Current concepts in the management of pyogenic brain abscess.
Current philosophy of treatment of brain abscess includes aspiration, appropriate antibiotics, treatment of sequelae and eradication of the primary source. Early clinical suspicion and diagnosis with CT is crucial. Small abscesses (<3 cm) in cerebritis or capsular stage located deep in clinically stable, poor surgical risk patients with diagnosis firmly supported by CT, may be treated with medical treatment only. Biweekly CT scan must be done to monitor the treatment response. CT or ultrasound guided aspiration should be performed in the event of clinical deterioration, failure of reduction in size or enlargement of abscesses. Encapsulated abscess (>3 cm), presence of significant neurological deficit or mass effect, doubt in the diagnosis and presumed resistant organisms are best treated with aspiration. Excision is required in large superficial abscesses resistant to multiple aspirations, post-traumatic abscess with a foreign body or fistula and multiloculated abscess of nocardial or actinomycotic aetiology. Results are directly related to the sensorium at the time of presentation. Stereotactic aspiration of all the loculi of multiloculated abscess in single or staged aspiration, and more completed drainage and lavage with endoscopic stereotactic evacuation may cut down indications of excision of brain abscess in future. It is concluded that, with diagnostic and technical advancements, a trend of adequate drainage of brain abscess via minimally invasive surgery is emerging. Confirmation of diagnosis and monitoring of treatment response with magnetic resonance spectroscopy may allow greater number of patients in future to be managed with medical treatment only.
The incidence of brain abscess varies from 1-2% of all intracranial space occupying lesions in developed countries, to 8% in the developing countries.,
Though potentially curable, brain abscess remains a diagnostic and therapeutic challenge. The past 20 years have seen major advances in the diagnosis and management of brain abscesses, with a corresponding improvement in the survival rate.
A brain abscess is initiated when micro-organisms are introduced into the brain tissue following trauma, contiguous pericranial infection, meningitis or haematogenous dissemination from a distant infective focus. Eighty percent of cases have a known predisposing factor. Otogenic source is the commonest cause with temporal lobe or cerebellar hemisphere as common locations.,, Histologically, there are four stages in brain abscess formation: early cerebritis (day 1-3), late cerebritis (day 4-9), early encapsulation (day 10-13) and late capsule stage (day 14 onwards). About two weeks are required for encapsulation, which is usually less complete on medial or ventricular side due to poor vascular supply.,
Clinically, brain abscess presents with features of rapidly expanding intracranial mass lesion i.e. raised intracranial pressure (ICP) in the form of constant progressive headache refractory to therapy, vomiting, papilloedema, focal deficits, convulsions, meningism and altered sensorium. The classical triad of headache, focal neurological deficits and fever is found in 25% cases only. The duration of symptoms is usually less than 2 weeks, with rapid onset and progression. Immunocompromised patients may have an insidious onset. Lumbar puncture prior to CT scan as part of diagnostic process remains pointless, hazardous and should be avoided. CT facilitates early detection, exact localization, accurate characterization, determination of number, size and staging of the abscess. It also detects hydrocephalus, raised ICP, oedema and associated infections like subdural empyema, ventriculitis and thus helps in treatment planning. It is invaluable in assessment of adequacy of treatment and sequential follow up.
An ill defined area of low density, on plain CT, corresponds to developing necrotic centre in the cerebritis stage. In the early capsule stage, a slightly hyperdense, faint ring is seen surrounding a necrotic hypodense centre. With contrast, the ring shows thin regular enhancement of uniform thickness and smooth contour on its inner surface with marked perilesional hypodense area suggestive of oedema. In the late capsule stage, the capsule is seen as a ring in plain CT. With contrast, it shows thick enhancement which gradually fades in delayed scans. Ring enhancement can be seen in the late cerebritis stage and is not an absolute evidence of encapsulation.,
Radiological features alone are inadequate to differentiate pyogenic brain abscess from fungal, nocardial or tuberculous abscess, inflammatory granuloma (tuberculoma), neurocysticercosis, toxoplasmosis, metastasis, glioma, resolving haematoma, infarct, hydatid cyst lymphoma and radionecrosis.,,, However, fever, meningism, raised ESR, multilocularity, leptomeningeal or ependymal enhancement, reduction of ring enhancement in delayed scan and finding of gas within the lesion favour a diagnosis of abscess.
Positive labelling in radionuclide imaging with III-Indium labelled leukocytes, C-reactive protein, 99m TC-hexamethylpropylene amine oxime leukocyte scintigraphy, diffusion weighted MR imaging, Thallium-201 single photon emission computed tomography and proton magnetic resonance spectroscopy (MRS) help in differentiating abscess from tumour.,,,,,,,
In general, the basic principles of treatment are appropriate antibiotics with or without aspiration, treatment of sequelae i.e. hydrocephalus, seizures etc. and eradication of primary source. The controversy of medical or surgical treatment has been well discussed by Rosenblum et al. The choice between conservative vs operative treatment is influenced by age, neurological status, location, number, size and stage of abscess formation. Each case must be individualised and treated on its own merits.
Conservative (Medical) Treatment
Medical treatment with antibiotics during early phase of cerebritis may abort the development of an abscess and result in a cure. Sole conservative management without surgery should be reserved for patients in whom the diagnosis is firmly supported by identification of a predisposing factor, imaging studies and in patients where the organism has been identified presumptively from culture elsewhere. The patient must be alert, clinically stable and should have a major risk for surgery and anaesthesia. High risk patients with bleeding diasthesis caused by thrombocytopenia (platelets <30,000) or coagulopathy, in whom even minimally invasive neurosurgery is contraindicated, are best treated with medical therapy only. Abscess in cerebritis stage, or walled off but smaller than 3 cm diameter could be treated non surgically with antibiotics alone. Serial CT scans are crucial as abscess may enlarge despite of antibiotics. The management should be done by a neurosurgeon who is prepared to operate at the first
sign of failure of medical therapy or where immediate neurosurgical help is available. Medical treatment alone should not be used when the diagnosis is in doubt.
i) Antibiotics: Antibiotic therapy should include agents that are specific, and bactericidal for the organism cultured, and cross blood-brain and blood-CSF barriers in adequate concentrations. If no organism is identified, the antibiotics are selected according to the predisposing cause (primary source) and the anatomic location of abscess., The complexity of microbial flora in brain abscess necessitates emperical antibiotic therapy against both aerobic and anaerobic organisms. More than one third otogenic and metastatic abscesses are polymicrobial (aerobic and/or anaerobic). Bacteroides, Peptostreptococcus and Fusobactrium are common anaerobes and are sensitive to metronidazole.,, Rhinogenic abscess is generally streptococcal. Staphylococcus is common in post traumatic and post operative cases. In infants and neonates, post meningitic abscess is caused by gram negative organisms. Sulpha drugs are most effective in Nocardia and vancomycin against Staphylococcus. Usually 'triple high dose' antibiotics intravenously for 2 weeks followed by four weeks of oral therapy is recommended. Penicillin and chloramphenicol have long been the main stay of empiric antimicrobial therapy. They have now been replaced by cefotaxime, vancomycin and metronidazole.
Opportunistic organisms which generally are not pathogenic to humans, cause brain abscess in immunocompromised patients. Antibiotics are given for 3-12 months. In patients with reduced lymphocytic function, infection with N. asteroides or T. gondii is common, and sulfonamide and pyrimethanium are most effective. In those with T-lymphocytic defect, Candida neoformans is common; therefore, 5 flucytosine and amphotericin-B are used. In renal transplant recipients, patients with blood cancer and those on steroid therapy, Listeria is common and ampicillin is most effective. In patients with leukaemia and lymphoma, Pseudomonas infection is common and aminoglycosides are most effective.
ii) Corticosteroids have beneficial effect of reducing brain oedema but retard immune responses and encapsulations., Therefore, corticosteroids should only be used to reduce mass effect or oedema that poses a threat of herniation and produces neurologic deficit by its location e.g. motor strip. Corticosteroids decrease enhancement of abscess wall on CT. Therefore reduction of ring enhancement should not
be interpreted as resolution of abscess and indication of effectiveness of therapy. Change in volume of abscess is more reliable for evaluating effectiveness of therapy. Steroids when used are tapered as rapidly as possible.
iii) Anticonvulsant therapy - Legg advocated anticonvulsant therapy for 5 years to all patients with cerebral abscess. Discontinuation of antiepileptic drugs can be considered when patient is seizure free for at least 2 years after surgery and EEG shows no epileptic activity.
If serial CT scans show growth of abscess any time during treatment with antibiotics or no decrease in size within four weeks, a surgical procedure should be performed to confirm the diagnosis, to obtain a sample for culture for identification of specific pathogen and sensitivity to particular antibiotics, and to remove as much purulent material as possible. Removal of pus load creates favourable local environment in which antibiotics can function better. Intracavitory instillation of antibiotics can be performed. A surgical approach allows immediate decompression of mass lesion. Reduction of ICP reduces duration of antibiotic therapy and hospital stay. It increases likelihood of cure. Walled off abscess larger than 3 cm diameter and a smaller deep seated white matter abscess are unlikely to respond to medical treatment alone. Standard therapy for such lesions should be surgical evacuation followed by appropriate antibiotic.,
Surgery should be performed in case of clinical deterioration, significant mass effect and neurological deficit, multiple lesions in surgically accessible locations, doubtful diagnosis and presumed resistant organisms. Spectroscopic monitoring during medical treatment may reveal alteration in metabolites indicating a positive response to therapy and allow greater number of patients being managed with medical therapy alone in the future. Many surgical techniques have been developed but there is no single best method., At present, aspiration and excision are two common procedures used.
Role of aspiration vs excision is controversial. The specific method of surgical treatment by aspiration or excision is of lesser importance than adherence to basic principles of abscess management. In choosing between aspiration or excision, various factors including surgical morbidity, success rate and sequelae such as recurrence and seizure disorders also must be considered. Aspiration is a rapid and safe procedure, especially with use of stereotactic techniques, ultrasound or CT scan guidance. It can be done under local anaesthesia, on bed side, even in seriously ill high risk patients. Aspiration can be done at any stage of evolution of abscess. If no pus is obtained, biopsy gives positive culture even in early cerebritis stage. A large, superficial, or accessible abscess can be aspirated via appropriately placed twistdrill or burr hole. Real time ultrasound, particularly in infants with open fontanelle and stereotaxy provides precise localization. Free hand needle aspiration can be a very effective life saving measure in the underdeveloped world where stereotaxy is not available. More than one aspiration may be needed. Repeat aspirations are often necessary for cure.
With free availability of CT scan, role of aspiration has increased, as abscesses can be detected easily and follow up is available immediately. Kondziolka et al recommended stereotactic aspiration/biopsy in all patients with suspected brain abscess regardless of size. Aspiration has a place, both as preparatory to eventual excision (secondary excision) and as a definitive procedure. Multiloculated abscesses have been treated with stereotactic aspiration of all loculi in single or staged aspiration. Recently, Hellwig et al have shown encouraging results with endoscopic stereotactic evacuation of brain abscess. Neuroendoscopic treatment, when compared to stereotactic aspiration, has additional advantage of more complete drainage and lavage.
Excision: Abscess may be excised during late capsular (chronic) stage (primary excision) or after aspiration (secondary excision). In the pre CT era, best results were obtained with excision (19% mortality) as compared to 38% mortality with aspiration. Large superficial abscesses resistant to multiple aspirations and not showing volume reduction because of adhesions to the dura, due to large brain surface area should be excised for cure. Abscesses containing gas are resistant to antibiotics and are better treated with excision. Post-traumatic abscess containing foreign body or contaminated retained bone fragments requires excision to prevent recurrence.,, Abscess resulting from fistulous communication e.g. trauma and congenital dermal sinus, require excision of infected granulation tissue and closure of fistula. Abscess localized to one lobe and contiguous to primary source i.e. frontal sinus osteomyelitis, is better treated with excision along with the primary focus. Multiloculated actinomycotic and nocardial abscess may need excision as simple aspiration may prove inadequate.[42-44] Excision reduces the incidence of seizures and prevents recurrence. However, excision is inappropriate in cerebritis stage, deep seated abscesses in eloquent areas and multiple abscesses.
With a trend towards non surgical management, there is potential for delay in operative intervention and death from raised ICP or rupture of abscess into ventricle or subarachnoid space. Early CT and surgery to identify offending organism contribute to low mortality. Yang found no difference in outcome attributable to the surgical procedure employed. Availability of CT scan provides rapid accurate diagnosis. It documents failure of therapy or resolution of abscess, paving way for alternative therapy (prompt surgery) and better understanding of pathophysiology of raised ICP. Improved microbial isolation technique particularly for anaerobes, availability of newer effective antibiotics with better blood brain barrier (BBB), penetration for gram negative and anaerobes and improvements in surgical techniques of aspiration with stereotactic or real time ultrasound localization has revolutionized treatment results and reduction in mortality rate from 40-60% in pre CT era to current rate of 0-
Altered sensorium at presentation is the most important single factor affecting mortality.,,,,, The prognosis is worse with intraventricular rupture, associated meningitis, ependymitis or empyema, unknown primary source, sterile pus on culture, large size, presence of hydrocephalus, metastatic abscesses, neonates and infants, multiple deep seated abscesses, inaccurate diagnosis and/or abscess with congenital cynotic heart disease. ,,,,,,,,,,,,,, 30-50% of survivors are found to have neurological sequelae.,, The incidence of residual neural deficits - hemiparesis, cognitive and learning deficits in children, is less with aspiration than excision. About 72% of patients can have epileptic seizures upto five years of diagnosis.,,,,, This incidence is less with aspiration than excision. About 5 to 10% abscesses recur due to inadequate or appropriate antibiotics, failure of removal of foreign body, dural fistula or failure of eradication of primary source. Hydrocephalus may also develop.
Cerebellar abscesses comprise 6-35% of all brain abscesses. They are often ominously silent and carry significant mortality., Associated supra or infra tentorial abscess or empyema may be present. The cerebellar abscess needs to be regarded differently from supratentorial abscess because of their ability to cause sudden total occlusion of CSF pathways early in the course of disease. A high index of suspicion and an aggressive surgical approach becomes mandatory in these cases. Nadvi et al adopted aggressive policy of immediate CSF diversion in presence of overt or incipient hydrocephalus by means of an external ventricular drain. Persistent hydrocephalus is treated with a shunting procedure. Presence of periventricular lucency is an absolute indication of immediate ventricular drainage regardless of level of consciousness i.e. even if patient is fully conscious.
In 1980s it was suggested that cerebellar abscess should be managed by primary excision, but in recent years burr hole aspiration has emerged as a satisfactory method.,, Radical or cortical mastoidectomy with preservation of hearing is performed concurrently with abscess drainage under same anaesthesia or as soon as possible afterwards.
Implantation or post traumatic abscess results from penetrating craniocerebral trauma and retained contaminated bone fragment or foreign body. Skull base fracture with CSF fistula, meningitis and previous cranial surgery can also cause abscess formation. Retained high velocity bullet fragments are less likely to form brain abscess because of heat sterilisation. Seizures are common sequelae in posttraumatic abscess.
Metastatic abscesses results from haematogenous dissemination of micro-organisms from remote site of infection. The three common causes are pulmonary, cardiac and cryptogenic. These abscesses occur deep at corticomedullary junction in the distribution of middle cerebral artery and have left sided predilection.
5-18% population with cynotic heart disease (CHD) develop brain abscess. Individuals with CHD are 10 times more prone to develop brain abscess than those with no CHD. Fallot's tetralogy is the most common cause. Intracardiac right to left shunt by-pass allows direct entry of blood containing bacteria to the cerebral circulation without pulmonary filtration. Hypoxaemia, metabolic acidosis and increased blood viscosity from compensatory polycythemia results in low perfusion areas (microinfarcts) in the brain. Microinfarcts provide a milieu where seeded microorganism can sustain growth and multiply to form abscess. Anaerobic streptococci are most
common agents. Sterile cultures are reported in 1668% of brain abscesses with CHD.,, These patients possess cardiopulmonary risk, wide variety of coagulation defects and variable degree of immuno deficient states increasing the risk of anaesthesia and surgery. Thus, a less invasive surgical procedure such as aspiration should be chosen. Deeply located parieto-occipital abscess larger than 2 cm diameter which causes mass effect, should be aspirated immediately even in late cerebritits stage using stereotactic or CT guided methods to decrease intracranial pressure and avoid intraventricular rupture of brain abscess. Intravenous ? -lactam antibiotics are started immediately.
5% to 50% of all brain abscess patients harbour multiple abscesses and their detection rate has increased since the advent of CT.,,,,,,, They are the result of haematogenous spread from systemic infections and the organisms may be found in peripheral source. Streptococcus and Staphylococcus are common organisms. Multiple abscesses are found more often in immunocompromised patients as compared to solitary abscess. The frequency of intraventricular rupture is also more in these cases. Risk factors include AIDS, organ transplant recipients, IV drug abuse, chemotherapy for lymphoma, cardiac anomaly or prosthetic cardiac valves, diabetes, and regional enteritis. However, in India, ear infection remains an important cause of multiple abscesses.
Empirical treatment with broad spectrum antibiotics along with follow up CT scans to assess response to treatment is advocated only when clinical and radiological improvement continues. However, it is not advised when antibiotic sensitivity of organisms is unknown, especially if there is no systemic disease from which cultures can be obtained. In these cases aspiration of most superficial or larger lesions producing neurological deficit and treating the remaining lesions with antibiotics and biweekly CT scan is advocated. If abscess recollects or fails to decrease or previously small abscess enlarges, serial or staged stereotactic aspiration can be performed.
All abscesses, > 3 cm diameter and those causing mass effect particularly deeply located in brain stem or close to ventricular wall should be aspirated with stereotactic technique. If all the abscesses are of
<2.5 cm size,still most accessible abscess should be aspirated. This permits aspiration of several lesions in a single sitting with minimal morbidity even in patients who are at poor risk for surgery or anaesthesia. In multiple abscesses antibiotics are continued for 3 months.