Localizing Thalamomesencephalic Afferent and Efferent Pupillary Defects

A 42-year-old Algerian man presented for binocular oblique diplopia, hypersomnolence with drop attacks, bilateral hearing loss, and thoracic pain. He had a right thalamomesencephalic hemorrhage due to an underlying cavernous malformation treated with subtotal surgical resection. On neuro-ophthalmic examination, the patient had a left relative afferent pupillary defect and a right oculosympathetic efferent pupillary defect (i.e., Horner syndrome) in addition to other thalamomesencephalic eye and neurologic signs (right fourth nerve palsy, hearing loss, hemiparesis, and thalamic pain). Clinicians should recognize the localizing value of this unique constellation of mesencephalic afferent and efferent pupillary defects.

Photo Essay Section Editors: Melissa W. Ko, MD Dean M. Cestari, MD Peter Quiros, MD Localizing Thalamomesencephalic Afferent and Efferent Pupillary Defects Ardalan Sharifi, MD, Rohini R. Sigireddi, MD, Lance J. Lyons, MD, Ashwini T. Kini, MD, Bayan A. Al Othman, MD, Andrew G. Lee, MD Downloaded from http://journals.lww.com/jneuro-ophthalmology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 05/04/2022 FIG. 1. Preoperative T1 sagittal and coronal MRI of the brain showing a heterogenous mass at the right thalamomesencephalic junction due to an underlying hemorrhage from cavernous malformation. Abstract: A 42-year-old Algerian man presented for binocular oblique diplopia, hypersomnolence with drop attacks, bilateral hearing loss, and thoracic pain. He had a right thalamomesencephalic hemorrhage due to an Department of Ophthalmology and Visual Sciences (AS, LJL, AGL), University of Texas Medical Branch, Galveston, Texas; Department of Ophthalmology (RRS, AGL), Baylor College of Medicine, Houston, Texas; Department of Ophthalmology (ATK, BAAO, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Departments of Ophthalmology (AGL), Neurology, and Neurosurgery, Weill Cornell Medicine, New York, New York; Section of Ophthalmology (AGL), University of Texas Maryland Anderson Cancer Center, Houston, Texas; and Department of Ophthalmology (AGL), The University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www. jneuro-ophthalmology.com). A. Sharifi and R. R. Sigireddi contributed equally to production of this article. 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] e136 underlying cavernous malformation treated with subtotal surgical resection. On neuro-ophthalmic examination, the patient had a left relative afferent pupillary defect and a right oculosympathetic efferent pupillary defect (i.e., Horner syndrome) in addition to other thalamomesencephalic eye and neurologic signs (right fourth nerve palsy, hearing loss, hemiparesis, and thalamic pain). Clinicians should recognize the localizing value of this unique constellation of mesencephalic afferent and efferent pupillary defects. Journal of Neuro-Ophthalmology 2021;41:e136–138 doi: 10.1097/WNO.0000000000000903 © 2020 by North American Neuro-Ophthalmology Society A 42-year-old Algerian man presented to the neuroophthalmology service with binocular oblique diplopia, hypersomnolence, bilateral hearing loss, and thoracic pain. He had developed unexplained coma resulting in left-sided hemiparesis 20 years prior, but had no other medical history. The patient was taking lisdexamfetamine dimesylate for somnolence, gabapentin for thoracic pain, and zolpidem for sleep. Sharifi et al: J Neuro-Ophthalmol 2021; 41: e136-e138 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo Essay He was stable for 20 years until 1 year before presentation, when the patient reported new-onset headache, nausea, vomiting, gait ataxia, worsening of his pre-existing left hemiparesis, and intermittent binocular horizontal and vertical diplopia. At that time, MRI of the brain (Fig. 1) revealed a heterogeneous mass with hemorrhage at the right thalamomesencephalic junction due to an underlying cavernous malformation. He underwent surgical resection through a right occipital transtentorial approach. Postoperative MRI showed residual susceptibility artifact at the level of the resected right thalamomesencephalic junction at the site of previous cavernous malformation (Fig. 2). After surgery, the patient had persistent left hemiparesis, left-sided facial droop, left facial and thoracic visceral pain, bilateral hearing loss, binocular horizontal and vertical diplopia, increased daytime sleepiness, and drop attacks. On neuro-ophthalmic examination, the patient’s visual acuity was 20/20 in both eyes, and Ishihara color plate testing was normal (14/14) in both eyes. Automated perimetry (Humphrey visual field 24-2) was normal in both eyes. The pupils measured 3 mm in the light and 4 and 5 mm in the dark with a dilation lag in the right eye consistent with a Horner syndrome. Administration of topical apraclonidine 0.5% showed reversal of anisocoria and dilation of the right pupil confirming the right Horner syndrome. A left relative afferent pupillary defect (RAPD) was noted (See Supplemental Digital Content 1, available at http://links.lww.com/WNO/A385). Slit-lamp examination was normal in both eyes. Fundus examination showed no disk edema nor optic atrophy, and optical coherence tomography of the optic nerve was normal in both eyes. Motility examination showed right hypertropia, and the three-step test implicated a right fourth nerve palsy producing the binocular diplopia. On follow-up examination, his horizontal diplopia was only intermittent, and he could fuse in the primary position. The remainder of the neuro-ophthalmic examina- tion was unchanged. The hypersomnolence was somewhat improved by lisdexamfetamine dimesylate treatment, and the thalamic thoracic pain was stable on gabapentin. This patient had an interesting combination of both ipsilateral oculosympathetic efferent defect (i.e., right Horner syndrome) and a tectal contralateral RAPD. The normal visual acuity, visual field testing, and optic nerve on examination and unremarkable optical coherence tomography are consistent with a tectal localization for the RAPD. The pretectal nucleus projects fibers to both the ipsilateral and contralateral Edinger–Westphal nuclei (1). A lesion on the right side of the mesencephalon can affect both ipsilateral descending efferent sympathetic fibers and contralateral projections from the left pretectal afferent fibers thus producing the unique and localizing constellation of clinical findings of a right Horner syndrome and left RAPD. This patient had diplopia, and the combination of an ipsilateral fourth nerve palsy and a contralateral RAPD is a well-known localizing finding to the inferior colliculus level of the midbrain (2). Interestingly, the involvement of the adjacent inferior colliculus, part of the tectal midbrain responsible for the auditory pathway, was also believed to be the cause of the patient’s hearing loss (3). Our patient suffered from hypersomnolence and drop attacks, the etiology of which is likely damage to the reticular activating system (RAS). The RAS promotes wakefulness and consciousness from its position at the paramedian tegmentum of the upper brainstem and can be damaged by thalamomesencephalic hemorrhage (4,5). Hypersomnolence from cerebral vascular damage to the ascending RAS has resolved with full resolution after comprehensive rehabilitation (5). Finally, our patient had thoracic pain, described as visceral, sharp, and radiating throughout the chest. We hypothesize that this pain is the result of damage to the thalamic nuclei, which are known to regulate and relay pain signals through the spinothalamic tract. Alternatively, insult to FIG. 2. Postoperative MRI of the brain showing residual susceptibility artifact at the level of the resected right thalamomesencephalic junction at the site of previous cavernous malformation. Sharifi et al: J Neuro-Ophthalmol 2021; 41: e136-e138 e137 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo Essay pain-modulatory centers in the rostral mesencephalon including the locus coeruleus, raphe nuclei, and periaqueductal gray disrupts descending inhibitory fibers which serve to extinguish ascending nocioceptive signals, potentially leading to the perception of pain. In conclusion, the finding of an ipsilateral oculosympathetic efferent pupillary defect (i.e., Horner syndrome) and a contralateral tectal RAPD is an interesting and unique combination of afferent and efferent pupillary defect that should suggest a midbrain localization. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: A. Sharifi, R. R. Sigireddi, L. J. Lyons, A. T. Kini, B. A. Al Othman, and A. G. Lee; b. Acquisition of data: A. Sharifi, R. R. Sigireddi, L. J. Lyons, A. T. Kini, B. A. Al Othman, and A. G. Lee; c. Analysis and interpretation of data: A. Sharifi, R. R. Sigireddi, L. J. Lyons, A. Kini, B. A. Al Othman, and A. G. Lee. Category 2: a. Drafting the manuscript: A. Sharifi, R. R. Sigireddi, L. J. Lyons, A. T. Kini, B. A. Al Othman, and e138 A. G. Lee; b. Revising it for intellectual content: A. Sharifi, R. R. Sigireddi, L. J. Lyons, A. T. Kini, B. A. Al Othman, and A. G. Lee. Category 3: a. Final approval of the completed manuscript: A. G. Lee. REFERENCES 1. 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