Features of diagnosing cerebrospinal fluid leak in patients with severe traumatic brain injury

Background. The frequency of traumatic cerebrospinal fluid (CSF) leaks in fractures of the skull base is 33–40 %, intracranial purulent complications occur in 10–37 % of cases, and mortality rate is 30 % even with antibiotic therapy. The difficulty of diagnosing CSF leaks in patients with severe traumatic brain injury is caused by several factors: impossibility of gathering complaints from a patient with decreased alertness; difficulty to position a patient for instrumental diagnostics due to concomitant injuries; artificial ventilation; cerebrospinal fluid leak being masked by hemorrhagic secretions from the nose.

Aim. To review the effectiveness of various diagnostic methods and algorithms for detection of cerebrospinal fluid leak and to access their feasibility in cases of potentially penetrating traumatic brain injury.

Results. The study identified the main challenges of diagnosing cerebrospinal fluid leaks in intensive care patients, including difficulties in  performing invasive neuroimaging methods, challenges in collecting nasal secretions for laboratory detection of CSF-specific markers, and the absence of fluorescein approved for intrathecal use in the Russian Federation. It was established that in severe cases, the most informative methods are brain CT and glucose oxidase test with radionuclide cisternography recommended in cases of uncertain results. Upon confirmation of cerebrospinal fluid leak, endoscopic nasal cavity revision and, if necessary, CSF fistula repair are advised.

Conclusion. The findings emphasize the need for further research and refinement of diagnostic algorithms to improve the accuracy of traumatic CSF leak detection in patients with severe traumatic brain injuries.

1. Schlosser R.J., Bolger W.E. Nasal cerebrospinal fluid leaks: critical review and surgical considerations. Laryngoscope 2004;114(2): 255–65. DOI: 10.1097/00005537-200402000-00015

2. Krylov V.V., Talypov A.E., Grin A.A., Levchenko O.V. Surgery for severe traumatic brain injury. Moscow: ABV-press, 2022. 880 p. (In Russ.).

3. Krylov V.V. Lectures on traumatic brain injury. M.: Medicine, 2010. 320 p. (In Russ.).

4. Teng T.S., Ishak N.L., Subha S.T., Bakar S.A. Traumatic transnasal penetrating injury with cerebral spinal fluid leak. EXCLI J 2019;18:223–8. DOI: 10.17179/excli2018-1971

5. Shao X., Wang Q., Shen J. et al. Treatment of traumatic depressed compound skull fractures. J Craniofac Surg 2019;30(7):2239–44. DOI: 10.1097/SCS.0000000000005982

6. Lloyd K.M., DelGaudio J.M., Hudgins P.A. Imaging of skull base cerebrospinal fluid leaks in adults. Radiology 2008;248(3):725–36. DOI: 10.1148/radiol.2483070362

7. Rocchi G., Caroli E., Belli E. et al. Severe craniofacial fractures with frontobasal involvement and cerebrospinal fluid fistula: Indications for surgical repair. Surg Neurol 2005;63(6):559–63. DOI: 10.1016/j.surneu.2004.07.047

8. Scholsem M., Scholtes F., Collignon F. et al. Surgical management of anterior cranial base fractures with cerebrospinal fluid fistulae: A single-institution experience. Neurosurgery 2008;62(2):463–471. DOI: 10.1227/01.neu.0000316014.97926.82

9. Yilmazlar S., Arslan E., Kocaeli H. et al. Cerebrospinal fluid leakage complicating skull base fractures: Analysis of 81 cases. Neurosurgical Review 2006;29(1):64–71. DOI: 10.1007/s10143-005-0396-3

10. Daudia A., Biswas D., Jones N.S. Risk of meningitis with cerebrospinal fluid rhinorrhea. Ann Otol Rhinol Laryngol 2007;116(12):902–5. DOI: 10.1177/000348940711601206

11. Wormald P.J., McDonogh M. The bath-plug closure of anterior skull base cerebrospinal fluid leaks. Am J Rhinol 2003;17(5):299–305. PMID: 14599134

12. Chan D.T., Poon W.S., Ip C.P. et al. How useful is glucose detection in diagnosing cerebrospinal fluid leak? The rational use of CT and Beta-2 transferrin assay in detection of cerebrospinal fluid fistula. Asian J Surg 2004;27(1):39–42. DOI: 10.1016/S1015-9584(09)60242-6

13. Steedman D.J., Gordon M. CSF rhinorrhoeae: Significance of the glucose oxidase strip test. Injury 1987;18(5):327–8. DOI: 10.1016/0020-1383(87)90053-2

14. Katz R.T., Kaplan P.E. Glucose oxidase sticks and cerebrospinal fluid rhinorrhea. Arch Phys Med Rehabil 1985;66(6):391–3. PMID: 4004538

15. Wood D.M., Brennan A.L., Philips B.J., Baker E.H. Effect of hyperglycaemia on glucose concentration of human nasal secretions. Clin Sci (Lond) 2004;106(5):527–33. DOI: 10.1042/CS20030333

16. Baker E.H., Wood D.M., Brennan A.L. et al. New insights into the glucose oxidase stick test for cerebrospinal fluid rhinorrhoea. Emerg Med J 2005;22:556–7. DOI: 10.1136/emj.2004.022111

17. Görögh T., Rudolph P., Meyer J.E. et al. Separation of beta2- transferrin by denaturing gel electrophoresis to detect cerebrospinal fluid in ear and nasal fluids. Clin Chem 2005;51(9):1704–10. DOI: 10.1373/clinchem.2005.054916

18. McCudden C.R., Senior B.A., Hainsworth S. et al. Evaluation of high resolution gel beta(2)-transferrin for detection of cerebrospinal fluid leak. Clin Chem Lab Med 2013;51:311–5. DOI: 10.1515/cclm-2012-0408

19. Korem M., Ovadia H., Paldor I. et al. False negative бета-2 transferrin in the diagnosis of cerebrospinal fluid leak in the presence of Streptococcus pneumoniae. Laryngoscope 2015;125(3):556–60. DOI: 10.1002/lary.24940

20. Bachmann-Harildstad G. Diagnostic values of beta-2 transferrin and beta-trace protein as markers for cerebrospinal fluid fistula. Rhinology 2008;46(2):82–5. PMID: 18575006

21. Schnabel C., Di Martino E., Gilsbach J.M. Comparison of beta2- transferrin and beta-trace protein for detection of cerebrospinal fluid in nasal and ear fluids. Clin Chem 2004;50(3):661–3. DOI: 10.1373/clinchem.2003.024158

22. Bleier B.S., Debnath I., O’Connell B.P. et al. Preliminary study on the stability of beta-2 transferrin in extracorporeal cerebrospinal fluid. Otolaryngol Head Neck Surg 2011;144:101–3. DOI: 10.1177/0194599810390887

23. Meco C., Oberascher G., Arrer E. et al. Beta-trace protein test: new guidelines for the reliable diagnosis of cerebrospinal fluid fistula. Otolaryngol Head Neck Surg 2003;129(5):508–17. DOI: 10.1016/s0194-5998(03)01448-7

24. Jeppsson Z.H. Tau in biofluids—relation to pathology, imaging and clinical features. Neuropathol Appl Neurobiol 2017;43:194–9. DOI: 10.1111/nan.12378

25. Hiremath S.B., Gautam A.A., Sasindran V. et al. Cerebrospinal fluid rhinorrhea and otorrhea: A multimodality imaging approach. Diagn Interv Imaging 2019;100(1):3–15. DOI: 10.1016/j.diii.2018.05.003

26. Reiber H. Dynamics of brain-derived proteins in cerebrospinal fluid. Clin Chim Acta 2001;310(2):173–86. DOI: 10.1016/s0009-8981(01)00573-3

27. Stone J.A., Castillo M., Neelon B., Mukherji S.K. Evaluation of CSF leaks: High-resolution CT compared with contrastenhanced CT and radionuclide cisternography. AJNR Am J Neuroradiol 1999;20(4):706–12. PMID: 10319986

28. Mostafa B.E., Khafagi A. Combined HRCT and MRI in the detection of CSF rhinorrhea. Skull Base 2004;14:157–162.

29. Zuckerman J.D., DelGaudio J.M. Utility of preoperative highresolution CT and intraoperative image guidance in identification of cerebrospinal fluid leaks for endoscopic repair. Am J Rhinol 2008;22:151–4.

30. La Fata V., McLean N., Wise S.K. et al. CSF leaks: Correlation of high-resolution CT and multiplanar reformations with intraoperative endoscopic findings. AJNR Am J Neuroradiol 2008;29(3):536–41. DOI: 10.3174/ajnr.A0885

31. Shetty P.G., Shroff M.M., Sahani D.V., Kirtane M.V. Evaluation of high-resolution CT and MR cisternography in the diagnosis of cerebrospinal fluid fistula. AJNR Am J Neuroradiol 1998;19:633–9.

32. Goel G., Ravishankar S., Jayakumar P.N. et al. Intrathecal gadolinium-enhanced magnetic resonance cisternography in cerebrospinal fluid rhinorrhea: Road ahead? J Neurotrauma 2007;24:1570–5.

33. Ozgen T., Tekkok I.H., Cila A., Erzen C. CT cisternography in evaluation of cerebrospinal fluid rhinorrhea. Neuroradiology 1990;32:481–4.

34. Mamo L., Cophignon J., Rey A. et al. A new radionuclide method for the diagnosis of posttraumatic cerebrospinal fistulas. A study of 308 cases. J Neurosurg 1982;57:92–8.

35. Flynn B.M., Butler S.P., Quinn R.J. et al. Radionuclide cisternography in the diagnosis and management of cerebrospinal fluid leaks: The test of choice. Med J Aust 1987;146:82–4. PMID: 3540552

36. DelGaudio J.M., Baugnon K.L., Wise S.K. et al. Magnetic resonance cisternogram with intrathecal gadolinium with delayed imaging for difficult to diagnose cerebrospinal fluid leaks of anterior skull base. Int Forum Allergy Rhinol 2015;5(4):333–8. DOI: 10.1002/alr.21475

37. Keerl R., Weber R.K., Draf W. et al. Use of sodium fluorescein solution for detection of cerebrospinal fluid fistulas: an analysis of 420 administrations and reported complications in Europe and the United States. Laryngoscope 2004;114(2):266–72. DOI: 10.1097/00005537-200402000-00016

38. Xie T., Sun W., Zhang X. et al. The value of 3D-FIESTA MRI in detecting non-iatrogenic cerebrospinal fluid rhinorrhoea: Correlations with endoscopic endonasal surgery. Acta Neurochir (Wien) 2016;158:2333–9. DOI: 10.1007/s00701-016-2988-9

39. Sillers M.J., Morgan C.E., El Gammal T. Magnetic resonance cisternography and thin coronal computerized tomography in the evaluation of cerebrospinal fluid rhinorrhea. Am J Rhinol 1997;11:387–92. DOI: 10.2500/105065897781286052

40. Shu Z., Cheng L., Yang J. [Etiology and treatment strategy of spontaneous cerebrospinal fluid rhinorrhea]. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Journal of clinical otorhinolaryngology head and neck surgery 2020;34(6):573–6. (In Chin.). DOI: 10.13201/j.issn.2096-7993.2020.06.022

41. Algin O., Hakyemez B., Gokalp G. et al. The contribution of 3DCISS and contrast-enhanced MR cisternography in detecting cerebrospinal fluid leak in patients with rhinorrhoea. Br J Radiol 2010;83:225–32. DOI: 10.1259/bjr/56838652

42. Kapitanov D.N., Lopatin A.S., Potapov A.A. Endoscopic diagnosis and treatment of nasal liquorrhea. M.: Prakticheskaya meditsina, 2015. Рp. 89–92. (In Russ.).

43. Constanzo F., Pinto J., Sedaghat S., Schmidt T. Pseudocerebrospinal fluid leaks of the anterior skull base: Algorithm for diagnosis and management. J Neurol Surg B Skull Base 2021;82(3):351–6. DOI: 10.1055/s-0039-3399519

44. Lloyd M.N., Kimber P.M., Burrows E.H. Posttraumatic cerebrospinal fluid rhinorrhoea: Modern high-definition computed tomography is all that is required for the effective demonstration of the site of leakage. Clin Radiol 1994;49:100–3. DOI: 10.1016/s0009-9260(05)83449-x

45. Zapalac J.S., Marple B.F., Schwade N.D. Skull base cerebrospinal fluid fistulas: A comprehensive diagnostic algorithm. Otolaryngol Head Neck Surg 2002;126:669–76. DOI: 10.1067/mhn.2002.125755/

46. Oakley G.M., Alt J.A., Schlosser R.J. et al. Diagnosis of cerebrospinal fluid rhinorrhea: An evidence-based review with recommendations. Int Forum Allergy Rhinol 2016;6:8–16. DOI: 10.1002/alr.21637