|Year : 2015 | Volume
| Issue : 1 | Page : 3-8
Tuberculoma of the brain - A diagnostic dilemma: Magnetic resonance spectroscopy a new ray of hope
Subhasis Mukherjee1, Runa Das2, Shabana Begum3
1 Department of Pulmonary Medicine, College of Medicine and Sagar Dutta Medical College and Hospital, Kamarhati, Kolkata, West Bengal, India
2 Department of Radiodiagnosis, College of Medicine and Sagar Dutta Medical College and Hospital, Kamarhati, Kolkata, West Bengal, India
3 Department of Anatomy, North Bengal Medical College and Hospital, Sushrutanagar, Siliguri, Darjeeling, West Bengal, India
|Date of Web Publication||12-Dec-2014|
181/2B, Roypur Road, Kolkata 700 047, West Bengal
Source of Support: None, Conflict of Interest: None
Tuberculoma of the brain is an important clinical entity. The main challenge in the management of brain tuberculoma is its diagnosis. Appearance in computed tomography (CT) scan of brain is common and consists of solitary or multiple ring-enhancing lesions with moderate perilesional edema, but these are not specific for tuberculoma as neurocysticercosis (NCC), coccidiomycosis, toxoplasmosis, metastasis and few other diseases may also have similar appearance on CT scan brain. Cerebrospinal fluid examination is often normal and biopsy and tissue culture from the lesion though the diagnosis of choice is technically too demanding and not feasible in most of the times. All these put the clinicians in a great dilemma as regard to a confidant diagnosis of tuberculoma of the brain. With advancement of imaging techniques, magnetic resonance imaging (MRI) of brain with magnetic resonance spectroscopy (MRS) has shown a great hope in this context as MRS shows a specific lipid peak in cases of tuberculoma which is not seen in any other differential diagnoses of tuberculoma. This review article is written to have an overview regarding the current diagnostic approach for brain tuberculoma with special emphasis on the role of MRS. Extensive literature review of the articles published in English was conducted using Google search, Google Scholar, PubMed and Medline using the keywords such as ring-enhancing lesions, etiology, tuberculoma, NCC, CT scan brain, MRI, MRS, images.
Keywords: Magnetic resonance spectroscopy, neurocysticercosis, ring-enhancing lesion, tuberculoma
|How to cite this article:|
Mukherjee S, Das R, Begum S. Tuberculoma of the brain - A diagnostic dilemma: Magnetic resonance spectroscopy a new ray of hope. J Assoc Chest Physicians 2015;3:3-8
|How to cite this URL:|
Mukherjee S, Das R, Begum S. Tuberculoma of the brain - A diagnostic dilemma: Magnetic resonance spectroscopy a new ray of hope. J Assoc Chest Physicians [serial online] 2015 [cited 2019 Jan 18];3:3-8. Available from: http://www.jacpjournal.org/text.asp?2015/3/1/3/146842
| Introduction|| |
Overall, tuberculosis of the central nervous system (CNS) accounts for approximately 1% of all of the diseases caused by Mycobacterium tuberculosis, but it comprises 10-15% of extrapulmonary tuberculosis. , Tuberculoma is the second commonest manifestation of CNS tuberculosis and constitutes a sizable proportion of intracranial space occupying lesions (SOL) in the developing countries where tuberculosis is still quite prevalent. The idea behind this review article is to have a clear understanding regarding the diagnostic protocol of tuberculoma of the brain in the present context as there has been a long prevailing uncertainty and grey areas in the diagnosis of tuberculoma of brain.
| Methods|| |
Extensive literature review of the articles published in English was conducted using Google search, Google Scholar, PubMed and Medline using the keywords such as ring-enhancing lesions, etiology, tuberculoma, neurocysticercosis (NCC), computed tomography (CT) scan brain, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), images. Review articles, original articles and case reports in this field that were published in the English language were considered for this review. In addition to the literature search using the internet, textbooks both in the field of Pulmonary Medicine and Radiology were also consulted.
Epidemiology and pathogenesis of tuberculoma of the brain
Tuberculoma has been defined as a mass of granulation tissue made up of a conglomeration of microscopic tubercles. The tuberculoma may be single or less commonly multiple, and their sizes may vary from a few millimeters to a diameter of 3-4 cm. 
The current understanding of the pathogenesis of CNS tuberculosis remains largely unaltered for last 80 years since the pioneering work by Arnold Rich and Howard McCordock in 1933. , CNS tuberculosis is a two-staged process. In the first stage, there are seeding of the tubercule bacilli forming "Rich foci" predominantly within the brain parenchyma following a hematogenous dissemination during primary or postprimary phase of the infection. After a quiescent period of about months or a few years, the second stage starts where either the bacilli and its antigenic components are released into the subarachnoid space causing tuberculous meningitis; or instead of rupturing into the subarachnoid space, the intracranial tubercles may enlarge within the brain parenchyma and give rise to a SOL known as tuberculoma. The tuberculoma is walled off from the brain parenchyma by a thick fibrous capsule. ,
Unlike tubercular meningitis, which has a stormy presentation, tuberculoma of the brain has an insidious course, but sometimes both may co-exist in the same patient.  Tuberculomas may attain a considerable size before producing symptoms. Clinical presentations are not due to tubercule bacilli or its antigens but due to pressure effects of SOL. Usual presentation is a single or repeated episodes of focal seizures (60-100%), signs of raised intracranial tension (56-93%) and focal neurological deficits (33-68%).  Exact nature, distribution and frequency of the neurological manifestations will depend on the site of the lesions, size of the lesions, number of tuberculomas and their rate of increase in size. In adults, supratentorial location is common for tuberculomas, but in children infratentorial the location is commoner. , The symptoms are due to increased intracranial pressure and are common for all intracranial SOL. In the developing world, tuberculoma accounts for around 20-30% of SOL in the brain and in the pediatric population, the percentage may even be higher. 
The conventional diagnostic principle can broadly be divided into:
- Search for tuberculosis elsewhere in the body
- Meticulous search for any peripheral lymphadenopathy
- Chest X-ray to look for any evidence of pulmonary tuberculosis, military mottlings, mediastinal lymphadenopathy or pleural effusion
- Sputum for Ziehl-Neelsen staining
- Ultrasound of the abdomen to look for any hepatosplenomegaly or the intra-abdominal lymphadenopathy.
If one or more of the above are found to be positive, these can be taken as a surrogate evidence favoring a diagnosis of intracranial tuberculoma.
In developing countries like India, single enhancing lesion in CT brain has been found to be the commonest lesion in children and young adults with focal seizures. ,, The etiology of these lesions also differ from the western counterparts with infective causes like NCC and tuberculoma being the commonest etiologies in India. It often becomes difficult to differentiate between tuberculoma and NCC because both the diseases are prevalent and share common clinic-radiological features. 
Different modalities of brain imaging are the cornerstones for a diagnosis of intracranial tuberculomas, these are also very useful to assess the extent of the lesions. But, the conventional imaging's like CT scan and MRI of brain have got definite limitations in regard to a specific and confidant diagnosis of tuberculoma as the findings are not specific to tuberculoma and can be found in certain other conditions mimicking tuberculoma, especially NCC. ,
- Computed tomography scan of the brain
Computed tomography scan appearances may vary according to the stages of the disease. Noncontrast CT scan of the brain may be normal or may show irregular hypodense lesion due to cerebritis during the early stage of the disease. With the development of inflammatory granuloma and central caseation, lesion appears hypodense or less commonly isodense with an irregular outline on noncontrast CT brain which enhances and shows a ring like an appearance with contrast. Sometimes, calcifications and target lesions are found. The lesions are usually larger than 20 mm, but sizes may vary from 1 to 6 cm. Lesions are commonly solitary, but multiple lesions are not infrequent. These are surrounded by considerable amount of vasogenic edema that frequently produces mass effect and midline shift. ,,,,,,, In the Indian scenario, a single ring-enhancing lesion in CT scan of brain has been found to be the commonest radiological finding in a young adult with a new onset partial seizure, and the two most common etiologies are NCC followed by tuberculoma. ,
Neurocysticercosis on the other hand classically presents with multiple, small (<20 mm) lesion with ring-enhancement, presence of eccentric nodules, moderate vasogenic edema that usually does not result in midline shift. ,,,,
Though, lesions with size >20 mm, irregular outline and midline shift in CT brain has been proposed to favor a diagnosis of tuberculoma by some authors, , these descriptions are not mutually very exclusive or specific for neither of the two conditions. , Moreover, pyogenic brain abscess, brain tumors (metastasis or primary), lymphoma, toxoplasmosis and cryptococcosis in immunocompromised subjects can also give rise to similar findings on CT scan of brain [Table 1] and [Table 2]. ,,
So, although CT scan of brain is primary investigation of choice and is very sensitive (100%) in detecting ring-enhancing lesions, it lacks specificity and has got a pretty low negative predictive value (31%). , This clearly emphasizes the limitation of CT scan of the brain with contrast as the sole diagnostic modality of intracranial tuberculoma.
|Table 1: Spectrum of differential diagnoses of single ring-enhancing lesion in CT Brain |
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|Table 2: Spectrum of differential diagnoses of multiple ring-enhancing lesion in CT Brain |
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- Magnetic resonance imaging
Conventional MRI brain is better than CT scan brain for anatomical delineation, but the findings are not always specific for tuberculoma and are often difficult to differentiate between tuberculoma and NCC in a conventional MRI. A non caseating tuberculoma is hyperintense on T2-weighted and but appears hypointense on T1-weighted images. But a caseating tuberculoma is seen as iso-to hypointense on both T1- and T2-weighted images, with an iso-to hyperintense rim on T2-weighted images. On contrast image nodular or ring-like enhancing lesions are seen. The diameter of these enhancing lesions usually ranges from 1 mm to 5 cm. The types of enhancement varies and may show complete ring, open rings, lobular patterns or may be irregular. Sometimes target lesions are found. ,,,,,
In the case of NCC, the appearance depends on the stage of the lesion. The wall of the cysticercus granuloma (a colloid cyst stage) becomes thick and hypointense, and there is mild to moderate perilesional edema on T2 image. Cysticercus granuloma also enhances and shows a ring pattern after administration of contrast. Usually, the lesions are <20 mm in diameter. Calcified eccentric scolex if seen can be diagnostic of NCC in MRI. The lesions are often multiple and most often do not have extensive edema. ,,,,
- Molecular tests-molecular tests like polymerase chain reaction based studies are very sensitive but cannot differentiate between infection and disease and also lack specificity and currently are not recommended as a diagnostic tool.
- Brain biopsy-although histopathology accompanied by tissue culture should be the gold standard for diagnosis, it is not always feasible especially in the developing countries with limited resources. 
Newer imaging modalities for the diagnosis of tuberculoma
- Magnetic resonance spectroscopy
Magnetic resonance spectroscopy of brain is a new and smart technique that measures the concentration of several biochemical compounds in the brain in health and various disease states. In contrast to conventional MRI showing images, MRS demonstrates spectra of resonances. The area under each peak in the spectrum actually reflects relative concentrations of that particular metabolite and is expressed in unit parts per million. , Historically, first MRS of biological tissues dates back to 1970s when Moon and Richards used Phosphorous-31 (P-31) to examine red blood cells and same P-31 was applied to excised leg muscle from rat by Hoult and his group. ,
In modern day, proton MRS is performed most commonly using 1 H as it is easy to perform and shows better spectra compared to sodium ( 23 Na) and phosphorous ( 31 P). MRS can be done within 10-15 min and can easily be supplemented with conventional MRI brain. , MRS has been found very useful in an array of diseases like brain tumor, infections, ring-enhancing lesions, abscesses, metabolic disorders, epilepsy and neurodegenerative disorders as MRS usually shows different characteristic spectral peak in different conditions. , However, MRS interpretation is best when its result is analyzed in the context of clinical and MRI data.
Magnetic resonance spectroscopy of normal brain shows predominant peaks of N-acetylaspartate (NAA), choline, creatinine and myo-inositol with the highest peak being NAA. NAA is a healthy neuronal marker, choline represents energy store and choline is a marker of cellular turnover [Figure 1]. ,
|Figure 1: Normal magnetic resonance spectroscopy of brain showing that N-acetylaspartate peak is highest, and there is no lipid or lactate peak|
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Magnetic resonance spectroscopy is of great value in the diagnosis of tuberculoma in cases of ring-enhancing lesions on CT scan or MRI imaging. It demonstrates a very high lipid peak, reduction in NAA and creatinine and a choline/creatinine ratio of >1 [Figure 2]. Lipid peak in MRS in the context of a ring-enhancing lesion is very much specific for tuberculoma and has not been seen in any cases of NCC, the other common differential diagnosis of a ring-enhancing lesion. ,,,,,,, NCC demonstrates a high lactate and proteins like alanine, succinate, glutamate, glycine levels with some reduction of NAA and creatinine [Figure 3].  A high choline peak is seen in MRS in case of tumors, primary or secondary, because of very high cellular turnover. MRS can also differentiate tuberculoma or tuberculous brain abscess from pyogenic brain abscess by the presence of elevated levels of amino acid peaks in pyogenic brain abscess. 
|Figure 2: The magnetic resonance spectroscopy brain in the case of tuberculoma showing grossly diminished N-acetylaspartate peak and a distinct lipid peak|
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|Figure 3: The magnetic resonance spectroscopy brain in the case of neurocysticercosis showing moderately diminished N-acetylaspartate and presence of a lactate peak but absence of a lipid peak|
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- Other newer and advanced MRI techniques like diffusion-weighted MRI, magnetization transfer ratio and three-dimensional constructive interference in steady state are also being studied and have shown encouraging results in the diagnosis of tuberculoma and tuberculous brain abscess. ,
| Conclusion|| |
Conventional neuroimaging like CT scan of the brain with contrast and MRI brain ± contrast alone are insufficient diagnostic tool for a confidant etiological diagnosis of intracranial ring-enhancing lesions like tuberculoma. In patients with focal seizures with solitary or multiple ring-enhancing lesions in CT or MRI brain, MRS of the brain should be done in all cases to look for the characteristic lipid peak to confirm a diagnosis of tuberculoma. Evidence of tuberculosis elsewhere in the body should also be searched for in all these cases as these can also support the diagnosis of intracranial tuberculoma. Integration of a good clinical insight, thorough search for tuberculosis outside the brain and use of newer imaging techniques like MRS is the key to overcome the prevailing diagnostic dilemma in cases of tuberculoma of the brain [Flow chart 1].
| References|| |
Henry M, Holzman RS. Tuberculosis of the brain, meninges and spinal cord. In: Rom WN, Garay SM, editors. Tuberculosis. Philadelphia: Lippincot Williams and Wilkins; 2004. p. 445-64.
Radhakrishnan K, Kishore A, Mathurnath PS. Neurological tuberculosis. In: Sharma SK, Mohan A, editors. Tuberculosis. New Delhi: Jaypee Brothers; 2009. p. 209-28.
Thwaites GE, Schoeman JF. Update on tuberculosis of the central nervous system: Pathogenesis, diagnosis and treatment. In: Zumla A, Schaaf HS, editors. Clinics in Chest Medicine: Tuberculosis. Philadelphia: Saunders; 2009. p. 745-54.
Garg RK. Diagnosis of intracranial tuberculoma. Ind J Tub 1996;43:35-9.
Mahato PS, Dabhi AS, Thorat PB. Clinical and investigative profile of ring-enhancing lesions on neuroimaging. Indian J Clin Pract 2012;22:512-8.
Garg RK. Single enhancing computerized tomography-detected lesion in immunocompetent patients. Neurosurg Focus 2002;12:e4.
Singhi P, Ray M. Focal seizures with single small ring-enhancing lesion. Semin Pediatr Neurol 1999;6:196-200.
Sethi PP, Wadia RS, Kiyawat DP, Ichaporia NR, Kothari SS, Sangle SA, et al.
Ring or disc enhancing lesions in epilepsy in India. J Trop Med Hyg 1994;97:347-53.
Shetty G, Avabratha KS, Rai BS. Ring-enhancing lesions in the brain: A diagnostic dilemma. Iran J Child Neurol 2014;8:61-4.
Rudresh K, Karthik MK, Sebastin J. Clinical and aetiological profile of ring-enhancing lesions on CT brain. J Indian Acad Clin Med 2008;9:100-2.
Lwakatare FA, Gabone J. Imaging features of brain tuberculoma in Tanzania: Case report and literature review. Afr Health Sci 2003;3:131-5.
Adam A, Dixon A, Gilard JH, Schaefer-prokop CM, editors. Grainger and Allison's Diagnostic Radiology: A Textbook of Medical Imaging. 6 th
ed. China: Churchill Livingstone; 2014.
Verma R, Gupta R. Multiple ring-enhancing lesions: Diagnostic dilemma between neurocysticercosis and tuberculoma. BMJ Case Rep 2014;2014.
Wasay M, Kheleani BA, Moolani MK, Zaheer J, Pui M, Hasan S, et al.
Brain CT and MRI findings in 100 consecutive patients with intracranial tuberculoma. J Neuroimaging 2003;13:240-7.
Kumar Garg R, Kumar Singh M, Misra S. Single-enhancing CT lesions in Indian patients with seizures: A review. Epilepsy Res 2000;38:91-104.
Rajshekhar V, Haran RP, Prakash GS, Chandy MJ. Differentiating solitary small cysticercus granulomas and tuberculomas in patients with epilepsy. Clinical and computerized tomographic criteria. J Neurosurg 1993;78:402-7.
Garg RK, Sinha MK. Multiple ring-enhancing lesions of the brain. J Postgrad Med 2010;56:307-16.
Selvapandian S, Rajshekhar V, Chandy MJ, Idikula J. Predictive value of computed tomography-based diagnosis of intracranial tuberculomas. Neurosurgery 1994;35:845-50.
Lucato LT, Guedes MS, Sato JR, Bacheschi LA, Machado LR, Leite CC. The role of conventional MR imaging sequences in the evaluation of neurocysticercosis: Impact on characterization of the scolex and lesion burden. AJNR Am J Neuroradiol 2007;28:1501-4.
Haaga JR, Dogra VS, Forsting M, Gilkeson Rc, Ha HK, Sundaram M. CT and MRI of the Whole Body. 5 th
ed. Philadelphia: Mosby; 2009.
Ross BD, Colletti P, Lin A. MR spectroscopy of the brain: Neurospectroscopy. In: Edelman RR, Hesselink JR, Zlatkin MB, Crues JV III, editors. Clinical Magnetic Resonance Imaging. 3 rd
ed. Philadelphia: Saunders; 2006. p. 1840-910.
Seth R, Kalra V, Sharma U, Jagannathan N. Magnetic resonance spectroscopy in ring enhancing lesions. Indian Pediatr 2010;47:803-4.
Khanna PC, Godinho S, Patkar DP, Pungavkar SA, Lawande MA. MR spectroscopy-aided differentiation: "Giant" extra-axial tuberculoma masquerading as meningioma. AJNR Am J Neuroradiol 2006;27:1438-40.
Trivedi R, Saksena S, Gupta RK. Magnetic resonance imaging in central nervous system tuberculosis. Indian J Radiol Imaging 2009;19:256-65.
Pretell EJ, Martinot C Jr, Garcia HH, Alvarado M, Bustos JA, Martinot C, et al.
Differential diagnosis between cerebral tuberculosis and neurocysticercosis by magnetic resonance spectroscopy. J Comput Assist Tomogr 2005;29:112-4.
Santy K, Nan P, Chantana Y, Laurent D, Nadal D, Richner B. The diagnosis of brain tuberculoma by (1) H-magnetic resonance spectroscopy. Eur J Pediatr 2011;170:379-87.
Gutch M, Jain N, Agrawal A, Modi A. MR spectroscopy in tuberculoma of brain. BMJ Case Rep 2012;2012.
Pandit S, Lin A, Gahbauer H, Libertin CR, Erdogan B. MR spectroscopy in neurocysticercosis. J Comput Assist Tomogr 2001;25:950-2.
Gupta RK, Vatsal DK, Husain N, Chawla S, Prasad KN, Roy R, et al.
Differentiation of tuberculous from pyogenic brain abscesses with in vivo
proton MR spectroscopy and magnetization transfer MR imaging. AJNR Am J Neuroradiol 2001;22:1503-9.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]
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