Tag Archives: CSF

“Running to stand still…”

When I started working as a Clinical Microbiologist in 2007, anti-NMDA receptor encephalitis had not yet been discovered. The diagnostic test, looking for anti-NMDA receptor antibodies, only appeared commercially around 2010.

Now it is the latest fashionable test to perform…

I am getting old.

The whole area of auto-immune encephalitis has progressed rapidly in the last 10 years, and this potentially treatable cause of encephalitis (options include steroids, IV immunoglobulins, plasma exchange and immunomodulators) is now thought to be similar in prevalence to some viral encephalitides.

Anti-NMDA receptor encephalitis represents the vast majority (approx. 80%) of all cases of autoimmune encephalitis. It usually presents with a short prodromal period followed by a range of symptoms such as auditory and visual hallucinations, delusions, behavioural change, decreased level of consciousness, seizures, and autonomic dysfunction. 

A majority of patients (58%) with anti-NMDA receptor encephalitis will have a CSF leucocytosis(Raised CSF protein and oligoclonal bands are also seen in a proportion of patients.) So testing for anti-NMDA receptor antibodies becomes the obvious default for a patient with a CSF leucocytosis and negative bacterial culture and negative CSF viral PCR…

Other causes of autoimmune encephalitis include unfamiliar names such as anti-LGl1, anti-AMPAR, anti GABA  and anti-CASPR to name but a few. You will likely see these crop up from time to time on CSF request forms.

It is of course not microbiology per se. However we need to know about it as we end up getting the CSF samples and we need to triage the test requests, and deal with the perennial problem of separating a ml or two of CSF for several different tests, which often get sent away to different laboratories…

I didn’t need to worry about these exotic tests 10 years ago. Now I do.

Sometimes it feels like you need to keep running just to stand still…


p.s.  For the academics amongst you, NMDA stands for N-methyl-D-aspartate.

“Lumbar Puncture: Creating headaches not only for the patient…”


25 years ago, examination of cerebro-spinal fluid (CSF) was a fairly straightforward process. You got a cell count, Gram stain, protein and glucose levels. For the really complex patient you might have added a couple more tests like an Indian Ink or a TB culture.

Not any more….

There are now dozens of tests that can potentially be performed on CSF, most of them molecular, and a particular increase in viral PCR, e.g HSV, EBV, CMV, VZV, HHV6, etc. etc. The acronymical list goes on…

If you work in a clinical microbiology lab, then the chances are you will have come across one of the following scenarios:

  • A CSF sample arrives into the lab with a long list of molecular tests requested. The cell counts, protein and glucose are then completely normal on initial testing.
  • A CSF sample arrives into the lab with a long list of molecular tests requested by a doctor who is in the process of studying for post-graduate exams and wants to show off his/her expertise.
  • A CSF sample arrives into the lab with a long list of molecular tests requested. By the time some of these tests are performed, the patient has long recovered and is sitting at home watching ER with a glass of wine in hand.

CSF testing can now be fairly problematic. Cost issues, poor positive predictive value of individual tests, available CSF volume, distributing bits of CSF to different reference labs, lack of clinical details can all contribute to this headache. Not to mention that the results of these tests often have little or no direct effect on the management of the patient. 

I am convinced that there are huge numbers of molecular tests performed on CSF samples which turn out to be completely unnecessary.

Good communication between the laboratory and clinicians is obviously key, but I also believe that more and more the laboratory needs to become the gatekeeper for complex CSF testing, as opposed to being the submissive, and passive recipient of such requests.


I have added a short powerpoint on toxoplasmosis to the website