ORCID Profile
0000-0002-4716-8578
Current Organisation
Chiba University
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Publisher: Wiley
Date: 2001
DOI: 10.1002/MUS.1175
Abstract: Recent evidence suggests that two conductances responsible for accommodation to changes in membrane potential (a slow K(+) conductance and inward rectification [I(H)]) are less active on cutaneous afferents in the sural nerve than on those in the median nerve, and it has been suggested that these axons would therefore respond differently to stress, whether natural or due to disease. The present study was undertaken in eight healthy volunteers to determine whether these afferents respond differently to the depolarizing and hyperpolarizing stresses that accompany ischemia for 13 min and subsequent recovery. During ischemia, the decrease in threshold was quantitatively less for the sural afferents, as were the changes in the other indices of axonal excitability, presumably because the ischemic depolarization was less for sural afferents. Following release of ischemia, there was, as predicted, a ergence in the pattern of threshold change. With median afferents there was evidence of a transient depolarization, believed to be due to inward rectification, superimposed on a long-lasting hyperpolarization. The response of sural afferents lacked this transient depolarizing threshold change. Cutaneous afferents in the median and sural nerves behave differently in response to ischemic and postischemic stresses, and it is likely that they will also respond differently to disease processes. In a number of respects the differences between sural and median afferents are analogous to differences between diabetic and normal nerves.
Publisher: Wiley
Date: 23-07-2002
DOI: 10.1002/ANA.10275
Abstract: Guillain-Barré syndrome is classified into acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) by electrodiagnostic and pathological criteria. In AMAN, the immune attack appears directed against the axolemma and nodes of Ranvier. Threshold tracking was used to measure indices of axonal excitability (refractoriness, supernormality, and threshold electrotonus) for median nerve axons at the wrist of patients with AMAN (n = 10) and AIDP (n = 8). Refractoriness (the increase in threshold current during the relative refractory period) was greatly increased in AMAN patients, but the abruptness of the threshold increases at short interstimulus intervals indicated conduction failure distal to the stimulation (ie, an increased refractory period of transmission). During the 4 week period from onset, the high refractoriness returned toward normal, and the litude of the compound muscle action potential increased, consistent with improvement in the safety margin for impulse transmission in the distal nerve. In contrast, refractoriness was normal in AIDP, even though there was marked prolongation of distal latencies. Supernormality and threshold electrotonus were normal in both groups of patients, suggesting that, at the wrist, membrane potential was normal and pathology was relatively minor. These results support the view that the predominantly distal targets of immune attack are different for AMAN and AIDP. Possible mechanisms for the reduced safety factor in AMAN are discussed.
Publisher: Elsevier BV
Date: 10-2008
DOI: 10.1016/J.CLINPH.2008.07.005
Abstract: The threshold tracking technique is a new approach to non-invasively assess biophysical properties of axonal membrane in human subjects. The aim of this study was to evaluate the effects of age and gender on excitability properties of human motor axons. Computerized threshold tracking was used to measure multiple excitability indices in median motor axons of 93 normal subjects (50 men age, 20-86 years). Regression analyses showed that the higher age was associated with longer strength-duration time constant (p=0.03), smaller threshold changes in depolarizing threshold electrotonus (p=0.02), smaller supernormality (p=0.01), and steeper slope of the current-threshold relationship for hyperpolarizing currents (p<0.001). There were slight sex differences in rheobase, threshold electrotonus, supernormality, late subnormality, and current-threshold slope, though they were significant only in the subgroup with age <50 years. Aging may increase persistent sodium currents, inward rectification, and possibly, outward potassium currents. The combination of changes raises the possibility of slight membrane depolarization in elderly people. For the sex-related differences, further studies will be required with the evaluation of sex hormonal effects. Age-related effects on excitability properties are subtle, but should be taken into consideration in the clinical application of nerve excitability testing, particularly in elderly subjects.
Publisher: Wiley
Date: 03-10-2002
DOI: 10.1002/MUS.10262
Abstract: The clinical and neurophysiological features of multifocal motor neuropathy (MMN) indicate selective involvement of motor axons, but pathological abnormalities in sensory axons suggest a more widespread disease process. The present study was undertaken to determine whether the focal abnormalities are associated with widespread subclinical abnormalities in motor axons. Threshold tracking was used to measure excitability properties (stimulus-response curves, strength-duration properties, recovery cycle, and threshold electrotonus) of the median nerve in five patients with MMN with lesions proximal to the site of testing. Patients were compared with 25 healthy controls. The changes in excitability indices were similar to those in controls, and in one patient there was no alteration after treatment with intravenous gammaglobulin. In this patient, indices of axonal excitability were also measured before, during, and after ischemia of the arm for 10 min. Again no differences were detected. This study provides no evidence for a generalized subclinical abnormality in MMN, at least when disease duration is less than 6 years.
Publisher: Wiley
Date: 02-2001
DOI: 10.1111/J.1469-7793.2001.0265J.X
Abstract: 1. Voluntary contraction of a muscle causes substantial hyperpolarization of the active motor axons due to activation of the electrogenic Na+-K+ pump. The present study was undertaken to determine whether voluntary effort produces a significant impairment in impulse transmission in normal axons and whether mechanisms other than membrane hyperpolarization contribute to the changes in axonal excitability. 2. The compound muscle action potential (CMAP) was recorded after median nerve stimulation at the wrist using sub- and supramaximal stimuli, delivered singly and in pairs at conditioning-test intervals of 2-15 ms. Axonal excitability parameters (threshold, refractoriness, supernormality, and strength-duration time constant (tauSD)) were measured using threshold tracking. Impulse transmission was assessed using supramaximal stimuli. 3. Maximal voluntary contractions of the abductor pollicis brevis for 1 min produced a substantial increase in threshold, an increase in supernormality and a decrease in tauSD, all of which lasted approximately 10 min and indicate axonal hyperpolarization. However, immediately after the contraction there was an unexpected increase in refractoriness. The post-contraction increase in refractoriness could not be mimicked by an imposed r of hyperpolarization that produced changes in the other indices to an extent that was similar to voluntary contraction. 4. The contraction had relatively little effect on the size of the unconditioned maximal CMAP. However, there was failure of transmission of supramaximal conditioned volleys when the conditioning-test interval was short. 5. The relationships between axonal excitability and supernormality and tauSD following voluntary contraction differed significantly from those recorded during the hyperpolarization produced by DC current. It is argued that these differences probably result from extra-axonal K+ accumulation with the voluntary contraction but not with the DC polarization. I6. It is concluded that, following maximal voluntary contraction of a normal muscle, the refractory period of transmission is impaired distal to the stimulus site sufficient to cause transmission failure of the second of a pair of closely spaced impulses. The site of transmission failure is likely to be the terminal axon, presumably at branch points, possibly in the unmyelinated pre-terminal segment.
Publisher: Wiley
Date: 28-01-2002
DOI: 10.1002/MUS.10030
Abstract: To investigate whether there are inter‐nerve differences in the extent and pattern of axonal excitability changes produced by voluntary contractions of tibialis anterior (TA) and abductor pollicis brevis (APB), threshold tracking was used to measure axonal excitability parameters [threshold, supernormality and strength‐duration time constant (τ SD )] of peroneal and median motor axons in 11 healthy subjects. Maximal contractions for 1 min resulted in an increase in threshold, an increase in supernormality, a decrease in τ SD and an increase in latency, all of which indicate axonal hyperpolarization. The increase in threshold was less in peroneal axons (18 ± 4%) than median axons (37 ± 6%, mean ± SEM, P 0.001), and was accompanied by smaller absolute changes in latency, supernormality, and τ SD . Peroneal axons had less supernormality at rest but a greater change in supernormality for the change in threshold. There were major contraction‐induced changes in the compound muscle action potential of TA but not that of APB. Voluntary contractions depress axonal excitability, but the changes are quantitatively different for motor axons innervating different muscles. There are three clinical implications. First, weakness and fatigue due to activity‐dependent conduction block may vary for different muscles, independent of disease severity, and therapeutic strategies to overcome activity‐dependent conduction block may not be equally effective for different muscles. Second, in motor control studies using the H reflex to document motoneuron excitability, a constant stimulus will not produce a constant neural volley if the stimulated axons have been activated by, for ex le, a voluntary contraction. Third, TA is probably not optimal for testing for activity‐dependent conduction block. © 2002 John Wiley & Sons, Inc. Muscle Nerve 25: 176–184, 2002 DOI 10.1002/mus.10030
Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.CLINPH.2011.11.002
Abstract: The aim of this study was to investigate differences in excitability properties of human median and superficial radial sensory axons (e.g., axons innervating the glabrous and hairy skin in the hand). Previous studies have shown that excitability properties differ between motor and sensory axons, and even among sensory axons between median and sural sensory axons. In 21 healthy subjects, threshold tracking was used to examine excitability indices such as strength-duration time constant, threshold electrotonus, supernormality, and threshold change at the 0.2 ms inter-stimulus interval in latent addition. In addition, threshold changes induced by ischemia for 10 min were compared between median and superficial radial sensory axons. Compared with radial sensory axons, median axons showed shorter strength-duration time constant, greater threshold changes in threshold electrotonus (fanning-out), greater supernormality, and smaller threshold changes in latent addition. Threshold changes in both during and after ischemia were greater for median axons. These findings suggest that membrane potential in human median sensory axons is more negative than in superficial radial axons, possibly due to greater activity of electrogenic Na(+)/K(+) pump. These results may reflect adaptation to impulses load carried by median axons that would be far greater with a higher frequency. Biophysical properties are not identical in different human sensory axons, and therefore their responses to disease may differ.
Publisher: Elsevier BV
Date: 05-2018
Publisher: Wiley
Date: 10-02-2009
DOI: 10.1002/MUS.21107
Abstract: The first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles are innervated by the same ulnar nerve, but studies have shown that the former is much more severely affected in amyotrophic lateral sclerosis. In this study, threshold tracking was used to investigate whether membrane properties differ between FDI and ADM motor axons. In 12 normal subjects, compound muscle action potentials were recorded from FDI and ADM after ulnar nerve stimulation at the wrist. The strength-duration time constant was significantly longer in the FDI axons than in the ADM axons, and latent addition studies showed greater threshold changes at the conditioning-test stimulus of 0.2 ms in FDI than in ADM axons. These findings suggest that nodal persistent sodium conductances are more prominent in FDI axons than in ADM axons, and therefore excitability is physiologically higher in FDI axons. Even in the same nerve at the same sites, membrane properties of FDI and ADM motor axons differ significantly, and thus their axonal/neuronal responses to disease may also differ.
Publisher: Wiley
Date: 12-2000
Publisher: Wiley
Date: 03-2019
DOI: 10.1111/JNS.12303
Publisher: BMJ
Date: 03-2001
Abstract: To investigate whether accommodation to depolarising and hyperpolarising currents differs for motor axons of human upper and lower limb nerves. The threshold tracking technique was used to measure threshold electrotonus for median and peroneal motor axons. The threshold current that produced a compound muscle action potential 50% of maximum was measured, and membrane potential was altered using subthreshold polarising currents of 330 ms duration but of variable intensity, from +40% (depolarising) to -100% (hyperpolarising) of the unconditioned threshold. The maximal threshold changes (the peak of the S1 phase of threshold electrotonus) were significantly greater in median axons for both depolarising and hyperpolarising currents. The subsequent phases of accommodation to depolarising currents (S2) and to hyperpolarising currents (S3) were also significantly greater in median axons. These findings raised the possibility that greater accommodation (S2 and S3) in median axons resulted from greater changes in membrane potential. However, regression of S2 against S1 to depolarising currents disclosed significantly greater accommodation (27.8%) for median axons, suggesting that slow K(+) conductances may be more prominent on median than peroneal axons. By contrast, the relation between S3 and S1 to hyperpolarising currents was similar for the two nerves, suggesting that the difference in inward rectification was merely because the conductance varies with the extent of hyperpolarisation. Slow K(+) conductances are more prominent for median motor axons than for peroneal axons. It would therefore be expected that axons innervating the lower limbs have less protection from depolarising stress and could develop ectopic activity more readily.
Publisher: Wiley
Date: 2000
DOI: 10.1002/1097-4598(200011)23:11<1719::AID-MUS8>3.0.CO;2-W
Abstract: In a number of clinical studies, measurement of axonal strength-duration properties has been used to provide indirect insight into conductances at the node of Ranvier, particularly persistent Na(+) conductance. However, the specificity of any changes is limited because other factors can affect strength-duration behavior. The present study was undertaken to define the relationship between different strength-duration measures at rest and at different membrane potentials, and also to determine the limits within which strength-duration behavior can be used as a measure of nodal conductances. The strength-duration time constant (tau(SD)) and rheobase of 20 single motor units in the flexor carpi ulnaris were calculated from thresholds defined using threshold tracking. "True" rheobase and rheobasic latencies were measured using test stimuli of 100-ms duration. For ten units, the technique of latent addition was used to measure threshold changes directly attributable to nodal conductances, and for six units these were compared with strength-duration properties at different membrane potentials. The data indicate that measurements of tau(SD) and rheobase can provide sensitive indicators of conductances present at the node of Ranvier when membrane potential changes. There is a reciprocal relationship between tau(SD) and rheobase for single motor units at different membrane potentials, and this relationship may allow changes in tau(SD) due to depolarization and demyelination to be differentiated.
Publisher: Wiley
Date: 15-02-2019
DOI: 10.1111/JNS.12302
Publisher: Wiley
Date: 12-2000
DOI: 10.1111/J.1469-7793.2000.00483.X
Abstract: To determine whether accommodation to depolarizing and hyperpolarizing stimuli differs for cutaneous afferents in the median and sural nerves, studies were performed in normal human subjects using threshold electrotonus. The changes in threshold for compound sensory action potentials of 50 % of maximum were recorded when the nerves were subjected to long-lasting depolarizing and hyperpolarizing DC. The premise was that the threshold changes largely mirror the underlying electrotonic changes in membrane potential. The maximal threshold changes produced by depolarizing and hyperpolarizing currents were greater for median afferents, suggesting that the DC produced greater changes in membrane potential in these afferents. Median afferents underwent greater accommodation to depolarizing currents than sural afferents and a greater threshold undershoot at the end of the currents, suggesting greater activity of a slow K+ conductance. Median afferents also underwent greater accommodation to hyperpolarizing currents, suggesting greater inward rectification. These conductances are voltage dependent, and the differences in accommodation could be due to greater changes in membrane potential for the median nerve. The changes in threshold produced by long-lasting depolarizing and hyperpolarizing currents of graded intensity were therefore measured. When the threshold changes were matched for the two nerves, median afferents underwent 22.4 % more accommodation to depolarizing currents and 28.7 % more accommodation to hyperpolarizing currents. We conclude that there is greater expression of two internodally located conductances responsible for accommodation on median afferents. The biophysical differences identified in this study might contribute to the finding that sural afferents have a greater tendency to dysfunction than median afferents.
Publisher: Elsevier BV
Date: 07-2008
DOI: 10.1016/J.CLINEURO.2008.04.004
Abstract: To investigate cutaneous sympathetic functions in carpal tunnel syndrome (CTS) using sympathetic sweat responses (SSwRs) and skin vasomotor reflexes (SVmRs). In 29 hands (20 patients) with idiopathic CTS, SSwRs were recorded with a sudorometer from the thenar eminence, and SVmRs were used to measure cutaneous blood flow using a Doppler flowmeter placed on the index finger tip. Normal data were obtained from 15 volunteers of similar age. SSwRs or SVmRs were abnormal in 23 (80%) hands SSwRs were absent in 38%, whereas SVmRs were abnormally decreased in 59%. Autonomic symptoms were present in 18 (62%) hands finger edema (38%) and dry hand (35%) were frequent symptoms. Autonomic symptoms, and abnormal SSwRs and SVmRs did not correlate with results of nerve conduction studies. Skin sudomotor or vasomotor sympathetic function is frequently impaired in CTS. Susceptibility to compression ischemia may be different in sympathetic unmyelinated and large myelinated fibers.
Publisher: Wiley
Date: 2000
DOI: 10.1002/1097-4598(200009)23:9<1365::AID-MUS7>3.0.CO;2-1
Abstract: Threshold tracking was used to compare excitability properties (stimulus-response curves, strength-duration properties, recovery cycle, and threshold electrotonus) of median motor axons at the wrist and peroneal motor axons at the ankle in 12 healthy subjects. Stimulus-response curves and strength-duration properties were similar, though higher stimulus intensities were required for peroneal axons. However, there were significant differences in the recovery cycle of excitability following a conditioning stimulus and in threshold electrotonus. In the recovery cycle, median axons had significantly greater supernormality and late subnormality. In threshold electrotonus, the initial slow threshold changes in response to subthreshold depolarizing and hyperpolarizing currents (S1) were significantly greater in median axons, and there was also greater accommodation to depolarizing currents (S2) and greater threshold undershoot after depolarization. Similar differences in supernormality and the S1 phase of threshold electrotonus were found between peroneal axons at ankle and knee, suggesting that these properties may be dependent on nerve length. When median motor axons at the wrist were compared with peroneal motor axons at the knee, there were no differences in refractoriness and supernormality and only small differences in S1, but the late subnormality and undershoot were significantly greater in the median axons. These findings suggest that, in addition to any length-dependent differences, peroneal axons have a less prominent slow K(+) conductance. We conclude that the properties of different motor axons are not identical and their responses to injury or disease may therefore differ.
Publisher: Wiley
Date: 18-12-2003
DOI: 10.1002/MUS.10551
Abstract: Threshold tracking was used to measure excitability indices (strength-duration properties, threshold electrotonus, and the current-threshold relationship) at the motor point of the abductor pollicis brevis, and the results were compared with those of the median nerve at the wrist. Using an accelerometer placed at the thumb tip, movement-related potentials were recorded as target responses. When stimulating at the same site, excitability measurements were no different, and their variability no greater, when the target responses were movements rather than muscle action potentials. Motor point stimulation resulted in significantly shorter strength-duration time-constant and higher rheobase than wrist stimulation. In addition, the technique of latent addition showed that a slow component was much smaller at the motor point than at the wrist. In threshold electrotonus, threshold changes in response to depolarizing and hyperpolarizing conditioning currents were significantly smaller at the motor point than at the wrist. The differences in strength-duration time-constant and latent addition suggest that persistent Na(+) current at the resting potential is smaller at the motor point. The differences in threshold electrotonus may depend in part on altered fiber geometry but suggest that inward and possibly outward rectification are increased distally. Motor point excitability testing may provide new insights into the pathophysiology of the nerve terminals in a variety of peripheral neuropathies and motor neuron disorders.
Publisher: BMJ
Date: 19-04-2016
Abstract: While the past 2 decades have witnessed an increasing understanding of amyotrophic lateral sclerosis (ALS) arising from East Asia, particularly Japan, South Korea, Taiwan and China, knowledge of ALS throughout the whole of Asia remains limited. Asia represents >50% of the world population, making it host to the largest patient cohort of ALS. Furthermore, Asia represents a erse population in terms of ethnic, social and cultural backgrounds. In this review, an overview is presented that covers what is currently known of ALS in Asia from basic epidemiology and genetic influences, through to disease characteristics including atypical phenotypes which manifest a predilection for Asians. With the recent establishment of the Pan-Asian Consortium for Treatment and Research in ALS to facilitate collaborations between clinicians and researchers across the region, it is anticipated that Asia and the Pacific will contribute to unravelling the uncertainties in ALS.
Publisher: Wiley
Date: 06-2002
DOI: 10.1113/JPHYSIOL.2002.017848
Abstract: This study compared directly the post-ischaemic behaviour of sensory and motor axons in the human median nerve, focusing on the excitability changes produced by ischaemia and its release and by continuous polarizing DC. The decrease in threshold during ischaemia for 13 min was greater, the post-ischaemic increase in threshold was more rapid, and the return to the pre-ischaemic excitability took longer in sensory axons. However, a transient depolarizing threshold shift developed in sensory axons a few minutes after release of ischaemia. This pattern could not be reproduced by polarizing currents designed to mimic the probable pump-induced changes in membrane potential, even though the applied currents produced greater changes in threshold. Hyperpolarizing currents of equivalent intensity produced a greater increase in threshold for motor axons than sensory axons and, in studies of threshold electrotonus using graded hyperpolarizing DC, accommodation was greater in sensory than motor axons. The post-ischaemic changes in threshold were not uniform for axons of different threshold, whether sensory or motor, the threshold increase was usually less prominent for low-threshold axons. A transient post-ischaemic depolarization could be produced in motor axons with ischaemia of 20 min duration. Greater ischaemic and post-ischaemic changes in threshold for sensory axons could reflect greater dependence on the electrogenic Na+-K+ pump to maintain resting membrane potential and/or greater extracellular K+ accumulation in ischaemic sensory axons. Inward K+ currents due to extracellular K+ accumulation would then be more likely to trigger a depolarizing shift in membrane potential, the degree of K+ accumulation and pump activity being dependent on the duration of ischaemia. In sensory axons the greater tendency to accommodate to hyperpolarizing stimuli presumably contributes to shaping their post-ischaemic behaviour but is probably insufficient to explain why their behaviour differs from that of motor axons.
No related grants have been discovered for Satoshi Kuwabara.