50 Years Ago in The Journal of Pediatrics

Choremis C, Papadatos C, Gargoulas A, and Drosos C. J Pediatr 1957;50:138-44 Tuberculosis remains a global health hazard, with an annual incidence of 8.8 million cases worldwide and 1.8 million deaths. Meningitis is a particularly severe form of tuberculosis, with death and severe neurological deficit being reported in a significant proportion of patients despite treatment. Rupture of a subependymal or parameningeal tubercle into the subarachnoid space initiates a cascade of inflammatory response that leads to complications such as intracranial vasculitis and communicating hydrocephalus. Adjunctive therapies to improve the clinical outcome of tuberculous meningitis have been studied for decades. The anti-inflammatory effect of corticosteroids remains the most biologically plausible way to abort the pathologic sequelae. Choremis et al reported in this journal 50 years ago their experience with the use of intrathecal corticosteroid in treating 82 children with tuberculous meningitis. They compared three different treatment regimens. In the first group of 24 patients, “standard” therapy of intramuscular and intrathecal streptomycin and isoniazid was given. The second group of 29 patients was given, in addition to the standard therapy, cortisone intramuscularly. In the third group of 29 patients, intrathecal streptomycin was replaced by intramuscular and/or intrathecal cortisone, which was given in addition to intrathecal and intramuscular isoniazid and intramuscular streptomycin. The three groups, though not formally controlled, were comparable to each other. Using the patient’s general condition, resolution of electroencephalographic abnormalities, and changes in sugar and protein levels in the cerebral spinal fluid as outcome measures, the authors concluded that patients who received the third treatment regimen had the best clinical improvement, even though no statistical analysis was presented. The authors also pointed out that in two cases allocated to the third treatment regimen, early blockage in the cerebral spinal fluid circulation was relieved by the cisternal infusion of hydrocortisone. The treatment for tuberculous meningitis has changed since the study was published. The use of anti-tuberculous drugs in the intrathecal route is rarely indicated nowadays, and adjunctive dexamethasone given systemically rather than intrathecally has been reported as effective. A recently published prospective, randomized, placebo-controlled trial involving 545 patients over 14 years of age with tuberculous meningitis in two hospitals in Vietnam showed that adjunctive treatment with dexamethasone significantly reduced mortality rates.1Thwaites G.E. Nguyen D.B. Nguyen H.D. et al.Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults.N Engl J Med. 2004; 351: 1741-1751Crossref PubMed Scopus (774) Google Scholar The burden of tuberculosis remains a global challenge, and research work similar to that by Choremis et al and Thwaites et al are essential in guiding us in the right direction.