Detection of neurofilament-H in serum as a diagnostic tool to predict injury severity in patients who have suffered mild traumatic brain injury

2014 ◽  
Vol 121 (5) ◽  
pp. 1232-1238 ◽  
Author(s):  
Joshua W. Gatson ◽  
Jennifer Barillas ◽  
Linda S. Hynan ◽  
Ramon Diaz-Arrastia ◽  
Steven E. Wolf ◽  
...  

Object In previous studies of traumatic brain injury (TBI), neural biomarkers of injury correlate with injury severity and predict neurological outcome. The object of this paper was to characterize neurofilament-H (NFL-H) as a predictor of injury severity in patients who have suffered mild TBI (mTBI). Thus, the authors hypothesized that phosphorylated NFL-H (pNFL-H) levels are higher in mTBI patients than in healthy controls and identify which subjects experienced a more severe injury such as skull fractures, intracranial hemorrhaging, and/or contusions as detected by CT scans. Methods In this prospective clinical study, blood (8 ml) was collected from subjects (n = 34) suffering from mTBI (as defined by the American Congress of Rehabilitation and Glasgow Coma Scale scores between 13 and 15) at Parkland Hospital, Dallas, Texas, on Days 1 and 3 after injury). Additional clinical findings from the CT scans were also used to categorize the TBI patients into those with and those without clinical findings on the scans (CT+ and CTgroups, respectively). The serum levels of pNFL-H were measured using the enzyme-linked immunosorbent assay. Results Compared with healthy controls, the mTBI patients exhibited a significant increase in the serum levels of pNFL-H on Days 1 (p = 0.00001) and 3 (p = 0.0001) after TBI. An inverse correlation was observed between pNFL-H serum levels and Glasgow Coma Scale scores, which was significant. Additionally, using receiver operating characteristic curve analysis to compare the mTBI cases with controls to determine sensitivity and specificity, an area under the curve of 100% was achieved for both (p = 0.0001 for both). pNFL-H serum levels were only significantly higher on Day 1 in mTBI patients in the CT+ group (p < 0.008) compared with the CT− group. The area under the curve (82.5%) for the CT+ group versus the CT− group was significant (p = 0.021) with a sensitivity of 87.5% and a specificity of 70%, using a cutoff of 1071 pg/ml of pNFL-H in serum. Conclusions This study describes the serum profile of pNFL-H in patients suffering from mTBI with and without CT findings on Days 1 and 3 after injury. These results suggest that detection of pNFL-H may be useful in determining which individuals require CT imaging to assess the severity of their injury.

2008 ◽  
Vol 109 (4) ◽  
pp. 678-684 ◽  
Author(s):  
Anne Vik ◽  
Torbjørn Nag ◽  
Oddrun Anita Fredriksli ◽  
Toril Skandsen ◽  
Kent Gøran Moen ◽  
...  

Object It has recently been suggested that the degree of intracranial pressure (ICP) above the treatment goal can be estimated by the area under the curve (AUC) of ICP versus time in patients with severe traumatic brain injury (TBI). The objective of this study was to determine whether the calculated “ICP dose”—the ICP AUC—is related to mortality rate, outcome, and Marshall CT classification. Methods Of 135 patients (age range 1–82 years) with severe TBI treated during a 5-year period at the authors' institution, 113 patients underwent ICP monitoring (84%). Ninety-three patients with a monitoring time > 24 hours were included for analysis of ICP AUC calculated using the trapezoidal method. Computed tomography scans were assessed according to the Marshall TBI classification. Patients with Glasgow Outcome Scale scores at 6 months and > 3 years were separated into 2 groups based on outcome. Results Sixty patients (65%) had ICP values > 20 mm Hg, and 12 (13%) developed severe intracranial hypertension and died secondary to herniation. A multiple regression analysis adjusting for Glasgow Coma Scale score, age, pupillary abnormalities and Injury Severity Scale score demonstrated that the ICP AUC was a significant predictor of poor outcome at 6 months (p = 0.034) and of death (p = 0.035). However, it did not predict long-term outcome (p = 0.157). The ICP AUC was significantly higher in patients with Marshall head injury Categories 3 and 4 (24 patients) than in those with Category 2 (23 patients, p = 0.025) and Category 5 (46 patients, p = 0.021) TBIs using the worst CT scan obtained. Conclusions The authors found a significant relationship between the dose of ICP, the worst Marshall CT score, and patient outcome, suggesting that the AUC method may be useful in refining and improving the treatment of ICP in patients with TBI.


Neurosurgery ◽  
2011 ◽  
Vol 70 (3) ◽  
pp. 666-675 ◽  
Author(s):  
Stefania Mondello ◽  
Akinyi Linnet ◽  
Andras Buki ◽  
Steven Robicsek ◽  
Andrea Gabrielli ◽  
...  

Abstract Background: Brain damage markers released in cerebrospinal fluid (CSF) and blood may provide valuable information about diagnosis and outcome prediction after traumatic brain injury (TBI). Objective: To examine the concentrations of ubiquitin C-terminal hydrolase-L1 (UCH-L1), a novel brain injury biomarker, in CSF and serum of severe TBI patients and their association with clinical characteristics and outcome. Methods: This case-control study enrolled 95 severe TBI subjects (Glasgow Coma Scale [GCS] score, 8). Using sensitive UCH-L1 sandwich ELISA, we studied the temporal profile of CSF and serum UCH-L1 levels over 7 days for severe TBI patients. Results: Comparison of serum and CSF levels of UCH-L1 in TBI patients and control subjects shows a robust and significant elevation of UCH-L1 in the acute phase and over the 7-day study period. Serum and CSF UCH-L1 receiver-operating characteristic curves further confirm strong specificity and selectivity for diagnosing severe TBI vs controls, with area under the curve values in serum and CSF statistically significant at all time points up to 24 hours (P &lt; .001). The first 12-hour levels of both serum and CSF UCH-L1 in patients with GCS score of 3 to 5 were also significantly higher than those with GCS score of 6 to 8. Furthermore, UCH-L1 levels in CSF and serum appear to distinguish severe TBI survivors from nonsurvivors within the study, with nonsurvivors having significantly higher and more persistent levels of serum and CSF UCH-L1. Cumulative serum UCH-L1 levels &gt; 5.22 ng/mL predicted death (odds ratio, 4.8). Conclusion: Serum levels of UCH-L1 appear to have potential clinical utility in diagnosing TBI, including correlating to injury severity and survival outcome.


2011 ◽  
Vol 71 (5) ◽  
pp. 1172-1178 ◽  
Author(s):  
Shelly D. Timmons ◽  
Tiffany Bee ◽  
Sharon Webb ◽  
Ramon R. Diaz-Arrastia ◽  
Dale Hesdorffer

2019 ◽  
Vol 9 (10) ◽  
pp. 269 ◽  
Author(s):  
Leonardo Lorente ◽  
María M. Martín ◽  
Agustín F. González-Rivero ◽  
Antonia Pérez-Cejas ◽  
Mónica Argueso ◽  
...  

Objective: Apoptosis increases in traumatic brain injury (TBI). Caspase-cleaved cytokeratin (CCCK)-18 in blood during apoptosis could appear. At the time of admission due to TBI, higher blood CCCK-18 levels were found in non-surviving than in surviving patients. Therefore, the objective of our study was to analyze whether serum CCCK-18 levels determined during the first week after TBI could predict early mortality (at 30 days). Methods: Severe TBI patients were included (considering severe when Glasgow Coma Scale < 9) in this observational and multicentre study. Serum CCCK-18 levels were determined at day 1 of TBI, and at days 4 and 8 after TBI. Results: Serum CCCK-18 levels at day 1 of TBI, and in the days 4 and 8 after TBI were higher (p < 0.001) in non-surviving than in surviving patients (34 and 90 patients, respectively) and could predict early mortality (p < 0.001 in the area under the curve). Conclusions: The new findings from our study were that serum CCCK-18 levels at any moment of the first week of TBI were higher in non-surviving patients and were able to predict early mortality.


2019 ◽  
Vol 85 (4) ◽  
pp. 370-375 ◽  
Author(s):  
Adel Elkbuli ◽  
Raed Ismail Narvel ◽  
Paul J. Spano ◽  
Valerie Polcz ◽  
Astrid Casin ◽  
...  

The effect of timing in patients requiring tracheostomy varies in the literature. The purpose of this study was to evaluate the impact of early tracheostomy on outcomes in trauma patients with and without traumatic brain injury (TBI). This study is a four-year review of trauma patients undergoing tracheostomy. Patients were divided into two groups based on TBI/non-TBI. Each group was divided into three subgroups based on tracheostomy timing: zero to three days, four to seven days, and greater than seven days postadmission. TBI patients were stratified by the Glasgow Coma Scale (GCS), and non-TBI patients were stratified by the Injury Severity Score (ISS). The primary outcome was ventilator-free days (VFDs). Significance was defined as P < 0.05. Two hundred eighty-nine trauma patients met the study criteria: 151 had TBI (55.2%) versus 138 (47.8%) non-TBI. There were no significant differences in demographics within and between groups. In TBI patients, statistically significant increases in VFDs were observed with GCS 13 to 15 for tracheostomies performed in four to seven versus greater than seven days ( P = 0.005). For GCS <8 and 8 to 12, there were significant increases in VFDs for tracheostomies performed at days 1 to 3 and 4 to 7 versus greater than seven days (P << 0.05 for both). For non-TBI tracheostomies, only ISS ≥ 25 with tracheostomies performed at zero to three days versus greater than seven days was associated with improved VFDs. Early tracheostomies in TBI patients were associated with improved VFDs. In trauma patients with no TBI, early tracheostomy was associated with improved VFDs only in patients with ISS ≥ 25. Future research studies should investigate reasons TBI and non-TBI patients may differ.


2008 ◽  
Vol 74 (3) ◽  
pp. 267-270 ◽  
Author(s):  
Grant V. Bochicchio ◽  
Kimberly Lumpkins ◽  
James O'Connor ◽  
Marc Simard ◽  
Stacey Schaub ◽  
...  

High-pressure waves (blast) account for the majority of combat injuries and are becoming increasingly common in terrorist attacks. To our knowledge, there are no data evaluating the epidemiology of blast injury in a domestic nonterrorist setting. Data were analyzed retrospectively on patients admitted with any type of blast injury over a 10-year period at a busy urban trauma center. Injuries were classified by etiology of explosion and anatomical location. Eighty-nine cases of blast injury were identified in 57,392 patients (0.2%) treated over the study period. The majority of patients were male (78%) with a mean age of 40 ± 17 years. The mean Injury Severity Score was 13 ± 11 with an admission Trauma and Injury Severity Score of 0.9 ± 0.2 and Revised Trauma Score of 7.5 ± 0.8. The mean intensive care unit and hospital length of stay was 2 ± 7 days and 4.6 ± 10 days, respectively, with an overall mortality rate of 4.5 per cent. Private dwelling explosion [n = 31 (35%)] was the most common etiology followed by industrial pressure blast [n = 20 (22%)], industrial gas explosion [n = 16 (18%)], military training-related explosion [n = 15 (17%)], home explosive device [n = 8 (9%)], and fireworks explosion [n = 1 (1%)]. Maxillofacial injuries were the most common injury (n = 78) followed by upper extremity orthopedic (n = 29), head injury (n = 32), abdominal (n = 30), lower extremity orthopedic (n = 29), and thoracic (n = 19). The majority of patients with head injury [28 of 32 (88%)] presented with a Glasgow Coma Scale score of 15. CT scans on admission were initially positive for brain injury in 14 of 28 patients (50%). Seven patients (25%) who did not have a CT scan on admission had a CT performed later in their hospital course as a result of mental status change and were positive for traumatic brain injury (TBI). Three patients (11%) had a negative admission CT with a subsequently positive CT for TBI over the next 48 hours. The remaining four patients (14%) were diagnosed with skull fractures. All patients (n = 4) with an admission Glasgow Coma Scale score of less than 8 died from diffuse axonal injury. Blast injury is a complicated disease process, which may evolve over time, particularly with TBI. The missed injury rate for TBI in patients with a Glasgow Coma Scale score of 15 was 36 per cent. More studies are needed in the area of blast injury to better understand this disease process.


2010 ◽  
Vol 27 (9) ◽  
pp. 1549-1555 ◽  
Author(s):  
Alexandra Brazinova ◽  
Walter Mauritz ◽  
Johannes Leitgeb ◽  
Ingrid Wilbacher ◽  
Marek Majdan ◽  
...  

2017 ◽  
Vol 41 (3) ◽  
Author(s):  
Anil Yalcin ◽  
Ahmet Baydin ◽  
Özgür Korhan Tuncel ◽  
Ali Kemal Erenler ◽  
Cengiz Çokluk ◽  
...  

AbstractBackground:The primary aim of this study was to investigate the diagnostic values of serum S100 calcium-binding protein B (S100B) and proenkephalin (P-ENK) levels in brain damage caused by traumatic brain injury (TBI).Methods:We prospectively collected serum blood samples of 58 adult patients admitted to our emergency department due to TBI. Serum S100B and P-ENK levels were measured and compared according to clinical findings and outcomes of the patients.Results:When patients with brain injury were compared to controls, statistical significance was determined in both S100B and P-ENK levels. According to the receiver operating characteristic (ROC) analysis, cut-off values for serum S100B and P-ENK levels for the differential diagnosis of patients with and without brain damage were found to be 785.944 ng/mL and 2.445 ng/mL, respectively. There was a statistical significance in both S100B and P-ENK levels when patients who were discharged and those who died were compared.Conclusions:Serum S100B and P-ENK levels are found to be elevated in patients with TBI when compared to controls. Additionally, serum levels of both markers are found to be elevated in patients with multiple lesions when compared to patients with a single lesion. Serum S100B and P-ENK levels may also be used as predictors of mortality in patients with TBI.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Leonardo Lorente ◽  
María M. Martín ◽  
Pedro Abreu-González ◽  
Luis Ramos ◽  
Juan J. Cáceres ◽  
...  

Abstract Objective Higher blood malondialdehyde (biomarker of lipid peroxidation) levels in the first hours of traumatic brain injury (TBI) have been found in patients with a worst prognosis. The objective of this study was to determine whether serum malondialdehyde levels during the first week of severe TBI could be used as mortality biomarkers. This was a multicenter, prospective and observational study performed in six Spanish Intensive Care Units. We included patients with severe TBI (defined as Glasgow Coma Scale < 9), and with Injury Severity Score in non-cranial aspects < 9. We determined serum malondialdehyde concentrations at days 1, 4 and 8 of TBI. We stablished 30-day mortality as the end-point study. Results We found that serum malondialdehyde concentrations at days 1 (p < 0.001), 4 (p < 0.001), and 8 (p < 0.001) of TBI were higher in non-survivor (n = 34) than in survivor (n = 90) patients. We found an area under curve of serum malondialdehyde concentrations at days 1, 4, and 8 of TBI to predict 30-day mortality of 77% (p < 0.001), 87% (p < 0.001) and 84% (p < 0.001) respectively. Thus, the new and most relevant findings of our study were serum malondialdehyde levels during the first week of TBI could be used as mortality biomarkers.


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