[Evidence-based rehabilitation of mobility after stroke]. / Evidenzbasierte Rehabilitation der Mobilität nach Schlaganfall.

BACKGROUND: Approximately two thirds of stroke patients initially suffer from at least impaired mobility. Various rehabilitation concepts have been proposed. OBJECTIVE: Based on the current literature, which rehabilitation methods can be recommended for improvement of gait, gait velocity, gait distance and balance? METHODS: A systematic literature search was carried out for randomized clinical studies and reviews with clinically relevant outcome variables. Formulation of recommendations, separated for target variables and time after stroke. RESULTS: Restoration and improvement of gait function relies on a high number of repetitions of gait movements, which for more severely affected patients is preferentially machine-based. For improvement of gait velocity for less severely affected patients intensive gait training does not necessarily rely on mechanical support. Gait distance can be improved by aerobic endurance exercises with a cardiovascular effect, which have to be performed in a functional context. Improvement of balance should be achieved by intensive functional gait training. Additional stimulation techniques are only effective when included in a functionally relevant training program. DISCUSSION: These guidelines not only provide recommendations for action but also provide pathophysiological insights into functional restoration of stance and gait after stroke.

Gene knockout and knockin by zinc-finger nucleases: current status and perspectives.

Zinc-finger nucleases (ZFNs) are engineered site-specific DNA cleavage enzymes that may be designed to recognize long target sites and thus cut DNA with high specificity. ZFNs mediate permanent and targeted genetic alteration via induction of a double-strand break at a specific genomic site. Compared to conventional homology-based gene targeting, ZFNs can increase the targeting rate by up to 100,000-fold; gene disruption via mutagenic DNA repair is similarly efficient. The utility of ZFNs has been shown in many organisms, including insects, amphibians, plants, nematodes, and several mammals, including humans. This broad range of tractable species renders ZFNs a useful tool for improving the understanding of complex physiological systems, to produce transgenic animals, cell lines, and plants, and to treat human disease.

Control mechanisms for restoring posture and movements in paraplegics.

The control mechanisms underlying undisturbed movements were analysed in two series of experiments: (1) normal physiological responses were investigated in neurologically intact subjects; (2) an artificial motor control system for paraplegic patients using functional neuromuscular stimulation (FNS) of the paralysed leg muscles was developed and tested. In both series of experiments standing-up from a chair and sitting-down were studied. A three-link model of the human body was used for recording and processing biomechanical data. In 5 normal subjects ground reaction forces and the surface electromyogram of different leg muscles were also recorded. Basic physiological aspects of FNS such as muscle force regulation and fatigue could be documented. For the standing-up and sitting-down experiments in 2 paraplegic patients the gluteal and quadriceps muscles were stimulated. The best results were achieved with a combination of open-loop and closed-loop stimulation with position and velocity feedback. The importance of feedforward and feedback control during undisturbed movements is discussed for natural and artificial motor control systems. It is concluded that the control of knee joint angle during standing-up and sitting-down represents an unstable system which cannot be controlled open-loop only. Different aspects of sensory feedback including the regulated variables, gain and stability of the system are discussed on the basis of the experimental data and the literature.

Stumbling reactions in man: release of a ballistic movement pattern.

Four different modes of perturbation were applied during gait, either alone or in combination, in order to determine the extent to which compensatory reactions in the leg are released as fixed patterns or, alternatively, are generated by feedback mechanisms. The first agonist burst of the usually triphasic pattern evoked by a perturbation was unchanged in amplitude and timing when a second disturbance of an opposite sense was induced a short time later. Following this burst, the remainder of the response evoked by the second disturbance appeared time locked to the second stimulus and was unchanged in form. It is concluded, that the first agonist burst induced by a perturbation is stimulus specific and immutable after release, while the appearance of the following bursts of the triphasic pattern is dependent on the actual conditions. This suggests that a similar mechanism as assumed for ballistic hand and finger movements is operative, with the difference that the compensatory reactions following gait perturbations are induced by peripheral signals.

Obstruction of the swing phase during gait: phase-dependent bilateral leg muscle coordination.

We have investigated bilateral leg muscle activation following an obstruction of the forward swinging leg during gait. When the holding impulse was released at the beginning of the swing phase, weak gastrocnemius (GM) and biceps femoris (BF) responses appeared in the contralateral, standing leg. When the holding impulse was released at the end of the swing phase, strong tibialis anterior (TA) and rectus femoris (RF) responses appeared in the swinging leg, and GM and BF responses in the standing leg. In the latter condition the TA response was followed by a premature impact associated with a GM activation. The latency between onset of impulse and appearance of the responses was 65-70 ms in both legs. While in the first condition the duration of GM and BF response corresponded to the duration of the impulse, it was independent for the duration of GM and BF response in the latter. It is concluded that different strategies for compensation are at work. In the first condition, body stability is maintained during the obstruction by the standing leg. In the second condition, body support is provided by a premature touchdown of the swinging leg. It is suggested that the appropriate pattern is, in part, released by a spinal generator.

Compensatory reactions to gait perturbations in man: short- and long-term effects of neuronal adaptation.

Short- and long-term changes in the cerebral potentials and the electromyographic (EMG) responses in the arms and legs evoked by gait perturbations were followed up over repeated trials in healthy subjects. Two different modes of muscle activation could be discerned. The first adapted to the specific motor task within a few trials and remained constant during the remaining experiments. This 'hard wired' and complex leg muscle reaction was shown to be task specific and necessary for an adequate compensation for the displacement. It was supposed that this reaction is mediated via a spinal pathway. The other mode, which included an early arm extension, disappeared successively as the motor task became familiar. These flexible EMG responses represent the 'protective' part of the reaction and are suggested to be mediated via a transcortical pathway, due to their close relationship to the cerebral potentials evoked by the perturbations.

Neuronal control of ballistic finger movements in man: task specific electromyographic patterns.

The electromyographic (EMG) patterns of finger flexor and extensor muscles have been studied during ballistic finger movements in three different conditions: (1) rapid isotonic finger flexion; (2) throwing and (3) catching a tennis ball. In 1 and 2 a three-burst pattern was observed. In the latter, the first agonist burst was shorter and of higher amplitude compared to condition 1. Catching a ball was connected with a coactivation of extensor and flexor muscles prior to and during ball contact and a contribution of segmental stretch reflexes to the flexor activation. The finger flexion movement was 10-15 times faster than in conditions 1 and 2. After ischaemic blocking of group I afferents and in patients with rigidity, a short inhibition of the increased extensor activation became predominant and was the basic mechanism underlying finger flexion for catching a ball. It is concluded that in natural ballistic finger movements, other neuronal mechanisms are of functional significance than those seen in the usual experimental paradigms.

Task-dependent gating of somatosensory transmission in two different motor tasks in man: falling and writing.

The cerebral potentials induced by an electrical stimulus (median nerve or finger) were recorded over the central region of the scalp and were analysed during falling onto the extended arms or during writing to investigate the influence of different motor tasks on the transmission of a synchronous afferent volley to the brain. During both falling (before landing) and writing, the first peaks (20-40 ms) were reduced. Later peaks (60-200 ms) were enhanced during writing but reduced during falling. A reduction of the first peak was also obtained after ischaemic blockade of group I afferents, suggesting that the cerebral transmission of group I afferents is inhibited during falling and writing. The subjects reported a corresponding reduction in the perception of the stimulus during falling. During writing, however, the large late waves indicate a task specific processing of the remaining afferent volley. Such a gating of sensory information to the brain is assumed to play a functional role in the respective motor tasks.

Cerebral evoked potentials associated with the compensatory reactions following stance and gait perturbation.

We have studied the gastrocnemius electromyographic (EMG) responses and the cerebral potentials evoked in normal subjects by perturbations of stance and gait in the form of short treadmill acceleration impulses. In the stance condition a small EMG response (LM1; latency around 40 ms) was followed by a strong muscle activation (LM2; latency 75-90 ms). Following perturbation during gait, LM1 was lacking and LM2 appeared a little earlier (65-75 ms). In the stance condition, the cerebral potentials appeared with shorter latency (42 ms as compared to 83 ms) and a larger amplitude (41 microV as compared to 21 microV) than those seen in the gait condition. These changes can be explained by a presynaptic inhibition of group I afferent signals during gait, which are assumed to be responsible for the early EMG and EEG responses. It is suggested that the LM2 and the cerebral responses evoked by gait perturbation are mediated by signals from group II and III afferents.

Corrective reactions to stumbling in man: functional significance of spinal and transcortical reflexes.

Stumbling reactions were studied in terms of bilateral leg muscle electromyographic (EMG) responses during locomotion on a treadmill. At random times, but fixed points in the stepping cycle, short impulses were applied to the treadmill, either accelerating or decelerating its progress. It was found that acceleration was compensated for by a strong ipsilateral gastrocnemius and contralateral tibialis anterior activation, and deceleration by a bilateral tibialis anterior activation. In both muscles the responses appeared with a latency of about 70 msec and lasted for about 150 msec. It is concluded that sudden displacements induced by acceleration or deceleration during gait are compensated for by a polysynaptic spinal pathway, with an associated depression of monosynaptic responses.

Motor unit involvement in spastic paresis. Relationship between leg muscle activation and histochemistry.

In 4 patients with spastic hemiparesis the electromyograms (EMG) of leg muscles were recorded during walking and the gastrocnemius medialis on both sides was investigated by histochemistry and morphometry. During walking a reciprocal mode of muscle activation was preserved on the spastic side, but the EMG amplitude was reduced. In one patient the discharge behaviour of single motor units was investigated during stance. The mean discharge rate on both the spastic and the unaffected side amounted to about 5.5 Hz. Modification of this rate over a wider range by manoeuvres of the trunk was only observed on the unaffected side. Histochemistry and morphometry of the spastic muscle revealed: Increased levels of muscle fibre atrophy (especially type II); A predominance of type I fibres during later stages, when spasticity was established; Structural changes, such as the appearance of target fibres, mainly in type I fibres. These results suggest that the low level of tonic activation in spastic muscle develops tension enough during the stance phase of gait to support the body. The histopathological profile of the spastic gastrocnemius muscle is considered to be indicative of denervation, due to the combined effects of an impaired supraspinal control of the lower motoneurone and a concurrent transsynaptic muscle membrane dysfunction, muscle cell atrophy and fibre type transformation.

Influence of visual and proprioceptive afferences on upper limb ataxia in patients with multiple sclerosis.

Our objective was to investigate how cooling of the arm and vision influence pointing movements in healthy subjects and patients with cerebellar limb ataxia due to clinically proven multiple sclerosis. An infrared video motion analysis system was used to record the unrestricted, horizontal pointing movements toward a target under three different conditions involving a moving, stationary, or imaginary target; a visual, or acoustic trigger; and vision or memory guidance. All three tasks were performed before and after cooling the arm in ice water. Patients had more hypermetric and slower pointing movements than controls under all tested conditions. Patients also had significantly larger three-dimensional finger sway paths during the postural phase and larger movement angles of the wrist joint. Memory-guided movements were the most hypermetric recorded in both groups. Cooling of the limb had no effect on amplitude or peak velocity of the pointing movement in either group under all tested conditions, but significantly reduced the three-dimensional finger sway path during the postural phase in patients with limb ataxia. Cooling-induced reduction of the finger sway was largest in those patients with the largest finger sway before cooling. In conclusion, the cooling-induced reduction of the proprioceptive afferent inflow, most probably of group I spindle afferents, reduces postural tremor of patients with cerebellar dysfunction.

Model-based control of FES-induced single joint movements.

A crucial issue of functional electrical stimulation (FES) is the control of motor function by the artificial activation of paralyzed muscles. Major problems that limit the success of current FES systems are the nonlinearity of the target system and the rapid change of muscle properties due to fatigue. In this study, four different strategies, including an adaptive algorithm, to control the movement of the freely swinging shank were developed on the basis of computer simulations and experimentally evaluated on two subjects with paraplegia due to a complete thoracic spinal cord injury. After developing a nonlinear, physiologically based model describing the dynamic behavior of the knee joint and muscles, an open-loop approach, a closed-loop approach, and a combination of both were tested. In order to automate the individual adjustments cited above, we further evaluated the performances of an adaptive feedforward controller. The two parameters chosen for the adaptation were the threshold pulse width and the scaling factor for adjusting the active moment produced by the stimulated muscle to the fitness of the muscle. These parameters have been chosen because of their significant time variability. The first three controllers with fixed parameters yielded satisfactory result. An additional improvement was achieved by applying the adaptive algorithm that could cope with problems due to muscle fatigue, thus permitting on-line identification of critical parameters of the plant. Although the present study is limited to a simplified experimental setup, its applicability to more complex and functional movements can be expected.

Biomechanical model of the human knee evaluated by neuromuscular stimulation.

A detailed model of the human knee was developed to predict shank motion induced by functional neuromuscular stimulation (FNS). A discrete-time model is used to characterize the relationship between stimulus parameters and muscle activation. A Hill-based model of the musculotendon actuator accounts for nonlinear static and dynamic properties of both muscle and tendon. Muscle fatigue and passive muscle viscosity are modeled in detail. Moment arms are computed from musculotendon paths of 13 actuators and from joint geometry. The model also takes nonlinear body-segmental dynamics into consideration. The simulated motion is visualized by graphic animation. Individual model parameters were identified by specific procedures such as anthropometric measurements, a passive pendulum test, and specific open-loop stimulation experiments. Model results were compared with experimental data obtained by stimulating the quadriceps muscle of paraplegic patients with surface electrodes. The knee moment, under isometric conditions, and the knee angle, under conditions of freely swinging shank, were measured. In view of the good correspondence obtained between model predictions and experimental data, we conclude that a biomechanical model of human motion induced by FNS can be used as a mathematical tool to support and accelerate the development of neural prostheses.

Analysis of passive elastic joint moments in paraplegics.

In the functional electrical stimulation of the lower extremity of paraplegics to achieve standing and walking, a mathematical model describing the passive elastic joint moments is essential in order to implement model-based control algorithms. In a previous investigation of ten normal persons we had found significant coupling of passive, elastic joint moments between neighboring joints due to muscle groups that span both joints (biarticular muscles). Thus, we now investigated the biarticular coupling in six paraplegic patients. A comparison to the averaged results of the ten normal persons showed that while the biarticular joint moment coupling due to the gastrocnemius muscle was well preserved in all patients, the coupling due to the rectus femoris was greatly reduced and the coupling due to the hamstring muscle group was negligible. We offer pathophysiologically based explanations for these characteristic differences including the speculation that the predominantly extensor-type spasticity in our patients exercises mainly the anti-gravity muscles such as the gastrocnemius and the rectus femoris, while permitting greater atrophy of the hamstring muscle group. A previously presented double-exponential equation that predicts the joint moments under consideration of the neighboring joint angles could be fitted well to the experimental data.

Instrumented staircase for ground reaction measurement.

A staircase was developed to record ground reactions during stair climbing at different slopes (inclinations). Each step is instrumented with six strain-gauge-based force transducers which allow the measurement of three-dimensional ground reaction force and moment as well as the centre of pressure (COP) location. A specific sensor arrangement permits accurate recording, especially of the COP location. The overall design of the staircase and details of a single instrumented step are presented. Static and dynamic characteristics have been evaluated by different experimental procedures. Preliminary results of ground reaction forces are shown.

[The electrical stimulation bicycle: a neuroprosthesis for the everyday use of paraplegic patients]. / Das Elektrostimulationsfahrrad als Neuroprothese. Querschnittgelähmte Patienten mit dem Fahrrad unterwegs.

Until recently, few patients with complete paraplegia could walk or stand with the help of functional electrical stimulation (FES) of the leg muscles regularly at home. In comparison, FES cycling with an adapted tricycle is easy to put into practice because the legs remain connected to the pedals and through the use of a tricycle or stationary bicycle, the balancing problems of the patient recedes into the background. In the first German feasibility studies for paraplegic cycling, eleven completely paraplegic patients have been tested so far. The goal is to make FES cycling a daily activity in the lives of as many patients as possible.

Afferent and efferent control of stance and gait: developmental changes in children.

Comparisons were made between the cerebral potentials (CPs) and EMG responses of leg muscles evoked by perturbation impulses during stance and gait in normal children aged from 1 to 10 years. Changes in the efferent arm of the reflex systems during development were reflected in parallel changes with age of the afferent system, expressed in the CP: in the youngest children (1-2 years of age) monosynaptic stretch reflex potentials appeared following perturbations during both stance and gait, together with a reduced level of longer latency EMG responses. The CP, too, had a profile that did not, at this early stage, differ in either condition. In children from 6 to 10 years of age, the adult pattern was reached, with the suppression of monosynaptic stretch reflexes and the early part of the CP during gait perturbation. This is interpreted as an inhibition of group I afferents at both segmental and supraspinal levels, involving suppression of both segmental stretch reflexes and group I signals to supraspinal centres. This control of afferent information had yet to be established in early infancy. The age group from 2 to 6 years showed progressive changes, with an increase in both the level and phasic nature of polysynaptic EMG responses and a corresponding transformation of the latency and shape of the CP. It is suggested that maturation of compensatory EMG responses during gait is achieved by the establishment of descending inhibition of group I afferents and facilitation of polysynaptic spinal reflexes via group II afferents.

Comparison of simulation and experiments of different closed-loop strategies for functional electrical stimulation: experiments in paraplegics.

Open-loop and closed-loop stimulation of the knee extensors for the control of the knee joint angle and torque were tested as a potential basis for more complex functional electrical stimulation (FES) systems to be used in human locomotion. The output of the biomechanical simulation model described previously was compared with stimulation experiments in patients with complete thoracic spinal cord injury. Good correspondence between simulation and experiments was obtained under both isometric conditions and conditions with a freely swinging shank. For closed-loop control, a simple proportional integral derivative (PID) controller yielded sufficient performance only under isometric conditions, especially if combined with (linear) feedforward. Because of additional nonlinearities of musculotendon and body segmental dynamics, more complex strategies have to be applied to the control of unconstrained movements. To compensate for these nonlinearities, an inverse model was derived from the direct biomechanical model. This inverse model had satisfactory agreement between the measured knee angle and the desired trajectory already under open-loop conditions. A combination of the inverse model in the feedforward part of the control loop and a PID controller provided robust and precise control of the knee angle. Further improvement may be achieved by including elements of spasticity into the simulation model and by controlling both agonistic and antagonistic muscles.