Pearls and Oy-sters: Tuberculous meningitis Not a diagnosis of exclusion

From the Department of Neurology (A.C.J.) and Department of Pathology and Laboratory Medicine (D.P.), New York Presbyterian Hospital, Columbia University College of Physicians and Surgeons, New York, NY.
Neurology (Impact Factor: 8.29). 01/2013; 80(4):e36-9. DOI: 10.1212/WNL.0b013e31827f0832
Source: PubMed


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.

Full-text preview

Available from:
  • Source
    • "However, many patients are diagnosed late because initial signs are aspecific, and rapid and sensitive diagnostic tests are lacking. Many patients are initially treated empirically with broad-spectrum antibiotics until clinical deterioration warrants adjustment of the differential diagnosis (9). In low-resource settings, limited access to health care, limited diagnostic capacity, and economic constraints frustrate early treatment initiation. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Tuberculous meningitis is the most severe form of tuberculosis. Microbiological confirmation is rare and treatment is often delayed, increasing mortality and morbidity. The Xpert MTB/RIF test was evaluated in a large cohort of patients with suspected tuberculous meningitis.379 patients presenting with suspected tuberculous meningitis to the Hospital for Tropical Diseases, Ho Chi Minh City, between 17 April 2011 and 31 December 2012 were included in the study. Cerebrospinal fluid samples were tested by Ziehl-Neelsen smear, MGIT culture and Xpert MTB/RIF. Rifampicin resistance results by Xpert were confirmed by MTBDR-Plus line probe assay and all positive cultures were tested by phenotypic MGIT drug susceptibility testing.Overall, 182/379 included patients (48.0%) were diagnosed with tuberculous meningitis. Sensitivities of Xpert, smear and MGIT culture among patients diagnosed with TBM were 59.3% (n=108/182 [95% CI 51.8; 66.5%]), 78.6% (n=143/182 [95% CI 71.9; 84.3%]) and 66.5% (n=121/182, [95% CI 59.1; 73.3%]), respectively. There was one false positive Xpert MTB/RIF test (99.5% specificity). Four cases of RIF resistance (n=4/109, 3.7%) were identified by Xpert of which 3 were confirmed to be Multi-drug resistant (MDR) TBM and one was culture negative.Xpert MTB/RIF is a rapid and specific test for the diagnosis of tuberculous meningitis.Addition of a vortex step to sample processing increased sensitivity for confirmed TBM by 20% (P=0.04) Meticulous examination of a smear from a large volume of CSF remains the most sensitive technique but is not practical in most laboratories. The Xpert MTB/RIF represents a significant advance in the early diagnosis of this devastating condition.
    Full-text · Article · Nov 2013 · Journal of clinical microbiology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Acute bacterial meningitis (ABM) is a life-threatening infectious disease requiring prompt antimicrobial therapy. ABM must be differentiated from systemic disorders with CNS manifestations that may mimic ABM. ABM should also be differentiated from acute meningoencephalitis (AME) and acute viral encephalitis (AVE). Nonviral causes of AME are treatable. Among the causes of AVE, Herpes simplex encephalitis (HSE) is treatable. This article reviews the clinical diagnostic approach to ABM, AME and AVE. Areas covered: The differential diagnostic (DDx) approach to ABM, AME and AVE is based on clinical and laboratory findings. A specific pathogen diagnosis is based on serum/cerebrospinal fluid (CSF) tests. This overview presents the diagnostic approach to ABM, AME and AVE in normal hosts (excluding brain abscesses and chronic CNS infections). Expert opinion: It is time critical to diagnose ABM and begin empiric antimicrobial therapy based on the known/most likely pathogen. The diagnosis of ABM depends on clinical features and the CSF profile. The CSF Gram stain and CSF lactic acid (LA) levels provide the most rapid, reliable and cost-effective tests to diagnose ABM. CSF LA levels are also the best way to diagnose partially treated acute bacterial meningitis (PTABM). In those cases of AME/AVE due to viruses with a CSF profile mimicking ABM, for example, HSE, unelevated CSF LA levels rapidly/reliably rule out ABM as a diagnostic possibility.
    No preview · Article · May 2013 · Expert Opinion on Medical Diagnostics
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic lymphocytic meningoencephalitis with low glucose and increased adenosine deaminase (ADA) levels in the CSF together with hydrocephalus represents a diagnostic challenge of varied etiology and only seldom is due to a viral (mumps) infection.
    Full-text · Article · Feb 2014 · Neurology
Show more