Volume 5, Case 8
Leo U. Pascua, MD
Kapiolani Medical Center For Women And Children
University of Hawaiʻi John A. Burns School of Medicine
This is a 12-month old male in previously good health presenting to a clinic with a history of fever for two weeks (highest recorded temperature 39.1 degrees). The fevers were initially attributed to teething. There is a dry, nonproductive cough for one week. He has had a decreased appetite, but no vomiting or diarrhea. Yesterday, he was noted to be lethargic with decreased movement of his right arm and left leg. His eyes would also roll. This morning, an aunt came over to the home and found him to be quite somnolent, poorly responsive and with abnormal twisting movements of his extremities. This aunt immediately brought him in to the nearest clinic.
Exam: T 37.3 (axillary), HR 165, RR 20, BP 143/97. He is well developed and well nourished. He is tired appearing, sometimes listless and somnolent. There is no spontaneous movement of the entire right side of his body. He has a modest left facial droop. Pupils are 5-6 mm bilaterally, sluggishly reactive to light, with intermittent nystagmus. TM's unremarkable. His head is turned to the left, with resistance felt when passively rotating his head to the right (refuses to bring his chin to the midline). Neck difficult to assess for rigidity. Heart regular, no murmurs. Lungs clear. Abdomen benign, scaphoid, no palpable masses, tenderness or hepatosplenomegaly. Extremities slightly cool, pulses somewhat diminished, but normal capillary refill time. Skin clear. DTR's 2+ bilaterally. He holds his left leg extended. His right hip is flaccid with the ipsilateral knee in fixed flexion. With noxious stimuli, he does not withdraw from pain at the right leg or right arm. His left leg and left arm react normally. His plantar reflexes are downgoing bilaterally.
A CT of the brain is immediately ordered.
View CT.
These two cuts from his CT scan series show multiple 2-3 cm diameter loculated cystic lesions consistent with multiple abscesses (dark areas with rims of enhancement). There is distention of the posterior fossa with a midline shift toward the right. There is no sign of cribiform fracture or mastoiditis.
He is admitted to the intensive care unit where infectious disease and neurosurgical consultations are obtained. His initial work-up includes a CBC and chemistry. A chest radiograph and an abdominal radiograph are performed to look for signs of other abscesses.
Admission labs: Na 141, K 3.4, Cl 99, bicarb 25, gluc 127, Ca 10.3, phos 5.3, Alb 3, SGPT 8, SGOT 22, BUN 10, creatinine 0.2. WBC 23.2 (49% segs, 14% bands, 7% monos, 28% lymphs). Hgb/Hct 9/37. Platelets 474,000. His chest radiograph is normal.
View abdominal flat plat.
An open safety pin is noted in his abdomen.
Shortly after admission, he developed seizures. He was treated with anticonvulsants, cerebral dehydration and controlled hyperventilation. Approximately 12 cc of foul smelling, thick, yellow-green, purulent material was needle aspirated through the lambdoidal suture. Gram stain showed gram positive cocci in clusters, chains and pairs. A burr hole was drilled into the right suboccipital area, and a large posterior fossa abscess was aspirated for yellow, creamy, opaque fluid. A left brain abscess was visualized by ultrasound and needle aspirated for 85 cc of purulent material sent for culture. He was initially started on ampicillin, clindamycin, and gentamicin. His initial culture grew peptostreptococcus, fusobacterium and alpha hemolytic streptococci, all of which are oral bacteria. His antibiotics were changed to vancomycin, ceftazidime, metronidazole, tobramycin, and chloramphenicol.
Two days after admission, a follow-up abdominal radiograph is obtained.
View follow-up abdominal film.
This abdominal film shows the safety pin to be broken into two pieces now. It has not moved much. There is residual barium in the bowel from a previous contrast study which was unremarkable. Two weeks later, the safety pin fragments are no longer seen.
An echocardiogram to rule out cardiac vegetations showed a possible left atrial appendage lesion. A repeat echo was normal, with no definite evidence of left atrial mass.
His overall clinical progress was poor. Follow-up CT scans showed recurrent abscesses and progressive cerebral atrophy.
How the safety pin relates to his brain abscesses is unclear. Cultures of the brain abscesses were not positive for bowel organisms, but rather oral flora. Perhaps the safety pin caused a perforation somewhere in his pharynx or esophagus as it was going down.
Discussion
The first reference to brain abscess was made by Hippocrates in 460 B.C. Farre recognized brain abscess as a complication of congenital heart disease in 1840. The first operative treatment of brain abscess was by Dupuytren in 1889.
Brain abscesses are the most frequent intracranial suppurative process occurring in children, the pathogenesis of which depends upon predisposing conditions that also influence the anatomic location of the abscess. The transmission of infection may occur by continuity, as with penetration of the dura, or by contiguity or juxtaposition. The membranous cranial bones are formed from both dura and galea; therefore, they derive their blood supply from both structures. This intracranial/extracranial vascular connection explains the mechanism for the development of cortical thrombophlebitis. The diploic veins of Breschet are valveless; therefore, blood may flow in either direction and bacterial infection or septic emboli may gain access intracranially. Cranial bone defects may occur and can be either acquired or congenital. The posterior wall of the frontal sinus, which is normally about one half the thickness of the anterior wall, may be eroded by a mucocele, infection, or neoplasm, or it may sustain disruption due to trauma. The epidural space may become infected in the dehiscent area, with abscess formation and possibly secondary intracranial spread throughout the dura.
Chronic otitis media, mastoiditis, meningitis and congenital heart disease are the most common predisposing factors, accounting for about 60% of brain abscesses in children. Contiguous spread from ear, nose or throat infections usually results in a single abscess formed in proximity to the infected area, i.e., frontal abscess arising from ethmoid sinusitis, or temporal or cerebellar abscess arising from mastoid infection. The average age of these children is 5 to 10 years. Extension occurs via anastomosing veins. Purulent material can also drain directly from an infected sinus through the cribiform plate of the frontal bone into the subdural space. Meningitis as a cause is more common in children less than 2 years of age.
About 2% of children with cyanotic congenital heart disease (i.e., right to left intracardiac shunts, pulmonary arteriovenous fistulas) develop brain abscess. Tetralogy of Fallot is the most common heart defect leading to brain abscess formation. Infection is usually with alpha-hemolytic streptococci. Organisms with a predilection for hypercarbic/hypoxic areas have been isolated. Mixed infections are uncommon.
Odontogenic (i.e., dental abscess), as well as massateric space and infratemporal infections may be the primary site. Head trauma (i.e., skull fracture), or penetrating head injury are known risks for brain abscess. P. multocida must be considered in a skull penetrating dog bite. Ocular trauma (i.e., orbital roof or temporal bone fracture) with wooden toys has been associated with cerebral abscesses. In such cases there is a male to female ratio of 3:1, with the most common item being a graphite pencil. Wood, as a penetrating agent carries a high risk of infectivity and fragmentation. MRI may be needed to identify the foreign body.
Abscess due to hematogenous spread (i.e., from endocarditis, osteomyelitis, etc.), is usually along the distribution of the middle cerebral artery in the posterior frontal or parietal regions. Immunosuppressed patients are also at risk. The presence of a ventroculoperitoneal shunt increases the risk of infection by S. epidermidis and S. aureus.
Citrobacter diversus or Proteus must be considered in neonates with multiple brain abscesses. The susceptibility of newborns to Gram-negative infection is well established, and is explained by the deficiency of both placentally transferred IgM antibodies and complement. The physiological right to left shunt of the neonatal blood circulation could explain the colonization of the brain during septicemia.
No discernible underlying disease or source of infection can be found in 30% of pediatric brain abscess patients. In adults, pulmonary disease is the most frequent cause for dissemination. This is not true for children.
Anatomic sites of infection are associated with certain organisms. Frontal lobe abscesses (the most frequent, 37%) are usually due to sinusitis, and usually include aerobic and anaerobic streptococci, S. aureus, S. pneumoniae, and H. flu. Cerebellar (2%) and ipsilateral temporal lobe abscesses (11%) are usually due to otitis media or mastoiditis. Common entities include S. pneumoniae, H. flu, Enterobacter and B. fragilis. Temporal, frontal and parietal lobe abscesses (28%) have been associated with congenital heart disease.
Multiple abscesses usually arise from meningitis, pulmonary and VP shunt site infections, as well as congenital heart disease. In the case of congenital heart disease, abscesses usually arise along the distribution of the middle cerebral artery. VP shunt infections can involve S. aureus, S. epidermidis, Gram negative enteric rods, and P. aeruginosa. Staph aureus is the most common organism in brain abscesses due to head trauma or surgical events. Enterobacter and anaerobes can spread from intra-abdominal or genitourinary sites.
Pathogenesis
Focal areas of ischemia or necrosis (i.e., due to suppurative vasculitis, hypoxic episode, embolism, hyperviscosity, etc.) are a prerequisite for invasion by microorganisms because the brain parenchyma is resistant to infection. In addition to epidural or cerebral abscess, the same mechanism applies to subdural empyema as well as septic thrombophlebitis of the emissary cortical veins or venous sinuses.
Four stages are recognized in the development of brain abscesses. The first stage (early cerebritis) lasts 1-3 days, and is characterized by perivascular cuffing with inflammatory cells in the region surrounding the developing necrotic center, with marked cerebral edema developing peripherally. During this cerebritic stage (pre-encapsulation), antibiotics may still be able to halt abscess development. The second stage (days 4 to 9) is characterized by early capsule formation via fibroblasts, as well as neovascularization. The third stage (days 10-13) shows definite capsule formation with concomitant increase in fibroblast numbers, as well as shrinkage of the necrotic center and diminishing cerebritis. In the fourth stage (days 14 on), a well defined necrotic center and a dense collagenous capsule with peripheral cerebral edema can be seen.
The degree of symptomatology is a poor indicator of whether the intracranial infection is still in the cerebritic stage or has become encapsulated.
Clinical Presentation
The most prominent clinical manifestations of brain abscesses result from space-occupying effects in the rigid cranial vault. Expansion of the lesion, bacterial breakdown products, or macrophage induced cerebral edema may result in increased intracranial pressure and subsequent potentially lethal uncal or brainstem herniation. The "classic" triad of fever, headache and focal neurological deficits occurs in less than 50% of patients (28% in one study; Saez-Llorens, 1989). Seizures, and lethargy are common, as are hemicranial headaches, alterations in consciousness, nausea, and vomiting. Papilledema, ataxia and aphasia were also reported. Sixth nerve palsy may indicate increased intracranial pressure. Infants frequently present with fever, meningismus, and/or a full fontanelle.
Symptoms can also depend upon the anatomic sites, i.e., cerebellar abscess presenting with nystagmus, ataxia, vomiting and dysmetria. The frontal lobe is thought to be a neurologically silent area, and thus abscess formation may not result in focal signs. Subtle affective changes, behavioral problems, abusive and profane language, depression, or euphoria may be more indicative of changes in this area.
Differential diagnosis
The differential diagnosis is extensive. Infectious entities include viral encephalitis (especially herpes simplex virus), subdural empyema, epidural abscess, pyogenic meningitis, tuberculoma, cysticercosis, echinococcosis, and cryptococcosis. Non-infectious entities include primary and metastatic brain tumors, subarachnoid or intracerebral hemorrhage, central venous thrombosis, cerebral infarct, mycotic aneurysm, chronic subdural hematoma, hemorrhagic leukoencephalitis, or migraine.
Lab findings
Lumbar puncture is contraindicated due to the risk of cerebral herniation. Cerebrospinal fluid is a poor source for isolating the organism (positive cultures in only 7%; Saez-Llorens, 1989), unless the abscess ruptures in to the ventricular system, in which case the CSF WBC count may be greater than 50,000 with a predominance of polymorphonuclear cells. The CBC may reflect peripheral leukocytosis with neutrophilia. Blood cultures may be sterile. Electrolytes are generally normal, unless hyponatremia suggests the development of SIADH.
Diagnostic Imaging
Between 1960 and 1974 the techniques used to diagnose brain abscess included pneumoencephalography, ventriculography, carotid arteriography and nuclear brain scan. Since 1984, CT of the brain has been the principal diagnostic technique.
Computed tomography remains the study of choice, as it can discern the number, size and locations of abscesses with a high degree of sensitivity and specificity. A brain abscess usually appears as a hypodense center with a surrounding ring which can be contrast-enhanced. Other patterns include nodular enhancement, and areas of low attenuation without enhancement. The degree of enhancement is thought to correlate with the degree of perivascular inflammatory cell infiltration and neovascular proliferation. Delayed films with an assessment of the degree of enhancement in the center of the lesion may differentiate between cerebritis (medical management possible) and true encapsulated abscess (surgical intervention more likely needed), the latter showing a paucity of central contrast.
Skull films may show bubbles (pneumocephalus) from gas-producing organisms within an abscess cavity or outside the cranium. An electroencephalogram may localize a focal lesion as opposed to a more generalized lesion such a encephalitis. Seizure activity and diffuse encephalopathic patterns have been reported. Low frequency delta waves commonly signify a cerebral abscess (slow wave foci). A brain scan should be considered for patients with a negative CT if there is still a strong suspicion of a brain abscess. Cerebral arteriograms have demonstrated avascular masses.
Management
The origin of the infection can dictate the choice of initial antibiotic treatment. An initial trial of antibiotic therapy may be warranted in patients who are considered poor surgical candidates, have multiple abscesses or abscesses in deep or difficult anatomical locations, concomitant meningitis, or whose abscess size is less than 4 cm or considered to be in the cerebritis stage.
Extensions of ENT infections can be treated with penicillin (strep coverage, including S.milleri), chloramphenicol (anaerobic coverage, high abscess penetration), metronidazole (bactericidal for most anaerobes, high abscess penetration, occasionally achieving abscess concentrations greater than serum, not degraded in purulent debris), or cefotaxime (active against Hemophilus, Enterobacter, strep and staph). Penetration is increased in infected tissue. Nonetheless, penicillin-susceptible bacteria can be cultured from abscesses for prolonged periods despite antibiotic therapy. Inactivation of antibiotics may occur by bacterial or leukocytic enzymes accumulating in the purulent material trapped by the encapsulation, subtherapeutic concentrations within the capsule, or antagonism in the case of multiple antimicrobial agents.
Infection from head trauma or cranial surgery warrants an antistaphylococcal agent, e.g. nafcillin. Vancomycin is indicated when methicillin-resistant S. aureus is prominent. With the exception of B. fragilis and some other anaerobic strains, most of the anaerobic pathogens are sensitive to penicillin. Ampicillin is inadequate for empiric treatment because of the increasing frequency of resistant E. coli and Proteus spp., as well as unreliable penetration. Aminoglycosides do not penetrate well into brain abscesses, and they have reduced activity in the anaerobic/acidic conditions associated with purulent material. A beta lactamase-resistant penicillin, e.g. nafcillin, oxacillin or methicillin versus S. aureus, should be added to metronidazole to cover aerobic and microanerophilic streptococci.
Third generation cephalosporins are options for treatment, given their efficacy against Gram negative bacillary infection, broad coverage, high degree of activity, and action against S. pneumoniae and H. flu. Ceftazidime penetrates the subarachnoid space and is active against P. aeruginosa. Older cephalosporins, clindamycin and erythromycin have generally been inadequate at achieving therapeutic concentrations. Trimethoprim-sulfamethoxazole may cover aerobic Gram-positive and Gram-negative rods.
Chloramphenicol may be bactericidal against S. pneumoniae, Hemophilus spp. and most of the obligate anaerobes including B. fragilis, but bacteriostatic against S. aureus and Enterobacter. Direct instillation of antibiotics in the abscess cavity during aspiration has been reported, but efficacy of this technique has not been formally assessed.
Corticosteroid use is controversial. It is thought to retard the encapsulation process, as well as decrease endothelial permeability of vessels associated with the inflammatory reaction, and thereby reduce the amount of brain water. However, it may increase necrosis, reduce antibiotic penetration into the abscess, and alter CT scan images of ring enhancement. Steroid therapy can also produce a rebound effect when discontinued. Thus, corticosteroid use to reduce cerebral edema should be as short a course a possible.
The duration of treatment depends upon the patient's clinical response, imaging findings, organisms isolated, and the extent and type of surgical drainage, if any. For those patients undergoing excision, 7 to 10 days for parenteral therapy has been suggested. Three to four weeks are probably required for patients treated with aspiration, and a minimum of 4 weeks for those treated with antibiotics alone.
Surgical management
Debate continues as to whether excision of the abscess wall is preferable to single or multiple aspirations of the cavity. The latter appears to be preferred in children, on the basis of comparable mortality rate and of less potential damage to the brain tissue from surgical trauma. Aspiration is used for brain abscess in early infancy, in large abscesses with poor capsule formation and in most centrally or deeply located abscesses. Stereotaxic aspiration or aspiration guided by operative neurosonography is performed in deep hemispheric abscesses or multiple abscesses with an intracranial mass effect. If the patient has increasing neurologic deficit, including deteriorating consciousness or signs of increasing intracranial pressure, surgery is necessary.
The predominant mode of surgical therapy was craniotomy with abscess resection. Intraoperatively, it is important to prevent ventricular or leptomeningeal contamination. Biopsy of brain tissue may be necessary if mucormycosis or neoplasm is suspected.
Complications
The mortality rate of brain abscess varies in the literature from 11 to 53%, and is increased with increased duration of symptoms before medical intervention, coma on admission, young age, larger abscess size, multiple abscess, and rupture into the cerebral ventricles or subarachnoid space.
Improvements include the use of CT scanning, improved methods for isolating anaerobic flora, and more effective antimicrobial treatment. Morbidity is increased in patients who undergo aspiration, rather than evacuation or resection.
Sequelae
Neurological sequelae (seizure disorders, hemiparesis, optic atrophy, spasticity, cranial nerve palsy, hydrocephalus, behavior disorder, school learning disabilities) can be present in up to 60% of patients. Conversely, complete recovery has been reported in 40% of patients. The incidence of neurologic sequelae has been lower when abscesses were aspirated (facilitated greatly by CT) rather than excised.
Serial CT scans are the mainstay of clinical follow-up, especially after antibiotics therapy is discontinued. A suggested regimen for serial CT's is every 2-4 weeks until resolution of the lesion, then at 2-4 month intervals for 1 year. Successful therapy would be indicated by a progressive decrease in the degree of ring enhancement, edema, mass effect, and size of the lesion.
References