18F-FDG brain PET hypometabolism in post-SARS-CoV-2 infection: substrate for persistent/delayed disorders?

Abstract

Purpose: Several brain complications of SARS-CoV-2 infection have been reported. It has been moreover speculated that this neurotropism could potentially cause a delayed outbreak of neuropsychiatric and neurodegenerative diseases of neuroinflammatory origin. A propagation mechanism has been proposed across the cribriform plate of the ethmoid bone, from the nose to the olfactory epithelium, and possibly afterward to other limbic structures, and deeper parts of the brain including the brainstem.

Methods: Review of clinical examination, and whole-brain voxel-based analysis of ¹⁸F-FDG PET metabolism in comparison with healthy subjects (p voxel < 0.001, p-cluster < 0.05, uncorrected), of two patients with confirmed diagnosis of SARS-CoV-2 explored at the post-viral stage of the disease.

Results: Hypometabolism of the olfactory/rectus gyrus was found on the two patients, especially one with 4-week prolonged anosmia. Additional hypometabolisms were found within amygdala, hippocampus, parahippocampus, cingulate cortex, pre-/post-central gyrus, thalamus/hypothalamus, cerebellum, pons, and medulla in the other patient who complained of delayed onset of a painful syndrome.

Conclusion: These preliminary findings reinforce the hypotheses of SARS-CoV-2 neurotropism through the olfactory bulb and the possible extension of this impairment to other brain structures. ¹⁸F-FDG PET hypometabolism could constitute a cerebral quantitative biomarker of this involvement. Post-viral cohort studies are required to specify the exact relationship between such hypometabolisms and the possible persistent disorders, especially involving cognitive or emotion disturbances, residual respiratory symptoms, or painful complaints.

Keywords: 18F-FDG-PET; Anosmia; Brainstem; COVID-19; Functional disorders; Limbic system; SARS-CoV-2.

Fig. 1

Brain ¹⁸F-FDG PET hypometabolism of the first patient. Bilateral hypometabolism of olfactory/rectal gyrus is visually identified (white arrow), and confirmed by whole-brain voxel-based SPM8 comparison, to healthy subjects (p voxel < 0.001, p-cluster < 0.05, uncorrected)

Fig. 2

Brain ¹⁸F-FDG PET hypometabolism of the second patient. Bilateral hypometabolism of olfactory/rectal gyrus (white arrow), medial temporal lobe (white*), and brainstem (white+) is visually identified, and confirmed by whole-brain voxel-based SPM8 comparison to healthy subjects (p voxel < 0.001, p-cluster < 0.05, uncorrected), also including the right pre-/post-central gyrus, the right superior temporal gyrus, bilateral thalamus, hypothalamus, and cerebellum