There are many causes of a lymphocytic CSF, both microbiological and non-microbiological. Here is a quick and non-exhaustive summary:

• Enteroviruses- probably the most common cause, in most parts of the world.
• Herpes Simplex Virus (HSV)- one of the most important to diagnose/exclude as HSV encephalitis is associated with a high mortality rate.
• “Lots of other viruses…”- There are many viruses which can cause a lymphocytic CSF, too many to list really. How many you test for depends on how much money your lab has, and how sick the patient is.
• TB- Look for the classical risk factors and a more sub-acute presentation.
• Cryptococcus- Usually in immunocompromised, particularly HIV. Remember cryptococcal antigen has essentially replaced Indian Ink stain as a diagnostic test.
• Leptospirosis- Other systems (i.e. renal, respiratory) usually involved.
• Non-infectious- Autoimmune, malignancies, drugs can all be causes of a lymphocytic CSF.

and the list goes on…

But one cause of a lymphocytic CSF that I have not mentioned is one that is often forgotten about.

Syphilis.

Syphilis is sometimes called “The Great Imitator” because of the diversity of clinical syndromes it can cause. In the words of William Osler “Those who know syphilis, know medicine.”

And with the massive increase in syphilis over the past few years in New Zealand (and many other parts of the world), that syndrome diversity is starting to reveal itself…

In the past two years, I have personally seen 5 cases of lymphocytic CSF due to neurosyphilis. Sometimes it has been anticipated, in others it has been completely unexpected.

So all cases of unexplained lymphocytic CSFs should really be getting treponemal serology performed on serum. A lymphocytic CSF and positive syphilis serology is neurosyphilis until proven otherwise. On those with positive syphilis serology, neurosyphilis can be confirmed by looking for VDRL and FTA in the CSF.

Neurosyphilis does not just present with an acute/subacute meningitis picture. Tertiary neurosyphilis can present with psychiatric or dementia symptoms (I have seen one case of neurosyphilis presenting as dementia). Again these cohorts of patients should all be screened for syphilis. 

Syphilis can affect the neurovasculature and present as a CVA (stroke). In the same manner as above, all patients who present clinically with stroke should get syphilis serology.

Yes, syphilis is indeed the great imitator.

We do about 25000 syphilis serology tests a year at my lab. When I started at my current position 12 years ago, we would maybe see 1 case of syphilis every month. Now we see 5 or 6 cases a week…

Syphilis is a fascinating disease, one of my favourites. But because it imitates so many other conditions, it is important to always think about it, so it isn’t missed. Missing cases of syphilis can have catastrophic consequences down the line…

Michael