MOG Antibody-Associated Optic Neuritis and Meningeal Enhancement Post Varicella in a Child

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Sir, Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described inflammatory demyelinating disorder affecting the central nervous system (CNS), commonly causing optic neuritis, transverse myelitis, acute disseminated encephalomyelitis (ADEM), and encephalitis. Though the etiology of MOGAD is subject to further study, there is rising evidence of MOGAD following antecedent infections such as severe acute respiratory syndrome coronavirus (SARS-CoV-2), viral respiratory infections, gastrointestinal infections, and even following vaccinations.[1,2] We report a case of bilateral optic neuritis due to myelin oligodendrocyte glycoprotein (MOG) antibody-mediated demyelination in a six-year-old girl following varicella infection with characteristic radiological findings of optic neuritis and meningeal enhancement, which aid in the diagnosis of MOGAD. A six-year-old female child presented with a history of headaches for 20 days, along with episodes of vomiting and diminution of vision, for two days before admission. Ten days before the onset of the headache, the child had a varicella infection, which was treated with antipyretics and emollients. On examination, her vitals were stable, and she had healing scars of varicella infection on her trunk and limbs. The CNS examination indicated reduced visual acuity in both eyes; with the right eye, she was able to discern only finger counting from a one-meter distance, and the left eye demonstrated the ability to perceive only light. Further neurological, general, and systemic examinations were unremarkable. Fundoscopy revealed disc edema with blurring of the optic disc margins, superficial hemorrhages, and tortuosity of vessels, indicating papillitis and raising suspicion of optic neuritis in both eyes. Magnetic resonance imaging (MRI) of the brain revealed hyperintensity of bilateral optic nerves on the fluid-attenuated inversion recovery (FLAIR) sequence and thickening and enhancement of optic nerves post gadolinium contrast [Figure 1]. Small enhancing foci at the gray-white matter junction in the left parietal lobe with a subtle increase in leptomeningeal enhancement along the bilateral cerebral hemispheres and tentorial enhancement of the meninges at the prepontine cisterns were noted. The MR venogram showed no features of venous sinus thrombosis. Cerebrospinal fluid (CSF) analysis revealed a total cell count of 14 cells (lymphocytes: 13 cells/cu. mm, neutrophils: 1 cell/cu. mm), glucose of 46 mg/dL (blood glucose at the time of lumbar puncture was 75 mg/dL), and protein (28 mg/dL). The CSF gram stain was negative, and culture revealed no growth. Manometric pressure was normal (26 centimeters of water). The CSF varicella deoxyribonucleic acid polymerase chain reaction (DNA PCR) was negative. Visual evoked potential (VEP) showed prolonged P-100 latency with normal negative-positive-negative peak (NPN) complex amplitude in both eyes (right: 183.9 ms, left: 147.9 ms).Figure 1: The T1 axial MRI brain and orbits post gadolinium contrast image shows enhancement of bilateral optic nerves (a) and the FLAIR axial image shows hyperintensity of bilateral optic nerves (b). Post-contrast T1 axial image shows leptomeningeal enhancement (c) and tentorial enhancement (d) and a subtle increase in meningeal enhancement along the prepontine cisterns (e)In view of optic neuritis, the child was started on intravenous methylprednisolone (30 mg/kg/day) for three days followed by oral prednisolone. A serum sample was sent for aquaporin-4 IgG, antineutrophil cytoplasmic antibody (ANCA), angiotensin-converting enzyme (ACE), and antinuclear antibody (ANA) levels, and a CSF sample for oligoclonal bands turned out to be negative for the same. However, MOG antibodies were strongly positive for the cell-based assay. Given the finding of optic neuritis and strongly positive MOG antibody titer, a diagnosis of MOGAD was made. An MRI of the whole spine done to screen for spinal cord demyelination revealed no abnormalities. Her visual acuity improved to 6/18 and 6/24 in the right and left eye, respectively, at one month of follow-up and became normal at three months. Serum MOG antibodies were repeated at one month and remained strongly positive. She was continued on a tapering dose of oral prednisolone for two more months, and the visual acuity at three months was normal. MOGAD is an inflammatory demyelinating condition of the CNS. MOGAD displays a range of clinical features that are highly characteristic, which include optic neuritis, myelitis, encephalitis, and ADEM.[3] Brainstem and cerebellar involvement are also seen in MOGAD. MOG is a membrane protein expressed both on the outermost surface of the myelin sheath and also on the surface of oligodendrocytes.[4] It serves to function as a cellular adhesive molecule, acts as a regulator of microtubule stability, and is a marker for oligodendrocyte maturation. Additionally, through the complement cascade, it mediates interactions between myelin and the immune system.[5] An increasing number of studies have shown that the pathogenesis of MOGAD is linked to infectious etiology. It is reported that 40.5% of patients have a history of flu-like symptoms before their present complaints.[6] Further, several cases of MOGAD arising following the coronavirus disease 2019 (COVID-19) infection and research in the area substantiate the observation of infections triggering MOGAD.[1,2] We observed a similar viral infection triggering the demyelinating event in our case. Varicella is among the most common infectious antecedents observed in neuromyelitis optica spectrum disorder (NMOSD).[7] Concerning the correlation between varicella infection and MOGAD, the literature is sparse, however, a couple of case reports have been published, and recently, a study highlighted the occurrence of MOGAD following an antecedent varicella infection.[8,9] The acute attacks in MOGAD are characterized by infiltration of the blood-brain barrier (BBB) by T cells and MOG antibodies. T cells are initially activated in the periphery, and the inflammatory environment of the CSF allows the T cells to invade the CNS parenchyma. Further reactivation of the T cells occurs in the perivascular and subarachnoid spaces by MOG-laden antigen-presenting cells (APCs). Peripheral activation of T cells, production of autoantibodies, and the consequent transfer of these immune mediators into the CNS start the autoimmune process.[1] An interesting finding seen in our case is the leptomeningeal and pachymeningeal enhancement observed in the contrast MRI of the brain. This is indicative of disruption of the BBB, and it has been hypothesized in similar infections such as the herpes simplex virus that the preceding infection alters the permeability of the BBB, allowing the antigen to cross it into the periphery, thus leading to the production of MOG antibodies. A similar pathogenesis is described in NMOSD, where at the time of leptomeningeal enhancement, 45% of patients were seen to suffer from clinical attacks of encephalopathy, while 70% of patients suffered from myelopathy.[10] Meningeal enhancement in MOGAD has been described in the literature.[11] Thus, the imaging findings of optic neuritis with meningeal enhancement in an individual with antecedent varicella infection may be an indication of possible MOGAD. It is therefore important to evaluate such cases for MOG antibodies for an accurate diagnosis and appropriate management. MOGAD should be considered among the differential diagnoses in cases presenting with optic neuritis following varicella infection. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will b

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