omotor nerve involvement and 3% for facial nerve involvement. The predominance of sixth nerve injury could not be attributed to elevated intracranial pressure, given the low incidence of associated papilledema (3%) in this series. As previously mentioned, cranial neuropathies in the setting of acute bacterial meningitis tend to be multiple and are often bilateral.108 Transient sixth nerve palsy has been reported as a possible meningitic complication in children with chicken pox.

Inflammatory Sixth Nerve Palsy

Children with antecedent viral infections may develop limitations of ocular movement characterized initially by bilateral sixth nerve palsies and, subsequently, by impaired adduction and vertical movement, resulting in a diffuse ophthalmoplegia. These neuro-ophthalmologic symptoms, when associated with areflexia, distal paresthesias, and cerebrospinal fluid (CSF) albuminocytologic dissociation, are clinical markers for anti-GQ1b IgG-antibody associated with ophthalmoplegia, which is considered a mild form of Miller Fisher syndrome or a regional variant of Guillain– Barré syndrome.616

The compilation of reported cases suggests that the abducens nerve is more vulnerable to the anti-GQ1b IgG antibody than the other cranial nerves, and that bilateral abducens palsy is a characteristic sign of the pathologic state.485 Sato and Yoshikawa485 described two boys, aged 10 and 12 years, who developed bilateral sixth nerve palsies with increased titers of serum anti-GQ1b IgG antibodies. The anti-GQ1b antibody is more often detected in the sera from patients during the acute phases of Miller–Fisher syndrome, Bickerstaff’s brainstem encephalitis, and Guillain– Barré syndrome with ophthalmoparesis.615 These cases seem to demonstrate a close relationship between ophthalmoparesis and serum anti-GQ1b antibody.103 Cases of external ophthalmoplegia without other neurologic symptoms associated with the anti-GQ1b antibody have also been reported.615 Patients with bilateral sixth nerve palsy and mild neurologic symptoms are sometimes classified as having atypical Miller Fisher syndrome.103 Conversely, this syndrome can produce ataxia in the absence of ophthalmoplegia.315 Many patients with atypical Miller Fisher syndrome improve spontaneously, even without plasmapheresis or intravenous immunoglobulin therapy.485

Although the abducens nerve appears more susceptible to the anti-GQ1b IgG antibody in young people, an immunohistochemical study showed that the GQ1b epitope was expressed mainly in the paranodal regions of the oculomotor, trochlear, and abducens nerves, and that the oculomotor nerve had the highest content.

Rare Causes of Sixth Nerve Palsy

Sixth nerve palsy is occasionally seen in children with otherwise typical features of ophthalmoplegic migraine.340 In this setting, lateral rectus muscle function can be expected to be recovered. In infantile botulism, total ophthalmoplegia has been reported to evolve into bilateral sixth nerve palsies and then into comitant esotropia with bilateral inferior oblique overaction.127 Schroeder and Brieden reported on a 17-year-old girl who developed a transient bilateral sixth nerve palsy associated with Ecstasy abuse.495

Children with elevated intracranial pressure or hydrocephalus occasionally develop a sixth nerve palsy following lumbar puncture or shunting procedures.162 Children without elevated intracranial pressure can also develop a sixth nerve palsy following diagnostic lumbar puncture or myelography.150,431 The mechanism of injury is thought to involve caudal displacement of the brain after loss of CSF support in the basal cisterns.549 The abducens nerve may be most susceptible to traction, as it changes direction at the petrous ridge to pass forward under the petroclinoid ligament.

Gradenigo syndrome is a vanishingly rare condition in which severe mastoiditis extends from the mastoid air cells to the tip of the petrous bone, producing localized inflammation of the meninges in the epidural space and paresis of the ipsilateral sixth nerve with very intense pain localized to the temporal and parietal regions.196,442 Ipsilateral facial weakness may also develop. More commonly, the association of sixth nerve palsy with mastoiditis in children results from contiguous inflammatory venous sinus thrombosis with elevation of intracranial pressure114,317,569,618 The treatment of true Gradenigo syndrome usually consists of mastoidectomy and antibiotics, but rare cases can be managed medically (Fig. 3.4).343

Differential Diagnosis

The differential diagnosis of sixth nerve palsy in childhood is summarized in Table 6.5.

Duane Retraction Syndrome

Duane syndrome is probably the most common pediatric disorder associated with an isolated abduction deficit.151 Although Duane syndrome is simply a congenital sixth nerve palsy with peripheral misdirection, its clinical features and prognosis differ from other forms of sixth nerve palsy and warrant a more detailed discussion. Duane syndrome is a common disorder of unknown etiology in which decreased or absent lateral rectus innervation by the sixth nerve occurs in conjunction with misdirected innervation to the lateral rectus muscle from a branch of the third nerve. This neural misdirection leads to