Absence of the fourth cranial nerve in congenital Brown syndrome

Authors


Prof. Dr Gerold Kolling,
Universitätsaugenklinik
Sektion Schielbehandlung und Neuroophthalmologie
Im Neuenheimer Feld 400
D-69120 Heidelberg
Germany
Tel: + 49 6 221 56 6634
Fax: + 49 6 221 5591
Email: gerold.kolling@med.uni-heidelberg.de

Abstract.

Purpose:  To elucidate the aetiology of congenital Brown syndrome.

Methods:  Four consecutive patients diagnosed with unilateral congenital Brown syndrome had a comprehensive standardized ocular motility examination. Any compensatory head posture was measured. Brain magnetic resonance imaging (MRI) with regard for the IV cranial nerve (CN) was performed in all patients. Orbital MRI was performed in 2/4 patients, with images acquired in eight directions of gaze and superior oblique (SO) muscle areas compared.

Results:  CN IV could not be identified bilaterally in two patients, but was absent only on the side of the Brown syndrome in the two other patients. On the normal side, orbital MRI revealed a smaller SO muscle area in upgaze than in downgaze, demonstrating normal actions of this muscle. On the side of the Brown syndrome, the SO area remained the same in upgaze and in downgaze and approximately symmetric to the area of SO in downgaze on the normal side.

Conclusions:  These cases add further anatomical support to the theory of paradoxical innervation in congenital Brown syndrome. CN IV was absent in two patients 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 a sign of constant innervation through branches of CN III.

Introduction

Brown syndrome refers to a clinical disorder characterized by impaired active and passive elevation in adduction. While acquired cases are thought to result from an injury to the superior oblique (SO) muscle tendon of various origins (inflammation, surgery, trauma), the aetiology of congenital cases is still debatable and potentially diverse. Some congenital cases may result from anatomical abnormalities of the SO tendon or trochlea, while others might be related to a neurodevelopmental problem, with the SO muscle paradoxically innervated by the third cranial nerve. This would induce co-contraction of the SO with the inferior oblique (IO) and superior rectus muscles on upgaze, causing a greater restriction of elevation in adduction than in abduction. We report four cases of congenital unilateral Brown syndrome where the fourth (trochlear) cranial nerve (CN) was studied by MRI. Orbital MRI was performed in two patients, with images acquired in eight directions of gaze, and SO muscles areas were compared.

Methods

Brain magnetic resonance imaging (MRI) was performed in four consecutive patients diagnosed with unilateral congenital Brown syndrome in the strabology department of Heidelberg University Eye Clinic. A comprehensive standardized ocular motility examination was performed in all patients, and ocular deviations were measured in all nine directions of gaze using the Harms tangent screen at 2.5 m. Any compensatory head posture was measured.

Brain 1.5 Tesla MRI targeting CN IV identification was performed in all four patients and the images analysed by an experienced neuro-radiologist (KB) without the knowledge of which side the Brown syndrome was on. A Siemens Symphony 1.5-Tesla magnetic resonance unit (Siemens, Erlangen, Germany) was used together with a conventional head coil. The images were obtained in coronal orientation on 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). The coronal sequence was tilted so that the imaging plane was parallel to the brainstem and the most posterior slice was located at the dorsal portion of the quadrigeminal plate.

The data sets were processed on the scanner console (Wizzard, Siemens). Using a standardized approach, sagittal and axial images were reconstructed with a slice thickness of 0.5 mm from T2-weighted sequences separately for both sides of the face along the course of the trigeminal nerve.

Functional MRI of the external ocular musculature was performed in two patients, with images acquired in nine directions of gaze, and SO muscle areas were compared.

Examinations were performed with a high-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 thickness 2 mm, gap 0.0, scan time 0:39 min; total examination time 7:41 min) were used to repeatedly display ocular muscles during the following different viewing directions: straight ahead, up/downgaze, horizontal gaze right/left, oblique upwards gaze right/left, and oblique downwards gaze right/left. Sequences were orientated perpendicular along the nasal septum (axial plane) and along the optic nerve (sagittal plane), covering both retro-orbital spaces symmetrically. To ensure constant gaze positioning during each sequence, a sheet with markers for the different viewing directions was attached inside the bore tunnel, in front of the patient’s head.

Changes in the diameter of the SO muscle as a function of gaze direction were evaluated on a visual basis and by measuring the cross-sectional area of the muscle approximately 1 cm behind the ocular bulb (S.R., G.K.).

This study was performed in accordance with the tenets of the Declaration of Helsinki. Institutional review board approval was obtained for this project and the research.

Results

The mean patient age was 33 years at the time of MRI (range 20–48 years), with a male–female ratio of 3:1 (Table 1). All patients had a history of ocular deviation and oculomotility disorders from birth. Oculomotility examination (Fig. 1) was compatible with unilateral (two left-sided, two right-sided) congenital Brown syndrome, with maximal deficiency in elevation in adduction (mean 5° below horizontal, range 0–10°), less in midline and only minimal deficiency in abduction in all patients (mean 13° over horizontal, range 10–15°). A slight ‘V’ pattern, with a downgaze to upgaze difference of 7°, was present in one patient, and a 15°‘A’ pattern was observed in one other patient. Downshoot in adduction was present in three cases. Three patients had an anomalous head posture, with head turn (mean 10°, range 5–15°) opposite to the side of the Brown syndrome in three patients, head tilt (mean 8°, range 5–10°) to the affected side in three patients, and chin up in three patients (mean 10°, range 5–15°). Primary position hypotropia of the affected eye was present in all patients (mean 12.3°, range 6–19°). A mean vertical deviation of 20.4° was present in adduction (range 11–33), which diminished in all patients in abduction by a mean of 14.8° (range 8–27°). Forced duction testing performed under general anaesthesia in all three patients requiring surgery was positive. Elevation in adduction was liberated after SO tendon detachment in all three operated patients (Patients 1, 2, 4).

Table 1.   Clinical characteristics.
PatientSexAge (at MRI)BrownVertical deviation (°)Oculomotility: elevation over/under horizontalDown-shoot addHead positionMRI: CN IV
ADDPPABDADDPPABDTurnChin upTilt
  1. F, female; M, male; L, left; R, right; ADD, adduction; PP, primary position; ABD, abduction; NA, non available; CN, cranial nerve; MRI, magnetic resonance imaging.

1M48L33196NANANA+R 10°L 5°L not found
2F20L2318155–10° under0–5° over10° over+R 10–15°15°L 10°L not found
3M44R116015° overR/L not found
4F22R14615° under5° over15° over+L 5°10°R 10°R/L not found
Figure 1.

 Patient 2, left congenital Brown syndrome. Pictures were taken at 6 years of age: (A) In primary position, right eye fixing, a 6° left eye (LE) hypotropia is present. (B) Left eye hypotropia increases in upgaze, because of severe impairment of elevation.

The fourth cranial nerve could not be identified bilaterally in two patients on MRI (patients 3 and 4) and was present only on the side opposite to the Brown syndrome in the two other patients (Fig. 2). Orbital MRI was performed in two patients (patients 1 and 4). There was no significant asymmetry of SO muscle diameter in downgaze, effectively no SO hypoplasia on the side with CN IV absence (Fig. 3). However, while significant SO diameter change was present on the normal side in upgaze relative to downgaze, SO diameter did not significantly change on the Brown syndrome side (Fig. 4).

Figure 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 imaging plane was parallel to the brainstem: (A) Image parallel to the brain stem. (B) Image at the dorsal portion of the quadrigeminal plate. CN IV is easily identified on the right side (arrow), but is absent on the left side.

Figure 3.

 Patient 4, right congenital Brown syndrome. Functional orbital MRI: in upgaze (A) optic nerve (arrowhead) is down and downgaze (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 difference in SO diameter is not present on the Brown syndrome side, where the SO diameter remains symmetric in upgaze (A, white arrow) and in downgaze (B, white arrow); no SO muscle relaxation is identifiable.

Figure 4.

 Patient 4, right congenital Brown syndrome. Superior oblique (SO) muscle diameter calculated on functional 3-tesla orbital MRT images acquired in eight directions of gaze. SO diameter of 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 an 12.8% variation, which reflects the lack of relaxation of the muscle. Right SO hypoplasia is ruled out by the fact that diameter is larger on the right Brown side than on the normal left side.

Discussion

Brown syndrome may be congenital or acquired and is characterized by the inability to actively or passively elevate the globe in adduction, with a better elevation in abduction (Wilson et al. 1989). When he first described the syndrome in 1950, Brown hypothesized that it resulted from a secondary shortening of the anterior sheath of the SO tendon because of congenital palsy of the ipsilateral inferior oblique (Brown 1950, 1957), but declared this theory invalid in 1973 after further clinical observations (Brown 1973). It had become evident by this time that various aetiologies could lead to the same clinical syndrome.

Acquired cases can result from any factor impeding the passage of the superior oblique tendon through the trochlea, and the cause can be identified in most cases (inflammation, trauma, post-operative – after shortening of the SO tendon).

The aetiology of congenital cases, however, remains mostly unidentified. Various theories have been proposed, and it is likely that different causes might result in the same clinical picture. Many anomalies of the superior oblique tendon between the trochlea and the eye have been mentioned: tendon sheath syndrome (Brown 1950), pseudo tendon sheath for which ablation would improve motility (Brown 1973; Parks & Brown 1975; Von Noorden 1996), fibrous cord between the posterior aspect of the SO tendon and the eye (Mühlendyck 1996), and overstretched SO tendon, with good results after tenotomy or SO tendon lengthening by xenotransplantation (Jacobi 1972; Crawford 1976; Eustis et al. 1987; Parks & Eustis 1987; Stärk & Fries 1991; Wright et al. 1992; Mühlendyck 1996; Von Noorden 1996). Embryologic remnants between the SO tendon and the trochlea could impair SO movements through the trochlea (Sevel 1981). Attention has also been brought to various SO muscle anomalies proximal to the trochlea: proximal SO tendon thickening with or without click syndrome (Girard 1956; Leone & Leone 1986), or short proximal SO tendon limiting passage through the trochlea (Thaller-Antlanger 1987). Two cases of congenital absence of the SO belly with the anterior tendon terminating directly on the trochlea have been recently published (Bhola et al. 2005).

Paradoxical innervation has been thought to be implicated in some cases of congenital Brown syndrome. In 1969, Papst performed simultaneous EMG on both the IO and the SO, showing co-contraction of the two muscles in elevation and adduction (Papst & Stein 1969). Ferig-Seiwerth also provided evidence of paradoxical innervation in one of three patients tested with EMG (Ferig-Seiwerth & Celic 1972). Brown syndrome could thereby be interpreted in analogy with Duane syndrome, with paradoxical innervation of a non-innervated SO muscle by CN III fibres (Neugebauer & Fricke 2010). Dysinnervation of a paretic SO muscle by CN III fibres intended for the IO muscle or various recti muscles (primarily medial rectus) would cause co-contraction of the muscles and result in limitation of elevation in adduction. Because both muscles have their functional origin anterior to the eye equator, co-contraction of the SO and IO would also explain the widening of the lid fissure in adduction, eliminate the typical upshoot in adduction present in CN IV palsy and limit the vertical and torsional deviations (Neugebauer & Fricke 2010). The presence of a preoperative SO palsy could explain why Brown patients do not generally complain of post-operative secondary effects due to an induced SO palsy (Gräf et al. 2005).

As in Duane syndrome, restriction does not disappear under general anaesthesia in congenital Brown syndrome. Restriction on forced duction testing could be accounted for by secondary changes in the SO muscle, tendon, trochlea and surrounding connective tissue (Neugebauer & Fricke 2010).

The cases we report here add further anatomical support to the theory of paradoxical innervation of a non-innervated SO muscle. Two of the four patients with congenital unilateral Brown syndrome had no identifiable CN IV on the side of the motility disorder. Because we have been using an in plane spacial resolution of 0.3*0.3 and a T2 True Fisp sequence which differentiates only between CSF and solid structures, a nerve which has a diameter of 0.5 mm will be detectable especially when reviewing the 3D data set on a workstation in an multiplanar approach. Usually the nerve is detected at the bottom of the quadrigeminal plate, where it leaves the brainstem and can be followed easily through the perimesencephalic cistern upto the cavernous sinus. Being aware of the anatomy, misinterpretation can be excluded having such a special resolution and image quality. In the two patients with no identifiable CN IV on the side of the Brown syndrome, SO muscle size was approximately symmetric. The SO hypoplasia observed in the case of congenital SO palsy with CN IV aplasia was not present (Kim & Hwang 2010). On functional MRI, SO size did not significantly vary in up- and downgaze, which we interpreted as the sign of constant paradoxical innervation through a branch of CN III intended for the IO muscle.

Superior oblique dysinnervation cannot explain all cases of congenital Brown syndrome, namely those showing spontaneous resolution (Dawson et al. 2009). Paradoxical innervation could, however, account for a subtype of the syndrome.

Financial disclosure

Kaeser PF has a grant from the Fondation SICPA and from the Société Académique Vaudoise; Kress G, Rohde S and Kolling G have nothing to disclose.

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