Cerebrospinal Fluid

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Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Lumbar Puncture (Spinal Tap) article more useful, or one of our other health articles.

Read COVID-19 guidance from NICE

Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.

Cerebrospinal fluid (CSF) is found in the subarachnoid space of the brain (within the ventricles) and spinal canal. It is produced by the choroid plexus in the ventricles of the brain and the cerebral vessels, at the rate of 500 ml/day. Production matches reabsorption so, at any one time in an adult, the average volume of CSF is about 150 ml.

For information on performing a lumbar puncture and sampling, see the separate Lumbar Puncture article.

  • To investigate or exclude meningitis: bacterial, viral, tuberculous, cryptococcal, chemical, carcinomatous.
  • To exclude subarachnoid haemorrhage in acute severe headache.
  • To investigate neurological disorders: multiple sclerosis, sarcoidosis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, mitochondrial disorders, leukoencephalopathies, paraneoplastic syndromes.
  • To demonstrate and manage disorders of intracranial pressure: idiopathic intracranial hypertension, spontaneous intracranial hypotension.
  • To administer therapeutic or diagnostic agents: spinal anaesthesia, intrathecal chemotherapy, intrathecal antibiotics, intrathecal baclofen, contrast media in myelography or cisternography.

It is helpful to note the appearance of CSF and the opening pressure (normal 10-20 cm H2O). Samples are usually sent for:

Biochemistry

  • Protein - high (>0.4 g/L) levels seen in infection and infiltration disorders (falsely high results are seen if the sample is contaminated with blood). Highly elevated levels (>1 g/L) are seen in Guillain-Barré syndrome and tuberculous meningitis.
  • Glucose - a blood sample for glucose should be taken at the same time as the lumbar puncture. CSF glucose is usually 60-80% of plasma glucose. A reduced level implies there is increased uptake of glucose in the CNS - eg, presence of micro-organisms.

Microscopy, culture and sensitivity

  • Cell count - white cells with differential (neutrophils and lymphocytes) and red cells. When performing a lumbar puncture, red cells may be present as a result of damage to a blood vessel during the procedure (commonly called a 'bloody tap'). In these instances, the initial CSF is red but this is followed by clearer CSF.
  • Gram stain - for bacterial organisms.
  • Culture - if appropriate.

Additional investigations

  • Xanthochromia - yellow appearance of centrifuged CSF resulting from red cell breakdown products, oxyhaemoglobin and bilirubin and representing a high likelihood of subarachnoid haemorrhage. This may be visualised by the naked eye but the use of spectrophotometry has superseded this. It is the last of three consecutively obtained samples which is examined.
  • Oligoclonal bands - seen in multiple sclerosis and neurosyphilis.
  • Virology.
  • Cytology - requires larger volumes of CSF than other tests.
  • Polymerase chain reaction (PCR) - eg, for tuberculosis (TB), and viral and partially treated bacterial meningitis.
  • Bacterial antigen testing - may be useful if PCR is not available and the patient partially treated.
  • India ink staining for cryptococcus.

Please note that the following are examples of results and often CSF results do not necessarily 'fit' into a standard set. Thus, CSF results should not be considered alone but in conjunction with history and examination findings and the results of other investigations. A good example of this is encephalitis - it is possible that the CSF is 'normal' (as defined below) but the clinical presentation and CT scan findings might be highly suggestive, in which case the diagnosis will most likely be encephalitis.

'Normal'

  • Clear and colourless appearance.
  • Protein level - 0.2-0.4 g/L (neonate <1.7 g/L).
  • Glucose level - 60-80% of plasma glucose.
  • WCC <5 per mm3 (higher in neonates up to 20 per mm3).
  • No organisms.
  • Opening pressure 10-20 cm H2O.

Bacterial meningitis

  • Cloudy and turbid CSF (if severe).
  • Raised protein >1.5 g/L.
  • Glucose level is <50% of the plasma level.
  • Cell count is high (>1,000 per mm3) and mostly neutrophils.
  • May see organisms - eg, Gram-negative diplococci in Neisseria meningitidis.
  • Opening pressure is usually high.

Viral/aseptic meningitis or encephalitis

  • Clear CSF.
  • Protein is raised or at the high end of normal.
  • Glucose level is usually within normal limits (may be reduced in some cases of mumps and herpes simplex).
  • Cell count is high and mostly lymphocytes.
  • No organisms usually and PCR or special stains may be needed to identify cause.
  • Opening pressure may or may not be raised.

Tuberculous meningitis

  • Clear or slightly cloudy appearance (there may be cobweb-like stranding).
  • Raised protein >1.5 g/L (much higher than bacterial meningitis).
  • Glucose level is <50% of the plasma level.
  • Cell count is high with a mixed pleocytosis and mainly lymphocytes.
  • Opening pressure is usually raised but can be high normal.
  • Negative PCR may help rule out TB quickly.

Subarachnoid haemorrhage

  • Rarely, CSF is continuously blood-stained to the naked eye and, if subsequent analysis reveals an equal number of RBCs in all three samples, this indicates a subarachnoid haemorrhage.
  • CSF should be examined for xanthochromia.
  • Protein is raised or at the high end of normal.
  • Glucose level is usually low.
  • High number of RBCs.
  • No organisms.
  • Opening pressure is usually high if excessive RBCs are present.

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Further reading and references

  1. Doherty CM, Forbes RB; Diagnostic Lumbar Puncture. Ulster Med J. 2014 May83(2):93-102.

  2. Majed B, Zephir H, Pichonnier-Cassagne V, et al; Lumbar punctures: use and diagnostic efficiency in emergency medical departments. Int J Emerg Med. 2009 Nov 192(4):227-35. doi: 10.1007/s12245-009-0128-5.

  3. Oxford Handbook of Clinical Medicine (9th ed) 2014

  4. Kumar and Clarke's Clinical Medicine (8th Ed) 2012

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