Optic Neuritis and Short-Segment Myelitis Following ChAdOx1 Adenovirus Vector-Based Vaccination: A Case Report

Sir, Adverse reactions following COVID-19 vaccination are generally mild. Severe COVID-19 vaccine–induced adverse reactions are cerebral venous thrombosis, acute disseminated encephalomyelitis (ADEM), myelitis, Bell’s palsy, Guillain–Barré syndrome and reactivation of cutaneous herpes zoster.[1] In this report, we describe an unusual case of acute demyelinating disorder following ChAdOx1 nCoV-19 (COVISHIELD AstraZeneca) vaccination. Case Report A 28-year-old woman presented with diminution of vision in the right eye for fifteen days duration. Three days later, she had difficulty in walking, lower limb numbness and urgency in urination. Six days before, she had received a second dose of the ChAdOx1 nCoV-19 (COVISHIELD AstraZeneca) vaccine. On neurological examination, right visual acuity was only finger counting from one meter. The right optic nerve disk was swollen and the margin was blurred. Power in lower limbs was 4/5 on the MRC scale, lower limb deep tendon reflexes were brisk. Plantar responses on both sides were extensor. He also had impaired vibration, joint and position sensations of up to T2 level and diminished pain, touch and temperature till nipple line. Romberg’s test was positive. She walked with a spastic gait. She had a negative SARS-CoV-2 RT-PCR test. All of her blood parameters including serum B12 level (319 picogram/ml) were normal. Serological studies for hepatitis B, hepatitis C, and HIV were negative. Serological tests (cell-based assays, immunofluorescence assay) for anti-aquaporin (AQP)-4 and myelin oligodendrocyte glycoprotein (MOG) antibodies were negative. Routine cerebrospinal fluid (CSF) parameters (cells 5/mm3, protein 30.3 mg/dl, and glucose 92.9 mg/dl) were normal. Oligoclonal bands (isoelectric focusing with immunofixation and immunoturbidimetry) in serum and CSF were absent. CSF tested negative for the varicella-zoster virus, Japanese encephalitis, cytomegalovirus, and herpes simplex 1). Her visual evoked potential showed prolonged latency on the right side (111.45 versus 97.65 ms). Magnetic resonance imaging of the brain (MRI brain) showed T2/FLAIR hyperintensity of the right optic nerve. The middle portion of the right optic nerve showed mild enhancement [Figure 1 upper panel]. MRI of the spinal cord demonstrated a short-segment T2/FLAIR hyperintensity in the cervicothoracic region [Figure 1 lower panel]. Meningeal enhancement was not seen.Figure 1: Upper panel (red arrows) - Magnetic resonance imaging of the brain shows right optic nerve high signal on T2-weighted images, secondary to optic neuritis. The left image shows enhancement of the right optic nerve. Lower panel (green arrows) - Magnetic resonance imaging of spinal cord shows fluid-attenuated inversion recovery (FLAIR) hyperintense lesion of the spinal cord affecting C7-T1 segments. The left image shows mild enhancement of spinal cord hyperintensityThe patient was treated with intravenous methylprednisolone for five days; after that, she continued to take oral methylprednisolone. After seven days, she improved significantly and was able to walk briskly. However, her vision remained unaltered. Discussion COVID-19 vaccination has been associated with a variety of central nervous system (CNS) demyelinating disorders. Ismail and Salama reviewed 32 cases of CNS demyelination following COVID-19 vaccination. The most frequent presentation was acute transverse myelitis which was reported in 12 patients. In another 12 instances, the patient had either a first episode or relapsed multiple sclerosis. Five patients had acute disseminated encephalomyelitis and the remaining 3 had neuromyelitis optica spectrum disorder like the picture. All kinds of COVID-19 vaccines are associated with CNS demyelination.[2] Neurological complications are generally reported after the first dose. Most cases with CNS demyelination following COVID-19 vaccination respond well to immunotherapy.[2] Our patient had short-segment myelitis and unilateral optic neuritis. After an extensive search, we came across another similar case. This patient developed bilateral optic or chiasm neuritis along with longitudinally extensive transverse myelitis, following COVID-19 vaccination. This patient had pre-existing and longstanding stable multiple sclerosis. He responded well to immunotherapy.[3] Optic neuritis is a common clinical manifestation of CNS demyelinating disorders. In multiple sclerosis, optic neuritis is generally unilateral. In patients with NMOSD and MOG antibody–associated optic neuritis, vision loss is often severe and bilateral. MOG antibody–associated optic neuritis manifests with severe disk edema. Lotan and colleagues reviewed 61 cases of optic neuritis that developed after the COVID-19 vaccination. The authors noted that a significant proportion of these optic neuritis cases were associated with MOG antibodies. MOG antibodies are generally detected in patients with either isolated optic neuritis or combined optic neuritis/myelitis.[4] Though MOG antibodies were not detected in our case, our case closely resembled MOG antibody-associated CNS demyelination. Netravathi et al. described a report of 29 Indian patients with post-vaccination CNS demyelination. The majority of cases (27 patients) occurred following ChAdOx1-S (COVISHIELD AstraZeneca) vaccination. In this series, 11 patients presented with myelitis, and 6 patients developed optic neuritis. In addition, 5 patients presented with acute demyelinating encephalomyelitis (ADEM), 3 presented with brainstem demyelination, and 4 patients had multiaxial involvement. MOG antibodies were detected in 10 patients. Authors opined that the temporal association with the vaccination and the presence of MOG antibodies suggested that an immune process triggered by the vaccine resulted in CNS demyelination.[5] Abrams et al. reported 5 cases of myelopathy and myeloradiculopathy in post-COVID-19 cases. In none of the patients, spinal imaging changes could be demonstrated. All of these 5 patients had either asymptomatic or mild-to-moderate COVID-19 disease. Serum SARS-COV-2 antibody estimations in all of the cases were strongly positive. Abrams et al. suggested that in addition to immunity mechanisms, small vessel spinal cord strokes could also be a possible pathogenetic mechanism responsible for imaging negative post-COVID-19 myelopathy. We did not perform serum SARS-COV-2 antibody estimation.[6] The phenomenon of molecular mimicry is the most likely pathogenic mechanism responsible for optic neuritis and myelitis in our case. Cross-reactivity between the SARS-CoV-2 spike protein and neuronal protein, like myelin basic protein, is likely to produce neuronal damage by inciting a cascade of inflammatory responses.[7-9] Similar autoimmune mechanism is considered responsible for MOG-associated post-vaccine demyelination as well.[5] In conclusion, this is an unusual case of short-segment myelitis and unilateral optic neuritis following ChAdOx1 nCoV-19 (COVISHIELD AstraZeneca) vaccination. The myelitis responded well to corticosteroids. However, it is difficult to establish a causal relationship between vaccination and CNS demyelination. 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 be made to conceal their identity, but anonymity cannot be guaranteed. Ethics statement We confirm that we have obtained written informed consent to publish the details from the patient herself. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.