Pearls and oy-sters: tuberculous meningitis: not a diagnosis of exclusion.

A 21-year-old man presented to his local emergency department with 5 days of headache, which was dull, occipital, bilateral, nonthrobbing, and progressively worsening. It was associated with mild fever, photophobia, and neck pain and stiffness. He had no history of headache, chronic illness, recent vaccinations, cutaneous rash, cough, diarrhea, arthralgia, or myalgia. He was from Ecuador and had been living in the United States for less than 1 year. He had been incarcerated while in Ecuador. Sublingual temperature on admission was 102.6°F. Other vital signs were within normal limits. On physical examination, he appeared thin but not cachectic. He had meningismus and photophobia, but no papilledema and his mental status was alert and attentive. There were no focal neurologic deficits. CSF contained red blood cells: 24 × 10(3)/μL; white blood cells: 85/μL (lymphocytic predominant); protein: 128 mg/dL; and glucose: 48 mg/dL (CSF/serum glucose ratio = 0.53). CSF Gram stain and cultures, PPD test, and blood and urine cultures were all negative. CT scan of the head on day of admission was entirely normal. MRI without gadolinium contrast showed a single punctate T2 hyperintensity in the left frontal periventricular white matter. Chest radiograph was clear. He received empiric vancomycin, ceftriaxone, and acyclovir. Corticosteroids were not given. The patient did not improve with antibiotics and continued to be intermittently febrile. On day 5, he became abruptly more somnolent, then comatose, opening eyes only to pain, his pupils were 5 mm and reactive, he had intact brainstem reflexes, withdrawing both arms and legs. Emergent head CT showed development of hydrocephalus and a ventriculoperitoneal shunt was emergently placed. The neurologic examination did not improve after shunt placement, and repeat head CT showed increased hydrocephalus with bilateral cerebral infarcts. On day 11, he was transferred to Columbia University Medical Center for intensive care. He was febrile and comatose. He did not open his eyes to pain, pupils were 7 mm minimally reactive, brainstem reflexes were intact, and he exhibited extensor posturing to pain. Mannitol was given, corticosteroid therapy was started, and an extraventricular drain was placed. The next day, his right pupil was 8 mm and nonreactive. MRI showed diffuse contrast enhancement of the arachnoid, extensive infarction of basal ganglia, midbrain, and pons, and small ring-enhancing lesions in the cerebellum (figure 1, A-D). Repeat lumbar puncture showed red blood cells: 550 × 10(3)/μL; white blood cells: 250/μL (14% neutrophils, 80% lymphocytes, 6% monocytes); protein: 65 mg/dL; and glucose: <10 mg/dL (CSF/serum glucose ratio = 0.08). CSF testing for Cryptococcus and toxoplasmosis was negative. CSF acid fast bacilli (AFB) smear was negative ×2, and CSF nucleic acid amplification test was also negative for tuberculosis. Serum HIV test was negative. Not until 14 days after initial presentation and 3 days after transfer to the intensive care unit was antituberculosis therapy finally started, because the pattern of infarcts on the MRI suggested basilar meningitis and he had not improved on broad-spectrum antibiotics. That same day, the first sputum AFB smear was positive, as were all succeeding daily sputum AFB smears. Tuberculosis nucleic acid amplification was positive from the sputum, but persistently negative from the CSF. Daily portable chest radiographs had been normal (read as likely atelectasis), but chest CT showed dense consolidations in the left lung and diffuse micronodular opacities throughout both lungs. Two days later, only 21 days after the onset of his headache, the patient died of cardiopulmonary arrest secondary to transtentorial cerebral herniation. Thirteen days later, the CSF culture became positive for Mycobacterium tuberculosis sensitive to streptomycin, isoniazid, ethambutol, rifampin, and pyrazinamide.