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      <h1 class="highwire-cite-title" id="page-title">Comment on “Global <em>N</em>-Acetylaspartate Declines Even in Benign Multiple Sclerosis”</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">F. Aboul-Enein</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">June 2011,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">32 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(6) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">E118; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A2528 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-9494--61581757783" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">F. Aboul-Enein </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.%2BAboul-Enein%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=Aboul-Enein%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.%2BAboul-Enein%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 class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" data-highwire-cite-ref-tooltip-instance="highwire_reflinks_tooltip" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article fulltext-view"><span class="highwire-journal-article-marker-start"></span><p id="p-1">We have read with great interest the article “Global <em>N</em>-Acetylaspartate Declines Even in Benign Multiple Sclerosis” by Rigotti et al.<sup><a id="xref-ref-1-1" class="xref-bibr" href="#ref-1">1</a></sup> It is generally accepted that axonal injury is the pathologic substrate for the symptoms and disability seen in patients with multiple sclerosis (MS), a supposed inflammatory central nervous system disease of unknown origin. The visualization of certain metabolites such as <em>N</em>-acetylaspartate (NAA) may represent axonal loss, axonal integrity, or axonal function.</p><p id="p-2">It remains completely unclear why each patient with MS follows his or her own individual disease course and why, until now, no marker could be established that may allow a reliable prediction.<sup><a id="xref-ref-2-1" class="xref-bibr" href="#ref-2">2</a></sup> NAA levels vary even in healthy controls and decline with age. A supposed NAA decline per year, extrapolated by a mathematic model including only 1 NAA baseline measurement, disease duration, and so forth, could never replace a long-term follow-up study (as already mentioned by the authors). However, it is still very intensely discussed whether axonal injury does really exist in all patients with MS and, if so, whether axonal injury already occurs in the very early disease stages and progresses steadily and “clinically silently,” even when patients with MS remain clinically stable. That the NAA levels of 43 patients with relapsing-remitting MS (RRMS) with very benign disease courses, very low lesion load, and, in part, very long disease duration (range, 15–35 years) are that low is astonishing and should have been discussed in detail and compared with the different data published recently.<sup><a id="xref-ref-3-1" class="xref-bibr" href="#ref-3">3</a><a id="xref-ref-4-1" class="xref-bibr" href="#ref-4"></a><a id="xref-ref-5-1" class="xref-bibr" href="#ref-5"></a>–<a id="xref-ref-6-1" class="xref-bibr" href="#ref-6">6</a></sup> Did the included patients with RRMS fulfill the Barkhof criteria and were oligoclonal bands detectable?</p><div class="section ref-list" id="ref-list-1"><h2>References</h2><ol class="cit-list ref-use-labels"><li><span class="ref-label">1.</span><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-journal" id="cit-32.6.E118.1" data-doi="10.3174/ajnr.A2254"><div class="cit-metadata"><ol class="cit-auth-list"><li><span class="cit-auth"><span class="cit-name-surname">Rigotti</span>  <span class="cit-name-given-names">DJ</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Gonen</span>  <span class="cit-name-given-names">O</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Grossman</span>  <span class="cit-name-given-names">RI</span></span>, </li><li><span class="cit-etal">et al</span></li></ol><cite>. <span class="cit-article-title">Global <em>N</em>-acetylaspartate declines even in benign multiple sclerosis</span>. <abbr class="cit-jnl-abbrev">AJNR Am J Neuroradiol</abbr> <span class="cit-pub-date">2011</span>;<span class="cit-vol">32</span>:<span class="cit-fpage">204</span>–<span class="cit-lpage">09</span></cite></div><div class="cit-extra"><a href="/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiYWpuciI7czo1OiJyZXNpZCI7czo4OiIzMi8xLzIwNCI7czo0OiJhdG9tIjtzOjIwOiIvYWpuci8zMi82L0UxMTguYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9" 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><span class="ref-label">2.</span><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-journal" id="cit-32.6.E118.2" data-doi="10.1177/1352458510366014"><div class="cit-metadata"><ol class="cit-auth-list"><li><span class="cit-auth"><span class="cit-name-surname">Gilmore</span>  <span class="cit-name-given-names">CP</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Cottrell</span>  <span class="cit-name-given-names">DA</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Scolding</span>  <span class="cit-name-given-names">NJ</span></span>, </li><li><span class="cit-etal">et al</span></li></ol><cite>. <span class="cit-article-title">A window of opportunity for no treatment in early multiple sclerosis?</span> <abbr class="cit-jnl-abbrev">Mult Scler</abbr> <span class="cit-pub-date">2010</span>;<span class="cit-vol">16</span>:<span class="cit-fpage">756</span>–<span class="cit-lpage">59</span></cite></div><div class="cit-extra"><a href="/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6MzoiUERGIjtzOjExOiJqb3VybmFsQ29kZSI7czo1OiJzcG1zaiI7czo1OiJyZXNpZCI7czo4OiIxNi82Lzc1NiI7czo0OiJhdG9tIjtzOjIwOiIvYWpuci8zMi82L0UxMTguYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9" class="cit-ref-sprinkles cit-ref-sprinkles-ijlink"><span><span class="cit-reflinks-full-text"><span class="free-full-text">FREE </span>Full Text</span></span></a></div></div>
</li><li><span class="ref-label">3.</span><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-journal" id="cit-32.6.E118.3" data-doi="10.1177/1352458509103714"><div class="cit-metadata"><ol class="cit-auth-list"><li><span class="cit-auth"><span class="cit-name-surname">Benedetti</span>  <span class="cit-name-given-names">B</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Rovaris</span>  <span class="cit-name-given-names">M</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Rocca</span>  <span class="cit-name-given-names">MA</span></span>, </li><li><span class="cit-etal">et al</span></li></ol><cite>. <span class="cit-article-title">In vivo evidence for stable neuroaxonal damage in the brain of patients with benign multiple sclerosis</span>. <abbr class="cit-jnl-abbrev">Mult Scler</abbr> <span class="cit-pub-date">2009</span>;<span class="cit-vol">15</span>:<span class="cit-fpage">789</span>–<span class="cit-lpage">94</span></cite></div><div class="cit-extra"><a href="/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NToic3Btc2oiO3M6NToicmVzaWQiO3M6ODoiMTUvNy83ODkiO3M6NDoiYXRvbSI7czoyMDoiL2FqbnIvMzIvNi9FMTE4LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==" 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><span class="ref-label">4.</span><a class="rev-xref-ref" href="#xref-ref-4-1" title="View reference 4. in text" id="ref-4">↵</a>

<div class="cit ref-cit ref-journal" id="cit-32.6.E118.4" data-doi="10.1136/jnnp.2009.176263"><div class="cit-metadata"><ol class="cit-auth-list"><li><span class="cit-auth"><span class="cit-name-surname">Kirov</span>  <span class="cit-name-given-names">II</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Patil</span>  <span class="cit-name-given-names">V</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Babb</span>  <span class="cit-name-given-names">JS</span></span>, </li><li><span class="cit-etal">et al</span></li></ol><cite>. <span class="cit-article-title">MR spectroscopy indicates diffuse multiple sclerosis activity during remission</span>. <abbr class="cit-jnl-abbrev">J Neurol Neurosurg Psychiatry</abbr> <span class="cit-pub-date">2009</span>;<span class="cit-vol">80</span>:<span class="cit-fpage">1330</span>–<span class="cit-lpage">36</span></cite></div><div class="cit-extra"><a href="/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiam5ucCI7czo1OiJyZXNpZCI7czoxMDoiODAvMTIvMTMzMCI7czo0OiJhdG9tIjtzOjIwOiIvYWpuci8zMi82L0UxMTguYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9" 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><span class="ref-label">5.</span><a class="rev-xref-ref" href="#xref-ref-5-1" title="View reference 5. in text" id="ref-5">↵</a>

<div class="cit ref-cit ref-journal" id="cit-32.6.E118.5" data-doi="10.1371/journal.pone.0011625"><div class="cit-metadata"><ol class="cit-auth-list"><li><span class="cit-auth"><span class="cit-name-surname">Aboul-Enein</span>  <span class="cit-name-given-names">F</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Krssák</span>  <span class="cit-name-given-names">M</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Höftberger</span>  <span class="cit-name-given-names">R</span></span>, </li><li><span class="cit-etal">et al</span></li></ol><cite>. <span class="cit-article-title">Reduced NAA levels in the NAWM of patients with MS is a feature of progression: a study with quantitative magnetic resonance spectroscopy at 3 Tesla</span>. <abbr class="cit-jnl-abbrev">PLoS One</abbr> <span class="cit-pub-date">2010</span>;<span class="cit-vol">5</span>:<span class="cit-fpage">e11625</span></cite></div><div class="cit-extra"><a href="/lookup/external-ref?access_num=10.1371/journal.pone.0011625&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=20652023&amp;link_type=MED&amp;atom=%2Fajnr%2F32%2F6%2FE118.atom" class="cit-ref-sprinkles cit-ref-sprinkles-medline"><span>PubMed</span></a></div></div>
</li><li><span class="ref-label">6.</span><a class="rev-xref-ref" href="#xref-ref-6-1" title="View reference 6. in text" id="ref-6">↵</a>

<div class="cit ref-cit ref-journal" id="cit-32.6.E118.6" data-doi="10.3174/ajnr.A1791"><div class="cit-metadata"><ol class="cit-auth-list"><li><span class="cit-auth"><span class="cit-name-surname">Aboul-Enein</span>  <span class="cit-name-given-names">F</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Krssák</span>  <span class="cit-name-given-names">M</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Höftberger</span>  <span class="cit-name-given-names">R</span></span>, </li><li><span class="cit-etal">et al</span></li></ol><cite>. <span class="cit-article-title">Diffuse white matter damage is absent in neuromyelitis optica</span>. <abbr class="cit-jnl-abbrev">AJNR Am J Neuroradiol</abbr> <span class="cit-pub-date">2010</span>;<span class="cit-vol">31</span>:<span class="cit-fpage">76</span>–<span class="cit-lpage">79</span></cite></div><div class="cit-extra"><a href="/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiYWpuciI7czo1OiJyZXNpZCI7czo3OiIzMS8xLzc2IjtzOjQ6ImF0b20iO3M6MjA6Ii9ham5yLzMyLzYvRTExOC5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=" 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>
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        	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-volume highwire-cite-metadata">Vol. 32</span>, <span  class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 6 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 Jun 2011 </div></div>
      
      
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