Oculomotor Palsy Due to Malignant Nerve Sheath Tumor: Aberrant Regeneration of the Third Nerve but Without Pupil Involvement

Letters to the Editor Downloaded from http://journals.lww.com/jneuro-ophthalmology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 05/04/2022 the patient has enjoyed considerable improvement in her symptomatic dry eye syndrome because of the scleral lenses (conversely, ptosis surgery is a known risk for worsening dry eye). Furthermore, the patient expressed reticence for a surgical procedure, given her extensive list of ailments and history of medical procedures. Thus, although ptosis repair is a therapeutic option for patients experiencing CPEO-related ptosis, scleral lenses may be a viable nonsurgical alternative for certain patients and confer the added benefits of comfort and ocular surface protection. Thank you for the opportunity to discuss this case further. Christina Cherny, BS State University of New York College of Optometry, New York, New York Suzanne W. Sherman, OD Lora R. Dagi Glass, MD Department of Ophthalmology, Columbia University Irving Medical Center, New York, New York The Department of Ophthalmology at Columbia University Irving Medical Center is funded by a nonrestricted grant from the Research to Prevent Blindness. The authors report no conflicts of interest. Oculomotor Palsy Due to Malignant Nerve Sheath Tumor: Aberrant Regeneration of the Third Nerve but Without Pupil Involvement O ur group thoroughly enjoyed the article from Professor Nancy Newman and her team, where they presented the very rare event of a third nerve palsy due to an intrinsic, malignant peripheral (oculomotor) sheath tumor. The literature demonstrates that this been reported on fewer than 10 occasions (1,2). It was very instructive to peruse the excellent photographs of their patient. Our group would like to make 2 observations accordingly. First, because the left upper lid was ptotic due to the third nerve palsy, the upper lid was passively elevated by the examiner's finger while the photograph was taken to demonstrate the pupil appearance and eye movements. This occurred in all the photographs except the top left photograph, where the patient is looking up to the right, 138 REFERENCES 1. Kearns-sayre syndrome. The Genetic and Rare Diseases Information Center (GARD). Available at https:// rarediseases.info.nih.gov/diseases/6817/kearns-sayresyndrome. Accessed June 8, 2020. 2. Pfeffer G, Sirrs S, Wade NK, Mezei MM. Multisystem disorder in late-onset chronic progressive external ophthalmoplegia. Can J Neurol Sci. 2011;38:119–123. 3. Barrera-Ramírez CF, Barragán-Campos HM, Ilarraza H, Iturralde P, Avila-Casado MC, Oseguera J. Afección cardíaca en el síndrome de Kearns-Sayre [Cardiac involvement in Kearns-Sayre syndrome]. Rev Esp Cardiol. 2005;58:443–446. 4. Goldstein A, Falk MJ. Mitochondrial DNA deletion syndromes. 2003 Dec 17 [Updated 2019 Jan 31]. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. Seattle, WA: University of Washington, Seattle; 1993–2020. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1203/. 5. Hanisch F, Kornhuber M, Alston CL, Taylor RW, Deschauer M, Zierz S. SANDO syndrome in a cohort of 107 patients with CPEO and mitochondrial DNA deletions. J Neurol Neurosurg Psychiatry. 2015;86:630–634. 6. Wabbels B, Ali N, Kunz WS, Roggenkämper P, Kornblum C. Chronisch-progressive externe Ophthalmoplegie und KearnsSayre-Syndrom: Interdisziplinäre Diagnostik und Therapie [Chronic progressive external ophthalmoplegia and KearnsSayre syndrome: interdisciplinary diagnosis and therapy]. Ophthalmologe. 2008;105:550–556. 7. Chong JW, Annuar AA, Wong KT, Thong MK, Goh KJ. Single mitochondrial DNA deletions in chronic progressive external ophthalmoplegia (CPEO) and Kearns-Sayre syndrome (KSS) patients from a multiethnic Asian population. Neurol Asia. 2014;19:27–36. 8. Sommer F, Fötzsch R, Pillunat LE, Wollensak G. Diagnostic and therapeutic problems in chronic progressive external ophthalmoplegia (CPEO). Klin Monbl Augenheilkd. 2003;220:315–319. 9. Kearns-Sayre syndrome. Orphanet: an online database of rare diseases and orphan drugs. Copyright, INSERM 1997. Available at https://www.orpha.net/consor/cgi-bin/OC_Exp.php? Lng=GB&Expert=480. Accessed June 4, 2020. the examiner's finger has elevated the upper lid. That maneuvre expressly prevented the readership from seeing whether there may have been left upper lid retraction in adduction, in adduction and downgaze, in adduction and upgaze, in downgaze, and in upgaze. However, in this top left photograph, the examiner's finger was on the brow, and the brows were of the same height as assessed by measuring vertical eyebrow height with a standard surgical ruler from the photograph. Therefore, the left upper lid seems to elevate in upgaze and adduction. This is entirely consistent with aberrant regeneration of the third nerve (Ab3), wherein Ab3 is well displayed in a schematic diagram (3). At the same time, there seemed to be no pupillary constriction in any of the fields of action of the extraocular muscles supplied by the oculomotor nerve. Our group questions whether, as there did indeed seem to be Ab3, the pupillary fibers might not be so definitively involved in patients with intrinsic peripheral nerve sheath tumors, as in their case. It is recognized that Ab3 tends to occur after a third nerve palsy in cases of tumor, trauma, or aneurysm. The literature is replete with descriptions of internal carotid/posterior Letters to the Editor: J Neuro-Ophthalmol 2021; 41: 135-140 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor communicating artery aneurysms causing oculomotor nerve palsy and in which Ab3 occurs in about 27% (4). The example of an extrinsic tumor in the ethmoidal sinuses producing a typical Ab3 has been demonstrated (2). There has also been one case of a gastric lymphoma producing a paraneoplastic third nerve palsy (5). An Australian report documented ophthalmoplegic migraine with an associated Ab3 (6), this too being a very rare cause of Ab3. As there have been fewer than 10 reported publications of oculomotor nerve palsy due to intrinsic peripheral malignant nerve sheath tumors, Professor Newman and team are clearly presenting the first of these with a purported Ab3 and accordingly, are to be congratulated. Our group wonders whether the fact that the pupillary fibers are represented on the external surface of the oculomotor nerve (7) was the reason why there was Ab3 in the lid but not in the pupil. The patient was stated to have a complete left external ophthalmoplegia. This is interesting because the patient did demonstrate a modest amount of abduction of the left eye, as seen in the photographs. Because of the fact that the patient lost vision due to presumed compressive optic neuropathy at the orbital apex, it is likely that the patient also had some sensory changes from the ophthalmic division of the trigeminal nerve, but this was not documented in the report. Furthermore, the patient likely had a left Horner's syndrome as well due to this compressive process. Thus, the amount of dilatation of the left pupil confirms the location neuro-ophthalmologically as being at the site of the orbital apex—had the patient only had an oculomotor palsy, the unopposed sympathetic pathway to the pupil could well have led to more pupillary dilation than seen in the photographs. The observation that the patient demonstrated defective abduction of the left eye was consistent with the patient having a sixth nerve palsy, and this could have been confirmed simply by clinical evaluation of the reduced velocity of the abducting saccade in this patient (8). Moreover, it would have been good to confirm that there was indeed a fourth nerve palsy, as the authors imply, demonstrated along the usual lines of dynamic inspection of intorsion of the left eye in rapid binocular downgaze in attempted abduction. We welcome Professor Newman's team's response, particularly in light of the possibility of a left Ab3. Thomas P. Toohey, BMed University of New South Wales, Sydney, Australia Elizabeth L. S. Wong, BMed University of New South Wales, Sydney, Australia Letters to the Editor: J Neuro-Ophthalmol 2021; 41: 135-140 Department of Ophthalmology, Prince of Wales Hospital, Sydney, Australia Eugene Ting, MMed, MBBS Royal Brisbane and Women's Hospital, Brisbane, Australia Nicholas Xiradis, BMedSc, MD Department of Ophthalmology, Prince of Wales Hospital, Sydney, Australia Muhammad Khan, BMed Zhi Wei Lim, BSc(Hons) University of New South Wales, Sydney, Australia Tyler Blah, BBiomedSci(Hons) University of Notre Dame, Sydney, Australia James Jiang, BSc, MD Yunding Li, MBBS Northern Beaches Hospital, Sydney, Australia Minas T. Coroneo, FRACS, MD Ashish Agar, FRANZCO, PhD University of New South Wales, Sydney, Australia Department of Ophthalmology, Prince of Wales Hospital, Sydney, Australia Ian C. Francis, FRACS, PhD University of New South Wales, Sydney, Australia Department of Ophthalmology, Prince of Wales Hospital, Sydney, Australia Northern Beaches Hospital, Sydney, Australia The authors report no conflicts of interest. REFERENCES 1. Kozic D, Nagulic M, Ostojic J, Samardzic M, Milic-Rasic V, Skender Gazibara M, Nuri Sener R. Malignant peripheral nerve sheath tumor of the oculomotor nerve. Acta Radiologica. 2006;47:595–598. 2. Fard MA, Montgomery E, Miller NR. Complete, pupilsparing third nerve palsy in a patient with a malignant peripheral nerve sheath tumor. Arch Ophthalmol. 2011;129:805–820. 139 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor 3. Rao A, Shah S, Sim B, Yun S, Jain N, Kalani MY, Francis IC. Neuroradiological endovascular intervention for diplopia in a case of aneurysmal aberrant regeneration of the third nerve. Cureus 2017;9:e1340. 4. Anan M, Nagai Y, Fudaba H, Kubo T, Ishii K, Murata K, Hisamitsu Y, Kawano Y, Hori Y, Nagatomi H, Abe T, Fujiki M. Third nerve palsy caused by compression of the posterior communicating artery aneurysm does not depend on the size of the aneurysm, but on the distance between the ICA and the anterior–posterior clinoid process. Clin Neurol Neurosurg. 2014;123:169–173. 5. Yan SY, Peng YJ, Lin CS, Peng GS, Chang PY. Isolated oculomotor nerve palsy as a paraneoplastic manifestation of gastric diffuse large B-cell lymphoma: a case report. Oncol Lett. 2014;8:1983–1985. 6. O'Day J, Billson F, King J. Ophthalmoplegic migraine and aberrant regeneration of the oculomotor nerve. Br J Ophthalmol. 1980;64:534–536. 7. Iaconetta G, de Notaris M, Cavallo LM, Benet A, Enseñat J, Samii M, Ferrer E, Prats-Galino A, Cappabianca P. The oculomotor nerve: microanatomical and endoscopic study. Neurosurgery. 2010;66:593–601. 8. Ling MLH, Tynan D, Ruan CW, Lau FS, Spencer SKR, Agar A, Francis IC. Assessment of saccadic velocity at the bedside. Neuroophthalmology 2020;44:71–75. Oculomotor Palsy Due to Malignant Nerve Sheath Tumor: Aberrant Regeneration of the Third Nerve but Without Pupil Involvement: Response abduction was detected in the left eye. The patient had complete ophthalmoplegia, and the velocity of the abducting saccade could not be assessed. Considering there was complete ophthalmoplegia and no torsion of the left eye in any direction (including with attempted downgaze), the fourth nerve was also involved in this case. Regarding involvement of the first sensory branch of the trigeminal nerve, the patient did have mild decreased sensation in that distribution on the left, with associated decreased left corneal sensation. We agree with the likelihood that the left sympathetic pathways were at least partially affected as well, given the ipsilateral mid-dilated nonreactive pupil. We appreciate the author's interest in our report, but aberrant regeneration of CN3 was not demonstrably present in our patient. W e would like to thank Toohey et al for their interest in our case report. In Figure 2, they note that the examiner's finger elevates the eyelid in all positions except when the patient looks up and to the right and indicate that they believe there is elevation of the left upper eyelid when the patient looks up and to the right. They go on to suggest that aberrant regeneration of the third cranial nerve (CN3) was present, specifically left eyelid retraction in adduction. We reviewed the figure in question and our original examination photographs and we did not detect any significant difference in the size of the palpebral fissure between left and right gaze. We include here an additional set of photographs without the examiner's hand in the frame to support this so that there is no confusion (Fig. 1). The examiner's finger was not elevating the eyelid when the patient looked up, up and right, and up and left. Rather, it was simply positioned in front of the brows in the upper frames of the figure holding the patient's head steady and making sure there was no brow overaction during testing of the extraocular movements. The patient's head did slightly turn right when he looked up and right, and this may be contributing to their observation. Toohey et al also reported that they noticed a minimal amount of abduction of the left eye. We reviewed the original photographs and our examination report and no Jonathan A. Micieli, MD, CM Department of Ophthalmology and Vision Sciences and Medicine (Neurology), University of Toronto, Toronto, Canada Nancy J. Newman, MD Departments of Ophthalmology, Neurology, and Neurological Surgery, Emory University School of Medicine, Atlanta, Georgia The authors report no conflicts of interest. FIG. 1. External photographs demonstrating no significant change in the size of the left palpebral fissure in right and left gaze. 140 Letters to the Editor: J Neuro-Ophthalmol 2021; 41: 135-140 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.