The cerebral network of COVID-19-related encephalopathy: a longitudinal voxel-based 18F-FDG-PET study

Abstract

Purpose: Little is known about the neuronal substrates of neuropsychiatric symptoms associated with COVID-19 and their evolution during the course of the disease. We aimed at describing the longitudinal brain metabolic pattern in COVID-19-related encephalopathy using 18F-FDG-PET/CT.

Methods: Seven patients with variable clinical presentations of COVID-19-related encephalopathy were explored thrice with brain 18F-FDG-PET/CT, once in the acute phase, 1 month later and 6 months after COVID-19 onset. PET images were analysed with voxel-wise and regions-of-interest approaches in comparison with 32 healthy controls.

Results: Patients' neurological manifestations during acute encephalopathy were heterogeneous. However, all of them presented with predominant cognitive and behavioural frontal disorders. SARS-CoV-2 RT-PCR in the CSF was negative for all patients. MRI revealed no specific abnormalities for most of the subjects. All patients had a consistent pattern of hypometabolism in a widespread cerebral network including the frontal cortex, anterior cingulate, insula and caudate nucleus. Six months after COVID-19 onset, the majority of patients clinically had improved but cognitive and emotional disorders of varying severity remained with attention/executive disabilities and anxio-depressive symptoms, and lasting prefrontal, insular and subcortical 18F-FDG-PET/CT abnormalities.

Conclusion: The implication of this widespread network could be the neural substrate of clinical features observed in patients with COVID-19, such as frontal lobe syndrome, emotional disturbances and deregulation of respiratory failure perception. This study suggests that this network remains mildly to severely impaired 6 months after disease onset.

Keywords: 18F-FDG-PET; COVID-19; Glucose metabolism; Prefrontal impairment; SARS-CoV-2.

Fig. 1

Brain metabolism changes in the whole group of patients (n = 7) vs. controls (n = 32) in the acute phase, 1 month later and 6 months after COVID-19 onset. Hot and cool color scales show regions with hypermetabolism and hypometabolism in patients vs. controls, respectively. The SPM maps are projected onto a surface rendering and onto axial views of the customized MRI template. The axial slices are shown using neurological conventions (right is right). R, right; L, left. At baseline, hypometabolism was found in the bilateral prefrontal cortex with right predominance, insula, anterior cingulate and caudate (p < 0.05 corrected). The analysis showed a mild hypermetabolism in the vermis, dentate nucleus and pons (p < 0.05). One month later, hypometabolism was limited to the mediofrontal, right dorsolateral areas, olfactory/rectus gyrus, bilateral insula, right caudate nucleus and cerebellum (p < 0.001). Six months after COVID-19 onset, metabolism decrease was observed in the same regions but they were less extended (p < 0.001)

Fig. 2

Brain metabolism changes in each patient vs. controls (n = 32) in the acute phase, 1 month later and 6 months after COVID-19 onset. SPM T maps generated from patient #1 to patient #7 are displayed with a hot color scale for brain hypermetabolism (p < 0.05) and with a cool color scale for brain hypometabolism (p < 0.05 corrected), in axial orthogonal views in neurological convention (right is right). R, right; L, left. 3D rendering shows for all patients the right hemisphere except in patient #4 who presented hypometabolism in the left frontal cortex due to focal seizure