Signs and Symptoms


The patient will present with horizontal uncrossed diplopia, which worsens at distance and in either right or left gaze. The patient will have an abduction deficit in the involved eye and either an esophoric or esotropic position, which is non-comitant. The onset is typically sudden. If the palsy is isolated, there will be neither visual acuity nor visual field loss. There may be some degree of head pain. The patient typically is older and has a concurrent history of hypertension and/or diabetes. The fundus is typically normal, except when the patient manifests a bilateral cranial nerve VI palsy, where there typically will also be papilledema.




Cranial nerve VI arises in the pons, in close association with the facial nerve and paramedian pontine reticular formation (PPRF). Due to this arrangement, damage to the sixth nerve within the brain stem will produce a sixth nerve palsy as well as a facial nerve palsy or an internuclear ophthalmoplegia. Associated findings may also include leg paralysis with sixth nerve palsy (Raymond's syndrome), or leg paralysis, facial paralysis and sixth nerve palsy (Millard-Gubler syndrome). These additional findings identify the location of damage as the pons, where ischemic infarct, tumor and demyelinization are the common causes.


The sixth nerve travels through the subarachnoid space where it ascends the clivus and enters the cavernous sinus. Within the subarachnoid space, the sixth nerve may be stretched against the clivus as the brain stem herniates through the foramen magnum due to increased intracranial pressure. This will give a bilateral sixth nerve palsy (which is often intermittent) and papilledema. As the sixth nerve passes over the petrous apex of the temporal bone, damage here can result in a sixth nerve palsy, facial pain and hearing loss. This occurs due to inflammation of the temporal bone (Gradenigo's syndrome) or nasopharyngeal carcinoma.


Within the cavernous sinus, the sixth nerve is joined by the oculosympathetic nerves, and cranial nerves III, IV and V-1. Damage here will yield a sixth nerve palsy and Horner's syndrome, as well as a concurrent CN III and IV palsy. The etiology may be aneurysm, meningioma, pituitary adenoma, inflammation, or fistula. The sixth nerve is also vulnerable to ischaemic infarct from diabetes and hypertension; this remains a prime cause of isolated sixth nerve palsy.




A sixth nerve palsy combined with any of the above mentioned neurological signs indicates a need for MRI of the appropriate area. In children, sixth nerve palsy often occurs from a presumed viral cause and has an excellent prognosis. However, if the palsy does not recover, or worsens over several weeks, the child should be examined for a pontine glioma. In the adult under 50 years, obtain MRI studies of the brain. Adult sover 50 with an isolated sixth nerve palsy require a workup for ischaemic vascular diseases such as diabetes and hypertension. If the patient is over the age of 65 years, order an erythrocyte sedimentation rate (ESR) to rule out giant cell arteritis.


If no etiology is discovered on MRI or hematology studies, monitor the patient monthly for several months until resolution (or until other signs develop which would indicate an etiology). The vast majority of CN VI palsies due to ischemic vasculopathy (or idiopathic etiology) will resolve without treatment in three to six months. Fresnel prism correction or unilateral occlusion will temporarily alleviate the diplopia.


Clinical Pearls


The etiology of isolated CN VI palsy in adults is undetermined in 25 percent of cases, despite full diagnostic evaluation. These palsies, and those due to diabetes or hypertension, resolve in three to six months without treatment. A diagnostic workup should include intracranial MRI, CBC with differential, fasting blood glucose, ESR, blood pressure measurement, Lyme titer and syphilis serology. If these tests are negative, monitor the patient for resolution. Clinical worsening over time indicates the need for more thorough or repeat investigation. Myasthenia gravis may mimic a sixth nerve palsy and should always be considered in the differential diagnosis, especially if the palsy takes on a variable course with exacerbations and remissions. Always consider the possibility of myasthenia gravis in cases of non-restrictive, pupil sparing CN III, IV and VI nerve palsy as well as unilateral and bilateral internuclear ophthalmoplegia.


Other reports in this section


                                                                                                     Anterior Ischemic Optic Neuropathy

                                                                                                     Optic Disc Edema & Papilledema

                                                                                                     Cranial Nerve III Palsy

                                                                                                     Cranial Nerve IV Palsy

                                                                                                     Cranial Nerve VI Palsy

                                                                                                     Cranial Nerve VII (Facial Nerve) Palsy

                                                                                                     Horner's Syndrome

                                                                                                     Internuclear Ophthalmoplegia

                                                                                                     Optic Nerve Head Hypoplasia

                                                                                                     Optic Pit

                                                                                                     Tonic Pupil

                                                                                                     The Many Faces of the Optic Nerve Head (Pictorial)