scholarly journals 0014 Reduced Cortical Thickness as a Biomarker of Daytime Sleepiness in Mild Traumatic Brain Injury

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A5-A6
Author(s):  
N S Dailey ◽  
A C Raikes ◽  
A Alkozei ◽  
M A Grandner ◽  
W D Killgore
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Cortical Thickness ◽  
Daytime Sleepiness ◽  
Healthy Controls ◽  
Inferior Parietal Lobule ◽  
Post Injury ◽  
Attention Network ◽  
Parietal Lobule

Abstract Introduction Sleep disruptions, including the increase of daytime sleepiness, are reported in roughly 70% of all individuals who have suffered a mild traumatic brain injury (mTBI). Prior research using magnetic resonance imaging (MRI) has identified associations between functional brain changes and daytime sleepiness following mTBI. In the present study, we aimed to identify whether structural differences in cortical thickness are associated with increased daytime sleepiness in adults with mTBI. Methods A total of 58 adults between 18 and 45 years of age (M=23.58±5.31) participated in the study, including 19 healthy controls and 39 individuals with a documented mTBI. Individuals with mTBI were further divided based on time-since-injury into a sub-acute (n=22) or chronic (n=17) group. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS) and cortical thickness was measured using high-resolution T1-weighted structural MRI. Whole-brain vertex-wise estimations of cortical thickness were calculated using FreeSurfer (v.6.0) and entered into a GLM to identify between-group differences in cortical thickness and the association with ESS. Results Significant differences in cortical thickness were found between the two mTBI groups (cluster-forming threshold p<.01; cluster-wise threshold p<.05; two-tailed; FWE-corrected). Specifically, lower cortical thickness in the left hemisphere was found in the inferior parietal lobule (p=.01), precuneus (p=.03), and pars triangularis (p=.04) for the sub-acute, compared to chronic group. Furthermore, a significant negative correlation was found between ESS and cortical thickness in the inferior parietal lobule (r=-.55, p=.009) for the sub-acute mTBI group. Conclusion More daytime sleepiness was associated with reduced inferior parietal cortical thickness in those 2 to 12-weeks post-injury, an association not observed in those 6 to 12-months post-injury or healthy controls. The inferior parietal lobule is part of the frontoparietal attention network and has been associated with vulnerability to sleep loss. Our findings suggest structural damage to the attention network following mTBI may be one factor affecting daytime sleepiness in mTBI. These findings may reflect a potential biomarker of sleep disturbances in mTBI. Support USAMRMC grant (W81XWH-12–0386).

scholarly journals A pilot study exploring pupil response measurement in mild traumatic brain injury

2015 ◽  
Vol 42 (S1) ◽  
pp. S40-S40
Author(s):  
W Ting ◽  
J Topolovec-Vranic ◽  
M McGowan ◽  
MD Cusimano
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Healthy Controls ◽  
Response Dynamics ◽  
Post Injury ◽  
Response Measurement ◽  
Pupil Response ◽  
Post Traumatic ◽  
Traumatic Symptoms

Background: Pupillometry, the measurement of pupil response dynamics via the pupillary light reflex, is seldom used in the assessment of mild traumatic brain injury (mTBI). We hypothesized that there would be quantifiable differences in detailed pupil response measurements in patients with acute and chronic mTBI. Methods: We conducted 49 bilateral pupillometry measurements, in acute mTBI patients at 1-week (N=11), 2-4w (N=9), and 3-7mo post-injury (N=3); 14 patients with persistent post-traumatic symptoms (PTS) once, and healthy controls across a first visit (N=7) and second visit 2-4w later (N=5). Results: The percentage of left pupil diameter change was significantly greater in the acute mTBI group at second visit (mean=36.3% (2.96)), compared to controls at second visit (mean=31.6% (4.39)) (F=5.87, p=0.0321). We did not identify significant differences between acute mTBI patients and controls at first visit, PTS patients versus controls, and within the acute mTBI group across three longitudinal visits. Conclusion: While these preliminary data suggest that pupillometry under these conditions does not distinguish between patients who had a recent mTBI or those with PTS and healthy controls, further research is warranted investigating pupil behavior and its clinical utility in mTBI.

scholarly journals Free-living Turning Rather Than Gait Differentiates People with Chronic Mild Traumatic Brain Injury from Controls

2021 ◽  
Author(s):  
Dylan Powell ◽  
Alan Godfrey ◽  
Lucy Parrington ◽  
Kody R. Campbell ◽  
Laurie A. King ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Physical Function ◽  
Mild Traumatic Brain Injury ◽  
Healthy Controls ◽  
Post Injury ◽  
Free Living ◽  
Sensitive Measure ◽  
Gait Characteristics

Abstract Background: Physical function remains a crucial component of mild traumatic brain injury (mTBI) assessment and recovery. Traditional approaches to assess mTBI lack sensitivity to subtle deficits post-injury, which can impact quality of life, daily function and can lead to chronic issues. Inertial measurement units (IMU) provide an objective alternative for measuring physical function of gait and turning and can be used in any environment. Our recent work has found that turning quality is more sensitive than the quantity of physical activity when comparing chronic mTBI and healthy controls. However, no studies have compared the quality of free-living gait and turning characteristics concurrently in chronic mTBI and healthy controls. This study aimed to determine whether free-living gait or turning is more sensitive in differentiating chronic mTBI from controls.Methods: Thirty-two people with chronic self-reported balance symptoms after mTBI (age: 40.88 ± 11.78 years, median days post injury: 440.68 days) and 23 healthy controls (age: 48.56 ± 22.56 years) were assessed for ~7 days using a single IMU at the waist on a belt. Free-living gait and turning characteristics were evaluated for chronic mTBI and controls using multi-variate analysis. Receiver operating characteristics (ROC) and Area Under the Curve (AUC) analysis were used to determine outcome sensitivity to chronic mTBI.Results: Free-living gait characteristics were not different in chronic mTBI and controls (all p>0.05). In contrast, all but two (number of turns and average velocity CV) free-living turning characteristics were significantly different between chronic mTBI and controls, whilst controlling for age and sex (Bonferroni adjusted p<0.002). The chronic mTBI group had larger turn angles and longer turn durations compared to controls. ROC and AUC analysis showed turn duration (AUC = 0.92) was the most sensitive measure for differentiating chronic mTBI from controls. Conclusions: Results show that turning rather than gait characteristics were significantly different between chronic mTBI and controls, with turn duration being the most sensitive measure. These results suggest turning is a suitable surrogate biomarker to assess and monitor chronic mTBI.

Severity of Ongoing Post-Concussive Symptoms as a Predictor of Cognitive Performance Following a Pediatric Mild Traumatic Brain Injury

2020 ◽  
pp. 1-11
Author(s):  
Veronik Sicard ◽  
Danielle C. Hergert ◽  
Sharvani Pabbathi Reddy ◽  
Cidney R. Robertson-Benta ◽  
Andrew B. Dodd ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cognitive Performance ◽  
Mild Traumatic Brain Injury ◽  
Parental Education ◽  
Visual Learning ◽  
Learning Task ◽  
Risk Scores ◽  
Group Differences ◽  
Post Injury

Abstract Objective: This study aimed to examine the predictors of cognitive performance in patients with pediatric mild traumatic brain injury (pmTBI) and to determine whether group differences in cognitive performance on a computerized test battery could be observed between pmTBI patients and healthy controls (HC) in the sub-acute (SA) and the early chronic (EC) phases of injury. Method: 203 pmTBI patients recruited from emergency settings and 159 age- and sex-matched HC aged 8–18 rated their ongoing post-concussive symptoms (PCS) on the Post-Concussion Symptom Inventory and completed the Cogstate brief battery in the SA (1–11 days) phase of injury. A subset (156 pmTBI patients; 144 HC) completed testing in the EC (∼4 months) phase. Results: Within the SA phase, a group difference was only observed for the visual learning task (One-Card Learning), with pmTBI patients being less accurate relative to HC. Follow-up analyses indicated higher ongoing PCS and higher 5P clinical risk scores were significant predictors of lower One-Card Learning accuracy within SA phase, while premorbid variables (estimates of intellectual functioning, parental education, and presence of learning disabilities or attention-deficit/hyperactivity disorder) were not. Conclusions: The absence of group differences at EC phase is supportive of cognitive recovery by 4 months post-injury. While the severity of ongoing PCS and the 5P score were better overall predictors of cognitive performance on the Cogstate at SA relative to premorbid variables, the full regression model explained only 4.1% of the variance, highlighting the need for future work on predictors of cognitive outcomes.

scholarly journals Exosomal MicroRNA Differential Expression in Plasma of Young Adults with Chronic Mild Traumatic Brain Injury and Healthy Control

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 36
Author(s):  
Rany Vorn ◽  
Maiko Suarez ◽  
Jacob C. White ◽  
Carina A. Martin ◽  
Hyung-Suk Kim ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Young Adults ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Pathophysiological Mechanism ◽  
Post Injury ◽  
Persistent Symptoms ◽  
Healthy Control ◽  
Underlying Mechanisms

Chronic mild traumatic brain injury (mTBI) has long-term consequences, such as neurological disability, but its pathophysiological mechanism is unknown. Exosomal microRNAs (exomiRNAs) may be important mediators of molecular and cellular changes involved in persistent symptoms after mTBI. We profiled exosomal microRNAs (exomiRNAs) in plasma from young adults with or without a chronic mTBI to decipher the underlying mechanisms of its long-lasting symptoms after mTBI. We identified 25 significantly dysregulated exomiRNAs in the chronic mTBI group (n = 29, with 4.48 mean years since the last injury) compared to controls (n = 11). These miRNAs are associated with pathways of neurological disease, organismal injury and abnormalities, and psychological disease. Dysregulation of these plasma exomiRNAs in chronic mTBI may indicate that neuronal inflammation can last long after the injury and result in enduring and persistent post-injury symptoms. These findings are useful for diagnosing and treating chronic mTBIs.

scholarly journals Structural brain connectivity predicts acute pain after mild traumatic brain injury

2021 ◽  
Author(s):  
Paulo Branco ◽  
Noam Bosak ◽  
Jannis Bielefeld ◽  
Olivia Cong ◽  
Yelena Granovsky ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Mild Traumatic Brain Injury ◽  
Acute Pain ◽  
Pain Perception ◽  
Strong Predictor ◽  
Pain Modulation ◽  
Acute Injury ◽  
Post Injury

Mild traumatic brain injury, mTBI, is a leading cause of disability worldwide, with acute pain manifesting as one of its most debilitating symptoms. Understanding acute post-injury pain is important since it is a strong predictor of long-term outcomes. In this study, we imaged the brains of 172 patients with mTBI, following a motorized vehicle collision and used a machine learning approach to extract white matter structural and resting state fMRI functional connectivity measures to predict acute pain. Stronger white matter tracts within the sensorimotor, thalamic-cortical, and default-mode systems predicted 20% of the variance in pain severity within 72 hours of the injury. This result generalized in two independent groups: 39 mTBI patients and 13 mTBI patients without whiplash symptoms. White matter measures collected at 6-months after the collision still predicted mTBI pain at that timepoint (n = 36). These white-matter connections were associated with two nociceptive psychophysical outcomes tested at a remote body site – namely conditioned pain modulation and magnitude of suprathreshold pain–, and with pain sensitivity questionnaire scores. Our validated findings demonstrate a stable white-matter network, the properties of which determine a significant amount of pain experienced after acute injury, pinpointing a circuitry engaged in the transformation and amplification of nociceptive inputs to pain perception.

scholarly journals Self-Reported Complaints as Prognostic Markers for Outcome After Mild Traumatic Brain Injury in Elderly: A Machine Learning Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Mayra Bittencourt ◽  
Sebastián A. Balart-Sánchez ◽  
Natasha M. Maurits ◽  
Joukje van der Naalt
Keyword(s):  
Machine Learning ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Elderly Patients ◽  
Neck Pain ◽  
Functional Outcome ◽  
Mild Traumatic Brain Injury ◽  
Prognostic Markers ◽  
The Elderly ◽  
Post Injury

Self-reported complaints are common after mild traumatic brain injury (mTBI). Particularly in the elderly with mTBI, the pre-injury status might play a relevant role in the recovery process. In most mTBI studies, however, pre-injury complaints are neither analyzed nor are the elderly included. Here, we aimed to identify which individual pre- and post-injury complaints are potential prognostic markers for incomplete recovery (IR) in elderly patients who sustained an mTBI. Since patients report many complaints across several domains that are strongly related, we used an interpretable machine learning (ML) approach to robustly deal with correlated predictors and boost classification performance. Pre- and post-injury levels of 20 individual complaints, as self-reported in the acute phase, were analyzed. We used data from two independent studies separately: UPFRONT study was used for training and validation and ReCONNECT study for independent testing. Functional outcome was assessed with the Glasgow Outcome Scale Extended (GOSE). We dichotomized functional outcome into complete recovery (CR; GOSE = 8) and IR (GOSE ≤ 7). In total 148 elderly with mTBI (median age: 67 years, interquartile range [IQR]: 9 years; UPFRONT: N = 115; ReCONNECT: N = 33) were included in this study. IR was observed in 74 (50%) patients. The classification model (IR vs. CR) achieved a good performance (the area under the receiver operating characteristic curve [ROC-AUC] = 0.80; 95% CI: 0.74–0.86) based on a subset of only 8 out of 40 pre- and post-injury complaints. We identified increased neck pain (p = 0.001) from pre- to post-injury as the strongest predictor of IR, followed by increased irritability (p = 0.011) and increased forgetfulness (p = 0.035) from pre- to post-injury. Our findings indicate that a subset of pre- and post-injury physical, emotional, and cognitive complaints has predictive value for determining long-term functional outcomes in elderly patients with mTBI. Particularly, post-injury neck pain, irritability, and forgetfulness scores were associated with IR and should be assessed early. The application of an ML approach holds promise for application in self-reported questionnaires to predict outcomes after mTBI.

Insufficient Sleep Following Pediatric Mild Traumatic Brain Injury Correlates With Neurocognitive Dysfunction

Neurology ◽  
2021 ◽  
Vol 98 (1 Supplement 1) ◽  
pp. S1.1-S1
Author(s):  
Bailey Hull ◽  
Patrick Karabon ◽  
Neal Alpiner
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sleep Disturbance ◽  
Mild Traumatic Brain Injury ◽  
Daytime Sleepiness ◽  
Epworth Sleepiness Scale ◽  
Neurocognitive Function ◽  
Neurocognitive Dysfunction ◽  
Neurocognitive Test ◽  
Test Outcomes

ObjectiveAnalyze the impact of sleep disturbance on neurocognitive function in children recovering from mild traumatic brain injury (mTBI).BackgroundSleep disturbance of any nature is reported in more than half of all mTBI patients. The pathophysiology of sleep disturbance following mTBI is associated with structural and functional disruptions of sleep circuitry and circadian rhythm. Specifically in the pediatric population, untreated sleep disturbance has been shown to delay mTBI recovery and compound other morbidities including neurocognitive dysfunction.Design/MethodsA retrospective chart review of 118 pediatric patients (mean age = 14.56 ± 2.03 years) recovering from mTBI was performed. Epworth Sleepiness Scale (SF-8) results were analyzed in relation to CNS Vital Signs (CNSVS) neurocognitive test outcomes. SF-8 is a subjective estimation of a patient's daytime sleepiness. CNSVS uses a multitude of domains to objectively evaluate the overall neurocognitive status of a patient. Pearson correlations were calculated using a type I error of p < 0.05 between variables.ResultsEpworth Sleepiness Scale (SF-8) results showed 28.82% of participants experienced excessive daytime sleepiness sufficient enough to recommend medical attention. Upon further analysis, there was a significant negative correlation between SF-8 and CNSVS neurocognitive test outcomes including complex attention (r = −0.37; p = 0.0004), cognitive flexibility (r = −0.24; p = 0.0151), executive function (r = −0.21; p = 0.0350), and simple attention (r = −0.36; p = 0.0003) scores. This means as SF-8 scores increased (participants defined as excessively sleepy), neurocognitive function scores in these domains decreased. There was not enough evidence to conclude a significant correlation between other CNSVS domains and SF-8 (all p > 0.05).ConclusionsOur findings support the concern of neurocognitive dysfunction among pediatric mTBI patients with sleep disturbance. Further analysis is needed to determine if mTBI is the primary source or an exacerbating factor of sleep disturbance within this population. Nonetheless, these findings suggest a need for thorough evaluation when treating sleep concerns, irrespective of a history of childhood mTBI.

scholarly journals Highly Sensitive Single Molecular Array Immunoassay Measurement of t-Tau, NF-L, GFAP, and UCH-L1 Biomarkers in Acute Concussion/Mild Traumatic Brain Injury (mTBI) Patient Serum and Saliva Samples

Neurology ◽  
2019 ◽  
Vol 93 (14 Supplement 1) ◽  
pp. S19.3-S20
Author(s):  
Ahmed Chenna ◽  
Christos Petropoulos ◽  
John Winslow
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Limited Information ◽  
Post Injury ◽  
Time Points ◽  
Highly Sensitive ◽  
Biomarker Analysis ◽  
T Tau ◽  
Control Samples

ObjectiveTo determine if t-Tau, NF-L, GFAP and UCH-L1 protein biomarkers are elevated in early time points of acute concussion/mild traumatic brain injury patient serum and saliva, relative to control samples.Backgroundt-Tau, NF-L, GFAP and UCH-L1 levels have been reported to increase in cerebral spinal fluid (CSF) and blood following head trauma within 24 hours or longer, and are candidate diagnostic and prognostic biomarkers of concussion and mild to moderate TBI. However, limited information exists on the relationship between these biomarkers at short time points post-injury, and detectability in saliva of mTBI patients.Design/MethodsBiomarker analysis of serum from a total of 120 participants, derived from two independent sample groups consisting of 60 concussion/mTBI patients each, with blood collected within 1-4 hr and 8-16 hr post-injury, respectively, was compared with 30 healthy control sera. Saliva samples were collected after 8-16 hr post-injury from a n = 30 subset of the same patients. Quanterix Simoa 4-plex immunoassay was used for highly sensitive measurements of these biomarkers.ResultsMedian levels of NF-L, GFAP and UCH-L1 were significantly higher in independent sets of patient serum samples (n = 60 each), both at early (1–4 hr) and later (8–16 hr) time points post-mTBI/concussion, relative to control samples (n = 30) (p < 0.0001, = 0.0001, <0.0001, respectively). Low levels of t-Tau are detected, but are significantly elevated post-concussion relative to controls (p = 0.0001). Significant correlations were observed between levels of t-Tau and UCH-L1, NF-L and GFAP, and t-Tau and GFAP in both post-injury time-point groups, and between NF-L and UCH-L1 levels in the 8-16 hr group. The four biomarkers were detected in saliva from concussion/mTBI patients (n = 30).ConclusionsThis study supports the utility of ultra-sensitive multiplex immunoassays to detect increases in CNS proteins at high sensitivity in serum and saliva within 1-4 and 8-16 hr of concussion/mTBI.

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