Brain tuberculomas due to miliary tuberculosis.

Abstract: Brain tuberculomas are a rare complication of tuberculosis arising through hematogenous spread from an extracranial source, most often of pulmonary origin. The clinical course is usually subacute or chronic, lasting weeks or months, and they typically occur in immunocompromised patients. Recognition and prompt diagnosis of this disorder is important because early treatment can prevent patient worsening and lead to clinical improvement. The authors report a 68-year-old diabetic man with headache and cognitive/behavioral changes in whom investigation revealed disseminated brain tuberculomas resulting from miliary tuberculosis. He received antituberculous treatment and had an excellent recovery.

Key Words: brain tuberculomas, magnetic resonance imaging, miliary tuberculosis

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Tuberculosis remains the leading cause of death worldwide due to a single infectious agent, killing approximately two million people each year. Currently, more than one third of the world population is infected with Mycobacterium tuberculosis, and approximately 8 million new cases are reported annually. (1) Intracranial tuberculomas are an unusual manifestation of central nervous system (CNS) tuberculosis. This article reports a case of disseminated brain tuberculomas, and emphasizes the importance of their diagnosis in individuals who are susceptible to be infected with M tuberculosis.

Case Report

A 68-year-old male presented with a 2-month history of headache and mental changes. During the last 3 months he had an intermittent, low-grade fever accompanied by weakness and anorexia. A computed tomographic (CT) scan of the brain performed 1 month before admission was negative. His history was remarkable for diabetes, but there was no cardiac, collagen, or hematologic disease.

At admission, neurologic examination revealed a patient with severe memory and concentration difficulties. His speech was dysarthric. Tendon reflexes were increased with extensor plantar reflexes bilaterally. An intention tremor was present with dysmetria and dysdiadochokinesia, especially on the left. Cranial nerve examination and optic fundi were normal. Neck stiffness and Kerning and Brudzinzki signs were absent. On auscultation, he had crackles in both lung fields. Laboratory investigation revealed a chronic anemia with leukopenia and an elevated erythrocyte sedimentation rate. Chest radiography and CT scan of the chest revealed multiple micronodular lesions in both lungs compatible with miliary tuberculosis (Fig. 1, A and B). Tuberculin skin test was negative. A sputum smear was also negative. However, bronchoalveolar lavage and transbronchial biopsy gave the bacteriologic confirmation of the disease, and tuberculous granulomas were evident in bone marrow biopsy specimens. Magnetic resonance imaging of the brain showed several nodular lesions, with ring enhancement (Fig. 2, A and B). The lesions showed no mass effect or edema. Cerebrospinal fluid (CSF) examination showed mild pleocytosis (32 white cells/[micro]L) with predominantly lymphocytes (90%), protein 74 mg/dL, and glucose 56 mg/dL (blood glucose, 148 mg/dL).

He was started on anti-tuberculous treatment with isoniazid (10 mg/kg per day), rifampicin (10 mg/kg per day), pyrazinamide (35 mg/kg per day), and steroid (dexamethasone, 0.15 mg/kg 4 times daily for 2 weeks, then discontinued in a tapering regimen over 4 weeks). Within 1 week, he started showing signs of recovery. During the following weeks, he continued making steady improvement in his clinical and cognitive neurologic status. The patient remained on the anti-tuberculous treatment for 12 months. (2) At the end of the treatment he had a full recovery, and a repeat MRI of the brain showed complete resolution of brain tuberculomas.

Discussion

Miliary tuberculosis follows blood-borne dissemination of M tuberculosis and may manifest as fever of unknown origin. Many patients who have the disease in developed countries are immunosuppressed. Alcohol, HIV infection, diabetes, underlying malignancies, chronic renal failure and immunosuppressive drugs are risk factors. The chest radiograph of miliary tuberculosis shows well-defined nodules, usually less than 5 mm in diameter throughout both lung fields. CT scanning may also be helpful in the assessment of patients with miliary tuberculosis revealing smaller nodules not seen on radiography. (3)

Although tuberculosis most commonly involves the lungs, it can affect virtually every organ. The most frequent manifestation of CNS tuberculosis is tuberculous meningitis. The spectrum of CNS involvement also includes parenchymal disease (tuberculoma and brain abscess) and spinal cord disease. Brain tuberculomas are uncommon manifestations of tuberculosis and present as one or more parenchymal granulomas that may show nonspecific neurologic symptoms or can cause seizures and focal signs or cognitive and behavioral changes. Tuberculomas are due to hematogenous spread of tubercle bacilli from a distant focus of tuberculous infection, usually the lung. Brain lesions are generally smaller than 2 cm. These small granulomas may be subtle on precontrast images, lacking demonstrable edema or mass effect. CSF analysis in intracranial tuberculomas without meningitis shows a mild lymphocytic pleocytosis with a nonspecific increase in protein content, whereas CSF bacteriology is usually negative. (4) They may coexist with meningitis in 10% of cases. The differential diagnosis of tuberculomas includes neoplasms and other granulomatous processes such as sarcoidosis and parasitic diseases such as cysticercosis and toxoplasmosis. Brain tuberculomas must also be differentiated from tuberculous abscesses. Tuberculous abscesses are usually larger than tuberculomas, and they often have mass effect and edema with an appearance resembling that of a typical pyogenic abscess. They present with fever, headache, and focal neurologic signs. (5) On MRI, which is more specific than the CT scan, brain tuberculomas appear as nodular lesions better demonstrated in contrast-enhanced images. (6)

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Conclusion

Physicians should be alert to cognitive changes in tuberculous population because brain tuberculomas can occur as a relatively silent clinical event. Detection of subtle brain involvement in this disorder is important, since early diagnosis prevents further deterioration after prompt administration of therapy.

[FIGURE 2 OMITTED]

The graveyards are full of indispensable men.
--Charles de Gaulle

Accepted October 4, 2004.

References

1. Ravoglion MC, Snider DE, Kochi A. Global epidemiology of tuberculosis. JAMA 1995;273:220-226.

2. Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med 2001;345:189-200.

3. Kwong JS, Carignan S, Kang E-Y, et al. Miliary tuberculosis: Diagnostic accuracy of chest radiography. Chest 1996;110:339-342.

4. Eide FF, Gean AD, So YT. Clinical and radiographic findings in disseminated tuberculosis of the brain. Neurology 1993;43:1427-1429.

5. Garg RK. Tuberculosis of the central nervous system. Postgrad Med J 1999;75:133-140.

6. Gupta RK, Jena A, Singh AK, et al. Role of magnetic resonance (MR) in the diagnosis and management of intracranial tuberculomas. Clin Radiol 1990;41:120-127.

RELATED ARTICLE: Key Points

* Brain tuberculomas are a rare, insidious complication of tuberculosis and occur as a result of hematogeneous spread from a primary focus, usually the lung.

* Brain tuberculomas usually occur in immunocompromised patients and may appear with nonspecific neurologic symptoms or can cause focal signs and cognitive and behavioral changes.

* Brain tuberculomas are presented as one or more parenchymal granulomas, and magnetic resonance imaging of the brain is highly helpful for their diagnosis and follow-up.

Nikolaos Akritidis, MD, Eftichia Galiatsou, MD, PHD, John Kakadellis, MD, Konstantinos Dimas, MD, and Konstantinos Paparounas, MD, PHD

From the Departments of Internal Medicine, Thoracic Surgery, and Neurology, Hatzikosta General Hospital of Ioannina, Ioannina, Greece.

Reprint requests to Dr. Konstantinos Paparounas, Department of Neurology, Hatzikosta General Hospital of Ioannina, Makrygianni Avenue, 45001 Ioannina, Greece. Email: [e-mail]