Introduction
Background
The introduction of infectious agents results in various responses from the central nervous system (CNS). In the earliest stage of purulent bacterial brain infection, the generalized initial reaction is cerebritis. Within the background of cellular response to the infection, cerebritis evolves into a localized abscess in a predictable series of stages. Neuroimaging of these stages reflects the underlying pathophysiology of abscess formation. Variations in the brain's reaction at different locations and similarities in the brain's reaction to certain agents and in the appearances of aggressive neoplasms all require correlation of medical history, neuroimaging, and results of microbiologic analysis.
For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Brain Infection.
Pathophysiology
Most commonly, infectious agents gain access to the CNS by spread from a contiguous focus of infection, such as otitis media, mastoiditis, infection of the paranasal sinuses, or dental infection. Infection spreads hematogenously from an extracranial site, via trauma, directly to the CNS through retrograde thrombophlebitis, which may be preceded by empyema, meningitis, or both. Congenital or acquired dural dehiscence and dermal sinuses are less common causes.
Specific organisms involved in cerebritis and abscess vary. In one third of patients, more than one organism is found. Most abscesses are produced by pyogenic bacteria. Overall, the organisms most frequently isolated from cerebral abscesses include streptococci (both aerobic and anaerobic) and staphylococci, although gram-negative organisms are an increasing cause of cerebral abscess. In neonates, the most frequently implicated organisms include Citrobacter, Proteus, Pseudomonas, and Serratia species, as well as Staphylococcus aureus. These abscesses are often large and have poorly formed capsules.
Occasionally, organisms other than pyogenic bacteria cause cerebral abscesses. Examples include Mycobacterium tuberculosis, nontuberculous mycobacteria, fungi, parasites, and Actinomyces and Nocardia species. Focal intracranial infections due to Salmonella organisms are rare and are associated with positive results in blood cultures in some patients.
Four stages have been described in abscess evolution: early cerebritis, late cerebritis, early capsule formation, and late capsule formation.
- Early cerebritis is the initial phase of abscess formation. The initial infection is focal but not localized. An unencapsulated mass of congested brain tissue is seen, with regional edema. Scattered necrotic foci and microscopic petechial hemorrhages are present, although no gross tissue destruction is seen. Early cerebritis lasts as long as 3-5 days.
- After 3-5 days, the reaction to the infectious agent progresses to late cerebritis. The infection becomes more focal with zones of necrosis. Blood vessels surrounding the infection proliferate. The central area of the infection becomes necrotic, surrounded by a ring of inflammatory cells, macrophages, granulation tissue, and fibroblasts. The late cerebritis stage lasts 5-14 days.
- With the beginning of the early capsule stage, collagen and reticulin form a well-delineated capsule. The central core consists of necrotic and inflammatory debris. The abscess capsule increasingly thickens with the addition of more collagen. With the formation of a well-defined capsule, the mass effect and surrounding edema begin to subside. Gliosis around the abscess periphery further defines the region.
- The wall of a well-defined late abscess consists of an inner inflammatory layer, a middle collagenous layer, and an outer gliotic layer. The late capsule stage may last for months.
Symptoms of brain abscess include an altered mental state, headache, fever, seizure, vomiting, unilateral weakness or hemiparesis, and cranial nerve signs. Imaging prior to a lumbar spinal puncture is critical because lumbar spinal puncture may lead to brain herniation in patients with mass effect. Following successful treatment, many patients are left with significant long-term morbidity. Cavernous sinus thrombosis or brain herniation may be fatal.
Frequency
United States
In developed countries, bacterial abscesses are rare in healthy adults. In children, cerebral abscesses are rare, even in patients with congenital heart disease and immune defects. The frequency of intracranial involvement as a complication of sinusitis is approximately 1.5%.
International
In developing countries, cerebral abscesses are more common than in the developed world. Cerebral abscesses due to Mycobacterium and Salmonella infection are more common in poorer nations in which tuberculosis and GI tract infections are common.
Mortality/Morbidity
Early and improved diagnostic imaging techniques have allowed the discovery of brain abscess at a much earlier stage. Antibiotic treatments have improved the prognosis of patients with cerebral abscess. Mortality rates have decreased from 40-50% to less than 5%.
Regarding altered immunity, the identification and treatment of cerebral abscess often is complicated in patients who are immunosuppressed. Brain abscess due to toxoplasmosis is most common in patients with AIDS. Nocardial infection is seen most commonly in patients with immunosuppression, including patients who have undergone organ transplantation. Fungal brain infections, including mucormycosis, are almost always associated with diabetes, renal failure, or another cause of immunosuppression.
Race
No particular association exists between cerebral abscesses and race.
Sex
No particular predilection is noted in either sex.
Age
Bacterial meningitis is the most common cause of cerebral abscess in neonates and infants. Fungal and nocardial infections tend to occur in patients with diabetes or other causes of immunosuppression that are more common in elderly patients. In neonates, cerebral abscess is caused more commonly by Citrobacter, Proteus, Pseudomonas, and Serratia species, as well as S aureus.
Anatomy
Cerebral abscess formation generally occurs at the corticomedullary (gray-white matter) junction within the frontal and parietal lobes. Fewer than 15% of intracranial abscesses occur in the posterior fossa. Most cerebral abscesses are single. Multiple abscesses are found most commonly in patients who are immunocompromised.
The location of an abscess may depend on the location of the primary infection. Abscesses secondary to otitis media usually are localized to the temporal lobe or cerebellum. Infection spread from the paranasal sinuses most commonly presents in the frontal and subfrontal brain. Fungal abscesses are often contiguous with an infection of the orbit or sinuses. Hematogenous pyogenic abscesses usually result from a cardiac, pulmonary, or vascular source. In these patients, abscess formation is seen most commonly in the supratentorial brain.
Other less commonly associated conditions include congenital or acquired dural dehiscence and dermal sinuses, which may provide a pathway for the spread of the infective agent.
Presentation
Clinical manifestations of cerebral abscess most commonly are a result of the size and location of the space occupied by the overall reaction of the brain to the presence of the organism. While the abscess cavity may be significant, the associated edema pattern is often a greater factor in producing midline and transtentorial shifts. Presentation and clinical progression of a brain abscess depends on the nature of infectious agents that have gained access to the CNS. Responses can be pyogenic or nonpyogenic.
Pyogenic inflammatory reaction to an infectious organism represents the host response. Abscess formed in reaction to infection by Pneumococcus species represents a prototypical pyogenic abscess. Other organisms, such as Nocardia species and certain fungi are opportunistic pathogens that cause serious disseminated disease in patients who are immunocompromised, such as patients who have undergone organ transplantation or patients with HIV infection or endstage renal disease.
Nocardia asteroides accounts for 80% of invasive nocardial infections resulting in systemic and CNS disease. Pulmonary infection is the most common initial infection, with hematogenous spread to other organs, such as the skin, soft tissues, CNS, bone, heart, and kidneys, which occurs later in the clinical course. Tissue infected with Nocardia species often demonstrates acute pyogenic inflammation with gram-positive, beaded, filamentous rods with variable acid-fast staining. The organism is best demonstrated in tissue sections by using silver staining.
Nocardial species stimulate little humoral immunity. Protective immune responses are primarily T-cell mediated. Both immunocompetent and immunocompromised hosts can be affected. Low CD4 cell counts and failure to receive prophylaxis were found in patients with HIV infection with Toxoplasma -related brain abscess. Seropositive patients with CD4 counts below 200 cells per cubic millimeter benefit from effective anti– Toxoplasma encephalitis prophylaxis.
Other organisms that may have similar clinical features include M tuberculosis, Actinomyces species, fungi, nontuberculous mycobacteria, and parasites.
Unusual agents have been recovered from neonates with no immunosuppression. Klebsiella pneumoniae is rarely a causative organism in the healthy neonate. When such infections occur, an antenatal infection in the mother may be the source.
Listeria monocytogenes infection may present as a mass within the brain with a confusing pattern that is difficult to differentiate without biopsy and culturing. Most Listeria -related brain abscesses occur in patients who have a compromised immune response.
Toxoplasma encephalitis is caused by Toxoplasma gondii. In the US, seropositivity has been reported in up to 70% of those tested. The primary transmission of Toxoplasma organisms is via raw meat, while bodily secretions, milk, transfusions, and organ transplantation are other sources of exposure. After the acute infection, the parasite becomes latent in the form of a bradyzoite. As cell-mediated immunity declines, the cytes rupture, releasing invasive tachyzoites.
Clinical Toxoplasma encephalitis represents a recurrent infection. In AIDS, the risk of recurrent infection is associated with CD4 counts of less than 100 cells per cubic millimeter. In AIDS patients, Toxoplasma encephalitis is often progressive and may be fatal, if untreated. The primary symptoms seen in the patient with AIDS include fever, altered mental status, seizure, and focal neurologic deficits.
The lesion of toxoplasmosis presents with a central zone, which contains few organisms and is avascular; an intermediate zone, which contains enlarged blood vessels and free extracellular and intracellular tachyzoites; and a peripheral zone, with few prominent blood vessels and mainly encysted organisms.
On nonenhanced CT, Toxoplasma encephalitis appears as areas of isointense or hypodense mass effect. The basal ganglia and the corticomedullary junction are most commonly affected. Contrast-enhanced CT demonstrates a ring or nodular enhancement pattern with lesions of 1-3 cm in diameter. The enhancement is greatest within the intermediate zone where inflammation is the greatest.
MRI of the brain both without and with intravenous gadolinium contrast enhancement is the most sensitive test for Toxoplasma encephalitis. Lesions with contrast may be hyperintense compared to normal brain tissue and may be difficult to identify compared to the edema pattern otherwise seen in the surrounding brain. The ring enhancement, which is best seen on T1-weighted gadolinium-enhanced studies, represents the enhancement within the most active area of the infection. Following treatment with pyrimethamine and sulfadiazine or clindamycin, the lesions become reduced in size with resolution of the ring of enhancement.
Preferred Examination
The preferred initial examination of the patient in whom brain abscess is suspected is MRI with and without gadolinium enhancement. Similar diagnostic results can be expected from cranial CT scans without and with the intravenous administration of iodinated contrast medium. Both imaging techniques help detect the mass effect of the abscess; however, findings in MRI with a diffusion protocol are more specific in differentiating cerebral tumor, stroke, and abscess. In particular, examination of the metabolite peaks with MR spectroscopy can help to specifically differentiate tumor, radiation necrosis, and abscess by identifying their different spectral profiles.
Perfusion MRI has also been used to differentiate these lesions by evaluating vascularity with blood flow analysis with dynamic intravenous gadolinium contrast injection studies.
Occasionally, distinguishing brain abscess from neoplasm or postoperative changes from infection is difficult. In these patients, a nuclear agent can be used to tag white blood cells or antibodies to help differentiation.
Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving
orstraightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.
Limitations of Techniques
Plain radiographs of the paranasal sinuses can only suggest a possible etiology for cerebral abscess. Early findings of CT examinations are not specific for cerebral abscess. The edema pattern and moderate mass effect cannot be differentiated from tumor or stroke in some patients. MRI findings in patients with cerebritis may resemble findings in stroke, while findings in the infarcts that result from vasculitis and cerebritis may resemble those of embolic strokes. Nuclear medicine single photon emission computed tomographic (SPECT) findings are not specific for brain abscess unless a white cell tag is used.
Follow-up scans for certain infectious agents, such as M tuberculosis, may be necessary because infection by these organisms may not follow a predictable response to treatment. Tuberculosis-related brain abscesses that retain positive results to culture and smears following 4 weeks of treatment may not represent treatment failure. In addition, treatment of fungal infections may require many weeks of treatment with interval follow-up imaging studies. Follow-up imaging during the treatment for toxoplasmosis is important in avoiding brain biopsy.
Differential Diagnoses
Other Problems to Be Considered
HIV encephalitis
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Further Reading
Keywords
intracranial infection, pyogenic infection, pyogenic bacterial infection, tuberculous infection, fungal infection, parasitic infection, brain infection, cerebritis, purulent brain infection, cerebral abscess, cerebral infection, bacterial brain infection, central nervous system infection, CNS infection, Nocardia asteroides, Toxoplasma encephalitis, Listeria monocytogenes
