CSF Evaluation in Subarachnoid Hemorrhage

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So, what constitutes a “positive” tap when evaluating for subarachnoid hemorrhage?

Traditional teaching is that a positive tap is Xanthochromia or blood in the CSF

What exactly is Xanthochromia?

Xanthochromia. By Dschafar (Own work) [CC0], via Wikimedia Commons

Xanthochromia. By Dschafar (Own work) [CC0], via Wikimedia Commons

The word xanthochromia is simply Greek for “yellow color.”  It refers to the yellow color that CSF can take in certain situations.  Some of these situations are listed below:

  • Elevated CSF protein            
  • Jaundice
  • Hypervitaminosis A
  • Rifampin Therapy
  • Elevated Bilirubin
  • Oxyhemoglobin

What we are especially interested in when evaluating for subarachnoid hemorrhage is bilirubin and oxyhemoglobin.

Now for a little on RBC Breakdown

When RBC’s lyse they release oxyhemoglobin.  This can be detected in CSF 2-4 hours afterwards.  Oxyhemoglobin can then be converted to bilirubin by the enzyme heme oxidase.  This enzyme is only found in vivo (in the arachnoid membrane, choroid plexus, and in macrophages).  Therefore, if there is bilirubin in CSF, we know that the bleed occurred prior to any lumbar puncture.

The conversion of oxyhemoglobin to bilirubin takes at least 9-10 hours.  So if we LP a patient within 12 hours after onset of headache, there is a theoretical chance we could miss xanthochromia caused by bilirubin in a patient with a bleed.  Furthermore, both oxyhemoglobin and bilirubin can turn the CSF yellow, so we have no way of knowing which is present.  

How do we detect Xanthochromia? 

There are two main methods:

  1. Visual Inspection: this is the primary method in North America.  CSF samples are compared to a clear control against a white background.  If the lab tech can detect a yellowing, then this is positive for xanthochromia.

  2. Spectrophotometry: this method distinguishes pigments by the different absorption of light.  So by looking at what wavelength of light is absorbed, yellow pigments can be detected.

Which way is better?

Most people believe that spectrophotometry is more sensitive since it can theoretically detect differences in color that are not discernable to the human eye.  However, a recent review looked at studies comparing both methods and found no difference between them.

What about detecting RBC’s in the CSF?

RBC’s in the CSF can indicate subarachnoid hemorrhage.  However, they can also be due to a traumatic tap, which is quite common.  Differentiating between the two has long been studied without any real success.  

RBC Clearance

  • Theoretically, the amount of RBCs in the CSF should be constant in a patient with SAH.  In a traumatic tap, the amount of RBCs should decrease from tube 1 to tube 4.  
  • The clearance of RBCs has been studied, but no reliable tool has been validated that we can rely on.

Absolute RBC Count

  • On average, traumatic taps tend to have less RBC’s in CSF than in SAH.  However, similar to RBC clearance, studies have not given us a reliable number to go by.

CSF D-dimer, opening pressure, ferritin, and bilirubin have all been studied to attempt to differentiate between SAH and a traumatic tap.  None have given us a reliable tool.

What about combining Xanthochromia and RBC counts?

This was recently studied by Perry et al.  They found that a lack of xanthochromia and a RBC count less than 2000 x 106/L excluded the diagnosis of aneurysmal SAH.  This rule was 100% sensitive.  You can see the numbers from their study below:

From Perry Jeffrey J, Alyahya Bader, Sivilotti Marco L A, Bullard Michael J, Émond Marcel, Sutherland Jane et al. Differentiation between traumatic tap and aneurysmal subarachnoid hemorrhage: prospective cohort study BMJ 2015; 350 :h568

From Perry Jeffrey J, Alyahya Bader, Sivilotti Marco L A, Bullard Michael J, Émond Marcel, Sutherland Jane et al. Differentiation between traumatic tap and aneurysmal subarachnoid hemorrhage: prospective cohort study BMJ 2015; 350 :h568

 

While this is promising, there is still more work to be done on this subject.

So what am I supposed to do?

Know the evidence, and make a decision for yourself on what constitutes a “positive” LP for SAH.

References

  1. Williams A. Xanthochromia in the cerebrospinal fluid. Pract Neurol 2004;4:174-5.

  2. Perry Jeffrey J, Alyahya Bader, Sivilotti Marco L A, Bullard Michael J, Émond Marcel, Sutherland Jane et al. Differentiation between traumatic tap and aneurysmal subarachnoid hemorrhage: prospective cohort study BMJ 2015; 350 :h568

  3. Chu K, Hann A, Greenslade J, Williams J, Brown A. Spectrophotometry or visual inspection to most reliably detect xanthochromia in subarachnoid hemorrhage: systematic review. Ann Emerg Med 2014;64:256-64.

  4. Gorchynski J, Oman J, Newton T. Interpretation of traumatic lumbar punctures in the setting of possible subarachnoid hemorrhage: who can be safely discharged? Cal J Emerg Med 2007;8:3-7.

  5. Page KB, Howell SJ, Smith CML, Dabbs DJW, Malia RG, Porter NR, et al. Bilirubin, ferritin, D-dimers and erythrophages in the cerebrospinal fluid of patients with suspected subarachnoid haemorrhage but negative computed tomography scans. J Clin Pathol 1994;47:989.

  6. Lang DT, Berberian LB, Lee S, Ault M. Rapid differentiation of subarachnoid hemorrhage from traumatic lumbar puncture using the D-dimer assay. Brief Scientific Reports 1990;93:403-5.

  7. Watson ID, Beetham R, Fahie-Wilson MN, Holbrook IB, O’Connell DM. What is the role of cerebrospinal fluid ferritin in the diagnosis of subarachnoid haemorrhage in computed tomography-negative patients? Ann Clin Biochem 2008;45:189-92.