Brain Abscess in Emergency Medicine

Brain abscess is a focal intracranial infection that may present with mild vague symptoms or as a life-threatening emergency. It begins with an area of unencapsulated inflammation, known as cerebritis, and develops into a collection of necrotic pus surrounded by a vascular capsule. Brain abscess occurs as the result of a complication of variety of infections, trauma, or surgery and carries significant morbidity and mortality.[1, 2]

For centuries, brain abscess was thought of as almost certainly fatal. In 460 BCE, Hippocrates cautioned his readers of the condition, "For there is danger that the man may become delirious and die" and recommended intracranial drainage as the only cure.[3] However, over the last half century, the epidemiology of this condition has shifted dramatically[4] ; improvements in the detection and treatment of ear, sinus, and orofacial infections has decreased the incidence of brain abscess as a consequence of direct spread of infection. Meanwhile, the population prevalence of chronic immune suppression and immunocompromise has grown, and with it there has been a rise in opportunistic and fungal brain abscess. Indeed, case fatality rates have decreased from 40% to 10% over the past 50 years.[5] Management of these complex patients may require close cooperation of specialists in infectious disease, radiology, and neurosurgery.

Animal and human modeling of brain abscess has demonstrated a 4-stage process of disease progression.[6, 7] The process begins with direct inoculation of microorganisms into the brain parenchyma, resulting in focal inflammation in the 1-3 days following, which is referred to as early cerebritis.[8] The increased permeability of the blood vessels without production of new blood vessels is noted on a microscopic level.[9]

Polymorphic neutrophils are then recruited, leading to edema. Glial cells are activated, and the area of inflammation continues to grow as the central zone develops coagulation necrosis; this is a hallmark of the second stage, called late cerebritis, which occurs at approximately 3-6 days.[10, 11]

A well-vascularized, ring-enhancing fibrotic capsule forms after approximately 2 weeks and may be seen on CT. As the host defenses mount, the capsule is walled off, thus completing the development of the abscess.

The fourth stage is often marked by considerable gliosis on the cortical surface of the abscess. Tissue destruction is likely dependent on the virulence of the organism and the exuberance of the host response.[12]

The pathogenesis of an invading organism that has inoculated the brain parenchyma is variable and dependent on the initial site of infection, host factors, and geographic location. Infection can be due to bacteria, fungi, or protozoa. Brain abscess has traditionally been classified by the primary source of the pathogen,[2, 13] with the most common etiologies being direct extension, metastatic spread, and intracranial penetrating trauma.

Direct extension

Brain abscess may be caused by the contiguous spread of pathogens from a primary focus of infection outside of the CNS that extends into the brain. Pathogens may originate from adjacent bone, teeth, sinus mucosa, internal auditory canal, or cochlear structures and travel into the intracranial vault via venous drainage or valveless emissary veins, thus inoculating the brain parenchyma.[13] Abscess caused by direct extension usually leads to a solitary lesion.

Although less common, brain abscess has been described as a complication of frontal, ethmoidal, or sphenoidal sinusitis.[14] Dental infections can lead to brain abscess via either contiguous or hematogenous routes. Meningitis rarely results in brain abscess by direct extension, particularly in adults, and therefore in most cases the finding of brain abscess should not prompt a search for meningeal infection via lumbar puncture.[15]

In the past, chronic otitis media and mastoiditis were the most common underlying etiologies; however, complications of these infections have decreased in incidence with improvements in diagnostic modalities and antibiotic therapy. Overall, abscess caused by direct extension now comprises 12-25% of all brain abscesses[2] ; however, where adequate healthcare infrastructure is lacking, direct extension continues to comprise approximately 50% of brain abscess collectively.[16, 17]

Metastatic spread

Hematogenous seeding of the brain from an extracranial source is the second most common etiology of brain abscess, accounting for approximately 25% of cases. While most bacteremias do not cause brain abscess, when they do, abscesses are frequently multiple and are often found in the distribution of the middle cerebral artery or watershed zones.[13, 18] When hematogenous spread is the underlying cause, there is often an additional predisposing factor; patients with comorbid conditions such as congenital heart disease with right-to-left shunt, pulmonary venous malformations, or hereditary hemorrhagic telangiectasia are at relatively high risk for brain abscess.[19]

Among extracranial sources, chronic pulmonary infections such as lung abscess, bronchiectasis, and empyema have been frequently associated with hematogenous brain abscess. Bacteremias associated with endocardial, abdominal, pelvic, or skin infections can lead to brain abscess. Approximately 15% of cases have no identifiable source.[1]

Intracranial trauma

The formation of brain abscess after intracranial trauma or neurosurgical intervention is well described. In the case of penetrating trauma, brain abscess may form as an immediate or delayed complication; direct inoculation of pathogens can quickly lead to abscess formation, whereas a retained foreign body or focus of necrotic tissue can serve as a nidus of infection months or years after the initial insult.[20, 21] Compared with earlier series, there has been an increase in the proportion of brain abscess caused by direct trauma or neurosurgical intervention; the incidence in recent studies has ranged from 2-37%.[2, 22, 23] One significant factor accounting for this trend is the relative decline in otogenic brain abscess. Variability in outcome depends greatly on the age and underlying condition of the patient.

Frequency

United States

The etiology, incidence, and outcome of brain abscess vary greatly across populations. In developed countries, brain abscess is now a rare entity in the general population, with approximately 1,500-2,500 cases reported annually in the United States and an estimated incidence rate of 0.3-1.3 cases per 100,000 per year.[24] Immunocompromised patients form a special subpopulation that sustains a higher incidence of brain abscess with a wider variety of causative organisms.[25, 26]

International

Populations in low-resource settings have a higher burden of brain abscess.[27] It accounts for less than 1% of intracranial lesions in the developed world, as opposed to roughly 8% in developing countries.[28, 29] Without access to advancements in diagnostic imaging and antibiotic regimens, the development of brain abscess from otogenic and odontogenic infections continues unabated. Additionally, populations with increasing prevalence of HIV infection have witnessed a concomitant increase in incidence of brain abscess.[30]

Underlying pathophysiology of brain abscess varies across locales, with mycobacterial infection (tuberculoma) being more common in parts of Asia. Neurocysticercosis is more prevalent in parts of Latin America and is also becoming more prevalent in the United States, particularly among immigrant communities.[31]

Mortality/Morbidity

In the preantibiotic era, mortality from brain abscess was nearly 100%.[27] Despite the introduction of antibiotics and improvements in neurosurgical drainage techniques, the mortality rate remained around 30-50% through the 1970s. The introduction of enhanced neuroimaging techniques, such as CT and MRI, allowed for rapid, accurate diagnosis and localization of brain abscess.[32] In most modern series, the mortality rate is typically less than 15%.[23, 33, 17] Rupture of a brain abscess is uncommon but is associated with a high mortality rate (up to 80%).[2]

Significant morbidity, including seizures, persistent weakness, aphasia, or cognitive impairment, affects an estimated at 20-30% of survivors.[23] In pediatric populations, outcomes have been shown to vary according to how rapidly antibiotics are initiated.[34] Favorable outcomes have been associated with a number of factors, including initial Glasgow Coma Scale score of higher than 12, absence of underlying disease, or sepsis.[23]

Race

No compelling evidence exists for racial differences in the incidence of brain abscess.

Sex

Although brain abscess can affect both sexes, in multiple series of both pediatric and adult patients, the male-to-female ratio of brain abscess has been demonstrated to range from 2:1 to as great as 4:1.[17, 35, 16, 5]

Age

Throughout the first half of the 20th century, the age distribution of brain abscess was bimodal, with the highest rates being among children and adults older than 60 years. However, advancement in vaccination trends and antibiotic strategies, as well as a growing population of chronically immunosuppressed patients, has led to a shift in the demographics towards the middle decades.[36] Overall, about 25% of cases of brain abscesses still occur in children, typically among those aged 4-7 years.[37] In pediatric series, congenital heart disease remains the most common predisposing factor.[38]

The mortality rate of brain abscess has improved over the years, but poor access to medical care in less-developed countries has affected the rates of improvement in those areas. Rates have continued to remain higher in immunocompromised individuals than in persons with stable immune systems.[9] Patients with a rapidly declining neurological status on initial presentation have a poorer prognosis.[23] Seizures remain the most common concern following treatment; long-term sequelae can occur in 30%-50% of affected patients.[39, 40]

The mortality rate of brain abscess has decreased to 15% in most developed countries, while mortality in resource-poor settings remains higher.[41]  One of the most important factors in prognosis is the availability of healthcare resources. Mortality rates among immunocompromised patients are higher, despite appropriate surgical and medical therapy.[42]  If immunosuppressive agents can be reduced, the chance of a positive outcome is improved.[1]

Key prognostic factors include associated with improved prognosis include the following:

• Young age
• Absence of severe neurologic defect on initial presentation. ^{[14, 23]}
• Absence of neurologic deterioration during initial presentation ^[39]
• Absence of comorbid disease ^{[2, 14]}

Worse prognosis of brain abscess is associated with the following:

• Advanced age
• Hematogenous spread ^[43]
• Immunosuppression ^[43]
• Evidence of intraventricular rupture ^[44]
• Evidence of herniation on initial presentation ^[45]
• Evidence of altered sensorium on initial presentation ^[17]
• Severity of abscess and abscess location on initial neuroimaging ^[46]
• Delay in diagnosis or definitive surgical intervention ^[47]
• Certain pathogens, including gram-negative bacteria, ^[28]  nocardial abscess, ^[48]  or aspergillosis ^[49]  portend a worse prognosis and higher mortality rates, particularly in immunocompromised patients

For excellent patient education resources, visit eMedicineHealth's Infections Center and Brain and Nervous System Center. Also, see eMedicineHealth's patient education articles Antibiotics and Brain Infection.

The natural history of brain abscess ranges from indolent to fulminant. The clinical presentation is dependent on multiple factors, including the location, size, and age of the lesion(s). The microbiology of the infection, the host’s immune status, and the mode of acquisition all contribute to the presentation.

The classic clinical triad of fever, headache, and focal neurologic deficit is present in less than 20% of cases.[17] Typically, clinical manifestations of brain abscess are due to local effect or mass effect and often are not heralded by signs and symptoms of systemic infection.[14, 23, 28, 50] When brain abscess is caused by direct spread of infection, symptoms often localize in predictable patterns; for example, otogenic infections are associated with cerebellar and temporal abscess, while sinus infection may lead to abscess in the frontal lobes.[1]

Headache is the most common presenting symptom and is observed in an average of 50-75% of patients.[2, 23] The headache is often nonspecific and may range from mild to severe and focal or generalized. Rupture of the abscess into the ventricular space may present as a sudden worsening of the headache and is often associated with high mortality.[51]

Fever is present in less than 50% of cases and may be particularly unreliable in patients with HIV infection or compromised immunological function.[52]

Focal neurological deficit such as hemiparesis or aphasia is present in 20-57% of patients and may correlate with the area of infection.[14, 50] Third or sixth cranial nerve palsies, anisocoria, or papilledema should all prompt concern for increased intracranial pressure and impending herniation.

Neck stiffness and meningeal signs have been reported in 25% of presentations[52, 53] ; when present, especially if associated with sudden worsening of headache, these signs may herald abscess rupture and subsequent poor outcome.[44]

Nausea and vomiting have been reported anywhere from 29-85% of cases, and the sign lacks sensitivity.[10, 12]

Seizure has been reported from 7–25% of patients in case series.[2, 11, 23]

Mental status changes are a common, but insensitive, marker. Glasgow Coma Scale score was less than 15 upon admission in 54% of patients in one large series.[52]

Initial manifestations of brain abscess may be nonspecific, and, therefore, delay in diagnosis is common. Mean time from symptom onset to diagnosis is 2 weeks.[54] Symptoms often correspond to increased intracranial pressure or local disruption of brain parenchyma. A thorough physical examination must include inspection of the external and middle ear, as well as inspection of the mastoid bone, sinuses, and dentition. Brain abscess should be strongly suspected in immunocompromised patients presenting with these symptoms.

Fever may be present in approximately half of all presentations and does not reliably aid diagnosis or exclusion.[52]

Focal neurological deficits may be present in 40-60% of patients and may correlate with the area of infection.[2, 50, 52] If the affected brain region(s) has redundant functions with an unaffected area, then focal deficits may more difficult to recognize. The presenting symptom of a localized headache typically correlates to the side of the abscess.[55]

Brainstem abscess may lead to facial weakness or hypothalamic dysfunction. Cerebellar abscess may cause nystagmus, ataxia, or dysmetria. Neck stiffness is typically associated with an occipital lobe abscess or an abscess that has ruptured into a lateral ventricle.[54] Temporal lobe abscess may be associated with headache, visual defects, or dysarthria. Frontal abscess may be associated with motor, sensory disorders, or headache.

Lethargy may be a sign of global cerebral edema and should prompt concern for increased intracranial pressure and impending herniation.

Neck stiffness and meningeal signs have been reported in 25% of presentations. For patients who display Kernig and Brudzinski signs, with concomitant neurological deficits, a careful evaluation should be conducted for brain abscess.[52, 53]

Seizures have been reported in 7-25% of patients and may be generalized or focal, but they are more likely generalized.[2, 23, 50] Status epilepticus is rare in these patients.[30]

Mental status changes are a common but insensitive finding.[8, 11]

Third or sixth cranial nerve palsies, anisocoria, and papilledema may also be indications of increasing pressure and may indicate that the disease process has caused substantial edema either during the cerebritis stage or as a periabscess inflammatory response[39] ; therefore, a cranial nerve and funduscopic examination should be performed. A bedside ocular ultrasound is a reasonable adjunct to funduscopic examination to assess for increased intracranial pressure.

Infants may present with irritability or seizure. Examination must evaluate for bulging fontanels and should include measurement of head circumference.[56]

The microbiological causes of brain abscess are highly variable and depend on the mode of acquisition, as well as host factors such as age, immune status, and geographic location. In up to 25% of cases, no underlying etiology is found.[2] Many infections may be polymicrobial.[57] In immunocompetent hosts, abscesses are largely bacterial in etiology. Abscess location typically depends on the source of infection. The frontal lobe is the most common location, especially with an associated sinus infection.[8] Odontogenic infections affect the temporal lobe and cerebellum.[33] Left-sided abscesses are more common in persons with traumatic infections. Many patients develop multiple abscesses.[17]

Direct extension

When the mode of acquisition is via direct extension, polymicrobial infections are common, occurring in approximately 20-25% of cases; these may involve aerobes and anaerobes, reflecting closely the flora of the contiguous site.[23, 50]

Aerobic and anaerobic streptococci are the most common isolates, found in approximately 70% of cases of bacterial brain abscess, and are frequently a component of mixed infections.[28] Streptococcus milleri is a particularly common isolate because its proteolytic enzymes can effectively necrose tissue and lead to the formation of abscesses.[58] In addition to Streptococcus species, site-specific pathogens include the following:

• Otitis media and mastoiditis: Bacteroides, Enterobacteriaceae, Pseudomonas, Fusobacterium, Prevotella, Peptococcus, Pseudomonas, and Propionibacterium

• Paranasal sinusitis: Bacteroides, Enterobacteriaceae, Staphylococcus aureus, Fusobacterium, and Haemophilus

• Odontogenic infection: Fusobacterium, Prevotella, Actinomyces, and Bacteroides

Brain abscesses that result from hematogenous spread are often multiple, poorly encapsulated, and found in the territory of the middle cerebral artery. These abscesses often involve bacteria from the source infection, as in the following:

• In pulmonary infections, common organisms are Streptococcus species , Fusobacterium species, anaerobic gram-negative bacilli, and aerobic and anaerobic streptococci. Infections with Actinomyces species and Nocardia species have been documented.

• In bacterial endocarditis, the most common organisms are Streptococcus viridans, Streptococcus anginosus, and Streptococcus intermedius.

• Congenital heart disease, as well as patent foramen ovale and other shunts, including intrapulmonary shunts, predispose to intracerebral spread of bacteremia.[59] Typically, cultures grow Streptococcus species. Evidence suggests that the severity of the grade of right-to-left intrapulmonary shunts is strongly associated with the prevalence of cerebral complications, such as brain abscess.[60]

• Intra-abdominal infections and genitourinary tract infections are another source of hematogenous spread of bacteria. These infections can be caused by aerobic or anaerobic pathogens, which usually reflect colonic or genitourinary flora.[2] Frequent constituents include anaerobic streptococci, Bacteroides, (including Bacteroides fragilis), Escherichia coli, Proteus, Pseudomonas, Salmonella, Enterobacter, Prevotella, Propionibacterium, Eubacterium, Fusobacterium, and Actinomyces. Brain abscesses infected with Klebsiella pneumoniae in patients with primary liver abscesses have been described in Asia.[61, 62]

• Skin infections can also lead to bacteremia, which can cause brain abscess. In addition to Streptococcus species, Staphylococcus aureus is frequently implicated.

Trauma and procedures

Penetrating intracranial trauma may be complicated by brain abscess with S aureus, coagulase-negative staphylococci, Pseudomonas aeruginosa, Enterobacter species, Enterobacteriaceae species , and Clostridium species.

Though less common, neurosurgical procedures may be complicated by similar infections. In particular, methicillin-resistant S aureus (MRSA) infection should be considered in neurosurgical patients, and treatment with antimicrobials must take into account CNS penetration.[63]

Rare cases of brain abscess after endoscopic procedure, tongue piercing, dental braces, near drowning, and foreign body aspiration have been documented.[64, 65, 66, 67, 68, 69, 70]

Immunocompromised state

In immunocompromised hosts, causes of brain abscess may differ and could be the result of either opportunistic or bacterial infections. In addition to transplantation patients and those living with HIV/AIDS, individuals with alcoholism, diabetes, or long-term steroid use may be at increased risk for the development of brain abscess.[11]

Transplant organ recipients have a higher incidence of fungal infection from Aspergillus, Candida, Cryptococcus, Enterobacteriaceae, and Mucorales species. However, these patients may also have opportunistic infection with Toxoplasma gondii or Nocardia species.[71]

HIV/AIDS patients with impaired cell-mediated immune response are at a particularly high risk of developing abscesses infected with T gondii, Mycobacterium species, Cryptococcus neoformans, or Listeria monocytogenes infection, often in the cerebral cortex. Additionally, tuberculosis should be considered in this population.[25] Patients have a higher rate of developing multiple abscesses.[72]

Neutropenic patients are at risk for infection with aerobic gram-negative bacilli, as well as infection with Aspergillus, Mucorales, and Candida species.

Long-term corticosteroid use predisposes to increased risk of bacterial abscess. The incidence of brain abscess colonized with Listeria is elevated in patients on long-term steroid use and carries an elevated risk of mortality compared with brain abscess colonized with other bacterial pathogens.[73]

Pediatric patients

Pediatric patients remain a special subgroup. although brain abscess is increasingly rare in infants and children, the proportion of abscesses found in immunocompromised pediatric patients is increasing, whereas improved detection and management of otogenic infection has led to a decrease in abscesses due to direct extension of infection.[38, 56] Of note, the etiology of brain abscess in this population is more likely due to congenital cyanotic heart disease.[74] Citrobacter koseri, a gram-negative bacillus, has a strong propensity to form cerebral abscesses, and multiple case reports have documented cases in infants and children.[75, 76]

Mycotic, protozoal, and helminthic infections

Several mycotic, protozoal, and helminthic infections may be endemic in certain regions. For example, Latin American populations have higher rates of neurocysticercosis from Taenia solium infection,[77] while countries with endemic HIV/AIDS and tuberculosis experience higher rates of tubercular brain abscess.[78] Parasites are the most frequent cause of abscess in individuals who have lived in or emigrated from low-resource settings. Note the following:

• Mycoses: Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides immitis

• Protozoal: Trypanosoma cruzi, Entamoeba histolytica, Schistosoma species, and Paragonimus species

• Helminthic: Neurocysticercosis caused by the larval form of T solium

Other etiologies

Other etiologies of brain abscess include formation after meningeal infection. Although this mode of infection is rare, it is occurs more commonly in children, especially when facultative gram-negative organisms are suspected.[79] Additionally, brain abscess has been seen in the setting of intracranial hemorrhage, as well as intracerebral neoplasm. Patients with a history of intravenous drug abuse have an increased risk of infection.[80] Some abscesses are cryptogenic, and, in some cases, an obvious source remains undetermined.

Complications of brain abscess may be localized or global and include persistent weakness, aphasia, or cognitive impairment, as well as life-threatening complications such as herniation or intraventricular abscess rupture.

Brain herniation is frequently secondary to increased intracranial pressure from profound periabscess edema.[50]

Rupture of abscess into ventricles or subarachnoid space is a complication that is often lethal. High-risk features for this complication include an abscess that is deep seated, multiloculated, and/or close to the ventricular wall.[53]

Morbidity, including persistent neurologic sequelae such as focal deficits, seizures, and headache, occurs in approximately 50% of patients.[1, 10, 13]

Although nondiagnostic, patients with suspected brain abscess should have routine laboratory tests drawn to aid in narrowing the differential diagnosis.[81] If surgical intervention appears likely, preoperative laboratory testing should be considered.

CBC count should be obtained. Elevation of white blood cell count is present in 30-60% of patients.[13, 23, 50]

Sedimentation rate and C-reactive protein may be obtained. Elevation of acute phase may be present, but results are nonsensitive, nonspecific findings. In one series, only 47% of patients had elevated erythrocyte sedimentation rate.[50]

Two sets of blood cultures should be obtained, optimally prior to antibiotic administration; positive blood cultures are found in approximately 10% of cases. Brain abscess secondary to L monocytogenes may be more likely to yield positive blood cultures.[10, 82]

When hematogenous spread is suspected, consider obtaining cultures from the suspected primary infection.[39]

In immunocompromised patients, laboratory testing may include tuberculin skin testing and serotesting for toxoplasmal and anticysticercal antibodies in the cerebrospinal fluid (CSF). Background seroprevalence of Toxoplasma immunoglobulin G is high, and more than 97% of HIV/AIDS patients with toxoplasmosis brain abscesses have positive titers. Therefore, a negative test in an HIV/AIDS patient may be helpful in excluding toxoplasmosis from the differential.[83]

Advanced neuroimaging modalities, such as CT and MRI are credited with a substantial reduction in morbidity and mortality of brain abscess[10] ; this is due, in part, to the reduction of diagnostic delay.[47] CT imaging is readily available in most emergency departments and may aid in rapid diagnosis of intracranial lesions; however, findings may vary with the stage of disease.

CT scans should be conducted with and without intravenous contrast. During the early stage of cerebritis, the lesion may appear irregular or hypodense and may be enhancing or nonenhancing with contrast. As the abscess begins to wall-off, CT imaging may reveal a classic ring-enhancing lesion. CT may be insufficient to detect infection during the cerebritis state, as well as for detecting posterior fossa lesions.[84] CT is not 100% sensitive and may miss early lesions or those abscesses that fail to wall-off. Additionally, it cannot reliably distinguish between abscess and other causes of ring-enhancing lesions, such as tumor. Despite these challenges, CT imaging is generally sufficient to mandate admission and further inpatient workup.

MRI is more sensitive and specific than CT imaging and may be used to aid in the diagnosis of brain abscess. MRI should be performed using gadolinium, which can increase the signal intensity of the lesion on T1.[85]

MRI can be particularly useful during the early cerebritis stage or when there is suspicion of a posterior fossa lesion or satellite lesions.[2] Moreover, unlike CT, MRI is capable of distinguishing between pyogenic and nonsuppurative lesions on diffusion-weighted imaging (DWI).[85] On MRI, cerebritis appears as an area of low-signal intensity on T1-weighted imaging and has increased signal intensity on T2-weighted imaging.[86, 87]

DWI is used for differentiating ring-enhancing lesions that are neoplastic in origin, versus infectious causes. Suppurative abscess fluid restricts diffusion, leading to a hyperintense appearance of the lesion on DWI. In contrast, neoplastic lesions are typically hypointense or varied in intensity on DWI.

Neuroimaging aids in the detection of abscess and it plays a critical role in microbiological sampling, disease management, and follow-up. The advent of stereotactic CT-guided aspiration of abscess fluid has allowed for greater yield of abscess fluid and can aid in directing antimicrobial therapy.

As ultrasonography is becoming widely used in the emergency department, bedside ocular ultrasonography may be performed to assess for increased intracranial pressure.[88]

Abscess aspiration and culture can be performed. Brain abscesses are aspirated by a neurosurgeon. Microbiological findings of the aspirate often help steer antimicrobial therapy.[57] Therefore, patients with suspected brain abscess warrant urgent neurosurgical consultation. Neurosurgical intervention may include brain biopsy for culture and histopathology. The abscess may be accessed by stereotactic CT-guided aspiration, open evacuation of the abscess, or with ultrasound guidance. CT guidance is the most common modality. Abscess fluid is typically evaluated by Gram stain and culture, including aerobes, anaerobes, acid-fast staining for mycobacteria, and modified acid-fast staining for Nocardia. Specific fungal staining, such as methenamine silver or mucicarmine, can be performed on the aspirate. In the case of suspected neurocysticercosis, serology may be obtained for anticysticercal antibodies.

Lumbar puncture

In instances in which meningitis is suspected, a lumbar puncture (LP) may have initially been obtained; however, lumbar puncture without prior CT imaging is contraindicated in the setting of focal neurological deficit or papilledema.[89] Furthermore, if neuroimaging reveals a mass lesion, LP is contraindicated. Occasionally, as is the case with early cerebritis, neuroimaging may not reveal a mass lesion. Although the risk of herniation may be low, CSF sampling to confirm diagnosis of brain abscess is rarely indicated and of very low yield.[90]

CSF findings may include increased or normal cell count, increased polymorphic neutrophils, elevated protein, and normal glucose—findings that are neither sensitive nor specific for brain abscess. Gram stain and cultures of CSF are rarely helpful.[2, 90] Some patients with brain abscess have normal CSF results, including cultures.[91]

In the case of intraventricular rupture, CSF may show an abundance of red blood cells and leukocytosis. Elevated CSF lactic acid levels have been reported and may aid in diagnosis.[92]

Although brain abscess is rare, the emphasis of prehospital care should be on expedient transport of the patient to the hospital. Given the typical vague presentation, early suspicion in the prehospital setting is often unlikely. If rupture is suspected as there may be some preceding symptoms, urgency in transport is even greater.

Initial management is a function of the severity of the patient’s presentation. Goals of initial therapy include stabilizing the patient and minimizing neurological impairment. Evaluation begins with the primary survey and confirmation of the patient’s airway, breathing, and circulatory function, followed by rapid initial assessment of the patient’s neurological function.

If the patient is unable to protect his or her airway, has unstable respiratory function, or is obtunded, emergent intubation is require, and, therefore, rapid-sequence intubation should use cerebroprotective medications.

After initial stabilization, patients in whom brain abscess is suspected should undergo neuroimaging. Contrast CT of the brain is of greater utility in this population than noncontrast scanning.

Frequent neurological evaluation is recommended, particularly when intraventricular rupture is suspected.

Antibiotics are the first-line treatment for brain abscess. High-dose, broad-spectrum, intravenous antibiotics should be administered as early as possible in the patient's course. Emergent consultation with neurosurgery is recommended; however, delay in consultation should not delay antibiotic administration. Attempt to obtain blood and other cultures prior to antibiotic administration; however, it is not advisable to delay administration.

Seizure prophylaxis with anticonvulsants is typically indicated in patients with suspected brain abscess, given the high risk of seizure, which often exacerbates intracranial pressure.[57] Patients presenting with active seizure should be treated aggressively in order to avoid worsening intracranial pressure.

The use of glucocorticoids is controversial and they should not be routinely administered. Patients who are rapidly decompensating may warrant corticosteroid therapy in order to reduce the life-threatening effects of vasogenic edema.[50] However, this approach is controversial given the risk that steroids can worsen inflammation, prevent abscess formation during cerebritis stage, exacerbate necrosis, and increase the risk of ventricular rupture.[1, 93, 94] If used, steroids are typically given for a short course but are not yet noted to be associated with increased mortality.[95]

A neuroradiologist and neurosurgeon must be consulted quickly once the diagnosis is suspected and made. A neurologist should also be consulted to continually reevaluate any neurological symptoms. Special patient populations include individuals with HIV/AIDS and those with immunocompromised status. This set of immunocompromised patients may require early consultation with infectious disease specialists. Although the prevalence is decreasing, patients with suspected brain abscess due to maxillofacial, otogenic, or odontogenic infections require additional consultation with an oromaxillofacial surgeon or otolaryngologist, as appropriate.

Serial neuroimaging, either with CT or MRI, is typically recommended in order to follow treatment successfully to resolution of the abscess. Management may vary from weekly to monthly reimaging, depending on local practice patterns, as well as the patient’s course and symptomatic resolution. Enhancement of the lesion on neuroimaging may persist for months. Data on the precise interval for when to obtain reimaging studies are currently insufficient. In some patients, brain abscess fails to respond to antimicrobial therapy, while in others the response is not durable and the abscess reaccumulates; in these instances, reaspiration may be necessary.[41]  If the patient developed neurological deficits, outpatient therapy with physical medicine and rehabilitation should be established in order to regain as much function as possible. Follow-up with a neurologist for seizure prophylaxis should continue for at least 3 months or until seizure activity has no longer been noted on electroencephalography (EEG).[96]

Despite considerable reductions in morbidity and mortality, brain abscess is a serious infection with potentially profound prognostic implications. Modern medical care of these patients often requires a swift, multidisciplinary approach.[41]

Initial management steps include confirmation of the size, location, and number of intracranial abscesses using CT with intravenous contrast, MRI, or both.

The decision to surgically manage the disease may vary with the characteristics of the abscess, and numerous practices are used. Typically, abscesses larger than 2.5 cm are excised or aspirated, often during emergent surgery. Patients in the early cerebritis stage or those with abscesses that are smaller than 2.5 cm may undergo aspiration for diagnosis only. Some neurosurgeons may prefer complete evacuation of the abscess capsule, while others may plan to reaspirate the lesions.[2, 53, 47]

Stereotactic CT or MRI-guided needle aspiration is a key procedure in facilitating expedient identification of the pathogen and may be a preferable approach compared with open craniotomy, with benefits of reduced morbidity and mortality.[97]  Culture data collected during aspiration are beneficial for targeting and narrowing antimicrobial regimens.

Empiric intravenous antibiotics given for several days have an unclear effect on the success of brain abscess aspiration culture data. A major trial looking at the use of antibiotic therapy for up to 10 days prior to aspiration showed that this practice does not alter culture growth.[39]  However, a second large study showed that approximately 40% of abscess cultures had no growth after empiric antibiotic therapy.[17]

The duration of intravenous antibiotic treatment is frequently 4-8 weeks or longer, with subsequent transition to oral antibiotics for another 4-8 weeks in order to ensure complete resolution and prevent relapse.[98]

A small body of literature on the effects of hyperbaric oxygen therapy as adjunctive therapy for brain abscess exists. Primary outcomes include reduction in length of stay and decreased duration of antibiotics therapy; however, at this time, evidence is insufficient.[99]

These patients frequently require neurosurgical management; thus, prompt transfer to a neurosurgical-capable hospital is appropriate if unavailable at the initial treating facility. Patients may also require ICU level of care, which is another indication for transfer.

Medical therapy alone may be adequate in a select group of patients[100] ; however, for most, surgical aspiration and drainage is required for definitive treatment.[81, 41]

Initial empiric parenteral antimicrobial selection must take into account host status, mode of transmission, and antimicrobial CNS penetration. Immunocompromised hosts may warrant empiric coverage for fungal and parasitic infections. In general, antimicrobial selection should attempt to maximize bactericidal activity and be tolerable for weeks to months of therapy.[57, 81]

When hematogenous spread is suspected, antibiotic selection should also take into account site penetration at the source of infection. Although empiric treatment with antibiotics for several days prior to biopsy may reduce the yield, the true effect is not known.

Seizures may occur at the time of presentation or may complicate the patient’s course during disease progression and resolution; therefore, prophylaxis with anticonvulsants is a mainstay of treatment. Anticonvulsant therapy may be initiated in the emergency department and may continue until complete disease resolution, or longer. First-line agents include phenytoin, carbamazepine, valproate, and levetiracetam.

Glucocorticoids remain controversial, and many authors recommend they only be considered as a life-saving measure in an unstable patient for whom there is concern for imminent brain herniation.

Class Summary

In an immunocompetent host with direct extension of infection from a contiguous site, infection is frequently polymicrobial and empiric therapy should be directed at covering anaerobes and aerobes, including Streptococcus species. In addition to Streptococcus, site-specific pathogens include the following:

- Otitis media and mastoiditis: Bacteroides, Enterobacteriaceae, Pseudomonas, Fusobacterium, Prevotella, Peptococcus, and Propionibacterium

- Sinusitis: Bacteroides, Enterobacteriaceae, S aureus, Haemophilus

- Odontogenic infection: Fusobacterium, Prevotella, Actinomyces, and Bacteroides

- Penetrating trauma or surgical: S aureus, Streptococcus, Enterobacteriaceae, and Clostridium

Treatment for these infections typically includes a third- or fourth-generation cephalosporin in combination with metronidazole. Penicillin G offers coverage for anaerobic and aerobic Streptococcus species and has excellent CNS penetration but must be used in combination with an agent that targets anaerobic gram-negative bacilli such as metronidazole. For penetrating head trauma or a postoperative patient, MRSA coverage is strongly advised.

When hematogenous infection is suspected, antimicrobial coverage must be directed towards site-specific pathogens, as follows:

- Endocarditis: S viridans, S aureus

- Pulmonary infections: Streptococcus, Fusobacterium, Corynebacterium, Peptococcus, Fusobacterium, Actinomyces, Bacteroides, Prevotella, and Nocardia

- Cardiac defects: Streptococcus and Haemophilus

- Intra-abdominal infections: Klebsiella, E coli, Enterobacteriaceae, and Streptococcus

- Urinary tract infections: Enterobacteriaceae and Pseudomonas

- Wound infection: S aureus

In many instances, antibiotics with beta-lactam–beta/lactamase inhibitor (eg, ampicillin-sulbactam, ticarcillin-clavulanate, or piperacillin-tazobactam) cross the blood-brain barrier and can be used effectively. However, overall evidence for appropriate therapy is lacking. A recent Cochrane review found that there are no randomized controlled trials addressing the effectiveness of antibiotic regimens for brain abscess in the setting of cyanotic congenital heart disease.[76]

Where MRSA is suspected, vancomycin is a frequent choice; however, some authors have argued that it has poor CNS penetration and favor linezolid.[63] MRSA infection should be suspected if the patient is postoperative following a neurosurgical procedure, in the case of penetrating head wounds, or from hematogenous spread of a known MRSA infection. MRSA infection can also be community acquired.[101, 102, 103]

For immunocompromised hosts, pathogens and treatment vary with host factors, as follows:

- HIV/AIDS infection: T gondii, Nocardia, Mycobacterium, L monocytogenes, or C neoformans

- Transplantation: Aspergillus, Candida, Mucorales, Enterobacteriaceae, Nocardia, or T gondii

- Neutropenia: Aerobic gram-negative bacilli, Aspergillus, Mucorales, or Candida

Aspergillus infection has been shown to respond to voriconazole, while amphotericin B remains a mainstay of treatment for most other fungal infections.[104, 49] First-line therapy for the protozoal infection T gondii is with pyrimethamine plus sulfadiazine. Effective first-line agents for Nocardia include sulfadiazine or trimethoprim-sulfamethoxazole. Finally, several mycotic, protozoal, and helminthic infections should be considered, in certain cases, where they are endemic to the region, as follows:

- Mycoses: H capsulatum, B dermatitidis, and C immitis

- Protozoal: T cruzi, E histolytica, Schistosoma, and Paragonimus

- Helminthic: Neurocysticercosis, caused by the larval form of T solium

In these instances, targeted therapy is required, and selection depends on the suspected organism.

When initial investigation does not reveal a likely cause of brain abscess, the recommended empiric coverage is a third- or fourth-generation cephalosporin, plus vancomycin, and metronidazole.

Ceftriaxone (Rocephin)

Ceftriaxone is a third-generation cephalosporins generally achieve effective levels in the CNS and is highly active against a broad spectrum of bacterial pathogens, including most gram-negative bacilli and aerobic streptococci. However, ceftriaxone has lower efficacy against gram-positive organisms and certain anaerobes and is therefore frequently used in combination with metronidazole. Its bactericidal effect is achieved via inhibiting cell wall synthesis by binding to one or more penicillin-binding proteins. Ceftriaxone is stable in the presence of beta-lactamases and frequently has better efficacy against resistant organisms.

Cefepime (Maxipime)

Cefepime is a fourth-generation cephalosporin with excellent pseudomonal coverage. Gram-negative coverage is similar to ceftazidime, but it has better gram-positive coverage (comparable to ceftriaxone).

Imipenem and cilastatin (Primaxin)

This combination agent is a carbapenem with broad-spectrum activity. It is given with cilastatin, which prevents renal metabolism of imipenem. Imipenem is used for the treatment of multiorganism infections in which other agents do not have wide-spectrum coverage or are contraindicated because of potential for toxicity. Caution should be used, given the association with seizure activity. It is considered to achieve somewhat poor concentrations in CSF.

Meropenem (Merrem IV)

Similar to imipenem, meropenem is a carbapenem with bactericidal broad-spectrum activity that inhibits cell-wall synthesis. It is effective against most gram-positive and gram-negative bacteria. It has slightly increased activity against gram-negatives and slightly decreased activity against staphylococci and streptococci, when compared with imipenem.

Penicillin G (Pfizerpen)

Given the high prevalence of streptococcal infection, high-dose intravenous penicillin G may be used as a first-line regimen for empiric treatment of brain abscess in the emergency department. It provides coverage for anaerobes and streptococci. It penetrates well into the CNS and, most often, the abscess cavity. However, emergence of beta-lactamase resistance limits its efficacy. It does not cover B fragilis and therefore must be used in conjunction with metronidazole.

Metronidazole (Flagyl)

Metronidazole is considered first-line therapy since it targets anaerobic bacteria as well as certain protozoal species and achieves high concentration in abscess fluid. It is frequently used in combination with a third- or fourth-generation cephalosporin or penicillin G therapy. It may be especially useful in otogenic brain abscesses.

Cefotaxime (Claforan)

Cefotaxime is a first-line agent. It covers streptococci, staphylococci, and Haemophilus and Enterobacter species. This third-generation cephalosporin has broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms than earlier-generation cephalosporins. It arrests bacteria cell wall synthesis and inhibits bacterial growth by binding to 1 or more penicillin-binding proteins.

Nafcillin (Unipen)

High-dose parenteral use of nafcillin is indicated for initial treatment of staphylococcal infections that are not methicillin resistant. It is effective against penicillinase-producing staphylococci. It may be changed to oral therapy after initial intravenous treatment response. Adverse effects of parenteral administration include thrombophlebitis, and therefore recommended parenteral administration is for when short-term (24-48 h) intravenous therapy is warranted; then change to the oral route if clinically possible. Ampicillin or ampicillin/sulbactam are other potential selections.

Vancomycin (Vancocin)

Vancomycin is reserved for cases when MRSA is suspected or if the patient is penicillin-allergic. Vancomycin is effective against gram-positive organisms and has activity against enterococci. Vancomycin is bactericidal at high concentrations. It is also useful in treating septicemia and skin structure infections. The narrow therapeutic window requires frequent monitoring and dose adjustment. Adverse effects may include renal injury or red man syndrome. Random drug levels and/or trough levels are frequently monitored to avoid toxic effects.

Ceftazidime (Fortaz, Ceptaz)

Ceftazidime can be added to empiric regimens if pseudomonads are suspected. It is a third-generation cephalosporin that has a broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms than many agents. It arrests bacteria cell wall synthesis and inhibits bacterial growth by binding to 1 or more penicillin-binding proteins.

Class Summary

The use of corticosteroids in brain abscess is controversial. Intravenous steroids are usually reserved for patients who have severely increased intracranial pressure, either from mass effect or substantial edema around the periphery of the abscess. Steroids are thought to reduce intracranial pressure by decreasing edema via their anti-inflammatory properties. However, steroid use may also decrease antibiotic penetration, as well as slow the encapsulation of the suppurative fluid, thus potentially offsetting the beneficial effects. Significant and potentially serious metabolic adverse effects can occur with high dosages.

Dexamethasone (Decadron, Dexasone)

Dexamethasone is the corticosteroid of choice for reducing intracranial pressure. It is used in the treatment of inflammatory diseases. It may decrease inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Class Summary

Since seizures may occur in patients with a brain abscess, early use of an anticonvulsant is recommended. Some studies suggest that prophylaxis can be stopped after 3 months if no further seizure activity is noted. [105, 106]