Epidemiology

Brain abscesses are not uncommon and occur in the United States at a rate of approximately 2,500 per year.1 The prevalence is highest in young men, and increased rates are also observed in young children and neonates; each of these groups exhibits different risk factors and therefore different microbial profiles. Worldwide, the prevalence probably varies significantly as the percentage of populations with immunocompromise, immunization rates, and prevalence of other risk factors vary. As the number of patients with immunocompromise due to human immunodeficiency virus (HIV) and to iatrogenic causes, such as solid-organ transplant and chemotherapy, increases, reports of bacterial brain abscess secondary to atypical etiologic agents appear to be on the rise.

Etiologic Agent

The most likely etiologic agent depends on the risk factors of the patient. In neonates, Proteus and Citrobacter species are the most frequently cultured organisms,2,3 whereas in older children and adult patients, the most common isolates in reported series are Streptococcus species, in particular Streptococcus milleri.4,5 Staphylococcal infections are most common among intravenous drug users as well as after craniotomy and trauma, as a result of inoculation from contaminated skin. Bacteroides species ( Fig. 8.1 ), which are anaerobic gram-negative bacilli that are part of the normal flora within the digestive system, are also not infrequently isolated.5

Aerobic gram-negative bacilli, including Escherichia coli, Haemophilus influenzae, Pseudomonas aeruginosa, and Klebsiella pneumoniae, are also isolated from brain abscesses with some frequency—the latter often in association with diabetes mellitus as a risk factor.6 Nocardia species are atypical bacteria that form branching filaments ( Fig. 8.2 ) and can cause brain abscess, particularly in immunocompromised patients. Nocardia brain abscesses are generally difficult to treat, and mortality rates are higher than those for other bacterial brain abscesses.7,8 Spread of Nocardia to the brain is most often hematogenous. Propionibacterium acnes can cause brain abscess, and as with other cases of Propionibacterium acnes CNS involvement, such infections tend to be less severe and may occur in a delayed fashion.9,10

A significant percentage of brain abscesses are polymicrobial. Most series also contain a significant number of brain abscesses that are sterile when cultured,5,6,11,12 which may be due to prior treatment with antibiotics13 or to issues related to the handling of collected samples.

Risk Factors

Risk factors for the development of brain abscess may be divided into those resulting from immunologic factors, those due to anatomic issues, and those due to increased exposure to pathogens.

Immunocompromised patients are at a higher risk for brain abscesses. HIV infection is in particular a risk factor for bacterial brain abscess; however, in this population, CNS lymphoma, Toxoplasma gondii ( Fig. 8.3 ) abscess, and metastatic disease are also relatively common. The evaluation of a ring-enhancing lesion in this population is therefore particularly challenging. Iatrogenic causes of immunocompromise, such as cancer chemotherapy and immunosuppression after solid-organ transplant, are also risk factors for brain abscess development. Transplant patients have an increased risk for developing nocardial brain abscesses,14–17 which may be part of disseminated infection. Diabetes mellitus and cystic fibrosis result in an increased risk for systemic infections and for brain abscess.

Anatomic risk factors include the presence of cyanotic heart disease and hereditary hemorrhagic telangiectasia (HHT). HHT results in a dramatically increased risk for brain abscess, which is likely the result of paradoxical emboli from pulmonary arteriovenous malformations ( Fig. 8.4 ) and most often due to Streptococcus species.18 A higher mortality rate has been reported for brain abscess associated with HHT.19,20 Cyanotic heart disease is a specific risk factor for pediatric patients.21,22 Dermoid cysts may contain a sinus tract in communication with the skin that can result in abscess formation, particularly within the cerebellum.23,24

Risk factors that derive from increased exposure to pathogens include intravenous drug use, a history of intracranial surgery (including a history of cervical traction or halo pin placement), a history of meningitis, dental surgery, and a history of recurrent sinusitis and otitis media. Otitis media and sinusitis account for the majority of abscesses in several series.25 Odontogenic abscesses are frequently mentioned in case reports,26 although the frequency of their true causality is uncertain.

Brain abscess after a neurosurgical procedure is a rare but well-known complication. Two large retrospective studies have been performed and found similar rates of brain abscess after craniotomy that were just under 0.2%.27,28 Similarly low rates have been described after transnasal endoscopic skull base surgery.29 Among neurosurgical procedures, the placement of halo pins, such as those used for cervical immobilization, is associated with numerous case reports of brain abscess formation, and the risk may be increased by retightening pins that have become loose after original placement.30–32

Pathophysiology

Brain abscesses may occur anywhere within the brain, although the most frequent sites are the frontal, temporal, and parietal lobes. Their origin is often within the white matter adjacent to the cerebral cortex. Abscesses that result from direct extension of sinus infection are located in the frontal lobe, and the temporal lobe is often the site of abscesses that are the result of mastoiditis ( Fig. 8.5 ). Cerebellar abscesses can have an otogenic origin. Abscesses of the brainstem are rare33 but do occur, and as expected, they carry a poor prognosis.

The stages of brain abscess development, from inoculation of the brain parenchyma to capsule development, have been described.34 These stages include the early and late cerebritis stages followed by the early and late capsule stages. During the early cerebritis stages, inflammation and edema develop in response to the presence of an infectious inoculum. An area of central necrosis starts to form, with fibroblast deposition of reticulin along the margin during the late cerebritis phase. The formation of a ring-enhancing margin defines the capsule stages ( Fig. 8.6 ); it starts as a vascular, gliotic structure (early) and then is sequestered within a completed collagen border (late).

A murine model of staphylococcal brain abscess has suggested that despite the fact that the purulent material is sequestered from the rest of the brain, localized inflammation mediated by tumor necrosis factor-α (TNF-α), interleukin-1b (IL-1b), and macrophage inflammatory protein-2 (MIP-2) may contribute to damage of the adjacent parenchyma.35 This inflammation, however, may be necessary for an optimal host response because animals deficient in TNF-α or IL-1 exhibit reduced survival after experimental abscess, the latter of which may be mediated downstream by the chemokines CXCL13 and CCL9.36 A member of the toll-like receptor family, toll-like receptor-2 (TLR-2), which is expressed on neutrophils and macrophages and recognizes molecular motifs associated with Staphylococcus species and other pathogens, appears to be a pathway of inflammatory initiation.37

Diagnosis

The diagnosis of brain abscesses is often delayed because of the nonspecific nature of the presentation. One of the pitfalls in recognition is the incorrect assumption that a patient with a brain abscess will present with signs and symptoms of infection. Because of the immune-privileged nature of the CNS and the size limitations of the intracranial space, brain abscesses most frequently present with signs and symptoms of a mass lesion. As such, headache, nausea, vomiting, lethargy, and focal neurologic deficits may be seen. Fever and meningismus are often absent.28 Papilledema is occasionally present and adds urgency to the patient assessment. Careful evaluation for the presence of risk factors is crucial in leading to the correct diagnosis. In neonates, signs of abscess may include seizures, enlarging head circumference, decreased feeding, and respiratory difficulties.2

Because the presentation is often essentially that of a mass lesion, clues that distinguish the clinical picture from that of a patient presenting with a brain tumor should be sought. A history of intravenous drug use, immunocompromise, or relevant infection is important, and the physical examination then focuses on signs of dental or otologic infection. A history of previous malignancy or tobacco exposure or a strong family history of cancer is similarly more suggestive that a ring-enhancing lesion may be a neoplasm. Finally, the time course is occasionally a clue because intraparenchymal brain abscesses often have a shorter time course than do malignancies.

Laboratory investigations may reveal an elevated white blood cell count and inflammatory markers, in particular C-reactive protein. Serum chemistries should also be obtained to assess for the presence of electrolyte imbalances, and the coagulation profile should be obtained in anticipation of surgical intervention.

Once the diagnosis of brain abscess is suspected, obtaining material for culture is critical in determining appropriate antibiotic therapy. Blood cultures should be obtained in any patient suspected of having a brain abscess, although these are positive in a minority of cases. Lumbar puncture should not be attempted because it carries a risk for neurologic deterioration when performed12 and is often nondiagnostic. Aspiration of the lesion (as described in the section on treatment) is often necessary to obtain positive cultures ( Fig. 8.7 ). Ideally, empiric antibiotic therapy should be delayed until a definitive culture is obtained because sterile cultures may otherwise occur.