What are the implications and considerations of xanthochromia (presence of yellow pigment in the cerebrospinal fluid)?

From the Guidelines

Xanthochromia detection through lumbar puncture and spectrophotometric analysis is crucial for diagnosing subarachnoid hemorrhage, especially when CT scans are negative or nondiagnostic, as it has a sensitivity of 100% and specificity of 95.2% 1. When a patient presents with suspected subarachnoid hemorrhage, but the initial head CT is negative or inconclusive, further workup is necessary to rule out this life-threatening condition.

• The American Heart Association/American Stroke Association recommends that physicians maintain a high level of awareness for this diagnosis and pursue appropriate workup, including head CT and, if necessary, LP for xanthochromia evaluation 1.
• Xanthochromia, a yellowish discoloration of cerebrospinal fluid, develops 6-12 hours after a subarachnoid hemorrhage and represents a critical diagnostic finding.
• The detection of xanthochromia through spectrophotometric analysis of CSF obtained by LP is more reliable than visual inspection, with a sensitivity of 100% and specificity of 95.2%, as reported by Walton et al in a study of 1235 patients 1.
• While CT scanning is the first-line diagnostic tool, lumbar puncture with CSF analysis for xanthochromia becomes essential when CT results are negative but clinical suspicion remains high, given the severe morbidity and potential mortality associated with a missed subarachnoid hemorrhage 1.
• The use of CTA as an alternative to LP has a lower sensitivity, especially for ruptured aneurysms < 3 mm, and does not directly evaluate for subarachnoid hemorrhage, making LP the preferred next step in the workup 1.

From the Research

Xanthochromia Implications

• Xanthochromia is a critical diagnostic marker for subarachnoid hemorrhage (SAH), which is a serious neurological event associated with high morbidity and mortality 2.
• The diagnosis of SAH is usually established by computed tomographic scanning, but in some cases, lumbar puncture to examine the cerebrospinal fluid for erythrocytes and xanthochromia is necessary 3.

Diagnostic Methods

• Spectrophotometry of cerebrospinal fluid for xanthochromia is a sensitive and specific test for diagnosing SAH, with a diagnostic sensitivity of 100% and a diagnostic specificity of 98.5% in patients with a negative computed tomography within six hours of symptom onset 2.
• Visual inspection of cerebrospinal fluid for xanthochromia lacks the sensitivity necessary to reliably exclude the diagnosis of SAH, with a sensitivity of 47.3% (95% confidence interval 24.4-71.1%) 4.
• A systematic review found that spectrophotometry had pooled estimates of sensitivity and specificity of 87% (95% confidence interval 71% to 96%) and 86% (95% confidence interval 84% to 88%), respectively, while visual inspection had pooled sensitivity and specificity of 83% (95% confidence interval 59% to 96%) and 96% (95% confidence interval 93% to 97%), respectively 5.

Considerations

• Gross xanthochromia on lumbar puncture may not always represent an acute subarachnoid hemorrhage, as there have been cases where gross xanthochromia was noted during lumbar puncture but the patients did not have an acute subarachnoid hemorrhage 6.
• The recommendation to delay lumbar puncture by 12 hours following onset of symptoms to ensure sufficient time has elapsed for xanthochromia to develop may need to be reassessed, as nearly all hospital clinical laboratories in the United States use visual inspection instead of spectrophotometry to evaluate for xanthochromia 3.