Internuclear ophthalmoplegia as a result of cerebral metastatic disease: Workup, pathophysiology, and clinical pearls

Veshesh Patel; Divy Mehra; Yanet Diaz-Martell; Lino Saavedra; Javier Alvarado; Jose Barros

doi:10.4103/ijo.IJO_1893_21

CASE REPORT

Year : 2022 | Volume : 2 | Issue : 2 | Page : 517-519

Internuclear ophthalmoplegia as a result of cerebral metastatic disease: Workup, pathophysiology, and clinical pearls

Veshesh Patel¹, Divy Mehra¹, Yanet Diaz-Martell², Lino Saavedra², Javier Alvarado², Jose Barros²
¹ Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, United States
² Department of Graduate Medical Education, Kendall Regional Medical Center, Kendall, FL, United States

Date of Submission	16-Jul-2021
Date of Acceptance	11-Oct-2021
Date of Web Publication	13-Apr-2022

Correspondence Address:
Divy Mehra
92 SW 3^rd St #505, Miami, FL 33130
United States

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_1893_21

Abstract

This case demonstrates an acute case of internuclear ophthalmoplegia (INO) caused by cerebral metastasis from a small cell lung cancer, the only such case documented in the literature. A 54-year-old male presented to the emergency department for worsening headache and diplopia, secondary to INO. On further examination, a CT scan of the chest revealed a 6.1 × 4.8 × 6.8 cm solid mass in the right lower lung consistent with small-cell lung cancer. T2-weighted MRI exhibited bilateral supratentorial and infratentorial lesions interpreted as metastatic cancer. The patient's symptoms, including INO, were caused by the mass effect from the metastatic brain lesions.

Keywords: Cancer, diplopia, double vision, internuclear ophthalmoplegia, metastasis

How to cite this article:
Patel V, Mehra D, Diaz-Martell Y, Saavedra L, Alvarado J, Barros J. Internuclear ophthalmoplegia as a result of cerebral metastatic disease: Workup, pathophysiology, and clinical pearls. Indian J Ophthalmol Case Rep 2022;2:517-9

How to cite this URL:
Patel V, Mehra D, Diaz-Martell Y, Saavedra L, Alvarado J, Barros J. Internuclear ophthalmoplegia as a result of cerebral metastatic disease: Workup, pathophysiology, and clinical pearls. Indian J Ophthalmol Case Rep [serial online] 2022 [cited 2022 May 24];2:517-9. Available from: https://www.ijoreports.in/text.asp?2022/2/2/517/342908

Internuclear ophthalmoplegia (INO) is an ocular movement disorder characterized by impaired adduction of the ipsilateral eye with nystagmus of the contralateral eye. It is caused by functional damage to the medial longitudinal fasciculus (MLF) in the dorsomedial brainstem tegmentum of either the pons or the midbrain.^[1] Nearly 80% of INO cases are the result of multiple sclerosis (MS) flare-ups and cerebrovascular disease (CVD) in the form of ischemic stroke, with more rare occurrences due to infectious etiologies, trauma, mass effect, and others.^[2] Suspicion should prompt magnetic resonance imaging (MRI) for evaluation.

Case Report

A 54-year-old man with a past medical history significant for adrenal and parathyroid mass resections, chronic cigarette and cocaine use, and multiple ischemic brain stem strokes presented to the emergency department with a one-day history of acute-onset headache and double vision, particularly in the right eye. One week prior, the patient reported that he first noticed an occipital headache that is described as dull, constant, with variable intensity, no radiation, and mildly improved with naproxen. The patient reported double vision in his right eye and his spouse reported that the patient's right eye had laterally deviated. The patient admitted to one episode of non-bloody, non-bilious vomiting. The patient denied any associated fever, myalgias, chest pain, shortness of breath, abdominal pain, changes in bowel habits, peripheral edema, weakness, numbness, or any focal neurological symptoms.

The gentleman was hemodynamically stable with unremarkable vital signs or laboratory workup. On physical exam, there was significant ptosis of the right eye, conjunctival hyperemia, and lateral deviation of the right eye at rest. Adduction of the right eye was impaired and associated with nystagmus of the left eye on left lateral gaze, findings consistent with INO.

This prompted several imaging tests, including a chest CT that revealed a 6.1 × 4.8 × 6.8 cm solid mass in the right lower lung highly concerning for malignancy. A brain CT revealed multiple bilateral cortical parenchymal lesions with vasogenic edema [Figure 1]. A T2-weighted MRI exhibited bilateral supratentorial and infratentorial lesions interpreted as metastatic with the largest lesion in the left posterior frontal lobe measuring 1.8 cm [Figure 1]. Abdominal and pelvis CT showed no evident hepatic metastatic disease.

Figure 1: Small-cell lung cancer in a chronic male smoker metastasizing to the brain causing internuclear ophthalmoplegia. This illustration shows a magnetic resonance imaging (MRI) of the brain in a chronic male smoker with small-cell lung cancer. This image depicts multiple cannonball lesions (yellow arrows) in the supratentorial and infratentorial areas on the brain consistent with metastatic cancer (a-c). These brain lesions are located in the cerebellum and brainstem (d) causing displacement, and as a result, causing internuclear ophthalmoplegia (INO) for the patient

Click here to view

Upon evaluation, the patient was administered steroids. Headache and visual deficits resolved in the following few days, and the patient was promptly referred for necessary oncologic management.

Discussion

This gentleman presented to the ED with worsening headache and double vision, particularly with the right eye deviated laterally at rest. This gentleman was a chronic cigarette smoker and a CT scan of the chest revealed a 6.8-cm solid mass in the right lower lung consistent with small-cell lung cancer. Despite any pulmonary symptoms, the patient had an advanced SCLC that had metastasized to the brain, one of the most frequent metastatic sites for lung cancer. In the current case, it was determined that metastasized lesions in the brain resulted in areas of focal edema that resulted in the patient's INO and headache.

In lateral gaze, the paramedian pontine reticular formation (PPRF), or conjugate gaze center, coordinates the function of the abducens nucleus, which contains two sets of neural tracts.^[3] The first set of axons innervates the ipsilateral lateral rectus muscle, and the second set of axons is known as the medical longitudinal fasciculus (MLF), which crosses the midline to innervate a subnucleus of the oculomotor complex. The MLF, critical for visual coordination of horizontal eye movements, are highly myelinated white matter fibers. The MLF tracks near the midline ventral to the fourth ventricle and cerebral aqueduct, extending through the dorsomedial pontine and midbrain tegmentum.^[4] When there is a MLF deficit, adduction on the ipsilateral side of the MLF lesion weakens and results in lateral deviation of the ipsilateral eye [Figure 2] and [Figure 3]. There will also be an abduction nystagmus in the contralateral eye due to skew deviation and alignment dysregulation.

Figure 2: Horizontal gaze presenting internuclear ophthalmoplegia. This illustration depicts internuclear ophthalmoplegia (INO) upon horizontal gaze. This picture shows an example of impaired adduction of the ipsilateral eye. The ocular movement deficit is defined by the side of adduction impairment, which is ipsilateral to the medial longitudinal fasciculus (MLF) lesion in the dorsomedial brainstem tegmentum of either the pons or the midbrain. (Adapted from the article “Orbital metastasis mimicking internuclear ophthalmoplegia: A case report and review” by Lin et al.)^[8]

Click here to view

Figure 3: Neuro-anatomical diagram of the medial longitudinal fasciculus pathway. As shown in this simplified diagram, the PPRF, also known as conjugate gaze center, coordinates the function of the abducens nucleus, which contains axons innervating the ipsilateral lateral rectus muscle and axons known as the MLF. The MLF crosses midline to innervate a subnucleus of the oculomotor complex which directly controls the contralateral eye medial rectus muscle. (Adapted from the article “Metastatic disease-producing internuclear ophthalmoplegia: a case report” by Bulson and Jun)^[9]

Click here to view

In this case, the patient's previously undiagnosed SCLC metastasized to the brain and the resultant swelling caused a disruption in the MLF pathway. For this patient, brain lesions likely caused displacement of the brainstem and thus abnormal communication between axons and muscle fibers.^[5] As a result of the mass effect, right eye adduction and MLF pathway were impaired. Additional symptoms of INO include horizontal diplopia, vertical diplopia, difficulty driving, visual confusion, oscillopsia, and loss of stereopsis.^[6] Additionally, convergence is intact as the medial rectus is unaffected. The imaging modality of choice for INO is MRI and should include axial T2 or proton dense images with 3-mm thickness.

Most etiologies of INO (approximately 70%–78%) are due to multiple sclerosis or cerebrovascular disease. Other cases may be due to infectious etiology, trauma, mass effect, Arnold– Chiari malformation ^{More Details}, hydrocephalus, lupus, and others. Diagnosis of INO includes physical exam and, in unclear circumstances, formal oculographic recordings demonstrating the velocity and acceleration of abductive and adductive movements.^[7] Optokinetic tape (OKN), which observes saccadic dysconjugacy, is highly sensitive in diagnosing INO. In certain cases, management of the underlying condition is the treatment of acute onset double vision. Prognosis varies depending on the etiology of the INO. It is important to maintain awareness of INO etiologies based on full patient history and consideration of underlying contributors.

Conclusion

The prevalence of brain mass causing INO has not been established. Documented cases of mass lesions include medulloblastoma, pontine glioma, lymphoma, epidermoid cancers, ganglioglioma, and brain metastases. This case of SCLC resulting in INO exemplifies the rarity but possibility of an oncological root cause of INO.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Cogan DG. Internuclear ophthalmoplegia, typical and atypical. Arch Ophthalmol 1970;84:583-9.
2.	Keane JR. Internuclear ophthalmoplegia: Unusual causes in 114 of 410 patients. Arch Neurol 2005;62:714-7.
3.	Glaser JS. Neuro-ophthalmolgy. Philadelphia, Pennsylvania: JB Lippincott Company; 1990.
4.	Miller NR, Newman NJ, Biousse V, Kerrison JB. Walsh and Hoyt's Clinical Neuro-Ophthalmology: The Essentials. 2^nd ed. Philadelphia, Pennsylvania: Lippincott Williams and Wilkins; 2008.
5.	Gray OM, Forbes RB, Morrow JI. Primary isolated brainstem injury producing internuclear ophthalmoplegia. Br J Neurosurg 2001;15:432-4.
6.	Kochar PS, Kumar Y, Sharma P, Kumar V, Gupta N, Goyal P. Isolated medial longitudinal fasciculus syndrome: Review of imaging, anatomy, pathophysiology and differential diagnosis. Neuroradiol J 2018;31:95-9.
7.	Zee DS, Hain TC, Carl JR. Abduction nystagmus in internuclear ophthalmoplegia. Ann Neurol 1987;21:383-8.
8.	Lin WV, Chevez-Barrios P, Sadaka A, Lee AG. Orbital metastasis mimicking internuclear ophthalmoplegia: A case report and review. Can J Ophthalmol 2017;52(4):e149-e51 doi: 10.1016/j.jcjo.2017.01.017.
9.	Bulson R, Jun W. Metastatic disease producing internuclear ophthalmolplegia: a case report. Clin Exp Optom 2014;97(5):468-70 doi: 10.1111/cxo.12176.