INTERNUCLEAR OPHTHALMOPLEGIA

SIGNS AND SYMPTOMS
Several underlying systemic diseases can cause this condition. There is a painless onset of visual disturbance, but often no diplopia in primary gaze. There will be horizontal diplopia in lateral gaze. The patient will manifest an adduction deficit on the involved side and a nystagmus of the fellow eye in extreme abduction.

Occasionally, the condition is bilateral with medial rectus palsy and adduction deficit in each eye and nystagmus upon abduction in both eyes (bilateral internuclear ophthalmoplegia, or BINO) While there appears to be medial recti palsy, most patients will be able to converge (posterior INO or BINO). In some cases, the patient will not be able to converge (anterior INO or BINO).

PATHOPHYSIOLOGY
To produce synchronous eye movements, cranial nerves III, IV and VI communicate through the medial longitudinal fasciculus (MLF), the neural pathway connecting the cranial nerve nuclei responsible for eye movements. In INO, a lesion disrupts this pathway, preventing communication between cranial nerves.

For example, for a patient to gaze to the left, the left supranuclear control center of horizontal eye movements [paramedian pontine reticular formation (PPRF)] must signal the left CN VI nucleus to turn the left eye outwards. At the same time, the PPRF must signal the right CN III nucleus, via the right MLF, to simultaneously turn the right eye inwards. A lesion of the right MLF would not allow the neural impulse to reach the right medial rectus. In this case, the left eye would abduct, but the right eye would not adduct. Further, the left eye would go into an abducting nystagmus.

Most lesions of the MLF are located in the pons, or caudal mesencephalon. Thus, patients with INO or BINO will be able to converge (posterior INO/BINO). However, if the lesion affects the MLF within the mesencephalon and involves the CN III nucleus, then the patient will not be able to converge (anterior INO/BINO).

Possible causes of INO/BINO:

multiple sclerosis
brainstem infarction
brainstem and fourth ventricular tumor
viral infection
trauma
syphilis
Lyme disease
drug intoxication (phenothiazines and tricyclic antidepressants)
subdural hematoma

Typically, multiple sclerosis causes a bilateral presentation, whereas ischemic vascular infarction causes a unilateral episode. Also, myasthenia gravis can produce a pseudo-INO/BINO with a motility pattern identical to true INO/BINO.

MANAGEMENT
Manage INO/BINO by identifying the underlying cause, and then obtaining appropriate medical treatment. In cases of ischemic vascular infarction, the motility pattern returns to normal over time. Appropriate testing includes MRI of the brainstem, FTA-ABS, VDRL, Lyme titre, fasting blood glucose, complete blood count with differential, blood pressure measurement, and toxicology screen.

CLINICAL PEARLS

Remember that myasthenia gravis can mimic the motility pattern of INO/BINO.
In younger patients, the etiology of INO/BINO is most commonly multiple sclerosis. In fact, INO/BINO is the most common ocular motility dysfunction in MS. Approximately 92 percent of patients who develop INO/BINO from demyelinization develop MS.
In older patients who develop INO/BINO, the most common etiology is ischemic vascular infarction. Beyond MRI studies, these patients need medical evaluation for ischemic vascular diseases such as diabetes and hypertension. These cases typically resolve over time.