ISSN 1941-5923
© Am J Case Rep, 2017; 18: 33-37
DOI: 10.12659/AJCR.900425
Received:
Accepted:
Published:

Aspergillus Terreus Brain Abscess Complicated
by Tension Pneumocephalus in a Patient with
Angiosarcoma

2016.07.05
2016.10.14
2017.01.10

Authors’ Contribution:
Study Design A
Data Collection B
Statistical Analysis C
Data Interpretation D
Manuscript Preparation E
Literature Search F
Funds Collection G

ABEF 1
ABCDEFG 2
AD 1
ABCDEFG 2

Thejal Srikumar
Smitha Pabbathi
Jorge Fernandez
Sowmya Nanjappa

1 Department of Internal Medicine, University of South Florida Morsani College of
Medicine, Tampa, FL, U.S.A.
2 Department of Internal Hospital Medicine, Moffitt Cancer Center, Tampa, FL,
U.S.A.

Corresponding Author:
Conflict of interest:

Sowmya Nanjappa, e-mail: sowmya.nanjappa@moffitt.org
None declared

Patient:
Final Diagnosis:
Symptoms:
Medication:
Clinical Procedure:
Specialty:

Male, 67
Aspergillus terreus brain abscess complicated by tension pneumocephalus
Blurred vision • hemiparesis
—
—
Infectious Diseases

Objective:
Background:

Case Report:

Conclusions:

MeSH Keywords:
Full-text PDF:

Rare co-existance of disease or pathology
Aspergillus terreus is an evolving opportunistic pathogen, and patients with A. terreus often have poor outcomes due to its intrinsic resistance to several systemic antifungal agents. Here we present a unique case of
intracranial abscesses of A. terreus in a patient with recurrent angiosarcoma, complicated by development of
tension pneumocephalus.
A 67-year old gentleman with history of scalp angiosarcoma with wide excision two years prior presented to
the hospital for left arm clumsiness, altered mental status, and low-grade fever. Staphylococcus aureus and
Proteus mirabilis bacteremia was detected, and Computed Tomography (CT) of the head showed right frontal
lobe abscesses. He was started on steroids, intravenous vancomycin and cefepime, and was eventually discharged. He presented to the hospital again due to persistent and worsening symptoms. MRI showed progression of the brain lesions, and surgical biopsy and culture of lesions revealed A. terreus and gram-positive cocci. He was started on trimethroprim/sulfamethoxazole and voriconazole and symptoms improved. On post-op
day four, he acutely decompensated with total loss of left arm strength; MRI demonstrated tension pneumocephalus. Conservative management was undertaken with continuous supplemental oxygen. Serial x-ray imaging over the next week demonstrated resolution of the pneumocephalus, and the patient was able to regain
all proximal lower and upper extremity strength.
Never before has a case of A. terreus been associated with angiosarcoma or tension pneumocephalus in the
literature. Proper identification and prompt diagnosis of species is crucial in the immunocompromised patient.
Tension pneumocephalus should be included in the differential diagnosis of nontraumatic hemiparesis for
emergent evaluation and management.
Aspergillosis • Aspergillus • Hemangiosarcoma • Neuroaspergillosis • Pneumocephalus
http://www.amjcaserep.com/abstract/index/idArt/900425

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33

Srikumar T. et al.:
Cerebral aspergillosis and pneumocephalus in angiosarcoma patient
© Am J Case Rep, 2017; 18: 33-37

Background
Aspergillus terreus is a saprophyte that has mainly been associated with immunocompromised patients, and has been
reported up to 15–23% percent of hematologic malignancy
patients with invasive aspergillosis (IA) [1]. Although not as
prevalent as other etiologies of IA, with A. fumigatus being the
most common, patients with A. terreus often have worse outcomes due to intrinsic resistance to amphotericin B [1]. Here
we present an unusual case of a patient with intracranial A.
terreus abscesses, which was further complicated by tension
pneumocephalus after surgical evacuation.

Case Report
A 67-year old Caucasian man with a history of hypertension,
dyslipidemia, and myocardial infarction with stent placement,
was diagnosed with angiosarcoma of the scalp in 2013. At the
time of diagnosis, the patient had a 30-pack-year smoking history, and no other significant alcohol or substance abuse history. He underwent wide excision of scalp in October 2013
with revision for positive margins. Attempted closure of scalp
wound via flap had failed twice, and patient had an epithelialized skull. Post-operatively, he underwent radiation therapy with 60 Gy over 6 weeks over 30 fractions to the surgical
bed and margin using intensity modulated radiation therapy
(IMRT) with image guidance, followed by chemotherapy with
6 cycles of single agent paclitaxel, 80 mg/m2 for four weeks
per cycle. However re-staging scans and biopsy in February
2015 showed metastatic disease with lymphadenopathy in the

posterior triangle bilaterally, and he was treated with doxorubicin 75 mg/m2 single agent for 5 cycles total. Re-staging
imaging showed further progression, and a concurrent chemotherapy with radiation therapy approach was used, with
dose-reduced paclitaxel for 3 cycles at 60 mg/m2, and radiation therapy with 66 Gy in 33 fractions using IMRT.
In September 2015, he presented with left arm clumsiness, altered mental status with mild confusion but otherwise no neurological dysfunction, and low-grade fever. Summary of clinical course is shown in Figure 1. Blood cultures were positive
for methicillin-sensitive Staphylococcus aureus and Proteus mirabilis bacteremia. A Computed Tomography (CT) of the head
revealed 2 right frontal lobe lesions with surrounding vasogenic edema. Brain MRI showed ring-enhancing intra-axial abscesses on the right side without evidence of recurrent scalp
tumor. The source of the bacteremia was thought to be secondary to his large scalp wound or a possible brain abscess.
He was empirically treated with dexamethasone 2 mg once
daily by mouth, intravenous vancomycin 1.75 mg every 12
hours, intravenous cefepime 2 mg every 8 hours, and metronidazole 500 mg three times daily by mouth, each for fourweek duration.
One month later, he presented with acute left-sided weakness
in upper and lower extremity, left-sided facial droop, symptoms of high order executive dysfunction such as word-finding difficulties, persistent low-grade fever, blurry vision, and
vomiting. Vitals on admission included temperature of 36.6°C,
pulse of 79 beats per minute, respiratory rate of 20 breaths
per minute, and blood pressure of 142/89 mmHg. Physical

• Patient presented with symptoms of altered mental status and left hand clumsiness
• CT of head revelaed abscesses in right temporal lobes, and blood cultures revelaed
bacteremia with Staphylococcus aureus and Proteus mirabilis
Presentation at • Patient was started empirically on steroids and vancomycin, cefepime,
outside hospital and metronidazole, and discharged

Figure 1. Summary of clinical course.
Description of sequence of events
from hospital stay.

• Patient started expereincing low-grade fevers, wosrening left hemibody weakness,
and confusion; presented to our institution
• MRI of brain showed evidence of interval growth of intracerebral abscess
Presentation at • Patient was sent for neurosurgical biopsy of lesion
our institution

Neurosurgical
biopsy

Recovery

34

• Biopsy of the abscesses on hospital day 4 revealed growth of Aspergillus terreus and
gram positive cocci in clusters
• Voriconazole and thrimethroprim-sulfamethoxazole were initiated
• Patient acutely decompensated on post-operative day four
• MRI brain showed development of Tension Pneumocepalus
• Conservative measures were undertaken with oxygen delivery via nasal cannula and
placement of vaseline gauze over wound
• Serial x-rays showed resolution of tension pneumocephalus over 1 week
• Patient worked with physical therapy and regained proximal muscle strength
• Patient was able to be discharged on hospital day 24 with oral voriconazole and minocycline

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Srikumar T. et al.:
Cerebral aspergillosis and pneumocephalus in angiosarcoma patient
© Am J Case Rep, 2017; 18: 33-37

B

C

D

E

F

Postoperative MRI

Preoperative MRI

A

T1 weighted

T2 weighted

T2 FLAIR

Figure 2. Pre- and post-operative T2-weighted MRI brain. (A–C) Pre-operative MRI from hospital day 2 which demonstrates abscess
in the temporal lobe area surrounded by significant vasogenic edema; T1-weighted (A), T2-weighted (B), and T2 FLAIR
(C) images included. (D–F) Post-operative MRI from hospital day 9 showing expansion of space from evacuated abscess,
demonstrating tension Pneumocephalus; T1-weighted (D), T2-weighted (E), and T2 FLAIR (F) images included.

examination revealed 4/5 strength of left upper and lower
extremities, bradykinesia, diminished alternating movements
in left hand, and word-finding difficulties. The remainder of
the neurological exam was intact. Laboratory values revealed
leukopenia with WBC 3.41 k/uL, normocytic anemia with hemoglobin 11.0 g/dL, hematocrit of 32.9, and mean cell volume 85.0 FL. Other laboratory values, including platelet count,
electrolytes, creatinine, and liver enzymes, were without significant abnormality (data not included). Repeat MRI showed
an interval progression of the brain lesions, with increase in
size of right frontal abscess and associated vasogenic edema
(Figure 2A). Therefore, he was empirically started intravenous
vancomycin 1.75 mg every 12 hours, intravenous cefepime 2
mg every 8 hours, and intravenous dexamethasone 4 mg twice
daily. Subsequent blood cultures were negative.
He underwent a stereotactic right frontal craniectomy, biopsy, and drainage of the abscesses. The biopsy of the abscess
wall was sent for both permanent fixation and culture. Four
to five mL of yellow purulent material was drained from another frontal abscess, and cultures were sent. Biopsies of the

bone, dura mater, and arachnoid mater did not reveal any evidence of recurrent malignancy. Deep wound cultures grew A.
terreus and gram-positive cocci in clusters and his antibiotic therapy was changed to trimethroprim/sulfamethoxazole
320–1600 mg twice daily and Voriconazole 200 mg twice daily.
He initially improved clinically, but on post-operative day four,
he acutely decompensated with total loss of left arm strength
and increased left-sided facial droop. Repeat MRI brain demonstrated that the dominant ring-enhancing lesions had been
completely removed, with a large amount of air under tension
in the corticectomy defect, with questionable midline shift.
The diagnosis of tension pneumocephalus was made based
on these radiologic findings (Figure 2B). Conservative management was undertaken with continuous supplemental oxygen via nasal cannula at 4 L/hr, and triple layer of vaseline
gauze was placed over scalp wound to prevent further accumulation of air. Serial x-ray imaging of the head over the next
week demonstrated resolution of the tension pneumocephalus by post-operative day eight (Figure 3). On post-operative day nine, basic metabolic panel revealed that patient had

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35

Srikumar T. et al.:
Cerebral aspergillosis and pneumocephalus in angiosarcoma patient
© Am J Case Rep, 2017; 18: 33-37

A

B

Figure 3. Serial Post-operative X-ray Imaging. (A) X-ray image from post-operative day 6 revealing intracranial air from tension
pneumocephalus and right frontal-parietal craniotomy site with dressing. (B) X-ray image from post-operative day 10
demonstrating resolution of tension pneumocephalus.

hyperkalemia with potassium of 5.1 mEq/L. Patient was given
kayexalate 30 mg, and trimethroprim-sulfamethoxazole was
discontinued as it was thought to be likely causative agent.
Minocycline 100 mg capsule twice daily was initiated for antibiotic coverage.
With physical and occupational therapy, the patient was able
to regain proximal muscle strength, though he continued to
suffer from loss of fine motor skills and wrist strength. He
was able to stand with assistance and ambulate with a rolling walker, and was eventually discharged on hospital day
24 to a sub-acute rehabilitation facility to continue physical
and occupational therapy. Dexamethasone 4 mg was tapered
over a 2-week course after discharge, and he was continued
on oral voriconazole 250 mg twice daily by mouth and minocycline 100 mg twice daily by mouth to complete a six-month
course with scheduled follow up brain imaging. Our patient is
currently followed as an outpatient in neuro-oncology, infectious disease, and sarcoma clinic.

Discussion
Aspergillus terreus is a very unusual cause of central nervous
system (CNS) invasion, though the highest prevalence has
been found in patients with hematologic malignancy. Few reports have been made directly linking A. terreus with CNS infections. A. terreus was recently reported as a cause of meningitis
in an immunocompetent adolescent patient [2]. Furthermore,
another recent case report detailed A. terreus in a brain abscess in a patient with glioblastoma multiforme; the authors
concluded that in patients with brain tumors who receive steroids for management of cerebral edema, as our patient had,
they maybe more susceptible to infection with this species [3].

36

A patient with Acute Myelogenous Leukemia (AML) was found
to have A. terreus growing in bilateral brain abscesses, thought
to have arisen hematogenously from a pulmonary infection after induction chemotherapy [4]. Our case is very unique in that
A. terreus has never been associated with angiosarcoma of the
scalp as per our review of the literature [5]. Of course, our patient had a much higher chance of intracranial infection considering that full scalp flap closure was never achieved, thus
greatly increasing the risk of contamination.
CNS aspergillosis has shown to have poor response to amphotericin B treatment, but this lack of response is further complicated in patients with A. terreus, as it is inherently resistant [5–7]. A recent retrospective study reviewing 20 years of
hematologic malignancy patients at one institution showed
that patients with A. terreus had a significantly higher mortality rate in comparison with other Aspergillus species, with 51%
versus 30% [1]. Azole therapies, such as voriconazole used in
this patient, have shown promise in patients with A. terreus.
One study showed that in retrospective analysis of 83 cases,
patients who received voriconazole had higher survival rates
in comparison to those who received amphotericin B at 12
weeks of therapy (64.7% vs. 26.2%) [8].
Another unique aspect of this case is that never has A. terreus been associated with tension pneumocephalus in the literature. Pneumocephalus is characterized by the accumulation
of intracranial air, and it is considered to be under ‘tension’
when air accumulates but is unable to escape the cranial
vault. In our patient, the tension pneumocephalus most likely developed secondary to the neurosurgical biopsy; however,
cases have been reported of tension pneumocephalus being
caused by fungal sinusitis as well [9,10]. Of note, in our review
of the literature one case recently described the development

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Srikumar T. et al.:
Cerebral aspergillosis and pneumocephalus in angiosarcoma patient
© Am J Case Rep, 2017; 18: 33-37

of tension pneumocephalus in a patient with scalp angiosarcoma as well [11].
Tension pneumocephalus can cause rapid clinical deterioration
due to increase in intracranial pressure due to mass effect, and
can lead to brain stem herniation, coma, and death. For patients with tension pneumocephalus, immediate neurosurgical intervention is most likely required to alleviate the elevated intracranial pressure if midline shift is present. Evacuation
of accumulated air can be accomplished by drilling a burr hole,
using needle and syringe aspiration, and then closing the dural
defect [12]. Conservative management involves placing the patient in Fowler position at 30 degrees, avoiding any behaviors
that would increase intracranial pressure like valsalva, coughing, or sneezing, and either using hyperbaric oxygenation or
continuous normobaric oxygenation [12]. Increasing the oxygenation is thought to enhance reabsorption of nitrogen into
the blood, which in turn decreases the volume of the accumulated air. Thus, the fact that our patient had complete resolution of his tension pneumocephalus via conservative management alone is yet another reportable factor of this case.

Conclusions
Here we present an unusual case of Aspergillus terreus brain
abscess in an angiosarcoma patient, further complicated by
tension pneumocephalus after evacuation. Never before has
A. terreus been associated with angiosarcoma or with tension
pneumocephalus. We believe this case highlights the importance of proper identification of infectious species in immunocompromised patients with brain abscesses in order to
initiate appropriate antibiotic therapy, especially in patients
with scalp defects, due to the open and contaminated nature
of the wound. Furthermore, it is important to note that due
to the fact that complete dural closure after biopsy and aspiration of brain abscesses cannot be achieved, close attention
should be paid to evaluate for symptoms of pneumocephalus.
Conflicts of interest
None.

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