Brain Abscess

(in the non-immunocompromised host)

  Internal Medicine Resident Grand Rounds

Introduction

Brain abscess consists of a focal suppurative infection within the brain parenchyma. This disease has been described in literature dating as early as the sixteenth century, and surgical treatment of brain abscess was first described in 1752. Dr. William Macewen produced a landmark text on pyogenic brain diseases in 1893 describing clinical diagnosis and surgical therapy of brain abscess. This technique included surgical drainage and irrigation with antiseptic solution. Ventriculography was introduced in 1918 and significantly aided the diagnosis and localization of abscesses. Later developments have included angiography, radionuclide brain scans, computed tomography scans and magnetic resonance imaging. Important early therapeutic adjuncts included chemotherapeutic agents (e.g. sulfanilamide in the 1930’s) followed by penicillin (first used on patients in 1941). With the introduction of antimicrobials the overall mortality rate from brain abscess decreased during the next two decades but remained high. A significant decrease in brain abscess mortality was eventually realized after development of the CT scan. Current treatment of brain abscess includes needle aspiration, possible surgical resection, and several weeks of parenteral antimicrobials along with possible corticosteroids to reduce edema. Despite these recent advances in diagnosis and therapy, brain abscess mortality rate is strongly related to the patient’s initial neurological status and early diagnosis is most important in achieving a favorable outcome.

Brain abscess incidence has remained stable during the last fifty years accounting for an estimated 1 in 10,000 hospital admissions and approximately 4-10 cases per year on neurosurgical services in developed countries (excluding immunocompromised patients). The etiology and incidence of brain abscess varies among different geographic areas, with an average male predominance of 2:1 and a median age of 30-45 years. Incidence is higher in underdeveloped countries, and has increased among the immunocompromised patient population (including transplant, chemotherapy and AIDS patients) with abscesses frequently caused by opportunistic organisms.

Brain abscess formation includes microorganism entry, initial focal cerebritis, necrosis, edema, petechial hemorrhage, pus formation, fibroblast entry, collagen deposition and finally encapsulation which is complete after approximately two weeks.^5,6 Capsule formation helps to limit infection spread and parenchymal destruction, and the late capsule stage is composed of five distinct zones: necrotic center, peripheral inflammatory cells and fibroblasts, collagen capsule, neovascularity and cerebritis immediately external to the capsule, and edema and reactive gliosis in the surrounding parenchyma.⁷ Abscesses may be single or multilobulated and act as an expanding mass lesion with surrounding cerebral edema.

Brain abscess develops in association with four principal conditions:

1) Contiguous infectious foci - Brain abscess formation resulting from local spread of infection accounts for approximately 40% of cases.^4,8 These lesions are usually solitary and the most common sources include paranasal sinuses, middle ear, mastoid and dental infections.⁵ Otitis media alone is responsible in approximately 20% of cases.⁹ In recent years otogenic brain abscesses have decreased in frequency possibly due to the common use of antimicrobials for upper respiratory infections.⁴

2) Hematogenous spread - Abscess formation secondary to spread from distant infectious sites accounts for approximately 25% of cases.^4,8 Sources include pulmonary infections, congenital heart disease with right-to-left shunt, diverticulitis, osteomyelitis, dental abscess, skin pustules and bacterial endocarditis.⁵ Other important preceding processes include cholecystitis, pelvic infections, intraabdominal abscesses, hereditary hemorrhagic telangiectasia, and endoscopic sclerosis of varices or dilation of esophageal strictures.⁴ These lesions distribute proportional to regional cerebral blood flow and may be multiple, usually occurring at the corticomedullary junction where blood flow is slowest. Most are located in the frontal and parietal lobes in a middle cerebral artery distribution.^4,5 Transient bacteremia is unlikely to result in brain abscess formation since the blood-brain barrier is resistant to infection. Children with congenital cyanotic heart disease are at increased risk secondary to presence of right-to-left shunt allowing blood-borne bacteria to bypass filtering at the pulmonary capillary bed. Endocarditis is not seen as an important cofactor, however. Hypoxemia with resultant polycythemia and increased blood viscosity lead to cerebral microinfarction and favorable conditions for abscess development. Brain abscess is one of the leading causes of morbidity and mortality in cyanotic heart disease.⁵

3) Trauma - Brain abscess as a result of trauma accounts for approximately 10-20% of cases.⁸ These infections occur relatively soon after insult and are usually a consequence of retained bone fragments and debris. Abscesses may also develop secondary to basal skull fractures with CSF fistulae and meningitis.⁵

4) Cryptogenic - Brain abscess formation without identified source of infection or predisposing condition occurs in approximately 15-20% of cases.⁴

An identifiable predisposing condition or source exists in 70-80% of brain abscess patients. In each setting a compromised area of brain is required for abscess development, and localized damage occurs by thrombophlebitis (with contiguous infections or localized infarction associated with emboli) or by increased blood viscosity (with congenital cyanotic heart disease or hereditary hemorrhagic telangiectasia).⁴

The microbiology of reported brain abscess cases has changed during the past 50 years. Streptococci, pneumococci, and Staphylococcus aureus were most commonly isolated several decades ago; followed by a decline in the incidence of S. aureus abscesses likely secondary to a reduced incidence of serious staphylococcal infections and more effective antimicrobial use.⁵ In more recent series aerobic bacteria account for approximately 60% of isolates with streptococci 30% and S. aureus 15% overall. Streptococci have been identified in approximately 70% of all abscesses (including mixed infections).⁴

Gram-negative aerobic abscesses have increased in incidence in recent years⁵ and comprise approximately 15% of isolates. The most frequently encountered aerobic gram-negative bacilli include Enterobacter, Klebsiella, Escherichia coli, Proteus and Pseudomonas species.⁴

Anaerobic isolates have also increased recently, likely due in part to improved anaerobic isolation techniques,⁵ and represent approximately 30% of isolates. The most common isolates include Bacteroides, anaerobic streptococci (Peptostreptococcus), Fusobacterium and Clostridium species. Anaerobes are frequently present with underlying chronic ear or pulmonary disease.⁴

Mixed infections are present in approximately 30-60% of brain abscess cases⁴ and are common with otogenic infections. Negative cultures occur in up to 25% of cases but are heavily dependent on early antimicrobial therapy, proper specimen handling, and isolation techniques.^5,8

The microbiological profile of a brain abscess is linked to the origin of infection and knowledge of common etiologies is very useful in planning initial antimicrobial therapy.⁵ For example, frontal lobe abscesses in the setting of sinusitis most often reveal streptococci, post-traumatic abscesses most often reveal staphylococci, and otitis media-related abscesses are most often mixed infections with streptococci, gram-negative aerobic bacilli, and Bacteroides species.³ This profile is significantly affected by an individual’s immune status as fungal and parasitic organisms are much more likely in immunocompromised patients.⁴

Clinical Manifestations

Symptomatology of a brain abscess is nonspecific and depends on several factors including abscess size, location and number along with organism virulence, patient immune status, host response, and severity of edema.^4,5 Tissue destruction and edema result in symptoms of elevated intracranial pressure and focal neurologic deficits. Presenting manifestations may be similar to those of a tumor or other mass lesion; however, abscess-related symptoms are usually more rapidly progressive than with a neoplasm, being present for less than 1-2 weeks on initial presentation.⁵

The classical triad of fever, headache, and focal neurologic deficit is present in less than 50% of cases.⁴ Headache is present in approximately 70% of patients, and nausea and vomiting occurs secondary to increased intracranial pressure in approximately 25-50% of patients.^4,5 Low grade fever develops in approximately 50% of cases; however, fever above 101.5° F is uncommon and may indicate systemic infection or meningitis. Mental status changes are present in 60-70% of patients and range from confusion and drowsiness to obtundation and coma.⁵ Focal neurologic deficits are evident in 50-60% of cases depending on size, number, and location of abscesses. Seizures occur in approximately 25-45% of cases.^4,5 Patients may also develop visual disturbances, papilledema, meningismus, and nuchal rigidity.^3,4,5 Other symptoms secondary to an extracranial infectious focus may be present and obscure brain abscess manifestations.³ As mentioned above, symptoms related to a brain abscess usually follow a rapid onset and progressive time course.

Brain abscess symptomatology can be divided into two groups: intracranial infection causing fever, elevated erythrocyte sedimentation rate, and leukocytosis; and expanding mass lesion resulting in headache, mental status changes, hemiparesis, seizures, nausea and vomiting, papilledema, or pupillary changes, depending on abscess location.⁶

Physical exam findings may be minimal in the absence of an identifiable primary focus of infection. Examination should carefully observe for signs of an infectious focus, and neurologic exam will usually suggest presence of a mass lesion in combination with the common symptoms mentioned above.³

The differential diagnosis of brain abscess includes subdural empyema, epidural abscess, pyogenic meningitis, neoplasm, encephalitis, infarction, mycotic aneurysms, chronic subdural hematoma, intracerebral or subarachnoid hemorrhage, and vasculitis.^3,4

Routine laboratory studies are not usually helpful in diagnosing brain abscess. Leukocyte counts are normal or only mildly elevated (less than 15,000) in 60-70% of cases.⁹ Erythrocyte sedimentation rate is elevated in up to 90% of patients but is nonspecific.⁵ Elevated C-reactive protein may be of some value in differentiating brain abscess from tumor.¹⁰

Lumbar puncture is not indicated when clinical findings suggest intracranial mass lesion, and this procedure should be delayed in patients with febrile CNS disorders and focal neurologic signs.³ Studies reveal that lumbar puncture performed in brain abscess patients may result in significant morbidity in addition to their low diagnostic yield¹¹. Elevated intracranial pressure is potentially dangerous, and CSF findings are nonspecific with wbc <100 (unless meningitis coexists), protein <100, glucose normal, and cultures usually remaining sterile.⁵

Brain abscess cultures should include sampling of the abscess cavity material, capsule, and surrounding tissue if available. Gram stain, aerobic and anaerobic cultures, histologic analysis, and mycobacterial and fungal cultures should be performed.⁸

The most important development in brain abscess diagnosis and management during the last 20 years has been the use of computed tomography scans. CT scanning has reduced diagnostic delay and has rendered other tests including angiography, ventriculography, pneumoencephalography, and radionuclide brain scanning obsolete.⁵ Sensitivity and specificity of the CT scan (with contrast) in diagnosing brain abscess approach 100%,¹² and this study allows early diagnosis, localization, and staging of abscesses into cerebritis or capsule stages.⁷ The characteristic CT finding is a ring-enhancing lesion with surrounding edema¹³ which develops in approximately 75% of cases. Contrast and ring enhancement occurs to varying degrees, and capsule features along with findings including multiloculation, multiplicity, location at corticomedullary junction, and leptomeningeal or ependymal enhancement help distinguish abscess from neoplasm.⁵ CT scan may also reveal a hypodense lesion center, presence of midline shift, hydrocephalus, or imminent ventricular rupture.³ Repeat scans should be obtained when a non-diagnostic scan is obtained in the clinical setting consistent with brain abscess.⁸ Careful interpretation and clinical correlation of findings are important since the differential diagnosis of ring-enhancing lesions includes malignant glioma, metastatic tumor, infarction, resolving hematoma, and radiation necrosis,¹² along with granuloma, arteriovenous malformation, or thrombosed aneurysm.¹⁴ The high sensitivity (95-99%) but lower specificity of CT scan in diagnosing brain abscess is due to this differential.¹⁵

Magnetic resonance imaging studies may be more sensitive in detecting early cerebritis, edema, and satellite lesions,¹⁶ but usually have no overwhelming advantage over the CT scan. Some authors, however, advocate MRI as the procedure of choice in brain abscess evaluation due to the better tissue characterization, multiplanar imaging, lack of radiation, lack of bone artifact, and decreased toxicity of gadolinium contrast agents with this study.⁴

¹¹¹Indium-labeled leukocyte scans may aid in brain abscess diagnosis when CT or MRI findings are inconclusive. A suppurative intracranial infection usually produces a significantly more intense inflammatory response than does a neoplasm, aiding differentiation of brain abscess versus tumor. Labeled leukocyte scanning can be a useful adjunct, but the principal disadvantage of a 24 hour delay for optimal images makes this study best suited for patients in stable condition and not requiring emergent intervention.¹⁷

Technetium-99 brain scans are also very sensitive in brain abscess detection and are the procedure of choice in areas where CT and MRI studies are unavailable.^3,8

Choice of antimicrobials in brain abscess treatment depends on several factors including drug efficacy against particular organisms, route and duration of therapy, host response, and drug concentration achieved at abscess site. Initial emperic therapy should be based on knowledge of the common organisms associated with a suspected abscess etiology (see Table 2). Culture and sensitivity data should be obtained whenever possible and treatment should be tailored once data is available. Intravenous antimicrobials should be continued for at least six weeks with follow-up imaging periodically to assess therapy.⁵

Traditional therapy has included intravenous penicillin G and chloramphenicol. In more recent years, metronidazole has replaced chloramphenicol for anaerobic therapy with its excellent CNS penetration and anaerobic activity. Nafcillin or vancomycin should be used if S. aureus is isolated, and third-generation cephalosporins are indicated for gram-negative and most streptococcal infections. Ceftazidime with or without an aminoglycoside is used for Pseudomonas aeruginosa isolates. Antimicrobials can be further tailored once sensitivity data is obtained from abscess cultures.⁴

Some authors have advocated medical therapy alone for brain abscess treatment,¹⁹ however, many disadvantages of this strategy exist. Without surgical intervention, culture and sensitivity data cannot be obtained, and a confirmation of the diagnosis is not possible. Surgical aspiration allows immediate reduction in mass effect and intracranial pressure, and removal of purulent material reduces abscess cavity acidity and provides a more favorable environment for antimicrobial therapy.⁵ Studies reveal that larger abscesses (greater than 2.5 cm. in diameter) do not usually resolve without surgical drainage,²⁰ but cerebritis in a neurologically stable patient may be effectively treated with antimicrobials prior to possible intervention.¹⁹

Corticosteroids are beneficial in reducing edema and mass effect, but their use remains controversial. These agents may hinder therapy by reducing antimicrobial entry into the CNS.⁴ Side effects include inhibition of leukocyte migration during early abscess stages and reduction of host defenses. Steroids also reduce CT contrast enhancement causing false interpretation of abscess size and resolution. This treatment is best used when mass effect is believed to cause neurologic deficits, and should be tapered as the clinical condition allows.⁵

Surgical options for brain abscess management include aspiration, complete excision, and continuous drainage. Procedure choice may depend on patient age, neurologic condition, abscess location and stage, abscess type, and presence of single or multiple lesions.⁵

CT-guided aspiration is easily accomplished via a single burr hole under local anesthesia, and precise abscess localization is performed by CT-guided stereotaxy or ultrasound exam. Multiple abscesses can be aspirated via a single approach. This procedure allows rapid diagnosis confirmation, provides useful culture material, and allows complete abscess decompression with minimal trauma to surrounding brain parenchyma. Aspiration results in an immediate reduction in mass effect and intracranial pressure and can be performed at any abscess stage. Evidence also suggests that pus removal creates a more favorable environment for antimicrobial effectiveness; however, no evidence exists to support direct instillation of antimicrobials which may even be deleterious and promote infection spread. This procedure is very useful in deep-seated or multiple abscesses and in areas where excision would risk significant dysfunction.⁵

Craniotomy and abscess excision is indicated in several situations. Post-traumatic abscesses may need excision to remove retained debris, and fungal abscesses are more likely to be cured if complete excision is performed.⁵ Excision is also indicated in gas-containing brain abscesses since presence of gas is most often secondary to a dural fistula which requires repair.¹⁸ Multiloculated abscesses may also need excision due to difficulty in completely aspirating such lesions.⁵

Disadvantages of craniotomy and excision include inappropriateness in early cerebritis stage which is better treated with aspiration. This procedure is not useful with deep lesions or with abscesses in sensitive areas risky for significant dysfunction. Excision is also not indicated when multiple lesions exist.⁵

Each case must be evaluated on an individual basis, and no standard treatment guidelines exist. CT-guided aspiration is useful in most cases and provides a relatively easy method of diagnosis, culture, and treatment. Well-encapsulated, post-traumatic, fungal, or multiloculated abscesses in silent areas may be best treated with complete excision.⁵ Antimicrobial therapy should be initiated immediately, with subsequent treatment dependent on clinical condition, radiological findings, and culture results. Multiple aspirations may be required, and continued neurologic deterioration or failure of the lesion to resolve may indicate that further surgery and excision is necessary.⁴

Diagnostic and therapeutic advances have allowed a significant reduction in brain abscess mortality, from 40-50% prior to 1970 reduced to approximately 10% by the late 1970’s.^9,21 Important advances have included improved microbiological isolation techniques, more effective antimicrobials, and improved surgical techniques. The single most important development has been the use of CT scanning²² along with CT-guided stereotaxy.⁵

A delay in surgical intervention can result in morbid consequences including herniation secondary to increased intracranial pressure, or rupture of the abscess into the ventricles or subarachnoid space. Mortality is also influenced by the patient’s clinical course, organism virulence, and abscess origin and location.⁵ The single most important factor influencing mortality is the patient’s neurologic status at presentation and diagnosis.⁹

Long term morbidity can result with seizures, cognitive dysfunction, and focal neurologic deficits being most common. Seizures occur in 30-50% of cases and are related to abscess location and method of surgical intervention. Up to 50% of patients may suffer long-term neurologic deficit and disability depending on patient age and abscess location. Recurrence occurs in 5-10% of cases despite adequate therapy, with most occurring within six weeks. Radiologic evidence of abscess resolution occurs later than clinical improvement, and reduction in size usually occurs within 2-3 weeks of treatment. Complete resolution may not be evident for up to 3-4 months, and occasionally contrast enhancement may last for up to 6-9 months.⁵

Despite recent advances, brain abscess remains a serious disease that commands rapid diagnosis and intervention. Clinical findings consistent with possible brain abscess must be recognized, and imaging studies should then be obtained to evaluate the diagnosis. Aspiration should be performed as soon as possible to confirm the diagnosis, obtain cultures, and provide therapeutic benefit. Rapid administration of intravenous antimicrobials directed against the most likely pathogens is very important, and culture data can later be used to tailor therapy. Treatment should be continued for at least six weeks with follow-up imaging studies at regular intervals to assess therapy. Underlying sources and predisposing conditions for abscess formation should be identified and treated whenever possible. As previously mentioned, the patient’s initial neurologic status is the most important prognostic factor, and rapid diagnosis with proper therapy is paramount in reducing morbidity and mortality of brain abscess.