J. Neurotrauma [JOURNAL]
Sun
200 papers
The Effect of Nonsurgical Critical Resuscitative Interventions on Mortality and Neurological Outcomes in Isolated Moderate-to-Severe Traumatic Brain Injury in a Resource-Limited Health System.
Dymond C, Xiao M, Dixon J … +12 more , Finck L, Lategan H, Vlok A, Oosthuizen G, de Vries S, Wylie C, Verster J, Gamboa J, Schauer SG, Dengler B, Mould-Millman NK, EpiC Study Site Collaborators
J Neurotrauma · 2026 Apr · PMID 41963280 · Publisher ↗
Traumatic brain injury (TBI) accounts for approximately 2.5 million deaths yearly, with patients living in low- and middle-income countries disproportionally affected. Nonsurgical critical resuscitation interventions (ns...
Traumatic brain injury (TBI) accounts for approximately 2.5 million deaths yearly, with patients living in low- and middle-income countries disproportionally affected. Nonsurgical critical resuscitation interventions (nsCRIs) studied individually have been shown to improve outcomes in moderate-to-severe TBI (msTBI) patients. This cohort study primarily assesses the relationship between timeliness of delivery of grouped nsCRIs and all-cause 7-day mortality among blunt and/or penetrating isolated msTBI patients, with secondary objectives of 3- and 30-day mortality and discharge Glasgow Coma Scale (GCS). Adult trauma patients with isolated msTBI from January 2022 to December 2024 were enrolled from facilities in a trauma referral pathway in the Western Cape of South Africa. Cohort patients were categorized into treatment subgroups of those receiving nsCRI ≤1 h or nsCRI within 1-3 h; the reference group was receiving nsCRI >3 h from injury or missed nsCRIs. Inverse probability weighted Cox proportional hazard regression was used to model mortality outcome. Subgroup and sensitivity analyses were performed. Of the 507 patients within the cohort, 68.6% of patients had blunt injuries, and one-half had severe TBI. 21.7% of all msTBI patients died within 3 days, 27.6% deceased by 7 days, and 31.2% deceased within 30 days. There was a 26% (hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.56, 0.98) 7-day mortality reduction among patients who received nsCRIs ≤1 h compared with the reference group. The subgroup of blunt and blunt with penetrating injured patients showed a 21% 7-day mortality benefit (HR = 0.79, 95% CI: 0.71, 0.88) and better discharge GCS categories among patients receiving timely nsCRIs (odds ratio = 1.79; 95% CI: 1.01, 3.19). Among severe TBI patients, there was a 29% 7-day mortality reduction in the nsCRI ≤1 h compared with >3 h or missed nsCRI (HR = 0.71, 95% CI: 0.5, 1.00). While those statistically significant subgroup findings should be interpreted with caution and several subgroup analyses did not show statistical significance, there was an overall trend towards survival benefit associated with nsCRIs at either ≤1 h and/or 1-3 h. Overall, in this cohort study of msTBI patients receiving care in a resource-limited trauma system, we found that nsCRIs delivered within 3 h were associated with improved 7-day mortality and neurological outcomes at discharge.
Consciousness Monitoring and Outcome Prediction Using EEG Connectivity in Severe Traumatic Brain Injury.
Anzalone L, Deschamps M, Cottin L … +7 more , Caroyer S, Damien C, De Maeseneire C, Depondt C, Legros B, Nonclercq A, Gaspard N
J Neurotrauma · 2026 Apr · PMID 41963278 · Publisher ↗
Neurological prognostication of patients in post-traumatic coma remains challenging due to the paucity of reliable markers in the acute phase. We aimed to assess whether early EEG features reflecting multiple levels of b...
Neurological prognostication of patients in post-traumatic coma remains challenging due to the paucity of reliable markers in the acute phase. We aimed to assess whether early EEG features reflecting multiple levels of brain connectivity related to consciousness and their temporal evolution were associated with awakening and long-term functional outcomes in severe traumatic brain injury (TBI). We retrospectively included 95 severe TBI patients who underwent >48 h of continuous EEG (cEEG) monitoring between 2015 and 2024. Quantitative and functional connectivity EEG features representing brainstem-forebrain, thalamocortical, and cortico-cortical connectivity were extracted at six time points within the first 48 h of recording. The primary outcome was functional independence at 12 months, defined as a score on the Glasgow Outcome Scale score ≥4; the secondary outcome was consciousness recovery at ICU discharge. We trained multiple XGBoost machine learning models to predict recovery using various combinations of EEG and International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) score features and compared their predictive performances, as measured by the area under the receiver operating characteristic curve (AUROC). The best-performing model achieved a median AUROC of 0.70 (IQR: 0.59-0.80) for 12-month outcome, combining EEG and IMPACT features, but did not significantly differ from the EEG and age model (AUROC: 0.69; IQR: 0.61-0.76). The EEG-only model outperformed the IMPACT model (AUROC: 0.65 vs. 0.56), whereas the IMPACT model without age showed no predictive value above chance (AUROC: 0.49; IQR: 0.41-0.57). Prediction of awakening at ICU discharge was predominantly influenced by age. Neither EEG alone nor IMPACT without age effectively predicted awakening at ICU discharge (AUROC: 0.52 [IQR: 0.43-0.59] and 0.54 [IQR: 0.46-0.62], respectively). The combined EEG and IMPACT model (AUROC: 0.63; IQR: 0.53-0.69) was not significantly superior to EEG-and-age alone (AUROC: 0.60; IQR: 0.53-0.67). Early EEG connectivity features demonstrated clinically relevant predictive value for long-term outcome following severe TBI, surpassing most IMPACT score features, except age, whose predictive contribution may be influenced by self-fulfilling prophecy. These findings indicate that EEG features from cEEG monitoring provide complementary prognostic information during the acute phase of severe TBI when clinical predictors alone may be insufficient.
Clinical Significance of Leakage Sign Patterns in Acute Subdural Hematoma.
Furuta K, Kikuchi J, Miyagi K … +3 more , Orito K, Takasu O, Morioka M
J Neurotrauma · 2026 Apr · PMID 41957976 · Publisher ↗
The leakage sign (LS), defined as contrast medium extravasation on the 5-minute delayed phase after computed tomography (CT) angiography, has been reported as a predictive imaging marker for hematoma expansion in acute s...
The leakage sign (LS), defined as contrast medium extravasation on the 5-minute delayed phase after computed tomography (CT) angiography, has been reported as a predictive imaging marker for hematoma expansion in acute subdural hematoma (ASDH). We recently identified two different patterns of LS: local and diffuse. This study aimed to evaluate the clinical importance of these LS types in predicting brain swelling and determining the appropriate surgical intervention. We retrospectively reviewed 98 patients with LS-positive ASDH on contrast-enhanced CT between January 2013 and September 2024. LS was classified as local-type when one or two positive areas were observed and as diffuse-type when three or more positive areas were present and/or when contrast medium extended along the brain surface. Brain swelling was defined based on radiological findings and the requirement for decompressive craniectomy. Clinical data, treatment modalities, and outcomes were analyzed in both groups. Among the 98 LS-positive patients, 40 were classified as having local-type and 58 as having diffuse-type. The diffuse-type LS group had a significantly greater proportion of patients in severe admission Glasgow Coma Scale category ( = 0.027), underwent decompressive craniectomy more frequently ( = 0.04), and had higher indicators of coagulopathy, including elevated activated partial thromboplastin time, prothrombin time-international normalized ratio, and D-dimer levels (all < 0.05). Brain swelling occurred in 70.7% of patients in the diffuse-type group compared with 17.5% in the local-type group ( < 0.001). Poor outcomes were significantly more common in the diffuse-type group (67.2% vs. 32.5%, = 0.001), along with a higher mortality rate (56.9% vs. 22.5%, < 0.001). Diffuse-type LS was independently associated with poor outcomes and was associated with clinical severity, coagulopathy, and brain swelling. Conversely, local-type LS was associated with favorable outcomes and a low rate of brain swelling. Because most patients with LS-positive ASDH show progressive ASDH, emergency hematoma evacuation is generally required. Patients with diffuse-type LS may be more likely to require decompressive craniectomy, whereas endoscopic hematoma removal via a small craniotomy may be a feasible option for local-type LS, where the bleeding point can be detected using the LS-positive area.
Pathophysiology of the Post-Traumatic Confusional State and Post-Traumatic Amnesia: A Scoping Review.
Katz DI, Bodien YG, Faerman A … +14 more , Schwertfeger J, Bogdanova Y, Blum S, Dwyer B, Gilmore N, Goncalves JV, Hays K, Graf MJP, Marino M, Mallas EJ, Shapiro-Rosenbaum A, Sherer M, Williams MW, Zhang B
J Neurotrauma · 2026 Jun · PMID 41944090 · Publisher ↗
The post-traumatic confusional state (PTCS) is a period of recovery that follows traumatic brain injury (TBI), characterized by post-traumatic amnesia (PTA), impairments in attention, and behavioral dysregulation, among...
The post-traumatic confusional state (PTCS) is a period of recovery that follows traumatic brain injury (TBI), characterized by post-traumatic amnesia (PTA), impairments in attention, and behavioral dysregulation, among other clinical symptoms. The pathophysiology of PTCS is unknown, contributing to the absence of neurobiologically based diagnostic criteria, prognostic models, and treatments. The workgroup conducted a scoping review of the literature in MEDLINE/PubMed database and manual searches of references to synthesize the existing knowledge on structural, functional, electroencephalographic (EEG), molecular, and genetic biomarkers underlying PTCS diagnosis and prognosis through five Population, Intervention, Comparison, and Outcome (PICO) questions. The search yielded 3,333 abstracts of which 69 were retained and included. Teams of two workgroup members independently reviewed abstracts and articles. Most articles addressed whether biomarkers differentiated patients with PTCS/PTA from those not in PTCS/PTA, and whether biomarkers were associated with severity or duration of PTCS/PTA. Our findings suggest that transition through PTCS/PTA from lower to higher states of consciousness involves increased thalamic function, restoration of default mode network dynamics, and normalizing of excessive slow wave activity on quantitative EEG. For patients with mild TBI, PTCS/PTA was associated with greater TBI lesion burden on structural imaging. PTCS/PTA severity and duration were associated with lesion burden, reduced white matter integrity, and electrophysiological signatures. Results across studies were variable with many finding no relationship between PTCS/PTA and biomarkers. In summary, while it is premature to include biomarkers in the definition of PTCS/PTA, our findings provide avenues for future research that is designed specifically to address the pathophysiology of this condition.
Cerebellar Volumes Are Smaller in Veterans with PTSD and a History of Mild Traumatic Brain Injury, but Not Mild Traumatic Brain Injury Alone.
Huggins AA, Martinez BS, Baird CL … +5 more , Hussain A, Clausen AN, Haswell CC, Morey RA, VA Mid-Atlantic MIRECC Workgroup
J Neurotrauma · 2026 Apr · PMID 41944052 · Publisher ↗
Mild traumatic brain injury (mTBI), a common health burden among combat veterans, has been associated with alterations in brain structure. Moreover, post-traumatic stress disorder (PTSD), frequently comorbid with mTBI, i...
Mild traumatic brain injury (mTBI), a common health burden among combat veterans, has been associated with alterations in brain structure. Moreover, post-traumatic stress disorder (PTSD), frequently comorbid with mTBI, is linked to smaller cerebellum volumes; however, little is known about whether mTBI (absent comorbid psychiatric symptoms) similarly affects cerebellar structure. The cerebellum may play a central role in common postconcussive symptoms due to its contributions to cognitive and emotional functions. In a sample of 122 combat veterans, we examined whether total cerebellum volumes differed among those with a remote history of mTBI with ( = 29) or without ( = 42) comorbid PTSD and healthy controls ( = 51). An automated cerebellum parcellation protocol was applied to T1-weighted anatomical scans to derive volumetric estimates of the cerebellum (and 28 subregions). Hierarchical regression analysis (adjusting for total intracranial volume, age, sex, and combat exposure) revealed that, compared with controls, participants with comorbid mTBI-PTSD had a significantly smaller volume of the total cerebellum ( = 0.010). There was no significant effect of mTBI-only on total cerebellum volume ( = 0.165). Follow-up exploratory analyses of subregional cerebellum volume differences suggested that volume differences in comorbid mTBI-PTSD were primarily localized to the posterior lobe (crus I, lobules VIIB, VIIIB). In sum, in a sample of combat veterans, mTBI was associated with a smaller volume of the cerebellum, but only when comorbid with PTSD. Consistent with recent work, exploratory subregional analyses indicated that volume differences were primarily attributable to regions of the cerebellum most prominently involved in cognition and emotion. These results underscore the profound effects of PTSD on brain health in military veterans and suggest that mTBI may not produce long-lasting structural damage to the cerebellum. Future work is needed, as it remains possible that subtle cerebellar volume changes may emerge in specific subgroups or as a function of injury-related factors (e.g., mechanism of injury, time since injury) not fully captured in the present study.
Follow-Up of Post-Traumatic Headache Patients: A Multicenter Prospective Study on Headache Phenotype and Impact after Mild Traumatic Brain Injury.
Atalar AÇ, Göçmez Yılmaz G, Baykan B … +29 more , Taşdelen B, Uludüz D, Bolay H, Togha M, Salami Z, Arabi S, Karacan Gölen M, Luvsannorov O, Batmagnai K, Oguz-Akarsu E, Mesut G, Durak VA, Ergin N, Polat B, Engin BE, Şahbaz FG, Örün MO, Gelener P, Öksüz N, Gozubatık-Çelik RG, Tutuncu M, Beydilli İ, Uzan A, Kaygısız Ş, Genç H, Arı BÇ, Demir M, Doğan S, Özge A
J Neurotrauma · 2026 Apr · PMID 41944049 · Publisher ↗
Post-traumatic headache (PTH) is one of the most disabling sequelae of mild traumatic brain injury (mTBI); however, its clinical determinants and long-term trajectories remain poorly defined. We conducted a large, multic...
Post-traumatic headache (PTH) is one of the most disabling sequelae of mild traumatic brain injury (mTBI); however, its clinical determinants and long-term trajectories remain poorly defined. We conducted a large, multicenter, prospective follow-up study to characterize the phenotypic spectrum of persistent PTH, identify predictors of persistence, and explore the role of pre-existing migraine in shaping headache outcomes after mTBI. A total of 478 adults (52.1% male, mean age 40.5 ± 18.7 years) with mTBI were recruited and evaluated by experienced neurologists at two time points: immediately after mTBI and at 6 months post injury. Demographic data and detailed headache features were collected using clinical examination and standardized questionnaires, administered face-to-face during the first visit and either face-to-face or by phone at the 6-month follow-up by physicians. Headache-related disability, depression, and insomnia were assessed using the Headache Impact Test (HIT-6), Beck Depression Inventory (BDI), and Insomnia Severity Index (ISI), respectively. Statistical analyses included classification tree analysis to identify predictors of persistent PTH and K-means clustering to delineate phenotypic subgroups. Overall, 22.6% of patients developed persistent PTH at 6 months. Pre-existing headache (PH) was reported in 31.4% of participants, predominantly migraine (57.3%). Patients with pre-existing migraine more frequently exhibited migraine-like PTH features (throbbing quality, unilateral localization, longer headache attack duration, and associated symptoms such as nausea, photophobia, and phonophobia) and scored significantly higher on the HIT-6, numeric rating scale (NRS) for headache severity, ISI, and BDI, indicating greater disability, pain severity, insomnia, and depressive symptoms ( < 0.01 for all). Classification tree analysis revealed two robust predictors of persistent PTH: acute PTH lasting more than 30 consecutive days and an initial HIT-6 score greater than 45. Furthermore, cluster analysis of patients with persistent PTH identified two phenotypic groups. Cluster 1 ( = 47) comprised patients with ≥ 180 days of continuous headache, high disability, and poor sleep quality, whereas Cluster 2 ( = 60) included patients with shorter headache duration following mTBI (<180 days), lower disability, and infrequent, shorter headache attacks. This study demonstrates that nearly one in four patients with mTBI experiences persistent PTH. Early indicators of persistence, particularly prolonged continuous headache and higher disability, may help identify high-risk individuals who warrant early aggressive, targeted interventions. Recognition of distinct PTH clusters reflects the heterogeneity of this frequent but under-investigated disorder with high burden and highlights the need for early and tailored management strategies.
Imaging Traumatic Brain Injuries in Mice with Potassium Channel PET Tracer [F]3F4AP.
Ramos-Torres KM, Tiss A, Radomski KL … +11 more , Kapolis A, Takahashi K, McDowell S, Mandeville ET, Park JH, Zhang L, Sun Y, Zhou YP, Lo EH, Armstrong RC, Brugarolas P
J Neurotrauma · 2026 Apr · PMID 41944018 · Publisher ↗
Traumatic brain injury (TBI) can lead to secondary injuries, including axon and myelin damage, which contributes to long-term neurological deficits. The positron emission tomography (PET) tracer [F]3F4AP, a fluorinated d...
Traumatic brain injury (TBI) can lead to secondary injuries, including axon and myelin damage, which contributes to long-term neurological deficits. The positron emission tomography (PET) tracer [F]3F4AP, a fluorinated derivative of the U.S. Food and Drug Administration (FDA)-approved drug 4-aminopyridine, selectively binds to voltage-gated potassium (K) channels, offering a novel approach to assess TBI-related node of Ranvier disruption and demyelination. This study evaluated [F]3F4AP PET in penetrating and non-penetrating TBI models. Either controlled cortical impact (CCI, penetrating) or concussive (non-penetrating) TBI models were used to induce TBI in mice. Dynamic PET imaging with [F]3F4AP was performed at time points of 0, 3, 7, 14, and/or 28-31 days post-injury (dpi), with quantitative analyses comparing tracer uptake in injured versus control regions. Luxol fast blue staining was conducted to evaluate histological myelin loss. In the CCI model, [F]3F4AP PET imaging demonstrated a 31% increase in tracer uptake at the injury site at 7 dpi, correlating with histological evidence of demyelination. Tracer uptake gradually declined over time, reflecting potential remyelination. The concussive TBI model showed a smaller and more diffuse increase in uptake at 7 dpi compared to CCI. [F]3F4AP PET imaging effectively detects demyelination following TBI with a very high sensitivity to penetrating injuries. These findings highlight the potential of [F]3F4AP as a valuable imaging biomarker for the assessment of TBI progression and/or therapeutic response. Further studies are warranted to explore its clinical applicability and comparison with other imaging modalities.
Infant Abusive Head Trauma Induces Seizures and Cellular Stress in a Pre-Clinical Mouse Model.
Harris S, Hudson M, Sgro M … +7 more , Salberg S, Li CN, Vlassopoulos E, Yamakawa GR, Semple BD, Chinnery HR, Mychasiuk R
J Neurotrauma · 2026 Apr · PMID 41944013 · Publisher ↗
Abusive head trauma (AHT) occurs when a child is grasped and shaken with such force that the brain moves within the skull. AHTs are not isolated events; repetition occurs in 30-50% of cases, with affected children experi...
Abusive head trauma (AHT) occurs when a child is grasped and shaken with such force that the brain moves within the skull. AHTs are not isolated events; repetition occurs in 30-50% of cases, with affected children experiencing ∼10 episodes. While many AHTs appear asymptomatic, there is often underlying cellular and neurological damage. Notably, seizures following AHT may be solely electrographic without overt behavioral signs and detectable only via electroencephalography (EEG). Thus, we examined electrographic seizures and indicators of cell stress in a mouse model of repeat AHT. On postnatal day (P)8, mice underwent hippocampal electrode surgery. On P10-12, 5 min of baseline EEG was recorded, followed by an AHT and 15 min of postinjury EEG recording. AHTs were modeled by securing a mouse to a shaking device at 400 rpm (5g) for 60 s. Sham mice underwent the same surgery and EEG recording procedures but were placed on the shaking device while it remained stationary. A separate cohort of mice forewent surgery but were exposed to the same AHT procedure and were euthanized on P21 or P45 for gene expression and telomere length (TL) analysis. Electrographic seizures occurred following 35.7% of AHTs, while no sham mice exhibited electrographic seizures. Repetitive AHTs affected gene expression in the hippocampus and olfactory bulbs, in genes related to cell stress (), and TL at P21. These findings suggest that despite the absence of observable behavioral deficits, repeat AHTs result in measurable cellular damage and electrographic seizure activity.
Injury Severity and Free-Water Volume Fraction Predict Regional White Matter Atrophy During the First Year Following Moderate-Severe Traumatic Brain Injury.
Brennan DJ, Ware JB, Diaz-Arrastia R … +1 more , Kim JJ
J Neurotrauma · 2026 Apr · PMID 41944006 · Publisher ↗
Traumatic axonal injury is a common endophenotype of traumatic brain injury (TBI) in which injury to axons is a dominant component. In previous investigations, we identified a significant reduction of white matter (WM) v...
Traumatic axonal injury is a common endophenotype of traumatic brain injury (TBI) in which injury to axons is a dominant component. In previous investigations, we identified a significant reduction of white matter (WM) volume from 3 to 12 months post-injury, an increased rate of atrophy during this period associated with a longer duration of post-traumatic amnesia (PTA), widespread reductions in white-matter fractional anisotropy (FA), and elevated free-water (FW) content in a cohort of moderate-to-severe TBI patients. To provide a more comprehensive characterization of the spatiotemporal trajectory of TBI-induced WM degeneration, we have estimated the spatial distribution of WM atrophy related to the duration of PTA in the first year following moderate-to-severe TBI (msTBI) ( = 33) and examined the degree to which baseline diffusion measures of WM integrity, FW and FW-corrected fractional anisotropy (F-FA), were each associated with subsequent WM atrophy. WM atrophy was observed diffusely across the brain, with the greatest effects in the splenium of the corpus callosum, corona radiata, and brainstem. Increased atrophy in the central WM was correlated with greater duration of PTA. Finally, elevated FW volume fraction at 3 months post-injury predicted greater subsequent WM atrophy, while F-FA did not show a significant relationship. These findings suggest that early FW elevation may serve as a biomarker of progressive WM neurodegeneration following TBI, and neuroinflammatory processes may underlie this relationship. Future research should directly investigate the underlying mechanisms of FW-related neuropathology and its role in progressive neurodegeneration following msTBI.
The Characteristics and Criteria Used to Define Persisting Symptoms in Children with Concussion: A Scoping Review.
Iuliano SG, Coupal J, Bacon S … +1 more , Teel EF
J Neurotrauma · 2026 Apr · PMID 41943482 · Publisher ↗
The objective was to characterize the definitions and criteria used to determine persisting symptoms after concussion in children. This scoping review followed a five-step framework. Four databases (PubMed, Scopus, Psych...
The objective was to characterize the definitions and criteria used to determine persisting symptoms after concussion in children. This scoping review followed a five-step framework. Four databases (PubMed, Scopus, PsychInfo, and Web of Science) were searched using the concepts of concussion, children, and persisting symptoms. Articles were included if they were (1) original peer-reviewed articles, (2) written in English or French, (3) exclusively sampled children and adolescents (≤19 years old) with persisting symptoms after concussion, and (4) provided an operational definition of persisting symptoms after concussion. Forty-seven studies were included. The term for labeling persisting symptoms after concussion has evolved over time. The most common term used to describe this phenomenon in children with concussion was persistent postconcussion symptoms ( = 26), first appearing in 2016 and peaked in the early 2020s. Persisting symptoms after concussion is an emerging term that debuted in 2022. The most used threshold was reporting ≥1 concussion symptoms ( = 30), followed by ≥3 new or worsening concussion symptoms ( = 14) relative to pre-injury levels. The most common minimum threshold to classify persisting symptoms was 1 month after concussion ( = 38). Only 6 studies directly cited clinical diagnostic criteria to justify their definition of persisting symptoms, while 12 studies cited another peer-reviewed article. Current definitions for defining persisting symptoms after concussion rely solely on self-reported symptoms but vary in relation to the term used and the number of symptoms/amount of time following concussion required. A more holistic, standardized definition for persisting symptoms should be adopted for better consistency in research and clinical practice.
Cerebral Autoregulation in Severe Traumatic Brain Injury: Source of Index, Timing, and Relationship to Spreading Depolarization.
Marino A, Kareddy A, Wang XQ … +4 more , Harge C, Jones TR, Shuttleworth CW, Carlson AP
J Neurotrauma · 2026 Apr · PMID 41937269 · Publisher ↗
Impaired cerebral autoregulation is a contributor to secondary injury in traumatic brain injury (TBI) and is associated with worse outcomes. The mechanism of injury progression from impaired autoregulation is suggested t...
Impaired cerebral autoregulation is a contributor to secondary injury in traumatic brain injury (TBI) and is associated with worse outcomes. The mechanism of injury progression from impaired autoregulation is suggested to be related to triggering of spreading depolarization (SDs) events-massive waves of cellular dysfunction implicated in secondary injury. The most-studied continuous measurement of autoregulation is the pressure reactivity index (PRx), a rolling correlation between waveform level mean arterial pressure (MAP) and intracranial pressure. However, alternative indices using correlation of MAP with brain tissue oxygen tension (PbtO), probe-derived cerebral blood flow (CBF), and regional brain oxygen saturation (rSO) can also be performed and may have advantages. Our objective was to evaluate the predictive value of different multimodal autoregulation indices for 30-day mortality in TBI and to assess the relationship between impaired autoregulation and SD. Autoregulation indices including PRx, oxygen reactivity index (ORx; from PbtO), CBF reactivity (CBFRx; from thermal diffusion), and oxygen saturation reactivity index (OSRx; from rSO) were obtained in a cohort of 218 patients with TBI requiring invasive monitoring. Associations between autoregulation indices and 30-day mortality were evaluated using multivariable logistic regression models, adjusting for age and admission Glasgow Coma Scale (GCS). A subset of postsurgical patients with SD monitoring was evaluated to assess for a potential relationship between SD and autoregulation. Within the first 24 h, univariable analysis demonstrated significant associations between 30-day mortality and ORx ( = 0.0078) or OSRx ( = 0.0014), but not other indices. In multivariable models adjusting for age and admission GCS, both ORx ( = 0.044) and OSRx ( = 0.027) remained significant predictors of 30-day mortality. In the overall monitoring time, only ORx ( = 0.008) and PRx from the parenchymal monitor ( = 0.027) were significantly associated with mortality. In patients with SD monitoring, we noted an inflection in the predicted probability of SD below MAP 85 mmHg, which may be supportive of the lower limit of autoregulation being a threshold for increased SD probability. We conclude that early (first 24 h) impairment in ORx and OSRx is associated with worse outcomes in TBI, while ORx and PRx are more strongly associated throughout the window of invasive monitoring. This effect may be mediated by increased SD with impaired autoregulation. OSRx can be derived from noninvasive near-infrared spectroscopy monitoring. This presents an opportunity to assess and optimize impaired autoregulation earlier in a patient's course without invasive monitoring. This could enhance outcome prediction and guide therapeutic strategies, particularly early after TBI.
Sharing Clinically Relevant Research Results with Active-Duty Special Operations Forces: Toward an Ethical Framework for Responsible Disclosure.
Young MJ, Tramazzo JC, McKinney IR … +13 more , Gilmore N, Hu CG, Ditzel RM, Modlin RE, McNamara C, Bonvie J, Tromly SL, Jewell JA, Mucciarone JJ, Mac Donald CL, Dams-O'Connor K, Bodien YG, Edlow BL
J Neurotrauma · 2026 Mar · PMID 41918487 · Publisher ↗
Structured acquisition and analysis of individual-level health data in the context of biomedical research can yield novel results with potential clinical or personal relevance to participants. While approaches to returni...
Structured acquisition and analysis of individual-level health data in the context of biomedical research can yield novel results with potential clinical or personal relevance to participants. While approaches to returning individual-level research results to study participants in civilian contexts have received some attention, unique ethical considerations informing approaches to sharing military research results, and particularly in research studies involving active-duty Special Operations Forces (SOF), are underexplored. As the number of research studies enrolling active-duty military personnel grows, an ethical framework to guide responsible handling and sharing of individual-level research results in these distinctive contexts is crucial to safeguard the rights and welfare of research participants and to elucidate appropriate practices for investigators. After exploring the landscape of ethical, clinical, legal, and logistical considerations, both motivating and complicating routine sharing of individual-level biomedical research results with active-duty SOF personnel, we propose a framework to guide responsible disclosure of results to capture potential benefits while mitigating possible risks.
Interferon-β Deficiency Selectively Modulates Chronic Microglial Pathways after Traumatic Brain Injury.
Barrett JP, Henry RJ, Vaida M … +4 more , Shirey KA, Vogel SN, Faden AI, Stoica BA
J Neurotrauma · 2026 Mar · PMID 41913445 · Publisher ↗
Traumatic brain injury (TBI) induces long-term, secondary injury processes that contribute to chronic neurodegeneration and associated neurological deficits. Previously, we demonstrated that controlled cortical impact in...
Traumatic brain injury (TBI) induces long-term, secondary injury processes that contribute to chronic neurodegeneration and associated neurological deficits. Previously, we demonstrated that controlled cortical impact in mice, a well-established experimental model of TBI, causes acute neuroinflammatory changes, including upregulation of interferon-β (IFN-β) and other type I interferon (IFN-I)-related genes in the injured cortex and hippocampus. Early inhibition of IFN-β signaling, either through intracerebroventricular administration of an anti-type I IFN receptor antibody or use of global IFN-β knockout mice (IFN-β), attenuates post-traumatic neuroinflammation and neurodegeneration and improves neurological outcomes for up to 28 days postinjury (dpi), with the knockout model showing more robust and sustained protective effects. However, the consequences of sustained suppression of these pathways after TBI have not been studied. Here, we examine the long-term effects of IFN-β deficiency on microglial activation, neuropathology, and neurological function during the chronic phase post-TBI (60-90 dpi). Transcriptomic analysis of isolated microglia from wild-type mice after TBI revealed persistent upregulation of IFN-I and other key neuroinflammatory genes, including classical pro-inflammatory and disease-associated microglia (DAM) at both 60 and 90 dpi. The IFN-I pathway was significantly attenuated in IFN-β mice at these later timepoints. However, IFN-β deficiency did not significantly alter the trauma-induced upregulation of DAM markers, indicating selectivity of chronic IFN-β modulation on injury-induced microglia-reactive phenotypes. Moreover, although IFN-β deficiency significantly attenuated pro-inflammatory phenotypes at 60 dpi, it enhanced the injury-mediated downregulation of homeostatic microglial genes at 90 dpi. In addition, no significant reduction in lesion volume or fine motor deficits was observed in IFN-β mice at chronic timepoints, although chronic post-traumatic cognitive impairment was attenuated. These findings suggest that global IFN-β deficiency has complex, time-dependent effects on chronic outcomes following TBI; although it improves cognitive function, it further suppresses homeostatic microglia that may partially limit long-term therapeutic benefits.
Quality of Life and Function from Initial Injury to Follow-up in the First Year after Traumatic Spinal Cord Injury.
Hemmerle DD, Wagner L, Hong OS … +21 more , Duong-Fernandez X, Huie JR, Mendoza E, Torres-Espin A, Keller AV, Hinson HE, Pan JZ, Singh V, Kyritsis N, DiGiorgio AM, Talbott JF, Whetstone WD, Weinstein PR, Kuo YH, Manley GT, Bresnahan JC, Beattie MS, Dhall SS, Pascual LU, Ferguson AR, TRACK-SCI Investigators
J Neurotrauma · 2026 Mar · PMID 41902637 · Publisher ↗
We assessed the extent to which initial injury severity, functional independence, and health-related quality of life (QoL) predict overall QoL in adults during their first year of recovery following a traumatic spinal co...
We assessed the extent to which initial injury severity, functional independence, and health-related quality of life (QoL) predict overall QoL in adults during their first year of recovery following a traumatic spinal cord injury (SCI). Data were collected from two level-I trauma centers and outpatient follow-up care as part of the longitudinal, prospective, and multicenter Transforming Research and Clinical Knowledge in SCI study. Participants included adults with traumatic SCI presenting acutely within 24-h of injury ( = 115). Functional independence was measured using the Spinal Cord Independence Measure Version III, health-related QoL was measured using 11 short-form questionnaires from the QoL in Neurological Disorders (Neuro-QoL) measurement system, and overall QoL was measured using the International SCI QoL Basic Data Set. Injury severity and functional independence measures were not significant predictors of overall QoL. Ten of the 11 Neuro-QoL questionnaires were strongly associated with overall QoL ( ≤ 0.001-0.015). In a multivariable regression model, depression ( = 0.002) and satisfaction with social roles/activities ( < 0.001) maintained significance with overall QoL at 6-12 months post-SCI. Findings indicate that patient-reported mental and social well-being may be more important to overall QoL than injury severity, functional independence, or physical health-related QoL during the first year of recovery following traumatic SCI. This reveals the importance of incorporating mental and social health care plans during early SCI rehabilitation.
Motor Score Patterns Complement the AIS Grade in the Analysis of Segmental Motor Recovery after Spinal Cord Injury.
Lukas LP, Bourguignon L, Rupp R … +13 more , Weidner N, Schubert M, Röhrich F, Waldmann J, Kalke YB, Abel R, Maier D, Chhabra HS, Liebscher T, Geisler F, Curt A, Brüningk SC, Jutzeler CR
J Neurotrauma · 2026 Mar · PMID 41902634 · Publisher ↗
Neurological recovery following spinal cord injury (SCI) is commonly studied through changes in high-level descriptors of injury severity, such as the American Spinal Injury Association Impairment Scale (AIS) grade, or t...
Neurological recovery following spinal cord injury (SCI) is commonly studied through changes in high-level descriptors of injury severity, such as the American Spinal Injury Association Impairment Scale (AIS) grade, or total upper and/or lower extremity motor scores. More recently, the analysis of segmental motor scores has attracted interest as it provides a more detailed understanding of the exact location and extent of changes occurring during recovery. We propose to augment the analysis of segmental motor recovery with a qualitative descriptor of local motor score patterns, which is defined for all upper and lower extremity myotomes below the neurological level of injury (NLI) and based on a categorization of the changes along the rostrocaudal motor score sequence. Our hypothesis is that recovery of segmental motor scores depends on the residual function as described by the newly proposed descriptors of local motor score patterns. Using data of 1385 patients from the European Multicenter Study about SCI, we analyze differences in recovery at approximately 6 months after injury between local motor score patterns and find an increased probability of full motor recovery for myotomes associated with increased motor scores in the caudal direction. We further use an aggregated descriptor of motor score patterns focusing on increases of motor scores in the caudal direction as an alternative or complementary feature to the AIS grade in prediction models for segmental motor scores at recovery. We observe equivalent predictive performance as measured by the root mean square error between actual and predicted motor scores below the NLI for models using the same set of features and additionally either the AIS grade (median = 0.79) or local pattern (median = 0.80). This is noteworthy as the definition of local motor score patterns requires only the examination of the 10 key muscles of the International Standards for Neurological Classification of SCI on each side of the body, while the AIS grade can only be reliably determined if extensive sensory testing is performed in addition. These results indicate the potential benefits of considering information inherent to the rostrocaudal sequence of motor scores for a better understanding of motor recovery. Furthermore, it supports the development and use of abbreviated sensorimotor examinations specifically in the early phase after SCI.
Non-Invasive Assessment of Acute Neuroinflammation and Demyelination after Spinal Cord Injury in Young and Aged Rodent Models Using Positron Emission Tomography.
Jaiswal S, Smith AN, Gregor A … +7 more , Purnomo S, Basuli F, Shi J, Swenson R, Hood M, Ho VB, Byrnes KR
J Neurotrauma · 2026 Mar · PMID 41902631 · Publisher ↗
According to the Global Burden of Disease Study 2019, there were approximately 0.9 million new cases of spinal cord injury worldwide. Injury to the spinal cord can lead to significant and often permanent loss of sensory...
According to the Global Burden of Disease Study 2019, there were approximately 0.9 million new cases of spinal cord injury worldwide. Injury to the spinal cord can lead to significant and often permanent loss of sensory and motor functions. The impairment of sensory and motor functions is a consequence of cellular and molecular events triggered by the injury, resulting in secondary complications. Inflammation and demyelination are two of the primary pathological processes that occur after SCI. Research suggests that these secondary complications are exacerbated in the aged population. This study aimed to assess neuroinflammation and demyelination in a rat model of SCI, comparing young and aged rats using non-invasive positron emission tomography/computed tomography (Positron Emission Tomography (PET)/CT) imaging. Young (3 months) and middle-aged (12 months) male Sprague-Dawley rats were imaged dynamically using inflammation ([F]DPA714) and demyelination (3[F]F4AP) PET tracers prior to injury and acutely after a moderate contusion T9 SCI. The tracer uptake was assessed by drawing a volume of interest (VOI), and the mean Standardized Uptake Value (SUV) was compared from baseline to post-injury time point for the two radiotracers. Alterations in the tracer SUV were also evaluated between the aged and young animals. Kinetic PET scans demonstrated that both injury and age altered the uptake patterns for demyelination and inflammation PET tracers. Compared to young animals, the aged animals showed increased tracer uptake at the injury site for the inflammation ([F]DPA714) marker only. No change in tracer uptake was observed in the uninjured regions distal to the injury site or baseline scans between age groups. Combined PET scans with histological analyses demonstrated that [F]DPA714 significantly correlated with gliosis, whereas 3[F]F4AP correlates with neuronal and white matter markers. The PET/CT imaging using these tracers has the potential to offer valuable insights into prognosis and treatment effectiveness following SCI.
Noninvasive Methods for Measurement of Intracranial Pressure in Patients with Acute Neurotrauma: A Systematic Review and Meta-Analysis.
Lind ANR, Kristensen MH, Hvingelby V … +8 more , Rasmussen M, Koch KU, Granfeldt A, Mikkelsen R, Rasmussen LK, Simonsen CZ, Gude MF, Korshøj AR
J Neurotrauma · 2026 Mar · PMID 41902625 · Publisher ↗
Invasive intracranial pressure (ICP) monitoring provides essential guidance for the treatment of patients with suspected head injuries; however, it remains incompatible with prehospital use. While several noninvasive ICP...
Invasive intracranial pressure (ICP) monitoring provides essential guidance for the treatment of patients with suspected head injuries; however, it remains incompatible with prehospital use. While several noninvasive ICP-measuring methods exist, previous studies have not adequately addressed their potential in a prehospital setting. In this systematic review and meta-analysis of diagnostic test accuracy, we explore the accuracy of existing noninvasive methods for ICP monitoring and assess their potential usefulness in prehospital screening for elevated ICP. This systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Embase, Scopus, PubMed, CENTRAL, and Cochrane databases were sought for relevant articles on June 23, 2025. All studies evaluating minimally invasive and transportable methods for ICP assessment were included. Animal studies, studies, reviews, and meta-analyses were excluded. Study selection was performed by two independent reviewers, and conflicts were resolved by a third reviewer. Potential for prehospital use of each method was evaluated using four predetermined criteria. Summary receiver operator characteristic curves and summarized sensitivity and specificity were reported if multiple studies investigating the same method were eligible for meta-analysis. The applicability and risk of bias of the included studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool for diagnostic test accuracy studies. Fifty-five articles were included. Ultrasound of optic nerve sheath diameter (ONSD) was the method with the highest potential for prehospital use. We found a summarized sensitivity of 92.6% (95% confidence interval [CI]: 87.0; 95.9%) and a summarized specificity of 85.1% (95% CI: 74.1; 92.0%) for detecting increased ICP through ONSD measurement. Other methods for diagnosing elevated ICP diagnosis showed poor diagnostic accuracy or low potential for prehospital use. We found ultrasound estimation of the ONSD to show the highest potential for prehospital use. Prospective studies are needed to verify their diagnostic capability in the prehospital setting.
Acute Neuroimaging Findings Are Associated with Poor Outcome after Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis.
Nelson BK, Saint SA, Farah LN … +4 more , Bagh TB, Silverberg ND, Stubbs JL, Panenka WJ
J Neurotrauma · 2026 Mar · PMID 41882969 · Publisher ↗
Previous studies have failed to determine whether acute neuroimaging findings after mild traumatic brain injury (mTBI) are associated with poor outcomes. We performed a systematic review and meta-analysis to determine wh...
Previous studies have failed to determine whether acute neuroimaging findings after mild traumatic brain injury (mTBI) are associated with poor outcomes. We performed a systematic review and meta-analysis to determine whether such indicators are associated with health outcomes, recovery-related outcomes, or concurrent indicators of injury severity. We searched MEDLINE, PsycINFO, and Web of Science in April 2024. We extracted data from prospective studies or retrospective analyses of prospective data, where computed tomography scans were acquired within 1 week of mTBI or magnetic resonance imaging scans were acquired within 3 months of injury, according to PRISMA guidelines. The primary outcome measure was the Glasgow Outcome Scale. Secondary outcomes and indicators of injury severity included self-reported loss of consciousness, post-traumatic amnesia, and post-concussion symptom scores. The protocol for this study was pre-registered (PROSPERO #CRD42020190659). We included 64 studies in the review and 25 studies in the meta-analyses. The presence of acute neuroimaging findings after mTBI was associated with higher odds of poor outcome (OR = 2.04 [1.29-3.24], = 0.0024, = 7, = 2,947) and loss of consciousness (OR = 1.42 [1.02-1.97], = 0.039, = 15, = 3,912) compared to those without acute neuroimaging findings, but not post-traumatic amnesia (OR = 1.27 [0.65-2.49], = 0.49, = 10, = 5,155) or post-concussion symptoms (Hedge's = 0.00 [-0.17-0.17], = 0.97, = 9, = 3,616). Results from qualitative analysis of outcome data that could not be synthesized quantitatively are congruent. Acute neuroimaging findings after mTBI are associated with poor functional outcome and may be clinically relevant for identifying patients at a higher risk for poor outcomes.
Expression of Concern.
J Neurotrauma · 2026 Mar · PMID 41882968 · Publisher ↗
Abstract loading — click title to view on PubMed.
Intraindividual Limb Comparisons of Motor and Neurophysiological Outcomes Using the European Multicenter Study About Spinal Cord Injury: Implications for Clinical Trials in Acute Cervical Spinal Cord Injury.
Missen KJ, Cragg JJ, Dengler J … +5 more , Fox IK, Curt A, Schubert M, Weidner N, Berger MJ
J Neurotrauma · 2026 Mar · PMID 41882963 · Publisher ↗
It is common for researchers in spinal cord injury (SCI) to treat limbs from the same individual as independent to increase sample size in limb-based analyses. However, this approach may violate independence assumptions...
It is common for researchers in spinal cord injury (SCI) to treat limbs from the same individual as independent to increase sample size in limb-based analyses. However, this approach may violate independence assumptions required for traditional statistical tests. This study investigated the dependence of bilateral upper-limb motor and neurophysiological outcomes through a retrospective analysis of participants from the European Multicenter Study about Spinal Cord Injury. Data from 118 participants with acute cervical SCI (236 limbs) were analyzed, including ulnar compound muscle action potentials (CMAPs) recorded in the abductor digiti minimi and manual muscle scores for the flexor digitorum profundus, bilaterally assessed at 12 and 48 weeks postinjury. Our analysis stratified participants by injury severity into two groups: motor complete ( = 55) and motor incomplete ( = 63). Interlimb dependence was assessed using Spearman's rank correlations. To illustrate the implications of such dependence for inference, bootstrap analyses of motor recovery (12 vs. 48-week CMAPs) compared three analytical approaches using a linear mixed-effects model framework: randomly selecting outcomes from one limb per participant, including both limbs but ignoring intraparticipant correlation, and including both limbs but accounting for intraparticipant correlation. Bootstrap resampling was performed across sample sizes ranging from = 10 to 50. Moderate-to-strong correlations (Spearman's rho = 0.44-0.91) were observed between bilateral CMAPs and bilateral strength scores in both groups at 12 and 48 weeks postinjury. All models yielded similar CMAP recovery estimates (∼1.6 to 1.8 mV), but the precision of these estimates and the empirical power, reflecting the probability of detecting a significant recovery effect given the observed effect size and variability, varied across methods. Treating limbs as independent overestimated precision, resulting in the highest power estimates, whereas including only one limb reduced statistical power, particularly at lower sample sizes. Accounting for intraparticipant dependence yielded intermediate estimates of precision and power. These findings demonstrate that bilateral upper-limb outcomes in SCI are statistically dependent and highlight the need for statistical procedures that account for intraparticipant correlation in SCI research to ensure valid study conclusions.
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