scholarly journals Plasma Phospholipid Metabolites Associate With Functional Outcomes Following Mild Traumatic Brain Injury in Older Adults

2020 ◽  
Vol 23 (1) ◽  
pp. 127-135
Author(s):  
Sarah R. Martha ◽  
Kuan-Fu Chen ◽  
Yvonne Lin ◽  
Hilaire J. Thompson

Objective: To compare differences using a metabolomics approach in older adults (≥55) with mild traumatic brain injury (mTBI) to control adults and to identify a signature profile related to functional outcome 3–6 months post-injury. Methods: We performed metabolomics analysis using LC-MS of untargeted aqueous metabolites on plasma samples taken from a parent prospective cohort study. Older adults with mTBI (n = 14) were purposively sampled to include participants with worsening (decrease in GOS-E of at least 1 level) and improved (increase in GOS-E of at least 1 level) outcomes from 3 to 6 months. The data were analyzed using PLS-DA with VIP scores, Random Forest, and spline fit between the different groups as a function of time for exposure on outcome. Results: Separation of comparisons were seen at 24 hours (negative ionization) and 6 months (positive ionization), revealing two metabolites of interest, phosphatidylcholine and phosphatidylethanolamine. Phosphatidylcholine levels were higher in those with mTBI compared to controls ( p < 0.05), while lower concentration of phosphatidylethanolamine was seen in those with mTBI compared to controls ( p < 0.05). Phosphatidylinositol-3,4,5-trisphosphate was significant in those with mTBI compared to controls (n = 10) based on improved (n = 6) versus worsened (n = 8) outcomes from 3 to 6 months. Conclusion: We identified plasma metabolites related to phospholipid metabolism in older adults following mTBI and associated with long-term functional outcome. These findings may underly pathological mechanisms of outcome differences in older adults who experience mTBI.

Brain Injury ◽  
2019 ◽  
Vol 34 (1) ◽  
pp. 26-33 ◽  
Author(s):  
Justin E. Karr ◽  
Grant L. Iverson ◽  
Ksenia Berghem ◽  
Anna-Kerttu Kotilainen ◽  
Douglas P. Terry ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Mayra Bittencourt ◽  
Sebastián A. Balart-Sánchez ◽  
Natasha M. Maurits ◽  
Joukje van der Naalt

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.


2020 ◽  
Vol 9 (5) ◽  
pp. 1525 ◽  
Author(s):  
Daphne C. Voormolen ◽  
Marina Zeldovich ◽  
Juanita A. Haagsma ◽  
Suzanne Polinder ◽  
Sarah Friedrich ◽  
...  

The objective of this study was to provide a comprehensive examination of the relation of complicated and uncomplicated mild traumatic brain injury (mTBI) with multidimensional outcomes at three- and six-months after TBI. We analyzed data from the Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) research project. Patients after mTBI (Glasgow Coma scale (GCS) score of 13–15) enrolled in the study were differentiated into two groups based on computed tomography (CT) findings: complicated mTBI (presence of any traumatic intracranial injury on first CT) and uncomplicated mTBI (absence of any traumatic intracranial injury on first CT). Multidimensional outcomes were assessed using seven instruments measuring generic and disease-specific health-related quality of life (HRQoL) (SF-36 and QOLIBRI), functional outcome (GOSE), and psycho-social domains including symptoms of post-traumatic stress disorder (PTSD) (PCL-5), depression (PHQ-9), and anxiety (GAD-7). Data were analyzed using a multivariate repeated measures approach (MANOVA-RM), which inspected mTBI groups at three- and six-months post injury. Patients after complicated mTBI had significantly lower GOSE scores, reported lower physical and mental component summary scores based on the SF-36 version 2, and showed significantly lower HRQoL measured by QOLIBRI compared to those after uncomplicated mTBI. There was no difference between mTBI groups when looking at psychological outcomes, however, a slight improvement in PTSD symptoms and depression was observed for the entire sample from three to six months. Patients after complicated mTBI reported lower generic and disease specific HRQoL and worse functional outcome compared to individuals after uncomplicated mTBI at three and six months. Both groups showed a tendency to improve from three to six months after TBI. The complicated mTBI group included more patients with an impaired long-term outcome than the uncomplicated group. Nevertheless, patients, clinicians, researchers, and decisions-makers in health care should take account of the short and long-term impact on outcome for patients after both uncomplicated and complicated mTBI.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 829-829
Author(s):  
David Robles ◽  
Ammar Dharani ◽  
Nikhil Chaudhari ◽  
Kenneth Rostowsky ◽  
Layal Wehbe ◽  
...  

Abstract The contributions of age, sex, and cerebral microbleeds (CMBs) to WM changes after mild traumatic brain injury (mTBI) have not been studied. We used diffusion tensor imaging (DTI) to map WM fractional anisotropy (FA) changes across the first ~6 months post-mTBI in 109 subjects aged 18-77 (46 females; age µ: 40 y, σ: 17 y) imaged within ~1 week post-injury and ~6 months later. After partialing out age, sex, and CMB counts, significant mean FA decreases were found in the anterior body, posterior body, and splenium of the corpus callosum (CC; p = 0.003, 0.009 and 0.015, respectively), left superficial frontal fasciculus (p = 0.008), and left branch of the corticospinal tract (CST; p = 0.007). Age contributed to mean FAs measured acutely in the CC body (p = 0.04), and chronically in the CC genu (p &lt; 0.001), CC body (p = 0.01), and middle longitudinal fasciculi (p = 0.04), older adults exhibiting larger decreases. CMB counts were positively associated with mean FA decreases in the CC body (p = 0.04) and middle longitudinal fasciculi (p = 0.04). Significant age-by-sex and CMB count-by-age interactions mediated FA decreases in the CC genu (p = 0.02 and p = 0.03, respectively), older males exhibiting larger decreases. Thus, the CC, longitudinal fasciculi, superficial frontal WM and CST are particularly vulnerable to post-traumatic neurodegeneration moderated by age, sex and CMB count, men and older adults being at highest risk for adverse effects. Future research should investigate our findings relative to cognitive function.


Author(s):  
Breton M. Asken ◽  
William G. Mantyh ◽  
Renaud La Joie ◽  
Amelia Strom ◽  
Kaitlin B. Casaletto ◽  
...  

Author(s):  
Veronik Sicard ◽  
Danielle C. Hergert ◽  
Sharvani Pabbathi Reddy ◽  
Cidney R. Robertson-Benta ◽  
Andrew B. Dodd ◽  
...  

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.


Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 36
Author(s):  
Rany Vorn ◽  
Maiko Suarez ◽  
Jacob C. White ◽  
Carina A. Martin ◽  
Hyung-Suk Kim ◽  
...  

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.


2021 ◽  
Author(s):  
Paulo Branco ◽  
Noam Bosak ◽  
Jannis Bielefeld ◽  
Olivia Cong ◽  
Yelena Granovsky ◽  
...  

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.


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