eMedicine Specialties > Radiology > Brain/Spine

Tuberculosis, CNS

Peter D Corr, MD, MB, ChB, FRCR, Professor of Radiology, United Arab Emirates University

Updated: Dec 30, 2008

Introduction

Contrast-enhanced computed tomography (CT) scan in a patient with tuberculous meningitis demonstrating marked enhancement in the basal cistern and meninges, with dilatation of the ventricles.

Petechial hemorrhages in the subcortical white matter of the brain as a result of tuberculous meningitis–associated vasculitis.

T1-weighted gadolinium-enhanced magnetic resonance image in a child with a tuberculous abscess in the left parietal region. Note the enhancing thick-walled abscess.

Background

Tuberculosis (TB) of the central nervous system (CNS) is a granulomatous infection caused by Mycobacterium tuberculosis. The disease predominantly involves the brain and meninges, but occasionally, it affects the spinal cord. Clinical diagnosis can be difficult; therefore, imaging has an important role in establishing the diagnosis.

For excellent patient education resources, visit eMedicine's Bacterial and Viral Infections Center and Brain and Nervous System Center. See also eMedicine's patient education articles Tuberculosis and Brain Infection.

Frequency

United States

The incidence of tuberculosis (TB) is 8 cases per 100,000 person-years. However, in a study in New York City, the incidence in patients receiving welfare was 744 cases per 100,000 person-years.¹ The prevalence is especially high in people infected with human immunodeficiency virus (HIV), those who abuse drugs and alcohol, immigrants, and homeless persons.²

International

The rates of tuberculosis (TB) and tuberculous meningitis (TBM) have increased globally, especially in developing countries of Africa and Asia that are affected by the HIV pandemic.² The incidence is 544 and 757 new patients per 100,000 population in Africa and India, respectively. Extensively drug-resistant TB (XDR TB) is becoming a public health problem in Africa.

Mortality/Morbidity

In 2005, mortality in the Americas for all tuberculosis (TB) patients was 5.5 deaths per 100,000 persons.³ The major causes of morbidity and mortality of CNS TB are the resulting complications of TBM, especially in pediatric patients. Primary complications include communicating hydrocephalus, vasculitis with resulting infarction, and ventriculitis.

• Hydrocephalus occurs in most patients who survive the first 4-8 weeks. Hydrocephalus may be communicating due to obstruction of the arachnoid granulations, or it may result from obstruction of the cerebral aqueduct or fourth ventricular foramina by tuberculous exudate in the acute phase and by pachymeningitis in the chronic phase of the disease.
• Infarction is common (>50% of patients) in the acute phase and results from a vasculitis that involves the pontine perforator, lenticulostriate, and thalamoperforating arteries. Small infarcts are common in the basal ganglia and brainstem, where they are responsible for the morbidity associated with the disease. These infarcts can lead to mental retardation, stroke, and blindness.
• Ventriculitis is a common complication and a major cause of morbidity, resulting in hydrocephalus.

Race

Tuberculosis is a disease of poverty, and the racial distribution varies with the socioeconomic status of the country.

Sex

The male-to-female ratio of tuberculosis is 1:1.

Age

All forms of tuberculosis, especially those with CNS involvement, are common in children and older persons because their immune systems are less robust than those of adults. In many developing countries, TB meningitis (TBM) is especially common in patients younger than 5 years.

Presentation

Natural history and presentation

Tuberculosis meningitis (TBM) preferentially involves the meninges and basal cisterns of the brain and spinal cord. Infection of the brain parenchyma and spinal cord also occurs and can result in tuberculous granulomas, tuberculous abscesses, or cerebritis.

CNS TB affects the brain and meninges. Infection is hematogenously spread from a primary focus, usually in the lung. Infection starts in a subpial or subependymal cortical focus (ie, Rich focus), resulting in a granuloma that erodes into the subarachnoid space, causing basal leptomeningitis. The meningitis usually causes communicating hydrocephalus, but it may also cause obstruction of the foramina of Luschka and Magendie, resulting in obstructive hydrocephalus. Vasculitis involving the lenticulostriate and thalamoperforatoring arteries may occur and cause small infarcts in the deep gray-matter nuclei and deep white matter.⁴

Other manifestations of TB are focal parenchymal granulomas (eg, tuberculomas), tuberculous abscesses, tuberculous cerebritis, and pachymeningitis. Spinal cord infection is less common; it results in either arachnoiditis or, rarely, focal intramedullary tuberculomas.

Patients with parenchymal tuberculomas often present with focal seizures.

In cases of spiral TB, radiologic interventions are usually limited to biopsy under ultrasonographic or fluoroscopic guidance.

Preferred Examination

Magnetic resonance imaging (MRI) with gadolinium enhancement is the preferred method of initial investigation. MRI is the most sensitive test for detecting the extent of leptomeningeal disease and is superior to computed tomography (CT) scanning in detecting parenchymal abnormalities, such as tuberculomas, abscesses, and infarctions. MRI also readily depicts hydrocephalus.^6,7,8

Cerebrospinal fluid (CSF) analysis is usually used to detect a decreased glucose level, elevated protein levels, and a slight pleocytosis. Results of CSF polymerase chain reaction (PCR) assays may be diagnostic.

Limitations of Techniques

Conventional MRI may cause early meningitis and early infarcts to be missed, and no MRI findings are pathognomonic for TBM. Diffusion-weighted imaging, if available, depicts infarctions in the hyperacute stage.

Differential Diagnoses

Meningitis, Bacterial

Other Problems to Be Considered

Sarcoidosis
Carcinomatous meningitis

Radiography

Findings

Skull radiographic findings are usually normal. Rarely, in healed tuberculosis meningitis, faint parenchymal calcification is evident.

Degree of Confidence

Calcifications on skull radiographs in patients with healed TBM or healed tuberculomas are nonspecific findings.

False Positives/Negatives

Skull calcification may indicate choroid plexus, pineal, and/or habenular calcification.

Computed Tomography

Contrast-enhanced computed tomography (CT) scan in a patient with tuberculous meningitis demonstrating marked enhancement in the basal cistern and meninges, with dilatation of the ventricles.

Extensive infarcts of the right basal ganglia and internal capsule after the appearance of vasculitis in the thalamoperforating arteries in a child treated for tuberculous meningitis.

Contrast-enhanced computed tomography (CT) scan of a child with tuberculous meningitis demonstrating acute hydrocephalus and meningeal enhancement.

Findings

In tuberculosis meningitis (TBM), contrast-enhanced CT scanning of the brain depicts prominent leptomeningeal and basal cistern enhancement. With ependymitis, linear periventricular enhancement is present. Ventricular dilatation (eg, dilatation of the third and fourth ventricles) due to hydrocephalus is usually seen. Often, low-attenuating focal infarcts are seen in the deep gray-matter nuclei, deep white matter, and pons; these infarcts result from associated vasculitis. The primary differential diagnoses are fungal meningitis, bacterial meningitis, carcinomatous meningitis, and neurosarcoidosis.

Parenchymal cerebritis may cause hypoattenuation with little or no enhancement. Parenchymal tuberculomas demonstrate various patterns. Noncaseating granulomas are homogeneously enhancing lesions. Caseating granulomas are rim enhancing; if these have a central calcific focus, they may form a targetlike lesion. Granulomas may also form a miliary pattern with multiple tiny nodules scattered throughout the brain. All lesions are surrounded by hypoattenuating edema. The differential diagnoses include fungal infections, bacterial infections, neurocysticercosis, and cerebral metastases.

Cryptococcal meningitis also occurs in patients with acquired immunodeficiency syndrome (AIDS); however, the history is longer (ie, months) than that of TBM, and perivascular cysts are often seen in the region of the basal ganglia. Perivascular cysts do not occur with TB. Toxoplasmosis usually causes a focal abscess in patients with AIDS.

Degree of Confidence

CT scan findings are typical of granulomatous meningitis with parenchymal involvement. Fungal infections and neurosarcoidosis may appear similar to CNS TB. At times, bacterial infections and metastatic disease also may mimic CNS TB. CSF analysis often helps in establishing the diagnosis.

Magnetic Resonance Imaging

T2-weighted magnetic resonance image of a biopsy-proven, right parietal tuberculoma. Note the low–signal-intensity rim of the lesion and the surrounding hyperintense vasogenic edema.

T1-weighted gadolinium-enhanced magnetic resonance image in a patient with multiple enhancing tuberculomas in both cerebellar hemispheres.

T1-weighted gadolinium-enhanced magnetic resonance image in a child with a tuberculous abscess in the left parietal region. Note the enhancing thick-walled abscess.

T1-weighted gadolinium-enhanced magnetic resonance image of the thoracic spinal cord in a patient with acquired immunodeficiency syndrome (AIDS) and leptomeningeal tuberculosis. Note the numerous granulomas on the dorsal surface of the cord and the dural enhancement.

T2-weighted magnetic resonance image of the thoracic spinal cord of a patient with 2 hyperintense intramedullary tuberculomas.

T2-weighted magnetic resonance image of a patient with a tuberculoma in the right parietal lobe.

Findings

MRI is more sensitive than CT scanning in determining the extent of meningeal and parenchymal involvement.^9,10

In tuberculosis meningitis (TBM), gadolinium-enhanced T1-weighted images demonstrate prominent leptomeningeal and basal cistern enhancement. With ependymitis, linear periventricular enhancement is present. Ventricular dilatation due to hydrocephalus is usually seen. Deep gray-matter nuclei, deep white matter, and pontine infarctions resulting from vasculitis are hyperintense on T2-weighted images. Diffusion-weighted MRI is especially sensitive in depicting early ischemic lesions when findings on the T2-weighted MRIs are normal. The primary differential diagnoses are fungal meningitis, bacterial meningitis, carcinomatous meningitis, and neurosarcoidosis.

Parenchymal cerebritis may show hyperintensity with little or no enhancement on T2-weighted images.

Parenchymal tuberculomas demonstrate various patterns. They are typically hypointense on T2-weighted images, but they may be hyperintense as well. Tuberculomas, like bacterial cerebral abscesses, have hypointense walls or rims on T2-weighted MRIs. The cause is unknown, but free oxygen radicals released by the inflammatory process are believed to decrease T2 values. Noncaseating granulomas are homogeneously enhancing lesions. Caseating granulomas are rim enhancing. Granulomas may also form a miliary pattern with multiple tiny, enhancing nodules scattered throughout the brain. Lesions are typically surrounded by hyperintense edema on T2-weighted images. The differential diagnoses include fungal infections, bacterial infections, neurocysticercosis, and cerebral metastases.

MR spectroscopy with a single-voxel proton technique can be used to characterize tuberculomas and differentiate them from neoplasms (see Image below and Image 11 in Multimedia). Tuberculomas show elevated fatty-acid spectra that are best seen by using the stimulated-echo acquisition mode technique and a short echo time. The necrosis of the waxy walls of mycobacteria within the granuloma is believed to cause the elevation of fatty-acid peaks. The lactate peak is caused by anaerobic glycolysis and is found in inflammatory, ischemic, and neoplastic lesions of the brain; this finding is nonspecific.

Proton spectroscopy trace of a patient with an intracerebral tuberculoma (same patient as in Image 10) demonstrating an elevated lactate peak (LA) with diminished N-acetyl aspartate (NAA) and choline (CH) peaks typical of an inflammatory mass in the brain.

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or magnetic resonance angiography scans. 

NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

Degree of Confidence

MRI improves diagnostic confidence, but images in patients with fungal infections can appear identical to those in patients with neurosarcoidosis. At times, metastatic disease and bacterial infections also can mimic CNS TB.

Ultrasonography

Findings

In infants, brain ultrasonography can be used to detect hydrocephalus.

Degree of Confidence

Usually, CT scanning or MRI is required for definitive diagnosis.

Nuclear Imaging

Findings

Single photon emission CT scanning with hexamethylpropyleneamine oxime (HMPAO) can be used to assess the degree and extent of cerebral ischemia resulting from TBM cerebral vasculitis.

Degree of Confidence

Findings are specific only for diminished cerebral perfusion.

Angiography

Findings

Although not currently in routine use in patients with CNS TB, cerebral angiography demonstrates findings of vasculitis. These findings include vascular irregularity, vascular narrowing, and vascular occlusion. Vessels commonly affected include the terminal portions of the internal carotid arteries, as well as the proximal parts of the middle and anterior cerebral arteries.

Degree of Confidence

Features of vasculitis and/or vascular occlusion are detected in other inflammatory and ischemic cerebral conditions.

Intervention

Medicolegal Pitfalls

• Failure to perform contrast-enhanced CT scanning or gadolinium-enhanced MRI if meningitis is suspected (Meningeal and cerebral involvement is easily missed without contrast enhancement.)

Special Concerns

• The diagnosis of CNS TB can be easily missed in pregnant patients.
  • Precautions should be taken when CT scanning is used during pregnancy.
  • A lead apron should be used to protect the fetus from radiation.
  • MRI that does not involve radiation is probably the best method of investigation; however, the use of intravenously administered gadolinium-based contrast agents during pregnancy is not recommended.
• In infants (in whom TBM is most common), follow-up examination can be performed by using brain ultrasonography rather than CT if the fontanel is patent. The use of ultrasonography reduces the patient's cumulative radiation dose.

Multimedia

Media file 1: Contrast-enhanced computed tomography (CT) scan in a patient with tuberculous meningitis demonstrating marked enhancement in the basal cistern and meninges, with dilatation of the ventricles.

Media file 2: Petechial hemorrhages in the subcortical white matter of the brain as a result of tuberculous meningitis–associated vasculitis.

Media file 3: Extensive infarcts of the right basal ganglia and internal capsule after the appearance of vasculitis in the thalamoperforating arteries in a child treated for tuberculous meningitis.

Media file 4: T2-weighted magnetic resonance image of a biopsy-proven, right parietal tuberculoma. Note the low–signal-intensity rim of the lesion and the surrounding hyperintense vasogenic edema.

Media file 5: T1-weighted gadolinium-enhanced magnetic resonance image in a patient with multiple enhancing tuberculomas in both cerebellar hemispheres.

Media file 6: T1-weighted gadolinium-enhanced magnetic resonance image in a child with a tuberculous abscess in the left parietal region. Note the enhancing thick-walled abscess.

Media file 7: T1-weighted gadolinium-enhanced magnetic resonance image of the thoracic spinal cord in a patient with acquired immunodeficiency syndrome (AIDS) and leptomeningeal tuberculosis. Note the numerous granulomas on the dorsal surface of the cord and the dural enhancement.

Media file 8: T2-weighted magnetic resonance image of the thoracic spinal cord of a patient with 2 hyperintense intramedullary tuberculomas.

Media file 9: Contrast-enhanced computed tomography (CT) scan of a child with tuberculous meningitis demonstrating acute hydrocephalus and meningeal enhancement.

Media file 10: T2-weighted magnetic resonance image of a patient with a tuberculoma in the right parietal lobe.

Media file 11: Proton spectroscopy trace of a patient with an intracerebral tuberculoma (same patient as in Image 10) demonstrating an elevated lactate peak (LA) with diminished N-acetyl aspartate (NAA) and choline (CH) peaks typical of an inflammatory mass in the brain.

References

1. Friedman LN, Williams MT, Singh TP, Frieden TR. Tuberculosis, AIDS, and death among substance abusers on welfare in New York City. N Engl J Med. Mar 28 1996;334(13):828-33. [Medline].

2. Corbett EL, Watt CJ, Walker N, et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med. May 12 2003;163(9):1009-21. [Medline].

3. World Health Organization. Global Tuberculosis Control: Surveillance, Planning, Financing. Geneva: WHO Press; 2007. [Full Text].

4. Rock RB, Olin M, Baker CA, Molitor TW, Peterson PK. Central nervous system tuberculosis: pathogenesis and clinical aspects. Clin Microbiol Rev. Apr 2008;21(2):243-61, table of contents. [Medline].

5. Rafi W, Venkataswamy MM, Ravi V, et al. Rapid diagnosis of tuberculous meningitis: a comparative evaluation of in-house PCR assays involving three mycobacterial DNA sequences, IS6110, MPB-64 and 65 kDa antigen. J Neurol Sci. Jan 31 2007;252(2):163-8. [Medline].

6. Srikanth SG, Taly AB, Nagarajan K, et al. Clinicoradiological features of tuberculous meningitis in patients over 50 years of age. J Neurol Neurosurg Psychiatry. May 2007;78(5):536-8. [Medline].

7. Smith AB, Smirniotopoulos JG, Rushing EJ. From the archives of the AFIP: central nervous system infections associated with human immunodeficiency virus infection: radiologic-pathologic correlation. Radiographics. Nov-Dec 2008;28(7):2033-58. [Medline].

8. Semlali S, El Kharras A, Mahi M, Hsaini Y, Benameur M, Aziz N, et al. [Imaging features of CNS tuberculosis]. J Radiol. Feb 2008;89(2):209-20. [Medline].

9. Janse van Rensburg P, Andronikou S, van Toorn R, Pienaar M. Magnetic resonance imaging of miliary tuberculosis of the central nervous system in children with tuberculous meningitis. Pediatr Radiol. Dec 2008;38(12):1306-13. [Medline].

10. Appenzeller S, Faria AV, Zanardi VA, Fernandes SR, Costallat LT, Cendes F. Vascular involvement of the central nervous system and systemic diseases: etiologies and MRI findings. Rheumatol Int. Oct 2008;28(12):1229-37. [Medline].

11. Garg RK. Tuberculosis of the central nervous system. Postgrad Med J. Mar 1999;75(881):133-40. [Medline].

12. Osborn AG. Diagnostic Neuroradiology. St Louis, Mo: Mosby; 1994.

13. Shah GV. Central nervous system tuberculosis: imaging manifestations. Neuroimaging Clin N Am. May 2000;10(2):355-74. [Medline].

14. Zimmerman RA, Gibby WA, Carmody RF, eds. Neuroimaging: Clinical and Physical Principles. New York, NY: Springer-Verlag; 1999.

Keywords

tuberculosis of the central nervous system, TB, Mycobacterium tuberculosis, cerebral tuberculosis, cerebral granulomas, tuberculomas, tuberculous granulomas, tuberculous abscesses, granulomatous meningitis, granulomatous infection, tuberculous meningitis, TBM

Contributor Information and Disclosures

Author

Peter D Corr, MD, MB, ChB, FRCR, Professor of Radiology, United Arab Emirates University
Peter D Corr, MD, MB, ChB, FRCR is a member of the following medical societies: American Roentgen Ray Society, International Skeletal Society, International Society for Magnetic Resonance in Medicine, Radiological Society of North America, Royal College of Radiologists, Royal College of Surgeons of Edinburgh, and South African Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Pamela W Schaefer, MD, Assistant Professor of Radiology, Harvard Medical School; Associate Director of Neuroradiology, Clinical Director of Magnetic Resonance Imaging, Department of Radiology, Massachusetts General Hospital
Disclosure: Nothing to disclose.

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

Managing Editor

C Douglas Phillips, MD, Professor, Departments of Radiology, Neurosurgery, and Otolaryngology, University of Virginia Health Sciences Center
C Douglas Phillips, MD is a member of the following medical societies: American College of Radiology, American Medical Association, American Society of Head and Neck Radiology, American Society of Neuroradiology, Association of University Radiologists, and Radiological Society of North America
Disclosure: Amirsys Royalty Consulting

CME Editor

Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

James G Smirniotopoulos, MD, Professor of Radiology, Neurology, and Biomedical Informatics, Chairman, Department of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences
James G Smirniotopoulos, MD is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, American Society of Head and Neck Radiology, American Society of Neuroradiology, American Society of Pediatric Neuroradiology, Association of University Radiologists, and Radiological Society of North America
Disclosure: Nothing to disclose.

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