Volitional and stimulation induced neuromyotonic discharges: unusual electrophysiological pattern in acquired neuromyotonia
- Department of Neurology, Faculty Hospital and Masaryk University Brno, Jihlavská 20, 639 00 Brno, The Czech Republic
- J Bednarík
Neuromyotonic discharges are electrophysiologically characterised as bursts of motor unit potentials firing at more than 150 Hz for 0.5 to 2 seconds. The amplitude of the response typically wanes. Discharges may occur spontaneously or be initiated by needle movement.1 Walsh described a case of a mediastinal tumour and neuromyotonia with very high frequency discharges that outlasted voluntary effort.2
We report a case of an acquired paraneoplastic neuromyotonia associated with thymoma, 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.
A 71 year old women presented with a 6 month history of muscle stiffness, paraesthesias provoked mostly by movement, disturbed speech, and difficult walking. At the time of examination she could not walk independently.
Clinical examination disclosed pronounced dysarthria and ataxic-like limb movement interrupted by superimposed tonic involuntary contractions. The muscle decontraction was prolonged and percussion myotonia was absent. Fasciculations and myokymia-like movements were seen 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 limbs.
Computed tomography disclosed a tumour in the mediastinum, which was totally removed after initial therapy and clinical improvement; the thymoma was confirmed histologically.
An examination of voltage gated K+ channel (VGKC) antibody titres was performed using immunoprecipitation of 125I-α 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).
During a course of intravenous immunoglobulin (IVIg) infusions at a normal dose (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 (administered 1 month before surgical removal of the thymoma), clinical signs and symptoms stabilised with the ability to walk independently for 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 (2 g/kg) and improved to the same degree as after the first treatment.
An EMG at the beginning of clinical follow up disclosed sparse fasciculations and myokymic discharges (with a short interburst interval of about 5–10 ms) and motor unit potentials with slightly higher amplitude, longer duration, mild waveform instability, and polyphasic pattern from distal muscles in the lower limbs. Voluntary contraction evoked repetitive bursts of high frequency discharges resembling motor unit potentials with amplitude decrement and a characteristic “pinging” sound (figure); the discharges lasted several hundred milliseconds and were present uniformly in all examined muscles.
Nerve conduction studies disclosed borderline or slightly reduced amplitudes of compound muscle action potentials (CMAPs) with no conduction blocks, temporal dispersion of CMAPs, or conduction slowing. The amplitudes of the sensory nerve action potentials were either unrecordable or decreased; sensory conduction velocities were borderline.
The supramaximal stimulation of upper and lower limb motor nerves (median, ulnar, peroneal, and tibial nerves bilaterally) evoked CMAPs followed immediately or after a short period—up to 30 ms—by repetitive “neuromyotonic” discharges of high frequency (about 230 Hz), waning amplitude, and duration of hundreds of milliseconds that could be recorded with the surface recording electrode.
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 axillary nerves performed at a stimulation frequency of 2 Hz showed no decrement.
The stimulation single fibre EMG from the extensor digitorum communis muscle on the right side showed a slightly abnormal jitter (19 recordings, mean jitter 34 μs, five recordings above 40 μs), which together with a slight incerease in fibre density (2.3) indicated the reinnervation process.
Second EMG and conduction studies performed 7 days after the end of the second IVIg treatment showed less frequent neuromyotonic discharges evoked by electrical stimulation of the motor nerves and the voluntary contraction and the ability to evoke them waned; after several contractions they disappeared.
Torbergsen et al 3 stated 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, whereas spontaneous neuromyotonic discharges without an obvious trigger are generated in the case of more increased hyperexcitability of axons.
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. Moreover, the movement provoked corresponding sensory phenomena of dysaesthesias and paraesthesias. It seems likely that these sensory phenomena of dysaesthesias and paraesthesias were evoked by similar types of sensory neural hyperactivity. The high frequency discharges in our patient with neuromyotonia consisted of motor unit potential-like waveforms, which did not arise spontaneously, but the high frequency of about 200 Hz clearly showed their ectopic origin.
We think that actual definitions of neuromyotonic discharges emphasising their spontaneous occurrence or initiation by needle movement should be reconsidered and modified.
The presence of VGKC antibodies and clinical, immunological, and electrophysiological response to IVIg treatment are in favour of the role of VGKC blockade in the generation of “evoked” neuromuscular discharges. Antibodies to VGKC found in our patient may have accessed the paranodal region (due to myelin disturbance in polyneuropathy) and blocked fast K+ channels similarly to 4-amidopyridine.4 5 This would enhance supernormality and could thereby allow a single action potential to trigger another discharge or a train to discharge.