Figure 8-5 Anatomical substrate for localizing lesions of the infranuclear ocular motor pathways. This schematic provides a lateral view of CNs III, IV, and VI from the brainstem nuclei to the orbit. A sequential consideration of these pathways could begin either within the brainstem or within the orbit. The cranial nerve segments within the brainstem are often referred to as being “intramedullary.” The subarachnoid space lies between the brainstem and cavernous sinus. The third nerve exits the midbrain anteriorly, crosses near the junction of the internal carotid and posterior communicating arteries in the subarachnoid space, and enters the cavernous sinus, where it runs in the lateral wall. The fourth nerve exits the midbrain posteriorly and crosses to the opposite side; it then courses through the subarachnoid space and into the cavernous sinus. The sixth nerve exits the pons anteriorly, ascends along the clivus, crosses the petrous apex, and passes below the petroclinoid ligament to enter the cavernous sinus, where it runs between the lateral wall and the carotid

artery. (Used with permission from Yanoff M, Duker JS, eds. Ophthalmology. 2nd ed. St Louis: Mosb y; 2004:1324, fig 199-1.)

Attempts at neural localization may fail or give false results in the presence of diffuse disease (eg, meningeal inflammation as in sarcoidosis); the approach also is not helpful in a clinical syndrome such as Wernicke encephalopathy in which imaging may not show the characteristic structural disturbances.

Supranuclear Causes of Diplopia

The supranuclear pathway for eye movement control includes any afferent input to the ocular motor nerves (cranial nerves [CNs] III, IV, and VI). The most important supranuclear pathways are those that drive volitional eye movement—that is, the corticobulbar pathways that are used, for example, to follow the command “Look to the right”—and the vestibular input to adjust the relative position of the eyes within the head. The vestibular input defines the eye position within the orbit and in relation to the rest of the body to allow accurate calculation of saccadic velocity and direction. The distance of the horizontal eye movement is controlled by the selection of particular populations of neurons in the paramedian pontine reticular formation (PPRF). The vestibular system analyzes the relative position of the head and the direction of the intended visual target and selects which neurons to activate to drive the saccadic eye movements.

Most supranuclear disorders affect both eyes equally and do not cause diplopia, as in the dorsal midbrain syndrome, in which neither eye is able to look upward (conjugate limitation of upgaze). However, certain supranuclear lesions do not result in a symmetric effect and thus may produce ocular misalignment and diplopia (Table 8-1).

Table 8-1

Skew Deviation

Skew deviation is an acquired vertical misalignment of the eyes resulting from asymmetric disruption of supranuclear input from the otolithic organs (the utricle and saccule of the inner ear, both of which contain otoliths, which are tiny calcium carbonate crystals). These organs sense linear motion and static head tilt via gravity and transmit information to the vertically acting ocular motoneurons, as well as to the interstitial nucleus of Cajal (INC), all of which are in the midbrain.

Peripheral and central lesions can produce skew deviation. Central lesions are more common causes of skew deviation and can occur anywhere within the posterior fossa (ie, brainstem and cerebellum). Skew deviation can be comitant or incomitant, and torsional abnormalities may be present. At times it may be difficult to distinguish some presentations of skew deviation from a fourth nerve palsy, and proper use of the Parks-Bielschowsky 3-step test (discussed later in the chapter) is essential. Skew deviation often produces diplopia and is an important exception to the general rule that supranuclear lesions do not produce double vision.

An alternating skew deviation on lateral gaze usually manifests as hypertropia of the abducting eye (ie, right hypertropia on right gaze) that switches when gaze is directed to the opposite side (ie, becoming left hypertropia on left gaze). Responsible lesions are located in the cerebellum, cervicomedullary junction, or dorsal midbrain. This disorder must be distinguished from bilateral fourth nerve palsies, in which the hyperdeviation increases on gaze to the opposite side (eg, right hypertropia is larger on gaze to the left) and excyclotropia is present.

Ocular tilt reaction is a combination of a head tilt, skew deviation, and cyclotorsional abnormalities of both eyes that can occur in tonic or, though rare, paroxysmal fashion. This syndrome typically develops because of loss of otolithic input to the INC from a central lesion, which may be in the medulla, pons, or midbrain. Such a lesion can alter the sense of true vertical, which in turn drives the head and rotates the eyes toward the same side in a compensatory response to correct to true vertical (see Chapter 7, Fig 7-2).

In the ocular tilt reaction, the head tilt is associated with a contralateral hypertropia (ie, right head tilt and left hypertropia) and rotation of the upper poles of both eyes toward the lower ear. The changes in head and eye position of an ocular tilt reaction should be distinguished from those of a normal response of head tilting, as well as from those of a fourth nerve palsy; the normal ocular reflexes induced by tilting the head cause both eyes to rotate toward the raised ear (ie, counter rolling), whereas the ocular tilt reaction causes the opposite response. With a fourth nerve palsy, the compensatory head tilt is typically contralateral to the side of the hypertropia (similar to ocular tilt reaction), but the higher eye is extorted—opposite the pattern of an ocular tilt reaction. Thus, in