Man presents with acute-onset horizontal binocular diplopia
He had an incomitant esotropia and right hypertropia that did not localize to a particular cranial nerve or muscle.
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A 42-year-old man was referred to the New England Eye Center for evaluation of binocular diplopia. Four months earlier, the patient developed acute-onset horizontal binocular diplopia that was present constantly but worsened later in the day. More recently, he began to notice left upper eyelid drooping. He otherwise felt well with no headache, weakness, difficulty swallowing, fever, fatigue or weight loss. He had been evaluated by an outside optometrist who prescribed prism glasses that were ineffective, so he was referred to the New England Eye Center for neuro-ophthalmologic evaluation.
The patient had no history of strabismus or trauma and denied prior episodes of diplopia. He had no medical or surgical history. He had no prescribed medications. The patient was a current smoker but did not use alcohol or recreational drugs.
Examination
On initial examination, the patient’s visual acuity measured 20/25 in the right eye and 20/20 in the left eye. The pupils were reactive bilaterally without afferent pupillary defect. Visual fields were full to confrontation, and color vision testing was intact in each eye.
On motility examination, the patient exhibited full ductions and versions. However, there was a question of subtle slowed adduction in each eye associated with possible contralateral bilateral abducting nystagmus. On alignment testing, the patient had an incomitant esotropia and right hypertropia that did not localize to a particular cranial nerve or muscle.
External examination revealed 2 mm of left upper eyelid ptosis (Figure 1). Slit lamp examination of the anterior segment and fundus was unremarkable. The patient’s cranial nerve examination revealed no additional abnormalities. He had a normal gait and full strength on neurologic exam.
What is your diagnosis?
See answer below.
Binocular diplopia
The differential diagnosis for acquired binocular diplopia is broad and includes a number of degenerative, inflammatory, neoplastic and vascular entities. A detailed clinical history is necessary to narrow the differential diagnosis and to triage workup and management.
Given our patient’s report of binocular diplopia that worsened late in the day with associated left eyelid drooping in the setting of non-localizing incomitant esotropia and right hypertropia, myasthenia gravis was considered. Myasthenia gravis is suspected in patients with fluctuating diplopia and ptosis without pupillary involvement, headaches or vision loss. Ocular myasthenia gravis is isolated to the extraocular muscles and orbicularis oculi, so it presents without systemic symptoms of difficulty swallowing, shortness of breath and extremity weakness.
The patient’s motility examination revealed possible slowed adduction bilaterally with contralateral abducting nystagmus concerning for bilateral internuclear ophthalmoplegia (INO). INO results from damage to the medial longitudinal fasciculus (MLF) and is characterized by an ipsilateral adduction deficit with abducting nystagmus of the fellow eye. Unilateral INO is commonly caused by infarction in older individuals, while bilateral INO is often due to demyelinating disease in younger patients. Other causes of INO are numerous and include trauma, neoplasm, infection and vasculitis. Patients with myasthenia gravis may present with a bilateral INO pattern that is termed pseudo-INO because it results from muscle weakness rather than an MLF lesion.
Other etiologies of acquired binocular incomitant diplopia include cranial nerve palsies, which were not suspected in this patient based on motility and alignment testing. Thyroid eye disease can cause ocular misalignment but is typically associated with lid retraction and exophthalmos. A skew deviation could be considered given the patient’s vertical misalignment and possible INO but would be unusual in the absence of other neurologic signs. A decompensated phoria is suspected in patients with a comitant tropia on exam who describe a history of long-standing intermittent diplopia that worsens suddenly.
Workup and management
Given the suspicion for myasthenia gravis, an ice test was attempted in the office. The ice test is reported to have a sensitivity of 93% to 97% and a specificity of 97% to 98% in the diagnosis of ocular myasthenia gravis. In this case, the test was equivocal with no clear improvement of left upper eyelid ptosis after administration.
The patient was sent for laboratory workup including anti-acetylcholine receptor antibodies, anti-muscle specific kinase antibodies and thyroid function testing. Due to concern for skew deviation and possible INO, the patient was scheduled for brain MRI, but this was organized on an outpatient basis given his lack of neurologic signs or symptoms.
A few days after his visit, the patient returned urgently to the primary care clinic at Tufts Medical Center with complaint of new-onset ataxia and left tongue numbness. He was sent to the emergency department for urgent neuroimaging.
Brain MRI revealed an expansile mass measuring approximately 2 cm located within the posterior aspect of the pons and midbrain with slight extension into the bilateral middle cerebellar peduncles (Figure 2). Based on the anatomic location and appearance of the lesion, it was thought to be consistent with high-grade glioma of the pons and midbrain.
The patient was admitted to Tufts Medical Center for initiation of high-dose steroid treatment with plans for temozolomide chemotherapy and radiation to the lesion.
Discussion
Adult brainstem gliomas are uncommon, accounting for only 2% of gliomas in adulthood. Males are more frequently affected, and the mean age at diagnosis is 34 years. Common presenting symptoms include gait abnormalities, headache, extremity weakness and diplopia. In one study by Guillamo and colleagues reviewing 48 adults with brainstem glioma, diplopia was identified in 40% of cases. Internuclear ophthalmoplegia and skew deviation have also been described in association with these tumors.
On neuroimaging, brainstem gliomas most commonly arise in the pons but can also originate in the midbrain or medulla. These lesions have a variable appearance, but contrast enhancement is observed in approximately 40% of cases. MR spectroscopy may be used to assist in the diagnosis. Depending on the size and location of the tumor, biopsy may be difficult and associated with a high risk for postoperative complications.
Treatment for high-grade brainstem gliomas in adults typically involves radiation and chemotherapy. Temozolomide is an alkylating agent that is commonly employed in this setting. Prognosis varies depending on tumor grade, location and patient age, but the median survival is in the range of 30 to 40 months for adults.
For a patient presenting with symptomatic diplopia, treatment options are limited but may include patching or prism glasses.
- References:
- Allerand CD. Neurology. 1962;doi:10.1212/WNL.12.8.520.
- Benatar M. Neuromuscul Disord. 2006;doi:10.1016/j.nmd.2006.05.006.
- Brazis PW, et al. Mayo Clin Proc. 1998;doi:10.1016/S0025-6196(11)63620-3.
- Brazis PW, et al. Mayo Clin Proc. 1999;doi:10.4065/74.9.907.
- Comer RM, et al. Eye (Lond). 2007;doi:10.1038/sj.eye.6702415.
- Feroze KB, et al. Internuclear Ophthalmoplegia. StatPearls; Aug. 2, 2019.
- Guillamo JS, et al. Brain. 2001;doi:10.1093/brain/124.12.2528.
- Hu J, et al. Front Oncol. 2016;doi:10.3389/fonc.2016.00180.
- Keane JR. Arch Neurol. 2005;doi:10.1001/archneur.62.5.714.
- McClard CK, et al. Am J Ophthalmol Case Rep. 2018;doi:10.1016/j.ajoc.2018.09.008.
- Strobel H, et al. Biomedicines. 2019;doi:10.3390/biomedicines7030069.
- For more information:
- Sarah E. Thornton, MD, and Laurel Vuong, MD, can be reached at New England Eye Center, Tufts University School of Medicine. 800 Washington Street, Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Alison J. Lauter, MD, and Sarah E. Thornton, MD. They can be reached at the New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.