Background
Intracranial abscesses are uncommon, serious, life-threatening infections. The complex array of etiologic agents that cause intracranial abscess has become better understood. They include brain abscess and subdural or extradural empyema and are classified according to the anatomic location or the etiologic agent. The term brain abscess is used in this article to represent all types of intracranial abscesses.
Intracranial abscesses can originate from infection of contiguous structures (eg, otitis media, dental infection, mastoiditis, sinusitis) secondary to hematogenous spread from a remote site (especially in patients with cyanotic congenital heart disease), after skull trauma or surgery, and, rarely, following meningitis. In at least 15% of cases, no source can be identified.
Brain abscess, one of the "big three" central nervous system infections, has historically received less research attention compared to meningitis and encephalitis. An analysis revealed a significant disparity in the volume of research, with brain abscess studies being substantially fewer and primarily retrospective, limiting their generalizability. Factors contributing to this neglect include the low incidence of brain abscess in developed countries, the diverse range of microorganisms involved, and the involvement of multiple medical specialties, which hampers collaborative research efforts.
However, advancements in research, particularly from Northern Europe, have begun to address this gap. Notably, Brouwer et al conducted a systematic review and meta-analysis of nearly 10,000 brain abscess cases, providing valuable insights into clinical characteristics and outcomes. Subsequent studies in Denmark, leveraging extensive national registries, have further elucidated the pathophysiology and outcomes of brain abscess. Bodilsen et al reported a 1-year mortality rate of 21% and a 32% prevalence of de novo epilepsy among survivors, while also identifying key risk factors such as neurosurgery, solid cancers, ear infections, and immunomodulating treatments. These findings underscore the importance of collaborative, multidisciplinary research in enhancing our understanding of brain abscess.
Pathophysiology
Brain abscess is caused by intracranial inflammation with subsequent abscess formation. The most frequent intracranial locations (in descending order of frequency) are frontal-temporal, frontal-parietal, parietal, cerebellar, and occipital lobes. In at least 15% of cases, the source of the infection is unknown (cryptogenic).
The most frequent causative pathogens in community-acquired brain abscess are oral cavity bacteria such as Streptococcus anginosus group, Fusobacterium spp, and Aggregatibacter spp, which are often associated with dental and chronic ear infections. Other less common etiologies include Staphylococcus aureus and Gram-negative bacilli in post-neurosurgical brain abscess, Mycobacterium tuberculosis in endemic areas, and Nocardia spp, fungi, and parasites in the severely immune-compromised.
Infection may enter the intracranial compartment directly or indirectly via three routes.
Contiguous suppurative focus (45%-50% of cases)
Direct extension usually causes a single brain abscess and may occur from necrotic areas of osteomyelitis in the posterior wall of the frontal sinus, the sphenoid and ethmoid sinuses, and mandibular dental infections, as well as from subacute and chronic otitis media and mastoiditis. This direct route of intracranial extension is more commonly associated with subacute and chronic otitic infection and mastoiditis than with sinusitis.
Subacute and chronic otitis media and mastoiditis generally spread to the inferior temporal lobe and cerebellum. Frontal or ethmoid sinusitis spread to the frontal lobes. Odontogenic infections can spread to the intracranial space via direct extension or a hematogenous route. Mandibular odontogenic infections also generally spread to the frontal lobe.
The frequency of brain abscesses resulting from ear infections has declined in developed countries. However, abscesses complicating sinusitis has not decreased in frequency. Contiguous spread could extend to various sites in the central nervous system, causing cavernous sinus thrombosis; retrograde meningitis; and epidural, subdural, and brain abscess.
The valveless venous network that interconnects the intracranial venous system and the vasculature of the sinus mucosa provides an alternative route of intracranial bacterial entry. Thrombophlebitis originating in the mucosal veins progressively involves the emissary veins of the skull, the dural venous sinuses, the subdural veins, and, finally, the cerebral veins. By this mode, the subdural space may be selectively infected without contamination of the intermediary structure; a subdural empyema can exist without evidence of extradural infection or osteomyelitis.
Intracranial extension of the infection by the venous route is common in paranasal sinus disease, especially in acute exacerbation of chronic inflammation. Chronic otitis media and mastoiditis generally spread to the inferior temporal lobe and cerebellum, causing frontal or ethmoid sinus infection and dental infection of the frontal lobe.
Trauma (10% of cases)
Trauma that causes an open skull fracture allows organisms to seed directly in the brain. Brain abscess can also occur as a complication of intracranial surgery, and foreign body, such as pencil tip, lawn dart, bullets, and shrapnel. Occasionally brain abscess can develop after trauma to the face. Brain abscess can occur months after neurosurgery.
Hematogenous spread from a distant focus (25% of cases)
These abscesses are more commonly multiple and multiloculated and are frequently found in the distribution of the middle cerebral artery. The most commonly affected lobes (in descending frequency) are the fontal, temporal, parietal, cerebellar, and occipital.
Hematogenous spread is associated with cyanotic heart disease (mostly in children), pulmonary arteriovenous malformations, endocarditis, chronic lung infections (eg, abscess, empyema, bronchiectasis), skin infections, abdominal and pelvic infections, neutropenia, transplantation, esophageal dilatation, injection drug use, and HIV infection.
Epidemiology
Frequency
United States
Before the emergence of the AIDS pandemic, brain abscesses were estimated to account for 1 per 10,000 hospital admissions, or 1500-2500 cases annually. The prevalence of brain abscess in patients with AIDS is higher, so the overall rate has thus increased. According to the European Society of Clinical Microbiology and Infectious Diseases, the annual incidence of brain abscess is estimated to be between 0.4 and 1.3 cases per 100,000 inhabitants in the United States, which corresponds to about 6700 cases annually in Europe.
The frequency of fungal brain abscess has increased because of the frequent administration of broad-spectrum antimicrobials, immunosuppressive agents, and corticosteroids.
International
Brain abscesses are rare in developed countries but are a significant problem in developing countries. The predisposing factors vary in different parts of the world.
Mortality/Morbidity
With the introduction of antimicrobics and the increasing availability of imaging studies, such as CT scanning and MRI, the mortality rate has decreased to less than 5%-15%. Stroke, older age, septicemia, pneumonia, meningitis, and hepatitis were associated with increased risk for in-hospital mortality. Case fatality rate decreased from 40% to 10% since approximately 1970, whereas the rate of patients with full recovery increased from 33% to 70%. Poor outcomes associated with recovery from a brain abscess include rupture into a ventricle, rapid progression prior to hospitalization, coma or stupor, Initial Glasgow Coma Scale (GCS) ≤14, comorbidities (Charlson scale ≥2), and significant mental status changes when admitted.
Ong et al reported that the in-hospital mortality rate increases with age, from 4.22% among patients aged 0-14 years to 17.34% among individuals older than 60 years. Rupture of a brain abscess, however, is associated with a high mortality rate (up to 80%).
The frequency of neurologic sequelae in persons who survive the infection varies from 20%-79% and is predicated on how quickly the diagnosis is reached and antibiotics administered.
Sex
Brain abscess is more common in males than in females.
Age
Brain abscess occurs more frequently in the first 4 decades of life. Because the main predisposing cause of subdural empyema in young children is bacterial meningitis, a decrease in meningitis due to the Haemophilus influenzae vaccine has reduced the prevalence in young children.
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CT scan of a brain abscess.
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MRI of a brain abscess.
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Brain abscess.
