Browsing by Author "Robertson, Claudia S."

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    Diffusion Tensor Imaging Reveals Elevated Diffusivity of White Matter Microstructure that Is Independently Associated with Long-Term Outcome after Mild Traumatic Brain Injury: A TRACK-TBI Study
    (Mary Ann Liebert, 2022) Palacios, Eva M.; Yuh, Esther L.; Mac Donald, Christine L.; Bourla, Ioanna; Wren-Jarvis, Jamie; Sun, Xiaoying; Vassar, Mary J.; Diaz-Arrastia, Ramon; Giacino, Joseph T.; Okonkwo, David O.; Robertson, Claudia S.; Stein, Murray B.; Temkin, Nancy; McCrea, Michael A.; Levin, Harvey S.; Markowitz, Amy J.; Jain, Sonia; Manley, Geoffrey T.; Mukherjee, Pratik; TRACK-TBI Investigators; Psychiatry, School of Medicine
    Diffusion tensor imaging (DTI) literature on single-center studies contains conflicting results regarding acute effects of mild traumatic brain injury (mTBI) on white matter (WM) microstructure and the prognostic significance. This larger-scale multi-center DTI study aimed to determine how acute mTBI affects WM microstructure over time and how early WM changes affect long-term outcome. From Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI), a cohort study at 11 United States level 1 trauma centers, a total of 391 patients with acute mTBI ages 17 to 60 years were included and studied at two weeks and six months post-injury. Demographically matched friends or family of the participants were the control group (n = 148). Axial diffusivity (AD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were the measures of WM microstructure. The primary outcome was the Glasgow Outcome Scale Extended (GOSE) score of injury-related functional limitations across broad life domains at six months post-injury. The AD, MD, and RD were higher and FA was lower in mTBI versus friend control (FC) at both two weeks and six months post-injury throughout most major WM tracts of the cerebral hemispheres. In the mTBI group, AD and, to a lesser extent, MD decreased in WM from two weeks to six months post-injury. At two weeks post-injury, global WM AD and MD were both independently associated with six-month incomplete recovery (GOSE <8 vs = 8) even after accounting for demographic, clinical, and other imaging factors. DTI provides reliable imaging biomarkers of dynamic WM microstructural changes after mTBI that have utility for patient selection and treatment response in clinical trials. Continued technological advances in the sensitivity, specificity, and precision of diffusion magnetic resonance imaging hold promise for routine clinical application in mTBI.
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    High-Sensitivity C-Reactive Protein is a Prognostic Biomarker of Six-Month Disability after Traumatic Brain Injury: Results from the TRACK-TBI Study
    (Mary Ann Liebert, 2021) Xu, Linda B.; Yue, John K.; Korley, Frederick; Puccio, Ava M.; Yuh, Esther L.; Sun, Xiaoying; Rabinowitz, Miri; Vassar, Mary J.; Taylor, Sabrina R.; Winkler, Ethan A.; Puffer, Ross C.; Deng, Hansen; McCrea, Michael; Stein, Murray B.; Robertson, Claudia S.; Levin, Harvey S.; Dikmen, Sureyya; Temkin, Nancy R.; Giacino, Joseph T.; Mukherjee, Pratik; Wang, Kevin K. W.; Okonkwo, David O.; Markowitz, Amy J.; Jain, Sonia; Manley, Geoffrey T.; Diaz-Arrastia, Ramon; TRACK-TBI Investigators; Psychiatry, School of Medicine
    Systemic inflammation impacts outcome after traumatic brain injury (TBI), but most TBI biomarker studies have focused on brain-specific proteins. C-reactive protein (CRP) is a widely used biomarker of inflammation with potential as a prognostic biomarker after TBI. The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study prospectively enrolled TBI patients within 24 h of injury, as well as orthopedic injury and uninjured controls; biospecimens were collected at enrollment. A subset of hospitalized participants had blood collected on day 3, day 5, and 2 weeks. High-sensitivity CRP (hsCRP) and glial fibrillary acidic protein (GFAP) were measured. Receiver operating characteristic analysis was used to evaluate the prognostic ability of hsCRP for 6-month outcome, using the Glasgow Outcome Scale-Extended (GOSE). We included 1206 TBI subjects, 122 orthopedic trauma controls (OTCs), and 209 healthy controls (HCs). Longitudinal biomarker sampling was performed in 254 hospitalized TBI subjects and 19 OTCs. hsCRP rose between days 1 and 5 for TBI and OTC subjects, and fell by 2 weeks, but remained elevated compared with HCs (p < 0.001). Longitudinally, hsCRP was significantly higher in the first 2 weeks for subjects with death/severe disability (GOSE <5) compared with those with moderate disability/good recovery (GOSE ≥5); AUC was highest at 2 weeks (AUC = 0.892). Combining hsCRP and GFAP at 2 weeks produced AUC = 0.939 for prediction of disability. Serum hsCRP measured within 2 weeks of TBI is a prognostic biomarker for disability 6 months later. hsCRP may have utility as a biomarker of target engagement for anti-inflammatory therapies.
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    Pathological Computed Tomography Features Associated With Adverse Outcomes After Mild Traumatic Brain Injury
    (American Medical Association, 2021) Yuh, Esther L.; Jain, Sonia; Sun, Xiaoying; Pisică, Dana; Harris, Mark H.; Taylor, Sabrina R.; Markowitz, Amy J.; Mukherjee, Pratik; Verheyden, Jan; Giacino, Joseph T.; Levin, Harvey S.; McCrea, Michael; Stein, Murray B.; Temkin, Nancy R.; Diaz-Arrastia, Ramon; Robertson, Claudia S.; Lingsma, Hester F.; Okonkwo, David O.; Maas, Andrew I. R.; Manley, Geoffrey T.; TRACK-TBI Investigators for the CENTER-TBI Investigators; Adeoye, Opeolu; Badjatia, Neeraj; Boase, Kim; Bodien, Yelena; Corrigan, John D.; Crawford, Karen; Dikmen, Sureyya; Duhaime, Ann-Christine; Ellenbogen, Richard; Feeser, V. Ramana; Ferguson, Adam R.; Foreman, Brandon; Gardner, Raquel; Gaudette, Etienne; Gonzalez, Luis; Gopinath, Shankar; Gullapalli, Rao; Hemphill, J. Claude; Hotz, Gillian; Keene, C. Dirk; Kramer, Joel; Kreitzer, Natalie; Lindsell, Chris; Machamer, Joan; Madden, Christopher; Martin, Alastair; McAllister, Thomas; Merchant, Randall; Nelson, Lindsay; Ngwenya, Laura B.; Noel, Florence; Nolan, Amber; Palacios, Eva; Perl, Daniel; Rabinowitz, Miri; Rosand, Jonathan; Sander, Angelle; Satris, Gabriella; Schnyer, David; Seabury, Seth; Toga, Arthur; Valadka, Alex; Vassar, Mary; Zafonte, Ross; Psychiatry, School of Medicine
    Importance: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood. Objective: To identify pathological CT features associated with adverse outcomes after mTBI. Design, setting, and participants: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021. Exposures: Acute nonpenetrating head trauma. Main outcomes and measures: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months. Results: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study. Conclusions and relevance: In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.
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    Recovery After Mild Traumatic Brain Injury in Patients Presenting to US Level I Trauma Centers: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study
    (American Medical Association, 2019-06-03) Nelson, Lindsay D.; Temkin, Nancy R.; Dikmen, Sureyya; Barber, Jason; Giacino, Joseph T.; Yuh, Esther; Levin, Harvey S.; McCrea, Michael A.; Stein, Murray B.; Mukherjee, Pratik; Okonkwo, David O.; Robertson, Claudia S.; Diaz-Arrastia, Ramon; Manley, Geoffrey T.; TRACK-TBI Investigators; McAllister, Thomas; Psychiatry, School of Medicine
    Question How common are persistent, injury-related functional limitations following mild traumatic brain injury vs orthopedic trauma? Findings In this cohort study of 1154 patients with mild traumatic brain injury and 299 patients with orthopedic trauma serving as controls, 53% of participants with mild traumatic brain injury reported impairment 12 months postinjury vs 38% of those with orthopedic trauma. Patients with intracranial abnormalities had the poorest outcomes; however, patients without abnormalities also reported problems at 12 months. Meaning Many patients who present to level I trauma centers with mild traumatic brain injury experience difficulties at 12 months postinjury, suggesting that this injury is not always benign; better follow-up and treatment appear to be needed.
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    Smaller Regional Brain Volumes Predict Posttraumatic Stress Disorder at 3 Months after Mild Traumatic Brain Injury
    (Elsevier, 2021) Stein, Murray B.; Yuh, Esther; Jain, Sonia; Okonkwo, David O.; Mac Donald, Christine L.; Levin, Harvey; Giacino, Joseph T.; Dikmen, Sureyya; Vassar, Mary J.; Diaz-Arrastia, Ramon; Robertson, Claudia S.; Nelson, Lindsay D.; McCrea, Michael; Sun, Xiaoying; Temkin, Nancy; Taylor, Sabrina R.; Markowitz, Amy J.; Manley, Geoffrey T.; Mukherjee, Pratik; TRACK-TBI Investigators; Psychiatry, School of Medicine
    Background: Brain volumes in regions such as the hippocampus and amygdala have been associated with risk for the development of posttraumatic stress disorder (PTSD). The objective of this study was to determine whether a set of regional brain volumes, measured by magnetic resonance imaging at 2 weeks following mild traumatic brain injury, were predictive of PTSD at 3 and 6 months after injury. Methods: Using data from TRACK-TBI (Transforming Research and Clinical Knowledge in TBI), we included patients (N = 421) with Glasgow Coma Scale scores 13-15 assessed after evaluation in the emergency department and at 2 weeks, 3 months, and 6 months after injury. Probable PTSD diagnosis (PTSD Checklist for DSM-5 score, ≥33) was the outcome. FreeSurfer 6.0 was used to perform volumetric analysis of three-dimensional T1-weighted magnetic resonance images at 3T obtained 2 weeks post injury. Brain regions selected a priori for volumetric analyses were insula, hippocampus, amygdala, superior frontal cortex, rostral and caudal anterior cingulate, and lateral and medial orbitofrontal cortices. Results: Overall, 77 (18.3%) and 70 (16.6%) patients had probable PTSD at 3 and 6 months. A composite volume derived as the first principal component incorporating 73.8% of the variance in insula, superior frontal cortex, and rostral and caudal cingulate contributed to the prediction of 3-month (but not 6-month) PTSD in multivariable models incorporating other established risk factors. Conclusions: Results, while needing replication, provide support for a brain reserve hypothesis of PTSD and proof of principle for how prediction of at-risk individuals might be accomplished to enhance prognostic accuracy and enrich clinical prevention trials for individuals at the highest risk of PTSD following mild traumatic brain injury.