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Biomedical subjects

M C Kiernan

Publications and source records attributed to M C Kiernan.

At least 19 recordsLinked to original sources
PubMed2006

Nocturnal hypoxia in motor neuron disease is not predicted by standard respiratory function tests.

BACKGROUND: With increasing awareness of motor neuron disease (MND) in Australia, the approach to respiratory management of patients with this disease will more commonly face the respiratory physician. AIM: The aim of this study was to determine if standard respiratory function tests could determine the presence of nocturnal hypoxia (NH) in patients with MND. METHODS: Respiratory function tests were used to examine daytime respiratory function, and sleep studies were used to detect NH in 16 consecutive patients with MND and in 9 healthy control subjects. Demographic data, clinical parameters, respiratory function tests and sleep studies were obtained. Statistical analyses were carried out using t-tests and anova, where appropriate. RESULTS: NH was detected in 50% of patients with MND, with no hypoxic events detected in the control group. Standard respiratory function tests were not able to predict the presence of NH. CONCLUSION: There was no correlation between respiratory function tests and NH. This study emphasizes the inability of standard respiratory function tests to predict NH that may arise early in the course of MND.

Adult↗
PubMed2006

Sensory nerve excitability and neuropathy in end stage kidney disease.

BACKGROUND: Peripheral neuropathy is present in 65% of patients with end stage kidney disease (ESKD) starting dialysis. Studies of membrane potential and axonal ion channel function may help explain the pathophysiology. OBJECTIVES: To follow changes in median sensory axon excitability in patients with ESKD treated with haemodialysis, and correlate them with clinical rating scales and serum levels of potential neurotoxins. METHODS: Sensory nerve action potentials were recorded from the second digit following stimulation of the median nerve in 12 ESKD patients. Stimulus-response behaviour using two stimulus durations, threshold electrotonus to 100 ms polarising currents, a current-threshold relation, and recovery of excitability following supramaximal stimulation were recorded before, during, and after haemodialysis. Serum concentrations of potential neurotoxins were measured. RESULTS: Before dialysis, there were changes in nerve excitability consistent with axonal depolarisation: refractoriness was increased; superexcitability and depolarising threshold electrotonus were reduced. Following dialysis there were improvements in all indices, with correlations between excitability abnormalities and serum potassium measurements. Neuropathic symptoms correlated with excitability changes. CONCLUSIONS: Nerves are depolarised before haemodialysis in ESKD patients. The correlation of excitability abnormalities with potassium indicates that the achievement of normokalaemia should be a priority in treating such patients.

Action Potentials↗
PubMed2003

Characteristics of late Na(+) current in adult rat small sensory neurons.

Na(+) currents were recorded using patch-clamp techniques from small-diameter (<25 micrometers) dorsal root ganglion neurons, cultured from adult rats (>150 g). Late Na(+) currents maintained throughout long-duration voltage-clamp steps (>/=200 ms) were of two types: a low-threshold, tetrodotoxin-sensitive (TTX-s) current that was largely blocked by 200 nM TTX, and a high-threshold, TTX-resistant (TTX-r) current. TTX-s late current was found in approximately 28% (10/36) of small-diameter neurons and was recorded only in neurons exhibiting TTX-s transient current. TTX-s transient current activation/inactivation gating overlap existed over a narrow potential range, centered between -30 and -40 mV, whereas late current operated over a wider range. The kinetics associated with de-inactivation of TTX-s late current were slow (tau approximately 37 ms at -50 mV), strongly suggesting that different subpopulations of TTX-s channel generate transient and late current. High-threshold TTX-r late current was only present in neurons generating TTX-r transient current. TTX-r late current operated over the same potential range as that for TTX-r transient current activation/inactivation gating overlap, and activation/inactivation gating overlap could be measured even after 1.5-s-duration pre-pulses. We suggest that TTX-s late sodium current results from channel openings different from those generating transient current. As in large-diameter sensory neurons, TTX-s channels generating late openings may play a key role in controlling membrane excitability. In contrast, a single population of high-threshold TTX-r channels may account for both transient and late TTX-r currents.

Action Potentials↗
PubMed2001

Clinical evaluation of excitability measures in sensory nerve.

A recently described method for recording multiple excitability parameters of human motor nerves has been adapted to the study of sensory nerves. The protocol measures stimulus-response behavior using two stimulus durations (from which the distribution of strength-duration time constants is estimated), threshold electrotonus to 100 ms polarizing currents, a current-threshold relationship (indicating inward and outward rectification), and the recovery of excitability following supramaximal activation. The method was tested on 50 healthy volunteers, stimulating the median nerve at the wrist and recording the antidromic compound sensory nerve action potential (SNAP) from digit 2. The excitability measurements were similar, where comparisons were possible, with published sensory nerve data, and confirmed differences from motor nerves, particularly in strength-duration behavior and recovery cycle, likely to reflect functional differences between sensory and motor nerves. Although slower than for motor nerves, the sensory nerve recordings were sufficiently quick (16 to 18 min) to allow them to be included in routine clinical studies. We propose that this method, which provides quite different and complementary information about nerve function to conventional conduction studies, provides a useful new approach for exploring the pathophysiology of sensory neuropathies.

Action Potentials↗
PubMed2001

Distal excitability properties of median motor axons.

Excitability properties were recorded from 14 volunteers following stimulation of the recurrent motor branch of the median nerve in the palm. Distal stimulation resulted in significantly lower strength-duration time constant and lower threshold during prolonged hyperpolarization than did wrist stimulation in the same subjects. These differences may be geometric in origin or alternatively may arise from functional changes distally, particularly reduced expression of persistent Na(+) conductances and more hyperpolarization-activated current. Excitability studies using palm stimulation provide information closer to the neuromuscular junction, where membrane properties are preferentially affected in a variety of clinical conditions.

Adult↗
PubMed2001

Excitability of human axons.

The excitability of human axons can be studied reliably using the technique of threshold tracking, which allows the strength of a test stimulus to be adjusted by computer to activate a defined fraction of the maximal nerve or muscle action potential. The stimulus current that just evokes the target response is considered the "threshold" for that response. More useful than the resting threshold are other indices of axonal excitability derived from pairs of threshold measurements, such as refractoriness, supernormality, strength-duration time constant and "threshold electrotonus" (i.e. the changes in threshold produced by long-lasting depolarizing or hyperpolarizing current pulses). Each of these measurements depends on membrane potential and on other biophysical properties of the axons. Together they can provide new information about the pathophysiology underlying abnormalities in excitability in neuropathy.

Action Potentials↗
PubMed2001

Butterfly lesion of the corpus callosum due to Schilder's disease.

A 50 year old woman developed memory impairment and confusion over a 2 week period. CT scans of the brain showed a 'butterfly lesion' of the corpus callosum extending into the frontal lobes bilaterally. Stereotactic biopsy determined the lesion to be du e to demyelination. Further diagnostic investigations and the subsequent clinical course support the diagnosis of Schilder's disease.

Biopsy↗
PubMed2001

Effects of temperature on the excitability properties of human motor axons.

The effects of temperature on parameters of motor nerve excitability were investigated in 10 healthy human subjects. The median nerve was stimulated at the wrist and compound muscle action potentials were recorded from the abductor pollicis brevis. Multiple excitability measures were recorded: stimulus-response curves, the strength-duration time constant (tauSD), threshold electrotonus, a current-threshold relationship and the recovery of excitability following supramaximal activation. Recordings were made at wrist temperatures of 35, 32 and 29 degrees C by immersing the arm proximal to the wrist in a water-bath. Cooling increased the relative refractory period by 7.8% per degree C (P < 0.0001), slowed the accommodation to depolarizing currents by 4.0% per degree C (P < 0.0001) and increased tauSD by 2.6% per degree C (P < 0.01), but most other excitability parameters were not affected significantly. The effects of temperature on threshold electrotonus were investigated further in separate studies on two subjects over the range 28-36 degrees C and found to be complex. Whereas the rate of accommodation to depolarizing current was closely related to instantaneous temperature, the threshold increase induced by hyperpolarizing current was most sensitive to changes in temperature, probably because warming the nerve causes a transient hyperpolarization by accelerating the electrogenic sodium pump. Consequently, it may be preferable to make allowances for differences in skin temperature when testing patients for abnormal excitability parameters, rather than to change the temperature to a standard value. For most excitability parameters, however, temperature control is not as important as it is for conduction velocity measurements.

Action Potentials↗
PubMed2001

Excitability properties of motor axons in patients with spontaneous motor unit activity.

OBJECTIVES: Measures of nerve excitability provide information about biophysical properties of peripheral axons in disease states. One measure, the strength duration time constant (tau(SD)), was previously reported to be prolonged in motor axons of patients with acquired neuromyotonia. The present study used a new protocol that applies a more comprehensive and sensitive panel of measures of axonal excitability, to determine firstly whether changes in tau(SD) were present in a group of patients with evidence of spontaneous motor unit activity; and secondly, if such changes in tau(SD) were present, whether other parameters of axonal excitability were affected, to clarify the mechanism of the change in tau(SD). METHODS: Eleven patients with both symptoms and EMG evidence of spontaneous motor unit activity were studied. Eight patients had autoimmune associated acquired neuromyotonia (aNMT) and three had the cramp fasciculation syndrome. The protocol first measured stimulus-response behaviour using two stimulus durations (from which the distribution of strength-duration time constants was estimated), and then threshold tracking was used to determine threshold electrotonus to 100 ms polarising currents, a current-threshold relation (indicating inward and outward rectification), and the recovery of excitability after supramaximal activation. RESULTS: The results were compared with previously published normal data. The value for tau(SD) of motor axons in the patient group was 0.43 (0. 02) ms (mean (SEM)), identical with the control value. Most other indices of axonal excitability, including those dependent on fast potassium channels, were also found to be normal. When compared with age matched controls however, the patients with acquired neuromyotonia had significantly greater late subexcitability after an impulse, greater excitability overshoots after depolarisation or hyperpolarisation, and more accommodation. CONCLUSIONS: No clear evidence for the mechanism of ectopic discharge in these patients was obtained, probably because the activity was generated focally, and most often at the motor nerve terminals. The unexpected finding of increased excitability overshoots and accommodation compared with age matched controls, suggests a relative up regulation of slow potassium conductance, possibly as a consequence of the continuous motor unit activity.

Adult↗
PubMed2000

Multiple measures of axonal excitability: a new approach in clinical testing.

From measurements of nerve excitability and the changes in excitability produced by nerve impulses and conditioning currents, it is possible to infer information about the membrane potential and biophysical properties of peripheral axons. Such information cannot be obtained from conventional nerve conduction studies. This article describes a new method that enables several such measurements to be made on a motor nerve quickly and reproducibly, with minimal operator intervention. The protocol measures stimulus-response behavior using two stimulus durations (from which the distribution of strength-duration time constants can be estimated), threshold electrotonus to 100-ms polarizing currents, a current-threshold relationship (indicating inward and outward rectification), and the recovery of excitability following supramaximal activation. The method was tested on 30 healthy volunteers, stimulating the median nerve at the wrist and recording from the abductor pollicis brevis. The results were comparable with previously published normal data, but the recordings took less than 10 min. The convenience and brevity of the new method make it appropriate for routine clinical use.

Action Potentials↗
PubMed2000

Effects of membrane polarization and ischaemia on the excitability properties of human motor axons.

Multiple nerve excitability measurements have been proposed for clinical testing of nerve function, since excitability measures can provide evidence of altered axonal membrane properties and are complementary to conventional nerve conduction studies. An important determinant of excitability is membrane potential, and this study was undertaken to determine the changes in a range of excitability properties associated with alterations in membrane potential. Membrane potential was varied directly using DC polarizing currents and indirectly by ischaemia. The median nerve was stimulated at the wrist and the resultant compound muscle action potentials recorded from abductor pollicis brevis. Stimulus-response behaviour, strength-duration time constant (tau(SD)), threshold electrotonus to 100-ms polarizing currents, a current-threshold relationship and the recovery of excitability following supramaximal activation were each followed in four normal subjects during the two manoeuvres, using a recently described protocol. Membrane depolarization and ischaemia produced an increase in axonal excitability, an increase in the slope of the current-threshold relationship, a 'fanning in' of responses during threshold electrotonus, a decrease in super-excitability, and increases in both tau(SD) and the refractory period. Changes in the opposite direction occurred with membrane hyperpolarization and during the post-ischaemic period. One excitability parameter differentiated between the direct and indirect changes in membrane potential: late subexcitability was sensitive to polarizing currents but relatively insensitive to ischaemia, probably because of compensatory changes in extracellular potassium ions. These results should enable multiple excitability measurements to be used as a tool to identify changes in axonal membrane potential in neuropathy.

Action Potentials↗
PubMed1999

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.

Action Potentials↗
PubMed1999

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.

Action Potentials↗
PubMed1998

Activity-dependent hyperpolarization of human motor axons produced by natural activity.

1. The changes in excitability of motor axons produced by natural activity were measured in six healthy subjects using voluntary contractions lasting 15 s, 30 s and 1 min, by recording the changes in stimulus current required to produce a compound muscle action potential of approximately 60 % of maximum. 2. On cessation of the contractions there was a prominent increase in the current required to produce the target potential, accompanied by an increase in rheobase, a decrease in strength-duration time constant, and an increase in axonal supernormality. These changes indicate that the hypoexcitability was due to axonal hyperpolarization. 3. The activity-dependent hypoexcitability increased in depth and duration the longer the contraction. Following a 1 min contraction, it produced a 24 % increase in threshold, waning over 15 min. The hypoexcitability was greater than in cutaneous afferents tetanized to produce an equivalent rate-dependent stress. 4. It is concluded that natural activity results in substantial hyperpolarization of active axons and that, for similar discharge rates, the degree of hyperpolarization is greater in motor axons than cutaneous afferents. The greater effect of activity on the excitability of motor axons could be due to less inward rectification and less persistent Na+ conductance than in sensory axons. It is suggested that motor axons may therefore be more susceptible than cutaneous afferents to conduction block at sites of impaired safety margin for impulse conduction.

Adult↗
PubMed1998

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.

Adult↗
PubMed1998

Quantitative description of the voltage dependence of axonal excitability in human cutaneous afferents.

The voltage dependence of indices of axonal excitability were quantified for cutaneous afferents in eight normal subjects, using the threshold for a target compound sensory action potential as a measure of membrane potential. The membrane potential was altered using subthreshold depolarizing and hyperpolarizing currents of various sizes (-50% to +50% of threshold). Refractoriness and supernormality were determined as the threshold change required to produce the target potential when preceded by a supramaximal stimulus at appropriate conditioning-test intervals. The strength-duration time constant (tauSD) was calculated from the threshold currents using unconditioned test stimuli of 0.1 and 1 ms. There was a near-linear relationship between each of these indices and the reciprocal of threshold (a measure of 'excitability'). It is argued that the voltage dependencies of refractoriness and tauSD largely reflect the behaviour of transient and persistent Na+ channels, respectively, and that the present data therefore quantify aspects of Na+ channel behaviour in human nerves.

Axons↗