Volitional and stimulation-induced neuromyotonic discharges: AN unusual electrophysiological pattern in acquired neuromyotonia

Josef Bednařík and Zdeněk Kadaňka

Department of Neurology, Faculty Hospital and Masaryk University Brno, Czech Republic

Correspondence to: Josef Bednařík, MD, PhD, Department of Neurology, Faculty Hospital and Masaryk University Brno, Jihlavská 20, 625 00 Brno, The Czech Republic, E-mail:

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Abstract

The case of a 71-year-old female patient suffering from acquired paraneoplastic neuromyotonia with an unusual electrophysiological pattern of neuromyotonic discharges (NMD) evoked exclusively by voluntary contraction or electrical stimulation is reported. The presence of anti-voltage-gated K+ channels (VGKC) antibodies and the clinical, immunological and electrophysiological response to intravenous immunoglobulin treatment supports the role of VGKC blockade in the generation of these ”evoked” NMD’s and raises the question of different pathophysiological mechanisms in subsets of neuromyotonic patients. Furthermore, a modification of the current electrophysiological definition of neuromyotonic discharges is suggested.

Key words: neuromyotonic discharges; acquired neuromyotonia; muscle stiffness; thymoma; anti-voltage-gated K+ channels antibodies

Introduction

According to ”A Glossary of Terms Used in Clinical Electromyography”, 1980, as compiled by the Nomenclature Committee of the American Association of Electromyography and Electrodiagnosis, neuromyotonic discharges are characterised as ”bursts of motor unit potentials firing at more than 150 Hz for 1/2 to 2 seconds. The amplitude of the response typically wanes. Discharges may occur spontaneously or be initiated by needle movement” (1). Walsh (2) described a case of a mediastinal tumour and neuromyotonia with very high frequency discharges that outlasted voluntary effort. A similar case was reported by Warmolts and Mendell (3); the frequency of the observed discharges evoked by voluntary effort or electrical stimulation (below 150 Hz), however, did not meet the electrophysiological criteria of neuromyotonic discharges.

We present here a case of an acquired paraneoplastic neuromyotonia associated with thymoma and clinically manifested myotonia-like muscle stiffness and an unusual electrophysiological pattern of neuromyotonic discharges that were evoked voluntarily or with electrical stimulation but were absent spontaneously and were not elicited by needle displacement.

 Case report

A 71-year-old female presented with a six-month history of muscle stiffness, paresthesias provoked mostly by movement, disturbed speech and difficulty walking. At the time of examination she could not walk independently.

The clinical examination revealed pronounced dysarthria and ataxic-like extremity movement interrupted by superimposed tonic involuntary contractions. The muscle decontraction was prolonged and percussion myotonia was absent. Fasciculations and myokymia-like movements were observed in her arms, but occurred only sparsely and intermittently. The distal foot and hand muscles were slightly paretic and atrophic. Tendon reflexes were weak in the arms and absent in the legs. A decreased perception of vibration was present distally in all extremities.

A CT scan revealed a tumour in the mediastinum, which was totally removed and thymoma was confirmed histologically.

An examination of anti-voltage-gated K+ channels (VGKC) antibody titres was performed using immunoprecipitation of 125I - a dendrotoxin labelled VGKCs extracted from human frontal cortex2 (Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK). The first titre was positive: 241 pM (positive titres > 200 pM; equivocal 100 – 200 pM; negative < 100 pM); following IVIG therapy the examination was repeated and the titre was still positive at a lower level: 219 pM.

 

Therapy and clinical course

Diphenylhydantoin administered either intravenously (EPANUTIN 500 mg, Parke Davis) or orally 300 mg daily (Epilan D, Gerot) elicited only a slight effect upon muscle stiffness. Carbamazepin (NEUROTOP Gerot) administered orally in a dose of 300 mg twice a day led to a moderate decrease in paresthesias and a slight decrease in muscle stiffness and has now been administered continuously for 2 years. During a course of intravenous immunoglobulin (IVIG) infusions at a normal dose (i.e. 0.4 g/kg on 5 subsequent days, total dose of 2 g/kg) both pseudomyotonic and sensory signs and symptoms started to improve and at the end of the IVIG treatment the patient was able to walk independently. After the initial IVIG therapy, clinical signs and symptoms stabilised with the ability to walk independently to a distance of 20 metres. After a year of stabilisation, the stiffness, dysarthria and walking ability worsened in the course of 3 months to the point at which the patient was once more unable to walk independently. The patient then received a second course of IVIG therapy (2g/kg) and improved to the same degree as after the first treatment.

 

Needle EMG

EMG performed at the beginning of clinical follow-up and therapy revealed no abnormal spontaneous or insertional activity from several proximal and distal muscles in both upper and lower extremities with the exception of sparse fasciculations and myokymic discharges (with a short interburst interval of about 5-10 msec). During a slight voluntary contraction, motor unit action potentials (MUPs) had normal parameters with the exception of distal muscles in the lower extremities that showed signs of slight reinnervation process: MUPs had slightly higher amplitude, longer duration, mild waveform instability and polyphasic pattern. The recruitment of MUPs and the interference pattern during maximum voluntary effort were slightly reduced in distal muscles. Voluntary contraction evoked repetitive bursts of high frequency discharges of MUP-like potentials with amplitude decrement and a characteristic ”pinging” sound (Fig. 1a); the discharges lasted several hundred milliseconds and were present uniformly in all examined muscles.

 

Conduction study

The amplitudes of compound muscle action potentials (CMAPs) were borderline or reduced (tibial nerve right, peroneal nerve left); no conduction blocks, temporal dispersion of CMAPs or conduction slowing (with the exception of median nerves across the wrist) were observed. The sensory nerve action potentials’ (SNAPs) amplitudes were either unrecordable or decreased, sensory conduction velocities were borderline. The focal slowing of both motor and sensory conduction of the median nerves on both sides across the wrist as signs of focal demyelinative lesion were found and interpreted as bilateral carpal tunnel syndrome. The results of the entry conduction study are summarised in table 1.

The supramaximal stimulation of upper and lower extremity motor nerves (median, ulnar, peroneal, and tibial nerves bilaterally) evoked CMAPs followed immediately or after a short period - up to 30 msec - by repetitive ”neuromyotonic” discharges of high frequency (cca 230 Hz), waning amplitude and duration of hundreds of msec that could be recorded with the surface recording electrode (Fig. 1b). The complete blockade of ulnar and median nerves at the elbow by lidocaine did not interrupt the ability of shocks delivered distally to the site of the block to evoke neuromyotonic discharges.

The repetitive motor nerve stimulation study of ulnar and axillar nerves performed at a stimulation frequency of 2 Hz revealed no decrement.

The stimulation single fibre electromyography from the extensor digitorum communis muscle on the right side showed a slightly abnormal jitter (19 recordings, mean jitter 34 µs, 5 recordings above 40 µs), probably as a sign of the reinnervation process.

In summary, electrophysiological findings were assessed as a predominantly distal axonal sensory-motor subacute polyneuropathy, bilateral carpal tunnel syndrome, and neuromyotonic discharges atypically evoked by volitional contraction and electrical stimulation.

Second EMG and conduction studies were performed 7 days after the end of the second IVIG treatment. The neuromyotonic discharges evoked by the voluntary contraction and electrical stimulation of the motor nerves were present in all examined muscles, but discharges evoked by voluntary contraction were less frequent and the ability to evoke them waned; after several contractions they disappeared.

 Discussion

The waveforms of discharges seen in motor unit and muscle fibre hyperactivity disorders are readily categorised into those that have and that have not motor unit potential configurations. It is possible for a motor unit to arise volitionally and to have recurrent discharges that are of ectopic origin. The ectopic nature of the recurrent discharges with motor unit potential waveforms, due to the inability of anterior horn cells to fire reliably at high frequencies, is often self-evident: high frequency motor unit-like action potentials (HF MULAPTAE) that arise ectopically. Neuromyotonic discharges are typically HF MULAPTAE (4).

Torbergsen (5) stated further that, in addition to spontaneous occurrence, neuromyotonic discharges could also be registered during voluntary activation or after nerve stimulation; it was assumed that such a type of electrophysiological abnormality is caused by the slightest degree of hyperexcitability of axons when neuromyotonic discharges are triggered after a preceding impulse, simply voluntary or electrical, has passed, while spontaneous neuromyotonic discharges without obvious trigger are generated in the case of more increased hyperexcitability of axons. However, they, did not mention the possibility that these ”evoked” neuromyotonic discharges might be the only electrophysiological abnormality found.

Clinically, as well as muscle stiffness, ataxia-like voluntary movement was present in our patient; this movement was interrupted repeatedly, probably due to repeated bursts of neuromyotonic discharges. The ataxic-like limb movement, gait and dysarthria dominated clinically, while neuromyotonic discharges evoked voluntarily or by electrical stimulation dominated electrophysiologically. Moreover, the movement provoked corresponding sensory phenomena of dysesthesias and paresthesias. It seems likely that these sensory phenomena of dysesthesias and paresthesias were evoked by similar types of sensory neural hyperactivity (6). The high frequency discharges in our patient with neuromyotonia consisted of MUP-like waveforms, which did not arise spontaneously, but the high frequency of about 200 Hz clearly showed their ectopic origin.

Though it is not an easy task to define the discharges in hyperirritable neuromuscular disorders, actual definitions of neuromyotonic discharges emphasising their spontaneous occurrence or initiation by needle movement should, however, be reconsidered and modified.

As far as the mechanism of the evoked neuromyotonic discharges in the reported case is concerned, the presence of anti-VGKC antibodies and clinical, immunological, and electrophysiological response to IVIG treatment are in favour of the role of VGKB blockade in the generation of ”evoked” NMD. It seems likely that a reduction in the number of functional VGKCs leads to an inability of the distal motor nerve and motor nerve terminal to repolarize sufficiently following each action potential so that an individual action potential recruited volitionally or after nerve stimulation leads to repetitive action potentials in the nerve terminals (7). It remains to be clarified whether such a different electrophysiological pattern could be explained simply by a lower degree of hyperexcitability or whether lesions additional to the reduction of VGKC (axonal damage, demyelination) are necessary to evoke spontaneous neuromyotonic discharges.

 References

1. Kimura J. Electrodiagnosis in Diseases of Nerve and Muscle: Principles and Practices. Philadelphia: FA Davis; 1983, 672 p.634.
2. Walsh JC. Neuromyotonia: an unusual presentation of intrathoracic malignancy. J Neurol Neurosurg Psychiatry 1976;39:1086-91.
3. Warmolts JR, Mendell JR. Neurotonia: impulse-induced repetitive discharge in motor nerves in peripheral neuropathy. Ann Neurol. 1980;7:245-50.
4. Walker FO: EMG in muscle cramp, myotonia and neuromyotonia. Annual courses AAN 1999 on disc.
5. Torbergsen T, Stalberg E, Brautaset NJ. Generator sites for spontaneous activity in neuromyotonia. An EMG study. Electroencephalogr Clin Neurophysiol 1996;101:69-78.
6. Lance JW, Burke D, Pollard J. Hyperexcitability of motor and sensory neurons in neuromyotonia. Ann Neurol 1979;5:523-532.
7. Vincent A. Understanding neuromyotonia. Muscle & Nerve 2000;23:655-657.

 

Figure captions

Fig.1a: Needle EMG from abductor pollicis brevis muscle showing high frequency (cca 200 Hz) ”neuromyotonic” discharge with waning amplitude and duration of 250 msec, provoked by voluntary contraction (arrow).

Fig.1b: Motor nerve conduction study (right median nerve), recording from the right abductor pollicis brevis using surface electrode. Supramaximal stimulation of the median nerve at the wrist (upper recording) and at the elbow (lower recording) evoked compound muscle action potential (dotted arrows) followed after 28 msec by repetitive ”neuromyotonic” discharges (full arrows) of high frequency (cca 230 Hz), waning amplitude and duration of about 200 msec.

Table 1: Results of the conduction studies – entry examination

	DML	MCV	CMAP ampl	SCV	SNAP ampl
Median nerve R	4.8 msec	50 m/sec	7.4 mV
Median nerve L	4.8 msec	48 m/sec	7.1 mV	41 m/sec	4.7 µV
Ulnar nerve R	2.8 msec	47 m/sec	7.9 mV
Ulnar nerve L	3.0 msec	48 m/sec	5,1 mV	42 m/sec	5 µV
Peroneal nerve R	5.3 msec	45 m/sec	5.6 mV
Peroneal nerve L	4.0 msec	39 m/sec	0.6 mV	38 m/sec	1.5 µV
Tibial nerve R	4.0 msec	40 m/sec	2.3 mV
Tibial nerve L	4.9 msec	47 m/sec	4.6 mV
Sural nerve R				37 m/sec	2.0 µV
Sural nerve L				unrecordable	unrecordable

R = right
L = left
DML = distal motor latency
MCV = motor conduction velocity
CMAP ampl = amplitude of the compound motor action potential
SCV = sensory conduction velocity
SNAP ampl = amplitude of the sensory nerve action potential

Professor C Kennard
Editor
Journal of Neurology, Neurosurgery & Psychiatry
Division of Neuroscience and Psychological Medicine
Room 10E 15
Imperial College School of Medicine
Charing Cross Hospital
Fulham Palace Road
London W6 8RF
UK

Brno, 27^th June, 2000.

Dear Prof. Kennard,

Please find enclosed the manuscript of a paper: Bednařík J, Kadaňka Z.: ”Volitional and stimulation-induced neuromyotonic discharges: an unusual electrophysiological pattern in acquired neuromyotonia” submitted as a short report for publication in the Journal of Neurology, Neurosurgery and Psychiatry.

Many thanks and kindest regards

Yours sincerely

                    Josef Bednařík, MD,PhD

 

Correspondence to:
Josef Bednařík, MD,PhD
Dept. of Neurology
University Hospital
Jihlavská 20
63900 Brno
Czech Republic
Fax.: 00 543192249
Tel.:00 543215110
E mail:

Statement

No work resembling the enclosed article has been published or is being submitted for publication elsewhere. We certify that we have each made a substantial contribution so as to qualify for authorship. We have disclosed all financial support for our work and other potential conflicts of interest.

 Josef Bednařík, Zdeněk Kadaňka