Neonatal brain abscess: An atypical presentation.

Brain abscesses occur as an uncommon complication of bacterial meningitis in the neonatal period. A 34 weeks preterm at-risk neonate presented with abnormal breathing pattern and inability to maintain the oxygen saturation in room air. Magnetic resonance imaging (MRI) study revealed intra-parenchymal brain abscesses in the left basal ganglion and bilateral fronto-parietal regions. Intravenous piperacillin - tazobactam was commenced and continued for 6 weeks in Neonatal Intensive Care Unit. No surgical intervention was required. The patient responded to the medical management and was discharged after the documentation of radiological clearance in repeat MRI study. No complications were recorded. An appropriate neuro-developmental outcome was observed on follow-up. Brain abscesses may not be preceded by meningitis in all neonates. A strong clinical suspicion is required for the diagnosis especially in cases with atypical presentation.

Introduction

The first report of brain abscess in a neonate was published 100 years ago.[1] The most commonly reported etiologic microorganisms of this rare condition are Citrobacter diversus Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens, and other Enterobacteriaceae.[2] We report a case of neonatal brain abscess presenting with atypical features.

Case Report

A male preterm of approximate 34 weeks gestation, weighing 1.9 kg, appropriate for gestational age was delivered vaginally to a primigravida mother at a private nursing home. The baby had cried immediately after birth and was asymptomatic on day 1 of life. On day 2, the baby was admitted in Neonatal Intensive Care Unit of a tertiary care hospital with complaints of excessive cry and refusal to feed. There was a history of leaking per vaginum for 3 days prior to the delivery. Otherwise, the antepartum period was uneventful. On day 3, the baby exhibited weak cry, shallow, and irregular breathing pattern with the inability to maintain oxygen saturation in room air. Fever, progressively worsening respiratory distress, apnea, cyanosis, seizures, bulging anterior fontanelle, vomiting, and pallor were, however not observed. Neurological examination revealed normal occipito-frontal circumference, wakefulness, reflexes and physiological hypotonia without a focal neurological deficit. Examination of other systems was normal. Laboratory investigations showed a positive sepsis screen – total leukocyte count = 4000/μl, absolute neutrophil count = 1800/μl, serum C-reactive protein = 4.8 mg/dl (Semiquantitative latex slide agglutination kit, Vital Diagnostics, Thane, India, normal cut-off limit = 0.6 mg/dl) normal blood sugar (4.62 mmol/l), serum calcium (2.35 mmol/l), normal chest X-ray and an arterial blood gas. The patient was administered a combination of cefotaxime at 50 mg/kg/dose q 12 hourly and amikacin at 7.5 mg/kg/dose q 12 hourly owing to laboratory confirmation of sepsis. Blood culture sent earlier was sterile. The cerebrospinal fluid examination was normal with sterile culture and with no micro-organisms seen in the Gram-stained slide, thus, indicating the absence of meningitis. Due to the persistent clinical features of sepsis, antibiotics were changed to intravenous vancomycin at 10 mg/kg/dose q 12 hourly and meropenem at 20 mg/kg/dose q 12 hourly after 48 h of initiation of therapy. The persistence of shallow and irregular breathing pattern prompted us for cranial ultrasonograms on day 5 which revealed multiple hypo-echoic lesions in bilateral parietal lobes. Magnetic resonance imaging (MRI) brain was subsequently performed on day 6 which showed multiple hypo-dense lesions with peripheral enhancement suggestive of intra-parenchymal abscesses in bilateral fronto-parietal and left basal ganglionic region [Figure 1a and b]. There was no hydrocephalous or extra-cranial collection of fluid. Intravenous vancomycin was continued in same doses, but dose of meropenem was increased to 40 mg/kg/dose q 12 hourly to facilitate the drug availability at the site of lesions. Repeat blood culture drawn at this time grew Kliebsiella pneumoniae after 48 h of incubation which was sensitive to ciprofloxacin and piperacillin – tazobactam. On day 10, due to minimal change in the general condition and respiratory pattern, vancomycin and meropenem were replaced by intravenous piperacillin – tazobactam at 75 mg/kg/dose q 8 hourly. An improvement in general condition was observed in the ensuing 72 h, following which, the neonate started feeding well and was subsequently discharged after 6 weeks of therapy. On a 3 months follow-up, a repeat MRI brain scan [Figure 2] revealed complete resolution of lesions as shown in the earlier report. The baby had a normal neurological examination and developmental milestones at 9 months of age.

Figure 1

MRI brain images prior to initiation of therapy: (a) Axial T2 image shows hyper-intense areas surrounded by hypo-intense rim seen involving the left basal ganglion, and in bilateral fronto-parietal locations. (b) Sagittal contrast T1 image shows thick peripheral rim enhancement of the lesions in left basal ganglion and in the left parietal lobe. Both images a and b are suggestive of parenchymal brain abscesses

Figure 2

MRI brain images post-therapy: Axial T1 (left) and sagittal (right) contrast MRI brain images on post-therapy follow-up scan at 3 months age shows no abscess in the corresponding regions of brain parenchyma and is suggestive of their complete resolution

Discussion

Brain abscesses occur as an uncommon complication of bacterial meningitis in 1.3–4.0% neonates.[3] Gram-negative micro-organisms commonly Citrobacter diversus, Proteus and Pseudomonas species have been implicated in the pathogenesis as they bear the propensity to invade nervous tissue and cause necrotizing vasculitis.[4] Klebsiella pneumoniae was isolated in the cited case of brain abscess. Although, Klebsiella is the most common organism causing neonatal sepsis in developing countries,[5], it has been reported in few cases of brain abscess in the world literature.[45] However, in one of the largest series of 30 neonates with brain abscess in a tertiary center, no case was attributed to Klebsiella species.[6] This could be due to its lesser tendency to cause necrotizing lesions as compared to Citrobacter and Proteus species.[5]

Volpe has emphasized that the bacteria cause meningitis and vasculitis initially, which may further, rarely complicate and result in the formation of a brain abscess.[7] In this case, there was history of leaking per vaginum in the mother for 3 days prior to delivery which was probably followed by neonatal sepsis and hematogenous seeding of the brain parenchyma resulting in the multiple abscesses with no initial meningeal involvement. Sundaram et al. have hypothesized that the direct hematogenous seeding of the parenchyma could be an equally important pathogenetic mechanism for an abscess to develop and a meningeal involvement may not be an essential prerequisite always.[4] The colonization of brain parenchyma during sepsis can be explained by the physiological right-to-left shunt of the neonatal circulation.[6]

The usual clinical presentation of brain abscess in neonatal period consists of irritability, bulging fontanelle, and rapid rise in head circumference with wide separation of sutures, vomiting, seizures, and poor feeding.[6] This case was characterized by the absence of the usual clinical features as mentioned. The presence and persistence of shallow and irregular respiratory pattern with the inability to maintain oxygen saturation in room air necessitated a cranial ultrasonography and MRI brain. This atypical and exclusive presentation has not been reported in previous studies.

The management of neonatal brain abscess is influenced not only by the anatomic location, number, size, stage, and nature of the abscesses but also by the age and neurological status of the patient.[8] Medical management saves the patient from the stress and surgical complications especially in a neonate, who may present with significant surgery-related neurological deficits and hemorrhage.[8] The duration of the antibiotic course is usually 6–8 weeks and longer for immunocompromised patients.[9] However, the right dose and duration of antimicrobial agents for neonatal brain abscess is poorly studied.[4] In this case, there was a poor response to empirical meropenem therapy despite an increase in its dose. Meropenem penetrates the blood-brain barrier well when the meninges are inflamed and achieves an excellent minimum inhibitory concentration for almost all Gram-negative pathogens[10] but neonatal data about its penetrative ability in the absence of meningeal inflammation or within an abscess cavity are lacking. On the other hand, surgical intervention provides samples for accurate diagnosis, reduces the mass of an abscess, improves the efficacy of the drugs used for treatment and in some conditions allows intrathecal, intra-ventricular or intra-cavitory administration of antibiotics.[11] Response to a 6 weeks course of piperacillin – tazobactam obviated the requirement for surgical intervention in this case. Abscess >2.5 cm of size requires neuro-surgical drainage.[9] Aspiration was not attempted in this case owing to smaller multiple lesions which were inaccessible to this procedure.

The long-term outcome of a neonatal brain abscess is not very encouraging. Various studies have highlighted the poor IQ scores and subsequent poor scholastic performance.[6] In this case, the patient exhibited appropriate developmental milestones on follow-up.

To conclude, brain abscesses may not be preceded by meningitis in all neonates. Apart from the typical features, a clinician should be aware of atypical features such as shallow and irregular breathing, inability to maintain oxygen saturation in room air, and absence of the usual clinical features. A strong clinical suspicion may thus be required for diagnosis in such cases.

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