Bilateral Optic Disc Edema in Multisystem Inflammatory Syndrome in Children Associated With COVID-19

Apediatric inflammatory multisystem disorder temporally associated with exposure to SARS-CoV-2 has been described in communities with high rates of COVID-19. We present the case of a 14-year-old boy who was treated for symptoms of shock, associated with elevated SARS-CoV-2 antibodies, who developed headaches, diplopia, and blurred vision and was found to have bilateral optic disc edema and an abducens palsy.

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Gour Wang, MD Bilateral Optic Disc Edema in Multisystem Inflammatory Syndrome in Children Associated With COVID-19 Marc Dinkin, MD, Devorah Segal, MD, PhD, Israel Zyskind, MD, Cristiano Oliveira, MD, Grace Liu, MD A pediatric inflammatory multisystem disorder temporally associated with exposure to SARS-CoV-2 has been described in communities with high rates of COVID-19. We present the case of a 14-year-old boy who was treated for symptoms of shock, associated with elevated SARS-CoV-2 antibodies, who developed headaches, diplopia, and blurred vision and was found to have bilateral optic disc edema and an abducens palsy. CASE REPORT A 14-year-old boy presented to the emergency department with fever, nausea, malaise, a maculopapillary chest rash (Fig. 1), and chest pain in April 2020. Blood pressure was 71/40. C-reactive protein (5.6 mg/dL) and D-dimer (657 ng/mL) were elevated. Blood cultures were negative, and he was diagnosed with toxic shock syndrome. He received broadspectrum antibiotics and pressors. SARS-CoV-2 PCR was negative twice. Systemic symptoms improved over days and he was discharged, but photophobia, blurred vision, diplopia, and severe headache supervened. Antibodies against SARSCoV-2 were elevated at 117 AU/mL (ref , 15), and he was diagnosed with multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2. Several days later, he presented to the authors. Visual acuity was normal but visual fields demonstrated subtle neurogenic defects in both eyes (Fig. 1B). Motility examination revealed a mild right abducens palsy. Dilated fundus examination revealed mild disc edema, left eye.right eye (Fig. 1C), confirmed on optical coherence tomography (OCT) in both eyes (Fig. 1D). Because the patient’s symptoms were already improving by the time he presented to us, a lumbar puncture was deferred and we did not treat him with acetazolamide. Repeat examination 2 weeks later Departments of Ophthalmology and Neurology (MD), Weill Cornell Medicine, New York City, New York; Departments of Neurology (DS) and Pediatrics (IZ), NYU Grossman School of Medicine, New York City, New York; Department of Ophthalmology (CO), Weill Cornell Medicine, New York City, New York; and New York Eye & Ear Infirmary (GL), New York City, New York. The authors report no conflicts of interest. Address correspondence to Marc Dinkin, MD, Weill Cornell Department of Ophthalmology, 1305 York Avenue, 11th Floor, New York, NY 10021; E-mail: [e-mail]. e318 revealed resolution of disc edema along with all symptoms (Fig. 1G, H). DISCUSSION Most children affected with SARS-CoV-2 manifest mild or no respiratory symptoms (1), with more severe disease seen mostly in children with pre-existing conditions (2). However, reports emerged in May 2020 of an illness affecting children in regions severely affected by the COVID-19 pandemic (3), characterized by high fever, gastrointestinal symptoms, rash, limb edema, conjunctivitis, and cardiovascular shock, with variable coronary artery dilation. Known as MIS-C, this condition bears some similarities to Kawasaki disease (KD), which is an acute, typically self-limiting postinfectious vasculitis, but in a series of 58 children with MIS-C, only 22% met diagnostic criteria for KD (4). In one series of MIS-C, 4 of the 27 children (14.8%) demonstrated neurological manifestations including encephalopathy, headache, dysarthria, ataxia, meningismus, proximal weakness, and hyporeflexia (5). All had T2 splenial hyperintensities, believed to reflect postinfectious intramyelinic edema. Of note, our patient’s MRI did not demonstrate enhancement of the splenium as seen in a majority of MIS-C cases, although there was one small T2 hyperintensity within the left parietal centrum semiovale. A more recent review from England found neurological involvement in 51.1% of 45 children with MIS-C, including headaches in 16 and encephalopathy in 14 (6). The first case of elevated intracranial pressure consistent with pseudotumor cerebri syndrome in association with MIS-C was reported in a child 6 days after extubation (7). Two more cases of MIS-C–associated intracranial hypertension with abducens palsies were subsequently reported by Baccarella et al, although papilledema was absent in one and opening pressure was normal at the time of LP in the second (8). Finally, four cases of intracranial hypertension in association with MIS-C were reported by Becker et al, but only one had documented neuro-ophthalmic findings of papilledema and abducens palsy, and 2 of the cases could be attributed to a meningitic process (9). We present a rare case of MIS-C associated with bilateral optic disc edema and an abducens palsy along Dinkin et al: J Neuro-Ophthalmol 2022; 42: e318-e322 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. A. A maculopapillary rash along the chest was present on presentation. B. Visual fields at presentation to neuroophthalmology revealed a mildly enlarged blind spot in the right eye (black arrow) and inferonasal defects in both eyes (red arrows). C. Funduscopy revealed grade I papilledema in both eyes. D. Optical coherence tomography (OCT) revealed mildly thickened retinal nerve fiber layer (RNFL) consistent with disc edema. E. MR venogram (MRV) did not show venous sinus thrombosis but did reveal severe stenosis (yellow arrow) of the right, dominant transverse sinus. F. MRI of the orbits revealed vertical tortuosity of both optic nerves (yellow arrow), also suggestive of elevated ICP. Repeat neuro-ophthalmic evaluation 2 weeks later revealed improved papilledema on funduscopy (G) and associated reduction in RNFL thicknesses on OCT (H). with severe headache, which together suggested intracranial hypertension. Although initial PCR testing for SARS-CoV-2 was negative and the positive serology could have reflected any previous COVID-19 infection, it is notable that in a large study of children with MIS-C, only 9 of the 23 patients had a positive SARS-CoV-2 PCR at the time of MIS-C and that the mean interval between clinical presentation of COVID-19 and MIS-C symptoms was 48 days (range 18–123). Because our patient presented with MIS-C in April 2020 and was unlikely to have had COVID-19 before March 2020, a causal link is probable. Our case is limited by the lack of opening pressure measurement, and it is possible that the disc edema reflected a postinfectious inflammatory papillitis. Indeed, several cases of optic neuritis, most with disc edema have been reported after COVID-19 in adults (Table 1). However, we hypothesize that the underlying mechanism of bilateral disc edema in our case was intracranial hypertension because it Dinkin et al: J Neuro-Ophthalmol 2022; 42: e318-e322 was accompanied by headache and abducens palsies and because the minimal degree of vision loss was more consistent with mild papilledema than an inflammatory papillitis. Intracranial hypertension in this setting could result from an infectious or inflammatory meningitis or from a disturbance in CSF fluid dynamics akin to the pseudotumor syndrome. Previous reports of papilledema and intracranial hypertension in association with COVID-19 or MIS-C can be found in Table 1. Vertical tortuosity of the optic nerves was present on MRI, a finding which showed a 95% specificity for IIH in one recent study (10). The presence of a focal stenosis of the dominant transverse sinus also suggested elevated intracranial pressure because 0% of pediatric controls in one series were found to have it (11), although neither of these radiological signs is definitive. Because our patient’s symptoms resolved completely, we did not repeat an MRV. The spontaneous improvement in our patient without the need for acetazolamide speaks to a self-limited postinfectious e319 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence TABLE 1. Optic nerve disease reported in association with COVID-19 Vision Loss Optic Neuritis Zou et al (12) Findings Serum and CSF OU Edema OU MOG+ Palao et al (13) OD Edema OS OCB in CSF Benitopascual et al (14) OS De Ruijter et al (15) Sawalha et al (16) OU Edema OS with — panuveitis and choroidal folds Edema OU MOG+ OU NR François et al (17) OD to HM Edema OD with panuveitis MOG+ — Sharma et al (18) OD Edema OD (mild) CRP high. RodríguezRodríguez et al (19) OS None OD Edema ACLAOD +retinal edema Edema CRP high OS +signs of CRVO Pallor OD — Presumed Ischemia Dumitrascu et al (20) Insausti-garcía et al (21) OS Rho et al (22) OD (IA) Papilledema With COVID-19 Noro et al (23) None “Funduscopy impaired” Silva et al (24) TVO OU OU Silva et al (24) TVO OU OU With MIS-C Verkuil et al (7) Baccarella et al (8) Baccarella et al (8) e320 OCB in CSF COVID-19 Testing Latency Few days after cough 2–3 weeks after anosmia PCR+ 2 weeks after URI, conjunctivitis, 10 days before PNA 10 days after cough, fever, and nausea 2 weeks after cough + SOB 2 days after admission with PNA 10 days after fever, sore throat, and fatigue No systemic symptoms; CT chest: PNA at time of ON Three weeks after intubated for resp. failure 6 weeks after fever, cough, and myalgia 2 weeks after fever, cough, and HA OP 40 cm H2O HA 2 days after fever, SOB, and weakness OP 21 cm HA 1 day after sore H2O throat, cough, anosmia, and fever HA 2 days after sore OP 35 cm H2O, OCB-, throat, cough, and serum anosmia, and AQP4fever None Disc edema (+diplopia) OU and abducens OP 36 cm H2O None None and (+diplopia) abducens None Disc edema (+diplopia) OU and abducens OP 34 cm H2O OP 14 cm H2O Abducens palsy 6 days after extubation for MIS-C 1 week 1 week MRI Bilateral enhancement PCR-, IgG Enhancement and IgM+ right ON and periventricular lesions PCR+ Negative Rx and Outcome IVMP Improvement IVMP Improvement Prednisone and steroid drops PCR+ Bilateral IVMP parents enhancement Improvement PCR+ Bilateral perineural IVMP enhancement Improvement PCR+ Negative Oral and topical steroids. No improvement PCR+ Negative (brain IVMP MRI only) Improvement PCR+ Mild T2 signal IVMP No improvement PCR+ Negative On apixaban No improvement IgG Not reported and IgM+ PCR+ Not done Dexamethasone implant; Improvement None PCR+ Prominent ON sheaths Spontaneous improvement PCR+ Negative Acetazolamide Partial recovery PCR+ White matter Acetazolamide + lesions in pons furosemide and cortex Partial recovery PCR- and IgG+ Findings of high intracranial pressure Acetazolamide Prednisone PCR- and Negative Acetazolamide Ab+ PCR+ and Optic nerve sheath None Ab+ distention, kinking and anterior bowing of discs Dinkin et al: J Neuro-Ophthalmol 2022; 42: e318-e322 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence (Continued ) Vision Loss Becker et al (9) Becker et al (9) Becker et al (9) Becker et al (9) Blurry vision Findings Disc edema OU and abducens Irritability Nuchal rigidity Serum and CSF Latency OP .36 cm H2O, +OCB 13 days OP 31 cm H2O, WBC 34/mL OP 38 cm H2O, WBC 218/mL 6 days Fever, Nuchal rigidity headache, emesis, and AMS Diarrhea, Nuchal OP 34 cm fever, rigidity and H2O emesis, conjunctivitis and AMS COVID-19 Testing PCR- and IgG+ MRI Radiological papilledema Rx and Outcome Acetazolamide, corticosteroids, and IVIg IVMP, IVIg, and anakinra 5 days PCR+, Ab+ CT head: cerebral edema PCR-, IgG+ Negative 9 days PCR-, IgG+ CT head: negative IVMP and IVIg IVMP, tocilizumab, and enoxaparin Organized by optic neuritis, presumed ischemia, and papilledema. Ab, antibody; AMS, altered mental status; ACLA-, anticardiolipin antibody negative; AQP4, aquaporin4 negative; CRP, C-reactive protein; CSF, cerebrospinal fluid; CRVO, central retinal vein occlusion; HA, headache; IVMP, intravenous methylprednisolone; IVIg, intravenous immunoglobulin; MOG, myelin oligodendrocyte glycoprotein; MIS-C, multisystem inflammatory syndrome in children; OCB, oligoclonal bands; ON, optic neuritis; PNA, pneumonia; PCR, nasal swab polymerase chain reaction; SOB, shortness of breath; TVO, transient visual obscuration. response to COVID-19. Similarly, in the case reported by Verkhuil et al, papilledema resolved despite noncompliance with acetazolamide. In summary, this case adds to the evidence that MIS-C can rarely be complicated by disc edema and highlights the importance of a dilated examination in children with MISC who complain of headache, blurry vision, or photophobia. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: M. Dinkin, D. Segal, I. 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