[A case of refractory tuberculous meningitis markedly improved by intrathecal administration of isoniazid (INH)]

We report a case of refractory tuberculous meningitis which was markedly improved by intrathecal administration of isoniazid (INH). The patient was a 35-year-old woman diagnosed with systemic lupus erythematosus (SLE) at age 25, who was being managed with steroid therapy. She was admitted to another hospital due to miliary tuberculosis at age 34, and after discharge continued with a regimen of 2 anti-tuberculosis drugs (INH. Rifampicin (RFP)). She was admitted to our hospital with severe headache and fever on June 18, 2001. She showed severe meningeal irritation, and cerebrospinal fluid (CSF) examination revealed cell counts of 207/microliter (72% polynuclear cells), protein level of 300 mg/dl, glucose level of 13 mg/dl, chloride (Cl) level of 104 mEq/l, adenosine deaminase (ADA) level of 10.0 IU/l. The CSF culture was negative for Mycobacterium tuberculosis (M. tuberculosis) and direct polymerase chain reaction (PCR) for M. tuberculosis DNA was negative, but nested PCR was positive in preserved CSF samples. Marked leptomeningeal enhancement at the basilar meninges was noted by cranial MRI on gadolinium (Gd)-DTPA enhanced T1-weighted images. We diagnosed her condition as tuberculous meningitis and administered a total of 5 anti-tuberculosis drugs over about 2 months. However, during this period, both her clinical and CSF findings worsened, and she developed severe consciousness disturbance showing marked hydrocephalus on cranial MRI in August 2001. Therefore, we initiated intrathecal administration of INH 100 mg 3 times a week for progressive tuberculous meningitis. After the initiation of intrathecal therapy, both her consciousness disturbance and CSF findings were improved almost immediately. Ventriculo-peritoneal shunt operation was performed for hydrocephalus on September 26, 2001, and her clinical symptoms were further improved. To our knowledge, this is the first reported case of refractory tuberculous meningitis markedly improved by intrathecal administration of INH. Our findings suggested that intrathecal administration of INH was useful for refractory tuberculous meningitis.