Open access, freely available online
Online Quiz
Test Your Knowledge: Ten Questions
about Abnormal Cerebrospinal Fluid Results
This quiz is related to the Learning Forum article in the October issue of PLoS Medicine (DOI: 10.1371/
journal.pmed.0010007).
Gavin Yamey*, William Lynn, Susan Lightman
Question 1. Which of the following is an abnormal Question 7. Which of the following is true about
cerebrospinal fluid (CSF) finding? Mollaret’s meningitis?
A glucose level that is less than 50% of the plasma glucose It is rarely recurrent
level It has been associated with herpes simplex virus
A protein level of less than 0.5 g/l It is characterized by the appearance of large lymphocytes
A cell concentration of 0–5 cells/µl in the CSF
Question 2. Which of the following CSF results Question 8. The CSF in Lyme meningitis typically shows
suggests fungal meningitis? which of the following?
Elevated CSF neutrophil count, raised protein, and low A low-grade lymphocytic pleocytosis, reduced glucose, and
glucose elevated protein
Elevated protein, 20 lymphocytes/µl, and normal glucose A neutrophil leucocytosis with a normal glucose and
Moderately elevated CSF lymphocyte count of 200 cells/µl, protein
raised protein, and low glucose A neutrophil leucocytosis, reduced glucose, and elevated
protein
Question 3. Which of the following is true about the
CSF changes in patients with tuberculous meningitis? Question 9. In the United Kingdom, which of
The cell count is often elevated, and the cells are mainly the following is the most common cause of viral
neutrophils meningitis in immunocompetent adults?
In detecting M. tuberculosis in the CSF by nucleic acid Mumps
amplification tests (such as polymerase chain reaction Herpes zoster
[PCR]), the sensitivity and specificity are close to 100% Enteroviruses
A normal CSF does not exclude cerebral tuberculosis
Question 10. The CSF in West Nile encephalitis typically
Question 4. Which of the following does not cause the shows which of the following?
CSF picture of “aseptic” meningitis? A moderate lymphocytic pleocytosis, moderately increased
Bacterial meningitis protein, and a normal CSF: plasma glucose ratio
Viral meningitis A normal cell count, highly elevated protein, and a
Drug-induced meningitis reduced CSF: plasma glucose ratio
No abnormalities
Question 5. Which of the following is true about CSF
analysis in bacterial meningitis?
A raised CSF lactate suggests tuberculous disease
Common bacterial pathogens may be identified by rapid Citation: Yamey G, Lynn W, Lightman S (2004) Test your knowledge: Ten questions
about abnormal cerebrospinal fluid results. PLoS Med 1(1): e011.
polysaccharide antigen detection
Antibiotic therapy should be delayed until after a lumbar Copyright: © 2004 Yamey et al. This is an open-access article distributed under the
terms of the Creative Commons Attribution License, which permits unrestricted
puncture to ensure that bacterial cultures are positive use, distribution, and reproduction in any medium, provided the original work is
properly cited.
Question 6. Which of the following is most likely to
Gavin Yamey is the Magazine Editor of PLoS Medicine. William Lynn and Susan Light-
cause a low CSF glucose? man are the Section Editors of the Learning Forum and are on the PLoS Medicine
editorial board.
Sarcoidosis
Enteroviral meningitis *To whom correspondence should be addressed. E-mail: [email protected]
Drug-induced meningitis DOI: 10.1371/journal.pmed.0010011
PLoS Medicine | www.plosmedicine.org 001 October 2004 | Volume 1 | Issue 1 | e11
Answer 1. A glucose level that is less than 50% of the plasma meningitis and should not be deferred if there is to be a
glucose level significant delay in performing a lumbar puncture [3].
Normal CSF findings are a glucose level greater than 50% of References
the plasma glucose level, a protein level of less than 0.5 g/l, 1. Bhisitkul DM, Hogan AE, Tanz RR (1994) The role of bacterial antigen
and 0–5 cells/µl (usually monocytes). detection tests in the diagnosis of bacterial meningitis. Pediatr Emerg Care
10: 67–71.
2. Leib SL, Boscacci R, Gratzl O, Zimmerli W (1999) Predictive value of
Answer 2. Moderately elevated CSF lymphocyte count of 200 cerebrospinal fluid (CSF) lactate level versus CSF/blood glucose ratio for
cells/µl, raised protein, and low glucose the diagnosis of bacterial meningitis following neurosurgery. Clin Infect Dis
29: 69–74.
In fungal meningitis, the CSF most commonly shows a 3. Heyderman RS, Lambert HP, O’Sullivan I, Stuart JM, Taylor BL, et
moderately elevated lymphocyte count [1]. Classically, the al. (2003) Early management of suspected bacterial meningitis and
glucose is low and protein elevated. Not all patients with meningococcal septicaemia in adults. J Infect 46: 75–77.
fungal meningitis have marked CSF changes—for example, Answer 6. Sarcoidosis
the cellular changes may be minimal in patients with Neurosarcoid produces an abnormal CSF in at least 80%
advanced AIDS and cryptococcal meningitis. of cases. Typical changes include a raised protein and
References an increased density of cells, which are predominantly
1. Razonable RR, Keating MR (2002) Meningitis. Available: http:⁄⁄www. monocytes. Low CSF glucose may occur with neurosarcoid,
emedicine.com/MED/topic2613.htm. Accessed 27 July 2004.
making distinction from tuberculosis difficult [1].
Answer 3. A normal CSF does not exclude cerebral References
1. Zajicek JP, Scolding NJ, Foster O, Rovaris M, Evanson J, et al (1999) Central
tuberculosis nervous system sarcoidosis—Diagnosis and management. QJM 92: 103–117.
Classical CSF changes in tuberculous meningitis are the
following: markedly elevated CSF protein, raised lymphocyte Answer 7. It has been associated with herpes simplex virus
count, and a low glucose. A small proportion of cases may Mollaret’s meningitis is a recurrent aseptic meningitis that
present with neutrophils in the CSF or a mixed picture with has been associated with herpes simplex virus [1] and that
both neutrophils and lymphocytes. is characterized by the appearance of large monocytes in
A systematic review and meta-analysis of nucleic acid the CSF [2]. The diagnosis is generally established by PCR
amplification tests for tuberculous meningitis found that detection of herpes simplex virus DNA within the CSF.
these tests have a sensitivity of 56% (95% CI 46%–66%) and a
References
specificity of 98% (95% CI 97%–99%) [1]. 1. Tang YW, Cleavinger PJ, Haijing L, Mitchell PS, Smith TF, et al. (2000)
The CSF may be normal or have only minor changes in Analysis of candidate–host immunogenetic determinants in herpes simplex
cerebral abscesses due to tuberculosis (tuberculomas). virus–associated Mollaret’s meningitis. Clin Infect Dis 30: 176–178.
2. Picard FJ, Dekaban GA, Silva J, Rice GP (1993) Mollaret’s meningitis
References associated with herpes simplex type 2 infection. Neurology 43: 1722–1727.
1. Pai M, Flores LL, Pai N, Hubbard A, Riley LW, et al. (2003) Diagnostic
accuracy of nucleic acid amplification tests for tuberculous meningitis: A Answer 8. A low-grade lymphocytic pleocytosis, reduced
systematic review and meta-analysis. Lancet Infect Dis 3: 633–643. glucose, and elevated protein
The CSF in Lyme meningitis, caused by Borrelia burgdorferi,
Answer 4. Bacterial meningitis is characterized by a low-grade lymphocytic pleocytosis,
Aseptic meningitis is usually taken to mean a CSF picture reduced glucose, and elevated protein [1]. The diagnosis
dominated by lymphocytes or mononuclear cells with no may be confirmed by the detection of specific Lyme disease
organisms seen on microscopy [1,2]. Viral meningitis is the immunoglobulins within the CSF or by CSF PCR.
most common cause. Tuberculosis must be considered in all
cases, as well as other atypical infections such as Lyme disease References
1. Razonable RR, Keating MR (2004) Meningitis. Available: http:⁄⁄www.
or brucellosis. Non-infectious causes include drug-induced emedicine.com/MED/topic2613.htm. Accessed 27 July 2004.
meningitis, Vogt-Koyanagi-Harada syndrome, connective
tissue diseases, and sarcoidosis. Answer 9. Enteroviruses
In the UK, enteroviruses are the most common cause of
References
1. Nelsen S, Sealy DP, Schneider EF (1993) The aseptic meningitis syndrome.
viral meningitis in immunocompetent adults. CSF changes
Am Fam Physician 48: 809–815. in viral meningitis are relatively nonspecific, with an elevated
2. Hasbun R (2000) The Acute Aseptic Meningitis Syndrome. Curr Infect Dis lymphocyte count and protein level and a normal CSF
Rep 2: 345–351.
glucose. PCR is now the diagnostic modality of choice for
central nervous system viral infections but is not available in
Answer 5. Common bacterial pathogens may be identified by
“real time” within most centers.
rapid polysaccharide antigen detection
The causative organism in bacterial meningitis may be Answer 10. A moderate lymphocytic pleocytosis, moderately
rapidly diagnosed by CSF detection of bacterial antigens for increased protein, and a normal CSF: plasma glucose ratio
Haemophilus influenzae, pneumococcus, and meningococcus Examination of the CSF in West Nile encephalitis typically
[1]. This can be particularly useful if recent antibiotic therapy shows a moderate lymphocytic pleocytosis, though sometimes
has led to the CSF culture being negative. PCR detection of there may be no cells, or neutrophils may predominate.
bacterial DNA is more sensitive, and PCR is becoming more Protein concentrations are moderately increased, and the
widespread, but in most laboratories it cannot be deployed glucose ratio is typically normal [1].
in “real time.” CSF lactate is raised in bacterial meningitis,
References
and this fact has been used to aid diagnosis in some settings 1. Solomon T, Ooi M, Beasley DW, Mallewa M (2003) West Nile encephalitis.
[2]. Early antibiotic administration is essential in bacterial BMJ 326: 865–869.
PLoS Medicine | www.plosmedicine.org 002 October 2004 | Volume 1 | Issue 1 | e11
References Pai M, Flores LL, Pai N, Hubbard A, Riley LW, et al. (2003) Diagnostic accuracy
Bhisitkul DM, Hogan AE, Tanz RR (1994) The role of bacterial antigen of nucleic acid amplification tests for tuberculous meningitis: A systematic
detection tests in the diagnosis of bacterial meningitis. Pediatr Emerg Care review and meta-analysis. Lancet Infect Dis 3: 633–643.
10: 67–71. Picard FJ, Dekaban GA, Silva J, Rice GP (1993) Mollaret’s meningitis associated
Hasbun R (2000) The Acute Aseptic Meningitis Syndrome. Curr Infect Dis Rep with herpes simplex type 2 infection. Neurology 43: 1722–1727.
2: 345–351. Razonable RR, Keating MR (2002) Meningitis. Available: http:⁄⁄www.
Heyderman RS, Lambert HP, O’Sullivan I, Stuart JM, Taylor BL, et al. (2003) emedicine.com/MED/topic2613.htm. Accessed 27 July 2004.
Early management of suspected bacterial meningitis and meningococcal Solomon T, Ooi M, Beasley DW, Mallewa M (2003) West Nile encephalitis. BMJ
septicaemia in adults. J Infect 46: 75–77. 326: 865–869.
Leib SL, Boscacci R, Gratzl O, Zimmerli W (1999) Predictive value of Tang YW, Cleavinger PJ, Haijing L, Mitchell PS, Smith TF, et al. (2000) Analysis
cerebrospinal fluid (CSF) lactate level versus CSF/blood glucose ratio for of candidate–host immunogenetic determinants in herpes simplex virus–
the diagnosis of bacterial meningitis following neurosurgery. Clin Infect Dis associated Mollaret’s meningitis. Clin Infect Dis 30: 176–178.
29: 69–74. Zajicek JP, Scolding NJ, Foster O, Rovaris M, Evanson J, et al (1999) Central
Nelsen S, Sealy DP, Schneider EF (1993) The aseptic meningitis syndrome. Am nervous system sarcoidosis—Diagnosis and management. QJM 92: 103–117.
Fam Physician 48: 809–815.
PLoS Medicine | www.plosmedicine.org 003 October 2004 | Volume 1 | Issue 1 | e11
