Acute disseminated encephalomyelitis (ADEM) following recent Oxford/AstraZeneca COVID-19 vaccination

Abstract

This report describes the clinical context and autopsy findings in the first reported fatal case of acute disseminated encephalomyelitis (ADEM), developed after being vaccinated using the Oxford/AstraZeneca COVID-19 vaccine. ADEM is a rare autoimmune disease, causing demyelination in the brain and spinal cord. A wide variety of precipitating factors can trigger ADEM, and it has long been known to be a rare adverse event following some types of vaccinations. Recently, ADEM has also been associated with COVID-19 infection and (very rarely) with COVID-19 vaccination. The reports of the latter however all pertain to living patients. Our case demonstrates that ADEM should be considered in patients developing neurological symptoms post COVID-19 vaccination, although that this adverse reaction is likely to remain extremely rare. Our report further emphasizes the added value of comprehensive post mortem investigation to confirm ante mortem diagnosis and to determine vaccination safety.

Keywords: ADEM; Acute disseminated encephalomyelitis; Adverse event; COVID-19; Forensic pathology; Vaccination.

Fig. 1

Ante mortem and post mortem radiology. (a) Image taken from MRI Brain FLAIR sequence, showing juxtacortical and periventricular white matter (circles). (b) Image taken from the post mortem CT scan, at the same level as (a)

Fig. 2

Histology of the ante mortem biopsy specimen, taken from the right frontal lesion on day nine of patient admission. (a) Perivascular pallor on hematoxylin and eosin stain. (b) Perivascular loss of positivity in Luxol fast blue stain, indicating demyelination. (c) Perivascular distribution of macrophages on CD68 immunohistochemistry. (d) Preservation of perivascular axons on neurofilament stain. All images at 40 × magnification

Fig. 3

Post mortem macroscopic neuropathology. (a) Right frontal cortex, with hemorrhage and disruption in the white matter due to ante mortem biopsy and demyelination of the adjacent white matter, visible as ill-defined geographical brown discoloration. (b) Higher power field of the demarcated area in (a)

Fig. 4

Post mortem microscopic neuropathology. (a) Perivascular palor of the white matter of the right frontal cortex. Compare with adjacent normal white matter and the cortex in the upper left corner. Hematoxylin and eosin, 4 × magnification. (b) Perivascular demyelination in Luxol fast blue stain, 10 × magnification. (c) Necrosis of white matter and abundant foamy macrophages in a pontine lesion. Hematoxylin and eosin, 20 × magnification. (d) Sparse perivascular lymphocytes in a lesion in the lumbar spinal cord. Hematoxylin and eosin, 40 × magnification