Surgical reconstruction of the anterior cruciate ligament (ACL) does not necessarily decrease the risk of developing osteoarthritis (OA). The inflammatory response and relative changes in pro-and anti-inflammatory cytokines could participate in triggering the development of OA. To test this hypothesis we measured the concentrations of IL-1b, IL-1ra, IL-6, IL-8, IL-10, and TNF-a at different times after ACL rupture. The sample population consisted of 48 patients with ACL tear which were assigned to different groups according to the time elapsed from the injury: 22 acute (A), 7 early sub-acute (ESA), 11 late sub-acute (LSA), and 8 chronic (C). In group A, there were high levels of IL-1b, IL-6, and IL-8, whereas levels of IL-1ra and TNF-a were significantly lower than usually reported. IL-1b and IL-8 concentrations returned with time to normal levels in the ESA group. Interestingly, IL-1ra levels remained always significantly lower than normally reported levels, and TNF-a levels did not increase after trauma. Our data show increased level of pro-inflammatory cytokines in the acute phase of inflammation which could be responsible for triggering cartilage catabolism and suggest that prompt neutralization of IL-6 and IL-8 accumulations in synovial fluid could help prevent development of OA in ACL-injured knees. ß

BackgroundMUNDUS is an assistive framework for recovering direct interaction capability of severely motor impaired people based on arm reaching and hand functions. It aims at achieving personalization, modularity and maximization of the user’s direct involvement in assistive systems. To this, MUNDUS exploits any residual control of the end-user and can be adapted to the level of severity or to the progression of the disease allowing the user to voluntarily interact with the environment. MUNDUS target pathologies are high-level spinal cord injury (SCI) and neurodegenerative and genetic neuromuscular diseases, such as amyotrophic lateral sclerosis, Friedreich ataxia, and multiple sclerosis (MS). The system can be alternatively driven by residual voluntary muscular activation, head/eye motion, and brain signals. MUNDUS modularly combines an antigravity lightweight and non-cumbersome exoskeleton, closed-loop controlled Neuromuscular Electrical Stimulation for arm and hand motion, and potentially a motorized hand orthosis, for grasping interactive objects.MethodsThe definition of the requirements and of the interaction tasks were designed by a focus group with experts and a questionnaire with 36 potential end-users.Five end-users (3 SCI and 2 MS) tested the system in the configuration suitable to their specific level of impairment. They performed two exemplary tasks: reaching different points in the working volume and drinking. Three experts evaluated over a 3-level score (from 0, unsuccessful, to 2, completely functional) the execution of each assisted sub-action.ResultsThe functionality of all modules has been successfully demonstrated. User’s intention was detected with a 100% success. Averaging all subjects and tasks, the minimum evaluation score obtained was 1.13 ± 0.99 for the release of the handle during the drinking task, whilst all the other sub-actions achieved a mean value above 1.6. All users, but one, subjectively perceived the usefulness of the assistance and could easily control the system. Donning time ranged from 6 to 65 minutes, scaled on the configuration complexity.ConclusionsThe MUNDUS platform provides functional assistance to daily life activities; the modules integration depends on the user’s need, the functionality of the system have been demonstrated for all the possible configurations, and preliminary assessment of usability and acceptance is promising.

The standard account of motor control considers descending outputs from primary motor cortex (M1) as motor commands and efference copy. This account has been challenged recently by an alternative formulation in terms of active inference: M1 is considered as part of a sensorimotor hierarchy providing top–down proprioceptive predictions. The key difference between these accounts is that predictions are sensitive to the current proprioceptive context, whereas efference copy is not. Using functional electric stimulation to experimentally manipulate proprioception during voluntary movement in healthy human subjects, we assessed the evidence for context sensitive output from M1. Dynamic causal modeling of functional magnetic resonance imaging responses showed that FES altered proprioception increased the influence of M1 on primary somatosensory cortex (S1). These results disambiguate competing accounts of motor control, provide some insight into the synaptic mechanisms of sensory attenuation and may speak to potential mechanisms of action of FES in promoting motor learning in neurorehabilitation.

Neurorehabilitation effective delivery for stroke is likely to be improved by establishing a mechanistic understanding of how to enhance adaptive plasticity. Functional electrical stimulation is effective at reducing poststroke foot drop; in some patients, the effect persists after therapy has finished with an unknown mechanism. We used fMRI to examine neural correlates of functional electrical stimulation key elements, volitional intent to move and concurrent stimulation, in a group of chronic stroke patients receiving functional electrical stimulation for foot-drop correction. Patients exhibited task-related activation in a complex network, sharing bilateral sensorimotor and supplementary motor activation with age-matched controls. We observed consistent separation of patients with and without carryover effect on the basis of brain responses. Patients who experienced the carryover effect had responses in supplementary motor area that correspond to healthy controls; the interaction between experimental factors in contralateral angular gyrus was seen only in those without carryover. We suggest that the functional electrical stimulation carryover mechanism of action is based on movement prediction and sense of agency/body ownership—the ability of a patient to plan the movement and to perceive the stimulation as a part of his/her own control loop is important for carryover effect to take place.

Two key ingredients of a successful neuro-rehabilitative intervention have been identified as intensive and repetitive training and subject's active participation, which can be coupled in an active robot-assisted training. To exploit these two elements, we recorded electroencephalography, electromyography and kinematics signals from nine healthy subjects performing a 2×2 factorial design protocol, with subject's volitional intention and robotic glove assistance as factors. We quantitatively evaluated primary sensorimotor, premotor and supplementary motor areas activation during movement execution by computing event-related desynchronization (ERD) patterns associated to mu and beta rhythms. ERD patterns showed a similar behavior for all investigated regions: statistically significant ERDs began earlier in conditions requiring subject's volitional contribution; ERDs were prolonged towards the end of movement in conditions in which the robotic assistance was present. Our study suggests that the combination between subject volitional contribution and movement assistance provided by the robotic device (i.e., active robot-assisted modality) is able to provide early brain activation (i.e., earlier ERD) associated with stronger proprioceptive feedback (i.e., longer ERD). This finding might be particularly important for neurological patients, where movement cannot be completed autonomously and passive/active robot-assisted modalities are the only possibilities of execution.

BackgroundCorrelating the features of the actual executed movement with the associated cortical activations can enhance the reliability of the functional Magnetic Resonance Imaging (fMRI) data interpretation. This is crucial for longitudinal evaluation of motor recovery in neurological patients and for investigating detailed mutual interactions between activation maps and movement parameters.Therefore, we have explored a new set-up combining fMRI with an optoelectronic motion capture system, which provides a multi-parameter quantification of the performed motor task.MethodsThe cameras of the motion system were mounted inside the MR room and passive markers were placed on the subject skin, without any risk or encumbrance. The versatile set-up allows 3-dimensional multi-segment acquisitions including recording of possible mirror movements, and it guarantees a high inter-sessions repeatability.We demonstrated the integrated set-up reliability through compatibility tests. Then, an fMRI block-design protocol combined with kinematic recordings was tested on a healthy volunteer performing finger tapping and ankle dorsal- plantar-flexion. A preliminary assessment of clinical applicability and perspectives was carried out by pre- and post rehabilitation acquisitions on a hemiparetic patient performing ankle dorsal- plantar-flexion. For all sessions, the proposed method integrating kinematic data into the model design was compared with the standard analysis.ResultsPhantom acquisitions demonstrated the not-compromised image quality. Healthy subject sessions showed the protocols feasibility and the model reliability with the kinematic regressor. The patient results showed that brain activation maps were more consistent when the images analysis included in the regression model, besides the stimuli, the kinematic regressor quantifying the actual executed movement (movement timing and amplitude), proving a significant model improvement. Moreover, concerning motor recovery evaluation, after one rehabilitation month, a greater cortical area was activated during exercise, in contrast to the usual focalization associated with functional recovery. Indeed, the availability of kinematics data allows to correlate this wider area with a higher frequency and a larger amplitude of movement.ConclusionsThe kinematic acquisitions resulted to be reliable and versatile to enrich the fMRI images information and therefore the evaluation of motor recovery in neurological patients where large differences between required and performed motion can be expected.

Concentrations of pro- and anti-inflammatory cytokines in synovial fluid samples collected from patients with chronic meniscal tears were investigated. An acute inflammatory response is generally reported 24-48 h after knee injury, but the largest body of data available in literature concerns anterior cruciate ligament injury and very little information is available about the balance of soluble factors in the synovial fluid of knees with chronic meniscal tears. Sixty-nine patients (46 males and 23 females) with meniscal tear that occurred more than 3 months earlier were enrolled. According to cartilage integrity assessment by arthroscopic examination, patients were assigned to one of the following groups: (i) no chondral damage (n = 18); (ii) chondral damage graded from I to II (n = 15); and (iii) chondral damage graded from III to IV (n = 37). In all groups, levels of IL-10 and inflammatory cytokines IL-6, TNF-α, and IL-8 where greater compared with those reported in the intact population; by contrast, levels of IL-1ra and IL-1β were significantly lower. Interestingly, IL-6 levels were higher in female than male patients. Cytokine levels did not correlate with degree of chondral damage. IL-6 and IL-1ra levels positively correlated with IL-1β, and negatively correlated with TNF-α. Interestingly, levels of IL-1β and TNF-α were inversely correlated. Our data demonstrate increased levels of pro-inflammatory cytokines (IL-6, IL-8, and TNF-α) in the chronic phase of meniscal trauma. This pro-inflammatory state is maintained in the joint from the time of initial injury to several months later and could be a key factor in hampering cartilage regeneration. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:340-346, 2017.

Stroke-related locomotor impairments are often associated with abnormal timing and intensity of recruitment of the affected and non-affected lower limb muscles. Restoring the proper lower limbs muscles activation is a key factor to facilitate recovery of gait capacity and performance, and to reduce maladaptive plasticity. Ekso is a wearable powered exoskeleton robot able to support over-ground gait training. The user controls the exoskeleton by triggering each single step during the gait cycle. The fine-tuning of the exoskeleton control system is crucial—it is set according to the residual functional abilities of the patient, and it needs to ensure lower limbs powered gait to be the most physiological as possible. This work focuses on the definition of an automatic calibration procedure able to detect the best Ekso setting for each patient. EMG activity has been recorded from Tibialis Anterior, Soleus, Rectus Femoris, and Semitendinosus muscles in a group of 7 healthy controls and 13 neurological patients. EMG signals have been processed so to obtain muscles activation patterns. The mean muscular activation pattern derived from the controls cohort has been set as reference. The developed automatic calibration procedure requires the patient to perform overground walking trials supported by the exoskeleton while changing parameters setting. The Gait Metric index is calculated for each trial, where the closer the performance is to the normative muscular activation pattern, in terms of both relative amplitude and timing, the higher the Gait Metric index is. The trial with the best Gait Metric index corresponds to the best parameters set. It has to be noted that the automatic computational calibration procedure is based on the same number of overground walking trials, and the same experimental set-up as in the current manual calibration procedure. The proposed approach allows supporting the rehabilitation team in the setting procedure. It has been demonstrated to be robust, and to be in agreement with the current gold standard (i.e., manual calibration performed by an expert engineer). The use of a graphical user interface is a promising tool for the effective use of an automatic procedure in a clinical context.