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-19related 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.

Neuropsychologic Profiles and Cerebral Glucose Metabolism in Neurocognitive Long COVID Syndrome

“…Again, technical factors may explain different findings (e.g., extraction of brain scans from whole-body examination, which may yield inferior data quality if whole-body PET acquisition parameters are not matched to brain acquisitions; retrospective use of brain images of oncological patients as control data, which limits standardization of behavior/sensory input during 18 F-FDG uptake; liberal statistical thresholds such as P<0.005 on voxel-level). Finally, a thorough qualitative and quantitative assessment of cognitive profiles and correlation to changes in cerebral glucose metabolism was not pursued by other studies (10)(11)(12), which underlines the particular value of the present work.…”

“…Postmortem neuropathological examinations in COVID-19 patients revealed pronounced glial activation and infiltration by cytotoxic T lymphocytes in brainstem and cerebellum (13), which is likely caused by a systemic inflammatory response or a cytokine release (14). Since the cortical grey matter is largely unaffected by inflammatory changes (8,13), reduction of cortical glucose metabolism in early subacute patients (8)(9)(10) might be caused by a functional decoupling from afferents, which is in line with recovery of cognitive deficits and cortical metabolism in long-term follow-up investigations (9,10,15). Thus, the question arises whether alterations in cerebral glucose metabolism are also present in patients with Long COVID-syndrome as a potential pathophysiological correlate of the neurocognitive symptoms.…”

Similar patterns of [18F]-FDG brain PET hypometabolism in paediatric and adult patients with long COVID: a paediatric case series

“…Several hypotheses have been proposed and still investigated to explain long COVID. These include, but are not limited to, inflammatory or viral neurotropism [1,3,[26][27][28][29] from persistent sites of infection, particularly from the olfactory pathways [30][31][32][33], dysimmune reaction [34], vascular abnormalities, disturbances of gut-brain relationships [35] and possible interactions with psychological factors.…”

“…Neurological manifestations of COVID-19 have been largely described [1,2]. In addition to those subjects usually identified by conventional explorations, others report persistent or delayed functional complaints beyond 3-4 weeks after the onset of the disease in the absence of obvious morphological lesions [3][4][5][6].…”

Die „vierte Welle“? COVID-19 und konsekutive kognitive Störungen

“…Ausgedehnte ischämische Infarkte finden sich bei besonders ungünstigen Verläufen [28]. Im 18 F-FDG-PET wurde ein Hypometabolismus im Präfrontalkortex, Gyrus cinguli anterior, in Insel und Nukleus caudatus nachgewiesen, und dieser Befund wäre geeignet, frontal-exekutive Defizite zu erklären [29].…”