facial colliculus syndrome).

Internuclear Causes of Diplopia

In the context of eye movement control, an “internuclear” lesion is one that disrupts the medial longitudinal fasciculus (MLF), a bundle of fibers that connects the sixth nerve nucleus on one side of the pons to the medial rectus subnucleus (of the third nerve) on the contralateral side of the midbrain (see Chapter 1, Fig 1-28). This type of lesion produces an internuclear ophthalmoplegia (INO).

The cardinal sign of a unilateral INO is slowed adducting saccadic velocity in 1 eye. This limitation is usually associated with abducting nystagmus of the fellow eye. The eye with the slowed adduction may have a full or limited range of adducting movement (Fig 8-6). Convergence may be spared or disrupted. A skew deviation, often with a hyperdeviation ipsilateral to the lesion, may be present. By convention, the INO is named for the side of limited adduction. That is, a right INO is one that limits adduction of the right eye secondary to a lesion of the MLF on the right side of the brainstem. Although patients with INO may report horizontal diplopia, they may also experience vertical-oblique diplopia due to an associated skew deviation, episodic diplopia related to head–eye movements if the lesion is partial, or difficulty tracking fast-moving objects (eg, when playing sports) because of the mismatch in saccadic velocity between the eyes. Quantitative measurement of the adducting saccadic velocity may be a useful research tool for determining the severity of multiple sclerosis and its progression.

Figure 8-6 Bilateral internuclear ophthalmoplegia in a 53-year-old man with diplopia on lateral gazes. A, Horizontal gaze in either direction results in full abduction of the ipsilateral eye but virtually no adduction of the contralateral eye. Alignment in primary gaze (center panel) is nearly orthotropic. B, Axial FLAIR MRI brain scan showing edema (bright signal indicated by arrows) in the area of the medial longitudinal fasciculus bilaterally at the level of the upper midbrain (left) and pons (right).

(Courtesy of Prem S. Sub ramanian, MD, PhD.)

A bilateral INO produces bilateral adduction lag, bilateral abducting nystagmus, and vertical, gaze-evoked nystagmus that is best appreciated in upgaze. This nystagmus is due to disruption of vertical vestibular pursuit and gaze-holding pathways, which ascend from the vestibular nuclei through the MLF. A large-angle exodeviation may occur in bilateral INO (ie, “wall-eyed” bilateral INO, or WEBINO, syndrome) and is often caused by a midbrain lesion near the third nerve nuclei; it may be transient and improve even though the INO persists.

The 2 most common causes of INO are demyelination and stroke. In adolescents and younger adults, INO is typically caused by demyelination. In older adults, microvascular disease is the most common cause. Myasthenia gravis can produce pseudo-INO; this scenario usually lacks the vertical gaze–evoked nystagmus of a true INO and is often accompanied by myasthenic eyelid signs. The adduction paresis of myasthenic pseudo-INO may resolve transiently after intravenous administration of edrophonium (edrophonium test) and typically responds to appropriate systemic therapy.

Davis SL, Frohman TC, Crandall CG, et al. Modeling Uhthoff’s phenomenon in MS patients with internuclear ophthalmoparesis. Neurology. 2008;70(13 pt 2):1098–1106. Epub 2008 Feb 20.