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<meta name="DC.Title" content="Brain Changes in Kallmann Syndrome" />
<meta name="DC.Identifier" content="10.3174/ajnr.A3946" />
<meta name="DC.Date" content="2014-05-22" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
<meta name="DC.Rights" content="© 2014 American Society of Neuroradiology" />
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<meta name="DC.Description" content="BACKGROUND AND PURPOSE: Kallmann syndrome is a rare inherited disorder due to defective intrauterine migration of olfactory axons and gonadotropin-releasing hormone neurons, leading to rhinencephalon hypoplasia and hypogonadotropic hypogonadism. Concomitant brain developmental abnormalities have been described. Our aim was to investigate Kallmann syndrome–related brain changes with conventional and novel quantitative MR imaging analyses.

MATERIALS AND METHODS: Forty-five male patients with Kallmann syndrome (mean age, 30.7 years; range, 9–55 years) and 23 age-matched male controls underwent brain MR imaging. The MR imaging study protocol included 3D-T1, FLAIR, and diffusion tensor imaging (32 noncollinear gradient-encoding directions; b-value = 800 s/mm2). Voxel-based morphometry, sulcation, curvature, and cortical thickness analyses and tract-based spatial statistics were performed by using Statistical Parametric Mapping 8, FreeSurfer, and the fMRI of the Brain Software Library.

RESULTS: Corpus callosum partial agenesis, multiple sclerosis–like white matter abnormalities, and acoustic schwannoma were found in 1 patient each. The total amount of gray and white matter volume and tract-based spatial statistics measures (fractional anisotropy and mean, radial, and axial diffusivity) did not differ between patients with Kallmann syndrome and controls. By specific analyses, patients with Kallmann syndrome presented with symmetric clusters of gray matter volume increase and decrease and white matter volume decrease close to the olfactory sulci; reduced sulcal depth of the olfactory sulci and deeper medial orbital-frontal sulci; lesser curvature of the olfactory sulcus and sharper curvature close to the medial orbital-frontal sulcus; and increased cortical thickness within the olfactory sulcus.

CONCLUSIONS: This large MR imaging study on male patients with Kallmann syndrome featured significant morphologic and structural brain changes, likely driven by olfactory bulb hypo-/aplasia, selectively involving the basal forebrain cortex.

### Abbreviations

KS
:   Kallmann syndrome
FA
:   fractional anisotropy
MNI
:   Montreal Neurological Institute
TBSS
:   tract-based spatial statistics
VBM
:   voxel-based morphometry" />
<meta name="DC.Contributor" content="R. Manara" />
<meta name="DC.Contributor" content="A. Salvalaggio" />
<meta name="DC.Contributor" content="A. Favaro" />
<meta name="DC.Contributor" content="V. Palumbo" />
<meta name="DC.Contributor" content="V. Citton" />
<meta name="DC.Contributor" content="A. Elefante" />
<meta name="DC.Contributor" content="A. Brunetti" />
<meta name="DC.Contributor" content="F. Di Salle" />
<meta name="DC.Contributor" content="G. Bonanni" />
<meta name="DC.Contributor" content="A.A. Sinisi" />
<meta name="article:published_time" content="2014-05-22" />
<meta name="article:section" content="BRAIN" />
<meta name="citation_title" content="Brain Changes in Kallmann Syndrome" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;Kallmann syndrome is a rare inherited disorder due to defective intrauterine migration of olfactory axons and gonadotropin-releasing hormone neurons, leading to rhinencephalon hypoplasia and hypogonadotropic hypogonadism. Concomitant brain developmental abnormalities have been described. Our aim was to investigate Kallmann syndrome–related brain changes with conventional and novel quantitative MR imaging analyses.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;Forty-five male patients with Kallmann syndrome (mean age, 30.7 years; range, 9–55 years) and 23 age-matched male controls underwent brain MR imaging. The MR imaging study protocol included 3D-T1, FLAIR, and diffusion tensor imaging (32 noncollinear gradient-encoding directions; b-value = 800 s/mm&lt;sup&gt;2&lt;/sup&gt;). Voxel-based morphometry, sulcation, curvature, and cortical thickness analyses and tract-based spatial statistics were performed by using Statistical Parametric Mapping 8, FreeSurfer, and the fMRI of the Brain Software Library.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;Corpus callosum partial agenesis, multiple sclerosis–like white matter abnormalities, and acoustic schwannoma were found in 1 patient each. The total amount of gray and white matter volume and tract-based spatial statistics measures (fractional anisotropy and mean, radial, and axial diffusivity) did not differ between patients with Kallmann syndrome and controls. By specific analyses, patients with Kallmann syndrome presented with symmetric clusters of gray matter volume increase and decrease and white matter volume decrease close to the olfactory sulci; reduced sulcal depth of the olfactory sulci and deeper medial orbital-frontal sulci; lesser curvature of the olfactory sulcus and sharper curvature close to the medial orbital-frontal sulcus; and increased cortical thickness within the olfactory sulcus.&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;This large MR imaging study on male patients with Kallmann syndrome featured significant morphologic and structural brain changes, likely driven by olfactory bulb hypo-/aplasia, selectively involving the basal forebrain cortex.&lt;/p&gt;" />
<meta name="citation_journal_title" content="American Journal of Neuroradiology" />
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<meta name="citation_author" content="R. Manara" />
<meta name="citation_author_institution" content="From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, Italy." />
<meta name="citation_author" content="A. Salvalaggio" />
<meta name="citation_author_institution" content="From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, Italy." />
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<meta name="citation_author_institution" content="From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, Italy." />
<meta name="citation_author" content="V. Palumbo" />
<meta name="citation_author_institution" content="From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, Italy." />
<meta name="citation_author" content="V. Citton" />
<meta name="citation_author_institution" content="From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, Italy." />
<meta name="citation_author" content="A. Elefante" />
<meta name="citation_author_institution" content="From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, Italy." />
<meta name="citation_author" content="A. Brunetti" />
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<meta name="citation_author_institution" content="From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, Italy." />
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<meta name="citation_author_institution" content="From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, Italy." />
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<meta name="twitter:title" content="Brain Changes in Kallmann Syndrome" />
<meta name="twitter:card" content="summary" />
<meta name="twitter:description" content="BACKGROUND AND PURPOSE: Kallmann syndrome is a rare inherited disorder due to defective intrauterine migration of olfactory axons and gonadotropin-releasing hormone neurons, leading to rhinencephalon hypoplasia and hypogonadotropic hypogonadism. Concomitant brain developmental abnormalities have been described. Our aim was to investigate Kallmann syndrome–related brain changes with conventional and novel quantitative MR imaging analyses.

MATERIALS AND METHODS: Forty-five male patients with Kallmann syndrome (mean age, 30.7 years; range, 9–55 years) and 23 age-matched male controls underwent brain MR imaging. The MR imaging study protocol included 3D-T1, FLAIR, and diffusion tensor imaging (32 noncollinear gradient-encoding directions; b-value = 800 s/mm2). Voxel-based morphometry, sulcation, curvature, and cortical thickness analyses and tract-based spatial statistics were performed by using Statistical Parametric Mapping 8, FreeSurfer, and the fMRI of the Brain Software Library.

RESULTS: Corpus callosum partial agenesis, multiple sclerosis–like white matter abnormalities, and acoustic schwannoma were found in 1 patient each. The total amount of gray and white matter volume and tract-based spatial statistics measures (fractional anisotropy and mean, radial, and axial diffusivity) did not differ between patients with Kallmann syndrome and controls. By specific analyses, patients with Kallmann syndrome presented with symmetric clusters of gray matter volume increase and decrease and white matter volume decrease close to the olfactory sulci; reduced sulcal depth of the olfactory sulci and deeper medial orbital-frontal sulci; lesser curvature of the olfactory sulcus and sharper curvature close to the medial orbital-frontal sulcus; and increased cortical thickness within the olfactory sulcus.

CONCLUSIONS: This large MR imaging study on male patients with Kallmann syndrome featured significant morphologic and structural brain changes, likely driven by olfactory bulb hypo-/aplasia, selectively involving the basal forebrain cortex.

### Abbreviations

KS
:   Kallmann syndrome
FA
:   fractional anisotropy
MNI
:   Montreal Neurological Institute
TBSS
:   tract-based spatial statistics
VBM
:   voxel-based morphometry" />
<meta name="og-title" property="og:title" content="Brain Changes in Kallmann Syndrome" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/early/2014/05/22/ajnr.A3946" />
<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: Kallmann syndrome is a rare inherited disorder due to defective intrauterine migration of olfactory axons and gonadotropin-releasing hormone neurons, leading to rhinencephalon hypoplasia and hypogonadotropic hypogonadism. Concomitant brain developmental abnormalities have been described. Our aim was to investigate Kallmann syndrome–related brain changes with conventional and novel quantitative MR imaging analyses.

MATERIALS AND METHODS: Forty-five male patients with Kallmann syndrome (mean age, 30.7 years; range, 9–55 years) and 23 age-matched male controls underwent brain MR imaging. The MR imaging study protocol included 3D-T1, FLAIR, and diffusion tensor imaging (32 noncollinear gradient-encoding directions; b-value = 800 s/mm2). Voxel-based morphometry, sulcation, curvature, and cortical thickness analyses and tract-based spatial statistics were performed by using Statistical Parametric Mapping 8, FreeSurfer, and the fMRI of the Brain Software Library.

RESULTS: Corpus callosum partial agenesis, multiple sclerosis–like white matter abnormalities, and acoustic schwannoma were found in 1 patient each. The total amount of gray and white matter volume and tract-based spatial statistics measures (fractional anisotropy and mean, radial, and axial diffusivity) did not differ between patients with Kallmann syndrome and controls. By specific analyses, patients with Kallmann syndrome presented with symmetric clusters of gray matter volume increase and decrease and white matter volume decrease close to the olfactory sulci; reduced sulcal depth of the olfactory sulci and deeper medial orbital-frontal sulci; lesser curvature of the olfactory sulcus and sharper curvature close to the medial orbital-frontal sulcus; and increased cortical thickness within the olfactory sulcus.

CONCLUSIONS: This large MR imaging study on male patients with Kallmann syndrome featured significant morphologic and structural brain changes, likely driven by olfactory bulb hypo-/aplasia, selectively involving the basal forebrain cortex.

### Abbreviations

KS
:   Kallmann syndrome
FA
:   fractional anisotropy
MNI
:   Montreal Neurological Institute
TBSS
:   tract-based spatial statistics
VBM
:   voxel-based morphometry" />
<meta name="og-type" property="og:type" content="article" />
<meta name="og-image" property="og:image" content="" />
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    <div class="highwire-article-citation highwire-citation-type-highwire-article node50662--5" data-node-nid="50662" id="top-node-50662--6352465548" data-pisa="ajnr;ajnr.A3946v2" data-pisa-master="ajnr;ajnr.A3946" data-apath="/ajnr/early/2014/05/22/ajnr.A3946.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">BRAIN</span></span></div>
  
      <div class="highwire-cite-access"><span class="highwire-citation-access highwire-citation-access-check" data-pisa-id="ajnr;ajnr.A3946" data-atom-uri="/ajnr/early/2014/05/22/ajnr.A3946.atom" data-request-view="full"></span></div>
  
      <h1 class="highwire-cite-title" id="page-title">Brain Changes in Kallmann Syndrome</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">R. Manara</span>, <span class="highwire-citation-author" data-delta="1">A. Salvalaggio</span>, <span class="highwire-citation-author" data-delta="2">A. Favaro</span>, <span class="highwire-citation-author" data-delta="3">V. Palumbo</span>, <span class="highwire-citation-author" data-delta="4">V. Citton</span>, <span class="highwire-citation-author" data-delta="5">A. Elefante</span>, <span class="highwire-citation-author" data-delta="6">A. Brunetti</span>, <span class="highwire-citation-author" data-delta="7">F. Di Salle</span>, <span class="highwire-citation-author" data-delta="8">G. Bonanni</span> and <span class="highwire-citation-author" data-delta="9">A.A. Sinisi</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">May 2014,  </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A3946 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-50662--6352465548" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">R. Manara </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, 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.%2BManara%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=Manara%20R&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AR.%2BManara%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">A. Salvalaggio </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, 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=A.%2BSalvalaggio%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=Salvalaggio%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 last"><a href="/search/author1%3AA.%2BSalvalaggio%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">A. Favaro </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, 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=A.%2BFavaro%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=Favaro%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 last"><a href="/search/author1%3AA.%2BFavaro%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">V. Palumbo </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, 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.%2BPalumbo%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=Palumbo%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 last"><a href="/search/author1%3AV.%2BPalumbo%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">V. Citton </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, 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.%2BCitton%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=Citton%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 last"><a href="/search/author1%3AV.%2BCitton%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">A. Elefante </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, 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=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 last"><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></ul></div><div class="author-tooltip-6"><div class="author-tooltip-name">A. Brunetti </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, 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=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 last"><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></ul></div><div class="author-tooltip-7"><div class="author-tooltip-name">F. Di Salle </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, 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=F.%2BDi%2BSalle%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=Di%20Salle%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 last"><a href="/search/author1%3AF.%2BDi%2BSalle%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-8"><div class="author-tooltip-name">G. Bonanni </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, 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.%2BBonanni%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=Bonanni%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 last"><a href="/search/author1%3AG.%2BBonanni%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-9"><div class="author-tooltip-name">A.A. Sinisi </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Neuroradiology (R.M., F.D.S.), University of Salerno, Salerno, Italy; Istituto di Ricovero e Cura a Carattere Scientifico S. Camillo (R.M., V.C.), Venezia, Italy; Departments of Neurology (A.S.), and Psychiatry (A.F.), Department of Neurosciences; Unità di Endocrinologia (G.B.), Department of Medicine, University of Padova, Padova, Italy; Department of Clinical and Experimental Medicine and Surgery (V.P., A.A.S.), Endocrinology and Medical Andrology Section, Second University of Napoli, Napoli, Italy; and Department of Neuroradiology (A.E., A.B.), Department of Scienze Biomediche Avanzate, and ENT section (R.M., A.S.), Department of Neurosciences, “Federico II” University, Napoli, 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=A.A.%2BSinisi%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=Sinisi%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 last"><a href="/search/author1%3AA.A.%2BSinisi%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div></div></div>  </div>

  
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<div id="sec-1" class="subsection">
<p id="p-3"><strong>BACKGROUND AND PURPOSE:</strong> Kallmann syndrome is a rare inherited disorder due to defective intrauterine migration of olfactory axons and gonadotropin-releasing hormone neurons, leading to rhinencephalon hypoplasia and hypogonadotropic hypogonadism. Concomitant brain developmental abnormalities have been described. Our aim was to investigate Kallmann syndrome–related brain changes with conventional and novel quantitative MR imaging analyses.</p></div>
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<p id="p-4"><strong>MATERIALS AND METHODS:</strong> Forty-five male patients with Kallmann syndrome (mean age, 30.7 years; range, 9–55 years) and 23 age-matched male controls underwent brain MR imaging. The MR imaging study protocol included 3D-T1, FLAIR, and diffusion tensor imaging (32 noncollinear gradient-encoding directions; b-value = 800 s/mm<sup>2</sup>). Voxel-based morphometry, sulcation, curvature, and cortical thickness analyses and tract-based spatial statistics were performed by using Statistical Parametric Mapping 8, FreeSurfer, and the fMRI of the Brain Software Library.</p></div>
<div id="sec-3" class="subsection">
<p id="p-5"><strong>RESULTS:</strong> Corpus callosum partial agenesis, multiple sclerosis–like white matter abnormalities, and acoustic schwannoma were found in 1 patient each. The total amount of gray and white matter volume and tract-based spatial statistics measures (fractional anisotropy and mean, radial, and axial diffusivity) did not differ between patients with Kallmann syndrome and controls. By specific analyses, patients with Kallmann syndrome presented with symmetric clusters of gray matter volume increase and decrease and white matter volume decrease close to the olfactory sulci; reduced sulcal depth of the olfactory sulci and deeper medial orbital-frontal sulci; lesser curvature of the olfactory sulcus and sharper curvature close to the medial orbital-frontal sulcus; and increased cortical thickness within the olfactory sulcus.</p></div>
<div id="sec-4" class="subsection">
<p id="p-6"><strong>CONCLUSIONS:</strong> This large MR imaging study on male patients with Kallmann syndrome featured significant morphologic and structural brain changes, likely driven by olfactory bulb hypo-/aplasia, selectively involving the basal forebrain cortex.</p>
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</div><div class="section glossary" id="glossary-1">
<h3>Abbreviations</h3>
<dl id="def-list-1"><dt id="def-item-1">KS<span class="def-item-dt-sep"></span></dt><dd>Kallmann syndrome<span class="def-item-dd-sep"></span></dd><dt id="def-item-2">FA<span class="def-item-dt-sep"></span></dt><dd>fractional anisotropy<span class="def-item-dd-sep"></span></dd><dt id="def-item-3">MNI<span class="def-item-dt-sep"></span></dt><dd>Montreal Neurological Institute<span class="def-item-dd-sep"></span></dd><dt id="def-item-4">TBSS<span class="def-item-dt-sep"></span></dt><dd>tract-based spatial statistics<span class="def-item-dd-sep"></span></dd><dt id="def-item-5">VBM<span class="def-item-dt-sep"></span></dt><dd>voxel-based morphometry</dd></dl>
</div><div class="section fn-group" id="fn-group-1"><h2>Footnotes</h2><ul><li class="fn-equal" id="fn-1"><p id="p-1">Renzo Manara and Alessandro Salvalaggio equally contributed to the study and should be considered first authors.</p></li><li class="fn-other" id="fn-2"><p id="p-2">Guglielmo Bonanni and Antoio Agostino Sinisis should be considered senior coauthors.</p></li></ul></div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2014 American Society of Neuroradiology</li></ul><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div></div>  </div>

  
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