Tag Archives: CSF parameters

“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.

“Accepting Rejection”

Apologies for the recent sparcity of posts as I continue my futile efforts at finding a suitable apartment in Paris…

A recent paper in the Journal of Clinical Microbiology caught my interest regarding the use of rejection parameters for deciding whether or not to test CSF for Herpes Simplex Virus (HSV) by PCR, according to the white cell count and other clinical parameters.

Click here for the abstract. (Unfortunately the full article needs subscription to JCM)

More and more laboratories are implementing rejection criteria for testing HSV in CSF. The test is often requested before the cell counts and protein are known (ie on the initial request form), and often the CSF parameters are completely normal. 

The researchers put forward a case for only testing HSV PCR if CSF samples had >10 cells/mmor if the sample was from an immunocompromised patient or a child aged <2 years. 

The researcher’s paper looks convincing. However before we accept such criteria we need to reflect on how serious HSV infection of the CNS is, particularly HSV encephalitis. This is not a diagnosis where as a laboratory we can afford to miss a positive diagnosis. The consequences could potentially be catastrophic. See this article  for some sort of an explanation.

Very very occasionally, as previous similar papers have demonstrated (a pseudo meta-analysis if you like..), HSV encephalitis does occur where the child is older than 2 years, doe not have “classical” immunocompromise and CSF parameters are plum normal.

So while we strive for laboratory efficiency (which I strongly support), we need to be very careful in our interpretation of such papers, maintain close co-operation between the clinician and the laboratory, and be prepared to be flexible in our testing protocols for individual patients.