Brain Abscess
Brain abscesses in children remain a rare entity and, as a result, their management is guided largely by clinical experience and the results of case series. Twenty-five percent of brain abscesses occur in children younger than 15 years, with a peak incidence at 4 to 7 years. In most patients, brain abscess results from predisposing factors, such as underlying disease (e.g., infection with the human immunodeficiency virus [HIV]), a history of treatment with immunosuppressive drugs, disruption of the natural protective barriers surrounding the brain (e.g., due to an operative procedure, trauma, mastoiditis, sinusitis, or dental infection), or a systemic source of infection (e.g., endocarditis or bacteremia). Bacteria enter the brain through contiguous spread in about half of cases and through hematogenous dissemination in about one-third of cases, with unknown mechanisms accounting for the remaining cases.
The outcome for patients with brain abscess has improved over the past 50 years following advances in cranial imaging techniques, the use of antimicrobial treatment regimens, and the introduction of minimally invasive neurosurgical procedures. Mortality has declined from 40% in 1960 to 15% in the past decade. Currently, 70% of patients with brain abscess have a good outcome, with no or minimal neurologic sequelae, although data on functional and neuropsychological evaluations after brain infection are lacking. Although the mortality rate seems to be decreasing, a significant percentage of children continue to have residual neurologic deficits, including epilepsy, permanent motor or sensory dysfunction, visual field defects, and personality changes. Some children also require placement of a ventriculoperitoneal shunt.
Pathogenesis and Pathology
Pathogenic mechanisms of infection are dependent on predisposing conditions. The first stage of brain abscess is early cerebritis, which may lead to a perivascular inflammatory response surrounding the necrotic center, with increased edema in the surrounding white matter. Subsequently, the necrotic center reaches its maximum size and a capsule is formed through the accumulation of fibroblasts and neovascularization. The capsule thickens with an abundance of reactive collagen, but inflammation and edema extend beyond the capsule. For practical purposes, brain abscesses usually are classified according to the likely entry point of the infection ( Table 32.1 ). Ear and mastoid infections are associated with formation of an abscess at the temporal or cerebellar locations; sinus and dental infections give rise to purulent collections in the frontal lobe; and metastatic spread from distant foci in children with congenital cardiac or pulmonary right-to-left shunts commonly results in involvement of any parenchymal area, including parietal or occipital regions.
| Primary Source | Location of Abscess | Associated Neurologic Findings |
|---|---|---|
| Sinusitis | Frontal lobe | Headache, behavioral changes, motor/speech disorders, depressed consciousness, forced grasping and sucking, hemiparesis |
| Chronic otitis/mastoiditis | Temporal lobe | Dyspraxia and aphasia (dominant hemisphere), ipsilateral third cranial nerve palsy, ipsilateral headache, upper homonymous hemianopsia, motor dysfunction of face and arm |
| Cerebellum | Dizziness, vomiting, ipsilateral ataxia and tremor, sixth cranial nerve palsy, nystagmus (toward lesion) | |
| Dental infection | Frontal lobe | |
| Head trauma | Related to injured site | Variable by region involved |
| Postoperative | At operative site | Variable by region involved |
| Metastatic spread | Multiple lesions | Variable by region involved |
| If parietal lobe involved | Visual field defects in inferior quadrant, homonymous hemianopsia, dysphasia (dominant hemisphere), dyspraxia, and contralateral spatial neglect (no dominant hemisphere) |
The most common origin of microbial infection in children remains direct or indirect cranial infection arising from the middle ear, paranasal sinuses, or teeth. Seeding of the brain presumably occurs via transit of infecting microbes through the valves and emissary veins that serve these regions. A direct erosion of skull and dura by osteomyelitis-induced sinus or middle ear infection can be another mechanism of bacterial spread. Resulting abscesses tend to be solitary and superficial. Metastatic inoculation of the brain from distant extracranial sources (pulmonary infection, endocarditis) tends to provoke multiple cerebral abscesses, with a distribution that reflects the regional cerebral blood flow of the area affected, usually the middle cerebral artery network.
In children with cyanotic congenital heart disease, bacteria are not filtered out by the pulmonary vascular bed, which allows for systemic spread. This situation rarely occurs in patients younger than 2 years, and the abscess or abscesses usually are in areas of brain perfused by the middle cerebral arteries. Evidence of associated endocarditis is rare in these cases, although acute bacterial endocarditis may be complicated by septic infarction of the brain and abscess formation.
Formation of an abscess by direct bacterial implantation may complicate compound skull fractures, scalp wounds, anterior cranial fossa or temporal bone fractures, and chronic cerebrospinal fluid (CSF) fistula. Abscesses also rarely may develop during the course of bacterial meningitis. Despite identification of all these potential routes, 20% to 30% of cases are classified as cryptic brain abscess for which no obvious predisposing factor can be identified.
The brain is remarkably resistant to microbial infection. Despite the common occurrence of occult bacteremia in infants and children, cerebral abscess is a quite rare disease. This resistance is attributable in part to the abundant blood supply of the brain and the relatively impermeable blood-brain barrier. Although certain underlying brain morbidities, such as previous stroke, intracerebral hematoma, or underlying neoplasm, may serve as a nidus of abscess formation in adults, affected children have no apparent predisposing brain lesion. In animal models of infection, induction of abscess usually requires direct inoculation of numerous organisms into the animal’s cerebrum.
Experimental animal studies and use of computed tomography (CT) imaging have provided evidence of the clinical evolution of a brain abscess. In the early stage of cerebritis (days 1–3), a focal area of acute inflammation, vascular dilation, microthrombosis, rupture of small vessels, and edema is present. The center of the lesion then undergoes liquefaction. Expansion of the cerebritis and formation of a necrotic central focus are seen in the late cerebritis stage (days 4–9). Establishment of a ring-enhancing dense collagenous capsule of well-vascularized tissue with peripheral gliosis or fibrosis or both occurs at the early capsule stage (days 10–14). Finally, during the late capsule stage (>14 days), host defenses act to wall off the abscess, and a well-developed capsule results.
Death can occur if the volume of pus and surrounding edema induce a significant increase of intracranial pressure leading to brain herniation. In addition, cerebral abscesses can rupture into the ventricular system or through the cortex into the subarachnoid space, resulting in acute deterioration and a life-threatening event. Fig. 32.1 shows the gross appearance of a well-defined abscess of hematogenous origin. Various microscopic features are illustrated in Figs. 32.2 through 32.4 .
The spectrum of microorganisms cultured from brain abscesses has changed with time. This change reflects improved microbiologic isolation techniques, early and aggressive treatment of primary infections, and better neurosurgical procedures. In more recent series, the predominance of Staphylococcus aureus has decreased and identification of anaerobes has increased. Nevertheless, community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a potential etiologic agent over the past decade.
Anaerobic bacteria isolated from brain abscesses include species of Bacteroides, Peptostreptococcus, Fusobacterium, Veillonella, Propionibacterium, Prevotella, and Actinomyces. Aerobic and microaerophilic streptococci, staphylococci, Haemophilus spp., gram-negative enteric bacilli, and Pseudomonas aeruginosa also are implicated frequently. In children with impaired host defenses, fungal etiology ( Candida, Aspergillus, Cryptococcus, Histoplasma, Coccidioides, and Mucor spp.) or uncommon pathogens, such as Toxoplasma, Nocardia, Mycobacterium, and Listeria spp., can be identified. Parasites such as amebae, Cysticercus, Schistosoma, or Paragonimus are very rare causative pathogens. Citrobacter koseri and Proteus spp. are the most commonly implicated organisms causing neonatal brain abscess in most reports published to date. Some reports of extended-spectrum β-lactamase (ESBL) Klebsiella pneumoniae in neonates have been documented.
In order of etiologic importance, the predominant organisms causing brain abscess in children are aerobic and anaerobic streptococci (60% to 70% of cases), gram-negative anaerobic bacilli (20% to 40%), Enterobacteriaceae (20% to 30%), S. aureus (10% to 15%), and fungi (1% to 5%). *
* References .
Multiple aerobic and anaerobic organisms are isolated in approximately one-third of patients, especially in patients with chronic otitis. No growth is reported from 30% of properly handled purulent specimens. A reasonable speculation of the likely causative microbes can be made according to the predisposing source of infection ( Table 32.2 ).| Primary Source | Usual Etiologic Microorganisms | Recommended Empiric Antibiotic Combination |
|---|---|---|
| Upper Respiratory Tract Infection | ||
| Sinusitis/dental infection | Viridans and anaerobic streptococci, Haemophilus spp., Fusobacterium spp., Bacteroides spp. (non- fragilis ) | Penicillin/amoxicillin or cefotaxime/ceftriaxone + metronidazole |
| Chronic otitis/mastoiditis | Aerobic and anaerobic streptococci, gram-negative enteric bacilli, Bacteroides spp. (including B. fragilis ), Pseudomonas aeruginosa | Penicillin/amoxicillin + metronidazole + ceftazidime/cefepime or meropenem |
| Head trauma | Staphylococcus aureus, aerobic streptococci, gram-negative enteric bacilli | Oxacillin/nafcillin/amoxicillin or vancomycin b + ceftazidime/cefepime or meropenem |
| Postoperative | Staphylococcus epidermidis, S. aureus, gram-negative rods, P. aeruginosa | Vancomycin b + ceftazidime/cefepime or meropenem c |
| Metastatic Spread | ||
| Endocarditis | S. aureus, viridans streptococci | Oxacillin/nafcillin/amoxicillin or vancomycin c + cefotaxime/ceftriaxone/cefepime + metronidazole |
| Pulmonary infection | Aerobic streptococci, Actinomyces, Fusobacterium | Oxacillin/nafcillin or vancomycin b + cefotaxime/ceftriaxone/cefepime + metronidazole |
| Congenital heart disease | Viridans streptococci, Haemophilus spp., Haemophilus aphrophilus | Cefotaxime/ceftriaxone/cefepime + metronidazole |
| Bacterial meningitis | Streptococcus pneumoniae, Haemophilus influenzae type b, Salmonella spp., Citrobacter (neonates), ESBL Enterobacteriaceae ( Klebsiella pneumoniae ) | Cefotaxime/ceftriaxone/cefepime ± vancomycin (resistant pneumococcal strains) Meropenem |
| Cryptogenic source and immunosuppression a | Any type of microorganism | Oxacillin/nafcillin or vancomycin b + ceftazidime/cefepime + metronidazole |
| Nocardia, fungi, Mycobacterium tuberculosis | Oxacillin/nafcillin or vancomycin b + ceftazidime/cefepime + metronidazole | |
a Vancomycin + ceftazidime/cefepime should be added either in areas with significant prevalence of methicillin-resistant staphylococcal strains or for patients with penicillin allergy. Antituberculous therapy should be considered for children with exposure to tuberculosis. Antibiotic regimens are likely to vary by geographic location based on resistant organisms.
b If susceptibility testing reveals methicillin-susceptible S. aureus , vancomycin should be replaced with nafcillin or oxacillin.
c To consider in areas where extended-spectrum β-lactamase (ESBL) either has been identified or represents a high probability of isolation.
Clinical Manifestations
The clinical presentation of a brain abscess depends on the size of the collection, its location, the multiplicity of lesions, the host’s immune status, and the age of the patient. Generally symptoms and signs can be related to the effect of a space-occupying mass, to the focal neuronal dysfunction of the parenchymal region involved (see Table 32.1 ), or to accompanying clinical findings of the underlying predisposing infection. Because on early evaluation most children with cerebral abscess present with vague or nonspecific signs and symptoms, the physician must have a high index of suspicion to recognize the condition as early as possible ( Table 32.3 ). When a patient develops significant alterations in mental status, the prognosis is most ominous.
| Symptoms | % | Signs | % |
|---|---|---|---|
| Headache | 60–70 | Focal neurologic deficits | 35–50 |
| Fever | 50–80 | Papilledema | 30–40 |
| Vomiting | 35–55 | Meningeal signs | 25–35 |
| Seizures | 30–45 | Hemiparesis | 20–30 |
| Mental changes | 30–40 | Nerve palsy | 10–20 |
| Coma | 15–20 | Ataxia | 5–15 |
In older children and adolescents, headache is the most common initial symptom. Irritability occurs more commonly in infants and small children. Neurologic signs depend on the site of the abscess and can be subtle for days to weeks. Behavioral changes may occur in patients with abscesses in the frontal or right temporal lobes. Patients with abscesses that involve the brainstem or cerebellum may present with cranial nerve palsy, gait disorder, or either headache or altered mental status owing to hydrocephalus. Up to 25% of patients present with seizures.
Fever is usually a nonspecific symptom at some phase in the illness in about 50% of patients; overall it may be found in up to 80% of children. Drowsiness, confusion, and vomiting occur frequently during the acute phase of disease. Lethargy, stupor, and coma usually are later events and potentially associated with adverse outcome. Papilledema is present in less than one-fourth of the cases, but its presence requires immediate neurosurgical assessment and neuroimaging.
Focal neurologic disturbances reflect the location of the abscess and can be detected in 30% to 50% of cases on presentation (see Tables 32.1 and 32.3 ). Frontal location is characterized by development of motor speech disorders, memory deficits, personality changes, and depressed consciousness. Hemiparesis occurs with lesions in the postfrontal region or as a consequence of uncal herniation. Abscess in the temporal lobe is characterized by a contralateral homonymous upper quadrantanopia. If the dominant hemisphere is affected, nominal dysphasia and aphasia are characteristic symptoms. Patients with cerebellar abscesses classically exhibit dizziness, nystagmus, defective conjugate eye movements, ataxia, tremor, and hypotonia. Seizures occur in at least 30% to 45% of patients, may be focal or generalized, and may occur at any time during the course of the disease. If the parietal region is involved, visual field defects, homonymous hemianopsia, dysphasia, and dyspraxia can be present.
The rapidity with which symptoms develop can vary substantially. Most patients are symptomatic within 1 week of the onset of formation of an abscess. Immunocompromised children can have a more insidious progression of clinical findings. The presentation of brain abscess in infancy can be suspected by bulging fontanelle, vomiting, irritability, and an enlarging head circumference. Seizures occur commonly, particularly in small infants, and at any time during the course of the disease. School-aged children with cyanotic congenital heart disease, notably tetralogy of Fallot or transposition of the great vessels, also can exhibit symptoms and signs related to their chronic cardiac disease.
Rupture of Brain Abscess Into the Ventricular System
Abscess rupture into the ventricular system results in ventriculitis, often leading to hydrocephalus, and is associated with a high mortality rate (27–85%). Frequently rupture occurs before the diagnosis of abscess has been established and surgical removal can occur. A sudden worsening in the patient’s clinical state heralds this event. High fever, shock, meningismus, and altered consciousness are prominent clinical signs.
Rupture of the abscess into the ventricle is seen more frequently in patients with deep-seated abscesses or in immunocompromised patients. Although a modest pleocytosis and elevated protein concentration in CSF may have been identified earlier, 50,000 to 100,000 polymorphonuclear leukocytes per microliter and markedly reduced glucose concentration in the CSF are usual findings. Organisms may be seen on smear of the CSF and cultured from the fluid. In other words, the patient has developed purulent meningitis, and treatment must include high doses of antibiotics and surgery (see “ Treatment ”). If an abscess is abutting but has not yet ruptured into the ventricular system, drainage should be considered to prevent rupture of the abscess and resulting ventriculitis.
The concurrence of abscess and meningitis in the past has led to the assumption that brain abscess can be a complication of meningitis; this rarely, if ever, is the case, although meningitis may develop during the incipient stages of abscess formation after intracranial invasion of organisms from a contiguous extracranial source. In such circumstances, the abscess may seem to be a consequence of the leptomeningitis. Given a potential source of infection in the ear or paranasal sinuses, the clinician must be wary and appreciate the possibility of this sequence of events. Abscess has been reported to complicate Citrobacter meningitis in infants, but careful pathologic study has shown vasculitis and liquefaction necrosis of the white matter without capsule formation.
Laboratory Diagnosis
Laboratory tests frequently are not helpful in supporting the clinical diagnosis of brain abscess. Children usually have unremarkable leukocyte counts, and the erythrocyte sedimentation rate can be normal. Blood cultures rarely are positive. Performance of a lumbar puncture is potentially dangerous because it can be associated with brainstem herniation. In addition, CSF analysis uncommonly provides useful clinical information. Usual CSF findings include an elevated protein, mild mononuclear pleocytosis, and hypoglycorrhachia. CSF cultures usually are negative, unless the abscess has drained into the ventricular system or has been a complication of meningitis.
Culturing abscess material obtained at the time of surgical drainage provides the best opportunity to make a microbiologic diagnosis. Proper handling and processing, with attention given to optimal anaerobic and aerobic isolation techniques, can identify the causative organism in most cases, especially when antimicrobial therapy has not been instituted previously. The high incidence of sterile cultures reported in the literature is probably because of the inadequacy of bacteriologic procedures. Under such conditions, sterile cultures may reach even unjustified rates higher than 32.2% or 40%. If a bacterial brain abscess is strongly suspected but the culture results are negative, PCR-based 16S ribosomal DNA sequencing may provide a definitive etiologic diagnosis, allowing for targeted antimicrobial therapy. When this test was performed on aspirates from brain abscesses in 71 patients, 30 (42%) of whom had positive cultures, bacterial DNA was detected in 59 patients (83%). The investigators identified 80 different bacterial taxa, 44 of which had not been described previously in brain abscesses, including 37 that have not been reported to be cultured. Although these data are indicative of the bacterial diversity within brain abscesses, it is unclear whether all these species are involved in the pathogenesis of abscesses and warrant treatment.
Diagnosis
Magnetic resonance imaging (MRI) is used at an increasing rate in evaluation of cerebral abscess both at the time of diagnosis and in follow-up. Similar MRI findings can be observed in infarction, demyelinating disorders, and neoplastic processes. Diffusion-weighted MRI and magnetic resonance spectroscopy have been shown to be effective methods in differentiating cerebral abscesses from tumors. CT scanning with contrast enhancement provides a rapid means of detecting the size, number, and localization of abscess. Also, proton MRI spectroscopy and diffusion-weighted imaging are useful as additional diagnostic modalities in differentiating intracranial lesions. Also, proton magnetic resonance spectroscopy and diffusion-weighted imaging are useful as additional diagnostic modalities in differentiating intracranial lesions. Fig. 32.5 illustrates CT and MRI studies of patients with tuberculous abscess with caseous material, irregular contours, tissue edema, and the important effect of mass displacement of the ventricular system and midline. CT remains an excellent alternative if MRI is unavailable; however intravenous administration of contrast material is advised because the abscess may be missed otherwise. Fig. 32.6 illustrates a CT scan showing a large mass in the right hemisphere causing an occupant mass effect, with tissue edema compression and displacement of the lateral ventricle and the midline, which are indirect signs of increased intracranial pressure. Serial CT or MRI performed weekly or biweekly provides evaluation of the response to therapy and of the need for repeating the surgical procedure. MRI is more accurate than CT for establishing the diagnosis of cerebritis, cerebellar abscess, edema formation, and brainstem purulent collections. On T1-weighted sequences, brain abscesses appear hypointense and show ring enhancement after administration of intravenous gadolinium. In contrast, on T2-weighted images, the typical mature abscess has a hyperintense central area of pus surrounded by a well-defined hypointense capsule and surrounding edema.
