Refractory Period Of Transmission Research Articles

Electrophysiological studies in mild idiopathic carpal tunnel syndrome

Many techniques have been reported to improve the diagnosis of carpal tunnel syndrome (CTS), but there is no agreement on the diagnostic yield of these different methods. We used an electrophysiological protocol including the assessment of the orthodromic sensory conduction velocity of the median nerve along the carpal tunnel, comparison of median and ulnar sensory conduction between the ring finger and wrist, short segment incremental median sensory nerve conduction across the carpal tunnel recording from the III digit (`inching test'), the study of the refractory period of transmission (RPT) and calculation of the distoproximal ratio obtained by dividing the nerve conduction velocity in the median nerve between the third digit and the palm and between the palm and wrist in 41 patients with mild CTS (75 symptomatic hands) and in 45 control subjects. The distoproximal ratio calculation was the most sensitive technique (81%), but was also the least specific. The `inching test', even though less sensitive, had the advantage of localising focal abnormalities of the median nerve along the carpal tunnel. RPT was abnormal in patients with recent symptoms. Combining the different techniques, an overall sensitivity of 92% was reached, 11% higher than the yield of the single best test suggesting that a multimodal approach could be useful. The best procedure for electrodiagnosis of mild CTS was to combine the median/ulnar comparison test with calculation of the disto-proximal ratio.

Conduction in Segmentally Demyelinated Mammalian Central Axons

The prominent symptoms associated with central demyelinating diseases such as multiple sclerosis (MS) are primarily caused by conduction deficits in affected axons. The symptoms may go into remission, but the mechanisms underlying remissions are uncertain. One factor that could be important is the restoration of conduction to affected axons, but it is not known whether demyelinated central axons resemble their peripheral counterparts in being able to conduct in the absence of repair by remyelination. In the present study we have made intra-axonal recordings from central axons affected by a demyelinating lesion, and then the axons have been labeled ionophoretically to permit their subsequent identification. Ultrastructural examination of 23 labeled preparations has established that some segmentally demyelinated central axons can conduct, and that they can do so over continuous lengths of demyelination exceeding several internodes (2500 micron). Such segmentally demyelinated central axons were found to conduct with the anticipated reduction in velocity and a refractory period of transmission (RPT) as much as 34 times the value obtained from the nondemyelinated portion of the same axon; the RPT was typically prolonged to 2-5 times the normal value. We conclude that some segmentally demyelinated central axons can conduct, and we propose that the restoration of conduction to such axons is likely to contribute to the remissions commonly observed in diseases such as MS.

Conduction properties of central nerve fibers remyelinated by Schwann cells

Demyelination of central axons arises from a number of conditions, including multiple sclerosis and spinal cord compression. The demyelination disrupts conduction and leads directly to the production of symptoms. Repair of the demyelination by peripheral myelinating cells could potentially relieve the symptoms, but the conduction properties of central axons remyelinated by Schwann cells have yet to be studied in detail. This paper examined the conduction properties of such axons. Large focal demyelinating and remyelinating lesions were induced in the dorsal columns of rats by the intraspinal injection of ethidium bromide. Recordings of compound action potentials conducted through these lesions were then made at various recovery times. Thus the changing conduction properties of the affected fibers could be correlated with the different stages of lesion development. During the early stages of demyelination there was widespread conduction block, with no evidence of appreciable conduction occurring with prolonged latency or refractory period of transmission (RPT). However, with the onset of remyelination by Schwann cells, conduction was restored in many axons, and most, if not all, of the affected axons eventually showed successful conduction through the lesion. Initially the conduction was characterized by very prolonged latency, long RPT, and an inability to conduct fast trains of impulses. These deficits became less prominent as remyelination progressed. In chronically remyelinated axons the RPT was restored to within normal limits, although some deficit in both conduction velocity and the ability to conduct trains of impulses persisted. Since these deficits were not severe we conclude that remyelination of central demyelinated axons by Schwann cells should be effective in promoting the restoration of normal function.

The refractory period of transmission in patients with carpal tunnel syndrome

In patients with the carpal tunnel syndrome (CTS) and in control subjects, pairs of shocks at intervals of 0.8 msec and 1.0 msec were used to stimulate the median nerve just above the wrist. Nerve action potentials were recorded at the elbow and from the index or middle finger. In patients but not in controls, recordings from the finger frequently showed loss of the second action potential of the pair, although a second action potential was present at the elbow. In these cases it seemed likely that impulse transmission through the carpal tunnel had failed because the damaged nerve at the level of the lesion had an increased refractory period of transmission (RPT) compared with its refractory period under the stimulating cathode. The possible diagnostic use of RPT measurement in CTS patients is discussed.

The Use of Sensory Action Potentials in the Diagnosis of Peripheral Nerve Disease

We review the different measurements that can be derived from recordings of compound sensory action potentials, and describe how less commonly measured aspects may be of use in clinical situations. In addition to the frequently obtained maximum conduction velocity and amplitude, minimum conduction velocity may be measured if near nerve electrodes and response averaging are used. Minimum conduction velocity is a sensitive measure of both axonal and demyelinating peripheral nerve pathology. Activity-dependent conduction is another aspect of sensory conduction that may provide additional information for the clinician. Refractory period of transmission has been used to diagnose subtle demyelinating lesions, as well as some axonal disorders. Supernormal period and the conduction of trains of stimuli may also be useful, although, at present, they remain predominantly research tools.

Conduction along myelinated and demyelinated nerve fibres during the recovery cycle: Model investigations

The membrane excitability changes as well as the underlying mechanisms of these changes in a normal and in a systematically paranodally demyelinated nerve fibre have been investigated by paired stimulation during the first 30 ms of the recovery cycle. The ionic current kinetics determining the observed changes in the action potential parameters are presented also. The simulation of the conduction in the normal fibre is based on the Frankenhaeuser and Huxley (1964) and Goldman and Albus (1968) equations, while in the case of a demyelinated fibre according to the same equations modified by Stephanova (1988a). It has been shown for the demyelinated membrane that increased demyelination increases both the threshold current for the second potential as well as the absolute refractory period. With increasing interpulse interval, the subnormality of the membrane excitability is followed by supernormality in the case of the demyelinated membrane. For the recovery cycle of 30 ms under consideration no supernormality of the normal membrane excitability is obtained. With interpulse interval from 8.8 to 10.9 ms, the highest degree of demyelination (l = 30 microns) is accompanied by a refractory period of transmission. The membrane properties of the normal and demyelinated fibres recover 20 ms after the first pulse. For short interpulse intervals, the amplitude of the second action potential is decreased, and a slower propagation velocity is obtained. The most sensitive phenomenon is the excitability of the demyelinated membrane, which remains unrecovered 30 ms after the first pulses has been applied.

Axonal physiology of chronic spinal cord injury in the cat: Intracellular recording in vitro

The properties of action potential conduction in single axons of the cat thoracic spinal cord were examined with microelectrode recording and electrical stimulation in vitro. The study included normal animals, animals chronically paralyzed by contusion of the cord, and animals showing some degree of locomotory recovery following a similar injury and several weeks of transient paralysis. The control studies were designed to compare the results of microelectrode sampling in vitro with morphological and in vivo physiological data. The pathophysiological studies were intended to investigate the continuity and function of axons identified morphologically in paralyzing lesions, and to examine the hypothesis that functional loss is associated with chronic axonal dysfunction, as well as direct axonal loss. Most of the recordings were made from dorsal columns and ventral tracts at 23–25°C. The conduction velocities recorded in the normal cord were consistent with morphological data on caliber spectra, given the selectivity of the microelectrodes for larger axons. The refractory period of transmission was approximately 2–4 ms at 23–25°C and 0.7–2 ms at 37°C. Prolonged depolarizing after-potentials were recorded, following action potentials greater than 70 mV amplitude. Axons outside the lesion in injured cord showed only slight reductions from control in the mean and range of conduction velocity and refractory period distributions. The number of axons impaled per electrode track was reduced by up to one half. Relatively few impaled axons conducted through the lesion site in the injured cords: 16% in recovering animals and 7% in chronically paralyzed, as compared with 61% in uninjured controls. The mean conduction velocity of these through-conducting axons was significantly less than that of the normal population, particularly in paralyzed animals, and refractory period was significantly prolonged for conduction through the lesion in the paralyzed group. When axons conducting through the middle of the isolated spinal tract were challenged by raising the temperature, conduction block occurred below physiological temperature (37°C) for 7% of axons in controls, 14% in recovering and 73% in paralyzed cats. The mean temperature of heat block in normal axons was 41°C. Some axons appear to survive in paralyzing contusion trauma of this type. Those axons that remain in the lesion site project through it but their conduction properties are abnormal, particularly in animals that remain chronically paralyzed. Action potentials in many axons may be effectively blocked at the chronic lesion site, contributing to the overall functional deficits.

Changes produced by a hypomyelinating neuropathy in muscle and its innervation. Morphological and physiological studies in the Trembler mouse.

The peripheral nerves of the Trembler mouse are hypomyelinated. The effects of the neuropathy on muscle and motor end-plate morphology, and on neuromuscular transmission in slow-twitch (soleus) and fast-twitch (extensor digitorum longus) muscle are reported. After forming normally, motor end-plates developed ultraterminal sprouts by about 18 days of age in deep, slow-twitch muscles. The only ultrastructural abnormality in muscle at this age was disruption of Z-lines. Ultraterminal sprouting progressed, and by about 3 months the innervation zone consisted of a mass of branching axons associated in places with cholinesterase activity. The ultrastructure of end-plates became abnormal. Fascicular atrophy was present in older Tremblers and the ultrastructural morphology of muscle fibres became disorganized with accumulation of subsarcolemmal granular material. Abnormal muscle fibres were innervated by axonal sprouts. The superficial, predominantly fast-twitch, muscles showed milder changes at all ages even though the nerves supplying them were hypomyelinated. Studies of neuromuscular transmission showed that soleus retained its slow-twitch and extensor digitorum longus its fast-twitch characteristics, and miniature end-plate potentials were of normal frequency and amplitude. The latency of end-plate potentials and the refractory period of transmission were prolonged in both soleus and extensor digitorum longus. With repetitive stimulation at 50 Hz a cyclical pattern of responses and failures occurred which was probably caused by intermittent conduction block along the peripheral nerve. Although the pathological changes in Trembler muscle were like those of partial denervation, atrophic muscles contained an abundance of axons and there was no evidence of axonal degeneration. The changes in muscle are therefore a consequence of hypomyelination without axonal loss. Since slow-twitch muscles are normally subjected to prolonged stimulation, failure of Trembler axons to conduct sustained trains of stimuli in vivo may contribute to the development of pathological changes in slow-twitch muscle. Hypomyelimated axons may be capable of conducting short bursts of impulses, however, which is the pattern of stimulation in fast-twitch muscle in vivo, so that fast-twitch muscle fibres and end-plates remain relatively spared.

The restoration of conduction by central remyelination.

Conduction has been examined serially through the experimental demyelinating lesion produced by the direct micro-injection of lysophatidyl choline into the cat spinal cord. Conduction was blocked during the phase of demyelination. Remyelination commenced during the latter part of the second week, and conduction through the lesion was restored in some fibres at this time. The refractory period of transmission was initially prolonged. As remyelination proceeded, conduction was restored in increasing numbers of fibres. Within three months the responses were stable and the refractory periods of transmission had returned to normal even though the new internodes were still abnormally thin and were generally shorter than normal. Restoration of conduction by remyelination is likely to contribute to recovery from compressive and traumatic lesions of the central nervous system but probably plays little part in the remissions of multiple sclerosis.

Refractory period, conduction of trains of impulses, and effect of temperature on conduction in chronic hypertrophic neuropathy.

The refractory period, the ability to transmit trains of impulses, and the effect of temperature on conduction, have been studied in the sciatic-tibial nerve trunks of Trembler mice, which suffer from a dominantly inherited hypertrophic neuropathy. Both the refractory period of transmission and the relative refractory period were increased in Trembler mice when compared with controls. The nerve trunks of Trembler mice were unable to conduct rapid trains of impulses, and conduction block occurred at rates of stimulation as low as 25 Hz. Cold block occurred at temperatures significantly higher in Trembler nerves than in controls. The conduction velocity increased in an approximately linear fashion in both Trembler and control nerves when the temperature was raised from 20 degrees C to 40 degrees C, and the slopes were not significantly different. The Q10 (27 degrees C-37 degrees C) was 1.5 and 1.6 for control and Trembler nerves respectively. Conduction block was regularly observed in Trembler nerves when the temperature was raised within the physiological range. The abnormalities are related to the pathological changes of chronic demyelination.