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<meta name="DC.Title" content="Determinants of Deep Gray Matter Atrophy in Multiple Sclerosis: A Multimodal MRI Study" />
<meta name="DC.Identifier" content="10.3174/ajnr.A5915" />
<meta name="DC.Date" content="2019-01-01" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
<meta name="DC.Rights" content="© 2019 by American Journal of Neuroradiology. Indicates open access to non-subscribers at www.ajnr.org" />
<meta name="DC.AccessRights" content="open-access" />
<meta name="DC.Description" content="BACKGROUND AND PURPOSE: Deep gray matter involvement is a consistent feature in multiple sclerosis. The aim of this study was to evaluate the relationship between different deep gray matter alterations and the development of subcortical atrophy, as well as to investigate the possible different substrates of volume loss between phenotypes.

MATERIALS AND METHODS: Seventy-seven patients with MS (52 with relapsing-remitting and 25 with progressive MS) and 41 healthy controls were enrolled in this cross-sectional study. MR imaging investigation included volumetric, DTI, PWI and Quantitative Susceptibility Mapping analyses. Deep gray matter structures were automatically segmented to obtain volumes and mean values for each MR imaging metric in the thalamus, caudate, putamen, and globus pallidus. Between-group differences were probed by ANCOVA analyses, while the contribution of different MR imaging metrics to deep gray matter atrophy was investigated via hierarchic multiple linear regression models.

RESULTS: Patients with MS showed a multifaceted involvement of the thalamus and basal ganglia, with significant atrophy of all deep gray matter structures ( P &lt; .001). In the relapsing-remitting MS group, WM lesion burden proved to be the main contributor to volume loss for all deep gray matter structures ( P ≤ .006), with a minor role of local microstructural damage, which, in turn, was the main determinant of deep gray matter atrophy in patients with progressive MS ( P ≤ .01), coupled with thalamic susceptibility changes ( P = .05).

CONCLUSIONS: Our study confirms the diffuse involvement of deep gray matter in MS, demonstrating a different behavior between MS phenotypes, with subcortical GM atrophy mainly determined by global WM lesion burden in patients with relapsing-remitting MS, while local microstructural damage and susceptibility changes mainly accounted for the development of deep gray matter volume loss in patients with progressive MS.

DD
:   disease duration
DGM
:   deep gray matter
DMT
:   disease-modifying treatment
EDSS
:   Expanded Disability Status Scale
FA
:   fractional anisotropy
HC
:   healthy controls
LL
:   lesion load
MD
:   mean diffusivity
PMS
:   progressive MS
QSM
:   Quantitative Susceptibility Mapping
rCBV
:   relative CBV
RRMS
:   relapsing-remitting MS" />
<meta name="DC.Contributor" content="G. Pontillo" />
<meta name="DC.Contributor" content="S. Cocozza" />
<meta name="DC.Contributor" content="R. Lanzillo" />
<meta name="DC.Contributor" content="C. Russo" />
<meta name="DC.Contributor" content="M.D. Stasi" />
<meta name="DC.Contributor" content="C. Paolella" />
<meta name="DC.Contributor" content="E.A. Vola" />
<meta name="DC.Contributor" content="C. Criscuolo" />
<meta name="DC.Contributor" content="P. Borrelli" />
<meta name="DC.Contributor" content="G. Palma" />
<meta name="DC.Contributor" content="E. Tedeschi" />
<meta name="DC.Contributor" content="V.B. Morra" />
<meta name="DC.Contributor" content="A. Elefante" />
<meta name="DC.Contributor" content="A. Brunetti" />
<meta name="article:published_time" content="2019-01-01" />
<meta name="article:section" content="Adult Brain" />
<meta name="citation_title" content="Determinants of Deep Gray Matter Atrophy in Multiple Sclerosis: A Multimodal MRI Study" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;Deep gray matter involvement is a consistent feature in multiple sclerosis. The aim of this study was to evaluate the relationship between different deep gray matter alterations and the development of subcortical atrophy, as well as to investigate the possible different substrates of volume loss between phenotypes.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;Seventy-seven patients with MS (52 with relapsing-remitting and 25 with progressive MS) and 41 healthy controls were enrolled in this cross-sectional study. MR imaging investigation included volumetric, DTI, PWI and Quantitative Susceptibility Mapping analyses. Deep gray matter structures were automatically segmented to obtain volumes and mean values for each MR imaging metric in the thalamus, caudate, putamen, and globus pallidus. Between-group differences were probed by ANCOVA analyses, while the contribution of different MR imaging metrics to deep gray matter atrophy was investigated via hierarchic multiple linear regression models.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;Patients with MS showed a multifaceted involvement of the thalamus and basal ganglia, with significant atrophy of all deep gray matter structures (&lt;i&gt;P&lt;/i&gt; &amp;lt; .001). In the relapsing-remitting MS group, WM lesion burden proved to be the main contributor to volume loss for all deep gray matter structures (&lt;i&gt;P&lt;/i&gt; ≤ .006), with a minor role of local microstructural damage, which, in turn, was the main determinant of deep gray matter atrophy in patients with progressive MS (&lt;i&gt;P&lt;/i&gt; ≤ .01), coupled with thalamic susceptibility changes (&lt;i&gt;P&lt;/i&gt; = .05).&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;Our study confirms the diffuse involvement of deep gray matter in MS, demonstrating a different behavior between MS phenotypes, with subcortical GM atrophy mainly determined by global WM lesion burden in patients with relapsing-remitting MS, while local microstructural damage and susceptibility changes mainly accounted for the development of deep gray matter volume loss in patients with progressive MS.&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="2019/01/01" />
<meta name="citation_mjid" content="ajnr;40/1/99" />
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<meta name="citation_issn" content="0195-6108" />
<meta name="citation_issn" content="1936-959X" />
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<meta name="citation_article_type" content="Research Article" />
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<meta name="citation_author" content="G. Pontillo" />
<meta name="citation_author_institution" content="aFrom the Departments of Advanced Biomedical Sciences (G.P., S.C., C.R., M.D.S., C.P., E.A.V., E.T., A.E., A.B.)" />
<meta name="citation_author_institution" content="dInstitute of Biostructure and Bioimaging (G.P.), National Research Council, Naples, Italy." />
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<meta name="citation_author" content="S. Cocozza" />
<meta name="citation_author_institution" content="aFrom the Departments of Advanced Biomedical Sciences (G.P., S.C., C.R., M.D.S., C.P., E.A.V., E.T., A.E., A.B.)" />
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<meta name="citation_author" content="A. Elefante" />
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<meta name="twitter:title" content="Determinants of Deep Gray Matter Atrophy in Multiple Sclerosis: A Multimodal MRI Study" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: Deep gray matter involvement is a consistent feature in multiple sclerosis. The aim of this study was to evaluate the relationship between different deep gray matter alterations and the development of subcortical atrophy, as well as to investigate the possible different substrates of volume loss between phenotypes.

MATERIALS AND METHODS: Seventy-seven patients with MS (52 with relapsing-remitting and 25 with progressive MS) and 41 healthy controls were enrolled in this cross-sectional study. MR imaging investigation included volumetric, DTI, PWI and Quantitative Susceptibility Mapping analyses. Deep gray matter structures were automatically segmented to obtain volumes and mean values for each MR imaging metric in the thalamus, caudate, putamen, and globus pallidus. Between-group differences were probed by ANCOVA analyses, while the contribution of different MR imaging metrics to deep gray matter atrophy was investigated via hierarchic multiple linear regression models.

RESULTS: Patients with MS showed a multifaceted involvement of the thalamus and basal ganglia, with significant atrophy of all deep gray matter structures ( P &lt; .001). In the relapsing-remitting MS group, WM lesion burden proved to be the main contributor to volume loss for all deep gray matter structures ( P ≤ .006), with a minor role of local microstructural damage, which, in turn, was the main determinant of deep gray matter atrophy in patients with progressive MS ( P ≤ .01), coupled with thalamic susceptibility changes ( P = .05).

CONCLUSIONS: Our study confirms the diffuse involvement of deep gray matter in MS, demonstrating a different behavior between MS phenotypes, with subcortical GM atrophy mainly determined by global WM lesion burden in patients with relapsing-remitting MS, while local microstructural damage and susceptibility changes mainly accounted for the development of deep gray matter volume loss in patients with progressive MS.

DD
:   disease duration
DGM
:   deep gray matter
DMT
:   disease-modifying treatment
EDSS
:   Expanded Disability Status Scale
FA
:   fractional anisotropy
HC
:   healthy controls
LL
:   lesion load
MD
:   mean diffusivity
PMS
:   progressive MS
QSM
:   Quantitative Susceptibility Mapping
rCBV
:   relative CBV
RRMS
:   relapsing-remitting MS" />
<meta name="og-title" property="og:title" content="Determinants of Deep Gray Matter Atrophy in Multiple Sclerosis: A Multimodal MRI Study" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/40/1/99" />
<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: Deep gray matter involvement is a consistent feature in multiple sclerosis. The aim of this study was to evaluate the relationship between different deep gray matter alterations and the development of subcortical atrophy, as well as to investigate the possible different substrates of volume loss between phenotypes.

MATERIALS AND METHODS: Seventy-seven patients with MS (52 with relapsing-remitting and 25 with progressive MS) and 41 healthy controls were enrolled in this cross-sectional study. MR imaging investigation included volumetric, DTI, PWI and Quantitative Susceptibility Mapping analyses. Deep gray matter structures were automatically segmented to obtain volumes and mean values for each MR imaging metric in the thalamus, caudate, putamen, and globus pallidus. Between-group differences were probed by ANCOVA analyses, while the contribution of different MR imaging metrics to deep gray matter atrophy was investigated via hierarchic multiple linear regression models.

RESULTS: Patients with MS showed a multifaceted involvement of the thalamus and basal ganglia, with significant atrophy of all deep gray matter structures ( P &lt; .001). In the relapsing-remitting MS group, WM lesion burden proved to be the main contributor to volume loss for all deep gray matter structures ( P ≤ .006), with a minor role of local microstructural damage, which, in turn, was the main determinant of deep gray matter atrophy in patients with progressive MS ( P ≤ .01), coupled with thalamic susceptibility changes ( P = .05).

CONCLUSIONS: Our study confirms the diffuse involvement of deep gray matter in MS, demonstrating a different behavior between MS phenotypes, with subcortical GM atrophy mainly determined by global WM lesion burden in patients with relapsing-remitting MS, while local microstructural damage and susceptibility changes mainly accounted for the development of deep gray matter volume loss in patients with progressive MS.

DD
:   disease duration
DGM
:   deep gray matter
DMT
:   disease-modifying treatment
EDSS
:   Expanded Disability Status Scale
FA
:   fractional anisotropy
HC
:   healthy controls
LL
:   lesion load
MD
:   mean diffusivity
PMS
:   progressive MS
QSM
:   Quantitative Susceptibility Mapping
rCBV
:   relative CBV
RRMS
:   relapsing-remitting MS" />
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    <div class="highwire-article-citation highwire-citation-type-highwire-article node65252--5" data-node-nid="65252" id="top-node-65252--6934504261" data-pisa="ajnr;40/1/99" data-pisa-master="ajnr;ajnr.A5915" data-apath="/ajnr/40/1/99.atom" data-hw-author-tooltip-instance="highwire_author_tooltip"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-article-title-complete clearfix has-author-tooltip highwire-citation-highwire-article-top-a">
  
  
      <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">Adult Brain</span></span></div>
  
      <div class="highwire-cite-access"><span class="highwire-citation-access"><i class="highwire-access-icon highwire-access-icon-open-access open-access hw-icon-open-access" title="Open Access" aria-hidden="true"></i><span  class="element-invisible highwire-access-icon highwire-access-icon-open-access" style="">Open Access</span></span></div>
  
      <h1 class="highwire-cite-title" id="page-title">Determinants of Deep Gray Matter Atrophy in Multiple Sclerosis: A Multimodal MRI Study</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">G. Pontillo</span>, <span class="highwire-citation-author" data-delta="1">S. Cocozza</span>, <span class="highwire-citation-author" data-delta="2">R. Lanzillo</span>, <span class="highwire-citation-author" data-delta="3">C. Russo</span>, <span class="highwire-citation-author" data-delta="4">M.D. Stasi</span>, <span class="highwire-citation-author" data-delta="5">C. Paolella</span>, <span class="highwire-citation-author" data-delta="6">E.A. Vola</span>, <span class="highwire-citation-author" data-delta="7">C. Criscuolo</span>, <span class="highwire-citation-author" data-delta="8">P. Borrelli</span>, <span class="highwire-citation-author" data-delta="9">G. Palma</span>, <span class="highwire-citation-author" data-delta="10">E. Tedeschi</span>, <span class="highwire-citation-author" data-delta="11">V.B. Morra</span>, <span class="highwire-citation-author" data-delta="12">A. Elefante</span> and <span class="highwire-citation-author" data-delta="13">A. Brunetti</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">January 2019,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">40 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(1) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">99-106; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A5915 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-65252--6934504261" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">G. Pontillo </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Advanced Biomedical Sciences (G.P., S.C., C.R., M.D.S., C.P., E.A.V., E.T., A.E., A.B.)</div><div class='author-affiliation'><span class='nlm-sup'>d</span>Institute of Biostructure and Bioimaging (G.P.), National Research Council, Naples, Italy.</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=G.%2BPontillo%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=Pontillo%20G&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%3AG.%2BPontillo%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/0000-0001-5425-1890" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for G. Pontillo</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">S. Cocozza </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Advanced Biomedical Sciences (G.P., S.C., C.R., M.D.S., C.P., E.A.V., E.T., A.E., A.B.)</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=S.%2BCocozza%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=Cocozza%20S&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%3AS.%2BCocozza%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/0000-0002-0300-5160" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for S. Cocozza</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">R. Lanzillo </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Neurosciences and Reproductive and Odontostomatological Sciences (R.L., C.C., V.B.M.), University of Naples “Federico II”, Naples, Italy</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=R.%2BLanzillo%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=Lanzillo%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"><a href="/search/author1%3AR.%2BLanzillo%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/0000-0001-6388-8180" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for R. Lanzillo</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">C. Russo </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Advanced Biomedical Sciences (G.P., S.C., C.R., M.D.S., C.P., E.A.V., E.T., A.E., A.B.)</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=C.%2BRusso%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=Russo%20C&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%3AC.%2BRusso%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/0000-0002-2256-7281" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for C. Russo</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">M.D. Stasi </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Advanced Biomedical Sciences (G.P., S.C., C.R., M.D.S., C.P., E.A.V., E.T., A.E., A.B.)</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=M.D.%2BStasi%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=Stasi%20M&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%3AM.D.%2BStasi%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/0000-0002-5406-6780" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for M.D. Stasi</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">C. Paolella </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Advanced Biomedical Sciences (G.P., S.C., C.R., M.D.S., C.P., E.A.V., E.T., A.E., A.B.)</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=C.%2BPaolella%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=Paolella%20C&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%3AC.%2BPaolella%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/0000-0001-6658-3358" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for C. Paolella</a></li></ul></div><div class="author-tooltip-6"><div class="author-tooltip-name">E.A. Vola </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Advanced Biomedical Sciences (G.P., S.C., C.R., M.D.S., C.P., E.A.V., E.T., A.E., A.B.)</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=E.A.%2BVola%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=Vola%20E&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%3AE.A.%2BVola%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/0000-0002-2445-0626" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for E.A. Vola</a></li></ul></div><div class="author-tooltip-7"><div class="author-tooltip-name">C. Criscuolo </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Neurosciences and Reproductive and Odontostomatological Sciences (R.L., C.C., V.B.M.), University of Naples “Federico II”, Naples, Italy</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=C.%2BCriscuolo%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=Criscuolo%20C&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%3AC.%2BCriscuolo%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/0000-0003-0087-2397" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for C. Criscuolo</a></li></ul></div><div class="author-tooltip-8"><div class="author-tooltip-name">P. Borrelli </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>c</span>IRCCS SDN (P.B.), Naples, Italy</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=P.%2BBorrelli%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=Borrelli%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%3AP.%2BBorrelli%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/0000-0002-9299-9661" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for P. Borrelli</a></li></ul></div><div class="author-tooltip-9"><div class="author-tooltip-name">G. Palma </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Advanced Biomedical Sciences (G.P., S.C., C.R., M.D.S., C.P., E.A.V., E.T., A.E., A.B.)</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=G.%2BPalma%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=Palma%20G&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%3AG.%2BPalma%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/0000-0002-0210-268X" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for G. Palma</a></li></ul></div><div class="author-tooltip-10"><div class="author-tooltip-name">E. Tedeschi </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Advanced Biomedical Sciences (G.P., S.C., C.R., M.D.S., C.P., E.A.V., E.T., A.E., A.B.)</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=E.%2BTedeschi%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=Tedeschi%20E&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%3AE.%2BTedeschi%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/0000-0002-0511-0132" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for E. Tedeschi</a></li></ul></div><div class="author-tooltip-11"><div class="author-tooltip-name">V.B. Morra </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Neurosciences and Reproductive and Odontostomatological Sciences (R.L., C.C., V.B.M.), University of Naples “Federico II”, Naples, Italy</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=V.B.%2BMorra%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=Morra%20V&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%3AV.B.%2BMorra%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/0000-0002-2807-6483" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for V.B. Morra</a></li></ul></div><div class="author-tooltip-12"><div class="author-tooltip-name">A. Elefante </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Advanced Biomedical Sciences (G.P., S.C., C.R., M.D.S., C.P., E.A.V., E.T., A.E., A.B.)</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=A.%2BElefante%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=Elefante%20A&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%3AA.%2BElefante%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/0000-0002-9093-7096" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for A. Elefante</a></li></ul></div><div class="author-tooltip-13"><div class="author-tooltip-name">A. Brunetti </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Advanced Biomedical Sciences (G.P., S.C., C.R., M.D.S., C.P., E.A.V., E.T., A.E., A.B.)</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=A.%2BBrunetti%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=Brunetti%20A&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%3AA.%2BBrunetti%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/0000-0001-7057-3494" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for A. Brunetti</a></li></ul></div></div></div>  </div>

  
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      <div class="highwire-cite-title">Determinants of Deep Gray Matter Atrophy in Multiple Sclerosis: A Multimodal MRI Study</div>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">G.</span> <span class="nlm-surname">Pontillo</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">S.</span> <span class="nlm-surname">Cocozza</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">R.</span> <span class="nlm-surname">Lanzillo</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">C.</span> <span class="nlm-surname">Russo</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">M.D.</span> <span class="nlm-surname">Stasi</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">C.</span> <span class="nlm-surname">Paolella</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">E.A.</span> <span class="nlm-surname">Vola</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">C.</span> <span class="nlm-surname">Criscuolo</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">P.</span> <span class="nlm-surname">Borrelli</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">G.</span> <span class="nlm-surname">Palma</span></span>, <span class="highwire-citation-author" data-delta="10"><span class="nlm-given-names">E.</span> <span class="nlm-surname">Tedeschi</span></span>, <span class="highwire-citation-author" data-delta="11"><span class="nlm-given-names">V.B.</span> <span class="nlm-surname">Morra</span></span>, <span class="highwire-citation-author" data-delta="12"><span class="nlm-given-names">A.</span> <span class="nlm-surname">Elefante</span></span>, <span class="highwire-citation-author" data-delta="13"><span class="nlm-given-names">A.</span> <span class="nlm-surname">Brunetti</span></span></span></div>
  
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    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">G.</span> <span class="nlm-surname">Pontillo</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">S.</span> <span class="nlm-surname">Cocozza</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">R.</span> <span class="nlm-surname">Lanzillo</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">C.</span> <span class="nlm-surname">Russo</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">M.D.</span> <span class="nlm-surname">Stasi</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">C.</span> <span class="nlm-surname">Paolella</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">E.A.</span> <span class="nlm-surname">Vola</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">C.</span> <span class="nlm-surname">Criscuolo</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">P.</span> <span class="nlm-surname">Borrelli</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">G.</span> <span class="nlm-surname">Palma</span></span>, <span class="highwire-citation-author" data-delta="10"><span class="nlm-given-names">E.</span> <span class="nlm-surname">Tedeschi</span></span>, <span class="highwire-citation-author" data-delta="11"><span class="nlm-given-names">V.B.</span> <span class="nlm-surname">Morra</span></span>, <span class="highwire-citation-author" data-delta="12"><span class="nlm-given-names">A.</span> <span class="nlm-surname">Elefante</span></span>, <span class="highwire-citation-author" data-delta="13"><span class="nlm-given-names">A.</span> <span class="nlm-surname">Brunetti</span></span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-oa-ind highwire-cite-metadata"><i class="highwire-oa-indicator"></i> </span><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">Jan 2019, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">40 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(1) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">99-106; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A5915 </span></div>
  
  
  
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