The incidence and impact of 'Tandem Neurotrauma'.

Introduction: The epidemiology and prognosis of the isolated traumatic brain injury (TBI) and spinal cord injury (SCI) are well studied. However, the knowledge of the impact of concurrent neurotrauma is very limited. Research questions: To characterize the longitudinal incidence of concurrent TBI and SCI and to investigate their combined impact on clinical care and outcomes, compared to a comparative but isolated SCI or TBI. Materials and methods: Data from 167,793 patients in the Trauma Audit and Research Network (TARN) registry collected in England and Wales between 2008 and 2018 were analysed. Tandem neurotrauma was defined as patients with concurrent TBI and SCI. The patient with isolated TBI or SCI was matched to the patient with tandem neurotrauma using propensity scores. Results: The incidence of tandem neurotrauma increased tenfold between 2008 and 2018, from 0.21 to 2.21 per 100,000 person-years. Patients in the tandem neurotrauma group were more likely to require multiple surgeries, ICU admission, longer ICU and hospital LOS, higher 30-day mortality, and were more likely to be transferred to acute hospitals and rehabilitation or suffer death at discharge, compared to patients with isolated TBI. Likewise, individuals with tandem neurotrauma compared to those with isolated SCI had a higher tendency to receive more than one surgery, ICU admission, longer LOS for ICU and higher mortality either at 30-day follow-up or at discharge. Discussion and conclusions: The incidence of tandem neurotrauma has increased steadily during the past decade. Its occurrence leads to greater mortality and care requirements, particularly when compared to TBI alone. Further investigations are warranted to improve outcomes in tandem neurotrauma.

Lived experience-centred word clouds may improve research uncertainty gathering in priority setting partnerships.

INTRODUCTION: AO Spine RECODE-DCM was a multi-stakeholder priority setting partnership (PSP) to define the top ten research priorities for degenerative cervical myelopathy (DCM). Priorities were generated and iteratively refined using a series of surveys administered to surgeons, other healthcare professionals (oHCP) and people with DCM (PwDCM). The aim of this work was to utilise word clouds to enable the perspectives of people with the condition to be heard earlier in the PSP process than is traditionally the case. The objective was to evaluate the added value of word clouds in the process of defining research uncertainties in National Institute for Health Research (NIHR) James Lind Alliance (JLA) Priority Setting Partnerships. METHODS: Patient-generated word clouds were created for the four survey subsections of the AO Spine RECODE-DCM PSP: diagnosis, treatment, long-term management and other issues. These were then evaluated as a nested methodological study. Word-clouds were created and iteratively refined by an online support group of people with DCM, before being curated by the RECODE-DCM management committee and expert healthcare professional representatives. The final word clouds were embedded within the surveys administered at random to 50% of participants. DCM research uncertainties suggested by participants were compared pre- and post-word cloud presentation. RESULTS: A total of 215 (50.9%) participants were randomised to the word cloud stream, including 118 (55%) spinal surgeons, 52 (24%) PwDCM and 45 (21%) oHCP. Participants submitted 434 additional uncertainties after word cloud review: word count was lower and more uniform across each survey subsections compared to pre-word cloud uncertainties. Twenty-three (32%) of the final 74 PSP summary questions did not have a post-word cloud contribution and no summary question was formed exclusively on post-word cloud uncertainties. There were differences in mapping of pre- and post-word cloud uncertainties to summary questions, with greater mapping of post-word cloud uncertainties to the number 1 research question priority: raising awareness. Five of the final summary questions were more likely to map to the research uncertainties suggested by participants after having reviewed the word clouds. CONCLUSIONS: Word clouds may increase the perspective of underrepresented stakeholders in the research question gathering stage of priority setting partnerships. This may help steer the process towards research questions that are of highest priority for people with the condition.

The development of lived experience-centered word clouds to support research uncertainty gathering in degenerative cervical myelopathy: results from an engagement process and protocol for their evaluation, via a nested randomized controlled trial.

OBJECTIVES: AO Spine REsearch objectives and Common Data Elements for Degenerative Cervical Myelopathy [RECODE-DCM] is a multi-stakeholder consensus process aiming to promote research efficiency in DCM. It aims to establish the top 10 research uncertainties, through a James Lind Alliance Priority Setting Partnership [PSP]. Through a consensus process, research questions are generated and ranked. The inclusion of people with cervical myelopathy [PwCM] is central to the process. We hypothesized that presenting PwCM experience through word cloud generation would stimulate other key stakeholders to generate research questions better aligned with PwCM needs. This protocol outlines our plans to evaluate this as a nested methodological study within our PSP. METHODS: An online poll asked PwCM to submit and vote on words associated with aspects of DCM. After review, a refined word list was re-polled for voting and word submission. Word clouds were generated and an implementation plan for AO Spine RECODE-DCM PSP surveys was subsequently developed. RESULTS: Seventy-nine terms were submitted after the first poll. Eighty-seven refined words were then re-polled (which added a further 39 words). Four word clouds were generated under the categories of diagnosis, management, long-term effects, and other. A 1:1 block randomization protocol to assess word cloud impact on the number and relevance of PSP research questions was generated. CONCLUSIONS: We have shown it is feasible to work with PwCM to generate a tool for the AO Spine RECODE-DCM nested methodological study. Once the survey stage is completed, we will be able to evaluate the impact of the word clouds. Further research will be needed to assess the value of any impact in terms of stimulating a more creative research agenda.

RE-CODE DCM (REsearch Objectives and Common Data Elements for Degenerative Cervical Myelopathy): A Consensus Process to Improve Research Efficiency in DCM, Through Establishment of a Standardized Dataset for Clinical Research and the Definition of the Research Priorities.

STUDY DESIGN: Mixed-method consensus process. OBJECTIVES: Degenerative cervical myelopathy (DCM) is a common and disabling condition that arises when mechanical stress damages the spinal cord as a result of degenerative changes in the surrounding spinal structures. RECODE-DCM (REsearch Objectives and Common Data Elements for Degenerative Cervical Myelopathy) aims to improve efficient use of health care resources within the field of DCM by using a multi-stakeholder partnership to define the DCM research priorities, to develop a minimum dataset for DCM clinical studies, and confirm a definition of DCM. METHODS: This requires a multi-stakeholder partnership and multiple parallel consensus development processes. It will be conducted via 4 phases, adhering to the guidance set out by the COMET (Core Outcomes in Effectiveness Trials) and JLA (James Lind Alliance) initiatives. Phase 1 will consist of preliminary work to inform online Delphi processes (Phase 2) and a consensus meeting (Phase 3). Following the findings of the consensus meeting, a synthesis of relevant measurement instruments will be compiled and assessed as per the COSMIN (Consensus-based Standards for the Selection of Health Measurement Instruments) criteria, to allow recommendations to be made on how to measure agreed data points. Phase 4 will monitor and promote the use of eventual recommendations. CONCLUSIONS: RECODE-DCM sets out to establish for the first time an index term, minimum dataset, and research priorities together. Our aim is to reduce waste of health care resources in the future by using patient priorities to inform the scope of future DCM research activities. The consistent use of a standard dataset in DCM clinical studies, audit, and clinical surveillance will facilitate pooled analysis of future data and, ultimately, a deeper understanding of DCM.

Estimation of Energy Expenditure in Wheelchair-Bound Spinal Cord Injured Individuals Using Inertial Measurement Units.

A healthy lifestyle reduces the risk of cardio-vascular disease. As wheelchair-bound individuals with spinal cord injury (SCI) are challenged in their activities, promoting and coaching an active lifestyle is especially relevant. Although there are many commercial activity trackers available for the able-bodied population, including those providing feedback about energy expenditure (EE), activity trackers for the SCI population are largely lacking, or are limited to a small set of activities performed in controlled settings. The aims of the present study were to develop and validate an algorithm based on inertial measurement unit (IMU) data to continuously monitor EE in wheelchair-bound individuals with a SCI, and to establish reference activity values for a healthy lifestyle in this population. For this purpose, EE was measured in 30 subjects each wearing four IMUs during 12 different physical activities, randomly selected from a list of 24 activities of daily living. The proposed algorithm consists of three parts: resting EE estimation based on multi-linear regression, an activity classification using a k-nearest-neighbors algorithm, and EE estimation based on artificial neural networks (ANNs). The mean absolute estimation error for the ANN-based algorithm was 14.4% compared to indirect calorimeter measurements. Based on reference values from the literature and the data collected within this study, we recommend wheeling 3 km per day for a healthy lifestyle in wheelchair-bound SCI individuals. Combining the proposed algorithm with a recommendation for physical activity provides a powerful tool for the promotion of an active lifestyle in the SCI population, thereby reducing the risk for secondary diseases.

Multi-Day Recordings of Wearable Sensors Are Valid and Sensitive Measures of Function and Independence in Human Spinal Cord Injury.

Wearable sensor assessment tools have proven to be reliable in measuring function in normal and impaired movement disorders during well-defined assessment protocols. While such assessments can provide valid and sensitive measures of upper limb activity in spinal cord injury (SCI), no assessment tool has yet been introduced into unsupervised daily recordings to complement clinical assessments during rehabilitation. The objective of this study was to measure the overall amount of upper-limb activity in subjects with acute SCI using wearable sensors and relate this to lesion characteristics, independence, and function. The overall amount of upper extremity activity counts, measures of wheeling (speed and distance), and limb-use laterality were measured in 30 in-patients with an acute cervical or thoracic SCI three months after injury. The findings were related to the international standards for neurological classification of SCI, the spinal cord independence measure, and the upper extremity motor scores of the Graded and Redefined Assessment of Strength, Sensibility, and Prehension. Overall upper extremity activity counts were successfully recorded in all patients and correlated with the neurological level of injury and independence. Clinical measures of proximal muscle strength were related to overall activity count and peak velocity of wheeling. Compared with paraplegics, tetraplegics showed significantly lower activity counts and increased limb-use laterality. This is the first cross-sectional study showing the feasibility and clinical value of sensor recordings during unsupervised daily activities in rehabilitation. The strong relationship between sensor-based measures and clinical outcomes supports the application of such technology to assess and track changes in function during rehabilitation and in clinical trials.

Monitoring Upper Limb Recovery after Cervical Spinal Cord Injury: Insights beyond Assessment Scores.

BACKGROUND: Preclinical investigations in animal models demonstrate that enhanced upper limb (UL) activity during rehabilitation promotes motor recovery following spinal cord injury (SCI). Despite this, following SCI in humans, no commonly applied training protocols exist, and therefore, activity-based rehabilitative therapies (ABRT) vary in frequency, duration, and intensity. Quantification of UL recovery is limited to subjective questionnaires or scattered measures of muscle function and movement tasks. OBJECTIVE: To objectively measure changes in UL activity during acute SCI rehabilitation and to assess the value of wearable sensors as novel measurement tools that are complimentary to standard clinical assessments tools. METHODS: The overall amount of UL activity and kinematics of wheeling were measured longitudinally with wearable sensors in 12 thoracic and 19 cervical acute SCI patients (complete and incomplete). The measurements were performed for up to seven consecutive days, and simultaneously, SCI-specific assessments were made during rehabilitation sessions 1, 3, and 6 months after injury. Changes in UL activity and function over time were analyzed using linear mixed models. RESULTS: During acute rehabilitation, the overall amount of UL activity and the active distance wheeled significantly increased in tetraplegic patients, but remained constant in paraplegic patients. The same tendency was shown in clinical scores with the exception of those for independence, which showed improvements at the beginning of the rehabilitation period, even in paraplegic subjects. In the later stages of acute rehabilitation, the quantity of UL activity in tetraplegic individuals matched that of their paraplegic counterparts, despite their greater motor impairments. Both subject groups showed higher UL activity during therapy time compared to the time outside of therapy time. CONCLUSION: Tracking day-to-day UL activity is necessary to gain insights into the real impact of a patient's impairments on their UL movements during therapy and during their leisure time. In the future, this novel methodology may be used to reliably control and adjust ABRT and to evaluate the progress of UL rehabilitation in clinical trials.

Self-directed arm therapy at home after stroke with a sensor-based virtual reality training system.

BACKGROUND: The effect of rehabilitative training after stroke is dose-dependent. Out-patient rehabilitation training is often limited by transport logistics, financial resources and a lack of motivation/compliance. We studied the feasibility of an unsupervised arm therapy for self-directed rehabilitation therapy in patients' homes. METHODS: An open-label, single group study involving eleven patients with hemiparesis due to stroke (27 ± 31.5 months post-stroke) was conducted. The patients trained with an inertial measurement unit (IMU)-based virtual reality system (ArmeoSenso) in their homes for six weeks. The self-selected dose of training with ArmeoSenso was the principal outcome measure whereas the Fugl-Meyer Assessment of the upper extremity (FMA-UE), the Wolf Motor Function Test (WMFT) and IMU-derived kinematic metrics were used to assess arm function, training intensity and trunk movement. Repeated measures one-way ANOVAs were used to assess differences in training duration and clinical scores over time. RESULTS: All subjects were able to use the system independently in their homes and no safety issues were reported. Patients trained on 26.5 ± 11.5 days out of 42 days for a duration of 137 ± 120 min per week. The weekly training duration did not change over the course of six weeks (p = 0.146). The arm function of these patients improved significantly by 4.1 points (p = 0.003) in the FMA-UE. Changes in the WMFT were not significant (p = 0.552). ArmeoSenso based metrics showed an improvement in arm function, a high number of reaching movements (387 per session), and minimal compensatory movements of the trunk while training. CONCLUSIONS: Self-directed home therapy with an IMU-based home therapy system is safe and can provide a high dose of rehabilitative therapy. The assessments integrated into the system allow daily therapy monitoring, difficulty adaptation and detection of maladaptive motor patterns such as trunk movements during reaching. TRIAL REGISTRATION: Unique identifier: NCT02098135 .

Novel Sensor Technology To Assess Independence and Limb-Use Laterality in Cervical Spinal Cord Injury.

After spinal cord injury (SCI), levels of independence are commonly assessed with standardized clinical assessments. However, such tests do not provide information about the actual extent of upper limb activities or the impact on independence of bi- versus unilateral usage throughout daily life following cervical SCI. The objective of this study was to correlate activity intensity and laterality of upper extremity activity measured by body-fixed inertial measurement units (IMUs) with clinical assessment scores of independence. Limb-use intensity and laterality of activities performed by the upper extremities was measured in 12 subjects with cervical SCI using four IMUs (positioned on both wrists, on the chest, and on one wheel of the wheelchair). Algorithms capable of reliably detecting self-propulsion and arm activity in a clinical environment were applied to rate functional outcome levels, and were related to clinical independence measures during inpatient rehabilitation. Measures of intensity of upper extremity activity during self-propulsion positively correlated (p < 0.05, r = 0.643) with independence measures related to mobility. Clinical measures of laterality were positively correlated (p < 0.01, r = 0.900) with laterality as measured by IMUs during "daily life," and increased laterality was negatively correlated (p < 0.01, r = -0.739) with independence. IMU sensor technology is sensitive in assessing and quantifying upper limb-use intensity and laterality in human cervical SCI. Continuous and objective movement data of distinct daily activities (i.e., mobility and day-to-day activities) can be related to levels of independence. Therefore, IMU sensor technology is suitable not only for monitoring activity levels during rehabilitation (including during clinical trials) but could also be used to assess levels of participation after discharge.

A novel algorithm for detecting active propulsion in wheelchair users following spinal cord injury.

Physical activity in wheelchair-bound individuals can be assessed by monitoring their mobility as this is one of the most intense upper extremity activities they perform. Current accelerometer-based approaches for describing wheelchair mobility do not distinguish between self- and attendant-propulsion and hence may overestimate total physical activity. The aim of this study was to develop and validate an inertial measurement unit based algorithm to monitor wheel kinematics and the type of wheelchair propulsion (self- or attendant-) within a "real-world" situation. Different sensor set-ups were investigated, ranging from a high precision set-up including four sensor modules with a relatively short measurement duration of 24 h, to a less precise set-up with only one module attached at the wheel exceeding one week of measurement because the gyroscope of the sensor was turned off. The "high-precision" algorithm distinguished self- and attendant-propulsion with accuracy greater than 93% whilst the long-term measurement set-up showed an accuracy of 82%. The estimation accuracy of kinematic parameters was greater than 97% for both set-ups. The possibility of having different sensor set-ups allows the use of the inertial measurement units as high precision tools for researchers as well as unobtrusive and simple tools for manual wheelchair users.

Chasing central nervous system plasticity: the brainstem's contribution to locomotor recovery in rats with spinal cord injury.

Anatomical plasticity such as fibre growth and the formation of new connections in the cortex and spinal cord is one known mechanism mediating functional recovery after damage to the central nervous system. Little is known about anatomical plasticity in the brainstem, which contains key locomotor regions. We compared changes of the spinal projection pattern of the major descending systems following a cervical unilateral spinal cord hemisection in adult rats. As in humans (Brown-Séquard syndrome), this type of injury resulted in a permanent loss of fine motor control of the ipsilesional fore- and hindlimb, but for basic locomotor functions substantial recovery was observed. Antero- and retrograde tracings revealed spontaneous changes in spinal projections originating from the reticular formation, in particular from the contralesional gigantocellular reticular nucleus: more reticulospinal fibres from the intact hemicord crossed the spinal midline at cervical and lumbar levels. The intact-side rubrospinal tract showed a statistically not significant tendency towards an increased number of midline crossings after injury. In contrast, the corticospinal and the vestibulospinal tract, as well as serotonergic projections, showed little or no side-switching in this lesion paradigm. Spinal adaptations were accompanied by modifications at higher levels of control including side-switching of the input to the gigantocellular reticular nuclei from the mesencephalic locomotor region. Electrolytic microlesioning of one or both gigantocellular reticular nuclei in behaviourally recovered rats led to the reappearance of the impairments observed acutely after the initial injury showing that anatomical plasticity in defined brainstem motor networks contributes significantly to functional recovery after injury of the central nervous system.

High-Impact, Self-Motivated Training Within an Enriched Environment With Single Animal Tracking Dose-Dependently Promotes Motor Skill Acquisition and Functional Recovery.

Functional recovery following central nervous system injuries is strongly influenced by rehabilitative training. In the clinical setting, the intensity of training and the level of motivation for a particular task are known to play important roles. With increasing neuroscience studies investigating the effects of training and rehabilitation, it is important to understand how the amount and type of training of individuals influences outcome. However, little is known about the influence of spontaneous "self-training" during daily life as it is often uncontrolled, not recorded, and mostly disregarded. Here, we investigated the effects of the intensity of self-training on motor skill acquisition in normal, intact rats and on the recovery of functional motor behavior following spinal cord injury in adult rats. We used a custom-designed small animal tracking system, "RatTrack," to continuously record the activity of multiple rats, simultaneously in a complex Natural Habitat-enriched environment. Naïve, adult rats performed high-intensity, self-motivated motor training, which resulted in them out-performing rats that were conventionally housed and trained on skilled movement tasks, for example, skilled prehension (grasping) and ladder walking. Following spinal cord injury the amount of self-training was correlated with improved functional recovery. These data suggest that high-impact, self-motivated training leads to superior skill acquisition and functional recovery than conventional training paradigms. These findings have important implications for the design of animal studies investigating rehabilitation and for the planning of human rehabilitation programs.

How Plastic Is the Brain after a Stroke?

Stroke is a common problem, and with an aging population, it is likely to become more so. Outcomes from stroke are wide ranging from death to complete recovery, but the majority result in severe motor impairments that affect quality of life and become a burden on health care systems, family, and friends. Therapeutically, removal of thromboses can greatly improve outcomes, but for many stroke sufferers, the only currently available therapy is rehabilitative training in which spared brain areas and fiber tracts are strengthened and trained to take over new functions. Experimental data in animals show that this is in part based on changes in the connectivity of the brain and spinal cord and on the growth of new nerve fiber branches, a process called structural plasticity. So, just how plastic is the brain after a stroke? In this review, we explore the factors that affect plasticity after strokes, such as age and the overall size and location of the lesion. We discuss the peri-infarct area as extensive research has shown that processes occurring there are likely to be involved mechanistically in plastic changes in cortical circuitry. Finally, we review promising interventions being tested preclinically and discuss those that have been translated into clinical research.

Rewiring of the corticospinal tract in the adult rat after unilateral stroke and anti-Nogo-A therapy.

Adult Long Evans rats received a photothrombotic stroke that destroyed >90% of the sensorimotor cortex unilaterally; they were subsequently treated intrathecally for 2 weeks with a function blocking antibody against the neurite growth inhibitory central nervous system protein Nogo-A. Fine motor control of skilled forelimb grasping improved to 65% of intact baseline performance in the anti-Nogo-A treated rats, whereas control antibody treated animals recovered to only 20% of baseline scores. Bilateral retrograde tract tracing with two different tracers from the intact and the denervated side of the cervical spinal cord, at different time points post-lesion, indicated that the intact corticospinal tract had extensively sprouted across the midline into the denervated spinal hemicord. The original axonal arbours of corticospinal tract fibres that had recrossed the midline were subsequently withdrawn, leading to a complete side-switch in the projection of a subpopulation of contralesional corticospinal tract axons. Anterograde tracing from the contralesional cortex showed a 2-3-fold increase of midline crossing fibres and additionally a massive sprouting of the pre-existing ipsilateral ventral corticospinal tract fibres throughout the entire cervical enlargement of the anti-Nogo-A antibody-treated rats compared to the control group. The laminar distribution pattern of the ipsilaterally projecting corticospinal tract fibres was similar to that in the intact spinal cord. These plastic changes were paralleled by a somatotopic reorganization of the contralesional motor cortex where the formation of an ipsilaterally projecting forelimb area was observed. Intracortical microstimulation of the contralesional motor cortex revealed that low threshold currents evoked ipsilateral movements and electromyography responses at frequent cortical sites in the anti-Nogo-A, but not in the control antibody-treated animals. Subsequent transection of the spared corticospinal tract in chronically recovered animals, treated with anti-Nogo-A, led to a reappearance of the initial lesion deficit observed after the stroke lesion. These results demonstrate a somatotopic side switch anatomically and functionally in the projection of adult corticospinal neurons, induced by the destruction of one sensorimotor cortex and the neutralization of the CNS growth inhibitory protein Nogo-A.

Chondroitinase ABC promotes compensatory sprouting of the intact corticospinal tract and recovery of forelimb function following unilateral pyramidotomy in adult mice.

Chondroitin sulphate proteoglycans (CSPGs) are extracellular matrix molecules whose inhibitory activity is attenuated by the enzyme chondroitinase ABC (ChABC). Here we assess whether CSPG degradation can promote compensatory sprouting of the intact corticospinal tract (CST) following unilateral injury and restore function to the denervated forelimb. Adult C57BL/6 mice underwent unilateral pyramidotomy and treatment with either ChABC or a vehicle control. Significant impairments in forepaw symmetry were observed following pyramidotomy, with injured mice preferentially using their intact paw during spontaneous vertical exploration of a cylinder. No recovery on this task was observed in vehicle-treated mice. However, ChABC-treated mice showed a marked recovery of function, with forelimb symmetry fully restored by 5 weeks post-injury. Functional recovery was associated with robust sprouting of the uninjured CST, with numerous axons observed crossing the midline in the brainstem and spinal cord and terminating in denervated grey matter. CST fibres in the denervated side of the spinal cord following ChABC treatment were closely associated with the synaptic marker vGlut1. Immunohistochemical assessment of chondroitin-4-sulphate revealed that CSPGs were heavily digested around lamina X, alongside midline crossing axons and in grey matter regions where sprouting axons and reduced peri-neuronal net staining was observed. Thus, we demonstrate that CSPG degradation promotes midline crossing and reinnervation of denervated target regions by intact CST axons and leads to restored function in the denervated forepaw. Enhancing compensatory sprouting using ChABC provides a route to restore function that could be applied to disorders such as spinal cord injury and stroke.

Reliability of movement workspace measurements in a passive arm orthosis used in spinal cord injury rehabilitation.

BACKGROUND: Robotic and non-robotic training devices are increasingly being used in the rehabilitation of upper limb function in subjects with neurological disorders. As well as being used for training such devices can also provide ongoing assessments during the training sessions. Therefore, it is mandatory to understand the reliability and validity of such measurements when used in a clinical setting. The aim of this study was to evaluate the reliability of movement measures as assessed in the Armeo Spring system for the eventual application to the rehabilitation of patients suffering from cervical spinal cord injury (SCI). METHODS: Reliability (intra- and inter-rater reliability) of the movement workspace (representing multiple ranges of movement) and the influence of varying seating conditions (5 different chair conditions) was assessed in twenty control subjects. In eight patients with cervical SCI the test-retest reliability (tested twice on the same day by the same rater) was assessed as well as a correlation of the movement workspace to retrieve self-care items as scored by the spinal cord independence measure (SCIM 3). RESULTS: Analysis of workspace measures in control subjects revealed intra-class correlation coefficients (ICC) ranging from 0.747 to 0.837 for the intra-rater reliability and from 0.661 to 0.855 for the inter-rater reliability. Test-retest analysis in SCI patients showed a similar high reliability with ICC = 0.858. Also the reliability of the movement workspace between different seating conditions was good with ICCs ranging from 0.844 to 0.915. The movement workspace correlated significantly with the SCIM3 self-care items (p < 0.05, rho = 0.72). CONCLUSION: The upper limb movement workspace measures assessed in the Armeo Spring device revealed fair to good clinical reliability. These findings suggest that measures retrieved from such a training device can be used to monitor changes in upper limb function over time. The correlation between the workspace measures and SCIM3 self-care items indicates that such measures might also be valuable to document the progress of clinical rehabilitation, however further detailed studies are required.

Versatile robotic interface to evaluate, enable and train locomotion and balance after neuromotor disorders.

Central nervous system (CNS) disorders distinctly impair locomotor pattern generation and balance, but technical limitations prevent independent assessment and rehabilitation of these subfunctions. Here we introduce a versatile robotic interface to evaluate, enable and train pattern generation and balance independently during natural walking behaviors in rats. In evaluation mode, the robotic interface affords detailed assessments of pattern generation and dynamic equilibrium after spinal cord injury (SCI) and stroke. In enabling mode,the robot acts as a propulsive or postural neuroprosthesis that instantly promotes unexpected locomotor capacities including overground walking after complete SCI, stair climbing following partial SCI and precise paw placement shortly after stroke. In training mode, robot-enabled rehabilitation, epidural electrical stimulation and monoamine agonists reestablish weight-supported locomotion, coordinated steering and balance in rats with a paralyzing SCI. This new robotic technology and associated concepts have broad implications for both assessing and restoring motor functions after CNS disorders, both in animals and in humans.

Anti-Nogo-A and training: can one plus one equal three?

Following spinal cord injury (SCI) the adult central nervous system (CNS) has a limited but substantial capacity for repair and plastic reorganisation. The degree of reorganisation is determined by a number of factors such as the extent and location of the lesion, the remaining circuit activity within the CNS and the age at injury. However, even in the best cases this spontaneous reorganisation does not lead to full recovery of the affected behaviour but instead often results in a functionally successful but compensatory strategy. Current SCI research focuses on enhancing fibre tract (re-)growth and recovery processes. Two currently promising approaches are the neutralisation of CNS growth inhibitory factors, and rehabilitative training of remaining networks. Independently, both approaches can lead to substantial functional recovery and anatomical reorganisation. In this review we focus on Nogo-A, a neurite growth inhibitory protein present in the adult CNS, and its role in regenerative and plastic growth following SCI. We then discuss the efforts of rehabilitative training and the potential combination of the two therapies.

Rehabilitative training following unilateral pyramidotomy in adult rats improves forelimb function in a non-task-specific way.

Spontaneous functional recovery following injury to the adult central nervous system can be enhanced with increased and focused activity, either through altered behaviour (skill learning, exercise or training) or by artificial stimulation (magnetic or electrical). In terms of training, the choice of paradigm plays a key role in the recovered behaviour. Here we show that task-specific training leads to improved forelimb function that can be translated to a novel forelimb task. Adult Long-Evans rats received a unilateral pyramidotomy and we studied the effects of different post-lesion training paradigms for their ability to recover function in the impaired limb. We trained rats on either the single pellet grasping or the horizontal ladder task. Rats were tested on both tasks regardless of the training paradigm and also on a related, but novel forelimb task, the Staircase. Horizontal ladder training led to full recovery of this task, and also limited recovery on the familiar but untrained single pellet grasping task. In comparison, single pellet grasping training led to a smaller improvement on the horizontal ladder, but interestingly the same degree of recovery on the single pellet grasping task as horizontal ladder trained animals. Both training groups performed equally well on a novel, untrained forelimb grasping task. These results show that task-specific forelimb training can lead to functional recovery also in non-trained, complex, forelimb movements. Anatomically, only single pellet grasping training was associated with enhanced sprouting of the intact corticospinal tract across the cervical spinal cord midline to innervate the denervated side of the spinal cord.

Profiling locomotor recovery: comprehensive quantification of impairments after CNS damage in rodents.

Rodents are frequently used to model damage and diseases of the central nervous system (CNS) that lead to functional deficits. Impaired locomotor function is currently evaluated by using scoring systems or biomechanical measures. These methods often suffer from limitations such as subjectivity, nonlinearity and low sensitivity, or focus on a few very restricted aspects of movement. Thus, full quantitative profiles of motor deficits after CNS damage are lacking. Here we report the detailed characterization of locomotor impairments after applying common forms of CNS damage in rodents. We obtained many objective and quantitative readouts from rats with either spinal cord injuries or strokes and from transgenic mice (Epha4−/−) during skilled walking, overground walking, wading and swimming, resulting in model-specific locomotor profiles. Our testing and analysis method enables comprehensive assessment of locomotor function in rodents and has broad application in various fields of life science research.