Pathogenesis

Pyogenic brain abscess is a focal collection of pus within the brain. This condition has been the subject of discussion and of surgical treatment for hundreds of years.¹ The incidence of pyogenic brain abscesses is 8% of intracranial masses in the developing countries, whereas in the West the incidence is 1% to 2%, with male predominance.^1,2 This condition is rare largely because of the brain natural resistance to infection, a property mediated by its abundant vascular supply, the relative impermeability of the blood–brain barrier,³ and improvement in the treatment of ear, sinus, and orofacial infections over the last decades. Peak ages vary, however, depending on predisposing influences; pediatric cases peak between the ages of 4 and 7, and a substantial minority of these children have congenital heart disease.² The overall occurrence of brain abscess does not appear to have changed significantly in the antibiotic era, and an active neurosurgical service in a hospital in a developed country can expect to see 4 to 10 cases annually.^2,4 Pyogenic brain abscess formation is initiated when bacteria gain entry into cerebral tissues with trauma, contiguous spread from a suppurative focus, or hematogenous dissemination from a distant infection. Most cases (40%-60%) are the result of contiguous spread of infection from the middle ear, oropharynx, and paranasal sinuses (Fig. 143-1).^5–7 These lesions are usually solitary, and their distribution in the brain reflects the predisposing lesion (Table 143-1). Seeding of the brain probably occurs via the valveless emissary veins draining the contiguous areas that allow microorganisms to flow into the venous system of the brain from adjacent sites.⁷ Middle ear infections, chronic otitis media, or chronic mastoiditis can lead to temporal lobe or cerebellar abscesses by direct spread via the tegmen tympani or by translabyrinthine spread. Paranasal sinusitis can lead to frontal or temporal lobe abscesses by retrograde thrombophlebitis of the diploic veins. Frontal sinus infection can also lead to frontal lobe brain abscess when complicated by osteomyelitis of the frontal bone of the skull with dehiscence of the posterior table.

FIGURE 143-1 This 50-year-old man with history of dental disease and excessive alcohol use initially presented with seizures of the right arm and leg, as well as expressive aphasia. A, A preoperative MRI coronal T1-weighted image with contrast revealed a ring-enhancing lesion on the area of the left frontal lobe. B, An axial FLAIR image revealed mass effect and edema. A diffusion-weighted signal (C) and ADC (D) showed restricted diffusion within the entirety of the lesion. The patient was taken to the operating room. E, A craniotomy with frameless surgical navigation was conducted, with preservation of the cortical veins draining to the superior sagittal sinus, which revealed a pocket of purulent material. The cultures revealed Fusobacterium brain abscess sensitive to penicillin. Workup for a source of brain abscess included a transesophageal echocardiogram, which showed 7 mm of vegetation of the aortic valve. The patient was treated with 6 weeks of penicillin. F, Immediate postoperative MRI coronal T1-weighted image with contrast showed good evacuation of the infection.

TABLE 143-1 Predisposing Lesions, Intracranial Location, and Bacteriology of a Pyogenic Brain Abscess

EBV, Epstein-Barr virus; TB, tubercle bacillus.

Penetrating cranial trauma such as open cranial fracture with dural tear is a well-described, though relatively infrequent, cause of pyogenic brain abscess, accounting for less than 10% of these infections.^5,6,8 The incidence of brain abscess was 3% in one large series of combat-acquired injuries from the Vietnam War, with most occurring in the setting of gunshot wounds to the head and retained bone fragments.⁹ The interval from the time of injury to diagnosis may be considerably delayed, averaging nearly 4 months in one study.⁸ A distinctive form of post-traumatic brain abscess that occurs largely in young children results from penetrating injuries secondary to a foreign body injury, such as to the orbital region and, less commonly, other areas of the skull, from pencil tips, wooden sticks, wooden toys, and lawn darts.¹⁰ The interval from injury to clinical presentation may extend from days to years. Treatment, as in other penetrating cranial injuries, involves early surgical debridement.¹¹

Brain abscesses are infrequent sequelae of neurosurgery, complicating approximately 0.1% of clean neurosurgical procedures.⁴ Microorganisms, introduced at the time of surgery, infect the wound or bone flap and form an intracranial focus of suppuration by contiguous spread. Hematogenous dissemination or metastatic seeding from a distant primary site of infection accounts for approximately 25% of brain abscesses.^4–6 These lesions are usually located in the distribution of the middle cerebral artery or parietal–occipital junction, tend to occur at the corticomedullary junction, where capillary flow is slowest, and are frequently multiple and multiloculated.⁴ Recognized sources of metastatic seeding include pulmonary lesions, such as arteriovenous fistulas,¹² often occurring with hereditary hemorrhagic telangiectasia¹³; infective endocarditis, rarely complicated by macroscopic brain abscess (less than 1%) but with microabscesses found at autopsy in 4%¹⁴; and deep-seated infections, such as osteomyelitis, pulmonary empyema, pelvic infections, and intra-abdominal infections.

An increasingly important problem occurs in intravenous drug users with infected valvular vegetations supplying emboli, resulting in cerebral infarction, cerebral hemorrhage, brain abscess formation, and spinal epidural abscesses. This population is prone to toxin-mediated diseases (tetanus and botulism) with inoculation of these agents at injection sites.¹⁵ In general, however, transient bacteremia is unlikely to result in brain abscess in the absence of breaches of the blood–brain barrier or predisposing cerebral lesions, such as previous stroke or primary or metastatic neoplasms.^7,16

Cerebral abscess complicates cyanotic congenital heart disease in 2% to 6% of cases,⁴ and cyanotic congenital heart disease is a leading underlying cause of pediatric brain abscess, accounting for 6% to 50% of cases.⁷ Tetralogy of Fallot and transposition of the great vessels underlie most cases, although any cardiac defect that results in significant right-to-left shunting appears to increase the risk. The pathogenesis probably involves increased blood viscosity as a result of chronic hypoxemia (due to right-to-left shunting), leading to areas of microinfarction within the brain that act as nidi for infection. The mortality from pyogenic brain abscess in this setting is high. Intrasellar, brain stem, basal ganglia, and thalamic abscesses are rare.⁴

Intrasellar abscesses generally occur in the setting of preexisting pituitary or sellar lesions, such as adenomas, craniopharyngiomas, or Rathke’s cleft cysts, or as a complication of trans-sphenoidal surgery.^17,18 These lesions may also occur as a result of intrasellar extension from sphenoid sinusitis. Abscesses of the brain stem are generally hematogenous in origin and may extend longitudinally over several levels of the brain stem.⁷ The incidence of these lesions appears to have decreased over the past decades, probably as a result of improvements in the management of pediatric ear infections. Of the brain abscesses, 20% are cryptogenic. In such cases, broad antimicrobial therapy is indicated. Many of these cases are the result of nondiagnosed dental infections.

Bacteriology

The bacteriology of brain abscesses is determined by the initial site of infection (Table 143-1). Streptococci (Streptococcus milleri and Streptococcus viridans) are the most common cause of pyogenic brain abscesses, involved in nearly two thirds of cases, because of their extension from the nasopharynx and oropharynx, as well as from endocarditis (S. viridans).^4,19 Staphylococcus aureus accounts for 10% to 21% of cases, generally in the setting of trauma, postoperatively, but is also seen among patients with brain abscesses resulting from endocarditis.^6,19–21 Methicillin-resistant S. aureus (MRSA) should be considered in hospitalized patients or among those who were known as MRSA colonized. Anaerobic bacteria (Bacteroides, Prevotella, Peptostreptococcus, Fusobacterium, and Actinomyces species) are also major causes of brain abscesses, usually part of polymicrobial infection.²⁰ Brain abscesses due to Actinomyces species are commonly associated with pulmonary and odontogenic infections. Gram-negative bacilli such as Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Serratia species, and Proteus species are associated with genitourinary or intra-abdominal infections, as well as commonly isolated from brain abscesses following head trauma and postoperative infection.^7,22,23 Pseudomonas species can cause brain abscess that results from otitis media or otitis externa.^7,20 Other bacterial species may be cultivated from brain abscesses in various clinical settings: Clostridium species, in association with an underlying malignancy or hemolytic–uremic syndrome²⁴; Propionibacterium acnes in the postneurosurgical patient²⁵; Bacillus species; Listeria monocytogenes, commonly a cause of meningitis or meningoencephalitis but rarely a cause of brain abscess; and Salmonella species, associated with intracerebral hematoma.⁴ Nocardia species such as N. asteroides and N. farcinica comprise 1% to 2% of all cerebral abscesses, with a mortality rate of 31%.²⁶ They are frequently seen in immunocompromised patients but also occur in immunocompetent patients.²⁶ Nocardia brain abscess (Fig. 143-2) may be in isolated cranial pathology or may result from dissemination of cutaneous or pulmonary infection.²⁰ Recently, the number of case reports describing Nocardia brain abscess have been increasing; this may be related to better diagnostic techniques but most likely results from an increase in their incidence.¹⁹ Fungal brain abscesses caused by yeast such as Candida or Cryptococcus species; dimorphic fungi such as Histoplasma, Coccidioides, or Blastomyces species; and molds such as Aspergillus or Rhizopus species are associated with immunocompromised states.²⁰ Protozoa and helminths can cause parasitic brain abscesses and may be relevant in certain cases, such as cat exposure or endemic areas. Toxoplasma gondii can cause central nervous system (CNS) toxoplasmosis and brain abscess (Fig. 143-3), and Taenia solium can cause neurocystcercosis.²⁰ Brain abscess in the neonatal period has a distinctive bacteriologic profile, with most of these lesions caused by Proteus species and Citrobacter diversus.²⁷ In contrast to meningitis caused by other pathogens, neonatal meningitis caused by these organisms is complicated by brain abscess in 40% to 75% of cases, so early computed tomography (CT) evaluation of neonates with meningitis or bacteremia caused by Proteus or Citrobacter species is recommended.⁷ Interestingly, the most common bacterial causes of acute pyogenic meningitis (Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis) are rarely associated with brain abscess.^4,28 The neuropathologic events that underlie brain abscess formation have been studied using α-streptococci in a canine model and found to correlate with CT scan findings.^29,30 A series of histopathologic stages has been described that appear to parallel the evolution of CT findings in human brain abscesses.^29,30 Early cerebritis (days 1-3) is a poorly circumscribed lesion characterized by acute inflammation and cerebral edema associated with bacterial invasion. Later (days 4-9), the zone of cerebritis expands, and necrosis develops, with pus forming at the center of the lesion. CT scanning reveals some ring enhancement with diffusion of contrast material into the necrotic center. The early capsule stage (days 10-13) demonstrates the establishment and maturation of a well-formed collagenous capsule associated with a reduction in the degree of cerebritis and some regression in the local edema. At the late capsule stage (day 14 and beyond), there is continued maturation of a thick capsule with extracapsular gliosis and dense ring enhancement with little contrast diffusion on CT scan.

FIGURE 143-2 This 49-year-old man has a history of long-term steroids for asthma and sarcoidosis. He presented with left-sided weakness, as well as increased lethargy and confusion. Preoperative MRI axial (A) and coronal (B) T1-weighted images with contrast revealed a ring-enhancing lesion on the area of the right thalamus with mass effect and edema. C, Diffusion-weighted signal hyperintensity in the center of the lesion suggests central necrosis, which could be compatible with an abscess. The patient was taken to the operating room. D, A stereotactic needle biopsy with frameless surgical navigation was conducted, which revealed a pocket of purulent material. The cultures revealed a Nocardia brain abscess. The patient received 2 months of intravenous imipenem and oral trimethoprim–sulfamethoxazole. Postoperative MRI axial (E) and coronal (F) T1-weighted images with contrast showed absolute resolution of the infection.

FIGURE 143-3 This 40-year-old man has a history of HIV, a CD4 count of 4, disseminating histoplasmosis, and Pneumocystis carinii pneumonia. He presented with a 2-week history of confusion and speech difficulties consistent with expressive and receptive aphasia. Preoperative MRI coronal (A), axial (B), and sagittal (C) T1-weighted images with contrast revealed an enhancing lesion on the area of the left basal ganglia with edema and mass effect. D, An axial FLAIR image revealed mass effect and edema. E, A diffusion-weighted signal revealed restricted diffusion within irregular areas and parts of the lesion. The patient was taken to the operating room. F, A left-sided supraorbital craniotomy with frameless surgical navigation was conducted to approach the dominant hemispheric lesion. The cultures revealed toxoplasmic encephalitis, and the patient was treated with an 8-week course of leucovorin, pyrimethamine, and sulfadiazine.

Capsule formation and ring enhancement on imaging studies are generally thinner and less complete on the ventricular side of the abscess.²⁹ This situation is probably related to the relatively poor vascularity of the deep white matter and reduced migration of fibroblasts into the area. This thinner area of capsule predisposes to ventricular rupture of the abscess.

The nature of the infecting organism influences encapsulation. Models using Bacteroides species show delayed capsule formation with multiple daughter abscesses, suggesting incomplete containment of the infection,³¹ whereas S. aureus experimental abscesses were larger, demonstrated delayed healing, and were associated with marked extracapsular abnormalities.³² The route of infection also appears to affect capsule formation: abscesses resulting from hematogenous spread tend to have less extensive encapsulation than those arising from a contiguous focus of infection.⁴ This situation is probably the result of microinfarcted areas of the brain arising from metastatic emboli, leading to tissue hypoxia, impaired angiogenesis, and impeded fibroblast migration. Host variables also contribute to encapsulation. For example, in a canine model of brain abscess, immunosuppression with prednisone and azathioprine before bacterial inoculation leads to delayed histopathologic evolution with incomplete encapsulation as assessed by the diffusion of contrast media into the necrotic center of the lesion on CT imaging.³³

Clinical Presentation

Most patients with pyogenic brain abscess have symptoms for less than 2 weeks, although the disease can present indolently.² The presenting features of brain abscess depend on the size and intracranial location of the lesions, the virulence of the infecting agents, the immunologic status of the host, and the cerebral edema caused by the expanding intracranial mass lesion. The classic triad of fever, headache, and focal neurologic deficit is present in less than 50% of cases.⁴ Headache, usually dull and poorly localized, is present in 50% to 70% of cases and is so nonspecific as to be a potential cause of diagnostic delays.^{5–7,19,20,22,34,35} Sudden worsening of a preexisting headache in a patient with a brain abscess, especially if accompanied by the acute onset of meningeal signs, suggests either herniation or intraventricular rupture of the abscess.⁷

Fever occurs in 25% to 50% of adults^{5-7,19,20,22,34,35} and is more common in children.⁴ Symptoms and signs related to any underlying disease (e.g., paranasal sinusitis or otitis media), if present, may aid in the diagnosis. Altered levels of consciousness are often present.⁵ Focal neurologic signs depend on the location of the lesions within the brain and the extent of cerebral edema²: frontal and parietal lobe abscesses are commonly associated with hemiparesis and aphasia, temporal lobe presentations may include aphasia or visual field disturbances, intrasellar lesions tend to mimic pituitary tumors, and cerebellar abscesses often present with ataxia and nystagmus.³⁶ Seizures occur in 25% to 35% of cases.⁴ Patients present with multiple brain abscesses in approximately 10% of cases.³⁵

Diagnosis