You are in: eMedicine Specialties > Radiology > BRAIN/SPINE Tuberculosis, CNSArticle Last Updated: Jun 28, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 12
  Author: Peter D Corr, MD, MB, ChB, FRCR, Professor of Radiology, United Arab Emirates University Peter D Corr 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 Editors: 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; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; C Douglas Phillips, MD, Professor, Departments of Radiology, Neurosurgery, and Otolaryngology, University of Virginia Health Sciences Center; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; 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 Author and Editor Disclosure Synonyms and related keywords: TB, Mycobacterium tuberculosis, cerebral tuberculosis, cerebral granulomas, tuberculomas, tuberculous granulomas, tuberculous abscesses, granulomatous meningitis, granulomatous infection, tuberculous meningitis, TBM INTRODUCTIONSection 2 of 12
  BackgroundTuberculosis (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. PathophysiologyCNS 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. 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. FrequencyUnited StatesThe incidence of 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 InternationalThe rates of 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/MorbidityIn 2005, mortality in the Americas for all 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.
RaceTB is a disease of poverty, and the racial distribution varies with the socioeconomic status of the country. SexThe male-to-female ratio is 1:1. AgeAll forms of TB, 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, TBM is especially common in patients younger than 5 years. AnatomyTBM 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. Clinical DetailsClinical diagnosis of TBM can be difficult, especially in low-prevalence regions of the world. TBM should be considered in the differential diagnosis if the patient has persistent low-grade fever, headache, and confusion. TBM is more common in patients who are immunosuppressed, such as older persons, young children, patients with HIV or diabetes, and patients taking steroids or cytotoxic drugs. Patients with parenchymal tuberculomas often present with focal seizures. Preferred ExaminationMagnetic 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. 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 TechniquesConventional 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. DIFFERENTIALSSection 3 of 12
Meningitis, Bacterial Other Problems to Be ConsideredSarcoidosis
RADIOGRAPHSection 4 of 12
FindingsSkull radiographic findings are usually normal. Rarely, in healed TBM, faint parenchymal calcification is evident. Degree of ConfidenceCalcifications on skull radiographs in patients with healed TBM or healed tuberculomas are nonspecific findings. False Positives/NegativesSkull calcification may indicate choroid plexus, pineal, and/or habenular calcification. CT SCANSection 5 of 12
FindingsIn 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 ConfidenceCT 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. MRISection 6 of 12
FindingsMRI is more sensitive than CT scanning in determining the extent of meningeal and parenchymal involvement. In 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. 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. MRI is especially useful in detecting leptomeningeal involvement of the spinal cord; cauda equina; and intramedullary tuberculomas, which, although rare, can be detected in patients with AIDS. Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently 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. As of late December 2006, the Food and Drug Administration (FDA) had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. 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 spotsonthe 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 ConfidenceMRI 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. ULTRASOUNDSection 7 of 12
FindingsIn infants, brain ultrasonography can be used to detect hydrocephalus. Degree of ConfidenceUsually, CT scanning or MRI is required for definitive diagnosis. NUCLEAR MEDICINESection 8 of 12
FindingsSingle 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 ConfidenceFindings are specific only for diminished cerebral perfusion. ANGIOGRAPHYSection 9 of 12
FindingsAlthough 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 ConfidenceFeatures of vasculitis and/or vascular occlusion are detected in other inflammatory and ischemic cerebral conditions. INTERVENTIONSection 10 of 12
In cases of spiral TB, radiologic interventions are usually limited to biopsy under ultrasonographic or fluoroscopic guidance. Medical/Legal Pitfalls
Special Concerns
MULTIMEDIASection 11 of 12
REFERENCESSection 12 of 12
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