[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.

[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.

[Paraplegic cycling using functional electrical stimulation. Experimental and model-based study of power output]. / Fahrradfahren Querschnittgelähmter mittels funktioneller Elektrostimulation. Eine experimentelle und modellbasierte Untersuchung der Leistungsabgabe.

Cycling using functional electrical stimulation offers paraplegics the possibility of muscle and cardiovascular training as well as the chance for independent locomotion. To investigate whether this method might be suitable for a large group of paraplegics, the first German feasibility study of functional electrical stimulation (FES) cycling with seven paraplegic patients was started at the beginning of 2003. Even at the beginning of the study, and without training, these patients were able to drive distances of 0.5-1.6 km. To stimulate cardiovascular adaptation processes in the case of FES ergometer training or to cover useful distances in the case of FES cycling, a minimum amount of generated mechanical output power is required, which as a rule cannot be achieved yet. In this study, we point out two particular aspects of FES cycling, which impair power output: prolonged fatigue mode and viscous joint friction of the paraplegic FES cyclist. We discuss current possibilities for increasing output power and endurance.

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.

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.

Different postural reaction patterns for expected and unexpected perturbations in patients with idiopathic Parkinson's disease and other parkinsonian syndromes.

Different postural reaction patterns after predictable and unpredictable perturbations during free stance were studied in 8 patients with idiopathic Parkinson's disease (iPD), in 4 patients with other parkinsonian syndromes (PS) and in 5 healthy controls. First, the amplitude of leaning maximally backward and forward was measured (condition I). Secondly, the body equilibrium was disturbed by self-paced, predictable, rapid arm elevations (condition II) and by sudden unpredictable toe-down and toe-up rotations of a supporting platform (condition III). Patients with PS particularly had difficulties in regaining body equilibrium after unexpected perturbations. In controls and patients with PS, unpredictable disturbances were better compensated in toe-down than in toe-up direction, whereas the opposite was true for patients with iPD. These results correspond to the fact that patients with PS had a specific leaning-backward impairment and patients with iPD, a leaning-forward impairment. The authors conclude that the differences in postural stability between patients with iPD and PS are caused by different pathophysiological mechanisms. These differences in postural stability could serve as an additional tool for differential diagnosis.

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.

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.

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.

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.

Functional neuromuscular stimulation for standing after spinal cord injury.

A study was undertaken to determine if functional neuromuscular stimulation could be used to obtain standing in patients with traumatic spinal cord injury. Twenty-five subjects were selected during the study, and standing was accomplished in 21 using bilateral quadriceps stimulation with the hips in hyperextension. Four subjects elected not to continue participation to the point of standing. Stimulation parameters were 0 to 120V pulse amplitude, frequency 13Hz or 20Hz, and pulse width of 0.4msec. Confirmation of standing with support of 95% of the body weight by the legs was verified by quantitative measurements with a dual-scale force platform or a biomechanics force platform. Subjects initially selected had injury levels between C7 and T11 and ranged in age from 22 to 47 years, with duration of injury from one to 13 years. The subjects had complete lesions, with no active motor function below the last normal level, and absent sensation or partial sparing of sensation with vague perception of pinprick, but no position sense. Six subjects stood at home and 15 stood only in the laboratory. This five-year experience indicates that paraplegic individuals may obtain standing with functional neuromuscular stimulation.

Visual postural performance in ametropia and with optical distortion produced by bifocals and multifocals.

Visual stabilization of posture depends strongly on the performance of the visual system and declines with experimentally induced reduction of visual image quality. We studied postural performance in subjects with median and high grade hyperopia or myopia. While body sway of median grade ametropic subjects increased slightly when measured without glasses, high grade ametropia showed no significant differences between postural performance with glasses on and off. We concluded that the increase in visual acuity when wearing glasses is outweighted by concurrent dioptric distortions such as size change and prismatic effects. In addition we could not find any difference between bifocal and multifocal lenses in their effect on sway when investigated in normals with either steady fixation or saccades or foveal pursuit.

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: significance of proprioceptive and pre-programmed mechanisms.

1. Electromyogram (e.m.g.) responses of the leg musculature and the corresponding joint movements were studied following a perturbation of the limb during walking on a treadmill, produced by a randomly timed treadmill acceleration impulse, either predictable, or unpredictable in its amplitude and rate of acceleration. 2. The rate of rise of ipsilateral gastrocnemius e.m.g. response following a perturbation was dependent on the rate of treadmill acceleration. For a given acceleration rate the amplitude of the e.m.g. response and the timing of its peak was dependent on the amplitude of the impulse and the rate of rise of the gastrocnemius response was the same for impulses of both small and large amplitude. The onset latency was shorter (65 ms) for high accelerations and longer (85 ms) for lower ones. 3. The amplitude of the ipsilateral biceps femoris response was much smaller than the gastrocnemius response but was larger following unpredictable than predictable impulses. 4. The initial gastrocnemius response was followed by a tibialis anterior activation associated with a gastrocnemius depression and sometimes with a second, weak gastrocnemius activation. The gastrocnemius depression ended within a fixed time range relative to the onset of the response. The tibialis anterior activation was most pronounced when unpredictable impulses with high acceleration but a small amplitude were induced. 5. It is concluded that generation of the first gastrocnemius response is obviously under continuous control by muscle proprioceptive information and can be best described in terms of a stretch reflex response. It is suggested that, on the evidence of the diphasic or triphasic e.m.g. pattern, a close interaction occurs between a central programme and muscle proprioceptive input in order to generate the appropriate e.m.g. pattern. 6. On the basis of earlier work (Berger, Dietz & Quintern, 1984a) and on the present results it is suggested that the e.m.g. responses may be mediated mainly by muscle proprioceptive input from group II afferents. This input is modulated and processed by spinal interneuronal circuits, closely connected with spinal locomotor centres. The mode of processing depends on various factors, such as the predictability of the nature of the impulse.

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.

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.

[Orthostatic tremor: clinical aspects, pathophysiology and therapy]. / Orthostatischer Tremor: Klinik, Pathophysiologie und Therapie.

Orthostatic tremor is characterized by its isolated occurrence in leg and trunk muscles during standing with undisturbed sitting, lying and walking. In a female patient with this tremor syndrome the basic electrophysiological feature of muscle activity was a 16 Hz, highly synchronized tremor in all leg muscles and sometimes in the arm muscles. This rhythmic EMG activity however, was not restricted to stance but occurred during all kinds of muscle activation in sitting, lying or standing positions, despite only standing was accompanied by a subjective sensation of unsteadiness and falling to the ground. Mechanical tremor analysis at the patella revealed an additional 8 Hz tremor caused by alternating large and small amplitudes of the 16 Hz tremor bursts. The occurrence of the 8 Hz tremor was much more related to the feeling of unsteadiness than the 16 Hz tremor. Single motor units mostly fired at a frequency of 8 Hz, but only at the time of tremor bursts. Hence the 16 Hz-pattern may not be explained as the result of a pure motoneuronal abnormality. There were no indications for abnormal reflexes contributing to tremor genesis. A fixed time relation of the tremor bursts in different muscles has been found suggesting a common generator within the CNS for the tremor. After successfully treatment with Primidon the pattern of muscle activation was normalized during sitting and lying, however, during standing and walking the 16 Hz tremor was still present. We believe that an unknown central oscillator is causing the tremor and central structures which are involved in stance regulation have a predominant access to switch on this oscillator.