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 <!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.0 20120330//EN" "http://jats.nlm.nih.gov/publishing/1.0/JATS-journalpublishing1.dtd"> <article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" article-type="in-brief" dtd-version="1.0" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JNRT</journal-id>
      <journal-title-group>
        <journal-title>Journal of Neurological Research And Therapy</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2470-5020</issn>
      <publisher>
        <publisher-name>Open Access Pub</publisher-name>
        <publisher-loc>United States</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">JNRT-16-1288</article-id>
      <article-id pub-id-type="doi">10.14302/issn.2470-5020.jnrt-16-1288</article-id>
      <article-categories>
        <subj-group>
          <subject>in-brief</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Surgical Managment of Intracranial Invasive Aspergillosis in Immunocompetent Patients: Results from 3 Case Reports</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>K</surname>
            <given-names>Quenum</given-names>
          </name>
          <xref ref-type="aff" rid="idm1808875644">1</xref>
          <xref ref-type="aff" rid="idm1808875500">*</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>L</surname>
            <given-names>Rifi</given-names>
          </name>
          <xref ref-type="aff" rid="idm1808875644">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>M</surname>
            <given-names>Boutarbouch</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Y</surname>
            <given-names>Arkha</given-names>
          </name>
          <xref ref-type="aff" rid="idm1808875644">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>S</surname>
            <given-names>Derraz</given-names>
          </name>
          <xref ref-type="aff" rid="idm1808875644">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>A</surname>
            <given-names>El Ouahabi</given-names>
          </name>
          <xref ref-type="aff" rid="idm1808875644">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>A</surname>
            <given-names>Khamlichi</given-names>
          </name>
          <xref ref-type="aff" rid="idm1808875644">1</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1808875644">
        <label>1</label>
        <addr-line>Service de Neurochirurgie, hôpital des spécialités– Rabat, Maroc</addr-line>
      </aff>
      <aff id="idm1808875500">
        <label>*</label>
        <addr-line>Corresponding author</addr-line>
      </aff>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Mourad</surname>
            <given-names>Tayebi</given-names>
          </name>
          <xref ref-type="aff" rid="idm1808718636">1</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1808718636">
        <label>1</label>
        <addr-line>The University of Surrey </addr-line>
      </aff>
            <author-notes>
        <corresp>
          Ignacio Casadei
          <addr-line>Centro de Especialidades Médicas, Asunción, Paraguay</addr-line>
          <email>ignacio.casadei@example.com</email>
        </corresp>
        <fn fn-type="conflict" id="idm1816989788">
          <p>The authors have declared that no competing interests exist.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub" iso-8601-date="2017-01-05">
        <day>05</day>
        <month>01</month>
        <year>2017</year>
      </pub-date>
      <volume>1</volume>
      <issue>4</issue>
      <fpage>20</fpage>
      <lpage>27</lpage>
      <history>
        <date date-type="received">
          <day>08</day>
          <month>09</month>
          <year>2016</year>
        </date>
        <date date-type="accepted">
          <day>06</day>
          <month>12</month>
          <year>2016</year>
        </date>
        <date date-type="online">
          <day>05</day>
          <month>01</month>
          <year>2017</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>© </copyright-statement>
        <copyright-year>2017</copyright-year>
        <copyright-holder>K Quenum, et al.</copyright-holder>
        <license xlink:href="http://creativecommons.org/licenses/by/4.0/" xlink:type="simple">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
        </license>
      </permissions>
      <self-uri xlink:href="http://openaccesspub.org/jnrt/article/405">This article is available from http://openaccesspub.org/jnrt/article/405</self-uri>
      <abstract>
        <p>Cerebral aspergillosis is a severe disease most commonly suspected in immunodeficient patients.</p>
        <p>The objective of this study is to determine the role of surgery in management of intracranial aspergillosis. We report three cases of immunocompetent patients presenting: posteriror fossa aspergillosis, sphenoidal extended to sellar region aspergillosis and post operative aspergillosis without extracerebral involvement. Microbiology and histological examination were carried out to provide the diagnosis. The patients underwent surgical procedure associated with medical treatment or not. In one case, surgical treatment was efficient. The outcome was good in two cases.</p>
        <sec id="idm1808717052">
          <title>Conclusion:</title>
          <p><bold/>Rapid diagnosis of invasive aspergillosis applying radiological and surgical procedures and immediate ignition of antifungal can be life saving.</p>
        </sec>
      </abstract>
      <kwd-group>
        <kwd>Invasive aspergillosis</kwd>
        <kwd>abscess</kwd>
        <kwd>immunocompetent patient</kwd>
        <kwd>surgical treatment.</kwd>
      </kwd-group>
      <counts>
        <fig-count count="7"/>
        <table-count count="0"/>
        <page-count count="8"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec id="idm1808716548" sec-type="intro">
      <title>Introduction</title>
      <p>Cerebral aspergillosis is severe parasitic disease which is rare in immunocompetent individual. The invasive form with multiple visual involvements is usually seen with immunosuppression. New therapeutic agents such as voriconazole and capsofungine which are more save and efficacious have changed the outcome of this fatale cerebral infection.</p>
    </sec>
    <sec id="idm1808716332" sec-type="cases">
      <title>Case 1</title>
      <p>A 47 year old patient with no previous medical history presented with features of raised intracranial pressure, statokinetic cerebellar syndrome as well as left sided hemiparesis. The diagnosis of posterior fossa space occupying lesion was made. Neuroradiologic investigations demonstrated posterior fossa lesions. Magnetic resonance imaging and spectroscopy were in favor of a multiple infective process (<xref ref-type="fig" rid="idm1808064964">Figure 1</xref>). Stereotatic biopsy was carried out on the patient and parasitological and histological examinations of the specimen concluded to a filamentous fungal infection of Aspergillus type. Culture and staining techniques categorized the specie as Aspergillus fumigatus (<xref ref-type="fig" rid="idm1808072236">Figure 2</xref>).</p>
      <fig id="idm1808064964">
        <label>Figure 1.</label>
        <caption>
          <title> cerebral MRI axial T1-weighted (A) and coronale (B), showing a multiples well circumscribed posterior fossa lesions </title>
        </caption>
        <graphic xlink:href="images/image1.jpg" mime-subtype="jpg"/>
      </fig>
      <fig id="idm1808072236">
        <label>Figure 2.</label>
        <caption>
          <title> ( A) filamentous fungal infection of Aspergillus type. (B) Culture and staining techniques categorized the specie as Aspergillus fumigatus  </title>
        </caption>
        <graphic xlink:href="images/image2.jpg" mime-subtype="jpg"/>
      </fig>
      <p>Patient was placed on intra veinous amphotéricin B but this was complicated with acute active hydrocephalus warranting external ventricular drainage (<xref ref-type="fig" rid="idm1808071372">Figure 3</xref>). Subsequently, he developped staphylococcal meningitis as day 8 post op, treated with intra veinous vancomycin. Patient developed renal insufficiency and hyperosmolar non ketotic coma for an unknown diabetis for which amphotéricine B therapy was stopped. His neurological status deteriorated with a Glasgow coma scale (GCS)7/15. Posterior fossa surgery was performed with excision of the fungal abscess (<xref ref-type="fig" rid="idm1808057652">Figure 4</xref>) and Voriconazol was instituded post operatively for fungal therapy with improvement of the neurological status to GCS 13/15. But the patient succumbed to acute cardiac failure.</p>
      <fig id="idm1808071372">
        <label>Figure 3.</label>
        <caption>
          <title> cerebral CT scan with axial view showing  acute hydrocephalus (A) and control after external ventricular drainage (B)</title>
        </caption>
        <graphic xlink:href="images/image3.jpg" mime-subtype="jpg"/>
      </fig>
      <fig id="idm1808057652">
        <label>Figure 4.</label>
        <caption>
          <title> cerebral CT scan pre operative (A) and post operative (B) after posterior fossa surgery with total removal or abscesses </title>
        </caption>
        <graphic xlink:href="images/image4.jpg" mime-subtype="jpg"/>
      </fig>
    </sec>
    <sec id="idm1808690028" sec-type="cases">
      <title>Case 2</title>
      <p>A 65 year-old man presented with progressive visual decrease and ptosis in the left eye. Neurological examination revealed paresis of the 3rd left cranial nerve. Fundoscopy revealed bilateral papillary paleness and visual acuity was: 4/10 at left; 7/10 at right. No signs of endocrine insufficiency or hypersecretion were assessed. There was no evidence of sinusitis. Chest X-ray, routine laboratory investigations and hormonal blood tests were normal. A CT scan showed a hypodense mass enlarging the sphenoid sinus and sellar region with calcification like images and bone erosion of the sellar floor (<xref ref-type="fig" rid="idm1808055564">Figure 5</xref>). MRI showed a mass of 26 mm x 33 mm x 25 mm in the sphenoidal sinus ans sellar region, with hypersignal intensity in T1-weighted (<xref ref-type="fig" rid="idm1808055060">Figure 6</xref>A) ans T2-weighted sequences, and hyposignal zone in T2-weighted sequences (<xref ref-type="fig" rid="idm1808055060">Figure 6</xref>B). Imaging investigations were suggestive of unusual pituitary macroadenoma. The patient underwent a transnasal transsphenoidal approach for excision of the mass. A yellow-brownish gluey material with gummy debris was aspirated from the sphenoid sinus, which was completely cleaned. The sellar floor was eroded which allowed a view of the intact inflammatory dura. An intra-operative presumptive diagnosis was made of caseating granuloma (i.e tuberculosis). The post-operative course was uneventful: the patient recovered from ptosis and visual acuity improve at discharge. Mycobacterium tuberculosis could not be cultured from specimens; and cultures on Sabouraud’s medium did not isolate Aspergillus. Pathologic findings were of non invasive aspergillosis, with many septated fungal hyphae being present without tissue invasion. The patient was not given antifungal drugs because the intrasphenoidal material was completely aspirated. At 6 month and 18 months follow up, the patient had no neurological complaint. No recurrence was observed on control CT scans.</p>
      <fig id="idm1808055564">
        <label>Figure 5.</label>
        <caption>
          <title> CT scan showing a hypodense mass enlarging the sphenoid sinus and sellar region with calcification like images and bone erosion of the sellar floor </title>
        </caption>
        <graphic xlink:href="images/image5.jpg" mime-subtype="jpg"/>
      </fig>
      <fig id="idm1808055060">
        <label>Figure 6.</label>
        <caption>
          <title> (a) Sagittal T1-weighted MRI showing a well circumscribed hyperintense process in the sphenoidal sinus and sellar region; (b) parasagittal T2-weighted MRI showing a regular hypointense zone into the hyperintense process which is specific to aspergillus infection and corresponds to iron accumulation </title>
        </caption>
        <graphic xlink:href="images/image6.jpg" mime-subtype="jpg"/>
      </fig>
    </sec>
    <sec id="idm1808694492" sec-type="cases">
      <title>Case 3</title>
      <p>A 45 year-old woman, operated 6 months before for left sphenoid wing meningoma revealed by raised intracranial pressure, with hemiplegia. She underwent surgery, with simpson I resection. The post operative outcome was good and the patient was discharge. Six months later, she presented a swelling on surgical site of skin incision. Blood check found inflammation with raised C-Reactive Protein. CT scan permitted to suggest brain abcess and she was operated in emergency with bone flap removal and the abscess complete excision. Bacteriologic and Histologic examination of the pus, revealed aspergillus flavius. The patient was treated by amphotéricin B because it was the antifungal avalailable in the hospital officine. Two months treatment was necessary to controle cerebral aspergillosis (<xref ref-type="fig" rid="idm1808052900">Figure 7</xref>) and the patient was discharged with good outcome.</p>
      <fig id="idm1808052900">
        <label>Figure 7.</label>
        <caption>
          <title> (A) pre operative MRI, axial T1 weighted with enhancement of sphenoid wing meningioma. (B) Ct scan showing an brain abscess in post op area. (C) CT scan after remoral sugery and 2 months medical treatment. </title>
        </caption>
        <graphic xlink:href="images/image7.jpg" mime-subtype="jpg"/>
      </fig>
    </sec>
    <sec id="idm1808678276" sec-type="discussion">
      <title>Discussion</title>
      <p>Cerebral aspergillosis is one of the common sites secondary to invasive aspergillosis from hematogenous dissemination <xref ref-type="bibr" rid="ridm1808824740">1</xref><xref ref-type="bibr" rid="ridm1808676028">8</xref> or contignous spread aspergillus from paranasal sinuses <xref ref-type="bibr" rid="ridm1808890564">2</xref><xref ref-type="bibr" rid="ridm1808899100">3</xref>. Pulmonary involvement is rarely seen in immunocompetent patient unlike the immunosuppressed. The quest for blood supply especially the thalamic perforators explains its localizations around the substancia nigra. Posterior fossa lesions without other sites are rare, like in our case 1. The clinical presentation is that of a posterior fossa space occupying lesions. Supra tentorial lesions are pleomorphic. They may present with functionnal neurological syndrome or raised intracranial pressure with sepsis syndrome. Risks factors for cerebral aspergillosis in an immunocompetents patients described in literature include old age, diabetes, alcoholism, illicit drug abuse and brain surgery like case 3 <xref ref-type="bibr" rid="ridm1808683900">6</xref><xref ref-type="bibr" rid="ridm1808663460">9</xref>. Our patient case 1, presented with undiagnosed diabetes which was confirmed on admission. Brain CT scan with contrast may not suggest the diagnosis because the lesions are not located in the substancia nigra <xref ref-type="bibr" rid="ridm1808683900">6</xref>. Only MRI with spectroscopy could suggest an infectious process rather than tumour. This indicated stereotatic biopsy in our patient as a first step followed by bacteriological and histological examinations of the specimen which confirmed the diagnosis. Amphotéricin B is the reference drug in our department for its efficacy, availability and cost. Voriconazol was substituted because of the sides’ effects in our patient. Side effect are well known draw backs of amphotéricin B therapy. With introduction of vancomycin for treatment of post op staphylococcal meningitis, renal failure was the consequence of its toxicity, warranting the stoppage of the therapy. But with neurological deterioration our patient was operated upon with excision of the focus of infection in the posterior fossa, duro plasty and introduction of voriconazol. </p>
      <p>In the literature, surgery was indicated in compressive (symptomatic) lesions or for diagnostic biopsy <xref ref-type="bibr" rid="ridm1808899100">3</xref><xref ref-type="bibr" rid="ridm1808689156">5</xref><xref ref-type="bibr" rid="ridm1808676028">8</xref>.  </p>
      <p>The treatment of choice for sino-orbital aspergillosis or sphenoidal is surgical excision of the aspergilloma, granulation tissue of the involved sinus for ventilation and drainage, as early as possible <xref ref-type="bibr" rid="ridm1808824740">1</xref><xref ref-type="bibr" rid="ridm1808689156">5</xref><xref ref-type="bibr" rid="ridm1808678908">7</xref><xref ref-type="bibr" rid="ridm1808676028">8</xref>. Furthermore, there was shown a beneficial effect of pre-surgical treatment with antifungal therapy <xref ref-type="bibr" rid="ridm1808663460">9</xref><xref ref-type="bibr" rid="ridm1808667996">10</xref>. In patients for whom total removal cannot be achieved, intensive therapy with antifungal agents must be started immediately. But for the case 1, pre operative medical treatment was not satisfactory.</p>
      <p>For the patient 3, it should be noted that all bacteriological samples performed in the theatre especially to identify nosocomial risks are unsuccessful.</p>
    </sec>
    <sec id="idm1808677988" sec-type="conclusions">
      <title>Conclusion</title>
      <p>Cerebral aspergillosis is a serious disease; the diagnosis of which should be suspected in case of immunosuppression with search for primary focus in the lungs or paranasal sinuses. Therapy with antifungal agents still remain delicate. Surgical removal of sphenoid sinus aspergillosis cases proved to be efficient. Other sites infections must be completed by antifungal treatment <xref ref-type="bibr" rid="ridm1808691748">4</xref></p>
    </sec>
  </body>
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