Isolated Fourth Nerve Palsy as the Presenting Sign of Clival Chordoma

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Isolated Fourth Nerve Palsy as the Presenting Sign of Clival Chordoma MacGregor N. Hall, BS, Subahari Raviskanthan, MBBS, Peter W. Mortensen, MD, Andrew G. Lee, MD F ourth cranial nerve (trochlear nerve) palsy is a common cause of paralytic strabismus in adults and children. The most common causes of an isolated fourth nerve palsy include presumed congenital (decompensated), traumatic, and microvascular ischemic etiologies. Intracranial neoplasms, however, rarely cause neurologically isolated fourth nerve palsy (1). Clival chordomas may present with isolated or multiple cranial neuropathies—the most commonly affected isolated cranial nerve is the abducens nerve, which runs rostrally along the clivus in isolation in this location. In contrast, the fourth nerve is very rarely associated with clival chordoma. To our knowledge, this is the first case of an isolated fourth nerve palsy as the presenting and only sign of an intracranial clival chordoma to be reported in the English language ophthalmic literature. CASE REPORT A 67-year-old woman presented with binocular oblique diplopia. Past medical history was significant for wellcontrolled hypertension and hypercholesterolemia. Past surgical, family, and social history were noncontributory. Her only medications were simvastatin and amlodipine. The patient developed painless and progressive binocular diplopia over the next year. Thyroid function studies were negative. The patient was referred to neuro-ophthalmology. Neuro-ophthalmologic exam showed a visual acuity of 20/25 in McGovern Medical School at the University of Texas Health Science Center at Houston (MNH), Houston, Texas ; Department of Ophthalmology (SR, PM, AGL), Blanton Eye Institute, 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; Texas A and M College of Medicine (AGL), Bryan, Texas; and Department of Ophthalmology (AGL), the University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Address correspondence to Andrew G. Lee, MD Chair, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin Street, 450 Houston, TX 77030; E-mail: aglee@ houstonmethodist.org Hall et al: J Neuro-Ophthalmol 2022; 42: e391-e393 both eyes. The pupils were isocoric and normally reactive to light in both eyes, with no relative afferent pupillary defect. External examination revealed a 10° head tilt to the right without ptosis or proptosis. Motility examination showed a right head tilt in primary gaze with a left hypertropia measuring 6 prism diopters (PD) that increased to 12 PD on right gaze and 8 PD on left head tilt (Fig. 1). Double Maddox rod testing revealed 9° of excyclotorsion in the left eye consistent with an isolated left fourth nerve palsy. The rest of her neurological examination revealed no evidence of facial sensory changes or weakness, intact hearing, symmetric palate elevation, and a midline tongue without atrophy. Her gag reflex was intact. Examination of her limbs was normal. She was able to ambulate without assistance, but was noted to have mild difficulty with tandem gait. MRI of the brain with and without contrast revealed a large left-sided extra-axial clival mass extending to the prepontine space and compressing the anterior pons eccentric to the left (Fig. 2). The lesion was hypointense on T1 weighted imaging and hyperintense on T2 with mild contrast enhancement. There was mild posterior displacement of the brainstem. Staged neurosurgical debulking via a middle fossa skull base and transpetrosal approach with resection of the petro-apex lesion was performed. Histopathology revealed multiple large cells with generous cytoplasm and myxoid background. Immunohistologic stains for brachyury, epithelial membrane antigen, pancytokeratin, and S-100 protein were all immunoreactive, consistent with a clival chordoma. Two months later, she was readmitted for Stage II resection via a transoral approach. Postoperative MRI revealed a 13-mm irregular area of enhancement and a 9mm focus that was nonenhancing anteriorly, which was believed to be residual tumor. She was treated with postoperative stereotactic radiation therapy. After surgical and radiation treatment, she had a persistent left fourth nerve palsy but no new complaints or neurologic findings. She wore a patch for symptomatic control of diplopia. DISCUSSION Chordomas arise from vestigial remnants of the notochord, an embryonic structure common to all animals in the phylum Chordata. In humans, the notochord produces signals that direct tissue development and provides axial e391 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Nine-gaze image showing a right head tilt in primary gaze with a left hypertropia, which increases on right gaze. support until the bony skeleton develops. The notochord remnant then becomes the nucleus pulposus of the intervertebral disc; however, tissue remnants can become trapped and presumably then undergo neoplastic transformation into a chordoma. Chordomas occur mostly in men aged 50–60 and have an overall incidence of 0.08 per 100,000 (2). They arise in roughly equal proportions in the sacrum, mobile spine, and skull base (2). Skull base chordomas usually form along the clivus, a portion of the cranial floor formed by the basilar occipital and sphenoid bones that slopes downward from the dorsum sellae to the foramen magnum. Chordomas commonly present with cranial neuropathies, most commonly of the abducens nerve (3). This is likely related to the proximity of the clivus to the Dorello canal, which surrounds the sixth cranial nerve as it enters the cavernous sinus. Isolated third nerve palsies have also been reported. The only fourth nerve palsies reported had concomitant third and sixth nerve palsies (4). The current patient, however, presented with an isolated left fourth nerve palsy, likely related to compression by the chordoma at the level of the left anterior pons. Cranial MRI with contrast is the best neuroimaging study for chordomas and typically reveals iso-intensity or hypointensity on T1 weighted images and hyperintensity on T2-weighted images with variable gadolinium enhancement (3). Histologically, chordomas are classi- cally characterized by cells with bubble-like vacuoles in the cytoplasm described as physaliferous (3). Biomarkers include cytokeratin and the nuclear transcription factor brachyury, which when combined has a sensitivity and specificity over 90% for diagnosing chordoma (3). The mainstay of therapy for intracranial chordoma is surgical resection, which provides decompression of neurovascular structures and allows for definitive histological diagnosis. Gross total resection is ideal but may not be possible because of the location of the tumor or extension through the skull base. Residual tumor burden can be managed with radiotherapy (5). Despite advances in therapy, local recurrence is still common and occurs more often after subtotal or partial resection (2,5). This patient experienced persistent diplopia following 2 resections, likely because of residual tumor burden. Ophthalmologists should be aware of the unique presentation of isolated fourth nerve palsy in the setting of intracranial neoplasms such as clival chordomas. Although traumatic, ischemic, or decompensated congenital palsies are the most common etiologies in adult patients with fourth nerve palsy, compressive lesions have rarely been reported in the literature. Neuroimaging studies are generally not helpful in most cases of neurologically isolated fourth nerve palsy, but patients with chronic and progressive fourth nerve palsy should be considered for neuroimaging, preferably with contrast-enhanced cranial MRI. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: M. N. Hall, S. Raviskanthan, P. Mortensen, and A. G. Lee; b. Acquisition of data: M. N. Hall, S. Raviskanthan, P. Mortensen, and A. G. Lee; c. Analysis and interpretation of data: M. N. Hall, S. Raviskanthan, P. Mortensen, and A. G. Lee. Category 2: a. Drafting the manuscript: M. N. Hall, S. Raviskanthan, P. Mortensen, and A. G. Lee; b. Revising it for intellectual content: M. N. Hall, S. Raviskanthan, P. Mortensen, and A. G. Lee. Category 3: a. Final approval of the completed manuscript: M. N. Hall, S. Raviskanthan, P. Mortensen, and A. G. Lee. FIG. 2. A. Axial T1 postcontrast MRI of the brain preoperatively shows a 3.1-cm hypointense mass within the left clivus with extraosseous invasion into the left prepontine space. B. Axial T1-weighted fluid-attenuated inversion recovery postcontrast MRI shows a 9- · 7-mm nonenhancing residual lesion after Stage II resection. e392 REFERENCES 1. Dosunmu EO, Hatt SR, Leske DA, Hodge DO, Holmes JM. Incidence and etiology of presumed fourth cranial nerve palsy: a population-based study. Am J Ophthalmol. 2018;185:110–114. Hall et al: J Neuro-Ophthalmol 2022; 42: e391-e393 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence 2. Erdem E, Angtuaco EC, Van Hemert R, Park JS, Al-Mefty O. Comprehensive review of intracranial chordoma. Radiographics. 2003;23:995–1009. 3. 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