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Bacteriophages represent a promising alternative for controlling pathogenic bacteria. They are ubiquitous in the environment, and their isolation is usually simple and fast. However, not every phage is suitable for biocontrol applications. It must be virulent (i.e., strictly lytic), non-transducing, and safe. We have developed a method for identifying selected types of virulent phages at an early stage of the isolation process to simplify the search for suitable candidates. Using the major capsid protein (MCP) as a phylogenetic marker, we designed degenerate primers for the identification of Felix O1-, GJ1-, N4-, SP6-, T4-, T7-, and Vi1-like phages in multiplex PCR setups with single phage plaques as templates. Performance of the MCP PCR assay was evaluated with a set of 26 well-characterized phages. Neither false-positive nor false-negative results were obtained. In addition, 154 phages from enrichment cultures from various environmental samples were subjected to MCP PCR analysis. Eight of them, specific for Salmonella enterica, Escherichia coli, or Erwinia amylovora, belonged to one of the selected phage types. Their PCR-based identification was successfully confirmed by pulsed-field gel electrophoresis of the phage genomes, electron microscopy, and sequencing of the amplified mcp gene fragment. The MCP PCR assay was shown to be a simple method for preliminary assignment of new phages to a certain group and thus to identify candidates for biocontrol immediately after their isolation. Given that sufficient sequence data are available, this method can be extended to any phage group of interest.

Locomotion relies on the fine-tuned coordination of different muscles which are controlled by particular neural circuits. Depending on the attendant conditions, walking patterns must be modified to optimally meet the demands of the task. Assessing neuromuscular control during dynamic conditions is methodologically highly challenging and prone to artifacts. Here we aim at assessing corticospinal involvement during different locomotor tasks using non-invasive surface electromyography. Activity in tibialis anterior (TA) and gastrocnemius medialis (GM) muscles was monitored by electromyograms (EMGs) in 27 healthy volunteers (11 female) during regular walking, walking while engaged in simultaneous cognitive dual tasks, walking with partial visual restriction, and skilled, targeted locomotion. Whereas EMG intensity of the TA and GM was considerably altered while walking with partial visual restriction and during targeted locomotion, dual-task walking induced only minor changes in total EMG intensity compared to regular walking. Targeted walking resulted in enhanced EMG intensity of GM in the frequency range associated with Piper rhythm synchronies. Likewise, targeted walking induced enhanced EMG intensity of TA at the Piper rhythm frequency around heelstrike, but not during the swing phase. Our findings indicate task- and phase-dependent modulations of neuromuscular control in distal leg muscles during various locomotor conditions in healthy subjects. Enhanced EMG intensity in the Piper rhythm frequency during targeted walking points toward enforced corticospinal drive during challenging locomotor tasks. These findings indicate that comprehensive time-frequency EMG analysis is able to gauge cortical involvement during different movement programs in a non-invasive manner and might be used as complementary diagnostic tool to assess baseline integrity of the corticospinal tract and to monitor changes in corticospinal drive as induced by neurorehabilitation interventions or during disease progression.

Objective: Abdominal aortic aneurysm (AAA) is a vascular disease relatively common in the elderly population. Although some events that contribute to the development and progression of AAA are known, there are limited data examining the association of Toll-like receptor 3 (TLR3) and RIG-I-like receptor expression with the pathogenesis of AAAs. In this study, we investigated the gene and protein expression of TLR3 and RIG-I-like receptors (RIG-I and MDA5) in aortic wall and blood of AAA patients and examined the relationship between their expression and immune response., Methods: Total RNA was extracted from aortic wall tissues and blood samples collected from 20 patients with AAA and blood samples of 17 healthy volunteers without aortic aneurysm. To evaluate the DDX58 (RIG-I), IFIH1 (MDA5), and TLR3 gene expression level, quantitative real-time polymerase chain reaction was used. Extracellular cytokine and pattern recognition receptor levels were quantified by enzyme-linked immunosorbent assays., Results: TLR3, RIG-I, and MDA5 were constitutively expressed in both aortic tissues and blood samples from AAA patients and healthy volunteers. In patients with AAA, higher TLR3 expression in aortic tissues than in blood was found (P = .004). The DDX58 messenger RNA expression was higher in blood of patients with AAA compared with healthy subjects (P = .021). A significantly higher level of plasma interleukin 4 was noticed in patients with AAA than in healthy individuals (P = .008)., Conclusions: This study suggests that RIG-I and TLR3 seem to be important factors in the pathogenesis of AAA., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Body weight support (BWS) is often provided to incomplete spinal cord injury (iSCI) patients during rehabilitation to enable gait training before full weight-bearing is recovered. Emerging robotic devices enable BWS during overground walking, increasing task-specificity of the locomotor training. However, in contrast to a treadmill setting, there is little information on how unloading is integrated into overground locomotion. We investigated the effect of a transparent multi-directional BWS system on overground walking patterns at different levels of unloading in individuals with chronic iSCI (CiSCI) compared to controls., Methods: Kinematics of 12 CiSCI were analyzed at six different BWS levels from 0 to 50% body weight unloading during overground walking at 2kmh - 1 and compared to speed-matched controls., Results: In controls, temporal parameters, single joint trajectories, and intralimb coordination responded proportionally to the level of unloading, while spatial parameters remained unaffected. In CiSCI, unloading induced similar changes in temporal parameters. CiSCI, however, did not adapt their intralimb coordination or single joint trajectories to the level of unloading., Conclusions: The findings revealed that continuous, dynamic unloading during overground walking results in subtle and proportional gait adjustments corresponding to changes in body load. CiSCI demonstrated diminished responses in specific domains of gait, indicating that their altered neural processing impeded the adjustment to environmental constraints. CiSCI retain their movement patterns under overground unloading, indicating that this is a viable locomotor therapy tool that may also offer a potential window on the diminished neural control of intralimb coordination.

Treadmill experiments suggest that left-dominant arm swing is common in healthy walking adults and is modulated by cognitive dual-tasking. Little is known about arm swing asymmetry in overground walking. We report directional (dASI) and non-directional arm swing symmetry indices (ndASI) from 334 adults (mean age 68.6 ± 5.9 y) walking overground at comfortable (NW) and fast (FW) speeds and while completing a serial subtraction task (DT). dASI and ndASI were calculated from sagittal shoulder range of motion data generated by inertial measurement units affixed to the wrist. Most (91%) participants were right-handed. Group mean arm swing amplitude was significantly larger on the left in all walking conditions. During NW, ndASI was 39.5 ± 21.8, with a dASI of 21.9 ± 39.5. Distribution of dASI was bimodal with an approximately 2:1 ratio of left:right-dominant arm swing. There were no differences in ndASI between conditions but dASI was smaller during DT compared to FW (15.2 vs 24.6; p = 0.009). Handedness was unrelated to ndASI, dASI or the change in ASI metrics under DT. Left-dominant arm swing is the norm in healthy human walking irrespective of walking condition or handedness. As disease markers, ndASI and dASI may have different and complementary roles.

Study Design: This is a focused review article., Objectives: To identify important concepts in lower extremity (LE) assessment with a focus on locomotor outcomes and provide guidance on how existing outcome measurement tools may be best used to assess experimental therapies in spinal cord injury (SCI). The emphasis lies on LE outcomes in individuals with complete and incomplete SCI in Phase II-III trials., Methods: This review includes a summary of topics discussed during a workshop focusing on LE function in SCI, conceptual discussion of corresponding outcome measures and additional focused literature review., Results: There are a number of sensitive, accurate, and responsive outcome tools measuring both quantitative and qualitative aspects of LE function. However, in trials with individuals with very acute injuries, a baseline assessment of the primary (or secondary) LE outcome measure is often not feasible., Conclusion: There is no single outcome measure to assess all individuals with SCI that can be used to monitor changes in LE function regardless of severity and level of injury. Surrogate markers have to be used to assess LE function in individuals with severe SCI. However, it is generally agreed that a direct measurement of the performance for an appropriate functional activity supersedes any surrogate marker. LE assessments have to be refined so they can be used across all time points after SCI, regardless of the level or severity of spinal injury., Sponsors: Craig H. Neilsen Foundation, Spinal Cord Outcomes Partnership Endeavor.

Objectives: The objective was primarily to identify risk factors for bloodstream infections (BSI) caused by different pathogens., Methods: A retrospective single-center cohort study was performed on 472 burn patients with an abbreviated burn severity index (ABSI)≥3, a total burn surface area (TBSA)≥10%, and an ICU stay of at least 24h. Risk factors for different BSI pathogens were analyzed by competing risks regression model of Fine and Gray., Results: A total of 114 burn patients developed 171 episodes of BSIs caused by gram-negative bacteria (n=78;46%), gram-positive bacteria (n=69;40%), and fungi (n=24;14%) median after 14days (range, 1-164), 16days (range, 1-170), and 16days (range, 0-89), respectively. A total of 24/114 patients (21%) had fatal outcomes. Isolation of the most common bloodstream isolates Enterococcus sp. (n=26), followed by Candida sp. and Pseudomonas sp. (n=22 for both) was significantly associated with increased TBSA (p≤0.006) and ABSI (p<0.0001) and need for fasciotomy (p<0.01). The death risk of patients with MDR gram-negative bacteremia was significantly increased by a hazard ratio of 12.6 (95% CI:4.8-32.8; p<0.0001)., Conclusions: A greater TBSA and ABSI were associated with a significantly higher incidence of BSIs caused by Pseudomonas sp., Enterococcus sp. and Candida sp., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Gait dysfunction is a common and relevant symptom in multiple sclerosis (MS). This study aimed to profile gait pathology in gait-impaired patients with MS using comprehensive 3D gait analysis and clinical walking tests. Thirty-seven patients with MS walked on the treadmill at their individual, sustainable speed while 20 healthy control subjects walked at all the different patient's paces, allowing for comparisons independent of walking velocity. Kinematic analysis revealed pronounced restrictions in knee and ankle joint excursion, increased gait variability and asymmetry along with impaired dynamic stability in patients. The most discriminative single gait parameter, differentiating patients from controls with an accuracy of 83.3% (χ 2 test; p = 0.0001), was reduced knee range of motion. Based on hierarchical cluster and principal component analysis, three principal pathological gait patterns were identified: a spastic-paretic, an ataxia-like, and an unstable gait. Follow-up assessments after 1 year indicated deterioration of walking function, particularly in patients with spastic-paretic gait patterns. Our findings suggest that impaired knee/ankle control is common in patients with MS. Personalised gait profiles and clustering algorithms may be promising tools for stratifying patients and to inform patient-tailored exercise programs. Responsive, objective outcome measures are important for monitoring disease progression and treatment effects in MS trials.

Opinion Statement: Bone health and breast cancer are two connected subjects, because breast cancer patients have a higher prevalence of osteopenia/osteoporosis and reduced bone health parameters than healthy woman of the same age. Therefore, the positive effect of adjuvant bisphosphonate therapy plays an important role in breast cancer treatment. Several randomized trials have studied bisphosphonates in the adjuvant setting in postmenopausal woman and demonstrated their potential to prevent treatment-induced bone loss. The prevention of fractures and the subsequent preservation of patients' quality of life are important arguments for the use of adjuvant bisphosphonates in postmenopausal breast cancer patients. In addition, trials of adjuvant bone-targeted agents showed a reduction of recurrences in and outside bone and an improved outcome in patients treated with bisphosphonates.

Reconstructing the colonization and demographic dynamics that gave rise to extant forests is essential to forecasts of forest responses to environmental changes. Classical approaches to map how population of trees changed through space and time largely rely on pollen distribution patterns, with only a limited number of studies exploiting DNA molecules preserved in wooden tree archaeological and subfossil remains. Here, we advance such analyses by applying high-throughput (HTS) DNA sequencing to wood archaeological and subfossil material for the first time, using a comprehensive sample of 167 European white oak waterlogged remains spanning a large temporal (from 550 to 9,800 years) and geographical range across Europe. The successful characterization of the endogenous DNA and exogenous microbial DNA of 140 (~83%) samples helped the identification of environmental conditions favouring long-term DNA preservation in wood remains, and started to unveil the first trends in the DNA decay process in wood material. Additionally, the maternally inherited chloroplast haplotypes of 21 samples from three periods of forest human-induced use (Neolithic, Bronze Age and Middle Ages) were found to be consistent with those of modern populations growing in the same geographic areas. Our work paves the way for further studies aiming at using ancient DNA preserved in wood to reconstruct the micro-evolutionary response of trees to climate change and human forest management., (© 2018 John Wiley & Sons Ltd.)

This study was undertaken to verify whether simvastatin modulates Cav-1/eNOS expression, and if this modulation is associated with changes in pro- and anti-inflammatory cytokine and Toll-like receptor 4 (TLR4) level in abdominal aortic aneurysm (AAA). It is a 1:2 case-control study of non-statin (n=12) and simvastatin-treated patients (n=24) who underwent open AAA repair. Simvastatin treatment decreased Cav-1 (p<0.05) and increased eNOS expression (p<0.01) in the AAA wall. These changes might be dose dependent. The changes in Cav-1 and eNOS were associated with a trend towards decreased IL-6 and IL-17 concentration (p>0.05) and increased IL-10 concentration (p=0.055); however, TLR4 expression was unaffected, suggesting that simvastatin influences Cav-1 and eNOS in the AAA wall by other mechanisms. Simvastatin may modulate Cav-1 and eNOS expression in the aneurysmal wall, indicating a potentially beneficial role for statins in AAA patients.

Background: The standardized Clavien-Dindo classification of surgical complications is applied as a simple and widely used tool to assess and report postoperative complications in general surgery. However, most documentation uses this classification to report surgery-related morbidity and mortality in a single field of surgery or even particular intervention. The aim of the present study was to present experiences with the Clavien-Dindo classification when applied to all patients on the general surgery ward of a tertiary referral care center., Methods: We analyzed a period of 6 months of care on a ward with a broad range of general and visceral surgery. Discharge reports and patient charts were analyzed retrospectively and reported complications rated according to the most recent Clavien-Dindo classification version. The complexity of operations was assessed with the Austrian Chamber of Physicians accounting system., Results: The study included 517 patients with 817 admissions, of whom 463 had been operated upon. Complications emerged in 12.5%, of which 19% were rated as Clavien I, 20.7% as Clavien II, 13.8% as Clavien IIIa, 27.6% as Clavien IIIb, 8.6% as Clavien IVa, and 10.3% as Clavien V. No Clavien grade IVb complication occurred within the investigation. Patients having undergone more complex surgery or with higher scores experienced significantly longer lengths of hospital stay., Conclusion: The Clavien-Dindo classification can easily be used to document complication rates in general surgery, even though this collective was not included in the original validation studies of Clavien et al. and consisted of more heavily impaired patients., Competing Interests: M. Bolliger, J.-A. Kroehnert, F. Molineus, D. Kandioler, M. Schindl, and P. Riss declare that they have no competing interests.Since this is a retrospective analysis, this article does not contain any studies with human participants or animals performed by any of the authors. The Ethics Committee of the Medical University of Vienna approved this study (vote 1877/2012).

Key factors positively influencing rehabilitation and functional recovery after spinal cord injury (SCI) include training variety, intensive movement repetition, and motivating training tasks. Systems supporting these aspects may provide profound gains in rehabilitation, independent of the subject's treatment location. In the present study, we test the hypotheses that virtual reality (VR)-augmented training at home (i.e., unsupervised) is feasible with subjects with an incomplete SCI (iSCI) and that it improves motor functions such as lower limb muscle strength, balance, and functional mobility. In the study, 12 chronic iSCI subjects used a home-based, mobile version of a lower limb VR training system. The system included motivating training scenarios and combined action observation and execution. Virtual representations of the legs and feet were controlled via movement sensors. The subjects performed home-based training over 4 weeks, with 16-20 sessions of 30-45 min each. The outcome measures assessed were the Lower Extremity Motor Score (LEMS), Berg Balance Scale (BBS), Timed Up and Go (TUG), Spinal Cord Independence Measure mobility, Walking Index for Spinal Cord Injury II, and 10 m and 6 min walking tests. Two pre-treatment assessment time points were chosen for outcome stability: 4 weeks before treatment and immediately before treatment. At post-assessment (i.e., immediately after treatment), high motivation and positive changes were reported by the subjects (adapted Patients' Global Impression of Change). Significant improvements were shown in lower limb muscle strength (LEMS, P  = 0.008), balance (BBS, P  = 0.008), and functional mobility (TUG, P  = 0.007). At follow-up assessment (i.e., 2-3 months after treatment), functional mobility (TUG) remained significantly improved ( P  = 0.005) in contrast to the other outcome measures. In summary, unsupervised exercises at home with the VR training system led to beneficial functional training effects in subjects with chronic iSCI, suggesting that it may be useful as a neurorehabilitation tool., Trial Registration: Canton of Zurich ethics committee (EK-24/2009, PB&#95;2016-00545), ClinicalTrials.gov: NCT02149186. Registered 24 April 2014.

Background: The benefit of 5 years of adjuvant endocrine therapy for women with hormone receptor-positive (HR + ) breast cancer (BC) is beyond discussion. Nevertheless, the risk of recurrence of luminal BC persists for 15 years or more after diagnosis. Consequently, approaches of extended adjuvant therapy have been investigated in large clinical trials, with the ultimate aim of further reducing the risk of recurrence in patients with HR + BC., Methods: A review of recently published trial data is presented to provide a solid basis for discussion. A discussion of the side effects of long-term endocrine treatment, multigenetic tests aiming to identify patients at particular risk, and an outlook for further promising targets are additional aims of this review., Conclusion: Extended adjuvant therapy seems beneficial in reducing distant relapse and contralateral BC for a selected group of patients with HR + BC, particularly if aromatase inhibitors (AIs) are used after initial tamoxifen therapy. However, patients with lower risk of recurrence and initial AI therapy may suffer more from side effects than benefit from extended therapy., Competing Interests: Conflict of interest statement: K.W., M.B., Y.D. and B.K. are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this review. R.E. has received travel and accommodation expenses reimbursement from Roche. S.S. has received personal fees from AstraZeneca, and travel or accommodation expenses reimbursement from Roche. F.F. has received travel or accommodation expenses reimbursement from Roche. M.G. has received institutional grants from Sanofi-Aventis, Novartis, Roche, GlaxoSmithKline, Pfizer, and Smith Medical, and personal fees from Novartis, Roche, GlaxoSmithKline, AstraZeneca, Nanostring Technologies, and Accelsiors, all outside this work.

The aim of this study was to evaluate the effect of a continuous locomotor training on leg muscle electromyographic (EMG) exhaustion during assisted stepping movements in a patient with motor complete spinal cord injury (SCI). EMG exhaustion and loss of potentials starts to develop in untrained patients at ∼6 months after injury. In the trained patient examined in this study, exhaustion was also observed but occurred with a delay of several months. In contrast to an untrained patient, no more EMG exhaustion was observed in the very chronic stage. At this time (12 years after injury) a basic locomotor pattern of leg muscle activity of reduced amplitude could still be elicited, but it was resistant to exhaustion and unchanged in amplitude after 12 min of assisted stepping. It is suggested that fatigue-resistant motor units prevail at this stage and can still be activated during stepping as a result of the training.

Patients with impaired walking function are often dependent on assistive devices to retrain gait and regain independence in life. To provide adequate support, gait rehabilitation devices have to be manually set to the correct support mode or have to recognize the type and starting point of a certain motion automatically. For automated motion type detection, machine learning-based classification algorithms using sensor signals from different body parts can achieve robust performance. However, until today, there is only little work available to detect motion onset. In this paper, we investigate task onset detection of sit-to-stand and stand-to-sit transitions. The focus of the current study is twofold: First, the optimal window size for the online classification algorithm shall be found. Second, the ideal sensor placement in a single sensor-setup, to detect movement onset with shortest detection delays possible is of interest. For our investigations a linear discriminant analysis classifier, basic kinematic features, and a leave-one-subject-out cross validation are used. As a result, an average detection time of 56 milliseconds (SD 111) for sit-to-stand and 48 milliseconds (SD 137) for stand-to-sit were achieved with a window size of 15 and 35 milliseconds respectively at a data rate of 200 hertz. For sit-to-stand transitions, a sensor close to the tenth vertebra and for stand-to-sit transitions close to the posterior pelvis provided the smallest detection times.

In healthy subjects, changes in arm swing symmetry while walking are observed when a cognitive dual task is added, with a tendency toward left-dominant arm swing as cognitive load increases. We applied a modified Stroop word/color naming paradigm to investigate this effect in spinal cord injured (SCI) patients. Six patients with cervical SCI (cSCI), 6 with thoracic injuries (tSCI; all 12 patients American Spinal Injury Association [ASIA] Injury Score [AIS]D), and 12 healthy, matched controls underwent three-dimensional 3D gait analysis while walking normally at a comfortable speed (NW) and when performing an additional congruent (CS) and incongruent (IS) Stroop task. An arm swing symmetry index (ASI)-in which positive values indicate proportionally more movement on the left and vice versa-was calculated. Even in the baseline NW condition, all three subject groups showed larger arm movements on the left. In controls, ASI increased (NW, 13.7 ± 6.3; CS, 16.6 ± 6.4; IS, 19.6 ± 7.8) as the task became more demanding. A larger shift in tSCI patients (NW, 15.8 ± 6.0; CS, 23.4 ± 3.8; IS, 30.7 ± 4.4) was driven by a significant reduction in right wrist trajectory (p = 0.014), whereas cSCI patients showed a small reduction in mean ASI with high variability (NW, 14.2 ± 10.7; CS, 9.3 ± 13.5; IS, 6.0 ± 12.9). The effect of the IS task on ASI compared to baseline (NW) was significantly different between tSCI (+12.5 ± 6.3) and cSCI (-8.2 ± 6.0) patients (p = 0.011). Disruption of the long propriospinal connections coordinating arm and leg movements during walking may explain the heightened sensitivity to manipulation of cognitive load in tSCI, whereas the more robust automaticity in cSCI may be attributed to impaired supraspinal inputs in the context of preserved intraspinal pathways.

Minimum toe clearance (MTC) occurs during a highly dynamic phase of the gait cycle and is associated with the highest risk of unintentional contact with obstacles or the ground. Age, cognitive function, attention and visual feedback affect foot clearance but how these factors interact to influence MTC control is not fully understood. We measured MTC in 121 healthy individuals aged 20-80 under four treadmill walking conditions; normal walking, lower visual field restriction and two Stroop colour/word naming tasks of two difficulty levels. Competition for cognitive and attentional resources from the Stroop task resulted in significantly lower mean MTC in older adults, with the difficult Stroop task associated with a higher frequency of extremely low MTC values and subsequently an increased modelled probability of tripping in this group. While older adults responded to visual restriction by markedly skewing MTC distributions towards higher values, this condition was also associated with frequent, extremely low MTC values. We reveal task-specific, age-dependent patterns of MTC control in healthy adults. Age-related differences are most pronounced during heavy, distracting cognitive load. Analysis of critically-low MTC values during dual-task walking may have utility in the evaluation of locomotor control and fall risk in older adults and patients with motor control deficits.

Background: Body weight supported locomotor training was shown to improve walking function in neurological patients and is often performed on a treadmill. However, walking on a treadmill does not mimic natural walking for several reasons: absent self-initiation, less active retraction of leg required and altered afferent input. The superiority of overground training has been suggested in humans and was shown in rats demonstrating greater plasticity especially in descending pathways compared to treadmill training. We therefore developed a body weight support system allowing unrestricted overground walking with minimal interfering forces to train neurological patients. The present study investigated the influence of different amounts of body weight support on gait in healthy individuals., Methods: Kinematic and electromyographic data of 19 healthy individuals were recorded during overground walking at different levels of body weight support (0, 10, 20, 30, 40, and 50%). Upper body inclination, lower body joint angles and multi-joint coordination as well as time-distance parameters were calculated. Continuous data were analyzed with regard to distinct changes within a gait cycle across all unloading conditions., Results: Temporal gait parameters were most sensitive to changes in body unloading while spatial variables (step length, joint angles) showed modest responses when unloaded by as much as 50% body weight. The activation of the gastrocnemius muscle showed a gradual decrease with increasing unloading while the biceps femoris muscle showed increased activity levels at 50% unloading. These changes occurred during stance phase while swing phase activity remained unaltered., Conclusions: Healthy individuals were able to keep their walking kinematics strikingly constant even when unloaded by half of their body weight, suggesting that the weight support system permits a physiological gait pattern. However, maintaining a given walking speed using close-to-normal kinematics while being unloaded was achieved by adapting muscle activity patterns. Interestingly, the required propulsion to maintain speed was not achieved by means of increased gastrocnemius activity at push-off, but rather through elevated biceps femoris activity while retracting the leg during stance phase. It remains to be investigated to what extent neurological patients with gait disorders are able to adapt their gait pattern in response to body unloading.

Human arm swing looks and feels highly automated, yet it is increasingly apparent that higher centres, including the cortex, are involved in many aspects of locomotor control. The addition of a cognitive task increases arm swing asymmetry during walking, but the characteristics and mechanism of this asymmetry are unclear. We hypothesized that this effect is lateralized and a Stroop word-colour naming task-primarily involving left hemisphere structures-would reduce right arm swing only. We recorded gait in 83 healthy subjects aged 18-80 walking normally on a treadmill and while performing a congruent and incongruent Stroop task. The primary measure of arm swing asymmetry-an index based on both three-dimensional wrist trajectories in which positive values indicate proportionally smaller movements on the right-increased significantly under dual-task conditions in those aged 40-59 and further still in the over-60s, driven by reduced right arm flexion. Right arm swing attenuation appears to be the norm in humans performing a locomotor-cognitive dual-task, confirming a prominent role of the brain in locomotor behaviour. Women under 60 are surprisingly resistant to this effect, revealing unexpected gender differences atop the hierarchical chain of locomotor control.

Background Clinical trials in spinal cord injury (SCI) primarily rely on simplified outcome metrics (ie, speed, distance) to obtain a global surrogate for the complex alterations of gait control. However, these assessments lack sufficient sensitivity to identify specific patterns of underlying impairment and to target more specific treatment interventions. Objective To disentangle the differential control of gait patterns following SCI beyond measures of time and distance. Methods The gait of 22 individuals with motor-incomplete SCI and 21 healthy controls was assessed using a high-resolution 3-dimensional motion tracking system and complemented by clinical and electrophysiological evaluations applying unbiased multivariate analysis. Results Motor-incomplete SCI patients showed varying degrees of spinal cord integrity (spinal conductivity) with severe limitations in walking speed and altered gait patterns. Principal component (PC) analysis applied on all the collected data uncovered robust coherence between parameters related to walking speed, distortion of intralimb coordination, and spinal cord integrity, explaining 45% of outcome variance (PC 1). Distinct from the first PC, the modulation of gait-cycle variables (step length, gait-cycle phases, cadence; PC 2) remained normal with respect to regained walking speed, whereas hip and knee ranges of motion were distinctly altered with respect to walking speed (PC 3). Conclusions In motor-incomplete SCI, distinct clusters of discretely controlled gait parameters can be discerned that refine the evaluation of gait impairment beyond outcomes of walking speed and distance. These findings are specifically different from that in other neurological disorders (stroke, Parkinson) and are more discrete at targeting and disentangling the complex effects of interventions to improve walking outcome following motor-incomplete SCI., (© The Author(s) 2015.)

Objective: To determine which single or combined upper limb muscles as defined by the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI); upper extremity motor score (UEMS) and the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP), best predict upper limb function and independence in activities of daily living (ADLs) and to assess the predictive value of qualitative grasp movements (QlG) on upper limb function in individuals with acute tetraplegia., Method: As part of a Europe-wide, prospective, longitudinal, multicenter study ISNCSCI, GRASSP, and Spinal Cord Independence Measure (SCIM III) scores were recorded at 1 and 6 months after SCI. For prediction of upper limb function and ADLs, a logistic regression model and unbiased recursive partitioning conditional inference tree (URP-CTREE) were used. Results: Logistic regression and URP-CTREE revealed that a combination of ISNCSCI and GRASSP muscles (to a maximum of 4) demonstrated the best prediction (specificity and sensitivity ranged from 81.8% to 96.0%) of upper limb function and identified homogenous outcome cohorts at 6 months. The URP-CTREE model with the QlG predictors for upper limb function showed similar results., Conclusion: Prediction of upper limb function can be achieved through a combination of defined, specific upper limb muscles assessed in the ISNCSCI and GRASSP. A combination of a limited number of proximal and distal muscles along with an assessment of grasping movements can be applied for clinical decision making for rehabilitation interventions and clinical trials., (© The Author(s) 2015.)

Objective: To investigate the internal and external responsiveness and recovery profiles of the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) instrument in revealing changes in upper limb function within the first year following cervical spinal cord injury (SCI)., Method: A European prospective, longitudinal, multicenter study assessing the GRASSP at 1, 3, 6, and 12 months after cervical SCI. Subtests of GRASSP were compared to the upper extremity motor (UEMS) and light touch scores (LT) according to the International Standards of Neurological Classification of Spinal Cord Injury (ISNCSCI), the Spinal Cord Independence Measure self-care subscore (SCIM-SS), as well as a clinician-rated outcome measure (CROM) of clinical relevance. Data were analyzed for GRASSP responsiveness and recovery rate over time., Results: Seventy-four participants entered the study. GRASSP subtests proved responsive (standardized response mean [SRM] ranged from 0.79 to 1.48 for strength, 0.50 to 1.03 for prehension, and 0.14 to 0.64 for sensation) between all examination time points. In comparison, UEMS and LT showed lower responsiveness (SRM UEMS ranged from 0.69 to 1.29 and SRM LT ranged from 0.30 to -0.13). All GRASSP subtests revealed significant, moderate-to-excellent correlations with UEMS, LT, and SCIM-SS at each time point, and changes in GRASSP subtests were in accordance with the CROM. GRASSP prehension and motor recovery was largest between 1 and 3 months., Conclusion: The GRASSP showed excellent responsiveness, detecting distinct changes in strength and prehension relating to the severity of cervical SCI. It detected clinically significant changes complimentary to the ISNCSCI and SCIM-SS assessments., (© The Author(s) 2015.)

Rehabilitative training has shown to improve significantly motor outcomes and functional walking capacity in patients with incomplete spinal cord injury (iSCI). However, whether performance improvements during rehabilitation relate to brain plasticity or whether it is based on functional adaptation of movement strategies remain uncertain. This study assessed training improvement-induced structural brain plasticity in chronic iSCI patients using longitudinal MRI. We used tensor-based morphometry (TBM) to analyze longitudinal brain volume changes associated with intensive virtual reality (VR)-augmented lower limb training in nine traumatic iSCI patients. The MRI data was acquired before and after a 4-week training period (16-20 training sessions). Before training, voxel-based morphometry (VBM) and voxel-based cortical thickness (VBCT) assessed baseline morphometric differences in nine iSCI patients compared to 14 healthy controls. The intense VR-augmented training of limb control improved significantly balance, walking speed, ambulation, and muscle strength in patients. Retention of clinical improvements was confirmed by the 3-4 months follow-up. In patients relative to controls, VBM revealed reductions of white matter volume within the brainstem and cerebellum and VBCT showed cortical thinning in the primary motor cortex. Over time, TBM revealed significant improvement-induced volume increases in the left middle temporal and occipital gyrus, left temporal pole and fusiform gyrus, both hippocampi, cerebellum, corpus callosum, and brainstem in iSCI patients. This study demonstrates structural plasticity at the cortical and brainstem level as a consequence of VR-augmented training in iSCI patients. These structural changes may serve as neuroimaging biomarkers of VR-augmented lower limb neurorehabilitation in addition to performance measures to detect improvements in rehabilitative training.

Background: There is inherent heterogeneity within individuals suffering from cervical spinal cord injury (SCI), and early prediction of upper limb function and self-care is challenging. As a result, considerable uncertainty exists regarding the prediction of functional outcome following cervical SCI within 1 year of injury., Objective: To evaluate the value of Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) in predicting upper limb function and self-care outcomes in individuals with cervical SCI., Method: A prospective longitudinal multicenter study was performed. Data from the GRASSP, the Spinal Cord Independence Measure (SCIM III), and the American Spinal Injury Association (ASIA) Impairment Scale were recorded at 1, 6, and 12 months after cervical SCI. For prediction of functional outcome at 6 and 12 months, a logistic regression model, receiver operating characteristics (ROC), and unbiased recursive partitioning conditional inference tree (URP-CTREE) were used with 8 different predictor variables., Results: Logistic regression analysis, ROC analysis, and URP-CTREE all revealed that the strength subtest within GRASSP is the strongest predictor for upper limb function and self-care outcomes. URP-CTREE provides useful information on the distribution of different outcomes in acute cervical SCI and can be used to predict cohorts with homogeneous outcomes., Conclusion: The GRASSP at 1 month can accurately predict upper limb function and self-care outcomes even in a heterogeneous group of individuals across a wide spectrum of neurological recovery. The application of URP-CTREE can reveal the distribution of outcome categories and, based on this, inform trial protocols with respect to outcomes analysis and patient stratification., (© The Author(s) 2014.)

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., (© The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To investigate the influence of different design characteristics of virtual reality exercises on engagement during lower extremity motor rehabilitation., Design: Correlational study., Setting: Spinal cord injury (SCI) rehabilitation center., Participants: Subjects with SCI (n=12) and control subjects (n=10)., Interventions: Not applicable., Main Outcome Measures: Heart rate and electromyographic activity from both legs at the tibialis anterior, the gastrocnemius medialis, the rectus femoris, and the biceps femoris were recorded., Results: Interactivity (ie, functionally meaningful reactions to motor performance) was crucial for the engagement of subjects. No significant differences in engagement were found between exercises that differed in feedback frequency, explicit task goals, or aspects of competition., Conclusions: Functional feedback is highly important for the active participation of patients during robotic-assisted rehabilitation. Further investigations on the design characteristics of virtual reality exercises are of great importance. Exercises should thoroughly be analyzed regarding their effectiveness, while user preferences and expectations should be considered when designing virtual reality exercises for everyday clinical motor rehabilitation., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Abstract Applied as a bedside test of gross dorsal column function, the testing of light touch (LT) sensation is of high clinical value in the diagnosis of human spinal cord injury (SCI). However, the assessment of overall dorsal column deficit by testing only LT may be limited, because the dorsal column pathway conveys several large diameter afferent modalities (e.g., sensation of touch, two-point discrimination, and proprioception). Therefore, the objective of this study was to compare the epicritic sensation assessed by LT, Semmes-Weinstein monofilament (SWM), and electrical perception threshold (EPT) across cervical dermatomes (C3-C8) in individuals with cervical SCI. A multicenter cross-sectional study was performed at 6 months after cervical SCI, applying combined measures of LT, SWM, and EPT, bilaterally over predefined key sensory points (C3-C8). A total of 300 left- and right-sided dermatomes were tested for each outcome measure in 25 participants. The percentage agreement between classifications according to LT and SWM/EPT testing for all dermatomes between C3 and C8 ranged from 95.5% to 36.2%. The degree of agreement showed considerably variable κ coefficients (-0.1≥kw≤0.7) for each dermatome between C3 and C8. The additional measurements of epicritic sensation by SWM and EPT increased sensitivity by detecting and quantifying differences in sensory thresholds above, at, and below the LT level of injury. This is relevant for early clinical trials (phase 1/2), in which disclosing any biological activity of an intervention may be revealed by subtle sensory changes that might gain a clinical relevance.

Gait and balance training is an essential ingredient for locomotor rehabilitation of patients with neurological impairments. Robotic overhead support systems may help these patients train, for example by relieving them of part of their body weight. However, there are only very few systems that provide support during overground gait, and these suffer from limited degrees of freedom and/or undesired interaction forces due to uncompensated robot dynamics, namely inertia. Here, we suggest a novel mechanical concept that is based on cable robot technology and that allows three-dimensional gait training while reducing apparent robot dynamics to a minimum. The solution does not suffer from the conventional drawback of cable robots, which is a limited workspace. Instead, displaceable deflection units follow the human subject above a large walking area. These deflection units are not actuated, instead they are implicitly displaced by means of the forces in the cables they deflect. This leads to an underactuated design, because the deflection units cannot be moved arbitrarily. However, the design still allows accurate control of a three-dimensional force vector acting on a human subject during gait. We describe the mechanical concept, the control concept, and we show first experimental results obtained with the device, including the force control performance during robot-supported overground gait of five human subjects without motor impairments.

Objective: Spinal neuronal function is impaired after a severe spinal cord injury (SCI) and can be assessed by the analysis of spinal reflex (SR) behavior. We applied transcutaneous spinal direct current stimulation (tsDCS) and locomotor activity, to determine whether the excitability of spinal neuronal circuitries underlying locomotion can be modulated after motor complete SCI., Method: SRs were evoked by non-noxious electrical stimulation of the tibial nerve. SR behavior was assessed before, immediately after, and 20 min after four different interventions (anodal, cathodal, sham tsDCS, or locomotion) in subjects with motor complete SCI and healthy subjects., Results: SR amplitudes in SCI subjects were increased after anodal tsDCS by 84% (p < 0.05). Cathodal, sham tsDCS and locomotion had no influence on SR amplitudes. In addition, reflex threshold was lower after anodal tsDCS and locomotion in SCI subjects (p < 0.05)., Conclusion: Anodal tsDCS is able to modulate spinal neuronal circuitries after SCI., Significance: This novel, noninvasive approach might be used as a tool to excite spinal neuronal circuitries. If applied repetitively within a training approach, anodal tsDCS might prevent adverse alterations in spinal reflex function in severely affected SCI subjects, i.e., a manifestation of a spinal neuronal dysfunction taking part below the level of a spinal lesion., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Rehabilitation robots being developed nowadays rely on force and/or impedance control. This is guided by clinical evidence showing better performance if the patient is left with the capacity to influence the robot trajectory. The simplest, yet fundamental, mode of force control is when the robot has to be transparent, i.e. to apply no forces/torques on the patient. This mode is useful both in scenarios where the robot has to apply pinpointed support during some training phases and be transparent otherwise, and for any force controller in general, to avoid the reference forces to be polluted by the robot own dynamics. This contribution proposes a method to improve transparency on a support robot for overground training. The method consists in learning the patient's movement by using adaptive oscillators and then anticipate its future evolution in order to synchronize the robot movement. In experiments with human subjects walking in the gait support robot FLOAT, this method can decrease the undesired oscillations of the support force applied to the human user by up to 50%.

Uncontrolled muscle spasms often develop after spinal cord injury. Structural and functional maladaptive changes in spinal neuronal circuits below the lesion site were postulated as an underlying mechanism but remain to be demonstrated in detail. To further explore the background of such secondary phenomena, rats received a complete sacral spinal cord transection at S(2) spinal level. Animals progressively developed signs of tail spasms starting 1 week after injury. Immunohistochemistry was performed on S(3/4) spinal cord sections from intact rats and animals were sacrificed 1, 4 and 12 weeks after injury. We found a progressive decrease of cholinergic input onto motoneuron somata starting 1 week post-lesion succeeded by shrinkage of the cholinergic interneuron cell bodies located around the central canal. The number of inhibitory GABAergic boutons in close contact with Ia afferent fibers was greatly reduced at 1 week after injury, potentially leading to a loss of inhibitory control of the Ia stretch reflex pathways. In addition, a gradual loss and shrinkage of GAD65 positive GABAergic cell bodies was detected in the medial portion of the spinal cord gray matter. These results show that major structural changes occur in the connectivity of the sacral spinal cord interneuronal circuits below the level of transection. They may contribute in an important way to the development of spastic symptoms after spinal cord injury, while reduced cholinergic input on motoneurons is assumed to result in the rapid exhaustion of the central drive required for the performance of locomotor movements in animals and humans., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

Central nervous system lesions, such as stroke or spinal cord injury (SCI), are followed by both cortical and spinal neuronal reorganization. In a severe chronic SCI a spinal neuronal dysfunction develops which is reflected in an exhaustion of leg muscle electromyographic (EMG) activity during assisted locomotion and a change in the dominance from an early to a late polysynaptic spinal reflex (SR) component. The aim of this study was to investigate the course of spinal neuronal function after a severe stroke, i.e., a unilateral deprivation of supraspinal input. In 30 hemiparetic stroke subjects locomotor and SR behavior were assessed. SR responses in the tibialis anterior muscle were evoked by non-noxious tibial nerve stimulation on both, the affected and the unaffected leg. In nine stroke subjects EMG activity of the leg muscles was recorded during assisted locomotion. In a similar way to SCI subjects, in severely affected chronic (>12 months post-incidence) stroke subjects a late SR component was prominent in the affected leg, while an early one dominated in the unaffected leg. The late SR component correlated with muscle paresis (rho=0.714) and walking ability (rho=0.493). In contrast to SCI subjects, no exhaustion of the EMG activity was observed in the affected leg muscles during prolonged assisted locomotion. It is concluded that spinal neuronal circuits undergo functional changes also after a stroke which have common as well as divergent features compared to SCI subjects. As a consequence, different rehabilitative strategies might be required., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Alterations in the function of spinal neuronal circuits underlying locomotion after a spinal cord injury (SCI) are associated with changes in the behavior of spinal reflexes (SRs) in both rats and humans. In healthy subjects, the SR consists of a dominant early reflex component, whereas in chronic, severely affected SCI subjects, a later component dominates., Objective: The aim of this study was to investigate the relationship between SR behavior and walking ability in para-/tetraplegic subjects., Method: The SR was evoked by nonnoxious tibial nerve stimulation. Walking ability was assessed by functional tests and questionnaires., Results: There was a correlation between walking ability and SR behavior in chronic SCI: Severely affected SCI subjects unable to walk showed dominant late SR components, whereas in ambulatory SCI subjects an early SR component dominated. A functional training with an improvement of locomotor ability was accompanied by both a shift from a dominant to a smaller late and the appearance of an early SR component., Conclusions: Our findings indicate that SR can serve as a marker for the locomotor ability of SCI subjects. Neuronal plasticity exploited by a functional training is reflected in both an improvement of locomotor ability and a change in balance of SR components toward the early SR component.

In complete spinal cord injured (cSCI) subjects a shift from dominant early (60-120ms latency) to dominant late (120-450ms latency) spinal reflex (SR) components occurs over time after injury. This shift is assumed to reflect a spinal neuronal dysfunction below the level of a spinal lesion. The neuronal pathways of SR are suggested to be closely connected with spinal locomotor circuits. The aim of this study was to explore the influence of the two SR components on the electromyographic (EMG) pattern induced by assisted locomotion in cSCI subjects. Leg muscle EMG activity was analysed during assisted locomotion in both healthy and motor cSCI subjects. SR were evoked by non-noxious tibial nerve stimulation during mid-stance phase of the gait cycle. Early and late SR components had a differential influence on the locomotor pattern. In healthy and cSCI subjects with a dominant early SR component the locomotor EMG pattern was modulated in the form of a short increase in leg flexors activity in the stance phase (tibialis anterior, biceps femoris). In contrast, in chronic cSCI subjects with a dominant late SR component no activation in biceps femoris but a long-lasting activation of tibialis anterior and rectus femoris muscles during the stance phase was evoked. It is concluded that the same tibial nerve stimuli activated two different neuronal pathways, resulting in divergent interactions with spinal locomotor circuitries. It is proposed that the two SR components have different physiological roles during locomotion., (Copyright © 2011 Elsevier B.V. All rights reserved.)

This review describes the changes of spinal neuronal function that occur after a motor complete spinal cord injury (cSCI) in humans. In healthy subjects, polysynaptic spinal reflex (SR) evoked by non-noxious tibial nerve stimulation consists of an early SR component and rarely a late SR component. Soon after a cSCI, SR and locomotor activity are absent. After spinal shock; however, an early SR component re-appears associated with the recovery of locomotor activity in response to appropriate peripheral afferent input. Clinical signs of spasticity take place in the following months, largely as a result of non-neuronal changes. After around 1 year, the locomotor and SR activity undergo fundamental changes, that is, the electromyographic amplitude in the leg muscles during assisted locomotion exhaust rapidly, accompanied by a shift from early to dominant late SR components. The exhaustion of locomotor activity is also observed in non-ambulatory patients with an incomplete spinal cord injury (SCI). At about 1 year after injury, in most cSCI subjects the neuronal dysfunction is fully established and remains more or less stable in the following years. It is assumed that in chronic SCI, the patient's immobility resulting in a reduced input from supraspinal and peripheral sources leads to a predominance of inhibitory drive within spinal neuronal circuitries underlying locomotor pattern and SR generation. Training of spinal interneuronal circuits including the enhancement of an appropriate afferent input might serve as an intervention to prevent neuronal dysfunction after an SCI.

Background: The overall goal of this paper was to investigate approaches to controlling active participation in stroke patients during robot-assisted gait therapy. Although active physical participation during gait rehabilitation after stroke was shown to improve therapy outcome, some patients can behave passively during rehabilitation, not maximally benefiting from the gait training. Up to now, there has not been an effective method for forcing patient activity to the desired level that would most benefit stroke patients with a broad variety of cognitive and biomechanical impairments., Methods: Patient activity was quantified in two ways: by heart rate (HR), a physiological parameter that reflected physical effort during body weight supported treadmill training, and by a weighted sum of the interaction torques (WIT) between robot and patient, recorded from hip and knee joints of both legs. We recorded data in three experiments, each with five stroke patients, and controlled HR and WIT to a desired temporal profile. Depending on the patient's cognitive capabilities, two different approaches were taken: either by allowing voluntary patient effort via visual instructions or by forcing the patient to vary physical effort by adapting the treadmill speed., Results: We successfully controlled patient activity quantified by WIT and by HR to a desired level. The setup was thereby individually adaptable to the specific cognitive and biomechanical needs of each patient., Conclusion: Based on the three successful approaches to controlling patient participation, we propose a metric which enables clinicians to select the best strategy for each patient, according to the patient's physical and cognitive capabilities. Our framework will enable therapists to challenge the patient to more activity by automatically controlling the patient effort to a desired level. We expect that the increase in activity will lead to improved rehabilitation outcome.

We present a case of an individual who stabbed himself through the heart with a large knife. Post mortem computed tomography (CT) and CT-angiography were used to assess the stab channel and to reconstruct the sequence of events. After penetrating injuries to the chest, both the intra-thoracic organs and the injury causing instrument may shift (e.g. from pnemothorax) and render forensic reconstructions more challenging. This case report illustrates the potentials and the pitfalls of CT for the reconstruction of penetrating injures to the chest., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

It is one of the most important tasks of the forensic pathologist to explain the forensically relevant medical findings to medical non-professionals. However, it is often difficult to comment on the nature and potential consequences of organ injuries in a comprehensive way to individuals with limited knowledge of anatomy and physiology. This rare case of survived pancreatic transaction after kicks to the abdomen illustrates how the application of dedicated software programs for three-dimensional reconstruction can overcome these difficulties, allowing for clear and concise visualization of complex findings., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Study Design: Retrospective, longitudinal analysis of sensory, motor and functional outcomes from individuals with thoracic (T2-T12) sensorimotor complete spinal cord injury (SCI)., Objectives: To characterize neurological changes over the first year after traumatic thoracic sensorimotor complete SCI., Methods: A dataset of 399 thoracic complete SCI subjects from the European Multi-center study about SCI (EMSCI) was examined for neurological level, sensory levels and sensory scores (pin-prick and light touch), lower extremity motor score (LEMS), ASIA Impairment Scale (AIS) grade, and Spinal Cord Independence Measure (SCIM) over the first year after SCI., Results: AIS grade conversions were limited. Sensory scores exhibited minimal mean change, but high variability in both rostral and caudal directions. Pin-prick and light touch sensory levels, as well as neurological level, exhibited minor changes (improvement or deterioration), but most subjects remained within one segment of their initial injury level after 1 year. Recovery of LEMS occurred predominantly in subjects with low thoracic SCI. The sensory zone of partial preservation (ZPP) had no prognostic value for subsequent recovery of sensory levels or LEMS. However, after mid or low thoracic SCI, ≥3 segments of sensory ZPP correlated with an increased likelihood for AIS grade conversion., Conclusion: The data suggest that a sustained deterioration of three or more thoracic sensory levels or loss of upper extremity motor function are rare events and may be useful for tracking the safety of a therapeutic intervention in early phase acute SCI clinical trials, if a significant proportion of study subjects exhibit such an ascent.

Many research groups are currently working with robotic devices for hand grasp rehabilitation and restoration. A common problem in this area is the fact that existing and commercially available robotic exoskeletons are able to provide gravity compensation of the shoulder and elbow but do not provide any support for the grasping and releasing movements of the hand. The lack of a flexible support technology for the hand reduces the possible ways in which clinicians can deal with the issue of a personalized, effective rehabilitation. This paper presents new software that allows FES assisted grasping to integrate with the ArmeoSpring (Hocoma AG). The system uses a Man-In-The-Loop control approach, whereby surface EMG signals from proximal muscles are used to trigger and modulate multichannel FES applied to distal muscles, thus allowing patient induced and strength adapted movement control of the hand. Combining volitionally controlled FES with arm-weight-compensation allows early adoption of FES assisted therapy for patients, augmenting their functionalities and extending training capabilities with the ArmeoSpring.

Robot-assisted treadmill training is an established intervention used to improve walking ability in patients with neurological disorders. Although it has been shown that attention to the task is a key factor for successful rehabilitation, the psychological state of patients during robot-assisted gait therapy is often neglected. We presented 17 nondisabled subjects and 10 patients with neurological disorders a virtual-reality task with varying difficulty levels to induce feelings of being bored, excited, and overstressed. We developed an approach to automatically estimate and classify a patient's psychological state, i.e., his or her mental engagement, in real time during gait training. We used psychophysiological measurements to obtain an objective measure of the current psychological state. Automatic classification was performed by a neural network. We found that heart rate, skin conductance responses, and skin temperature can be used as markers for psychological states in the presence of physical effort induced by walking. The classifier achieved a classification error of 1.4% for nondisabled subjects and 2.1% for patients with neurological disorders. Using our new method, we processed the psychological state data in real time. Our method is a first step toward real-time auto-adaptive gait training with potential to improve rehabilitation results by optimally challenging patients at all times during exercise.

Purpose: To evaluate the feasibility and reliability of a novel stiffness assessment tool implemented in the driven gait orthosis Paediatric Lokomat; to investigate the influence of single robotic-assisted gait training (RAGT) on muscle stiffness in children with cerebral palsy (CP)., Methods: Ten children with spastic CP conducted a single standard RAGT session and stiffness was assessed before and after the RAGT. Nine of the ten subjects were tested twice on the same day to investigate test-retest reliability, intraclass correlation coefficients (ICCs), standard error of measurement (SEM), coefficient of variation of the method error (CV(ME)) and resistive torques during passive leg movements (stiffness in Nm/°) were calculated., Results: ICCs showed high reliability (0.83-0.97) for hip and knee movements. SEM and CV(ME) indicated 0.028-0.085 Nm/°, 9.5-23.0% of test-retest variability in hip and 0.018-0.064 Nm/°, 13.3-43.5% in knee measures. Using the assessment tool, a significant decrease in muscle stiffness in participants, especially in children with high levels of muscle tone, could be shown after a single session of RAGT., Conclusions: The assessment tool L-STIFF is a feasible tool for automated measurement of stiffness in children with CP, but it is not sensitive enough to record small changes in muscle tone.

Objective: In healthy subjects, spinal reflexes (SR) evoked by non-noxious tibial nerve stimulation consist of an early (60-120ms latency) and an occasional late-appearing (120-450ms latency) component in the ipsilateral tibialis anterior. In chronic (>1year) complete spinal cord injured (cSCI) subjects early components are small or lacking while late components are dominant. Here we report on the modulation of SR by assisted locomotion in healthy and chronic motor cSCI subjects., Methods: SR was evoked by tibial nerve stimulation at the terminal stance phase during assisted locomotion and was compared to SR recorded during upright stance., Results: In chronic cSCI subjects only a late SR component was consistently present during upright stance. However during assisted locomotion, an early SR component appeared, while amplitude of the late SR component became small. In contrast, in healthy subjects the early SR component dominated in all conditions, but a small late component appeared during assisted locomotion., Conclusion: A more balanced activity of early and late SR components occurred in both subject groups if an appropriate proprioceptive input was provided., Significance: Early and late SR components are assumed to reflect the activity of separate neuronal circuits, which are associated with the locomotor circuitry possibly by shaping the pattern., (Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

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.

Locomotor activity and spinal reflexes (SRs) show common features in different mammals, including humans. Here we report the time-course of the development of locomotor activity and SRs after a complete spinal cord injury in humans. SRs evoked by tibial nerve stimulation were studied, as was the leg muscle electromyography activity evoked by mechanically assisted locomotion (Lokomat) in biceps femoris, rectus femoris, tibialis anterior and gastrocenmius medialis. Around 8 weeks after the injury, an early SR component (latency 60-120 ms) appeared, as in healthy subjects, and a well-organized leg muscle activity was present during assisted locomotion. At around 6 months after injury an additional, late reflex component (latency 120-450 ms) appeared, which remained even 15 years after the spinal cord injury. In contrast, the early component had markedly decreased at 18 months after injury. These changes in SR were associated with a loss of electromyography activity and a successively stronger electromyography exhaustion (i.e. decline of electromyography amplitude), when comparing the level of electromyography activity at 2 and 10 min, respectively, during assisted locomotion. These changes in electromyography activity affected mainly the biceps femoris, gastrocenmius medialis and tibialis anterior but less so the rectus femoris. When the amplitude relationship of the early to late SR component was calculated, there was a temporal relationship between the decrease of the early component and an increase of the late component and the degree of exhaustion of locomotor activity. In chronic, severely affected but sensori-motor incomplete spinal cord injury subjects a late SR component, associated with an electromyography exhaustion, was present in subjects who did not regularly perform stepping movements. Our data are consistent with the proposal of a common mechanism underlying the changes in SR activity and locomotor activity after spinal cord injury. These findings should be taken into consideration in the development of novel rehabilitation schemes and programs to facilitate regeneration-inducing therapies in spinal cord injury subjects.

Visual biofeedback with information about the patients' degree of activity is a valuable adjunct to robot-assisted gait training as means of increasing the motivation and participation of the patients during highly repetitive training sessions. In the driven gait orthosis (DGO) Lokomat, an estimation of the patient's activity level was based on man-machine interaction forces as measured at the hip and knee actuators of the exoskeletal device. In an early approach, theoretical assumptions about the expected man-machine interaction forces, due to the varying behavior of the patients, were formulated for the calculation of quantitative biofeedback. In contrast to this theory-based approach, we have developed a novel method where the biofeedback calculations were based on measured reference man-machine interaction force profiles of healthy subjects when walking with different degrees of activity. To account for intrasubject and intersubject variability, reference force profiles were processed in a model to generate multiple force profiles describing each activity state. To estimate the activity of a subject walking in the DGO, the man-machine interaction force profile was measured, matched to each of the generated force profiles, and the best fitting profile of the different activity states was identified by the smallest Euclidian distance, respectively. By calculating the difference between these Euclidian distances, a quantitative estimate of the patient's degree of activity was obtained. The novel method was evaluated and compared to the conventional approach in a study with 18 healthy subjects. This comparison showed that the novel method was more reliable in detecting different activity states and is, therefore, a promising approach for future biofeedback systems.

Background: Isometric force measurements in the lower extremity are widely used in rehabilitation of subjects with neurological movement disorders (NMD) because walking ability has been shown to be related to muscle strength. Therefore muscle strength measurements can be used to monitor and control the effects of training programs. A new method to assess isometric muscle force was implemented in the driven gait orthosis (DGO) Lokomat. To evaluate the capabilities of this new measurement method, inter- and intra-rater reliability were assessed., Methods: Reliability was assessed in subjects with and without NMD. Subjects were tested twice on the same day by two different therapists to test inter-rater reliability and on two separate days by the same therapist to test intra-rater reliability., Results: Results showed fair to good reliability for the new measurement method to assess isometric muscle force of lower extremities. In subjects without NMD, intraclass correlation coefficients (ICC) for inter-rater reliability ranged from 0.72 to 0.97 and intra-rater reliability from 0.71 to 0.90. In subjects with NMD, ICC ranged from 0.66 to 0.97 for inter-rater and from 0.50 to 0.96 for intra-rater reliability., Conclusion: Inter- and intra- rater reliability of an assessment method for measuring maximal voluntary isometric muscle force of lower extremities was demonstrated. We suggest that this method is a valuable tool for documentation and controlling of the rehabilitation process in patients using a DGO.

Background and Purpose: Robotic devices for walking rehabilitation allow new possibilities for providing performance-related information to patients during gait training. Based on motor learning principles, augmented feedback during robotic-assisted gait training might improve the rehabilitation process used to regain walking function. This report presents a method to provide visual feedback implemented in a driven gait orthosis (DGO). The purpose of the study was to compare the immediate effect on motor output in subjects during robotic-assisted gait training when they used computerized visual feedback and when they followed verbal instructions of a physical therapist., Subjects: Twelve people with neurological gait disorders due to incomplete spinal cord injury participated., Methods: Subjects were instructed to walk within the DGO in 2 different conditions. They were asked to increase their motor output by following the instructions of a therapist and by observing visual feedback. In addition, the subjects' opinions about using visual feedback were investigated by a questionnaire., Results: Computerized visual feedback and verbal instructions by the therapist were observed to result in a similar change in motor output in subjects when walking within the DGO. Subjects reported that they were more motivated and concentrated on their movements when using computerized visual feedback compared with when no form of feedback was provided., Discussion and Conclusion: Computerized visual feedback is a valuable adjunct to robotic-assisted gait training. It represents a relevant tool to increase patients' motor output, involvement, and motivation during gait training, similar to verbal instructions by a therapist.