Review of Brain Abscesses

Review of Brain Abscesses Leroy Sims, MS, Michael Lim, MD, and Griffith R. Harsh IV, MD, MBA A brain abscess is a focus of infected brain parenchyma. Most brain abscesses result from infection, trauma, or surgery. Although some abscesses cause localizing neurological signs or symptoms, most present with nonspecific symptoms such as headache, fever, lethargy, and malaise. Because the presentation is often nonspecific, a high index of suspicion is crucial to early detection and diagnosis. Although computed tomography and magnetic resonance imaging are highly sensitive detectors of brain abscess, they are less specific. Except in cases with accessible systemic infection, brain biopsy, or resection is often needed to confirm the diagnosis and to obtain tissue for culture. Patient outcome is usually favorable with early detection and aggressive treatment. Abscess rupture, particularly into the cerebral ventricles, often has dire neurological consequences that may prove fatal. Oper Tech Neurosurg 7:176-181 © 2005 Elsevier Inc. All rights reserved. KEYWORDS brain abscess, intraventricular rupture of brain abscess, management

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ach year, between 1500 and 2500 cases of brain abscess are diagnosed in the United States. The prevalence of brain abscess is higher in immunocompromised individuals than in those with normal immune function.1,2 Although brain abscesses can occur in individuals of any age or gender, they occur most frequently in men 30 to 50 years old. Earlier detection resulting from advances in computed tomography (CT) and magnetic resonance imaging (MRI) and the increased efficacy of modern antimicrobial drugs have led to better patient outcomes. The mortality rate of patients with a brain abscess has decreased to less than 10%, except for those with brain abscesses complicated by intraventricular rupture, whose mortality rate can approach 80%.3-9

Etiology Brain abscesses arise after direct extension of infection from neighboring structures, hematogenous seeding of infectious agents, or trauma. Direct extension of sinusitis, otitis, or a dental infection causes almost half of all brain abscesses.10,11 As a result, the location of a brain abscess often suggests the site of primary infection. Frontal lobe abscesses are usually associated with frontal, ethmoidal, or both sinusitis and, less frequently, dental infection. Intracranial abscesses related to sphenoid sinusitis occur most often in the temporal lobe or pituitary gland. Infections of

Department of Neurological Surgery, Stanford University Medical Center, Stanford, CA. Address reprint requests to Griffith R. Harsh IV, MD, MBA, Stanford University Medical Center, Department of Neurological Surgery, Edwards Building R-297, 300 Pasteur Drive, Stanford, CA 94305-5327; E-mail: [email protected].

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otogenic origin commonly occur in the temporal lobe or cerebellum. Hematogenous spread from distant sites accounts for approximately 25% of cases of brain abscess. Hematogenous seeding usually produces multiple brain lesions, most often in the distribution of the middle cerebral artery.12-14 The most common distant foci of primary infection are chronic pulmonary infection and bacterial endocarditis. Infections of skin, bone, and abdominal or pelvic viscera also may seed the blood and then the brain. Structural abnormalities, such as congenital heart disease defects, the most common cause of brain abscess in children, and pulmonary arteriovenous malformations, also increase the risk of hematogenous spread of infection.15 Finally, trauma, including surgery, accounts for 10% of cases of brain abscess. Brain disrupted by a penetrating head injury, particularly one that implants a foreign body, provides a fertile environment for infection.16,17 The type of microorganism involved in an abscess is influenced by the patient’s age, his or her immune status, and the origin of the infection (Table 1). Bacteria causes most brain abscesses. Many abscesses contain multiple species. In the immunocompromised patient, a wider spectrum of organisms, such as fungi, atypical bacteria, and parasites, must be considered.18 Anaerobic bacteria causing brain abscesses usually arise from otorhinolaryngeal infections and produce solitary brain abscesses. The most frequently cultured anaerobic organisms are anaerobic streptococci, Bacteroides, Prevotella, and Fusobacterium species. Staphylococcus aureus and Streptococci are common aerobic bacteria. S. aureus also predominates after head trauma or a neurosurgical procedure. In the immunocompromised patient, the list expands to include Toxoplasma gondii, Mycobacterium tuberculosis, Aspergillus species, and other opportunistic pathogens.19 Finally, para-

Review of brain abscesses

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Table 1 Common Sources, Pathogens, and Treatments for Brain Abscesses Predisposing Condition Paranasal Sinusitis

Otitis media, mastoiditis

Dental infections Pulmonary infections

Congenital heart disease

Penetrating head trauma

Neurosurgical procedure HIV infection

Transplantation

Neutropenia

Associated Organisms

Antibiotic Treatment

Streptococci, Fusobacterium, S. aureus, Enterobacteriaceae, Pseudomonas aeruginosa, Bacteroides spp. (nonfragilis), Haemophilus spp Aerobic and anaerobic streptococci, Enterobacteriaceae, Pseudomonas aeruginosa, Bacteroides spp. (including B. fragilis), Provetella spp. Streptococci, Mixed Bacteroides spp., Prevotella, and Fusobacterium Aerobic and anaerobic streptococci, anaerobic gram-negative bacilli (eg, Prevotella, Porphyromonas, Bacteroides), Fusobacterium, Actinomyces, Nocardia Aerobic and microaerophilic streptococci, S. aureus, Haemophilus spp. S. aureus, Enterobacteriaceae, Clostridium

Penicillin or a third-generation cephalosporin (cefotaxime or ceftriaxone) plus metronidazole Penicillin plus metronidazole plus ceftazidime

Staphylococci, Enterobacteriaceae, Pseudomonaceae T. gondii, Mycobacterium spp., Cryptococcus neoformans, Nocardia spp., Listeria monocytogenes Aspergillus, Candida, Cryptococcus, Mucorales, Nocardia, T. gondii, Enterobacteriaceae Aerobic gram-negative bacilli, Aspergillus spp., Candida spp., Mucorales

Penicillin plus metronidazole Penicillin plus metronidazole plus ceftazidime

Penicillin or third-generation cephalosporin plus metronidazole Nafcillin or vancomycin plus third-generation cephalosporin Vancomycin plus ceftazidime *,†

*,†

*

Notes: *Amphotericin B is administered for Candida, Cryptococcus, and Mucorales infections; voriconazole for Aspergillus. †T. gondii infection is treated with pyrimethamine and sulfadiazine. ‡Aminoglycosides, erythromycin, tetracyclines, and first-generation cephalosporins should not be used to treat brain abscesses because these drugs do not cross the blood-brain barrier. ¶When increased intracranial pressure produces symptoms, it should be treated vigorously with controlled hyperventilation (PaCO2, 25 to 30 mmHg), mannitol (0.25 to 0.50 g/kg IV), and dexamethasone (4 mg IV every 4 h). Modified from Reference 2 and 21. HIV, human immunodeficiency virus; IV, intravenous.

sites should be included in the differential diagnosis, especially for individuals who have lived outside the United States.

Pathophysiology Brain abscesses develop in four stages (Table 2): First, the early lesion, often referred to as cerebritis, involves acute inflammation but not tissue destruction. Over the first 3 days of infection, vasodilation and infiltration of infected brain by inflammatory cells (polymorphonuclear leukocytes, lymphocytes, and mononuclear cells) produce a poorly demarcated lesion with incipient central necrosis and peripheral edema. A nonenhanced CT scan may be normal or may demonstrate a poorly marginated hypodense subcortical area. There is minimal, if any, enhancement with intravenous contrast. MRI may more readily identify any edema that is present. Second, the late cerebritis stage usually occurs between 4 and 9 days. During this phase, the central area of the infection becomes necrotic and surrounded by a ring of inflammatory

cells, macrophages, and fibroblasts. On CT, patchy enhancement occurs at the beginning of this stage, and ring-enhancement develops later. The central low-attenuating region may enhance on a delayed image. On MRI, ring enhancement is more discernible earlier; surrounding edema appears hypointense relative to normal brain. Third, early capsule formation is usually visible between 10 and 13 days. Necrosis and liquefaction occur, and a fibrotic collagenous capsule begins to form. Isolation of the process within this capsule helps limit surrounding edema and its mass effect. Radiographically, a distinct, thin-walled capsule is visible before contrast administration. It often enhances brightly with contrast. Finally, late capsule formation is visible after 2 weeks. A thick, brightly enhancing fibrotic capsule is quite apparent on imaging.20,21 An intraparenchymal abscess may preferentially extend toward and then rupture into a ventricle. Capsule formation is more complete on the superficial than on the deep side of most abscesses.22 This thinner capsule may reflect a less abundant vascularity. Encapsulation is also less extensive in

L. Sims, M. Lim, and G.R. Harsh

178 Table 2 Pathological Stages of Brain Abscess Development

Stage

Time course (days)

Early cerebritis

1-3

Late cerebritis

4-9

Early capsule formation

10-13

Late capsule formation

>14

Histopathology

CT findings

Vasodilation and infiltration of infected brain by inflammatory cells produces poorly demarcated lesion with incipient central necrosis and peripheral edema Central area of infection becomes necrotic and surrounded by ring of inflammatory cells, macrophages, and fibroblasts

Nonenhanced scan normal or may demonstrate poorly marginated hypodense subcortical area. Minimal, if any, enhancement with intravenous contrast

MRI findings Better visualization of edema

Ring enhancement more discernible earlier; surrounding edema appears hypointense relative to normal brain Distinct, thin-walled capsule visible The capsule appears as a dark rim encircling before contrast administration. the bright core and Capsule enhances brightly with bright surrounding contrast brain tissue Patchy enhancement occurs earlier and ring-enhancement develops later during this stage. Central low-attenuating region may enhance on delayed image

Necrosis and liquefaction occur, and fibrotic collagenous capsule begins to form. Isolation of the process within capsule helps limit surrounding edema and mass effect Thick collagenous capsule formed Thick, brightly enhancing fibrotic capsule apparent on imaging

Modified from Reference 21.

abscesses resulting from hematogenous spread than in those arising from contiguous infections.23

Clinical Course The clinical course varies from indolent to fulminant. A triad of fever, headache (usually localized), and focal neurological deficit is described. This, triad, however, is nonspecific and thus obscures the urgency in obtaining the correct diagnosis. Nonetheless, most abscesses are diagnosed within 2 weeks of symptom onset.12 Seizures occur in 30 to 60% of patients.24 Patients with a frontal brain abscess are particularly vulnerable to recurrent seizures. Other signs and symptoms include nuchal rigidity and indications of increased intracranial pressure—mental status change, vomiting, and papilledema. If the abscess ruptures, patients report acute worsening of headaches and confusion. Lethargy can also progress acutely to somnolence or coma.2,24

tinguish abscesses from other ring-enhancing lesions such as necrotic or cystic neoplasms. Abscesses appear hyperintense on DWI, while tumors are hypointense.25 CT or MRI can also detect intraventricular rupture of a brain abscess. On CT the abscess may appear to be continuous with the ependymal surface of the ventricle, and puru-

Diagnosis Brain abscesses are diagnosed by CT or MRI and biopsy (Figs. 1-3). CT with contrast reveals the size, number, and location of abscesses; however, ring enhancement on CT is not specific for brain abscesses. Although CT is also used to monitor the response to treatment, CT findings can lag behind clinical findings.23 CT is less sensitive and less specific than MRI for the diagnosis of brain abscesses. MRI is the preferred imaging modality for both diagnosis and monitoring the pataient’s response to treatment. MRI can detect both early cerebritis and satellite lesions (Fig. 2). It also can accurately estimate the extent of central necrosis and edema. Furthermore, it depicts brain anatomy with high resolution.2 Diffusion-weighted MR imaging (DWI) helps dis-

Figure 1 Axial noncontrast CT scan shows a left frontal abscess with surrounding edema.

Review of brain abscesses

Figure 2 Axial T1-weighted MRI with contrast of the same left frontal abscess also shows a satellite lesion not seen on CT.

lence may be seen within the ventricle (Fig. 4). On MRI, the relation of the abscess to the ventricle is better defined. Associated ventriculitis may also be apparent (Fig. 5). Imaging and autopsy studies have revealed the following order of frequency of abscess location: temporal lobe, frontal

Figure 3 Axial T2-weighted MRI of the same left frontal abscess shows a rim of hypointensity surrounding the primary lesion.

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Figure 4 An axial noncontrast CT scan of a brain abscess after intraventricular rupture shows purulence forming a fluid-fluid level in the body of the left lateral ventricle.

lobe, parietal lobe, occipital lobe, and cerebellum26 (Table 3). Despite the valuable information provided by CT or MRI, tissue diagnosis is often needed. Suspicion of an intracranial mass precludes lumbar puncture before imaging. If mass effect is only local and limited, lumbar puncture can be per-

Figure 5 Axial T1-weighted MRI with contrast of a brain abscess after intraventricular rupture shows ventriculitis.

L. Sims, M. Lim, and G.R. Harsh

180 Table 3 Locations and Frequencies of Brain Abscesses Abscess Location Temporal Lobe Frontal Lobe Parietal Lobe Occipital Lobe Cerebellum Basal Ganglia Brain Stem Pituitary Fossa

Frequency (%) 29 24 21 11 9 3 2 0.4

Modified from ref. 26

formed safely. Cerebrospinal fluid (CSF) from a patient with an isolated parenchymal abscess rarely yields the diagnosis; common findings are elevated opening pressure, elevated protein (usually less than 100 mg/dL), pleocytosis with white cell counts less than 100 cells/mL, normal glucose, and sterile cultures. Lumbar puncture is of value in excluding bacterial meningitis. The CSF profile resulting from intraventricular rupture of an abscess resembles that of fulminant meningitis: white blood cell counts of 100 cells/mL or higher, hypoglycorrhachia, elevated protein, and lactic acid level above 500 mg/dL.27,28

Treatment Successful management of a brain abscess usually requires a combination of surgery and antibiotics. When unobtainable from elsewhere in the body, infected tissue samples for culture must be obtained from the brain. If CSF cannot be obtained or is unrevealing on culture, the abscess must be sampled. Sampling is usually more easily and less invasively accomplished by stereotactic biopsy than by craniotomy. Simultaneous aspiration of any fluid within the abscess of sufficiently low viscosity to pass through the biopsy needle may reduce the volume of infected tissue, thus diminishing mass effect within the brain and enhancing the effect of antibiotics. As a minimally invasive procedure, stereotactic aspiration is valuable in treating deep lesions, lesions in eloquent areas, and multiple abscesses. Occasionally, multiple stereotactic aspirations are warranted. Indications for surgical excision rather than biopsy include rapid neurological deterioration from mass effect, incipient rupture of the abscess into a ventricle, impenetrability of the abscess capsule to a biopsy needle, lack of clinical recovery within a week of antibiotic therapy, and failure of the abscess to involute radiographically during 2 weeks of antibiotic therapy. Craniotomy is also often preferred for traumatic brain abscesses (allowing foreign bodies to be removed), abscesses associated with a CSF leak (allowing repair of a CSF fistula), encapsulated fungal abscesses (because of relative resistance to antibiotic therapy), cerebellar abscesses (because unsuccessful treatment leads to rapid deterioration and death), abscesses containing gas (because it allows bacteriological diagnosis, removal of the mass lesion, and permanent closure of any external communication), and abscesses that reaccumulate after repeated aspirations. Excision also may reduce the required duration of antibiotic therapy and the frequency of recurrence. The craniotomy should minimize the eloquent cortex to be

traversed; computer-assisted navigation may help plan a safe, minimally disruptive trajectory. The abscess should be removed as a single specimen, avoiding spillage of its contents and minimizing resection of surrounding brain. Broad-spectrum antibiotics should be administered as soon as an abscess is suspected. Fear of rendering cultures sterile does not warrant delay in instituting treatment. The responsible organism will often be identified by Gram stain or culture of pus inside the resected abscess. The choice of antibiotics before microbial results are available is based on predisposing factors and potential pathogens. Identification of the organism(s) and their sensitivities to various antibiotics often prompts modification of the drug regimen. The regimen should be a combination of agents chosen to be active against a broad spectrum of bacteria and be able to reach adequate levels within the brain parenchyma. Antibiotics are administered for at least 4 weeks (Table 1). Clinical and radiographic change is monitored by monthly neurological examinations and CT or MRI studies to determine the duration of therapy. Antibiotics should usually be continued until the sequestered pus is completely obliterated, enhancement of the abscess wall is substantially diminished, and local edema and mass effect are significantly improved. Corticosteroids (intravenous dexamethasone, 4 mg every 6 hours) should be administered if edema-related mass effect threatens brain herniation or severely depresses mental status. However, they should not be continued beyond the acute clinical phase (1 week).29,30 The optimal treatment for intraventricular rupture of an abscess is controversial. Some have recommended a combination of intrathecal and intravenous antibiotic therapy. Others advocate placement of a ventricular drain to reduce intracranial pressure, ventricular lavage, or delivery of antibiotics.31 An external ventricular drain is particularly helpful in relieving acute hydrocephalus (present in 30% of cases) or in decompressing a ventricle trapped by abscess debris or inflammation. Still others favor urgent craniotomy for evacuation of spilled pus and lavage of the ventricles under direct vision.32,33 The use of corticosteroids for incipient intraventricular rupture of an abscess is also controversial. Steroids should reduce cerebral edema and mass effect, but they also may hamper the penetration of antibiotics into the abscess, retard encapsulation, and increase the risk of rupture. Discontinuance of steroids can also prompt a rebound of cerebral edema.

Prognosis Patient outcome is critically dependent on treating the abscess before it ruptures into the ventricles: the mortality rate of a treated unruptured abscess climbs from less than 10% to more than 80% after its rupture. Other unfavorable factors include rapid progression of the infection before treatment, delayed diagnosis or misdiagnosis, coma, multiple abscesses, deeply located abscesses, inadequate treatment, and specific organisms (eg, Aspergillus species, other fungi, and Pseudomonas species).26,34,35 Positive prognostic indicators are earlier detection, age less than 21 years, a single abscess, normal mental status at diagnosis, and a long interval between onset of symptoms and rupture into a ventricle. The size of the abscess is not significant.

Review of brain abscesses Despite appropriate therapies, 5% to 10% of abscesses recur. A recurrence is typically evident within 6 weeks of the completion of treatment. The latency of some recurrences, however, has been several years. The leading causes of recurrence are incorrect choice, insufficient dose, or too brief administration of antibiotic and failure to eradicate the primary source of infection.

Summary A brain abscesses is a serious condition that must be treated aggressively. MRI and CT are invaluable tools for facilitating diagnosis and monitoring treatment. Successful management of patients with intracranial abscesses depends on a high index of suspicion that subtle clinical changes manifest an infection, early detection by imaging, appropriate surgical intervention and correct antimicrobial therapy. Intraventricular rupture of a brain abscess is associated with a grim prognosis.

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