MRI Mucosal Restricted Diffusion and Reduced Enhancement In Sino-Orbital Invasive Fungal Sinusitis

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD MRI Mucosal Restricted Diffusion and Reduced Enhancement In Sino-Orbital Invasive Fungal Sinusitis Ahmad Halawa, MD, John Kim, MD, Toshio Moritani, MD, Jonathan D. Trobe, MD P rompt diagnosis of sino-orbital invasive fungal sinusitis (IFS) is critical in preserving vision and life (1). Segmental restricted diffusion and reduced enhancement in the mucosa of the paranasal sinuses, which can signify ischemic necrosis, are sparsely documented early signs (2). We report a case in which failure to recognize these often subtle abnormalities may have delayed the diagnosis and treatment and adversely affected the clinical course of the illness. A 75-year-old man developed blurred vision in the left eye and left temporal headache. He had myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria treated with prednisone and with ravulizumab, a humanized monoclonal antibody complement inhibitor. The best-corrected visual acuity was 20/50 in the right eye and finger counting in the left eye. There was an afferent pupillary defect in the left eye. Confrontation visual fields were full in the right eye but revealed dense deficits in all 4 quadrants in the left eye. The rest of the ophthalmologic examination was normal, and there were no systemic or neurologic abnormalities. Westergren sedimentation rate, complete blood count, and standard chemistries were normal, but C-reactive protein was 5.4 (normal ,0.6). Brain MRI, performed on the day of presentation, was interpreted as showing left apical orbital optic nerve sheath enhancement (Fig. 1A, B). However, in retrospect, subtle segmental restricted diffusion and reduced enhancement were present in the mucosa of the posterior and lateral wall of the left sphenoid sinus (Fig. 1C–E). Head CT demonstrated a softtissue density in the left sphenoid sinus corresponding to the abnormal mucosal thickening on MRI (Fig. 1F). Based strictly on the orbital signs, a presumptive diagnosis of optic neuritis was made, and the patient was treated with methylprednisolone 1 g/day for 3 days and discharged on prednisone 60 mg daily. Departments of Ophthalmology and Visual Sciences, Kellogg Eye Center (AH, JDT), Radiology (Neuroradiology) (JK, TM), and Neurology (JDT), University of Michigan, Ann Arbor, Michigan. The authors report no conflicts of interest. Address correspondence to Jonathan D. Trobe, MD, Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI 48105, E-mail: [e-mail] Halawa et al: J Neuro-Ophthalmol 2022; 42: e401-e403 Seven days after his initial presentation, he came to the outpatient clinic with no light perception in the left eye, complete left upper lid ptosis, a fixed, dilated left pupil, left ophthalmoplegia, and numbness in the V1 distribution. In retrospect, MRI performed on that day showed more conspicuous segmental restricted diffusion (Fig. 2A, B) and reduced enhancement in the same region of the sphenoid sinus (Fig. 2C), but these abnormalities were again not described. The report did mention that the left cavernous sinus and adjacent pachymeninges now showed enhancement (Fig. 2C) and that restricted diffusion had appeared in the left optic nerve (Fig. 2D). In the face of the worsening clinical course, the presumptive diagnosis was changed to IFS, and the patient underwent nasal endoscopy, left maxillary antrostomy, total ethmoidectomy, sphenoidotomy, and left middle turbinate resection, which disclosed necrotic sinus mucosa in the very region highlighted by the overlooked MRI signs. The pathologic specimen revealed fungal elements, which later cultured Aspergillus fumigatus. He was treated with intravenous amphotericin, voriconazole, and vancomycin. Despite aggressive antifungal treatment, the patient later developed no light perception and ophthalmoplegia in the right eye. The patient died 27 days after initial presentation. The MRI segmental lack of enhancement and restricted diffusion in the mucosa of the left lateral sphenoid sinus were finally acknowledged in a review conducted 14 days after initial presentation. The widely recognized CT abnormalities of sino-orbital IFS include paranasal sinus mucosal and periantral thickening, bone dehiscence, and extraconal orbital invasion (3). The well-known MRI abnormalities are paranasal mucosal thickening, restricted diffusion in the optic nerve (4) and brain parenchyma. Less widely reported are the signs we present here: segmental lack of enhancement and restricted diffusion in the mucosa of the adjacent paranasal sinus, especially that of the sphenoid and ethmoid sinuses and nasal turbinates (2,5). We highlight the paranasal mucosal signs, which reflect the necrotizing effects of vaso-occlusion because they probably occur before the disease has affected the orbit. We call attention to the segmental nature of these signs. Each sign by itself might be ignored, but when e401 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. MRI studies performed at initial presentation. Axial (A) and coronal (B) fat-saturated postcontrast T1 scans show left apical optic nerve sheath enhancement (arrows). Axial diffusion-weighted study (C) shows high signal intensity in a segment of the left lateral sphenoid sinus mucosa (arrows). The corresponding ADC map (D) shows low signal intensity in that segment (arrowheads), confirming restricted diffusion. Coronal postcontrast T1 image (E) shows segmental reduced enhancement in the same lateral sinus mucosal region (arrowheads). Head CT (F) demonstrates a soft-tissue density in the left sphenoid sinus (arrows) in the location of the abnormal mucosal thickening on MRI. These mucosal abnormalities were recognized only late in the course of the patient’s illness. reduced enhancement and restricted diffusion overlap, they should be considered as signs of a necrotic fungal process. Given the importance of early diagnosis and e402 treatment, careful scrutiny of this region in the setting of optic neuropathy in an immunocompromised patient is particularly important. Halawa et al: J Neuro-Ophthalmol 2022; 42: e401-e403 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. MRI studies performed 7 days after initial presentation. Axial diffusion-weighted imaging (A) and corresponding ADC map (B) show that the segmental restricted diffusion of the left lateral sphenoid sinus mucosa (arrowhead) has become more obvious (arrows). The coronal postcontrast T1 fat-saturated image (C) shows reduced enhancement of that segment of the sinus mucosa (arrowheads), as well as exuberant enhancement of the left cavernous sinus and adjacent pachymeninges (arrows). Restricted diffusion is present in the entire length of the left optic nerve (arrow, D). STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: A. Halawa, J. Kim, T. Moritani, and J. D. Trobe; b. Acquisition of data: A. Halawa, J. Kim, T. Moritani, and J. D. Trobe; c. Analysis and interpretation of data: A. Halawa, J. Kim, T. Moritani, and J. D. Trobe. Category 2: a. Drafting the manuscript: A. Halawa and J. D. Trobe; b. Revising it for intellectual content: J. D. Trobe. Category 3: a. Final approval of the completed manuscript: A. Halawa, J. Kim, T. Moritani, and J. D. Trobe. REFERENCES 1. Turner JH, Soudry E, Nayak JV, Hwang PH. Survival outcomes in acute invasive fungal sinusitis: a systematic review and Halawa et al: J Neuro-Ophthalmol 2022; 42: e401-e403 2. 3. 4. 5. quantitative synthesis of published evidence. Laryngoscope. 2013;123:1112–1118. Safder S, Carpenter JS, Roberts TD, Bailey N. The “Black Turbinate” sign: an early MR imaging finding of nasal mucormycosis. AJNR Am J Neuroradiol. 2010;31:771– 774. Middlebrooks EH, Frost CJ, De Jesus RO, Massini TC, Schmalfuss IM, Mancuso AA. 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