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Table of Contents    
Year : 2021  |  Volume : 69  |  Issue : 4  |  Page : 1027-1031

Cerebral Phaeohyphomycosis: Subacute Meningoencephalitic Presentation in a Child

1 Department of Pediatrics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
2 Department of Neurosurgery, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
3 Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
4 Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

Date of Web Publication2-Sep-2021

Correspondence Address:
Karthi Nallasamy
Department of Pediatrics, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.323890

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 » Abstract 

Cerebral phaeohyphomycosis is a rare but serious fungal infection of the central nervous system caused by dematiaceous septate fungi characterized by the presence of melanin-like pigment within the cell wall that is a pale brown to black. It is associated with poor prognosis despite aggressive treatment. We report a previously well 3-year boy with cerebral phaeohyphomycosis who had subacute meningoencephalitic presentation with refractory raised intracranial pressure and had fatal outcomes. The diagnosis was confirmed by histopathological examination of brain tissue obtained by brain biopsy.

Keywords: Fungus, ICP, phaeohyphomycosis, raised
Key Message: Cerebral phaeohyphomycosis is a rare but serious fungal infection of central nervous system. Diagnosis requires a high index of suspicion, histopathological examination, and culture. Treatment includes prompt antifungal therapy and aggressive surgical resection. Despite aggressive treatment, the outcome is usually fatal.

How to cite this article:
Angurana SK, Ismail J, Suthar R, Muralidharan J, Sankhyan N, Tripathi M, Radotra BD, Singh P, Nallasamy K. Cerebral Phaeohyphomycosis: Subacute Meningoencephalitic Presentation in a Child. Neurol India 2021;69:1027-31

How to cite this URL:
Angurana SK, Ismail J, Suthar R, Muralidharan J, Sankhyan N, Tripathi M, Radotra BD, Singh P, Nallasamy K. Cerebral Phaeohyphomycosis: Subacute Meningoencephalitic Presentation in a Child. Neurol India [serial online] 2021 [cited 2021 Oct 23];69:1027-31. Available from:

Cerebral phaeohyphomycosis is an uncommon fungal infection of the central nervous system (CNS) caused by environmental pigmented dematiaceous septate fungi. The common causative organisms for cerebral phaeohyphomycosis are Cladophialophora bantiana, Rhinocladiella mackenziei, Exophiala dermatitidis, Ochroconis gallopavum, and Exserohilum rostratum.[1],[2] These fungi involve organs including pulmonary, CNS, subcutaneous, cutaneous, or fatal disseminated disease. Cerebral phaeohyphomycosis can occur in immunocompetent (in about 50%) or immunocompromised hosts (including transplant recipients). Among immunocompetent patients, CNS infection may occur in the absence of pulmonary lesions.[2],[3] The CNS may be involved in up to 50% of patients with infection with these moulds and associated with poor outcomes. The organisms usually reach the CNS through the bloodstream, lymphatics, direct spread (from sinuses), or accidental inoculation.[4] The signs and symptoms of cerebral phaeohyphomycosis include fever, seizures, headache, cerebral irritation, hemiparesis, hemisensory loss, and psychotic behavioral changes. Sometimes the patients with cerebral phaeohyphomycosis may present as slowly expanding space-occupying lesion causing headache, seizure, and localizing neurologic signs. Cases with spinal osteomyelitis, epidural abscess, septic arthritis, or osteomyelitis have been reported.[2],[4]

Radiological features include hyperdense and hypodense lesions with ring-enhanced signs. Histopathological examination reveals black-to-brown necrotic tissue, granulomatous inflammation, giant cell vasculitis, dark-colored pus, and pigmented fungal elements, which can be easily identified on potassium hydroxide smear. Black fungi can be cultured from a biopsy specimen.[2],[3] Prolonged antifungal therapy and aggressive surgical resection of abscesses are mainstays of treatment and despite aggressive treatment mortality is high. There may be persistence or recurrence of the disease.[1],[5] There are limited case reports of cerebral phaeohyphomycosis in children from India.[6],[7],[8],[9],[10] We report an apparently well 3-year-male with cerebral phaeohyphomycosis who had subacute meningoencephalitis presentation with refractory raised intracranial pressure (ICP) and fatal outcome.

 » Case Report Top

A 3-years old boy presented with fever for 25 days, multiple episodes of left focal seizures followed by generalized seizures for ten days, a left-sided weakness for five days, and altered sensorium for three days. There was no history of ear discharge, head trauma, recent travel, contact with tuberculosis, or serious infections in the past. He was admitted at a private hospital for eight days before being referred to us where he received intravenous antibiotics (ceftriaxone, vancomycin, and metronidazole), phenytoin, and underwent contrast-enhanced computerized tomography (CECT) of the head, magnetic resonance imaging (MRI) brain, and cerebrospinal fluid (CSF) examination and referred to us in view of worsening of sensorium and frequent seizures.

On examination, weight was 14 kg (−0.21 z-score), height 95 cm (−0.1 z-score), and he was afebrile. His pulse rate was 136/min, respiratory rate 22/min, and blood pressure 110/66 mmHg. CNS examination revealed the Glasgow Coma Scale (GCS) of 9, normal muscle bulk, left-sided hemiparesis, increased tone in all four limbs, exaggerated deep tendon reflexes, and bilateral upgoing planters; and no cranial nerve palsy (limited examination), signs of meningeal irritation, or papilledema. Due to encephalopathy, higher mental function, sensory system, the cerebellar system could not be tested. The per abdominal, cardiovascular system and respiratory system examination were normal.

The provisional diagnosis of acute pyogenic meningitis with complication (infarct, brain abscess, subdural empyema), and chronic meningitis (tubercular, fungal, other unusual organisms) with raised ICP were considered. He was intubated and started on mechanical ventilation for low GCS and raised ICP. He was started on intravenous ceftriaxone, metronidazole, and cloxacillin; measures to control ICP (head in midline, head-end elevation, minimal stimulation, fever control, sedo-analgesia, that is, midazolam infusion 2 μg/kg/min and fentanyl 2 μg/kg/h, and 3% saline infusion); and phenytoin for seizures.

Investigations revealed hemoglobin of 8.6 g/dL, total leukocyte count (TLC) 32,300/cumm (neutrophils 80%, lymphocytes 16%), platelet count 3,47,000/cumm; and normal renal and liver functions, coagulation profile, and chest radiograph. CT head (non-contrast) done on the day-18 of illness (private hospital) suggestive of ill-defined hypodensity involving the right frontal region [Figure 1]a. CSF examination revealed turbid appearance, TLC 20600/cumm (neutrophils 65%, lymphocytes 30%), glucose 48 mg%, protein 36 mg%, negative gram stain and ZN stain, and sterile culture. MRI brain done on day-22 of illness (private hospital) was suggestive of an extensive area of heterogeneous T2 and fluid-attenuated inversion recovery (FLAIR) hyperintensities involving right frontal lobe, genu and body of corpus callosum, and right cingulate gyrus with extension into the left frontal periventricular deep white matter [Figure 1]b.
Figure 1: (a) non-contrast CT head (day-18 of illness) shows ill-defined hypodensity in the right frontal region. (b) MRI brain (day-22 of illness) shows heterogeneous T2 hyperintensities in the right frontal lobe, genu and body of corpus callosum, and right cingulate gyrus extending into the left frontal lobe. (c) MRI brain (day-27 of illness) revealed progressive lesion involving right frontal lobe, parietal region, basal ganglia and thalamus, left frontal region with subfalcine herniation. (d) Contrast-enhanced CT head (day-33 of illness) shows hypodensity involving the right cerebral hemisphere and left frontal lobe with chinked ventricles

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On arrival at our hospital, MRI brain was repeated on day-27 of illness, which revealed progression of heterogeneous T1 hypointensities and T2/FLAIR hyperintensities in the right frontal lobe with extension into the parietal region, basal ganglia and thalamus with subfalcine herniation. There was also the involvement of the left frontal region (increased as compared to the previous image) [Figure 1]c.

There was further clinical deterioration with multiple episodes of seizures which were managed with the addition of valproate, phenobarbitone, levetiracetam, and midazolam infusion up to 15 μg/kg/min. ICP catheter (intraparenchymal) was inserted and ICP ranged from 30 to 50 cm of H2O. In view of clinical deterioration and progression on imaging despite broad-spectrum antibiotics, we considered the addition of antitubercular drugs (isoniazid, rifampicin, pyrazinamide, and ethambutol), and amphotericin to cover for tuberculosis, fungus, and primary amebic meningoencephalitis or granulomatous amebic meningoencephalitis. He was also given dexamethasone. Since diagnosis was not clear, he underwent right frontal craniotomy and brain tissue biopsy on day-31 of illness which revealed (on frozen section) inflammatory lesion with necrotizing epitheloid cell granuloma with multinucleated giant cells with a septate pigmented fungal profile which stained positive on PAS stain suggestive of phaeohyphomycosis [Figure 2]a and [Figure 2]b. ZN stain for acid-fast bacilli was negative. Voriconazole was added and amphotericin-B was continued and the rest of antimicrobial agents were stopped. CECT was again done at day-33 of illness which revealed ill-defined hypodensity involving the right cerebral hemisphere and left frontal lobe with associated compression of lateral ventricles [Figure 1]d. There was progressive worsening in clinical status and ICP for which mannitol and thiopentone were also added without much benefit and he succumbed on day-35 of illness (day 10 of hospital stay).
Figure 2: Photomicrographs from brain biopsy showing (a) Inflammatory lesion with necrotizing epithelioid cell granuloma and multinucleated giant cells. (b) Some of these inflammatory lesions had pigmented fungal hyphae having septations that stained positive on PAS stain suggestive of phaeohyphomycosis

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Other investigations revealed normal chest radiograph, negative Mantoux test and gastric aspirates for AFB; sterile blood and urine cultures; β-D glucan 244 pg/mL (>80 positive), negative cold agglutinin test nonreactive HIV ELISA; and normal reduction on nitroblue tetrazolium test, and normal immunoglobulin profile. Based on brain biopsy findings [Figure 2], the diagnosis of cerebral phaeohyphomycosis was considered.

 » Discussion Top

We present a case of cerebral phaeohyphomycosis with subacute meningoencephalitic presentation in a previously well child. In order to highlight an unusual clinical course in an immunocompetent child, the an unusual response to treatment and unusual CNS imaging findings made us report this case. The pigment in the fungal cell wall is responsible for the localization of these pathogens to CNS and adds to virulence.[4] Also, this infection is important to be recognized as its treatment is different from other fungal infections.[2],[4] In contrast to Aspergillus, Mucorales, and Fusarium, dematiaceous fungi (phaeohyphomycosis) commonly affect immunocompetent hosts (about 50% are immunocompetent).[1] Spread to the brain may occur through hematogenous dissemination, lymphatic vessels, and contiguous spread from adjacent organs such as orbits/sinuses.[1],[5] However, we did not find any source of infection in the index case.

Mostly, the CNS lesion of phaeohyphomycosis is single whereas immunocompromised patients may have multiple lesions.[4] MRI brain reveals ring-enhancing lesions on T1-weighted images, hypointensity of the ring on T2-weighted images, and low-to-high signal intensity on diffusion-weighted imaging. The low attenuation core suggests the presence of necrotic tissue or pus, whereas the ring-enhancing sign usually represents a granulomatous lesion.[4] In contrast, we note a heterogenous lesion without much contrast enhancement.

The mortality in untreated cases is near 100% and with surgery and antifungal agents, it is about 65–70%.[1],[4] So, any delay in starting antifungal therapy may affect the outcome. Once suspected an urgent stereotactic guided aspiration of pus and histopathological examination, fungal staining, and culture should be done. Sequencing is recommended for accurate species identification.[11]

Treatments should be individualized with surgical resection and optimization of antifungal therapy. Complete excision of brain abscesses has a better outcome than only aspiration or partial excision.[2],[11] Azoles (itraconazole, voriconazole, and posaconazole) demonstrate the most consistent in-vitro activity against dematiaceous fungi.[2],[7],[11] Voriconazole is superior because it achieves good cerebrospinal fluid levels. Posaconazole is a well-tolerated alternative drug with excellent salvage treatment results after the failure of other antifungals. Other effective antifungals include amphotericin B, echinocandins (caspofungin, micafungin, and anidulafungin), terbinafine, and flucytosine. Generally, a combination therapy (echinocandin plus amphotericin B or azole; and flucytosine plus amphotericin plus azole or echinocandin) is preferred especially when surgery is not possible or for disseminated infections in immunocompromised patients.[2],[11] The clinical and radiological improvement usually appears within 1–2 weeks of starting treatment and it is the best sign of clinical efficacy of the treatment. The duration of therapy to eradicate the infection depends on multiple factors, including the immune status of the patient, underlying cause of disease, and whether the surgical intervention was performed or not. The successful treatment courses used have been as short as 3 months and as long as up to one year. Therapy should be continued until complete radiographical resolution.[4]

There are limited case reports of cerebral phaeohyphomycosis involving the pediatric population.[6],[7],[8],[9],[10] [Table 1]. Revankar et al. reported 17 children with cerebral phaeohyphomycosis and among these eight died (47% mortality) and the outcome was unknown in three.[1],[10] Mani et al.[6] reported an apparently well 18-year-male with cerebral phaeohyphomycosis caused by Scytalidium dimidiatum who died despite aggressive antifungal therapy. Madhugiri et al.[7] reported an 8-year-girl with cerebral phaeohyphomycosis caused by Fonsecaea pedrosoi who survived after surgery and antifungal treatment. Shukla et al.[8] reported a 15-year-male with phaeohyphomycosis involving the right frontoparietal lobe. Earlier, we also reported an apparently well 8-year-boy with cerebral phaeohyphomycosis who had an acute encephalitic presentation with refractory raised (ICP) and fatal outcome.[9]
Table 1: Table showing summary of case series and reports of cerebral phaeohyphomycosis in children

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The clinical features are not very specific for cerebral phaeohyphomycosis. In any child or adult with acute or subacute meningoencephalitis with poor clinical response and progression of involvement on CNS imaging despite appropriate antibiotics, antivirals, and or antitubercular drugs, the unusual pathogens should be thought of and cerebral phaeohyphomycosis is one such unusual and rare pathogen.

 » Conclusion Top

Cerebral phaeohyphomycosis is a fatal disease even in immunocompetent individuals despite aggressive treatment. A high index of suspicion, histopathological examination, and culture, prompt antifungal treatment, aggressive surgical resection may help in improved outcomes.

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 » References Top

Revankar SG, Sutton DA, Rinaldi MG. Primary central nervous system phaeohyphomycosis: A review of 101 cases. Clin Infect Dis 2004;38:206-16.  Back to cited text no. 1
McCarthy M, Rosengart A, Schuetz AN, Kontoyiannis DP, Walsh TJ. Mold infections of the central nervous system. N Engl J Med 2014;371:150-60.  Back to cited text no. 2
Shoham S, Pic-Aluas L, Taylor J, Cortez K, Rinaldi MG, Shea Y, et al. Transplant-associated Ochroconis gallopava infections. Transpl Infect Dis 2008;10:442-8.  Back to cited text no. 3
Li DM, de Hoog GS. Cerebral phaeohyphomycosis--a cure at what lengths? Lancet Infect Dis 2009;9:376-83.  Back to cited text no. 4
Ravisankar S, Chander RV. Cerebral pheohyphomycosis: Report of a rare case with review of literature. Neurol India 2013;61:526-8.  Back to cited text no. 5
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Mani RS, Chickabasaviah YT, Nagarathna S, Chandramuki A, Shivprakash MR, Vijayan J, et al. Cerebral phaeohyphomycosis caused by Scytalidium dimidiatum: A case report from India. Med Mycol 2008;46:705-11.  Back to cited text no. 6
Madhugiri VS, Bhagavatula ID, Mahadevan A, Siddaiah N. An unusual infection, an unusual outcome--Fonsecaea pedrosoi cerebral granuloma. J Neurosurg Pediatr 2011;8:229-32.  Back to cited text no. 7
Shukla A, Bansal M, Husain M, Chhabra DK. Central nervous system mycosis: Analysis of 10 cases. Indian J Pathol Microbiol 2014;57:591-4.  Back to cited text no. 8
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Angurana SK, Suthar R, Mehta A, Nallasamy K, Garg R, Bal A, et al. Cerebral phaeohyphomycosis: Fulminant encephalitic presentation. Indian J Pediatr 2017;84:955-6.  Back to cited text no. 9
Revankar SG, Patterson JE, Sutton DA, Pullen R, Rinaldi MG. Disseminated phaeohyphomycosis: Review of an emerging mycosis. Clin Infect Dis 2002;34:467-76.  Back to cited text no. 10
Chowdhary A, Meis JF, Guarro J, de Hoog GS, Kathuria S, Arendrup MC, et al. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of systemic phaeohyphomycosis: Diseases caused by black fungi. Clin Microbiol Infect 2014;20(Suppl 3):47-75.  Back to cited text no. 11


  [Figure 1], [Figure 2]

  [Table 1]


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