Cerebral Micro-Structural Changes in COVID-19 Patients – An MRI-based 3-month Follow-up Study, 2020, Lu et al

Dolphin · Aug 4, 2020

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https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30228-5/fulltext

Cerebral Micro-Structural Changes in COVID-19 Patients – An MRI-based 3-month Follow-up Study

Yiping Lu, MD 1

Xuanxuan Li, MD 1

Daoying Geng, MD 1

Nan Mei, MD 1

Pu-Yeh Wu, PhD

Chu-Chung Huang, PhD

et al.

Open AccessPublished:August 03, 2020DOI:https://doi.org/10.1016/j.eclinm.2020.100484

Abstract

Background
Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the micro-structural changes in the central nervous system after infection. We aimed to identify the existence of potential brain micro-structural changes related to SARS-CoV-2.

Methods
In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 60 recovered COVID-19 patients (56.67% male; age: 44.10 ± 16.00) and 39 age- and sex-matched non-COVID-19 controls (56.41% male; age: 45.88 ± 13.90). Registered fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were quantified for DTI, and an index score system was introduced. Regional volumes derived from Voxel-based Morphometry (VBM) and DTI metrics were compared using analysis of covariance (ANCOVA). Two sample t-test and Spearman correlation were conducted to assess the relationships among imaging indices, index scores and clinical information.

Findings
In this follow-up stage, neurological symptoms were presented in 55% COVID-19 patients. COVID-19 patients had statistically significantly higher bilateral gray matter volumes (GMV) in olfactory cortices, hippocampi, insulas, left Rolandic operculum, left Heschl's gyrus and right cingulate gyrus and a general decline of MD, AD, RD accompanied with an increase of FA in white matter, especially AD in the right CR, EC and SFF, and MD in SFF compared with non-COVID-19 volunteers (corrected p value <0.05). Global GMV, GMVs in left Rolandic operculum, right cingulate, bilateral hippocampi, left Heschl's gyrus, and Global MD of WM were found to correlate with memory loss (p value <0.05). GMVs in the right cingulate gyrus and left hippocampus were related to smell loss (p value <0.05). MD-GM score, global GMV, and GMV in right cingulate gyrus were correlated with LDH level (p value <0.05).

Interpretation
Study findings revealed possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting the long-term consequences of SARS-CoV-2.

Funding
Shanghai Natural Science Foundation, Youth Program of National Natural Science Foundation of China, Shanghai Sailing Program, Shanghai Science and Technology Development, Shanghai Municipal Science and Technology Major Project and ZJ Lab.
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Dolphin · Aug 4, 2020

Research in context

Evidence before this study
We searched PubMed and the China National Knowledge Infrastructure database for articles published up to June 10, 2020, using the keywords “COVID-19”, “SARS-CoV-2”, and “neurological”, “DTI”, and “brain”. A total of 29 case reports/series reports and 106 reviews, among which 8 were systematic reviews, about the neurological findings in the central nervous system. No data has been reported about the structural changes in the brain from COVID-19 patients by functional MRI in a prospective way.

Added value of this study
In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 60 recovered COVID-19 patients and 39 age- and sex-matched non-COVID-19 controls. We found that these recovered COVID-19 patients were more likely to have enlarged olfactory cortices, hippocampi, insulas, Heschl's gyrus, Rolandic operculum and cingulate gyrus, and a general decline of Mean Diffusivity (MD), Axial Diffusivity (AD), Radial Diffusivity (RD) accompanied with an increase of Fractional Anisotropy (FA) in white matter, especially AD in the right Coronal Radiata (CR), External Capsule (EC) and Superior Frontal-occipital Fasciculus (SFF), and MD in SFF compared with non-COVID-19 volunteers. Global Gray Matter Volume (GMV), GMVs in left Rolandic operculum, right cingulate, bilateral hippocampi, left Heschl's gyrus, and Global MD of WM were found to correlate with memory loss. GMVs in right cingulate gyrus and left hippocampus were related to smell loss. MD-GM score, global GMV, and GMV in right cingulate gyrus were correlated with Lactate Dehydrogenase (LDH) level.

Implications of all the available evidence
Our findings revealed possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting neuro-invasion potential of SARS-CoV-2. This requires attention since even if the patients recover well from the pneumonia condition, the neurological changes may cause a great burden. More research in the mechanism and route of neuro-invasion of SARS-CoV-2 is expected.
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adambeyoncelowe · Aug 4, 2020

Wasn't 'increase of FA in white matter' found in some ME studies too?

Andy · Aug 27, 2020

adambeyoncelowe said: ↑

Wasn't 'increase of FA in white matter' found in some ME studies too?
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This might be what you are thinking of.

Bilateral white matter atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right anterior arcuate FA may serve as a biomarker for CFS.
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Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome, 2014, Zeineh, Montoya et al

This also has some similarities to the Covid19 study results.

Elevated GM volume in CFS is seen in areas related to processing of interoceptive signals and stress. Reduced WM volume in the patient group partially supports earlier findings of WM abnormalities in regions of the midbrain and brainstem.
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Grey and white matter differences in Chronic Fatigue Syndrome – A voxel-based morphometry study, 2018, Finkelmeyer et al

adambeyoncelowe · Aug 27, 2020

Andy said: ↑

This might be what you are thinking of.

Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome, 2014, Zeineh, Montoya et al

This also has some similarities to the Covid19 study results.

Grey and white matter differences in Chronic Fatigue Syndrome – A voxel-based morphometry study, 2018, Finkelmeyer et al
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Thanks. That's what I thought. Very helpful.

adambeyoncelowe · Aug 28, 2020

Re-reading, one is right arcuate 'fasciculus abnormality' (FA) and the other is fractional anisotropy (FA), so totally different. My bad.

Andy · Aug 28, 2020

adambeyoncelowe said: ↑

Re-reading, one is right arcuate 'fasciculus abnormality' (FA) and the other is fractional anisotropy (FA), so totally different. My bad.
Click to expand...

The Montoya study says

Advances in Knowledge

■ Patients with severe chronic fatigue syndrome (CFS) have increased fractional anisotropy (FA) in the anterior right arcuate fasciculus when compared with control subjects (P = .0015), with most right-handed patients having maximal FA in the anterior 10% of the arcuate of higher than 0.6, while in the same region, most right-handed control subjects have an FA of less than 0.6.

■ The right hemisphere in younger patients with CFS exhibits regions of cortical thickening that are connected via the right arcuate fasciculus, specifically in the right middle temporal and precentral gyri.

■ White matter volumes are lower in patients with CFS compared with control subjects (467 581 mm3 ± 47 610 vs 504 864 mm3 ± 68 126, P = .0026).

Implication for Patient Care

■ Right anterior arcuate FA may be a biomarker for CFS.

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adambeyoncelowe · Aug 28, 2020

Andy said: ↑

The Montoya study says
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Oh that's good. I was getting so confused by all the acronyms!

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