Internuclear Ophthalmoplegia as the Presenting Sign of Giant Cell Arteritis

A62-year-old man presented with the acute onset of diplopia. His medical history included well-controlled hypertension, hypercholesterolemia, and polymyalgia rheumatica (PMR) that was treated 2 years previously with steroids.

Clinical Correspondence Internuclear Ophthalmoplegia as the Presenting Sign of Giant Cell Arteritis Garrett L. Jensen, BS, Bayan Al Othman, MD, Ashwini Kini, MD, Claudia M. Prospero Ponce, MD, Andrew G. Lee, MD CASE REPORT A 62-year-old man presented with the acute onset of diplopia. His medical history included well-controlled hypertension, hypercholesterolemia, and polymyalgia rheumatica (PMR) that was treated 2 years previously with steroids. The PMR was in remission at the time of presentation. The patient presented to an outside ophthalmologist with binocular vertical diplopia and moderate-to-severe headache of 1-week duration. On examination, he was found to have a 10-prism diopter exotropia with reduced adduction of the left eye and horizontal dissociated abduction nystagmus of the right eye on right gaze, suggestive of an internuclear ophthalmoplegia (INO). He also had a left hypertropia in right gaze (Fig. 1). FIG. 1. Ocular motility examination. Ocular motility examination demonstrating evidence of adduction deficit of the left eye on right gaze. Texas A&M College of Medicine (GLJ, AGL), Bryan, Texas; Department of Ophthalmology (BAO, AK, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Department of Pathology and Genomic Medicine, Ocular Pathology (CMPP), Houston Methodist Hospital, Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery (AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas Medical Branch, Galveston, Texas; University of Texas MD Anderson Cancer Center (AGL), Houston, Texas; and Department of Ophthalmology (AGL), The University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Address correspondence to Andrew G. Lee, MD, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin Street, Suite 450, Houston, TX 77030; E-mail: [e-mail] 92 The patient was referred to an outside hospital for a full evaluation to rule out the possibility of stroke. MRI scan of the brain and MR angiography revealed only mild nonspecific white matter ischemic changes. The erythrocyte sedimentation rate (ESR) was normal for his age at 21 mm per hour, and his C-reactive protein (CRP) was mildly elevated at 2.7 mg/dL (normal ,1 mg/dL). The patient was subsequently referred to our neuroophthalmology unit, where his examination was unchanged from that previously noted. A temporal artery biopsy, performed due to persistent headache, demonstrated transmural lymphocytic infiltration that was also present at the Jensen et al: J Neuro-Ophthalmol 2020; 40: 92-94 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence TABLE 1. Summary of the literature Author Age Sex Symptoms at Presentation Ahmad (13) 72 Female Askari (14) 84 Female Diplopia, headache, malaise, INO, and ataxic nystagmus. Headache, dizziness, malaise, INO, Horner syndrome, and divergence on upward gaze. Crompton (15) 63 Male Hughes (16) 57 Male Thompson (17) 72 Male Thompson (17) 51 Male Trend (18) 81 Female Trend (18) 85 Male Laboratory Studies ESR 85. Normal MRI and CSF analysis. ESR 105, leukocytosis, Alkaline phosphatase 226, GGT 102. Peripheral Smear RBC rouleaux formation. CT confirmed left temporal infarct. Treatment Outcome Oral prednisone and bisphosphonates Oral steroids Chronic diplopia requiring prism correction. ESR returned to baseline, constitutional symptoms resolved, and neurologic symptoms did not change. Slow recovery of convergence and diplopia without recurrence. Horizontal double vision, bilateral INO, weak convergence and divergence of the left eye. Confusion, gait disturbance, scalp tenderness, jaw claudication, and malaise. First presentation: diplopia, bilateral, facial, and temporal pain. Painful third nerve palsy. Second presentation (5 weeks after the initial presentation): bilateral UE weakness, shortness of breath, left ptosis, bilateral INO, ataxic nystagmus, muscle wasting, and weakness. Headache, fever, weight loss, jaw claudication, scotoma, blurry vision, INO, horizontal and vertical diplopia, and nystagmus. ESR 92. Neutrophilic leukocytosis. Normal CT head. Oral steroids ESR 31, normal CBC, negative VDRL. CT head demonstrated pituitary tumor, and cerebral angiography demonstrated ophthalmic artery aneurysm. ESR 90. Normal MRI and CSF analysis. Oral steroids Slow resolution of diplopia and constitutional symptoms. ESR 80. Oral steroids Diplopia, headache, malaise, impaired balance, partial right INO, nystagmus, complete left INO with paralysis of adduction and exotropia, absent convergence, ataxia, and left-sided intention tremor. Anorexia, weight loss, confusion, diplopia on left gaze, jaw claudication, headache, right INO, and temporal artery tenderness. Headache, Horner syndrome, weight loss, scalp tenderness, horizontal diplopia on right gaze, left INO, and vertical nystagmus. ESR 69 at presentation, 14 on recurrence. Oral steroids Initial recovery with symptomatic recurrence after therapy deescalation. Persistence of INO for 2 years. Persistent mild convergence insufficiency with recovery of ataxia and diplopia. ESR 84, Hb 9. Oral steroids Persistent INO. ESR 100, elevated alkaline phosphatase. Hb 10. Oral steroids Steadily improving Horner and INO. CBC, complete blood count; CSF, cerebrospinal fluid; CT, computed tomography; ESR, erythrocyte sedimentation rate; GGT, gamma glutamine transferase; Hb, hemoglobin concentration; INO, internuclear ophthalmoplegia; UE, upper extremity; VDRL, venereal disease research lab. Jensen et al: J Neuro-Ophthalmol 2020; 40: 92-94 93 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence adventitia, vasa vasorum, and vasa nervorum. Multiple giant cells at the level of the media with significant disruption of the internal elastic lamina were found; all of these findings were consistent with active giant cell arteritis (GCA). The patient was started on prednisone 80 mg per day and experienced complete resolution of symptoms and normalization of his CRP after 8 weeks of therapy. INO can occur in the setting of a lesion to the medial longitudinal fasciculus (MLF), which includes interneurons connecting the sixth nerve nucleus and the contralateral nucleus of the third nerve. Injury to the MLF occurs from a variety of etiologies and results in characteristic signs of adduction deficit on the side of the lesion with an abducting nystagmus of the contralateral eye. INO is often accompanied by skew deviation. It is most commonly caused by vertebrobasilar insufficiency or inflammatory demyelination (1,2). Pseudo- internuclear ophthalmoplegia (pseudo-INO) presents similarly to INO but occurs secondary to myasthenia gravis or can occur with medial rectus ischemia (3). Although we believe our patient experienced a pseudoINO due to GCA-mediated ocular muscle ischemia, it is possible that he had a true INO with brainstem ischemia despite an apparently normal brain MRI. In addition, abducting nystagmus is classically associated with an INO but has been reported in patients with pseudoINO (3-5). In GCA, T-cell-mediated chronic inflammation results in myofibroblast migration and intimal hyperplasia, leading to arterial occlusion and ischemia. Special stains may demonstrate histiocytic infiltrates at the level of the elastic lamina, a finding that can impact prognosis. Ischemia of the central retinal artery leads to vision loss, whereas ischemia due to disease of the basilar and ophthalmic arteries can cause INO and pseudo-INO, respectively (6-9). Diplopia is an uncommon finding in GCA, occurring in only 6% of patients, and may be caused by ischemia of the cranial nerves, extraocular musculature, or brainstem (8-12). An INO or pseudo-INO (from extraocular muscle involvement) as a cause of diplopia is an extremely rare finding in GCA. Our search revealed only 6 previous publications that report 8 cases of INO in patients with GCA. These are summarized in Table 1 (13-18). Our patient had a history of PMR and had a normal ESR at the time of presentation. A normal ESR is not unusual and may be seen in almost 20% patients with GCA cases. It is estimated that up to 10% of patients with a history PMR will develop GCA. We mention these findings to highlight the lack of typical symptoms in this patient and to illustrate the importance of the medical history in determining the etiology of an INO (19,20). This case reveals the importance of considering GCA in the differential diagnosis of INO (or pseudo-INO) in elderly patients. 94 STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: G. L. Jensen; b. Acquisition of data: B. Al Othman; c. Analysis and interpretation of data: A. Kini. Category 2: a. Drafting the manuscript: B. Al Othman; b. Revising it for intellectual content: A. Lee. Category 3: a. Final approval of the completed manuscript: A. Lee. REFERENCES 1. Swisher J, Kini A, Lee AG. 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