Josephina Rau, Rose Joseph, Lara Weise, Jessica Bryan, Jad Wardeh, Alekya Konda, Landon Duplessis, Michelle A Hook
{"title":"Acute Opioid Administration Undermines Recovery after SCI: Adverse Effects Are Not Restricted to Morphine.","authors":"Josephina Rau, Rose Joseph, Lara Weise, Jessica Bryan, Jad Wardeh, Alekya Konda, Landon Duplessis, Michelle A Hook","doi":"10.1089/neu.2024.0375","DOIUrl":"https://doi.org/10.1089/neu.2024.0375","url":null,"abstract":"<p><p>Previous studies have shown that administration of high doses of morphine in the acute phase of spinal cord injury (SCI) significantly undermines locomotor recovery and increases symptoms of chronic pain in a rat spinal contusion model. Similarly, SCI patients treated with high doses of opioid for the first 24 h postinjury have increased symptoms of chronic pain 1 year later. Whether these adverse effects are driven by morphine only or all opioids compromise recovery after SCI, however, is unknown. Based on our previous findings we hypothesized that activation of the kappa opioid receptor (KOR) is key in the morphine-induced attenuation of locomotor recovery after SCI. Thus, we posited that opioids that engage KOR-mediated signaling pathways (morphine, oxycodone) would undermine recovery, and clinically relevant opioids with less KOR activity (fentanyl and buprenorphine) would not. To test this, we compared the effects of the clinically relevant opioids on locomotor recovery and pain in a male rat spinal contusion model. Rats were given a moderate spinal contusion injury followed by 7 days of intravenous morphine, oxycodone, fentanyl, buprenorphine, or saline, and recovery was assessed for 28 days. All opioids produced analgesia on tests of thermal, mechanical, and incremented shock reactivity. However, tolerance developed rapidly with buprenorphine administration, particularly with daily administrations of 5 morphine milligram equivalent (MME) buprenorphine. Opioid-induced hyperalgesia (OIH) also developed across days following administration of higher doses (10 MME, 20 MME) of morphine and oxycodone. Fentanyl and buprenorphine did not produce OIH. Contrary to our hypothesis, however, we found that high doses of all opioids reduced recovery of locomotor function. Unlike the other opioids, the effects of buprenorphine on locomotor recovery appeared transient, but it also produced chronic pain. Morphine, oxycodone, and buprenorphine decreased reactivity thresholds on tests of mechanical and incremented shock stimulation. In sum, all opioids undermined long-term recovery in the rat model. Further interrogation of the molecular mechanisms driving the adverse effects is essential. This study provides critical insight into pain management strategies in the acute phase of SCI and potential long-term consequences of early opioid administration.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali Mansour, Elena Badillo, Ronald Alvarado-Dyer, Olga Pasternak, Huy Tram N Nguyen, Farima Fakhri, Elaine Lo, Joseph Wilson, Mark DeGuzman, Molly Lawrence, John Nugent, Harsh Desai, William Roth, Jordan Fuhrman, Peleg Horowitz, Paramita Das, Andrii Sirko, Tracey Fan, Elizabeth Carroll, Susan Rowell, Christos Lazaridis, Maryellen Giger, Fernando D Goldenberg
{"title":"Brain Imaging Features in Patients with Gunshot Wounds to the Head.","authors":"Ali Mansour, Elena Badillo, Ronald Alvarado-Dyer, Olga Pasternak, Huy Tram N Nguyen, Farima Fakhri, Elaine Lo, Joseph Wilson, Mark DeGuzman, Molly Lawrence, John Nugent, Harsh Desai, William Roth, Jordan Fuhrman, Peleg Horowitz, Paramita Das, Andrii Sirko, Tracey Fan, Elizabeth Carroll, Susan Rowell, Christos Lazaridis, Maryellen Giger, Fernando D Goldenberg","doi":"10.1089/neu.2024.0464","DOIUrl":"https://doi.org/10.1089/neu.2024.0464","url":null,"abstract":"<p><p>To introduce the UChicago PBI Imaging score, a novel characterization of imaging features using head computed tomography (HCT) in patients with gunshot wounds to the head (GSWH) resulting in penetrating brain injury (PBI) and to quantify the association with mortality. We retrospectively collected and analyzed data from 230 patients with GSWH admitted to our Level 1 trauma center between May 1, 2018, and October 31, 2023. HCT images obtained on hospital arrival were evaluated for predefined imaging features by two blinded readers and arbitrated, when needed, by a third. The average contribution of each radiological feature to mortality at hospital discharge was assessed using a SuperLearner ensemble model trained on ∼77% of the cohort. Each feature's contribution was scaled to ensure the additive final score per patient ranged between 0 and 100. The HCT features predicting in-hospital mortality, ranked from highest to lowest importance, were transhemispheric projectile below the level of the third ventricle (18 [16.8, 19.9]), presence of blood in the lateral ventricles (ventricles casted) (18[16.8, 19.6]), brainstem involvement (14 [12.7, 15.1]), transhemispheric projectile above the level of the third ventricle (11 [9.7, 11.6]), presence of any amount of blood in the ambient cistern (9[8.2, 10]), presence of any amount of blood in the lateral ventricles (9 [7.9, 9.8]), cerebellar involvement (9 [7.9, 9.5]), any evidence of ventricular effacement (4 [3.4, 4.6]), midline shift (MLS) >0 mm (4 [3.4, 4.4]), perforating injury (3 [2.4, 3.2]), and presence of an intracerebral hematoma (ICH) >20 mm in the largest diameter (2 [1.4, 1.9]). The UChicago PBI Imaging score showed a strong performance, achieving an area under the curve (AUC) of 0.86 (95% CI: [0.77, 0.96]) on a test set of 56 patients who were not included in model training. This indicates better prediction accuracy compared to both the Rotterdam score (AUC 0.8, 95% CI: [0.68, 0.96]) and the Marshall score (AUC 0.66, 95% CI: [0.52, 0.81]). Our model performed particularly well for patients with a Glasgow Coma Scale (GCS) score between 5 and 9. In this range, our model's performance (AUC 0.86) remained stable, while the Rotterdam and Marshall Scores showed notably lower predictive accuracy, with AUCs of 0.61 and 0.52, respectively. A dedicated evaluation of GSWH HCT reveals an association between disease burden, as quantified by unique features not native to blunt TBI imaging models, and mortality. Specifically, transhemispheric injury below the level of the third ventricle along with blood-casting bilateral ventricles and brainstem involvement was highly associated with mortality. The model is optimized for intermediate GCS scores where greater prognostic uncertainty exists. This study parallels efforts to refine TBI classification, underscoring the necessity for precise imaging-based classification in PBI to identify imaging biomarkers and ultimately enhance prognostication and targeted","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Justin Maldonado, Jason H Huang, Ed W Childs, Binu Tharakan
{"title":"Response to Thompson and Moore.","authors":"Justin Maldonado, Jason H Huang, Ed W Childs, Binu Tharakan","doi":"10.1089/neu.2023.0622","DOIUrl":"https://doi.org/10.1089/neu.2023.0622","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Attenuation of Blood-Brain Barrier Disruption in Traumatic Brain Injury via Inhibition of NKCC1 Cotransporter: Insights into the NF-κB/NLRP3 Signaling Pathway.","authors":"Zehan Zhang, Hui Wang, Bingyan Tao, Xudong Shi, Guilin Chen, Hengchao Ma, Ruiyun Peng, Jun Zhang","doi":"10.1089/neu.2023.0580","DOIUrl":"https://doi.org/10.1089/neu.2023.0580","url":null,"abstract":"<p><p>Following traumatic brain injury (TBI), inhibition of the Na<sup>+</sup>-K<sup>+</sup>-Cl<sup>-</sup> cotransporter1 (NKCC1) has been observed to alleviate damage to the blood-brain barrier (BBB). However, the underlying mechanism for this effect remains unclear. This study aimed to investigate the mechanisms by which inhibiting the NKCC1 attenuates disruption of BBB integrity in TBI. The TBI model was induced in C57BL/6 mice through a controlled cortical impact device, and an <i>in vitro</i> BBB model was established using Transwell chambers. Western blot (WB) analysis was used to evaluate NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor-kappaB (NF-κB) pathway proteins. Flow cytometry and transendothelial electrical resistance (TEER) were employed to assess endothelial cell apoptosis levels and BBB integrity. ELISA was utilized to measure cytokines interleukin-1β (IL-1β) and matrix metalloproteinase-9 (MMP-9). Immunofluorescence techniques were used to evaluate protein levels and the nuclear translocation of the rela (p65) subunit. The Evans blue dye leakage assay and the brain wet-dry weight method were utilized to assess BBB integrity and brain swelling. Inhibition of NKCC1 reduced the level of NLRP3 inflammasome and the secretion of IL-1β and MMP-9 in microglia. Additionally, NKCC1 inhibition suppressed the activation of the NF-κB signaling pathway, which in turn decreased the level of NLRP3 inflammasome. The presence of NLRP3 inflammasome in BV2 cells led to compromised BBB integrity within an inflammatory milieu. Following TBI, an upregulation of NLRP3 inflammasome was observed in microglia, astrocytes, vascular endothelial cells, and neurons. Furthermore, inhibiting NKCC1 resulted in a decrease in the positive rate of NLRP3 inflammasome in microglia and the levels of inflammatory cytokines IL-1β and MMP-9 after TBI, which correlated with BBB damage and the development of cerebral edema. These findings demonstrate that the suppression of the NKCC1 cotransporter protein alleviates BBB disruption through the NF-κB/NLRP3 signaling pathway following TBI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah L Schantz, Kylee J Duberstein, Erin E Kaiser, Franklin D West
{"title":"Human Neural Stem Cell Therapy for Traumatic Brain Injury-A Systematic Review of Pre-Clinical Studies.","authors":"Sarah L Schantz, Kylee J Duberstein, Erin E Kaiser, Franklin D West","doi":"10.1089/neu.2024.0544","DOIUrl":"https://doi.org/10.1089/neu.2024.0544","url":null,"abstract":"<p><p>Human neural stem cells (hNSCs) possess significant therapeutic potential for the treatment of traumatic brain injury (TBI), a leading cause of global death and disability. Recent pre-clinical studies have shown that hNSCs reduce tissue damage and promote functional recovery through neuroprotective and regenerative signaling and cell replacement. Yet the overall efficacy of hNSCs for TBI indications remains unclear. Therefore, this systematic review aims to evaluate hNSC interventions compared with controls in pre-clinical TBI models. Through this process, variations in hNSC administration protocols were consolidated, and key knowledge gaps were identified. Meta-analysis was applied to primary outcomes of lesion volume, Morris Water Maze (MWM) performance, modified Neurological Severity Scores (mNSS), and the rotarod task. Narrative review of secondary outcomes included hNSC survival and differentiation, endogenous neuron survival, axonal injury, and inflammation. Overall, hNSC intervention reduced lesion volume, enhanced MWM performance, and led to trending decreases in acute and chronic neurological deficits at acute and chronic time points. These results suggest hNSCs demonstrate clear efficacy in pre-clinical TBI models. However, further studies are needed to address key questions regarding optimal hNSC administration (e.g., dosing, treatment window) and underlying mechanisms of action prior to progressing to human clinical trials.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jean-Francois Payen, Antoine Vilotitch, Tobias Gauss, Anais Adolle, Jean-Luc Bosson, Pierre Bouzat
{"title":"Sex Differences in Neurological Outcome at 6 and 12 Months Following Severe Traumatic Brain Injury. An Observational Analysis of the OXY-TC Trial.","authors":"Jean-Francois Payen, Antoine Vilotitch, Tobias Gauss, Anais Adolle, Jean-Luc Bosson, Pierre Bouzat","doi":"10.1089/neu.2024.0390","DOIUrl":"https://doi.org/10.1089/neu.2024.0390","url":null,"abstract":"<p><p>The effect of sex in outcomes after severe traumatic brain injury (TBI) remains uncertain. We explored whether outcomes differed between women and men after standardized care management during the first 5 days in the intensive care unit (ICU). This study was an observational analysis of the OXY-TC multicenter randomized clinical trial between June 15, 2016 and April 17, 2021. Recruited patients had a pre-hospital Glasgow Coma Scale (GCS) score of 3-8, mechanical ventilation, and intracranial pressure (ICP) with or without brain tissue oxygen pressure (PbtO<sub>2</sub>) monitoring. Objectives were to maintain ICP at 20 mmHg or below and PbtO2 above 20 mmHg at all times. The primary end-point was the proportion of women and men with poor outcomes at 6 months, corresponding to an extended Glasgow Outcome Scale (GOSE) score of 1-4 (death to upper severe disability). Of 318 randomized patients, 200 men and 71 women were analyzed. They were comparable in age, comorbidities, and initial injury severity scores. However, women had larger doses of ICP as the proportion of monitoring time of ICP above 20 mmHg 8% (3-18; median, interquartile range) versus 3% (1-10), respectively (<i>p</i> = 0.002). They required more often at least one tier-3 treatment, i.e., barbiturate coma and therapeutic hypothermia, for refractory intracranial hypertension during the first 5 days in the ICU: 33/68 (48%) versus 60/193 (31%), respectively (<i>p</i> = 0.012). At 6 months, the proportion of women with GOSE 1-4 was significantly higher than men: 48/71 (68%) versus 94/200 (47%), respectively (odds ratio 2.35 [1.33-4.16]; <i>p</i> = 0.003]. Similar differences were found using Disability Rating Scale and Functional Independence Measure at 6 and 12 months, and GOSE at 12 months. Sex differences in neurological outcomes persisted after adjustment for other determinants of outcome such as age, initial GCS score, and dose of ICP during the 5-day monitoring. In conclusion, women sustained more severe ICP and required more active treatment, both of which would explain a worse outcome after severe TBI. Prospective research is required to confirm these findings and identify possible mechanisms. Trial registration: ClinicalTrials.gov Identifier NCT02754063 (April 28, 2016).</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hannah L Radabaugh, Neil G Harris, Ina B Wanner, Mark P Burns, Joseph T McCabe, Alexandru V Korotcov, Bernard J Dardzinski, Jinyuan Zhou, Raymond C Koehler, Jieru Wan, Javier Allende Labastida, Babak Moghadas, Adnan Bibic, Marcelo Febo, Firas H Kobeissy, Jiepei Zhu, Richard Rubenstein, Jiamei Hou, Prodip K Bose, Seza Apiliogullari, Michael S Beattie, Jacqueline C Bresnahan, Susanna Rosi, J Russell Huie, Adam R Ferguson, Kevin K W Wang
{"title":"Translational Outcomes Project in Neurotrauma (TOP-NT) Pre-Clinical Consortium Study: A Synopsis.","authors":"Hannah L Radabaugh, Neil G Harris, Ina B Wanner, Mark P Burns, Joseph T McCabe, Alexandru V Korotcov, Bernard J Dardzinski, Jinyuan Zhou, Raymond C Koehler, Jieru Wan, Javier Allende Labastida, Babak Moghadas, Adnan Bibic, Marcelo Febo, Firas H Kobeissy, Jiepei Zhu, Richard Rubenstein, Jiamei Hou, Prodip K Bose, Seza Apiliogullari, Michael S Beattie, Jacqueline C Bresnahan, Susanna Rosi, J Russell Huie, Adam R Ferguson, Kevin K W Wang","doi":"10.1089/neu.2023.0654","DOIUrl":"https://doi.org/10.1089/neu.2023.0654","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) has long been a leading cause of death and disability, yet research has failed to successfully translate findings from the pre-clinical, animal setting into the clinic. One factor that contributes significantly to this struggle is the heterogeneity observed in the clinical setting where patients present with injuries of varying types, severities, and comorbidities. Modeling this highly varied population in the laboratory remains challenging. Given feasibility constraints, individual laboratories often focus on single injury types and are limited to an abridged set of outcome measures. Furthermore, laboratories tend to use different injury or outcome methodologies from one another, making it difficult to compare studies and identify which pre-clinical findings may be best suited for clinical translation. The NINDS-funded Translational Outcomes Project in Neurotrauma (TOP-NT) is a multi-site consortium designed to address the reproducibility, rigor, and transparency of pre-clinical development and validation of clinically relevant biomarkers for TBI. The current overview article provides a detailed description of the infrastructure and strategic approach undertaken by the consortium. We outline the TOP-NT strategy to address three goals: (1) selection and cross-center validation of biomarker tools, (2) development and population of a data infrastructure to allow for the sharing and reuse of pre-clinical, animal research following findable, accessible, interoperable, and reusable data guidelines, and (3) demonstration of feasibility, reproducibility, and transparency in conducting a multi-center, pre-clinical research trial for TBI biomarker development. The synthesized scientific analysis and results of the TOP-NT efforts will be the topic of future articles.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ina-Beate Wanner, Joseph T McCabe, J Russell Huie, Neil G Harris, Afshin Paydar, Chloe McMann-Chapman, Anthony Tobar, Alexandru Korotcov, Mark P Burns, Raymond C Koehler, Jieru Wan, Javier Allende Labastida, Jonathan Tong, Jinyuan Zhou, Lex Maliga Davis, Hannah L Radabaugh, Adam R Ferguson, Timothy E Van Meter, Marcelo Febo, Prodip Bose, Kevin K Wang, Firas Kobeissy, Seza Apiliogullari, Jiepei Zhu, Richard Rubenstein, Hibah O Awwad
{"title":"Prospective Harmonization, Common Data Elements, and Sharing Strategies for Multicenter Pre-Clinical Traumatic Brain Injury Research in the Translational Outcomes Project in Neurotrauma Consortium.","authors":"Ina-Beate Wanner, Joseph T McCabe, J Russell Huie, Neil G Harris, Afshin Paydar, Chloe McMann-Chapman, Anthony Tobar, Alexandru Korotcov, Mark P Burns, Raymond C Koehler, Jieru Wan, Javier Allende Labastida, Jonathan Tong, Jinyuan Zhou, Lex Maliga Davis, Hannah L Radabaugh, Adam R Ferguson, Timothy E Van Meter, Marcelo Febo, Prodip Bose, Kevin K Wang, Firas Kobeissy, Seza Apiliogullari, Jiepei Zhu, Richard Rubenstein, Hibah O Awwad","doi":"10.1089/neu.2023.0653","DOIUrl":"https://doi.org/10.1089/neu.2023.0653","url":null,"abstract":"<p><p>Effective team science requires procedural harmonization for rigor and reproducibility. Multicenter studies across experimental modalities (domains) can help accelerate translation. The Translational Outcomes Project in NeuroTrauma (TOP-NT) is a pre-clinical traumatic brain injury (TBI) consortium charged with establishing and validating noninvasive TBI assessment tools through team science. Here, we present practical approaches for harmonization of TBI research across five centers providing needed vocabulary and structure to achieve centralized data organization and use. This includes data sharing as an essential step that enables validating data between domains, evaluating reproducibility between sites, and performing multimodal analyses. As part of this process, TOP-NT (1) produced a library of TBI-relevant standard operating procedures to coordinate workflow, (2) aligned 481 pre-clinical and clinical common data elements (CDEs), and (3) generated 272 new pre-clinical TBI CDEs. This consortium then (4) connected diverse data types to validate assessments across domains and to allow multivariable TBI phenotyping. Lastly, TOP-NT (5) specified technical quality controls for pre-clinical studies. These harmonization tools can facilitate reproducibility in team science, help distinguish a wide injury spectrum from technical variability, apply quality-controls, and ease higher level data analyses. TOP-NT uses three rat TBI models across four sites. Each site collects primary outcome measures, including magnetic resonance imaging (MRI) protocols and blood biomarkers of neuronal and glial injury, validated by histopathology and behavioral outcomes. Collected data are organized using the 481 TOP-NT pre-clinical CDEs, covering surgical, behavioral, biomarker, MRI, and quantitative histopathological methods. We report data curation steps suited for data storage using the Open Data Commons for TBI as a centralized data repository, allowing unbiased cross-site analysis. This approach leads to introducing a higher level, syndromic understanding of TBI signatures. TOP-NT authors outline a semantic and structural framework suggesting strategies for robust pre-clinical research in multicenter trials to improve translatability for TBI assessments. [Figure: see text].</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nabil Awan, Justin Weppner, Raj G Kumar, Shannon B Juengst, Kristen Dams-O'Connor, Mitch Sevigny, Ross D Zafonte, William C Walker, Jerzy P Szaflarski, Amy K Wagner
{"title":"Impact of Post-Traumatic Epilepsy on Mental Health and Multidimensional Outcome and Quality of Life: An NIDILRR TBIMS Study.","authors":"Nabil Awan, Justin Weppner, Raj G Kumar, Shannon B Juengst, Kristen Dams-O'Connor, Mitch Sevigny, Ross D Zafonte, William C Walker, Jerzy P Szaflarski, Amy K Wagner","doi":"10.1089/neu.2024.0117","DOIUrl":"https://doi.org/10.1089/neu.2024.0117","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) and subsequent post-traumatic epilepsy (PTE) often impair daily activities and mental health (MH), which contribute to long-term TBI-related disability. PTE also affects driving capacity, which impacts functional independence, community participation, and satisfaction with life (SWL). However, studies evaluating the collective impact of PTE on multidimensional outcomes are lacking. Thus, we generated a model to investigate how PTE after moderate-to-severe (ms)TBI affects TBI-associated impairments, limits activities and participation, and influences SWL. Of 5108 participants with msTBI enrolled into the National Institute for Disability, Independent Living, and Rehabilitation Research TBI Model Systems between 2010 and 2018 and with seizure-event data available at year-1 post-TBI, 1214 had complete outcome data and 1003 had complete covariate data used for analysis. We constructed a conceptual framework illustrating hypothesized interrelationships between year-1 PTE, driving status, functional independence measure (FIM), depression and anxiety, as well as year-2 participation, and SWL. We performed univariate and multivariable linear and logistic regressions. A covariate-adjusted structural equation model (SEM), using the lavaan package (R), assessed the conceptual framework's suitability in establishing PTE links with outcomes 1-2 years post-injury. Multiple parameters were evaluated to assess SEM fit. Year-1 PTE was correlated with year-1 FIM motor (standardized coefficient, β<sub>std</sub> = -0.112, <i>p</i> = 0.007) and showed a trend level association with year-1 FIM cognition (β<sub>std</sub> = -0.070, <i>p</i> = 0.079). Individuals with year-1 PTE were less likely to drive independently at year 1 (β<sub>std</sub> = -0.148, <i>p</i> < 0.001). In addition, FIM motor (β<sub>std</sub> = 0.323, <i>p</i> < 0.001), FIM cognition (β<sub>std</sub> = 0.181, <i>p</i> = 0.012), and anxiety (β<sub>std</sub> = -0.135, <i>p</i> = 0.024) influenced driving status. FIM cognition was associated with year-1 depression (β<sub>std</sub> = 0.386, <i>p</i> < 0.001) and year-1 anxiety (β<sub>std</sub> = 0.396, <i>p</i> < 0.001), whereas year-1 FIM motor (β<sub>std</sub> = 0.186, <i>p</i> = 0.003), depression (β<sub>std</sub> = -0.322, <i>p</i> = 0.011), and driving status (β<sub>std</sub> = 0.233, <i>p</i> < 0.001) directly affected year-2 objective life participation metrics. Moreover, year-1 depression (β<sub>std</sub> = -0.382, <i>p</i> = 0.001) and year-2 participation (β<sub>std</sub> = 0.160, <i>p</i> < 0.001) had direct effects on year-2 SWL. SWL was influenced indirectly by year-1 variables, including functional impairment, anxiety, and driving status-factors that impacted year-2 participation directly or indirectly, and consequently year-2 SWL, forming a complex relationship with year-1 PTE. A sensitivity analysis SEM showed that the number of MH disorders was associated with participation and SWL (<i>p</i> < 0.001), an","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Noah D Silverberg, Kathy Lee, Ana Mikolić, Mark T Bayley, David L Brody, E Wesley Ely, Joseph T Giacino, Cathra Halabi, Flora M Hammond, Daniel A Ignacio, Caterina Mosti, Joukje van der Naalt, Monique R Pappadis, Olli Tenovuo, Vincent Y Wang, Monica Verduzco-Gutierrez, Geoffrey T Manley
{"title":"Priority Clinical Actions for Outpatient Management of Nonhospitalized Traumatic Brain Injury.","authors":"Noah D Silverberg, Kathy Lee, Ana Mikolić, Mark T Bayley, David L Brody, E Wesley Ely, Joseph T Giacino, Cathra Halabi, Flora M Hammond, Daniel A Ignacio, Caterina Mosti, Joukje van der Naalt, Monique R Pappadis, Olli Tenovuo, Vincent Y Wang, Monica Verduzco-Gutierrez, Geoffrey T Manley","doi":"10.1089/neu.2024.0414","DOIUrl":"https://doi.org/10.1089/neu.2024.0414","url":null,"abstract":"<p><p>Outpatient care following nonhospitalized traumatic brain injury (TBI) is variable, and often sparse. The National Academies of Sciences, Engineering, and Medicine's 2022 report on <i>Traumatic Brain Injury: A Roadmap for Accelerating Progress</i> highlighted the need to improve the consistency and quality of TBI care in the community. In response, the present study aimed to identify existing evidence-based guidance and specific clinical actions over the days to months following nonhospitalized TBI that should be prioritized for implementation in primary care. In systematic literature searches, 17 clinical practice guidelines met our eligibility criteria and an additional expert consensus statement was considered highly relevant. We extracted 73 topics covered by one or more existing clinical practice guidelines. After removing redundant and out-of-scope topics, those deemed essential (not requiring prioritization), 42 topics were subjected to a prioritization exercise. Experts from the author group (<i>n</i> = 14), people with lived experience (<i>n</i> = 112), and clinicians in the community (<i>n</i> = 99) selected and ranked topics they considered most important. There were areas of agreement (e.g., early education was ranked highly by all groups) and discordance (e.g., people with lived experience perceived diagnostic tests/investigations as more important than the other groups). We synthesized the prioritization survey results into a top-10 list of the highest priority clinical actions. This list will inform implementation efforts aimed at improving post-acute care for nonhospitalized TBI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}