Bursztyn, Lulu L. C. D. MD, MSc; Makar, Inas MBChB
Department of Ophthalmology, Western University, London, Ontario, Canada.
Address correspondence to Lulu L. C. D. Bursztyn, MD, MSc, Ivey Eye Institute, St Joseph's Hospital, 268 Grosvenor Street, London, Ontario, Canada N6A 4V2; E-mail: firstname.lastname@example.org
The authors report no conflicts of interest.
Abstract: Synkinesis of the extraocular muscles forms a subset of congenital ocular motility abnormalities termed congenital cranial dysinnervation disorders. Synkinesis most frequently involves the abducens or oculomotor nerves and rarely the trochlear nerve. Only 3 such patients have been described in the literature. We report an isolated case of trochlear–oculomotor synkinesis in a healthy 6-year-old boy and discuss the proposed pathophysiology of this disorder.
The congenital cranial dysinnervation disorders encompass a wide range of congenital ocular motility abnormalities with a presumed neurogenic etiology. This continually expanding group includes congenital fibrosis of the extraocular muscles and various synkinetic disorders of extraocular muscles. The common theme of these disorders is a congenital abnormality of ocular and/or facial muscle innervation, several of which now have an identified genetic basis (1). Many are uncommon, making their phenotypic and genotypic characterization challenging. Although aberrant innervation of the extraocular muscles occurs in Duane retraction syndrome and Marcus–Gunn jaw-winking ptosis, synkinesis involving the trochlear nerve rarely has been reported (2).
A 6-year-old boy was evaluated by the pediatric ophthalmology service due to parental concern that the child's right eye did not fully depress. The boy was the product of a full-term pregnancy and unremarkable delivery and was otherwise healthy and neurologically normal. There was no family history of strabismus or ptosis.
Visual acuity was 20/20 in each eye, and stereopsis measured 40 arcseconds. Pupillary reactions and extraocular movements were normal. There was no pupil constriction associated with horizontal or vertical gaze, and no ptosis. Ocular alignment was orthophoric in all fields of gaze and on head tilt to either side. Retraction of the right upper eyelid occurred with depression of the right eye in adduction (Fig. 1). Lid retraction did not occur with chewing or other jaw movement, and the remainder of the ocular and cranial nerve examination was normal. Magnetic resonance imaging of the brain revealed a moderately sized right posterior communicating artery in contact with the right oculomotor nerve (Fig. 2). The resolution of the scan did not allow visualization of the trochlear nerves.
Synkinesis is an aberrant innervation, causing involuntary stimulation of a muscle or structure not normally supplied by that nerve. Dysinnervation of the extraocular muscles manifests most frequently as Duane retraction syndrome (oculomotor–abducens synkinesis), occurring in 1%–4% of strabismus patients (2). In addition to Marcus–Gunn jaw-winking ptosis (trigemino–oculomotor synkinesis), synkinetic lid retraction due to aberrant innervation of the levator palpebrae by a variety of cranial nerves has been reported, including inverse Duane syndrome with adduction and pseudo-Graefe with depression (oculomotor–oculomotor synkinesis) (3), with abduction (abducens–oculomotor synkinesis) (4), and with head tilt (vestibulo–oculomotor synkinesis) (5).
Trochlear–oculomotor synkinesis has been reported previously. Martorina and Porte (6) described a 4-year-old girl with a history of forceps delivery and congenital left ptosis and exophoria. Extraocular movements were full, and left eyelid retraction was noted on right downgaze. Due to forceps delivery, she was presumed to have traumatic oculomotor and trochlear nerve palsies with aberrant regeneration. Lim et al (7) reported the case of a 4-year-old girl, born prematurely with tetralogy of Fallot. She had no ptosis and was orthophoric in all gaze directions, but demonstrated left lid retraction on downgaze, more pronounced on right downgaze. The third case reported by Kothari et al (8) was of a 7-year-old healthy boy with esophoria, left ptosis, excyclotorsion, and limitation of elevation of the left eye. He was also found to have left lid retraction when looking down and right. The authors suggested that congenital paresis of the superior division of the left oculomotor nerve resulted in aberrant innervation of the levator muscle by the trochlear nerve, either by misdirection of regenerating axons or by ephaptic transmission.
To date, all cases of presumed trochlear–oculomotor synkinesis demonstrate ipsilateral upper eyelid retraction associated with depression of the eye in adduction. As depression of the eye in adduction is mainly accomplished by the superior oblique muscle, it would seem that the most likely abnormality involves aberrant innervation of the levator palpebrae muscle by a segment of the ipsilateral trochlear nerve. However, no reported case, including the present one, has demonstrated direct anatomical or electrophysiologic evidence of a connection between these nerves. In addition, a single case of deglutition–trochlear synkinesis has been reported (9). The trochlear nerve is unique, in that it is the only cranial nerve to decussate within the brainstem and the only cranial nerve to exit the brainstem dorsally. These anatomical factors may limit dysinnervation due to lack of proximity of the trochlear nerve to other cranial nerve roots.
Mechanisms of aberrant innervation that have been proposed include ephaptic transmission between nearby nerves or misdirected regeneration of axonal sprouts (2,8). Ephaptic transmission occurs when depolarization of a neuron or group of neurons induces an action potential in a nearby nerve, despite the lack of a synaptic connection. Asymmetry of the magnitude or duration of an action potential or variable defects in myelination can cause unidirectional ephaptic transmission between 2 adjacent nerves (10).
Embryonic cranial nerve axon growth is, at least, partly directed by expression of transcription factors within the nerve and release of certain growth factors, which attract the nerve to the appropriate muscle(s). In utero injury to the oculomotor nerve may lead to aberrant regeneration. In our patient, this may have been due to compression by the posterior communicating artery. Unlike the abducens nerve, the trochlear and oculomotor nerves respond to the same growth factors (e.g., fibroblast growth factor, hepatocyte growth factor, and semaphonin-3F) (11). The trochlear nerve could potentially respond inappropriately to these signals and supply innervation to the levator muscle.
Axonal misdirection may occur during neuronal development at the level of the nucleus, brainstem, or peripheral nerve (1). We propose that trochlear–oculomotor synkinesis is unlikely to be central in origin. Although these cranial nerve nuclei lie in close proximity, the levator nucleus supplies innervation to both eyelids, and cases of aberrant regeneration have unilateral lid retraction. The oculomotor and trochlear nerve fascicles extend in opposite directions through the brainstem, with the oculomotor nerve exiting on the ventral surface and the trochlear nerve exiting dorsally. As they course anteriorly toward the superior orbital fissure, the trochlear nerve crosses over the superior division of the oculomotor nerve to enter the orbital apex outside the annulus of Zinn. This crossing is the location of closest proximity for the 2 nerves, suggesting that this may be another potential location for coinnervation.
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