J. Neurol. Neurosurg. Psychiat., 1961, 24, 319.

A SYNDROME OF CONTINUOUS MUSCLE-FIBRE ACTIVITYBY

HYAM ISAACS*

Johannesburg

The purpose of this paper is to describe two casesof a hitherto unknown syndrome superficiallyresembling myotonia. Detailed studies have helpedto separate this syndrome of continuous muscle-fibre activity from a group of 100 myotonic subjects,and it will be referred to in this paper as the'syndrome of continuous muscle-fibre activity'.This descriptive label has been chosen, though themore imaginative may favour 'armadillo disease', aname by which these cases are likened to the slowmoving, armour-plated quadruped.

Case ReportsCase 1.-M.P., aged 12, was referred for investigation

with a complaint of stiffness of the muscles which hadbeen progressive over the past three years. The patient(Fig. 1), according to his parents, was reasonably normalup to the age of 9 years, quite able to run about andcompete with his friends. They stated, however, thatfrom the age of 5 years he had some difficulty in walking

FIG. 1.-Note stiff postureand contraction ofmuscles (Case 1); con-

..... ...traction of trapeziusis not be be mistaken

N,X < - " ....... t 211for webbing.

*201 Lister Buildmgs 276 Bree Street, Johannesburg.

and for the past three years he had been severely incapaci-tated by increasing muscle stiffness, present night andday. The stiffness was increased by voluntary muscle con-traction, particularly obvious after the third and fourthmovements after which the condition improved and hewas able to use his limbs more freely for a time, beforethey stiffened up again despite continued movement.At times he has had the greatest difficulty with the initialmovements and occasionally complained of stiffness ofthe jaw and tongue while eating and talking. His speechhad not been affected but he had at times experienceddifficulty in breathing due to stiffness of the chest.Defaecation and micturition were normal. He sweated agreat deal and always felt warm. There was no familyhistory of muscle disease; his parents were alive and welland showed no evidence of myopathy. His past illnessesincluded measles and chickenpox, from which he re-covered in the usual time without complications and whichwere not related to the onset of the present difficulties.On examination, the patient was found to be under-

weight and undersized for his 12 years, his height being48 in., span 47 in., and weight 45 lb. Pulse rate was124/minute, blood pressure 120/80 mm. Hg. The heartwas normal. The abdominal wall was extremely tense butno hepatosplenomegaly or masses were felt. The genitaliawere small, the testes pea-sized and soft. The child wasintellectually and emotionally normal. Tendon reflexeswere impossible to elicit, but the plantar response wasnormal. Motor power was generally poor. The cranialnerves were intact. Sensation and coordination seemednormal. His posture was stiff and all muscles were in astate of persistent contraction. The chest moved poorlywith respiration; there was hardly any subcutaneoustissue; the muscles were well-defined and firm.

All muscles showed evidence of fasciculation and wereweaker than normal. The weakness affected particularlythe extensor muscles of the forearms, arms, extensor andperoneal muscles of the legs, and the small muscles of thehands and feet. He walked with extreme difficulty in arigid manner. The degree of stiffness was more markedin the distal than proximal muscles, being unaffected bythe warmth of summer or the cold of winter. The patientwas constantly covered by a thin film of perspiration andhad a persistent tachycardia of 120/minute with the bodytemperature averaging 99°F. The upper limbs could onlybe fully extended passively and then with difficulty as itappeared that some degree of contracture had occurred.Passive extension was quite painless.Radiographs of the skull, chest, and spine revealed no

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HYAM ISAACS

TABLE IRESULTS OF LABORATORY INVESTIGATIONS

Haemoglobin (g. %)Leucocytes (thousands/c. mm.)Neutrophils (°)Eosinophils (%)Basophils (%)Monocytes (%)Lymphocytes (%)Bone marrowErythrocyte sedimentation

rate (mm./hr.)Wassermann reactionFasting blood sugar (mg./100

ml.)Blood urea (mg./100 ml.)Thymol flocculationThymol turbidity (units)Colloidal red testTakata Ara reactionCephalin cholesterol floccula-

tion (24-hour reading)Alkaline phosphatase (King-Armstrong units)

SerumBilirubin total (mg./100 ml.)Proteins (g./100 ml.)Albumin (g./100 ml.)Globulin (g./100 ml.)V GlobulinCholinesterases % of normal

activityIron (ug./100 ml.)Cos content (mEq./litre)PotassiumG.O. transaminase units

(normal, 34-107)G.P. transaminase units

(normal, 13-95)Sodium (mEq./litre)Chloride (mEq./litre)Amylase (Street-close units)Calcium (mEq./litre)Magnesium (mEq./litre)Creatinine (mg./100 ml.)Cholesterol (mg./100 ml.)Total lipids (mg./100 ml.)

Case 1

1486-7

572-01-040

36-0Normal cellularity

4Negative

9717

Negative2

NegativeNegative

Negative

10

046 54-22-30-72

10010021-03-6

60

65138101354.91-71-0

150451

Case 2

14-77-2

651%06

28Normal cellularity

Negative

12036

Negative1-5+

Negative

Negative

7-6

046-93-43-51-21

9010023-04-4

70

85139102274-61-21 2

207451

Serum-continuedProtein-bound iodine

(JAg./100 ml.)Plasma inorganic phosphorus

(mg./100 ml.)

Urine analysisSodium (mEq./litre)Potassium (mEq./litre)Chlorides (mEq./litre)Calcium (mg./litre)Phosphorus (mg./litre)Creatinine (mg./litre)Creatine24 hr. volume average (ml.)17-Ketosteroids (as dehydro-isoandrosterone)(mg./24 hr.)

17-Hydroxycorticosteroids(P.S.C.)

Total 17-hydroxycortico-steroids

F.S.H. 24 hr. (mouse units)Porphyrin excretionAS and Pb excretion

Insulin sensitivity testGlucose tolerance test

Cerebrospinal fluidPressure (mm. H,O)CellsProtein (mg./ 100 ml.)Sugar (mg./100 ml.)Chloride (mg./100 ml.)Lange's colloidal gold testBasal metabolic rate under

sedation

02 consumption (ml./min.)ElectroencephalogramChromatographic analysis

of urineC- reactive proteinMucoprotein (mg./100 ml.)Chromosomal pattern

abnormality. Electrocardiograms appeared normal butwere difficult to interpret because of the interference fromthe contracting muscles. The metabolic studies are listedin Table I.

A kymographic recording of the rate of contraction ofthe muscles of the hand and forearm is shown in Fig. 2.Electromyography carried out with concentric needleelectrodes recorded a state of constant rapid dys-rhythmic discharge of independent muscle fibres (Fig. 3).The spontaneous activity was increased by voluntarycontraction, an increase which peristed for 30 secondsafter this stimulus had ceased. This period was followedby a curious period of reduced activity lasting for i 10seconds. This relatively silent period could be interruptedat any stage by further voluntary effort. The electricalresponse to percussion was normal and did not aggravatethe discharge. Electrical stimulation of the nerve, as withvoluntary contraction, aggravated the condition. Thespontaneous discharge persisted despite local nerve block,but disappeared locally after infiltrating the muscles withprocaine. General anaesthesia with pentothal had no

effect, but blocking and depolarization of the motor end-plate with curare and succinylcholine abolished thespontaneous discharge and the muscle relaxed.

Several muscle biopsy specimens were obtained from

proxymal and distal muscles (Fig. 4) which revealed a

slight degree of variation in fibre size together with some

proliferation of sarcolemmal nuclei, which tended tooccur in chains, especially in relation to some of the smallfibres. Most of the nuclei were dark and in some placesformed small knots. There was a doubtful increase inendomysal collagen and fat.No improvement occurred following upon the admin-

istration of quinidine, procaine amide, cortisone, or

potassium depletion by exchange resins. Each of thesewas given for periods of at least a month in doses pushedto the point of maximum tolerance. A short-lived im-provement followed injections of Dimercaprol.Progress.-Over the next two years the patient was

further investigated during the school holidays wheneverpossible. His condition appeared static; splints were

made and applied at night to prevent flexion deformitiesat the elbows and wrists and to counteract the developingpes cavus. Growth remained retarded, muscle bulk haddiminished, and he had several brief attacks of acuterespiratory embarrassment due to chest and diaphrag-matic stiffness.

After the successful treatment of Case 2 this patientwas again admitted to hospital and treated in a similarfashion with dramatic results.

320

Case 1

4-3

36

1522715681

6721,040500700

5.5

40

7-36

NormalNormalNormalNormal

120Nil2080

700Negative

+74+84+68240

Normal

NormalAbsent

102Male

Case 2

3-3

4-8

15688148110900

2,664216

1,080

8-3

8-7

1486-12

NormalNormalNormalNormal

130Nil2167

727Negative

+65

360Normal

NormalAbsent

110MaleI

y

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FIG. 2.-Kymographic tracings with the drum rotating from left toright, demonstrating the slow voluntary contraction and re-laxation of the forearm muscles in the act of making a fist.

FIG. 3.-In normal muscle there is no electrical activity at rest.Note continuous dysrhythmic discharge of single muscle fibres atrest.

FIG. 4.-Muscle biopsy from left deltoid showing variations in fibresize, clumping of dark staining nuclei, row of sercolemmalnuclei, and atrophic fibres.

I1.. ........I .i r r I t ..R.. .

i-F||F l-- - E Pi .P H e

........

*- - M a~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~. --t. ....

t;8^.t:tl; ;"{ t' ; ' tt t--- o.:.4...:4..::....:....:.:~~~~~~~~~~~~.........._ii~- It''li I~ .*';1 g ^ 1-t ...l'~

.. I .. .. |i 1.$

... $-...... . .... L_ .. .. ... ..

r---J r8 7 6..... .... ....

vf V ij! *F ; #* - j;;~~~~~~~~~~~~.1

HG. 2

JIti. 4

IST DORSAL INTEROSSEOUS AT REST

Al J1 Lk |A.&

t ~ ~,

[ 0.5 MILLIVOLT

5. SECOND__ -_

0.5 SECOND;lit~ J. * | '|SiKt ?,'t* l;)*&A:1<$ ^';#@

AT REST F 0.5 MILLIVOLT

*i

::

I SECOND

HG. 3

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322

Fio. 5.-A three-channel simultaneous electromyographic recordingof first dorsal interosseous (top), extensor communis (middle),and flexor profundus (bottom) muscles at rest, showing markedreduction in activity after three days' therapy in Case 1.

The patient's movement is now quite free and hismuscle strength improves daily, aided by intensivephysiotherapy. The temperature remains normal, theB.M.R. has fallen to the normal level of + 5 and theoxygen consumption is now 160 ml./minute. Electro-myography at rest (see Fig. 3) and on effort has largelyreturned to normal. For the first time in four years thepatient has obtained relief.

Case 2.-Mr. V.C., a butcher by trade, aged 53 years,was referred for investigation complaining of increasingstiffness of muscles over the previous six months. Upto this time he had been in perfect health. The stiff-ness began in the feet, spreading to the legs and laterinvolved the arms, hands, and abdominal musculature.He noticed a hoarseness in his voice and stiffness of histongue over this period. Associated with the stiffnessthere was a generalized weakness of all muscles. He hadalso noticed twitching in the muscles over the previousthree months. He had had no difficulty with vision.Swallowing was occasionally difficult and at times thechest had become very stiff, leading to respiratoryembarrassment on two occasions. The stiffness of themuscles first increased with effort, then improved withrepetitive movements. He could then walk a shortdistance interrupted by occasional stiffening of muscles,paradoxically relieved by resting for a few seconds. Thecondition was growing worse. He lost 60 lb. in weight insix months.There was no family history of muscle disorder and his

five children were all well. The patient had recoveredwithout complications from the common childhoodillnesses and had remained well all his life. He had in thepast consumed up to two bottles of brandy per week overa period of eight years, but had stopped drinking for thepast three years. He complained of persistent sweating.The muscle stiffness was painless.

Examination revealed a middle-aged male with firmmusculature which was in a state of continuous contrac-tion. Fasciculation was noticeable in most muscles. Thepulse was 100/minute, blood pressure 110/76 mm. Hg.The temperature fluctuated between 98-4 and 99-4°F.The respiratory, cardiovascular, and genito-urinary

systems were normal. Palpation of the abdomen wasdifficult because of the muscle activity but there was nogross enlargement of the liver or spleen or abnormalmasses. Rectal examination was negative.The cranial nerves were intact, strenuous eye closure

produced difficulty in opening the eyes, most noticeable

ISAACS

after the second and third closure. All modalities ofsensation were normal. Coordination was normal. Themuscles were in a state of constant contraction. Powerwas reduced in all muscles and in particular the extensormuscles of the forearm. Tendon reflexes were impossibleto elicit, the plantar response was flexor. There was nomyotonic response to percussion of the muscles includingthe tongue.

Special investigations as in Case 1 were essentiallynegative (see Table I), including barium studies of thegastrointestinal tract, an air encephalogram, and electro-encephalography. The electromyographic studies wereidentical to those of Case 1. The patient was anaesthetizedwith thiopentone 500 mg. in a 5% solution and maintainedon oxygen and nitrous oxide. There was no change inmuscle activity during this procedure. Succinylcholine ina dose of 500 mg. produced diminution and disappearanceof all electrical activity within three minutes, lasting for10 minutes. Curare in a total dose of 10 mg. producedelectrical silence after five minutes, lasting for a period of40 minutes even though breathing began after a period of30 minutes. During this stage irritation of the muscle ormovement of the limb failed to produce electrical activity.On a separate occasion a brachial block was performedusing 25 ml. of 1% xylocaine; although the arm wasparalysed and anaesthetic, the motor activity persisted.This brachial block confirmed the findings of previousulnar and median blocks which affected only the motorsupply to the small muscle of the hand.

It was decided to determine the sensitivity of the motor-end plate to curare. The purpose of this test was two-foldin that it might add further information to the finalelucidation of the abnormality and, secondly, mightprovide a therapeutic tool. The patient was prepared asfor a general anaesthetic and then given 1 mg. of curareintravenously; three minutes later he complained ofgeneralized weakness which persisted for 10 minutes. Afurther 1 mg. curare was then given and two minutes laterhe began to have difficulty with breathing and swallowing,breathing becoming rapid and shallow. There was markedgeneralized weakness which completely overshadowedthe reduction in the state of persistent muscle activity.Curare was therefore useless therapeutically, owing tothe marked sensitivity at the motor end-plate to thisblocking agent. Prostigmine was given to overcome theblock but response was slow and even after 15 mg. hadbeen given intravenously slight generalized weaknesspersisted for the next hour. On another occasion, thepatient was resistent to 1-5 mg. of decamethonium butdeveloped generalized weakness after an additional 1-0mg. had been given intravenously, which was not alteredby 20 mg. of edrophonium. The weakness was assessedby the ulnar nerve stimulatory method described byChurchill-Davidson and Richardson (1952) and showeda normal response with perhaps slightly resistant end-plates.

Several muscle biopsy specimens were taken andrevealed a similar histopathological picture to those ofCase 1.

Arterial perfusions of the muscles of the forearm werecarried out; there did not seem to be any increase in sen-sitivity to acetylcholine or potassium, but owing to the

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A SYNDROME OF CONTINUOUS MUSCLE-FIBRE ACTIVITY

continuous spontaneous activity the results were difficultto interpret. There was, however, increased activityfollowing on injection of both substances given in doseswhich would evoke contractions in normal subjects.Calcium and magnesium infusions produced somedecrease in activity but this was associated with markedmuscle weakness. The discharge was unaffected byatropine, quinine, cortisone, artane, adenosine tri-ophosphate, thiamine diphosphate, or procaine amide.Progress.-The condition steadily deteriorated over the

next year, so that the patient became unable to walk andbegan developing contractures in the upper and lowerlimbs, producing flexion deformities at the elbows andwrists and per cavus respectively. There were severalepisodes of respiratory embarrassment and dysphagia.

After having exhausted the possibilities of deficient orexcessive ions concerned in the maintenance of normalneuromuscular response, and having abandoned bothblocking and depolarising agents as therapeutic toolsowing to the occurrence of severe muscle weakness,sodium hydantoinate was used in an attempt to diminishthe bizarre uncontrolled discharge from the lower motorneurone which characterizes this condition. The initialdose given was 100 mg. four hourly. A marked improve-ment occurred over the next two days and the drug wasthen reduced to a maintenance dose of 100 mg. six hourly.Six months later he was quite mobile and has been ableto go back to his trade. The electromyography is vastlyimproved both at rest and on voluntary effort, the B.M.R.was + 7, and the oxygen consumption had fallen to280 ml./minute after two weeks' therapy.

DiscussionThere are a few pathological conditions which

merit comment in that they have one or two featuresin common with this syndrome ofcontinuous muscle-fibre activity. The similarities, however, are at thebest only superficial.

Wechsler and Brock (1922) described a myostaticvariant of dystonia musculorum deformans. In thisdisease, however, the myostatic manifestations were'part of the disorder and always co-exists with thekinetic disturbance of which it is only a comple-ment'. The postures assumed, muscle tone, andother manifestations of central nervous disorderbear no similarity to the cases with continuousmuscle-fibre activity. Furthermore, as pointed outby Ramsay Hunt (quoted by Wechsler and Brock,1922) this myostatic variety of torsion dystoniashould be considered in the same light as paralysisagitans with tremor on the one hand and rigidity onthe other.McArdle (1951) described the case of a young

adult male who complained of weakness, stiffness,and painful muscles after exercise. The muscleswere of normal size and consistency at rest, butafter exercise the respective muscles became hardand shortened, and developed areas of painfulswelling. On resting the condition gradually im-

proved and returned to normal. Passive extension ofthe affected muscles during this time met with con-siderable resistance and was painful. Electromyo-graphy revealed no activity at rest, normal actionpotentials during contraction and the painful areasof shortened muscle were electrically silent. McArdlecompared the muscles in this case to the muscle incases of iodioacetate and heavy metal poisoning andshowed that the defect in his case was due to defec-tive glycolysis. This was thought to be due tofailure of the sulphydryl-splitting enzymes. McArdlegave his patient Dimercaprol with definite improve-ment, which was unfortunately shortlived. Thedefective glycolysis in McArdle's case has now beenlocalized to a deficiency of phosphorylase, and thetemporary improvement to Dimercaprol remains amystery (McArdle, 1960). This and similar cases areobviously very different from the cases described inthis paper which gave no evidence of defectiveglycolysis but are characterized by continuousmuscle-fibre activity. The shortlived improvementfollowing on Dimercaprol in Case 1 is, as withMcArdle's case, difficult to explain.Moersch and Woltman (1956) recorded 14 cases

described as the 'stiff-man' syndrome. These caseswere collected over a period of 30 years and includedfour women. The conditions appeared usually inthe fifth decade with gradually increasing rigidityassociated with intermittent painful spasms whichcould be precipitated by external stimuli or suddenvoluntary or passive movement. The muscles firstaffected varied from those of the trunk, neck, andshoulders to those of the extremities, eventuallyspreading to involve all except the jaw muscles. Theultimate picture demonstrated marked involvementof the proximal musculature and to a lesser extentthe distal. The muscles were described as rigid andboard-like, fluctuating in severity. The tendonreflexes were brisk. An undetermined reducing sub-stance was found in the urine of four cases, other-wise biochemical investigations were normal.Electromyographic studies in five cases gave anormal pattern. Muscle biopsy findings in two caseswere normal. The conditions failed to respond tobarbiturates, cortisone, antispasmodics, and relaxantdrugs; 11 cases were followed for periods up to 15years. There was a gradual deterioration in each.The severe proximal muscle involvement, the sparingof the jaw muscles, the brisk tendon jerks, the severeintermittent spasms with agonizing pain, the normalelectromyographs and muscle biopsies, absence offasciculation, increased B.M.R., and involuntarycontraction of muscle fibres serve to distinguish the'stiff-man' syndrome from the syndrome of con-tinuous muscle-fibre activity.

There are some points of similarity between the

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HYAM ISAACS

cases with continuous muscle-fibre activity and themyotonic disorders of muscle. Continuous muscle-fibre activity is slightly aggravated by cold, a featureshared by a large number of myotonia sufferers.After strong voluntary contraction of any musclethere is a sustained shortening of the muscle lastinglong after the initial stimulus has stopped, as inmyotonia, though the mechanism is entirely different.In the former the shortening is maintained by per-sistent contraction, whereas in the latter it is a delayin relaxation. With continuous muscle-fibre activitythe first movement is usually the most difficult toovercome but eases on repetition, whereas, at othertimes the first few movements are relatively free,becoming more difficult with repetition up to a pointafter which the movement becomes easier. Theformer progression is common in myotonia, and thelatter, though rare, is occasionally seen and has beenreferred to as paradoxical myotonia. If the firstmovement, however, represents a maximum con-traction, it is doubtful if this paradoxical progressionexists. Marshall (1952) described a curious case ofparadoxical myotonia in which the failure to respondto quinine or deteriorate with potassium, togetherwith the absence of myotonic response to percussionmakes one wonder whether this is in fact myotoniaand not a variant of continuous muscle-fibreactivity. The rates of discharge of electric activityvary between 5 and 250/sec. which covers themyotonic range.There are many points of distinction between these

cases of continuous muscle-fibre activity and thosewith myotonia. Patients with myotonia are normalat rest, whereas those with continuous muscle-fibreactivity show continuous muscular activity in boththe waking and sleeping states. Electrical activityvirtually ceases in myotonia with the onset ofrelaxation, with the exception of a low-voltage after-discharge and the occasional phenomenon of reflexafterspasm (Denny-Brown and Nevin, 1941). Thecases under discussion show continuous high-voltage electrical activity at rest, recruiting withvoluntary effort, but on relaxation the activity con-tinues for some time well above the abnormalpattern which was present before the voluntary con-traction. The activity at rest is not affected by localblocking of the motor nerves. In contrast to myo-tonia, the activity of continuous muscle-fibre activityis abolished by blocking conduction at the motor end-plates. The electrical activity at rest in continuousmuscle-fibre activity does not have the appearanceof normal motor unit potentials, but suggests bizarrespontaneous contraction of large numbers of musclefibres. A notable feature in these cases is the lack ofresponse to direct mechanical stimulation as opposedto that which occurs in the case of myotonia. These

cases of continuous muscle-fibre activity haveobvious fasciculation involving all muscles in vary-ing degree, whereas fasciculation is rarely if everseen in myotonia. In myotonia, the abnormalelectrical response occurs only with the initialshortening of the muscle and not with sustainedcontraction, so that relaxation, though not neces-sarily complete, must be attempted before themyotonic discharges can be reproduced with furthermovements of that muscle. Though aggravatedseverely by contraction, patients with continuousmuscle-fibre activity actively maintain a persistentdischarge at all times with the exception of a curiousperiod of dampening down of electrical activityapproximately half a minute after a strong contrac-tion and lasting for about 10 seconds. This dampen-ing down is not a manifestation of fatigue andmight suggest that some product of muscle nervemetabolism or motor end-plate activity is responsiblefor the apparent improvement.

Localization of the lesion is aided by noting thatthe persistent activity continues after interruption ofthe lower motor neurone by local nerve blockade.This would tend to take the lesion beyond the peri-pheral nerve, with the exception of the terminalnetwork which seems to possess, in addition to theconductive function of the nerve, certain peculiaritiesof its own and may be the site of abnormal electricaldischarges. The electromyographic studies wouldsupport the fact that the discharge is occurring froma site within the terminal branchings or the myo-neural junction itself.The possibility of a primary muscle cell membrane

disorder is excluded by the response obtained withmyoneural blocking agents, barbituric acid deriva-tives, quinine, and the absence of irritability toneedle electrodes or to percussion.

Evidence of abnormal function at the myoneuraljunction is shown by the increased sensitivity to thecompetitive blocking action of d-tubocurare. Thisfinding suggests either excessive destruction of or aninadequate production of acetylcholine. Both theseconditions are made improbable by the presence ofcontinuous muscle activity, the fasciculation of themuscles, the failure to respond to prostigmine orquinine, and the normal pseudocholinesterase level.An alternative explanation for this increased sen-sitivity to curare suggests that the motor end-plateitself may have become relatively resistant as a resultof the continuous acetylcholine stimulation, aphenomenon which was demonstrated by Brown(1938) and more recently by Thesleff (1955). Theresponse to calcium and magnesium may furtherindicate the presence of a somewhat resistant motorend-plate. When given parenterally these sub-stances produced marked weakness in dosages which

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did not affect normal controls. Magnesium sup-presses the formation of acetylcholine in the nerveendings, while high calcium dosage increases theresistance of the motor end-plate (Brink, 1954).Carcinoma of the bronchus may be associated withextreme sensitivity to curare as shown by Eatonand Lambert (1957) so that unknown substancesacting at the myoneural junction must also be keptin mind as a possible explanation for this finding.

Fasciculation may occur with lesions at the myo-neural junction as is seen following the administra-tion of depolarizing drugs. The electromyographicfindings during this period resemble the discharge ofcontinuous muscle-fibre activity, including theoccasional motor unit potential formed by anti-dromic spread along the terminal branches as shownby Masland and Wigton (1940). With depolarizationof the motor end-plate, however, there occurs aresistance to the action of blocking agents as opposedto the increased sensitivity in patients with con-tinuous muscle-fibre activity.Most of the evidence would favour an abnormal

discharge from the terminal network of the motorneurone or myoneural junction with antidromicspread giving rise to fasciculation. The response tohydantionates in restoring these cases for practicalpurposes to normal would also favour an abnormalneuronal discharge rather than a metabolic defect atthe myoneural junction.

Finally, in addition to these observations themodulating influence of the central nervous systemmust be considered. Lesions affecting central controlmay possibly result in the loss of specific inhibitionaffecting the production of mediating substances inthe terminal network or myoneural junction, as wassuggested for the lower motor neurone by Eccles(1957). Eccles was of the opinion that substancessuch as strychnine and tetanus toxin act by blockingan inhibitory transmitter substance in the lowermotor neurone.

Considering the available information on thesecases with continuous muscle-fibre activity, oneconcludes that a defect has been acquired at the levelof the terminal network of the lower motor neurone,producing the bizarre and persistent neural activitywhich may be demonstrated electromyographicallyas a uncoordinated pattern of continuous muscle-

fibre activity. This phenomenon is shown to beindependent of transmission from the proximal partof the lower motor neurone and central nervoussystem though temporarily aggravated by voluntarymovement.The bizarre uncontrolled discharge from the

terminal network has been restored to normal by theuse of the anticonvulsant drug sodium hydantoinatewhich acts principally by increasing the sodiumpumping action of nerve and muscle tissue as shownby Woodbury, Koch, and Vernadakis (1958).

SummaryTwo cases demonstrating a syndrome of con-

tinuous muscle-fibre activity are presented and dis-cussed, together with a therapeutic approach whichhas virtually restored normal mobility.The syndrome is acquired, one case occurring in

childhood and the other in middle age. The conditionis separated from the group of myotonic disordersand some aspects of aetiology are discussed.

I wish to thank Dr. A. L. Agranat, senior physician,and Dr. F. K. Mills, medical superintendant, Johannes-burg General Hospital, for their cooperation. AlsoDr. D. Perk, Dr. Max Feldman, Dr. H. P. J. Pretorious,Dr. W. L. Vosloo, and Dr. K. I. Furman for referring thecases for investigation. Thanks are also due to Mr.Keigh Allen and the Princess Nursing Home Neuro-surgical Unit for the use of the electromyograph, Dr. D.Glauber for administering the anaesthetics, Dr. M. Berkfor catheterizing the brachial arteries, and Dr. J. Kauf-mann for the histopathological studies.

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Brink, F. (1954). Pharmacol. Rev., 6, 243.Brown, G. L. (1938). J. Physiol. (Lond.), 92, 23P.Churchill-Davidson, H. C., and Richardson, A. T. (1952). Proc. roy.

Soc. Med., 45, 179.Denny-Brown, D., and Nevin, S. (1941). Brain, 64, 1.Eaton, L. M., and Lambert, E. H. (1957). J. Amer. med. Ass., 163,

1117.Eccles, J. C. (1957). The Physiology of Nerve Cells. John Hopkins

Press, Baltimore.Marshall, J. (1952). J. Neurol. Neurosurg. Psychiat., 15, 206.Masland, R. L., and Wigton, R. S. (1940). J. Neurophysiol., 3, 269.McArdle, B. (1951). Clin. Sci., 10, 13.

(1960). Personal Communication.Moersch, F. P., and Woltman, H. W. (1956). Proc. Mayo Clin., 31,

421.Thesleff, S. (1955). Acta physiol. scand., 34, 218.Wechsler, 1. S., and Brock, S. (1922). Arch. Neurol. Psychiat.

(Chicago), 8, 538.Woodbury, D. M., Koch, A., and Vernadakis, A. (1958). Neurology,

8, Suppl. 1, p. I13.

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