ABSTRACT
BackgroundFatigue and cognitive complaints are the most frequent persistent symptoms in patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to assess fatigue and neuropsychological performance and investigate changes in the thickness and volume of gray matter (GM) and microstructural abnormalities in the white matter (WM) in a group of patients with mild-to-moderate coronavirus disease 2019 (COVID-19). MethodsWe studied 56 COVID-19 patients and 37 matched controls using magnetic resonance imaging (MRI). Cognition was assessed using Montreal Cognitive Assessment and Cambridge Neuropsychological Test Automated Battery, and fatigue was assessed using Chalder Fatigue Scale (CFQ-11). T1-weighted MRI was used to assess GM thickness and volume. Fiber-specific apparent fiber density (FD), free water index, and diffusion tensor imaging data were extracted using diffusion-weighted MRI (d-MRI). d-MRI data were correlated with clinical and cognitive measures using partial correlations and general linear modeling. ResultsCOVID-19 patients had mild-to-moderate acute illness (95% non-hospitalized). The average period between real-time quantitative reverse transcription polymerase chain reaction-based diagnosis and clinical/MRI assessments was 93.3 ({+/-}26.4) days. The COVID-19 group had higher CFQ-11 scores than the control group (p < 0.001). There were no differences in neuropsychological performance between groups. The COVID-19 group had lower FD in the association, projection, and commissural tracts, but no change in GM. The corona radiata, corticospinal tract, corpus callosum, arcuate fasciculus, cingulate, fornix, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus were involved. CFQ-11 scores correlated with microstructural changes in patients with COVID-19. ConclusionsQuantitative d-MRI detected changes in the WM microstructure of patients recovering from COVID-19. This study suggests a possible brain substrate underlying the symptoms caused by SARS-CoV-2 during medium- to long-term recovery. Key pointsO_LIPatients with COVID-19 had microstructural changes in the WM at a mean follow-up of 3 months. C_LIO_LIThere is a possible brain substrate underlying the symptoms caused by SARS-CoV-2 during medium- to long-term recovery. C_LIO_LIA serial d-MRI study following up on a non-hospitalized sample of patients with milder COVID-19 forms is warranted. C_LI
ABSTRACT
Although post-acute cognitive dysfunction and neuroimaging abnormalities have been reported after hospital discharge in patients recovered from COVID-19, little is known about persistent, long-term alterations in patients who did not require hospitalization. Therefore, we conducted a cross-sectional study of 87 consecutive, non-hospitalized recovered individuals, with a median of 54 days after the laboratory confirmation of COVID-19. We performed structured interviews, neurological examination, and 3T-MRI scans. The MRI study included white matter investigation with diffusion tensor images (DTI) and seed-based resting-state functional MRI (fMRI) connectivity analyses of the default mode network (DMN). In addition, we used validated instruments to examine fatigue, symptoms of anxiety and depression, somnolence, language, memory, and cognitive flexibility. Individuals self-reported a high frequency of headaches (40%) and memory difficulties (33%). The quantitative analyses confirmed symptoms of fatigue (68% of participants), excessive somnolence (35%), symptoms of anxiety (29%), impaired cognitive flexibility (40%) and language dysfunction (33%). In addition, we observed a correlation between DTI fractional anisotropy (FA) and abnormal attention and cognitive flexibility measured by the Trail Making Test part B. The resting-state fMRI study of the DMN showed an association between higher connectivity of the posterior cingulate cortex (PCC) and higher levels of fatigue and somnolence. While greater connectivity of the PCC with bilateral angular gyri was associated with higher fatigue levels, the elevated levels of somnolence correlated with higher connectivity between the PCC and both the left thalamus and putamen.
ABSTRACT
Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, the long-term neuropsychiatric dysfunction has been frequently observed after mild infection. Here we show the spectrum of the cerebral impact of SARS-CoV-2 infection ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal trans-ethmoidal approach) from individuals who died of COVID-19. We used surface-based analyses of 3T MRI and identified orbitofrontal cortical atrophy in a group of 81 mildly infected patients (77% referred anosmia or dysgeusia during acute stage) compared to 145 healthy volunteers; this atrophy correlated with symptoms of anxiety and cognitive dysfunction. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection, and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these 5 patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a non-canonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes and consequently leads to neuronal death or dysfunction. These deregulated processes are also likely to contribute to the structural and functional alterations seen in the brains of COVID-19 patients.
ABSTRACT
Objective: to investigate the relationship between hippocampal atrophy (HA) and surgical outcome in patients with mesial temporal lobe epilepsy (MTLE). Methodology: we compared 34 patients free of seizure (GroupA) with 33 patients with persistent seizures after surgery (GroupB). All had preoperative diagnosis of unilateral MTLE by EEG and MRI evidence of unilateral hippocampal sclerosis (HS) by visual analysis. We performed hippocampal volumetry using high resolution T1 MRI (1mm) in all patients and in 30 healthy controls. Results: Z-score (Mean±SD) of affected hippocampus was -2.58±1.29 in GroupA and -2.57±1.47 in Group-B (p=0.98). The Z-Score of contralateral hippocampus was significantly lower in GroupB, compared to GroupA (p=0.038). Grouping all patients, smaller hippocampal volumes in the affected side were associated with history of meningitis (p=0.049), febrile seizures (p=0.049) and absence of family history of epilepsy (p=0.049). Conclusions: Ipsilateral HA was more severe in patients who had febrile seizures and meningitis, and in those without family history of epilepsy, supporting the notion that in the absence of genetic predisposition, more severe cerebral insult is necessary to induce epileptogenesis. Less favorable surgery outcome for unilateral MTLE was associated with smaller hippocampal volumes contralateral to the operated side, suggesting that surgery is less effective when bilateral damage exists, even when it is not detectable by visual MRI analysis...
Objetivo: investigar a relação entre atrofia hipocampal (AH) e resultado cirúrgico de pacientes com epilepsia de lobo temporal mesial (ELTM). Methodology: comparamos 34 pacientes livres de crises (grupoA) com 33 pacientes que permaneceram com crises após cirurgia (GrupoB). Todos apresentavam o diagnóstico pré-operatório de ELTM unilateral por EEG e RM com sinais de atrofia hipocampal (AH) unilateral na análise visual. Realizamos volumetria do hipocampo utilizando imagens T1 de RM de alta resolução (1mm) em todos os pacientes e em 30 controles sadios. Resultados: o Z-score (Média±DP) dos hipocampos afetados foi -2.58±1.29 no GrupoA e -2.57±1.47 no GrupoB (p=0.98). O Z-score dos hipocampos contralaterais foi significativamente menor no grupoB comparado ao grupoA (p=0.038). Agrupando todos os pacientes, volumes hipocampais menores no lado afetado foram associados à história de meningite (p=0.049), crises febris (p=0.049) e ausência de história familiar de epilepsia (p=0.049). Conclusão: AH ipsilateral foi mais acentuada em pacientes com antecedente de crises febris e meningite, e naqueles sem história familiar de epilepsia, reforçando a ideia de que na ausência de predisposição genética, um maior insulto cerebral seria necessário para induzir epileptogenesis. Um resultado cirúrgico menos favorável na cirurgia para ELTM unilateral foi associado a menores volumes hipocampais no lado contralateral ao lado operado, sugerindo que a cirurgia é menos efetiva quando há dano bilateral, mesmo quando não detectado por analise visual...
