Congenital adduction and synergistic divergence: clinical and · ocular torticollis, head turned to the right; and (4) inverse nystagmus ofthe left eye, occurring spontaneously as

British Journal of Ophthalmology, 1989, 73, 68-75

Congenital adduction palsy and synergisticdivergence: a clinical and electro-oculographic studyJOHAN R M CRUYSBERG,l ALI T MTANDA ,'KIRSTI U DUINKERKE-EEROLA,' AND PATRICK L M HUYGEN2

From the 'Institute of Ophthalmology and the 2Institute of Otolaryngology, University ofNijmegen, Nijmegen,The Netherlands

SUMMARY We studied two patients with a peculiar congenital disturbance of ocular motility inwhich the horizontal movements of the left eye were always opposite the normal expecteddirection. The common features were: (1) congenital monocular adduction palsy and exotropia ofthe left eye; (2) simultaneous abduction of both eyes (divergence) on attempted dextroversion; (3)ocular torticollis, head turned to the right; and (4) inverse nystagmus of the left eye, occurringspontaneously as well as during optokinetic and vestibular testing. Clinical and electro-oculographic findings suggested a close relationship to Duane's retraction syndrome and supportedthe concept that innervational mechanisms were responsible for the phenomenon.

Congenital unilateral paralysis of adduction associ-ated with simultaneous bilateral abduction onattempted gaze into the field of action of the pareticmedial rectus muscle is a rare entity. We have beenable to find nine reported cases.'-7 Although themajor defect is a congenital failure of adduction, themost striking clinical finding is that on attemptedadduction the affected eye moves further into abduc-tion and thus causes extreme divergence.

In this communication we briefly review thefeatures of the reported cases and analyse the clinicaland electro-oculographic findings in two personallyexamined cases.

Case reports

CASE 1A 3-year-old girl was referred to the Institute ofOphthalmology because of congenital adductionparalysis and variable exotropia of the left eyeassociated with torticollis to the right. Neurologicalexamination at the age of 8 months revealed nosignificant abnormalities except for borderline skullmeasurements.We examined the child in 1981. The visual acuity

was RE 20/25 and LE 20/80. Cycloplegic refractionCorrespondence to Dr J R M Cruysberg, Institute of Ophthal-mology, Sint Radboud Hospital, PO Box 9101, 6500 HBNijmegen, The Netherlands.

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was +3-5 D in both eyes. There was a permanenthead turn to the right; this kept the eyes straight (Fig.1A). With forced straightening of the head, the righteye abducted beyond the midline while the left eyeremained exotropic (Fig. 1B). Attempted dextrover-sion resulted in first, extreme exotropia due todivergence of both eyes (Fig. IC); secondly, simul-taneous abduction nystagmus in both eyes with thefast phase beating temporally; and, thirdly, narrow-ing of the left palpebral fissure. On levoversion theright eye adducted normally and the extropia of theleft eye decreased, so that the eyes became parallel(Fig. 1D). Adduction of the left eye beyond themidline could not be provoked by the oculocephalicmanoeuvre or optokinetic stimulation.No pupillary reactions accompanied any of these

ocular movements. Under general anaesthesia theforced ductions confirmed the increased resistance toadduction of the left eye. Abduction of the left eyeand the forced ductions of the right eye were normal.Audiometry, x-ray films of the skull and cervicalspine, and cerebral computed tomography werenormal.

CASE 2A 23-year-old male with multiple congenital abnor-malities described as arthrogryposis multiplexcongenita was referred to the Institute of Ophthal-mology in 1983 because of congenital exotropia and

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Congenital addiction palsy and synergistic divergence

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Fig. 1 Case l. A: Lookingforward with permanent head turn to the right. B: Exotropia on forced straightening ofthe head.C: Extreme exotropia on attempted gaze to the right. Note that the left eye movesfurther into abduction, and there is narrowingofthe left palpebralfissure. D: Decreased exotropia ofthe left eye on gaze to the left. Note that the exoptropia ofthe left eye ismaximal on gaze to the right and minimal on gaze to the left.

adduction paralysis of the left eye. At previousstrabismus surgery, under general anaesthesia, hewas found to have a short and tight left lateral rectusmuscle and a thin and atrophic left medial rectusmuscle. Following maximal recession of the leftlateral rectus muscle and 10 mm resection of the leftmedial rectus muscle the eyes were parallel for ashort time, while the adduction palsy persisted.

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The visual acuity was 20/20 in the right eye and20/200 in the left eye. Cycloplegic refraction was RE+ 1-0 D, and LE + 1.25 D. Slit-lamp examination andfunduscopy were normal in both eyes. There was ahead turn to the right (Fig. 2A). In the primaryposition there was a left exotropia of 400 andhypotropia of 150 with absent adduction of the lefteye (Fig. 2B). On attempted dextroversion both eyes

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Fig. 2 Case 2. A: Lookingforward with permanent head turn to the right, exotropia and hypotropia ofthe left eye.B: Increasing exotropia onforced straightening ofthe head. C: Extreme exotropia on attempted gaze to the right. Note that theleft eye moves further into abduction, and there is narrowing ofthe left palpebralfissure. D: Decreased exotropia ofthe left eyeon gaze to the left. Note that the exotropic position ofthe left eye is maximal on gaze to the right and minimal on gaze to the left.

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Johan R M Cruysberg, Ali TMtanda, Kirsti UDuinkerke-Eerola, and Patrick L M Huygen

rig. 3 rlexion contractures ortepirst ana seconadngers inpatient 2.

abducted and became extremely divergent (Fig.2C); this was associated with retraction of the leftglobe and narrowing of the palperbral fissure. Onlevoversion the right eye adducted normally and theexotropia of the left eye decreased (Fig. 2D). Theamounts of exotropia and hypotropia of the left eyewere clearly less in levoversion (Fig. 2D) than indextroversion (Fig. 2C). There was underaction ofthe depressor and levator muscles of the left eye.

General examination disclosed flexion con-tractures of the first and second fingers of both hands(Fig. 3), a short atrophic club-footed right leg, and adeformed left foot. The face was narrow and the

Fig. 4 Absence ofleft lateral rectus muscle insertion, as aresult ofprevious strabismus surgery, demonstrated duringthe second surgical procedure in patient 2.

palate high. Otolaryngological examination dis-closed deformation of the external ears. Audiometrywas normal. X-ray films of the cervical spine andskull and cerebral CT scans were all normal. Therewere no cardiopulmonary abnormalities and theintelligence was normal.Because of the severe exotropia and the ugly head

posture the patient requested another surgical inter-vention. A large loop recession of the left lateralrectus and resection of the left medial rectus wereplanned. Under general anaesthesia forced ductiontesting of the left eye showed moderate restriction ofadduction; forced ductions of the right eye were

Fig. 5A Fig. 5BFig. 5 Electro-oculographic recordings in case 1. Tracings from top to bottom in Figs. 5, 6, 7A, 8 time (seconds), right andleft eye position. Upward deflection signals eye movement to the right; downward deflection signals eye movement to the left.Position calibration was notfeasible in the case. Note that the movement ofthe left eye is always opposite to the movement ofthe right eye, and that the divergent-convergent nystagmus in the primary position (A) is enhanced by gaze to the right (righthalfofpanel B) and disappears on gaze to the left (left halfofpanel B).

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Fig. 6A (left) Fig. 6A (right)

Fig. 6B

normal. It was also noted that there was severescarring of the conjunctiva and Tenon's capsule as aresult of previous surgery. After a limbal incision andcareful dissection the site of the left lateral rectus wascarefully inspected. Despite a thorough search deepinto the orbit no lateral rectus muscle was seen (Fig.4). Inspection of the medial rectus muscle revealed avery thin, atrophic muscle, on which a 6mm resectionwas performed. Postoperatively there was practicallyno change in either the deviation of the eye or thehead posture.

Methods

The procedure for recording and analysis of eyemovements has previously been described.8 Tonniesequipment was used for both optokinetic androtatory stimulation. Saccade velocity and accelera-tion profiles were calculated from monocular eyepositions sampled at 250 Hz during a 20° horizontalcalibration of saccades by means of a method ofnumerical smoothing and differentiation.

Results

With forced fixation in the primary position case 1displayed dysconjugate nystagmus with divergent

Fig. 6 Responses to evokednystagmus in case 2: right eye givesnormal responses, left eye givesabnormal (opposite) responses. A:Optokinetic stimulation; black-and-white stripes, each of 7-50width, moving at 40" per second, tothe left (left panel) or to the right(rightpanel). B: Vestibularstimulation by sinusoidalstimulation in darkness (maximumvelocity 28"/s at 0 05 Hz).Calibration applies to right eyeonly.

fast phases (Figs. 5A, B). The nystagmus increased inintensity on gaze to the right and was virtually absenton gaze to the left. Spontaneously left gaze up to 200was achieved through a compensatory torticollis. Incase 2 a similar nystagmus was noted in primary gaze.As in case 1, the nystagmus increased on gaze to theright, but there was no neutral zone. In completedarkness no spontaneous nystagmus occurred ineither patient.We used evoked nystagmus to find out which eye

was correctly controlled by the ocular motor plant inthe brain stem. In both patients this appeared to bethe right eye, for with this eye both the slow and thefast phases of optokinetic and vestibular nystagmuswere in the expected direction (Figs. 6A, B). On theother hand the left eye moved in the oppositedirection, that is, it adducted when the right eyeadducted and abducted when the right eye abducted.Adduction in the present context implied only amedially directed movement, since in both patientsadduction of the left eye beyond the midline waslacking. Vertical optokinetic nystagmus was normalin both patients.

Voluntary saccade analysis was possible only incase two (Figs. 7A, B). Correct calibration wasfeasible for the right eye only; the calibration valuewas assigned also to the left eye channel because in

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Fig. 7AFig. 7 Voluntary saccade testing, case 2. A: Electro-oculographic recording; the position step ofthe right eye (2ndtracingfrom top) presumably is 200.

monocular viewing the left eye could not attain anamplitude of 200. Abduction of the right eye was

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Fig. 7B

normal in the sense that the velocity and accelerationprofiles had the expected shapes and the saccadeparameters were within normal limits.9 On theassumption that calibration is also applicable to theleft eye, adduction of both eyes was slow, that ofthe left eye being more severely impaired. Theappearances of the saccade profiles resembled thatencountered in cases of bilateral internuclearophthalmoplegia (INO). This applied particularly tothe acceleration profiles.During intense fixation both patients had saccadic

back-to-back oscillations. This interesting phenome-non was more prominent in the right eye of case 2.This eye showed frequency sweeps, that is, a progres-sive increase of frequency of saccades reaching afrequency of 12 Hz. The saccadic frequency increasewas associated with a decrease in amplitude (Figs.8A, B).

Discussion

As reviewed in Table 1, congenital adduction palsywith synergistic divergence is usually noted during

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Fig. 7 B: Superposition display of20° saccadesfor right eye (CHI) and left eye (CH2). Correct calibration applies to the righteye only (see text). Adduction is clearly impaired in both eyes relative to abduction. Allowing for an overallfilter effect ofapproximately second-order low-pass with a cut-offfrequency of 15 Hz, the maximum abduction velocity ofthe right eye isnormal.

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Fig. 8 Electro-oculographicrecordings during intensefixation incase I (A) and case 2 (B). Noteback-to-back saccadic oscillationsespecially in case 2, which alsoshows afrequency sweep ofsaccades.~~~~~~~~A4~1100

Fig. 8B

childhood as an adduction deficit, involving the lefteye in 75% of the cases, and associated with syner-gistic divergence during attempted adduction of theapparently paretic eye. In the primary position thereis always an exotropia of the affected eye and, inthree of the 11 reported cases, a spontaneousabduction nystagmus. Evoked inverse nystagmus ofthe affected eye has been demonstrated in all casestested. The disorder shows a moderate male pre-ponderance.The clinical findings in our two cases conform to

this presentation. However, to the best of ourknowledge our case 2 is the first patient in whomarthrogryposis multiplex has been recorded as anassociated congenital disorder. Arthrogryposismultiplex is, on the other hand, seen with the Mobiussyndromes a disorder which shows a close rela-tionship to Duane's retraction syndrome both inpathogenesis," 12 and in its association with seg-mental developmental anomalies. 13 Our secondpatient is also unique in the sense that synergistricdivergence was noted both clinically and electro-oculographically, and yet at subsequent surgicalexploration the lateral rectus muscle was found to beabsent. Although it is most likely that this was a caseof a 'lost muscle' following the first surgical interven-

tion, it is also equally clear that the observedsynergistic abduction did not result from lateralrectus muscle innervation alone. We believe that inthis case the abduction movement was carried out asa secondary action of the inferior rectus and/orinferior oblique muscles. We draw our assumptionfrom anatomical evidence' and from evidencederived from two histopathologically examined casesof Duane's retraction syndrome, in which anomalousinnervation between the oculomotor nerve and thelateral rectus muscle has usually involved the inferiordivision of the oculomotor nerve.' 16 Such a mecha-nism is in accord with the innervational hypothesisadvanced to explain synergistic divergence.

Previously the apparent medial rectus muscle palsywas attributed to internuclear ophthalmoplegia orselective destruction in the medial rectus musclenucleus, whereas the abduction movement wasattributed to anomalous connections between theabducens nuclei.23 Our electro-oculographic study ofthese two patients showed impairment of adductionassociated with bilateral abduction nystagmus, andthe affected eye showed an inverse nystagmus duringoptokinetic and vestibular testing. We were unable,however, to demonstrate dysmetric waveforms of theabducting saccades.8'7 It seems unlikely therefore

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Table 1 Congenital unilateral adduction palsy and synergistic divergence

Authors Patients Primary position Adduction Synergistic Evoked Associated Aetiology: Proposedsex and age palsy divergence nystagmus features mechanism for divergence

BArAny' F, 3 ±Straight, bilateral Left eye On right Inverse in - Birth trauma connectionsabduction nystagmus gaze LE of L+R nucleus VI

Worth and M, 3 Exotropia left eye Left eye On right - - Medial rectus palsy allowsChavassel gaze superior+inferior

oblique to abduct theeye further

Burian and M, 5 Exotropia left eye Left eye On right Inverse in - Anomalous innervationCahill3 gaze LE

Burian et al.4 F, 9 Exotropia right eye Right eye On right and Covergent Mental Related to Duane'sleft gaze nystagmus retardation syndrome

Znajda and M, 4 Exotropia left eye Left eye On right - - Congenital anomaly ofKrill' gaze innervation

Wilcox et al.,6 M, 7 Exotropia right eye Right eye On left gaze Inverse in - Related to Duane'sRE syndrome

Wagner et al. F, 5 Exotropia left eye Left eye On right Inverse in - Variant of type 2 Duane'sgaze LE syndrome

F, 8 Exotropia left eye Left eye On right - -gaze

M, 4 Exotropia right eye Right eye On left gaze - -Cruysberg et al. F, 4 Exotropia left eye, Left eye On right Inverse in - Related to Duane's

(present bilateral abduction gaze LE syndrome. Oculomotorstudy) nystagmus innervation intended

for the medial rectusmuscle supplies thelateral rectus muscleand other extraocularmuscles

M, 23 Exotropia left eye, Left eye On right Inverse in Arthrogryposisbilateral abduction gaze LE multiplexnystagmus congenita

that internuclear disturbances were responsible forthese patients' movement disorder. This is corrobor-ated by the finding that the adduction had a normalduration, whereas in internuclear ophthalmoplegia itis significantly prolonged.Wilcox et al.6 studied by electromyography a case

of congenital adduction palsy with synergisticdivergence. They found that limitation of adductionin their patient resulted from anomalous and greaterinnervation of the antagonistic lateral rectus muscle.This mechanism placed this disorder in the samecategory of innervational disturbances as Duane'sretraction syndrome. Like Huber's'8 Duane type IIcase, failure of adduction was regarded as the majordefect. However, in the present cases, instead ofretracting on adduction the eye moves further intoabduction.

Wilcox et al.6 proposed an innervational mecha-nism whereby the abducens nerve was supposed to beeither hypoplastic or absent and most of the oculo-motor innervation intended for the medial rectusmuscle supplied the lateral rectus muscle. The motorsupply to the medial rectus muscle arises from theinferior branch of the oculomotor nerve, which alsoinnervates the inferior oblique and the inferior rectusmuscles. This anatomical fact would explain the

maintenance of synergistic divergence by the inferiormuscles in the absence of the lateral rectus muscle, asnoted in our second patient.

In this patient, the slowing of adduction of the lefteye is sufficiently explained by the finding of a thin,atrophic medial rectus muscle, but the apparentlysimilar slowing of adduction observed in the right eyecalls for another explanation. It might be that, on theright side also, some of the innervation intended forthe medial rectus muscle aberrantly reaches theinferior oblique and the inferior rectus muscles. Thiswould then result in cocontraction impairing theadduction of that eye to some extent, but apparentlyless than in the left eye.Because synergistic divergence shows such close

relationship to Duane's retraction syndrome, itshould also be considered a developmental anomalycharacterised by absence of the abducens nucleus andsubsequent innervation of the lateral rectus muscleby the inferior branch of the oculomotor nerve,"' 16probably owing to a teratogenic disturbance duringthe second month of pregnancy.'9High frequency saccadic oscillations with back-to-

back saccades occur in voluntary nystagmus2" and inocular flutter,2' an ocular movement disorder indicat-ing pontine-cerebellar dysfunction. The occurrence

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Congenital adduction palsy and synergistic divergence

of these movements in both our patients may beinterpreted as an indication of the brain stem originof their movement disturbance. However, it is alsopossible that the saccadic oscillations are actually atype of fixation instability caused by the peculiarinnervation which results in conflicting retinal infor-mation being sent to the brain.

References

1 BArAny R. Ein Fall von monocularer Lahmung aller seitlichenwillkurlichen Blickbewegungen, bei Intaktheit der vertikalenBlickbewegungen, mit horizontalem Konvergenz- undDivergenznystagmus im Bereich des fur die Wilikurbewegungengelahmten Abducens. Arch Klin Exp Ohren NasenKehlkopfheilkd 1930; 26: 237-44.

2 Worth C, Chavasse FB. Isolated paralysis of the medial rectus.In: Lyle TK, ed. Squint. Philadelphia: Blakiston, 1950: 106.

3 Burian HM, Cahill JE. Congenital paralysis of medial rectusmuscle with unusual synergism of the horizontal muscles. TransAm Ophthalmol Soc 1952; 50: 87-102.

4 Burian HM, Van Allen MW, Sexton RR, Baller RS. Substitu-tion phenomena in congenital and acquired supranuclear dis-orders of eye movement. Ophthalmology 1965; 69:1105-14.

5 Znajda JP, Krill AE. Congenital medial rectus palsy withsimultaneous abduction of the two eyes. Am J Ophthalmol 1969;68:1050-2.

6 Wilcox LM, Gittinger JW, Breinin GM. Congenital adductionpalsy and synergistic divergence. Am J Ophthalmol 1981; 91:1-7.

7 Wagner RS, Caputo AR, Frohman LP. Congenital unilateraladduction deficit with simultaneous abduction. Ophthalmology1987; 94: 1049-53.

8 Huygen PLM. Vestibular hyperreactivity in patients withmultiple sclerosis. Adv Otorhinolaryngol 1983; 30: 141-9.

9 Baloh RW, Sills AW, Kumley WE, Honrubia V. Quantitativemeasurement of saccade amplitude, duration and velocity.Neurology 1975; 25: 1025-70.

10 Wishnick MM, Nelson LB, Huppert L, Reich EW. Mobiussyndrome and limb abnormalities with dominant inheritance.Ophthalmic Pediatr Genet 1983; 2: 77-81.

11 Pitner SE, Edwards JE, McCormick WF. Observations on thepathology of Mobius syndrome. J Neurol Neurosurg Psychiatry1965; 28: 362-74.

12 Towfighi J, Marks K, Palmer E, Vannucci R. Mobius syndrome:neuropathologic observations. Acta Neuropathol (Berl) 1979; 48:11-7.

13 Gadoth N, Biedner B, Torok G. Mobius syndrome and Polandanomaly: case report and review of the literature. J PediatrOphthalmol Strabismus 1979; 16: 374-6.

14 Hoyt WF, Nachtigaller H. Anomalies of ocular motor nerves.Neuro-anatomic correlates of paradoxical innervation inDuane's syndrome and related congenital ocular motor dis-orders. Am J Ophthalmol 1965; 60: 443-8.

15 Hotchkiss MG, Miller NR, Clark AW, Green WR. BilateralDuane's retraction syndrome: a clinical-pathologic case report.Arch Ophthalmol 1980; 98: 870-4.

16 Miller NR, Kiel SM, Green WR, Clarck AW. UnilateralDuane's retraction syndrome (Type 1). Arch Ophthalmol 1982;100: 1468-72.

17 Crane TB, Yee RD, Baloh RW, Helper RS. Analysis ofcharacteristic eye movement abnormalities in internuclearophthalmoplegia. Arch Ophthalmol 1983; 101: 206-10.

18 Huber A. Electrophysiology of the retraction syndromes. Br JOphthalmol 1974; 58: 293-300.

19 Pfaffenbach DD, Cross HE, Kearns TP. Congenital anomalies inDuane's retraction syndrome. Arch Ophthalmol 1972; 88:635-9.

20 Coren S, Komada MK. Eye movement control in voluntarynystagmus. Am J Ophthalmol 1972; 74: 1161-5.

21 Cogan DG. Ocular dysmetria, flutter-like oscillations of theeyes, and opsoclonus. Arch Ophthalmol 1954; 51: 318-35.

Acceptedfor publication 3 December 1987.

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Congenital adduction and synergistic divergence: clinical and · ocular torticollis, head turned to the right; and (4) inverse nystagmus ofthe left eye, occurring spontaneously as