Purpose We evaluated brain metabolic dysfunctions and associations with neurological and biological parameters in acute, subacute and chronic COVID-19 phases to provide deeper insights into the pathophysiology of the disease. Methods Twenty-six patients with neurological symptoms (neuro-COVID-19) and [ 18 F]FDG-PET were included. Seven patients were acute (< 1 month (m) after onset), 12 subacute (4 ≥ 1-m, 4 ≥ 2-m and 4 ≥ 3-m) and 7 with neuro-post-COVID-19 (3 ≥ 5-m and 4 ≥ 7-9-m). One patient was evaluated longitudinally (acute and 5-m). Brain hypo-and hypermetabolism were analysed at single-subject and group levels. Correlations between severity/extent of brain hypo-and hypermetabolism and biological (oxygen saturation and C-reactive protein) and clinical variables (global cognition and Body Mass Index) were assessed.
ResultsThe "fronto-insular cortex" emerged as the hypometabolic hallmark of neuro-COVID-19. Acute patients showed the most severe hypometabolism affecting several cortical regions. Three-m and 5-m patients showed a progressive reduction of hypometabolism, with limited frontal clusters. After 7-9 months, no brain hypometabolism was detected. The patient evaluated longitudinally showed a diffuse brain hypometabolism in the acute phase, almost recovered after 5 months. Brain hypometabolism correlated with cognitive dysfunction, low blood saturation and high inflammatory status. Hypermetabolism in the brainstem, cerebellum, hippocampus and amygdala persisted over time and correlated with inflammation status. Conclusion Synergistic effects of systemic virus-mediated inflammation and transient hypoxia yield a dysfunction of the fronto-insular cortex, a signature of CNS involvement in neuro-COVID-19. This brain dysfunction is likely to be transient and almost reversible. The long-lasting brain hypermetabolism seems to reflect persistent inflammation processes.
KeywordsNeuro-COVID • [ 18 F]FDG • Hypometabolism • Hypermetabolism • Recovery This article is part of the Topical Collection on Neurology.
Oxygen radical production is suspected of being a major cause of aging. We have studied the effect of acetyl-L-carnitine (ALC) on oxygen metabolites toxicity in fibroblast cell lines derived from skin biopsies taken from apparently normal subjects. Fibroblast damage was produced by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde with 50 mU of xanthine oxidase (XO). We measured lactate dehydrogenase (LDH) activity in the culture medium and cell viability in fibroblast cultures, both 4 days preincubated with 50 µg/ml ALC and not treated, after a 2-hour XO incubation in order to quantify the cell damage. We found a significant increase of LDH activity in cells without ALC exposed to free radical formation. No significant increase of the LDH activity was observed in the same cell lines, in the same experimental conditions after 4 days’ preincubation with 50 µg/ml ALC.
Cerebral glucose metabolism was investigated with 2-['8F]-fluoro-2-deoxy-D-glucose ([''FIFDC)and positron emission tomography (PET) in seven members belonging to two Italian families with familial Alzheimer's disease (FAD) and APP717 Val to Ileu mutation. The aim of the study was to identify the pattern of cerebral hypometabolism in the affected patients and the possible occurrence of brain metabolic changes in the APP mutated subjects. The two patients with FAD, when compared with normal age matched controls, showed a severe bilateral hypometabolism in parietal and temporal regions, as well as in the prefrontal areas, which were more affected on the left side. Subcortical thalamic structures were also involved in one patient. In a comparison with a group of patients with sporadic AD, the most affected cerebral areas in the FAD patients were the prefrontal regions and the thalamus, bilaterally. One of the four mutated subjects, with an age close to the family age of disease onset, in a comparison with normals, showed metabolic reductions in the right thalamus, in the left dorsolateral frontal cortex and, bilaterally, in the frontal orbital regions. This regional brain hypometabolism was present in a preclinical phase, 1 year before the onset of dementia. In the three younger subjects carrying the mutation, a metabolic reduction was detected in the thalamus, bilaterally. These results demonstrate that a pattern of cerebral hypometabolism involving cortical and subcortical structures is present in FAD patients with APP717 Val to Ileu mutation. Cerebral hypometabolism may occur in pre-symptomatic and young asymptomatic APP717 mutated FAD subjects and it can be detected by a highly sensitive procedure such as PET.
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