IntroductionBrown syndrome refers to a clinicaldisorder characterized by impaired

active and passive elevation inadduction. While acquired cases arethought to result from an injury tothe superior oblique (SO) muscle

tendon of various origins (inflamma-tion, surgery, trauma), the aetiologyof congenital cases is still debatableand potentially diverse. Some congeni-tal cases may result from anatomicalabnormalities of the SO tendon ortrochlea, while others might be relatedto a neurodevelopmental problem,with the SO muscle paradoxicallyinnervated by the third cranial nerve.This would induce co-contraction ofthe SO with the inferior oblique (IO)and superior rectus muscles on up-gaze, causing a greater restriction ofelevation in adduction than in abduc-tion. We report four cases of congeni-tal unilateral Brown syndrome wherethe fourth (trochlear) cranial nerve(CN) was studied by MRI. OrbitalMRI was performed in two patients,with images acquired in eight direc-tions of gaze, and SO muscles areaswere compared.

MethodsBrain magnetic resonance imaging(MRI) was performed in four consec-utive patients diagnosed with unilat-eral congenital Brown syndrome inthe strabology department of Heidel-berg University Eye Clinic. A compre-hensive standardized ocular motilityexamination was performed in allpatients, and ocular deviations weremeasured in all nine directions of gaze

Absence of the fourth cranialnerve in congenital BrownsyndromePierre-Francois Kaeser,1 Bodo Kress,2 Stefan Rohde3 andGerold Kolling4

1Hopital Ophtalmique Jules Gonin, Lausanne University OphthalmologyDepartment, Lausanne, Switzerland

2Zentralinstitut fur Radiologie und Neuroradiologie, Krankenhaus NordwestGmbH, Frankfurt, Germany

3Department of Neuroradiology, University of Heidelberg, Heidelberg, Germany4Heidelberg University Eye Clinic, Heidelberg, Germany

ABSTRACT.Purpose: To elucidate the aetiology of congenital Brown syndrome.Methods: Four consecutive patients diagnosed with unilateral congenitalBrown syndrome had a comprehensive standardized ocular motility examina-tion. Any compensatory head posture was measured. Brain magnetic resonanceimaging (MRI) with regard for the IV cranial nerve (CN) was performed inall patients. Orbital MRI was performed in 2 ⁄4 patients, with images acquiredin eight directions of gaze and superior oblique (SO) muscle areas compared.Results: CN IV could not be identified bilaterally in two patients, but wasabsent only on the side of the Brown syndrome in the two other patients. Onthe normal side, orbital MRI revealed a smaller SO muscle area in upgazethan in downgaze, demonstrating normal actions of this muscle. On the sideof the Brown syndrome, the SO area remained the same in upgaze and indowngaze and approximately symmetric to the area of SO in downgaze on thenormal side.Conclusions: These cases add further anatomical support to the theory of par-adoxical innervation in congenital Brown syndrome. CN IV was absent in twopatients on the side of the Brown syndrome, but without muscle hypoplasia.SO muscle size did not vary in up- and downgaze, which we interpreted as asign of constant innervation through branches of CN III.

Key words: Brown syndrome – congenital absence of trochlear nerve – congenital cranial dys-innervation disorders (CCDD) – fourth cranial nerve – magnetic resonance imaging – trochlearnerve

Acta Ophthalmol. 2012: 90: e310–e313ª 2012 The AuthorsActa Ophthalmologica ª 2012 Acta Ophthalmologica Scandinavica Foundation

doi: 10.1111/j.1755-3768.2011.02354.x

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using the Harms tangent screen at2.5 m. Any compensatory head pos-ture was measured.

Brain 1.5 Tesla MRI targeting CNIV identification was performed in allfour patients and the images analysedby an experienced neuro-radiologist(KB) without the knowledge of whichside the Brown syndrome was on. ASiemens Symphony 1.5-Tesla magneticresonance unit (Siemens, Erlangen,Germany) was used together with aconventional head coil. The imageswere obtained in coronal orientationon the basis of the following protocol:T2TRUE FISP (TE: 3.7 ms; TR:7.3 ms; FOV: 223 · 223 mm; matrix:706 · 1024; slice thickness: 0.3 mm;scan time: 9 min 29 seconds). Thecoronal sequence was tilted so thatthe imaging plane was parallel to thebrainstem and the most posterior slicewas located at the dorsal portion ofthe quadrigeminal plate.

The data sets were processed on thescanner console (Wizzard, Siemens).Using a standardized approach, sagit-tal and axial images were reconstructedwith a slice thickness of 0.5 mm fromT2-weighted sequences separately forboth sides of the face along the courseof the trigeminal nerve.

Functional MRI of the externalocular musculature was performed intwo patients, with images acquired innine directions of gaze, and SO mus-cle areas were compared.

Examinations were performed with ahigh-field MRI (three Tesla, TRIO;Siemens) using an 8-canal head coil.Coronal T1-TSE-weighted sequences(TR ⁄TE: 457 ⁄ 5.5 ms; FOV 180 ·180 mm; Matrix 240 · 320, slice thick-ness 2 mm, gap 0.0, scan time0:39 min; total examination time7:41 min) were used to repeatedly dis-play ocular muscles during the follow-ing different viewing directions:straight ahead, up ⁄downgaze, horizon-

tal gaze right ⁄ left, oblique upwardsgaze right ⁄ left, and oblique downwardsgaze right ⁄ left. Sequences were orien-tated perpendicular along the nasalseptum (axial plane) and along theoptic nerve (sagittal plane), coveringboth retro-orbital spaces symmetri-cally. To ensure constant gaze position-ing during each sequence, a sheet withmarkers for the different viewing direc-tions was attached inside the bore tun-nel, in front of the patient’s head.

Changes in the diameter of the SOmuscle as a function of gaze directionwere evaluated on a visual basis andby measuring the cross-sectional areaof the muscle approximately 1 cmbehind the ocular bulb (S.R., G.K.).

This study was performed in accor-dance with the tenets of the Declara-tion of Helsinki. Institutional reviewboard approval was obtained for thisproject and the research.

ResultsThe mean patient age was 33 years atthe time of MRI (range 20–48 years),with a male–female ratio of 3:1(Table 1). All patients had a history ofocular deviation and oculomotility dis-orders from birth. Oculomotility exam-ination (Fig. 1) was compatible withunilateral (two left-sided, two right-sided) congenital Brown syndrome,with maximal deficiency in elevation inadduction (mean 5! below horizontal,range 0–10!), less in midline and onlyminimal deficiency in abduction in allpatients (mean 13! over horizontal,range 10–15!). A slight ‘V’ pattern,with a downgaze to upgaze differenceof 7!, was present in one patient, and a15! ‘A’ pattern was observed in oneother patient. Downshoot in adductionwas present in three cases. Threepatients had an anomalous head pos-ture, with head turn (mean 10!, range5–15!) opposite to the side of the

Brown syndrome in three patients,head tilt (mean 8!, range 5–10!) to theaffected side in three patients, and chinup in three patients (mean 10!, range5–15!). Primary position hypotropia ofthe affected eye was present in allpatients (mean 12.3!, range 6–19!).A mean vertical deviation of 20.4! waspresent in adduction (range 11–33),which diminished in all patients inabduction by a mean of 14.8! (range 8–27!). Forced duction testing performedunder general anaesthesia in all threepatients requiring surgery was positive.Elevation in adduction was liberatedafter SO tendon detachment in all threeoperated patients (Patients 1, 2, 4).

The fourth cranial nerve could notbe identified bilaterally in two patientson MRI (patients 3 and 4) and waspresent only on the side opposite tothe Brown syndrome in the two otherpatients (Fig. 2). Orbital MRI wasperformed in two patients (patients 1and 4). There was no significant asym-metry of SO muscle diameter indowngaze, effectively no SO hypopla-sia on the side with CN IV absence(Fig. 3). However, while significantSO diameter change was present on

Table 1. Clinical characteristics.

Patient Sex Age (at MRI) Brown

Verticaldeviation (!)

Oculomotility: elevationover ⁄ under horizontal

Down-shootadd

Head position

MRI: CN IVADD PP ABD ADD PP ABD Turn Chin up Tilt

1 M 48 L 33 19 6 NA NA NA + R 10! 5! L 5! L not found2 F 20 L 23 18 15 5–10! under 0–5! over 10! over + R 10–15! 15! L 10! L not found3 M 44 R 11 6 0 0! 0! 15! over ) 0! 0! 0! R ⁄L not found4 F 22 R 14 6 1 5! under 5! over 15! over + L 5! 10! R 10! R ⁄L not found

F, female; M, male; L, left; R, right; ADD, adduction; PP, primary position; ABD, abduction; NA, non available; CN, cranial nerve; MRI, mag-netic resonance imaging.

(A)

(B)

Fig. 1. Patient 2, left congenital Brown syn-drome. Pictures were taken at 6 years of age:(A) In primary position, right eye fixing, a 6!left eye (LE) hypotropia is present. (B) Lefteye hypotropia increases in upgaze, becauseof severe impairment of elevation.

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the normal side in upgaze relative todowngaze, SO diameter did not signif-icantly change on the Brown syn-drome side (Fig. 4).

DiscussionBrown syndrome may be congenitalor acquired and is characterized bythe inability to actively or passivelyelevate the globe in adduction, with abetter elevation in abduction (Wilsonet al. 1989). When he first describedthe syndrome in 1950, Brown hypoth-esized that it resulted from a second-ary shortening of the anterior sheath

of the SO tendon because of congeni-tal palsy of the ipsilateral inferior obli-que (Brown 1950, 1957), but declaredthis theory invalid in 1973 after fur-ther clinical observations (Brown1973). It had become evident by thistime that various aetiologies couldlead to the same clinical syndrome.

Acquired cases can result from anyfactor impeding the passage of thesuperior oblique tendon through thetrochlea, and the cause can be identi-fied in most cases (inflammation,trauma, post-operative – after short-ening of the SO tendon).

The aetiology of congenital cases,however, remains mostly unidentified.Various theories have been proposed,and it is likely that different causesmight result in the same clinical pic-ture. Many anomalies of the superioroblique tendon between the trochlea

and the eye have been mentioned: ten-don sheath syndrome (Brown 1950),pseudo tendon sheath for which abla-tion would improve motility (Brown1973; Parks & Brown 1975; VonNoorden 1996), fibrous cord betweenthe posterior aspect of the SO tendonand the eye (Muhlendyck 1996), andoverstretched SO tendon, with goodresults after tenotomy or SO tendonlengthening by xenotransplantation(Jacobi 1972; Crawford 1976; Eustiset al. 1987; Parks & Eustis 1987; Stark& Fries 1991; Wright et al. 1992;Muhlendyck 1996; Von Noorden1996). Embryologic remnants betweenthe SO tendon and the trochlea couldimpair SO movements through thetrochlea (Sevel 1981). Attention hasalso been brought to various SO mus-cle anomalies proximal to the troch-lea: proximal SO tendon thickeningwith or without click syndrome (Gir-ard 1956; Leone & Leone 1986), orshort proximal SO tendon limitingpassage through the trochlea (Thaller-Antlanger 1987). Two cases ofcongenital absence of the SO bellywith the anterior tendon terminatingdirectly on the trochlea have beenrecently published (Bhola et al. 2005).

Paradoxical innervation has beenthought to be implicated in some casesof congenital Brown syndrome. In1969, Papst performed simultaneousEMG on both the IO and the SO,showing co-contraction of the twomuscles in elevation and adduction(Papst & Stein 1969). Ferig-Seiwerthalso provided evidence of paradoxicalinnervation in one of three patientstested with EMG (Ferig-Seiwerth &

(A) (B)

Fig. 2. Patient 1, left congenital Brown syndrome. Brain magnetic resonance imaging (MRI),coronal orientation, T2TRUE FISP protocol. The coronal sequence was tilted so that the imag-ing plane was parallel to the brainstem: (A) Image parallel to the brain stem. (B) Image at thedorsal portion of the quadrigeminal plate. CN IV is easily identified on the right side (arrow),but is absent on the left side.

(A)

(B)

Fig. 3. Patient 4, right congenital Brown syn-drome. Functional orbital MRI: in upgaze(A) optic nerve (arrowhead) is down anddowngaze (B) optic nerve (arrowhead) is up.On the normal left side, superior oblique(SO) diameter is larger in downgaze (B, star),where the SO is contracted, than in upgaze(A, star), where the SO is relaxed. The differ-ence in SO diameter is not present on theBrown syndrome side, where the SO diameterremains symmetric in upgaze (A, whitearrow) and in downgaze (B, white arrow); noSO muscle relaxation is identifiable.

Fig. 4. Patient 4, right congenital Brown syndrome. Superior oblique (SO) muscle diameter calcu-lated on functional 3-tesla orbital MRT images acquired in eight directions of gaze. SO diameterof the normal left eye (LE) is 37.2% larger in downgaze in adduction (main field of SO action –SO is fully contracted) than in upgaze in adduction (SO is fully relaxed). On the Brown’s side(RE), the SO diameter remains constant from downgaze to upgaze in adduction, with only an12.8% variation, which reflects the lack of relaxation of the muscle. Right SO hypoplasia is ruledout by the fact that diameter is larger on the right Brown side than on the normal left side.

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Celic 1972). Brown syndrome couldthereby be interpreted in analogy withDuane syndrome, with paradoxicalinnervation of a non-innervated SOmuscle by CN III fibres (Neugebauer &Fricke 2010). Dysinnervation of a pare-tic SO muscle by CN III fibres intendedfor the IO muscle or various recti mus-cles (primarily medial rectus) wouldcause co-contraction of the musclesand result in limitation of elevation inadduction. Because both muscles havetheir functional origin anterior to theeye equator, co-contraction of the SOand IO would also explain the widen-ing of the lid fissure in adduction, elim-inate the typical upshoot in adductionpresent in CN IV palsy and limit thevertical and torsional deviations (Neu-gebauer & Fricke 2010). The presenceof a preoperative SO palsy couldexplain why Brown patients do notgenerally complain of post-operativesecondary effects due to an induced SOpalsy (Graf et al. 2005).

As in Duane syndrome, restrictiondoes not disappear under generalanaesthesia in congenital Brown syn-drome. Restriction on forced ductiontesting could be accounted for by sec-ondary changes in the SO muscle, ten-don, trochlea and surroundingconnective tissue (Neugebauer &Fricke 2010).

The cases we report here add fur-ther anatomical support to the theoryof paradoxical innervation of a non-innervated SO muscle. Two of thefour patients with congenital unilat-eral Brown syndrome had no identifi-able CN IV on the side of the motilitydisorder. Because we have been usingan in plane spacial resolution of0.3*0.3 and a T2 True Fisp sequencewhich differentiates only between CSFand solid structures, a nerve whichhas a diameter of 0.5 mm will bedetectable especially when reviewingthe 3D data set on a workstation inan multiplanar approach. Usually thenerve is detected at the bottom of thequadrigeminal plate, where it leavesthe brainstem and can be followedeasily through the perimesencephaliccistern upto the cavernous sinus.Being aware of the anatomy, misinter-pretation can be excluded having sucha special resolution and image quality.In the two patients with no identifi-able CN IV on the side of the Brownsyndrome, SO muscle size wasapproximately symmetric. The SO

hypoplasia observed in the case ofcongenital SO palsy with CN IVaplasia was not present (Kim &Hwang 2010). On functional MRI,SO size did not significantly vary inup- and downgaze, which we inter-preted as the sign of constant para-doxical innervation through a branchof CN III intended for the IO muscle.

Superior oblique dysinnervationcannot explain all cases of congenitalBrown syndrome, namely those show-ing spontaneous resolution (Dawsonet al. 2009). Paradoxical innervationcould, however, account for a subtypeof the syndrome.

Financial disclosureKaeser PF has a grant from the Fon-dation SICPA and from the SocieteAcademique Vaudoise; Kress G, Ro-hde S and Kolling G have nothing todisclose.

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Received on July 25th, 2011.Accepted on November 27th, 2011.

Correspondence:Prof. Dr Gerold Kolling,UniversitatsaugenklinikSektion Schielbehandlung undNeuroophthalmologieIm Neuenheimer Feld 400D-69120 HeidelbergGermanyTel: + 49 6 221 56 6634Fax: + 49 6 221 5591Email: gerold.kolling@med.uni-heidelberg.de

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