Serial sampling of serum protein biomarkers for monitoring human traumatic brain injury dynamics: A systematic review

Eric Peter Thelin, Frederick Adam Zeiler, Ari Ercole, Stefania Mondello, A. Büki, Bo Michael Bellander, Adel Helmy, David K. Menon, David W. Nelson

Research output: Contribution to journalReview article

22 Citations (Scopus)

Abstract

Background: The proteins S100B, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and neurofilament light (NF-L) have been serially sampled in serum of patients suffering from traumatic brain injury (TBI) in order to assess injury severity and tissue fate. We review the current literature of serum level dynamics of these proteins following TBI and used the term "effective half-life" (t1/2) in order to describe the "fall" rate in serum. Materials and methods: Through searches on EMBASE, Medline, and Scopus, we looked for articles where these proteins had been serially sampled in serum in human TBI. We excluded animal studies, studies with only one presented sample and studies without neuroradiological examinations. Results: Following screening (10,389 papers), n = 122 papers were included. The proteins S100B (n = 66) and NSE (n = 27) were the two most frequent biomarkers that were serially sampled. For S100B in severe TBI, a majority of studies indicate a t1/2 of about 24 h, even if very early sampling in these patients reveals rapid decreases (1-2 h) though possibly of non-cerebral origin. In contrast, the t1/2 for NSE is comparably longer, ranging from 48 to 72 h in severe TBI cases. The protein GFAP (n = 18) appears to have t1/2 of about 24-48 h in severe TBI. The protein UCH-L1 (n = 9) presents a t1/2 around 7 h in mild TBI and about 10 h in severe. Frequent sampling of these proteins revealed different trajectories with persisting high serum levels, or secondary peaks, in patients with unfavorable outcome or in patients developing secondary detrimental events. Finally, NF-L (n = 2) only increased in the few studies available, suggesting a serum availability of >10 days. To date, automated assays are available for S100B and NSE making them faster and more practical to use. Conclusion: Serial sampling of brain-specific proteins in serum reveals different temporal trajectories that should be acknowledged. Proteins with shorter serum availability, like S100B, may be superior to proteins such as NF-L in detection of secondary harmful events when monitoring patients with TBI.

Original languageEnglish
Article number300
JournalFrontiers in Neurology
Volume8
Issue numberJUL
DOIs
Publication statusPublished - Jul 3 2017

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Blood Proteins
Biomarkers
Phosphopyruvate Hydratase
Proteins
Intermediate Filaments
Serum
Ubiquitin Thiolesterase
Glial Fibrillary Acidic Protein
Light
Brain Concussion
Traumatic Brain Injury
Physiologic Monitoring
Half-Life
Wounds and Injuries
Brain

Keywords

  • Biomarkers
  • Glial fibrillary acidic protein
  • Neurofilament light
  • Neuron-specific enolase
  • S100B
  • Serum
  • Traumatic brain injury
  • Ubiquitin carboxy-terminal hydrolase L1

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Serial sampling of serum protein biomarkers for monitoring human traumatic brain injury dynamics : A systematic review. / Thelin, Eric Peter; Zeiler, Frederick Adam; Ercole, Ari; Mondello, Stefania; Büki, A.; Bellander, Bo Michael; Helmy, Adel; Menon, David K.; Nelson, David W.

In: Frontiers in Neurology, Vol. 8, No. JUL, 300, 03.07.2017.

Research output: Contribution to journalReview article

Thelin, EP, Zeiler, FA, Ercole, A, Mondello, S, Büki, A, Bellander, BM, Helmy, A, Menon, DK & Nelson, DW 2017, 'Serial sampling of serum protein biomarkers for monitoring human traumatic brain injury dynamics: A systematic review', Frontiers in Neurology, vol. 8, no. JUL, 300. https://doi.org/10.3389/fneur.2017.00300
Thelin, Eric Peter ; Zeiler, Frederick Adam ; Ercole, Ari ; Mondello, Stefania ; Büki, A. ; Bellander, Bo Michael ; Helmy, Adel ; Menon, David K. ; Nelson, David W. / Serial sampling of serum protein biomarkers for monitoring human traumatic brain injury dynamics : A systematic review. In: Frontiers in Neurology. 2017 ; Vol. 8, No. JUL.
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abstract = "Background: The proteins S100B, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and neurofilament light (NF-L) have been serially sampled in serum of patients suffering from traumatic brain injury (TBI) in order to assess injury severity and tissue fate. We review the current literature of serum level dynamics of these proteins following TBI and used the term {"}effective half-life{"} (t1/2) in order to describe the {"}fall{"} rate in serum. Materials and methods: Through searches on EMBASE, Medline, and Scopus, we looked for articles where these proteins had been serially sampled in serum in human TBI. We excluded animal studies, studies with only one presented sample and studies without neuroradiological examinations. Results: Following screening (10,389 papers), n = 122 papers were included. The proteins S100B (n = 66) and NSE (n = 27) were the two most frequent biomarkers that were serially sampled. For S100B in severe TBI, a majority of studies indicate a t1/2 of about 24 h, even if very early sampling in these patients reveals rapid decreases (1-2 h) though possibly of non-cerebral origin. In contrast, the t1/2 for NSE is comparably longer, ranging from 48 to 72 h in severe TBI cases. The protein GFAP (n = 18) appears to have t1/2 of about 24-48 h in severe TBI. The protein UCH-L1 (n = 9) presents a t1/2 around 7 h in mild TBI and about 10 h in severe. Frequent sampling of these proteins revealed different trajectories with persisting high serum levels, or secondary peaks, in patients with unfavorable outcome or in patients developing secondary detrimental events. Finally, NF-L (n = 2) only increased in the few studies available, suggesting a serum availability of >10 days. To date, automated assays are available for S100B and NSE making them faster and more practical to use. Conclusion: Serial sampling of brain-specific proteins in serum reveals different temporal trajectories that should be acknowledged. Proteins with shorter serum availability, like S100B, may be superior to proteins such as NF-L in detection of secondary harmful events when monitoring patients with TBI.",
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T2 - A systematic review

AU - Thelin, Eric Peter

AU - Zeiler, Frederick Adam

AU - Ercole, Ari

AU - Mondello, Stefania

AU - Büki, A.

AU - Bellander, Bo Michael

AU - Helmy, Adel

AU - Menon, David K.

AU - Nelson, David W.

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N2 - Background: The proteins S100B, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and neurofilament light (NF-L) have been serially sampled in serum of patients suffering from traumatic brain injury (TBI) in order to assess injury severity and tissue fate. We review the current literature of serum level dynamics of these proteins following TBI and used the term "effective half-life" (t1/2) in order to describe the "fall" rate in serum. Materials and methods: Through searches on EMBASE, Medline, and Scopus, we looked for articles where these proteins had been serially sampled in serum in human TBI. We excluded animal studies, studies with only one presented sample and studies without neuroradiological examinations. Results: Following screening (10,389 papers), n = 122 papers were included. The proteins S100B (n = 66) and NSE (n = 27) were the two most frequent biomarkers that were serially sampled. For S100B in severe TBI, a majority of studies indicate a t1/2 of about 24 h, even if very early sampling in these patients reveals rapid decreases (1-2 h) though possibly of non-cerebral origin. In contrast, the t1/2 for NSE is comparably longer, ranging from 48 to 72 h in severe TBI cases. The protein GFAP (n = 18) appears to have t1/2 of about 24-48 h in severe TBI. The protein UCH-L1 (n = 9) presents a t1/2 around 7 h in mild TBI and about 10 h in severe. Frequent sampling of these proteins revealed different trajectories with persisting high serum levels, or secondary peaks, in patients with unfavorable outcome or in patients developing secondary detrimental events. Finally, NF-L (n = 2) only increased in the few studies available, suggesting a serum availability of >10 days. To date, automated assays are available for S100B and NSE making them faster and more practical to use. Conclusion: Serial sampling of brain-specific proteins in serum reveals different temporal trajectories that should be acknowledged. Proteins with shorter serum availability, like S100B, may be superior to proteins such as NF-L in detection of secondary harmful events when monitoring patients with TBI.

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KW - Neurofilament light

KW - Neuron-specific enolase

KW - S100B

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KW - Traumatic brain injury

KW - Ubiquitin carboxy-terminal hydrolase L1

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