Tuberculous brain abscesses in immunocompetent patients: A decade long experience with nine patients
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.173639
Source of Support: None, Conflict of Interest: None
Objective: To describe the clinical presentation, radiological findings, management details, and outcome in nine cases of tuberculous brain abscess (TBA).
Keywords: Antituberculous therapy; excision; magnetic resonance imaging scan; tuberculous brain abscess
Tuberculous brain abscess (TBA) is a rare presentation of central nervous system (CNS) tuberculosis.,, These abscesses are devoid of the classical “giant cell and epithelioid cell granulomatous” reaction associated with tuberculosis. TBAs often present with focal neurological signs and are associated with a past history of tuberculosis., Rarely, a TBA has been reported in an intra-ventricular location. The present case series of nine patients outlines the demographic and clinical profiles, radiological findings, surgical intervention, and long-term functional outcomes in these cases.
From January 1997 to December 2011, nine patients harboring a TBA were managed under neurosurgical services. Their demographic profile, clinical presentation, radiological investigations, and management strategies are detailed in this study and in [Table 1].
Female patients were afflicted more often than males (female:male = 5:4). The patients' age ranged from 2.5 years to 45 years (mean = 23.9 years) with patients equitably distributed among all age groups. Four patients had infra-tentorial abscesses (case 1, 3, 6, 7), four had supra-tentorial lesions (case 2, 4, 8, 9), while the entire brain (in both supra- and infra-tentorial compartments) was studded with innumerable abscesses in one patient (case 5).
Associated tuberculous pathology in the form of tuberculous meningitis was noted in two patients (case 4, 6), while one each had tuberculous mastoiditis (case 1) and pulmonary tuberculosis (case 2). The signs and symptoms of raised intracranial pressure (ICP) were noted in all those cases who harbored a supra-tentorial abscess; while, all patients with an infra-tentorial abscess (n = 4, case 1, 3, 6, 7) had obstructive hydrocephalus, but presented with much smaller-sized abscesses as compared to the supra-tentorial group. All patients were screened for human immunodeficiency virus (HIV) infection by the enzyme linked immunosorbent assay (ELISA) technique and tested negative for HIV.
The radiological investigations [Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5],[Figure 6] included contrast-enhanced magnetic resonance imaging (MRI) scans for eight cases, while one case (case 6) underwent abscess excision based on a contrast enhanced computed tomography (CT) scan alone. Eight patients underwent a burr-hole aspiration of their abscess at least once. The aspirated material showed acid-fast Bacilli (AFB) in all cases, and a 4-drug antituberculous therapy (ATT) was initiated. Surgical intervention in the form of abscess excision was undertaken in all patients in the study as burr-hole aspiration of the abscesses, along with a 4-drug ATT (isoniazid, rifampicin, ethambutol, pyrazinamide) remained unsuccessful in achieving a complete cure. The diagnosis of TBA was established in all patients based on histopathological examination of the excised abscess walls [Figure 1]f, [Figure 6]f, and [Figure 7]. All cases in this series fulfilled the Whitener's criteria for the diagnosis of TBAs. Surgical excision was required twice in two cases (case 3, 4), while seven patients (case 1, 2, 5, 6, 8, 9) had a successful resection at the first attempt. One patient (case 2) was administered a 4 drug-ATT for a 9-month, 1 (case 9) for a 12-month and 1 (case 1) for a 15-month duration. Three patients (case 4, 5, 6) received all 4-drugs for 2 months, and only isoniazid and rifampicin were continued for more than 9 months. There were two deaths (case 3, 7) in the present series. One patient (case 3) expired on account of cerebrospinal fluid fistula from the surgical wound leading to pyogenic meningitis after undergoing posterior fossa exploration twice. Another fatality (case 7) occurred due to micro-vascular infarcts in the ponto-medullary region, 5 days after the surgical excision of cerebellar TBA. The follow-up ranged from 2 years to 12 years, with a mean of 5.7 years. None of the patients had Karnofsky Performance scale of 100, while it was 90 for 3, 80 for 3, and 70 for 1 [Table 1]. The histopathology of the walls of all the excised lesions confirmed the presence of tuberculous brain abscess. There was predominant vascular granulation tissue containing acute and chronic inflammatory cells, particularly polymorphs with a few AFB [Figure 7].
In 1978, Whitener described three essential criteria for establishing the diagnosis of TBAs. They include: (i) Macroscopic evidence from surgical or autopsy material of true abscess formation within the brain substance; (ii) histological confirmation that inflammation in the abscess was composed predominantly of vascular granulation tissue containing acute and chronic inflammatory cells, particularly polymorphonuclear leukocytes; and, (iii) positive culture of the pus for Mycobacterium tuberculosis or demonstration of acid-fast organisms in the pus or abscess wall. These criteria are being stringently followed in diagnosing this uncommon presentation of CNS tuberculosis. The incidence of TBA is only 4–8% among cases of CNS tuberculosis without HIV infection.,
In the spectrum of CNS tuberculosis, TBA represents one end of the spectrum, which corresponds to down-regulated cell-mediated immunity in the host [Table 2] and [Table 3]. Hematogenous dissemination from lungs is the most probable source of TBA. The tissue reaction to tubercle Bacilli depends on the state of the individual's immunity to tuberculosis, the size of the infecting inoculum, the specific tissue infected, and whether or not chemotherapy has been initiated. In a sensitized host, inoculation of a small number of Bacilli leads to tubercle formation. Inoculation of a large number of Bacilli in the same individual may lead to an exaggerated exudative phase with extensive caseation. Softening of the caseum may occur, either with no cellular infiltration or massive influx of acute inflammatory cells resulting in true pus formation. This softened caseum shows a high-density of AFBs. For tuberculous necrosis to occur, tuberculous Bacilli and their products need to be present in tissues. The major cytokine releasing molecule in M. tuberculosis is “lipoarabinomannan,” to which host cells are rendered more sensitive in the presence of tumor necrosis factor-α (TNF-α). Therefore, even protective levels of TNF-α become toxic to the host, causing extensive tissue necrosis.
Depending on the size of the inoculum, and in the absence of an adequate immune response, the area surrounding the focus of the “inoculum” may develop into a tuberculous abscess. TBAs, thus formed, are characterized by the lack of giant cells and epitheloid granulomatous reaction. Hence, TBAs are seen to closely resemble pyogenic abscesses, except for the high yield of AFBs in the pus. Cystic tuberculomas, on the other hand, are formed in the presence of adequate immune response and are characterized by the presence of inflammatory cells, giant cells, and epitheloid granulomas in their walls.
The patients may present with focal neurological deficits corresponding to the site of the TBA and the degree of surrounding edema , or with signs and symptoms of raised ICP. Most symptoms of TBA follow an indolent time-course (rather than a rapid course seen in other bacterial infections), evolving over a period as long as 3 months. A positive history of pulmonary tuberculosis is present in a significant number of TBA patients. In the present case series, 2 patients (case 4, 6) had tuberculous meningitis, while one each had tuberculous mastoiditis (case 1) and pulmonary involvement (case 2). Cerebellar signs may be present depending upon the abscess location. We had four cases (case 1, 3, 6, 7) with purely infra-tentorial TBAs, of whom 3 had cerebellar signs, while all had obstructive hydrocephalus.
Diagnosis on imaging
On a CT scan, both pyogenic and tuberculous abscesses show a rim of contrast enhancement, encircling an area of low-density and the whole lesion is surrounded by a low-density brain parenchyma, indicating peri-lesional brain edema [Figure 1]a, [Table 2] and [Table 3]. Radiologically, there are no significant differentiating features between TBAs and pyogenic abscesses, except for the slower evolution and thicker walls of TBAs. Benign pediatric cystic neoplasms (pilocytic astrocytomas) also have similar CT scan findings. Tuberculomas are usually seen as conglomerate, solid, contrast-enhancing lesions with no central cystic area. These features differentiating it from an abscess.,
MRI is required for confirming the diagnosis in all cases of cystic, contrast-enhancing lesions, which may be uni- or multi-loculated. On MRI, TBAs are circular or elliptical lesions, which are T1-hypointense and T2-hyperintense and classically rim-enhancing on contrast administration. T2-weighted scans show surrounding hyperintense signals from the perilesional edematous brain. The mural nodule is easily detectable on MRI scans and hence, pilocytic astrocytomas can be differentiated from TBAs. Hydatid cysts are usually nonenhancing, exactly spherical lesions and do not elicit perilesional edema, unless they get infected., Arachnoid and glio-ependymal cysts are developmental cysts and are nonenhancing lesions, causing no perilesional edema.
On the basis of radiology, the primary differential diagnosis of TBA is a pyogenic abscess., On the basis of conventional CT and MRI, it is difficult to differentiate between these two entities., According to Luthra et al., pyogenic and tuberculous abscesses may be differentiated by their unique metabolite pattern on in vivo MR spectroscopy, with recognition of amino acids, acetate, and succinate, in pyogenic abscesses and lipid peak in tuberculous abscesses. In the study from the same Institute, Luthra et al., have found the magnetization transfer (MT) ratio in MRI, which is influenced by the concentration of proteins and amino acids, to be significantly higher in the wall of pyogenic abscesses as compared to that of the tuberculous abscesses. These authors state that MT MRI in combination with in vivo MR spectroscopy may be effectively used to differentiate tuberculous from pyogenic brain abscesses., As compared to pyogenic abscesses, TBAs can be easily differentiated from CNS tuberculomas, as the latter are solid, conglomerating lesions with heterogenous intensity on both T1- and T2-weighted images and exhibit a variegated enhancement. Solid tuberculomas with caseation are characterized by T2-hypointensity within the lesion, which is attributed to the cheesy material (high in lipid content), which is present within the tuberculoma.
Management of TBAs
Surgical intervention for TBA has three aims: (1) To reduce the size of the space-occupying lesion and relieve the raised ICP; (2) to decrease the bacterial load; (3) to histopathologically examine the wall of the TBA for definitively establishing the diagnosis of a TBA. Even though there is limited literature available in managing a TBA, most of the reports favor surgical intervention in conjunction with medical treatment.,
There are reports describing complete cure of tuberculous abscesses with multiple aspirations and chemotherapy, but based on the results of our series, we believe that large-sized (more than 3 cm in diameter) lesions would invariably require excision and smaller ones resolve completely with adequate duration of appropriate ATT regimen. Burr-hole and aspiration of TBAs should be undertaken under stereotactic guidance in the case of a deeply located TBA in eloquent brain areas., The aspirated purulent material, when cultured, usually reveals AFB  and alerts the treating clinician that the patient is suffering from a TBA. Treatment options include simple aspiration (single time), continuous drainage, fractional drainage, repeated aspiration through a burr-hole, stereotactic aspiration, and craniotomy followed by excision. As there are few reports describing this entity, there is no consensus on any single modality of treatment for these lesions. Indications for surgical excision include the presence of a multi-loculated abscess, a relatively thick abscess wall on imaging, and TBA occurring in the posterior fossa. However, larger TBAs fail to resolve without excision as noted in the present case series. Microsurgical excision is advantageous as excision is being performed under vision and ensures total excision of the abscess wall. This approach, however, exposes the patient to the risk of damaging perilesional brain parenchyma, especially when the lesion is located in an eloquent region of the brain (case 7).
Preoperative administration of corticosteroids along with ATT is presumed to reduce morbidity and mortality, but no convincing scientific data is available for confirming this assumption. As none of our patients was unconsciousness, we avoided the administration of steroids so as not to compromise the immunity of our patients. Spillage of abscess contents poses a risk of tuberculous meningitis, and early initiation of ATT is recommended to prevent the occurrence of meningitis. We did not encounter postoperative tuberculous meningitis in any of our cases. We initiated a 4-drug ATT in all our cases after obtaining purulent material from the TBA through the burr-hole tap. Following this procedure, all our patients had received ATT for more than 1 week before undergoing TBA excision. All 4 first-line ATT drugs are recommended in this situation, considering that isoniazid and pyrazinamide penetrate the blood-brain barrier well and rifampicin crosses partially.
Abscess drainage provides evidence of the offending organism for a definite diagnosis and decreases the bacterial load. However, a definitive treatment warrants surgical excision of the abscess supplemented with a prolonged course of ATT for 12–18 months., In our experience, surgical excision seems necessary to obtain a complete cure of the disease. We have given ATT for a minimum period of 12 months in our patients, and we feel it is imperative that regular clinical and radiological assessment at follow-up be used to guide the duration of ATT, rather than having a fixed duration of treatment for this disease entity., In the absence of guidelines regarding the duration of administration of ATT, we tailored the medication according to the follow-up radiological scans in our cases, and withdrew chemotherapy only on noting the complete resolution of contrast-enhancing inflammatory pathology. The problem of drug resistance was not encountered in any of our cases. Established treatment guidelines for TBAs are not available owing to the rarity of these lesions, but most of the reports highlight the necessity of complete surgical excision of these TBAs to achieve cure. Burr-hole aspiration as the first line intervention for such lesions should be discouraged, but this procedure continues to be in vogue as a definitive diagnosis cannot be reached on the basis of radiology alone. In spite of the availability of newer antibiotics, TBAs are thought to carry a relatively poorer outcome with the clinicians having a considerably nihilistic attitude towards these lesions. This is because mortality remains high in patients suffering from this entity and functional outcome is far from satisfactory.
Establishing the diagnosis of TBA is a challenge. The presence of AFB on Z–N staining or a positive culture of M. tuberculosis is the gold-standard for its diagnosis, as clinical, radiological, and basic pathological findings are very similar to that seen in pyogenic brain abscesses. Hence, a high index of suspicion is necessary. All pus samples from intracranial abscesses should be tested for the evidence of tuberculous involvement. TBAs, once diagnosed, require surgical intervention to promote the efficacy of ATT. As patients who have once had a TBA, harbor a definite risk of recurrence of the disease, these patients warrant a long-term follow-up. The requirement of repeated surgical procedures and a prolonged duration of ATT in these cases add to the morbidity in this type of tuberculous brain infection. Surgical excision of TBAs (more than 3 cm in size) along with prolonged ATT based on a serial clinical and radiological evaluation at follow-up, help in achieving a successful outcome in patients with TBAs.
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Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3]