Question 3.3

The following is a CSF sample from a 56-year-old woman with severe rheumatoid arthritis who has presented with fever, malaise and altered mental state



Normal Range

Cell count

75 cells / mm3*

0 – 5

(90% lymphocytes)


890 mg/L*

170 – 550


2.0 mmol/L*

2.8 – 4.5

Gram stain


Describe 4 further tests you would perform upon the CSF to establish an infective cause.


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College Answer

  • Herpes Simplex PCR
  • Mycobacterium Tuberculosis PCR 
  • Mycobacterial Stain and Cultures
  • India Ink Stain, Cryptococcal Ag 
  • Fungal cultures
  • Bacterial PCR


The question is really asking, "what pathogens can cause a meningitis, but wont be picked up on a routine gram stain?" The answer is "anything that is not a classical bacterium". This is what one might call "aseptic meningitis". LITFL has an excellent summary of this topic.

The list contains the following bugs:

  • Mycobacteria:
    • M.tuberculosis
  • Fungi:
    • Cryptococcus neoformans
  • Viruses:
    • HSV
    • VZV
    • CMV
    • HIV
    • Enterovirus
  • Random:
    • Treponema pallidum
    • Borrelia burgdorferi (Lyme disease)

Additionally, one might wish to consider non-infectious causes, such as lymphoma, vasculitis, or drug-induced meningitis (eg. due to cotrimoxazole or azathiaprine)

Interestingly, the most likely causes of CSF lymphocytosis are the common meningitis pathogens -S.pneumoniaeH.influenzae and N.meningitides.

The richness of this pathology is serenaded in a dedicated chapter on meningitis.


Powers, William J. "Cerebrospinal fluid lymphocytosis in acute bacterial meningitis." The American journal of medicine 79.2 (1985): 216-220.