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Biomedical subjects

Helmut Kern

Publications and source records attributed to Helmut Kern.

14 recordsLinked to original sources

Posterior root-muscle reflexes elicited by transcutaneous stimulation of the human lumbosacral cord.

Continuous epidural stimulation of lumbar posterior root afferents can modify the activity of lumbar cord networks and motoneurons, resulting in suppression of spasticity or elicitation of locomotor-like movements in spinal cord-injured people. The aim of the present study was to demonstrate that posterior root afferents can also be depolarized by transcutaneous stimulation with moderate stimulus intensities. In healthy subjects, single stimuli applied through surface electrodes placed over the T11-T12 vertebrae with a mean intensity of 28.6 V elicited simultaneous, bilateral monosynaptic reflexes in quadriceps, hamstrings, tibialis anterior, and triceps surae by depolarization of lumbosacral posterior root fibers. The nature of these posterior root-muscle reflexes was demonstrated by the duration of the refractory period, and by modifying the responses with vibration and active and passive movements. Stimulation over the L4-L5 vertebrae selectively depolarized posterior root fibers or additionally activated anterior root fibers within the cauda equina depending on stimulus intensity. Transcutaneous posterior root stimulation with single pulses allows neurophysiological studies of state- and task-dependent modulations of monosynaptic reflexes at multiple segmental levels. Continuous transcutaneous posterior root stimulation represents a novel, non-invasive, neuromodulative approach for individuals with different neurological disorders.

Adult↗

Recovery of long-term denervated human muscles induced by electrical stimulation.

We investigated the restorative potential of intensive electrical stimulation in a patient with long-standing quadriceps denervation. Stimulation started 18 months after injury. After 26 months, the thighs were visibly less wasted. Muscle cross-sectional areas, measured by computerized tomography, increased from 36.0 cm(2) to 57.9 cm(2) (right) and from 36.1 cm(2) to 52.4 cm(2) (left). Knee torque had become sufficient to maintain standing without upper extremity support. Biopsies revealed evidence of both growth and regeneration of myofibers. The results suggest that electrical stimulation may offer a route to the future development of mobility aids in patients with lower motor neuron lesions.

Cauda Equina↗

Muscle fiber regeneration in human permanent lower motoneuron denervation: relevance to safety and effectiveness of FES-training, which induces muscle recovery in SCI subjects.

Morphologic characteristics of the long-term denervated muscle in animals suggest that some original fibers are lost and some of those seen are the result of repeated cycles of fiber regeneration. Muscle biopsies from lower motoneuron denervated patients enrolled in the EU Project RISE show the characteristics of long-term denervation. They present a few atrophic or severely atrophic myofibers dispersed among adipocytes and connective tissue (denervated degenerated muscle, DDM). Monoclonal antibody for embryonic myosin shows that regenerative events are present from 1- to 37-years postspinal cord injury (SCI). After 2- to 10-years FES-training the muscle cryosections present mainly large round myofibers. In the FES-trained muscles the regenerative events are present, but at a lower rate than long-term denervated muscles (myofiber per mm2 of cryosection area: 0.8 +/- 1.3 in FES vs. 2.3 +/- 2.3 in DDM, mean +/- SD, P = 0.011). In our opinion this is a sound additional evidence of effectiveness of the Kern's electrical stimulation protocol for FES of DDM. In any case, the overall results demonstrate that the FES-training is safe: at least it does not induce more myofiber damage/regeneration than denervation per se.

Electric Stimulation↗

Electrical stimulation of denervated muscles: first results of a clinical study.

To evaluate the effects of electrical stimulation on denervated muscles in spinal cord injured humans, the EU Project RISE was started in 2001. The aims of this project are: to design and build sufficient stimulators; to develop stimulation protocols by means of mathematical models, animal experiments, and practice in humans with denervated lower limbs; to develop examination methods and devices for evaluation of electrical stimulation training effects; and to acquire basic scientific knowledge on denervated and stimulated denervated muscle. In the clinical study 27 spinal cord injured individuals were included, furthermore 13 pilot patients participated. After a series of initial examinations they underwent an electrical stimulation program for their denervated lower limb muscles. Some of the patients have already follow up examinations. A marked increase of muscle mass and quality was observed, the trophic situation of the denervated lower limbs had improved obviously.

Adult↗

Evaluation of FES-induced knee joint moments in paraplegics with denervated muscles.

The pendulum test was applied to evaluate functional electrical stimulation (FES)-induced joint moments in paraplegics with denervated muscles. Therefore a manipulandum was connected to the knee joint and programmed to elicit gravity-induced leg oscillations. The FES-induced output torque was compensated for in order to keep the leg in a mean vertical position (knee angle 90 degrees ). A second-order dynamical model was applied to extract the elastic and viscous moments from the recorded leg oscillations. This model provided an almost adequate description of the relaxed and FES-contracted states. In the relaxed state the elastic moment was 15.3 +/- 2.37 Nm/rad and the viscous moment was 0.41 +/- 0.21 Nms/rad. The FES-induced elastic moment was 29.4 +/- 28.5 Nm/rad and the FES-induced viscous moment was 1.53 +/- 1.03 Nms/rad (N = 10, before FES-training).

Adult↗

Determination of the chronaxie and rheobase of denervated limb muscles in conscious rabbits.

Measurements of the rheobase and chronaxie can be used to define the excitability of nerves and muscles. The aim of this study was to obtain a record over many weeks of changes in the rheobase and chronaxie of denervated rabbit tibialis anterior muscle (TA). A custom-built electronic stimulator was implanted into the peritoneal cavity of New Zealand White rabbits. Large stainless steel electrodes were placed on the denervated TA muscle. Rheobase and chronaxie were measured noninvasively at weekly intervals by means of a laptop PC, which communicated with the stimulator via a radio-frequency link. At each setting the denervated TA was palpated manually to detect the response of the muscle. During the first few days after denervation the rheobase increased transiently to 0.8 +/- 0.13 mA, approximately twice the value for normal innervated muscle, then decreased to normal for the remainder of the experimental period. Chronaxie underwent a significant 3-fold increase from 4.5 +/- 1.1 ms to 14.1 +/- 1.1 ms during the first two weeks of denervation and remained elevated throughout. The custom-built implantable electronic stimulator allowed changes in muscle excitability to be studied over a long period of denervation within individual animals, providing an accurate assessment of the time course of denervation-induced changes in muscle excitability.

Analysis of Variance↗

Motor control in the human spinal cord.

Features of the human spinal cord motor control are described using two spinal cord injury models: (i) the spinal cord completely separated from brain motor structures by accidental injury; (ii) the spinal cord receiving reduced and altered supraspinal input due to an incomplete lesion. Systematic studies using surface electrode polyelectromyography were carried out to assess skeletal muscle reflex responses to single and repetitve stimulation in a large number of subjects. In complete spinal cord injured subjects the functional integrity of three different neuronal circuits below the lesion level is demonstrated: first, simple mono- and oligosynaptic reflex arcs and polysynaptic pathways; second, propriospinal interneuron system with their cell in the gray matter and the axons in the white matter of the spinal cord conducting activity between different spinal cord segments; and third, internuncial gray matter neurons with short axons and dense neuron contact within the spinal gray matter. All of these three systems participate continuously in the generation of spinal cord reflex output activating muscles. The integration of these systems and their relative degree of excitation and set-up produces characteristic functions of motor control. In incomplete spinal cord injured patients, the implementation of brain motor control depends on the profile of residual brain descending input and its integration with the functional neuronal circuits below the lesion. Locomotor patterns result from the establishment of a new structural relationship between brain and spinal cord. The functions of this new structural relationship are expressed as an alternative, but characteristic and consistent neurocontrol. The more we know about how the brain governs spinal cord networks, the better we can describe human motor control. On the other hand such knowledge is essential for the restoration of residual functions and for the construction of new cord circuitry to expand the functions of the injured spinal cord.

Electric Stimulation↗

Stimulation parameter optimization for FES supported standing up and walking in SCI patients.

Functional Electrical Stimulation (FES) to restore leg movement for standing up and walking (stepping) in SCI patients with intact lower motor neuron is used by several groups. Usually quadriceps muscles are stimulated for hip and knee extension, gluteus muscles for hip stabilization, and the common peroneal nerve to elicit the flexion reflex. The requirement to get a natural movement would need a huge number of stimulation channels--a request that could be easily fulfillled from the engineer's point of view but not from the point of practicability since each stimulated muscle requires two skin-attached electrodes resulting in a prolonged time for donning and doffing. In the described project a newly developed eight channel stimulator that can vary the stimulation parameters in many ways and over a wide range is used. The goal is to achieve a natural movement with a minimum of surface electrodes by optimizing the stimulation parameters. Seven experienced FES users and five unexperienced persons (all between Th4-Th11) participate in this study. Standing up can be significantly improved by optimizing the time delay between the onset of quadriceps and gluteus muscles (0.2-0.4 s) and the duration of the ramp. A 0.2 s delay gives good results in heavy patients while slower ramps (0.4 s) are required in slim patients. During stepping, gluteus muscle timing is not very crucial. Gluteus stimulation is turned off 0.1-0.2 s before quadriceps muscle and with the same delay turned on again. Of major influence on the gait quality is the timing during heel strike when peroneal stimulation is switched off and quadriceps stimulation is turned on. Six patients require 0.0-0.1 s where neither peroneal nor quadriceps stimulation is applied, the others require an overlap of 0.1-0.2 s. Activation of adductor muscles during standing up and during the swing phase helps to avoid hip abduction and improves knee trajectories.

Electric Stimulation Therapy↗

In vivo assessment of conduction velocity and refractory period of denervated muscle fibers.

Stimulation needle electromyography was used to study the muscle fiber conduction velocity and refractory period in 4 patients with long-term denervation of the lower limb muscles due to lesion of the conus cauda or cauda equina (2 untrained and 2 trained by functional electrical stimulation). In untrained patients, the results demonstrated that propagation velocity is reduced and refractory period of the muscle fiber is increased with time of denervation. The patients performing electrical stimulation training showed higher conduction velocities and reduced refractory period despite longer lasting denervation. This suggests that electrical stimulation training is effective to improve the electrical properties of the muscle fiber. Since the obtained data show a good correlation to other clinical tests and biopsy investigations, this method could serve as an additional measurement technique to specify the status of the denervated muscle. Further animal experiments and clinical studies are necessary to proof the results in comparison to more invasive established techniques.

Electric Stimulation↗

Long-term denervation in humans causes degeneration of both contractile and excitation-contraction coupling apparatus, which is reversible by functional electrical stimulation (FES): a role for myofiber regeneration?

Over the last 30 years there has been considerable interest in the use of functional electrical stimulation (FES) to restore movement to the limbs of paralyzed patients. Spinal cord injury causes a rapid loss in both muscle mass and contractile force. The atrophy is especially severe when the injury involves lower motoneurons because many months after spinal cord injury, atrophy is complicated by fibrosis and fat substitution. In this study we describe the effects of long-term lower motoneuron denervation of human muscle and present the structural results of muscle trained using FES. By means of an antibody for embryonic myosin, we demonstrate that many regenerative events continue to spontaneously occur in human long-term denervated and degenerated muscle (DDM). In addition, using electron microscopy, we describe i) the overall structure of fibers and myofibrils in long-term denervated and degenerated muscle, including the effects of FES, and ii) the structure and localization of calcium release units, or triads; the structures reputed to activate muscle contraction during excitation-contraction coupling (ECC). Both apparatus undergo disarrangement and re-organization following long-term denervation and FES, respectively. The poor excitability of human long-term DDM fibers, which extends to the first periods of FES training, may be explained in terms of the spatial disorder of the ECC apparatus. Its disorganization and re-organization following long-term denervation and FES, respectively, may play a key role in the parallel disarrangement and re-organization of the myofibrils that characterize denervation and FES training. The present structural studies demonstrate that the protocol used during FES training is effective in reverting long-term denervation atrophy and dystrophy. The mean fiber diameter in FES biopsies is 42.2 +/- 14.8 SD (p < 0.0001 vs DDM 14.9 +/- 6.0 SD); the mean percentile of myofiber area of the biopsy is 94.3 +/- 5.7 SD (p < 0.0001 vs DDM 25.7 +/- 23.7 SD); the mean percentile fat area is 2.1 +/- 2.4 SD (p < 0.001 vs DDM 12.8 +/- 12.1 SD); and the mean percentile connective tissue area is 3.6 +/- 4.6 SD (p < 0.001 vs DDM 61.6 +/- 20.1 SD). In DDM biopsies more than 50% of myofibers have diameter smaller than 10 microm, while the FES-trained subjects have more that 50% of myofibers larger than 30 microm. The recovery of muscle mass seems to be the result of both a size increase of the surviving fibers and the regeneration of new myofibers.

Action Potentials↗

Denervated muscles in humans: limitations and problems of currently used functional electrical stimulation training protocols.

Prior clinical work showed that electrical stimulation therapy with exponential current is able to slow down atrophy and maintain the muscle during nonpermanent flaccid paralysis. However, exponential currents are not sufficient for long-term therapy of denervated degenerated muscles (DDMs). We initiated a European research project investigating the rehabilitation strategies in humans, but also studying the underlying basic scientific knowledge of muscle regeneration from satellite cells or myoblast activity in animal experiments. In our prior study, we were able to show that high-intensity stimulation of DDMs is possible. At the beginning of training, only single muscle twitches can be elicited by biphasic pulses with durations of 120-150 ms. Later, tetanic contraction of the muscle with special stimulation parameters (pulse duration of 30-50 ms, stimulation frequency of 16-25 Hz, pulse amplitudes of up to 250 mA) can improve the structural and metabolic state of the DDMs. Because there are no nerve endings for conduction of stimuli, large-size, anatomically shaped electrodes are used. This ensures an even contraction of the whole muscle. Contrary to the current clinical knowledge, we were able to stimulate and train denervated muscle 15-20 years after denervation. The estimated amount of muscle fibers that have to be restored is about 2-4 million fibers in each m. quadriceps. To rebuild such a large number of muscle fibers takes up to 3-4 years. Despite constant stimulation parameters and training protocols, there is a high variation in the developed contraction force and fatigue resistance of the muscle during the first years of functional electrical stimulation.

Electric Stimulation Therapy↗

The Vienna functional electrical stimulation system for restoration of walking functions in spastic paraplegia.

An eight-channel stimulation system, currently intended for stimulation of lower extremities, was developed and is introduced. The major development goals were easy handling, modularity to make the system easily adaptable for other functional electrical stimulation (FES) applications, and a wide stimulation parameter range for application-specific parameter optimization. For paraplegic stepping, the system worn by the patient consists of 2 four-channel stimulation modules, a central unit holding the battery and circuitry for power management and communication control, a wireless remote control unit, and a palmtop computer as the main control and input device. A software package for Microsoft Windows supports the design and optimization of stimulation sequences in the rehabilitation center. First tests with patients familiar with FES showed smoother movements during stepping and acceptable good handling. In combination with the PC software, the required stimulation sequences could be created in a very short time.

Computer Systems↗

A stimulator for functional activation of denervated muscles.

In recent years various studies proved that electrical stimulation can improve contractile capability and restore muscle function in long-term denervated degenerated muscles. The low excitability of the muscle cells at the initial stage of training and surrounding connective tissue, acting as an electrical shunt, require special stimulation parameters. Until now, no appropriate devices (stimulators) are commercially available. Therefore, we were forced to design our own stimulators. The control unit of the stimulators is based on a microprocessor for maximum flexibility regarding the generation of the parameters such as pulse amplitudes, pulse width, frequency, stimulation times, ramps, and so on. In addition, the microprocessor design allows recording of compliance data such as stimulation date, time, duration, and used programs. The constant voltage output stage of the stimulator is able to generate biphasic charge balanced stimulation impulses with a pulse width of 1 to 300 ms, voltage amplitudes up to +/-80 V (160 VPP), and stimulation currents up to 250 mA. To prevent direct current due to inexact charge compensation, the electrode outputs are decoupled capacitively. Simultaneous 2 channel stimulation with independent intensity levels is possible. The stimulators are programmed using a notebook or a personal digital assistant via infrared serial interface. This concept guarantees the application of correct stimulation parameters because the patient has only access to parameters that are preprogrammed for him in the outpatient clinic. For the home based training, access is limited to variation of intensity within preprogrammed limits. For safety reasons, the portable unit is powered by an internal rechargeable battery. High efficiency switched voltage regulators are used to provide the different required voltage levels while ensuring an acceptable operating time of the stimulator.

Electric Power Supplies↗

Muscle biopsies show that FES of denervated muscles reverses human muscle degeneration from permanent spinal motoneuron lesion.

This paper presents biopsy analyses in support of the clinical evidence of muscle recovery induced by a new system of life-long functional-electrical-stimulation (FES) training in permanent spinal-motoneuron-denervated human muscle. Not earlier than 1 year after subjects experienced complete conus cauda lesion, their thigh muscles were electrically stimulated at home for several years with large skin surface electrodes and an expressly designed stimulator that delivered much longer impulses than those presently available for clinical use. The poor excitability of long-term denervated muscles was first improved by several months of twitch-contraction training. Then, the muscles were tetanically stimulated against progressively increased loads. Needle biopsies of vastus lateralis from long-term denervated subjects showed severe myofiber atrophy or lipodystrophy beginning 2 years after spinal cord injury (SCI). Muscle biopsies from a group of 3.6- to 13.5-year denervated subjects, who underwent 2.4 to 9.3 years of FES, show that this progressive training almost reverted long-term muscle atrophy/degeneration.

Adult↗