Journal of neurotrauma最新文献

{"title":"Serum Biomarkers as Adjuncts to the National Institute for Health and Care Excellence Head Injury Guidelines (NG232, 2023) When Selecting Patients with Traumatic Brain Injury for Computed Tomography: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study.","authors":"Daniel Whitehouse, Ana Mikolić, Endre Czeiter, Sophie Richter, Andras Buki, Kevin K Wang, Ewout Steyerberg, Andrew Maas, David Menon, Fiona Lecky, Virginia Newcombe","doi":"10.1089/neu.2024.0276","DOIUrl":"10.1089/neu.2024.0276","url":null,"abstract":"<p><p>This article explores the diagnostic performance of a panel of six biomarkers (glial fibrillary acidic protein [GFAP], neurofilament light [NFL], neuron-specific enolase [NSE], S100 calcium-binding protein B [S100B], total tau [t-tau], and ubiquitin C-terminal hydrolase L1 [UCH-L1]) in the context of the \"2023 UK National Institute for Health and Care Excellence (NICE) Head Injury: Assessment and early management (NG232)\" guideline. Emphasis is placed on subjects where clinical equipoise remains concerning the decision for head computed tomography (CT), medium-risk subjects. All adult subjects from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) dataset with a complete biomarker profile and interpretable CT scan within 24 h of injury were classified as high, medium, and low-risk according to the NICE NG232 Clinical Decision Rule (CDR) for CT head imaging following head injury. In subjects classified as medium-risk, the area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic performance of biomarkers to identify those with (1) CT abnormality or (2) potential neurosurgical lesion, with CT considered the gold standard diagnosis. A time-to-biomarker sub-analysis was performed in subjects with a time from injury to sampling within 6 h, in keeping with current clinical usage of biomarkers. Among 1979 CENTER-TBI participants with sufficient clinical information to facilitate classification, 385 subjects were classified as medium-risk. Biomarker concentrations were significantly higher in those with traumatic CT abnormalities as compared with those without for all biomarkers aside from NSE (all <i>p</i> < 0.05). When sampled within 24 h of injury, GFAP demonstrated the best diagnostic performance for CT abnormality (AUC 0.81 [0.77-0.86]), with NFL, t-tau, and UCH-L1 showing moderate performance. At a threshold to provide a 95% sensitivity, GFAP, NFL, t-tau, and UCH-L1 demonstrated specificities ranging from 18% to 33% corresponding to a potential reduction of total CT images performed in these subjects by 14-23%. S100B and UCH-L1 showed improved performance when biomarker sampling time was limited to 6 h following injury. In intoxicated subjects with a persistent Glasgow Coma Score of 13-14, biomarker levels were significantly higher in subjects with CT abnormality as compared with those without. In conclusion, serum biomarkers demonstrate potential for the reduction in CT scan requirements in those classified as medium-risk in reference to the NG232 CDR criteria. These results highlight a need for further prospective studies on the use of diagnostic TBI biomarkers in current emergency medicine practice, with future consideration given to the integration of biomarkers in the NICE NG232 head injury guidelines.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1509-1523"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040494","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":"First-Year Psychiatric Outcome of Pediatric Mild Traumatic Brain Injury: A Prospective Longitudinal Controlled Study.","authors":"Jeffrey E Max, Nicholas Judd, Erin D Bigler, Elisabeth A Wilde, Jo Ellen Patterson, Todd M Edwards, Ainara Calahorra, Elise Zimmerman, John R Hesselink, Mingxiong Huang, Tony T Yang, Emily A Troyer, Annemarie Angeles-Quinto, Wenjing Meng, Emily L Dennis, Florin Vaida","doi":"10.1089/neu.2024.0460","DOIUrl":"10.1089/neu.2024.0460","url":null,"abstract":"<p><p>The objective of this study was to clarify the occurrence, phenomenology, and risk factors for novel psychiatric disorder (NPD) in the first 12 months after mild traumatic brain injury (mTBI) and orthopedic injury (OI). Children aged 8-15 years with mTBI (<i>n</i> = 220) and with OI but no TBI (<i>n</i> = 110) from consecutive admissions to Rady Children's Hospital Emergency Department were followed prospectively at baseline, 3-, 6-, and 12-month postinjury with semi-structured psychiatric interviews to document the presence of NPDs that developed in each participant. Preinjury child variables (academic, adaptive, and cognitive function, and psychiatric disorder), preinjury family variables (family function, family psychiatric history, and socioeconomic status), and injury severity were assessed and analyzed as potential confounders and predictors of NPD that occurred at any assessment in the 12 months after injury. This study extends our analyses of counts of NPD that were limited to the first 3 months of follow-up published in this journal. In multipredictor analyses adjusted for potential confounders, NPD risk increased over time in children with OI: 6-month versus 3-month adjusted odds ratio (aOR) = 17.766, CI₉₅ (1.712, 184.376), <i>p</i> = 0.020; 12-month versus 3-month aOR = 21.165, CI₉₅ (1.481, 302.473), <i>p</i> = 0.020, but not in the mTBI arm, corresponding to a significant group-by-time interaction: adjusted ratio of ORs for mTBI versus OI at 6-month versus 3-month aROR = 0.029, CI₉₅ (0.002, 0.411), <i>p</i> = 0.012, and at 12-month versus 3-month aROR = 0.024, CI₉₅ (0.001, 0.496), <i>p</i> = 0.012. Higher NPD risk was associated in unadjusted analyses with preinjury lifetime psychiatric disorder (OR = 8.995, CI₉₅ [1.935, 41.802], <i>p</i> = 0.003) and poorer preinjury family function (OR = 0.383, CI₉₅ [0.171, 0.861], <i>p</i> = 0.014), and in adjusted analyses with poorer preinjury family function, adjusted OR = 0.491, CI₉₅ [0.243, 0.989], <i>p</i> = 0.047, and with preinjury lifetime psychiatric disorder (OR = 5.081, CI₉₅ [0.997, 25.901], <i>p</i> = 0.050). These findings demonstrate that when considering the entire first postinjury year, mild injury to the brain and OI had similar effects on psychiatric outcome, but the onset of deleterious effects was earlier in the mTBI group. NPD in the first year after mTBI and OI is predicted primarily by preinjury family function.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"1534-1549"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575687","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":"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":"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":"1524-1533"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","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}

{"title":"<i>Letter:</i> Exoskeletal-Assisted Walking During Acute Inpatient Rehabilitation Enhances Recovery for Persons with Spinal Cord Injury-A Pilot Randomized Controlled Trial.","authors":"Jing Chen","doi":"10.1177/08977151251371713","DOIUrl":"https://doi.org/10.1177/08977151251371713","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957619","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":"Repetitive Mild Traumatic Brain Injury Disrupts Learning and Memory: A Novel Olfactory Approach to Detection.","authors":"Fernanda Guilhaume-Correa, Eva J Melendes, Yugin Yin, Gabriella Orbach, Kaitlyn Warren, Nadia Nosek, Ava Tillman-Schwartz, Cara Leahy, Elisabeth A Kheir, Jin Lu, Ryan Luke Sodemann, Rebekah Mannix, William P Meehan, Jianhua Qiu","doi":"10.1177/08977151251365669","DOIUrl":"https://doi.org/10.1177/08977151251365669","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) leads to significant public health concerns due to cognitive decline and increased risks of neurological conditions like Alzheimer's disease and chronic traumatic encephalopathy. Preclinical models are essential for exploring how mild TBI leads to neuronal dysfunction and neurodegeneration. Using a mouse model, we applied repetitive, mild, side-alternating impacts to induce rapid head rotational acceleration-deceleration. A novel odor-based learning and memory task was developed to address TBI-related vision impairments. Our findings revealed that this side-impact model specifically affects the hippocampus, evidenced by activated CD68+ microglia appearing in the dentate gyrus, stratum lacunosum-moleculare, and corpus callosum. Importantly, no olfactory dysfunction was observed. However, injured mice exhibited learning and memory deficits in an olfaction-based task. These results suggest that repetitive mild TBI damages hippocampal regions, leading to cognitive dysfunction characterized by impaired learning and memory, as demonstrated by this novel behavioral method.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957759","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":"STARSHIP Part 2: Disturbed Pressure Reactivity Duration and Magnitude in Pediatric Severe Traumatic Brain Injury-Outcome Implications.","authors":"Claudia Ann Smith, Stefan Yu Bögli, Michał Placek, Manuel Cabeleira, Deborah White, Esther Daubney, Adam Young, Erta Beqiri, Riaz Kayani, Roddy O'Donnell, Nazima Pathan, Suzanna Watson, Anna Maw, Matthew Garnett, Hari Krishnan Kanthimathinathan, Harish Bangalore, Santosh Sundararajan, Gayathri Subramanian, Dusan Raffaj, Simona Lampariello, Avishay Sarfatti, Anton Mayer, Oliver Ross, Marek Czosnyka, Peter John Hutchinson, Peter Smielewski, Shruti Agrawal","doi":"10.1177/08977151251367052","DOIUrl":"10.1177/08977151251367052","url":null,"abstract":"<p><p>Cerebral autoregulation (CA) plays a critical role in maintaining cerebral blood flow (CBF) amid fluctuations in systemic blood pressure, with dysfunction increasing vulnerability to secondary brain injury, particularly after traumatic brain injury (TBI). While extensively studied in adults, CA dynamics in pediatric TBI (pTBI) remain relatively unexplored. Studying Trends in AutoRegulation in Severe Head Injury in Pediatrics (STARSHIP), the first multicenter, prospective study on CA in pTBI, investigates the pressure reactivity index (PRx) and its association with outcomes. PRx, calculated as the Pearson's correlation between mean arterial pressure and intracranial pressure, provides insights into the patient's CA status. In this article, STARSHIP Part 2 characterizes PRx disturbances using dose metrics that take the magnitude of PRx disturbance, and the time in which the patient experiences this derangement, into consideration. We calculated the dose (overall and hourly) and percentage time spent with a PRx above thresholds 0-0.4 in 135 children with TBI. Associations with outcome were explored via summary metrics and over time, using uni- and multivariable, and ordinal regression with propensity score matching, correcting for known outcome predictors. Patients with poor outcomes exhibited higher PRx dose and percentage time above threshold, even after adjusting for clinical predictors. Time trend analyses highlighted elevated PRx metrics in poor outcome groups during the first-week post-injury. Duration of impaired pressure reactivity, as denoted by the percentage time a patient spent with a PRx >0, is robustly and independently associated with dichotomized outcome at 12 months post-ictus. Our results highlight the predictive strength of PRx metrics, with percentage time above a threshold of 0 emerging as the most robust indicator of 12-month outcome. This work supports further investigation into the feasibility and impact of interventions guided by real-time CA monitoring in severe pTBI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe Pediatric Traumatic Brain Injury Presenting Characteristics: Abusive Versus Accidental Trauma.","authors":"Caitlin R McNamara, Rachel P Berger, James F Luther, Michael J Bell, Sandra Dw Buttram, Subramanian Subramanian, Jessica L Carpenter, Srikala Narayanan, Stephen R Wisniewski, Patrick M Kochanek, Nikki Miller Ferguson","doi":"10.1177/08977151251366322","DOIUrl":"10.1177/08977151251366322","url":null,"abstract":"<p><p>Abusive head trauma (AHT) is a leading cause of death in infants and toddlers. The objective of this study was to conduct an age-stratified comparison between children with AHT and accidental Traumatic brain injury TBI (aTBI) in the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury (ADAPT) data. Children with severe TBI and an intracranial pressure monitor placed at a study site in the United States were enrolled from February 1, 2014, to September 31, 2017, and subjects <5 years of age and admitted to a US site were selected for analysis. Subjects were stratified by mechanism ('definite' or 'probable' concern for AHT classified as AHT; 'possible' or 'no' concern for AHT as aTBI) and age (<1 year, 1-2.9-years-, 3-4.9-years). Clinical data including epidemiological, clinical events, and imaging that occurred before monitor placement were compared. Of the 313 subjects (n = 111 AHT), apnea, seizures, and bilateral fixed pupils were more frequently observed in AHT (35.1% vs. 21.8%, <i>p</i> = 0.01; 43.2% vs. 20.8, <i>p</i> < 0.001; 31.5% vs. 15.8%, <i>p</i> = 0.008). Subdural hemorrhages, midline shift, and ischemia were more frequently observed in AHT (96.4% vs. 73.1%, <i>p</i> < 0.001; 54.1% vs. 35.0%, <i>p</i> = 0.001; 40.9% vs. 12.2%, <i>p</i> < 0.001) while contusion, subarachnoid hemorrhage and diffuse axonal injury were less frequently observed (20.2% vs. 49.7%; 38.5% vs. 58.4%; 3.7% vs. 20.8%, all <i>p</i> < 0.001). Among the patients <1 year-old, there was no difference in apnea and seizures between AHT and aTBI (40.6% vs. 34.3%, <i>p</i> = 0.53; 44.9% vs. 40.0%, <i>p</i> = 0.63) while ischemia was more commonly observed in AHT (47.1% vs. 20.0%, <i>p</i> < 0.001). AHT subjects exhibited unique clinical characteristics and radiological findings compared to aTBI, even after this age-stratified comparison. Further study is needed on the effects of both guidelines-based and novel therapies for this vulnerable and unique patient population.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144847157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous Reactive Change in Unmyelinated and Myelinated Axon Segments Following Experimental Diffuse Traumatic Brain Injury.","authors":"Brian J Kelley, Hailong Song, Alexandra Tomasevich, Douglas H Smith","doi":"10.1177/08977151251365569","DOIUrl":"https://doi.org/10.1177/08977151251365569","url":null,"abstract":"<p><p>Diffuse axonal injury (DAI) is a leading cause of traumatic brain injury (TBI) morbidity and has well-studied molecular pathobiology. Historically, white matter DAI studies indicated unmyelinated axons are more susceptible to injury than myelinated axons, with myelin posited to protect axons from diffuse TBI shear/tensile forces through unresolved mechanisms. Similarly, preclinical studies have also identified gray matter DAI localized to the perisomatic domain (i.e., the unmyelinated axon initial segment [AIS] and first one-to-two nodes of Ranvier). With these concepts in mind, we hypothesized unmyelinated segments are selectively vulnerable to TBI-mediated shear/tensile forces and serve as initiating sites for DAI pathobiology. Using murine midline fluid percussion injury, neocortical layer V pyramidal cell perisomatic domains at the gray-white matter interface were spatiotemporally examined for initiating pathology using antibodies to cytoskeletal proteins to demarcate unmyelinated segments and amyloid precursor protein (i.e., the gold-standard DAI marker) to identify injury. In cells expressing yellow fluorescent protein to enhance injury visualization, axonal swellings were observed simultaneously within perisomatic unmyelinated segments (e.g., AIS; nodes) as well as immediately adjacent myelinated segments, indicating concomitant reactive axonal changes. These data suggest non-selective axonal susceptibility and that myelin may not protect against diffuse injury forces. While expanding DAI topography to the gray-white matter junction, these findings also have implications for action potential initiation, axonal protein trafficking, and cortical circuit connectivity. Furthermore, studies are needed to determine if DAI pathological mechanisms are shared between white and gray matter axons, which have common and differentiating cytoarchitectural components.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804300","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":"Traumatic Brain Injury Severity Measured by Clinical, Radiographical, and Blood Biomarker Measures Is Associated with Non-Neurological Organ Dysfunction: A Secondary Analysis of ProTECT III and Bio-ProTECT.","authors":"David J Barton, Erica K Fan, Ian G Gober, Nabil Awan, Raj G Kumar, Jenna C Carlson, Michael R Frankel, David W Wright, Amy K Wagner","doi":"10.1177/08977151251362234","DOIUrl":"https://doi.org/10.1177/08977151251362234","url":null,"abstract":"<p><p>Non-neurological organ dysfunction (NNOD) is a prevalent complication and contributes to poor outcome after traumatic brain injury (TBI). Contributing factors to NNOD may include initial TBI severity, but this relationship has not been rigorously studied. The objectives of this study were to describe the frequency and timing of NNOD after TBI, evaluate the association between NNOD and outcome (mortality and Glasgow Outcome Score-Extended [GOSE] at 6 months post-injury), and examine the relationship between multimodal markers of initial TBI severity and NNOD. We performed a secondary analysis of data from participants in both the ProTECT III clinical trial (progesterone vs. placebo in participants with moderate-to-severe TBI) and the embedded Bio-ProTECT blood biomarker study (<i>N</i> = 536 individuals). We reviewed laboratory and clinical data to determine the prevalence of NNOD in renal, hematological, hepatic, cardiovascular, and respiratory systems, based on the sequential organ failure assessment system. TBI severity was assessed using index Glasgow coma scale score (iGCS-first GCS post-primary resuscitation), Rotterdam computed tomography (CT) score, head-region abbreviated injury scale scores, and baseline TBI biomarkers (S100 calcium binding protein B [S100b], glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCHL1], and spectrin breakdown products [SBDP]). NNOD frequencies by organ system were 72% (respiratory), 52% (cardiovascular), 45% (hematological), 8% (renal), and 2% (hepatic). All TBI severity markers were positively correlated (using Spearman coefficients) with the number of systems in dysfunction. To examine effects of NNOD on outcome independent of TBI severity, we used logistic regression and adjusted for age, sex, iGCS, Rotterdam CT score, and biomarker load score (mean biomarker quartile), wherein each additional system of dysfunction resulted in a 1.30× higher odds of unfavorable GOSE (95% confidence interval [CI]: [1.01-1.67], <i>p</i> = 0.04). Stratification analyses revealed the relationship between greater NNOD and worse outcome was most pronounced among individuals with more severe Rotterdam CT and lower GCS scores. In conclusion, NNOD occurs frequently after moderate-to-severe TBI, is associated with higher odds of unfavorable GOSE at 6 months, and is positively associated with multimodal biomarkers of baseline TBI severity. This is the first study to demonstrate a relationship between TBI blood biomarker levels and NNOD. Future study is needed to determine mechanisms of NNOD and their relationships to subsequent neurological injury. While TBI research has historically focused on brain-centric measures and outcomes, this study builds on mounting evidence that non-neurological organ systems play an important role in injury response after TBI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804315","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":"Biological Markers of Brain Network Connectivity and Pain Sensitivity Distinguish Low Coping from High Coping Veterans with Persistent Post-Traumatic Headache.","authors":"Katrina S Monroe, Dawn M Schiehser, Aaron W Parr, Alan N Simmons, Chelsea C Hays Weeks, Barbara A Bailey, Bahar Shahidi","doi":"10.1177/08977151251360246","DOIUrl":"10.1177/08977151251360246","url":null,"abstract":"<p><p>Headache is the most common pain complaint following mild traumatic brain injury. Roughly half of those with persistent post-traumatic headache (PPTH) also report neck pain, which is associated with greater severity and functional impact of headache. This observational cohort study aimed to identify biological phenotypes to help inform mechanism-based approaches in the management of PPTH with co-occurring neck pain. Thirty-three military veterans [mean (standard deviation) = 37 ± 16 years, 29 males] with PPTH completed a clinical assessment, quantitative sensory testing, and magnetic resonance imaging of the brain and cervical spine. Multidimensional phenotyping was performed using a Random Forest analysis and Partitioning Around Medoids clustering of input features from three biological domains: (1) resting state functional connectivity (rsFC) of the periaqueductal gray (PAG), (2) quality and size of cervical muscles, and (3) mechanical pain sensitivity and modulation. Two subgroups were distinguished by biological features that included forehead pressure pain threshold and rsFC between the PAG and selected nodes within the default mode, salience, and sensorimotor networks. Compared to the High Pain Coping group, the Low Pain Coping group exhibited higher pain-related anxiety (<i>p</i> = 0.009), higher pain catastrophizing (<i>p</i> = 0.004), lower pain self-efficacy (<i>p</i> = 0.010), and greater headache-related disability (<i>p</i> = 0.012). Although limited by a modest sample size, findings suggest that greater functional connectivity of pain modulation networks involving the PAG combined with impairments in craniofacial pain sensitivity, but not cervical muscle health, distinguish a clinically important subgroup of individuals with PPTH who are less able to cope with pain and more severely impacted by headache.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804299","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}