Characterization of Cerebrospinal Fluid Ubiquitin C-Terminal Hydrolase L1 as a Biomarker of Human Acute Traumatic Spinal Cord Injury

Stukas, Sophie; Gill, Jasmine; Cooper, Jennifer; Bélanger, Lise; Ritchie, Leanna; Tsang, Angela; Dong, Kevin; Streijger, Femke; Street, John; Paquette, Scott; Ailon, Tamir; Dea, Nicolas; Charest-Morin, Raphaële; Fisher, Charles G.; Dhall, Sanjay S.; Mac-Thiong, Jean-Marc; Wilson, Jefferson R.; Bailey, Chris; Christie, Sean; Dvorak, Marcel F.; Wellington, Cheryl L.

doi:10.1089/neu.2020.7352

Cited by 13 publications

(13 citation statements)

References 23 publications

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“…During initial resuscitation for TBI, effective and accurate prediction factors for DAI can contribute to support medical decisions for physicians and caregivers, from diagnosis to interventions (6,9). In recent years, many DAI biomarkers have been discovered by previous studies, such as tau protein, β-APP, NSE, S-100 calcium-binding protein B(S-100B), Ubiquitin C-terminal hydrolase-L1 (UCH-L1), spectrin, glial fibrillar acidic protein (GFAP), and neurofilament light (NfL) (5,9,18,19,(23)(24)(25)(26). GFAP and UCH-L1 have been shown to discriminate patients regarding the presence or absence of brain lesions on initial CT scan (26) and authorized for clinical use in the evaluation of mild TBI.…”

Section: Discussionmentioning

confidence: 99%

The ratio of serum neuron-specific enolase level to admission glasgow coma scale score is associated with diffuse axonal injury in patients with moderate to severe traumatic brain injury

et al. 2022

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BackgroundModerate to severe traumatic brain injury (TBI) is frequently accompanied by diffuse axonal injury (DAI). Considering the low sensitivity of computed tomography (CT) examination for microbleeds and axonal damage, identification of DAI is difficult using conventional diagnostic methods in the acute phase. Neuron-specific enolase (NSE) has been demonstrated to be increased in serum following various types of TBI and is already clinically/commercially available. We conjecture that serum NSE level to admission GCS score ratio (NGR) may be a useful indicator for the early diagnosis of DAI.MethodsThis study included 115 patients with moderate-to-severe TBI who underwent NSE measurements within 6 h after injury and brain magnetic resonance imaging (MRI) within 30 days. The positive and negative DAI groups were divided according to MRI findings.ResultsAmong the 115 patients, 49 (42.6%) were classified into the DAI group and 66 (57.4%) patients into the non-DAI group by clinical MRI. The NGR of patients without DAI was found to be significantly lower than those of patients with DAI (p < 0.0001). NGR presented the largest Pearson r value (r = 0.755, 95% CI 0.664–0.824, p < 0.0001) and high diagnostic accuracy for DAI [area under the curve (AUC) = 0.9493; sensitivity, 90.91%; and specificity, 85.71%]. Patients with TBI presenting with higher NGR were more likely to suffer an unfavorable neurological outcome [6-month extended Glasgow Outcome Scale (GOSE) 1–4].ConclusionsThe NGR on admission could serve as an independent predictor of DAI with moderate-to-severe TBI.

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Section: Discussionmentioning

confidence: 99%

The ratio of serum neuron-specific enolase level to admission glasgow coma scale score is associated with diffuse axonal injury in patients with moderate to severe traumatic brain injury

et al. 2022

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“…In addition, a recent study of 32 patients with acute SCI revealed that CSF UCH-L1 levels increased dramatically after injury in a severity-and time-dependent way, with 100% sensitivity and 86% specificity for predicting ASIA conversion, despite no differences in serum UCH-L1 levels. Furthermore, a consistent increase in CSF UCH-L1 up to 96 hours and relatively higher CSF levels 24 hours after injury were correlated with a lack of AIS grade improvement and motor function amelioration, respectively (Stukas et al, 2021). An ultrasensitive immunosensor has recently been developed for the rapid detection of UCH-L1 in biofluids in patients with TBI or SCI (Khetani et al, 2019).…”

Section: Astroglial Injury Biomarkers For Spinal Cord Injurymentioning

confidence: 96%

Application value of biofluid-based biomarkers for the diagnosis and treatment of spinal cord injury

Wang

Wei

et al. 2022

Neural Regen Res

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Recent studies in patients with spinal cord injuries (SCIs) have confirmed the diagnostic potential of biofluid-based biomarkers, as a topic of increasing interest in relation to SCI diagnosis and treatment. This paper reviews the research progress and application prospects of recently identified SCI-related biomarkers. Many structural proteins, such as glial fibrillary acidic protein, S100-β, ubiquitin carboxy-terminal hydrolase-L1, neurofilament light, and tau protein were correlated with the diagnosis, American Spinal Injury Association Impairment Scale, and prognosis of SCI to different degrees. Inflammatory factors, including interleukin-6, interleukin-8, and tumor necrosis factor α, are also good biomarkers for the diagnosis of acute and chronic SCI, while non-coding RNAs (microRNAs and long non-coding RNAs) also show diagnostic potential for SCI. Trace elements (Mg, Se, Cu, Zn) have been shown to be related to motor recovery and can predict motor function after SCI, while humoral markers can reflect the pathophysiological changes after SCI. These factors have the advantages of low cost, convenient sampling, and ease of dynamic tracking, but are also associated with disadvantages, including diverse influencing factors and complex level changes. Although various proteins have been verified as potential biomarkers for SCI, more convincing evidence from large clinical and prospective studies is thus required to identify the most valuable diagnostic and prognostic biomarkers for SCI.

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“…In a rat SCI model, Yang et al 19 found that CSF and serum UCH-L1 levels increased quickly at 4 hours after damage. Additionally, Stukas et al 12 reported that in an injury severity and time-dependent manner, CSF UCH-L1 was considerably higher compared to controls, but failed to show such a difference in serum UCH-L1 levels and mentioned that technique may not be sufficiently sensitive. Patients’ selection criteria, sampling time, and ethnic differences may be additional factors.…”

Section: Discussionmentioning

confidence: 99%

“…5,11 The lack of biomarkers that can objectively stratify injury severity and predict outcome is a major barrier to translational research in acute TSCI. 12 Therefore, the present study aimed to investigate the circulating NGB and UCH-L1 expressions in various TSCI and correlate their initial levels with the severity and outcomes of these injuries.…”

Section: Introductionmentioning

confidence: 99%

Circulating Ubiquitin Carboxyl Terminal Hydrolase L1 and Neuroglobin Levels in Traumatic Spinal Cord Injuries: Relation to Severity and Outcomes

Abuhamdah¹,

Saleem²,

Elsadek³

et al. 2022

IJGM

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Introduction Traumatic spinal cord injury (TSCI) is a life-threatening neurological disorder and there is a lack of biomarker research, particularly human studies that could help to categorize the severity and predict the outcome. We aimed to assess the role of serum Ubiquitin C-terminal hydrolase L1 (UCH-L1) and Neuroglobin (NGB) in predicting severity and outcome of TSCI. Methods This prospective study included 63 participants categorized into 33 patients with various types of TSCI and 30 unrelated healthy volunteers. Neurosurgical [American spinal injury association (ASIA) impairment score (AIS)] and radiological [using spine computed tomography (CT) and magnetic resonance imaging (MRI)] assessments were performed on the included patients to determine the severity and the level of injury with neurological follow-up of patients within 6 months post-injury. Serum UCH-L1 and NGB were measured for all participants using commercially available ELISA assay kits. Results Of the included patients, 20 (60.60%) had partial SCI and the remaining 13 patients (39.39%) had complete SCI. On follow-up, 19 patients (57.57%) showed improved AIS, while 14 cases (42.42%) did not show any improvement in their AIS scores. There was significantly higher median serum UCHL1 value among cases compared to controls (1723 pg/mL and 657 pg/mL, respectively), p ˂ 0.05. There was an insignificant rise of serum NGB levels among cases in comparison with the controls (15.2pg/mL and 7.52pg/mL, respectively, p ˃ 0.05). Significantly lower initial median serum UCHL1 levels (pg/mL) were observed in patients with improved AIS during the neurological follow-up compared with those who did not show any improvement in their AIS score (1723, and 4700 respectively, p ˂ 0.05), with lack of significant difference in the initial median serum NGB levels, p ˃ 0.05. Conclusion Initial serum UCHL1 assay could be a helpful marker in reflecting the degree of TSCI and predicting its outcome, though NGB needs further assessment.

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Characterization of Cerebrospinal Fluid Ubiquitin C-Terminal Hydrolase L1 as a Biomarker of Human Acute Traumatic Spinal Cord Injury

Cited by 13 publications

References 23 publications

The ratio of serum neuron-specific enolase level to admission glasgow coma scale score is associated with diffuse axonal injury in patients with moderate to severe traumatic brain injury

The ratio of serum neuron-specific enolase level to admission glasgow coma scale score is associated with diffuse axonal injury in patients with moderate to severe traumatic brain injury

Application value of biofluid-based biomarkers for the diagnosis and treatment of spinal cord injury

Circulating Ubiquitin Carboxyl Terminal Hydrolase L1 and Neuroglobin Levels in Traumatic Spinal Cord Injuries: Relation to Severity and Outcomes

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