Corticosteroids In The Treatment of Tuberculous Meningitis
Schoeman and colleagues in south Africa randomized 141 consecutive children to receive or not receive prednisone; all also received INH, rifampin, ethionamide, and pyrazinamide. Prednisone was administered to the first 16 patients assigned this treatment in a dose of 2 mg/kg/d; the dose was increased in the remaining 54 patients in this group to 4 mg/kg/d because of concerns about possibly inadequate serum concentration in the face of coadministration of rifampin. The antituberculous drugs were administered for six months and the prednisone for one month.
All patients underwent lumbar CSF pressure monitoring and contrast-enhanced CT scanning prior to randomization and at intervals during treatment. Children (25) with non-communicating hydrocephalus underwent ventriculoperitoneal shunting, while those with communicating hydrocephalus were given azetazolamide and furosemide for one month.
After the first month of treatment, there was no difference in the treatment groups in either ventricular size or intracranial pressure. Approximately one-fifth of patients in each group had basal ganglia infarcts on admission, and new infarcts were seen on CT scanning at one month in 16% of the steroid group and 24% of the nonsteroid group (P = 0.14). No difference in infarct rate was observed at six months either.
Moderate-to-marked basilar enhancement on contrast CT was significantly more common in the non steroid than the steroid group at one month (P = 0.004). Tuberculomas were seen at baseline in 5% of patients, with new tuberculomas evident on CT scan at one month in two patients in the steroid group and nine in the non-steroid group (P = 0.03). Tuberculomas also improved to a significantly greater extent in the steroid group (P = 0.05).
Eight of 17 deaths occurred during the first two weeks of treatment: one in the steroid group and seven in the non-steroid group. Six-month mortality was significantly higher in the nonsteroid than the steroid group among patients with the most severe disease on admission (P = 0.015). Also at six months, the IQ of the steroid group was significantly higher than the non steroid patients (P = 0.038), but there was no significant difference in motor deficits, blindness, or deafness. Approximately one-fourth of patients were hemiplegic, and approximately one-eighth were quadriplegic. Five percent were blind.
COMMENT BY STAN DERESINSKI, MD, FACP
While commonly recommended in the clinical setting, the potential benefit of adjunctive corticosteroid in the management of tuberculous meningitis has not previously been well defined in randomized clinical trials using modern imaging techniques as well as measurement of CSF pressure.
The current study, while being the best of its kind, still has a number of deficits. Varying doses of prednisone were used, and there was no masking or placebo. There are no microbiological data provided and, therefore, no correlation of microbiologic outcome with clinical outcome. In addition, there is no discussion of adverse effects associated with corticosteroid administration. Nonetheless, this study provides enough evidence for me to drop any remaining skepticism about the value of adjunctive corticosteroid therapy in this disease.
It is likely, however, that administration of cortico-steroids for one month is longer than is necessary. It would be useful to have better information on the optimal dose and duration of this treatment.
Another point of clinical value from this study relates to the duration of antituberculous therapy. Assuming that bacteriologic cure without relapse was achieved in these children, it appears that antituberculous therapy need only be administered for six months. This is a shorter duration than recommended by many in the United States, but the rationale for prolonged treatment has always escaped me.
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