Protein (CSF)

Diagnostic Use

CSF protein varies with age. The reference interval of 0.15-0.45g/L was historically derived from small studies which involved mainly healthy young adults <30yrs of age. CSF protein is actually higher in newborns and it gradually decreases to close to adult levels by around 3- 6 months (the 95th percentile for infants between 1-2 months is around 0.90g/L). From 40 years onwards, there is incremental rise in CSF protein.

The estimated upper reference limits are :

• 0.57g/L at age 40;
• 0.59g/L at age 50;
• 0.62g/L at age 60;
• 0.66g/L at age 70

Although there is age related rise in CSF protein, in order to maintain sensitivity for CNS (central nervous system) pathological conditions, we prefer not to adopt age-adjusted upper reference limits as it is not uncommon to observe CSF proteins in the range between 0.45g/L and age-related upper reference limits in different CNS diseases.

CSF protein also varies with site of collection –   lumbar region derived CSF has higher protein content than CSF from brain ventricles. CSF albumin (normally account for at least 50% of CSF protein) positively varies with body mass index or abdominal circumference. The hypothesis is that in obesity, there is increase in venous pressure causing mild impairment in rate of CSF reabsorption from subarachnoid space.

CSF protein can be raised as a result of blood contamination during lumbar puncture. However, formula using RBC count to correct for plasma protein contribution is generally inaccurate and its use is discouraged. CSF protein in subarachnoid haemorrhage is usually <2.0g/L.

Albumino-cytologic dissociation (ACD) (or protein cell dissociation) refers to elevated CSF protein without pleocytosis. It can occur in Guillain-Barre syndrome, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) or epileptic seizures.  ACD especially with very high protein content is typically observed in spinal stenosis or compression arising from e.g. trauma, tumour, disc herniation or abscess (part of Froin’s syndrome).

Cerebrospinal fluid protein analysis (performed at LabPLUS) allows calculation of CSF IgG index. Together with the CSF oligoclonal band test, they can help to determine blood brain barrier dysfunction and intrathecal IgG production. The latter if present can be used to support diagnosis of CNS conditions like multiple sclerosis.

Reference Intervals

• For lumbar puncture specimens.  Lower values will be found in CSF from other sites.
• Blood contamination can cause false elevations of “CSF protein”.