Microscopic examination

Normal CSF has no or very few cells present and appears clear. If the CSF sample appears clear, a small drop of undiluted CSF is examined under a microscope and cells are counted manually. If the number of cells present are very few (for example, 5 or less), the laboratory may or may not perform a cell differential (see below). If cells are numerous (such as greater than 5), a differential will most likely be done. To perform a differential, laboratories will often use a special centrifuge (cytocentrifuge) to concentrate the cells at the bottom of a test tube. A sample of the concentrated cells is placed on a slide, treated with special stain, and an evaluation of the different kinds of WBCs present is performed.

However, if the CSF is very cloudy or bloody, which can indicate the presence of many cells, the specimen may be run on an automated cell counter to count the different types of cells present. These samples may be cytocentrifuged, but if there are too many cells present in the centrifuged sample, an accurate differential may be difficult to perform. In those cases, the specimen may be diluted, cytocentrifuged, and then stained.

If cancer is suspected or has been previously diagnosed, the sample is usually cytocentrifuged regardless of the number of cells counted, and a differential is performed.

CSF total cell counts

  • Red blood cell (RBC) count. Normally no red blood cells are present in the CSF. The presence of red blood cells may indicate bleeding into the CSF or may indicate a “traumatic tap” - blood that leaked into the CSF sample during collection.
  • White blood cell (WBC) count. Normally less than 5 cells/µL are present in the adult. A significant increase in white blood cells in the CSF is seen with infection or inflammation of the CNS.
  • CSF WBC differential. Small numbers of lymphocytes, monocytes (and, in neonates, neutrophils) are normal in a sample of CSF. There may be:
    • an increase in neutrophils with a bacterial infection
    • an increase in lymphocytes with a viral infection
    • sometimes an increase in eosinophils with a parasitic infection
    • abnormal and increased numbers of WBCs may be seen with leukaemia that is present in the CNS
    • abnormal cells may be present with cancerous tumours
    • immune disorders of the CSF, such as multiple sclerosis, may also cause a slight increase in lymphocytes.

There may be an increase in the different types of WBCs with a variety of other conditions, including brain abscess, following seizures or bleeding within the brain or skull, metastatic tumour, Guillain-Barré syndrome, and inflammatory disorders such as sarcoidosis.

CSF cytology - a cytocentrifuged sample is treated with a special stain and examined under a microscope for abnormal cells. This is often done when a CNS tumour or metastatic cancer is suspected. The presence of certain abnormal cells, such as tumour cells or immature blood cells, can indicate what type of cancer is involved.


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