Could Cerebrospinal Fluid Biomarkers Offer Better Predictive Value for Spinal Cord Ischaemia Than Current Neuromonitoring Techniques During Thoracoabdominal Aortic Aneurysm Repair - A Systematic Review

Harky, Amer; Fok, Matthew; Fraser, Holly; Howard, Callum; Rimmer, Lara; Bashir, Mohamad

doi:10.21470/1678-9741-2018-0375

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Brazilian Journal of Cardiovascular Surgery

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Español English

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Sumário

REVIEW ARTICLE • Braz. J. Cardiovasc. Surg. 34 (4) • Jul-Aug 2019 • https://doi.org/10.21470/1678-9741-2018-0375 copy

Could Cerebrospinal Fluid Biomarkers Offer Better Predictive Value for Spinal Cord Ischaemia Than Current Neuromonitoring Techniques During Thoracoabdominal Aortic Aneurysm Repair - A Systematic Review

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective:

Cerebrospinal fluid (CSF) drainage is a technique that has significantly reduced the incidence of spinal cord ischaemia (SCI). We present results of a systematic review to assess the literature on this topic in relation to thoracoabdominal aortic aneurysm repair (TAAR).

Methods:

Major medical databases were searched to identify papers related to CSF biomarkers measured during TAAAR.

Results:

Fifteen papers reported measurements of CSF biomarkers with 265 patients in total. CSF biomarkers measured included S-100ß, neuron-specific endolase (NSE), lactate, glial fibrillary acidic protein A (GFPa), Tau, heat shock protein 70 and 27 (HSP70, HSP27), and proinflammatory cytokines. Lactate and S-100ß were reported the most, but did not correlate with SCI, which was also the case with NSE and TAU. GFPa showed significant CSF level rises, both intra and postoperative in patients who suffered SCI and warrants further investigation, similar results were seen with HSP70, HSP27 and IL-8.

Conclusions:

Although there is significant interest in this topic, there still remains a significant lack of high-quality studies investigating CSF biomarkers during TAAR to detect SCI. A large and multicentre study is required to identify the significant role of each biomarker.

Keywords:
Spinal Cord Ischemia; Thoracic Aortic Aneurysm; Lactic Acid; Cytokines; Biomarkers

Abbreviations, acronyms & symbols
CSF	= Cerebrospinal fluid	MeSH	= Medical subject headings
DTAAR	= Descending thoracic aortic aneurysm repair	NSE	= Neuron-specific endolase
GFPa	= Glial fibrillary acidic protein A	OR	= Odds ratio
HSP	= Heat shock protein	SCI	= Spinal cord ischaemia
IONM	= Intraoperative neurophysiological monitoring	SSEP	= Somatosensory evoked potentials
LD	= Lactate dehydrogenase	TAAR	= Thoracoabdominal aortic aneurysm repair
MEPs	= Motor evoked potentials	TNF-α	= Tumor necrosis fator-alpha

Author	Year	Country	Total number of patients	Number of male patients (%)	Average age (range)	Number with neurological deficits	CSF biomarker studied
Lases et al.^[¹⁷17 Lases EC, Schepens MA, Haas FJ, Aarts LP, ter Beek HT, van Dongen EP, et al. Clinical prospective study of biochemical markers and evoked potentials for identifying adverse neurological outcome after thoracic and thoracoabdominal aortic aneurysm surgery. Br J Anaesth. 2005;95(5):651-61. doi:10.1093/bja/aei239. https://doi.org/10.1093/bja/aei239... ^]	2005	Netherlands	69	26 (55)	64 (35-89)	4 (5.8)	S-100B, NSE, LD
Casiraghi et al.^[²⁴24 Casiraghi G, Poli D, Landoni G, Buratti L, Imberti R, Plumari V, et al. Intrathecal lactate concentration and spinal cord injury in thoracoabdominal aortic surgery. J Cardiothorac Vasc Anesth. 2011;25(1):120-6. doi:10.1053/j.jvca.2010.03.006. https://doi.org/10.1053/j.jvca.2010.03.0... ^]	2011	Italy	16	10 (62.5)	63 (38-75)	4 (26.7)	Lactate
Drenger et al.^[²⁵25 Drenger B, Parker SD, Frank SM, Beattie C. Changes in cerebrospinal fluid pressure and lactate concentrations during thoracoabdominal aortic aneurysm surgery. Anesthesiology. 1997;86(1):41-7.^]	1997	Jerusalem, Baltimore and Nashville	21	N/A	65.3	3 (14.3)	Lactate
Brunnekreef et al.^[¹⁸18 Brunnekreef GB, Heijmen RH, Gerritsen WB, Schepens MA, ter Beek HT, van Dongen EP. Measurements of cerebrospinal fluid concentrations of S100beta protein during and after thoracic endovascular stent grafting. Eur J Vasc Endovasc Surg. 2007;34(2):169-72. doi:10.1016/j.ejvs.2007.01.013. https://doi.org/10.1016/j.ejvs.2007.01.0... ^]	2007	Netherlands	8	3 (37.5)	68 (58-76)	0	S-100B
Kunihara et al.^[²⁰20 Kunihara T, Shiiya N, Yasuda K. Changes in S100beta protein levels in cerebrospinal fluid after thoracoabdominal aortic operations. J Thorac Cardiovasc Surg. 2001;122(5):1019-20. doi:10.1067/mtc.2001.115151. https://doi.org/10.1067/mtc.2001.115151... ^]	2001	Japan	15	9 (60)	60.6 (26-75)	1 (6.7%)	TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12
van Dongen et al.^[¹⁹19 van Dongen EP, Ter Beek HT, Boezeman EH, Schepens MA, Langemeijer HJ, Aarts LP. Normal serum concentrations of S-100 protein and changes in cerebrospinal fluid concentrations of S-100 protein during and after thoracoabdominal aortic aneurysm surgery: is S-100 protein a biochemical marker of clinical value in detecting spinal cord ischemia? J Vasc Surg. 1998;27(2):344-6. doi:10.1016/S0741-5214(98)70365-9. https://doi.org/10.1016/S0741-5214(98)70... ^]	1998	Netherlands	8	7 (87.5)	63 (35-75)	1 (12.5)	S-100B
Kunihara et al.^[²⁰20 Kunihara T, Shiiya N, Yasuda K. Changes in S100beta protein levels in cerebrospinal fluid after thoracoabdominal aortic operations. J Thorac Cardiovasc Surg. 2001;122(5):1019-20. doi:10.1067/mtc.2001.115151. https://doi.org/10.1067/mtc.2001.115151... ^]	2001	Japan	23	12 (52.2)	64	4 (17.4)	S100-B
Anderson et al.^[²¹21 Anderson RE, Winnerkvist A, Hansson LO, Nilsson O, Rosengren L, Settergren G, et al. Biochemical markers of cerebrospinal ischemia after repair of aneurysms of the descending and thoracoabdominal aorta. J Cardiothorac Vasc Anesth. 2003;17(5):598-603. doi:10.1016/S1053-0770(03)00203-9. https://doi.org/10.1016/S1053-0770(03)00... ^]	2003	Sweden	11	N/A	64	2 (18.2)	S100-B, NSE, GFAp, lactate
Shiiya et al.^[²²22 Shiiya N, Kunihara T, Miyatake T, Matsuzaki K, Yasuda K. Tau protein in the cerebrospinal fluid is a marker of brain injury after aortic surgery. Ann Thorac Surg. 2004;77(6):2034-8. doi:10.1016/j.athoracsur.2003.12.057. https://doi.org/10.1016/j.athoracsur.200... ^]	2004	Japan	28	16	64 (26-79)	6 (21.4)	S100-B, Tau
Khaladj et al.^[²³23 Khaladj N, Teebken OE, Hagl C, Wilhelmi MH, Tschan C, Weissenborn K, et al. The role of cerebrospinal fluid S100 and lactate to predict clinically evident spinal cord ischaemia in thoraco-abdominal aortic surgery. Eur J Vasc Endovasc Surg. 2008;36(1):11-9. doi:10.1016/j.ejvs.2008.01.011. https://doi.org/10.1016/j.ejvs.2008.01.0... ^]	2008	Germany	13	8	63 (27-71)	2	S100-B, lactate, glucose
Hecker et al.^[²⁶26 Hecker JG, Sundram H, Zou S, Praestgaard A, Bavaria JE, Ramchandren S, et al. Heat shock proteins HSP70 and HSP27 in the cerebral spinal fluid of patients undergoing thoracic aneurysm repair correlate with the probability of postoperative paralysis. Cell Stress Chaperones. 2008;13(4):435-46. doi:10.1007/s12192-008-0039-z. https://doi.org/10.1007/s12192-008-0039-... ^]	2008	Philadelphia	37	20	N/A (40-80)	14	HSP70 and HSP27
Brock et al.^[²⁸28 Brock MV, Redmond JM, Ishiwa S, Johnston MV, Baumgartner WA, Laschinger JC, et al. Clinical markers in CSF for determining neurologic deficits after thoracoabdominal aortic aneurysm repairs. Ann Thorac Surg. 1997;64(4):999-1003. doi:10.1016/S0003-4975(97)00621-8. https://doi.org/10.1016/S0003-4975(97)00... ^]	1997	Baltimore	16	6	68.5	4 (25)	Glutamate, aspartate and glycine

Author	Number of patients	Number with neurological deficit (%)	Mean baseline S100b concentration	Peak S100b concentration in paraplegic group (µg/l-1)
Lases et al.^[¹⁷17 Lases EC, Schepens MA, Haas FJ, Aarts LP, ter Beek HT, van Dongen EP, et al. Clinical prospective study of biochemical markers and evoked potentials for identifying adverse neurological outcome after thoracic and thoracoabdominal aortic aneurysm surgery. Br J Anaesth. 2005;95(5):651-61. doi:10.1093/bja/aei239. https://doi.org/10.1093/bja/aei239... ^]	69	4 (5.8)	5.625 µg/litre	10.375
Brunnekreef et al.^[¹⁸18 Brunnekreef GB, Heijmen RH, Gerritsen WB, Schepens MA, ter Beek HT, van Dongen EP. Measurements of cerebrospinal fluid concentrations of S100beta protein during and after thoracic endovascular stent grafting. Eur J Vasc Endovasc Surg. 2007;34(2):169-72. doi:10.1016/j.ejvs.2007.01.013. https://doi.org/10.1016/j.ejvs.2007.01.0... ^]	8	0	1.3 µg/litre	n/a
van Dongen et al.^[¹⁹19 van Dongen EP, Ter Beek HT, Boezeman EH, Schepens MA, Langemeijer HJ, Aarts LP. Normal serum concentrations of S-100 protein and changes in cerebrospinal fluid concentrations of S-100 protein during and after thoracoabdominal aortic aneurysm surgery: is S-100 protein a biochemical marker of clinical value in detecting spinal cord ischemia? J Vasc Surg. 1998;27(2):344-6. doi:10.1016/S0741-5214(98)70365-9. https://doi.org/10.1016/S0741-5214(98)70... ^]	8	1(12.5)	1.23 µg/litre	10.03
Kunihara et al.^[²⁰20 Kunihara T, Shiiya N, Yasuda K. Changes in S100beta protein levels in cerebrospinal fluid after thoracoabdominal aortic operations. J Thorac Cardiovasc Surg. 2001;122(5):1019-20. doi:10.1067/mtc.2001.115151. https://doi.org/10.1067/mtc.2001.115151... ^]	23	4 (17.4)	1.5 µg/litre	275
Anderson et al.^[²¹21 Anderson RE, Winnerkvist A, Hansson LO, Nilsson O, Rosengren L, Settergren G, et al. Biochemical markers of cerebrospinal ischemia after repair of aneurysms of the descending and thoracoabdominal aorta. J Cardiothorac Vasc Anesth. 2003;17(5):598-603. doi:10.1016/S1053-0770(03)00203-9. https://doi.org/10.1016/S1053-0770(03)00... ^]	11	2 (18.2)	3.7 (1 [in log ng/l])	4.4 (in log ng/l)
Shiiya et al.^[²²22 Shiiya N, Kunihara T, Miyatake T, Matsuzaki K, Yasuda K. Tau protein in the cerebrospinal fluid is a marker of brain injury after aortic surgery. Ann Thorac Surg. 2004;77(6):2034-8. doi:10.1016/j.athoracsur.2003.12.057. https://doi.org/10.1016/j.athoracsur.200... ^]	28	6 (21.4)	1.60	42.35^* * Original values 72.2 [±40.8] and 12.5 [±5.5].
Khaladj et al.^[²³23 Khaladj N, Teebken OE, Hagl C, Wilhelmi MH, Tschan C, Weissenborn K, et al. The role of cerebrospinal fluid S100 and lactate to predict clinically evident spinal cord ischaemia in thoraco-abdominal aortic surgery. Eur J Vasc Endovasc Surg. 2008;36(1):11-9. doi:10.1016/j.ejvs.2008.01.011. https://doi.org/10.1016/j.ejvs.2008.01.0... ^]	13	2	1.3	19.4[±14]

Author	Number of patients	Number with neurological deficit (%)	Mean baseline lactate concentration	Peak lactate concentration in paraplegic group
Lases et al.^[¹⁷17 Lases EC, Schepens MA, Haas FJ, Aarts LP, ter Beek HT, van Dongen EP, et al. Clinical prospective study of biochemical markers and evoked potentials for identifying adverse neurological outcome after thoracic and thoracoabdominal aortic aneurysm surgery. Br J Anaesth. 2005;95(5):651-61. doi:10.1093/bja/aei239. https://doi.org/10.1093/bja/aei239... ^]	69	4 (5.8)	17.75 µg/l	25.625 µg/l
Anderson et al.^[²¹21 Anderson RE, Winnerkvist A, Hansson LO, Nilsson O, Rosengren L, Settergren G, et al. Biochemical markers of cerebrospinal ischemia after repair of aneurysms of the descending and thoracoabdominal aorta. J Cardiothorac Vasc Anesth. 2003;17(5):598-603. doi:10.1016/S1053-0770(03)00203-9. https://doi.org/10.1016/S1053-0770(03)00... ^]	11	2 (18.2)	1.5 µg/l	3 µg/l
Khaladj et al.^[²³23 Khaladj N, Teebken OE, Hagl C, Wilhelmi MH, Tschan C, Weissenborn K, et al. The role of cerebrospinal fluid S100 and lactate to predict clinically evident spinal cord ischaemia in thoraco-abdominal aortic surgery. Eur J Vasc Endovasc Surg. 2008;36(1):11-9. doi:10.1016/j.ejvs.2008.01.011. https://doi.org/10.1016/j.ejvs.2008.01.0... ^]	13	2	2.2 µg/l	9.3 µg/l

Author	Number of patients	Number with neurological deficit (%)	Mean baseline NSE concentration	Peak NSE concentration in paraplegic group
Lases et al.^[¹⁷17 Lases EC, Schepens MA, Haas FJ, Aarts LP, ter Beek HT, van Dongen EP, et al. Clinical prospective study of biochemical markers and evoked potentials for identifying adverse neurological outcome after thoracic and thoracoabdominal aortic aneurysm surgery. Br J Anaesth. 2005;95(5):651-61. doi:10.1093/bja/aei239. https://doi.org/10.1093/bja/aei239... ^]	69	4 (5.8)	12.625 µg/l	19 µg/l
Anderson et al.^[²¹21 Anderson RE, Winnerkvist A, Hansson LO, Nilsson O, Rosengren L, Settergren G, et al. Biochemical markers of cerebrospinal ischemia after repair of aneurysms of the descending and thoracoabdominal aorta. J Cardiothorac Vasc Anesth. 2003;17(5):598-603. doi:10.1016/S1053-0770(03)00203-9. https://doi.org/10.1016/S1053-0770(03)00... ^]	11	2 (18.2)	12 µg/l	17 µg/l

Author	Number of patients	Number with neurological deficit (%)	Mean baseline TAU concentration	Peak Tau concentration in paraplegic group
Shiiya et al.^[²²22 Shiiya N, Kunihara T, Miyatake T, Matsuzaki K, Yasuda K. Tau protein in the cerebrospinal fluid is a marker of brain injury after aortic surgery. Ann Thorac Surg. 2004;77(6):2034-8. doi:10.1016/j.athoracsur.2003.12.057. https://doi.org/10.1016/j.athoracsur.200... ^]	28	6 (21.4)	134.25 pg/ml	989 pg/ml (massive confidence intervals)

Author	Number of patients	Number with neurological deficit (%)	Mean baseline GFAp concentration	Peak GFAp concentration in paraplegic group
Anderson et al.^[²¹21 Anderson RE, Winnerkvist A, Hansson LO, Nilsson O, Rosengren L, Settergren G, et al. Biochemical markers of cerebrospinal ischemia after repair of aneurysms of the descending and thoracoabdominal aorta. J Cardiothorac Vasc Anesth. 2003;17(5):598-603. doi:10.1016/S1053-0770(03)00203-9. https://doi.org/10.1016/S1053-0770(03)00... ^]	11	2 (18.2)	2.8	5

Author's roles & responsibilities
AH	Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; final approval of the version to be published
MF	Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; final approval of the version to be published
HF	Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; final approval of the version to be published
CH	Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; final approval of the version to be published
LR	Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; final approval of the version to be published
MB	Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; final approval of the version to be published

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[1] Correspondence Address: Mohamad Bashir, https://orcid.org/0000-0001-9095-6994, Department of Aortovascular Surgery - Manchester Royal infirmary - Manchester, UK, Zip code: M13 9WL. E-mail: drmbashir@mail.com