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 (95 th 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; 0.59 g/L at age 50; 0.62g/L at age 60; and 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

Interpretation

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 t ypically 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 ? entry in this testguide) 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.

References:

Allen JA et al. CIDP diagnostic pitfalls and perception of treatment benefit. Neurology 2015; 85:498-504

Birch K et al. Cerebrospinal fluid total protein cannot reliably distinguish true subarachnoid haemorrhage from other causes of raised cerebrospinal fluid net bilirubin and net oxyhaemoglobin absorbances. Ann Clin Biochem 2014; 51(6): 657-661

Breiner A et al. Adult CSF total protein upper reference limits should be agepartitioned

and significantly higher than 0.45 g/L: a systematic review.   J of Neurology 2019; 266:616-624

Brooks JA   Causes of albuminocytological dissociation and the impact of age adjusted

cerebrospinal fluid protein reference intervals: a retrospective chart review of 2627 samples collected at tertiary care centre. BMJ Open 2019; 9; e025348

Deisenhammer J et al. Guidelines on routein cerebrospinal fluid analysis. Report from an EFNS taskforce. Eur J Neurol 2006; 13:913-922

Liu Z et al. Age-specific reference values for cerebrospinal fluid protein concentrations in children in southern China. Medicine 2019;98 (41): e17500

Seyfert S et al.   Determinants of lumbar CSF protein concentration. Journal of Neurology 2002; 249:1021-1026

Shah SS et al. Age-Specific Reference Values for Cerebrospinal Fluid Protein Concentration in Neonates and Young Infants   J Hosp Med 2011; 6:22-27

Reference Intervals

For lumbar puncture specimens.  Lower values will be found in CSF from other sites. 

Units: g/L

• Blood contamination can cause false elevations of “CSF protein”