Skip to main content
Log in

Spectrophotometry for cerebrospinal fluid pigment analysis

  • Review
  • Published:
Neurocritical Care Aims and scope Submit manuscript

Abstract

The use of spectrophotometry for the analysis of the cerebrospinal fluid (CSF) is reviewed The clinically relevant CSF pigments—oxyhemoglobin and bilirubin—are introduced and discussed with regard to clinical differential diagnosis and potentially confounding variables (the four T's: traumatic tap, timing, total protein and total bilirubin). The practical laboratory aspects of spectrophotometry and automated techniques are presented in the context of analytical and clinical specificity and sensitivity. The perceptual limitations of human color vision are highlighted and the use of visual assessment of the CSF is discouraged in light of recent evidence from a national audit in the United Kingdom. Finally, future perspectives including the need for longitudinal CSF profiling and routine spectrophotometric calibration are outlined.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Edlow JA, Bruner KS, Horowitz GL. Xanthochromia. Arch Pathol Lab Med 2002;126:413–415.

    PubMed  Google Scholar 

  2. Judge B, Laboratory Analysis of xanthochromia in patients with suspected subarachnoid hemorrhage: a national survey: Pa: Scientific Assembly, American College of Physicians, 2000

  3. Petzold A, Keir G, Sharpe LT. Spectrophotometry for xanthochromia. N Engl J Med 2004;351:1695–1696

    Article  PubMed  CAS  Google Scholar 

  4. Petzold A, Keir G, Sharpe TL. Why human color vision cannot reliably detect cerebrospinal fluid xanthochromia. Stroke 2005, 36:1295–1297.

    Article  PubMed  Google Scholar 

  5. Beetham R, Fahie-Wilson MN, Park D. What is the role of CSF spectrophotometry in the diagnosis of subarachnoid haemorrhage? Ann Clin Biochem 1998;35:1–4.

    PubMed  Google Scholar 

  6. Edlow JA Diagnosis of subarachnoid hemorrhage. Neuroerit Care 2005;2:99–109.

    Article  Google Scholar 

  7. Barrows LJ, Hunter FT, Banker BQ. The nature and clinical significance of pigments in the cerebrospinal fluid. Brain 1955;78:59–80.

    Article  PubMed  CAS  Google Scholar 

  8. Buruma OJS, Janson H, Den Bergh F, Bots G. Blood-stained cere brospinal fluid: traumatic puncture or haemorrhage? J Neurol Neurosurg Psychiatry 1981;44:144–147.

    PubMed  CAS  Google Scholar 

  9. Edlow JA, Caplan LR, Avoiding pitfalls in the diagnosis of subarachnoid hemorrhage. N Engl J Med 2000:342:29–36.

    Article  PubMed  CAS  Google Scholar 

  10. UK NEQAS. National guidelines for analysis of crebrosoinal fluid for bilirubin in suspected subarachnoid haemorrhage. Ann Clin Biochem 2003;40:481–488.

    Article  Google Scholar 

  11. Shah KH, Edlow JA. Distinguishing traumatic lumbar puncture from true subarachnoid hemorrhage. J Emerg Med 2002;23:67–74.

    Article  PubMed  Google Scholar 

  12. van Gijn J. Slip-ups in diagnosis of subarachnoid haemorrhage Lancet 1997;349:1492.

    Article  PubMed  Google Scholar 

  13. Vermeulen M, van Gijn J. The diagnosis of subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 1990;53:365–372.

    PubMed  CAS  Google Scholar 

  14. Wahlgren NG, Lindquist C. Haem derivates in the cerebrospinal fluid after intracranial haemorrhage. Eur Neurol 1987;26:216–221.

    PubMed  CAS  Google Scholar 

  15. van der Wee N Rinkel GJ, Hasan D, van Gijn J. Detection of subarachnoid haemorrhage on early CT: is lumbar puncture still needed after a negative scan? J Neurol Neurosurg Psychiatry 1995;58:357–359.

    PubMed  Google Scholar 

  16. Vermeulen M, Hasan D, Blijenberg BG, Hijdra A, van Gijn J. Xanthochromia after subarachnoid haemorrhage needs no revisitation. J Neurol Neurosurg Psychiatry 1989;52:826–828.

    PubMed  CAS  Google Scholar 

  17. Linn FH, Rinkel GJ, Algra A, van Gijn J. Incidence of subarachnoid hemorrhage: role of region, year, and rate of computed tomography: a meta-analysis. Stroke 1996:27:625–629.

    PubMed  CAS  Google Scholar 

  18. Mayberg MR, Batjer HH, Dacey R, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage. A statement for healthcare professionals from a special writing group of the stroke Council, American Heart Association. Stroke 1994;25: 2315–2328.

    PubMed  CAS  Google Scholar 

  19. van Gijn J, Rinkel GJ. Subarachnoid haemorrhage: diagnosis, causes and management. Brain 2001;124:249–278.

    Article  PubMed  Google Scholar 

  20. Molyneux A, Kerr R, Stratton I, et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 2003;360:1267–1274.

    Article  Google Scholar 

  21. van Gijn J, van Dongen KJ. The time course of aneurysmal haemorrhage on computed tomograms. Neuroradiology 1982;23:153–156.

    PubMed  Google Scholar 

  22. Adams HP, Kassel NF, Torner JC, et al. CT and clinical correlatrons the Co-operative Aneurysm Study. Neurology 1983;33:981–988.

    PubMed  Google Scholar 

  23. MacDonald A, Mendelow AD. Xanthochromia revisited: a reevaluation of lumbar puncture and CT scanning in the diagnosis of subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 1988;51:342–344.

    PubMed  CAS  Google Scholar 

  24. Edlow JA, Wyer PC. Evidence-based emergency medicine/clinical question. how good is a negative cranial computed tomographic scan result in excluding subarachnoid hemorrhage? Ann Emerg Med 2000;36:507–516.

    PubMed  CAS  Google Scholar 

  25. Wood MJ, Dimeski G, Nowitzke AM. CSF spectrophotometry in the diagnosis and exclusion of spontaneous subarachnoid haemorrhage. J Clin Neurosci 2005;12:142–146.

    Article  PubMed  CAS  Google Scholar 

  26. Berstad AE, Bo SH, Sortland O. [Cerebral computer tomography in subarachnoid hemorrhage]. Tidsskr Nor Laegeforen 2002;122: 267–271.

    PubMed  Google Scholar 

  27. Cruickshank A, Beetham R, Holbrook I, et al. Spectrophotometry of cerebrospinal fluid in suspected subarachnoid haemorrhage. BMJ 2005;330:138.

    Article  PubMed  Google Scholar 

  28. Gunawardena H, Beetham R, Scolding N, Lhatoo SD, Is cerebrospinal fluid spectrophotometry useful in CT scan-negative suspected subarachnoid hemorrage? Eur Neurol 2004;52:226–229.

    Article  PubMed  CAS  Google Scholar 

  29. Sidman R, Connolly E, Lemke T. Subarachnoid hemorrhage diagnosis: lumbar puncture is still needed when the computed tomography scan is normal. Acad Emerg Med 1996;3:827–831.

    PubMed  CAS  Google Scholar 

  30. Noguchi K, Ogawa T, Seto H, et al. Subacute and chronic subarachnoid hemorrhage: diagnosis with fluid-attenuated inversion-recovery MR imaging. Radiology 1997;203:257–262.

    PubMed  CAS  Google Scholar 

  31. Ogawa T, Inugami A, Fujita H, et al. MR diagnosis of subacute and chronic subarachnoid hemorrhage: comparison with CT. AIR Am J Roentgenol 1995;165:1257–1262.

    CAS  Google Scholar 

  32. Griffiths PD, Wilkinson ID, Mitchell P, et al. Multimodality MR imaging depiction of hemodynamic changes and cerebral ischemia in subarachnoid hemorrhage. AJNR Am J Neuroradiol 2001;22:1690–1697.

    PubMed  CAS  Google Scholar 

  33. Mitchell P, Wilkinson ID, Hoggard N, et al. Detection of subarachnoid haemorrhage with magnetic resonance imaging. J Neurol Neurosurg Psychiatry 2001;70:205–211.

    Article  PubMed  CAS  Google Scholar 

  34. Rumboldt Z, Kalousek M, Castillo M: Hyperacute subarachnoid hemorrhage on T2-weighted MR images. AJNR Am J Neuroradiol 2003;24:472–475.

    PubMed  Google Scholar 

  35. Wiesmann M, Mayer TE, Yousry I, Medele R, Hamann GF, Bruckmann H. Detection of hyperacute subarachnoid hemorrhage of the brain by using magnetic resonance imaging. J Neurosurg 2002;96:684–689.

    PubMed  Google Scholar 

  36. Woodcock RJ Jr, Short J, Do HM, Jensen ME, Kallmes DF. Imaging of acute subarachnoid hemorrhage with a fluid-attenuated inversion recovery sequence in an animal model: comparison with non-contrast enhanced CT. AJNR Am J Neuroradiol 2001; 22:1698–2303.

    PubMed  Google Scholar 

  37. Quincke, H. Die Lumbalpunktion des Hydrocephalus. Berliner Klinische Wochenschrift 1891;28:929–932.

    Google Scholar 

  38. Eskey CJ, Ogilvy CS. Fluoroscopy-guided lumbar puncture: decreased frequency of traumatic tap and implications for the assessment of CT-negative acute subarachnoid hemorrhage. AJNR Am J Neuroradiol 2001;22:571–576.

    PubMed  CAS  Google Scholar 

  39. Marton KI, Gean AD. The spinal tap: a new look at an old test. Ann Intern Med 1986;104:840–848.

    PubMed  CAS  Google Scholar 

  40. Kjellin KG, Soderstrom CE. Diagnostic significance of CSF spectrophotometry in cerebrovascular diseases. J Neurol Sci 1974;23: 359–369.

    Article  PubMed  CAS  Google Scholar 

  41. Tourtelotte WW, Metz LN, Bryan ER, DeJong RN. Spontaneous subarachnoid hemorrhage—Factors affecting the rate of clearing of the cerebrospinal fluid. Neurology 1964;14:302–306.

    Google Scholar 

  42. Boring EG. Sensation and perception in the history of experimental psychology. New York: Appleton-Century-Crofts, 1942.

    Google Scholar 

  43. Wright WD, Pitt FHG. Hue discrimination in normal colour-vision. Proceedings of the Physical Society (London) 1934;46:459–473.

    Article  Google Scholar 

  44. Chevreul ME. De la loi du contraste simultane des couleurs. Pitois Levreault (Paris) 1839.

  45. Stockman A, Sharpe LT. Spectral sensitivities of the middle-and long-wavelength sensitive cones derived from measurements in observers of known genotype. Vision Res 2000;40:1711–1737.

    Article  PubMed  CAS  Google Scholar 

  46. Linn FH, Voorbij HA, Rinkel GJ, Algra A, van Gijn J. Visual inspection versus spectrophotometry in detecting bilirubin in cerebrospinal fluid. J Neurol Neurosurg Psychiatry 2005;76: 1452–1454.

    Article  PubMed  CAS  Google Scholar 

  47. Petzold A, Sharpe LT. Hue memory and discrimination in young children. Vision Res 1998;38:3759–3772.

    Article  PubMed  CAS  Google Scholar 

  48. Soderstrom CE. Diagnostic significance of CSF spectrophotometry and computer tomography in cerebrovascular disease: A comparative study in 231 cases. Stroke 1977;8:606–612.

    PubMed  CAS  Google Scholar 

  49. Chalmers AH, Cerebrospinal fluid xanthochromia testing simplified. Clin Chem 2001;47:147–148.

    PubMed  CAS  Google Scholar 

  50. Chalmers AH, Kiley M. Detection of xanthochromia in cerebrospinal fluid. Clin Chem 1998;44:1740–1742.

    PubMed  CAS  Google Scholar 

  51. Ungerer JPJ, Southby SH, Florkowski M, George PM. Automated measurement of cerebrospinal fluid bilirubin in suspected subarachnoid hemorrhage. Clin Chem 2004;50(10):1854–1856.

    Article  PubMed  CAS  Google Scholar 

  52. Chan KM, Scott MG, Wu TW, et al. Inaccurate values for direct bilirubin with some commonly used direct bilirubin procedures. Clin Chem 1985;31:1560–1563.

    PubMed  CAS  Google Scholar 

  53. Patel D, White P, Egner W, Beetham R. National guidelines for analysis of CSF bilirubin and their impact. Proceedings of the ACB National Meeting, ISSN 0959-9029;116, 18-20 May 2005.

  54. Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 1980;6:1–9.

    Article  PubMed  CAS  Google Scholar 

  55. Rejdak K, Petzold A, Sharpe MA, et al. Cerebrospinal fluid nitrite/ nitrate correlated with oxyhemoglobin and outcome in patients with subarachnoid hemorrhage. J Neurol Sci 2004;219:71–76.

    Article  PubMed  CAS  Google Scholar 

  56. Pluta RM, Afshar JK, Boock RJ, Oldfield EH, Temporal changes in perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin after subarachnoidhem orrhage. J Neurosurg 1998;88:557–561.

    Article  PubMed  CAS  Google Scholar 

  57. Wahlgren NG, Bergstrom K. Determination of haem derivatives in the cerebrospinal fluid-a. J Neurol Neurosurg Psychiatry 1983;46:653–658.

    PubMed  CAS  Google Scholar 

  58. Duiser HJ, Roelandse FW, Lentjes EG, van Loon J, Souverijn JH, Sturk A. Iterative model for the calculation of oxyhemoglobin. methemoglobin, and bilirubin in absorbance spectra of cerebro spinal fluid. Clin Chem 2001;47:338–341.

    PubMed  CAS  Google Scholar 

  59. Laterza OF, Smith CH, Wilhite TR, Landt M. Accurate direct spectrophotometric bilirubin measurement combined with blood gas analysis. Clin Chim Acta 2002;323:115–120.

    Article  PubMed  CAS  Google Scholar 

  60. Stroes JW, van Rijn HJ. Quantitative measurement of blood pigments in cerebrospinal fluid by derivative spectrophotometry. Ann Clin Biochem 1987;24(Pt2):189–197.

    PubMed  CAS  Google Scholar 

  61. Gillingham FJ. The management of ruptured intracranial aneurysm. Ann R Coll Surg (English) 1958:23:89–117.

    CAS  Google Scholar 

  62. Janjua N, Mayer SA. Cerebral vasospasm after subarachnoid hemorrhage. Curr Opin Crit Care 2003;9:113–119.

    Article  PubMed  Google Scholar 

  63. Weir B, Grace M, Hansen J, Rothberg C. Time course of vasospasm in man. J Neurosurg 1978;48:173–178.

    PubMed  CAS  Google Scholar 

  64. Keir G, Tasdemir N, Thompson EJ. Cerebrospinal-fluid ferritin in brain necrosis-evidence for local synthesis. Clin Chim Acta 1993;216:153–166.

    Article  PubMed  CAS  Google Scholar 

  65. Campbell DR, Skikne BS, Cook JD. Cerebrospinal fluid ferritin levels in screening for meningism. Arch Neurol 1986;43:1257–1260.

    PubMed  CAS  Google Scholar 

  66. Gruener N, Gozlan O, Goldstein T, Davis J, Besner I, Iancu TC. Tron, transferrin and ferritin in cerebrospinal fluid of children. Clin Chem 1991;37:263–265.

    PubMed  CAS  Google Scholar 

  67. Hallgren R, Terent A, Wide ssL, Birgegard G. Cerebrospinal fluid ferritin in patients with cerebral infarction or bleeding. Acta Neurol Scand 1980;61:384–392.

    Article  PubMed  CAS  Google Scholar 

  68. Sindic CJ, Collet-Cassart D, Cambiaso CL, Masson PL, Laterre EC. The clinical relevance of ferritin concentration in the cerebrospinal fluid. J Neurol Neurosurg Psychiatry 1981;44:320–333.

    Article  Google Scholar 

  69. Petzold A, Sharpe LT. Visual assessment for xanthochroma needs no revisitation. J Neurol Neurosurg Psychiatry 2005:76:http:// jnnp.bmjjournals.com/cgi/eletters/76/10/1452. Date accessed: 11/25/05.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Axel Petzold.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Petzold, A., Sharpe, L.T. & Keir, G. Spectrophotometry for cerebrospinal fluid pigment analysis. Neurocrit Care 4, 153–162 (2006). https://doi.org/10.1385/NCC:4:2:153

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/NCC:4:2:153

Key Words

Navigation