Neurophysiology 2: Peripheral Nerve System
Chair: Carel Meskers
MOTOR UNIT PROPERTIES IN THE BICES BRACHII OF CHRONIC HEMIPARETIC STROKE PATIENTS ASSESSED WITH HIGH-DENSITY SURFACE EMG|
Laura Kallenberg, Hermie Hermens
Abstract: As a consequence of a stroke, motor control and motor unit (MU) characteristics may change. Amongst others, results from electrohpysiological studies suggest that MU size may increase due to re-innervation. The aim of this study was to investigate the MU characteristics of the biceps brachii in chronic stroke patients using high-density surface electromyography (sEMG).
Fifteen hemiparetic chronic stroke subjects participated in this study. The Fugl-Meyer score for the upper extremity, a clinical scale for motor recovery, was assessed. The protocol consisted of isometric step contractions (10 force levels from 5% to 50% of maximal voluntary contraction) as well as cyclic passive and active elbow flexion and extension movements.
sEMG of the biceps brachii was recorded with a two dimensional 16-channel electrode array placed on the skin above the muscle. This was repeated for both sides. Motor unit action potentials (MUAPs) were extracted from the sEMG signals using an algorithm based on the Continuous Wavelet Transform. From the MUAPs, root-mean-square value (RMSMUAP, reflecting MU size) and mean frequency of the power spectrum (FMEANMUAP, reflecting recruitment threshold) were calculated.
In the step contractions, 7 out of 15 subjects showed larger RMSMUAP values at the affected side than at the unaffected side, 5 subjects showed smaller values and 3 subjects did not show differences. Interestingly, the median Fugl-Meyer score was considerably higher in the group with larger RMSMUAP values at the affected side (Fugl-Meyer score 42 versus 20 out of 66). The ratio of RMSMUAP of the affected side divided by that of the unaffected side correlated with the Fugl-Meyer score for the force levels from 15% to 45% (Spearman’s rho between 0.6 and 0.74, p<0.039). FMEANMUAP was slightly smaller at the affected side (108 vs 114 Hz, p<0.001).
For the cyclic contractions, higher RMSMUAP values were found in the stroke group than in the control group and RMSMUAP during the stretch phase of the passive contractions showed a significant positive correlation with the Fugl-Meyer score (rho=0.54). In both groups, RMSMUAP was considerably smaller during passive than during active contractions (median values healthy: 19.7 vs 5.9 uV, stroke: 29.2 vs 14.3 uV).
Since RMSMUAP is related to MU size, RMSMUAP and RMSMUAP ratio might reflect the extent to which re-innervation, resulting in larger MUs, has occurred. Re-innervation is a compensation strategy for paresis and is therefore likely to be related to the functional capacity of the muscle, which may explain the correlation between RMSMUAP ratio and Fugl-Meyer score. The lower FMEANMUAP values might be related to muscle atrophy at the affected side, and/or to an increased contribution of low-threshold motor units. The MUAPs during the stretch phase of the passive movements were considerably smaller than the MUAPs that were recruited voluntarily during the active momvents. Apparently, the recruitment during the stretch reflex is limited to the smaller MUs while a much larger part of the MU pool can be recruited voluntarily.
COMPUTATIONAL EVIDENCE OF POTENTIAL AVERAGING OVER THE FINITE SURFACE OF A BIOELECTRIC SURFACE ELECTRODE|
Madeleine Lowery, Dick Stegeman, Hans van Dijk
Abstract: Any bio-electric signal is not only a function of time, but also has a complex spatial distribution. However, in practical applications pursuing decreased signal variability it is common practice to summarize this spatial distribution. For instance, in electrodiagnostic medicine, the spatial pattern of a surface EMG signal is often summarized using a large electrode over the skin [1, 2]. The implicit assumption is that the signal from such a large electrode approximates the average of the potential distribution beneath the electrode, or more precisely, how it would appear without the presence of the electrode. This behaviour is sometimes denoted as integration, a term that falsely suggests that the potential increases with increasing electrode size.
In this contribution, we will first introduce a simple electrical equivalent model to delineate this principal of averaging being valid under idealized conditions. However, it is a simplified theoretical approximation requiring confirmation under specific conditions. In particular, it is assumed that the electrode itself does not noticeably participate as part of the electrical circuits. Two assertions are implicit: (i) The distribution of the electric potential in the volume conductor, specifically at the skin surface under the electrode, is not altered by the presence of the electrode, and (ii) the electrode signal is the true average of the potential at the skin surface under the electrode.
As a next step in our evaluation, we used a realistic finite element model of EMG generation . This model showed that the voltage distribution in the volume conductor after electrode application is not significantly changed once the impedance of the electric double layer between the electrode and the skin per cm2 (determining the electrode impedance) is sufficiently large. However, too large an impedance causes a drop in potential across that layer. Simulations also revealed that skin conductivity plays an important role. It is concluded that the precision of averaging appears sufficient for all practical EMG situations one may conceive. It is “saved” by the relative high impedance of the double layer in combination with a relatively low skin impedance. Considering the specific conditions during ECG and EEG
IMPLEMENTATION OF THRESHOLD TRACKING TECHNIQUES FOR THE STUDY OF HUMAN PERIPHERAL NERVES|
Leonard van Schelven, Rolf Struikmans, Hessel Franssen
Abstract: Threshold Tracking  is a promising but little used examination method in Clinical Neurophysiology. It can give information on the membrane potential and membrane properties, measured in vivo at a spot of a human peripheral nerve. This provides a valuable extension to the common neurophysiological tests, which inform mostly on impulse conduction over a length of nerve.
In conventional neurophysiological tests, response amplitudes and delays are measured using electrical stimuli of various strengths. In Threshold Tracking, the nerve response is kept constant by dynamically controlling the electrical test stimulus, while the excitation threshold of the nerve is manipulated by e.g. nerve cooling, ischemia, prolonged nerve activity or the application of electrical 'conditioning' currents. Threshold Tracking can be used with single motor units, where the threshold is defined as the stimulus level that excites the nerve in e.g. 50% of the cases, or with compound action potentials. In the latter case, the size of the response is controlled to a fixed level.
An important practical obstacle for the use of Threshold Tracking is the required technical setup. We will show all parts of the Threshold Tracking setup currently in use at the UMC Utrecht. The system measures and analyses nerve responses in real time, and based on this result, a controller (tracker) adapts the strength of the next test pulse. Concurrently, appropriate conditioning stimuli are generated according to the test protocol. A big hurdle in realizing this system was the hardware for safe delivery of the complex electrical stimuli. Suitable electrical stimulators with CE approval for medical use have become commercially available only recently.
The tests in a typical Threshold Tracking protocol  will be shown, and the effect of nerve cooling on the results of these tests. This includes a Threshold Electrotonus test, which shows the effect in time of long (200 ms) subthreshold polarizing or depolarizing conditioning currents, and a Recovery Cycle test, which shows the recovery of nerve excitability after a short supramaximal conditioning pulse.
Currently ongoing research at the UMC Utrecht using Threshold Tracking will be briefly described. More on the possibilities of Threshold Tracking and the interpretation of results will be presented in a related abstract 'Excitability tests: a new method to assess peripheral nerve function'.
 H. Bostock, K. Cikurel, and D. Burke. Threshold tracking techniques in the study of human peripheral nerve. Muscle Nerve 21 (2):137-158, 1998.
 M. C. Kiernan, D. Burke, K. V. Andersen, and H. Bostock. Multiple measures of axonal excitability: a new approach in clinical testing. Muscle Nerve 23 (3):399-409, 2000.
EXCITABILITY TESTS: A NEW METHOD TO ASSESS PERIPHERAL NERVE FUNCTION|
Hessel Franssen, Leonard van Schelven
Abstract: Peripheral nerve diseases form an important part of clinical neurology. For their diagnosis, nerve conduction studies are often employed. These assess loss of parts of the nerve but not the physiological mechanisms underlying nerve function. Recently, excitability tests were developed which may fill this gap. This abstract discusses the physiological principles of excitability tests and an accompanying abstract the technical aspects ('Implementation of Threshold Tracking techniques for the study of human peripheral nerves.').
A nerve is formed by hundreds of long axons (extensions of nerve cells). At rest, the inside of the axon has a high K+ and a low Na+ ion concentration and is negatively charged with respect to the outside, yielding a membrane potential (Vm) of -70mV. To maintain the concentration differences, the axon membrane contains separate ion channels for Na+ and K+ ions and pumps which remove Na+ from and enter K+ into the axon. With a nerve impulse, Na+ channels open and Na+ flows into the axon giving rise to a positive Vm (depolarization). After the impulse the resting state is restored by K+ channel and pump activity.
Excitability tests assess the above described mechanisms at one site of a nerve. Electrical conditioning stimuli are given to induce a change in membrane excitability. This change is measured by short electrical test-stimuli which determine the current required to evoke a nerve response of 40% of maximal. If less current is required for this response, excitability is increased i.e., the membrane is more excitable e.g., due to depolarization. The following can be assessed: (1) whether Vm at rest is pathologically depolarized or hyperpolarized (i.e., too negative), (2) K+ channel activity, (3) Na+ channel activity and inactivation, (4) axon membrane resistance.
 Burke D, Kiernan MC, Bostock H. Excitability of human axons. Clin Neurophysiol 2001; 112: 1575-85.
 Koester J, Siegelbaum SA. Membrane potential. In: Kandel ER, Schwartz JH, Jessell TM, editors. Principles of neural science, 4th edition. New York: McGraw-Hill; 2000. p.125-139.
A NEW METHOD TO DIAGNOSE SMALL FIBER NEUROPATHY – FIRST MEASUREMENTS|
Vera Lagerburg, Arjen Smit, Hugo Spruijt, Ingemar Merkies
Abstract: Introduction: Small fiber neuropathy (SFN) mainly involves small diameter myelinated and unmyelinated nerve fibers (A and C fibres) and typically presents with pain and/or symptoms of autonomic dysfunction [1, 2, 3, 4]. The diagnosis of SFN can be difficult, because conventional electrodiagnostic studies primarily investigate large myelinated fibre functions, which are relatively unaffected in SNF. Contact heat evoked potentials (CHEPs) might be a usefool tool in the diagnosis of SFN [5, 6, 7]. To use CHEPs as a diagnostic tool, normal values have to be found for the latency and amplitude of the response. Literature suggests that these values might be dependent on gender, age and pain thresholds [8, 9, 10, 11].
In this study we present a standard examination protocol to measure CHEP responses.
Methods and materials: A Contact Heat Evoked Potential Stimulator (Medoc, Ramat Yishai, Israel) was used to selectively stimulate A and C fibres in the skin. Heat pulses were applied to the volar side of both forearms. The baseline temperature of the thermode was set at 32°C, while the maximum temperature of the heat pulses depended on the pain threshold of the subject, with a maximum of 51°C. Pain thresholds were determined with the Advanced Thermal Stimulator module of the CHEPS. The interstimulus interval was randomly set between 10 and 18s. CHEPs were recorded using the Keypoint.NET EP machine (Medtronic, Minneapolis, USA) with electrodes placed on Cz, Pz and Fz acoording to the international 10-20 system. The reference electrode was placed on the left tragus and the earth electrode was placed cortical. The evoked potentials were filtered with a band pass filter at 0.2 – 100 Hz. A total number of 25 stimuli was given to each arm. To avoid influence of any shock reaction due to the stimulus the first response was not included in the evaluation. The responses were averaged after each 12 stimuli. This was done to study the influence of sensitization to the heat pulses. Artefact rejection was automatically done based on the amplitude of the response.
Results: Until now 13 healthy subjects were included in this study. Twelve out of 13 showed responses on the EEG, with the clearest responses at the Cz position. The N-top occurred at 409 ± 9 ms and the P-top at 522 ± 11 ms after stimulation. The mean peak-peak amplitude was 27,4 ± 2,2 μV. After a couple of heat pulses the amplitude of the response declined which was caused by sensitization to the heat pulses. No significant left-right differences were found and the values for latency and amplitude were reproducible. Responses varied between subjects and seemed to be dependent on the pain threshold.
Conclusion: It is possible to measure the contact heat evoked potentials with this examination protocol.
Future: With the examination protocol developed, we will start a study to include 100 healthy subjects to obtain normal values for amplitude and latency of the response. The subjects will be stratified for age and gender. A basic neurological investigation will be part of the study.
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