1 study assessed the safety, pharmacokinetics and bioavailability of silver ions delivered intracrevicularly with a resorbable LDD (PocketGuard™) in a group of 9 volunteers affected with periodontitis. In each subject, a PLGA/PEG LDD loaded with 12% silver nitrate (w/w) was inserted in each of 4 selected pockets >5 mm. Serum, gingival fluid and subgingival plaque samples were evaluated before and at various time points after LDD placement for 21 days. At each time point, the concentration of silver in gingival crevicular fluid (GCF) was quantified with an Inductively Coupled Plasma-Mass Spectrometer. Subgingival plaque samples were processed for evaluation of total anaerobic and aerobic counts (CFU/ml). The maximum mean silver concentration in GCF was 1493 ± 709 μg/ml (range 589-2245). It decayed exponentially with a half-life of 7.1 ± 6.1 days (2.7-20.4). Average silver concentrations in excess of 10 μg/ml were detected in each patient for 14 days after LDD placement with the average concentration for all patients in excess of 25 μg/mL at day 21. Total anaerobic counts decreased an average of 1.7 ± 1.9 × 10 6 CFU/ml (p = 0.0078) from baseline to day 7, indicating that the silver was biologically active. A mild increase in cervical root discoloration was observed at day 21: 0.25 ± 0.31 stain index units. Discoloration that did not resolve spontaneously could be removed at the end of the study with polishing. No systemic effects were observed. It is concluded that local silver concentrations above the MBC in serum were maintained for at least 21 days. A specific microbiologic effect was also observed.link_to_subscribed_fulltex