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Severe spinal cord injury in humans leads to a progressive neuronal dysfunction in the chronic stage of the injury. This dysfunction is characterized by premature exhaustion of muscle activity during assisted locomotion, which is associated with the emergence of abnormal reflex responses. Here, we hypothesize that undirected compensatory plasticity within neural systems caudal to a severe spinal cord injury contributes to the development of neuronal dysfunction in the chronic stage of the injury. We evaluated alterations in functional, electrophysiological and neuromorphological properties of lumbosacral circuitries in adult rats with a staggered thoracic hemisection injury. In the chronic stage of the injury, rats exhibited significant neuronal dysfunction, which was characterized by co-activation of antagonistic muscles, exhaustion of locomotor muscle activity, and deterioration of electrochemically-enabled gait patterns. As observed in humans, neuronal dysfunction was associated with the emergence of abnormal, long-latency reflex responses in leg muscles. Analyses of circuit, fibre and synapse density in segments caudal to the spinal cord injury revealed an extensive, lamina-specific remodelling of neuronal networks in response to the interruption of supraspinal input. These plastic changes restored a near-normal level of synaptic input within denervated spinal segments in the chronic stage of injury. Syndromic analysis uncovered significant correlations between the development of neuronal dysfunction, emergence of abnormal reflexes, and anatomical remodelling of lumbosacral circuitries. Together, these results suggest that spinal neurons deprived of supraspinal input strive to re-establish their synaptic environment. However, this undirected compensatory plasticity forms aberrant neuronal circuits, which may engage inappropriate combinations of sensorimotor networks during gait execution.

Facilitation of leg muscle activity by active arm movements during locomotor tasks could be beneficial during gait rehabilitation after spinal cord injury. The present study explored the effects of arm movements on leg muscle activity during submaximal recumbent stepping. Healthy subjects exercised on a recumbent stepping machine both with and without arm movements. Activity of five leg muscles was recorded and compared for stepping with and without arm movements. To determine which arm movements are optimal for leg muscle facilitation, subjects were instructed to step with 1) mechanically coupled vs. decoupled arm and leg movements, 2) synchronous vs. asynchronous arm movements, and 3) at 50 vs. 70 RPM. Leg muscle activity was increased by active arm movements in all muscles, except the vastus lateralis muscle. Activity of other extensors (soleus, medial gastrocnemius, and biceps femoris) was primarily increased during the extension phase, whereas activity of flexors (tibialis anterior) was also increased during the flexion phase. Facilitation was more or less consistent for both frequencies and for synchronous and asynchronous movements. For coupled arm movements, facilitation tended to be diminished or absent. The observed facilitation in the present study is probably of neuromuscular rather than biomechanical origin, since the arms are probably hardly involved in postural control or weight-bearing during recumbent stepping. Further studies in patients should explore the possibility to integrate neuromuscular facilitation in rehabilitation programs.

Advances in our understanding of the physiological basis of locomotion enable us to optimize the neurorehabilitation of patients with lesions to the central nervous system, such as stroke or spinal cord injury (SCI). It is generally accepted, based on work in animal models, that spinal neuronal machinery can produce a stepping-like output. In both incomplete and complete SCI subjects spinal locomotor circuitries can be activated by functional training which provides appropriate afferent feedback. In motor complete SCI subjects, however, motor functions caudal to the spinal cord lesion are no longer used resulting in neuronal dysfunction. In contrast, in subjects with an incomplete SCI such training paradigms can lead to improved locomotor ability. Appropriate functional training involves the facilitation and assistance of stepping-like movements with the subjects' legs and body weight support as far as is required. In severely affected subjects standardized assisted locomotor training is provided by body weight supported treadmill training with leg movements either manually assisted or moved by a driven gait orthosis. Load- and hip-joint related afferent input is of crucial importance during locomotor training as it leads to appropriate leg muscle activation and thus increases the efficacy of the rehabilitative training. Successful recovery of locomotion after SCI relies on the ability of spinal locomotor circuitries to utilize specific multisensory information to generate a locomotor pattern. It seems that a critical combination of sensory cues is required to generate and improve locomotor patterns after SCI. In addition to functional locomotor training there are numbers of other promising experimental approaches, such as tonic epidural electrical or magnetic stimulation of the spinal cord, which both promote locomotor permissive states that lead to a coordinated locomotor output. Therefore, a combination of functional training and activation of spinal locomotor circuitries, for example by epidural/flexor reflex electrical stimulation or drug application (e.g. noradrenergic agonists), might constitute an effective strategy to promote neuroplasticity after SCI in the future.

Background: The description of the natural course of recovery from a spinal cord injury (SCI) with spontaneous improvement of neurological, neurophysiological, and functional measures is an important prerequisite in appraising effects of upcoming interventional therapies., Objective: To describe the spontaneous evolution of motor-evoked potentials of the anterior tibial muscle (TA-MEP) and their relation to outcomes of lower extremity motor scores (LEMS) and walking function in patients recovering from an acute SCI., Methods: TA-MEPs were assessed in 255 SCI subjects within 5 time intervals throughout the first year after SCI with combined neurological and functional measures. Tibial nerve conduction studies were performed to screen for peripheral nerve damage., Results: TA-MEP allowed stratification of SCI according to lesion severity and outcome. As MEP amplitudes increased over 12 months after SCI, this was paralleled by a significant improvement of LEMS and walking function. TA-MEP latencies remained usually stable., Conclusion: Clinical outcome and walking function after SCI can be predicted independent of clinical measures by assessment of TA-MEP reflecting corticospinal tract integrity.

Diffusion tensor imaging (DTI) is rarely applied in spinal cord injury (SCI). The aim of this study was to correlate diffusion properties after SCI with electrophysiological and neurological measures. Nineteen traumatic cervical SCI subjects and 28 age-matched healthy subjects participated in this study. DTI data of the spinal cord were acquired with a Philips Achieva 3 T MR scanner using an outer volume suppressed, reduced field of view (FOV) acquisition with oblique slice excitation and a single-shot EPI readout. Neurological and electrophysiological measures, American Spinal Injury Association (ASIA) impairment scale scores, and motor (MEP) and somatosensory evoked potentials (SSEP) were assessed in SCI subjects. Fractional anisotropy (FA) values were decreased in the SCI subjects compared to the healthy subjects. In upper cervical segments, the decrease in FA was significant for the evaluation of the entire cross-sectional area of the spinal cord, and for corticospinal and sensory tracts. A decreasing trend was also found at the thoracic level for the corticospinal tracts. The decrease of DTI values correlated with the clinical completeness of SCI, and with SSEP amplitudes. The reduced DTI values seen in the SCI subjects are likely due to demyelination and axonal degeneration of spinal tracts, which are related to clinical and electrophysiological measures. A reduction in DTI values in regions remote from the injury site suggests their involvement with wallerian axonal degeneration. DTI can be used for the quantitative evaluation of the extent of spinal cord damage, and eventually to monitor the effects of future regeneration-inducing treatments.

In patients suffering an incomplete spinal cord injury (SCI) an improvement in walking function can be achieved by providing a functional training with an appropriate afferent input. In contrast, in immobilized incomplete and complete subjects a negative neuroplasticity leads to a neuronal dysfunction. After an SCI, neuronal centers below the level of lesion exhibit plasticity that either can be exploited by specific training paradigms or undergo a degradation of function due to the loss of appropriate input. Load- and hip-joint-related afferent inputs seem to be of crucial importance for the generation of a locomotor pattern and, consequently, the effectiveness of the locomotor training. In severely affected SCI subjects rehabilitation robots allow for a longer and more intensive training and can provide feedback information. Conversely, in severely affected chronic SCI individuals without functional training the locomotor activity in the leg muscles exhausts rapidly during assisted locomotion. This is accompanied by a shift from early to dominant late spinal reflex components. The exhaustion of locomotor activity is also observed in non-ambulatory patients with an incomplete SCI. It is assumed that in chronic SCI the patient's immobility results in a reduced input from supraspinal and peripheral sources and leads to a dominance of inhibitory drive within spinal neuronal circuitries underlying locomotor pattern and spinal reflex generation. A training with an enhancement of an appropriate proprioceptive input early after an SCI might serve as an intervention to prevent neuronal dysfunction., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The aim of this study was to explore the neural basis of adaptation, memory and skill transfer during human stepping over obstacles. Whilst walking on a treadmill, subjects had to perform uni- and bilateral obstacle steps. Acoustic feedback information about foot clearance was provided. Non-noxious electrical stimuli were applied to the right tibial nerve during the mid-stance phase of the right leg, i.e. 'prior' to the right or 'during' the left leg swing over the obstacle. The electromyogram (EMG) responses evoked by these stimuli in arm and leg muscles are known to reflect the neural coordination during normal and obstacle steps. The leading and trailing legs rapidly adapted foot clearance during obstacle steps with small further changes when the same obstacle condition was repeated. This adaptation was associated with a corresponding decrease in arm and leg muscle reflex EMG responses. Arm (but not leg) muscle EMG responses were greater when the stimulus was applied 'during' obstacle crossing by the left leg leading compared with stimulation 'prior' to right leg swing over the obstacle. A corresponding difference existed in arm muscle background EMG. The results indicate that, firstly, the somatosensory information gained by the performance and adaptation of uni- and bilateral obstacle stepping becomes transferred to the trailing leg in a context-specific manner. Secondly, EMG activity in arm and leg muscles parallels biomechanical adaptation of foot clearance. Thirdly, a consistently high EMG activity in the arm muscles during swing over the obstacle is required for equilibrium control. Thus, such a precision locomotor task is achieved by a context-specific, coordinated activation of arm and leg muscles for performance and equilibrium control that includes adaptation, memory and skill transfer., (© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

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.

Antispastic medications that are directed to reduce clinical signs of spasticity, such as exaggerated reflexes and muscle tone, do not improve the movement disorder. Medication can even increase weakness which might interfere with functional movements, such as walking. In this chapter we address how spasticity affects mobility and how this should be taken into account in the treatment of spasticity. In clinical practice, signs of exaggerated tendon tap reflexes associated with muscle hypertonia are the consequence of spinal cord injury (SCI). They are generally thought to be responsible for spastic movement disorders. Most antispastic treatments are, therefore, directed at the reduction of reflex activity. In recent years, a discrepancy between spasticity as measured in the clinic and functional spastic movement disorder was noticed, which is primarily due to the different roles of reflexes in passive and active states, respectively. We now know that central motor lesions are associated with loss of supraspinal drive and defective use of afferent input with impaired behavior of short-latency and long-latency reflexes. These changes lead to paresis and maladaptation of the movement pattern. Secondary changes in mechanical muscle fiber, collagen tissue, and tendon properties (e.g., loss of sarcomeres, subclinical contractures) result in spastic muscle tone, which in part compensates for paresis and allows functional movements on a simpler level of organization. Antispastic drugs should primarily be applied in complete SCI. In mobile patients they can accentuate paresis and therefore should be applied with caution., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In recent decades, several novel approaches of spinal cord repair have revealed promising findings in animal models. However, for a successful translation of these into a clinical trial in humans the specific conditions pertaining to human spinal cord injuries (SCI) have to be appreciated. Firstly, transection of the spinal cord is commonly applied in animal models, whereas spinal cord contusion is the predominant type of injury in humans, and generally leads to more extensive injury in two to three spinal cord segments. Secondly, the quadrupedal organization of locomotion in animals and the more complex autonomic functions in humans challenge the translation of animal behavior into recovery from human SCI. Thirdly, so far, no adequate animal model has been developed to resemble spastic movement disorder in human SCI. Fourthly, the extensive damage to spinal motor neurons and nerve roots in human cervical and thoracolumbar in spine trauma is but little addressed in current translational studies. This damage has direct implications for rehabilitation and repair strategies. Fifthly, there is increasing evidence for a neuronal dysfunction below the level of the lesion in chronic complete SCI. The relevance of this dysfunction for a regeneration-inducing treatment needs to be investigated. Lastly, an approach to facilitate an appropriate reconnection of regenerating tract fibers by functional training in the postacute stage has yet to be confirmed., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Little is known about the impact of supraspinal centers on the control of human locomotion. Analyzing brain activity can help to clarify their impact and to improve the effects of locomotor training. A fMRI-compatible pneumatic robotic device is presented that can generate freely programmable, highly repetitive periodic active and passive leg movements comprised by hip, knee, and ankle joint displacements. Forces of up to 400N can be applied to each foot while the subject is lying in a supine position. Magnetic interference of the device with the magnetic field of the scanner is measurable, but does not affect the image quality as obtained by a usual image analysis procedure. In a first experiment, brain activity of one healthy subject was acquired during nine different gait-like movement conditions. Brain activity in the somatosensory and motor function related areas increased more when the subject actively moved the legs than when the legs were passively moved by the device. In almost all conditions, mean head motion could be limited to 2mm within the duration of one fMRI scan by a specifically developed head and trunk fixation system. Based on these results, it is concluded that our device will significantly contribute to a better understanding of human locomotor control and related therapeutic effects in spinal cord injured and stroke patients, and thereby, to improve training approaches., (Copyright © 2011 Elsevier B.V. All rights reserved.)

During recent years, evidence has come up that bipedal locomotion is based on a quadrupedal limb coordination. A task-dependent neuronal coupling of upper and lower limbs allows one to involve the arms during gait but to uncouple this connection during voluntarily guided arm/hand movements. Hence, despite the evolution of a strong cortico-spinal control of hand/arm movements in humans, a quadrupedal limb coordination persists during locomotion. This has consequences for the limb coordination in movement disorders such as in Parkinson's disease (PD) and after stroke. In patients suffering PD, the quadrupedal coordination of gait is basically preserved. The activation of upper limb muscles during locomotion is strong, similar as in age-matched healthy subjects although arm swing is reduced. This suggests a contribution of biomechanical constraints to immobility. In post-stroke subjects a close interactions between unaffected and affected sides with an impaired processing of afferent input takes place. An afferent volley applied to a leg nerve of the unaffected leg leads to a normal reflex activation of proximal arm muscles of both sides. In contrast, when the nerve of the affected leg was stimulated, neither on the affected nor in the unaffected arm muscles EMG responses appear. Muscle activation on the affected arm becomes normalized by influences of the unaffected side during locomotion. These observations have consequences for the rehabilitation of patients suffering movement disorders.

Background: A large proportion of patients with spinal cord injury (SCI) regain ambulatory function. However, during the first 3 months most of the patients are not able to walk unsupported. To enable ambulatory training at such an early stage the body weight is partially relieved and the leg movements are assisted by two therapists. A more recent approach is the application of robotic based assistance which allows for longer training duration. From motor learning science and studies including patients with stroke, it is known that training effects depend on the duration of the training. Longer trainings result in a better walking function. The aim of the present study is to evaluate if prolonged robot assisted walking training leads to a better walking outcome in patients with incomplete SCI and whether such training is feasible or has undesirable effects., Methods/design: Patients from multiple sites with a subacute incomplete SCI and who are not able to walk independently will be randomized to either standard training (3-5 sessions per week, session duration maximum 25 minutes) or an intensive training (3-5 sessions per week, session duration minimum 50 minutes). After 8 weeks of training and 4 months later the walking ability, the occurrence of adverse events and the perceived rate of exertion as well as the patients' impression of change will be compared between groups., Trial Registration: This study is registered at clinicaltrials.gov, identifier: NCT01147185.

The aim of this study was to evaluate the sensorimotor interactions between unaffected and affected sides of post-stroke subjects during locomotion. In healthy subjects, stimulation of the tibial nerve during the mid-stance phase is followed by electromyography responses not only in the ipsilateral tibialis anterior, but also in the proximal arm muscles of both sides, with larger amplitudes prior to swing over an obstacle compared with normal swing. In post-stroke subjects, the electromyography responses were stronger on both sides when the tibial nerve of the unaffected leg was stimulated compared with stimulation of the affected leg. This difference was more pronounced when stimuli were applied prior to swing over an obstacle than prior to normal swing. This indicates an impaired processing of afferent input from the affected leg resulting in attenuated and little task-modulated reflex responses in the arm muscles on both sides. In contrast, an afferent volley from the unaffected leg resulted in larger electromyography responses, even in the muscles of the affected arm. Arm muscle activations were stronger during swing over an obstacle than during normal swing, with no difference in electromyography amplitudes between the unaffected and affected sides. It is concluded that the deficits of the affected arm are compensated for by influences from the unaffected side. These observations indicate strong mutual influences between unaffected and affected sides during locomotion of post-stroke subjects, which might be used to optimize rehabilitation approaches.

This study investigated the interactions of supraspinal with spinal neuronal circuits during obstacle steps by recordings of electroencephalography (EEG), reflex activity and limb muscle electromyography (EMG). Subjects walking with reduced vision on a treadmill were acoustically informed about an approaching obstacle and received feedback about task performance. Only following a task-relevant acoustic signal, spinal reflex responses, evoked by tibial nerve stimulation during mid-stance, were enhanced in proximal arm and leg flexor muscles prior to obstacle compared to normal swing, reflecting the neuronal preparation of the task. During swing over the obstacle, limb muscle EMG activity was greater than in normal swing. Both the preparation and the performance (i.e. ascending movement slope of the obstacle-crossing leg) were associated with an enhanced EEG signal mainly in the prefrontal cortex of the right hemisphere. Adaptational changes in performance, reflex activity and muscle activation during repetitive obstacle stepping were not reflected in the EEG activity, probably due to an insufficient resolution of the EEG. The observations suggest that drive from supraspinal centers initiates and maintains spinal neuronal activity underlying obstacle task preparation and performance., (© 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

This short review summarizes developments and achievements made during the last few years in spinal neurology and includes all relevant papers published in the Journal of Neurology during this time. A focus of the review concerns the debate about the significance of translational medicine in spinal cord injury with the introduction of new drugs directed to achieve some spinal cord repairs.

Objective: Spinal cord injury (SCI) leads to permanent motor and sensory deficits due to the damage of ascending and descending fiber tracts. In addition, malfunctions such as neuropathic pain or muscle spasms develop in many patients, possibly caused by injury-induced plastic changes of neuronal circuits above and below the lesion. New treatment strategies for spinal cord injury aim at enhancing plasticity and neurite growth, for example, by blocking the key neurite growth inhibitor Nogo-A or its downstream effectors. It is therefore crucial to investigate potential effects of such treatments on malfunctions such as muscle spasms. In addition, locomotor training, now a standard therapeutic tool to improve walking ability in incomplete SCI subjects, can be expected to influence the rearrangement of spinal cord circuits and the development of muscle spasms and other malfunctions., Methods and Results: Here we present and validate a new rat model for muscle spasms after incomplete SCI and show that both intrathecal anti-Nogo-A antibody treatment and locomotor training, started early after injury, permanently reduce the development of muscle spasms., Interpretation: The results show that an antibody-mediated suppression of the growth inhibitory protein Nogo-A leads to functional recovery and a lower level of malfunctions, suggesting the formation of functionally meaningful connections in the damaged spinal cord. Treadmill training early after SCI also has a beneficial effect.

This Review discusses the spinal neuronal changes that occur after a complete spinal cord injury (SCI) in humans. Early after an SCI, neither locomotor nor spinal reflex activity can be evoked. Once spinal shock has resolved, locomotor activity and an early spinal reflex component reappear in response to appropriate peripheral afferent input. In the subsequent 4-8 months, clinical signs of spasticity appear, largely as a result of non-neuronal (for example, muscular) changes, whereas locomotor and spinal reflex activity undergo little change. At 9-12 months, the electromyographic amplitude in the leg muscles during assisted locomotion declines, accompanied by a decrease in the amplitude of the early spinal reflex component and an increase in the amplitude of a late spinal reflex component. This exhaustion of locomotor activity also occurs in nonambulatory patients with incomplete SCI. Neuronal dysfunction is fully established 1 year after the injury without further alterations in subsequent years. In chronic SCI, the absence of input from supraspinal sources has been suggested to lead to degradation of neuronal function below the level of the lesion or, alternatively, a predominance of inhibitory signaling to the locomotor pattern generator. Appropriate training and/or provision of afferent input to spinal neurons might help to prevent neuronal dysfunction in chronic SCI.

The extent of ambulatory recovery after motor incomplete spinal cord injury (miSCI) differs considerably amongst affected persons. This makes individual outcome prediction difficult and leads to increased within-group variation in clinical trials. The aims of this study on subjects with miSCI were: (1) to rank the strongest single predictors and predictor combinations of later walking capacity; (2) to develop a reliable algorithm for clinical prediction; and (3) to identify subgroups with only limited recovery of walking function. Correlation and logistic regression analyses were performed on a dataset of 90 subjects with tetra- or paraparesis, recruited in a prospective European multicenter study. Eleven measures obtained in the subacute injury period, including clinical examination, tibial somatosensory evoked potentials (tSSEP), and demographic factors, were related to ambulatory outcome (WISCI II, 6minWT) 6 months after injury. The lower extremity motor score (LEMS) alone and in combination was identified as most predictive for later walking capacity in miSCI. Ambulatory outcome of subjects with tetraparesis was correctly predicted for 92% (WISCI II) or 100% (6minWT) of the cases when LEMS was combined with either tSSEP or the ASIA Impairment Scale, respectively. For individuals with paraparesis, prediction was less distinct, mainly due to low prediction rates for individuals with poor walking outcome. A clinical algorithm was generated that allowed for the identification of a subgroup composed of individuals with tetraparesis and poor ambulatory recovery. These data provide evidence that a combination of predictors enables a reliable prediction of walking function and early patient stratification for clinical trials in miSCI.

The purpose of the present study was to explore factors that influence the occurrence of the Babinski sign (BS) in complete spinal cord injury patients. At Balgrist University Hospital, Zurich, Switzerland, thirty-five subjects suffering from a complete traumatic spinal cord injury (ASIA A) were examined for the occurrence of the BS, tendon reflex excitability and spastic muscle tone (Modified Ashworth Scale). Five subjects were acute/subacute (1-6 months after spinal cord injury (SCI)), 30 were chronic (SCI > 1 year). In one subject, the measures were examined before and after injection of intrathecal Baclofen. Subjects with a negative BS were investigated electrophysiologically for possible peripheral nerve damage. In 17 subjects (49%), the BS was present, while it was absent in 18 subjects (51%). The occurrence of the BS did not depend on the level of lesion. Most patients with a positive BS also presented a high spastic muscle tone, while those with a negative BS showed low level or absent spastic muscle tone. In 11 SCI subjects, absence of the BS was associated with peripheral nerve damage. In one patient, the BS along with spastic signs disappeared after intrathecal injection of Baclofen. In complete SCI subjects, the occurrence of the BS is connected with spastic muscle tone. The absence of the BS is frequently due to associated peripheral nerve damage.

Advances in our understanding of the control of locomotion enable us to optimize the rehabilitation of patients with a spinal cord injury (SCI). Based on various animal models, it is generally accepted that central pattern generators (CPG) exists for the rhythmic generation of stepping movements, and that this is also the case in humans. However, in humans supraspinal control is also essential for the performance of locomotion. For regaining locomotor function, incomplete SCI subjects strongly depend on visual input to compensate for proprioceptive deficits and impaired balance. In addition, they require additional attentional capacity to stand, walk and handle their walking aids. These factors might contribute to their higher risk of falling. During the last decade, task-specific functional training performed by physiotherapists, combined with manual or robotic assisted bodyweight supported treadmill training have improved the regaining of ambulatory function in patients with incomplete SCI. At present, there is no difference in effectiveness between these three types of training. In the future, rehabilitation programs should be optimized to maximally exploit spontaneous and induced neural plasticity, leading to improved ambulation. To evaluate the efficacy of rehabilitation programs and of experimental treatments that might be translated from bench to bedside within the next few years, several objective assessments such as the 10 meter walk test and Walking Index for Spinal Cord Injury have been successfully introduced in the field of SCI rehabilitation.

The objective of this retrospective analysis was to determine whether outcome of body functions and activities as well as length of stay of inpatient rehabilitation is related to age in patients with traumatic spinal cord injury (SCI). Data were collected from a European network of 17 SCI rehabilitation centers (EM-SCI); a total of 237 traumatic SCI subjects were included. Assessments were performed at 1, 6, and 12 months after SCI. The measures analyzed were motor score according to the American Spinal Injury Association, Spinal Cord Independence Measure (SCIM), gait speed, and length of stay. Correlation analysis was applied to quantify the association between age and change in the outcome measures. A positive relationship was found between age and neurological recovery in both the first and second 6-month periods of assessment. A negative relationship was found between age and change in SCIM in the second 6-month period after SCI. A negative relationship between age and gait speed was observed in the first half year. Length of stay was not associated with age. It was concluded that age is an important determining factor for functional outcome after SCI and that elderly patients have difficulties in translating an improvement in neurological outcome into functional changes. Therefore, rehabilitation approaches in elderly subjects should focus on functional training.

A large percentage of spinal cord-injured subjects suffer from neuropathic pain below the level of the lesion (bNP). The neural mechanisms underlying this condition are not clear. The aim of this study was to elucidate the general effects of spinal deafferentiation and of bNP on electroencephalographic (EEG) activity. In addition, the relationship between the presence of bNP and impaired function of the spinothalamic tract was studied. Measurements were performed in complete and incomplete spinal cord-injured subjects with and without bNP as well as in a healthy control group. Spinothalamic tract function, assessed by contact heat evoked potentials, did not differ between subjects with and without bNP; nevertheless, it was impaired in 94% of subjects suffering from bNP. In the EEG recordings, the degree of deafferentiation was reflected in a slowing of EEG peak frequency in the 6-12-Hz band. Taking into account this unspecific effect, spinal cord-injured subjects with bNP showed significantly slower EEG activity than subjects without bNP. A discrimination analysis in the subjects with spinothalamic tract dysfunction correctly classified 84% of subjects as belonging to either the group with bNP or the group without bNP, according to their EEG peak frequency. These findings could be helpful for both the development of an objective diagnosis of bNP and for testing the effectiveness of new therapeutic agents.

During evolution, the increased influence of a direct cortical-motoneuronal system in parallel with a more specialized hand function might have replaced phylogenetically older systems that organized locomotor movements. However, recent research indicates that interlimb coordination during human locomotion is organized in a way similar to that in the cat. During locomotion, corticospinal excitation of upper-limb motoneurons is mediated indirectly, via propriospinal neurons in the cervical spinal cord. This allows a task-dependent neuronal linkage of cervical and thoracolumbar propriospinal circuits controlling leg and arm movements during human locomotor activities. During obstacle avoidance steps, an anticipatory quadrupedal limb coordination is up-regulated, with an involvement of proximal arm muscles during the acquisition and performance of this precision locomotor task.

Patients with Parkinson's disease (PD) have difficulties in performing complex bimanual movements. Here we have examined acquisition and performance of a bilateral obstacle stepping task to see whether these difficulties are also present during bipedal movements. Subjects had to minimize foot clearance when repeatedly stepping on a treadmill over randomly approaching obstacles on either side. The subjects had full vision and received acoustic feedback information about task performance. Foot clearance improved in healthy and PD subjects during the acquisition of the task. However, PD subjects showed a slower improvement and achieved a poorer performance level. Thus, in contrast to unilateral obstacle stepping, where no deficits in performance after task repetition were found in PD subjects, bilateral obstacle stepping was poorer in these subjects compared to healthy subjects. The present results extend findings from upper to lower limb movements, namely that PD subjects have difficulties in the performance of bilateral motor tasks.

Objective: This study assessed the validity and responsiveness of the Spinal Cord Independence Measure (SCIM II) items indoor mobility, mobility for moderate distances, and outdoor mobility., Methods: The data of 886 spinal cord injury subjects were derived from the European Multicenter Study for Human Spinal Cord Injury (EM-SCI) and analyzed at 2 weeks and 1, 3, 6, and 12 months after injury. The SCIM II items were compared using the preferred walking speed and the Walking Index for Spinal Cord Injury (WISCI II). The responsiveness to assess differences over time was determined. The analyses were performed for subjects with varying impairment scales according to the American Spinal Injury Association (ASIA)., Results: An initially moderate correlation between walking capacity and the SCIM II mobility items improved to excellent at 6 and 12 months after injury. The correlations were higher for indoor mobility compared with outdoor mobility. These correlations increased in ASIA C, but decreased over time in ASIA D subjects. The SCIM II mobility items showed initially positive responsiveness in ASIA A and B subjects. In ASIA C and D subjects, SCIM II responsiveness was significant within the first 6 months., Conclusions: The SCIM II items assess mobility (wheelchair and walking) during daily life. They show good validity and responsiveness, including postdischarge. They can be considered appropriate for evaluating the efficacy of new interventions on ambulatory function. Depending on the severity of the initial lesion and time of assessment, clinically applied walking tests can accurately predict walking performance during daily life.

We studied the influence of levodopa (L-Dopa) on training effects in subjects with spinal cord injury (SCI). A low-dose of L-Dopa per day is known to enhance the effects of physical training after stroke. This is tested here in subjects suffering a SCI. Twelve subacute, incomplete SCI (iSCI) subjects (ASIA C and D) were randomized in a trial with a double-blind, crossover design to receive 6 weeks of L-Dopa (200 mg), followed by 6 weeks of placebo, or vice versa. Outcome measures were ASIA Motor-Score (AMS) reflecting motor recovery; walking ability, assessed by the Walking Index of Spinal Cord Injury (WISCI); and Activities of Daily Living (ADL), as monitored by the Spinal Cord Independence Measure (SCIM). Both placebo and L-Dopa, in combination with physiotherapy, produced a significant motor recovery after SCI. The combination of L-Dopa and physiotherapy had no greater effect on the outcome than placebo and physiotherapy. The possible reasons for the different effect of L-Dopa in stroke and iSCI subjects are discussed.

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.

Background: This study investigated whether loading the legs during the swing phase of walking enhances flexor muscle activity in ambulatory patients with incomplete spinal cord injury (SCI)., Methods: Nine patients had surface electromyography (EMG) and joint kinematics recorded from the lower extremities during treadmill walking. Swing phase loading of the legs was achieved by weights (1-3 kg) attached to each lower extremity or by a velocity-dependent resistance applied by the Lokomat robotic gait orthosis., Results: When patients walked with the weights, there was a consistent increase in the activity of the knee flexors and sometimes of hip or ankle flexor activity during swing. Similarly, when the robot applied the velocity-dependent resistance during walking, swing phase flexor EMG activity tended to be greater. Enhanced knee flexion was observed in all patients after the weights or the robot-generated resistance was removed., Conclusions: Flexor muscle activity during swing can be enhanced through additional proprioceptive input in patients with incomplete SCI with brief aftereffects. Further testing of this strategy is necessary to determine if it can improve the gait of ambulatory patients.

Clinical recovery after a lesion of the central nervous system (CNS) can be attributed to mechanisms of functional compensation, neural plasticity, and/or repair. The relative impact of each of these mechanisms after a human spinal cord injury (SCI) has been explored in a prospective European multi-center study in 460 acute traumatic SCI subjects. Functional (activities of daily living and ambulatory capacity), neurological (sensory-motor deficits), and spinal conductivity (motor- and somato-sensory evoked potentials) measures were repeatedly followed over 12 months. In accordance with previous studies, complete SCI subjects (cSCI; n = 217) improved in activities of daily living unrelated to changes of the neurological condition, while incomplete SCI subjects (iSCI; n = 243) showed a greater functional and neurological recovery. The functional recovery in iSCI subjects was not related to an improvement of spinal conductivity, as reflected in unchanged latencies of the evoked potentials. This is in line with animal studies, where spinal conductivity of damaged spinal tracts has been reported to remain unchanged. These findings support the assumption that functional recovery occurs by compensation, especially in cSCI and by neural plasticity leading to a greater improvement in iSCI. Relevant repair of damaged spinal pathways does not take place.

Background: The assessment of rehabilitation efficacy in spinal cord injury (SCI) should be based on a combination of neurological and functional outcome measures. The Spinal Cord Independence Measure II (SCIM II) is an independence scale that was specifically developed for subjects with SCI. However, little is know about the changes in SCIM II scores during and after rehabilitation., Objective: The aims of this study were to evaluate changes in functional recovery during the first year after a complete SCI as measured by the SCIM II compared with neurological recovery (motor scores according to the American Spinal Injury Association [ASIA])., Methods: SCIM II data and ASIA motor scores 1, 3, 6, and 12 months after injury (derived from the database of the European Multicenter Study of Human Spinal Cord Injury) of 64 patients with complete paraplegia and 36 patients with complete quadriplegia were analyzed., Results: In patients with complete paraplegia, the SCIM II total score improved significantly during the 1-year follow-up, even after discharge from rehabilitation. In contrast, the ASIA motor scores showed little recovery. In patients with quadriplegia, functional and motor recovery developed in parallel during rehabilitation and after discharge., Conclusions: The SCIM II is responsive to functional changes in patients with a persistent motor complete SCI. It is clinically useful for monitoring functional improvement during rehabilitation and after discharge. The SCIM II and the clinical examination based on the ASIA protocol are of complementary value and separately describe changes in independence and sensorimotor deficits in SCI patients.

Objectives: Motor evoked potential (MEP) amplitudes have the disadvantage of a high variability when repeatedly assessed. This affects the reliability of MEP amplitude measurements taken during the course of motor incomplete spinal cord injury (iSCI). The study investigated the reliability of anterior tibial (TA) MEP measures controlled for dorsal flexion torque and motor task., Methods: TA MEPs were recorded at 10, 20, 40 and 60% of maximal voluntary contraction (MVC) during a static and dynamic (isometric increase of dorsal flexion torque) motor task. To determine reliability, 20 healthy and five chronic iSCI subjects were tested twice (> or =7 days) by the same investigator. Intraclass correlation coefficients (ICCs) were calculated. MEP amplitudes and latencies were compared between 20 healthy and 29 iSCI subjects., Results: The reliability of MEP amplitude was in general good (ICC > or = 0.52) and was highest during the static task at 40% MVC (ICC = 0.77). The increased facilitation by the dynamic motor task showed the best reliability at 20% MVC (ICC = 0.48). The reliability was good to excellent for MEP latency (0.46 < or = ICC < or = 0.81), MVC (ICC > or = 0.90) and for the TMS threshold required to evoke a MEP response (ICC > or = 0.77). The torque generated by the MEP response ()0.02 < or = ICC < or = 0.55) and the duration of the silent period (0.07 < or = ICC < or = 0.50) were not reliable. Both MEP amplitudes and latencies differed significantly between healthy and iSCI subjects., Conclusions: Controlling for torque generation and motor task establishes a reliability of TA MEP amplitudes that is sufficient for longitudinal assessments in motor incomplete SCI.

In clinical practice, signs of exaggerated tendon tap reflexes associated with muscle hypertonia are generally thought to be responsible for spastic movement disorders. Most antispastic treatments are, therefore, directed at the reduction of reflex activity. In recent years, however, researchers have noticed a discrepancy between spasticity as measured in the clinic and functional spastic movement disorders, which is primarily due to the different roles of reflexes in passive and active states, respectively. We now know that central motor lesions are associated with loss of supraspinal drive and defective use of afferent input with impaired behaviour of short-latency and long-latency reflexes. These changes lead to paresis and maladaptation of the movement pattern. Secondary changes in mechanical muscle fibre, collagen tissue, and tendon properties (eg, loss of sarcomeres, subclinical contractures) result in spastic muscle tone, which in part compensates for paresis and allows functional movements on a simpler level of organisation. Antispastic drugs can accentuate paresis and therefore should be applied with caution in mobile patients.

Objective: Responses to afferent input during locomotion are organized at the spinal level but modulated by supraspinal centers. The study aim was to examine whether supraspinal influences affect the behavior of complex electromyographic (EMG) responses to single limb perturbations during walking., Methods: Subjects with motor-complete (MCSCI), motor-incomplete spinal cord injury (MISCI), and non-disabled (ND) subjects participated. Hip or knee joint trajectory was briefly arrested by a robotic device at early or late swing phase. EMG responses from muscles of both legs were analyzed., Results: Perturbation-induced EMG responses of spinal cord injured and ND individuals were similar in basic structure, with the exception that tibialis anterior onset times were delayed for SCI subjects. Across all groups, perturbations in late swing (i.e., near the swing-to-stance transition) were associated with shorter muscle onset times and higher EMG amplitudes. Knee perturbations were associated with shorter muscle response onset times, while hip perturbations elicited higher response amplitudes. EMG responses were also evoked in muscles contralateral to the perturbation., Conclusions: These data indicate that neuronal circuits within the spinal cord deprived of normal supraspinal input respond to swing phase perturbations in a manner that is similar to that of the intact spinal cord., Significance: The adult human spinal cord is capable of generating complex, phase-appropriate responses much as has been observed in studies of human infants and in spinal animals.

Background: The 10-meter walk test and 6-minute walk test are increasingly used to evaluate the recovery of walking in patients with incomplete spinal cord injury. So far, there is no evidence whether the application of different walking distances provides complementary information about ambulatory capacity in patients with incomplete spinal cord injury. Studies about testing preferred and maximum speeds in subjects with incomplete spinal cord injury are lacking., Objective: To determine whether the combined testing of short and long distances as well as preferred and maximum speeds provides additional information about walking capacity in subjects with incomplete spinal cord injury., Methods: Depending on the objective, the subjects with incomplete spinal cord injury and age-matched control subjects had to perform the 10-meter walk test or 6-minute walk test at preferred and/or maximum walking speed., Results: During recovery, the preferred walking speed increased but did not differ when assessed during short or long distances in 51 subjects with incomplete spinal cord injury at 1, 3, and 6 months after injury (mean and SD, 6-minute walk test: 0.37 +/- 0.52, 0.87 +/- 0.56, and 1.14 +/- 0.52 ms( -1); 10-meter walk test: 0.40 +/- 0.53, 0.88 +/- 0.51, and 1.12 +/- 0.51 ms(-1), respectively). In 18 subjects with incomplete spinal cord injury, both preferred and maximum walking speeds assessed with the 10-meter walk test predicted the walking speeds of the 6-minute walk test well. Subjects with incomplete spinal cord injury prefer to walk closer to their maximum walking speed (74% +/- 10%) compared to control subjects (59% +/- 8%)., Conclusions: The velocity used for the 6-minute walking distance and the 10-meter walking speed provides comparable information in patients with incomplete spinal cord injury who can perform both tests. However, tests of the preferred and maximum walking speed add information about walking capacity. Due to the easier applicability of the 10-meter walk test in the clinical setting, the authors suggest performing this test at the preferred and maximum speeds for the assessment of walking capacity by 1 month after incomplete spinal cord injury.

The myelin protein Nogo-A is a potent inhibitor of neurite outgrowth in the central nervous system, thus contributing to the incapacity of fiber tracts in the adult spinal cord to regenerate after injury. In this review we report on a joint approach of different research groups to develop a therapy applying anti-Nogo-A antibodies to the injured spinal cord. While basic researchers took the initiative to provide means of neutralizing the inhibitory effect of Nogo-A and demonstrated enhanced fiber growth, regeneration and functional recovery both in rodent and primate models, clinical groups and rehabilitation engineers have sought to translate this novel strategy into a clinical setting., ((c) 2007 S. Karger AG, Basel.)

Objectives: To relate locomotor function improvement, within the first 6 months after spinal cord injury (SCI), to an increase in Lower Extremity Motor Score (LEMS) and to assess the extent to which the level of lesion influenced the outcome of ambulatory capacity., Design: Longitudinal and cross-sectional analyses., Setting: Seven SCI rehabilitation centers., Participants: Patients (N=178) were analyzed longitudinally (group A, motor complete; group B, motor incomplete; nonwalking or group C, motor incomplete and able to stand). The cross-sectional analysis included 86 patients (paraplegic, n=46; tetraplegic, n=40; group 1 with limited and group 2 with unrestricted walking function 6 mo after SCI)., Interventions: Not applicable., Main Outcome Measures: Walking Index for Spinal Cord Injury (WISCI), gait speed, and LEMS., Results: For group A, 24.8% of the patients improved in LEMS (median range, 0-10) and 7.7% in walking function (WISCI median range, 0-8; mean gait speed range, 0 to .14+/-.10 m/s). For group B, LEMS improved in 93.5% of the patients (median range, 14-28) and walking function in 84.8% of the patients (WISCI median range, 0-10; mean gait speed range, 0 to .41+/-.45 m/s) (P<.001). For group C, LEMS and walking function improved in 100% of the patients (LEMS median range, 29-41; WISCI median range, 8-16; mean gait speed range, .36+/-.29 m/s to .88+/-.44 m/s) (P=.001). In groups B and C, the improvement of walking function was greater than in LEMS. The cross-sectional analysis showed that group 1 patients with tetraplegia had more muscle strength (median LEMS, 31.5), and equal walking function (WISCI, 8; walking speed, 0.4+/-0.3 m/s) compared with patients with paraplegia (LEMS, 23; P<.01; WISCI, 12; P=0.6; speed, 0.4+/-0.3 m/s; P=.68). In group 2, patients with tetraplegia had slightly more strength (LEMS, 48) and equal walking function (WISCI, 20; walking speed, 1.4+/-0.3 m/s) compared with patients with paraplegia (LEMS, 45; P<.05; WISCI, 20; P=1.0; speed, 1.4+/-0.3 m/s; P=.89)., Conclusions: An improvement in locomotor function does not always reflect an increase in LEMS, and LEMS improvement is not necessarily associated with improved locomotor function. LEMS and ambulatory capacity are differently associated in patients with tetra- and paraplegia. Functional tests seem to complement clinical assessment.

During the past few years, several approaches to spinal-cord repair have been successfully established in animal models. For their use in trials of spinal-cord injury (SCI) in human beings, specific difficulties that affect the success of clinical trials have to be recognised. First, transection of the spinal cord is commonly applied in animal models, whereas contusion, which generally leads to injury in two to three segments, represents the typical injury mechanism in human beings. Second, the quadrupedal organisation of locomotion in animals and the more complex autonomic functions in human beings, challenge translation of animal behaviour into recovery from SCI in people. Third, the extensive damage of motor neurons and roots associated with spinal-cord contusion is not addressed in current translational studies. This damage has direct implications for rehabilitation strategies and functional outcome. Fourth, there is increasing evidence for a degradation of neuronal function below the level of the lesion in chronic complete SCI. The relevance of this degradation for a regeneration-inducing treatment needs to be investigated. Fifth, the prerequisites to enable appropriate reconnection of regenerating tract fibres in a postacute stage have still to be established.

We evaluated the acquisition and performance of a high-precision locomotor task in patients with Parkinson's disease (PD) and healthy subjects. All subjects walked on a treadmill and had to step repetitively as low as possible over an obstacle without touching it. During blocks 1 and 2, the subjects had full vision and received additional acoustic warning and feedback signals. During block 3, vision became restricted. Changes in foot clearance and the number of obstacle hits were evaluated. Initially, PD patients performed poorer and improved foot clearance slower. After task repetition, the groups performed similarly. Restricting vision deteriorated performance in both groups. The similar performance of PD patients after task repetition might indicate that adequate training could improve adaptive locomotor behavior in PD patients., ((c) 2005 Movement Disorder Society.)

The aim of this study was to examine the strategies used by human subjects to adapt their walking pattern to a velocity-dependent resistance applied against hip and knee movements. Subjects first walked on a treadmill with their lower limbs strapped to an exoskeletal robotic gait orthosis with no resistance against leg motions (null condition). Afterward, a velocity-dependent resistance was applied against left hip and knee movements (force condition). Catch trials were interspersed throughout the experiment to track the development of adaptive changes in the walking pattern. After 188 steps in the force condition, subjects continued to step in the null condition for another 100 steps (washout period). Leg muscle activity and joint kinematics were recorded and analyzed. The adaptive modifications in the locomotor pattern suggest the involvement of both feedback and feedforward control strategies. Feedback-driven adaptations were reflected in increases in rectus femoris and tibialis anterior activity during swing, which occurred immediately, only in the presence of resistance, and not during the catch trials. Locomotor adaptations involving feedforward strategies were reflected in enhanced pre-swing activity in the biceps femoris and medial hamstrings muscles, which required experience and persisted in the catch trials. During washout subjects showed a gradual deadaptation of locomotor activity to control levels. In summary, adaptive changes in the walking pattern were driven by both feedback and feedforward adjustments in the walking pattern appropriate for overcoming the effects of resistance.

Objectives: To improve the diagnosis of damaged spinal motor pathways in incomplete spinal cord injury (iSCI) by assessing the facilitation of lower limbs motor evoked potentials (MEP)., Methods: Control subjects (n = 12) and iSCI patients (n = 21) performed static and dynamic isometric foot dorsiflexions. MEPs induced by transcranial magnetic stimulation and EMG background of tibialis anterior muscle (TA) were analyzed. Static and dynamic muscle activation was performed at comparable levels of maximal voluntary contraction (MVC). The influence of the motor tasks on the excitability and facilitation of MEPs was compared between controls and iSCI patients., Results: In the controls an increased facilitation of TA MEP at lower levels of dynamic compared with static activation (10-20% MVC) could be shown. At matched EMG background level the MEP responses were significantly increased. In the iSCI patients at a comparable level of TA activation the MEP responses were significantly reduced and 3 different patterns of MEP responses could be distinguished: i) preserved increment of TA MEP in the dynamic motor task, ii) unchanged MEP size in the dynamic and static motor task, and iii) elicitable MEPs in the dynamic motor task,which were abolished in the static motor task., Conclusions: Static and dynamic motor tasks have different effects on TA MEP facilitation. The task-dependent modulation of TA MEPs is comparable to that described for upper limb muscles. Complementary to the MEP delay this approach allows for an estimation of the severity of spinal tract damage. The task-dependent modulation of TA MEPs is an additional diagnostic tool to improve the assessment and monitoring of motor function in iSCI.

Task-oriented repetitive movements can improve motor performance in patients with neurological or orthopaedic lesions. The application of robotics and automation technology can serve to assist, enhance, evaluate, and document neurological and orthopedic rehabilitation. This paper deals with the application of "patient-cooperative" techniques to robot-aided gait rehabilitation of neurological disorders. We define patient-cooperative to mean that, during movement, the technical system takes into account the patient's intention and voluntary efforts rather than imposing any predefined movements or inflexible strategies. It is hypothesized that such cooperative robotic approaches can improve the therapeutic outcome compared to classical rehabilitation strategies. New cooperative strategies are presented that detect the patient's voluntary efforts. First, this enables the patient increased freedom of movement by a certain amount of robot compliance. Second, the robot behavior adapts to the existing voluntary motor abilities. And third, the robotic system displays and improves the patient contribution by visual biofeedback. Initial experimental results are presented to evaluate the basic principle and technical function of proposed approaches. Further improvements of the technical design and additional clinical testing is required to prove whether the therapeutic outcome can be enhanced by such cooperative strategies.

Objective: To determine whether automated locomotor training with a driven-gait orthosis (DGO) can increase functional mobility in people with chronic, motor incomplete spinal cord injury (SCI)., Design: Repeated assessment of the same patients or single-case experimental A-B design., Setting: Research units of rehabilitation hospitals in Chicago; Heidelberg, Germany; and Basel and Zurich, Switzerland., Participants: Twenty patients with a chronic (>2 y postinjury), motor incomplete SCI, classified by the American Spinal Injury Association (ASIA) Impairment Scale with ASIA grades C (n=9) and D (n=11) injury. Most patients (n=16) were ambulatory before locomotor training., Intervention: Locomotor training was provided using robotic-assisted, body-weight-supported treadmill training 3 to 5 times a week over 8 weeks. Single training sessions lasted up to 45 minutes of total walking time, with gait speed between .42 and .69 m/s and body-weight unloading as low as possible (mean +/- standard deviation, 37%+/-17%)., Main Outcome Measures: Primary outcome measures included the 10-meter walk test, the 6-minute walk test, the Timed Up & Go test, and the Walking Index for Spinal Cord Injury-II tests. Secondary measures included lower-extremity motor scores and spastic motor behaviors to assess their potential contribution to changes in locomotor function. All subjects were tested before, during, and after training., Results: Locomotor training using the DGO resulted in significant improvements in the subjects' gait velocity, endurance, and performance of functional tasks. There were no significant changes in the requirement of walking aids, orthoses, or external physical assistance. There was no correlation between improvements in walking speed or changes in muscle strength or spastic motor behaviors., Conclusions: Intensive locomotor training on a treadmill with the assistance of a DGO results in improved overground walking.

Objective: To assess the validity and reliability of 3 timed walking tests (Timed Up & Go [TUG], 10-meter walk test [10MWT], 6-minute walk test) in subjects with spinal cord injury (SCI)., Design: Cross-sectional study and repeated assessments., Setting: The SCI center of a university hospital in Switzerland., Participants: Validity was assessed by using the data of 75 patients with SCI, and reliability was determined with 22 patients with SCI., Intervention: Patients performed the timed tests and the Walking Index for Spinal Cord Injury II (WISCI II) on the same day. Three measurements within 7 days were taken to assess reliability., Main Outcome Measures: The measures were scatterplots, correlation coefficients ( r ), and the Bland-Altman plot. Validity was determined in patients with different walking abilities., Results: Overall, correlation of the 3 timed walking tests was excellent with each other (| r |>.88) and moderate with the WISCI II (| r |>.60). The correlation between the timed tests for patients with poor walking ability remained high (| r |>.70) but decreased in WISCI II (| r |<.35). High correlation coefficients ( r >.97) were found for intra- and interrater reliability. However, TUG and 10MWT reliability were negatively influenced by a poor walking function., Conclusions: The 3 timed tests are valid and reliable measures for assessing walking function in patients with SCI.

In reduced animal preparation (cat fictive locomotion) most of our knowledge on the phase-dependent modulation of cutaneous reflexes concerns early- (P1 responses) rather than medium-latency (P2) responses. In contrast, in humans, virtually only P2 responses have been studied because P1 responses are relatively rare in adults. In this work, human P1 and P2 responses following sural nerve stimulation were compared in BF (biceps femoris). Some 14% of all subjects showed P1 responses, which could be either suppressive or facilitatory. The suppressive responses were most common, and they occurred primarily at end swing. When a subject showed both suppressive P1 and P2 responses, the P2 suppressions were stronger than the P1 suppressions (as measured in the same phase at end swing). However, the P2 suppressions were less consistent across subjects than the P1 suppressions. In some subjects, there were also facilitatory P1 responses, mostly throughout stance (when facilitatory P2 responses occur as well). These facilitatory P1 responses were consistent across experimental conditions in these subjects. Similar to the cat, the facilitatory P1 responses were much smaller than the facilitatory P2 responses. It is concluded that P1 and P2 reflexes can appear independently from each other, but that their modulation in the step cycle is mostly quite similar in some phases of the step cycle (end swing).