Xanthochromia

Physiology

Cerebrospinal fluid, which fills the subarachnoid space between the arachnoid membrane and the pia mater surrounding the brain, is normally clear and colorless. When there has been bleeding into the subarachnoid space, the initial appearance of the cerebrospinal fluid can range from barely tinged with blood to frankly bloody, depending on the extent of bleeding. Within several hours, the red blood cells in the cerebrospinal fluid are destroyed, releasing their oxygen-carrying molecule heme, which is then metabolized by enzymes to bilirubin, a yellow pigment. The most common cause for bleeding into the subarachnoid space is a subarachnoid hemorrhage from a ruptured cerebral aneurysm.

The most frequently employed initial test for subarachnoid hemorrhage is a computed tomography scan of the head, but it detects only 98% of cases in the first 12 hours after the onset of symptoms, and becomes less useful afterwards. Therefore, a lumbar puncture ("spinal tap") is recommended to obtain cerebrospinal fluid if someone has symptoms of a subarachnoid hemorrhage (e.g., a thunderclap headache, vomiting, dizziness, new-onset seizures, confusion, a decreased level of consciousness or coma, neck stiffness or other signs of meningismus, and signs of sudden elevated intracranial pressure), but no blood is visible on the CT scan.

Heme from red blood cells (RBC) that are in the cerebrospinal fluid because a blood vessel was damaged during the lumbar puncture (a "traumatic tap") has no time to be metabolized, and therefore no bilirubin is present.

After the cerebrospinal fluid is obtained, a variety of its parameters can be checked, including the presence of xanthochromia. If the cerebrospinal fluid is bloody, it is centrifuged to determine its color.

Spectrophotometry

Many laboratories rely on only the color of the cerebrospinal fluid to determine the presence or absence of xanthochromia. However, recent guidelines suggest that spectrophotometry should be performed. Spectrophotometry relies on the different transmittance, or conversely, absorbance, of light by different substances or materials, including solutes. Bilirubin absorbs light at wavelengths between 450 and 460 nm. Spectrophotometry can also detect the presence of oxyhemoglobin and methemoglobin, which absorb light at 410-418 nm and 403-410 nm, respectively, and also may indicate that bleeding has occurred; to identify substances in cerebrospinal fluid that absorb light at other wavelengths but are not due to bleeding, such as carotenoids; and to detect very small amounts of yellow color saturation (about 0.62%) which may be missed by visual inspection, especially when the cerebrospinal fluid has been examined under incandescent lighting or a tungsten desk lamp (corresponding to International Commission on Illumination standard illuminant A).

Visual inspection is the most frequent method used in the United States to assess cerebrospinal fluid for xanthochromia, while spectrophotometry is used on up to 94% of specimens in the United Kingdom.

History

The concept was introduced in 1902 in a French report on a case of pneumococcal meningitis.

References

References

1. (May 2008). "Revised National Guidelines for Analysis of Cerebrospinal Fluid for Bilirubin in Suspected Subarachnoid Haemorrhage". Annals of Clinical Biochemistry.
2. (Mar 10, 2014). "Spectrophotometry or Visual Inspection to Most Reliably Detect Xanthochromia in Subarachnoid Hemorrhage: Systematic Review.". Annals of Emergency Medicine.
3. (2007). "Subarachnoid Haemorrhage". Lancet.
4. (March 1995). "Detection of Subarachnoid Haemorrhage on Early CT: Is Lumbar Puncture Still Needed After a Negative Scan?". Journal of Neurology, Neurosurgery, and Psychiatry.
5. (July 2011). "Sensitivity of Computed Tomography Performed Within Six Hours of Onset of Headache for Diagnosis of Subarachnoid Haemorrhage: Prospective Cohort Study". British Medical Journal.
6. (September 2014). "LP or not LP, That is the Question: Gold Standard or Unnecessary Procedure in Subarachnoid Haemorrhage?". Emergency Medicine Journal.
7. (July 2004). "The Worst Headache". Agency for Healthcare Research and Quality.
8. Williams, Anna. (2004). "Xanthochromia in the cerebrospinal fluid". Practical Neurology.
9. (2004). "Spectrophotometry for Xanthochromia". New England Journal of Medicine.
10. (April 2002). "Xanthochromia". Archives of Pathology and Laboratory Medicine.
11. (1902). "Meningite a pneumocoques. Xanthochromie du liquide cephalo-rachidien. 1902; 4: 550-2.". Bull Soc Anat Paris.