Sex Differences in Behavioral Symptoms and the Levels of Circulating GFAP, Tau, and NfL in Patients With Traumatic Brain Injury

Traumatic brain injury (TBI) affects millions of Americans each year and has been shown to disproportionately impact those subject to greater disparities in health. Female sex is one factor that has been associated with disparities in health outcomes, including in TBI, but sex differences in biomarker levels and behavioral outcomes after TBI are underexplored. This study included participants with both blunt and blast TBI with majority rating their TBI as mild. Time since injury was 5.4 (2.0, 15.5) years for females and 6.8 (2.4, 11.3) years for males. The aim of this cross sectional study is to investigate the relationship between postconcussive, depression, and post-traumatic stress disorder (PTSD) symptoms, as well as health related quality of life (HRQOL), and the levels of glial fibrillary acidic protein (GFAP), total tau (t-tau), neurofilament light chain (NfL), and ubiquitin C-terminal hydrolase-L1 (UCH-L1). Behavioral outcomes were evaluated with the Neurobehavioral Symptom Inventory (NSI), Patient Health Questionnaire-9 (PHQ-9), PTSD Checklist- Civilian Version (PCL-C), short form (SF)-36, and plasma levels of total tau, GFAP, NfL, and UCHL-1 measured with the Simoa-HDX. We observed that females had significantly higher levels of GFAP and tau (ps < 0.05), and higher PHQ-9 scores, NSI total scores, NSI- vestibular, NSI-somatosensory, NSI-affective sub-scale scores (ps < 0.05)), than males. In addition, females had lower scores in HRQOL outcomes of role limitations due to emotional problems, vitality, emotional well-being, social functioning, and pain compared to males (ps < 0.05). Correlation analysis showed positive associations between levels of tau and the NSI-total and NSI-cognitive sub-scale scores (ps < 0.05) in females. No significant associations were found for NfL or GFAP with NSI scores. For female participants, negative correlations were observed between tau and NfL concentrations and the SF-36 physical function subscale (ps < 0.05), as well as tau and the social function subscale (p < 0.001), while GFAP levels positively correlated with role limitations due to emotional problems (p = 0.004). No significant associations were observed in males. Our findings suggest that sex differences exist in TBI-related behavioral outcomes, as well as levels of biomarkers associated with brain injury, and that the relationship between biomarker levels and behavioral outcomes is more evident in females than males. Future studies are warranted to corroborate these results, and to determine the implications for prognosis and treatment. The identification of candidate TBI biomarkers may lead to development of individualized treatment guidelines.

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Galveston Orientation and Amnesia Test: applicability and relation with the Glasgow Coma Scale

Revista Latino-Americana de Enfermagem ◽

10.1590/s0104-11692007000400020 ◽

2007 ◽

Vol 15 (4) ◽

pp. 651-657 ◽

Cited By ~ 6

Author(s):

Silvia Cristina Fürbringer e Silva ◽

Regina Marcia Cardoso de Sousa

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Glasgow Coma Scale ◽

Prospective Study ◽

Trauma Care ◽

Coma Scale ◽

Traumatic Amnesia ◽

Scale Scores ◽

Post Traumatic ◽

The Relationship

Restrictions in the application of the Galveston Orientation and Amnesia Test and questionings about the relationship between conscience and post-traumatic amnesia motivated this study, which aims to identify, through the Glasgow Coma Scale scores, when to initiate the application of this amnesia test, as well to verify the relationship between the results of these two indicators. The longitudinal prospective study was carried at a referral center for trauma care in São Paulo - Brazil. The sample consisted of 73 victims of blunt traumatic brain injury, admitted at this institution between January 03rd and May 03rd 2001. Regarding the applicability, the test could be applied in patients with a Glasgow Coma Scale score > 12; however, the end of post traumatic amnesia was verified in patients who scored > 14 on the scale. A significant relationship (r s = 0.65) was verified between these measures, although different kinds of relationship between the end of the amnesia and changes in consciousness were observed.

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The relationship between brain tissue oxygen partial pressure thresholds and microdialysis markers of ischaemia in traumatic brain injury

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9591524.0561 ◽

2005 ◽

Vol 25 (1_suppl) ◽

pp. S561-S561

Author(s):

Jurgens Nortje ◽

Peter J Hutchinson ◽

David A Zygun ◽

Pippa G Al-Rawi ◽

Mark T O'Connell ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Oxygen Partial Pressure ◽

Partial Pressure ◽

Brain Tissue ◽

Tissue Oxygen ◽

Brain Tissue Oxygen ◽

The Relationship ◽

Tissue Oxygen Partial Pressure

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NEUROPSYCHOLOGICAL CHANGES IN PATIENTS WITH A CONSEQUENCE OF TRAUMATIC BRAIN INJURY

JOURNAL OF NEUROLOGY AND NEUROSURGICAL RESEARCH ◽

10.26739/2181-0982-2020-3-9 ◽

2020 ◽

Vol 3 (1) ◽

pp. 44-46

Author(s):

Istatillo Shodjalilov ◽

◽

Saoda Igamova ◽

Aziza Djurabekova

Keyword(s):

Traumatic Brain Injury ◽

Cognitive Impairment ◽

Brain Injury ◽

Neuropsychological Testing ◽

Anxiety And Depression ◽

Psychopathological Symptoms ◽

Neuropsychological Changes ◽

The Relationship

The incidence of cognitive impairment in TBI is high, depending on the severity. At the same time, psychopathological symptoms in the form of asthenia, increased anxiety and depression are encountered among patients with TBI. The work studied the relationship between cognitive and psychopathological symptoms in patients with TBI using neuropsychological testing on scales.

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Intracranial Pressure during External Ventricular Drainage Weaning Is an Outcome Predictor of Traumatic Brain Injury

BioMed Research International ◽

10.1155/2020/8379134 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Jia-cheng Gu ◽

Hong Wu ◽

Xing-zhao Chen ◽

Jun-feng Feng ◽

Guo-yi Gao ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Intracranial Pressure ◽

External Ventricular Drainage ◽

Unfavorable Outcome ◽

Ventricular Drainage ◽

Outcome Group ◽

Significant Difference ◽

The Mean ◽

The Relationship

External ventricular drainage (EVD) is widely used in patients with a traumatic brain injury (TBI). However, the EVD weaning trial protocol varies and insufficient studies focus on the intracranial pressure (ICP) during the weaning trial. We aimed to establish the relationship between ICP during an EVD weaning trial and the outcomes of TBI. We enrolled 37 patients with a TBI with an EVD from July 2018 to September 2019. Among them, 26 were allocated to the favorable outcome group and 11 to the unfavorable outcome group (death, post-traumatic hydrocephalus, persistent vegetative state, and severe disability). Groups were well matched for sex, pupil reactivity, admission Glasgow Coma Scale score, Marshall computed tomography score, modified Fisher score, intraventricular hemorrhage, EVD days, cerebrospinal fluid output before the weaning trial, and the complications. Before and during the weaning trial, we recorded the ICP at 1-hour intervals to calculate the mean ICP, delta ICP, and ICP burden, which was defined as the area under the ICP curve. There were significant between-group differences in the age, surgery types, and intensive care unit days (p=0.045, p=0.028, and p=0.004, respectively). During the weaning trial, 28 (75.7%) patients had an increased ICP. Although there was no significant difference in the mean ICP before and during the weaning trial, the delta ICP was higher in the unfavorable outcome group (p=0.001). Moreover, patients who experienced death and hydrocephalus had a higher ICP burden, which was above 20 mmHg (p=0.016). Receiver operating characteristic analyses demonstrated the predictive ability of these variables (area under the curve AUC=0.818 [p=0.002] for delta ICP and AUC=0.758 [p=0.038] for ICP burden>20 mmHg). ICP elevation is common during EVD weaning trials in patients with TBI. ICP-related parameters, including delta ICP and ICP burden, are significant outcome predictors. There is a need for larger prospective studies to further explore the relationship between ICP during EVD weaning trials and TBI outcomes.

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Comparing Plasma Phospho Tau, Total Tau, and Phospho Tau–Total Tau Ratio as Acute and Chronic Traumatic Brain Injury Biomarkers

JAMA Neurology ◽

10.1001/jamaneurol.2017.0655 ◽

2017 ◽

Vol 74 (9) ◽

pp. 1063 ◽

Cited By ~ 74

Author(s):

Richard Rubenstein ◽

Binggong Chang ◽

John K. Yue ◽

Allen Chiu ◽

Ethan A. Winkler ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Total Tau

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THE RELATIONSHIP BETWEEN EARLY BLOOD PRESSURE VARIABILITY AND SHORT-TERM PROGNOSIS IN SEVERE TRAUMATIC BRAIN INJURY PATIENTS

Heart ◽

10.1136/heartjnl-2012-302920r.15 ◽

2012 ◽

Vol 98 (Suppl 2) ◽

pp. E255.4-E256

Author(s):

Chen Hui ◽

Wu Xiaoying ◽

Chen Hui

Keyword(s):

Blood Pressure ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Severe Traumatic Brain Injury ◽

Blood Pressure Variability ◽

Short Term ◽

The Relationship

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Relationship of “dose” of intracranial hypertension to outcome in severe traumatic brain injury

Journal of Neurosurgery ◽

10.3171/jns/2008/109/10/0678 ◽

2008 ◽

Vol 109 (4) ◽

pp. 678-684 ◽

Cited By ~ 127

Author(s):

Anne Vik ◽

Torbjørn Nag ◽

Oddrun Anita Fredriksli ◽

Toril Skandsen ◽

Kent Gøran Moen ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Intracranial Hypertension ◽

Scale Score ◽

Severe Traumatic Brain Injury ◽

Injury Severity ◽

Area Under The Curve ◽

Term Outcome ◽

Long Term Outcome ◽

Scale Scores

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.

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