Acute Inflammatory Diseases of the Central Nervous System After SARS-CoV-2 Vaccination

Abstract

Background and ObjectivesAcute inflammatory CNS diseases include neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). Both MOGAD and acute disseminated encephalomyelitis (ADEM) have been reported after vaccination. Consequently, the mass SARS-CoV-2 vaccination program could result in increased rates of these conditions. We described the features of patients presenting with new acute CNS demyelination resembling NMOSDs or MOGAD within 8 weeks of SARS-CoV-2 vaccination.MethodsThe study included a prospective case series of patients referred to highly specialized NMOSD services in the UK from the introduction of SARS-CoV-2 vaccination program up to May 2022. Twenty-five patients presented with new optic neuritis (ON) and/or transverse myelitis (TM) ± other CNS inflammation within 8 weeks of vaccination with either AstraZeneca (ChAdOx1S) or Pfizer (BNT162b2) vaccines. Their clinical records and paraclinical investigations including MRI scans were reviewed. Serologic testing for antibodies to myelin oligodendrocyte glycoprotein (MOG) and aquaporin 4 (AQP4) was performed using live cell–based assays. Patients' outcomes were graded good, moderate, or poor based on the last clinical assessment.ResultsOf 25 patients identified (median age 38 years, 14 female), 12 (48%) had MOG antibodies (MOGIgG+), 2 (8%) had aquaporin 4 antibodies (AQP4IgG+), and 11 (44%) had neither. Twelve of 14 (86%) antibody-positive patients received the ChAdOx1S vaccine. MOGIgG+ patients presented most commonly with TM (10/12, 83%), frequently in combination with ADEM-like brain/brainstem lesions (6/12, 50%). Transverse myelitis was longitudinally extensive in 7 of the 10 patients. A peak in new MOGAD cases in Spring 2021 was attributable to postvaccine cases. Both AQP4IgG+ patients presented with brain lesions and TM. Four of 6 (67%) seronegative ChAdOx1S recipients experienced longitudinally extensive TM (LETM) compared with 1 of 5 (20%) of the BNT162b2 group, and facial nerve inflammation was reported only in ChAdOx1S recipients (2/5, 40%). Guillain-Barre syndrome was confirmed in 1 seronegative ChAdOx1S recipient and suspected in another.DiscussionChAdOx1S was associated with 12/14 antibody-positive cases, the majority MOGAD. MOGAD patients presented atypically, only 2 with isolated ON (1 after BNT162b2 vaccine) but with frequent ADEM-like brain lesions and LETM. Within the seronegative group, phenotypic differences were observed between ChAdOx1S and BNT162b2 recipients. These observations might support a causative role of the ChAdOx1S vaccine in inflammatory CNS disease and particularly MOGAD. Further study of this cohort could provide insights into vaccine-associated immunopathology.

Relapsing Encephalomyelitis After COVID-19 Infection and Vaccination

“…Other studies have posited that there may be an association between the AstraZeneca vaccine and neurologic autoimmunity, possibly attributable to the viral vector of this vaccine, although it must be noted that these studies did not demonstrate an increase in the incidence of such events after the roll out of the mass vaccination program. 16 - 18 Weighing the results of our findings and those in the literature, as COVID-19 constitutes a life-threatening infection in some patients, we feel that the benefits of vaccination outweigh the extremely rare event of unmasking an immune-related condition or leading to another neuroinflammatory event.…”

“…Regardless of the type of demyelinating event, all events were far more likely (73% of transverse myelitis, 77% of optic neuritis, and 74% of encephalomyelitis) to occur in association with SARS-CoV-2 infection in comparison to vaccination. [7][8][9][10][11][12][13][14][15][16][17][18] Our case was unusual in the degree of brain and spinal cord involvement, particularly the perivascular distribution of the inflammation, as well as the insidious degree of inflammation, with symptoms progressing over several months. Vascular complications and endothelial dysfunction have become increasingly identified in COVID-19, possibly mediated by SARS-CoV-2 targeting angiotensin-converting enzyme 2 receptors that are expressed in multiple organs, including the brain, although the exact pathogenesis remains unknown.…”

Acute disseminated encephalomyelitis (ADEM) following COVID-19 vaccination: A systematic review

“…Next, 88 studies were excluded via title and abstract evaluation. Finally, after the full-text screening, 20 studies with a total of 54 cases were entered into our systematic review [ [6] , [18] , [20] , [21] , [22] , [23] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] ].

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“…Also, 10–40 % of cases with negative AQP4 antibody have positive MOG antibody which is mostly present in ADEM [ 61 ]. Among included studies, two cases by Francis et al reported being positive for AQP4 antibody [ 39 ]. Based on the new criteria, MOGAD is typically linked to acute disseminated encephalomyelitis, optic neuritis, or transverse myelitis, and is less frequently connected with cerebral cortical encephalitis, brainstem presentations, or cerebellar presentations.…”

Impact of COVID-19 vaccination or infection on disease activity in a radiologically isolated syndrome cohort: The VaxiRIS study

“…22 Finally, a recent prospective study hypothesized that the AstraZeneca vaccine could be associated with a higher risk of developing myelin oligodendrocyte glycoprotein antibody-associated disease. 30 Still, no relationship with MS onset was recorded. Moreover, only 11 individuals in our study population received this vaccine (3.9%)…”