Although xanthochromia literally means yellow color, when it comes to describing the color of the cerebrospinal fluid (CSF), a more liberal—but perhaps misleading— definition of xanthochromia extending to other colors, such as pink and orange, is commonly found in the literature. 1-5
In the presence of red blood cells (RBCs) in the subarachnoid space, as seen in subarachnoid hemorrhage (SAH), 3 pigments are formed by the breakdown of hemoglobin in the CSF: oxyhemoglobin, methemoglobin, and bilirubin. Oxyhemoglobin is typically red but has also been reported to appear orange or orange-yellow with dilution.6 Methemoglobin is brown and bilirubin is yellow. Of these pigments, only bilirubin can be formed solely from in vivo conversion, while oxyhemoglobin and methemoglobin may also form after CSF has been obtained (eg, in tubes). Due to the suboptimal reliability of visual inspection, some have argued for the routine use of spectrophotometry of the CSF instead in patients with suspected SAH.7
In our patient, the “pink xanthochromia” may be related to RBC breakdown either due to a SAH or as a result of hemolysis in the sample tubes themselves, especially if there was a delay in processing the specimen. Even if he had “true xanthochromia” with yellow discoloration of CSF, make sure to exclude other causes besides SAH, such as high CSF protein, hyperbilirubinemia, rifampin therapy, and high carotenoid intake (eg, carrots).
- Seehusen DA, Reeves MM, Fomin DA. Cerebrospinal fluid analysis. Am Fam Phys 2003;68:1103-8. https://www.aafp.org/afp/2003/0915/p1103.pdf
- Edlow JA, Bruner KS, Horowitz GL. Xanthochromia. A survey of laboratory methodology and its clinical implications. Arch Pthol Lab Med 2002;126:413-15.
- Lo BM, Quinn SM. Gross xanthochromia on lumbar puncture may not represent an acute subarachnoid hemorrhage. Am J Emerg Med 2009;27:621-23.
- Koenig M. Approach to the patient with bloody or pigmented cerebrospinal fluid. In Irani DN, ed, Cerebrospinal fluid in clinical practice. 2009. https://doi.org/10.1016/B978-1-4160-2908-3.X0001-6
- Welch H, Hasbun R. Bacterial infections of the central nervous system. In Handbook of Clinical Neurology, 2010. https://www.sciencedirect.com/handbook/handbook-of-clinical-neurology/vol/96/suppl/C
- Barrows LJ, Hunter FT, Banker BQ. The nature and clinical significance of pigments in the cerebrospinal fluid. Brain 1955; 58: 59-80. https://www.ncbi.nlm.nih.gov/pubmed/14378450
- Cruickshank A, Auld P, Beetham R, et al. Revised national guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage. Ann Clin Biochem 2008;45:238-44. https://www.ncbi.nlm.nih.gov/pubmed/18482910
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Although the clinical diagnosis of meningitis is often supported by the presence of abnormal number of WBCs in the CSF (AKA pleocytosis), meningitis may be present despite its absence.
Among viral causes of meningitis in adults, enteroviruses are associated with lower CSF WBC count compared to herpes simplex and varicella zoster, with some patients (~10%) having 0-2 WBC’s/mm31,2. Of interest, among children, parechovirus (formerly echovirus 22 and 23) meningitis is characterized by normal CSF findings3.
Though uncommon, bacterial meningitis without CSF pleocytosis has been reported among non-neutropenic adults, including Neisseria meningitidis, Streptococcus pneumoniae, Hemophilus influenzae, Listeria monocytogenes, E. coli, and Proteus mirabilis4. A European study also reported normal CSF WBC in nearly 10% of patients with Lyme neuroborreliosis (including meningitis) caused primarily by Borrelia garinii5.
Cryptococcal meninigitis may also be associated with normal CSF profile in 25% of patients with HIV infection6.
- Ihekwaba UK, Kudesia G, McKendrick MW. Clinical features of viral meningitis in adult:significant differences in cerebrospinal fluid findings among herpes simplex virus, varicella zoster virus, and enterovirus infections. Clin Infect Dis 2008;47:783-9. https://www.ncbi.nlm.nih.gov/pubmed/18680414
- Dawood N, Desjobert E, Lumley J et al. Confirmed viral meningitis with normal CSF findings. BMJ Case Rep 2014. Doi:10.1136/bcr-2014-203733. http://casereports.bmj.com/content/2014/bcr-2014-203733.abstract
- Wolthers KC, Benschop KSM, Schinkel J, et al. Human parechovirus as an important viral cause of sepsis like illness and meningitis in young children. Clin Infect Dis 2008;47:358-63. https://www.ncbi.nlm.nih.gov/pubmed/18558876
- Hase R, Hosokawa N, Yaegashi M, et al. Bacterial meningitis in the absence of cerebrospinal fluid pleocytosis: A case report and review of the literature. Can J Infect Dis Med Microbiol 2014;25:249:51. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211346/pdf/idmm-25-249.pdf
- Ogrinc K, Lotric-Furlan S, Maraspin V, et al. Suspected early Lyme neuroborreliosis in patients with erythema migrans. Clin Infect Dis 2013; 57:501-9. https://www.ncbi.nlm.nih.gov/pubmed?term=23667259
- Darras-Joly C, Chevret S, Wolff M, et al. Cryptococcus neoformans infection in France: epidemiologic features of and early prognostic parameters for 76 patients who were infected with human immunodeficiency virus. Clin Infect Dis 1996;23:369-76. https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cid/23/2/10.1093/clinids/23.2.369/2/23-2-369.pdf?Expires=1501035620&Signature=FhHMHUHAMmT3rz4ld8QAMet-weu-BWgm5YR6nA4jjSGVGIeaVlMNPgeOkW2fniiel54HQhIs1Kkp3PpzT1glxhJeZvQiGXQCSOoF-jS1SK7S~kBb-oHs4qsIJzN0OJxNAXfoJi4bl7OeKaLTyIE3P8~slwH0BBi7RncSYVgVR4NkOnFpYgn27~wY7pDSUNWvzGFKoSeYGeM0TsAqna-QmXzodITB5bgr1mO6Q6OGUxCsqRwhr6xNb~4G93oqRcsO19gyUluCE0xYt0KbKWuQxJeh8AbtJkNrS08~XInMR50bQZOUb80j0~dtg9jRTGzXQaDllVByoX2Alr48hlhogw__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q