Accepted Manuscript

Forgotten? Not yet- Cardiogenic brain abscess in children – a case series based
review

Suhas Udayakumaran, Chiazor U. Onyia, R. Krishnakumar

PII: S1878-8750(17)31244-5
DOI: 10.1016/j.wneu.2017.07.144
Reference: WNEU 6206

To appear in: World Neurosurgery

Received Date: 25 June 2017

Revised Date: 21 July 2017
Accepted Date: 24 July 2017

Please cite this article as: Udayakumaran S, Onyia CU, Krishnakumar R, Forgotten? Not yet-
Cardiogenic brain abscess in children – a case series based review, World Neurosurgery (2017), doi:
10.1016/j.wneu.2017.07.144.

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 ACCEPTED MANUSCRIPT

Forgotten? Not yet- Cardiogenic brain abscess in children – a case series based review

Suhas Udayakumaran 1, Chiazor U. Onyia 2 , R. Krishnakumar3

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1

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Division of Paediatric Neurosurgery, Department of Neurosurgery, Amrita Institute of Medical
Sciences and Research Centre, Kochi, Kerala, India.

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Neurosurgery Division, Department of Surgery, Obafemi Awolowo University Teaching
Hospitals Complex, Ile-Ife, Nigeria.

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Department of Pediatric cardiology
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Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala, India.
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*Corresponding author: Suhas Udayakumaran

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Mailing address: Division of Paediatric Neurosurgery, Department of Neurosurgery, Amrita

Institute of Medical Sciences and Research Centre, Kochi 682 041, Kerala, India.
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E-mail address: dr.suhas@gmail.com

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Telephone: +91 – 9745309990

Fax: 0484 – 4006035

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Key words: Cerebral abscess; Congenital Cyanotic heart disease; Cardiogenic cerebral abscess;
Cerebral infection; Cerebral suppuration

Running head: Cardiogenic brain abscess in children

Funding/material support: None

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Note: No portion of this work has been published elsewhere.

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Abstract

Introduction:

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Brain abscess is a significant cause of morbidity in patients with uncorrected or partially
palliated congenital cyanotic heart disease (CCHD). Unfortunately, in the developing world, the

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majority of the patients with CCHD remain either uncorrected or partially palliated. Furthermore,
a risk of this feared complication also exists even among those undergoing staged corrective

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operations in the interval in between operations. There have been no recent articles in the
literature on surgical outcomes of management of cardiogenic brain abscess in children.

Objective:
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To describe the clinical and demographic profile of patients with cardiogenic cerebral abscess
and to highlight the fact that uncorrected or palliated CCHD continue to be at risk for brain
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abscess.

Material and methods:

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Retrospective analysis of 26 children (age below 19 years) being managed for CCHD who were
diagnosed with cerebral abscess managed surgically (26/ 39 of cerebral abscess in children), at
AIMS, Kochi, India from December 2000 to January of 2014 was done. Details of variables were
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retrospectively collected included demographics, modes of presentation, diagnosis, location of

abscess, details of the underlying heart disease, management of the cerebral abscess and the
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outcome of the management.

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Results:

Mean age for all 26 patients was 7.19 years, with a wide range of 1.5 years to 19 years. There
were 16 males and 10 females. 10 of the 26 patients (38%) required reaspiration after the initial
surgery. On follow up, all the patients improved symptomatically and were cured for the cerebral
abscess.
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Conclusions: Cardiogenic origin of cerebral abscess is the commonest cause of cerebral abscess
amongst children. Unresolved cyanotic heart disease is a risk for occurrence, persistence and
recurrence of cerebral abscess

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Introduction

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“Fatal cerebrovascular accident or cerebral abscess was once looked upon almost as
welcome release from the miserable existence of a cardiac cripple” – Matson1.

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Four decades back, an occurrence of cerebral abscess in child with congenital cyanotic heart
disease (CCHD) used to be a fatal blow in these severely afflicted children.

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CCHD accounts for 12.8–69.4% of all cases of brain abscesses, with the incidence being higher
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in children2. Besides from chronic ear infection and paranasal sinusitis, CCHD is the most
common cause of brain abscess in reviews involving children2,3. The incidence of brain abscess
in the population with congenital heart disease varies from 5 to 18.7%2. Mortality as a result of
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brain abscess was previously high (30% and 45% in some series9), but has decreased
dramatically over the last few decades. This change has been attributed to the advent of
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computerized tomographic (CT) scan, magnetic resonance imaging (MRI) as well as improved
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medical and surgical therapies2,3,4,5,6,8,10,12. Brain abscess remains a significant cause of morbidity
in patients with uncorrected or partially palliated congenital cyanotic heart disease. Furthermore,
in the developing world, the majority of the patients with CCHD remain either uncorrected or
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partially palliated. A risk of this feared complication also exists even among those undergoing
staged corrective operations in the interval in between operations.
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There have been no recent articles in the literature on surgical outcomes of management
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cardiogenic brain abscess in children. In this case series based review, we aim to describe the
clinical and demographic profile of patients and to assess the surgical outcomes in children with
CCHD presenting with cerebral abscess.
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Materials and Methods

Retrospective analysis of data of 26 patients managed at the Division of Pediatric Neurosurgery

and Department of Pediatric Cardiology, Amrita Institute of Medical Sciences and Research

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Centre, Kochi, Kerala, India between December 2000 and January 2014 was done using an Excel
database. Only patients who underwent surgical intervention for management of abscess were

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included in this series. Information was carefully extracted from the Excel database based on the
age and gender of the patients, location of the abscess within the brain, the cardiac diagnosis in

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each case, presenting symptoms, neuroimaging findings (on MRI or CT), result of culture of the
abscess, improvement of symptoms and outcome. The post-operative clinical and radiological

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details were available for the period of follow-up. The subsequent outcomes were compared at
various intervals from the intervention.
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On diagnosis
1. Imaging, blood culture, Infective profile( WBC counts,C-Rea

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Protien)
2.Empirical broad spectrum antibiotics after blood collection f
culture

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3. Change to culture sensitive antibiotics
4. Time early correction of CCHD

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If blood culture is positive Monitor response

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Change -antibiotics according to 1.Decrease in infective profile (C-reactive

culture protein, procalcitonin, WBC count, all of
which may or may may not be elevated)
2.Clinical status
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Antibiotics for a duration of 6 weeks with

atleast 3 weeks intravenous antibiotics 3.With decrease in size on imaging
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Our imaging protocol are as follow:

• Repeat imaging immediately post aspiration, subsequently once in 2 weeks until

completion of 6 weeks of antibiotics. This is to demonstrate satisfactory response to the
antibiotics. Additional MRI may be indicated-
- if the patient shows unsatisfactory response
-new clinical indications including adverse infective profile viz. raising CRP

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• Our follow up protocol is to do a repeat imaging at 3 weeks of satisfactory completion of
antibiotics and then monthly, at least for 3 months and until the abscess is insignificant in

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size or remains stable and infective profile is insignificant.

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Results

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There were about 26 children of cerebral abscess in children with known CCHD in a total cohort
of 39 children of cerebral abscess (below age of 15). Mean age of patients (n= 26) was 7.19
years, with a wide range of 1.5 years to 19 years. There were 16 males and 10 females. The
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average number of days of admission was 35 days. 56% of the patients had their abscess
collection located in the left cerebral hemisphere, while the remaining 44% had their abscess
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within the right cerebral hemisphere.

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Figure 1 shows the breakdown of location of the abscess within left cerebral hemisphere, and the
right hemisphere of the brain (with frontal region of the brain being the most common for both
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hemispheres).

Figure 2 is a summary distribution of the various presenting symptoms in all 26 patients, with
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headaches being the most common symptom while seizure was the least occurring symptom in
these children. The infective profile was altered in only 20% (WBC Count, CRP, ESR).
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On neuroimaging with either CT scan or MRI of the brain (in the early part of the series later
MRI was done preferentially), only 8 of the patients had multiple abscess collections, while the
remaining 18 had single solitary abscess cavities.

18/26 (69%) trial of conservative management was considered but had to be abandoned due to
nonresponse or worsening (Rest viz. 8/26 were subjected to surgical intervention as they
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considered not suitable for conservative management as per protocol described in the flow chart
in the materials and methods section). The initial surgical management involved burr hole and
aspiration in 21 (76%) of the patients as the primary procedure, while the remaining 5 (24%) had
craniotomy and excision of the abscess (most in earlier part of the series). 10 of the 26 patients
(38%) required reaspiration after the initial surgery, in comparison with 13 in total cohort of

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cerebral abscess of 39 (Only 7.6% of reaspiration in abscess secondary to the non-cardiac
causes). The interval to reaspiration from the initial surgery ranged from 3 weeks to 11 months.

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There were about 3 other patients who required more than 3 aspirations. All 3 patients underwent
craniotomy and excision. The mean hemoglobin level in the patients with recurrence of abscess

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was 18.6 compared to 17.1gm% in the non- recurrent group. This although not statistically
significant due to the small sample size, the odds ratio of recurrence of abscess if a patient has a

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higher hematocrit was 1.8. Only 2 patients (not included in the series) underwent total
conservative management.
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Streptococci was the commonest organism isolated (in 21 patients i.e. 76%). The culture results
of the remaining 5 were negative. Out of the 10 patients requiring reaspiration, 7 of them still
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grew streptococci on culture.

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Table 1 shows a summary of the cardiac outcome that occurred during the follow-up period after
surgical care. Also, additional remarks are added in the table with regards to prognosis in terms
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of future possibility of cerebral abscess

During the follow-up period, none of the patients required anticonvulsants for long term (by 6th
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month of follow up and afterwards). In addition, no neurological deficit occurred at 6 months

follow up, and no hospital fatality was recorded during admission, except for one unrelated
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mortality in the cohort of 26 patients. This death was due to respiratory infection.
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Discussion

Pathophysiology

To fully appreciate the burden of the problem, a clear understanding of the pathophysiology
regarding brain abscess formation in these children is necessary. First, with the occurrence of
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intracardiac right to left shunt in these patients, bacteria tend to bypass the natural phagocytic
component of the pulmonary circulation and then enter the cerebral circulation unfiltered2,4,10 .
Secondly, decreased arterial oxygenation can result in compensatory polycythemia. This
resultant polycythemia leads to tissue hypoxia and metabolic acidosis2,4,10. In addition, increase
in blood viscosity can also cause a focal area of ischemia within the brain parenchyma that then

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serves as a nidus for infection2,4. Shunted blood containing micro-organisms may be seeded in
such lesions, forming a cerebral abscess. Hematogenous mode of spread is what accounts for the

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multiple number of abscesses commonly seen in these patients4. Some authors however, believe
the pathophysiology to be unclear inspite of the above knowledge5,1.

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Aetiology AN
Tetralogy of Fallot is the commonest CCHD associated with intracranial suppuration2,3,4,9. Other
congenital cardiac problems which have been implicated are transposition of great vessels,
tricuspid atresia, pulmonary stenosis, and double-outlet right ventricle4. Organisms commonly
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isolated in cardiogenic brain abscess include Streptococcus viridans, microaerophilic

Streptococci, anaerobic Streptococci, and occasionally, Haemophilus species8. Before the advent
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of antibiotics, the most common organism isolated from a brain abscess was Staphylococcus
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aureus4. However, the use of penicillin and improved antibiotic therapy, has led to replacement
of Staphylococcus spp. with Streptococcus spp. as the most common organisms and the source
may be the oropharynx2,4.
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Demographic characteristics and symptomatology

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Most of the series reported an predominance of in first decade and children in general5.
Interestingly, a cerebral abscess in less than 2 years has not been reported6. Mean age in our
series was 7.19 years with youngest being 1.5 years.

Amongst our 26 patients in this review, headache and vomiting were the most common symptom
while seizure was the least occurring symptom in these children as in other reports and
reviews3,4,6,7,94. Fever occurred in about 30% in our series and others, means, it is such a poor
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pointer to the diagnosis. The classical triad of headache, fever and focal neurological deficit
occurs in about 15- 30% (15% in our series). Other associated symptoms include hemiparesis,
speech disturbance and changes in mental status, multiple cranial nerve deficits and unsteady
gait3,8.

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Location and Radiologic characteristics

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Location of the abscess in our patient cohort was in the frontal region of both hemispheres of the
brain (Figures 1). This is quite comparable to both frontal and temporal lobes being the

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commonest in a review of 130 children with brain abscess (about 55%) by Tekkok et al3.
Commonly, frontal lobe and parietal lobe abscesses tend to be asymptomatic for a long time,

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until a mass effect is achieved8. Occasional large collections in the brainstem have also been
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reported11. In other reviews, there were more in the supratentorial than in the infratentorial
compartment2,3,4. CT and MRI scan of the brain along with administration of contrast material
will often demonstrate it as a ring-enhancing lesion, well-defined lesion with a hypodense centre
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and commonly with surrounding cerebral edema4,8(Figure 3). In addition, its rim will usually be
thinner than that of a neoplastic lesions4. MRI imaging with diffusion weighted is another useful
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method which is even more sensitive in differentiating an abscess from other cystic brain
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lesions4,8. In children in whom the anterior fontanelle is still patent, an ultrasonogram can be
useful in the diagnosis of an abscess4.
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Management options
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Management of brain abscesses has been a subject of controversy in neurosurgery. A few

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previously reported cases in the literature suggest that medical therapy should be considered as a
reasonable first option2,7. Steroids use for treatment of these patients is quite controversial
because steroids are known to retard the encapsulation process, increase necrosis, reduce
antibiotic penetration into the abscess and alter CT scan images8. They can also produce a
rebound effect when discontinued8. Yet, steroids use can be life saving for patients with
extremely increased intracranial pressure8.
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Varying rates of culture positivity has been reported with conventional culture methods but
availability of PCR based diagnosis may make these issues a thing of past. The organism
involved has been uniformly reported as anaerobic streptococcus spp. milleri 7,8.

With regards to antibiotics, current evidence shows that it is better to avoid empirical antibiotics

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as much as possible, unless the child is too ill to undergo any form of intervention4. There are
however no randomized controlled trials yet on the effectiveness of antibiotic regimens for
treating patients with CCHD who develop a brain abscess1. The preferred antibiotic therapy has

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been penicillin with chloramphenicol, with a recent shift toward third-generation
cephalosporins4. Third generation cephalosporins, either cefotaxime or ceftriaxone have a good

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central nervous system penetration 9,10 and excellent in vitro activity against many pathogens
isolated from bacterial brain abscess. Metronidazole is highly active against anaerobic bacteria,

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including Bacteroides fragilis, the most resistant anaerobe. Therefore, metronidazole is usually
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combined with third generation cephalosporins or penicillin G for the treatment of cardiogenic
brain abscess 9,11,12. Polymicrobial infection has been identified in some patients with brain
abscess13 making it logical to use an antibiotic combination inspite of culture sensitivity to
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specific antibiotics.
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“There are no randomized controlled trials about the effectiveness of antibiotic regimens for
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treating people with CCHD who developed a brain abscess. Currently, the antibiotic regimens
used are based on previous retrospective studies and clinical experience. There is a need for a
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well - designed multicentre randomized controlled trial to evaluate the effects of different
antibiotic regimens”– COCHRANE REVIEW (2013)12
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Review of literature suggests, medical therapy alone is a recommended option for neurologically
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stable patients without increased intracranial pressure, who have symptoms for less than 2
weeks, and with abscess smaller than 2 cm where close monitoring with imaging is possible2,8.
However, the key benefits of available surgical interventions are that apart from being
therapeutic and helping in establishing the diagnosis, they also provide pathological and
bacteriological proof of an infectious process by creating the opportunity of obtaining a
specimen for culture and above all, they reduce the mass effect responsible for progressive
neurological deterioration2,3.
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Surgical management of cerebral abscess has been controversial2. Drainage of the abscess by
burr hole and aspiration seems adequate and standard of treatment14. The goal of all different
available surgical techniques including real-time image-guidance intraoperative (high-frequency
ultrasound guidance, intraoperative low-field/high-field MRI guidance) or image-guidance based
on trajectories (stereotactic frame or navigation-guidance) or endoscopic assisted surgery

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consists of diagnosis of the infectious agent and reduction of the mass effect15-19, 20
. Some
authors propose the open resection of the abscess capsule in addition to drainage, however an

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advantage regarding recurrence rate and patient outcome is not proven in a prospective study and
14,17,21,22
not generally recommended . We have strict reservation in using any options other than

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burr hole and aspiration of abscess for children with CCHD in view of their high risk to any
forms of intervention. Notably, we did not encounter any procedure related complication.

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Serial imaging studies and inflammatory markers are done to monitor the therapeutic response
and identify recurrent or secondary lesions that may require repeated drainage (Figure 3).
Inadequate aspiration, lack of catheter drainage of larger abscesses, chronic immunosuppression
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and inappropriate suboptimal antibiotic therapy were factors described associated with initial
surgical treatment failure23.
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Notable feature of our series was the high rate of reaspiration in this cohort around 38% (10/26)
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compared to 13/39 in the cohort of all pediatric cerebral abscess. Interestingly, 70% (7/10) of the
reaspirated samples continued to exhibit positive culture. Both these findings may be explained
by the basic pathophysiological factors in play viz. relative ischaemia secondary to
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polycythemia. One study, also demonstrated reduced bactericidal and phagocytic functions of
leucocytes in children with CCHD24.
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Summary of proposed recommendation for follow up imaging and criteria for timing of
corrective/palliative surgery for the cyanotic physiology in a known child with an episode of
cardiogenic cerebral abscesss
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1. Repeat imaging immediately post procedure and subsequently once in 2 weeks until the
completion of the parenteral course of antibiotics, unless the patient shows new clinical
indications including adverse infective profile viz. raising CRP.

2. Our recommendation for follow up imaging protocol is to do a repeat imaging at 3 weeks

of satisfactory completion of parenteral antibiotics and then monthly until insignificant

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size/ progressive decrease in size at least for 3 regular months beyond completion of
treatment

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Criteria of timing of intervention for correction of cyanotic physiology in a known child with an
episode of cardiogenic abscesss.

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We propose that all the below criteria be met before any suggested inervention

1. Completion of antibiotics course, which we recommend atleast 3 weeks of parenteral

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and 3 weeks of oral antibiotics.
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2. Improving and stable imaging characteristics
3. And insignificant infective profile

This criteria is based on our experience and our pediatric cardiology unit protocol. Unfortunately,
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there is paucity of current literature on this subject to substantiate our protocol. Early corrective
management of the cyanotic physiology, ideally will remain key to avoidance of the recurrence and
the outcome.
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Whether there is any role for prophylaxis until the CCHD is corrected, or in situations where
corrections may not possible, is not known and difficult to acertain considering the low incidence.
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Prognosis

Generally, the prognosis of a cardiogenic abscess is often worse than that of other brain
abscesses arising from other causes2. Surgery for brain abscess among patients suffering from
CCHD is faced with peculiar challenges2. First, not only the inherent cardiopulmonary pathology
is a risk but also a wide variety of coagulation defects2,4which are associated with these
conditions add risk to any intervention. Additionally, a high reaspiration and recurrence rate,
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attributable to the altered physiology, adds to the morbidity and prognosis in this group of
patients.

Common to all cerebral abscess, long-term problems commonly encountered are impaired
cognitive function and delayed onset of seizures as well as focal neurological deficits4.

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Intraventricular rupture of the abscess is also a strong factor for poor prognosis in these patients4.

Prognosis also depends on the underlying cardiac condition. Certain condition where the

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physiology can be reversed, have an excellent prognosis and with no possibility of cerebral
abscess recurrence due to the condition once the underlying condition is resolved. Cyanotic

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physiology where the correction is not possible surgically are at risk for cerebral abscess
lifelong, not to mention the poor prognosis of the primary cardiac condition (Table 1).

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We did not have any mortality directly related to the cerebral abscess. We believe this is
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attributable to early imaging, improved antibiotics, better surgical conditions and early correction
of the cyanotic physiology. As there are no recent literature in on cardiogenic cerebral abscess, it
would be difficult to comment and compare with the trend elsewhere.
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Conclusions
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• Cardiogenic origin of cerebral abscess is the commonest cause of the problem amongst
children with CCHD.
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• Infrequently, cerebral abscess can be a presentation of an undiagnosed CCHD.

Recurrence and need for reaspiration is very high in this cohort of cerebral abscess
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secondary to CCHD.
• High haematocrit may indicate the possibility of indolence of cerebral abscess and hence
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the requirement for reaspiration.

• In view of no clear antibiotics guidelines yet in managing this problem, we recommend
cover for streptococci (aerobic and anaerobic) viz. penicillin, ceftriaxone or cefotaxime
with metronidazole.
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Early correction of the underlying CCHD is ideal to avoid recurrence. The timing of correction
vis-a-vis the episode of cerebral abscess, should depend on the well-controlled and the resolving
nature of cerebral abscess as determined by the imaging, infective profile and completion atleast
of the parenteral course of antibiotics.

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• Unresolved/ palliated CCHD disease may remain high risk for occurrence, persistence
and recurrence of cerebral abscess.

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Figure legends
Figure 1: a) Distribution of cerebral abscess among hemispheres
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b) Distribution of cardiogenic abscesses in the left cerebral c) Distribution in the right

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cerebral hemisphere. In both cerebral hemispheres, commonest region involved is frontal.

Figure 2: Diagrammatic representation of the distribution of symptoms in the patients.

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As shown, headache was the commonest symptom

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Figure 3: The pre-operative magnetic resonance imaging (MRI) of one of our 26

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patients. Note the hypodense centre with the well-defined ring enhancement, as well as
the surrounding area of edema. Notable, the infective profile (CRP, WBC count et.) may
reflect the treatment response, inadequate response or recurrence (Figure inset showed
CRP rise corresponding to the recurrence -Figure C)
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Competing interests

The authors declare that they have no competing interests.

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Table 1: Summary of management and outcome of cardiac pathology and its
relation to cerebral abscess

Cardiac outcome Number Comments Risk of abscess

of

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patients
Complete 6 Anatomical and Cured for

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two ventricle physiological correction abscess with
correction no possibility

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of abscess sec.
To CCHD

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Complete 5 Single ventricle but Cured for
single near normal abscess with
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ventricle physiological no possibility

correction corrrection of abscess sec.
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(fontan to CCHD
procedure)
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Single 7 Always at risk

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ventricle for abscess

palliation(
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bidirectional
glenn shunt)
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Complete
correction
deferred in
view of poor
anatomy and
high risk
surgery
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Not operated 2 Always at

(unfavorable cardiac risk for abscess
anatomy)

Eisenmenger 2 Always at
physiology risk for abscess

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(inoperable)

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Lost to follow up 3

Expired 1

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• Brain abscess remains a significant cause of morbidity in patients with uncorrected or
partially palliated congenital cyanotic heart disease.
• There have been no recent articles in the literature on surgical outcomes of
management cardiogenic brain abscess in children.
• Cardiogenic origin of cerebral abscess is the commonest cause of the problem
amongst children with CCHD.
• Recurrence and need for reaspiration is very high in this cohort of cardiogenic

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cerebral abscess.
• Unresolved CCHD disease is high risk for occurrence, persistence and recurrence of

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cerebral abscess.
• No clear antibiotics guidelines yet in managing this problem

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Abbreviations

CCHD: Congenital Cyanotic Heart Disease

MRI: Magnetic resonance imaging

CT: Computer Tomography

CRP: C-Reactive Protein

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WBC Count: White blood Cell Count

ESR: Erythrocyte Sedimentation Rate

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Declaration

We wish to confirm that there are no known conflicts of interest associated with this
publication and there has been no significant financial support for this work that
could have influenced its outcome. We confirm that the manuscript has been read
and approved by all named authors and that there are no other persons who
satisfied the criteria for authorship but are not listed. We further confirm that the

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order of authors listed in the manuscript has been approved by all of us. We confirm
that we have given due consideration to the protection of intellectual property

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associated with this work and that there are no impediments to publication,

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including the timing of publication, with respect to intellectual property. In so doing
we confirm that we have followed the regulations of our institutions concerning
intellectual property.

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We understand that the Corresponding Author is the sole contact for the Editorial
process (including Editorial Manager and direct communications with the office).
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He/she is responsible for communicating with the other authors about progress,
submissions of revisions and final approval of proofs. We confirm that we have
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provided a current, correct email address which is accessible by the Corresponding

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Author and which has been configured to accept email from dr.suhas@gmail.com
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Suhas Udayakumaran
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Kochi, India
25/06/2017