Ts 0148-396 /90/2703-0418$02.00/0 NEUROSURGERY Copyright ¢ 1990 by the Congress of Neurological Surgeons Vol. 27. No. 3. 1990 Printed in U.S.A. Whither Short-Course Chemotherapy for Tuberculous Meningitis? Atul Goel, M.Ch., Sunil K. Pandya, M.S., and Abhay R. Satoskar, M.B.B.S. Departments of Neurosurgery (AG, SKP) and Pathology (ARS), Seth GS Medical College and KEM Hospital, Parel, Bombay 400 012, India Short-course chemotherapy is well established for the treatment of pulmonary tuberculosis but not for extrapulmonary disease. We present a series of 35 cases in which chemotherapy for tuberculous meningitis was given for a period of less than 2 years. Short-term therapy was associated with recrudescence of tuberculous meningitis and. in some cases. with the development of deep cerebral infarcts and permanent neurological deficits. We think short-term chemotherapy for tuberculosis of the central nervous system is inadequate. (Neurosurgery 27:418-421, 1990) Key words: Chemotherapy, Tuberculoma, Tuberculous meningitis INTRODUCTION Meningitis is a dreaded complication of tuberculosis. It is a devastating illness in terms of mortality and morbidity and has a wide range of permanent neurological sequelae. To minimize a bad outcome, treatment should be timely, vigor- ous, and complete. With the introduction of streptomycin in the 1940s and isoniazid in the 1950s and the recent addition of other drugs, we have sufficient means to eradicate the tubercle bacillus. Although many specific antituberculous drugs are now avail- able, the main drawback to adequate and effective drug therapy is the length of treatment that is required. Rifampicin and isoniazid have been used successfully against pulmonary tuberculosis in short-course chemotherapy. Although various combinations of drugs have been effective in short-course chemotherapy for pulmonary tuberculosis, no definite data are available with regard to efficacy against tuberculous men- ingitis. We report a series of 35 patients who had recurrence of tuberculosis in the brain and had discontinued treatment before the end of the recommended period of 2 years. METHODS We analyzed 1056 cases of tuberculosis of the brain and meninges seen by us at a general hospital between 1980 and 1987. These patients belonged to the low- or middle-socioeco- nomic group and were referred for consideration of neurosur- gical therapy. They represented 5.73% of the total number of cases that were seen in the neurosurgery outpatient depart- ment. Of the 1056 patients, 781 patients were diagnosed as having tuberculous meningitis, and 275 had tuberculomas at various sites. In all patients, examination of the cerebrospinal fluid (CSF) showed lymphocytic meningitis with raised pro- tein levels and low glucose levels. Of the 781 patients with tuberculous meningitis, 280 patients had hydrocephalus with evidence of raised intracranial pressure and underwent surgery to shunt the CSF: the remainder of the patients were treated conservatively. All patients were advised to maintain antitu- berculous therapy for 2 years according to the treatment schedule shown in Table |. Of the drugs utilized, streptomycin. rifampicin. isonicotinic acid hydrazide (INH). and pyrazinamide are bactericidal. whereas ethambutol is bacteriostatic. Fifty-seven patients with tuberculous meningitis expired during their hospital stay. After discharge from the hospital. patients were followed up regularly, initially every 15 days for the first 2 months, then every 3 months for the next 6 months, and finally every 6 months until the completion of therapy (2 years). Thereafter, they were followed up for 18 to 20 months. During each follow-up visit, they were examined clinically in detail and checked for any evidence of recurrence. Of the 724 patients with tuberculous meningitis discharged from the hospital, 236 were available for the regular follow-up mentioned above and were cured at the end of 2 years of therapy. Thirty-seven patients stopped antituberculous treatment prematurely against advice. Of these, 35 patients were readmitted with recurrent tuberculous meningitis. Of the two who stopped drug treatment early but had no recurrence, one had been treated for 8 months and the other for 10 months. The remainder of the patients (451) were not available for follow- up after discharge from the hospital. The 35 patients who were readmitted for recurrence were analyzed in detail. Analysis of cases Table 2 shows the age of patients who received complete antituberculous drug therapy for 2 years (Group A) and those who were readmitted for recurrence after inadequate treat- ment (Group B). Most of the patients in both groups were below 5 years of age. In Group A, there were 148 (62.7%) males and 88 (37.2%) females, whereas 20 (57.1%) of 35 patients with recurrence (Group B) were males. The duration of symptoms in both groups ranged from 5 to 8 days. The treatment was started immediately. The severity of the initial illness on admission was graded using the criteria described by Gordon and Parsons (6). Accordingly, of the group that received complete chemotherapy for 2 years (Group A). 19.5% were Grade 1, 61% were Grade 2, and 19.5% were Grade 3: of those that had inadequate treatment (Group B). 20% were Grade |, 62.8% were Grade 2, and 17.1% were Grade 3. Ninety-four (39.8%) of 236 (Group A) and 14 (40%) of 35 patients (Group B) underwent shunt surgery. Table 3 shows the duration from the date of discharge until readmission for recurrence in 35 patients. Twenty-seven pa- tients had to be readmitted for treatment of recurrent tuber- culosis of the brain within 2 years of discharge from the hospital. whereas 6 patients sought treatment for recurrence 3 years or more after discharge from the hospital. This is in contrast to the 236 patients who received the full course of treatment and in which not a single case recurred. Table 4 gives the duration of treatment received by the 35 September 1990 TABLE | Schedule of Treatment for Tuberculous Meningitis and Tuberculoma Medication’ Dosage Streptomycin (injection) 1 g/d (appropriate dose for children) x 90 20 mg/kg/d for 3 mo 10 mg/kg/d for 9 mo 5 mg/kg/d for 2 yr 15 mg/kg/d for 2 yr 10-40 mg/d * First 3 months: streptomycin, pyrizinamide, rifampicin + isoni- azid; next 6 months: rifampicin, isoniazid + ethambutol; next 15 months: isoniazid + ethambutol. INH, isoniazid. Pyrizinamide (tablet) Rifampicin (capsule) INH? (tablet) Ethambutol (tablet) Pyridoxine (tablet) TABLE 2 Age Distribution of the Patients 7 Group ae Group B: Patients i a Age Group ‘Comeletn Patients with (yr) P 8 Inadequate 2 Years of Therapy (%) Therapy (%) PY “ s5 145 (61.5) 18 (51.4) 6-10 28 (11.8) 4 (11.4) 11-15 13 (5.5) 3 (8.6) 16-20 11 (4.6) 2 (5.7) 21-25 14 (5.9) 1 (2.8) 26-30 7 (2.9) 2 (5.7) 231 18 (7.6) 5 (14.3) Total 236 35 TABLE 3 Duration from the Date of Discharge until Readmission for Recurrence in 35 Patients Receiving Inadequate Therapy Duration (yr) Number of Patients CHEMOTHERAPY FOR TUBERCULOUS MENINGITIS 419 patients who were readmitted for recurrent central nervous system tuberculosis. Twenty-eight had received treatment for a period of less than | year. whereas 7 patients had recurrence between | and 2 years after cessation of treatment. Illiteracy and poverty were the main reasons for discontinuation of drugs. Table 5 gives the main signs and symptoms in the 35 patients who had recurrence. The recrudescence of tubercu- lous meningitis in general was more severe with greater mor- bidity and mortality. The main presenting symptoms were headache, vomiting, convulsions, fever. and worsening sen- sorium. Ten patients were critically ill, Five patients had bilateral decerebration, 10 patients had hemiparesis, and 10 patients had optic atrophy. Eight patients were diagnosed as having tuberculomas, and the rest had tuberculous meningitis with different degrees of hydrocephalus diagnosed on the basis of computed tomography (CT), angiography, and ventricu- lography. Nine patients with evidence of raised intracranial pressure underwent CSF diversion with shunts and 2 under- went surgery for tuberculoma. All these cases were again put on the antituberculous drug schedule as in Table 1. Thirteen of the 35 patients (37.1%) expired during their hospital stay. The remainder had different degrees of recovery. Illustrative case reports Case 1. In July 1983, this boy was found to have tubercu- lous complex in the chest and was treated with streptomycin, isoniazid, and rifampicin. In September, streptomycin was omitted and ethambutol was started; the other drugs were continued. In November 1983, despite continued therapy, he developed tuberculous meningitis, which resolved with treat- ment. After 18 months of uninterrupted antituberculous chemotherapy, the child was well. In January 1985, on the pediatrician’s advice, antituberculous drug therapy was stopped. He was readmitted to the hospital 2 weeks later, when lumbar CSF showed recurrent tuberculous meningitis. A CT scan revealed enhancing exudates in the basal cisterns and sylvian fissures. The ventricles were distended and there were periventricular lucencies. Resumption of antitubercu- lous treatment and insertion of a ventricular atrial shunt resulted in slow recovery.