Progressive visual field loss, confusion, headache for 2 months

Authors:

Peter G. Pappas,

  • 64 yo black male with recent onset of progressive visual loss on R visual field, confusion and headache. Symptoms have progressed over 2 months
  • Until then the patient was in his usual state of health, no recent hospitalizations, procedures or history of trauma.
  • Otherwise the patient denies fever, seizures, paresthesias, paresis, vertigo, or falls.
  • Has a history of Evans Syndrome for which he takes low dose prednisone daily (10-20 mg/d)

PMH:

  • HTN
  • Evan’s Syndrome
  • Meds: Prednisone, Lisinopril, albuterol, HCTZ
  • Social: From Birmingham, AL, no travel hx, no pets, denies ETOH, tobacco, drugs
  • Occupation- Physical Therapist- at a local hospital

Physical Examination:

  • VS: BP 135/80 HR 75 Temp 36.9
  • General: Alert and oriented.
  • HEENT: PERRLA, EOMI. No oral lesions
  • Neck: Supple, no LAD.
  • Lungs are clear to auscultation.
  • CV: RRR, no MGR.
  • Abd: soft, NT, ND. No VCM.
  • Neurologic: R homonymous hemianopsia, normal sensory, 5/5 strength and normal sensory. Up-going toes on L foot. No clonus. 2+ LE reflexes.

Laboratory Examination:

  • WBC 8.95
    • Diff: Neu 71/ Ly 16/ Mo 8/ Eo 4
  • H/H 12 gms/36%
  • PTL 123K
  • BMP wnl
  • CXR wnl
  • HIV neg

 

Imaging: MRI- March 2016

(MRI-1)

Hospital course:

  • Left parietal craniotomy and partial resection of abscess

“The abscess was gray in color and chalky in consistency. It was removed by establishing margins.”

 

Pathology: Brain Biopsy (Histology 1, 2, 3, 4)

Question: What is your diagnosis?

Microbiology:

  • GS: fungal elements 2+
  • Culture:
    • Abundant Cladophialophora bantiana
      • Amphotericin B = 0.5
      • Posaconazole = 0.125
      • Voriconazole = 1

(MICRO1)

Diagnosis: Cerebral Phaeohyphomycosis; Species: Cladophialophora bantiana

Clinical Course:

Medical management:

  • Ampho B, voriconazole, decadron, phenytoin started after brain biopsy.
  • Improved slowly over 2 weeks, then transferred to rehab facility

Discussion:

Phaeohyphomycosis

  • Dematiaceous fungi (melanin-like pigments)
    • Phaeo is Greek for “dark”.
  • Variety of infections in humans
    • Subcutaneous, deep soft tissue
    • Invasive
      • Brain abscess

Nomenclature:

  • Cerebral phaeohyphomycosis:
    • Most common:
      • Cladosporium trichoides
      • Xylohypha bantiana
      • Cladosporium bantianum
      • Cladophialophora bantiana
    • Other causative fungi:
      • Wangiella dermatitidis (Exophiala dermatitidis)
      • Dactylaria gallopava (Ochroconis gallopava)
      • Fonsecaea pedrosoi,
      • Bipolaris spicifera (Drechslera spicifera), Rhinocladiella mackenziei (Ramichloridium mackenziei and Ramichloridium obovoideum) and Aureobasidium species.

Pathogenesis of CNS Disease:

  • Extension from the adjacent paranasal sinuses
    • Inhalation and proliferation of spores
  • Directly from penetrating trauma to the head
  • Hematogenous dissemination
    • Localized skin lesions
    • Injection drug use
    • Heart-lung transplant patient with pneumonitis

Epidemiology/Clinical Features:

  • Half of the cases had no apparent immunossupression (Clin Infect Dis. 2004;38(2):206)
  • Cases present with focal neurologic deficits and/or generalized seizures.
    • Fever and headache are uncommon.
    • Symptomatic sinusitis or localized infection due to dematiaceous fungi at another site is very rare.
    • Meningeal involvement is unusual.

Diagnosis and Treatment:

  • Microscopic examination
    • Branching, brown septate hyphae on H&E or KOH
    • Rarely, the hyphae do not have pigment
      • Special stains for melanin (Fontana-Masson stain)
      • Grow relatively quickly from clinical specimens.
      • Identification is based on morphology of cultures
        • Reference laboratories
      • Surgical resection + antifungals
        • Susceptibly cut offs are not standardized
        • Voriconazole, posaconazole, amphotericin B

Outcomes:

In March 2017, worsening CNS symptoms while taking voriconazole. Pt. was switched to posaconazole 300 mg/d

 

(Brain MRI 2)

Despite posaconazole therapy, patient developed progressive symptoms. Repeat biopsy was performed due to progressive symptoms and for decompression, debulking of the lesion.

(Brain MRI 3)

10/8/2017 Cladophialophora bantana
Drug FDIL
5-Flurocytosine 0.25
Amphotericin-B 1
Itraconazole </= 0.03
Posaconazole <= 0.03
Voriconazole 0.125

Cladophilalophora bantana

  • Terbinafine 0.03 ug/ml
  • Isavuconazole 0.125 ug/ml

Ultimately patient switched to isavuconazole, flucytosine, and terbinafine. Symptoms progressed; patient died February 2018.

 

(Brain MRI 4)

References:

Revankar SG. Cladophialophora bantiana brain abscess in an immunocompetent patient. The Canadian Journal of Infectious Diseases & Medical Microbiology. 2011;22(4):149-150.

M.E. Brandt & D.W. Warnock (2013) Epidemiology, Clinical Manifestations, and Therapy of Infections Caused by Dematiaceous Fungi, Journal of Chemotherapy,15:sup2, 36-47, DOI: 10.1179/joc.2003.15.Supplement-2.36

Sutton DA, Slifkin M, Yakulis R, Rinaldi MG. U.S. Case Report of Cerebral Phaeohyphomycosis Caused by Ramichloridium obovoideum (R. mackenziei): Criteria for Identification, Therapy, and Review of Other Known Dematiaceous Neurotropic Taxa. Journal of Clinical Microbiology. 1998;36(3):708-715.