Gadoxetate Disodium-Enhanced Imaging of Gradenigo Syndrome in End-Stage Renal Disease

A 65-year-old man with end-stage renal disease on peritoneal dialysis was admitted for new onset binocular double vision, failure to thrive, and debilitating right-sided headaches. Medical history was significant for tympanomastoidectomy for polymicrobial mastoiditis and treatment with IV antibiotics. MRI brain without contrast was read by radiology initially as showing expected postsurgical changes; however, given patient's history of mastoiditis infection, there was a high clinical suspicion for Gradenigo syndrome. MRI brain was repeated with gadoxetate contrast to minimize the risk of nephrogenic systemic fibrosis (NSF) in a patient with severe renal disease and this revealed an intracranial empyema involving both the trigeminal and abducens nerves confirming the diagnosis of Gradenigo syndrome. This case presented a diagnostic challenge because of suboptimal visualization on initial nonenhanced MRI. Gadoxetate was chosen because of its unique properties including high hepatobiliary excretion making it a safer form of gadolinium-based contrast agent that may not have the potential to precipitate NSF.

Photo and Video Essay Section Editors: Melissa W. Ko, MD Dean M. Cestari, MD Peter Quiros, MD Gadoxetate Disodium-Enhanced Imaging of Gradenigo Syndrome in End-Stage Renal Disease Victoria Sattarova, MD, MSc, Mehmet Gencturk, MD, Michael S. Lee, MD, Collin M. McClelland, MD FIG. 1. Axial FLAIR image demonstrates tentorial thickening (solid arrows) and decreased cavernous sinus hyperintense signal on the right (dashed arrows). Abstract: A 65-year-old man with end-stage renal disease on peritoneal dialysis was admitted for new onset binocular double vision, failure to thrive, and debilitating right-sided headaches. Medical history was significant for tympanomastoidectomy for polymicrobial mastoiditis and treatment with IV antibiotics. MRI brain without contrast was read by radiology initially as showing expected postsurgical changes; however, given patient’s history of mastoiditis infection, there was a high clinical suspicion for Gradenigo syndrome. MRI brain was repeated with gadoxetate contrast to minimize the risk of nephrogenic systemic fibrosis (NSF) in a patient with severe renal disease and this revealed an intracranial empyema involving both the trigeminal and abducens nerves confirming the diagnosis of Gradenigo syndrome. This case presented a diagnostic challenge because of suboptimal visualization on initial nonenhanced MRI. Gadoxetate was chosen because of its unique properties including high hepatobiliary excretion making it a safer form of gadolinium-based contrast agent that may not have the potential to precipitate NSF. Departments of Ophthalmology and Visual Neurosciences (VS, MSL, CMM) and Radiology (MG), University of Minnesota, Minneapolis, Minnesota. Journal of Neuro-Ophthalmology 2021;41:e375–377 doi: 10.1097/WNO.0000000000001218 © 2021 by North American Neuro-Ophthalmology Society The authors report no conflicts of interest. Address Correspondence to Collin M. McClelland, MD, Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Phillips-Wangensteen Building, Floor 9, 516 Delaware Street SE, Minneapolis, MN 55455; E-mail: [e-mail] Sattarova et al: J Neuro-Ophthalmol 2021; 41: e375-e377 A 65-year-old man with end-stage renal disease (ESRD) on daily peritoneal dialysis was admitted to the neue375 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay rology service for new onset binocular double vision and failure to thrive. Extraocular movements showed a right complete abduction deficit. He had undergone radical tympanomastoidectomy 5 months before admission, followed by a .6 week course of IV antibiotics for polymicrobial pseudomonas aeruginosa, coagulase negative staphylococcus, and corynebacterium mastoiditis resulting in a right facial nerve palsy with severe exposure keratopathy. Several weeks after completion of antibiotics, he developed rightsided debilitating headaches in the V1–V2 distribution and a decrease in appetite leading to 45 lbs weight loss. MRI brain without contrast was obtained given patient’s ESRD that demonstrated tentorial thickening and decreased signal in the cavernous sinus on the right (Fig. 1). After the initial MRI, the diagnosis remained unclear and neuroophthalmology was consulted. Given the recent history of mastoiditis requiring debridement, severe right V1–V2 distribution pain, and new right CN VI palsy, there was a high clinical suspicion for Gradenigo syndrome. After consultation with neuro-radiology, MRI brain was repeated with gadoxetate contrast to minimize the risk of nephrogenic systemic fibrosis (NSF). This revealed an empyema along the right cerebellar tentorium extending along right trigeminal nerve, right abducens nerve, and right cavernous sinus with adjacent right petrous apicitis (Fig. 2A, B). These findings along with cerebrospinal fluid pleocytosis solidified the diagnosis of Gradenigo syndrome, and the patient was started on appropriate IV antibiotics. Gradenigo syndrome presents as a triad of suppurative otitis media, pain in the V1 and V2 distribution, and abducens nerve palsy. This results from the spread of infection to the petrous apex of the temporal bone causing apical petrositis and the close anatomical proximity of the affected trigeminal ganglion and abducens nerve (1). Early diagnosis is vital given the potential for progressive basilar meningitis and intracranial abscess (2). This case presented an initial diagnostic challenge because of suboptimal visualization on initial nonenhanced neuroimaging. Gadolinium was withheld by the primary team because of a concern for inducing NSF that is a rare, but potentially life-threatening complication that follows administration of a gadolinium-based contrast agent (GBCA) in patients with the following: ESRD on dialysis, chronic kidney disease with estimated GFR ,60 mL min21 1.73m22, or acute kidney injury (3). NSF results in progressive fibrosis of connective tissue throughout the body affecting the skin and joints, and less commonly, the myocardium, pleura, nerves and skeletal muscle. First described in 2000 (4) and linked to a GBCA in 2006 (5), the precise pathophysiology of NSF remains unclear. It typically presents within 1–8 weeks of GBCA administration and has no definitive treatment. Thus, the prevention of the disease through identification of patients who are at risk is key. Awareness of this disease and modifications in GBCA administration protocols based on renal function after the 2007 FDA warning as well as international radiological societies guidelines in at risk populations has led to a near extinction of NSF. Transmetallation (dechelation) has been proposed as a potential mechanism underlying NSF. This theory proposes that poor renal function leads to longer GBCA excretion time and transmetallation enhancing gadolinium deposition in tissues (6). This correlates, although not perfectly, with the observation that macrocyclic and ionic GBCAs are more tightly bound to protein than linear and nonionic GBCAs and that the latter forms of gadolinium contrast have a higher tendency to dechelate and exist in free form resulting in higher associated rates of NSF (6). FIG. 2. A. Postcontrast T1axial image with fat saturation demonstrates peripherally enhancing fluid intensity along the right tentorium (white arrows) corresponding with the tentorial thickening seen on FLAIR in Figure 1. Empyema abuts the cisternal trigeminal nerve, abducens nerve, and extends to the cavernous sinus (black arrow). Also of note is decreased enhancement in the right cavernous sinus (dashed white arrows). B. Postcontrast T1 axial image at the level of petrous apex shows mild asymmetric enhancement on the right (white arrows), consistent with petrous apicitis. e376 Sattarova et al: J Neuro-Ophthalmol 2021; 41: e375-e377 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay As of 2016, there are 9 GBCAs approved by FDA. The 3 contraindicated inpatients with renal disease are linear GBCAs including gadodiamide, gadopentetate dimeglumine, and gadoversetamide. On the other hand, agents associated with few, if any cases of NSF include gadobenate dimeglumine, gadobutrol, gadoteric acid, gadoteridol, and gadoxetate (7). Gadoxetate, used in our clinical scenario, is a linear, ionic GBCA and has the highest hepatobiliary excretion (50%) of the GBCA and is often used to evaluate liver pathology (8). In addition, its ionic nature leads to a lower dissociation rate (2%) compared with nonionic linear GBCAs, such as gadodiamide and gadoversetamide. A 2018 report studying NSF cases associated with GBCAs from 2006 to 2016 found that after more than 3.6 million administrations of gadoxetate, there were no reports of associated NSF (3). In addition, a prospective multicenter study by Endrikat et al report that of the 193 patients with renal impairment there were no cases of NSF after gadoxetate administration for liver imaging during 24month follow-up (9). A recent retrospective study found no cases of NSF among 7,820 MRI examinations using gadoxetate including 482 examinations among patients with moderate and severe renal failure (10). When contrast administration becomes necessary in patients at high risk for NSF, gadoxetate could be considered as a significantly safer form of GBCA that may not have the potential to precipitate NSF. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: V. Sattarova, M. Gencturk, M. S. Lee, and C. M. McClelland; b. Acquisition of data: V. Sattarova, M. Gencturk, and C. M. McClelland; c. Analysis and interpretation of data: V. Sattarova, M. Gencturk, M. S. Lee, and C. M. McClelland. Category 2: a. Drafting the manuscript: V. Sattarova, and C. M. McClelland; b. Revising it for intellectual content: V. Sattarova, M. Gencturk, M. S. Lee, and C. M. McClelland. Category 3: a. Final Sattarova et al: J Neuro-Ophthalmol 2021; 41: e375-e377 approval of the completed manuscript: V. Sattarova, M. 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Radiology. 2020;297:556–562. e377 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.