Slowly Progressive Optic Perineuritis as the First Clinical Manifestation of Sarcoidosis

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Slowly Progressive Optic Perineuritis as the First Clinical Manifestation of Sarcoidosis Federica Garrì, MD, Francesca Rinaldi, MD, Paola Perini, MD, Alessandro Miscioscia, MD, Davide Simonato, MD, Marco Pizzi, MD, Monica Margoni, MD, Paolo Gallo, MD, PhD Downloaded from http://journals.lww.com/jneuro-ophthalmology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 05/04/2022 N eurosarcoidosis occurs approximately in 5%–10% of all patients with sarcoidosis and may involve any part of the brain, resulting in a wide spectrum of clinical syndromes. Although cranial nerves are often affected, the isolated involvement of the optic nerve is a rare event (1). The inflammation of the optic nerve sheath, that is, optic perineuritis, is even more rare especially at clinical onset (2,3). We report a quite unique case of slowly progressive bilateral visual loss due to increased thickness of optic nerve sheath with optic perineuritis, as the first presenting manifestation of sarcoidosis. CASE DESCRIPTION In November 2018, a previously healthy 56-year-old white man developed a painless blurred vision in the right eye, associated with mild photophobia. In January 2019, he underwent an ophthalmological examination that revealed a reduction in visual acuity (6/10), a mild papilla edema and a full loss of vision on standard perimetry in the right eye. Slit-lamp examination and intraocular pressure were within normal limits. Spectral domain optical coherence tomography was unremarkable. Fluorescein angiography ruled out any abnormalities of the retinal vascular system (including optociliary shunt vessels) or pigment epithelium. In the left eye, a concentric peripheral narrowing of visual field was also found. Neurological examination and brain MRI, with details of orbital and retroorbital structures and gadolinium enhancement, were normal. Visual evoked potential (VEP) disclosed reduced amplitude in the right eye, while latency was in the upper limits of normality. In the following months, he complained of a progressive painless worsening of the vision, that is, 3/10 in the right eye Neurology Unit (FG, FR, PP, AM, MM, PG), University Hospital of Padova, Padova, Italy; Neuroradiology Unit (DS), University Hospital of Padova, Padova, Italy; and General Pathology and Cytopathology Unit (MP), Department of Medicine-DIMED, University Hospital of Padova, Padova, Italy. The authors report no conflicts of interest. F. Garrì and F. Rinaldi are co-first authors. Address correspondence to Paolo Gallo, MD, PhD, Neurology Unit, University Hospital of Padova, Via Giustiniani 2, Padova 35128, Italy; E-mail: [e-mail] Garrì et al: J Neuro-Ophthalmol 2021; 41: e39-e41 and 2/10 in the left eye. VEP revealed an increased latency in both eyes, suggesting a demyelinating pathology of the retrobulbar nerve optic. Detailed hematological and immunological screenings were unremarkable. The patients arrived at our attention on April 2019. He reported a further marked reduction in visual acuity. A 3 T brain MRI disclosed the gadolinium enhancement with tram track and doughnut signs of the right optic nerve, suggestive of optic perineuritis (OPN), while no abnormality in the left optic nerve was detected (Fig. 1A–C). Intracranial Doppler ultrasound revealed increased velocity of blood flow in the right ophthalmic artery (peak systolic velocity 62 cm/s R vs. 35 cm/s L) suggestive of moderate stenosis of the vessel. Cerebral spinal fluid (CSF) examination showed a very mild leucocytosis (7 leucocytes/mL), a slight increase in total protein (520 mg/L), and a normal polyclonal immunoglobulin G isoelectrophoretic pattern. A detailed search for virus and bacteria in blood and CSF gave negative results. Angiotensin-converting enzyme was negative in blood and CSF. Antinuclear antibody, extractable nuclear antigen, antineutrophil cytoplasmic antibody, Lupus anticoagulant, anti-Ro/anti-La antibodies, AQP4, and myelin oligodendrocyte glycoprotein antibodies were also negative. Blood cell count and differential showed a grade II lymphopenia (0.65 · 109/L) and an increased CD4/CD8 ratio (5.49). The patient’s visual acuity continued to worsen, and brain and orbit 3 T MRI performed in June 2019 showed a diffuse, tubular thickening of the right optic nerve sheath encasing the optic nerve and the appearance of 2 focal areas of dura mater thickening at the convexity (Fig. 1D). Thus, a brain and whole body combined FDG PET/MRI (Figs. 1E and 2A) was performed showing the hypermetabolic signal of the 2 dura mater thickenings (Fig. 1E) as well as multiple round-shaped hypermetabolic areas in the lungs, spleen, liver, right lobe of thyroid, myocardium, portacaval space, mediastinum, and in right supraclavicular region, including a hypermetabolic lymph node .2 cm in diameter (Fig. 2A). Biopsy of this lymph node was performed, and histology disclosed a typical sarcoid granuloma (Fig. 2B–E). Treatment with high-dose methylprednisolone (i.e., 500 mg, intravenously, for e39 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. A. Coronal T1 image with fat saturation of optic nerves shows a slightly enlarged right ON (arrowhead). B. Gadoliniumenhanced coronal T1 sequence showing the characteristic pattern of enhancement around the right ON (“doughnut sign” arrowhead). C. Gadolinium-enhanced axial T1 sequence showing the typical “tramtrack” enhancement (double arrowhead). PET-MRI images confirmed the hypermetabolism of the dural lesions at the convexity (D, arrows), endowed with an homogeneous contrast enhancement (E, arrows). 5 days) was initiated with rapid clinical improvement, and monthly pulsed intravenous cyclophosphamide therapy was subsequently started. At the last visit, performed in November 2019, 6 months after therapy initiation, no further relapses were scored, and a significant improvement in visual acuity was observed. DISCUSSION Sarcoidosis has a well-known propensity to affect the eye with a broad spectrum of ocular manifestations, while the primary involvement of the optic nerve is quite rare, especially at clinical onset. Optic disc edema secondary to posterior uveitis, optic neuritis, optic atrophy secondary to FIG. 2. Coronal FDG PET/MRI image shows (A) multiple roundshaped hypermetabolic areas including the hypermetabolic lymph node (arrow) in the right supraclavicular region which was analysed by biopsy. Lymph node biopsy showed confluent epithelioid granulomas (B) with multinucleated giant cells (C) and focal necrosis (D). Ziehl–Neelsen stain was consistently negative (E). H&E and Ziehl–Neelsen stains; original magnification ·20, ·40, and ·63. e40 Garrì et al: J Neuro-Ophthalmol 2021; 41: e39-e41 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence compression or infiltration from a primary central nervous system lesion, and primary granuloma of the optic nerve head are described (3). Compared with the very few cases available in the literature (2,3), our OPN case is worth of consideration for the following aspects: i) the peculiar clinical course characterized by a slowly progressive visual loss over months; ii) the completely negative hematological and immunological tests in blood and CSF during the entire disease course; iii) the PET/MRI pictures, which revealed multiple areas of hypermetabolism in front of a clinically silent disease; iv) the evolution of MRI images that were normal 2 months after clinical onset and disclosed the typical OPN signs after 5 months and areas of meningeal thickenings after 7 months; and v) absence of focal white matter or gray matter lesions, that constitute a common finding in neurosarcoidosis, often associated with a vasculitis. A paraclinical finding that we would like to point out is the increased velocity of blood flow in the right ophthalmic artery presumably due to the compression of the artery by the thickened optic sheaths. The possible diagnostic value of B-scan ocular ultrasound imaging in OPN has been recently suggested (4), but no previous report has described the diagnostic utility of transcranial ultrasound Doppler in OPN. In conclusion, our case discloses that OPN, although rare and most often idiopathic, has to be considered among the possible clinical presentations of sarcoidosis. Brain and orbit MRI are fundamental for OPN diagnosis but may be unrevealing if performed early in the disease course. Thus, serial MRI scans, that is, after 3–6 months from the clinical Garrì et al: J Neuro-Ophthalmol 2021; 41: e39-e41 onset, have to be performed. Even in the presence of normal MRI and immunological tests, whole body 18F-FDG PET/ MRI has to be considered because it may provide evidence of a systemic pathology and a suitable site of biopsy (5). Indeed, rapid diagnosis and treatment are crucial to prevent irreversible optic nerve damage. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: F. Garrì, F. Rinaldi, P. Perini, A. Miscioscia, M. Pizzi, D. Simonato, M. Margoni, and P. Gallo; b. Acquisition of data: F. Garrì, F. Rinaldi, P. Perini, A. Miscioscia, M. Pizzi, D. Simonato, M. Margoni, and P. Gallo; c. Analysis and interpretation of data: F. Garrì, F. Rinaldi, M. Pizzi, D. Simonato, M. Margoni, and P. Gallo. Category 2: a. Drafting the manuscript: F. Garrì, F. Rinaldi, M. Pizzi, D. Simonato, M. Margoni, and P. Gallo; b. Revising it for intellectual content: F. Garrì, F. Rinaldi, M. Pizzi, D. Simonato, M. Margoni, and P. Gallo. Category 3: a. Final approval of the completed manuscript: F. Garrì, F. Rinaldi, P. 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