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<meta name="citation_funding_source" content="citation_grant_number=CTSA grant number 1UL1TR003098;" />
<meta name="citation_funding_source" content="citation_funder_id=https://doi.org/10.13039/100000025;citation_grant_number=K23MH118070l;" />
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<meta name="DC.Title" content="Macro- and Microstructural White Matter Differences in Neurologic Postacute Sequelae of SARS-CoV-2 Infection" />
<meta name="DC.Identifier" content="10.3174/ajnr.A8481" />
<meta name="DC.Date" content="2024-12-01" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
<meta name="DC.Rights" content="© 2024 by American Journal of Neuroradiology" />
<meta name="DC.AccessRights" content="restricted" />
<meta name="DC.Description" content="BACKGROUND AND PURPOSE: Neuropsychiatric complications of SARS-CoV-2 infection, also known as neurologic postacute sequelae of SARS-CoV-2 infection (NeuroPASC), affect 10%–60% of infected individuals. There is growing evidence that NeuroPASC is a multi system immune dysregulation disease affecting the brain. The behavioral manifestations of NeuroPASC, such as impaired processing speed, executive function, memory retrieval, and sustained attention, suggest widespread WM involvement. Although previous work has documented WM damage following acute SARS-CoV-2 infection, its involvement in NeuroPASC is less clear. We hypothesized that macrostructural and microstructural WM differences in NeuroPASC participants would accompany cognitive and immune system differences.

MATERIALS AND METHODS: In a cross-sectional study, we screened a total of 159 potential participants and enrolled 72 participants, with 41 asymptomatic controls (NoCOVID) and 31 NeuroPASC participants matched for age, sex, and education. Exclusion criteria included neurologic disorders unrelated to SARS-CoV-2 infection. Assessments included clinical symptom questionnaires, psychometric tests, brain MRI measures, and peripheral cytokine levels. Statistical modeling included separate multivariable regression analyses of GM/WM/CSF volume, WM microstructure, cognitive, and cytokine concentration between-group differences.

RESULTS: NeuroPASC participants had larger cerebral WM volume than NoCOVID controls (β = 0.229; 95% CI: 0.017–0.441; t = 2.16; P = .035). The most pronounced effects were in the prefrontal and anterior temporal WM. NeuroPASC participants also exhibited higher WM mean kurtosis, consistent with ongoing neuroinflammation. NeuroPASC participants had more self-reported symptoms, including headache, and lower performance on measures of attention, concentration, verbal learning, and processing speed. A multivariate profile analysis of the cytokine panel showed different group cytokine profiles (Wald-type-statistic = 44.6, P = .046), with interferon (IFN)-λ1 and IFN-λ2/3 levels higher in the NeuroPASC group.

CONCLUSIONS: NeuroPASC participants reported symptoms of lower concentration, higher fatigue, and impaired cognition compatible with WM syndrome. Psychometric testing confirmed these findings. NeuroPASC participants exhibited larger cerebral WM volume and higher WM mean kurtosis than NoCOVID controls. These findings suggest that immune dysregulation could influence WM properties to produce WM volume increases and consequent cognitive effects and headaches. Further work will be needed to establish mechanistic links among these variables.

COVID
:   SARS-CoV-2 infection
DKI
:   diffusional kurtosis imaging
dMRI
:   diffusion MRI
FA
:   fractional anisotropy
FWE
:   family-wise error
IL
:   interleukin
IFN
:   interferon
NeuroPASC
:   neurologic postacute sequelae of SARS-CoV-2 infection
NeuroQOL
:   neuro-quality of life
PASC
:   postacute sequelae of SARS-CoV-2 infection
SD
:   standard deviation
TFCE
:   threshold-free cluster enhancement
WTS
:   Wald-type statistic" />
<meta name="DC.Contributor" content="Erin E. O’Connor" />
<meta name="DC.Contributor" content="Rosangela Salerno-Goncalves" />
<meta name="DC.Contributor" content="Nikita Rednam" />
<meta name="DC.Contributor" content="Rory O’Brien" />
<meta name="DC.Contributor" content="Peter Rock" />
<meta name="DC.Contributor" content="Andrea R. Levine" />
<meta name="DC.Contributor" content="Thomas A. Zeffiro" />
<meta name="article:published_time" content="2024-12-01" />
<meta name="article:section" content="Ultra-High-Field MRI/Imaging of Epilepsy/Demyelinating Diseases/Inflammation/Infection" />
<meta name="citation_title" content="Macro- and Microstructural White Matter Differences in Neurologic Postacute Sequelae of SARS-CoV-2 Infection" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;Neuropsychiatric complications of SARS-CoV-2 infection, also known as neurologic postacute sequelae of SARS-CoV-2 infection (NeuroPASC), affect 10%–60% of infected individuals. There is growing evidence that NeuroPASC is a multi system immune dysregulation disease affecting the brain. The behavioral manifestations of NeuroPASC, such as impaired processing speed, executive function, memory retrieval, and sustained attention, suggest widespread WM involvement. Although previous work has documented WM damage following acute SARS-CoV-2 infection, its involvement in NeuroPASC is less clear. We hypothesized that macrostructural and microstructural WM differences in NeuroPASC participants would accompany cognitive and immune system differences.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;In a cross-sectional study, we screened a total of 159 potential participants and enrolled 72 participants, with 41 asymptomatic controls (NoCOVID) and 31 NeuroPASC participants matched for age, sex, and education. Exclusion criteria included neurologic disorders unrelated to SARS-CoV-2 infection. Assessments included clinical symptom questionnaires, psychometric tests, brain MRI measures, and peripheral cytokine levels. Statistical modeling included separate multivariable regression analyses of GM/WM/CSF volume, WM microstructure, cognitive, and cytokine concentration between-group differences.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;NeuroPASC participants had larger cerebral WM volume than NoCOVID controls (β = 0.229; 95% CI: 0.017–0.441; &lt;i&gt;t&lt;/i&gt; = 2.16; &lt;i&gt;P&lt;/i&gt; = .035). The most pronounced effects were in the prefrontal and anterior temporal WM. NeuroPASC participants also exhibited higher WM mean kurtosis, consistent with ongoing neuroinflammation. NeuroPASC participants had more self-reported symptoms, including headache, and lower performance on measures of attention, concentration, verbal learning, and processing speed. A multivariate profile analysis of the cytokine panel showed different group cytokine profiles (Wald-type-statistic = 44.6, &lt;i&gt;P&lt;/i&gt; = .046), with interferon (IFN)-λ1 and IFN-λ2/3 levels higher in the NeuroPASC group.&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;NeuroPASC participants reported symptoms of lower concentration, higher fatigue, and impaired cognition compatible with WM syndrome. Psychometric testing confirmed these findings. NeuroPASC participants exhibited larger cerebral WM volume and higher WM mean kurtosis than NoCOVID controls. These findings suggest that immune dysregulation could influence WM properties to produce WM volume increases and consequent cognitive effects and headaches. Further work will be needed to establish mechanistic links among these variables.&lt;/p&gt;" />
<meta name="citation_journal_title" content="American Journal of Neuroradiology" />
<meta name="citation_publisher" content="American Journal of Neuroradiology" />
<meta name="citation_publication_date" content="2024/12/01" />
<meta name="citation_mjid" content="ajnr;45/12/1910" />
<meta name="citation_id" content="45/12/1910" />
<meta name="citation_public_url" content="http://ajnr-stage2.stage.highwire.org/content/45/12/1910" />
<meta name="citation_abstract_html_url" content="http://ajnr-stage2.stage.highwire.org/content/45/12/1910.abstract" />
<meta name="citation_full_html_url" content="http://ajnr-stage2.stage.highwire.org/content/45/12/1910.full" />
<meta name="citation_pdf_url" content="http://ajnr-stage2.stage.highwire.org/content/ajnr/45/12/1910.full.pdf" />
<meta name="citation_issn" content="0195-6108" />
<meta name="citation_issn" content="1936-959X" />
<meta name="citation_doi" content="10.3174/ajnr.A8481" />
<meta name="citation_pmid" content="39389778" />
<meta name="citation_volume" content="45" />
<meta name="citation_issue" content="12" />
<meta name="citation_article_type" content="Research Article" />
<meta name="citation_section" content="Ultra-High-Field MRI/Imaging of Epilepsy/Demyelinating Diseases/Inflammation/Infection" />
<meta name="citation_firstpage" content="1910" />
<meta name="citation_lastpage" content="1918" />
<meta name="citation_author" content="Erin E. O’Connor" />
<meta name="citation_author_institution" content="aFrom the Department of Diagnostic Radiology &amp; Nuclear Medicine (E.E.O., N.R., T.A.Z.), University of Maryland School of Medicine, Baltimore, Maryland" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0002-9483-1117" />
<meta name="citation_author" content="Rosangela Salerno-Goncalves" />
<meta name="citation_author_institution" content="bDepartment of Pediatrics (R.S.-G.), University of Maryland School of Medicine, Baltimore, Maryland" />
<meta name="citation_author" content="Nikita Rednam" />
<meta name="citation_author_institution" content="aFrom the Department of Diagnostic Radiology &amp; Nuclear Medicine (E.E.O., N.R., T.A.Z.), University of Maryland School of Medicine, Baltimore, Maryland" />
<meta name="citation_author" content="Rory O’Brien" />
<meta name="citation_author_institution" content="cLantern Lab (R.O.), Fulton, Maryland" />
<meta name="citation_author" content="Peter Rock" />
<meta name="citation_author_institution" content="dDepartment of Anesthesiology (P.R.), University of Maryland School of Medicine, Baltimore, Maryland" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0003-2250-5926" />
<meta name="citation_author" content="Andrea R. Levine" />
<meta name="citation_author_institution" content="eDepartment of Medicine (A.R.L.), Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore, Maryland" />
<meta name="citation_author" content="Thomas A. Zeffiro" />
<meta name="citation_author_institution" content="aFrom the Department of Diagnostic Radiology &amp; Nuclear Medicine (E.E.O., N.R., T.A.Z.), University of Maryland School of Medicine, Baltimore, Maryland" />
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<meta name="twitter:title" content="Macro- and Microstructural White Matter Differences in Neurologic Postacute Sequelae of SARS-CoV-2 Infection" />
<meta name="twitter:card" content="summary_large_image" />
<meta name="twitter:image" content="http://ajnr-stage2.stage.highwire.org/sites/default/files/highwire/ajnr/45/12.cover-source.jpg" />
<meta name="twitter:description" content="BACKGROUND AND PURPOSE: Neuropsychiatric complications of SARS-CoV-2 infection, also known as neurologic postacute sequelae of SARS-CoV-2 infection (NeuroPASC), affect 10%–60% of infected individuals. There is growing evidence that NeuroPASC is a multi system immune dysregulation disease affecting the brain. The behavioral manifestations of NeuroPASC, such as impaired processing speed, executive function, memory retrieval, and sustained attention, suggest widespread WM involvement. Although previous work has documented WM damage following acute SARS-CoV-2 infection, its involvement in NeuroPASC is less clear. We hypothesized that macrostructural and microstructural WM differences in NeuroPASC participants would accompany cognitive and immune system differences.

MATERIALS AND METHODS: In a cross-sectional study, we screened a total of 159 potential participants and enrolled 72 participants, with 41 asymptomatic controls (NoCOVID) and 31 NeuroPASC participants matched for age, sex, and education. Exclusion criteria included neurologic disorders unrelated to SARS-CoV-2 infection. Assessments included clinical symptom questionnaires, psychometric tests, brain MRI measures, and peripheral cytokine levels. Statistical modeling included separate multivariable regression analyses of GM/WM/CSF volume, WM microstructure, cognitive, and cytokine concentration between-group differences.

RESULTS: NeuroPASC participants had larger cerebral WM volume than NoCOVID controls (β = 0.229; 95% CI: 0.017–0.441; t = 2.16; P = .035). The most pronounced effects were in the prefrontal and anterior temporal WM. NeuroPASC participants also exhibited higher WM mean kurtosis, consistent with ongoing neuroinflammation. NeuroPASC participants had more self-reported symptoms, including headache, and lower performance on measures of attention, concentration, verbal learning, and processing speed. A multivariate profile analysis of the cytokine panel showed different group cytokine profiles (Wald-type-statistic = 44.6, P = .046), with interferon (IFN)-λ1 and IFN-λ2/3 levels higher in the NeuroPASC group.

CONCLUSIONS: NeuroPASC participants reported symptoms of lower concentration, higher fatigue, and impaired cognition compatible with WM syndrome. Psychometric testing confirmed these findings. NeuroPASC participants exhibited larger cerebral WM volume and higher WM mean kurtosis than NoCOVID controls. These findings suggest that immune dysregulation could influence WM properties to produce WM volume increases and consequent cognitive effects and headaches. Further work will be needed to establish mechanistic links among these variables.

COVID
:   SARS-CoV-2 infection
DKI
:   diffusional kurtosis imaging
dMRI
:   diffusion MRI
FA
:   fractional anisotropy
FWE
:   family-wise error
IL
:   interleukin
IFN
:   interferon
NeuroPASC
:   neurologic postacute sequelae of SARS-CoV-2 infection
NeuroQOL
:   neuro-quality of life
PASC
:   postacute sequelae of SARS-CoV-2 infection
SD
:   standard deviation
TFCE
:   threshold-free cluster enhancement
WTS
:   Wald-type statistic" />
<meta name="og-title" property="og:title" content="Macro- and Microstructural White Matter Differences in Neurologic Postacute Sequelae of SARS-CoV-2 Infection" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/45/12/1910" />
<meta name="og-site-name" property="og:site_name" content="American Journal of Neuroradiology" />
<meta name="og-description" property="og:description" content="BACKGROUND AND PURPOSE: Neuropsychiatric complications of SARS-CoV-2 infection, also known as neurologic postacute sequelae of SARS-CoV-2 infection (NeuroPASC), affect 10%–60% of infected individuals. There is growing evidence that NeuroPASC is a multi system immune dysregulation disease affecting the brain. The behavioral manifestations of NeuroPASC, such as impaired processing speed, executive function, memory retrieval, and sustained attention, suggest widespread WM involvement. Although previous work has documented WM damage following acute SARS-CoV-2 infection, its involvement in NeuroPASC is less clear. We hypothesized that macrostructural and microstructural WM differences in NeuroPASC participants would accompany cognitive and immune system differences.

MATERIALS AND METHODS: In a cross-sectional study, we screened a total of 159 potential participants and enrolled 72 participants, with 41 asymptomatic controls (NoCOVID) and 31 NeuroPASC participants matched for age, sex, and education. Exclusion criteria included neurologic disorders unrelated to SARS-CoV-2 infection. Assessments included clinical symptom questionnaires, psychometric tests, brain MRI measures, and peripheral cytokine levels. Statistical modeling included separate multivariable regression analyses of GM/WM/CSF volume, WM microstructure, cognitive, and cytokine concentration between-group differences.

RESULTS: NeuroPASC participants had larger cerebral WM volume than NoCOVID controls (β = 0.229; 95% CI: 0.017–0.441; t = 2.16; P = .035). The most pronounced effects were in the prefrontal and anterior temporal WM. NeuroPASC participants also exhibited higher WM mean kurtosis, consistent with ongoing neuroinflammation. NeuroPASC participants had more self-reported symptoms, including headache, and lower performance on measures of attention, concentration, verbal learning, and processing speed. A multivariate profile analysis of the cytokine panel showed different group cytokine profiles (Wald-type-statistic = 44.6, P = .046), with interferon (IFN)-λ1 and IFN-λ2/3 levels higher in the NeuroPASC group.

CONCLUSIONS: NeuroPASC participants reported symptoms of lower concentration, higher fatigue, and impaired cognition compatible with WM syndrome. Psychometric testing confirmed these findings. NeuroPASC participants exhibited larger cerebral WM volume and higher WM mean kurtosis than NoCOVID controls. These findings suggest that immune dysregulation could influence WM properties to produce WM volume increases and consequent cognitive effects and headaches. Further work will be needed to establish mechanistic links among these variables.

COVID
:   SARS-CoV-2 infection
DKI
:   diffusional kurtosis imaging
dMRI
:   diffusion MRI
FA
:   fractional anisotropy
FWE
:   family-wise error
IL
:   interleukin
IFN
:   interferon
NeuroPASC
:   neurologic postacute sequelae of SARS-CoV-2 infection
NeuroQOL
:   neuro-quality of life
PASC
:   postacute sequelae of SARS-CoV-2 infection
SD
:   standard deviation
TFCE
:   threshold-free cluster enhancement
WTS
:   Wald-type statistic" />
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      <div class="highwire-cite-overline"><span  class="highwire-cite-metadata-article-type highwire-cite-metadata">Research Article</span><span class="separator-pipe"></span><span  class="highwire-cite-metadata-art-cat highwire-cite-metadata"><span class="wrapper">Ultra-High-Field MRI/Imaging of Epilepsy/Demyelinating Diseases/Inflammation/Infection</span></span></div>
  
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      <h1 class="highwire-cite-title" id="page-title">Macro- and Microstructural White Matter Differences in Neurologic Postacute Sequelae of SARS-CoV-2 Infection</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">Erin E. O’Connor</span>, <span class="highwire-citation-author" data-delta="1">Rosangela Salerno-Goncalves</span>, <span class="highwire-citation-author" data-delta="2">Nikita Rednam</span>, <span class="highwire-citation-author" data-delta="3">Rory O’Brien</span>, <span class="highwire-citation-author" data-delta="4">Peter Rock</span>, <span class="highwire-citation-author" data-delta="5">Andrea R. Levine</span> and <span class="highwire-citation-author" data-delta="6">Thomas A. Zeffiro</span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">December 2024,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">45 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(12) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1910-1918; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A8481 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-112057--61361009186" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">Erin E. O’Connor </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Department of Diagnostic Radiology & Nuclear Medicine (E.E.O., N.R., T.A.Z.), University of Maryland School of Medicine, Baltimore, Maryland</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Erin%2BE.%2BO%E2%80%99Connor%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=O%E2%80%99Connor%20EE&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AErin%2BE.%2BO%25E2%2580%2599Connor%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0002-9483-1117" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Erin E. O’Connor</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">Rosangela Salerno-Goncalves </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Department of Pediatrics (R.S.-G.), University of Maryland School of Medicine, Baltimore, Maryland</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Rosangela%2BSalerno-Goncalves%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Salerno-Goncalves%20R&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3ARosangela%2BSalerno-Goncalves%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">Nikita Rednam </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Department of Diagnostic Radiology & Nuclear Medicine (E.E.O., N.R., T.A.Z.), University of Maryland School of Medicine, Baltimore, Maryland</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Nikita%2BRednam%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Rednam%20N&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3ANikita%2BRednam%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">Rory O’Brien </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>c</span>Lantern Lab (R.O.), Fulton, Maryland</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Rory%2BO%E2%80%99Brien%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=O%E2%80%99Brien%20R&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3ARory%2BO%25E2%2580%2599Brien%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">Peter Rock </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>d</span>Department of Anesthesiology (P.R.), University of Maryland School of Medicine, Baltimore, Maryland</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Peter%2BRock%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Rock%20P&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3APeter%2BRock%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0003-2250-5926" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Peter Rock</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">Andrea R. Levine </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>e</span>Department of Medicine (A.R.L.), Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore, Maryland</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Andrea%2BR.%2BLevine%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Levine%20AR&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AAndrea%2BR.%2BLevine%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-6"><div class="author-tooltip-name">Thomas A. 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    <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" data-highwire-cite-ref-tooltip-instance="highwire_reflinks_tooltip" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article abstract-view "><span class="highwire-journal-article-marker-start"></span><div class="section abstract" id="abstract-2"><h2>Abstract</h2><div id="sec-1" class="subsection"><p id="p-2"><strong>BACKGROUND AND PURPOSE:</strong> Neuropsychiatric complications of SARS-CoV-2 infection, also known as neurologic postacute sequelae of SARS-CoV-2 infection (NeuroPASC), affect 10%–60% of infected individuals. There is growing evidence that NeuroPASC is a multi system immune dysregulation disease affecting the brain. The behavioral manifestations of NeuroPASC, such as impaired processing speed, executive function, memory retrieval, and sustained attention, suggest widespread WM involvement. Although previous work has documented WM damage following acute SARS-CoV-2 infection, its involvement in NeuroPASC is less clear. We hypothesized that macrostructural and microstructural WM differences in NeuroPASC participants would accompany cognitive and immune system differences.</p></div><div id="sec-2" class="subsection"><p id="p-3"><strong>MATERIALS AND METHODS:</strong> In a cross-sectional study, we screened a total of 159 potential participants and enrolled 72 participants, with 41 asymptomatic controls (NoCOVID) and 31 NeuroPASC participants matched for age, sex, and education. Exclusion criteria included neurologic disorders unrelated to SARS-CoV-2 infection. Assessments included clinical symptom questionnaires, psychometric tests, brain MRI measures, and peripheral cytokine levels. Statistical modeling included separate multivariable regression analyses of GM/WM/CSF volume, WM microstructure, cognitive, and cytokine concentration between-group differences.</p></div><div id="sec-3" class="subsection"><p id="p-4"><strong>RESULTS:</strong> NeuroPASC participants had larger cerebral WM volume than NoCOVID controls (β = 0.229; 95% CI: 0.017–0.441; <em>t</em> = 2.16; <em>P</em> = .035). The most pronounced effects were in the prefrontal and anterior temporal WM. NeuroPASC participants also exhibited higher WM mean kurtosis, consistent with ongoing neuroinflammation. NeuroPASC participants had more self-reported symptoms, including headache, and lower performance on measures of attention, concentration, verbal learning, and processing speed. A multivariate profile analysis of the cytokine panel showed different group cytokine profiles (Wald-type-statistic = 44.6, <em>P</em> = .046), with interferon (IFN)-λ1 and IFN-λ2/3 levels higher in the NeuroPASC group.</p></div><div id="sec-4" class="subsection"><p id="p-5"><strong>CONCLUSIONS:</strong> NeuroPASC participants reported symptoms of lower concentration, higher fatigue, and impaired cognition compatible with WM syndrome. Psychometric testing confirmed these findings. NeuroPASC participants exhibited larger cerebral WM volume and higher WM mean kurtosis than NoCOVID controls. These findings suggest that immune dysregulation could influence WM properties to produce WM volume increases and consequent cognitive effects and headaches. Further work will be needed to establish mechanistic links among these variables.</p></div></div><div class="section glossary" id="glossary-1"><h2 class="">ABBREVIATIONS:</h2><dl id="def-list-1"><dt id="def-item-1">COVID<span class="def-item-dt-sep"></span></dt><dd>SARS-CoV-2 infection<span class="def-item-dd-sep"></span></dd><dt id="def-item-2">DKI<span class="def-item-dt-sep"></span></dt><dd>diffusional kurtosis imaging<span class="def-item-dd-sep"></span></dd><dt id="def-item-3">dMRI<span class="def-item-dt-sep"></span></dt><dd>diffusion MRI<span class="def-item-dd-sep"></span></dd><dt id="def-item-4">FA<span class="def-item-dt-sep"></span></dt><dd>fractional anisotropy<span class="def-item-dd-sep"></span></dd><dt id="def-item-5">FWE<span class="def-item-dt-sep"></span></dt><dd>family-wise error<span class="def-item-dd-sep"></span></dd><dt id="def-item-6">IL<span class="def-item-dt-sep"></span></dt><dd>interleukin<span class="def-item-dd-sep"></span></dd><dt id="def-item-7">IFN<span class="def-item-dt-sep"></span></dt><dd>interferon<span class="def-item-dd-sep"></span></dd><dt id="def-item-8">NeuroPASC<span class="def-item-dt-sep"></span></dt><dd>neurologic postacute sequelae of SARS-CoV-2 infection<span class="def-item-dd-sep"></span></dd><dt id="def-item-9">NeuroQOL<span class="def-item-dt-sep"></span></dt><dd>neuro-quality of life<span class="def-item-dd-sep"></span></dd><dt id="def-item-10">PASC<span class="def-item-dt-sep"></span></dt><dd>postacute sequelae of SARS-CoV-2 infection<span class="def-item-dd-sep"></span></dd><dt id="def-item-11">SD<span class="def-item-dt-sep"></span></dt><dd>standard deviation<span class="def-item-dd-sep"></span></dd><dt id="def-item-12">TFCE<span class="def-item-dt-sep"></span></dt><dd>threshold-free cluster enhancement<span class="def-item-dd-sep"></span></dd><dt id="def-item-13">WTS<span class="def-item-dt-sep"></span></dt><dd>Wald-type statistic</dd></dl></div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2024 by American Journal of Neuroradiology</li></ul><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div><a href="http://ajnr-stage2.stage.highwire.org/content/45/12/1910.full" class="hw-link hw-link-article-full-text" data-icon-position="" data-hide-link-title="0">View Full Text</a></div>  </div>

  
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        	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-volume highwire-cite-metadata">Vol. 45</span>, <span  class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 12 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 Dec 2024 </div></div>
      
      
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    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">Dec 2024, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">45 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(12) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1910-1918; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A8481 </span></div>
  
  
  
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    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">Dec 2024, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">45 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(12) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1910-1918; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A8481 </span></div>
  
  
  
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