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The treatment of tuberculous meningitis consists of the administration of a combination of drugs isoniazid (INH), rifampin (RMP), and a third and sometimes a fourth drug, which may be ethambutal (EMB), ethionamide (ETA), or preferably pyrazinamide (PZA) All of these drugs have the capacity to penetrate the blood-brain barrier, with INH, ETA, and PZA ranked higher than the others in this respect Resistant strains of tuberculous organisms are emerging, which require the use of PZA and ETA in addition to the two main drugs (INH and RMP) It has been pointed out that immigrants from certain countries (eg, Vietnam, Haiti, Philippines) have high rates of INH-resistant organisms Antibiotics must be given for a prolonged period, 18 to 24 months as a general rule (although it may not be necessary to give all three or four drugs for the entire period) Isoniazid is the single most effective drug It can be given in a single daily dose of 5 mg/kg in adults and 10 mg/kg in children Its most important adverse effects are neuropathy (see page 1133) and hepatitis, particularly in alcoholics Neuropathy can be prevented by the administration of 50 mg pyridoxine daily In patients who develop the symptoms of hepatitis or have abnormal liver function tests, INH should be discontinued The usual dose of RMP is 600 mg daily for adults, 15 mg/kg for children Ethambutal is given in a single daily dose of 15 mg/kg The dosage of ETA is 15 to 25 mg/kg daily for adults; because of its tendency to produce gastric irritation, it is given in divided doses, after meals The latter two drugs (EMB and ETA) may cause optic neuropathy, so that patients taking them should have regular examinations of visual acuity and red-green color discrimination Pyrazinamide is given once daily in doses of 20 to 35 mg/kg Rash, gastrointestinal disturbances, and hepatitis are the main adverse effects Except for INH, all these drugs can be given only orally or by stomach tube Isoniazid may be given parenterally, in the same dosage as with oral use Corticosteroids may be used in patients whose lives are threatened by the effects of subarachnoid block or raised intracranial pressure, and only in conjunction with antituberculous drugs It should be noted that in a randomized study conducted in Vietnam, including patients with and without AIDS, the addition of intravenous dexamethasone (04 mg/kg daily for a week and then tapering doses for 3 weeks) reduced mortality from 41 percent to 32 percent but had no effect on residual disability (Thwaites et al) Intracranial tuberculoma calls for a similar course of antibiotics, as outlined above Under the in uence of these drugs, the tuberculoma(s) may decrease in size and small ones ultimately disappear or calcify, as judged by the CT scan; if they do not, and especially if there is mass effect, excision may be necessary Patients with spinal osteomyelitis or localized granulomas with spinal cord compression (Pott paraplegia) should also be explored surgically after an initial course of chemotherapy, and an attempt should be made to excise the tuberculous focus We have, however, dealt successfully with tuberculous osteomyelitis of the cervical spine (without significant abscess or cord compression) by immobilizing our patient in a hard collar and administering triple-drug therapy (at the suggestion of the patient s father, who was a physician in India), once it was established that the spinal column was stable.

The overall mortality of patients with CNS tuberculosis is still signi cant (about 10 percent), infants and the elderly being at greatest risk Among HIV-infected patients, the mortality from tuberculous meningitis is considerably higher (21 percent in the series of Berenguer et al) the result of delays in diagnosis and, more importantly, of resistance to antituberculous drugs in some patients (Snider and Roper) (see also page 1061) Early diagnosis, as one might expect, enhances the chances of survival In patients who are treated late in the disease, when coma has supervened, the mortality rate is nearly 50 percent Between 20 and 30 percent of survivors manifest a variety of residual neurologic sequelae, the most important of which are diminished intellectual function, psychiatric disturbances, recurrent seizures, visual and oculomotor disorders, deafness, and hemiparesis A detailed account of these has been given by Wasz-Hockert and Donner

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