Title

Brain Abscess as a Manifestation of Hereditary Hemorrhagic Telangiectasia in a Pediatric Patient: A Case Report

Publication/Presentation Date

Winter 2015

Abstract

Hereditary Hemorrhagic Telangiectasia (HHT)

is a disease defined by abnormal endothelial cell

development thatmanifests as cutaneous telangiectasias,

recurrent epistaxis, and visceral organ

arteriovenous malformations. This report’s objective

is to exhibit a unique presentation of an

uncommon disease within the pediatric population.

It also provides excellent educational value

through prioritizing the investigation of alternative

diagnoses in a pediatric patient who develops

a brain abscess without any known risk factors.

Herein we report the case of a previously

healthy 17-year-old femalewho developed sudden

aphasia and a newonset tonic-clonic seizure

after 3 days of headache and shortness of breath.

She had a past medical history of migraines and

recurrent epistaxis. Imaging confirmed a ringenhancing

lesion in her frontal lobe, which suggested

a brain abscess. She was treated with intravenous

antibiotics and steroids. Her neurological

symptoms subsided and she was discharged

home. Continuedwork-up revealed numerous

arteriovenous malformations, which

likely contributed to her brain abscess, and she

was diagnosed with HHT. HHT should be suspected

in pediatric patients who develop brain

abscesswithout any other risk factors.Additionally,

new onset neurological symptoms in pediatric

patients should be investigated promptly

with head imaging. Timely identification and

initiation of therapy is crucial due to the high

morbidity and mortality associated with brain

abscess, especially in HHT patients.

A 17-year-old female was transported to the

emergency department after suffering from a

sudden episode of inability to speak followed by

a single seizure episode at school. While in her

classroom, she reported a difficulty “finding

words” and stood up in panic fromher desk. She

approached the teacher to ask permission to

leave the room. Unable to speak, she began to

write on a sheet of paper, but her writing soon

became incoherent to both the teacher and to

herself.Her teacher sent her to the nurse’s office,

where she suffered a new-onset generalized tonic-

clonic seizure and the emergency medical

Brain Abscess as a Manifestation of Hereditary

Hemorrhagic Telangiectasia in a Pediatric Patient

¹University of South Florida College of Medicine, Tampa, FL

²Children’s Hospital at Lehigh Valley Health Network, Allentown, PA

Jose M. Soto, BS¹; Tibisay Villalobos, MD²

Corresponding Author: Jose M. Soto, BS, University of South

Florida College of Medicine, 12901 Bruce B Downs Blvd,

Tampa, FL 33612.

Email: Jose.Soto@lvhn.org

The authors claim no conflicts of interest or disclosures.

AMSRJ 2015; 2(1):48-53

http://dx.doi.org/10.15422/amsrj.2015.05.005

ABSTRACT

CASE PRESENTATION

AMSRJ 2015 Volume 2, Number 1 49

service (EMS) was called. This seizure lasted a

few minutes and resolved by the time the EMS

arrived. During the seizure, she also suffered an

episode of epistaxis. She was able to communicate

on arrival to the ED, although with some

difficulty, and stated that she had a 3-day history

of headaches and shortness of breath. She also

reported a history of headaches since the age of

twelve. She stated her headaches usually begin

with an aura of “shimmering prisms and cones of

lights.” The pain is typically unilateral and acetaminophen

provides some relief. These

headacheswere sometimes associatedwith nausea

and mild photophobia. They typically resolvedwith

sleep.Over the last three days, however,

the headaches had worsened, and ibuprofen

became ineffective. She denied any recent

head trauma.

Her vital signs included a blood pressure of

120/73 mmHg, heart rate of 117 beats/minute,

respiratory rate of 16 breaths/minute, temperature

of 99.6° Fahrenheit.On exam, she appeared

anxious and in mild distress. Her cranial nerves

II-XII were grossly intact, and her pupils were

equally round and reactive to light. Dried blood

was found in both of her nostrils; there was no

active bleeding. There were no meningeal signs

during her neck exam. Her cardiovascular, pulmonary,

and abdominal exams were all within

normal limits. Her neurological exam was also

grossly normal with a Glasgow Coma Scale

score of 15, but she continued having difficulty

“finding words.” A complete blood count with

differential was drawn: hemoglobin was 14.8 g/

dL, hematocrit was 45.7%, white blood cells

were 14.8 cells/mcL (71% neutrophils, 18%

lymphocytes, 6% monocytes, 5% eosinophils),

and platelets were 245,000/mcL. A computed

tomography (CT) scan of her head without contrast

(Figure 1) showed an area of abnormally

low density in the left frontal lobe that was suggestive

of vasogenic edema as the grey-white

matter differentiation was maintained and the

edema primarily involved the white matter. No

evidence of intracranial hemorrhagewas found.

While air or maturing hematomas may also

cause lowdensity on CT scans, thesewere ruled

out due to the lack of a history of head trauma.

Given the history of rapid onset neurologic

symptoms and the elevated white blood cell

count, as well as imaging that suggested an area

of edemawithout obvious intracranial bleeding,

a brain abscess was suspected. Therefore, she

was admitted to the pediatric intensive care unit

and started on empiric intravenous antibiotic

therapy with ceftriaxone, metronidazole, and

vancomycin as well as levetiracetamfor seizure

prophylaxis.

Amagnetic resonance imaging (MRI) scanwith

and without contrast (Figures 2 and 3) confirmed

an area of vasogenic edema surrounding

a ring-enhancing lesion in the left frontal lobe.

Themidline shift seen on the earlierCTscanwas

also evident on theseMRI images.Although the

differential diagnosis for ring-enhancing lesions

includes glioblastoma multiforme, brain metastasis,

infarct, contusion, and neurocysticerosis,

Figure 1. Initial CT scan taken at presentation to the hospital showing an

area suggestive of vasogenic edema in the left frontal lobe (arrow) and

mild midline shift.

BRIEF REPORTS

BRAIN ABSCESS

AMSRJ 50 2015 Volume 2, Number 1

thesewere ruled out due to history and age of the

patient. A follow up magnetic resonance angiogram

(MRA) of the head (Figure 4) demonstrated

mass effect of the lesion on the medial

cerebral artery branches on the left side, but

there was no evidence of aneurysms, arteriovenous

malformations, or major vessel occlusion.

These findingswere also consistentwith a brain

abscess.

The patient continued to have headaches and six

days after admission, she became increasingly

confused and developed right upper extremity

weakness in addition to left facial drooping. A

Figure 2. T1-weighted coronalMRIwith contrast demonstrating

a left sided ring-enhancing lesion (arrow) surrounded by

vasogenic edema and also a midline shift.

Figure 3. T2-weighted transverse MRI with contrast that

highlights the area of vasogenic edema (arrow) and also further

demonstrates the midline shift seen in previous images.

Figure 4. Coronal MRA of the head showing mass effect of the

lesion on the branches of the left middle cerebral artery (arrow).

Figure 5. Repeat coronal MRI with the blue arrow pointing to

the original lesion and the red arrow pointing to the new lesion.

BRAIN ABSCESS

BRIEF REPORTS

AMSRJ 2015 Volume 2, Number 1 51

repeatMRI (Figure 5) demonstrated a new area

of enhancement and diffusion restriction inferolaterally

to the original lesion as well as increased

vasogenic edema. The following day,

she underwent a CT-guided biopsy of the original

lesion with cultures. The tissue culture grew

Micrococcus luteus/lylae. After the procedure,

IV dexamethasone was added to her antibiotics

to reduce brain tissue swelling. She continued

this treatment regime for two additional weeks

as her neurological symptoms began to subside.

The patient was then discharged home for the

remaining five weeks of IV antibiotics. During

this time frame, her facial palsy resolved and she

regained strength in her right upper extremity.

Her headaches also improved.

During her admission, itwas discovered that she

had a past medical history significant for migraine

headaches since the age of twelve and

recurrent episodes of epistaxis. It was also revealed

that her mother had hereditary hemorrhagic

telangiectasia (HHT). There was a high

level of suspicion forHHT due to family history

and recent events, so studies of the chest to

search for pulmonary arteriovenous malformations

(PAVMs) aswell as a transcranialDoppler

studywere performed.Numerous PAVMswere

found in the patient’s left upper lobe aswell as in

her right middle lobe (Figure 6). The transcranial

Doppler study with agitated saline also

demonstrated an arteriovenous shunt in themiddle

cerebral artery. The patient met 3 of the 4

diagnostic Curacao criteria for HHT¹ (Table 1)

and itwas concluded that her undiagnosedHHT

had predisposed her to this brain abscess.

The patient completed her IV antibiotic course

and followupMRI studies demonstrated that the

brain abscess had resolved. The majority of the

PAVMs seen on arteriogram have since been

obliterated.

Figure 6. Pulmonary arteriogram demonstrating a dominant

arteriovenous malformation in the inferior aspect of the upper

lobe (arrow) along with numerous smaller malformations.

Curacao Criteria for HHT

1. Recurrent Epistaxis

2. Telangiectasias

3. Visceral Manifestations

4. Affected 1st degree relative

3-4 criteria met: definitive HHT

2 criteria met: suspected HHT

1 criteria met: unlikely to be HHT

!

Table 1. Curacao Criteria for the diagnosis of HHT

BRIEF REPORTS

BRAIN ABSCESS

AMSRJ 52 2015 Volume 2, Number 1

Epidemiology and Pathophysiology

HHT is an autosomal dominant inherited disorder

that affects 1 in 10,000 people with no preference

for either sex.² It is most common in the

Caucasian population and is 97%penetrant.²Almost

30%of patients do not have a family history

of the disease.² The genes affected by this

disorder both code for Transforming Growth

Factor-β receptors: ENG on chromosome

9q34.1 andACVRL-1 (activinAreceptor type IIlike

1) on chromosome 12q13.13.³ These genes

are crucial in the development of vascular endothelial

cells during angiogenesis and either

mutation will manifest in the same manner.

Clinical Manifestations

The syndrome is defined by telangiectasias, or

dilated post-capillary venules, of the skin, mucousmembranes

and internal organs.Cutaneous

telangiectasias typically occur on the face,

hands, and lips. When telangiectasias occur in

the nasal mucosa, they may cause spontaneous

recurrent epistaxis which is the first symptom

formore than 90%of patients.4,5More than 50%

of patients with HHT will manifest with this

symptom before the age of twenty.¹ The bleeding

can be so severe that 10-30%of patientswill

require blood transfusions over the course of

their lifetime. In roughly 40% of patients, the

gastrointestinal system is involved and can also

be the source of significant blood loss.3,6

The diagnostic Curacao criteria¹ (Table 1) require

three of the following four findings: recurrent

epistaxis, cutaneous telangiectasias, visceral

organ involvement (i.e., arteriovenous malformations

thatmay bleed) and an affected firstdegree

relative. Few patients, however, manifest

enough signs and symptoms within the first

three decades of life to meet the criteria, and

therefore, it is recommended that asymptomatic

children of HHT patients be genetically

screened for the disease.¹

Neurological manifestations

In a healthy patient, the lung capillary beds function

to filter the blood before it is pumped to the

brain, but pulmonary vascular malformations

(PAVMs) found in HHT patients compromise

this protection system.7 Large PAVMs can result

in paradoxical micro-emboli entering cerebral

circulation and subsequent ischemic brain

injury (i.e., stroke). Abscess formation can be

caused by direct seeding of pathogenic bacteria

into the brain parenchyma or secondarily after

an anoxic brain injury creates an environment

suitable for bacteria growth. About 1% of HHT

patients can develop cerebral abscess or septic

meningitis, which is significantly higher than

the general population.7 For the reasons noted

above, PAVMs are a significant source of morbidity

and mortality in HHT patients7 and they

can also lead to high-output cardiac failure in

later life.²

Brain abscesses are usually of poly-microbial

origin; only the slow growing members of the

Micrococcus genuswere isolated in this case because

empiric antimicrobial therapy had already

begun by the time of the biopsy.8, 9 It is important

to note that brain abscesses do not commonly

present with the typical cardinal signs of infection:

fever, leukocytosis, or positive blood cultures.

10

The neurological symptoms of brain abscesses

are due in large part to the mass effect of the

lesion on surrounding structures.Consequently,

the symptoms can include a wide spectrum of

neurologic symptoms such as aphasia, seizures,

and headaches depending on the location of the

lesion. HHT patients can also develop cerebral

vascular malformations (CAVMs), which can

manifest as various neurological symptoms.

Approximately one-quarter of HHT patients

DISCUSSION

BRAIN ABSCESS

BRIEF REPORTS

AMSRJ 2015 Volume 2, Number 1 53

will have a CAVM in their lifetime and there is

a 0.5%bleeding risk per year.¹ The treatment of

choice for arteriovenousmalformations remains

embolization of the feeding blood vessels.11

•The differential diagnosis for a pediatric

patient without any known risk factors who

develops a brain abscess should include

HHT.

•Brain abscesses are typically poly-microbial

in nature and do not present with the

usual signs of infection, such as fever, leukocytosis,

or positive blood cultures.

1. Faughnan ME, Palda VA, Garcia-Tsao G, et al. International

guidelines for the diagnosis and management of hereditary

haemorrhagic telangiectasia. Journal of medical genetics. 2011;48

(2):73-87.

2. Daroff R, ed. Bradley's Neurology in Clinical Practice. 6th ed.

Philadelphia, PA: W.B. Saunders; 2012.

3.Mark Feldman LF, Lawrence Brandt, eds. Sleisenger and Fordtran's

gastrointestinal and liver disease: pathophysiology, diagnosis,

management. Philadelphia, PA: Saunders Elsevier; 2010.

4. Sadick H, Sadick M, Gotte K, et al. Hereditary hemorrhagic

telangiectasia: an update on clinical manifestations and diagnostic

measures. Wiener klinische Wochenschrift. 2006;118(3-4):72-80.

5. Murtagh B, Fulgham JR. 23-year-old woman with increasing

frequency ofmigraine headaches.MayoClinic proceedings. 2002;77

(10):1105-8.

6.ChenCW, Jao SW,WuCC, et al.Red spots on the hands and red blood

in the stools. Lancet. 2008;371(9619):1190.

7. Moradi M, Adeli M. Brain abscess as the first manifestation of

pulmonary arteriovenous malformation: A case report. Advanced

biomedical research. 2014;3:28.

8. Frazier JL, Ahn ES, Jallo GI. Management of brain abscesses in

children. Neurosurgical focus. 2008;24(6):E8.

9.SelladuraiBM,SivakumaranS,AiyarS, et al. Intracranial suppuration

caused by Micrococcus luteus. British journal of neurosurgery.

1993;7(2):205-7.

10. Dong SL, Reynolds SF, Steiner IP. Brain abscess in patients with

hereditary hemorrhagic telangiectasia: case report and literature

review. The Journal of emergency medicine. 2001;20(3):247-51.

11. Meek ME, Meek JC, Beheshti MV. Management of pulmonary

arteriovenous malformations. Seminars in interventional radiology.

2011;28(1):24-31.

REFERENCES

LEARNING POINTS

BRIEF REPORTS

BRAIN ABSCESS

Volume

2

Issue

1

First Page

48

Last Page

53

Disciplines

Medicine and Health Sciences | Pediatrics

Department(s)

Department of Pediatrics, Department of Pediatrics Faculty, Department of Pediatrics Residents

Document Type

Article

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