ILLUSTRATIVE CASE
Tuberculosis Meningitis
AUTHOR Kelly Wood, MD, FAAP Division of General Pediatrics and Adolescent Medicine, University of Iowa Children’s Hospital, Iowa City, Iowa KEY WORDS meningitis, infectious diseases, clinical, altered mental status, neurology www.hospitalpediatrics.org doi:10.1542/hpeds.2011-0013 Address correspondence to Kelly Wood, MD, Division of General Pediatrics and Adolescent Medicine, University of Iowa Children’s Hospital, 200 Hawkins Dr, Iowa City, IA 52242. E-mail: [email protected] HOSPITAL PEDIATRICS (ISSN Numbers: Print, 0031 - 4005; Online, 1098 - 4275). Copyright © 2012 by the American Academy of Pediatrics
Introduction: Aseptic meningitis has multiple etiologies with viral infection being the most common. Hospitalists should recognize atypical features suggestive of an alternative etiology. This case and literature review will focus on an atypical cause. Case: A 6-year-old previously healthy, fully immunized Hispanic American boy was admitted to the hospital during spring with a 2-week history of headache, vomiting, and fever. He was born in the United States and had never traveled. No one in his home was ill, but a classmate had viral meningitis. One week into his illness, he was evaluated at an outside emergency department. The results of a noncontrasted cranial computed tomography scan, comprehensive metabolic panel, complete blood count, and C-reactive protein were normal. Lumbar puncture and cerebrospinal fluid (CSF) analysis were significant for lymphocytic pleocytosis with 376 white blood cells, low glucose, elevated protein, negative enterovirus and herpes simplex virus polymerase chain reaction, and subjective increased opening pressure. He was admitted to the outside hospital, treated with empirical parenteral antibiotics until CSF bacterial culture results were negative, and discharged from the hospital with a diagnosis of viral meningitis. After discharge, his symptoms progressed with the development of diplopia from a new right sixth cranial nerve palsy. He was admitted to a pediatric children’s hospital after reevaluation in the emergency department with a normal findings on noncontrasted cranial computed tomography scan, laboratory tests, and analogous CSF analysis. His diagnosis at admission was viral meningitis. Question: The patient has aseptic meningitis, but is his clinical course most consistent with a viral etiology or are his progressive symptoms with new cranial nerve palsy suggestive of an alternative, less common cause? Discussion: Aseptic meningitis includes all causes of meningitis with negative results from bacterial CSF cultures. Viral infection, notably enteroviruses with late summer and fall seasonal outbreaks, is the most common cause.1,2 Symptom progression, seizures, neurologic deficits, and obtundation are rare other than in certain nonviral infectious causes.1 No single component of the CSF fluid analysis accurately discriminates between bacterial and viral meningitis.3 Hypoglycorrhachia, low CSF glucose, supports a bacterial etiology.2 An elevated serum procalcitonin level (>0.5 ng/mL) is most predictive of distinguishing between bacterial and viral etiologies, but is not universally available.4,5 Lymphocytic meningitis is seen
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with infectious and noninfectious processes. Infectious etiologies include viruses, Mycobacterium, spirochetes, rickettsia, and fungi as well as less common bacteria such as Listeria. Noninfectious etiologies include autoimmune diseases, malignancies, and medication side-effects.6 The progression and duration of symptoms, cranial nerve sixth palsy, nonenteroviral season presentation, and CSF analysis with lymphocytes, and low glucose and elevated protein concentrations suggested an alternative infectious etiology. Case Continuation: Upon admission, specific questioning disclosed an aunt who had a chronic cough of unknown etiology. Tuberculosis (TB) meningitis was suspected, and empirical therapy with isoniazid, rifampin, pyrazinamide, ethambutol, and prednisone was initiated. He underwent repeat lumbar puncture with a documented elevated opening pressure of 350 mm H2O (normal, 50–200 mm H2O) and a large-volume CSF collection of 20 mL (normal collection volume, 3–4 mL). A brain MRI with gadolinium contrast revealed basal enhancement supporting the diagnosis of Mycobacterium tuberculosis meningitis. The results of the tuberculin skin test (TST) were negative. The findings of the serum QuantiFERON-TB Gold test and CSF M tuberculosis polymerase chain reaction were positive. CSF acidfast bacilli culture grew pansensitive M tuberculosis after 4 weeks of incubation. Chest radiographic findings were unremarkable. The results of HIV testing were negative. His aunt who had multiple negative TST results before the patient’s presentation, but never had her sputum cultured, was identified as the index case. All immediate family members had latent tuberculosis infection. The patient successfully 112 |
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completed 12 months of treatment with no residual deficits. Discussion: Tuberculosis infection is caused by the acid-fast bacillus M tuberculosis. Clinical manifestations of M tuberculosis infection are dependent on the host’s immune response primarily mediated by T lymphocytes and macrophages ranging from asymptomatic infection to active disease. Latent TB infection (LTBI) is described by a positive TST without clinical symptoms, physical examination findings, or radiographic changes. Five to ten percent of cases of untreated LTBI progress to disease.7 TB disease is characterized by clinical or radiographic manifestations with or without a positive
TST. Pulmonary disease is most common, but hematogenous dissemination may occur to almost any site. Risk factors for developing TB disease (especially extrapulmonary disease) include immunocompromised conditions, untreated HIV infection, recent LTBI, malnutrition, and age
Tuberculosis Meningitis
AUTHOR Kelly Wood, MD, FAAP Division of General Pediatrics and Adolescent Medicine, University of Iowa Children’s Hospital, Iowa City, Iowa KEY WORDS meningitis, infectious diseases, clinical, altered mental status, neurology www.hospitalpediatrics.org doi:10.1542/hpeds.2011-0013 Address correspondence to Kelly Wood, MD, Division of General Pediatrics and Adolescent Medicine, University of Iowa Children’s Hospital, 200 Hawkins Dr, Iowa City, IA 52242. E-mail: [email protected] HOSPITAL PEDIATRICS (ISSN Numbers: Print, 0031 - 4005; Online, 1098 - 4275). Copyright © 2012 by the American Academy of Pediatrics
Introduction: Aseptic meningitis has multiple etiologies with viral infection being the most common. Hospitalists should recognize atypical features suggestive of an alternative etiology. This case and literature review will focus on an atypical cause. Case: A 6-year-old previously healthy, fully immunized Hispanic American boy was admitted to the hospital during spring with a 2-week history of headache, vomiting, and fever. He was born in the United States and had never traveled. No one in his home was ill, but a classmate had viral meningitis. One week into his illness, he was evaluated at an outside emergency department. The results of a noncontrasted cranial computed tomography scan, comprehensive metabolic panel, complete blood count, and C-reactive protein were normal. Lumbar puncture and cerebrospinal fluid (CSF) analysis were significant for lymphocytic pleocytosis with 376 white blood cells, low glucose, elevated protein, negative enterovirus and herpes simplex virus polymerase chain reaction, and subjective increased opening pressure. He was admitted to the outside hospital, treated with empirical parenteral antibiotics until CSF bacterial culture results were negative, and discharged from the hospital with a diagnosis of viral meningitis. After discharge, his symptoms progressed with the development of diplopia from a new right sixth cranial nerve palsy. He was admitted to a pediatric children’s hospital after reevaluation in the emergency department with a normal findings on noncontrasted cranial computed tomography scan, laboratory tests, and analogous CSF analysis. His diagnosis at admission was viral meningitis. Question: The patient has aseptic meningitis, but is his clinical course most consistent with a viral etiology or are his progressive symptoms with new cranial nerve palsy suggestive of an alternative, less common cause? Discussion: Aseptic meningitis includes all causes of meningitis with negative results from bacterial CSF cultures. Viral infection, notably enteroviruses with late summer and fall seasonal outbreaks, is the most common cause.1,2 Symptom progression, seizures, neurologic deficits, and obtundation are rare other than in certain nonviral infectious causes.1 No single component of the CSF fluid analysis accurately discriminates between bacterial and viral meningitis.3 Hypoglycorrhachia, low CSF glucose, supports a bacterial etiology.2 An elevated serum procalcitonin level (>0.5 ng/mL) is most predictive of distinguishing between bacterial and viral etiologies, but is not universally available.4,5 Lymphocytic meningitis is seen
Downloaded from http://hosppeds.aappublications.org/ by guest on March 30, 2015
| 111
HOSPITAL Pediatrics ®
AN OFFICIAL JOURNAL OF THE AMERICAN ACADEMY OF PEDIATRICS
with infectious and noninfectious processes. Infectious etiologies include viruses, Mycobacterium, spirochetes, rickettsia, and fungi as well as less common bacteria such as Listeria. Noninfectious etiologies include autoimmune diseases, malignancies, and medication side-effects.6 The progression and duration of symptoms, cranial nerve sixth palsy, nonenteroviral season presentation, and CSF analysis with lymphocytes, and low glucose and elevated protein concentrations suggested an alternative infectious etiology. Case Continuation: Upon admission, specific questioning disclosed an aunt who had a chronic cough of unknown etiology. Tuberculosis (TB) meningitis was suspected, and empirical therapy with isoniazid, rifampin, pyrazinamide, ethambutol, and prednisone was initiated. He underwent repeat lumbar puncture with a documented elevated opening pressure of 350 mm H2O (normal, 50–200 mm H2O) and a large-volume CSF collection of 20 mL (normal collection volume, 3–4 mL). A brain MRI with gadolinium contrast revealed basal enhancement supporting the diagnosis of Mycobacterium tuberculosis meningitis. The results of the tuberculin skin test (TST) were negative. The findings of the serum QuantiFERON-TB Gold test and CSF M tuberculosis polymerase chain reaction were positive. CSF acidfast bacilli culture grew pansensitive M tuberculosis after 4 weeks of incubation. Chest radiographic findings were unremarkable. The results of HIV testing were negative. His aunt who had multiple negative TST results before the patient’s presentation, but never had her sputum cultured, was identified as the index case. All immediate family members had latent tuberculosis infection. The patient successfully 112 |
VOLUME 2 • ISSUE 2
completed 12 months of treatment with no residual deficits. Discussion: Tuberculosis infection is caused by the acid-fast bacillus M tuberculosis. Clinical manifestations of M tuberculosis infection are dependent on the host’s immune response primarily mediated by T lymphocytes and macrophages ranging from asymptomatic infection to active disease. Latent TB infection (LTBI) is described by a positive TST without clinical symptoms, physical examination findings, or radiographic changes. Five to ten percent of cases of untreated LTBI progress to disease.7 TB disease is characterized by clinical or radiographic manifestations with or without a positive
TST. Pulmonary disease is most common, but hematogenous dissemination may occur to almost any site. Risk factors for developing TB disease (especially extrapulmonary disease) include immunocompromised conditions, untreated HIV infection, recent LTBI, malnutrition, and age
