New face of the old foe: central nervous system tuberculosis.

The Centers for Disease Control reported 14,511 confirmed tuberculosis (TB) cases in the United States for the year 2004, with a rate of 4.9/100,000 representing a 3.3% decline from the previous year. This finding indicates that although the 2004 TB rate was the lowest recorded since 1953, the rate of decline was the smallest since 1993. In the pre-AIDS era, the annual decline of the TB case rate was approximately 7%. In 2004, Hispanics, Blacks and Asians had TB case rates of 7.5, 8.3, and 20.0 times higher than whites respectively. (1) While multidrug-resistant (MDR) TB posed a great challenge in 2002, MDR TB cases represented only 1% of the total cases in 2004. It is a sad reality that TB continues to remain a major health problem worldwide. The World Health Organization estimates 8 million new cases in 2004 with one million deaths from a disease that is both treatable and preventable.

In 2003, 20.4% of all TB cases in the U.S. were extrapulmonary, a proportion that is higher than that noted in the pre-AIDS era. One hundred and fifty-nine of 3,029 (5.2%) cases of extrapulmonary TB had meningeal involvement. The central nervous system (CNS) TB rate was higher in children and the elderly, thus affecting the two extremes of the human life span. In this issue of the Journal, Blaivas (2) reports a case of CNS TB with two sequelae despite appropriate anti-TB therapy. The patient was a 22-year-old Hispanic male with a negative HIV test. They raise an appropriate question: Why did this patient develop complications, in spite of the adequate therapy?

Farinha (3) reported a 20-year survey from a British pediatric tertiary center. Out of 38 children with CNS TB, five patients developed tuberculoma during treatment. Neurosurgical procedures were required in 76% of the cases. Appropriate anti-TB therapy and steroids did not prevent tuberculoma formation. Titone (of Palermo, Italy) (4) identified 80 patients with CNS TB over a 32-year period. Thirty-two percent of the total cases had permanent sequela and 15 subjects (19%) died.

Earlier treatment reduces the chance of complications. Clinical staging based on neurologic findings may help in predicting the prognosis. In stage I, patients are fully conscious and, except for meningismus, have a normal neurologic examination. In stage II, patients have confusion and a focal neurologic abnormality. Stage III patients are comatose or delirious. Neurologic examination is likely to show hemiplegia. Most patients in stage I recover without complications. Stage II and III patients have high mortality and morbidity in spite of adequate therapy. Sequelae of CNS TB include tuberculoma, brain abscess, hydrocephalus, syringomyelia, radiculomyelitis, and encephalopathy. MRI seems to be more sensitive than CT in detecting tuberculoma. In recent studies, tuberculoma is a prominent manifestation of neurotuberculosis in AIDS patients with a worldwide range of 37 to 80% of all CNS TB cases. Clearly, adequate chemotherapy does not guarantee freedom from complications.

These and many such studies indicate that complications are common in CNS TB, in spite of appropriate medical treatment. The "take home messages" can be summarized as follows:

Immune status of the host and virulence of the mycobacterium are important in determining the outcome.

* Age of the patient is also important. Younger children have higher morbidity and mortality.

* In addition to anti-TB drug therapy, corticosteroids are beneficial to those in stages II and III. Some patients require surgical intervention.

* Diagnosis is difficult because cerebrospinal fluid findings are nonspecific, and acid-fast bacillus smears are frequently negative.

* Stage of the disease at the time of diagnosis or at the beginning of therapy plays a very important role in influencing the outcome.

TB is an ancient disease. The tuberculosis case rate is declining in the US, but TB continues to remain a public health problem, both in the US and the world at large. Atypical presentation and complications are rapidly changing the clinical picture of tuberculosis. HIV infection and emergence of drug resistance adds to this complexity. Our old foe now has many atypical presentations, perhaps like a new mask on the old face. As the disease becomes rare and clinicians lose their skill in recognizing it, there is a risk of delay in diagnosis. Routine cerebrospinal fluid examination is frequently useful but nonspecific. Potential benefits of newer tests like tuberculous antigens by ELISA, latex agglutination, radioimmunoassay, and polymerase chain reaction, are reported in several case studies, however, their true sensitivity and specificity remain to be established. (6) Unless there is a drastic improvement in the diagnostic technology, CNS TB will continue to have a high morbidity and mortality. A high threshold of suspicion, early diagnosis, and prompt treatment are absolutely essential to success.

References

1. CDC. Reported Tuberculosis in the United States, 2003. Atlanta, GA: U.S. Department of Health and Human Services, CDC, September 2004.

2. Blaivas AJ, Lardizabal A, McDonald RJ. Two unusual sequelae of tuberculous meningitis despite treatment. South Med J 2005;98:1027-1029.

3. Farinha NJ, Razali KA, Holzel H, et al. Tuberculosis of the central nervous system in children: a 20-year survey. J Infect 2000;41:61-68.

4. Titone L, Di Carlo P, Romano A, et al. Tuberculosis of the central nervous system in children: 32 years survey. Minerva Pediatr. 2004;56:611-617.

5. Rossman MD, MacGregor RR. Tuberculosis: clinical management and new challenges. In: Norris AH, Buckley RM, eds: Central Nervous System Tuberculosis. New York, McGraw-Hill, 1995, pp 157-171.

6. Berenguer J, Moreno S, Laguna F, et al. Tuberculous meningitis in patients infected with the human immunodeficiency virus. N Engl J Med 1992;326:668.

Jay B. Mehta, MD, FCCP

From the Department of Internal Medicine, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN.

Reprint requests to Jay B. Mehta, MD, FCCP, East Tennessee State University, Department of Internal Medicine, James H. Quillen College of Medicine, Box 70622, Bldg. 1, Dogwood Avenue, Johnson City, TN 37614-1709. Email: [e-mail]

Accepted June 28, 2005.