230 Journal ofNeurology, Neurosurgery, and Psychiatry 1991;54:230-235

Neuromyotonia in hereditary motor neuropathy J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.3.230 on 1 March 1991. Downloaded from

A F Hahn, A W Parkes, C F Bolton, S A Stewart

Abstract Case II2 Two siblings with a distal motor This 15 year old boy had always been clumsy. neuropathy experienced cramping and Since the age of 10, he had noticed generalised difficulty in relaxing their muscles after muscle stiffness which increased with physical voluntary contraction. Electromyogra- activity such as walking upstairs, running and phic recordings at rest revealed skating. For some time, he was aware of repetitive high voltage spontaneous elec- difficulty in releasing his grip and his fingers trical discharges that were accentuated tended to cramp on writing. He had noticed after voluntary contraction and during involuntary twitching of his fingers, forearm ischaemia. Regional neuromuscular muscles and thighs at rest and it was more blockage with curare indicated hyperex- pronounced after a forceful voluntary con- citability of peripheral nerve fibres and traction. Muscle cramping and spontaneous nerve block suggested that the ectopic muscle activity were particularly unpleasant activity originated in proximal segments when he re-entered the house in the winter, of the nerve. Symptoms were improved for example, after a game of hockey. Since the with diphenylhydantoin, carbamazepine age of twelve, he had noticed a tendency to and tocainide. trip. Subsequently he developed bilateral foot drop and weakness of his hands. He denied sensory symptoms and perspired only with The term "neuromyotonia" was coined by exertion. Mertens in 1965' to define a syndrome He was muscular with well-developed prox- of delayed muscle relaxation after voluntary imal muscles. This contrasted with moderate contraction resulting from a disorder of peri- wasting and weakness of the wrist and finger pheral nerve rather than muscle. Affected extensors, the intrinsic hand muscles and also patients complain of muscle stiffness and the peroneal and intrinsic fott muscles. Sen- cramping and show fasciculations and myo- sory examination was normal. Deep tendon kymia. Regional neuromuscular blockade with reflexes were reduced and ankle jerks were curare established the neural origin;'2 in fact, absent. The plantar responses were flexor. hyperexcitability and ectopic impulse genera- When he was fully relaxed, brief, repetitive tion may occur along the whole length of the twitching of his fingers and myokymia and motor axon, including the terminal arborisa- fasciculations in the proximal muscles were tions.3 Moreover, hyperexcitability of nerve clearly apparent. After forceful flexion of the http://jnnp.bmj.com/ membranes may be present in sensory, as well fingers, the grip release was slow and delayed, as motor axons, in spite of few sensory symp- with the appearance of action myotonia, yet toms.2 percussion of the thenar eminence produced Neuromyotonia has been observed with or no abnormal muscle contraction. Percussion without overt peripheral neuropathy.4 There of the tongue, however, resulted in a focal are, however, few descriptions of hereditary tonic contraction, lasting several seconds,

neuropathies with associated neuro- which subsided into fasciculations. Strong on October 1, 2021 by guest. Protected copyright. myotonia,259 and the precise mechanisms of voluntary contraction of his quadriceps was the neuromyotonia are still in some doubt. followed for 10 to 30 seconds by a persisting, Department of We Clinical Neurological report our observations in two siblings involuntary contraction of the muscles, which Sciences, University of of Chinese origin, born to unrelated, healthy subsided into myokymic activity and fas- Western Ontario, parents. Symptoms of neuromyotonia had ciculations. The Trousseau sign was positive. London and the been present since Victoria Hospital, early childhood, accom- Within 10 seconds after inflation of a blood London, Ontario panied by a progressive motor deficit in distal pressure cuff, the fingers began to twitch and A F Hahn muscles of the upper and lower limbs. Elec- by 35 seconds they were drawn into a carpal A W Parkes trophysiological studies provided further C F Bolton clues on the mechanisms of the abnormal St Joseph's Hospital, 1 2 London, Ontario, spontaneous nerve activity. A favourable Canada therapeutic response was seen with diphenyl- I S A Stewart hydantoin, carbamazepine and tocainide. Correspondence to: Dr Hahn, Department of Clinical Neurological Sciences, Victoria Hospital, Case reports 375 South Street, London, The family tree is illustrated in fig 1. All Ontario N6A 4G5, Canada family members received a full clinical and Received 2 April 1990 and in Figure 1 Family tree, only II2 and II5 were affected. revised form 13 July 1990. electrophysiological examination. Only II2 Detailed electrophysiological testing and biopsies were Accepted 23 July 1990 and II5 were affected. performed in I2. Neuromyotonia in hereditary motor neuropathy 231

spasm, which resolved quickly when the cuff Regional neuromuscular blockade: an intraven- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.3.230 on 1 March 1991. Downloaded from was deflated. ous regional infusion of delta-tubocurare was Treatment with carbamazepine, 400 mg/ given to patient II2 in the right forearm. This day resulted in a marked improvement of the was erformed after informed consent with neuromyotonic symptoms in that he could proper precautions according to the methods of release his grip promptly, movements were Torda and Klonymus.' A total of 17 ml of a smooth and he could run up two flights of 0-028% solution of delta-tubocurare was injec- stairs with only mild muscle stiffening. ted over a period of 21 minutes. This resulted Tongue myotonia was no longer present. in the gradual disappearance of all abnormal Unfortunately, carbamazepine had to be spontaneous activity. discontinued after two weeks because of Ulnar nerve block: 7 ml of 2% xylocaine were thrombocytopenia. Diphenylhydantoin, injected near the ulnar nerve at the elbow. 300 mg/day was less effective. While there was Assessment ofthe block was made by recording little spontaneous muscle activity at rest, it the maximum hypothenar muscle compound was readily recorded with surface and action potential in response to supramaximal needle electrodes after voluntary contraction stimulation of the ulnar nerve at the wrist, and during ischaemia. Tocainide, 1200 mg/ below the elbow and above the elbow, before, day resulted in excellent symptomatic during and after the xylocaine injection. improvement of the delayed muscle relaxation Polygraph recordings of spontaneous activity and generalised muscle stiffness. Yet involun- from both hypothenar muscles were made with tary, brief muscle twitching persisted, surface electrodes before, during and after provoked by muscle activation and nerve recovery of the xylocaine block. ischaemia. The favourable therapeutic Polygraph recordings: simultaneous recordings response has been maintained, but muscle were made with surface electrodes from all four cramping recurred promptly when the drug limbs, while monitoring EKG and respiration. was discontinued. Muscle Biopsy: cryostat sections of the anterior tibial muscle were stained or reacted for Case 115 haematoxylin and eosin, Gomori trichrome, Symptoms were much milder in his younger DPNH and ATPase. A piece of muscle was sister who was examined at the age of 11. She fixed in 2-5% buffered glutaraldehyde and denied any limitations. Examination showed processed for electron microscopy according to no spontaneous involuntary muscle activity at standard techniques. One micron toluidine rest. Muscle tone was normal. Selective weak- blue-stained sections were examined with the ness was demonstrable in wrist and finger light microscope; ultrathin sections of selected extensors and peroneal muscles. Definite per- areas were viewed with an electron microscope cussion myotonia was present in the tongue (Philips 410). but none in the thenar eminence. Grip release was not delayed. Deep tendon reflexes and the sensory examination were normal. In spite of Results only mild clinical findings, bursts of high vol- Laboratory examinations were normal, includ- tage, spontaneous electrical activity were ing serum sodium, potassium, chloride, cal- recorded in many proximal and distal limb bicarbonate, inorganic cium, magnesium, http://jnnp.bmj.com/ muscles at rest and accentuated after activity. phosphate, creatinine and thyroid indices. Creatinine phosphokinase was elevated in II2 to Material and methods 1248 U/L (36-188). It was normal in all other Electrophysiology family members. Standard nerve conduction studies were per- Electrophysiology: nerve conduction studies in formed-orthodromic for motor and II2 and II5 revealed entirely normal motor and antidromic for sensory, utilising surface elec- sensory conduction velocities, however, com- trodes. Needle electromyography was carried pound muscle action potentials were reduced on October 1, 2021 by guest. Protected copyright. out with a concentric needle electrode. in amplitude and distal latencies were con- Polygraph recordings were made with a Model siderably prolonged (table). F-wave latencies 8-16 Grass EEG machine while respiration could not be measured, due to the persistent was recorded with a Phipps and Bird neuromyotonia. Needle electromyography of pneumograph. distal muscles revealed reduced motor unit Table Electrophysiological studies of affected individuals Action potential amplitude Nerve studied Patient Conduction Velocity (mls) Distal latency(m/s) sensory p V: Motor mV

Median (M) II2II, ~~~50-85701 4-85-2 14-0710 Ulnar (M) 12 64-1 4-2 8-0 Peroneal (M) II,112 42-8unrecordable 7-67 6 1-4 Tibial II2 40 9 5-2 2-8 (M) II, - 53 1 2 6 38-0 Median (S) II2II, 57-5 2-4 40-0 Ulnar (S) II2 50 0 2-5 30-0 397 Sural (S) II2II, 45-03062-4 228028-0 232 Hahn, Parkes, Bolton, Stewart

@') J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.3.230 on 1 March 1991. Downloaded from I1 III, II,J11,.I 11 ,l l ,1 .11 ,b 7ll, t ill"' tli

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I 1 OOAV J100 1iV 5s 5s Figure 2 Illustrations of the types of abnormal electrical activity recorded in Case I12: A) Two typical neuromyotonic discharges, the first ending, and the second beginning, quite suddenly. Recorded with a concentric needle electrode in the tongue. B) A typical myokymic discharge recorded with a concentric needle electrode in the deltoid muscle. The grouped discharges recurred at the rate of 10/s. C) A single neuromyotonic discharge in the hypothenar muscle of high enough amplitude to be recorded with skin surface electrodes. D) Abundant abnormal spontaneous activity recorded with a concentric needle electrode in the hypothenar muscle. The discharges were neuromyotonic. The muscle was at a normal temperature 37-5°C. E) The same hypothenar muscle as in D, but cooled to 22°C, at which time much of the abnormal activity had disappeared.

recruitment patterns, but considerably voluntary muscle activation also gradually dis- increased amplitudes of single motor unit appeared. A further 3 ml were injected at 12 action potentials. Firing rates were also minutes and 2 ml at 20 and 21 minutes. At this increased. The motor unit action potentials point, after a total of 17 ml had been injected, were often polyphasic and mildly increased in there was EMG silence. Further insertion of duration. These electrophysiological findings the needle electrode into the muscle failed to indicated a motor neuropathy, with chronic evoke any abnormal discharges. The first partial denervation of muscle and collateral abnormal EMG activity began within five min- reinnervation. utes after the cuff was deflated. Initially, the The unusual feature of these cases was the discharges looked like discrete normal motor presence in resting muscles, of frequent, very unit action potentials, then neuromyotonic high voltage, spontaneous discharges which discharges began to reappear and after 20 appeared in a variety of forms, the most con- minutes all forms ofabnormal activity could be stant being typical neuromyotonic discharges, recorded. These test results indicate that the but also occasional myokymic and random abnormal discharges were arising from the http://jnnp.bmj.com/ discharges. These were recorded from the nerve and not from the muscle membrane. tongue and from proximal and distal limb To further study the ectopic impulse genera- muscles (fig 2). In the relaxed patient, frequent, tion along the length of the nerve, a right ulnar repetitive bursts of high voltage electrical nerve block was induced at the elbow. The local activity were easily recorded with surface elec- injection of 7 ml 2% xylocaine resulted in an trodes from the hypothenar eminence. The almost complete ulnar nerve block and in abnormal electrical activity in resting muscle virtual disappearance of the neuromyotonic on October 1, 2021 by guest. Protected copyright. was increased by voluntary activation of the discharges recorded from the right hypothenar muscle, but not by mechanical or electrical muscles (fig 3). With the gradual recovery from stimulation of the nerve supplying the muscle. the nerve block neuromyotonic discharges The spontaneous activity was also greatly returned after 60 minutes. enhanced by nerve ischaemia after tourniquet Polygraph recordings disclosed that application. Cooling ofthe limb to 22°C almost neuromyotonic discharges occurred randomly eliminated all abnormal spontaneous activity and in a multifocal fashion in all four limbs and yet it was prominent during rewarming (fig 2). had no relationship to either respiration or A regional curare test was given to assist in EKG. determining the origin of the abnormal dis- Treatment effect: no electrophysiological recor- charges. During the test, frequent recordings dings were performed while the patient was on were made from the hypothenar muscle with a carbamazepine. The complicating thrombo- concentric needle electrode. Inflation of the cytopenia precluded needle electromyography. tourniquet resulted in a marked increase in the During treatment with diphenylhydantoin amount of abnormal electromyographic abnormal spontaneous discharges were almost (EMG) activity. Five millilitres of delta- totally abolished at rest. Yet high voltage, tubocurare were injected at one and three spontaneous activity was quite marked during minutes after tourniquet application. This nerve ischaemia. While medicated with tocain- promptly reduced the EMG activity and the ide-which successfully reduced the symptoms carpal spasm. EMG activity provoked by of generalised muscle stiffness and cramping- Neuromyotonia in hereditary motor neuropathy 233

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Figure 3 Effect of a xylocaine block on the neuromyotonia. Tracing on the left shows Polygraph recordingsfrom hypothenar muscles of the right and left hand. The figures on the right show hypothenar compound muscle action potentialsfrom stimulation of the right ulnar nerve at the wrist, below the elbow and above the elbow, before, during and after the xylocaine block. The block of the right ulnar nerve at the elbow resulted in an almost complete disappearance of the hypothenar compound muscle action potential when the ulnar nerve was maximally stimulated above the elbow. The neuromyotonic discharges also disappeared almost completely (B). The upper (A) and lower (C) figures depict results immediately before and after the xylocaine block. Note also that discharges were ofsuch high amplitude that they could be recorded with surface electrodes, and at this time they were occurring asynchronously between the two hands, but semi-rhythmically on the left at approximately 2-3/s.

abnormal spontaneous activity could still be sidered an abnormality of the autonomic http://jnnp.bmj.com/ recorded in resting muscle and after voluntary nervous system as their cause. Gamstorp and activity and ischaemia. A variety of forms was Wohlfahrt5 described two patients (Cases 2 and observed from single to repetitive discharges of 3 of their report) with classic clinical and myokymic or neuromyotonic pattern, yet there electrophysiological signs of neuromyotonia in were no prolonged trains of high frequency association with a profound, slowly progressive discharges. distal motor neuropathy. Case 2 appears to Muscle biopsyfindings: The muscle biopsy of II2 have been sporadic, while case 3 was inherited, showed typical findings of chronic partial den- with onset of symptoms in early childhood. on October 1, 2021 by guest. Protected copyright. ervation and reinnervation. Groups of small angular fibres ofeither fibre type were seen next to largegroupsofhypertrophicmusclefibres (fig 4). Examination with the electron microscope revealed changes of denervation. Endplate regions and intramuscular nerve twigs were not observed. An attempted biopsy of the sural nerve was technically unsatisfactory. A*-

Discussion It is likely that the two children in this report have an inherited motor neuropathy with accompanying neuromyotonia. The first description of such a familial occurrence of distal muscle atrophy, delayed grip release, muscle cramping and fascicula- tions in two brothers is by Grund.78 Grund Figure 4 Biopsy ante;or tibial muscle haematoxylin accurately recognised the myokymic features as and eosin; bar = 500 alm small and large grouped being possibly neuronal in origin, but con- atrophy ofmusclefibres indicating chronic denervation. 234 Hahn, Parkes, Bolton, Stewart

When examined in his early twenties, the neuropathy23161' (and personal observation). J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.3.230 on 1 March 1991. Downloaded from patient showed advanced atrophy ofall muscles Wallis et al3 in an unusual case of 2-4D below the knee and moderate wasting of the insecticide poisoning, observed a 53% reduc- small hand muscles. The patient's father had tion of spontaneous electrical activity recorded had signs of a neuropathy since early life, yet from the hypothenar muscle, with an ulnar apparently had no neuromyotonic symptoms. nerve block at the elbow. A subsequent ulnar There is, however, no record of an electro- block at the wrist, further reduced the abnor- myographic examination. As illustrated by our mal potentials, thus indicating hyperex- case I15 abnormal spontaneous nerve activity citability of the axonal membrane throughout may not be detected on clinical examination, its length. In our patient the majority of even when it is abundant on electromyography. spontaneous ectopic impulses appeared to be The most detailed documentation of a generated at a proximal site, since the nerve familial axonal form of this condition is that of block at the elbow resulted in such a marked Lance et al.2 The two siblings both had chronic reduction of the neuromyotonic discharges. weakness and atrophy in distal muscles and Our observations also differ from previous associated symptoms of neuromyotonia and reports2417 in that the abnormal spontaneous myokymia, dating back to early childhood. In activity was enhanced by voluntary muscle elegant electrophysiological studies, the auth- activation, but could not be elicited by either ors documented an abnormal hyperexcitability electrical or mechanical stimulation of the of motor and sensory nerve fibres. Although nerve supplying the muscle. Localised forearm there were no clinical sensory abnormalities, ischaemia, however, induced a marked examination of a sural nerve biopsy illustrated enhancement of distal spontaneous activity. mild, longstanding degeneration of sensory These observations suggest that the nerve axons. Thus their findings indicated a hyperexcitability is a generalised phenomenon, hereditary motor and sensory neuropathy. possibly related to a functional or structural Similar observations were made in two abnormality of the axonal membrane. unrelated families by Vasilescue et al6. Given the beneficial effects of diphenyl- In a subsequent second report, Lance and hydantoin and carbamazepine one may colleagues9 pointed out, that neuromyotonia speculate on possible pathomechanisms. Both may also be associated with what they consider medications were shown to improve the to be a pure motor and spinal form of Charcot- neuromyotonia in a dose dependent fashion Marie-Tooth disease. They describe a family and to significantly reduce abnormal spon- in which eight affected members in three gen- taneous discharges recorded from resting erations showed moderately severe, distal atro- muscle2381618 (personal observation). How- phy, absent deep tendon reflexes but no sensory ever, repetitive brief bursts of spontaneous abnormalities, neither on clinical, electro- activity continued to be provoked by nerve physiological or pathological examination. The ischaemia. Voltage clamp examinations ofperi- clinical findings in these cases bear close resem- pheral nerves have shown that both diphenyl- blance to our patients. hydantoin and carbamazepine reduce sodium Hereditary forms of neuromyotonia without conductance by specifically blocking sodium muscle weakness or atrophy4 11-13 may con- channels in a manner similar to tetrodo- stitute separate entities. toxin.' 22 Diphenylhydantoin thus increases Although the principal pathological proces- the threshold of rabbit nerve to electrical http://jnnp.bmj.com/ ses may vary in these different forms of excitation and abolishes repetitive nerve dis- hereditary degenerative conditions, they share charges in response to supramaximal or long the pathophysiological phenomenon of duration currents.23 hyperexcitability of peripheral nerve axons. Local anaesthetics such as lidocaine and its The exact mechanisms and the site of the derivative tocainide also block sodium channels abnormal impulse generation remain and modify their gatinggatigpoperproperties.242'This unknown, and in fact, they may differ in the constitutes the principal mechanism of action various conditions. In cases of neuromyotonia oftocainide in its antiarrhythmic properties25 27 on October 1, 2021 by guest. Protected copyright. without overt peripheral neuropathy, mor- and of its beneficial effect on myotonia26 and phological changes have been described in the paramyotonia.2- Tocainide is also as effective terminal arborisations of motor axons and as carbamazepine in the modification ofpain in electrophysiological studies suggested a very trigeminal neuralgia.' This likely relates to the distal trigger zone for the abnormal electrical property of both drugs to block sodium chan- discharges."41415 The myokymic activity nels and stabilise hyperexcitable nerve mem- recorded by needle electromyography consis- branes. A beneficial effect of tocainide on ted ofnormal motor unit potentials. It was thus neuromyotonia has, to our knowledge, not been postulated that impulses, originating in the described before. We found tocainide to be terminal branches of motor nerves, are equal to carbamazepine in the control ofmuscle propagated antidromically and activate the stiffness and cramping. Electrically, both drugs entire motor unit by an axon reflex. This abolished the long trains of neuromyotonic concept is based on the observation that the discharges at rest, yet they did not eliminate abnormal discharges are not abolished by a the repetitive, brief bursts of high voltage peripheral nerve block, but disappear after discharges that were particularly prominent administration of curare. after muscle activation and during nerve Ectopic impulses appear to be generated at ischaemia. multiple trigger sites or along the entire length Motor axons are well known to accommodate of the axon in cases with overt peripheral rapidly to a sustained depolarisation. This, Neuromyotonia in hereditary motor neuropathy 235

according to a recent report by Baker et al,5' is 12 Ashizawa T, Butler IJ, Harati Y, Roongta SM. A dominan- tly inherited syndrome with continuous motor neuron J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.3.230 on 1 March 1991. Downloaded from mediated primarily by a slow, rectifying potas- discharges. Ann Neurol 1983;13:285-90. sium outward current that can be specifically 13 Black JT, Garcia-Mullin R, Good E, Brown S. Muscle rigidity in a newborn due to continuous peripheral nerve blocked by tetraethylammonium (TEA). hyperactivity. Arch Neurol 1972;27:413-25. These TEA-sensitive potassium channels are 14 Isaacs H. Continuous muscle fibre activity in an Indian male with additional evidence of terminal motor fibre abnor- localised at the nodes of Ranvier. Their role mality. J Neurol Neurosurg Psychiatry 1967;30:126-33. seems to be to provide accommodation and 15 Oda K, Fukushima N, Shibasaki H, Ohnishi A. Hypoxia- sensitive hyperexcitability of the intramuscular nerve spike frequency adaptation during prolonged axons in Isaacs' syndrome. Ann Neurol 1989;25:140-5. depolarisation. Such depolarisation is, for 16 Lutschg J, Jerusalem F, Ludin HP, Vassella F, Mumenth- aler M. The syndrome of "continuous muscle fiber instance, generated by prolonged voluntary activity." Arch Neurol 1978;35:198-205. muscle contraction or during nerve 17 Warmolts JR, Mendell JR. Neurotonia: Impulse-induced repetitive discharges in motor nerves in peripheral ischaemia.32 The hyperexcitability of nerve neuropathy. Ann Neurol 1980;7:245-50. membranes in these patients with 18 Bady B, Girard PF, Jallade S, Gaillard L. Une observation de pseudomyotonie gu&rie par la carbamazepine. Rev neuromyotonia may be caused by an abnormal Neurol 1969;120:277-86. behaviour of membrane ion channels and a 19 Lipicky RJ, Gilbert DL, Stillman IM. Diphenylhydantoin inhibition of sodium conductance in squid giant axon. failure of accommodative mechanism. Proc Nat Acad Sci USA 1972;69:1758-60. 20 De Weer P. Phenytoin: Blockage ofresting sodium channels. In: Glaser GH, Penrv JK, Woodbury DM, eds. We thank Mrs Jane Morehouse for excellent preparation of the Antiepiliptic drugs: mechanisms of action. New York: manuscript. We are indebted to Dr J Gilbert for the use of the Raven Press 1980:353-61. biopsy material. 21 Schwarz JR. Vogel W. Diphenylhydantoin: Excitability reducing action in single myelinated nerve fibres. Europ J Pharmacol 1977;44:241-9. 22 SchaufCL, Davis FA, Marder J. Effects ofcarbamazepine on 1 Mertens HG, Zschocke S. Neuromyotonie. Klin Wochenschr the ionic conductances of myxicola giant axons. J Phar- 1965;43:917-25. macol Exp Ther 1974;189:538-43. 2 Lance JW, Burke D, Pollard J. Hyperexcitability of motor 23 Morrell F, Bradley W, Ptashne M. Effect of diphenylhydan- and sensory neurons in neuromyotonia. Ann Neurol toin on peripheral nerve. Neurology 1958;8:140-4. 1979;5:523-32. 24 Cahalan MD, Almers W. Interactions between quaternary 3 Wallis WE, Van Poznak A, Plum F. Generalized muscular lidocaine, the sodium channel gates, and tetrodotoxin. stiffness, fasciculations, and myokymia ofperipheral nerve Biophys J 1979;27:39-56. origin. Arch Neurol 1968;21:270-89. 25 Sheldon RS, Cannon NJ, Nies AS, Duff HJ. Stereospecific 4 Auger RG, Daube JR, Gomez MR, Lambert EH. interaction of tocainide with the cardiac sodium channel. Hereditary form ofsustained muscle activity ofperipheral Mol Pharmacol 1988;33:327-31. nerve origin causing generalized myokymia and muscle 26 Rudel R, Dengler R, Ricker K, Haass A, Emser W. stiffness. Ann Neurol 1 984;15: 13-21. Improved therapy of myotonia with the lidocaine 5 Gamstorp I, Wohlfart G. A syndrome characterized by derivative tocainide. J Neurol 1980;222:275-8. myokymia, myotonia, muscular wasting and increased 27 Ricker K, Haass A, Rudel R, Bohlen R, Mertens HG. perspiration. Acta Psychiatr Scand 1959;34:181-94. Successful treatment of paramyotonia congenita (Eulen- 6 Vasilescu C, Alexianu M, Dan A. Neuronal type ofCharcot- burg): Muscle stiffness and weakness prevented by tocain- Marie-Tooth disease with a syndrome of continuous ide. J Neurol, Neurosurg, Psychiatry 1980;43:268-71. motor unit activity. J Neurol Sci 1984;63:11-25. 28 Streib EW. Paramyotonia congenita: Successful treatment 7 Grund G. Zur Frage des Vorkommens erworbener with tocainide. Clinical and electrophysiologic findings in Myotonie. Dtsche Z. Nervenheilk 191 1;42:110-27. seven patients. Muscle and Nerve 1987;10:155-62. 8 Grund G. tJber genetische Beziehungen zwischen 29 Lehmann-Horn F, Rudel R, Dengler R, Lorkovic H, Haass Myotonie, Muskelkrampfen und Myokymie. (Zugleich A, Ricker K. Membrane defects in paramyotonia congen- Beitrag zur Pathologie der neuralen Muskelatrophie). ita with and without myotonia in a warm environrment. Dtsche Z Nervenheilk 1938;146:3-14. Muscle and Nerve 1981;4:396-406. 9 Lance JW, Burke D, Pollard J. Neuromyotonia in the spinal 30 Lindstrom P, Lindblom U. The analgesic effect of tocainide form of Charcot-Marie-Tooth disease. Clin Exp Neurol in trigeminal neuralgia. Pain (Netherlands) 1987;8:45-50. 1979;16:49-56. 31 Baker M, Bostock H, Grafe P, Martius P. Function and 10 Torda TAG, Klonymus DH. Regional neuromuscular distribution of three types of rectifying channel in rat block. Acta Anaesthesiol Scand 1966;24:177-82. spinal root myelinated axons. J Physiol 1987;383:45-67. 11 McGuire SA, Tomasovic JJ, Ackerman N. Hereditary 32 Stohr M, Gilliatt RW, Willison RG. Supernormal continuous muscle fiber activity. Arch Neurol excitability ofhuman sensory fibers after ischemia. Muscle

1984;41:395-6. and Nerve 1981;4:73-5. http://jnnp.bmj.com/ on October 1, 2021 by guest. Protected copyright.