A Case of Isolated Bilateral Trochlear Nerve Schwannomas

An otherwise healthy 34-year-old man presented to a neuro-ophthalmology clinic for the evaluation and management of slowly worsening vertical diplopia and head- aches over a span of 7 years.

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD A Case of Isolated Bilateral Trochlear Nerve Schwannomas Colin P. Froines, BA, Alexandra J. Van Brummen, MD, Courtney E. Francis, MD A n otherwise healthy 34-year-old man presented to a neuro-ophthalmology clinic for the evaluation and management of slowly worsening vertical diplopia and headaches over a span of 7 years. Family ocular history was limited to a sister with pediatric strabismus. The Snellen visual acuity was 20/20 bilaterally with hyperopic correction. Pupils were equal, and no afferent pupillary defect was present. Slit-lamp and funduscopic examinations were unremarkable. Ocular motility testing noted 21 infraduction and 23 superior oblique underaction in the right eye and apparent 21 supraduction in the left eye, likely secondary to the relative overelevation of the more severely affected right eye. Alternate cover testing revealed an alternating hypertropia with a V-pattern esotropia with a right hypertropia of 13 prism diopters in primary gaze. The patient’s preferred head position was a left head tilt. Brain MRI identified 2 isointense lesions along the proximal trochlear nerves that enhanced intensely with gadolinium contrast consistent with bilateral (right larger than left) trochlear schwannomas (Fig. 1). General examination showed no evidence of cutaneous stigmata of neurofibromatosis. Genetic testing for neurofibromatosis-2 was negative, and the patient had no known family history. His vertical diplopia was corrected by ground-in prism glasses with net 8 prism diopters of vertical prism. The patient was then followed with serial MRIs and examinations and identified to have both gradual growth of the masses and worsening headaches with increasing need for prism correction. As a result, he elected to proceed with right-sided stereotactic radiosurgery after observation vs treatment was offered by the radiation oncology and neurosurgery teams, receiving a single dose of 12 Gy to the 50% isodose line of the lesion. One year after radiotherapy, the patient had a stable right hypertropia in primary gaze, and interval MRI revealed no changes. Eighteen months after radiotherapy, his vertical deviation had marginally increased to a total of 14 prism diopters from 12 prism diopters 3 months after treatment, and he elected to proceed with strabismus surgery. He underwent left inferior rectus recession with resolution of his diplopia. Schwannomas are benign nerve sheath tumors arising from Schwann cells in the outer sheath of peripheral nerves. Schwannomas represent roughly 8% of primary intracranial tumors and are an unusual cause of superior oblique palsy (1,2). Schwannomas that arise from cranial nerves most commonly affect the auditory vestibular and trigeminal nerves and are exceedingly rare within the ocular motor (third, fourth, and sixth) nerves outside of neurofibromatosis (1,3). Diagnosis is primarily through contrast-enhanced MRI with 85% of trochlear schwannomas being identified in the interpeduncular cistern (1). The development of multiple schwannomas can be concerning for a genetic component given an association with a set of autosomal dominant inherited tumor suppressor Departments of Ophthalmology (CPF, AJV, CEF) and Neurological Surgery (CEF), University of Washington School of Medicine, Seattle, Washington. Unrestricted departmental grant from Research to Prevent Blindness. The authors report no conflicts of interest. Address correspondence to Courtney E. Francis, MD, Department of Ophthalmology, University of Washington School of Medicine, 325 9th Avenue, Box 359608, Seattle, WA 98104; E-mail: francis3@uw. edu e394 FIG. 1. MRI with fat suppression and gadolinium contrast showing bilateral enhancing masses of right and left trochlear nerves in interpeduncular cisterns. Findings consistent with bilateral trochlear nerve schwannomas right “A” (1.4 · 0.8 · 0.8 cm) larger than left “B” (0.4 · 0.6 · 0.5 cm). Froines et al: J Neuro-Ophthalmol 2022; 42: e394-e395 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence mutations classified broadly as neurofibromatosis (4). Typical presentation of neurofibromatosis is varied among syndromes with hallmark tumors including neuromas, vestibular schwannomas, and schwannomas for neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis, respectively. Classification as neurofibromatosis 1, neurofibromatosis 2, or schwannomatosis is based on mutations of NF1, NF2, or SMARCB1/LZTR1, respectively. Neurofibromatosis 1 is a frequent target for genetic testing. Neurofibromatosis 2 is most often characterized clinically because of incomplete penetrance and high degree of genetic mosaicism limiting the frequency of genetic testing. Schwannomatosis is mostly a sporadic gene mutation with incomplete penetrance, whose hallmark is schwannoma development. Patients with schwannomatosis often develop schwannomas in the spine (74%) and peripheral nerves (89%), with cranial nerves (8%) being less frequent and most often involving the trigeminal nerve (4). All these diagnoses should be considered and ruled out in cases of multiple nerve schwannomas. At a minimum, a detailed history, including family history, along with dermatologic and neurologic examinations should be performed. Some patients may benefit from further neuroimaging of the spine and/or targeted genetic testing. The genetic testing pursued in our patient may not have been of high yield given his negative family history and otherwise normal examination. Trochlear nerve schwannomas specifically remain uncommon in the literature, and there is no standard recommendation for clinical management (1–5). Lock and colleagues recently published a case report of a patient followed serially for a presumed trochlear nerve schwannoma with ocular motility examination and imaging remaining stable without progression over 22 years (5). A systematic review performed by Torun et al in 2018 described the treatment and outcome of 85 cases of trochlear nerve schwannomas (2). Of cases published, diplopia was present in 76% of patients and was the isolated symptom in over half of patients. In patients who presented with more severe symptoms, the most common were paresis, sensory changes, ataxia, and other cranial nerve palsies. Modalities of treatment include observation, prism glasses, strabismus surgery, surgical resection, or stereotactic radiosurgery. Schwannomas affecting ocular motor cranial nerves are associated with decreased quality of life secondary to worsening diplopia, and symptoms often drive treatment. Froines et al: J Neuro-Ophthalmol 2022; 42: e394-e395 All patients who presented with severe symptoms underwent surgical resection. For patients who presented with diplopia alone, a subsection underwent treatment with radiosurgery (N = 12), a Gamma Knife single shot, 12–14 Gy at 50%–70% isodose. At 22 months after treatment, 67% had improved symptoms. In addition to stereotactic surgery, 2 of the 12 patients also underwent strabismus surgery. Unfortunately, the related cranial nerve palsy often persists after surgical treatment with 80% of cases reporting persistent fourth nerve palsy at follow-up (1,2). Given the impact on patient quality of life and rare nature of trochlear schwannomas, seeking expertise from a multidisciplinary tumor board review may be appropriate. Among published cases, no bilateral trochlear schwannomas were identified. This report represents, to the best of our knowledge, the first documented case of isolated bilateral schwannomas. We hope to illustrate that bilateral trochlear schwannomas may be a cause of fourth nerve palsies, even in the absence of signs of neurofibromatosis. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: C. Francis; b. Acquisition of data: C. Francis and A. Van Brummen; c. Analysis and interpretation of data: C. Francis and A. Van Brummen. Category 2: a. Drafting the manuscript: C. Froines and A. Van Brummen; b. Revising it for intellectual content: C. Froines, A. Van Brummen, and C. Francis. Category 3: a. Final approval of the completed manuscript: C. Francis. REFERENCES 1. Elmalem VI, Younge BR, Biousse V, Leavitt JA, Moster ML, Warner J, Kupersmith MJ, Landau K, Brodsky MC, Frohman LP, May EF, Tomsak RL, Newman NJ. Clinical course and prognosis of trochlear nerve schwannomas. 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