Journal of Neurology, Neurosurgery, and Psychiatry, 1976, 39, 44-47

Transient eyelid retraction in myasthenia gravisJ. E. PUKLIN, J. G. SACKS1, AND B. BOSHES

From the Departments of Ophthalmology and Neurology, Northwestern Medical School,Chicago, Illinois, U.S.A.

SYNOPSIS Three patients with myasthenia gravis had transient retraction of the upper eyelidswhich usually followed prolonged upgaze and which persisted for many seconds. This could resultfrom post-tetanic facilitation, myotonia, or a transient contracture. Retraction of this type is to bedistinguished from both the long-standing unilateral retraction associated with ptosis of the contra-lateral eyelid and the fleeting lid twitch sign.

Retraction of the upper eyelids in myastheniagravis is so uncommon and seemingly para-

doxical that its presence might inappropriatelymake myasthenia gravis one of the least likelyconsiderations in the differential diagnosis of a

patient's neuromuscular disorder. This is es-

pecially true because myotonic lid lag occurs inthe hyperkalaemic form of periodic paralysis(Layzer et al., 1967) and in its hypokalaemictype (Resnick and Engel, 1967). Although thisunusual sign has been previously reported tooccur in myasthenia gravis (Buzzard, 1900;Bramwell, 1927; Walsh, 1943; Chavanne et al.,1955; Cogan, 1965; Gay et al., 1967), otherauthors have not distinguished between fleeting,transient, and long-standing retraction. Webelieve that separate mechanisms underly eachof these three categories. It is our purpose to callattention to the unusual association of uppereyelid retraction with myasthenia gravis and tocomment on the mechanisms which possiblyunderlie this clinical sign.

CASE 1

(CWMH 2-023836-0) A 50 year old man had beenwell until September 1968 when he awoke with ptosisof the left upper eyelid. A diagnosis of myastheniagravis was made elsewhere and the patient was

treated with neostigmine bromide. After initial im-provement, the patient's condition deterioratednecessitating a tracheostomy in December 1968.

1 Address for reprint requests: Dr J. G. Sacks, 303 East ChicagoAvenue, Chicago, Illinois 60611, U.S.A.

(Accepted 15 August 1975.)44

In January 1969, the patient was seen at the MayoClinic where a diagnosis of myasthenia gravis wasmade. Electromyographic tests performed thereshowed a definite decrement in the compoundmuscle action potentials of the thenar and hypo-thenar muscles during 2 Hz stimulation of themedian and ulnar nerves respectively. Intracellularmicroelectrode studies of external intercostal muscleobtained at biopsy showed low amplitude miniatureendplate potentials.He was found to have a thymoma which was

removed. It weighed 40 g.Except for occasional diplopia and dysphagia the

patient slowly improved.When we first examined the patient in April 1971

he was receiving neostigmine and ephedrine. He hadno diplopia, but abduction nystagmus was presentin the left eye; there was no accompanying delay ofabduction of the right eye. During the examinationwe observed at various times a right ptosis, a leftptosis, a bilateral lid retraction, and an alternatingasymmetrical lid retraction (Fig. 1).

It seemed as though prolonged upgaze made theretraction more likely to appear. Neither interruptingfixation of either eye nor intravenous injection ofedrophonium chloride had any effect on the retrac-tion. At various times, edrophonium chloride didbeneficially affect the ptosis and voice.

Other positive neurological findings included nasalspeech, an inability to elevate the soft palate, andabsence of the gag reflex. General muscle strengthwas normal but easy fatiguability could be demon-strated.The blood count, urinalysis, electrocardiogram,

chest radiographs, serum glutamic oxaloacetictransaminase, lactate dehydrogenase, serum potas-sium, and thyroxine were normal.

Protected by copyright.

on March 18, 2021 by guest.

http://jnnp.bmj.com

/J N

eurol Neurosurg P

sychiatry: first published as 10.1136/jnnp.39.1.44 on 1 January 1976. Dow

nloaded from

Transient eyelid retraction in myasthenia gravis

......;.

.~ -W."

(c

FIG. 1 Case 1. Eyelidpos

(a) Right ptosis,(b) Left ptosis.(c) Bilateral eyelid retracti4(d) and (e) Asymmetrical e.(Reproducedfrom Kodachr

FIG. 2 Case 2. Left eyelid

(1~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~1

CASE 2

(CWMH 2041037-3) A 50 year old woman had beenwell until 1969 when she developed intermittentdiplopia. In October 1971 her symptoms worsenedand were noted to be more severe as the day pro-gressed. She was therefore hospitalized for furtherevaluation. No medications for the weakness werebeing given at the time of examination.

Visual acuity was 6/6 in each eye. The left uppereyelid was ptotic. The eyes were straight in theprimary position. On upgaze a 12 to 15 prism dioptre

itions. left hypotropia was present; after prolonged upgazethe hypotropia increased. Then, as the patient lookeddown, retraction of the left upper eyelid occasionallyoccurred in both the primary position and in down-

on. gaze (Fig. 2). When the eyes returned to the primaryyelid retraction. position from downgaze, the upper eyelids brieflyome movi film), retracted and then came down (the 'lid twitch' sign

of Cogan). Interrupting fixation and the intravenousadministration of edrophonium chloride had noeffect on these findings. The remainder of thephysical examination was normal.The patient had a mild iron deficiency anaemia.

The urinalysis, electrocardiogram, chest radiograph,cerebrospinal fluid, serum potassium, and brainscan were normal. A left cerebral angiogram showedgeneralized atherosclerosis. An electroencephalo-gram showed nonspecific subcortical changes in theleft hemisphere. A Jolly test showed a 20% decre-ment in the right abductor digiti minimi even though

retraction. the patient was receiving pyridostigmine, thus help-

45

Protected by copyright.

on March 18, 2021 by guest.

http://jnnp.bmj.com

/J N

eurol Neurosurg P

sychiatry: first published as 10.1136/jnnp.39.1.44 on 1 January 1976. Dow

nloaded from

J. E. Puklin, J. G. Sacks, antd B. Boshies

ing to confirm the clinical diagnosis of myastheniagravis.The patient has been seen regularly at the North-

western University Medical Clinics since her dis-charge from the hospital. While she has not developedevidence of myasthenia gravis anywhere else in herbody, she has required either neostigmine orambenonium chloride for the control of the diplopia.

gram revealed an old anterior wall infarction. Aglucose tolerance test confirmed the presence ofdiabetes mellitus. A 15.8% decrement was noted on aJolly test performed on the abductor digiti minimi.The patient was readmitted to Northwestern

Memorial Hospital in November 1973 with com-plaints of generalized weakness. Pyridostigmine wasdiscontinued and she was given a course of therapywith prednisone to which she responded favourably.

CASE 3

(NMH 2-050333-4) A 50 year old woman developeddiplopia at the age of 22 years and a diagnosis ofmyasthenia gravis was made elsewhere. She was nottreated for 14 years; then neostigmine methylsul-phate therapy was started. Later, pyridostigminebromide was substituted. At the age of 45 yearsdiabetes mellitus was diagnosed and was controlledby diet. A thyroidectomy was performed for acolloid adenoma when she was 48 years old. Sincethen she has been clinically euthyroid while takingsodium levothyroxine 0.3 mg daily.She experienced infrequent intermittent ptosis and

the diplopia became more annoying. She wasreferred to Northwestern Memorial Hospital forevaluation and was receiving pyridostigmine bromideat the time of examination in March 1972.The best corrected visual acuity was 5/6 and 6/6 in

the right and left eyes respectively. Exophthal-mometry readings were 16 mm in each eye, which isnormal. There was slight but definite weakness ofboth lateral recti. A left hypertropia of 4 prismdioptres in the primary position and 6 prismdioptres on left gaze was noted. In the primaryposition she showed neither ptosis nor eyelidretraction. The bilateral lid twitch response of Coganwas present. After prolonged upgaze, bilateral eyelidretraction was present both in the primary positionand in downgaze. Occasionally eyelid retraction wasunilateral (Fig. 3); neither interrupting fixation norintravenous injection of edrophonium chloride hadany effect on the eyelid retraction, although after theinjection the diplopia disappeared.The blood count, urinalysis, serum potassium, and

chest radiograph were normal. An electrocardio-

r

FIG. 3 Case 3. Unilateral eyelid retraction.

DISCUSSION

Retraction of the upper eyelids is frequently dueto a dysthyroid state. However, lid retraction ofendocrine origin persists for months to years andshould not be confused with the transientphenomenon we have observed in patients withmyasthenia gravis, especially since our patientsseemed to be euthyroid.Three distinct types of eyelid retraction in

myasthenia gravis can now be distinguished onthe basis of the duration of the retraction:transient, which occurs over many seconds;fleeting, which lasts for less than one second;and long-standing, which persists for months oryears.The first type, transient, is represented by our

patients. To our knowledge, this type has notbeen reported previously in myasthenia gravis.Transient eyelid retraction may be due to post-tetanic facilitation of the levator palpebraesuperioris, similar to the mechanism describedin small muscles of the hands of myasthenics byDesmedt (1959), and in an in vitro preparationby Elmqvist et al. (1964). In our patients theretraction was most likely to appear after eitherprolonged upgaze or staring straight ahead.These activities cause prolonged contraction ofthe levator and may be similar to a machine-induced tetany.

Tending to point away from this hypothesis,however, is the fact that the retraction waspresent in downgaze. Since Loeffler et al. (1966)demonstrated that the levator in normal patientshas little or no electrical activity in downgaze, itmight be inferred that its motor nerve is elec-trically silent. By definition, the concept of invivo post-tetanic facilitation requires that themuscle be stimulated by a neural impulse.Myotonia or a transient contracture of the

levator are alternative explanations. Myotoniais a delay in relaxation of contracted muscle,

46

Protected by copyright.

on March 18, 2021 by guest.

http://jnnp.bmj.com

/J N

eurol Neurosurg P

sychiatry: first published as 10.1136/jnnp.39.1.44 on 1 January 1976. Dow

nloaded from

Transienit eyelid retraction in myasthenia gravis

while contracture is a mechanical shortening ofmuscle which is maintained without accompany-ing muscle action potentials. The two couldtheoretically be distinguished electromyogra-phically, but the levator palpebrae superiorisdoes not lend itself to routine electrophysio-logical study. More importantly, our concern

here is with the clinical significance of a readilyobservable sign.The second type, fleeting, has been described

by Cogan (1965) as the 'lid twitch'. This isessentially an overshoot of the upper eyelidswhen the eyes are directed to the primary positionfrom downgaze. Since the levators are at rest in

downgaze, they momentarily respond morevigorously than they otherwise would.The third type, long-standing retraction, has

been the most commonly reported variety inmyasthenia gravis and is associated with weak-ness of the contralateral levator palpebraesuperioris (Buzzard, 1900; Walsh, 1943;Chavanne et al., 1955; Gay et al., 1967). Theexplanation offered by Gay et al. (1967) seems

most acceptable in these cases. They hypothe-sized that the levator muscles are true yokemuscles which follow Hering's law of equalinnervation. They believed that the myasthenicdefect in the ptotic lid should lead to increasedinnervation of both levators, resulting inretraction of the stronger eyelid. In confirmationof this, they noted that covering the eye whichhad the ptotic lid lessened the contralateralretraction. When edrophonium chloride was

administered, the ptosis improved and thecontralateral retraction was relieved.To help validate the distinction between

cases of transient and long-standing lid retrac-tion, we administered edrophonium chlorideintravenously to our patients. This had no effecton the retraction, thus tending to support our

contention.Finally, transient retraction with generalized

muscular weakness should no longer be con-sidered to be a sign peculiar to periodic paralysis.Layzer et al. (1967) considered that the lid lagwas possibly unique to the hyperkalaemic formof this disease. Later, however, Resnick andEngel (1967) showed it to be present in thehypokalaemic form, thus indicating that thesign is not a reliable indicator of the type ofperiodic paralysis. They attributed the retractionto myotonia, but did not test the hypothesiselectromyographically, presumably because ofthe difficulties inherent in such studies of thelevator.

REFERENCES

Bramwell, E. (in discussion of Collier, J.) (1927). Nuclearophthalmoplegia with especial reference to retraction ofthe lids and ptosis and to lesions of the posterior commis-sure. Brain, 50, 488-498.

Buzzard, T. (1900). Clinical lecture on cases of myastheniagravis pseudo-paralytica. British Medical Journal, 1, 493-496.

Chavanne, H., Girard, P. F., and Rougier, J. (1955). R6trac-tion palp6brale et myasth6nie oculaire. Revue d'Oto-Neuro-ophthalmologie, 27, 18-21.

Cogan, D. G. (1965). Myasthenia gravis: A review of thedisease and a description of lid twitch as a characteristicsign. Archives of Ophthalmology, 74, 217-221.

Desmedt, J. E. (1959). The physio-pathology of neuro-muscular transmission and the trophic influence of motorinnervation. American Journal of Physical Medicine, 38,248-261.

Elmqvist, D., Hofmann, W. W., Kugelberg, J., and Quastel,D. M. J. (1964). An electrophysiological investigation ofneuromuscular transmission in myasthenia gravis. JournalofPhysiology, 174, 417-434.

Gay, A. J., Salmon, M. L., and Windsor, C. E. (1967).Hering's law, the levators, and their relationship in diseasestates. Archives of Ophthalmology, 77, 157-160.

Layzer, R. B., Lovelace, R. E., and Rowland, L. P. (1967).Hyperkalemic periodic paralysis. Archives of Neurology,16, 455-472.

Loeffler, J. D., Slatt, B., and Hoyt, W. F. (1966). Motorabnormalities of the eyelids in Parkinson's disease.Archives of Ophthalmology, 76, 178-185.

Resnick, J. S., and Engel, W. K. (1967). Myotonic lid lag inhypokalaemic periodic paralysis. Journal of Neurology,Neurosurgery, and Psychiatry, 30, 47-51.

Walsh, F. B. (1943). Myasthenia gravis and its ocular signs:A review. Transactions of the American OphthalmologicalSociety, 41, 556-624.

47

Protected by copyright.

on March 18, 2021 by guest.

http://jnnp.bmj.com

/J N

eurol Neurosurg P

sychiatry: first published as 10.1136/jnnp.39.1.44 on 1 January 1976. Dow

nloaded from