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

Abstract

Objectives-Measures of nerve excitability provide information about biophysical properties of peripheral axons in disease states. One measure, the strength duration time constant ( 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 SD were present in a group of patients with evidence of spontaneous motor unit activity; and secondly, if such changes in SD were present, whether other parameters of axonal excitability were aVected, to clarify the mechanism of the change in 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 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. (J Neurol Neurosurg Psychiatry 2001;70:56-64)

A possible mechanism of repetitive firing of myelinated axon

“…Besides, the axonal activity with rather long interspike intervals (> 30 ms) was also reported [19,24]. All these features were combined with normal or even reduced axonal excitability in patients with APNH [22] and with positive effect of medicines containing sodium channel blockers [27]. The present study demonstrates that, if the active internodal processes include ionic accumulation, the repetitive firing becomes finite (Figs.…”

“…Therefore, not having any abnormal measurements of axonal excitability in patients with APNH [22] is natural. Only, after a passage of saltatorial AP, the deficit of internodal potassium channels causes formation of the transition zone that can repetitively activate MA.…”

Assessment of cortical excitability using threshold tracking techniques

“…3,18 In this method, a constant target MEP amplitude is tracked online by a test stimulus using different conditioning-test paradigms. Although threshold tracking has been validated in electrical studies of peripheral ax-ons in healthy controls 23,24,30,35 and in the investigation of disease pathophysiology in a wide array of neurological disorders, 5,6,8,[25][26][27][28]31,33 limited data exist for the application of threshold tracking to TMS to study cortical excitability. Consequently, the aim of the present study was to determine the adaptability of threshold tracking to TMS techniques to investigate the processes of intracortical inhibition and facilitation.…”

Nerve excitability properties in lower‐limb motor axons: Evidence for a length‐dependent gradient

“…10,12 Patterns of abnormalities in a wide array of excitability parameters associated with changes in membrane potential have been established 24 and have proved useful in the interpretation of findings from patients with a variety of neurological disturbances. 21,23,27,28,30 A number of generalized disease processes appear to affect selectively the peripheral nerves of the lower limbs in advance of upper-limb involvement. This is apparent with the metabolic neuropathies, particularly diabetic and uremic neuropathy.…”