Too little, too late: When lack of access makes a rare disease less rare

LEARNING OBJECTIVE #1: To list the clinical and CSF features of tuberculous meningitis LEARNING OBJECTIVE #2: To describe the appropriate treatment regimen for tuberculous meningitis CASE: A 39 year old undocumented male Guatemalan immigrant with history of alcohol abuse presented with nausea, emesis, headache, and lethargy. One week prior to admission he developed headache, which progressively worsened to include nausea and non-bloody, non-bilious emesis. On the day of admission, he became severely lethargic. He denied fevers, cough, diarrhea, or rash. He endorsed weight loss of 30 lb over the preceding 6 months. Vital signs were unremarkable on admission. On exam, the patient was somnolent but arousable to voice. A neurologic exam yielded no focal deficits. Labs were remarkable for leukopenia and anemia. CT of the chest demonstrated calcified granulomas. HIV-1 testing was positive with viral load 328,000 and CD4 count of 2. Antiretroviral therapy was initiated with raltegravir, tenofovir, and emtricitabine. The patient remained somnolent, and subsequently became febrile. He was empirically started on vancomycin, ceftriaxone, ampicillin, and acyclovir. CT scan and MRI of the brain were unremarkable. Lumbar puncture demonstrated normal opening pressure, WBC 311 (8 % N, 78 % L, 14 % mono), RBC 25, glucose 15, protein 447. CSF cultures returned negative and antibiotics were discontinued. Given these CSF findings, the patient was started on rifabutin, isoniazid, pyrazinamide, and levofloxacin as well as prednisone for suspected TB meningitis. However, he developed severe hyponatremia requiring ICU transfer, and quickly progressed to multi-organ failure and death. Autopsy pathology showed necrotizing granulomatous meningitis. DISCUSSION: Tuberculous meningitis must be included in the differential when lumbar puncture results yield a lymphocytic pleiocytosis with low glucose (hypoglycorrhachia) and markedly elevated protein. Our patient displayed all three of these characteristic findings. The disease course consists of three stages: a prodromal phase lasting 2-3 weeks with malaise, headache, and low-grade fever, a meningitic phase with neurologic features including confusion, lethargy, and occasionally focal deficits, and finally, a paralytic phase with coma, seizures, and possible hemiparesis. Diagnosis is made by visualization of acid-fast bacilli in the CSF and/ or by nucleic acid testing (PCR) of CSF. Empiric therapy should not be delayed until the diagnosis has been made. Treatment of TB meningitis differs from that of pulmonary tuberculosis in two main aspects: moxifloxacin or levofloxacin is substituted for ethambutol due to higher CNS penetration, and corticosteroids are added to the antibiotic regimen. Rifabutin was chosen in this case due to interaction of rifampin with raltegravir. The four-drug regimen is continued for 2 months, after which rifampin and isoniazid are continued for an additional 9 to 12 months.