Higher limbic and basal ganglia volumes in surviving COVID-negative patients and the relations to fatigue

Hafiz, Rakibul; Gandhi, Tapan Kumar; Mishra, Sapna S.; Prasad, Alok; Mahajan, Vidur; Di, Xin; Natelson, Benjamin H.; Biswal, Bharat B.

doi:10.1016/j.ynirp.2022.100095

Cited by 23 publications

(26 citation statements)

References 39 publications

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“…Using high resolution T1 weighted anatomical images from the same subjects, we have also reported significant gray matter volume alterations in multiple brain regions from the limbic system and basal ganglia obtained using Voxel-Based Morphometry (VBM) analysis in [51]. The results from the present report complements the findings of the aforementioned conventional T1-weighted MR study.…”

Section: Discussionsupporting

confidence: 76%

“…A functional connectivity analysis [50] has reported a negative correlation between fatigue and connectivity in the precuneus network which involves the left superior parietal lobule, the superior occipital gyrus, the angular gyrus, and precuneus. A volumetric study [51] on the brain of COVID affected patients has reported fatigue to be positively correlated to volume of the left posterior cingulate cortex, precuneus, and the superior parietal lobule. Another study [18] on blood perfusion in non-hospitalized COVID patients has reported increased CBF in superior occipital and parietal regions along with decreased perfusion in the inferior occipital regions.…”

Section: Discussionmentioning

confidence: 99%

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Brain Alterations in COVID Recovered Revealed by Susceptibility-Weighted Magnetic Resonance Imaging

Mishra¹,

Hafiz

Misra³

et al. 2022

Preprint

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The increasing number of reports of mild to severe psychological, behavioral, and cognitive sequelae in COVID-19 survivors motivates a need for a thorough assessment of the neurological effects of the disease. In this regard, we have conducted a neuroimaging study to understand the neurotropic behavior of the coronavirus. We hypothesize that the COVID-recovered subjects have developed alterations in the brain which can be measured through susceptibility differences in various regions of the brain when compared to healthy controls (HCs). Hence, we performed our investigations on susceptibility-weighted imaging (SWI) volumes. Fatigue, being of the most common symptoms of Long COVID, has also been studied in this work. SWI volumes of 46 COVID and 30 HCs were included in this study. The COVID patients were imaged within six months of their recovery. We performed an unpaired two-sample t-test over the pre-processed SWI volumes of both groups and multiple linear regression was performed to observe group differences and correlation of fatigue with SWI values. The group analysis showed that COVID recovered subjects had significantly higher susceptibility imaging values in regions of the frontal lobe and the brain stem. The clusters obtained in the frontal lobe primarily show differences in the white matter regions. The COVID group also demonstrated significantly higher fatigue levels than the HC group. The regression analysis on the COVID group yielded clusters in the anterior cingulate gyrus and midbrain, which exhibited negative correlations with fatigue scores. This study suggests an association of Long COVID with prolonged effects on the brain and also indicates the viability of the SWI modality for analysis of post-COVID symptoms.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Brain Alterations in COVID Recovered Revealed by Susceptibility-Weighted Magnetic Resonance Imaging

Mishra¹,

Hafiz

Misra³

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

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“…Besteher et al using 3D VBM found significantly enlarged GM volumes in long-COVID patients involving hippocampus, thalamus, fronto-temporal areas, insula, amygdala, and basal ganglia in both hemispheres in a series of 30 patients with neuropsychiatric disorders when compared to controls [ 40 ]. Additionally, a study of 46 COVID-19 infected patients with chronic fatigue who were scanned with MRI 2 weeks after hospital discharge (and after converting to COVID PCR negative), were found to have higher GM volumes within the basal ganglia (putamen, pallidum) and limbic system (bilateral hippocampus, parahippocampal gyrus, left amygdala, insulas, and right entorhinal area) [ 41 ]. Hippocampal GM enlargement was also found in patients with long term memory deficits following the occurrence of transient global amnesia (TGA) which was attributed to adult hippocampal neurogenesis and macroscopic changes [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers”

Rothstein

2023

BMC Neurol

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Objective COVID-19 (SARS-CoV-2) has been associated with neurological sequelae even in those patients with mild respiratory symptoms. Patients experiencing cognitive symptoms such as “brain fog” and other neurologic sequelae for 8 or more weeks define “long haulers”. There is limited information regarding damage to grey matter (GM) structures occurring in COVID-19 “long haulers”. Advanced imaging techniques can quantify brain volume depletions related to COVID-19 infection which is important as conventional Brain MRI often fails to identify disease correlates. 3-dimensional voxel-based morphometry (3D VBM) analyzes, segments and quantifies key brain volumes allowing comparisons between COVID-19 “long haulers” and normative data drawn from healthy controls, with values based on percentages of intracranial volume. Methods This is a retrospective single center study which analyzed 24 consecutive COVID-19 infected patients with long term neurologic symptoms. Each patient underwent Brain MRI with 3D VBM at median time of 85 days following laboratory confirmation. All patients had relatively mild respiratory symptoms not requiring oxygen supplementation, hospitalization, or assisted ventilation. 3D VBM was obtained for whole brain and forebrain parenchyma, cortical grey matter (CGM), hippocampus, and thalamus. Results The results demonstrate a statistically significant depletion of CGM volume in 24 COVID-19 infected patients. Reduced CGM volume likely influences their long term neurological sequelae and may impair post COVID-19 patient’s quality of life and productivity. Conclusion This study contributes to understanding effects of COVID-19 infection on patient’s neurocognitive and neurological function, with potential for producing serious long term personal and economic consequences, and ongoing challenges to public health systems.

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“…There have been efforts to characterize COVID‐19 based on symptoms, with the hope of predicting severity and likelihood of the post‐COVID‐19 condition. 37 Others have observed fatigue‐related differences in brain structure and function in those recovering from COVID‐19, 38 such as functional connectivity alterations in parietal regions. Interestingly, the post‐COVID‐19 condition shares many common features with chronic fatigue syndrome (i.e.…”

Section: Discussionmentioning

confidence: 99%

MRI Assessment of Cerebral Blood Flow in Nonhospitalized Adults Who Self‐Isolated Due to COVID‐19

Kim

Roudaia

et al. 2022

Magnetic Resonance Imaging

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Background Neurological symptoms associated with coronavirus disease 2019 (COVID‐19), such as fatigue and smell/taste changes, persist beyond infection. However, little is known of brain physiology in the post‐COVID‐19 timeframe. Purpose To determine whether adults who experienced flu‐like symptoms due to COVID‐19 would exhibit cerebral blood flow (CBF) alterations in the weeks/months beyond infection, relative to controls who experienced flu‐like symptoms but tested negative for COVID‐19. Study Type Prospective observational. Population A total of 39 adults who previously self‐isolated at home due to COVID‐19 (41.9 ± 12.6 years of age, 59% female, 116.5 ± 62.2 days since positive diagnosis) and 11 controls who experienced flu‐like symptoms but had a negative COVID‐19 diagnosis (41.5 ± 13.4 years of age, 55% female, 112.1 ± 59.5 since negative diagnosis). Field Strength and Sequences A 3.0 T; T1 ‐weighted magnetization‐prepared rapid gradient and echo‐planar turbo gradient‐spin echo arterial spin labeling sequences. Assessment Arterial spin labeling was used to estimate CBF. A self‐reported questionnaire assessed symptoms, including ongoing fatigue. CBF was compared between COVID‐19 and control groups and between those with ( n = 11) and without self‐reported ongoing fatigue ( n = 28) within the COVID‐19 group. Statistical Tests Between‐group and within‐group comparisons of CBF were performed in a voxel‐wise manner, controlling for age and sex, at a family‐wise error rate of 0.05. Results Relative to controls, the COVID‐19 group exhibited significantly decreased CBF in subcortical regions including the thalamus, orbitofrontal cortex, and basal ganglia (maximum cluster size = 6012 voxels and maximum t ‐statistic = 5.21). Within the COVID‐19 group, significant CBF differences in occipital and parietal regions were observed between those with and without self‐reported on‐going fatigue. Data Conclusion These cross‐sectional data revealed regional CBF decreases in the COVID‐19 group, suggesting the relevance of brain physiology in the post‐COVID‐19 timeframe. This research may help elucidate the heterogeneous symptoms of the post‐COVID‐19 condition. Evidence Level 2. Technical Efficacy Stage 3.

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Higher limbic and basal ganglia volumes in surviving COVID-negative patients and the relations to fatigue

Cited by 23 publications

References 39 publications

Brain Alterations in COVID Recovered Revealed by Susceptibility-Weighted Magnetic Resonance Imaging

Brain Alterations in COVID Recovered Revealed by Susceptibility-Weighted Magnetic Resonance Imaging

Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers”

MRI Assessment of Cerebral Blood Flow in Nonhospitalized Adults Who Self‐Isolated Due to COVID‐19

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