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    <div class="highwire-article-citation highwire-citation-type-highwire-article node14180--5" data-node-nid="14180" id="top-node-14180--6595133890" data-pisa="ajnr;36/12/E69" data-pisa-master="ajnr;ajnr.A4581" data-apath="/ajnr/36/12/E69.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">
  
  
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      <h1 class="highwire-cite-title" id="page-title">Ipilimumab Therapy for Melanoma: A Mimic of Leptomeningeal Metastases</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">S. Ali</span> and <span class="highwire-citation-author" data-delta="1">S.-K. Lee</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">December 2015,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">36 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(12) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">E69-E70; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A4581 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-14180--6595133890" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">S. Ali </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>Department of Radiology, Section of Neuroradiology
University of Chicago Medical Center
Chicago, Illinois</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=S.%2BAli%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=Ali%20S&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AS.%2BAli%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/0000-0001-9366-3513" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for S. Ali</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">S.-K. Lee </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>Department of Radiology, Section of Neuroradiology
University of Chicago Medical Center
Chicago, Illinois</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=S.-K.%2BLee%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=Lee%20S&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AS.-K.%2BLee%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/0000-0002-6526-8820" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for S.-K. Lee</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 recently observed that patients with malignant melanoma on treatment with ipilimumab can demonstrate leptomeningeal enhancement on brain MR imaging mimicking metastatic disease. In <a id="xref-fig-1-1" class="xref-fig" href="#F1">Fig 1</a> is shown one such case of a 40-year-old man presenting with subacute onset of headaches, right-sided facial hemiparesis, and facial paresthesias. He also showed evidence of tongue deviation on neurologic examination suggestive of cranial neuropathy. The patient had a history of stage IIIC melanoma from an unknown primary site with metastasis to the axilla and was undergoing therapy with ipilimumab. MR imaging demonstrated multifocal leptomeningeal and cranial nerve enhancement. Lumbar puncture revealed CSF lymphocytosis and mildly elevated proteins (findings that can be seen with inflammatory processes) and cultures and cytology negative for infection and malignancy, despite repeat examinations. Following drug discontinuation and high-dose steroid therapy, the patient gradually recovered. Lymphocytosis in the CSF also resolved.</p><div id="F1" class="fig pos-float  odd"><div class="highwire-figure"><div class="fig-inline-img-wrapper"><div class="fig-inline-img"><a href="http://ajnr-stage2.stage.highwire.org/content/ajnr/36/12/E69/F1.large.jpg?width=800&amp;height=600&amp;carousel=1" title="Postcontrast T1-weighted images demonstrate nodular enhancement involving the right facial nerve in the meatal (A) and mastoid (B) segments and the bilateral trigeminal nerves (C and D). Leptomeningeal enhancement along the cerebellar surface (E) and abnormal enhancement along the perivascular spaces in the pons and cerebral hemispheres (E and F) are also seen." class="highwire-fragment fragment-images colorbox-load" rel="gallery-fragment-images-866626525" data-figure-caption="&lt;div class=&quot;highwire-markup&quot;&gt;&lt;div xmlns=&quot;http://www.w3.org/1999/xhtml&quot;&gt;Postcontrast T1-weighted images demonstrate nodular enhancement involving the right facial nerve in the meatal (&lt;em&gt;A&lt;/em&gt;) and mastoid (&lt;em&gt;B&lt;/em&gt;) segments and the bilateral trigeminal nerves (&lt;em&gt;C&lt;/em&gt; and &lt;em&gt;D&lt;/em&gt;). Leptomeningeal enhancement along the cerebellar surface (&lt;em&gt;E&lt;/em&gt;) and abnormal enhancement along the perivascular spaces in the pons and cerebral hemispheres (&lt;em&gt;E&lt;/em&gt; and &lt;em&gt;F&lt;/em&gt;) are also seen.&lt;/div&gt;&lt;/div&gt;" data-icon-position="" data-hide-link-title="0"><span class="hw-responsive-img"><img class="highwire-fragment fragment-image lazyload" alt="Fig 1." src="data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7" data-src="http://ajnr-stage2.stage.highwire.org/content/ajnr/36/12/E69/F1.medium.gif" width="440" height="295"/><noscript><img class="highwire-fragment fragment-image" alt="Fig 1." src="http://ajnr-stage2.stage.highwire.org/content/ajnr/36/12/E69/F1.medium.gif" width="440" height="295"/></noscript></span></a></div></div><ul class="highwire-figure-links inline"><li class="download-fig first"><a href="http://ajnr-stage2.stage.highwire.org/content/ajnr/36/12/E69/F1.large.jpg?download=true" class="highwire-figure-link highwire-figure-link-download" title="Download Fig 1." data-icon-position="" data-hide-link-title="0">Download figure</a></li><li class="new-tab"><a href="http://ajnr-stage2.stage.highwire.org/content/ajnr/36/12/E69/F1.large.jpg" class="highwire-figure-link highwire-figure-link-newtab" target="_blank" data-icon-position="" data-hide-link-title="0">Open in new tab</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/45150" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div><div class="fig-caption" xmlns:xhtml="http://www.w3.org/1999/xhtml"><span class="fig-label">Fig 1.</span> <p id="p-2" class="first-child">Postcontrast T1-weighted images demonstrate nodular enhancement involving the right facial nerve in the meatal (<em>A</em>) and mastoid (<em>B</em>) segments and the bilateral trigeminal nerves (<em>C</em> and <em>D</em>). Leptomeningeal enhancement along the cerebellar surface (<em>E</em>) and abnormal enhancement along the perivascular spaces in the pons and cerebral hemispheres (<em>E</em> and <em>F</em>) are also seen.</p><div class="sb-div caption-clear"></div></div></div><p id="p-3">To our knowledge, these brain imaging findings have not been shown in the literature. Ipilimumab, also known as MDX-010, is a human monoclonal antibody that augments T-cell-mediated immunity by blocking inhibitory signals that suppress T-cell function (more specifically, it blocks cytotoxic T lymphocyte antigen-4).<sup><a id="xref-ref-1-1" class="xref-bibr" href="#ref-1">1</a></sup> It is approved for the treatment of late-stage melanoma and is currently undergoing clinical trials for other cancers. Manousakis et al<sup><a id="xref-ref-2-1" class="xref-bibr" href="#ref-2">2</a></sup> reported a case of an inflammatory multifocal radiculoneuropathy during ipilimumab therapy with a lumbar spine MR image in their article showing leptomeningeal enhancement along the cauda equina nerve roots. Their patient also had clinical evidence of cranial neuropathies with facial nerve enhancement, though the brain MR images were not included in the article. Carpenter et al<sup><a id="xref-ref-3-1" class="xref-bibr" href="#ref-3">3</a></sup> showed 3 cases of hypophysitis associated with ipilimumab, which was also thought to represent an immune-mediated response. Our case shows leptomeningeal enhancement and perivascular enhancement in the cerebral hemispheres and pons, findings perhaps analogous to an inflammatory process such as neurosarcoidosis or chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Prominent perivascular enhancement may therefore be a subtle clue to an inflammatory process rather than metastatic disease, though supportive clinical and laboratory findings are needed to make a confident diagnosis.</p><p id="p-4">As immunotherapeutics are increasingly used as antineoplastic agents, neuroradiologists must be aware of their unusual adverse effects and imaging findings. Brain MR imaging to evaluate for metastatic melanoma is not an uncommon study, and oncologists may plan chemotherapy or radiation treatment without histologic or CSF cytologic proof of intracranial metastasis. We should therefore be aware of this potential pitfall and are reminded to be cognizant of the specific chemotherapeutic agents our patients are receiving when providing interpretations.</p><div class="section ref-list" id="ref-list-1"><h2 class="">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-36.12.E69.1" data-doi="10.1097/CJI.0b013e318174a4fe"><div class="cit-metadata"><ol class="cit-auth-list"><li>
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</li><li><span class="cit-auth"><span class="cit-name-surname">Manousakis</span>  <span class="cit-name-given-names">G</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Koch</span>  <span class="cit-name-given-names">J</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Sommerville</span>  <span class="cit-name-given-names">RB</span></span>, <span class="cit-etal">et al</span></li></ol><cite>. <span class="cit-article-title">Multifocal radiculoneuropathy during ipilimumab treatment of melanoma</span>. <abbr class="cit-jnl-abbrev">Muscle Nerve</abbr> <span class="cit-pub-date">2013</span>;<span class="cit-vol">48</span>:<span class="cit-fpage">440</span>–<span class="cit-lpage">44</span><span class="cit-pub-id-sep cit-pub-id-doi-sep"> </span><span class="cit-pub-id cit-pub-id-doi"><span class="cit-pub-id-scheme-doi">doi:</span>10.1002/mus.23830</span><span class="cit-pub-id-sep cit-pub-id-pmid-sep"> </span><span class="cit-pub-id cit-pub-id-pmid"><span class="cit-pub-id-scheme-pmid">pmid:</span>23447136</span></cite></div><div class="cit-extra"><a href="/lookup/external-ref?access_num=10.1002/mus.23830&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=23447136&amp;link_type=MED&amp;atom=%2Fajnr%2F36%2F12%2FE69.atom" class="cit-ref-sprinkles cit-ref-sprinkles-medline"><span>PubMed</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-36.12.E69.3" data-doi="10.3174/ajnr.A1623"><div class="cit-metadata"><ol class="cit-auth-list"><li>
</li><li><span class="cit-auth"><span class="cit-name-surname">Carpenter</span>  <span class="cit-name-given-names">KJ</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Murtagh</span>  <span class="cit-name-given-names">RD</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Lilienfeld</span>  <span class="cit-name-given-names">H</span></span>, <span class="cit-etal">et al</span></li></ol><cite>. <span class="cit-article-title">Ipilimumab-induced hypophysitis: MR imaging findings</span>. <abbr class="cit-jnl-abbrev">AJNR Am J Neuroradiol</abbr> <span class="cit-pub-date">2009</span>;<span class="cit-vol">30</span>:<span class="cit-fpage">1751</span>–<span class="cit-lpage">53</span><span class="cit-pub-id-sep cit-pub-id-doi-sep"> </span><span class="cit-pub-id cit-pub-id-doi"><span class="cit-pub-id-scheme-doi">doi:</span>10.3174/ajnr.A1623</span><span class="cit-pub-id-sep cit-pub-id-pmid-sep"> </span><span class="cit-pub-id cit-pub-id-pmid"><span class="cit-pub-id-scheme-pmid">pmid:</span>19474123</span></cite></div><div class="cit-extra"><a href="/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiYWpuciI7czo1OiJyZXNpZCI7czo5OiIzMC85LzE3NTEiO3M6NDoiYXRvbSI7czoyMDoiL2FqbnIvMzYvMTIvRTY5LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==" 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></ol></div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2015 by American Journal 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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        	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-volume highwire-cite-metadata">Vol. 36</span>, <span  class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 12 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 Dec 2015 </div></div>
      
      
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      <div class="highwire-cite-title">Ipilimumab Therapy for Melanoma: A Mimic of Leptomeningeal Metastases</div>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">S.</span> <span class="nlm-surname">Ali</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">S.-K.</span> <span class="nlm-surname">Lee</span></span></span></div>
  
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