History of Management of Tuberculosis of the Central Nervous System in Children

Understanding of Disease

• 1768 – TB meningitis: Robert Whyth published the first clinical description of TB meningitis in his monogram on ‘Dropsy in the brain’ in children (2).
• 1847 – TB meningitis: Charles Morehead described the autopsy findings in children with TB meningitis. Ford described the tuberculoma (3).
• 1882 – tuberculoma excision: Excision of a tuberculoma was reported by Wernicke and Hahn (4).
• 1882 – Mycobacterium tuberculosis: M. tuberculosis was described on 24 March 1882 by Robert Koch (2).

Robert H.H. Koch, M.D. (1843 –1910):



• 1921 – BCG vaccine: The first genuine success in immunizing humans against tuberculosis was developed from attenuated bovine-strain tuberculosis by Albert Calmette and Camille Guérin in 1906. BCG vaccine was first used on humans in France (1).
• 1943 – antibiotics discovered: Albert Schatz, Elizabeth Bugie, and Selman Waksman isolated Streptomyces griseus, which produces streptomycin, the first antibiotic and first bacterial agent effective against M. tuberculosis (5).
• 1993 – W.H.O. declaration of emergency: The resurgence of TB resulted in the declaration of a global health emergency by the W.H.O. in 1993. Every year, nearly half a million new cases of multidrug-resistant TB are estimated to occur worldwide (6).

Technological Development

• Diagnostic assays: Currently available molecularly based techniques include commercially available nucleic acid amplification (NAA) methods and other polymerase chain reaction (PCR)-based methods, antibody detection, antigen detection, and chemical assays such as adenosine deaminase (ADA) and tuberculostearic acid measurements.
• Vaccines: The TB vaccine pipeline is showing progress, with seven vaccine candidates currently in clinical development including candidates being evaluated in pediatric populations (7).
• Antibiotics for multidrug-resistant TB: At present, the global TB development pipeline has nine candidates, but a key issue is to develop them concomitantly in combination trials to identify the best regimen in the shortest period of time. The challenge is to develop new regimens of investigational drugs with existing TB drugs or drug candidates to avoid developing each drug sequentially and thereby shortening the development timelines that might otherwise spread over decades (8).

Surgical Technique

• Tuberculomas/TB brain abscesses/vertebral TB: During the twentieth century a growing sense of confidence in medical management relegated surgery to a secondary position in the management of CNS TB. Surgery is now used for diagnosis, to manage cases of medical failure, and for certain complications of the disease.
• Early 21st century – minimally invasive options: Stereotactic biopsy (modern frame-based and frameless techniques) and ETV offer minimally invasive options for surgical treatment of CNS TB.
• Management of hydrocephalus: Hydrocephalus, either acute or chronic, may require serial lumbar punctures, EVD, or shunting. The development of modern shunt valves revolutionized the treatment of hydrocephalus.