ABSTRACT
Objective: This study investigates the effects of COVID-19 on brain microstructure among those recently recovering from COVID-19 through self isolation. Background: Microstructural differences have previously been detected in comparisons of COVID-19 patients with controls, particularly in regions related to the olfactory system. The olfactory system is connected with the caudate, putamen, thalamus, precuneus, and cingulate regions. Design/Methods: Here we report diffusion magnetic resonance imaging (3 T Siemens MRI) findings from 40 patients (mean age: 43.7, 68% female) who self-isolated after testing positive for COVID (COV+), and 14 COVID negative (COV-) subjects (mean age: 43, 64% female) who had flu-like symptoms. This is part of the Canadian-based NeuroCOVID-19 study. Fractional anisotropy (FA), mean diffusivity (MD), mode of anisotropy (MO), free water fraction (F), tissue-specific FA (FAt) and tissue-specific MD (MDt) were obtained using data with b=700 and 1400 (DIPY free-water model). Regions of interest in the grey matter and white matter were delineated using FreeSurfer. Differences between groups were assessed using an analysis of variance (ANOVA), the Kruskal-Wallis Test and the Mann-Whitney Test, corrected for false-discovery rate of 0.05. Effect size (Cohen's d) was also computed (d>0.45 deemed large effect). Results: In the COV+ group, all three tests revealed decreased FA and FAt in the insula, and increased MD in the parstriangularis cortex. Increased FA and FAt in the cuneus (along with decreased MD) was also found. MD was reduced in COV+ in the temporal and supramarginal areas. MO was lower in COV+ in the insula and amygdala regions. Conclusions: In patients, higher MD with lower FA and MO suggest increased extracellular fluids, while lower MD with decreased FA and MO may suggest necrotic debris built up following inflammation. The cuneus and insula are involved in visual and taste processing, respectively. This study highlights the need to study neurological effects of COVID-19.
ABSTRACT
Background-Aim: Cognitive impairment may represent a long lasting symptom after COVID-19 resolution and FDG brain PET is useful to evaluate if brain metabolic changes are transient or long lasting. Hypometabolism was shown in many brain areas, i.e. cingulate cortex, bilateral gyrus rectus, prefrontal and orbitofrontal cortex and cerebellar vermis. Methods: We report the case of a 62 years old man with type 2 diabetes, affected by COVID-19 infection in October 2020. After resolution, the patient had short-term memory loss and speech deficit affecting daily living and working activities and referred to the Gerontology and Geriatrics Institute (Univ. of Perugia). Neurological examination and neuropsychological tests were carried out and no alterations were found. In October 2021, the neurological examination was still normal, as well as neuropsychological tests. Brain MRI showed only two small chronic ischemic foci without bi-hemispheric white matter clinically significant abnormalities. In November 2021, the patient underwent FDG brain PET/CT (discovery ST, G.E.) according to standard protocols and images were evaluated both qualitatively and semiquantitatively. Results: An area of moderate significant hypometabolism was identified in the precuneus (predominant on the right side) and others multiple small and mild hypometabolic regions were localized in bilateral pre-frontal cortex, sensorimotor and parietal cortex both on left hemisphere. PET and MRI fusion images (Syngo.via VB10B image processing software, Siemens) showed that hypometabolic areas corresponded to structurally intact parenchyma at MRI. In January 2022 clinical and neuropsychological follow up did not evidence cognitive impairment, although the patient still felt depressed and impaired in memory, attention and daily living activities. Conclusions: In this case, FDG brain PET/CT was the only diagnostic procedure showing findings consistent with patient symptoms. In particular, precuneus hypometabolism may represent in this patient an early hallmark of dementia (i.e. Alzheimer's disease-AD), although other characteristic brain areas are not significantly impaired (i.e. cingulate cortex). In this case, FDG brain PET use, during follow up, could be crucial to evaluate if the metabolic changes may evolve into a chronic state, thus supporting mild cognitive impairment clinical suspect due to AD or confirming a stable COVID related neuronal damage. Furthermore, a second normal FDG brain PET/CT scan may suggest a post-acute infection transient phase, preluding to normal functional status. In conclusion, FDG brain PET/CT may represent an important diagnostic tool in modifying subsequent diagnostic assessment suggesting or routinely clinical follow up or other investigations for dementia (i.e. amyloid PET, amyloid and Tau protein liquor measurement). In our study, fused PET and MRI images were used, although hybrid PET/MRI system could be the choice option if available.
ABSTRACT
Background-Aim: A potential link has been investigated between hyposmia after COVID-19 and an increased risk to develop neurological long-term sequelae also in patients who experienced mild or moderate disease. Hyposmia is a common feature PD and parkinsonism has been reported after COVID-19 suggesting a potential link between SARS-CoV2 infection and PD. [18F]FDG PET may represent a suitable tool to capture potential common metabolic signature of hyposmia after COVID-19 and in PD patients. We aimed to evaluate brain metabolic correlates of isolated persistent hyposmia after mild-to-moderate COVID-19 and to compare them with metabolic signature of hyposmia in drug-naive PD patients. Methods: Forty-four patients who experienced hyposmia after SARSCOV2 infection underwent brain [18F]FDG-PET in the first 6 months after recovery. Olfaction was assessed by means of the 16-item ''Sniffin-Sticks'' test and patients were classified as with or without persistent hyposmia (COVID-hyposmia and COVID-no-hyposmia respectively). Brain [18F]FDG-PET of post-COVID subgroups were compared in SPM12. COVID-hyposmia patients were also compared with eighty-two drug-naïve PD patients with hyposmia. Multiple-regression- analysis was used to identify correlations between olfactory test-scores and brain metabolism in patients' subgroups. Results: COVID-hyposmia patients (n = 21) exhibited significant hypometabolism in bilateral gyrus rectus and orbitofrontal cortex with respect to COVID-non-hyposmia (n = 23) (p<0.002) and in middle and superior temporal gyri, medial/middle frontal gyri and right insula with respect to PD-hyposmia (p<0.012). With respect to COVIDhyposmia, PD-hyposmia patients showed hypometabolism in inferior/ middle occipital gyri and cuneus bilaterally. Olfactory test-scores were directly correlated with metabolism in bilateral rectus and medial frontal gyri and in right middle temporal and anterior-cingulate gyri in COVID-hyposmia patients (p<0.006) and with bilateral cuneus/precuneus and left lateral occipital-cortex in PD-hyposmia patients (p<0.004). Conclusions: Metabolic signature of persistent hyposmia after COVID-19 encompasses cortical regions involved in olfactory perception and does not overlap metabolic correlates of hyposmia in PD. An impairment in olfactory judgement seem to underlie hyposmia in PD patients while a more restricted perception deficit seems to explain hyposmia in COVID-19. The potential long term neurological sequelae of COVID-19 are of interest from the clinical and economical point of view. Studies targeting symptoms common to COVID-19 and chronic neurological diseases and aiming to explore potential common pathways are of interest also to avoid unjustified claims about a future high incidence of neurodegenerative diseases secondary to the SARS-CoV-2 pandemic.