Blood Biomarkers Relate to Cognitive Performance Years after Traumatic Brain Injury in Service Members and Veterans

2020 ◽  
pp. 1-7
Author(s):  
Sara M. Lippa ◽  
Jessica Gill ◽  
Tracey A. Brickell ◽  
Louis M. French ◽  
Rael T. Lange
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cognitive Outcome ◽  
Service Members ◽  
Neurocognitive Performance ◽  
Blood Biomarkers ◽  
Post Injury ◽  
Blood Draw ◽  
Neurofilament Light ◽  
History Of

Abstract Objective: This study examines the relationship of serum total tau, neurofilament light (NFL), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) with neurocognitive performance in service members and veterans with a history of traumatic brain injury (TBI). Method: Service members (n = 488) with a history of uncomplicated mild (n = 172), complicated mild, moderate, severe, or penetrating TBI (sTBI; n = 126), injured controls (n = 116), and non-injured controls (n = 74) prospectively enrolled from Military Treatment Facilities. Participants completed a blood draw and neuropsychological assessment a year or more post-injury. Six neuropsychological composite scores and presence/absence of mild neurocognitive disorder (MNCD) were evaluated. Within each group, stepwise hierarchical regression models were conducted. Results: Within the sTBI group, increased serum UCH-L1 was related to worse immediate memory and delayed memory (R2Δ = .065–.084, ps < .05) performance, while increased GFAP was related to worse perceptual reasoning (R2Δ = .030, p = .036). Unexpectedly, within injured controls, UCH-L1 and GFAP were inversely related to working memory (R2Δ = .052–.071, ps < .05), and NFL was related to executive functioning (R2Δ = .039, p = .021) and MNCD (Exp(B) = 1.119, p = .029). Conclusions: Results suggest GFAP and UCH-L1 could play a role in predicting poor cognitive outcome following complicated mild and more severe TBI. Further investigation of blood biomarkers and cognition is warranted.

scholarly journals Serum Neurofilament Light as a Biomarker of Traumatic Brain Injury in the Presence of Concomitant Peripheral Injury

2021 ◽  
Vol 16 ◽  
pp. 117727192110534
Author(s):  
Ker Rui Wong ◽  
William T O’Brien ◽  
Mujun Sun ◽  
Glenn Yamakawa ◽  
Terence J O’Brien ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Elevated Serum ◽  
Serum Levels ◽  
Long Bone ◽  
Post Injury ◽  
Neurofilament Light ◽  
Peripheral Injury ◽  
Long Bone Fracture ◽  
Severe Tbi

Introduction: Serum neurofilament light (NfL) is an emerging biomarker of traumatic brain injury (TBI). However, the effect of peripheral injuries such as long bone fracture and skeletal muscle injury on serum NfL levels is unknown. Therefore, the aim of this study was to determine whether serum NfL levels can be used as a biomarker of TBI in the presence of concomitant peripheral injuries. Methods: Rats were randomly assigned to one of four injury groups: polytrauma (muscle crush + fracture + TBI; n = 11); peripheral injuries (muscle crush + fracture + sham-TBI; n = 12); TBI-only (sham-muscle crush + sham-fracture + TBI; n = 13); and triple-sham (n = 7). At 2-days post-injury, serum levels of NfL were quantified using a Simoa HD-X Analyzer. Results: Compared to triple-sham rats, serum NfL concentrations were higher in rats with peripheral injuries-only, TBI-only, and polytrauma. When compared to peripheral injury-only rats, serum NfL levels were higher in TBI-only and polytrauma rats. No differences were found between TBI-only and polytrauma rats. Conclusion: Serum NfL levels did not differ between TBI-only and polytrauma rats, indicating that significant peripheral injuries did not affect the sensitivity and specificity of serum NfL as a biomarker of moderate TBI. However, the finding of elevated serum NfL levels in rats with peripheral injuries in the absence of a TBI suggests that the presence of such injuries may limit the utility of NfL as a biomarker of less severe TBI (eg, concussion).

306 GCS Does Not Predict Cognitive Outcome 30 Years After Severe Traumatic Brain Injury

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 264-265
Author(s):  
Molly E Hubbard ◽  
Abdullah Bin Zahid ◽  
Gabrielle Meyer ◽  
Kathleen Vonderhaar ◽  
David Y Balser ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Assessment Tool ◽  
Cognitive Status ◽  
Cognitive Outcomes ◽  
Cognitive Outcome ◽  
Symptom Severity Score ◽  
History Of ◽  
Severe Tbi

Abstract INTRODUCTION Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the US. The effects of TBI on quality of life may not become apparent for years after the injury. There are conflicting reports in the literature regarding long term outcomes. Physicians are often asked to predict long term functional and cognitive outcomes, with limited data available. METHODS Patients with severe TBI (GCS = 9) who previously participated in a clinical trial during the 1980s were followed up with and compared to healthy controls without history of TBI. A health questionnaire, sports concussion assessment tool version 3 (SCAT3) and the Telephone Interview for Cognitive Status-modified (TICS-m) were completed over the phone and compared with controls using t-test. GCS at admission and 12-month GRS were used to predict to TICS-M at 30 years using linear regression. RESULTS >45 of the initial 168 subjects were confirmed alive, and 37 (13 females; mean age: 52.43 years S.D. 10.7) consented. Controls (n = 58; 23 females; mean age = 54 years, S.D. 11.5) had lower symptom severity score (6.7 S.D. 12.6 versus 20.6 S.D. 25.3; P = 0.005), lower total number of symptoms (3.4 S.D. 4.7 versus 7.12 S.D. 6.5; P = 0.006), higher standardized assessment of concussion score (25.6 S.D. 2.8 versus 21.2 S.D. 6.9; P = 0.001), and lower corrected MPAI-4 (22.3 S.D. 17.0 versus 43.7 S.D. 12.8; P < 0.001). GCS at admission did not predict cognitive status at 30-years assessed using TICS-M (P = 0.345). The Glasgow Outcome Scale score at 12-months was correlated to TICS-M at 30 years (R = 0.548, P < 0.001); each point decrease in GOS decreasing the score at TICS-M by 5.6 points. CONCLUSION Remote history of TBI disrupts the lives of survivors long after injury. Admission GCS does not predict cognitive status 30 years after TBI. The GOS at 12-months predicted the cognitive status assessed using TICS-M score at 30 years.

scholarly journals A-116 Predicting Chronic Neurobehavioral Symptoms based on Acute Injury Characteristics and Symptoms in U.S. Military Service Members with and without history of TBI

2020 ◽  
Vol 35 (6) ◽  
pp. 909-909
Author(s):  
Lippa S ◽  
Bailie J ◽  
Brickell T ◽  
French L ◽  
Hungerford L ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Military Service ◽  
Service Members ◽  
Injury Characteristics ◽  
Military Service Members ◽  
History Of ◽  
Neurobehavioral Symptoms ◽  
Severe Tbi

Abstract Objective Recovery following traumatic brain injury (TBI) is complex. Often following mild TBI, recovery occurs within days or weeks, though this is not always the case. Following more severe TBI, some recover quickly, while many never fully recover. This study examines acute predictors of chronic neurobehavioral symptoms in U.S. military service members (Age: M = 33.9 years, SD = 10.2) without injury (n = 86), or with history of uncomplicated mild traumatic brain injury (TBI; n = 56), complicated mild, moderate, or severe TBI (mod-sev TBI; n = 43), or bodily injury (n = 25). Method Participants completed the Neurobehavioral Symptom Inventory (NSI), Posttraumatic Stress Disorder Checklist, Alcohol Use Disorder Checklist, Combat Exposure Scale, and TBI Quality of Life and passed symptom validity tests at 0–8 months and ≥ 2 years post-injury. Forward stepwise logistic regression included 26 potential predictors (demographics, injury characteristics, military characteristics, and self-report measures at baseline) of International Statistical Classification of Diseases and Related Health Problems-10 Postconcussional Syndrome (PCSy) at follow-up. Results Cognitive Concerns (Exp(B) = .896, p = .001), Sleep (Exp(B) = 1.874, p &lt; .001), Somatosensory Symptoms (Exp(B) = 1.194, p = .012), and mod-sev TBI (Exp(B) = 2.959, p = .045) significantly predicted follow-up PCSy. When baseline NSI symptoms were removed from the model, Cognitive Concerns (Exp(B) = .902, p &lt; .001), Post-traumatic stress (Exp(B) = 1.173, p = .001), and Resilience (Exp(B) = .950, p &lt; .031) significantly predicted PCSy. For all included measures in both models, higher symptoms at baseline predicted increased likelihood of follow-up PCSy. Both models correctly classified 81.3% of participants. Conclusion Findings suggest patients reporting psychological distress and cognitive concerns acutely should be targeted for treatment to mitigate prolonged neurobehavioral symptoms.

scholarly journals Bioinformatic analysis of brain-specific miRNAs for identification of candidate traumatic brain injury blood biomarkers

2019 ◽  
Author(s):  
Christine Smothers ◽  
Chris Winkelman ◽  
Grant C. O’Connell
Keyword(s):  
Traumatic Brain Injury ◽  
Spinal Cord ◽  
Brain Injury ◽  
Brain Tissue ◽  
Tissue Sample ◽  
Surrogate Marker ◽  
Final Analysis ◽  
Blood Biomarkers ◽  
Post Injury ◽  
Original Analysis

AbstractBackgroundDetection of brain-specific miRNAs in the peripheral blood could serve as a surrogate marker of traumatic brain injury (TBI). Here, we systematically identified brain-enriched miRNAs, and tested their utility for use as TBI biomarkers in the acute phase of care.MethodsPublically-available microarray data generated from 31 postmortem human tissues was used to rank 1,364 miRNAs in terms of their degree of brain-specific expression. Levels of the top five ranked miRNAs were then prospectively measured in serum samples collected from 10 TBI patients at hospital admission, as well as from 10 controls.ResultsThe top five miRNAs identified in our analysis (miR-137, miR-219a-5p, miR-128-3p, miR-124-3p, and miR-138-5p) exhibited 31 to 74-fold higher expression in brain relative to other tissues. Furthermore, their levels were elevated in serum from TBI patients compared to controls, and were collectively able to discriminate between groups with 90% sensitivity and 80% specificity. Subsequent informatic pathway analysis revealed that their target transcripts were significantly enriched for components of signaling pathways which are active in peripheral organs such as the heart.ConclusionsThe five candidate miRNAs identified in this study have promise as blood biomarkers of TBI, and could also be molecular contributors to systemic physiologic changes commonly observed post-injury.A FINAL PEER REVIEWED VERSION OF THIS ARTICLE HAS BEEN PUBLISHED IN BRAIN INJURY AT THE FOLLOWING DOI: 10.1080/02699052.2020.1764102There are some notable differences between the analysis presented in this preprint and our final peer-reviewed article. There was a single tissue sample originating from spinal cord that we had classified as a non-brain tissue in our original analysis outlined in this preprint. Because the composition of spinal cord and brain are highly similar in terms of gene expression, classifying this sample as a non-brain tissue dramatically reduced the levels of brain enrichment observed in the analysis. Because brain and spinal cord are molecularly highly similar, but technically distinct anatomical structures, we simply decided to exclude this sample from our final analysis published in Brain Injury to avoid confounds. The top 5 miRNAs identified in our original analysis still fell within the top 7 of this final analysis. In addition, the final analysis identified two additional miRNAs which could be candidate biomarkers based on levels of brain enrichment.The final article published in Brain Injury also reports an additional confirmatory tissue specificity analysis performed in a second independent dataset, as well as additional analysis examining the brain specificity of several notable previously proposed miRNA TBI biomarkers, which is not described in this preprint.

scholarly journals Impaired visual working memory and reduced connectivity in undergraduates with a history of mild traumatic brain injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hector Arciniega ◽  
Jorja Shires ◽  
Sarah Furlong ◽  
Alexandrea Kilgore-Gomez ◽  
Adelle Cerreta ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Working Memory ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Resting State Fmri ◽  
Underlying Mechanism ◽  
Post Injury ◽  
Behavioral Deficits ◽  
Specific Outcome ◽  
History Of

AbstractMild traumatic brain injury (mTBI), or concussion, accounts for 85% of all TBIs. Yet survivors anticipate full cognitive recovery within several months of injury, if not sooner, dependent upon the specific outcome/measure. Recovery is variable and deficits in executive function, e.g., working memory (WM) can persist years post-mTBI. We tested whether cognitive deficits persist in otherwise healthy undergraduates, as a conservative indicator for mTBI survivors at large. We collected WM performance (change detection, n-back tasks) using various stimuli (shapes, locations, letters; aurally presented numbers and letters), and wide-ranging cognitive assessments (e.g., RBANS). We replicated the observation of a general visual WM deficit, with preserved auditory WM. Surprisingly, visual WM deficits were equivalent in participants with a history of mTBI (mean 4.3 years post-injury) and in undergraduates with recent sports-related mTBI (mean 17 days post-injury). In seeking the underlying mechanism of these behavioral deficits, we collected resting state fMRI (rsfMRI) and EEG (rsEEG). RsfMRI revealed significantly reduced connectivity within WM-relevant networks (default mode, central executive, dorsal attention, salience), whereas rsEEG identified no differences (modularity, global efficiency, local efficiency). In summary, otherwise healthy current undergraduates with a history of mTBI present behavioral deficits with evidence of persistent disconnection long after full recovery is expected.

scholarly journals Exosomal neurofilament light

Neurology ◽  
2020 ◽  
Vol 94 (23) ◽  
pp. e2412-e2423 ◽  
Author(s):  
Vivian A. Guedes ◽  
Kimbra Kenney ◽  
Pashtun Shahim ◽  
Bao-Xi Qu ◽  
Chen Lai ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Plasma Levels ◽  
Depression Symptoms ◽  
Neurofilament Light ◽  
Tnf Α ◽  
Ultrasensitive Assay ◽  
Postconcussive Syndrome ◽  
History Of ◽  
Endothelial Growth Factor

ObjectiveTo measure exosomal and plasma levels of candidate blood biomarkers in veterans with history of mild traumatic brain injury (mTBI) and test their relationship with chronic symptoms.MethodsExosomal and plasma levels of neurofilament light (NfL) chain, tumor necrosis factor (TNF)–α, interleukin (IL)–6, IL-10, and vascular endothelial growth factor (VEGF) were measured using an ultrasensitive assay in a cohort of 195 veterans, enrolled in the Chronic Effects of Neurotrauma Consortium Longitudinal Study. We examined relationships between candidate biomarkers and symptoms of postconcussive syndrome (PCS), posttraumatic stress disorder (PTSD), and depression. Biomarker levels were compared among those with no traumatic brain injury (TBI) (controls), 1–2 mTBIs, and repetitive (3 or more) mTBIs.ResultsElevated exosomal and plasma levels of NfL were associated with repetitive mTBIs and with chronic PCS, PTSD, and depression symptoms. Plasma TNF-α levels correlated with PCS and PTSD symptoms. The total number of mTBIs correlated with exosomal and plasma NfL levels and plasma IL-6. Increased number of years since the most recent TBI correlated with higher exosomal NfL and lower plasma IL-6 levels, while increased number of years since first TBI correlated with higher levels of exosomal and plasma NfL, as well as plasma TNF-α and VEGF.ConclusionRepetitive mTBIs are associated with elevated exosomal and plasma levels of NfL, even years following these injuries, with the greatest elevations in those with chronic PCS, PTSD, and depression symptoms. Our results suggest a possible neuroinflammatory and axonal disruptive basis for symptoms that persist years after mTBI, especially repetitive.

scholarly journals Correlates of Depression in U.S. Military Service Members With a History of Mild Traumatic Brain Injury

2019 ◽  
Vol 184 (Supplement_1) ◽  
pp. 148-154 ◽  
Author(s):  
Jan E Kennedy ◽  
Lisa H Lu ◽  
Matthew W Reid ◽  
Felix O Leal ◽  
Douglas B Cooper
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Military Service ◽  
Depressive Disorders ◽  
Service Members ◽  
Data Repository ◽  
Military Health ◽  
Increased Risk ◽  
History Of ◽  
Combat Deployments

AbstractObjectivesPost-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) are identified as signature injuries of the Wars in Iraq and Afghanistan. Statistics have confirmed a high incidence of PTSD among military personnel with mild TBI (mTBI) who served in these conflicts. Although receiving less attention, individuals with a history of mTBI are also at increased risk for depressive disorders. This study examines the incidence and correlates of depression in service members with a history of mTBI received an average of 4–1/2 years prior to evaluation.MethodsRetrospective analysis of 184 service members with a history of mTBI extracted from a data repository maintained at a military medical center.ResultsOne-third of the sample (34.2%) was clinically diagnosed with a depressive disorder in the month preceding evaluation. Of those with depression, 81% (51 of 63) were also diagnosed with PTSD. Proportionately more women than men had depression. Depression was more common among those who were undergoing a Military Evaluation Board and those who served in more than three combat deployments.ConclusionsResults confirm chronically elevated the rates of depressive disorders and PTSD comorbidity among service members with a history of mTBI. Depression screening and treatment within the Military Health System should remain a priority for service members reporting a remote history of mTBI. Individuals with chronic PTSD, women, service members undergoing MEB and those who served in greater than three combat deployments are at particular risk.

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