Brain, Vol. 126, No. 4, 1001-1008,
April 2003
© 2003 Guarantors of Brain
doi: 10.1093/brain/awg087
Activity-dependent hyperpolarization and impulse conduction in motor axons in patients with carpal tunnel syndrome
1 Prince of Wales Medical Research Institute, University of New South Wales, 2 Department of Clinical Neurophysiology, Prince of Wales Hospital and 3 College of Health Sciences, University of Sydney, Australia
Correspondence to: Professor David Burke, Office of Research and Development, College of Health Sciences, Medical Foundation Building-K25, University of Sydney, NSW 2006, Australia E-mail: d.burke{at}chs.usyd.edu.au
Received August 8, 2002. Revised November 19, 2002. Accepted November 21, 2002.
 |
Summary |
|---|
 Top Summary IntroductionMethodsResultsDiscussionReferences |
|---|
The differing contributions of axonal attenuation, ischaemia, demyelination and remyelination to the pathophysiology of carpal tunnel syndrome remain unresolved. Previous studies indicate that the hyperpolarization of motor axons produced by voluntary contractions may precipitate conduction block in chronic acquired demyelinating polyneuropathies. The present study investigated whether this axonal hyperpolarization can produce or accentuate conduction block in carpal tunnel syndrome, thereby implicating demyelination as a significant factor in its pathogenesis. Studies were performed in 12 patients with mild to moderate carpal tunnel syndrome and compared with 12 healthy control subjects. Using the technique of threshold tracking, the compound muscle action potential (CMAP) of abductor pollicis brevis (APB) was recorded in response to supramaximal stimuli to the median nerve at the wrist, alternating with measurements of axonal excitability. After a voluntary contraction of APB for 60 s, there was a lesser hyperpolarizing threshold increase in the patients (
18%), than in controls (37%). The changes in strength–duration time constant and supernormality were appropriately smaller in the patients. The amplitude and area of the maximal CMAP was not significantly altered in either group. Activity-dependent conduction block was not precipitated in the carpal tunnel syndrome patients even though this degree of axonal hyperpolarization was sufficient to produce conduction block in chronic inflammatory demyelinating polyneuropathy. These studies support the view that demyelination may not be a critical factor in the slowing of impulse conduction in mild to moderate carpal tunnel syndrome. Keywords: carpal tunnel syndrome; axonal excitability; activity-dependent hyperpolarization; conduction block
Abbreviations: APB= abductor pollicis brevis; CIDP = chronic inflammatory demyelinating polyneuropathy; CMAP = compound muscle action potential; 
SD = strength–duration time constant
|
Introduction |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Carpal tunnel syndrome is the most common focal compressive neuropathy in human subjects and is due to entrapment of the nerve beneath the transverse carpal ligament at the wrist. The conduction slowing in carpal tunnel syndrome can be localized to the distal 1–2 cm of the tunnel (Brown et al., 1976
; Kimura, 1979). This localized slowing suggests an underlying focal pathology at which the safety margin for conduction may be impaired. The pathological findings described in carpal tunnel syndrome support this, and include displacement of myelin from the node with resulting paranodal demyelination, remyelination and axonal attenuation (Ochoa and Marotte, 1973; Gilliatt, 1980; Brown, 1984). Although carpal tunnel syndrome undoubtedly results from nerve compression, the relative contributions of these factors and of ischaemia and mechanical deformation to the pathophysiology of carpal tunnel syndrome remain uncertain. In patients with carpal tunnel syndrome, symptoms are often worse following use of the hand, and this raises the possibility that the deficits might be activity dependent.
The transmission of a train of impulses results in hyperpolarization of the active axons and a decrease in axonal excitability. In pathological nerves, this can result in conduction block at sites of impaired safety margin, be that due to focal demyelination (Bostock and Grafe, 1985) or to focal injury (Inglis et al., 1998). In healthy axons, the reduction in excitability following the conduction of a train of impulses is associated with two positive afterpotentials (Gasser, 1935). The mechanisms responsible for the reduction in excitability vary according to the length of the impulse train. The activity-dependent depression in excitability that follows a brief train of impulses results from activation of a slow K+ conductance (Bergmans, 1970; Baker et al., 1987; Taylor et al., 1992; Burke, 1993; Miller et al., 1995). A more profound hyperpolarization of longer duration can be produced by long trains of impulses and is associated with activation of the Na+/K+ pump (Bergmans, 1970, 1982; Bostock and Grafe, 1985; Morita et al., 1993).
Voluntary contraction of the human thenar muscles has been documented to produce axonal hyperpolarization of the active motor axons, the extent and duration of which are determined by the duration of the contraction (Vagg et al., 1998). This axonal hyperpolarization is believed to be due to activation of the Na+/K+ ATPase pump (Vagg et al., 1998). Previous studies have presented evidence that the axonal hyperpolarization produced by a maximal voluntary contraction can produce conduction block at pathologically demyelinated nerve segments in patients with symptomatic chronic acquired demyelinating neuropathies, whether diffuse (Cappelen-Smith et al., 2000) or focal (Kaji et al., 2000). Accordingly, focal pathology due to demyelination (or injury) would be expected to render axons susceptible to conduction block when they conduct trains of impulses.
Previous studies in patients with carpal tunnel syndrome have failed to demonstrate activity-dependent conduction block in cutaneous afferents (Kiernan et al., 1996b; Miller et al., 1996). However, it would be prudent to remain circumspect about these findings because there are biophysical differences between sensory and motor axons that render sensory axons more susceptible to ectopic activity and motor axons more susceptible to conduction block (Burke et al., 1997; Bostock et al., 1998). The present study was therefore undertaken to determine whether the axonal hyperpolarization produced by a voluntary contraction can produce activity-dependent conduction block in motor axons of patients with mild to moderate carpal tunnel syndrome, thereby producing deficits not obvious at rest. Such a finding might be expected if focal demyelination played an important role in the pathophysiology of this disorder and, in particular, in the slowing of impulse conduction that is characteristic of carpal tunnel syndrome.
|
Methods |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Experiments were performed on 12 patients with carpal tunnel syndrome (eight female, four male, aged 31–58 years), and 12 healthy control subjects (four female, eight male, aged 24–56 years), all of whom gave informed consent to experimental procedures, which had the approval of the Research Ethics Committee of the South Eastern Sydney Area Health Service (Eastern Division). A number of the healthy control subjects have been used in other studies (Cappelen-Smith et al., 2000
; Kuwabara et al., 2002). None of the control subjects had clinical or neurophysiological evidence of a peripheral nerve disorder.
Patients
The patient data are summarized in Table 1. Patients with mild to moderate carpal tunnel syndrome on routine neurophysiological testing were selected. These studies included comparison of the digital sensory potentials and conduction velocity from digit II to wrist and elbow, and from digit V to wrist, the radial and median latencies for digit I, and the median and ulnar latencies from digit IV. The median compound muscle action potential (CMAP) was recorded from the abductor pollicis brevis (APB), with stimulation at the wrist and elbow, allowing terminal latency measures and forearm conduction velocity calculation. Terminal latency index calculations were made in eight of the 12 patients, using the following formula: terminal distance/[proximal conduction velocity x distal motor latency] (Simovic and Weinberg, 1997, 1999). Each patient had a clinical diagnosis of carpal tunnel syndrome with neurophysiological evidence of focal slowing of conduction in the median nerve at the wrist (Goadsby and Burke, 1994). None had objective sensory loss in the median-innervated territory or weakness of the thenar muscles. The patients were healthy apart from carpal tunnel syndrome, and none had a history of a concurrent medical condition known to affect nerve function.
|
Measurements of axonal excitability
Computerized threshold tracking (QTRAC version 4.3, © Professor H. Bostock, Institute of Neurology, London, see Bostock et al., 1998
) was used to follow the excitability of motor axons in the median nerve at the wrist innervating the APB before and after maximal voluntary abduction of the thumb for 60 s. The median nerve was stimulated using surface electrodes 4 cm apart at the wrist. Care was taken to ensure that ulnar motor axons were not stimulated inadvertently by the supramaximal stimuli. The CMAP was recorded from APB with the active electrode at the motor point and the reference on the proximal phalanx. The amplitude of the CMAP was measured from onset to negative peak, and latency was measured to half-peak, the latter because automatic identification of onset latency is prone to error, particularly with small potentials. Recordings of the area of the CMAP were not possible using the QTRAC software, but potentials were monitored and recorded on a separate oscilloscope to ensure that, if changes in amplitude occurred, they were associated with changes in area (see Fig. 1). Amplitude measurements were made on-line in response to a sequence of five test stimuli (stimulus ‘channels’) delivered sequentially at 0.8 s intervals. A fixed supramaximal stimulus of 0.2 ms was delivered on channel 1 to produce a CMAP of maximal amplitude. This stimulus exceeded that required to produce a maximal CMAP by 20–30%. To ensure that the maximal CMAP was truly maximal after the contraction, a second fixed supramaximal stimulus 20% stronger than the first was introduced after the voluntary contraction on channel 2. The maximal CMAP was considered truly maximal only if the CMAPs produced by these two stimuli were identical.
|
On the other three channels (3–5), the test stimulus was adjusted continuously by computer to maintain a CMAP that was 70% of the maximal CMAP (as recorded in response to stimulus 1). The stimulus current was adjusted such that changes in excitability would result in changes in the stimulus current necessary to produce the target CMAP. The current required to produce the target CMAP is referred to as the ‘threshold’ for the CMAP. On these ‘tracking’ channels, ‘proportional tracking’ was used (Bostock et al., 1998
), such that the extent to which the stimulus current increased or decreased was proportional to the difference between the target and the measured response. On two of these channels (3 and 4), threshold was recorded using test stimuli of 0.1 and 1.0 ms, and these were used to calculate the strength–duration time constant (SD) according to Weiss’ Law. SD was calculated using the following formula (Weiss, 1901; Bostock and Bergmans, 1994; Mogyoros et al., 1996):
SD = ta(Ia – tb x Ib)/(Ib – ta x Ia)
where ta and tb are the test stimulus durations for the threshold currents Ia and Ib, respectively. This reduces to:
SD = 0.1 (I0.1 – I1.0)/(I1.0 – 0.1 I0.1)
when the two stimuli are of 0.1 and 1.0 ms duration. Rheobase (Irh) is the threshold current if the test stimulus could be infinitely long, and was calculated from the same data using the formula:
Irh = [I1.0 – (0.1 x I0.1)]/0.9
The last tracking channel (5) was used to follow changes in supernormality. Supernormality reflects predominantly internodal properties and results from the increased axonal excitability that follows immediately after the refractory period, when the test stimulus is preceded by a single supramaximal conditioning stimulus. On this channel, the test stimulus (0.1 ms duration) was delivered 7 ms after a fixed supramaximal conditioning stimulus, the interval being that at which supernormal excitability normally is maximal (Kiernan et al., 1996a). The conditioned CMAP was measured after the maximal CMAP produced by the conditioning stimulus had been eliminated on-line by subtraction of the CMAP produced by the supramaximal stimulus alone. Supernormality is expressed as a negative threshold change, representing the amount by which the test stimulus could be reduced to produce the target CMAP.
Subjects performed maximal isometric voluntary abduction of the thumb against resistance provided by one of the authors, and were encouraged to maintain maximal effort for 60 s. The hand was stabilized at the wrist and fingers during contraction to prevent displacement of the stimulating and recording electrodes. Stimuli were stopped during and recommenced after the contraction. Skin temperature was measured near the stimulating site and maintained above 32°C (33.1 ± 0.2°C; mean ± SEM) using blankets and radiant heat. Differences between the patients and healthy controls were tested with unpaired Student’s t test. Data are given as mean ± SEM (unless otherwise indicated) with, where appropriate, the extremes of the range.
|
Results |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Resting CMAP amplitude and latency
The routine conduction studies in the patients are summarized in Table 1. In all patients, there was evidence of focal conduction slowing across the carpal tunnel segment of the median nerve, with normal conduction in distal and proximal segments. The resting CMAP is shown for two of the patients in Fig. 1. The amplitude of the maximal CMAP was 9.8 ± 0.6 mV (mean ± SEM, range 6.5–12.6 mV) in healthy controls and 6.8 ± 0.9 mV (range 3.3–13 mV) in the patients with carpal tunnel syndrome (P = 0.01, Student’s unpaired t test). The latency to half-peak of the maximal CMAP was 4.4 ± 0.1 ms (range 3.8–4.9 ms) in the healthy control group and 7 ± 0.5 ms (range 5.4–9.9 ms) in the patients (P = 0.0002, Student’s unpaired t test).
On routine clinical neurophysiological testing, the median motor terminal latency (to CMAP onset) was >4.8 ms in eight of the patients, and <4.8 ms in the remaining four patients (mean all patients: 5.5 ± 0.3 ms). The median motor conduction velocity in the wrist–forearm segment (mean ± SD) was 50.9 ± 5.0 m/s in the patients, compared with the normal for this laboratory of 56 ± 3.8 m/s. The median sensory conduction velocity in the index finger–wrist segment (mean ± SD) was 35.2 ± 6.9 m/s (range 22–44.3 m/s), compared with the normal for this laboratory of 59.4 ± 3.4 m/s.
Activity-dependent changes in axonal excitability
In the healthy controls at rest, the threshold current required to produce the target CMAP 70% of the maximum was 4.3 mA using a 1.0 ms stimulus duration, lower than in the patients (5.7 mA; P = 0.049). In Fig. 2A, threshold data were normalized to pre-contraction values, so eliminating the background difference in threshold, but this is clear in Fig. 2D which plots the rheobasic threshold for the two groups.
|
The voluntary contraction reduced the excitability of motor axons as reflected by an increase in the threshold current required to produce a 70% CMAP, by
1.591 and 1.026 mA, in the control and patient groups, respectively. After contraction, the mean increase in threshold required to produce the test CMAP in controls was 37 ± 2% (mean ± SEM) of the pre-contraction level using a 1.0 ms stimulus. The threshold increased by a smaller extent in the patients, 18 ± 3% (Fig. 2A).
In the healthy controls, resting supernormality was –19 ± 1%. In other words, the test stimulus could be decreased by 19% when delivered 7 ms after a supramaximal conditioning stimulus. After voluntary contraction, supernormality increased to –27 ± 1% in the controls. At rest, supernormality was marginally less in the patients –17 ± 1% and, after the voluntary contraction, it increased, much as in the healthy controls, to –21 ± 2% (Fig. 2B).
Before the contraction, the SD in the controls was 392 ± 23 µs and decreased by 45 µs after the contraction to 347 ± 22 µs (see Fig. 2C). In the patients, resting SD was 419 ± 12 µs and decreased by 37 µs after the voluntary contraction to 382 ± 19 µs. The contraction-induced changes in supernormality and SD involve indices dependent on internodal and nodal properties, respectively, and the pattern of change is that expected with axonal hyperpolarization.
Relationship between excitability indices
The changes in supernormality and SD were less in the patients, but so too was the increase in threshold. This raises the possibility that the smaller changes in the patients were due to a lesser hyperpolarization.
To assess the dependence of supernormality and SD on the change in membrane potential, supernormality and SD were plotted against threshold (a surrogate measure of membrane potential) for the first 5 min after the end of the voluntary contraction (Fig. 3A and B). There was no clear difference in the relationships for the patients and controls for either supernormality or SD, despite the limited change in threshold in the patient group. These findings indicate that activity had similar effects on motor axons in patients and controls, allowing for the lesser hyperpolarization in the patients.
|
There was no relationship between the changes in threshold,
SD or supernormality and pre-contraction distal motor latency.
The effect of activity on impulse conduction in carpal tunnel syndrome
The changes in amplitude and latency of the maximal CMAP are shown in Fig. 4A and B for the patients and the healthy controls. In both groups, there were negligible changes in the amplitude of the maximal CMAP after a voluntary contraction (mean reduction 4% in patients and 3% in controls). The small reduction was maximal immediately the contraction ceased, and in both groups the CMAP recovered to the pre-contraction amplitude within 5 min. Within the patient group, there was no tendency for greater reduction in the patients with longer distal motor latencies. There was a parallel increase in latency in both groups, in the patients by 5% and, to a greater extent in the controls, by 14%, presumably reflecting the greater axonal hyperpolarization that occurred in the controls.
|
Figure 1 shows the maximal CMAPs recorded before and after a maximal voluntary contraction from patients 1 and 2 listed in Table 1. In both panels, the first trace shows the superimposed baseline maximal responses. The second trace shows the maximal responses immediately after the contraction, and the subsequent traces are successive maximal traces at intervals of 0.8 s. In patient 1, baseline latency was 6.8 ms, and in patient 2 it was 7.4 ms. There were minimal changes in the amplitude, area and latency of the maximal CMAP after maximal voluntary contraction.
|
Discussion |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
The present study documents that the axonal hyperpolarization produced by a voluntary contraction has little effect on the security of impulse conduction in motor axons in patients with mild to moderate carpal tunnel syndrome. This was despite the fact that the maximal CMAP was significantly smaller, by 30%, in the patients than the controls, presumably the result of axonal loss and/or conduction block at rest in the patients. Other notable findings were that thresholds at the wrist were higher in the patients, and that the contraction-induced changes in excitability were less in the patients. The discussion will address, first, the limitations of the stress produced by the voluntary contraction and, secondly, the pathophysiology of the conduction slowing in carpal tunnel syndrome.
Adequacy of the stress produced by voluntary contraction
The post-contraction reduction in amplitude of the CMAP is likely to reflect changes in the EMG potential associated with contraction-induced slowing of muscle fibre conduction velocity (Lindeström et al., 1970; Marsden et al., 1971), rather than conduction block in axons or failure of neuromuscular transmission (see Kuwabara et al., 2002). This view is supported by the data in Fig. 1, in which there is a change in CMAP morphology for both patients but no loss of CMAP area.
Voluntary contraction raised the threshold of motor axons in the patients and the control subjects, and the parallel changes in other indices of axonal excitability indicate that motor axons underwent axonal hyperpolarization. However, it is likely that the extent of hyperpolarization was less in the patients, presumably because the impulse load associated with the voluntary effort was less, the reasons for which are discussed below. The question then arises of whether the degree of hyperpolarization in the patients would be sufficient to produce conduction block. In chronic inflammatory demyelinating polyneuropathy (CIDP), the maximal CMAP was reduced by >2 SDs of the control value when threshold had increased by 14% (Cappelen-Smith et al., 2000). If the cause of conduction slowing in carpal tunnel syndrome was attributable solely to demyelination with similar physiological consequences to those in CIDP, an average increase in threshold of 18% should have been sufficient to produce conduction block in some patients. In the previous study, latency to half-peak of the CMAP was 8.8 ± 1.1 ms (range 6.1–11.9 ms) in symptomatic CIDP patients, as compared with 7.0 ± 0.5 ms (range 5.4–9.9 ms) in the present carpal tunnel syndrome patients.
Pathophysiology of conduction slowing in carpal tunnel syndrome
The threshold current necessary to produce a CMAP 70% of maximum was higher in the patients with carpal tunnel syndrome than in the control subjects, and this implies that there is pathology proximal to the site of compression at the distal edge of the flexor retinaculum. The cause of this abnormality is not known, but it is unlikely to be a hyperpolarizing shift in membrane potential in the patients because there was no appropriate change in supernormality or SD. It is possible that the cause is not primarily axonal, but due to some other factor such as current shunting due to neural or tissue oedema or greater resistance due to intraneural fibrosis. The raised threshold is, however, consistent with the common clinical finding that forearm conduction is slightly slow, much as in the present patients (mean forearm motor conduction velocity 50.8 m/s as compared with the control value of 56 m/s).
The lesser change in all measured indices of axonal excitability implies that the voluntary contraction produced a lesser hyperpolarization in the patients. This presumably resulted from a lower impulse load reaching the test site at the wrist in the patients. The lower impulse load is unlikely to be due to a more proximal lesion (as was probably the case in patients with proximal lesions due to multifocal motor neuropathy in the study of Cappelen-Smith et al., 2000). It is likely that patients with carpal tunnel syndrome did not drive or were unable to drive motoneurons innervating the thenar muscles as effectively as the control subjects. Under these circumstances, not even twitch interpolation could have been used to distinguish between lower effort and a limitation acting on the motoneuron pool. Patients were exhorted to produce maximal effort no less strongly than the control subjects and, while a slightly lesser effort cannot be excluded, it is also possible that the pathology resulted in a central inability to translate maximal effort into maximal motor output. It is relevant that deafferentation can have profound effects on the ability to sustain maximal motor drive to involved muscles (Gandevia et al., 1990, 1993; Macefield et al., 1993).
Compression-induced interference with the myelin sheath does not produce morphological changes similar to those in chronic acquired immune demyelinating neuropathies. It was never implied that the pathology in carpal tunnel syndrome is similar to that in CIDP. However, it was a premise of the present study that, if the slowing of impulse conduction in carpal tunnel syndrome could be attributed to demyelination, there would be an impaired safety margin for impulse conduction, and the stress created by conducting an impulse train might then precipitate conduction block. The negative findings of the present study question this premise.
A number of morphological and physiological factors can cause conduction slowing, apart from demyelination. These include tapering of axons, remyelination with shorter internodes, nodal intussusception, axonal depolarization, axonal hyperpolarization, Na+ channel blockade and cooling. Any or all of these factors could contribute to the conduction slowing and possibly explain some of the symptoms in patients. The classical worsening of the symptoms of carpal tunnel syndrome at night may result from ischaemia-induced axonal depolarization ‘block’. These symptoms characteristically are relieved by hand movement, which presumably restores function by relieving the ischaemia and thereby the depolarization block. Further to this, the association of carpal tunnel syndrome and arteriovenous fistulae in patients on chronic haemodialysis also suggests a contribution of ischaemia to the pathogenesis of carpal tunnel syndrome.
We conclude that the safety margin for impulse conduction is not demonstrably impaired in motor axons (or in sensory axons, see Kiernan et al., 1996b; Miller et al., 1996), and that demyelination is probably a minor factor in the conduction slowing typical of carpal tunnel syndrome.
|
Acknowledgements |
|---|
This study was supported by Multiple Sclerosis Australia and the National Health and Medical Research Council of Australia.
|
References |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Baker M, Bostock H, Grafe P, Martius P. Function and distribution of three types of rectifying channel in rat spinal root myelinated axons. J Physiol 1987; 383: 45–67.
Bergmans J. Physiology of single nerve fibres [PhD thesis]. Louvain: University of Louvain, Vander; 1970.
Bergmans J. Repetitive activity induced in single human motor axons: a model for pathological repetitive activity. In: Culp WJ, Ochoa JL, editors. Abnormal nerves and muscles as impulse generators. New York: Oxford University Press, 1982. p. 393–418.
Bostock H, Bergmans J. Post-tetanic excitability changes and ectopic discharges in a human motor axon. Brain 1994; 117: 913–28.
Bostock H, Grafe P. Activity-dependent excitability changes in normal and demyelinated rat spinal root axons. J Physiol 1985; 365: 239–57.
Bostock H, Cikurel K, Burke D. Threshold tracking techniques in the study of human peripheral nerve. Muscle Nerve 1998; 21: 137–58.[CrossRef][Web of Science][Medline]
Brown WF. The physiological and technical basis of electromyography. Boston: Butterworths; 1984.
Brown WF, Ferguson GG, Jones MW, Yates SK. The location of conduction abnormalities in human entrapment neuropathies. Can J Neurol Sci 1976; 3: 111–22.[Medline]
Burke D. Microneurography, impulse conduction, and paresthesias. Muscle Nerve 1993; 16: 1025–32.[CrossRef][Web of Science][Medline]
Burke D, Kiernan MC, Mogyoros I, Bostock H. Susceptibility to conduction block: differences in the biological properties of cutaneous afferents and motor axons. In: Kimura J, Kaji R, editors. Physiology of ALS and related diseases. Amsterdam: Elsevier; 1997. p. 43–53.
Cappelen-Smith C, Kuwabara S, Lin CS-Y, Mogyoros I, Burke D. Activity-dependent hyperpolarization and conduction block in chronic inflammatory demyelinating polyneuropathy. Ann Neurol 2000; 48: 826–32.[CrossRef][Web of Science][Medline]
Gandevia SC, Macefield G, Burke D, McKenzie DK. Voluntary activation of human motor axons in the absence of muscle afferent feedback: the control of the deafferented hand. Brain 1990; 113: 1563–81.
Gandevia SC, Macefield VG, Bigland-Ritchie B, Gorman RB, Burke D. Motoneuronal output and gradation of effort in attempts to contract acutely paralyzed leg muscles in man. J Physiol 1993; 471: 411–27.
Gasser HS. Changes in nerve potentials produced by rapidly repeated stimuli and their relation to the responsiveness of nerve to stimulation. Am J Physiol 1935; 111: 35–50.
Gilliatt RW. Chronic nerve compression and entrapment. In: Sumner AJ, editor. The physiology of peripheral nerve disease. Philadelphia: W.B. Saunders; 1980. p. 316–39.
Goadsby PJ, Burke D. Deficits in the function of small and large afferent fibers in confirmed cases of carpal tunnel syndrome. Muscle Nerve 1994; 17: 614–22.[CrossRef][Web of Science][Medline]
Inglis JT, Leeper JB, Wilson LR, Gandevia SC, Burke D. The development of conduction block in single human axons following a focal nerve injury. J Physiol 1998; 513: 127–33.
Kaji R, Bostock H, Kohara N, Murase N, Kimura J, Shibasaki H. Activity-dependent conduction block in multifocal motor neuropathy. Brain 2000; 123: 1602–11.
Kiernan MC, Mogyoros I, Burke D. Differences in the recovery of excitability in sensory and motor axons of human median nerve. Brain 1996a; 119: 1099–105.
Kiernan MC, Mogyoros I, Burke D. Changes in excitability and impulse transmission following prolonged repetitive activity in normal subjects and patients with a focal nerve lesion. Brain 1996b; 119: 2029–37.
Kimura J. The carpal tunnel syndrome: localization of conduction abnormalities within the distal segment of the median nerve. Brain 1979; 102: 619–35.
Kuwabara S, Cappelen-Smith C, Lin CSY, Mogyoros I, Burke D. Effects of voluntary activity on the excitability of motor axons in the peroneal nerve. Muscle Nerve 2002; 25: 176–84.[CrossRef][Web of Science][Medline]
Lindeström L, Magnusson R, Petersén I. Muscular fatigue and action potential conduction velocity studied with frequency analysis of EMG signals. Electromyography 1970; 10: 341–56.[Medline]
Macefield VG, Gandevia SC, Bigland-Ritchie B, Gorman RB, Burke D. The firing rates of human motoneurones voluntarily activated in the absence of muscle afferent feedback. J Physiol 1993; 471: 429–43.
Marsden CD, Meadows JC, Merton PA. Isolated single motor units in human muscle and their rate of discharge during maximal voluntary effort. J Physiol 1971; 217: 12P–13P.
Miller TA, Kiernan MC, Mogyoros I, Burke D. Activity-dependent changes in impulse conduction in normal human cutaneous axons. Brain 1995; 118: 1217–24.
Miller TA, Kiernan MC, Mogyoros I, Burke D. Activity-dependent changes in impulse conduction in a focal nerve lesion. Brain 1996; 119: 429–37.
Mogyoros I, Kiernan MC, Burke D. Strength–duration properties of human peripheral nerve. Brain 1996; 119: 439–47.
Morita K, David G, Barrett JN, Barrett EF. Posttetanic hyperpolarization produced by electrogenic Na(+)-K+ pump in lizard axons impaled near their motor terminals. J Neurophysiol 1993; 70: 1874–84.
Ochoa J, Marotte L. The nature of the nerve lesion caused by chronic entrapment in the guinea-pig. J Neurol Sci 1973; 19: 491–5.[CrossRef][Web of Science][Medline]
Simovic D, Weinberg DH. Terminal latency index in the carpal tunnel syndrome. Muscle Nerve 1997; 20: 1178–80.[CrossRef][Web of Science][Medline]
Simovic D, Weinberg DH. The median nerve terminal index in carpal tunnel syndrome: a clinical case selection study. Muscle Nerve 1999; 22: 573–7.[CrossRef][Web of Science][Medline]
Taylor JL, Burke D, Heywood J. Physiological evidence for a slow K+ conductance in human cutaneous afferents. J Physiol 1992; 453: 575–89.
Vagg R, Mogyoros I, Kiernan M, Burke D. Activity-dependent hyperpolarization of human motor axons produced by natural activity. J Physiol 1998; 507: 919–25.
Weiss C. Sur la possibilité de rendre comparables entre eux les appareils servant l’excitation électrique. Arch Ital Biol 1901; 35: 418–46.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||