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

Parameter	Value	Normal Range
Cell count	75 cells / mm3*	0 – 5
	(90% lymphocytes)
Protein	890 mg/L*	170 – 550
Glucose	2.0 mmol/L*	2.8 – 4.5
Gram stain	Negative

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

Discussion

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.pneumoniae, H.influenzae and N.meningitides.

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

References

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

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