Cerebrospinal fluid analysis

Question 1

What are the indications for CSF analysis

Answer 1

PUO
Diffuse or multifocal CNS disease
Spinal disease where there is pain (assuming imaging done first)
Diseases of the meninges

Question 2

When is CSF sampling contraindicated?

Answer 2

• Cervical vertebral instability. This may be the result of a congenital malformation or trauma (resulting in
  atlantoaxial instability). A good rule of thumb is to always suspect cervical instability in any small breed dog with neck pain and to perform a neutral cervical radiograph as the first step in the investigation;
  Raised intracranial pressure (ICP)
  Dermatitis. CSF should not be collected from a site where the overlying skin is infected.
  In addition, CSF must not be collected from patients that are critically ill and unfit for general anaesthesia.

Question 3

What are the signs of raised ICP

Answer 3

Abnormal mentation
Loss of vestibulocochlear eye movements
Anisocoria/ abnormal pupil size
Impaired motor function

Question 4

How does CSF colour affect interpretation

Answer 4

A red or pink appearance to CSF may be due to haemorrhage within the CNS or iatrogenic contamination. To determine which of these situations has occurred, the sample should be spun down; a clear supernatant suggests an artefactual (iatrogenic) finding or recent CNS bleeding, while a yellow supernatant implies an old CNS haemorrhage. When CSF is collected during the acute phase of a disease (ie, less than 24 hours after it began), a true haemorrhagic process may be difficult to distinguish from iatrogenic haemorrhage. It is important to note that a subjectively clear sample cannot be automatically regarded as normal.

Question 5

Which proteins make up CSF?

Answer 5

Albumin is the main protein in CSF (accounting for 50 to 70 per cent of the total protein), with globulin
concentration being very low (5 to 12 per cent)
The low-protein content of CSF (normally around 200 to 400 times less concentrated than serum) means that the standard techniques used to measure protein concentration in other body fluids are inaccurate when applied to CSF
The more caudal in the CSF the higher the protein levels

Question 6

Outline the measurement of immunoglobulins

Answer 6

IgG is non-specific and has been found in many inflammatory CNS disorders, so it is of little
diagnostic value
IgA, in contrast, has been found to be intrathecally and peripherally elevated in steroid-responsive meningitis- arteritis, making it a useful adjunct for the diagnosis of this condition
IgM is diagnostically useful when elevated as it suggests an active humoral immune
response and, hence, infection. It returns to normal very soon after an infectious agent is cleared from the body,
so its elevation is more significant than other immunoglobulins for detecting ‘active’ infection

Question 7

Outline infectious disease testing in CSF

Answer 7

Can do PCR, but often not very sensitive
Can do serology, although can be affected by vaccines and blood contamination (e.g. vaccinated would have high titre in blood but low in CSF)

Question 8

What can dx bacterial meningitis

Answer 8

culture (although not v sensitive)
neutrophilic pleocytosis
Sometimes can see intracellular bacteria

Question 9

What can cause an increase in protein but no increase in cells?
(Albumin cytological dissociation)

Answer 9

• Increased production of protein within the CNS. In some diseases, there is an increase in secreted globulins (eg, steroidresponsive meningitis-arteritis, canine distemper and multiple myeloma);
  Increased permeability of the BBB. When the BBB is damaged, protein leaks into the CSF. Albumin enters in
  the greatest quantities because the concentration of these proteins is highest in the blood. Inflammatory
  diseases causing vasculitis may result in protein leakage into the CSF. However, the protein is frequently accompanied by inflammatory cells;
  Destruction of neural structures. Degenerative diseases (eg, degenerative myelopathy), traumatic injuries,
  ischaemic necrosis (eg, fibrocartilaginous embolism) and neoplastic processes may cause breakdown of CNS parenchyma;
  Blockage of the CSF outflow pathways. Congenital malformations (eg, hydrocephalus and syringomyelia in
  Chiari-like malformation) may cause this phenomenon. Any extradural lesions compressing CNS structures can
  also have this effect whether it be around the spinal cord (eg, intervertebral disc disease) or the brain (eg, cystic lesions).