An Unusual Sudden Onset of Diplopia

A local physician assistant called me on a Monday morning to discuss a patient she had seen the day before with diplopia. At first, I assumed this would be the usual—an older patient with ischemia-induced nerve palsy. I quickly learned that this was not the case. The caller explained that the patient was a 43-year-old man describing what he thought was an acute onset of diplopia for a total of 4 days. I welcomed an urgent evaluation in our office that morning.

INITIAL FINDINGS

The patient described a medical history including seasonal allergies and an unremarkable ocular history. He reported taking no medications and had entering distance UCVA of 20/20 OD and 20/25 OS. Confrontation visual fields were full to finger count OU, and extraocular muscle movements were full without restriction in any position of gaze. A distance cover test showed a constant right hypertropia with reports of vertical diplopia. The diplopia was correctable with two prism diopters of base-down prism OD. Parks three-step testing revealed diplopia worse in left gaze and right shoulder tilt. This test confirmed involvement of the right superior oblique muscle. The patient accurately identified 12 of 12 color plates with each eye.

Pupil diameter was 6 mm in each eye in dim lighting, with very minimal to no response to light. My initial thought was that the technician had dilated the patient. But, after I confirmed that no drops had been used, it was obvious that this patients’ pupils showed little response to light. I then evaluated the pupil’s response to a near accommodative target, which showed a rather abrupt brisk response.

Anterior segment examination revealed a small pterygium in the right eye and unremarkable findings in the left. Posterior segment examination was unremarkable, with minimal cupping of the optic nerves.

DIFFERENTIAL INVESTIGATION

Optometrists are accustomed to seeing the vast majority of our patients with normal pupillary reactions to light. When I observed this patient’s lack of pupillary response to light, I assumed that he was demonstrating bilateral light near dissociation. Far from common, but attention-grabbing, light near dissociation is the way to describe a patient who shows an intact near accommodative pupillary response with lack of normal pupillary light response. I recalled a short list of differentials to consider when light near dissociation is seen (see Differential Diagnoses of Light Near Dissociation).¹

Keeping the light near dissociation in mind, I also considered the presence of vertical diplopia, consistent with superior oblique muscle weakness in the right eye. I knew that the superior oblique muscle innervation processed the next steps based on a right fourth (trochlear) nerve palsy. Commonly considered differentials of a fourth nerve palsy include a congenital decompensated palsy, an acquired palsy from ischemic risk factors, a traumatic palsy, or a structural lesion affecting the pathway of the fourth nerve.²

The trochlear nerve has the longest course of all the cranial nerves. The four potential structural lesion locations are the midbrain, the subarachnoid space, the cavernous sinus, and the orbit. I was most suspicious of a structural lesion, considering this patient’s clinical presentation of light near dissociation and fourth nerve palsy.³

I knew that neuroimaging would be the most appropriate next step, so I ordered a stat MRI of the brain with and without contrast. I included specific instructions to the radiologist to pay attention to the dorsal midbrain region. I also ordered basic lab work, including a complete blood count, rapid plasma reagin (RPR), fluorescent treponemal antibody absorption (FTA-ABS), and Lyme titer.

RESULTS

The patient had an immediate MRI of the brain with and without contrast, and results were available the next morning (Figure 1). The MRI impression read as follows:

“Enhancing mass centered in the pineal gland, mass effect on the tectum is likely. This typically causes Parinaud syndrome (dorsal midbrain syndrome). The tumor measures 1.1 x 1.1 x 0.9 cm in size. This most likely represents a pineocytoma with no evidence of aqueductal closure or hydrocephalus. No evidence of white matter lesions to suggest multiple sclerosis.”

A few days later, the lab results showed a normal complete blood count, a negative Lyme titer, a nonreactive RPR, and a nonreactive FTA-ABS.

SHARED CARE

This patient was a healthy man with acute onset of vertical diplopia secondary to fourth nerve palsy and abnormal pupillary response consistent with light near dissociation secondary to an enhancing mass in the pineal gland. I previously had no experience with this diagnosis, and I knew that the patient most likely needed an urgent neurosurgical evaluation. Our practice is fortunate to have a close working relationship with a neuro-ophthalmologist colleague who commonly works with local neurosurgeons. Our colleague saw the patient urgently, confirmed my findings, and was able to schedule him with a neurosurgeon at a large university within a few days.

The neurosurgeon performed a lumbar puncture that showed normal findings without abnormality of the cerebrospinal fluid and elected to conservatively monitor the patient. At the initial 1-month follow-up the patient reported less symptomatic diplopia, and he was scheduled to have repeat neuroimaging in another 6 months.

Repeat neuroimaging showed a pineal gland tumor very similar in size and configuration to baseline imaging with no change in enhancement. The patient reported being asymptomatic, and therefore no further intervention was recommended at the time. The last correspondence on this patient was received 3 years ago, and he has now been lost to our follow-up.

MAKING CORRELATIONS

The pineal gland is a small gland located in the midline of the brain (Figure 2) and attached to the roof of the third ventricle. The superior colliculi of the midbrain are in close proximity to the pineal gland.⁴ Melatonin production is the primary function of the pineal gland.

A pineocytoma is a rare, usually slow-growing tumor of the pineal gland that uncommonly spreads. The tumor arises from the parenchymal cells of the pineal gland. The ideal treatment for pineocytoma is neurosurgery to surgically remove the tumor.⁵ The location of these tumors is deep in the brain, making surgical removal difficult. In the case of our patient, it appears obvious that the neurosurgeon weighed the risk versus benefit of surgery and opted to observe when the patient became less symptomatic and stable.

Dorsal midbrain syndrome, also referred to as Parinaud syndrome, is a result of lesions affecting the dorsal midbrain region. This syndrome can occur in the setting of tumors, demyelination, inflammation, infection, trauma, hydrocephalus, arteriovenous malformations, infarction, or hemorrhage.⁶ Tumor causes are more common in younger patients, and vascular changes are more common in older patients.

Light near dissociation is explained by differences in the pupillary light and accommodation reflexes. The pupillary light reflex pathway begins with afferent pupillary fibers traveling from the retinal ganglion cells through the optic nerve, optic chiasm, and optic tract. They join the brachium of the superior colliculus and travel to the pretectal area of the midbrain, which sends fibers bilaterally to the efferent Edinger-Westphal nucleus. Efferent pupillary parasympathetic fibers leave the Edinger-Westphal nucleus and travel on the oculomotor nerve to synapse in the ciliary ganglion, which sends axons in the short ciliary nerve to innervate the iris sphincter.⁷

The accommodation pupillary reflex pathway starts similarly to the light reflex pathway, originating in the retinal ganglion cells and traveling through the optic nerve, optic chiasm, and optic tract. It diverges when most of the fibers synapse in the lateral geniculate nucleus of the thalamus. Neurons then carry the impulses through the optic radiations to the visual cortex. Impulses from the visual cortex travel to the prefrontal cortex, with fibers then reaching the midbrain. Fibers there synapse with the oculomotor nucleus and Edinger-Westphal nucleus and complete the same course as the light reflex pathway to produce pupillary constriction.⁸

This patient’s pineocytoma, acting as a structural lesion, produced his light near dissociation due to damage to the pretectal and Edinger-Westphal nucleus. Compression resulted in loss of parasympathetic innervation to the iris sphincter, inhibiting the pupil’s ability to respond to light. The pupillary light reflex nuclei are believed to be more dorsally located, making them more sensitive to compression.⁶ The pineocytoma also caused compression to the fourth nerve as it traveled through the midbrain, producing the vertical diplopia.

LESSONS LEARNED

Cases such as this one remind me to expect the unexpected. Acquired diplopia is not always going to be ischemic, age-related, or congenital in nature. Pupils are not always going to react briskly to light.

Researching neuroanatomy is worth your time and will always make you better prepared for the next unusual case. I recommend welcoming as many referrals as you can, maintaining relationships with colleagues who can share in the care of these challenging patients, and maximizing the care you are trained to provide.