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.
Similar content being viewed by others
References
Edlow JA, Bruner KS, Horowitz GL. Xanthochromia. Arch Pathol Lab Med 2002;126:413–415.
Judge B, Laboratory Analysis of xanthochromia in patients with suspected subarachnoid hemorrhage: a national survey: Pa: Scientific Assembly, American College of Physicians, 2000
Petzold A, Keir G, Sharpe LT. Spectrophotometry for xanthochromia. N Engl J Med 2004;351:1695–1696
Petzold A, Keir G, Sharpe TL. Why human color vision cannot reliably detect cerebrospinal fluid xanthochromia. Stroke 2005, 36:1295–1297.
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.
Edlow JA Diagnosis of subarachnoid hemorrhage. Neuroerit Care 2005;2:99–109.
Barrows LJ, Hunter FT, Banker BQ. The nature and clinical significance of pigments in the cerebrospinal fluid. Brain 1955;78:59–80.
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.
Edlow JA, Caplan LR, Avoiding pitfalls in the diagnosis of subarachnoid hemorrhage. N Engl J Med 2000:342:29–36.
UK NEQAS. National guidelines for analysis of crebrosoinal fluid for bilirubin in suspected subarachnoid haemorrhage. Ann Clin Biochem 2003;40:481–488.
Shah KH, Edlow JA. Distinguishing traumatic lumbar puncture from true subarachnoid hemorrhage. J Emerg Med 2002;23:67–74.
van Gijn J. Slip-ups in diagnosis of subarachnoid haemorrhage Lancet 1997;349:1492.
Vermeulen M, van Gijn J. The diagnosis of subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 1990;53:365–372.
Wahlgren NG, Lindquist C. Haem derivates in the cerebrospinal fluid after intracranial haemorrhage. Eur Neurol 1987;26:216–221.
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.
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.
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.
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.
van Gijn J, Rinkel GJ. Subarachnoid haemorrhage: diagnosis, causes and management. Brain 2001;124:249–278.
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.
van Gijn J, van Dongen KJ. The time course of aneurysmal haemorrhage on computed tomograms. Neuroradiology 1982;23:153–156.
Adams HP, Kassel NF, Torner JC, et al. CT and clinical correlatrons the Co-operative Aneurysm Study. Neurology 1983;33:981–988.
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.
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.
Wood MJ, Dimeski G, Nowitzke AM. CSF spectrophotometry in the diagnosis and exclusion of spontaneous subarachnoid haemorrhage. J Clin Neurosci 2005;12:142–146.
Berstad AE, Bo SH, Sortland O. [Cerebral computer tomography in subarachnoid hemorrhage]. Tidsskr Nor Laegeforen 2002;122: 267–271.
Cruickshank A, Beetham R, Holbrook I, et al. Spectrophotometry of cerebrospinal fluid in suspected subarachnoid haemorrhage. BMJ 2005;330:138.
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.
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.
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.
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.
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.
Mitchell P, Wilkinson ID, Hoggard N, et al. Detection of subarachnoid haemorrhage with magnetic resonance imaging. J Neurol Neurosurg Psychiatry 2001;70:205–211.
Rumboldt Z, Kalousek M, Castillo M: Hyperacute subarachnoid hemorrhage on T2-weighted MR images. AJNR Am J Neuroradiol 2003;24:472–475.
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.
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.
Quincke, H. Die Lumbalpunktion des Hydrocephalus. Berliner Klinische Wochenschrift 1891;28:929–932.
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.
Marton KI, Gean AD. The spinal tap: a new look at an old test. Ann Intern Med 1986;104:840–848.
Kjellin KG, Soderstrom CE. Diagnostic significance of CSF spectrophotometry in cerebrovascular diseases. J Neurol Sci 1974;23: 359–369.
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.
Boring EG. Sensation and perception in the history of experimental psychology. New York: Appleton-Century-Crofts, 1942.
Wright WD, Pitt FHG. Hue discrimination in normal colour-vision. Proceedings of the Physical Society (London) 1934;46:459–473.
Chevreul ME. De la loi du contraste simultane des couleurs. Pitois Levreault (Paris) 1839.
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.
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.
Petzold A, Sharpe LT. Hue memory and discrimination in young children. Vision Res 1998;38:3759–3772.
Soderstrom CE. Diagnostic significance of CSF spectrophotometry and computer tomography in cerebrovascular disease: A comparative study in 231 cases. Stroke 1977;8:606–612.
Chalmers AH, Cerebrospinal fluid xanthochromia testing simplified. Clin Chem 2001;47:147–148.
Chalmers AH, Kiley M. Detection of xanthochromia in cerebrospinal fluid. Clin Chem 1998;44:1740–1742.
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.
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.
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.
Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 1980;6:1–9.
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.
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.
Wahlgren NG, Bergstrom K. Determination of haem derivatives in the cerebrospinal fluid-a. J Neurol Neurosurg Psychiatry 1983;46:653–658.
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.
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.
Stroes JW, van Rijn HJ. Quantitative measurement of blood pigments in cerebrospinal fluid by derivative spectrophotometry. Ann Clin Biochem 1987;24(Pt2):189–197.
Gillingham FJ. The management of ruptured intracranial aneurysm. Ann R Coll Surg (English) 1958:23:89–117.
Janjua N, Mayer SA. Cerebral vasospasm after subarachnoid hemorrhage. Curr Opin Crit Care 2003;9:113–119.
Weir B, Grace M, Hansen J, Rothberg C. Time course of vasospasm in man. J Neurosurg 1978;48:173–178.
Keir G, Tasdemir N, Thompson EJ. Cerebrospinal-fluid ferritin in brain necrosis-evidence for local synthesis. Clin Chim Acta 1993;216:153–166.
Campbell DR, Skikne BS, Cook JD. Cerebrospinal fluid ferritin levels in screening for meningism. Arch Neurol 1986;43:1257–1260.
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.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Rights 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
Issue Date:
DOI: https://doi.org/10.1385/NCC:4:2:153