Sphenoid Sinus Fungal Ball Presenting as Ipsilateral Primary Aberrant Regeneration of the Third Cranial Nerve

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Sphenoid Sinus Fungal Ball Presenting as Ipsilateral Primary Aberrant Regeneration of the Third Cranial Nerve Michael Lin, BMed, BSc(Med)Hons, MD, Jessica J. M. Huang, BMed, Ivy W. Jiang, BMed, Sascha K. R. Spencer, BMed, MD, Raewyn G. Campbell, FRACS, BMed(Hons), BAppSc(Physio), GradDipEx&SportSc, FARS, Ben Panizza, MBA, FRACS, FACS, Toos A. Sach, FRANZCR, Ian C. Francis, FRANZCO, FRACS, PhD A well 93-year-old woman presented for routine review of her normal pressure glaucoma. On examination, she was noted to have left upper lid retraction, augmented in downgaze, a slightly dilated but reactive left pupil, and miosis on adduction of the left eye. There was defective adduction of the left eye (23/4), with reduced adducting saccadic velocity. Defective elevation and depression confirmed a typical left aberrant regeneration of the third cranial nerve (Ab3). Despite this, the patient was asymptomatic. She did not have diabetes and was not immunosuppressed. She denied neurological symptoms, and there had been no recent head trauma. Her visual acuity was 6/9 bilaterally. Intraocular pressures were normal on her customary ocular hypotensive therapy. Computed tomography (CT) of the sinuses revealed a completely opacified left sphenoid sinus with hyperdensities. The sinus margins demonstrated bony sclerosis, with erosion of the bone laterally along with osteitis (Fig. 1A). Brain MRI and angiography demonstrated soft tissue hypointense and hyperintense signal changes within the left sphenoid sinus (Fig. 1B). There was no evidence of intracranial aneurysm or focal abnormalities along the course of the third nerve. However, there was narrowing of the left superior orbital fissure (SOF) from the lateral expansion of the lateral wall of Faculty of Medicine (ML, JJMH, IWJ, SKRS, ICF), University of New South Wales, Sydney, Australia; Department of Ophthalmology (ML), Sydney and Sydney Eye Hospital, Sydney, Australia; Department of Ophthalmology (SKRS, ICF), Prince of Wales Hospital, Sydney, Australia; Department of Otolaryngology – Head and Neck Surgery (RGC), Macquarie University Hospital, Sydney, Australia; Department of Otolaryngology – Head and Neck Surgery (RGC), Royal Prince Alfred Hospital, Sydney, Australia; Department of Otolaryngology – Head and Neck Surgery (BP), Princess Alexandra Hospital, Brisbane, Australia; Faculty of Medicine (BP), University of Queensland, Brisbane, Australia; and San Radiology and Nuclear Medicine (TAS), Sydney Adventist Hospital, Sydney, Australia. The authors report no conflicts of interest. Address correspondence to Ian C. Francis, FRANZCO, FRACS, PhD, 38B Albert Avenue, Chatswood, NSW 2067, Australia; E-mail: [e-mail] Lin et al: J Neuro-Ophthalmol 2023; 43: e253-e255 left sphenoid sinus (Fig. 2), with reactive changes suggesting inflammation extending into the SOF. Otorhinolaryngological review led to the diagnosis of a sphenoid sinus fungal ball (SSFB), which was removed by endoscopic transethmoidal/transsphenoidal surgery. Typical black fungal material with pus was seen at surgery. Aspergillus fumigatus complex was cultured. The patient’s neuroophthalmological findings resolved. On review at 9 months postoperatively, the left sphenoidal sinus was clear and normally aerated. In Ab3, regenerating fibers of the third nerve were miswired, resulting in muscle cocontraction and pupil changes. Ab3 occurs in third-degree nerve injuries, where both axon and endoneurium are disrupted, sometimes resulting in regenerating axons growing into incorrect tracts (1). Although Ab3 is most commonly secondary, occurring after tumor, trauma, or aneurysm (1), primary Ab3, with no preceding third cranial nerve palsy, is most commonly associated with slow-growing cavernous sinus lesions such as aneurysms (2) and meningiomas (3). Although controversial, it is considered that simultaneous subclinical nerve damage and regeneration can lead to electrical cross talk between individual fibers of the third nerve, known as ephaptic transmission (1). SSFB is a relatively rare form of noninvasive fungal sinusitis, commonly caused by Aspergillus species, and typically involving a single sinus (4). Although common symptoms include headache, facial pain, nasal congestion, rhinorrhea, and postnasal drip, the presentation of SSFB can be nonspecific and indolent (4,5). Affected patients are usually female and elderly. CT imaging is the mainstay for diagnosis, typically demonstrating near-complete opacification of the affected sinus, often with adjacent thinning and bony erosion from pressure, and/or an osteitic reaction with sclerosis and thickening. This may represent a chronic inflammatory response, with opportunistic bacterial infections likely contributing (4). Commonly cultured fungi include Aspergillus species such as A. fumigatus and A. flavus (4). Despite being classified as noninvasive, gradual erosion of the surrounding bone can potentially cause compression and e253 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Coronal computed tomography (CT) (bone window) (A) and T2 MRI (B) images demonstrating a left sphenoid sinus fungal ball. A. Coronal CT showing erosion (solid arrow) and osteitis (dashed arrow) involving the superolateral wall of the sphenoid. The walls of the sphenoid sinus are uniformly widened and sclerotic. These changes are commonly seen in chronic bone inflammation. The sphenoid sinus demonstrates complete soft tissue opacity, with CT hyperdensities and calcification within the fungal ball (arrowhead). B. Coronal T2 MRI showing a rounded expansile appearance of the left sphenoid sinus as compared with the right, with visible convexity superolaterally in the region of the superior orbital fissure (dashed arrow). The sinus contents demonstrate a particulate low signal consistent with the fungal material (solid arrow), lying within the hyperintense chronic inflammatory infiltrate (arrowhead). The hyperintense widened appearance of the surrounding bone correlated with the sclerosis seen on CT and is consistent with progressive osteitis. damage of adjacent neurovascular structures, including the optic nerve, oculomotor nerve, and internal carotid artery. Consequently, significant morbidity or mortality may ensue if an SSFB is left untreated. Treatment with endoscopic sphenoidotomy, either transnasally or transethmoidally, is effective and safe, with minimal disease recurrence (4,5). Ab3 from fungal sinusitis has been described twice previously. In 1992, Dooley et al (6) reported a 45-year-old man with an indolent orbital apex syndrome caused by occult mucormycosis. The patient was treated intensively with surgical debridement and intravenous antifungals, with clinical improvement. Eighteen months later, he was noted to have Ab3. In 2016, Rosenvald et al (7) reported a 55- e254 FIG. 2. Coronal T2 MRI (A) and axial T1 postcontrast (B) images demonstrating narrowing of the superior orbital fissure (SOF) from lateral expansion of the lateral wall of the left sphenoid sinus. A. Coronal T2 showing the expected position of the oculomotor nerve in the SOF indicated by the dashed closed arrow. The oculomotor nerve and adjacent nerves are closely apposed to the relatively thickened inferomedial wall of the SOF and the osteitic and inflamed lateral wall of the sphenoid sinus (arrowhead), with inflammatory change extending into the SOF. The fungal ball in the left sphenoid sinus is labeled with the dashed open arrow. The lateral bony wall of the SOF (solid closed arrow) and the ophthalmic artery (solid open arrow) are indicated. B. Axial T1 postcontrast image showing a high-signal irregular profile of enhancement circumferentially surrounding the left sphenoid sinus fungal ball. This has a crenated, convex lateral profile (arrowhead), representing a mucoperiosteal reaction. The left oculomotor nerve in the inflamed SOF is labeled (solid open arrow). The medial bony wall of the left SOF is indicated with a dashed closed arrow while the lateral bony wall of the SOF is labeled with a solid closed arrow. The right orbital apex is normal (dashed open arrow). year-old with a secondary Ab3, occurring 12 years after a third nerve palsy due to invasive A. fumigatus. Thus, the literature demonstrates that the current case is the first in which an Ab3 developed in association with an SSFB. In this case, the chronic bony erosion and expansion of the osteitic changes in the lateral sphenoid sinus wall led to the narrowing of the SOF (Fig. 2). There was also extension of inflammatory changes into the SOF. These slowly developing Lin et al: J Neuro-Ophthalmol 2023; 43: e253-e255 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence changes could have predisposed to the simultaneous subclinical nerve damage and regeneration that is believed to produce Ab3. Only the oculomotor nerve was clinically involved, perhaps because of its medial and inferior anatomic position within the SOF, being closely apposed to the inflammatory change on the lateral wall of the sphenoid sinus. The incidental finding of a left Ab3 was, therefore, a unique presentation of a left SSFB and led to the clinical diagnosis in a well patient. This diagnosis, clarified by the appropriate radiology, allowed definitive surgical treatment by minimally invasive endoscopic sphenoidotomy, potentially saving the patient’s life. This case emphasizes the importance of recognizing an Ab3 and attempting to determine its cause. STATEMENT OF AUTHORSHIP Conception and design: M. Lin, I. C. Francis; Acquisition of data: M. Lin, S. K. R. Spencer, R. G. Campbell, T. Sach, I. C. Francis; Analysis and interpretation of data: M. Lin, J. J. M. Huang, I. W. Jiang, S. K. R. Spencer, R. G. Campbell, B. Panizza, T. Sach, I. C. Francis. Drafting the manuscript: M. Lin and I. C. Francis; Revising it for intellectual Lin et al: J Neuro-Ophthalmol 2023; 43: e253-e255 content: M. Lin, J. J. M. Huang, I. W. Jiang, S. K. R. Spencer, R. G. Campbell, B. Panizza, T. Sach, I. C. Francis. Final approval of the completed manuscript: M. Lin, J. J. M. Huang, I. W. Jiang, S. K. R. Spencer, R. G. Campbell, B. Panizza, T. Sach, I. C. Francis. REFERENCES 1. Weber ED, Newman SA. Aberrant regeneration of the oculomotor nerve: implications for neurosurgeons. Neurosurg Focus. 2007;23:E14. 2. Cox TA, Wurster JB, Godfrey WA. Primary aberrant oculomotor regeneration due to intracranial aneurysm. Arch Neurol. 1979;36:570–571. 3. Schatz NJ, Savino PJ, Corbett JJ. Primary aberrant oculomotor regeneration: a sign of intracavernous meningioma. Arch Neurol. 1977;34:29–32. 4. Bowman J, Panizza B, Gandhi M. Sphenoid sinus fungal balls. Ann Otol Rhinol Laryngol. 2007;116:514–519. 5. Karkas A, Rtail R, Reyt E, Timi N, Righini CA. Sphenoid sinus fungus ball. Eur Arch Otorhinolaryngol. 2013;270:893–898. 6. Dooley DP, Hollsten DA, Grimes SR, Moss JJ. Indolent orbital apex syndrome caused by occult mucormycosis. J Clin Neuroophthalmol. 1992;12:245–249. 7. Rosenvald OR, Lessell S. Pupillary sign of aberrant regeneration of the third nerve. Neurology. 2016;86:1746. e255 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.