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<meta name="DC.Title" content="Hypomyelination and Congenital Cataract: Neuroimaging Features of a Novel Inherited White Matter Disorder" />
<meta name="DC.Identifier" content="10.3174/ajnr.A0792" />
<meta name="DC.Date" content="2008-02-01" />
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<meta name="DC.Description" content="BACKGROUND AND PURPOSE: Hypomyelination and congenital cataract (HCC) is an autosomal recessive white matter disease caused by deficiency of hyccin, a membrane protein implicated in both central and peripheral myelination. We aimed to describe the neuroimaging features of this novel entity.

MATERIALS AND METHODS: A systematic analysis of patients with unclassified leukoencephalopathies admitted to our institutions revealed 10 children with congenital cataract, slowly progressive neurologic impairment, and diffuse white matter abnormalities on neuroimaging. Psychomotor developmental delay was evident after the first year of life. Peripheral neuropathy was demonstrated by neurophysiologic studies in 9 children. The available neuroimaging studies were retrospectively reviewed.

RESULTS: In all patients, neuroimaging revealed diffuse involvement of the supratentorial white matter associated with preservation of both cortical and deep gray matter structures. Supratentorial white matter hypomyelination was detected in all patients; 7 patients also had evidence of variably extensive areas of increased white matter water content. Deep cerebellar white matter hypomyelination was found in 6 patients. Older patients had evidence of white matter bulk loss and gliosis. Proton MR spectroscopy showed variable findings, depending on the stage of the disease. Sural nerve biopsy revealed hypomyelinated nerve fibers. Mutations in the DRCTNNB1A gene on chromosome 7p15.3, causing complete or severe deficiency of hyccin, were demonstrated in all patients.

CONCLUSIONS: HCC is characterized by a combined pattern of primary myelin deficiency and secondary neurodegenerative changes. In the proper clinical setting, recognition of suggestive neuroimaging findings should prompt appropriate genetic investigations." />
<meta name="DC.Contributor" content="A. Rossi" />
<meta name="DC.Contributor" content="R. Biancheri" />
<meta name="DC.Contributor" content="F. Zara" />
<meta name="DC.Contributor" content="C. Bruno" />
<meta name="DC.Contributor" content="G. Uziel" />
<meta name="DC.Contributor" content="M.S. van der Knaap" />
<meta name="DC.Contributor" content="C. Minetti" />
<meta name="DC.Contributor" content="P. Tortori-Donati" />
<meta name="article:published_time" content="2008-02-01" />
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<meta name="citation_title" content="Hypomyelination and Congenital Cataract: Neuroimaging Features of a Novel Inherited White Matter Disorder" />
<meta name="citation_abstract" lang="en" content="&lt;p&gt;&lt;b&gt;BACKGROUND AND PURPOSE:&lt;/b&gt; Hypomyelination and congenital cataract (HCC) is an autosomal recessive white matter disease caused by deficiency of hyccin, a membrane protein implicated in both central and peripheral myelination. We aimed to describe the neuroimaging features of this novel entity.&lt;/p&gt;&lt;p&gt;&lt;b&gt;MATERIALS AND METHODS:&lt;/b&gt; A systematic analysis of patients with unclassified leukoencephalopathies admitted to our institutions revealed 10 children with congenital cataract, slowly progressive neurologic impairment, and diffuse white matter abnormalities on neuroimaging. Psychomotor developmental delay was evident after the first year of life. Peripheral neuropathy was demonstrated by neurophysiologic studies in 9 children. The available neuroimaging studies were retrospectively reviewed.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS:&lt;/b&gt; In all patients, neuroimaging revealed diffuse involvement of the supratentorial white matter associated with preservation of both cortical and deep gray matter structures. Supratentorial white matter hypomyelination was detected in all patients; 7 patients also had evidence of variably extensive areas of increased white matter water content. Deep cerebellar white matter hypomyelination was found in 6 patients. Older patients had evidence of white matter bulk loss and gliosis. Proton MR spectroscopy showed variable findings, depending on the stage of the disease. Sural nerve biopsy revealed hypomyelinated nerve fibers. Mutations in the &lt;i&gt;DRCTNNB1A&lt;/i&gt; gene on chromosome 7p15.3, causing complete or severe deficiency of hyccin, were demonstrated in all patients.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS:&lt;/b&gt; HCC is characterized by a combined pattern of primary myelin deficiency and secondary neurodegenerative changes. In the proper clinical setting, recognition of suggestive neuroimaging findings should prompt appropriate genetic investigations.&lt;/p&gt;" />
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<meta name="twitter:title" content="Hypomyelination and Congenital Cataract: Neuroimaging Features of a Novel Inherited White Matter Disorder" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: Hypomyelination and congenital cataract (HCC) is an autosomal recessive white matter disease caused by deficiency of hyccin, a membrane protein implicated in both central and peripheral myelination. We aimed to describe the neuroimaging features of this novel entity.

MATERIALS AND METHODS: A systematic analysis of patients with unclassified leukoencephalopathies admitted to our institutions revealed 10 children with congenital cataract, slowly progressive neurologic impairment, and diffuse white matter abnormalities on neuroimaging. Psychomotor developmental delay was evident after the first year of life. Peripheral neuropathy was demonstrated by neurophysiologic studies in 9 children. The available neuroimaging studies were retrospectively reviewed.

RESULTS: In all patients, neuroimaging revealed diffuse involvement of the supratentorial white matter associated with preservation of both cortical and deep gray matter structures. Supratentorial white matter hypomyelination was detected in all patients; 7 patients also had evidence of variably extensive areas of increased white matter water content. Deep cerebellar white matter hypomyelination was found in 6 patients. Older patients had evidence of white matter bulk loss and gliosis. Proton MR spectroscopy showed variable findings, depending on the stage of the disease. Sural nerve biopsy revealed hypomyelinated nerve fibers. Mutations in the DRCTNNB1A gene on chromosome 7p15.3, causing complete or severe deficiency of hyccin, were demonstrated in all patients.

CONCLUSIONS: HCC is characterized by a combined pattern of primary myelin deficiency and secondary neurodegenerative changes. In the proper clinical setting, recognition of suggestive neuroimaging findings should prompt appropriate genetic investigations." />
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<meta name="og-description" property="og:description" content="BACKGROUND AND PURPOSE: Hypomyelination and congenital cataract (HCC) is an autosomal recessive white matter disease caused by deficiency of hyccin, a membrane protein implicated in both central and peripheral myelination. We aimed to describe the neuroimaging features of this novel entity.

MATERIALS AND METHODS: A systematic analysis of patients with unclassified leukoencephalopathies admitted to our institutions revealed 10 children with congenital cataract, slowly progressive neurologic impairment, and diffuse white matter abnormalities on neuroimaging. Psychomotor developmental delay was evident after the first year of life. Peripheral neuropathy was demonstrated by neurophysiologic studies in 9 children. The available neuroimaging studies were retrospectively reviewed.

RESULTS: In all patients, neuroimaging revealed diffuse involvement of the supratentorial white matter associated with preservation of both cortical and deep gray matter structures. Supratentorial white matter hypomyelination was detected in all patients; 7 patients also had evidence of variably extensive areas of increased white matter water content. Deep cerebellar white matter hypomyelination was found in 6 patients. Older patients had evidence of white matter bulk loss and gliosis. Proton MR spectroscopy showed variable findings, depending on the stage of the disease. Sural nerve biopsy revealed hypomyelinated nerve fibers. Mutations in the DRCTNNB1A gene on chromosome 7p15.3, causing complete or severe deficiency of hyccin, were demonstrated in all patients.

CONCLUSIONS: HCC is characterized by a combined pattern of primary myelin deficiency and secondary neurodegenerative changes. In the proper clinical setting, recognition of suggestive neuroimaging findings should prompt appropriate genetic investigations." />
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    <div class="highwire-article-citation highwire-citation-type-highwire-article node7876--5" data-node-nid="7876" id="top-node-7876--6149916160" data-pisa="ajnr;29/2/301" data-pisa-master="ajnr;ajnr.A0792" data-apath="/ajnr/29/2/301.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">PEDIATRICS</span></span></div>
  
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      <h1 class="highwire-cite-title" id="page-title">Hypomyelination and Congenital Cataract: Neuroimaging Features of a Novel Inherited White Matter Disorder</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">A. Rossi</span>, <span class="highwire-citation-author" data-delta="1">R. Biancheri</span>, <span class="highwire-citation-author" data-delta="2">F. Zara</span>, <span class="highwire-citation-author" data-delta="3">C. Bruno</span>, <span class="highwire-citation-author" data-delta="4">G. Uziel</span>, <span class="highwire-citation-author" data-delta="5">M.S. van der Knaap</span>, <span class="highwire-citation-author" data-delta="6">C. Minetti</span> and <span class="highwire-citation-author" data-delta="7">P. Tortori-Donati</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">February 2008,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">29 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(2) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">301-305; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A0792 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-7876--6149916160" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">A. Rossi </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.%2BRossi%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=Rossi%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.%2BRossi%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">R. 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Zara </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.%2BZara%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=Zara%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.%2BZara%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">C. 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    <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" xmlns:xhtml="http://www.w3.org/1999/xhtml" class="section ref-list" id="ref-list-1"><h2>References</h2><ol class="cit-list"><li><a class="rev-xref-ref" href="#xref-ref-1-1" title="View reference 1 in text" id="ref-1">↵</a><div class="cit ref-cit ref-other" id="cit-29.2.301.1" data-doi="10.1148/radiology.213.1.r99se01121"><div class="cit-metadata"><cite>van der Knaap MS, Breiter SN, Naidu S, et al. <strong>Defining and categorizing leukoencephalopathies of unknown origin: MR imaging approach</strong>. <span class="cit-source">Radiology</span> <span class="cit-pub-date">1999</span>;<span class="cit-vol">213</span>:<span class="cit-fpage">121</span>–33</cite></div><div class="cit-extra"><a href="/lookup/external-ref?access_num=10.1148/radiology.213.1.r99se01121&amp;link_type=DOI" class="cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref"><span>CrossRef</span></a><a href="/lookup/external-ref?access_num=10540652&amp;link_type=MED&amp;atom=%2Fajnr%2F29%2F2%2F301.atom" class="cit-ref-sprinkles cit-ref-sprinkles-medline"><span>PubMed</span></a><a href="/lookup/external-ref?access_num=000082771900024&amp;link_type=ISI" class="cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience"><span>Web of Science</span></a></div></div></li><li><a class="rev-xref-ref" href="#xref-ref-2-1" title="View reference 2 in text" id="ref-2">↵</a><div class="cit ref-cit ref-other" id="cit-29.2.301.2" data-doi="10.1097/00019052-200404000-00017"><div class="cit-metadata"><cite>Schiffmann R, van der Knaap MS. <strong>The latest on leukodystrophies</strong>. <span class="cit-source">Curr Opin Neurol</span> <span class="cit-pub-date">2004</span>;<span class="cit-vol">17</span>:<span class="cit-fpage">187</span>–92</cite></div><div class="cit-extra"><a href="/lookup/external-ref?access_num=10.1097/00019052-200404000-00017&amp;link_type=DOI" class="cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref"><span>CrossRef</span></a><a href="/lookup/external-ref?access_num=15021247&amp;link_type=MED&amp;atom=%2Fajnr%2F29%2F2%2F301.atom" class="cit-ref-sprinkles cit-ref-sprinkles-medline"><span>PubMed</span></a><a href="/lookup/external-ref?access_num=000220680000016&amp;link_type=ISI" class="cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience"><span>Web of Science</span></a></div></div></li><li><a class="rev-xref-ref" href="#xref-ref-3-1" title="View reference 3 in text" id="ref-3">↵</a><div class="cit ref-cit ref-other" id="cit-29.2.301.3" data-doi="10.1038/ng1870"><div class="cit-metadata"><cite>Zara F, Biancheri R, Bruno C, et al. <strong>Deficiency of hyccin, a newly identified membrane protein, causes hypomyelination and congenital cataract</strong>. <span class="cit-source">Nat Genet</span> <span class="cit-pub-date">2006</span>;<span class="cit-vol">38</span>:<span class="cit-fpage">1111</span>–13. 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class="cit-reflinks-full-text"><span class="free-full-text">FREE </span>Full Text</span></span></a></div></div></li><li><div class="cit ref-cit ref-other no-rev-xref" id="cit-29.2.301.8"><div class="cit-metadata"><cite>Brismar J, Brismar G, Gascon G, et al. <strong>Canavan disease: CT and MR imaging of the brain.</strong> <span class="cit-source">AJNR Am J Neuroradiol</span> <span class="cit-pub-date">1990</span>;<span class="cit-vol">11</span>:<span class="cit-fpage">805</span>–10</cite></div><div class="cit-extra"><a href="/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiYWpuciI7czo1OiJyZXNpZCI7czo4OiIxMS80LzgwNSI7czo0OiJhdG9tIjtzOjE5OiIvYWpuci8yOS8yLzMwMS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=" class="cit-ref-sprinkles cit-ref-sprinkles-ijlink"><span><span class="cit-reflinks-abstract">Abstract</span><span class="cit-sep cit-reflinks-variant-name-sep">/</span><span 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class="cit-source">Neurology</span> <span class="cit-pub-date">2005</span>;<span class="cit-vol">65</span>:<span class="cit-fpage">701</span>–06</cite></div><div class="cit-extra"><a href="/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToibmV1cm9sb2d5IjtzOjU6InJlc2lkIjtzOjg6IjY1LzUvNzAxIjtzOjQ6ImF0b20iO3M6MTk6Ii9ham5yLzI5LzIvMzAxLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==" class="cit-ref-sprinkles cit-ref-sprinkles-ijlink"><span><span class="cit-reflinks-abstract">Abstract</span><span class="cit-sep cit-reflinks-variant-name-sep">/</span><span class="cit-reflinks-full-text"><span class="free-full-text">FREE </span>Full Text</span></span></a></div></div></li><li><a class="rev-xref-ref" href="#xref-ref-12-1" title="View reference 12 in text" id="ref-12">↵</a><div class="cit ref-cit ref-other" id="cit-29.2.301.12"><div class="cit-metadata"><cite>Varho T, Komu M, Sonninen P, et al. <strong>A new metabolite contributing to N-acetyl signal in 1HMRS of the brain in Salla disease.</strong> <span class="cit-source">Neurology</span> <span class="cit-pub-date">1999</span>;<span class="cit-vol">52</span>:<span class="cit-fpage">1668</span>–72</cite></div><div class="cit-extra"><a href="/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToibmV1cm9sb2d5IjtzOjU6InJlc2lkIjtzOjk6IjUyLzgvMTY2OCI7czo0OiJhdG9tIjtzOjE5OiIvYWpuci8yOS8yLzMwMS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=" class="cit-ref-sprinkles cit-ref-sprinkles-ijlink"><span><span class="cit-reflinks-abstract">Abstract</span><span class="cit-sep cit-reflinks-variant-name-sep">/</span><span class="cit-reflinks-full-text"><span class="free-full-text">FREE </span>Full Text</span></span></a></div></div></li><li><a class="rev-xref-ref" href="#xref-ref-13-1" title="View reference 13 in text" id="ref-13">↵</a><div 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        	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-volume highwire-cite-metadata">Vol. 29</span>, <span  class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 2 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">February 2008 </div></div>
      
      
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    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">A.</span> <span class="nlm-surname">Rossi</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">R.</span> <span class="nlm-surname">Biancheri</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">F.</span> <span class="nlm-surname">Zara</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">C.</span> <span class="nlm-surname">Bruno</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">G.</span> <span class="nlm-surname">Uziel</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">M.S.</span> <span class="nlm-surname">van der Knaap</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">C.</span> <span class="nlm-surname">Minetti</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">P.</span> <span class="nlm-surname">Tortori-Donati</span></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">Feb 2008, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">29 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(2) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">301-305; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A0792 </span></div>
  
  
  
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    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">A.</span> <span class="nlm-surname">Rossi</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">R.</span> <span class="nlm-surname">Biancheri</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">F.</span> <span class="nlm-surname">Zara</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">C.</span> <span class="nlm-surname">Bruno</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">G.</span> <span class="nlm-surname">Uziel</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">M.S.</span> <span class="nlm-surname">van der Knaap</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">C.</span> <span class="nlm-surname">Minetti</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">P.</span> <span class="nlm-surname">Tortori-Donati</span></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">Feb 2008, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">29 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(2) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">301-305; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A0792 </span></div>
  
  
  
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