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Patients with ankylosing spondylitis (AS) are vulnerable to cervical spine fractures. Long-standing pain may mask the symptoms of the fracture. Radiological imaging of the cervical spine may fail to identify the fracture due to the distorted anatomy, ossified ligaments and artefacts leading to delay in diagnosis and increased risk of neurological complications. The objectives are to identify the incidence and risk factors for delay in presentation of cervical spine fractures in patients with AS. Retrospective case series study of all patients with AS and cervical spine fracture admitted over a 12-year period at Queen Elizabeth National Spinal Injuries Unit, Scotland. Results show that total of 32 patients reviewed with AS and cervical spine fractures. In 19 patients (59.4%), a fracture was not identified on plain radiographs. Only five patients (15.6%) presented immediately after the injury. Of the 15 patients (46.9%) who were initially neurologically intact, three patients had neurological deterioration before admission. Cervical spine fractures in patients with long-standing AS are common and usually under evaluated. Early diagnosis with appropriate radiological investigations may prevent the possible long-term neurological cord damage. [ABSTRACT FROM AUTHOR]

Xi-cam is an extensible platform for data management, analysis and visualization. Xi-cam aims to provide a flexible and extensible approach to synchrotron data treatment as a solution to rising demands for high-volume/high-throughput processing pipelines. The core of Xi-cam is an extensible plugin-based graphical user interface platform which provides users with an interactive interface to processing algorithms. Plugins are available for SAXS/WAXS/GISAXS/GIWAXS, tomography and NEXAFS data. With Xi-cam's `advanced' mode, data processing steps are designed as a graph-based workflow, which can be executed live, locally or remotely. Remote execution utilizes high-performance computing or de-localized resources, allowing for the effective reduction of high-throughput data. Xi-cam's plugin-based architecture targets cross-facility and cross-technique collaborative development, in support of multi-modal analysis. Xi-cam is open-source and cross-platform, and available for download on GitHub.

Correction for 'Films of bacteria at interfaces: three stages of behaviour' by Liana Vaccari et al., Soft Matter, 2015, 11, 6062-6074.

Diffusion through biological gels is crucial for effective drug delivery using nanoparticles. Here, we demonstrate a new method to measure diffusivity over a large range of length scales - from tens of nanometers to tens of micrometers - using photoactivatable fluorescent nanoparticle probes. We have applied this method to investigate the length-scale dependent mobility of nanoparticles in fibrin gels and in sputum from patients with cystic fibrosis (CF). Nanoparticles composed of poly(lactic-co-glycolic acid), with polyethylene glycol coatings to resist bioadhesion, were internally labeled with caged rhodamine to make the particles photoactivatable. We activated particles within a region of sample using brief, targeted exposure to UV light, uncaging the rhodamine and causing the particles in that region to become fluorescent. We imaged the subsequent spatiotemporal evolution in fluorescence intensity and observed the collective particle diffusion over tens of minutes and tens of micrometers. We also performed complementary multiple particle tracking experiments on the same particles, extending significantly the range over which particle motion and its heterogeneity can be observed. In fibrin gels, both methods showed an immobile fraction of particles and a mobile fraction that diffused over all measured length scales. In the CF sputum, particle diffusion was spatially heterogeneous and locally anisotropic but nevertheless typically led to unbounded transport extending tens of micrometers within tens of minutes. These findings provide insight into the mesoscale architecture of these gels and its role in setting their permeability on physiologically relevant length scales, pointing toward strategies for improving nanoparticle drug delivery., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Study Design: A pilot randomised controlled trial., Objectives: The aims of this study were to evaluate the effectiveness and participant satisfaction of web-based physiotherapy in people with spinal cord injury (SCI)., Setting: Community patients of a national spinal injury unit in a university teaching hospital, Scotland, UK., Methods: Twenty-four participants were recruited and randomised to receive 8 weeks of web-based physiotherapy (intervention), twice per week, or usual care (control). Individual exercise programmes were prescribed based on participants' abilities. The intervention was delivered via a website (www.webbasedphysio.com) and monitored and progressed remotely by the physiotherapist., Results: Participants logged on to the website an average of 1.4±0.8 times per week. Between-group differences, although not significant, were more pronounced for the 6-min walk test. Participants were positive about using web-based physiotherapy and stated that they would be happy to use it again and would recommend it to others. Overall, it was rated as either good or excellent., Conclusions: Web-based physiotherapy was feasible and acceptable for people with SCI. Participants achieved good compliance with the intervention and rated the programme highly and beneficial for health and well-being at various states after injury. The results of this study warrant further work with a more homogeneous sample., Sponsorship: This study was funded by the Queen Elizabeth National Spinal Injuries Unit, Glasgow, UK.

Context: Respiratory complications, attributed to the build-up of secretions in the airway, are a leading cause of rehospitalisation for the tetraplegic population. Previously, we observed that the application of Abdominal Functional Electrical Stimulation (AFES) improved cough function and increased demand for secretion removal, suggesting AFES may aid secretion clearance. Clinically, secretion clearance is commonly achieved by using Mechanical insufflation-exsufflation (MI-E) to simulate a cough. In this study the feasibility of combining AFES with MI-E is evaluated., Findings: AFES was successfully combined with MI-E at eight fortnightly assessment sessions conducted with one sub-acute participant with tetraplegia. By using the signal from a pressure sensor, integrated with the MI-E device, AFES was correctly applied in synchrony with MI-E with an accuracy of 96.7%. Acute increases in exhaled volume and peak flow were observed during AFES assisted MI-E, compared to MI-E alone, at six of eight assessment sessions., Conclusion: The successful integration of AFES with MI-E at eight assessment sessions demonstrates the feasibility of this technique. The acute increases in respiratory function observed at the majority of assessment sessions generate the hypothesis that AFES assisted MI-E may be more effective for secretion clearance than MI-E alone.

Objective: One of the brain signatures of the central neuropathic pain (CNP) is the theta band over-activity of wider cortical structures, during imagination of movement. The objective of the study was to investigate whether this over-activity is reversible following the neurofeedback treatment of CNP., Methods: Five paraplegic patients with pain in their legs underwent from twenty to forty neurofeedback sessions that significantly reduced their pain. In order to assess their dynamic cortical activity they were asked to imagine movements of all limbs a week before the first and a week after the last neurofeedback session. Using time-frequency analysis we compared EEG activity during imagination of movement before and after the therapy and further compared it with EEG signals of ten paraplegic patients with no pain and a control group of ten able-bodied people., Results: Neurofeedback treatment resulted in reduced CNP and a wide spread reduction of cortical activity during imagination of movement. The reduction was significant in the alpha and beta band but was largest in the theta band. As a result cortical activity became similar to the activity of other two groups with no pain., Conclusions: Reduction of CNP is accompanied by reduced cortical over-activity during movement imagination., Significance: Understanding causes and consequences mechanism through which CNP affects cortical activity., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Spinal cord injury caused by stab wounds (SCISW) results from a partial or complete transection of the cord, and presents opportunities for interventional research. It is recognized that there is low incidence, but little is known about the natural history or the patient's suitability for long-term clinical outcome studies. This study aims to provide population-based evidence of the demographics of SCISW, and highlight the issues regarding the potential for future research. The database of the Queen Elizabeth National Spinal Injuries Unit (QENSIU), the sole center for treating SCI in Scotland, was reviewed between 1994 and 2013 to ascertain the incidence, demographics, functional recovery, and mortality rates for new SCISW. During this 20 year period, 35 patients with SCISW were admitted (97.1% male, mean age 30.0 years); 31.4% had a cervical injury, 60.0% had a thoracic injury, and 8.6% had a lumbar injury. All had a neurological examination, with 42.9% diagnosed as motor complete on admission and 77.1% discharged as motor incomplete. A total of 70.4% of patients with an American Spinal Injury Association Impairment Scale (AIS) level of A to C on admission had an improved AIS level on discharge. Nine (25.7%) patients have died since discharge, with mean life expectancy for these patients being 9.1 years after injury (20-65 years of age). Patients had higher levels of comorbidities, substance abuse, secondary events, and poor compliance compared with the general SCI population, which may have contributed to the high mortality rate observed post-discharge. The low incidence, heterogeneous nature, spontaneous recovery rate, and problematic follow-up makes those with penetrating stab injuries of the spinal cord a challenging patient group for SCI research.

Study Design: A retrospective cohort study., Objectives: To review demographic trends in traumatic spinal cord injury (TSCI) and non-traumatic spinal cord injury (NTSCI)., Setting: The Queen Elizabeth National Spinal Injuries Unit (QENSIU), sole provider of treatment for TSCI in Scotland; a devolved region of the UK National Health Service., Methods: A retrospective review of the QENSIU database was performed between 1994 and 2013. This database includes demographic and clinical data from all new TSCI patients in Scotland, as well as patients with severe NTSCI., Results: Over this 20-year period there were 1638 new cases of TSCI in Scotland; 75.2% occurring in males. TSCI incidence increased non-significantly (13.3 per million population to 17.0), while there were significant increases in mean age at time of TSCI (44.1-52.6 years), the proportion of TSCIs caused by falls (41-60%), the proportion of TSCIs resulting in an American Spinal Injury Association Impairment Scale score of C and D on admission (19.7-28.6% and 34.5-39.5%, respectively) and the proportion of cervical TSCIs (58.4-66.3%). The increase in cervical TSCI was specifically due to an increase in C1-C4 lesions (21.7-31.2%). NTSCI patients (n=292) were 5 years older at injury, more likely to be female (68.1% male) and had a range of diagnoses., Conclusion: This study supports the suggestion that demographic profiles in SCI are subject to change. In this population, of particular concern is the increasing number of older patients and those with high level tetraplegia, due to their increased care needs. Prevention programmes, treatment pathways and service provision need to be adjusted for optimum impact, improved outcome and long-term care for their target population.

After spinal cord injury (SCI), bone loss in the paralysed limbs progresses at variable rates. Decreases in bone mineral density (BMD) in the first year range from 1% (slow) to 40% (rapid). In chronic SCI, fragility fractures commonly occur around the knee, with significant associated morbidity. Osteoporosis treatments await full evaluation in SCI, but should be initiated early and targeted towards patients exhibiting rapid bone loss. The potential to predict rapid bone loss from a single bone scan within weeks of a SCI was investigated using statistical shape modelling (SSM) of bone morphology, hypothesis: baseline bone shape predicts bone loss at 12-months post-injury at fracture-prone sites. In this retrospective cohort study 25 SCI patients (median age, 33 years) were scanned at the distal femur and proximal tibia using peripheral Quantitative Computed Tomography at <5 weeks (baseline), 4, 8 and 12 months post-injury. An SSM was made for each bone. Links between the baseline shape-modes and 12-month total and trabecular BMD loss were analysed using multiple linear regression. One mode from each SSM significantly predicted bone loss (age-adjusted P<0.05 R(2)=0.37-0.61) at baseline. An elongated intercondylar femoral notch (femur mode 4, +1 SD from the mean) was associated with 8.2% additional loss of femoral trabecular BMD at 12-months. A more concave posterior tibial fossa (tibia mode 3, +1 SD) was associated with 9.4% additional 12-month tibial trabecular BMD loss. Baseline bone shape determined from a single bone scan is a valid imaging biomarker for the prediction of 12-month bone loss in SCI patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to test how the presence of central neuropathic pain (CNP) influences the performance of a motor imagery based Brain Computer Interface (BCI)., Methods: In this electroencephalography (EEG) based study, we tested BCI classification accuracy and analysed event related desynchronisation (ERD) in 3 groups of volunteers during imagined movements of their arms and legs. The groups comprised of nine able-bodied people, ten paraplegic patients with CNP (lower abdomen and legs) and nine paraplegic patients without CNP. We tested two types of classifiers: a 3 channel bipolar montage and classifiers based on common spatial patterns (CSPs), with varying number of channels and CSPs., Results: Paraplegic patients with CNP achieved higher classification accuracy and had stronger ERD than paraplegic patients with no pain for all classifier configurations. Highest 2-class classification accuracy was achieved for CSP classifier covering wider cortical area: 82±7% for patients with CNP, 82±4% for able-bodied and 78±5% for patients with no pain., Conclusion: Presence of CNP improves BCI classification accuracy due to stronger and more distinct ERD., Significance: Results of the study show that CNP is an important confounding factor influencing the performance of motor imagery based BCI based on ERD., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Central neuropathic pain has a prevalence of 40% in patients with spinal cord injury. Electroencephalography (EEG) studies showed that this type of pain has identifiable signatures, that could potentially be targeted by a neuromodulation therapy. The aim of the study was to investigate the putative mechanism of neurofeedback training on central neuropathic pain and its underlying brain signatures in patients with chronic paraplegia., Methods: Patients' EEG activity was modulated from the sensory-motor cortex, electrode location C3/Cz/C4/P4 in up to 40 training sessions Results. Six out of seven patients reported immediate reduction of pain during neurofeedback training. Best results were achieved with suppressing Ɵ and higher β (20-30 Hz) power and reinforcing α power at C4. Four patients reported clinically significant long-term reduction of pain (>30%) which lasted at least a month beyond the therapy. EEG during neurofeedback revealed a wide spread modulation of power in all three frequency bands accompanied with changes in the coherence most notable in the beta band. The standardized low resolution electromagnetic tomography analysis of EEG before and after neurofeedback therapy showed the statistically significant reduction of power in beta frequency band in all tested patients. Areas with reduced power included the Dorsolateral Prefrontal Cortex, the Anterior Cingulate Cortex and the Insular Cortex., Conclusions: Neurofeedback training produces both immediate and longer term reduction of central neuropathic pain that is accompanied with a measurable short and long term modulation of cortical activity. Controlled trials are required to confirm the efficacy of this neurofeedback protocol on treatment of pain. The study is a registered UKCRN clinical trial Nr 9824.

Particle tracking is a powerful microscopy technique to quantify the motion of individual particles at high spatial and temporal resolution in complex fluids and biological specimens. Particle tracking's applications and impact in drug and gene delivery research have greatly increased during the last decade. Thanks to advances in hardware and software, this technique is now more accessible than ever, and can be reliably automated to enable rapid processing of large data sets, thereby further enhancing the role that particle tracking will play in drug and gene delivery studies in the future. We begin this review by discussing particle tracking-based advances in characterizing extracellular and cellular barriers to therapeutic nanoparticles and in characterizing nanoparticle size and stability. To facilitate wider adoption of the technique, we then present a user-friendly review of state-of-the-art automated particle tracking algorithms and methods of analysis. We conclude by reviewing technological developments for next-generation particle tracking methods, and we survey future research directions in drug and gene delivery where particle tracking may be useful., (Copyright © 2015 Elsevier B.V. All rights reserved.)

We report an investigation of the formation of films by bacteria at an oil-water interface using a combination of particle tracking and pendant drop elastometry. The films display a remarkably varied series of dynamical and mechanical properties as they evolve over the course of minutes to hours following the creation of an initially pristine interface. At the earliest stage of formation, which we interrogate using dispersions of colloidal probes, the interface is populated with motile bacteria. Interactions with the bacteria dominate the colloidal motion, and the interface displays canonical features of active matter in a quasi-two-dimensional context. This active stage gives way to a viscoelastic transition, presumably driven by the accumulation at the interface of polysaccharides and surfactants produced by the bacteria, which instill the interface with the hallmarks of soft glassy rheology that we characterize with microrheology. Eventually, the viscoelastic film becomes fully elastic with the capability to support wrinkling upon compression, and we investigate this final stage with the pendant drop measurements. We characterize quantitatively the dynamic and mechanical properties of the films during each of these three stages - active, viscoelastic, and elastic - and comment on their possible significance for the interfacial bacterial colony. This work also brings to the forefront the important role that interfacial mechanics may play in bacterial suspensions with free surfaces.

Background: Severe impairment of the major respiratory muscles resulting from tetraplegia reduces respiratory function, causing many people with tetraplegia to require mechanical ventilation during the acute stage of injury. Abdominal Functional Electrical Stimulation (AFES) can improve respiratory function in non-ventilated patients with sub-acute and chronic tetraplegia. The aim of this study was to investigate the clinical feasibility of using an AFES training program to improve respiratory function and assist ventilator weaning in acute tetraplegia., Methods: AFES was applied for between 20 and 40 minutes per day, five times per week on four alternate weeks, with 10 acute ventilator dependent tetraplegic participants. Each participant was matched retrospectively with a ventilator dependent tetraplegic control, based on injury level, age and sex. Tidal Volume (VT) and Vital Capacity (VC) were measured weekly, with weaning progress compared to the controls., Results: Compliance to training sessions was 96.7%. Stimulated VT was significantly greater than unstimulated VT. VT and VC increased throughout the study, with mean VC increasing significantly (VT: 6.2 mL/kg to 7.8 mL/kg VC: 12.6 mL/kg to 18.7 mL/kg). Intervention participants weaned from mechanical ventilation on average 11 (sd: ± 23) days faster than their matched controls., Conclusion: The results of this study indicate that AFES is a clinically feasible technique for acute ventilator dependent tetraplegic patients and that this intervention may improve respiratory function and enable faster weaning from mechanical ventilation., Trial Registration: ClinicalTrials.gov NCT02200393.

Background: Disuse osteoporosis occurs in response to long-term immobilization. Spinal cord injury (SCI) leads to a form of disuse osteoporosis that only affects the paralyzed limbs. High rates of bone resorption after injury are evident from decreases in bone mineral content (BMC), which in the past have been attributed in the main to loss of trabecular bone in the epiphyses and cortical thinning in the shaft through endocortical resorption., Methods: Patients with motor-complete SCI recruited from the Queen Elizabeth National Spinal Injuries Unit (Glasgow, UK) were scanned within 5weeks of injury (baseline) using peripheral Quantitative Computed Tomography (pQCT). Unilateral scans of the tibia, femur and radius provided separate estimates of trabecular and cortical bone parameters in the epiphyses and diaphyses, respectively. Using repeat pQCT scans at 4, 8 and 12months post-injury, changes in BMC, bone mineral density (BMD) and cross-sectional area (CSA) of the bone were quantified., Results: Twenty-six subjects (5 female, 21 male) with SCI (12 paraplegic, 14 tetraplegic), ranging from 16 to 76years old, were enrolled onto the study. Repeated-measures analyses showed a significant effect of time since injury on key bone parameters at the epiphyses of the tibia and femur (BMC, total BMD, trabecular BMD) and their diaphyses (BMC, cortical BMD, cortical CSA). There was no significant effect of gender or age on key outcome measures, but there was a tendency for the female subjects to experience greater decreases in cortical BMD. The decreases in cortical BMD in the tibia and femur were found to be statistically significant in both men and women., Conclusions: By carrying out repeat pQCT scans at four-monthly intervals, this study provides a uniquely detailed description of the cortical bone changes that occur alongside trabecular bone changes in the first year of complete SCI. Significant decreases in BMD were recorded in both the cortical and trabecular bone compartments of the tibia and femur throughout the first year of injury. This study provides evidence for the need for targeted early intervention to preserve bone mass within this patient group., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background and Purpose: Impaired hand function decreases quality of life in persons with tetraplegia. We tested functional electrical stimulation (FES) controlled by a hybrid brain-computer interface (BCI) for improving hand function in participants with tetraplegia., Methods: Two participants with subacute tetraplegia (participant 1: C5 Brown-Sequard syndrome, participant 2: complete C5 lesion) took part in this proof-of-concept study. The goal was to determine whether the BCI system could drive the FES device by accurately classifying participants' intent (open or close the hand). Participants 1 and 2 received 10 sessions and 4 sessions of BCI-FES, respectively. A novel time-switch BCI strategy based on motor imagery was used to activate the FES. In one session, we tested a hybrid BCI-FES based on 2 spontaneously generated brain rhythms: a sensory-motor rhythm during motor imagery to activate a stimulator and occipital alpha rhythms to deactivate the stimulator. Participants received BCI-FES therapy 2 to 3 times a week in addition to conventional therapy. Imagery ability and muscle strength were measured before and after treatment., Results: Visual feedback was associated with a 4-fold increase of brain response during motor imagery in both participants. For participant 1, classification accuracy (open/closed) for motor imagery-based BCI was 83.5% (left hand) and 83.8% (right hand); participant 2 had a classification accuracy of 83.8% for the right hand. Participant 1 had moderate improvement in muscle strength, while there was no change for participant 2., Discussion and Conclusion: We demonstrated feasibility of BCI-FES, using 2 naturally generated brain rhythms. Studies on a larger number of participants are needed to separate the effects of BCI training from effects of conventional therapy.Video Abstract available. (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A84) for more insights from the authors.

Purpose: Abdominal functional electrical stimulation (AFES) is a technique intended to improve respiratory function in tetraplegia where breathing is affected due to abdominal muscle paralysis. Although it is known that optimal muscle contraction is achieved when electrical stimulation is applied close to the muscle motor point, AFES studies have used a variety of electrode positions. This study aims to investigate the feasibility of using Neuromuscular Electrical Stimulation to detect the motor points of the abdominal muscles, and to evaluate the intrasubject repeatability and intersubject uniformity of their positions, to find the most suitable AFES electrode location., Methods: Low frequency stimulation (0.5 Hz) was applied to the abdominal muscles of 10 able bodied and five tetraplegic participants. The electrode positions which achieved the strongest muscle contractions were recorded as the motor point positions, with measurements repeated once. For five able bodied participants, assessments were repeated after 18 months, in seated and supine positions., Results: Intersubject uniformity ranged from 2.8 to 8.8%. Motor point positions were identified with intrasubject repeatability of <1.7 cm, deemed adequate relative to standard AFES electrode size. Intrasubject repeatability shows motor point positions changed little (<1.7 cm) after 18 months but varied between seated and supine positions with repeatability of up to 3.1 cm., Conclusions: A simple technique to locate the motor points of the abdominal muscles is presented and shown to have an adequate intrasubject repeatability, enabling the optimum AFES electrode location to be identified for each user.

We present a coarse-grained model to describe the adsorption and deformation of proteins at an air-water interface. The interface is introduced empirically in the form of a localized field that couples to a hydropathy scale of amino acids. We consider three kinds of proteins: protein G, egg-white lysozyme, and hydrophobin. We characterize the nature of the deformation and the orientation of the proteins induced by their proximity to and association with the interface. We also study protein diffusion in the layer formed at the interface and show that the diffusion slows with increasing concentration in a manner similar to that for a colloidal suspension approaching the glass transition.

We report experiments studying the mechanical evolution of layers of the protein lysozyme adsorbing at the air-water interface using passive and active microrheology techniques to investigate the linear and nonlinear rheological response, respectively. Following formation of a new interface, the linear shear rheology, which we interrogate through the Brownian motion of spherical colloids at the interface, becomes viscoelastic with a complex modulus that has approximately power-law frequency dependence. The power-law exponent characterizing this frequency dependence decreases steadily with increasing layer age. Meanwhile, the nonlinear microrheology, probed via the rotational motion of magnetic nanowires at the interface, reveals a layer response characteristic of a shear-thinning power-law fluid with a flow index that decreases with age. We discuss two possible frameworks for understanding this mechanical evolution: gelation and the formation of a soft glass phase.

Unlabelled: Central neuropathic pain (CNP) is believed to be accompanied by increased activation of the sensorimotor cortex. Our knowledge of this interaction is based mainly on functional magnetic resonance imaging studies, but there is little direct evidence on how these changes manifest in terms of dynamic neuronal activity. This study reports on the presence of transient electroencephalography (EEG)-based measures of brain activity during motor imagery in spinal cord-injured patients with CNP. We analyzed dynamic EEG responses during imaginary movements of arms and legs in 3 groups of 10 volunteers each, comprising able-bodied people, paraplegic patients with CNP (lower abdomen and legs), and paraplegic patients without CNP. Paraplegic patients with CNP had increased event-related desynchronization in the theta, alpha, and beta bands (16-24 Hz) during imagination of movement of both nonpainful (arms) and painful limbs (legs). Compared to patients with CNP, paraplegics with no pain showed a much reduced power in relaxed state and reduced event-related desynchronization during imagination of movement. Understanding these complex dynamic, frequency-specific activations in CNP in the absence of nociceptive stimuli could inform the design of interventional therapies for patients with CNP and possibly further understanding of the mechanisms involved., Perspective: This study compares the EEG activity of spinal cord-injured patients with CNP to that of spinal cord-injured patients with no pain and also to that of able-bodied people. The study shows that the presence of CNP itself leads to frequency-specific EEG signatures that could be used to monitor CNP and inform neuromodulatory treatments of this type of pain., (Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Background: Performing gait analysis in a clinical setting can often be challenging due to time, cost and the availability of sophisticated three-dimensional (3D) gait analysis systems. This study has developed and tested a portable wireless gait assessment tool (wi-GAT) to address these challenges., Aim: To investigate the concurrent validity of the wi-GAT in measuring spatio-temporal gait parameters such as stride length, stride duration, cadence, double support time (DST), stance and swing time compared to a 3D Vicon motion analysis system., Methods: Ten healthy volunteers participated in the study (age range 23-30 years). Spatio-temporal gait parameters were recorded simultaneously by the Vicon and the wi-GAT systems as each subject walked at their self-selected speed., Results: The stride length and duration, cadence, stance duration and walking speed recorded using the wi-GAT showed strong agreement with those same parameters recorded by the Vicon (ICC of 0.94-0.996). A difference between the systems in registering "toe off" resulted in less agreement (ICC of 0.299-0.847) in gait parameters such as %stance and %swing and DST., Discussion and Conclusion: The study demonstrated good concurrent validity for the wi-GAT system. The wi-GAT has the potential to be a useful assessment tool for clinicians., (Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.)

The disuse-related bone loss that results from immobilisation following injury shares characteristics with osteoporosis in post-menopausal women and the aged, with decreases in bone mineral density leading to weakening of the bone and increased risk of fracture. The aim of this study was to use the finite element method to: (i) calculate the mechanical response of the tibia under mechanical load and (ii) estimate of the risk of fracture; comparing between two groups, an able-bodied group and spinal cord injury patients group suffering from varying degrees of bone loss. The tibiae of eight male subjects with chronic spinal cord injury and those of four able-bodied age-matched controls were scanned using multi-slice peripheral quantitative computed tomography. Images were used to develop full three-dimensional models of the tibiae in Mimics (Materialise) and exported into Abaqus (Simulia) for calculation of stress distribution and fracture risk in response to specified loading conditions - compression, bending and torsion. The percentage of elements that exceeded a calculated value of the ultimate stress provided an estimate of the risk of fracture for each subject, which differed between spinal cord injury subjects and their controls. The differences in bone mineral density distribution along the tibia in different subjects resulted in different regions of the bone being at high risk of fracture under set loading conditions, illustrating the benefit of creating individual material distribution models. A predictive tool can be developed based on these models, to enable clinicians to estimate the amount of loading that can be safely allowed onto the skeletal frame of individual patients who suffer from extensive musculoskeletal degeneration (including spinal cord injury, multiple sclerosis and the ageing population). The ultimate aim is to reduce fracture occurrence in these vulnerable groups.

Background: Strength changes in lower limb muscles following robot assisted gait training (RAGT) in subjects with incomplete spinal cord injury (ISCI) has not been quantified using objective outcome measures., Objective: To record changes in the force generating capacity of lower limb muscles (recorded as peak voluntary isometric torque at the knee and hip), before, during and after RAGT in both acute and subacute/chronic ISCI subjects using a repeated measures study design., Methods: Eighteen subjects with ISCI participated in this study (Age range: 26-63 years mean age = 49.3 ± 11 years). Each subject participated in the study for a total period of eight weeks, including 6 weeks of RAGT using the Lokomat system (Hocoma AG, Switzerland). Peak torques were recorded in hip flexors, extensors, knee flexors and extensors using torque sensors that are incorporated within the Lokomat., Results: All the tested lower limb muscle groups showed statistically significant (p < 0.001) increases in peak torques in the acute subjects. Comparison between the change in peak torque generated by a muscle and its motor score over time showed a non-linear relationship., Conclusions: The peak torque recorded during isometric contractions provided an objective outcome measure to record changes in muscle strength following RAGT.

Objective: To demonstrate the effect of a passive abdominal functional electrical stimulation (AFES) training program on unassisted respiratory measures in tetraplegia., Design: Longitudinal feasibility study., Setting: National spinal injuries unit in a university teaching hospital., Participants: Twelve patients with tetraplegic spinal cord injury, who could breathe independently, with reduced vital capacity and no visible abdominal movement., Intervention: Three weeks of abdominal muscle conditioning using transcutaneous AFES., Main Outcome Measures: Forced vital capacity (FVC), forced exhaled volume in 1 second (FEV1), peak expiratory flow rate (PEF), and maximum exhaled pressure (MEP)., Results: Mean (SD) FVC increased by 0.36 l (0.23) during training (P = 0.0027). Mean (SD) FEV1 and PEF tended to increase by 0.18 l (0.16) and 0.39 l/seconds (0.35), respectively, but this was not significant. No significant change was found in the outcome measures during a 1-week pre-training control phase and during a 3-week post-training phase., Conclusions: The increase in FVC over the training period and the absence of change before or after training suggest that passive abdominal FES training can be used for respiratory rehabilitation in tetraplegia.

Spinal cord injury (SCI) is a devastating condition with limited capacity for repair. Cell transplantation is a potential strategy to promote SCI repair with cells from the olfactory system being promising candidates. Although transplants of human olfactory mucosa (OM) are already ongoing in clinical trials, the repair potential of this tissue remains unclear. Previously, we identified mesenchymal-like stem cells that reside in the lamina propria (LP-MSCs) of rat and human OM. Little is known about these cells or their interactions with glia such as olfactory ensheathing cells (OECs), which would be co-transplanted with MSCs from the OM, or endogenous CNS glia such as oligodendrocytes. We have characterized, purified, and assessed the repair potential of human LP-MSCs by investigating their effect on glial cell biology with specific emphasis on CNS myelination in vitro. Purified LP-MSCs expressed typical bone marrow MSC (BM-MSC) markers, formed spheres, were clonogenic and differentiated into bone and fat. LP-MSC conditioned medium (CM) promoted oligodendrocyte precursor cell (OPC) and OEC proliferation and induced a highly branched morphology. LP-MSC-CM treatment caused OEC process extension. Both LP and BM-MSCs promoted OPC proliferation and differentiation, but only myelinating cultures treated with CM from LP and not BM-MSCs had a significant increase in myelination. Comparison with fibroblasts and contaminating OM fibroblast like-cells showed the promyelination effect was LP-MSC specific. Thus LP-MSCs harvested from human OM biopsies may be an important candidate for cell transplantation by contributing to the repair of SCI., (Copyright © 2012 Wiley Periodicals, Inc.)

Damage to the spinal cord compromises motor function and sensation below the level of injury, resulting in paralysis and progressive secondary health complications. Inactivity and reduced energy requirements result in reduced cardiopulmonary fitness and an increased risk of coronary heart disease and cardiovascular complications. These risks may be minimized through regular physical activity. It is proposed that such activity should begin at the earliest possible time point after injury, before extensive neuromuscular degeneration has occurred. Robotic-assisted tilt-table therapy may be used during early-stage spinal cord injury (SCI) to facilitate stepping training, before orthostatic stability has been achieved. This study investigates whether such a stimulus may be used to maintain pulmonary and coronary health by describing the acute responses of patients with early-stage (<1 yr) motor-complete SCI (cSCI) and motor-incomplete SCI (iSCI) to passive, active, and electrically stimulated robotic-assisted stepping. Active participation was found to elicit an increased response from iSCI patients. The addition of electrical stimulation did not consistently elicit further increases. Extensive muscle atrophy was found to have occurred in those patients with cSCI, thereby limiting the potential effectiveness of electrical stimulation. Active participation in robotic-assisted tilt-table therapy may be used to improve cardiopulmonary fitness in iSCI patients if implemented as part of a regular training program.

Purpose: People with spinal cord injury (SCI) experience bone loss and have an elevated rate of fracture in the paralysed limbs. The literature suggests an exponential time course of bone loss after SCI, but true rates may vary between patients. We propose systematic evaluation of bone status in the early stages of SCI to identify fast bone losers., Method: A case series of six patients with complete SCI were scanned using peripheral quantitative computed tomography within 5 weeks and at 4, 8 and 12 months post-injury. Bone mineral density (BMD) and bone mineral content (BMC) were measured at fracture-prone sites in the tibia and femur. Patient-specific-predictions (PSP) of expected rates of bone loss were produced by individualising published model equations according to each patient's measured values at baseline. Wilcoxon Signed-Rank tests were used to identify changes between time-points; chi-squared tests for differences between measured and PSP values., Results: In the lower limbs, mean values decreased significantly between baseline and 8 months post-injury, by 19-31% for trabecular BMD, 21-32% for total BMD, and 9-29% for BMC. Most subjects showed no significant differences between PSP and measured values, but individuals with significantly faster rates of bone loss than predicted should be investigated further., Conclusions: There was considerable intersubject variability in rates of bone loss after SCI. Patients showing the fastest bone loss could benefit from continued follow-up and possibly treatment.

Rehabilitation of walking is an essential element in the treatment of incomplete spinal cord injured (SCI) patients. During the early post injury period, patients find it challenging to practice upright walking. Simulating stepping movements in a supine posture may be easier and promote earlier rehabilitation. A robotic orthotic device for early intervention in spinal cord injury that does not require the patient to be in an upright posture has been modelled. The model comprises a two-bar mechanical system that is configured and powered to provide limb kinematics that approximate normal overground walking. The modelling work has been based on gait analysis performed on healthy subjects walking at 50 per cent, 75 per cent, and 100 per cent of normal cadence. Simulated angles of hip, knee, and ankle joints show a comparable range of motion (ROM) to the experimental walking data measured in healthy subjects. The model provides operating parameters for a prospective recumbent gait orthosis that could be used in early walking rehabilitation of incomplete SCI patients.

Background: The ability to objectively analyze gait in a clinical environment is challenging due to time, space and cost constraints. This study investigated the validity of a portable gait assessment tool in objectively assessing the temporal gait parameters in subjects with spinal cord injury. The portable gait assessment tool consisted of a pair of insoles instrumented with force sensing resistors that were strategically positioned over the sole of each foot., Aim: To demonstrate the validity of the gait assessment tool by assessing the change in walking ability in incomplete spinal cord injured (ISCI) subjects, who participated in a robot-assisted gait training program., Methods: Eighteen subjects with either an acute or chronic ISCI participated in this study (age range 26-63 years). Each subject participated in a robot assisted gait training programme for 6 weeks. Assessments were performed using the gait assessment tool before during and after the intervention., Results: The gait assessment tool showed greater sensitivity to the change in the subject's gait, when compared to clinical assessments such as the walking index in spinal cord injury (WISCI II). Subjects with an acute ISCI showed a statistically significant (p<0.05) change in temporal gait parameters within the first 3 weeks of training., Discussion and Conclusion: This study for the first time has used the gait assessment tool in an ISCI population and has demonstrated that gait parameters can be measured and changes can be quantified within a clinical environment. The statistically significant changes during the first 3 weeks of training may indicate that an effective dose of robotic training can be administered within a relatively short period in ISCI subjects during the acute phase., (Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.)

The ability to detect physiological changes associated with treatments to effect axonal regeneration, or novel rehabilitation strategies, for spinal cord injury will be challenging using the widely employed American Spinal Injuries Association (ASIA) impairment scales (AIS) for sensory and motor function. Despite many revisions to the AIS standard neurological assessment, there remains a perceived need for more sensitive, quantitative and objective outcome measures. The purpose of Stage 1 of the Clinical Initiative was to develop these tools and then, in Stage 2 to test them for reliability against natural recovery and treatments expected to produce functional improvements in those with complete or incomplete spinal cord injury (SCI). Here we review aspects of the progress made by four teams involved in Stage 2. The strategies employed by the individual teams were (1) application of repetitive transcranial magnetic stimulation (rTMS) to the motor cortex in stable (chronic) SCI with intent to induce functional improvement of upper limb function, (2) a tele-rehabilitation approach using functional electrical stimulation to provide hand opening and grip allowing incomplete SCI subjects to deploy an instrumented manipulandum for hand and arm exercises and to play computer games, (3) weight-assisted treadmill walking therapy (WAT) comparing outcomes in acute and chronic groups of incomplete SCI patients receiving robotic assisted treadmill therapy, and (4) longitudinal monitoring of the natural progress of recovery in incomplete SCI subjects using motor tests for the lower extremity to investigate strength and coordination., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Study Design: Retrospective cohort study., Objective: To describe functional outcome and discharge destination of elderly patients with traumatic spinal cord injuries., Setting: National Spinal Injuries Unit, Glasgow, UK., Methods: We collected data for 5 years on all patients >65 years old with a traumatic spinal cord injury treated at the National Spinal Injuries Unit., Results: We identified 39 patients. Of these, nine patients died during admission; all had cervical spine injuries. The mean age of the 30 survivors was 73 years (range 65-88). The most common cause of injury was a fall: 26 patients (87%). In addition, 21 (70%) sustained injury to cervical cord, 3 (10%) had thoracic and 6 (20%) had lumbar spine fractures. In all, 23 patients (77%) were treated by orthosis and 7 (23%) underwent surgical intervention. Twelve (40%) patients showed an improvement in American Spinal Injury Association impairment scale. The median hospital stay was 136 days. Thus, 11 patients (37%), all with incomplete injuries, were discharged home, 10 (33%) were transferred to nursing homes/community hospitals and 9 patients (30%) were discharged back to the referring hospital, while they were awaiting adjustments at home. Patients who were discharged home had significantly higher Functional Independence Measure scores, both at the onset of rehabilitation and at discharge, than those who were discharged to a nursing home or other hospitals (P<0.01 and <0.001, respectively)., Discussion and Conclusion: Although the elderly patients may benefit from the services of a dedicated spinal injuries centre, they should be carefully selected. The patient, relatives as well as the referring doctors should be alerted to the likely long-term outcomes early in the course of the injury. Elderly patients with complete lesions of the spinal cord will almost certainly remain institutionalized. Early endeavour should be made to find alternate rehabilitation settings with a lower-intensity treatment.

Objective: To establish occurrence, method of injury, length of stay (LOS), psychiatric diagnosis, rehabilitation outcome, and demographic data for those admitted to a Scottish Spinal Injuries Rehabilitation Unit as a consequence of deliberate self-harm (DSH)., Design: A retrospective audit of case-notes and electronic databases of admissions and rehabilitation outcome in a spinal cord injury (SCI) unit where the mechanism of injury was (DSH)., Results: Forty-six (44 having detailed data available) patients were identified with 95% of injuries resulting from falls. Thirty-six people had pre-existing mental health problems (82%) with 15 (34%) having this diagnosis established shortly after admission. Seventy-five per cent received follow-up from mental health services. Ninety-five per cent returned to their pre-injury (or similar) residence. LOS and functional independence measure (FIM) for the DSH group were compared with a non-DSH group. No differences were found in those with SCI. LOS was significantly longer in the patients with vertebral fracture and no neurological impairment (32 versus 22 days). Sixty-four per cent of those who had self-harmed had substance dependence problems. The predominance of falls (63%) occurred in a residential setting. Annual admissions due to individuals self-harming were stable across the studied period., Conclusions: Spinal column fracture in the DSH group is predominantly caused by falls. High levels of mental health and substance abuse problems are noted necessitating formal mental health assessment and follow-up. DSH as a mechanism for injury appears to have a significant impact on LOS only if the patient has fracture without SCI. Immediate rehabilitation outcomes are similar to that of non-DSH group.

Background: We are investigating the potential of robotics-assisted treadmill technology as a mode of exercise in people with spinal cord injury (SCI). People with incomplete SCI can actively contribute to this form of exercise, but in the clinical setting they often walk passively in the system. It is not known whether in doing so they are meeting the recommended guidelines for increasing cardiopulmonary fitness., Objective: The aims of this study were twofold: to characterise the intensity of passive walking during robotics-assisted treadmill exercise (RATE) in incomplete SCI; and to determine if this intensity meets the recommended guidelines for cardiopulmonary training in this population., Methods: 10 subjects with incomplete SCI twice performed an exercise test on a robotics-assisted treadmill. The test comprised a period of passive walking and a ramp phase to the limit of tolerance. Oxygen uptake VO(2) heart rate (HR) were continuously measured., Results: VO(2) during passive exercise was on average 1.4 times higher than resting VO(2R), but this was only 29% of peak VO(2) (VO(2 peak))(range 16-43%). Relative to rest, passive VO(2) (VO(2P) was only 12% of VO(2 peak). HR did not increase from rest to passive walking (81 ± 10 bpm to 81 ± 13 bpm respectively). The HR associated with passive walking was on average 50% of peak HR (HR(peak)) (161 ± 13 bpm). Test-retest reliability was moderate for VO(2R) (R=0.62) and resting HR (HR(R)) (R=0.68), high for VO(2P) (R=0.81), passive HR (HR(P)) (R=0.87) and HR(peak) (R=0.88), and very high (R=0.95) for VO(2 peak). Only HR(p) differed significantly between tests (p=0.029)., Conclusions: The intensity of passive walking during RATE is low and is insufficient to increase cardiopulmonary fitness in people with SCI. Subjects must actively contribute to the exercise in order to achieve the recommended training intensity.

Objective: Disuse osteoporosis is a major long-term health consequence of spinal cord injury (SCI) that still needs to be addressed. Its management in SCI should begin with accurate diagnosis, followed by targeted treatments in the most vulnerable subgroups. We present data quantifying disuse osteoporosis in a cross-section of the Scottish paraplegic population to identify subgroups with lowest bone mineral density (BMD)., Materials and Methods: Forty-seven people with chronic SCI at levels T2-L2 were scanned using peripheral quantitative computed tomography at four tibial sites and two femoral sites, at the Queen Elizabeth National Spinal Injuries Unit, Glasgow (UK). At the distal epiphyses, trabecular BMD (BMDtrab), total BMD, total bone cross-sectional area (CSA) and bone mineral content (BMC) were determined. In the diaphyses, cortical BMD, total bone CSA, cortical CSA and BMC were calculated. Bone, muscle and fat CSAs were estimated in the lower leg and thigh., Results: BMDtrab decreased exponentially with time since injury at different rates in the tibia and femur. At most sites, female paraplegics had significantly lower BMC, total bone CSA and muscle CSA than male paraplegics. Subjects with lumbar SCI tended to have lower bone values and smaller muscle CSAs than in thoracic SCI., Conclusion: At the distal epiphyses of the tibia and femur, there is generally a rapid and extensive reduction in BMDtrab after SCI. Female subjects, and those with lumbar SCI, tend to have lower bone values than males or those with thoracic SCI, respectively.

We describe the use of peripheral Quantitative Computed Tomography (pQCT) to identify musculoskeletal responses to partial body-weight supported treadmill training (BWSTT) in incomplete spinal cord injury (SCI). Long-term health consequences of SCI include extensive muscle atrophy, severe bone loss and an increased fracture risk in the affected limbs, mostly at both tibial epiphyses and the distal femoral epiphysis. Regular treadmill training may slow or reverse bone loss by recruiting available lower-limb musculature and loading the leg bones dynamically. The potential for detailed analysis of musculoskeletal changes using pQCT is illustrated with a single case study (14.5 years post-SCI), who completed seven months of partial BWSTT. Pre- and post-training lower-limb pQCT scans were taken to quantify changes in trabecular bone, cortical bone, and soft-tissue. Trabecular bone mineral density increased by 5% (right) and 20% (left) in the distal tibia. Changes in proximal tibia and distal femur were negligible. Increases in muscle cross-sectional area were 6% (right) and 12% (left) in the lower leg, 7% (right) and 5% (left) in the thigh. We suggest that treadmill training may lead to positive musculoskeletal adaptations at clinically-relevant sites. Such changes can be measured in detail using pQCT.

Body weight supported (BWS) treadmill exercise could potentially improve the cardiopulmonary fitness of those with an incomplete spinal cord injury (SCI). Despite this, methods for estimating key cardiopulmonary performance parameters have not been investigated. We investigated whether new exercise test protocols for BWS treadmill exercise in incomplete SCI enable accurate determination of key cardiopulmonary performance parameters and examined how these parameters change with training. Two subjects with incomplete SCI carried out 20 weeks of BWS treadmill training (BWSTT). They performed an incremental exercise test (IET) and constant load step exercise test (SET) at baseline and 4-week intervals. After training, peak work rate had increased from 1.41 to 9.37 W in subject A and from 6.22 to 43.99 W in subject B. Peak oxygen uptake changed in subject A from 8.23 to 10.19 ml.kg-1.min-1 and from 13.84 to 13.91 ml.kg-1.min-1 in subject B. Dynamic O2 cost decreased from 115 to 29.03 ml.min-1.W-1 (subject A) and from 66.57 to 4.52 ml.min-1. W-1 (subject B). Gas exchange thresholds could not be identified from the IETs. VO2 kinetics could be identified during only 2 of subject B's SETs. Accurate estimation of key cardiopulmonary performance parameters was limited. The new protocols have the potential to characterise cardiopulmonary status and monitor adaptations to training interventions, but require testing with a larger subject cohort.

Incremental exercise testing with a linear increase in work rate is the recommended method for clinical exercise testing. A recent protocol (A), incorporating a linear increase in speed and a nonlinear increase in gradient, has been developed which addresses some limitations of traditional testing methods. It does not account for those with an impaired gait pattern. We propose and assess a novel protocol (B) incorporating nonlinear increases in both speed and gradient. We theoretically develop a new treadmill control protocol (B), determine oxygen uptake response linearity, initial metabolic rate and cardiopulmonary response parameters (peak oxygen uptake, lactate threshold, dynamic O2 cost) and compare the outcome measures with two previously verified IET protocols (A and C (constant speed with linear increase in gradient)). Feasibility and outcomes were explored with a subject with incomplete spinal cord injury. The average initial metabolic rate (VO2) was substantially lower during protocol A (0.49 (+/-0.12) l min(-1)) and protocol B (0.52 (+/-0.05) l min(-1)) than during protocol C (1.35 (+/-0.04) l min(-1)). The average linearity of the VO2 response during protocols A and B (correlation co-efficients 0.97 (+/-0.00) and 0.95 (+/-0.02), and co-efficients of determination 0.94 (+/-0.01) and 0.91 (+/-0.02), respectively) were higher than during protocol C (correlation co-efficient 0.91 (+/-0.02) and co-efficient of determination 0.84 (+/-0.02)). The average dynamic O2 cost for protocol C (6.53 (+/-0.46) ml min(-1)W(-1)) was lower than that of protocol A (10.02 (+/-1.16) ml min(-1) W(-1)) and protocol B (10.03 (+/-0.91) ml min(-1) W(-1)). No differences were found in these parameters between protocols A and B. The new protocol B performs better than protocol C and is comparable with protocol A. When testing subjects with an impaired gait pattern, it may be advantageous to use the new protocol B due to the gradual increases in both speed and gradient throughout the test.