Brain Abscesses in Children With Cancer

Nuno Lobo Antunes, MD,* Subramanian Hariharan, MD, andLisa M. DeAngelis, MD

Background. Brain abscesses in pediatricpatients are rare events, and the causative or-ganism and prognosis vary with the populationunder study. Children with cancer seem to beparticularly susceptible to the development ofbrain abscesses because of the immunologicalchanges induced by cancer and its treatment.We reviewed the records of children who de-veloped a brain abscess during treatment of amalignancy to define the clinical characteris-tics, prognosis, and management of these pa-tients. Procedure. We performed a retrospec-tive review of the clinical and laboratory char-acteristics of all cancer patients younger thanage 20 years who were admitted to our institu-tion between 1980 and 1996 for a brain ab-scess. Results. Twelve children were identified.Cancer diagnoses were brain tumor in two, sys-temic PNET in two, and leukemia in eight. Six

patients had multiple abscesses. Eleven re-ceived prior chemotherapy. Abscesses weresurgically excised or aspirated in seven, andempiric antibiotics were given to the other five.At surgery, Listeria monocytogenes, Aspergillusfumigatus (3), Fusarium, and Candida lusitaneawere cultured. Aspergillus was identified inother locations in four patients. Abscesses weresuccessfully treated in seven patients, two ofwhom received antibiotics only; five patients(42%) died from infection. Conclusions. Mor-tality is high in this immunosuppressed popu-lation, in part due to the preponderance of fun-gal infection. The finding of very rare organismssuggests that drainage and culture should beperformed whenever possible; empiric antibi-otics that include an antifungal agent may, onoccasion, be successful. Med. Pediatr. Oncol.31:19–21, 1998. © 1998 Wiley-Liss, Inc.

Key words: brain abscess; pediatric oncology; fungal infection

INTRODUCTION

Brain abscesses are uncommon in children, even whenpredisposing conditions such as cyanotic heart disease,otitis, sinusitis, and immunosuppression are present [1–3]. The individual importance of each predisposing factorvaries with the population studied, as does the causativeorganism and prognosis [4–7].

Recent years have seen a remarkable improvement insurvival from brain abscesses, with fatality decreasingfrom 50–60% in the early 1970s to 5% in more currentseries [8–10]. However, children with cancer constitute aparticular group, owing to the systemic consequences ofthe underlying malignancy and the immunosuppressiveeffects of its treatment. We reviewed the records of pe-diatric cancer patients admitted to Memorial Sloan-Kettering Cancer Center between 1980 and 1996 with abrain abscess, to define the clinical characteristics, prog-nosis, and management of these patients.

MATERIALS AND METHODS

The records of all patients younger than 20 years withconfirmed malignancy and a discharge diagnosis code ofbrain abscess were reviewed. Patients with subdural orepidural empyema were excluded; 12 patients with docu-mented brain abscess were identified. Diagnosis of brainabscess was established at surgery or through radiologi-

cal studies in the setting of documented systemic infec-tion. Sex, age, underlying cancer, abscess location, clini-cal features, bacteriology, treatment, and outcome wereanalyzed.

RESULTS

There were seven girls and five boys (F:M of 1.4),with a median age of 14 years (range: 6–19). Headachewas the presenting symptom in six patients (50%). De-lirium or lethargy were noted in three patients, while fourhad progressive hemiparesis (Table I). Seizures devel-oped in two patients, and on neurological examinationlateralizing motor signs were found in eight. One patientwas asymptomatic, and the abscess was identified on aroutine follow-up CT scan.

MRI and CT scans were available in nine patients andCT scan alone in three. Ring-enhancing lesions were de-tected in all patients. Six patients had multiple abscesses,and six had single lesions that varied in diameter from

Department of Neurology, Memorial Sloan-Kettering Cancer Center,New York, New York

*Correspondence to: Nuno Lobo Antunes, 1275 York Avenue, NewYork, NY 10021. E-mail: AntunesN@mskcc.org

Received 8 October 1997; Accepted 8 February 1998

Medical and Pediatric Oncology 31:19–21 (1998)

© 1998 Wiley-Liss, Inc.

0.5 to 6 cm. All areas of the brain with the exception ofthe brainstem were affected.

Brainstem glioma was the underlying cancer in twopatients, eight had leukemia, and two had systemicprimitive neuroectodermal tumors. Except for one patientwith a brainstem glioma treated with dexamethasone formonths, all had received cytotoxic chemotherapy. Threepatients with leukemia were recovering from allogeneicbone marrow transplant. Fever was present at diagnosisin nine patients, and neutropenia in six. Because of con-current systemic infection, ten patients were beingtreated with multiple antibiotics before or at the time ofdiagnosis; in nine, the systemic infection included organ-isms additional to those responsible for the brain abscess.Surgical excision or aspiration was performed in sevenpatients. Antibiotics alone were given empirically in theremaining five. Treatment was successful in seven pa-tients, five in the surgical group and two in the medicalgroup, as judged by resolution of the radiological andclinical abnormalities. Eight patients died, and the causeof death in five was abscess related and in three was dueto tumor progression. Patients who died from brain ab-scess survived a mean of 5 weeks after the abscess wasdiagnosed (range: 2–12). Autopsy was performed in twopatients; in one it was possible to confirm theAspergillusinfection; in the other no organism was recovered al-though the abscess was confirmed.

Fungi were the causative organism in 11 of the 12patients. Organisms were identified in six patients byculture or examination of infected tissue obtained at sur-gery: Aspergillus fumigatus(3), Fusarium, Candida lu-sitanea,andListeria monocytogenesin one each. In theremaining six patients, organisms were isolated at extra-cerebral sites. In four patients,Aspergilluswas culturedfrom sinuses, sputum, or lymph node biopsy. One patienthad an unidentified fungus recovered from a lymph nodeand liver biopsy and another had a positive blood culturefor Candida albicans.A lumbar puncture was performedin four patients; the cerebrospinal fluid (CSF) was nor-

mal in three and showed mild protein elevation in one.All CSF cultures were negative.

DISCUSSION

Our cohort represents a select group of pediatric pa-tients who developed a brain abscess in the course oftheir treatment for a malignancy. As such, it differs fromthe general population in a number of features. The peakincidence of brain abscess in children without cancer isbetween 6 and 8 years [2,3]. Our population was consid-erably older, the majority being adolescents. This shifttoward an older age group reflects not only the pediatriccancer population but is also influenced by the fact thatthese patients were often in advanced stages of their dis-ease, after prolonged immunosuppression. Previous se-ries of childhood brain abscesses reported a majority ofmales [2,3], whereas we saw a slight female predomi-nance.

In a large cooperative study [3] that reviewed 83 chil-dren with brain abscesses, in which congenital heart dis-ease was the most common predisposing factor, 24% hadmultiple abscesses. In our series, 46% had multiple ab-scesses, which is similar to the experience with brainabscess following bone marrow transplantation at theFred Hutchinson Cancer Research Center, where the ma-jority of patients had multiple lesions, particularly ifAs-pergillus was the offending organism [10].

As in other series, headache was the predominantsymptom in our patients [12]. Since fever is common inthe cancer population, and the interpretation of the labo-ratory studies is confounded by treatment, headache maybe an important complaint, raising the possibility of astructural brain lesion. However, headache was only pres-ent in 7% of bone marrow transplant recipients who de-veloped a brain abscess [10]. Neurological examinationshowed focal findings in the majority, with a few patientsdemonstrating diffuse cerebral dysfunction.

CT and MRI make the identification of brain abscess

TABLE I. Case Summaries

No. Cancer Symptoms Examination Abscess Organism Therapy Cure

1 ALL Altered mental status Hemiparesis Multiple C. lusitaniae Medical Yes2 CML Altered mental status Hemiparesis Multiple Aspergillusa Medical No3 ALL Headache Normal Multiple Fusarium Surgical Yes4 ALL Headache, hemiparesis Hemiparesis Single Listeria monocytogenes Surgical Yes5 PNET Headache, seizure Hemiparesis Multiple Aspergillus Surgical No6 ALL Headache Normal Single Fungala Surgical Yes7 ALL Seizure Todd’s Paralysis Multiple Aspergillusa Medical No8 Glioma Hemiparesis Hemiparesis Single Aspergillus Surgical Yes9 AML Headache visual obscuration Normal Multiple Aspergillusa Medical Yes

10 PNET Altered mental status, hemiparesis Hemiparesis Single C. albicansa Medical No11 Glioma Headache Unchanged Single Aspergillusa Surgical Yes12 AML Hemiparesis Hemiparesis Single Aspergillus Surgical No

aOrganism isolated from systemic site; ALL, acute lymphoblastic leukemia; CML, chronic myeloid leukemia; AML, acute myeloid leukemia;PNET, primitive neuroectodermal tumor.

20 Antunes et al.

lesions relatively easy. Every patient had an abnormalscan, with visualization of ring-enhancing lesions;As-pergillus has been reported to produce nonenhancingmultifocal hypodense lesions [10].

We observed a predominance of hematological malig-nancies, which is explained by their relative frequencyamong childhood cancers, as well as by the intensity andduration of immunosuppression in these patients, three ofwhom underwent bone marrow transplant. Two of ourpatients had primary brain tumors, but their brain abscessdeveloped away from the tumor, and surgery was not acontributing factor.

Treatment for brain abscess may include surgery, ei-ther excision or aspiration, and antibiotics [11]. Surgeryis often required if the abscess is large, there is impend-ing rupture into the ventricular system, diagnosis is un-certain, or a foreign body is present. The duration ofantibiotic treatment may be shorter if excision is elected.Antibiotics alone may be sufficient treatment if closeclinical and radiological follow-up is provided. In gen-eral, medical therapy is indicated in those patients withcerebritis, multiple lesions, or with abscesses in delicateanatomical locations. Five of our patients did not un-dergo surgery, two because of multiple small lesions.Poor medical condition prevented surgery in the rest. Inthese patients, the diagnosis of brain abscess had a sig-nificant impact, switching the therapeutic goals, with anincreased focus on palliation.

The poor prognosis of brain abscess in immunosup-pressed patients was well documented in the Fred Hutch-inson Cancer Research Center series, in which 56 of 58patients who developed a brain abscess in the course ofa bone marrow transplant died shortly after diagnosis[10]. In our series mortality was 62%, but the cause ofdeath was progression of the underlying cancer in ap-proximately half. Of particular relevance, two of our pa-tients were successfully treated without surgical inter-vention.

The microbiology of brain abscesses varies markedlywith the underlying condition. In immunocompetent pa-tients, anaerobic and aerobic bacteria are usually iso-lated, whereas in immunosuppressed patients fungi areoften found. Although a presumptive organism could berecognized in all patients, only half had definitive iden-tification of the abscess organism, reflecting the fact thatinfected brain tissue was not obtained in all patients andthatAspergillusspecies is difficult to culture from blood.

The marked preponderance ofAspergillus and otherfungi in this series of children, almost all treated withchemotherapeutic agents, is similar to the organisms seenin the bone marrow transplant population. Of the organ-isms identified, two are rarely pathogenic in man. To ourknowledge,Candida lusitanaehas not been isolated pre-viously from a brain abscess, and only two other in-stances ofFusariumbrain abscess have been described[13–15]. The finding of very rare organisms suggests thatdrainage and culture should be performed whenever pos-sible; however, empiric antibiotics that include an anti-fungal agent may occasionally be successful.

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