Home Medicine Evaluation of revised UK-NEQAS CSF-xanthochromia method for subarachnoid hemorrhage: outcome data provide evidence for clinical value
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Evaluation of revised UK-NEQAS CSF-xanthochromia method for subarachnoid hemorrhage: outcome data provide evidence for clinical value

  • Khin Moe Sam ORCID logo EMAIL logo and Hans G. Schneider ORCID logo
Published/Copyright: October 30, 2024

Abstract

Objectives

Subarachnoid haemorrhage (SAH) has a high morbidity and mortality and requires prompt diagnosis. In patients with negative findings on computed-tomogram of the brain (CT-Brain) cerebrospinal fluid (CSF)-xanthochromia is considered the test of choice if performed 12 h or more after symptom onset. We audited the accuracy, usefulness and timing of CSF-xanthochromia testing and the interpretation of equivocal CSF-xanthochromia findings. We also investigated mortality outcomes for defined subsets of patients.

Methods

A retrospective audit of CSF-xanthochromia tests over 8 years was performed. The service uses the revised UK-NEQAS (United Kingdom National External Quality Assessment Service) method.

Results

We analysed 543 cases (F=299, median age 44yrs) with 19 cases (3.5 %) having SAH. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CSF-xanthochromia testing were 100 , 98.1, 65.9, 100 % respectively (equivocal results were counted as positives). 280 cases (F=153, median age 43yrs) had LP performed more than 24 h after the onset of headache (median time to LP=72 h). The sensitivity and specificity of the CSF-xanthochromia were 100 and 97.4 % in this group with NPV 100 % and PPV 66.6 %. 183 (65.4 %) CSF-xanthochromia negative cases in this subgroup had follow up data and survived without SAH occurring in the 12 months follow up.

Conclusions

In this study, supported by followup outcome data, we show that CSF-xanthochromia testing using the revised UK-NEQAS method is fit-for-purpose for the use as a second line test to exclude SAH in patients with negative CT-brain including delayed presentation more than 24 h after headache onset.


Corresponding author: Khin Moe Sam, Clinical Biochemistry Unit, Alfred Pathology Service, Melbourne, VIC, Australia; and School of Clinical Science, Monash University Clayton, Melbourne, VIC, Australia, E-mail:
This paper is based on a poster presentation of intial findings originally given at the 2022 AACB (Australasia Association of Clinical Biochemists) Annual Scientific Meeting.
  1. Research ethics: Ethics approval obtained fromthe Alfred Ethics Committee (Project No: 686/22).

  2. Informed consent: Not applicable.

  3. Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interests: None declared.

  6. Research funding: None declared.

  7. Data availability: Not applicable.

References

1. Cruickshank, A, Auld, P, Beetham, R, Burrows, G, Egner, W, Holbrook, I, et al.. UK NEQAS specialist advisory group for external quality assurance of CSF proteins and biochemistry. Revised national guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage. Ann Clin Biochem 2008;45:238–44. https://doi.org/10.1258/acb.2008.007257. PMID: 18482910.Search in Google Scholar PubMed

2. Beetham, R. National guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage. Ann Clin Biochem 2003;40:481–8. https://doi.org/10.1258/000456303322326399.Search in Google Scholar PubMed

3. Rankin, S, McGuire, J, Chekroud, M, Alakandy, L, Mukhopadhyay, B. Evaluating xanthochromia in the diagnosis of subarachnoid haemorrhage in scotland in the era of modern computed tomography. Scot Med J 2022;67:71–7. https://doi.org/10.1177/00369330211072264.Search in Google Scholar PubMed

4. Perry, JJ, Stiell, IG, Sivilotti, MLA, Bullard, MJ, Hohl, CM, Sutherland, J, et al.. Clinical decision rules to rule out subarachnoid hemorrhage for acute headache. JAMA 2013;310:1248–55. https://doi.org/10.1001/jama.2013.278018.Search in Google Scholar PubMed

5. Singer, RJ, Ogilvy, CS, Rordorf, G. Aneurysmal subarachnoid haemorrhage: Clinical manifestations and diagnosis. In: Biller, J, Rabinstein, AA, Edlow, JA, Goddeau, RP, editors. Waltham (MA): UpToDate Inc; 2023. [Online] [updated 2013 Jul 24; cited 2023 Aug 23]. Available from: https://www.uptodate.com/contents/aneurysmal-subarachnoid-hemorrhage-clinical-manifestations-and-diagnosis.Search in Google Scholar

6. Jones, M, Power, R, Subarachnoid haemorrhage. BMJ best Practice [Internet]. BMJ Publishing Group; 2023. [updated 2023 Jul 04; cited 2023 Aug 23]. Available from: https://bestpractice.bmj.com/topics/en-gb/3000106.Search in Google Scholar

7. Chee, C, Roji, AM, Lorde, N, Divyateja, H, Dow, G, Shah, J, et al.. Excluding subarachnoid haemorrhage within 24 hours: to LP or not to LP? Br J Neurosurg.2021;35: 203–8. https://doi.org/10.1080/02688697.2020.1781055.Search in Google Scholar PubMed

8. Dubosh, NM, Fernanda Bellolio, M, Rabinstein, AA, Edlow, JA. Sensitivity of early brain computed tomography to exclude aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. Stroke 2016;47:750–5. https://doi.org/10.1161/strokeaha.115.011386.Search in Google Scholar PubMed

9. Byyny, RL, Mower, WR, Shum, N, Gabayan, GZ, Fang, S, Baraff, LJ. Sensitivity of noncontrast cranial computed tomography for the emergency department diagnosis of subarachnoid hemorrhage. Ann Emerg Med 2008;51:697–703. https://doi.org/10.1016/j.annemergmed.2007.10.007.Search in Google Scholar PubMed

10. Broder, JS. Comments on ‘sensitivity of noncontrast cranial computed tomography for the emergency department diagnosis of subarachnoid hemorrhage. Ann Emerg Med 2008;52:767–8. https://doi.org/10.1016/j.annemergmed.2008.06.473.Search in Google Scholar PubMed

11. Vermeulen, M, Hasan, D, Blijenberg, BG, Hijdra, A, Van Gijn, J. Xanthochromia after subarachnoid haemorrhage needs No revisitation. J Neurol Neurosurg Psychiatry. 1989;52:826–8. https://doi.org/10.1136/jnnp.52.7.826.Search in Google Scholar PubMed PubMed Central

12. Clarin, M, Petersson, A, Zetterberg, H, Ekblom, K. Detection of subarachnoid haemorrhage with spectrophotometry of cerebrospinal fluid – a comparison of two methods. Clin Chem Lab Med 2022;60:1053–7. https://doi.org/10.1515/cclm-2021-1320.Search in Google Scholar PubMed

13. Wulff, AB, Højgaard, JLS, Hilsted, L. Spectrophotometry of cerebrospinal fluid for xanthochromia is a sensitive and specific test for subarachnoid bleeding but adds little to computed tomography. Scand J Clin Lab Invest 2020;80:681–6. https://doi.org/10.1080/00365513.2020.1846208.Search in Google Scholar PubMed

14. Ahmed, F, Gibbons, S, El-Kadiki, A. CSF xanthochromia: correlation with brain imaging and its usefulness as an out-of-hours test. J Clin Pathol 2014;67:736–8. https://doi.org/10.1136/jclinpath-2014-202193.Search in Google Scholar PubMed

15. Perry, JJ, Sivilotti, MLA, Stiell, IG, Wells, GA, Raymond, J, Mortensen, M, et al.. Should spectrophotometry be used to identify xanthochromia in the cerebrospinal fluid of alert patients suspected of having subarachnoid hemorrhage? Stroke 2006;37:2467–72. https://doi.org/10.1161/01.str.0000240689.15109.47.Search in Google Scholar

16. Chu, K, Hann, A, Greenslade, J, Williams, J, Brown, A. Spectro-photometry or visual inspection to most reliably detect xanthochromiain subarachnoid hemorrhage: systematic review. Ann Emerg Med 2014;64:257–64. https://doi.org/10.1016/j.annemergmed.2014.01.023.Search in Google Scholar PubMed

17. Nagy, K, Skagervik, I, Tumani, H, Petzold, A, Wick, M, Kühn, HJ, et al.. Cerebrospinal fluid analyses for the diagnosis of subarachnoid haemorrhage and experience from a Swedish study. What method is preferable when diagnosing a subarachnoid haemorrhage? Clin Chem Lab Med 2013;51:2073–86. https://doi.org/10.1515/cclm-2012-0783.Search in Google Scholar PubMed

18. MedCalc Software Ltd. Diagnostic test evaluation calculator. Version 22.009 https://www.medcalc.org/calc/diagnostic_test.php [Accessed 27 Aug 2023].Search in Google Scholar

19. China, M, Matloob, SA, Samir, A, Grieve, JP, Toma, AK. The value of repeated lumbar puncture to test for xanthochromia, in patients with clinical suspicion of subarachnoid haemorrhage, with CT-negative and initial traumatic tap. Br J Neurosurg 2021;35:476–9. https://doi.org/10.1080/02688697.2021.1875398.Search in Google Scholar PubMed

20. Leblanc, RJ. The minor leak preceding subarachnoid hemorrhage. J Neurosurg 1987;66:35–9. https://doi.org/10.3171/jns.1987.66.1.0035.Search in Google Scholar PubMed

21. Hann, A, Chu, K, Greenslade, J, Williams, J, Brown, A. Benefit of cerebrospinal fluid spectrophotometry in the assessment of CT scan negative suspected subarachnoid haemorrhage: a diagnostic accuracy study. J Clin Neurosci 2015;22:173–9. https://doi.org/10.1016/j.jocn.2014.07.025.Search in Google Scholar PubMed

22. Martin, S, Page, M, Godber, I, McGregor, C. CSF xanthochromia analysis takes longer following centralisation of the laboratories testing samples - how can we improve the time to result? BMJ Open Qual 2013;2. https://doi.org/10.1136/bmjquality.u202450.w1177.Search in Google Scholar PubMed PubMed Central

23. Müller, T, Sandvei, MS, Kvistad, KA, Rydland, J, Håberg, A, Vik, A, et al.. Unruptured intracranial aneurysms in the Norwegian nord-trøndelag health study (HUNT): risk of rupture calculated from data in a population-based cohort study. Neurosurgery 2013;73:256–61. https://doi.org/10.1227/01.neu.0000430295.23799.16.Search in Google Scholar PubMed

24. Siddiq, F, Khan, AS. Perimesencephalic nonaneurysmal subarachnoid hemorrhoage. In: Biller, J, Rabinstein, AA, editors. Waltham (MA): UpToDate Inc; 2023. [Internet] [updated 2023 Mar 23; cited 2024 Apr 09]. Available from: https://www.uptodate.com/contents/1114.Search in Google Scholar

Received: 2024-05-06
Accepted: 2024-08-27
Published Online: 2024-10-30
Published in Print: 2025-03-26

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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