David C. Snow
Central nervous system (CNS) infections are uncommon, yet they can produce serious morbidity and mortality if their diagnosis is delayed. CNS suppurative infections include brain abscess, cranial subdural empyema, cranial epidural abscess, and spinal epidural abscess (SEA). These disease entities must be considered when evaluating patients who present with headache, fever, alteration of consciousness, back pain, or new neurologic deficits. Early identification with the administration of appropriate antibiotics and immediate neurosurgical consultation results in an improved outcome (1).
BRAIN ABSCESS
Brain abscess is a focal infection of the brain parenchyma, accounting for approximately 1 in 10,000 hospital admissions (2). It begins with a localized region of cerebritis, and evolves into a collection of pus surrounded by a capsule (3). Due to improvements in the treatment of ear, sinus, and dental infections the overall incidence of this disease process is decreasing, with only 1,500 to 2,500 cases each year in the United States (4). However, an increase in incidence may be seen as a result of enhanced use of neurosurgical procedures, improved imaging techniques, and increased population of immunocompromised patients (5). It remains the most common intracranial focal suppurative process and occurs about 2% as often as brain tumors.
There is a 2:1 male-to-female predominance. The age distribution relates to the predisposing condition or risk factor. Brain abscesses from an otic origin usually occur in patients younger than 20 years old or older than 40 years old. Most patients with a paranasal sinus focus are 10 to 30 years of age. Approximately 25% of cases occur in children younger than 15 years old. These cases are most commonly caused by cyanotic congenital heart disease or otic sources. An abscess rarely occurs in children younger than 2 years of age, sometimes occurring secondary to gram-negative bacterial meningitis (2,5).
Brain abscesses can arise from bacterial, mycobacterial, fungal or parasitic infections. They result from either direct spread from a contiguous focus of infection or through hematogenous seeding in the setting of bacteremia (6).
Bacterial brain abscesses are typically the result of contiguous spread from the oropharynx, middle ear, and paranasal sinuses (7). These infections can lead to abscess formation by two mechanisms: by direct extension through infected bone or by retrograde thrombophlebitis from emissary and diploic veins (7). Otitis media (chronic) and mastoiditis classically spread to the temporal lobe (50% to 75% of cases) and the cerebellum (one-third of cases). Approximately 85% to 99% of cerebellar abscesses are from an otic source. Frontal and ethmoidal sinusitis spread to the frontal lobe. Dental sources also tend to affect the frontal lobe (2,5). Penetrating trauma and postneurosurgical procedure abscesses account for between 1% and 12% depending on the case series (8–10).
About 25% of cases arise from hematogenous spread from a cardiac or pulmonary source, including lung abscess, bronchiectasis, cyanotic congenital heart disease (tetralogy of Fallot), and bacterial endocarditis. Most of these sources of hematogenous spread occur from areas of relatively low oxygen tension, leading to a strong predominance of anaerobic organisms. Hematogenously spread abscesses tend to be multiple and lie in the distribution of the middle cerebral artery at the gray-white junction where microcirculatory flow is the poorest. Other causes include hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease), dental extractions, abdominal or pelvic infections, and following esophageal stricture dilation and endoscopic sclerosis of esophageal varices (2,5). There is no clearly identifiable cause in the remaining 10% to 15% of cases (2).
The blood–brain barrier (BBB) is quite resistant to penetration of these microorganisms from the blood into the brain, which is why this condition is so rare despite the frequency of bacteremia. Improved microbiologic culture techniques have yielded a better understanding of the microbiology of brain abscesses. The most commonly isolated microorganisms are gram-positive cocci and anaerobes (9,10). Aerobic and microaerophilic streptococci (Streptococcus milleri, Streptococcus viridans) are the most common gram-positive bacteria isolated, being found in up to 70% of abscesses (5). The most commonly isolated anaerobes are Bacteroides sp. (from ear or sinus infection) and anaerobic streptococci (from dental and chronic pulmonary infections). Staphylococcus aureus and Staphylococcus epidermis are frequently isolated from posttraumatic or postsurgical abscesses (10). Gram-negative bacilli, found in 23% to 33% of cases, are associated with chronic otitis, postoperative infections, and abdominopelvic infection (2,5).
Granulocytopenia, cellular dysfunction, and humoral-mediated immune dysfunction are predisposing factors to the development of CNS infections in immunocompromised patients. Acquired immunodeficiency syndrome (AIDS) and the increasing use of immunosuppressive drug therapy have lead to more atypical, fungal, and protozoal brain abscesses such as Nocardia sp., Listeria sp., Cryptococcus sp., Mycobacterium sp., Aspergillus sp., and Candida sp. Fungi in the order Mucorales (Mucor, Rhizomucor) can cause abscesses in the setting of chronic sinusitis, most commonly in patients with diabetes mellitus (6). Toxoplasmosis gondii is the most common cause of brain abscess in patients with AIDS, and is most commonly seen in those with CD4 counts of less than 100 cells/mm3 (5,10).
Another important subgroup of patients with a compromised immune system is transplant patients. Brain abscesses occur in approximately 1% of transplant recipients. Fungi, particularly Aspergillus sp., are the most frequent etiologic agent (6).
CLINICAL PRESENTATION
The classic triad of fever, headache, and focal neurologic deficit is present in less than half of the patients with a brain abscess (4,5). There are no pathognomonic signs for a brain abscess; therefore, history and a high clinical suspicion are important features for proper diagnosis.
Headache, the earliest presenting symptom, is present in 70% to 80% of patients. The headache is usually insidious, occurring over days to weeks. Abrupt onset of the headache is a poor prognostic indicator. Fever is absent in more than 50% of patients. Alterations in consciousness, ranging from drowsiness to coma, occur in 50% of cases, as do nausea and vomiting. A focal neurologic deficit is seen in 50% to 75% of patients and can include aphasia, hemiparesis, visual field deficits, nystagmus, or ataxia. Cerebellar abscesses are usually associated with ataxia and dizziness. Cranial nerve findings are suggestive of a brainstem abscess. Focal or generalized seizures occur in approximately 30% of cases (1,4,9).
DIFFERENTIAL DIAGNOSIS
Primary or metastatic brain tumor can mimic cerebral abscess on a computed tomography (CT) scan. History and CT appearance easily differentiate other infectious diseases such as viral encephalitis, subdural empyema, epidural abscess, and meningitis.
Immunocompromised patients account for a large proportion of patients presenting to the emergency department (ED) with intracranial mass lesions. Because of the wide variety of pathologic processes involving the CNS of immunocompromised patients, brain biopsy is often needed for definitive diagnosis and treatment. Other considerations in this patient population include Cryptococcus sp., Candida sp., lymphoma, Kaposi sarcoma, and progressive multifocal leukoencephalopathy.
ED EVALUATION
The history and physical examination should focus on sites of potential infection and the possibility of life-threatening complications. Routine laboratory evaluation is rarely helpful. Leukocytosis may be present, but approximately 50% of patients will have a normal white blood cell count (9). An elevated erythrocyte sedimentation rate is seen in only 40% of cases; however, the C-reactive protein may help to distinguish abscess from tumor. Blood cultures are positive in about 10% of cases but should be obtained even if the patient is afebrile. Chest films may reveal a pulmonic source of infection; sinus or mastoid CT scans may identify infection in these areas.
Lumbar puncture for cerebrospinal fluid (CSF) analysis has a relative contraindication when evaluating for brain abscess. The risk of brainstem herniation is significant and the CSF analysis results typically do not aid in the diagnosis (7,9).
When it comes to neuroimaging, it is important to note that the imaging features of the abscess depend on its stage at the time of the imaging procedure. During the “early cerebritis” stage (first 3 days), a CT scan reveals an irregular area of low density representing focal inflammation and edema. This area does not enhance with contrast and represents the necrotic center of the abscess. In the late cerebritis stage (days 4 to 9), patchy enhancement is present, and the necrotic center develops. As the abscess evolves into the early capsule stage (days 10 to 14), a homogenous central area of low density is seen, and a thick, diffuse, ring-like vascular capsule is present. This enhancement correlates with formation of the collagen capsule. During the late capsule stage (after day 14), the ring becomes thinner as the capsular development progresses, and it is narrower on the ventricular surface of the abscess (3). Features that help to identify the mass as an abscess include gas within the center of the mass, a thinner rim (<5 mm), and ependymal enhancement. Patients given corticosteroids may have diminished enhancement of the abscess ring (5).
Magnetic resonance imaging (MRI) and CT scan are the studies of choice when evaluating a patient for a brain abscess. CT is the imaging study of choice for the initial evaluation of a patient with a suspected brain abscess, with a reported sensitivity of 95% to 99% (5). MRI has better sensitivity and specificity than contrast CT. MRI is better at detecting mass effect, edema, petechial hemorrhage, smaller lesions, and multifocal involvement (11). Thus, if clinical suspicion is high and a CT scan is negative, an MRI should be performed.
KEY TESTING
• CT (initial imaging) and MRI (higher sensitivity and specificity than CT) are the studies of choice.
ED MANAGEMENT
Initial management of the patient with a suspected brain abscess includes airway control and maintenance of adequate ventilation and circulation. If signs of elevated intracranial pressure and/or impending herniation are present, one must act rapidly to reduce the pressure. These treatments are only temporizing measures and include intubating and hyperventilating the patient, elevating the head of the bed 30 degrees, and instituting pharmacologic therapy with mannitol or hypertonic saline. Corticosteroids remain a controversial topic, but for patients with life-threatening cerebral edema or impending herniation, high-dose corticosteroids may be appropriate (12). Immediate neurosurgical consultation is required, but know that an abscess of less than 2.5 cm in size should do well with medical management alone (10).
Definitive management includes antibiotic therapy and neurosurgical evaluation. The recommended treatment for most abscesses is CT-guided stereotactic or free-hand needle aspiration, with cultures sent to ensure appropriate antibiotic therapy (12). These culture results will not be available during the initial ED evaluation, so antibiotics based on the most likely pathogens should be initiated. Table 183.1 outlines the choices of empiric antibiotics based on the suspected source of the abscess and organisms involved. Pending culture and sensitivity results, one standard regimen includes a third-generation cephalosporin plus metronidazole. In postsurgical abscesses, vancomycin or an antistaphylococcal penicillin should be used to cover methicillin-resistant S. aureus (MRSA) (2,5,10,12).
TABLE 183.1
Choices of Empiric Antibiotics Based on the Suspected Source of the Abscess and Pathogens Involved
DISPOSITION
All patients diagnosed with a brain abscess in the ED require admission to the hospital and immediate neurosurgical consultation. If a neurosurgeon is not available, arrangements should be made for transfer to a neurosurgical center after stabilization. Young persons, patients without underlying disease, and patients without neurologic deterioration or mental status changes have a better prognosis. With early diagnosis, advanced neuroradiologic imaging, and rapid treatment, mortality is <30%, but patients presenting with signs of herniation have mortality >50% (2,5). Persistent neurologic deficits, including seizure, intellectual or behavioral impairment, and motor deficits, are seen in 30% to 55% of patients (5).
CRANIAL EPIDURAL AND SUBDURAL SPACE INFECTIONS
Intracranial subdural empyema and cranial epidural abscess are rare but life-threatening intracranial suppurative infections. Subdural empyema accounts for 15% to 25% of focal intracranial infections, and cranial epidural abscess is much less common. Subdural empyema is a disease of teenagers and young adults, with 70% of cases occurring in the second and third decades of life (13). Epidural abscess rarely occurs in young children and has been reported in patients from ages 12 to 68 years. Both conditions exhibit a 3:1 male-to-female predominance (5,13).
Subdural empyema forms between the dura mater and arachnoid mater, and cranial epidural abscess forms outside the dura mater. Both entities share a similar pathogenesis and etiology, and the two infections can coexist. Subdural empyema is typically a complication of sinusitis, and less frequently of otitis media or mastoiditis. Less frequent is the spread of organisms through Haversian canals in bone as a complication of osteomyelitis (12,13). Other causes include cranial osteomyelitis, mastoiditis, otitis media, head trauma, cranial surgery, ventriculoperitoneal shunt, halo traction pins, orbital infections, and chronic subdural hematoma (5,14). In children, bacterial meningitis is the most common predisposing condition (2).
Multiple pathogens are typically responsible for these infections and are dependent on the initial site of infection. Aerobic, microaerophilic, and anaerobic streptococci, including S. milleri and Streptococcus anginosus, are common organisms with an otorhinogenic origin. S. aureus and coagulase-negative staphylococci are found in sinus, otic, postoperative, and posttraumatic cases, with as many as 46% of postsurgical subdural empyemas caused by S. aureus (15). Gram-negative bacilli can usually be seen in otic and posttraumatic sources. Polymicrobial infections are common and a sterile culture may be found in 20% to 30% of cases. In children, the most common causative agents are those responsible for the underlying meningitis (2,5,12,13,15).
CLINICAL PRESENTATION
The clinical presentation of subdural empyema is fever, headache, and nuchal rigidity. The nonspecific symptoms of a sinus or ear infection, fever, and malaise rapidly progress to severe headache and meningismus (13). The headache, present in 90% of cases, is focal, but becomes more generalized. Nausea and vomiting are common. Varying degrees of encephalopathy can be seen, ranging from mild confusion to coma. Third and sixth cranial nerve palsies are seen rarely. Seizures, however, have been reported in 50% of patients (13,14). Postoperative and posttraumatic subdural empyemas have a very indolent course caused by slow accumulation of fluid. Headache is often absent and the disease course is more benign (5).
The presentation of epidural abscess is more insidious. Symptoms can take weeks to months to develop. Patients often present with a long history of nonspecific symptoms without focal signs or mental status changes. Once the fluid mass reaches critical size, nausea, vomiting, headache, drowsiness, and lethargy occur. Focal neurologic signs, seizure, and coma do not occur unless the infection spreads to the subdural space, or cerebral herniation occurs. A patient with an epidural abscess involving the petrous bone may present with pain in the distribution of the fifth cranial nerve, and a sixth cranial nerve motor palsy (Gradenigo syndrome) (16).
DIFFERENTIAL DIAGNOSIS
The initial presentation of subdural empyema and epidural abscess is similar to other intracranial processes. Meningitis, brain abscess, subdural hematoma, subarachnoid hemorrhage, herpes encephalitis, venous sinus thrombosis, and tumor should be considered.
ED EVALUATION
History and physical examination should focus on finding potential sources of infection. A detailed neurologic examination should be performed. Routine laboratory evaluation is of limited value. The white blood cell count may be only mildly elevated and is often normal. The sedimentation rate may be elevated if osteomyelitis is present. Cerebral spinal fluid analysis is usually not helpful and is relatively contraindicated because of the risk of herniation (13).
CT scanning with IV contrast remains the mainstay of ED diagnosis for both subdural empyema and cranial epidural abscess, yet the diagnostic procedure of choice is MRI with gadolinium (13). Subdural empyema reveals a crescent-shaped, hypodense fluid collection in the subdural space with displacement of the arachnoid. A mass effect is common and an enhancing rim may be seen. Epidural abscess appears as a poorly defined, lentiform, extra-axial area of low or intermediate density. These entities can be easily missed by CT, given the proximity of the cranial vault, so MRI should be used when CT scanning is negative in the face of high clinical suspicion (13,17).
KEY TESTING
• Routine laboratory evaluation is of low yield.
• MRI and CT scanning are the studies of choice, with MRI considered the diagnostic test of choice for both disease processes.
ED MANAGEMENT
Once the diagnosis is made, immediate neurosurgical consultation is required. If signs of impending herniation are present, temporizing measures must be employed.
Antibiotic coverage should begin in the ED. The choice of antibiotic should be tailored to the suspected source until culture results are available. A scheme for antibiotic selection is outlined in Table 183.1.
DISPOSITION
All patients require admission. If neurosurgical services are not available, the patient, once stabilized, should be transferred to an appropriate center with available neurosurgical services. Patients with an isolated cranial epidural abscess have an excellent prognosis. Most recover with good neurologic outcome. The mortality for subdural empyema ranges from 9% to 48% (18). Of those patients who survive, 15% to 44% have a persistent neurologic deficit (seizure disorder, hemiparesis, aphasia). Outcome is directly related to advanced patient age, degree of encephalopathy present, and delay to appropriate therapy (18).
SPINAL EPIDURAL ABSCESS
SEA, although still a rare entity, has doubled in incidence in the past 20 years, with 1.2 to 3 cases per 10,000 patients. This increase is likely due to an aging population, increased use of spinal instrumentation, and the increase in intravascular drug use (19,20). The most important risk factors are diabetes, trauma (e.g., spinal instrumentation), intravenous drug use, alcoholism, advanced age, and an immunocompromised state. Diabetes remains the single most important risk factor, and presents in 15% to 33% of cases (19). Bacteria gain access by hematogenous dissemination in 50% of cases, by contiguous spread in 33% of cases, and in the remaining percentage the source is not identified (20). The most frequently isolated organism is S. aureus, with up to 40% being the methicillin-resistant strain. Streptococcus sp., Escherichia coli, Pseudomonas sp., Klebsiella sp., Acinetobacter sp., and Mycobacterium tuberculosis have also been found (19–21).
CLINICAL PRESENTATION
Back pain (75% of patients), fever (50%), and neurologic deficit (33%) are the classic triad of this disease process, but is only present in a minority of patients, 8% in one case report (20,21). There is a staging system detailing the progression of symptoms and physical findings: in stage 1 there is back pain at the level of the affected spine only; in stage 2 there is nerve-root pain radiating from the involved spinal area; in stage 3 there is motor weakness, sensory deficit, and bladder and bowel dysfunction; and stage 4, paralysis (20).
Irreversible paralysis remains the most feared complication of SEA, with delayed diagnosis one of the main culprits. About half of the cases are initially misdiagnosed (20), so considering this disease in your differential is of the upmost importance.
DIFFERENTIAL DIAGNOSIS
The presentation of an SEA is similar to many types of back pain. Other diagnoses to keep in mind when evaluating a patient with back pain include intervertebral disc herniation, metastatic epidural spinal cord compression, spinal epidural hematoma, and simple back strain. Separating these diagnoses requires a thorough history and physical examination. MRI and CT scan provide further information as to the cause of the back pain.
ED EVALUATION
The diagnosis of SEA is suspected on the basis of clinical findings and supported by laboratory data and imaging studies. Leukocytosis is present in two-thirds of patients, and inflammatory markers (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]) are almost always elevated, with 100% sensitivity for ESR noted in one study (22). Bacteremia is noted in 60% of patients, so blood cultures should also be utilized (20). CSF analysis should be entertained with caution, as there is a risk of spread of infection if the needle traverses the abscess.
Contrast CT of the spine is better than noncontrast imaging for identifying an abscess, but is still inferior to MRI. MRI is the most useful study for demonstrating an abscess with sensitivity reported to be between 90% and 100% (19–21,23). MR images also demonstrate discitis and osteomyelitis when present, which coexist with up to 80% of patients (20).
KEY TESTING
• Inflammatory markers (ESR and CRP) help with the diagnosis of SEA (22).
• MRI and CT scanning remain the studies of choice for this disease processes, with MRI (preferably with gadolinium) considered the diagnostic test of choice if available (19–21,23).
ED MANAGEMENT
Surgery and antibiotics are the mainstays of therapy. Antibiotics should be started as soon as the diagnosis is established. Appropriate antibiotic choices should provide coverage against staphylococci (typically with vancomycin for MRSA coverage), and gram-negative bacilli with a third- or fourth-generation cephalosporin (e.g., ceftazidime or cefepime). Antibiotics are usually continued for 6 weeks (19,20).
CRITICAL INTERVENTIONS
• Suspect CNS abscess or other suppurative infection in high-risk patients with headache, neck pain, or back pain and order CT or MRI.
• Administer antibiotics in the ED.
• Obtain neurosurgical consultation (or orthopedic spine consultation as appropriate).
DISPOSITION
All patients with an SEA require admission to a neurosurgical or spinal orthopedic surgery service. If these are not available, the patient should be stabilized, should have antibiotics started, and should be transferred to an appropriate center. Neurologic deficits for greater than 48 hours, immunocompromised patients, involvement of the thoracic spinal cord, and MRSA as the causative organism all worsen the prognosis for a complete recovery.
Common Pitfalls
• Failure to suspect a suppurative CNS infection in patients presenting with headache, neck pain, or back pain
• Inappropriate antibiotic selection because the probable origin of the infection was not considered
• Delay in initiating treatment for increased intracranial pressure and obtaining neurosurgical consultation
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