Background
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.
Pathophysiology
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.
Epidemiology
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]
Prognosis
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:
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Young age
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Absence of neurologic deterioration during initial presentation [39]
Worse prognosis of brain abscess is associated with the following:
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Advanced age
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Hematogenous spread [43]
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Immunosuppression [43]
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Evidence of intraventricular rupture [44]
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Evidence of herniation on initial presentation [45]
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Evidence of altered sensorium on initial presentation [17]
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Severity of abscess and abscess location on initial neuroimaging [46]
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Delay in diagnosis or definitive surgical intervention [47]
Patient Education
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.
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Brain abscess.
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Sagittal (a) and axial (b) gadolinium-enhanced T1-weighted MRI images from a patient who presented with headache, word-finding difficulties, stuttering speech, and right hand/foot numbness. Note the peripheral enhancement of a lesion in the left insula with surrounding edema.
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CT (a) and T2 fluid-attenuated inversion recovery (FLAIR) MRI (b, c) images from the same patient as the first image. Images a and b were obtained at the time of initial diagnosis, and image c was obtained 5 months later following successful treatment.
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Diffusion-weighted (a), T2 fluid-attenuated inversion recovery (FLAIR) (b), and post-gadolinium enhanced T1-weighted (c) images from a patient who presented initially with vomiting, followed by fever and coma. Numerous abscesses are demonstrated with coalescence in the right occipital and basal ganglia with surrounding edema and midline shift.
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Axial (a) and coronal (b) CT images from the same patient as the third image. Multiple hypodensities with cerebral edema and mass effect are noted.
