Differences in responses of cutaneous afferents in the human median and sural nerves to ischemia.

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 divergence 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.

Membrane properties in chronic inflammatory demyelinating polyneuropathy.

Threshold tracking was used to compare excitability properties (stimulus-response curves, strength-duration properties, recovery cycle and threshold electrotonus) of the median nerve in 11 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 25 healthy controls. Stimulus-response curves were significantly different: threshold was much higher, the slope of the curves reduced and the spread of the thresholds greater in the CIDP group. The strength-duration time constant (tau(SD)) was significantly shorter and the rheobase higher in the CIDP group. In the recovery cycle, the CIDP group had less refractoriness, supernormality and late subnormality than healthy controls, but the duration of the relatively refractory period was normal. These changes in tau(SD) and the recovery cycle were not those previously predicted. There were no consistent changes in threshold electrotonus, suggesting that, for the studied axons, there are no consistent changes in accommodation properties that depend on internodal conductances. It is difficult to explain these changes in excitability on the basis of a change in membrane potential, or solely as the result of demyelination, and it is possible that other morphological factors such as variable remyelination and inflammatory oedema affected axonal excitability in the patients.

Voluntary contraction impairs the refractory period of transmission in healthy human axons.

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 ramp 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.

Differences in accommodative properties of median and peroneal motor axons.

OBJECTIVES: To investigate whether accommodation to depolarising and hyperpolarising currents differs for motor axons of human upper and lower limb nerves. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Accommodation to depolarizing and hyperpolarizing currents in cutaneous afferents of the human median and sural nerves.

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.

Activity-dependent hyperpolarization and conduction block in chronic inflammatory demyelinating polyneuropathy.

Voluntary activity produces activity-dependent hyperpolarization of the active motor axons. The present study investigated whether this hyperpolarization produces conduction block in chronic inflammatory demyelinating polyneuropathy (CIDP). Studies were performed in 10 healthy control subjects, 7 patients with CIDP, and 3 patients with multifocal motor neuropathy. The compound muscle action potential (CMAP) of the abductor pollicis brevis was recorded in response to supramaximal stimuli to the median nerve at the wrist, alternating with measurements of axonal excitability. After a maximal voluntary contraction for 60 seconds, the amplitude of the maximal CMAP was significantly reduced in symptomatic CIDP patients by 40%, but there were only slight changes in the CMAPs of healthy controls, asymptomatic CIDP patients, and multifocal motor neuropathy patients. In symptomatic CIDP patients, the activity-dependent conduction block paralleled the activity-dependent hyperpolarization and was presumably precipitated by it. In these patients, the safety margin for impulse conduction was estimated to be about 12%. Activity-dependent conduction block may be clinically important in chronic demyelinating diseases and can be demonstrated electrophysiologically if testing occurs across pathological sites.

Strength-duration properties and their voltage dependence as measures of a threshold conductance at the node of Ranvier of single motor axons.

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.

Excitability properties of median and peroneal motor axons.

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.

Recovery of excitability of cutaneous afferents in the median and sural nerves following activity.

In acquired polyneuropathies, symptoms and signs are typically distal and symmetrical, more prominent in the lower limbs than the upper limbs. This study was undertaken to measure the extent of the decrease in excitability produced by single impulses and by impulse trains in cutaneous afferents in the median and sural nerves, and to compare the resulting changes in excitability of these afferents. Threshold tracking was used in 10 healthy subjects to measure the changes in threshold for a compound sensory action potential of 50% maximum produced by conditioning stimuli. Following a single supramaximal conditioning stimulus, the threshold changes occurring during the refractory and supernormal periods were identical for the two nerves, but there was a greater increase in threshold during the late subnormal period for median afferents. Following a train of 10 supramaximal conditioning stimuli, threshold increased by approximately 40% for median afferents and by approximately 20% for sural afferents. These differences are consistent with differences in a slow K(+) conductance. It is suggested that the hypo-excitability produced by brief trains of impulses may be sufficient to disturb conduction in diseased nerve fibers, and that the lesser expression of slow K(+) conductances on cutaneous afferents in the sural nerve could render them more sensitive to depolarizing stresses than median afferents. This could be a factor in the ease with which sural afferents become ectopically active in polyneuropathies.

Ischaemic changes in refractoriness of human cutaneous afferents under threshold-clamp conditions.

1. A technique was developed to counteract the changes in threshold to electrical stimuli of large myelinated cutaneous afferents in the human median nerve induced by ischaemia for 13 min. Intermittent application of polarizing currents was used in five subjects, in whom refractoriness, supernormality and the strength-duration time constant (tauSD) were tracked to determine whether compensating for the ischaemia-induced changes in threshold also controlled the ischaemic changes in these excitability parameters. 2. The threshold compensation prevented the ischaemic changes in tauSD, an excitability parameter dependent on nodal Na+ channels. Threshold compensation did not prevent the changes in refractoriness and supernormality, whether the compensation began 10, 100 or 200 ms prior to the test stimuli. 3. In three subjects, continuous polarizing current was injected for 13 min to compensate for the ischaemic change in threshold, thus clamping threshold at the pre-ischaemic level. Again, tauSD was effectively controlled, but there were still ischaemic changes in refractoriness and supernormality. 4. The effective control of tauSD suggests that both the intermittent threshold compensation and the continuous threshold clamp effectively controlled membrane potential at the node of Ranvier. 5. The ischaemic increase in refractoriness when threshold was kept constant could be due to interference with the processes responsible for refractoriness by a metabolic product of ischaemia. The ischaemic change in supernormality during effective compensation probably results from the intrusion of refractoriness into the conditioning-test intervals normally associated with maximal supernormality. 6. The present results indicate that ischaemia has effects on axonal excitability that cannot be readily explained by changes in membrane potential. Specifically, it is suggested that ischaemic metabolites interfere with the recovery of Na+ channels from inactivation.

Mechanisms of paresthesias arising from healthy axons.

Paresthesias are common manifestations of central and peripheral pathological processes and are due to ectopic impulse activity in cutaneous afferents or their central projections. Cutaneous afferents are more excitable than motor axons, due to differences in their biophysical properties. These differences probably include more persistent Na(+) conductance and inward rectification on cutaneous afferents, properties which probably confer greater protection from impulse-dependent conduction failure but create a greater tendency to ectopic activity. Ectopic discharges can be induced in normal afferents by four maneuvers: hyperventilation, ischemia, release of ischemia, and prolonged tetanization. The alkaline shift produced by hyperventilation selectively increases the persistent Na(+) conductance, while the membrane depolarization produced by ischemia affects both transient and persistent Na(+) channels. Postischemic and posttetanic paresthesias occur when hyperpolarization by the Na(+)/K(+) pump is transiently prevented by raised extracellular K(+). The electrochemical gradient for K(+) is reversed, and inward K(+) currents trigger regenerative depolarization. These mechanisms of paresthesia generation can account for paresthesias in normal subjects and may be relevant in some peripheral nerve disorders.

Reproducibility of indices of axonal excitability in human subjects.

OBJECTIVES: Different indices of axonal excitability are now being measured in human subjects, both normal volunteers undergoing some test manoeuvre and patients with a variety of peripheral nerve disorders. The reproducibility of these indices has not previously been established, and was determined for cutaneous afferents in the median nerve of 12 healthy subjects, using threshold tracking techniques. METHODS: Refractoriness and supernormality were determined as the change in stimulus current required to produce a predetermined target potential when conditioned by a supramaximal stimulus at appropriate conditioning-test intervals. Strength-duration time constant was calculated from the threshold currents using unconditioned test stimuli of 0.1 ms and 1.0 ms. The effects of changes in membrane potential on these indices was assessed by applying subthreshold DC currents (from 50% depolarizing to 50% hyperpolarizing), using the reciprocal of threshold (i.e., 'excitability') as an indicator of membrane potential. The intraindividual reproducibility was determined by repeating the study on each subject up to 10 times. RESULTS: Refractoriness and supernormality were variable between subjects (mean +/- SD of 31.5 +/- 9.5% and 13.2 +/- 3.8%, respectively) and within subjects (coefficient of variation 0.2104 and 0.21849, respectively). TauSD showed even greater interindividual variability (499.2 +/- 115 micros) and intraindividual variability (coefficient of variation 0.2339). The slopes of relationships between each of the indices and axonal 'excitability' suggest that refractoriness is extremely sensitive to changes in excitability (0.9767 +/- 0.1907), tauSD less so (0.3766 +/- 0.1322), supernormality least (0.2223 +/- 0.1268). CONCLUSIONS: Under controlled conditions, refractoriness is the most sensitive and least variable of the indices of axonal excitability. However, small decreases in temperature greatly increase refractoriness but have little effect on tauSD. Given that 3 indices reflect different biophysical mechanisms, nodal and internodal, greater insight into the functional state of peripheral nerve axons will come when there are coherent changes in all 3 indices.

Strength-duration properties and their voltage dependence at different sites along the median nerve.

OBJECTIVES: There is some evidence that the ease with which ectopic activity can be induced varies systematically along the course of a nerve and is greater at more proximal sites. Recent studies have implicated a non-inactivating threshold conductance, possibly due to persistent Na+ channels, in ectopic activity associated with ischaemia and hyperventilation. This conductance is largely responsible for the voltage dependence of strength-duration time constant (tauSD), and changes in it can explain the time constant changes that occur during hyperventilation and ischaemia. METHODS: To determine whether the strength-duration properties of motor axons of the median nerve vary along the course of the nerve, tauSD and rheobase were calculated at wrist, elbow and axilla in 15 healthy subjects, and the relationship of these properties to threshold was assessed using DC polarizing current to change axonal excitability. RESULTS: tauSD was similar at the 3 stimulating sites but increased less at the axilla with depolarizing current. CONCLUSIONS: These data indicate that the greater tendency for ectopic activity to arise from proximal segments of motor axons cannot be explained by differences in the conductances that contribute to tauSD and underlie its dependence on axonal excitability. The findings provide further support for the view that the precise relationship of the stimulating electrodes to the nerve has little effect on tauSD, at least when it is measured in the forearm.

Reproducibility of tendon jerk reflexes during a voluntary contraction.

OBJECTIVES: The present study explored whether testing tendon jerks during voluntary contraction of the test muscle would improve reproducibility by effectively 'clamping' the excitability of the motoneurone pool at firing threshold. METHODS: Tendon jerk reflexes of soleus, tibialis anterior and vastus lateralis and the soleus H reflex were recorded in 12 healthy subjects at rest and during voluntary contractions of 10-20% of maximum. Recordings were repeated 8-10 times in 5 subjects, in whom reflex symmetry was also determined. RESULTS: Not all tendon jerk reflexes could be recorded at rest, and the variability of latency and amplitude was high. All reflexes could be recorded in each subject during contractions. The latency of tendon jerk reflexes decreased by approximately 2 ms during contractions, but H-reflex latency decreased by only 0.2-0.3 ms. For the tendon jerks, an asymmetry of >3.0 ms at rest and >2.5 ms contracting would be outside 3 SD of the normal mean. In repeat studies, the coefficient of variation of reflex latency was <4% for the tendon jerk. CONCLUSIONS: A voluntary contraction could potentiate the tendon jerk by a number of mechanisms, but the most important is probably enhancement of the excitability of the motoneurone pool. The present techniques should increase the value of tendon reflex testing when assessing possible peripheral nerve, plexus and root disturbances.

Conduction block in carpal tunnel syndrome.

Wrist extension was performed in six healthy subjects to establish, first, whether it would be sufficient to produce conduction block and, secondly, whether the excitability changes associated with this manoeuvre are similar to those produced by focal nerve compression. During maintained wrist extension to 90 degrees, all subjects developed conduction block in cutaneous afferents distal to the wrist, with a marked reduction in amplitude of the maximal potential by >50%. This was associated with changes in axonal excitability at the wrist: a prolongation in latency, a decrease in supernormality and an increase in refractoriness. These changes indicate axonal depolarization. Similar studies were then performed in seven patients with carpal tunnel syndrome. The patients developed conduction block, again with evidence of axonal depolarization prior to block. Mild paraesthesiae were reported by all subjects (normals and patients) during wrist extension, and more intense paraesthesiae were reported following the release of wrist extension. In separate experiments, conduction block was produced by ischaemic compression, but its development could not be altered by hyperpolarizing currents. It is concluded that wrist extension produces a 'depolarization' block in both normal subjects and patients with carpal tunnel syndrome, much as occurs with ischaemic compression, but that this block cannot be altered merely by compensating for the axonal depolarization. It is argued that conduction slowing need not always be attributed to disturbed myelination, and that ischaemic compression may be sufficient to explain some of the intermittent symptoms and electrodiagnostic findings in patients with carpal tunnel syndrome, particularly when it is of mild or moderate severity.

Changes in excitability indices of cutaneous afferents produced by ischaemia in human subjects.

1. The present study was undertaken to determine whether mechanisms other than membrane depolarization contribute to the changes in excitability of cutaneous afferents of the median nerve under ischaemic conditions. 2. In six healthy subjects, axonal excitability was measured as the reciprocal of the threshold for a compound sensory action potential (CSAP) of 50% maximal amplitude. Refractoriness and supernormality were measured as threshold changes 2 and 7 ms, respectively, after supramaximal conditioning stimuli. The strength-duration time constant (tauSD) was calculated from the thresholds for unconditioned CSAPs using test stimuli of 0.1 and 1.0 ms duration. Changes in these indices were measured when subthreshold polarizing currents lasting 10 or 100 ms were applied, before, during and after ischaemia for 13 min. 3. At rest, the change in supernormality produced by polarizing currents was greater with the longer polarizing current, indicating that it took up to 100 ms to charge the internodal capacitance. 4. Refractoriness and its dependence on excitability increased more than expected during ischaemia. Supernormality was abolished during ischaemia, and reached a maximum after ischaemia but was then barely altered by polarizing current. tauSD had a similar relationship to excitability before, during and after ischaemia. 5. By contrast, during continuous depolarizing current for 8 min to mimic the depolarization produced by ischaemia, the relationship between excitability and refractoriness was the same during the depolarization as before it. 6. It is suggested that the large increase in refractoriness during ischaemia might be due to interference with the recovery from inactivation of transient sodium channels by an intra-axonal substrate of ischaemia. The post-ischaemic increase in supernormality and the lack of change with changes in axonal excitability can be explained by blockage of voltage-dependent potassium channels.

Temperature dependence of excitability indices of human cutaneous afferents.

The temperature dependence of different indices of axonal excitability (threshold, latency, refractoriness, supernormality, strength-duration time constant, and rheobase) was studied for cutaneous afferents of 8 healthy human volunteers using threshold tracking. Cooling from approximately 32 - approximately 22 degrees C dramatically increased the threshold for a conditioned potential evoked during the relatively refractory period (average increase 573%) but had little effect on the threshold for unconditioned potentials (increased by 4% with 0.1-ms test stimuli), strength-duration time constant (increased by 18%), or rheobase (decreased by 12%). Cooling increased the latency of the unconditioned test potential by 41%, but this slowing was small compared with the effect of cooling on the latency slowing attributable to refractoriness. This measure of refractoriness was initially 0.17 ms at a conditioning-test interval of 2 ms, and increased with cooling to 1.30 ms at the same interval. With cooling, refractoriness was both greater at any one conditioning-test interval and longer in duration, extending into intervals normally associated with supernormality. It is concluded that, although cooling affects all excitability indices to some extent, the most prominent feature is the increase in refractoriness. By contrast, strength-duration time constant is influenced little by temperature.

Value of homonymous and heteronymous monosynaptic reflexes in the diagnosis and follow-up of cervical spinal injuries.

Needle electromyographic examination constitutes the only neurophysiological test used routinely to assess the integrity of proximal nerve pathways. A heteronymous reflex, with a latency consistent with a monosynaptic pathway, can be evoked in the contracting biceps brachii muscle by stimulation of the median nerve at the elbow. This reflex response provides a complementary technique to the biceps and supinator jerks for accessing the C(5)/C(6)motoneuron pool because its afferent limb involves the median nerve and the C(5)/C(6)posterior roots. Three cases are described to illustrate the clinical value of this heteronymous monosynaptic reflex of biceps brachii and of conventional H reflexes in the diagnosis and follow-up of lesions involving the C(5)/C(6)segments. Reflex function can be assessed for most spinal segments innervating the upper and lower limbs, thus allowing both objective confirmation of the clinical findings and documentation of changes over time. Copyright 1999 Harcourt Publishers Ltd.

Ischemic resistance of cutaneous afferents and motor axons in patients with amyotrophic lateral sclerosis.

Compared with control subjects, patients with amyotrophic lateral sclerosis (ALS) have been reported to experience less or no paresthesias during and after release of ischemic compression of the upper arm for 10 min. This is reminiscent of the resistance to ischemia of diabetic patients, in whom sensory and motor axons undergo less ischemic depolarization and less postischemic hyperpolarization than in control subjects. The present study compared the changes in axonal excitability produced by ischemia for 10 min in 21 patients with ALS and 14 age-matched control subjects. Fewer patients reported intraischemic or postischemic paresthesias and the intensity of paresthesias was less, but this was significant only for postischemic paresthesias. There were quantitatively similar changes in refractoriness, supernormality, and strength-duration time constant during ischemic compression, but the increase in excitability of motor axons was less during the second half of ischemia in the patients. After release of ischemia the postischemic hyperpolarization was greater in the ALS patients, the opposite of what occurs in diabetes. These changes could reflect reduced intraneural K+ accumulation due to loss of motor axons or an alteration in nerve metabolism or membrane properties. Either way, the present study has failed to confirm previous reports of "ischemic resistance" in ALS, and indicates that the changes in axonal properties in ALS are not analogous to those in diabetes mellitus.