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<meta name="HW.identifier" content="/ajnr/early/2016/09/29/ajnr.A4952.atom" />
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<meta name="DC.Title" content="Hippocampal and Deep Gray Matter Nuclei Atrophy Is Relevant for Explaining Cognitive Impairment in MS: A Multicenter Study" />
<meta name="DC.Identifier" content="10.3174/ajnr.A4952" />
<meta name="DC.Date" content="2016-09-29" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
<meta name="DC.Rights" content="© 2017 American Society 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: The structural MR imaging correlates of cognitive impairment in multiple sclerosis are still debated. This study assessed lesional and atrophy measures of white matter and gray matter involvement in patients with MS acquired in 7 European sites to identify the MR imaging variables most closely associated with cognitive dysfunction.

MATERIALS AND METHODS: Brain dual-echo, 3D T1-weighted, and double inversion recovery scans were acquired at 3T from 62 patients with relapsing-remitting MS and 65 controls. Patients with at least 2 neuropsychological tests with abnormal findings were considered cognitively impaired. Focal WM and cortical lesions were identified, and volumetric measures from WM, cortical GM, the hippocampus, and deep GM nuclei were obtained. Age- and site-adjusted models were used to compare lesion and volumetric MR imaging variables between patients with MS who were cognitively impaired and cognitively preserved. A multivariate analysis identified MR imaging variables associated with cognitive scores and disability.

RESULTS: Twenty-three patients (38%) were cognitively impaired. Compared with those with who were cognitively preserved, patients with MS with cognitive impairment had higher T2 and T1 lesion volumes and a trend toward a higher number of cortical lesions. Significant brain, cortical GM, hippocampal, deep GM nuclei, and WM atrophy was found in patients with MS with cognitive impairment versus those who were cognitively preserved. Hippocampal and deep GM nuclei atrophy were the best predictors of cognitive impairment, while WM atrophy was the best predictor of disability.

CONCLUSIONS: Hippocampal and deep GM nuclei atrophy are key factors associated with cognitive impairment in MS. These MR imaging measures could be applied in a multicenter context, with cognition as clinical outcome.

### Abbreviations

CI
:   cognitively impaired
CL
:   cortical lesion
CP
:   cognitively preserved
DIR
:   double inversion recovery
EDSS
:   Expanded Disability Status Scale
HC
:   healthy controls
LV
:   lesion volumes
WCST
:   Wisconsin Card Sorting Test" />
<meta name="DC.Contributor" content="D. Damjanovic" />
<meta name="DC.Contributor" content="P. Valsasina" />
<meta name="DC.Contributor" content="M.A. Rocca" />
<meta name="DC.Contributor" content="M.L. Stromillo" />
<meta name="DC.Contributor" content="A. Gallo" />
<meta name="DC.Contributor" content="C. Enzinger" />
<meta name="DC.Contributor" content="H.E. Hulst" />
<meta name="DC.Contributor" content="A. Rovira" />
<meta name="DC.Contributor" content="N. Muhlert" />
<meta name="DC.Contributor" content="N. De Stefano" />
<meta name="DC.Contributor" content="A. Bisecco" />
<meta name="DC.Contributor" content="F. Fazekas" />
<meta name="DC.Contributor" content="M.J. Arévalo" />
<meta name="DC.Contributor" content="T.A. Yousry" />
<meta name="DC.Contributor" content="M. Filippi" />
<meta name="article:published_time" content="2016-09-29" />
<meta name="article:section" content="ADULT BRAIN" />
<meta name="citation_title" content="Hippocampal and Deep Gray Matter Nuclei Atrophy Is Relevant for Explaining Cognitive Impairment in MS: A Multicenter Study" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;The structural MR imaging correlates of cognitive impairment in multiple sclerosis are still debated. This study assessed lesional and atrophy measures of white matter and gray matter involvement in patients with MS acquired in 7 European sites to identify the MR imaging variables most closely associated with cognitive dysfunction.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;Brain dual-echo, 3D T1-weighted, and double inversion recovery scans were acquired at 3T from 62 patients with relapsing-remitting MS and 65 controls. Patients with at least 2 neuropsychological tests with abnormal findings were considered cognitively impaired. Focal WM and cortical lesions were identified, and volumetric measures from WM, cortical GM, the hippocampus, and deep GM nuclei were obtained. Age- and site-adjusted models were used to compare lesion and volumetric MR imaging variables between patients with MS who were cognitively impaired and cognitively preserved. A multivariate analysis identified MR imaging variables associated with cognitive scores and disability.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;Twenty-three patients (38%) were cognitively impaired. Compared with those with who were cognitively preserved, patients with MS with cognitive impairment had higher T2 and T1 lesion volumes and a trend toward a higher number of cortical lesions. Significant brain, cortical GM, hippocampal, deep GM nuclei, and WM atrophy was found in patients with MS with cognitive impairment versus those who were cognitively preserved. Hippocampal and deep GM nuclei atrophy were the best predictors of cognitive impairment, while WM atrophy was the best predictor of disability.&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;Hippocampal and deep GM nuclei atrophy are key factors associated with cognitive impairment in MS. These MR imaging measures could be applied in a multicenter context, with cognition as clinical outcome.&lt;/p&gt;" />
<meta name="citation_journal_title" content="American Journal of Neuroradiology" />
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<meta name="citation_author" content="D. Damjanovic" />
<meta name="citation_author_institution" content="From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK." />
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<meta name="citation_author" content="A. Rovira" />
<meta name="citation_author_institution" content="From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK." />
<meta name="citation_author_orcid" content="http://orcid.org/0000-0002-2132-6750" />
<meta name="citation_author" content="N. Muhlert" />
<meta name="citation_author_institution" content="From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK." />
<meta name="citation_author_orcid" content="http://orcid.org/0000-0002-6414-5589" />
<meta name="citation_author" content="N. De Stefano" />
<meta name="citation_author_institution" content="From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK." />
<meta name="citation_author_orcid" content="http://orcid.org/0000-0003-4930-7639" />
<meta name="citation_author" content="A. Bisecco" />
<meta name="citation_author_institution" content="From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK." />
<meta name="citation_author_orcid" content="http://orcid.org/0000-0002-7202-4445" />
<meta name="citation_author" content="F. Fazekas" />
<meta name="citation_author_institution" content="From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK." />
<meta name="citation_author_orcid" content="http://orcid.org/0000-0001-8155-7799" />
<meta name="citation_author" content="M.J. Arévalo" />
<meta name="citation_author_institution" content="From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK." />
<meta name="citation_author_orcid" content="http://orcid.org/0000-0003-0626-5555" />
<meta name="citation_author" content="T.A. Yousry" />
<meta name="citation_author_institution" content="From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK." />
<meta name="citation_author_orcid" content="http://orcid.org/0000-0003-3295-0628" />
<meta name="citation_author" content="M. Filippi" />
<meta name="citation_author_institution" content="From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK." />
<meta name="citation_author_orcid" content="http://orcid.org/0000-0002-5485-0479" />
<meta name="citation_fulltext_world_readable" content="" />
<meta name="twitter:title" content="Hippocampal and Deep Gray Matter Nuclei Atrophy Is Relevant for Explaining Cognitive Impairment in MS: A Multicenter Study" />
<meta name="twitter:card" content="summary" />
<meta name="twitter:description" content="BACKGROUND AND PURPOSE: The structural MR imaging correlates of cognitive impairment in multiple sclerosis are still debated. This study assessed lesional and atrophy measures of white matter and gray matter involvement in patients with MS acquired in 7 European sites to identify the MR imaging variables most closely associated with cognitive dysfunction.

MATERIALS AND METHODS: Brain dual-echo, 3D T1-weighted, and double inversion recovery scans were acquired at 3T from 62 patients with relapsing-remitting MS and 65 controls. Patients with at least 2 neuropsychological tests with abnormal findings were considered cognitively impaired. Focal WM and cortical lesions were identified, and volumetric measures from WM, cortical GM, the hippocampus, and deep GM nuclei were obtained. Age- and site-adjusted models were used to compare lesion and volumetric MR imaging variables between patients with MS who were cognitively impaired and cognitively preserved. A multivariate analysis identified MR imaging variables associated with cognitive scores and disability.

RESULTS: Twenty-three patients (38%) were cognitively impaired. Compared with those with who were cognitively preserved, patients with MS with cognitive impairment had higher T2 and T1 lesion volumes and a trend toward a higher number of cortical lesions. Significant brain, cortical GM, hippocampal, deep GM nuclei, and WM atrophy was found in patients with MS with cognitive impairment versus those who were cognitively preserved. Hippocampal and deep GM nuclei atrophy were the best predictors of cognitive impairment, while WM atrophy was the best predictor of disability.

CONCLUSIONS: Hippocampal and deep GM nuclei atrophy are key factors associated with cognitive impairment in MS. These MR imaging measures could be applied in a multicenter context, with cognition as clinical outcome.

### Abbreviations

CI
:   cognitively impaired
CL
:   cortical lesion
CP
:   cognitively preserved
DIR
:   double inversion recovery
EDSS
:   Expanded Disability Status Scale
HC
:   healthy controls
LV
:   lesion volumes
WCST
:   Wisconsin Card Sorting Test" />
<meta name="og-title" property="og:title" content="Hippocampal and Deep Gray Matter Nuclei Atrophy Is Relevant for Explaining Cognitive Impairment in MS: A Multicenter Study" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/early/2016/09/29/ajnr.A4952" />
<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: The structural MR imaging correlates of cognitive impairment in multiple sclerosis are still debated. This study assessed lesional and atrophy measures of white matter and gray matter involvement in patients with MS acquired in 7 European sites to identify the MR imaging variables most closely associated with cognitive dysfunction.

MATERIALS AND METHODS: Brain dual-echo, 3D T1-weighted, and double inversion recovery scans were acquired at 3T from 62 patients with relapsing-remitting MS and 65 controls. Patients with at least 2 neuropsychological tests with abnormal findings were considered cognitively impaired. Focal WM and cortical lesions were identified, and volumetric measures from WM, cortical GM, the hippocampus, and deep GM nuclei were obtained. Age- and site-adjusted models were used to compare lesion and volumetric MR imaging variables between patients with MS who were cognitively impaired and cognitively preserved. A multivariate analysis identified MR imaging variables associated with cognitive scores and disability.

RESULTS: Twenty-three patients (38%) were cognitively impaired. Compared with those with who were cognitively preserved, patients with MS with cognitive impairment had higher T2 and T1 lesion volumes and a trend toward a higher number of cortical lesions. Significant brain, cortical GM, hippocampal, deep GM nuclei, and WM atrophy was found in patients with MS with cognitive impairment versus those who were cognitively preserved. Hippocampal and deep GM nuclei atrophy were the best predictors of cognitive impairment, while WM atrophy was the best predictor of disability.

CONCLUSIONS: Hippocampal and deep GM nuclei atrophy are key factors associated with cognitive impairment in MS. These MR imaging measures could be applied in a multicenter context, with cognition as clinical outcome.

### Abbreviations

CI
:   cognitively impaired
CL
:   cortical lesion
CP
:   cognitively preserved
DIR
:   double inversion recovery
EDSS
:   Expanded Disability Status Scale
HC
:   healthy controls
LV
:   lesion volumes
WCST
:   Wisconsin Card Sorting Test" />
<meta name="og-type" property="og:type" content="article" />
<meta name="og-image" property="og:image" content="" />
<link rel="shortlink" href="/node/51674" />
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    <div class="highwire-article-citation highwire-citation-type-highwire-article node51674--5" data-node-nid="51674" id="top-node-51674--61899681400" data-pisa="ajnr;ajnr.A4952v1" data-pisa-master="ajnr;ajnr.A4952" data-apath="/ajnr/early/2016/09/29/ajnr.A4952.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">Hippocampal and Deep Gray Matter Nuclei Atrophy Is Relevant for Explaining Cognitive Impairment in MS: A Multicenter Study</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">D. Damjanovic</span>, <span class="highwire-citation-author" data-delta="1">P. Valsasina</span>, <span class="highwire-citation-author" data-delta="2">M.A. Rocca</span>, <span class="highwire-citation-author" data-delta="3">M.L. Stromillo</span>, <span class="highwire-citation-author" data-delta="4">A. Gallo</span>, <span class="highwire-citation-author" data-delta="5">C. Enzinger</span>, <span class="highwire-citation-author" data-delta="6">H.E. Hulst</span>, <span class="highwire-citation-author" data-delta="7">A. Rovira</span>, <span class="highwire-citation-author" data-delta="8">N. Muhlert</span>, <span class="highwire-citation-author" data-delta="9">N. De Stefano</span>, <span class="highwire-citation-author" data-delta="10">A. Bisecco</span>, <span class="highwire-citation-author" data-delta="11">F. Fazekas</span>, <span class="highwire-citation-author" data-delta="12">M.J. Arévalo</span>, <span class="highwire-citation-author" data-delta="13">T.A. Yousry</span> and <span class="highwire-citation-author" data-delta="14">M. Filippi</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">September 2016,  </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A4952 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-51674--61899681400" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">D. Damjanovic </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.</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=D.%2BDamjanovic%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=Damjanovic%20D&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%3AD.%2BDamjanovic%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="http://orcid.org/0000-0002-2970-6125" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for D. Damjanovic</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">P. Valsasina </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.</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.%2BValsasina%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=Valsasina%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.%2BValsasina%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="http://orcid.org/0000-0001-5390-2655" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for P. Valsasina</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">M.A. Rocca </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.</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.A.%2BRocca%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=Rocca%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.A.%2BRocca%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="http://orcid.org/0000-0003-2358-4320" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for M.A. Rocca</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">M.L. Stromillo </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.</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.L.%2BStromillo%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=Stromillo%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.L.%2BStromillo%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="http://orcid.org/0000-0001-6909-623X" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for M.L. Stromillo</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">A. Gallo </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.</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.%2BGallo%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=Gallo%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.%2BGallo%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="http://orcid.org/0000-0002-2203-6237" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for A. Gallo</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">C. Enzinger </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.</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.%2BEnzinger%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=Enzinger%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.%2BEnzinger%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="http://orcid.org/0000-0001-9764-7617" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for C. Enzinger</a></li></ul></div><div class="author-tooltip-6"><div class="author-tooltip-name">H.E. Hulst </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.</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=H.E.%2BHulst%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=Hulst%20H&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%3AH.E.%2BHulst%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="http://orcid.org/0000-0002-5039-1359" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for H.E. Hulst</a></li></ul></div><div class="author-tooltip-7"><div class="author-tooltip-name">A. Rovira </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.</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.%2BRovira%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=Rovira%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.%2BRovira%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="http://orcid.org/0000-0002-2132-6750" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for A. Rovira</a></li></ul></div><div class="author-tooltip-8"><div class="author-tooltip-name">N. Muhlert </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.</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=N.%2BMuhlert%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=Muhlert%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"><a href="/search/author1%3AN.%2BMuhlert%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="http://orcid.org/0000-0002-6414-5589" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for N. Muhlert</a></li></ul></div><div class="author-tooltip-9"><div class="author-tooltip-name">N. De Stefano </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.</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=N.%2BDe%2BStefano%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=De%20Stefano%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"><a href="/search/author1%3AN.%2BDe%2BStefano%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="http://orcid.org/0000-0003-4930-7639" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for N. De Stefano</a></li></ul></div><div class="author-tooltip-10"><div class="author-tooltip-name">A. Bisecco </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.</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.%2BBisecco%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=Bisecco%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.%2BBisecco%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="http://orcid.org/0000-0002-7202-4445" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for A. Bisecco</a></li></ul></div><div class="author-tooltip-11"><div class="author-tooltip-name">F. Fazekas </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.</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=F.%2BFazekas%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=Fazekas%20F&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%3AF.%2BFazekas%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="http://orcid.org/0000-0001-8155-7799" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for F. Fazekas</a></li></ul></div><div class="author-tooltip-12"><div class="author-tooltip-name">M.J. Arévalo </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.</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.J.%2BAr%C3%A9valo%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=Ar%C3%A9valo%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.J.%2BAr%25C3%25A9valo%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="http://orcid.org/0000-0003-0626-5555" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for M.J. Arévalo</a></li></ul></div><div class="author-tooltip-13"><div class="author-tooltip-name">T.A. Yousry </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.</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=T.A.%2BYousry%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=Yousry%20T&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%3AT.A.%2BYousry%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="http://orcid.org/0000-0003-3295-0628" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for T.A. Yousry</a></li></ul></div><div class="author-tooltip-14"><div class="author-tooltip-name">M. Filippi </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) and Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy; MRI Center “SUN-FISM” (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy; I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; Department of Neurology (C.E., F.F.) and Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria; Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands; Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; and NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.</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.%2BFilippi%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=Filippi%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.%2BFilippi%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="http://orcid.org/0000-0002-5485-0479" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for M. 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