Intracranial Tuberculoma in a Liver Transplant Patient: First Reported Case and Review of the Literature
2003; Elsevier BV; Volume: 3; Issue: 1 Linguagem: Inglês
10.1034/j.1600-6143.2003.30117.x
ISSN1600-6143
AutoresCorey Henderson, Brandon M. Meyers, Sakir H. Gultekin, Bin Liu, David Y. Zhang,
Tópico(s)Neurological Complications and Syndromes
ResumoA 66‐year‐old female who had undergone an orthotopic liver transplant two years before admission was admitted with fever and neurological symptoms of several days' duration. Following an extensive work‐up, which revealed positive intracranial lesions on computed typography and magnetic resonance imaging, the patient was begun on broad spectrum antimicrobials including corticosteroids. The patient responded though the etiology of infection remained unclear. After a stereotactic biopsy was performed revealing granulomas and acid‐fast bacilli, the patient was started on antituberculous medications. A review of the literature reveals that the rare occurrence of intracranial tuberculoma should be considered in an orthotopic liver transplant (OLT) patient with central nervous system pathology. A 66‐year‐old female who had undergone an orthotopic liver transplant two years before admission was admitted with fever and neurological symptoms of several days' duration. Following an extensive work‐up, which revealed positive intracranial lesions on computed typography and magnetic resonance imaging, the patient was begun on broad spectrum antimicrobials including corticosteroids. The patient responded though the etiology of infection remained unclear. After a stereotactic biopsy was performed revealing granulomas and acid‐fast bacilli, the patient was started on antituberculous medications. A review of the literature reveals that the rare occurrence of intracranial tuberculoma should be considered in an orthotopic liver transplant (OLT) patient with central nervous system pathology. The incidence and factors associated with tuberculosis in liver transplant patients are not clear (1Meyers B Halpern M Sheiner P Mendelson M Neibart E Miller C Tuberculosis in liver transplant patients.Transplantation. 1994; 58: 301-306Crossref PubMed Google Scholar, 2Kishikawa K Kajiyama K Uchiyama H et al.Tuberculosis following liver transplantation: report of a case and review of the literature.Transplant Int. 1996; 9: 589-592Crossref PubMed Google Scholar). Tuberculosis involving the central nervous system occurs in only 0.53% of cases of systemic tuberculosis in this country (3Grayeli A Redondo A Salama J Tuberculoma of the cavernous sinus: case report.Neurosurgery. 1998; 42: 179-182Crossref PubMed Scopus (37) Google Scholar). Though intracranial tuberculoma is a common entity in developing countries, cases of tuberculosis involving the central nervous system (either tuberculomas or meningitis) have rarely been reported (4Gropper M Schulder M Ashwini S Central nervous system tuberculosis: medical management and surgical indications.Surgical Neurology. 1995; 44: 378-385Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 5MacDonell ??? Baird R Bronze M Intrameduallary tuberculomas of the spinal cord. case report and review.Reviews of infectious diseases. 1990; 12: 432-439Crossref PubMed Scopus (77) Google Scholar). Intracranial tuberculoma in the liver transplant patient has not been previously described. We report a case of a patient who developed neurological symptoms, likely related to intracranial tuberculoma, and died from cerebral hemorrhage. An indigenous 66‐year‐old hispanic female with a history of noninsulin dependent diabetes mellitus, who had a cadaveric liver transplantation for cirrhosis two years earlier, was admitted for confusion, headache, fever, vomiting and diarrhea. The patient was recently discharged after being hospitalized for fever, headache, and confusion without a diagnosis. There was no previous history of tuberculosis in the patient or her family; her purified protein derivative (PPD) status before admission and transplantation was unknown. The patient was in good health several days earlier and was taking prednisone 10 mg qd, cyclosporine 25 mg bid, nystatin, cardiazem and neurontin. The patient denied recent travel, any contact with illness and had no pets. On examination, the patient was febrile, 40.1 °C, pulse 110 beats/min, blood pressure 133/71 mmHg, respiratory rate 20 breaths/min, and was saturating 98% on room air. She was alert, yet disoriented. No meningismus or adenopathy was noted. Examination of the heart, lungs, and the abdomen was normal. Cranial nerves were intact, and muscle strength was within normal limits, including deep tendon reflexes. Laboratory analysis revealed: hemoglobin, 11.0 g/dL; hematocrit, 31.6%; platelets, 345 × 109/L; white blood cells (WBC), 11.8 × 109/L, with 83.7% neutrophils; sodium, 136 mmol/L; potassium, 3.8 mmol/L; chloride, 101 mmol/L; carbon dioxide, 19; BUN, 60 mmol/L; creatinine, 2.5 mg/dL; glucose, 128 mg/dL; total bilirubin 0.7 mg/dL, direct bilirubin 0.3 mg/dL, AST = 41 U/L, ALT = 15 U/L, AP = 194 U/L; a PPD was not performed. Computerized tomography (without contrast) of the brain revealed multiple areas of low attenuation within the white matter of both cerebral hemispheres (seeFigure 1). A lumbar puncture yielded: CSF‐glucose, 68 mg/dL; protein, 78 mg/dL; RBC, 400/µL; and WBC, 3/µL, with 20% neutrophils and 70% lymphocytes. A Gram stain of the cerebral spinal fluid was negative for cells and organisms. The culture yielded no growth. Computerized tomography of the abdomen and pelvis was unremarkable, as was the chest roentgenogram. A computerized tomography (CT) of the lungs was not performed. Initially, the patient was empirically placed on Cefepime and metronidazole for presumed bacterial infection. Within the hour, the antimicrobials were changed to Amphotericin B and trimethoprim/sulfamethoxazole, for possible fungal etiologies and Nocardia sp./Listeria sp. Pulse steroids were added overnight, and the patient's fever resolved. Orientation also returned, and the vomiting and diarrhea abated. Magnetic resonance imaging was carried out with gadolinium. It showed multiple ring‐enhancing lesions with possible central enhancement suggestive of infection (seeFigures 2–5). Subsequently a stereotactic biopsy was performed. Pathology was remarkable for necrotizing granuloma (Figure 6). On Acid‐fast staining, rare isolated beaded acid‐fast bacilli were noted (Figure 7). Other special stains to elucidate microorganisms were negative; including gram stain, trichrome, giemsa, periodic acid‐Schiff stain, and Gormori's methenamine‐silver stain.Figure 2-5Magnetic resonance imaging with contrast: multiple ring‐enhancing lesions measuring less than 1 cm in diameter, scattered throughout the cerebral hemisphere; many of these appear to lie at the gray/white matter junction. There is suggestion of possible central enhancement in several of these lesionsView Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 2-5Magnetic resonance imaging with contrast: multiple ring‐enhancing lesions measuring less than 1 cm in diameter, scattered throughout the cerebral hemisphere; many of these appear to lie at the gray/white matter junction. There is suggestion of possible central enhancement in several of these lesionsView Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 2-5Magnetic resonance imaging with contrast: multiple ring‐enhancing lesions measuring less than 1 cm in diameter, scattered throughout the cerebral hemisphere; many of these appear to lie at the gray/white matter junction. There is suggestion of possible central enhancement in several of these lesionsView Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 6Pathology from brain biopsy: necrotizing granuloma involving neural parenchymaView Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 7On acid‐fast staining: rare isolate acid‐fast bacilli are noted in the necrotic regionView Large Image Figure ViewerDownload Hi-res image Download (PPT) As the patient could take oral medications, isoniazid (300 mg/day) and rifampin (600 mg/day) were started. Within 24 h after the biopsy the patient became unresponsive secondary to an enlarging hematoma. Palliative measures were instituted as per the next of kin, and the patient died within two days. The final culture from the brain biopsy was culture negative for all organisms including Mycobacteria tuberculosis. However, DNA sequences specific for M. tuberculosis were amplified on the biopsy tissues by nested PCR using primers specific for the IS6110 element of M. tuberculosis, and confirmed the diagnosis (6Nagesh S Rish J Eisenach K Cave M Bates J Polymerase chain reaction to detect mycobacterium tuberculosis in histologic specimens.Am J Respir Crit Care Med. 1998; 158: 1150-1155Crossref PubMed Scopus (84) Google Scholar, 7Eisenach K Cave M Bates J Crawford J polymerase chain reaction of a repetitive DNA sequence specific for mycobacterium tuberculosis.J Infect Dis. 1990; 161: 977-981Crossref PubMed Scopus (586) Google Scholar) (Figure 8). In developed nations, the frequency of intracranial tuberculomas has decreased (3Grayeli A Redondo A Salama J Tuberculoma of the cavernous sinus: case report.Neurosurgery. 1998; 42: 179-182Crossref PubMed Scopus (37) Google Scholar, 8Harder E Al‐Kawi M Carney P Intracranial tuberculoma: conservative management.Am J Med. 1983; 74: 570-576Abstract Full Text PDF PubMed Scopus (88) Google Scholar, 9Wilkinson H Ferris E Muggia A Cantu RC Central nervous system tuberculosis a persistent disease.J Neurosurg. 1971; 34: 13-22Crossref Scopus (31) Google Scholar, 10Sibley W O'Brien J Intracranial tuberculosis a review of clinical features and treatment.Neurology (Minneap). 1956; 6: 157-165Crossref PubMed Google Scholar, 11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar, 12Al‐Mefty O Intracranial tuberculoma.J Neurosurg. 1986; 65: 572-573PubMed Google Scholar, 13DeAngelis L Intracranial tuberculoma. case report and review of the literature.Neurology. 1981; 31: 1133-1136Crossref PubMed Google Scholar), accounting for only 15–30% of central nervous system (CNS) tuberculosis (3Grayeli A Redondo A Salama J Tuberculoma of the cavernous sinus: case report.Neurosurgery. 1998; 42: 179-182Crossref PubMed Scopus (37) Google Scholar). The lesions usually occur in the cerebral and cerebellar hemisphere because of their high vascular supply (3Grayeli A Redondo A Salama J Tuberculoma of the cavernous sinus: case report.Neurosurgery. 1998; 42: 179-182Crossref PubMed Scopus (37) Google Scholar, 14Talamas O Del Brutto O Garcia‐Ramos G Brain‐stem tuberculoma.Arch Neurol. 1989; 46: 529-535Crossref PubMed Scopus (79) Google Scholar); brain stem tuberculomas are rare. In a large series of patients with intracranial tuberculomas the incidence ranges from 2.5% to 8% (8Harder E Al‐Kawi M Carney P Intracranial tuberculoma: conservative management.Am J Med. 1983; 74: 570-576Abstract Full Text PDF PubMed Scopus (88) Google Scholar), and is usually observed in patients with milary disease (4Gropper M Schulder M Ashwini S Central nervous system tuberculosis: medical management and surgical indications.Surgical Neurology. 1995; 44: 378-385Abstract Full Text PDF PubMed Scopus (58) Google Scholar). Tuberculomas are usually solitary lesions, although 15–34% of cases comprise multiple lesions (13DeAngelis L Intracranial tuberculoma. case report and review of the literature.Neurology. 1981; 31: 1133-1136Crossref PubMed Google Scholar). In liver transplant patients, central nervous system lesions are usually secondary to vascular events. Fungi are the main cause of ring‐enhancing lesions in the brain of liver transplant patients. In addition to fungal etiologies, other etiologies include pyogenic abscesses, including Nocardia and Listeria, Toxoplasma, tuberculosis, malignancy, and those induced by medication. In a 4‐year prospective cohort study of 1730 liver transplant patients, 60 CNS lesions were observed; infections accounted for only 18% of the lesions. All were fungal in etiology, with Aspergillius fumigatus accounting for the majority of the isolates (15Bonham CA Paterson D Pankey G et al.Central nervous system lesions in liver transplant recipients.Transplantation. 1998; 66: 1596-1604Crossref PubMed Scopus (88) Google Scholar). The symptoms are nonspecific and may occur months to several years before medical attention is sought (8Harder E Al‐Kawi M Carney P Intracranial tuberculoma: conservative management.Am J Med. 1983; 74: 570-576Abstract Full Text PDF PubMed Scopus (88) Google Scholar, 16Ohaegbulam S Amuta J Saddeqi Tuberculoma of the central nervous system in Eastern Nigeria.Tubercle. 1979; 60: 163-166Abstract Full Text PDF PubMed Scopus (5) Google Scholar, 17Whitener D Tuberculosis brain abscess.Arch Neurol. 1978; 35: 148-155Crossref PubMed Scopus (128) Google Scholar). Symptoms may be related to mass effect, depending on the site (4Gropper M Schulder M Ashwini S Central nervous system tuberculosis: medical management and surgical indications.Surgical Neurology. 1995; 44: 378-385Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar). The size and location of the lesion determines the clinical findings (11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar). Intracranial hypertension may be present (e.g. papilledema/headache) in 72% of patients (8Harder E Al‐Kawi M Carney P Intracranial tuberculoma: conservative management.Am J Med. 1983; 74: 570-576Abstract Full Text PDF PubMed Scopus (88) Google Scholar, 11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar, 13DeAngelis L Intracranial tuberculoma. case report and review of the literature.Neurology. 1981; 31: 1133-1136Crossref PubMed Google Scholar, 17Whitener D Tuberculosis brain abscess.Arch Neurol. 1978; 35: 148-155Crossref PubMed Scopus (128) Google Scholar, 18Arseni C Two hundred and ones cases of intracranial tuberculoma treated surgically.J Neurol Neurosurg Psychiatry. 1958; 21: 308-311Crossref PubMed Scopus (102) Google Scholar), as well as focal neurologic deficits (14Talamas O Del Brutto O Garcia‐Ramos G Brain‐stem tuberculoma.Arch Neurol. 1989; 46: 529-535Crossref PubMed Scopus (79) Google Scholar, 17Whitener D Tuberculosis brain abscess.Arch Neurol. 1978; 35: 148-155Crossref PubMed Scopus (128) Google Scholar). Seizures occur in 50–85% of reported cases (13DeAngelis L Intracranial tuberculoma. case report and review of the literature.Neurology. 1981; 31: 1133-1136Crossref PubMed Google Scholar, 18Arseni C Two hundred and ones cases of intracranial tuberculoma treated surgically.J Neurol Neurosurg Psychiatry. 1958; 21: 308-311Crossref PubMed Scopus (102) Google Scholar, 19Mayers M Kaufman D Miller M Recent cases of intracranial tuberculomas.Neurology (Ny). 1978; 28: 256-260Crossref PubMed Google Scholar). Constitutional symptoms such as fever, night sweats, and weight loss are usually absent (8Harder E Al‐Kawi M Carney P Intracranial tuberculoma: conservative management.Am J Med. 1983; 74: 570-576Abstract Full Text PDF PubMed Scopus (88) Google Scholar, 11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar, 13DeAngelis L Intracranial tuberculoma. case report and review of the literature.Neurology. 1981; 31: 1133-1136Crossref PubMed Google Scholar, 16Ohaegbulam S Amuta J Saddeqi Tuberculoma of the central nervous system in Eastern Nigeria.Tubercle. 1979; 60: 163-166Abstract Full Text PDF PubMed Scopus (5) Google Scholar). The diagnosis of intracranial tuberculoma without evidence of tuberculosis elsewhere is difficult. The cerebrospinal fluid is often normal without evidence of acid‐fast bacilli on Ziehl‐Neelsen staining (8Harder E Al‐Kawi M Carney P Intracranial tuberculoma: conservative management.Am J Med. 1983; 74: 570-576Abstract Full Text PDF PubMed Scopus (88) Google Scholar, 14Talamas O Del Brutto O Garcia‐Ramos G Brain‐stem tuberculoma.Arch Neurol. 1989; 46: 529-535Crossref PubMed Scopus (79) Google Scholar, 17Whitener D Tuberculosis brain abscess.Arch Neurol. 1978; 35: 148-155Crossref PubMed Scopus (128) Google Scholar, 20Barnes P Bloch A Davidson P Snider D Tuberculosis in patients with human immunodeficiency virus infection.N Engl J Med. 1991; 324: 1644-1650Crossref PubMed Scopus (959) Google Scholar), and CSF cultures are usually negative (8Harder E Al‐Kawi M Carney P Intracranial tuberculoma: conservative management.Am J Med. 1983; 74: 570-576Abstract Full Text PDF PubMed Scopus (88) Google Scholar, 21Rangel‐Guerra R Martinez H Garza H Garza J Ancer J Brain‐stem tuberculoma.Arch Neurol. 1991; 48: 358-359Crossref PubMed Scopus (3) Google Scholar). Computed tomography and magnetic resonance imaging (MRI) without contrast show isodense lesions with edema (3Grayeli A Redondo A Salama J Tuberculoma of the cavernous sinus: case report.Neurosurgery. 1998; 42: 179-182Crossref PubMed Scopus (37) Google Scholar, 8Harder E Al‐Kawi M Carney P Intracranial tuberculoma: conservative management.Am J Med. 1983; 74: 570-576Abstract Full Text PDF PubMed Scopus (88) Google Scholar, 11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar, 13DeAngelis L Intracranial tuberculoma. case report and review of the literature.Neurology. 1981; 31: 1133-1136Crossref PubMed Google Scholar, 14Talamas O Del Brutto O Garcia‐Ramos G Brain‐stem tuberculoma.Arch Neurol. 1989; 46: 529-535Crossref PubMed Scopus (79) Google Scholar, 22Farrar D Flanigan T Gordon N Gold R Rich J Tuberculous brain abscess in a patient with HIV Infection. Case report and review.Am J Med. 1997; 102: 297-301Abstract Full Text PDF PubMed Scopus (59) Google Scholar). Studies with contrast reveal enhanced space‐occupying lesions (3Grayeli A Redondo A Salama J Tuberculoma of the cavernous sinus: case report.Neurosurgery. 1998; 42: 179-182Crossref PubMed Scopus (37) Google Scholar, 8Harder E Al‐Kawi M Carney P Intracranial tuberculoma: conservative management.Am J Med. 1983; 74: 570-576Abstract Full Text PDF PubMed Scopus (88) Google Scholar, 11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar, 14Talamas O Del Brutto O Garcia‐Ramos G Brain‐stem tuberculoma.Arch Neurol. 1989; 46: 529-535Crossref PubMed Scopus (79) Google Scholar, 20Barnes P Bloch A Davidson P Snider D Tuberculosis in patients with human immunodeficiency virus infection.N Engl J Med. 1991; 324: 1644-1650Crossref PubMed Scopus (959) Google Scholar, 22Farrar D Flanigan T Gordon N Gold R Rich J Tuberculous brain abscess in a patient with HIV Infection. Case report and review.Am J Med. 1997; 102: 297-301Abstract Full Text PDF PubMed Scopus (59) Google Scholar), which appear avascular on angiography (8Harder E Al‐Kawi M Carney P Intracranial tuberculoma: conservative management.Am J Med. 1983; 74: 570-576Abstract Full Text PDF PubMed Scopus (88) Google Scholar, 11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar, 13DeAngelis L Intracranial tuberculoma. case report and review of the literature.Neurology. 1981; 31: 1133-1136Crossref PubMed Google Scholar). These image techniques cannot differentiate tuberculomas from other intracranial mass lesions (3Grayeli A Redondo A Salama J Tuberculoma of the cavernous sinus: case report.Neurosurgery. 1998; 42: 179-182Crossref PubMed Scopus (37) Google Scholar, 11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar, 12Al‐Mefty O Intracranial tuberculoma.J Neurosurg. 1986; 65: 572-573PubMed Google Scholar, 17Whitener D Tuberculosis brain abscess.Arch Neurol. 1978; 35: 148-155Crossref PubMed Scopus (128) Google Scholar, 23Tandon PN Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1992; 30: 301Crossref PubMed Scopus (16) Google Scholar). In one report 80% of cases were false‐positive; rapid growth of the lesions within 3 weeks was noted (11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar, 24Naim‐Ur‐Rahman ntracranial tuberculomas.I Diagnosis and management.Acta Neurochir (Wien). 1987; 88: 109-115Crossref PubMed Scopus (32) Google Scholar). These false‐positive lesions consisted of lymphomas, one multicentric glioma, one malignant myelinoclastic plaque, and one ring‐enhancing meningioma (11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar). Biopsy of a suspected tuberculoma is necessary (4Gropper M Schulder M Ashwini S Central nervous system tuberculosis: medical management and surgical indications.Surgical Neurology. 1995; 44: 378-385Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 16Ohaegbulam S Amuta J Saddeqi Tuberculoma of the central nervous system in Eastern Nigeria.Tubercle. 1979; 60: 163-166Abstract Full Text PDF PubMed Scopus (5) Google Scholar). Pathology is not absolute (3Grayeli A Redondo A Salama J Tuberculoma of the cavernous sinus: case report.Neurosurgery. 1998; 42: 179-182Crossref PubMed Scopus (37) Google Scholar, 4Gropper M Schulder M Ashwini S Central nervous system tuberculosis: medical management and surgical indications.Surgical Neurology. 1995; 44: 378-385Abstract Full Text PDF PubMed Scopus (58) Google Scholar); caseating granulomas with typical Langhans‐type giant cells may be the only evidence of mycobacterial infection; acid‐fast bacilli may not be found (3Grayeli A Redondo A Salama J Tuberculoma of the cavernous sinus: case report.Neurosurgery. 1998; 42: 179-182Crossref PubMed Scopus (37) Google Scholar, 4Gropper M Schulder M Ashwini S Central nervous system tuberculosis: medical management and surgical indications.Surgical Neurology. 1995; 44: 378-385Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 5MacDonell ??? Baird R Bronze M Intrameduallary tuberculomas of the spinal cord. case report and review.Reviews of infectious diseases. 1990; 12: 432-439Crossref PubMed Scopus (77) Google Scholar, 13DeAngelis L Intracranial tuberculoma. case report and review of the literature.Neurology. 1981; 31: 1133-1136Crossref PubMed Google Scholar, 25Garcia‐Monco J Beldarrain M Collazos J Resolution of a brainstem abscess through antituberculosis therapy.Neurology. 1998; 50: 1929-1930Crossref PubMed Google Scholar). Several cases have been reported of intracranial tuberculomas and tuberculous abscesses that are consistent on histopathology yet were culture negative (3Grayeli A Redondo A Salama J Tuberculoma of the cavernous sinus: case report.Neurosurgery. 1998; 42: 179-182Crossref PubMed Scopus (37) Google Scholar, 11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar, 13DeAngelis L Intracranial tuberculoma. case report and review of the literature.Neurology. 1981; 31: 1133-1136Crossref PubMed Google Scholar). On pathological evaluation, histology was consistent with a granuloma or abscess and positive acid‐fast bacilli were observed but not cultured (3Grayeli A Redondo A Salama J Tuberculoma of the cavernous sinus: case report.Neurosurgery. 1998; 42: 179-182Crossref PubMed Scopus (37) Google Scholar, 4Gropper M Schulder M Ashwini S Central nervous system tuberculosis: medical management and surgical indications.Surgical Neurology. 1995; 44: 378-385Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 5MacDonell ??? Baird R Bronze M Intrameduallary tuberculomas of the spinal cord. case report and review.Reviews of infectious diseases. 1990; 12: 432-439Crossref PubMed Scopus (77) Google Scholar, 13DeAngelis L Intracranial tuberculoma. case report and review of the literature.Neurology. 1981; 31: 1133-1136Crossref PubMed Google Scholar). The number of acid‐fast bacilli in these lesions is low. Excessive amounts of tissue destruction through inflammation with granuloma formation and necrosis may account for this finding. Polymerase chain reaction appears to be a rapid, sensitive, and specific assay when performed on the CSF of patients with AIDS who also have tuberculous meningitis (26Garcia‐Monco J Beldarrain M Canton F Capelastegui A Collazos J Resolution of a brainstem abscess through antituberculosis therapy.Neurology. 1997; 49: 265-267Crossref PubMed Scopus (22) Google Scholar, 27Folgueira L Delgado R Palenque E Noriega A Polymerase chain reaction for rapid diagnosis of tuberculous meningitis in AIDS patients.Neurology. 1994; 44: 1336-1338Crossref PubMed Google Scholar). Using the segment IS6110 in the M. tuberculosis chromosome as a target for amplification, polymerase chain reaction was found to be very sensitive (100%) and specific (93%) on tissue samples including brain and spinal cord from these patients (6Nagesh S Rish J Eisenach K Cave M Bates J Polymerase chain reaction to detect mycobacterium tuberculosis in histologic specimens.Am J Respir Crit Care Med. 1998; 158: 1150-1155Crossref PubMed Scopus (84) Google Scholar). This test may be the only way to prove the diagnosis. Patients given empiric therapy with antituberculous medication may respond with a decrease in lesion size (11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar, 14Talamas O Del Brutto O Garcia‐Ramos G Brain‐stem tuberculoma.Arch Neurol. 1989; 46: 529-535Crossref PubMed Scopus (79) Google Scholar) obviating the need of a biopsy in certain patient groups (11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar, 28Bouchama A Al‐Kawi Z Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1992; 30: 301Crossref Google Scholar). Variability in response to therapy makes this approach difficult. There are also cases reporting a paradoxical expansion of the tuberculoma while on treatment with no clinical deterioration (11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar, 14Talamas O Del Brutto O Garcia‐Ramos G Brain‐stem tuberculoma.Arch Neurol. 1989; 46: 529-535Crossref PubMed Scopus (79) Google Scholar). Biopsy is often required to determine antibiotic sensitivity. Empiric therapy is practical in countries where intracranial tuberculomas are common or in patients with evidence of extracranial tuberculoma (11Bouchama A Al‐Kawi Z Kanaan I Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1991; 28: 405-409Crossref PubMed Scopus (68) Google Scholar, 23Tandon PN Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1992; 30: 301Crossref PubMed Scopus (16) Google Scholar). A prolonged therapeutic trial without evidence of improvement on imaging, CT scan or MRI, and the use of corticosteroids during the therapeutic trial, should be avoided because misinterpretation of clinical improvement on imaging techniques may be observed (28Bouchama A Al‐Kawi Z Brain biopsy in tuberculoma: the risks and benefits.Neurosurgery. 1992; 30: 301Crossref Google Scholar). Tuberculin skin testing is unreliable to aid in the diagnosis of tuberculoma (8Harder E Al‐Kawi M Carney P Intracranial tuberculoma: conservative management.Am J Med. 1983; 74: 570-576Abstract Full Text PDF PubMed Scopus (88) Google Scholar, 12Al‐Mefty O Intracranial tuberculoma.J Neurosurg. 1986; 65: 572-573PubMed Google Scholar, 13DeAngelis L Intracranial tuberculoma. case report and review of the literature.Neurology. 1981; 31: 1133-1136Crossref PubMed Google Scholar, 22Farrar D Flanigan T Gordon N Gold R Rich J Tuberculous brain abscess in a patient with HIV Infection. Case report and review.Am J Med. 1997; 102: 297-301Abstract Full Text PDF PubMed Scopus (59) Google Scholar). Results vary from 25% to 75% (19Mayers M Kaufman D Miller M Recent cases of intracranial tuberculomas.Neurology (Ny). 1978; 28: 256-260Crossref PubMed Google Scholar, 29Asenjo A Valladares H Fierro J Tuberculomas of the brain.Arch Neurology (Minneap). 1956; : 157-165Google Scholar) and may be negative in these patients (12Al‐Mefty O Intracranial tuberculoma.J Neurosurg. 1986; 65: 572-573PubMed Google Scholar). The role of tuberculin skin testing in liver transplant patients is unclear because half the patients in a series with proven tuberculosis in OLT were PPD‐negative before transplantation (1Meyers B Halpern M Sheiner P Mendelson M Neibart E Miller C Tuberculosis in liver transplant patients.Transplantation. 1994; 58: 301-306Crossref PubMed Google Scholar). Standard treatment for tuberculous infection of the CNS is based on studies of tuberculous meningitis (13DeAngelis L Intracranial tuberculoma. case report and review of the literature.Neurology. 1981; 31: 1133-1136Crossref PubMed Google Scholar); the recommendations are isonazid (INH), rifampin, pyrazinamide and ethambutol for 2 months, followed by a 10‐month course of INH and rifampin (4Gropper M Schulder M Ashwini S Central nervous system tuberculosis: medical management and surgical indications.Surgical Neurology. 1995; 44: 378-385Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 30Starke J Jacobs R O'Brien R American Academy of Pediatrics Committee on Infectious Diseases: chemotherapy for tuberculosis in infants and children.Pediatrics. 1992; 89: 161-165Crossref PubMed Google Scholar). Corticosteroids have been included as adjuvant therapy in some studies (4Gropper M Schulder M Ashwini S Central nervous system tuberculosis: medical management and surgical indications.Surgical Neurology. 1995; 44: 378-385Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 8Harder E Al‐Kawi M Carney P Intracranial tuberculoma: conservative management.Am J Med. 1983; 74: 570-576Abstract Full Text PDF PubMed Scopus (88) Google Scholar, 30Starke J Jacobs R O'Brien R American Academy of Pediatrics Committee on Infectious Diseases: chemotherapy for tuberculosis in infants and children.Pediatrics. 1992; 89: 161-165Crossref PubMed Google Scholar, 31Jacobs R Sunakorn P Chotpitayasunonah T Intensive short course chemotherapy for tuberculosis meningitis.Pediatr Infect J. 1992; 11: 194-198Crossref PubMed Scopus (71) Google Scholar). Harder et al. report favorable results with corticosteroids, without evidence of deterioration or spread of the tuberculosis (8Harder E Al‐Kawi M Carney P Intracranial tuberculoma: conservative management.Am J Med. 1983; 74: 570-576Abstract Full Text PDF PubMed Scopus (88) Google Scholar). The optimal duration of treatment is unknown (13DeAngelis L Intracranial tuberculoma. case report and review of the literature.Neurology. 1981; 31: 1133-1136Crossref PubMed Google Scholar). Several cases report good results after 18 months of medical management. If surgery was indicated, 18 months of treatment was given from the time of surgery (4Gropper M Schulder M Ashwini S Central nervous system tuberculosis: medical management and surgical indications.Surgical Neurology. 1995; 44: 378-385Abstract Full Text PDF PubMed Scopus (58) Google Scholar). Improvement was seen in 6–8 weeks (4Gropper M Schulder M Ashwini S Central nervous system tuberculosis: medical management and surgical indications.Surgical Neurology. 1995; 44: 378-385Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 8Harder E Al‐Kawi M Carney P Intracranial tuberculoma: conservative management.Am J Med. 1983; 74: 570-576Abstract Full Text PDF PubMed Scopus (88) Google Scholar, 12Al‐Mefty O Intracranial tuberculoma.J Neurosurg. 1986; 65: 572-573PubMed Google Scholar). In liver transplant patients, induction therapy with four drugs has been recommended (1Meyers B Halpern M Sheiner P Mendelson M Neibart E Miller C Tuberculosis in liver transplant patients.Transplantation. 1994; 58: 301-306Crossref PubMed Google Scholar, 32Meyers B Papanicolaou G Sheiner P Emre S Miller C Tuberculosis in orthotopic liver transplant patients: increased toxicity of recommended agents; cure of disseminated infection with nonconventional regimens.Transplantation. 2000; 69: 64-69Crossref PubMed Scopus (76) Google Scholar), while the length of therapy has not been studied in these patients. Therapy for a total of 12–18 months is recommended (1Meyers B Halpern M Sheiner P Mendelson M Neibart E Miller C Tuberculosis in liver transplant patients.Transplantation. 1994; 58: 301-306Crossref PubMed Google Scholar, 32Meyers B Papanicolaou G Sheiner P Emre S Miller C Tuberculosis in orthotopic liver transplant patients: increased toxicity of recommended agents; cure of disseminated infection with nonconventional regimens.Transplantation. 2000; 69: 64-69Crossref PubMed Scopus (76) Google Scholar). Hepatic toxicity is a concern with isonazid in liver transplant patients. Schluger et al. reported that five of 13 patients (38%) given INH for tuberculosis, therapy or prophylaxis, developed biochemical and histological evidence of INH hepatotoxicty. Hepatotoxicity has been demonstrated when isonazid was combined with rifampin (33Guarrera J Fiel I Meyers B Berk P Isoniazid hepatotoxicity after orthotopic liver transplantation.Mt Sinai J Med. 1996; 63: 364-369PubMed Google Scholar). Rifampin stimulates the P450 enzyme pathway and may decrease the levels of systemic corticosteroids, cyclosporine, and tacrolimus, leading to possible organ rejection (2Kishikawa K Kajiyama K Uchiyama H et al.Tuberculosis following liver transplantation: report of a case and review of the literature.Transplant Int. 1996; 9: 589-592Crossref PubMed Google Scholar, 32Meyers B Papanicolaou G Sheiner P Emre S Miller C Tuberculosis in orthotopic liver transplant patients: increased toxicity of recommended agents; cure of disseminated infection with nonconventional regimens.Transplantation. 2000; 69: 64-69Crossref PubMed Scopus (76) Google Scholar, 34Michell L Gordon P Lopez T et al.Ten years of liver transplantation at Groote Schuur Hospital.S Afr Med J. 2000; 90: 880-883PubMed Google Scholar). Orthotopic liver transplant patients who developed hepatotoxicty were given ethambutol and ofloxacin for the remainder of their treatment periods, to avoid all potential hepatotoxic medications (33Guarrera J Fiel I Meyers B Berk P Isoniazid hepatotoxicity after orthotopic liver transplantation.Mt Sinai J Med. 1996; 63: 364-369PubMed Google Scholar). Meyers et al. found this nonconventional regimen to be successful in treating disseminated tuberculosis in liver transplant patients. Nine patients with disseminated tuberculosis, including two with tuberculous meningitis, were studied. Standard induction therapy with three to four drugs was given for a mean of 2 months followed by ethambutol and ofloxacin for a mean duration of 6 months (32Meyers B Papanicolaou G Sheiner P Emre S Miller C Tuberculosis in orthotopic liver transplant patients: increased toxicity of recommended agents; cure of disseminated infection with nonconventional regimens.Transplantation. 2000; 69: 64-69Crossref PubMed Scopus (76) Google Scholar). The tuberculosis‐associated mortality was 22.2% (two of three; one patient died before therapy, and another died with concomitant bacterial sepsis during the induction therapy). One patient died of recurrent Hepatitis C with graft failure without evidence of tuberculosis. The role for prophylaxis in liver transplant patients is unclear (1Meyers B Halpern M Sheiner P Mendelson M Neibart E Miller C Tuberculosis in liver transplant patients.Transplantation. 1994; 58: 301-306Crossref PubMed Google Scholar). Patients given isoniazid alone or with ethambutol for chemoprophylaxis did not develop hepatotoxicty. No correlation between INH hepatitis and donor age, initial LFTs, or immunosuppressive agents was noted. Hepatitis strongly correlated with the multidrug regimen (p < 0.001) (33Guarrera J Fiel I Meyers B Berk P Isoniazid hepatotoxicity after orthotopic liver transplantation.Mt Sinai J Med. 1996; 63: 364-369PubMed Google Scholar). In summary, it is apparent that OLT patients with CNS lesions without etiological evidence of fungal infections or other systemic diagnoses may have tuberculosis of the brain. It is necessary to biopsy these lesions, as empiric therapy including corticosteroids may lead to an initial improvement and thereby delay instituting antituberculous therapy.
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