High frequency discharge of a fraction (f) of motor unit action potential

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Electroencephalography and clinical Neurophysiology 101 (1996) 201-205

High frequency discharge of a fraction (f) of motor unit action potential P. Soichot",*, G. R o t h b aEEG-EMG Laboratory, Neurological Clinic, Regional and University Hospital, 212033 Dijon, France bElectroneuromyographic Unit, Neurological Clinic, UniversityHospital, Geneva, Switzerland Accepted for publication: 4 December 1995

Abstract Two repetitive discharges, firing at 105 and 180 Hz, were evoked in muscles with chronic denervation. They were delayed following a motor unit action potential (M), and their maximum duration was 800 and 50 ms, respectively. The potential of both high frequency discharges was of low amplitude and short duration. It was considered to be a fraction (f) of the motor unit potential, and to depend on muscle fibres re-innervated by an axonal branch. The repetitive mechanism was tested by double stimulation. It seemed to be an ephaptic re-excitation of the axonal branch by a sprout rather than an ectopic trigger locus on the latter. The antidromic waves, associated with the repetitive discharges on the axonal branch, failed to be transmitted to the main axon. This failure, assimilated to a conduction block, was complete in the first case as M was not repetitive. It was intermittent in the second case as M was firing intermittently. Repetitive activity associated with 'terminal multifocal block' could be relevant to the fractional activation observed by others in some disease states. Keywords: Chronic denervation; Conduction block; Double stimulation; Ephapse; High frequency discharge; Neuromyotonia

1. Introduction A repetitive discharge is 'the recurrence of an action potential with the same or nearly the same form (...) recorded in muscle at rest, during voluntary contraction, or in response to single nerve stimulus' (Nomenclature Committee, 1987). High frequency discharges (HFDs), are usually made up of short duration and low amplitude action potentials. Such HFDs have been recorded in: (i) neuromyotonia (Auger et al., 1984), (ii) familial ataxia and myokymia (Brunt and Van Weerden, 1990), (iii) neurotonia (Warmolts and Mendell, 1980), (iv) chemical poisonings (Wallis et al., 1970), (v) entrapment syndromes (St6hr, 1981). When involving 'a small action potential separated from the main M U A P by an isoelectric interval and firing in a time-locked relationship to the main action potential' they can be ascribed to one satellite potential (Nomenclature Committee, 1987). HFD of a satellite potential has sometimes been reported (Partanen et al., 1980) and its generation in a hyperexcitable axonal sprout has already been discussed (Serra et al., 1984). Involving * Corresponding author.

very small potentials, the HFDs presented here probably occur in a fraction (f) of a MUAP, i.e. in a sprout of reinnervation. Their firing, partially or totally independent of the main MUAP, would mean blocking their antidromic waves.

2. Methods and patients HFDs were recorded during routine electroneuromyography. Signals were recorded with concentric needle electrodes (0.07 mm 2 leading-off area), and displayed on a Disa 1500 EMG-System (Disa Electronik, Skovlunde, Denmark), or a Tektronix RM 564 (Tek. Inc., Beaverton, OR, USA). Double stimulation was used, the second shock being sometimes randomly delivered during an HFD. Traces were recorded on direct-print photorecording paper or photographed with a Polaroid camera (Polaroid, Cambridge, MA). The mean of the consecutive interval difference (MCD) of HFDs (Trontelj and St~ilberg, 1983) was calculated from magnified sweep records (2-20 ms/cm). Patient 1, a 64-year-old man, was suffering from a diabetic polyneuropathy. The motor unit action potentials

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P. Soichot, G. Roth /Electroencephalography and clinical Neurophysiology 101 (1996) 201-205

(MUAPs) in the leg muscles were reduced in number and increased in amplitude. Patient 2, a 43-year-old woman, had suffered from an incomplete traumatic ulnar nerve lesion at the wrist 6 months previously. A reduced number of high amplitude and long duration MUAPs was also recorded in the relevant muscles of the hand. Motor axon reflexes and late potentials were also elicited in these muscles•

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M (main MUAP) 2 14 8.5

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Fig. 1. Patient 1. Recording of the tibialis anterior muscle with a needle electrode. Stimulation (O) of the peroneal nerve behind the fibula neck, at 0.5 Hz. A high frequency discharge of a fraction of motor unit (HFDf) is constantly evoked late after the M wave. (1, 3, 5) One or two small potentials follow the first discharge. They come from other muscle fibres as they do not modify the first interdiseharge interval or the amplitude of the second discharge. (6) A double stimulation (O O) with an interval of l0 ms constantly cancels the HFD-f. Thus the first discharge of the latter is not a usual late potential.

stimulation performed during its time course• A double shock with an interval of 10 ms constantly cancelled the HFD-f (Fig. 1(6))• A potential of comparable shape was recorded at the end of the M wave. During a slight voluntary effort, the HFD-f sometimes followed a MUAP of 2 mV (Fig. 2, Table 1). When the latter appeared during an ongoing HFD-f, it did not interrupt the discharge or modify its rhythm• At rest, no HFD-f was detected with slight needle movements.

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Proximal and distal stimulation (distance 5 cm) at the fibula neck, triggered in the tibialis anterior muscle an M wave of 2 mV followed by the HFD-f of a potential of short duration and low amplitude (f). At both sites of stimulation the time interval between the M wave and HFD-f was identical and varied up to 1.7 ms, and no fdischarge was absent. Smaller potentials often followed the first f-discharge without modifying the first interdischarge interval or the amplitude of the second discharge (Fig. 1). The HFD-f was not evoked at stimulation frequencies higher than 0.5 Hz, and was not interrupted by

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Stimulating the ulnar nerve at the wrist evoked in the abductor digiti minimi muscle a delayed HFD of a potential of 3 mV (M) with a latency of 29 ms (Figs• 3(1) and 4(1))• The M potential was often evoked as a doublet after the M-wave, i.e. the compound muscle potential (Fig. 4(2)). The only large potential recorded during voluntary activity, as single or multiple discharge, was identical to

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Fig. 2. Same recording place as in Fig. 1; 4 continuous EMG traces during slight voluntary activity• The first discharge of an MU (O) is followed by a high frequency discharge of a fraction of motor unit (HFD-f). The latter is not interrupted by the next MUAPs that are not accompanied by an HFD-f. The last MUAP (e) is again followed by an HFD-f.

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Fig. 3. Patient 2. Recording from the abductor digiti minimi muscle with a needle electrode. Stimulation of the ulnar nerve at the wrist. (1) Threshold stimulation for: the MUAP in the M-wave (identified by its doublet; see Fig. 4); (A) the fraction of the motor unit; (B) the high frequency discharge of the MUAP (HFD-M); (C) the high frequency discharge of a fraction of motor unit (HFD-f). The latter may be absent (third trace), and sometimes one discharge is missing. (2) Stimulation above threshold• Two successive discharges are missing within both HFD-M. (D) The first discharge of the HFD-f is visible on the first trace. (3-5) Double stimulation with intervals of 10, 18. 36 ms. (E) A discharge of the HFD-M is absent or cancelled by the second stimulation.

Fig. 4. Same recording place as in Fig. 3. The stimulation of maximal intensity evokes: (1) the high frequency discharge of the MUAP (HFDM); (2) a frequent double discharge (DD). The geometrical subtraction with reference to a horizontal line (below the DD) shows that the DD and the potential of the HFD-M have an identical shape. (3) The MUAP recorded during voluntary contraction often appears as doublet, triplet or quadruplet with a different interdischarge interval from that of the HFD-M.

M (Fig. 4(3)). T h e H F D - M was not c o n s t a n t l y e v o k e d (Fig. 3), a n d its i r r e g u l a r r h y t h m w a s d u e to the a b s e n c e of o n e or several d i s c h a r g e s w i t h i n the train, T h e first i n t e r d i s c h a r g e interval was shorter, by a b o u t 0.7 ms, t h a n t h o s e f o l l o w i n g (Fig. 3). T h e H F D - M c o u l d not b e e v o k e d for s o m e s e c o n d s after v o l u n t a r y activity. It was not c a n c e l l e d by a d o u b l e s t i m u l a t i o n w i t h an inters t i m u l u s interval e q u a l to or g r e a t e r t h a n 10 ms, a n d was not e v o k e d at the e l b o w . T h e M - w a v e was f o l l o w e d b y a stable late p o t e n t i a l (f) o f low a m p l i t u d e , s h o r t d u r a t i o n , a n d l a t e n c y o f 11.5 m s (Fig. 3, T a b l e 1). T h i s f r e s p o n s e w a s also o f t e n e v o k e d as H F D - f with a l a t e n c y o f 43 ms. T h e r h y t h m w a s regular, the first i n t e r d i s c h a r g e interval b e i n g shorter, b y a b o u t 0.7 ms. A d i s c h a r g e of the H F D - f was rarely absent. E v e r y H F D - f was o f the s a m e or l o n g e r d u r a t i o n t h a n the associated H F D - M . T h e r e was a close r e l a t i o n b e t w e e n the f o u r e v o k e d res p o n s e s (M, H F D - M , f, H F D - f ) as: (i) they h a d an identical t h r e s h o l d o f s t i m u l a t i o n ; (ii) the f a n d H F D - f w e r e not e v o k e d w i t h o u t M ; (iii) the H F D - M d i d n o t a p p e a r without M a n d the H F D - f ; (iv) the first a n d f o l l o w i n g inter-

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P. Soichot, G. Roth / Electroencephalography and clinical Neurophysiology 101 (1996) 201-205

discharge intervals of both H F D - M and H F D - f were identical. During voluntary activity the M potential was often recorded as double, triple or quadruple discharges (Fig. 4(3)) with a regular internal rhythm (120 Hz). No HFD was detected at rest or with needle insertion. 4. Discussion W e assume that the M and f potentials of both patients are two parts of the same M U A P as: (i) both had the same stimulation threshold, and f was never recorded without M; (ii) the H F D - f of the first patient followed the M potential during slight voluntary activity; (iii) the first and following interdischarge intervals of both H F D - M and H F D - f of the second patient were identical, and there was a close relation between the responses M, HFD-M, f, and HFD-f. The f potentials were recorded in muscles with signs of reinnervation (see Section 2). Their low amplitude and short duration probably resulted from the synchronised potentials of a few muscle fibres reinnervated by an axonal branch with a distal origin. Indeed the delay from the M wave to H F D - f was identical when the nerve was stimulated at different sites. The starting impulse of both H F D - f is neural and does not result from a muscle-to-muscle ephaptic transmission, like complex H F D s (StAlberg and Trontelj, 1982) because: (i) H F D - f did not occur spontaneously or when the needle was moved, but only by passing axonal impulses (patient 1); (ii) the M C D of both H F D - f was too large for such a mechanism to apply (Table 1); (iii) the antidromic wave associated with H F D - f could re-excite the main potential in patient 2. These repetitive discharges may be compared to the HFDs of M U A P s , carefully studied by Serra et al. (1984), that were attributed to a muscle-to-nerve ephaptic reverberating loop. However, for our patient 1 at least, the main compound muscle action potential did not participate in the repetitive mechanism. As already stated, both H F D - f only represented a fraction of a M U A P . The re-excitation mechanism of the H F D - f must have consisted either of an ectopic trigger situated on an axonal branch, or of an axono-axonal or myo-axonal ephaptic transmission between two branches resulting in a reexcitation loop. In the case of an ectopic re-excitation, only the first discharge of an H F D - f would have been cancelled by a double stimulation in patient 1. The failure to evoke any H F D - f with proximal nerve stimulation in patient 2 does not support an ectopic re-excitation mechanism, usually triggered by any stimulation along the nerve (Roth, 1980). An ephaptic re-excitation seems to be more probable. Whatever the repetitive mechanism, it does not appear to be situated on the main axon as the main M U A P was not repeated in patient 1, or irregularly in patient 2. The evoked M doublet and the high frequency discharges recorded during voluntary activity of patient 2 present a different interdischarge interval

from the HFD-M, and probably has an origin on the main axon.

The following patho-physiological hypothesis, illustrated in Fig. 5, attempts to explain all the observed facts. An axonal branch supplies a fraction of the muscle fibres of the M U that are responsible for the f potential. The repetitive re-excitation of this axonal branch by another sprout evokes both the H F D - f and repetitive antidromic waves. The latter never invade the main axon (patient 1) or only intermittently (patient 2). In patient 1, the direct conduction time of the axonal branch was so brief that the f potential was included at the end of the M wave. So, the first discharge of the H F D - f was not a usual late potential as it was cancelled by a second shock and never present during voluntary activity. In patient 2, the conduction time of the branch was longer, the f response appearing as a stable late potential preceding the H F D - f by a large interval (Figs. 3 and 5). The reexcitation mechanism of both H F D - f could not be directly situated on the f branch, as f and H F D - f maintain some independence and a large interval between them. The reexcitation, whatever its mechanism, must have been generated in an other sprout of the axonal branch. That the H F D - f of patient 1 was not accompanied by

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Fig. 5. Schematic diagrams that may account for a fraction (f) and the main part (M) of a MUAP. Both are evoked by axonal stimulation (S) or the voluntary activity. The pathway of the excitation wave is depicted near the diagram, and the responses to the stimulation below the model. The re-excitation mechanism is due either to (A) an ectopic trigger zone, or (B) a myo-axonal or an axono-axonal ephapse (~). The re-excitation site (O) is on a twig of the axonal branch (Ab). The conduction time of Ab is short for the first patient (PI) and f follows the M wave, and long for the second patient (P2). The antidromic wave is probably blocked at the most distal branching point (2~). Re-excitation of the axon leading to HFR-M is not depicted. Such a mechanism explains why the HFD-M of patient 2 has a shorter latency than the HFDf if the branching of the twig is proximal the axonal branch.

P. Soichot, G. Roth / Electroencephalography and clinical Neurophysiology 101 (1996) 201-205

an HFD-M implies the presence of a constant one-way conduction block of the antidromic waves in the axonal branch. For patient 2, the conduction block was intermittent as the repetitive excitation sometimes propagated to the axon and, evoked the M potential. Why the antidromic wave did not propagate from the axonai branch in the main axon, or more likely from the twig to the axonal branch, probably relates to a marked difference in their diameters. In asymmetrical branching, a depolarisation wave may sometimes only propagate from the branch with the largest diameter to another (Standaert, 1963; Rambn et al., 1975). Once initiated, the HFD-f of the patient 1 is not interrupted or modified by a second stimulus. The antidromic waves associated with the HFD-f follow each other in the axonal branch with an interval of 9.5 ms and cancel any orthodromic wave. The reason why a second stimulus with an interval longer than 10 ms did not cancel the first discharge of the HFD-M of patient 2 remains obscure. An orthodromic blocking at the branching dependent on the inter-stimulus-interval may be responsible. The periodic bursts of repetitive potentials with short duration and low amplitude recorded in several neuromuscular disorders (see Brunt and Van Weerden, 1990 for references) have sometimes been ascribed to the fractional activation of an MU. This activation would involve hyperexcitable twigs involved in collateral reinnervation, which might present an unstable polarization (Wallis et al., 1970; Layzer and Rowland, 1971; Partanen et al., 1980; Besser and Gutman, 1988). Such a repetitive activity could be secondary to 'terminal multifocal conduction block.'

Acknowledgements We wish to thank Dr. M. Magistris for his suggestions, and for his aid in the translation of the manuscript.

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References Auger, R.G., Daube, J.R., Gomez, M.R. and Lambert, E.H. Hereditary form of sustained muscle activity of peripheral nerve origin causing generalized myokymia and muscle stiffness. Ann. Neurol., 1984, 15: 13-21. Besser, R. and Gutman, L. Muscle action potential precipitated complex repetitive discharge. Muscle Nerve, 1988, 11:1190-I 191. Brunt, E.R.P. and Van Weerden, T.W. Familial paroxysmal kinesigenic ataxia and continuous myokymia. Brain, 1990, 113: 1361-1382. Layzer, R.B. and Rowland, L.P. Cramps. N. Engl. J. Med., 1971, 285: 31-40. Nomenclature Committee of the American Association of Electromyography and Electrodiagnosis. Glossary of terms in clinical electromyography, 2nd edn. Muscle Nerve, 1987, 10 (Suppl.). Partanen, V.S.J., Soininen, H., Saksa, M. and Riekkinen, P. Electromyographic and nerve conduction findings in a patient with neuromyotonia, normocalcemic tetany and small-cell lung cancer. Acta Neurol. Scand., 1980, 61: 216--226. Rambn, F., Joyner, R.W. and Moore, J.W. Propagation of action potentials in inhomogeneous axon regions. Fed. Proc., 1975, 34: 13571363. Roth, G. Double discharges of distal origin. J. Neurol. Sci., 1980, 47: 35-48. Serra, G., Aiello, I., De Grandis, D., Tugnoli, V. and Carreras, M. Muscle-nerve ephaptic excitation in some repetitive afterdischarges. Electroenceph. clin. Neurophysiol., 1984, 57: 416-422. Sthlberg, E. and Trontelj, J.V. Abnormal discharges generated within the motor unit as observed with single-fiber electromyography. In: W.J. Culp and J. Ochoa (Eds.), Abnormal Nerves and Muscles as Impulse Generators. Oxford University Press, Oxford, 1982, pp. 443-474. Standaert, F.G. Post-tetanic repetitive activity in the cat soleus nerve. J. Gen. Physiol., 1963, 47: 53-70. St6hr, M. Repetitive impulse-induced EMG discharges in neuromuscular diseases. Ann. Neurol., 1981, 9: 204. Trontelj, J. and St~lberg, E. Bizarre repetitive discharges recorded with single fibre EMG. J. Neurol. Neurosurg. Psychiat., 1983, 46: 310316. Wallis, W.E., Poznak, A.V. and Plum, F. Generalized muscular stiffness, fasciculations, and myokymia of peripheral nerve origin. Arch. Neurol., 1970. 22: 430-439. Warmolts, J.R. and Mendell, J.R. Neurotonia: impulse-induced repetitive discharges in motor nerves in peripheral neuropathy. Ann. Neurol., 1980, 7: 245-250.