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CASE REPORT  
Year : 2020  |  Volume : 63  |  Issue : 3  |  Page : 488-490
Aspergillus fumigatus meningitis in an immunocompetent young woman


1 Department of Internal Medicine, Aster Medcity, Kochi, Kerala, India
2 Department of Infectious Diseases, Aster Medcity, Kochi, Kerala, India
3 Department of Rheumatology, Aster Medcity, Kochi, Kerala, India

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Date of Submission30-Mar-2019
Date of Decision30-Apr-2019
Date of Acceptance03-May-2019
Date of Web Publication7-Aug-2020
 

   Abstract 


Aspergillus meningitis is a rare clinical entity that is much more frequently observed among immunocompetent patients. Here we present the case of a 28 year old immunocompetent lady with Aspergillus fumigatus meningitis possibly following spinal anaesthesia for her caesarean section. The diagnosis of Aspergillus meningitis is very difficult and challenging. Even after diagnosis, clinical outcomes remain poor with treatment. We wish to highlight the need for high index of suspicion for Fungal meningitis in patients presenting with meningism after Neurosurgeries and procedures involving invasion into the CSF compartment.

Keywords: Aspergillus, fungal meningitis, meningitis

How to cite this article:
Rathish B, Wilson A, Warrier A, Pillay R, Thomas J. Aspergillus fumigatus meningitis in an immunocompetent young woman. Indian J Pathol Microbiol 2020;63:488-90

How to cite this URL:
Rathish B, Wilson A, Warrier A, Pillay R, Thomas J. Aspergillus fumigatus meningitis in an immunocompetent young woman. Indian J Pathol Microbiol [serial online] 2020 [cited 2020 Sep 24];63:488-90. Available from: http://www.ijpmonline.org/text.asp?2020/63/3/488/291662





   Introduction Top


Aspergillus meningitis is a rare clinical entity that is much more frequently observed among immunocompetent patients.[1] Cryptococcus neoformans infection is still the most common CNS fungal infection, whereas Aspergillus and Mucor are relatively uncommon causes of CNS infection.[2] An outbreak of Aspergillus fumigatus meningitis occurred in 5 women following spinal anaesthesia, performed for caesarean section, in Colombo, Sri Lanka.[3] Here we present the case of a 28-year-old immunocompetent lady with Aspergillus fumigatus meningitis possibly following spinal anaesthesia for her caesarean section.


   Case History Top


A 28-year-old lady, post Caesarean section 2 months prior, was referred to us with complaints of fever and headache which started 2 weeks following the surgery and persisted. She had been admitted and evaluated in another centre and she had negative blood, urine and Cerebro-spinal fluid (CSF) cultures. CSF examination was done twice, with both times showing lymphocytic predominant picture with mild elevation in proteins and low normal sugars. CSF was negative for Tuberculosis (TB) Polymerase Chain reaction (PCR) and Xcyton® Panel. Chest Xray was clear. Trans-thoracic echocardiography revealed no vegetations while Magnetic Resonance (MR) brain with contrast revealed a normal study. She was empirically started on Anti-tubercular treatment (ATT) and Dexamethasone in view of suspected meningeal TB 2 weeks ago. On our clinical examination, she appeared well, with only anomaly being tachycardia and she was afebrile. Her ATT was stopped, and she was admitted for detailed workup. Inflammatory markers were negative. An auto-immune workup including Wegener's, IgG4 disease, and Sarcoidosis was negative. Repeat Blood, urine and CSF cultures were negative. MR Brain and Cervical Cord, revealed significant inflammatory lesion in the dura of the cord at C5 with extension into the nerve root [Figure 1]. Open biopsy with laminectomy was offered but deferred due to the risk of neurological worsening and the patient's wishes. Based on radiographic findings, empirical ATT with Dexamethasone was initiated. The fever responded rapidly to high dose Dexamethasone. She was then discharged and put on weekly follow up. Her symptoms showed subjective improvement and her steroid dose was gradually tapered to lower dosage over the course of 1 month. She had recurrence of her symptoms after 5 weeks after discharge, with throbbing occipital headache and fundoscopy showed papilloedema. Repeat MR brain and spine showed moderate degree of communicating hydrocephalus. The previously noted lesion in the spinal cord at C5/6 level had improved to a good extent. CSF study showed an elevated opening pressure, high protein, normal sugar and the CSF Adenosine Deaminase, Acid Fast Bacilli (AFB) smear, GeneXpert®, Fungal smear and stain, Cryptococcal antigen and Bacterial as well as Fungal culture were negative. She was continued on ATT with Dexamethasone with a plan for continuing it and repeat imaging after 6 weeks. 10 days later, she returned to the OPD with worsening headache and visual disturbances, and a new symptom of left sided radicular pain and lower back pain. Examination showed Straight Leg Raising Test (SLRT) positive on the left side. MR Brain and Spine, showing a left lumbar L1-L2 nerve root lesion with hydrocephalus [Figure 2]. She also had significant papilloedema. She was taken up for a theco-peritoneal shunt and a biopsy with tissue culture from the left L1-L2 lumbar root lesion. The tissue biopsy frozen section showed features suggestive of an inflammatory lesion with suppuration with branching septate hyphae with regular walls, suggestive of fungal infection. Histopathology showed extensive areas of necrosis, dense and diffuse acute and chronic inflammatory infiltrate composed of lymphocytes, neutrophils, histiocytes, plasma cells, and scattered variably sized granulomas composed of epithelioid histiocytes and multinucleate foreign body type cells. Within the necrotic debris, fungal balls composed of branching septate hyphae with regular walls and obtuse angle branching and positive for Periodic acid-Schiff and Gomori's methanamine silver stains, suggestive of invasive fungal infection with necrotizing granulomatous reaction with suppuration, morphologically suggestive of invasive aspergilloma. Definite confirmation was made based on fungal culture growth of Aspergillus fumigatus from the intra operative sample [Figure 3]. She was started on Voriconazole, the dexamethasone was rapidly tapered and ATT stopped, and discharged with a plan to continue Voriconazole. 6 weeks later, she presented with headache and vomiting. Clinical examination revealed bilateral papilloedema. Since she was still having symptoms on high dose Voriconazole, Autoimmune meningitis, Xcyton® and Paraneoplastic panels were sent for and these were negative. While admitted, she developed hypotension and hence, an Ommaya reservoir was placed and she was initiated on Intraventricular Amphoterecin-B for a total of 14 days, along with Voriconazole. She was also initiated on antibiotics to cover for possible secondary bacterial sepsis. She still persisted to have headache and vomiting while on these 2 antifungals and 2 antibiotics. She also continued deteriorating with episodes of hypotension, requiring inotropic support. Repeat CSF studies showed similar picture to previous taps and TB panel was again negative. CSF cultures were also negative. Her antibiotic was hiked to empirical Carbapenem, following which she still did not clinically improve. She was discharged at request to another center, where she succumbed 2 weeks later.
Figure 1: MR Cervical cord showing significant inflammatory lesion in the dura of the cord at C5 with extension into the nerve root (Arrow)

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Figure 2: MR Spine showing a left lumbar L1-L2 nerve root lesion (Arrow)

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Figure 3: (a) Hematoxylin and Eosin (H and E) staining showing hyphae with acute angle branching and septae suggestive of Aspergillus (blue arrow). (b) Fungal hyphae suggestive of Aspergillus seen on Periodic acid–Schiff (PAS) stain. (c) Gomori methenamine silver (GMS) stain suggestive of Aspergillus

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   Discussion Top


The diagnosis of Aspergillus meningitis is very difficult and challenging. In fact, a diagnosis during life was obtained only in 55.9% of patients although with a much higher frequency among immunocompetent patients (69.2%) as opposed to immunocompromised individuals (39%).[1] In our patient, the whole armamentarium of investigations were carried out, and she had been on empirical ATT for a period of time, before the diagnosis was established. Then too, the organism was grown from a surgical tissue sample, and not from CSF. Even after establishment of the diagnosis, the patient did not respond adequately to Voriconazole. High dose Voriconazole was tried without significant symptom resolution. During her final admission, an Ommaya reservoir was placed and she was given intraventricular Amphoterecin B in addition to the Voriconazole despite which she deteriorated.

In a study done by Antinori et al., of those patients who had received at least one dose of antifungal agent, 51.7% died after an interval of time ranging from few days up to 6 years. An overall case-fatality rate of 72.1% was observed, with significant differences between immunocompetent (63.5%) as opposed to immunocompromised patients (82.9%) patients.[1] Hence, we wish to highlight the need for high index of suspicion for Fungal meningitis in patients presenting with similar symptoms after Neurosurgeries and procedures involving invasion into the CSF compartment. We also wish to highlight the therapeutic challenge such cases pose, and hence the need for absolute prevention and aseptic measures while doing the afore-mentioned procedures.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgements

Dept of Neurosurgery, Aster Medcity, Kochi, India

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Antinori S, Corbellino M, Meroni L, Resta F, Sollima S, Tonolini M, et al. Aspergillus meningitis: A rare clinical manifestation of central nervous system aspergillosis. Case report and review of 92 cases. J Infect 2013;66:218-38.  Back to cited text no. 1
    
2.
Qi X-K. Diagnosis and therapy of rare central nervous system infections. Neuroimmunol Neuroinflamm 2014;1:8-12.  Back to cited text no. 2
    
3.
Gunaratne P, Wijeyaratne C, Seneviratne H. Aspergillus meningitis in Sri Lanka — A post-Tsunami effect? N Engl J Med 2007;356:754-6.  Back to cited text no. 3
    

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Correspondence Address:
Balram Rathish
Department of Internal Medicine, Aster Medcity, Kochi, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_252_19

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    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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