Tuberculosis of the CNS

Joseph R Berger MD (

Dr. Berger of the Perelman School of Medicine, University of Pennsylvania, received honorariums from Amgen, Biogen, Celegene, Encycle, ExcisionBio, Genentech/Roche, Inhibikase, Merck/Serono, Millennium/Takeda, Novartis, Sanofi/Genzyme, and Shire for his role as a consultant.

John E Greenlee MD, editor. (Dr. Greenlee of the University of Utah School of Medicine has no relevant financial relationships to disclose.)
Originally released December 18, 1995; last updated November 6, 2020; expires November 6, 2023


The frightening appearance of multidrug resistant tuberculosis has focused new attention on this ancient human scourge. Although tuberculosis remains a common infectious disorder in the underdeveloped and developing world, immigration has resulted in an increased frequency in developed countries. The author describes the large number of neurologic complications, particularly tuberculous meningitis, that occur with this microorganism. In developed countries, tuberculous infection is often unsuspected and a high level of suspicion is required to establish the diagnosis. Cultures of CSF are time consuming and, therefore, of little diagnostic value at the time of presentation. However, polymerase chain reaction for M tuberculosis is now widely employed to assist in early diagnosis. Corticosteroid therapy, although controversial, is increasingly employed as an adjunctive therapy to decrease the complications that attend tuberculous meningitis.

Key points


• Although relatively rare in the developed world, neurologic disease resulting from tuberculosis remains a common problem in the developing world.


• Meningitis is the most common neurologic complication and is often associated with cranial nerve palsies.


• Cultures for M tuberculosis are time consuming and frequently negative; CSF PCR has become a routine method for diagnosing tuberculous meningitis with sensitivities equal to or exceeding 90%.


• Treatment has been complicated by the increasing emergence of multidrug-resistant forms of the organism.

Historical note and terminology

Tuberculosis is the world's leading cause of death from a single infectious agent; neurologic complications of tuberculosis are not uncommon. Tuberculous meningitis remains a serious health threat in both developing and developed countries. Tuberculous meningitis is hardly a new health problem. The first descriptions of this disorder are often said to be those of Robert Whytt in his report in 1768 of hydrocephalus in children with a febrile illness. However, polymerase chain reaction technology has demonstrated Mycobacterium tuberculosis in human mummies predating the writings of Hippocrates, Galen, and other early physicians who described the illness (MacGregor 1993). Despite these and other early characterizations, the unequivocal association between tuberculosis and meningitis occurred with the discovery of the tubercle bacillus by Koch in 1882. Over 50 years later, in 1946, streptomycin was introduced as a treatment for tuberculosis, and was demonstrated to be effective for pulmonary and meningeal disease. Shortly afterwards, isoniazid and pyrazinamide were introduced. Although in 1900 the annual mortality rate in the United States was 200 per 100,000 individuals, by the initial years of the antibiotic era in 1953, that rate had fallen to 12.4 per 100,000 (MacGregor 1993). Still widely prevalent in some countries, tuberculosis appeared close to being defeated by sanitation and chemotherapy in the second half of the 20th century, especially in developed countries. With the epidemic of the human immunodeficiency virus, however, a second epidemic of tuberculosis emerged worldwide. In the era of AIDS, not only has the evolution of multidrug-resistant strains of M tuberculosis become a problem of increasing concern, but there has also been an increasing recognition of central nervous system disease due to mycobacteria other than M tuberculosis.

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