User login
THE CASE
A 59-year-old woman from the Democratic Republic of the Congo presented to our family medicine clinic with acute worsening of longstanding headaches. Using a Swahili interpreter, the patient reported a 15-year history of recurrent, intermittent headaches that had been previously diagnosed as migraines. Over the prior 2 months, the headaches had intensified with new symptoms of dizziness, ocular pain, and blurred vision with red flashes. She had no hemiplegia, dysarthria, respiratory symptoms, night sweats, or weight loss. A neurologic exam was negative.
Before immigrating to the United States 14 years earlier, the patient lived for 6 months in a refugee camp in the Congo. At the time of her immigration, she was negative for human immunodeficiency virus (HIV), and a tuberculosis (TB) skin test was positive. A chest x-ray was normal and she had no respiratory symptoms. Shortly after her immigration, she completed 6 months of isoniazid treatment for latent TB.
THE DIAGNOSIS
A computed tomography (CT) scan of the patient’s head demonstrated a large right frontal mass. The differential diagnosis included neoplasm, sarcoidosis, or, less likely, an infectious etiology. A contrast-enhanced magnetic resonance image (MRI) of the brain showed multiple heterogeneous enhancing lesions, with the largest measuring 4.4 cm x 4.6 cm x 3 cm (FIGURE 1). Significant surrounding edema caused a 1.6-cm midline shift, subfalcine herniation, and impending uncal herniation. A CT of the abdomen and chest showed no pulmonary masses or metastatic disease, but did reveal a single 1-cm lymph node in the mediastinum and a 1.2-cm right axillary node.
A craniotomy was performed, which confirmed a large mass adhered to the dura. Surgeons removed the mass en bloc; pathology was consistent with a necrotizing granuloma. Acid-fast bacilli (AFB) staining of 3 specimens was negative. Because the tissue was preserved in formalin, mycobacterial cultures could not be obtained. A cerebrospinal fluid analysis showed lymphocytosis and elevated protein, consistent with neurotuberculosis. Blood testing for Mycobacterium tuberculosis with interferon gamma release assay (IGRA) was negative, as was testing for HIV 1 and 2. In addition, induced sputum was AFB-smear negative, as was an M tuberculosis polymerase chain reaction test.
Despite the negative AFB stain and negative IGRA, the patient’s findings were suspicious for TB, so we began to treat her empirically for neurotuberculosis with a 4-drug regimen (isoniazid, rifampin, pyrazinamide, and ethambutol).
In an attempt to confirm the diagnosis of TB and determine sensitivities, we performed a right axillary lymph node biopsy and sent it to the Centers for Disease Control and Prevention (CDC), along with the preserved neural tissue. Using a newly developed technique, the CDC amplified and sequenced mycobacterial DNA from both the central nervous system (CNS) mass and the axillary node, confirming M tuberculosis complex species. Cultures from the axillary node grew pan-sensitive M tuberculosis.
DISCUSSION
About one-third of the world’s population has either active or latent TB.1 In areas where TB is endemic, tuberculomas have accounted for up to 20% of intracranial masses.2 In non-endemic regions, however, they are relatively uncommon. The 3 manifestations of active CNS TB are meningitis, tuberculoma, and abscess.3 The clinical presentation and imaging studies of CNS TB are often indistinguishable from those of patients with malignant neoplasms or metastatic disease. Biopsies may be necessary to distinguish tuberculomas from other intracranial lesions such as pyogenic abscesses or necrotic tumors.4 Mycobacterial cultures were not done on the brain biopsies of our patient because of the high clinical suspicion for neoplasm. Axillary lymph node tissue ultimately confirmed the diagnosis and provided sensitivities.
A diagnosis of CNS tuberculoma without meningitis can be challenging because the clinical presentation is often vague, mild, or even asymptomatic. Constitutional symptoms may include headache, fever, and anorexia.5
In our patient, IGRA testing was also negative. For latent TB, IGRAs are considered to be at least as sensitive as, and considerably more specific than TB skin testing, but their use in CNS TB is less well understood. Studies evaluating IGRA sensitivity for TB meningitis show variable results. In one study, IGRAs were positive in only 50% of culture-confirmed cases of TB meningitis in an HIV-negative population.6
Obtain sputum samples for all patients with extrapulmonary TB
The CDC recommends sputum sampling for all patients with extrapulmonary TB, even in the absence of pulmonary symptoms or radiographic findings, to determine the level of infectivity and potential need for a contact investigation.7
Due to low sensitivity of currently available rapid diagnostic tests and high mortality associated with delayed treatment, initiation of empiric treatment is recommended when the probability of CNS TB is high.5
Treatment duration for CNS tuberculomas is based on one randomized controlled trial,8 a small number of observational studies, a prospective cohort study looking at radiographic resolution,9 and expert opinion. Treatment recommendations often do not distinguish CNS tuberculomas from TB meningitis.10 CNS tuberculomas are commonly treated with a minimum of 12 months of therapy, generally using the same medications and dosages used in the treatment of pulmonary TB, starting with 4 first-line agents: isoniazid, rifampin, pyrazinamide, and ethambutol. Modification of the treatment regimen may be made once sensitivities are available.10
Our patient. After cultures were determined to be pan-sensitive, our patient’s treatment regimen was simplified to rifampin and isoniazid, which she continued for the remainder of her treatment course. Her treatment was discontinued after 18 months when quarterly MRIs showed stabilization of the tuberculomas (FIGURE 2).
Following her surgery, she was started on levetiractam for seizure prophylaxis. She subsequently had a seizure on 2 occasions when the medication was discontinued or decreased, so we chose to continue it. The patient is asymptomatic from her disease with no residual deficits.
THE TAKEAWAY
A change in headache patterns in a patient over the age of 50 is a red flag that warrants imaging. In patients from countries where TB is endemic,11 consider neurotuberculosis in the differential diagnosis of worsening headaches and progressive neurologic symptoms.
A diagnosis of CNS TB can be difficult and requires a high level of clinical suspicion, but early diagnosis and treatment of neurotuberculosis can minimize the high risk of morbidity and mortality. Treatment for TB shouldn’t be withheld in cases in which there’s a strong clinical suspicion for TB, but for which a definitive diagnosis is still pending.
1. World Health Organization. 10 facts on tuberculosis. Available at: http://www.who.int/features/factfiles/tuberculosis/en/. Accessed September 19, 2014.
2. Dastur DK, Iyer CG. Pathological analysis of 450 intracranial space-occupying lesions. Ind J Cancer. 1966;3:105-115.
3. Chin JH, Mateen FJ. Central nervous system tuberculosis: Challenges and advances in diagnosis and treatment. Curr Infect Dis Rep. 2013;15:631-635.
4. Bayindir C, Mete O, Bilgic B. Retrospective study of 23 pathologically proven cases of central nervous system tuberculomas. Clin Neurol Neurosurg. 2006;108:353-357.
5. Thwaites G, Fisher M, Hemingway C, et al; British Infection Society. British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. J Infect. 2009;59:167-187.
6. Simmons CP, Thwaites GE, Quyen NT, et al. Pretreatment intracerebral and peripheral blood immune responses in Vietnamese adults with tuberculous meningitis: diagnostic value and relationship to disease severity and outcome. J Immunol. 2006;176:2007-2014.
7. Centers for Disease Control and Prevention (CDC). Core curriculum on tuberculosis: What the clinician should know. 6th ed. Centers for Disease Control and Prevention, Atlanta, GA; 2013.
8. Rajeswari R, Sivasubramanian S, Balambal R, et al. A controlled clinical trial of short-course chemotherapy for tuberculoma of the brain. Tuber Lung Dis. 1995;76:311-317.
9. Poonnoose SI, Rajshekhar V. Rate of resolution of histologically verified intracranial tuberculomas. Neurosurgery. 2003;53:873-878.
10. American Thoracic Society; CDC; Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep. 2003;52:1-77. Erratum in: MMWR Recomm Rep. 2005;53:1203.
11. Stop TB Partnership. High burden countries. Available at: http://www.stoptb.org/countries/tbdata.asp. Accessed November 7, 2016.
THE CASE
A 59-year-old woman from the Democratic Republic of the Congo presented to our family medicine clinic with acute worsening of longstanding headaches. Using a Swahili interpreter, the patient reported a 15-year history of recurrent, intermittent headaches that had been previously diagnosed as migraines. Over the prior 2 months, the headaches had intensified with new symptoms of dizziness, ocular pain, and blurred vision with red flashes. She had no hemiplegia, dysarthria, respiratory symptoms, night sweats, or weight loss. A neurologic exam was negative.
Before immigrating to the United States 14 years earlier, the patient lived for 6 months in a refugee camp in the Congo. At the time of her immigration, she was negative for human immunodeficiency virus (HIV), and a tuberculosis (TB) skin test was positive. A chest x-ray was normal and she had no respiratory symptoms. Shortly after her immigration, she completed 6 months of isoniazid treatment for latent TB.
THE DIAGNOSIS
A computed tomography (CT) scan of the patient’s head demonstrated a large right frontal mass. The differential diagnosis included neoplasm, sarcoidosis, or, less likely, an infectious etiology. A contrast-enhanced magnetic resonance image (MRI) of the brain showed multiple heterogeneous enhancing lesions, with the largest measuring 4.4 cm x 4.6 cm x 3 cm (FIGURE 1). Significant surrounding edema caused a 1.6-cm midline shift, subfalcine herniation, and impending uncal herniation. A CT of the abdomen and chest showed no pulmonary masses or metastatic disease, but did reveal a single 1-cm lymph node in the mediastinum and a 1.2-cm right axillary node.
A craniotomy was performed, which confirmed a large mass adhered to the dura. Surgeons removed the mass en bloc; pathology was consistent with a necrotizing granuloma. Acid-fast bacilli (AFB) staining of 3 specimens was negative. Because the tissue was preserved in formalin, mycobacterial cultures could not be obtained. A cerebrospinal fluid analysis showed lymphocytosis and elevated protein, consistent with neurotuberculosis. Blood testing for Mycobacterium tuberculosis with interferon gamma release assay (IGRA) was negative, as was testing for HIV 1 and 2. In addition, induced sputum was AFB-smear negative, as was an M tuberculosis polymerase chain reaction test.
Despite the negative AFB stain and negative IGRA, the patient’s findings were suspicious for TB, so we began to treat her empirically for neurotuberculosis with a 4-drug regimen (isoniazid, rifampin, pyrazinamide, and ethambutol).
In an attempt to confirm the diagnosis of TB and determine sensitivities, we performed a right axillary lymph node biopsy and sent it to the Centers for Disease Control and Prevention (CDC), along with the preserved neural tissue. Using a newly developed technique, the CDC amplified and sequenced mycobacterial DNA from both the central nervous system (CNS) mass and the axillary node, confirming M tuberculosis complex species. Cultures from the axillary node grew pan-sensitive M tuberculosis.
DISCUSSION
About one-third of the world’s population has either active or latent TB.1 In areas where TB is endemic, tuberculomas have accounted for up to 20% of intracranial masses.2 In non-endemic regions, however, they are relatively uncommon. The 3 manifestations of active CNS TB are meningitis, tuberculoma, and abscess.3 The clinical presentation and imaging studies of CNS TB are often indistinguishable from those of patients with malignant neoplasms or metastatic disease. Biopsies may be necessary to distinguish tuberculomas from other intracranial lesions such as pyogenic abscesses or necrotic tumors.4 Mycobacterial cultures were not done on the brain biopsies of our patient because of the high clinical suspicion for neoplasm. Axillary lymph node tissue ultimately confirmed the diagnosis and provided sensitivities.
A diagnosis of CNS tuberculoma without meningitis can be challenging because the clinical presentation is often vague, mild, or even asymptomatic. Constitutional symptoms may include headache, fever, and anorexia.5
In our patient, IGRA testing was also negative. For latent TB, IGRAs are considered to be at least as sensitive as, and considerably more specific than TB skin testing, but their use in CNS TB is less well understood. Studies evaluating IGRA sensitivity for TB meningitis show variable results. In one study, IGRAs were positive in only 50% of culture-confirmed cases of TB meningitis in an HIV-negative population.6
Obtain sputum samples for all patients with extrapulmonary TB
The CDC recommends sputum sampling for all patients with extrapulmonary TB, even in the absence of pulmonary symptoms or radiographic findings, to determine the level of infectivity and potential need for a contact investigation.7
Due to low sensitivity of currently available rapid diagnostic tests and high mortality associated with delayed treatment, initiation of empiric treatment is recommended when the probability of CNS TB is high.5
Treatment duration for CNS tuberculomas is based on one randomized controlled trial,8 a small number of observational studies, a prospective cohort study looking at radiographic resolution,9 and expert opinion. Treatment recommendations often do not distinguish CNS tuberculomas from TB meningitis.10 CNS tuberculomas are commonly treated with a minimum of 12 months of therapy, generally using the same medications and dosages used in the treatment of pulmonary TB, starting with 4 first-line agents: isoniazid, rifampin, pyrazinamide, and ethambutol. Modification of the treatment regimen may be made once sensitivities are available.10
Our patient. After cultures were determined to be pan-sensitive, our patient’s treatment regimen was simplified to rifampin and isoniazid, which she continued for the remainder of her treatment course. Her treatment was discontinued after 18 months when quarterly MRIs showed stabilization of the tuberculomas (FIGURE 2).
Following her surgery, she was started on levetiractam for seizure prophylaxis. She subsequently had a seizure on 2 occasions when the medication was discontinued or decreased, so we chose to continue it. The patient is asymptomatic from her disease with no residual deficits.
THE TAKEAWAY
A change in headache patterns in a patient over the age of 50 is a red flag that warrants imaging. In patients from countries where TB is endemic,11 consider neurotuberculosis in the differential diagnosis of worsening headaches and progressive neurologic symptoms.
A diagnosis of CNS TB can be difficult and requires a high level of clinical suspicion, but early diagnosis and treatment of neurotuberculosis can minimize the high risk of morbidity and mortality. Treatment for TB shouldn’t be withheld in cases in which there’s a strong clinical suspicion for TB, but for which a definitive diagnosis is still pending.
THE CASE
A 59-year-old woman from the Democratic Republic of the Congo presented to our family medicine clinic with acute worsening of longstanding headaches. Using a Swahili interpreter, the patient reported a 15-year history of recurrent, intermittent headaches that had been previously diagnosed as migraines. Over the prior 2 months, the headaches had intensified with new symptoms of dizziness, ocular pain, and blurred vision with red flashes. She had no hemiplegia, dysarthria, respiratory symptoms, night sweats, or weight loss. A neurologic exam was negative.
Before immigrating to the United States 14 years earlier, the patient lived for 6 months in a refugee camp in the Congo. At the time of her immigration, she was negative for human immunodeficiency virus (HIV), and a tuberculosis (TB) skin test was positive. A chest x-ray was normal and she had no respiratory symptoms. Shortly after her immigration, she completed 6 months of isoniazid treatment for latent TB.
THE DIAGNOSIS
A computed tomography (CT) scan of the patient’s head demonstrated a large right frontal mass. The differential diagnosis included neoplasm, sarcoidosis, or, less likely, an infectious etiology. A contrast-enhanced magnetic resonance image (MRI) of the brain showed multiple heterogeneous enhancing lesions, with the largest measuring 4.4 cm x 4.6 cm x 3 cm (FIGURE 1). Significant surrounding edema caused a 1.6-cm midline shift, subfalcine herniation, and impending uncal herniation. A CT of the abdomen and chest showed no pulmonary masses or metastatic disease, but did reveal a single 1-cm lymph node in the mediastinum and a 1.2-cm right axillary node.
A craniotomy was performed, which confirmed a large mass adhered to the dura. Surgeons removed the mass en bloc; pathology was consistent with a necrotizing granuloma. Acid-fast bacilli (AFB) staining of 3 specimens was negative. Because the tissue was preserved in formalin, mycobacterial cultures could not be obtained. A cerebrospinal fluid analysis showed lymphocytosis and elevated protein, consistent with neurotuberculosis. Blood testing for Mycobacterium tuberculosis with interferon gamma release assay (IGRA) was negative, as was testing for HIV 1 and 2. In addition, induced sputum was AFB-smear negative, as was an M tuberculosis polymerase chain reaction test.
Despite the negative AFB stain and negative IGRA, the patient’s findings were suspicious for TB, so we began to treat her empirically for neurotuberculosis with a 4-drug regimen (isoniazid, rifampin, pyrazinamide, and ethambutol).
In an attempt to confirm the diagnosis of TB and determine sensitivities, we performed a right axillary lymph node biopsy and sent it to the Centers for Disease Control and Prevention (CDC), along with the preserved neural tissue. Using a newly developed technique, the CDC amplified and sequenced mycobacterial DNA from both the central nervous system (CNS) mass and the axillary node, confirming M tuberculosis complex species. Cultures from the axillary node grew pan-sensitive M tuberculosis.
DISCUSSION
About one-third of the world’s population has either active or latent TB.1 In areas where TB is endemic, tuberculomas have accounted for up to 20% of intracranial masses.2 In non-endemic regions, however, they are relatively uncommon. The 3 manifestations of active CNS TB are meningitis, tuberculoma, and abscess.3 The clinical presentation and imaging studies of CNS TB are often indistinguishable from those of patients with malignant neoplasms or metastatic disease. Biopsies may be necessary to distinguish tuberculomas from other intracranial lesions such as pyogenic abscesses or necrotic tumors.4 Mycobacterial cultures were not done on the brain biopsies of our patient because of the high clinical suspicion for neoplasm. Axillary lymph node tissue ultimately confirmed the diagnosis and provided sensitivities.
A diagnosis of CNS tuberculoma without meningitis can be challenging because the clinical presentation is often vague, mild, or even asymptomatic. Constitutional symptoms may include headache, fever, and anorexia.5
In our patient, IGRA testing was also negative. For latent TB, IGRAs are considered to be at least as sensitive as, and considerably more specific than TB skin testing, but their use in CNS TB is less well understood. Studies evaluating IGRA sensitivity for TB meningitis show variable results. In one study, IGRAs were positive in only 50% of culture-confirmed cases of TB meningitis in an HIV-negative population.6
Obtain sputum samples for all patients with extrapulmonary TB
The CDC recommends sputum sampling for all patients with extrapulmonary TB, even in the absence of pulmonary symptoms or radiographic findings, to determine the level of infectivity and potential need for a contact investigation.7
Due to low sensitivity of currently available rapid diagnostic tests and high mortality associated with delayed treatment, initiation of empiric treatment is recommended when the probability of CNS TB is high.5
Treatment duration for CNS tuberculomas is based on one randomized controlled trial,8 a small number of observational studies, a prospective cohort study looking at radiographic resolution,9 and expert opinion. Treatment recommendations often do not distinguish CNS tuberculomas from TB meningitis.10 CNS tuberculomas are commonly treated with a minimum of 12 months of therapy, generally using the same medications and dosages used in the treatment of pulmonary TB, starting with 4 first-line agents: isoniazid, rifampin, pyrazinamide, and ethambutol. Modification of the treatment regimen may be made once sensitivities are available.10
Our patient. After cultures were determined to be pan-sensitive, our patient’s treatment regimen was simplified to rifampin and isoniazid, which she continued for the remainder of her treatment course. Her treatment was discontinued after 18 months when quarterly MRIs showed stabilization of the tuberculomas (FIGURE 2).
Following her surgery, she was started on levetiractam for seizure prophylaxis. She subsequently had a seizure on 2 occasions when the medication was discontinued or decreased, so we chose to continue it. The patient is asymptomatic from her disease with no residual deficits.
THE TAKEAWAY
A change in headache patterns in a patient over the age of 50 is a red flag that warrants imaging. In patients from countries where TB is endemic,11 consider neurotuberculosis in the differential diagnosis of worsening headaches and progressive neurologic symptoms.
A diagnosis of CNS TB can be difficult and requires a high level of clinical suspicion, but early diagnosis and treatment of neurotuberculosis can minimize the high risk of morbidity and mortality. Treatment for TB shouldn’t be withheld in cases in which there’s a strong clinical suspicion for TB, but for which a definitive diagnosis is still pending.
1. World Health Organization. 10 facts on tuberculosis. Available at: http://www.who.int/features/factfiles/tuberculosis/en/. Accessed September 19, 2014.
2. Dastur DK, Iyer CG. Pathological analysis of 450 intracranial space-occupying lesions. Ind J Cancer. 1966;3:105-115.
3. Chin JH, Mateen FJ. Central nervous system tuberculosis: Challenges and advances in diagnosis and treatment. Curr Infect Dis Rep. 2013;15:631-635.
4. Bayindir C, Mete O, Bilgic B. Retrospective study of 23 pathologically proven cases of central nervous system tuberculomas. Clin Neurol Neurosurg. 2006;108:353-357.
5. Thwaites G, Fisher M, Hemingway C, et al; British Infection Society. British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. J Infect. 2009;59:167-187.
6. Simmons CP, Thwaites GE, Quyen NT, et al. Pretreatment intracerebral and peripheral blood immune responses in Vietnamese adults with tuberculous meningitis: diagnostic value and relationship to disease severity and outcome. J Immunol. 2006;176:2007-2014.
7. Centers for Disease Control and Prevention (CDC). Core curriculum on tuberculosis: What the clinician should know. 6th ed. Centers for Disease Control and Prevention, Atlanta, GA; 2013.
8. Rajeswari R, Sivasubramanian S, Balambal R, et al. A controlled clinical trial of short-course chemotherapy for tuberculoma of the brain. Tuber Lung Dis. 1995;76:311-317.
9. Poonnoose SI, Rajshekhar V. Rate of resolution of histologically verified intracranial tuberculomas. Neurosurgery. 2003;53:873-878.
10. American Thoracic Society; CDC; Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep. 2003;52:1-77. Erratum in: MMWR Recomm Rep. 2005;53:1203.
11. Stop TB Partnership. High burden countries. Available at: http://www.stoptb.org/countries/tbdata.asp. Accessed November 7, 2016.
1. World Health Organization. 10 facts on tuberculosis. Available at: http://www.who.int/features/factfiles/tuberculosis/en/. Accessed September 19, 2014.
2. Dastur DK, Iyer CG. Pathological analysis of 450 intracranial space-occupying lesions. Ind J Cancer. 1966;3:105-115.
3. Chin JH, Mateen FJ. Central nervous system tuberculosis: Challenges and advances in diagnosis and treatment. Curr Infect Dis Rep. 2013;15:631-635.
4. Bayindir C, Mete O, Bilgic B. Retrospective study of 23 pathologically proven cases of central nervous system tuberculomas. Clin Neurol Neurosurg. 2006;108:353-357.
5. Thwaites G, Fisher M, Hemingway C, et al; British Infection Society. British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. J Infect. 2009;59:167-187.
6. Simmons CP, Thwaites GE, Quyen NT, et al. Pretreatment intracerebral and peripheral blood immune responses in Vietnamese adults with tuberculous meningitis: diagnostic value and relationship to disease severity and outcome. J Immunol. 2006;176:2007-2014.
7. Centers for Disease Control and Prevention (CDC). Core curriculum on tuberculosis: What the clinician should know. 6th ed. Centers for Disease Control and Prevention, Atlanta, GA; 2013.
8. Rajeswari R, Sivasubramanian S, Balambal R, et al. A controlled clinical trial of short-course chemotherapy for tuberculoma of the brain. Tuber Lung Dis. 1995;76:311-317.
9. Poonnoose SI, Rajshekhar V. Rate of resolution of histologically verified intracranial tuberculomas. Neurosurgery. 2003;53:873-878.
10. American Thoracic Society; CDC; Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep. 2003;52:1-77. Erratum in: MMWR Recomm Rep. 2005;53:1203.
11. Stop TB Partnership. High burden countries. Available at: http://www.stoptb.org/countries/tbdata.asp. Accessed November 7, 2016.
