Journal of Neurotrauma

Traumatic brain injury (TBI), particularly sports- and recreational activity related mild TBI (mTBI), is common in young adults and can be followed by persistent attentional and executive complaints. This study investigated chronic ([≥]6 months post-injury) structural brain alterations in gray matter (GM) and white matter (WM) and their associations with self-reported inattentive and hyperactive/impulsive symptoms, with a focus on sex-differentiated patterns. Structural brain properties in gray matter (GM) and white matter (WM) were acquired from 44 subjects with TBI and 45 matched controls, by utilizing structural MRI and diffusion tensor imaging techniques. Behavioral measures assessing severities of post TBI inattentive and hyperactive/impulsive symptoms were collected from each participant. Between-group and sex-specific differences of these brain and behavioral measures were conducted. Interactions among the TBI-induced significant brain- and behavioral-alterations, and their sex-specific patterns, were assessed as well. Male-dominated pattern of increased cortical thickness in superior parietal lobule (SPL) and female-dominated pattern of higher superior longitudinal fasciculus and superior fronto-occipital fasciculus (sFOF) fractional anisotropy (FA) were observed in the TBI group, when compared to controls. In males with TBI, greater SPL cortical thickness was significantly correlated with increased inattentive behaviors. In females with TBI, higher FA of sFOF was significantly correlated with decreased hyperactive/impulsive behaviors. Findings suggest that TBI-induced superior parietal cortical GM abnormalities may significantly cause attention deficits in patients with TBI, especially in males; while optimal post-TBI WM recovery in sFOF significantly contributes to maintenance of inhibitive control in patients with TBI, especially in females.

Repetitive head impacts (RHI) from contact and collision sports have been associated with later-life cognitive and neurobehavioral impairments, as well as neurodegenerative conditions such as chronic traumatic encephalopathy (CTE). RHI-associated clinical sequelae among female former soccer players, specifically, are not well understood. This cross-sectional study aimed to examine the relationship of RHI exposure proxies (e.g., total years of soccer play, highest level of play, and estimated cumulative heading frequency) with clinical measures (e.g., subjective cognitive complaints, objective cognitive performance, behavioral dysregulations, and depressive symptoms) among 3,174 women, aged 40 years or above, enrolled in the Head Impact and Trauma Surveillance Study (HITSS), all of whom played organized soccer. HITSS participants completed an online battery that elicited self-reported cognitive and behavioral complaints and depressive symptoms, and that assessed cognitive performing via computerized tests. Multivariable linear and logistic regression models estimated associations between soccer-related RHI proxies and outcome measures, adjusting for age and education. Among the former soccer players, longer duration of soccer play, higher level of play, and greater estimated cumulative heading frequency were significantly associated with worse self-reported cognitive functioning, greater behavioral dysregulation, and elevated depressive symptom severity (range of significant unstandardized B coefficients: 0.02 to 0.52). Higher estimated cumulative heading exposure was associated with higher odds of clinically meaningful elevations on subjective measures (OR range: 1.05 to 1.13) There were no associations between any of the RHI proxies and performance on the objective computerized cognitive assessments. Among middle-aged women who played organized soccer, cumulative RHI exposure was associated with small but statistically significant effects for measures of subjective cognitive complaints, behavioral functioning, and depressive symptoms. We found no associations for objective outcomes of cognitive function. Continued monitoring of this large cohort of female former soccer players will improve understanding of long-term consequences of soccer play.

BACKGROUNDThe recovery from sport-related concussion (SRC) is highly heterogenous, with many individuals experiencing symptoms that persist beyond typical recovery timeframes. The early identification of individuals at risk of prolonged symptoms is therefore critical to inform timely interventions and set realistic recovery expectations. Although acute symptom burden is one predictor of future symptom burden, reliance on self-reported measures may limit objectivity and reduce clinical utility in settings where symptom evaluation may be unreliable. In this prospective cohort study, we evaluated the discriminatory accuracy of the CogState Brief Battery, alone and in combination with the Sport Concussion Assessment Tool (SCAT), to classify Australian football players with SRC from Australian footballers without SRC at 24-hours post-injury/match. Furthermore, we examined whether CogState performance and symptom severity at 24 hours were associated with symptom outcomes at one-week post-injury. Adult amateur Australian football players (n=181) were recruited following SRC (n=109 SRC, 86% male) or after a non-injured match (n=72, 90% male). Participants completed the CogState Brief Battery, SCAT and Rivermead Post Concussion Questionnaire (RPQ) at 24-hours and one-week post-injury or match. Area under the receiver operating characteristic (AUC) analyses quantified the ability of 24-hour CogState task performance and SCAT symptom severity to distinguish SRC from controls. Linear regression models examined associations between CogState performance and symptom severity (SCAT and RPQ), within and across the 24-hour and one-week time points. Additional models evaluated whether combining 24-hour symptom severity assessments with CogState performance improved prediction of one-week symptom burden and symptomatic status. SCAT symptom severity demonstrated excellent discriminatory classification accuracy for SRC versus controls at 24-hours post-injury (AUC [95% CI]: 0.949 [0.916 - 0.981]). CogState task performance showed lower discriminatory accuracy but demonstrated fair classification and prognostic utility (e.g., Identification task AUC [95% CI]: 0.666 [0.582 - 0.750]). CogState performance at 24-hours was significantly associated with overall symptom severity at both 24-hours and one-week, as well as with symptom severity across individual symptom domains. In combined models, 24-hour symptom severity and CogState performance independently contributed to the prediction of symptomatic from asymptomatic individuals at one-week post-SRC (e.g., Identification task AUC [95% CI]: 0.721 [0.606 - 0.835] for classification based on <4 versus [&ge;]4 symptoms). These findings indicate that CogState performance at 24-hours post-SRC may serve as an objective adjunct to subjective symptom-based reporting, supporting both diagnosis and early prognostication in the clinical evaluation of SRC.

ObjectiveDespite substantial variability in the severity of post-anoxic encephalopathy, all comatose patients after cardiac arrest are usually treated according to the same standardized intensive care protocol, including sedation, mechanical ventilation, and targeted temperature management (TTM). We hypothesize that patients with a favourable EEG pattern (continuous EEG within 12 hours after cardiac arrest) may not benefit from prolonged sedation and TTM. We studied the feasibility and safety of early cessation of sedation and TTM in this subgroup. MethodsWe conducted a non-randomized, controlled intervention study including 40 adult patients admitted to the ICU with postanoxic encephalopathy after cardiac arrest and an early (< 12 hours) favourable EEG pattern. The control group received standard care with sedation and TTM for at least 24-48 hours, whereas the intervention group underwent early cessation of sedation and TTM as soon as possible after establishing a favourable EEG, followed by weaning from mechanical ventilation. The primary outcome was duration of mechanical ventilation. Secondary outcomes included ICU length of stay, total sedation time, number of ICU complications, and neurological outcomes at 3 and 6 months. ResultsDuration of mechanical ventilation was significantly shorter in the intervention than in the control group (median 12 vs 28 h, p < 0.001). Median ICU length of stay and median total sedation time were also reduced by more than 50% in the intervention group, from respectively 2.5 to 1.2 days (p = 0.001) and 27 to 12 h (p < 0.001). There was no increase in ICU complications in the intervention group. No statistically significant differences in neurological outcomes at 3 or 6 months were observed. ConclusionEarly withdrawal of sedation is feasible and safe in patients with an early favourable EEG following cardiac arrest. The study was underpowered to detect possible differences in long-term neurological recovery. SignificanceShortening sedation and mechanical ventilation is likely to result in direct reductions in healthcare costs and contribute to more appropriate care. Larger studies are needed to evaluate the impact on long-term neurological outcomes.

IntroductionIdiopathic normal pressure hydrocephalus (iNPH) is a partially reversible neurological disorder in which imaging biomarkers support diagnosis and surgical decision-making. The callosal angle (CA) is one of the most robust radiological markers of iNPH and has also been associated with postoperative shunt outcome. However, several manual measurement variants exist and artificial intelligence (AI)-based tools now enable automatic CA measurement. Materials and MethodsIn total 71 patients (40 with confirmed iNPH and 31 controls) were included. Six predefined manual methods for measuring CA were applied to preoperative 3D T1-weighted MRI and evaluated for diagnostic performance and interobserver agreement. An AI-derived automatic CA (cMRI from Combinostics) was included as a seventh method and compared with the traditional manual method (perpendicular to the bicommissural plane and through the posterior commissure). Automatic measurements were additionally assessed in pre- and postoperative scans to evaluate robustness against shunt-related artifacts. ResultsAll seven CA variants significantly differentiated iNPH patients from controls (p < 0.05). The traditional method showed the highest discriminative performance (AUC = 0.986, SE = 0.012), while alternative planes demonstrated slightly lower accuracy (AUC range = 0.957-0.978). Interobserver agreement for manual measurements was good to excellent (ICC = 0.687-0.977). Automatic CA measurements showed excellent correlation with the traditional method, preoperative ICC = 0.92; postoperative ICC = 0.96. ConclusionAlthough several CA positions perform comparably, the traditional method remains marginally superior and is best supported by the literature. Automated CA measurements closely match expert manual assessment in pre- and postoperative imaging, supporting clinical implementation.

ObjectiveThis study aimed to characterize the activation of lower urinary tract (LUT) targets in response to pudendal nerve stimulation (PNS) in awake human participants. Materials and MethodsIn this single center study, recruited participants had an implanted pudendal neurostimulator for treatment of their symptoms including overactive bladder, incontinence, urinary retention, and/or pelvic pain. Participants came in for a modified urodynamic study where a multichannel manometry catheter was placed in the lower urinary tract alongside a dual sensor urodynamics catheter. The bladder was filled and after each participant expressed a strong desire to void, PNS was applied and LUT pressures were measured. Participants attempted voids with the catheters in place to characterize LUT behavior and voiding efficiency with and without stimulation. ResultsThe study consisted of 15 participants including 13 women. Across 133 total trials contractions were observed at the distal urethra 52 times (39%) and at the proximal urethra 46 times (35%). The maximum observed pressure change occurred significantly more often at the proximal urethra than the distal urethra (p = 0.007). There was a significantly higher maximum tolerable stimulation amplitude for low frequency stimulation (2-3.1 Hz) when compared to high frequency stimulation (30-33 Hz) (p = 0.041). In one participant there were four instances of stimulation driven bladder contractions with an average pressure change of 24.3 cmH2O (standard deviation = 10.5). There was not a significant difference in voiding efficiency or maximum flow rate with and without stimulation (p = 0.76 and p = 0.45, respectively). ConclusionsPNS can affect LUT pressures at tolerable stimulation amplitudes. The absence of an effect of PNS on voiding characteristics suggests a similar mechanism of action as sacral neuromodulation.

IntroductionRecent evidence has shown that vitamin C has analgesic properties in immediate postoperative context. However, while a clinical trial is currently underway to evaluate vitamin C for reducing opioid consumption in acute musculoskeletal (MSK) injuries emergency department (ED) patients, its direct analgesic effect in this population has not yet been established. This pilot study evaluated the feasibility of conducting a randomized placebo-controlled trial to determine the analgesic effect of vitamin C alone compared with placebo in acute MSK injured ED patients. MethodsWe conducted a double-blind, randomized controlled pilot trial stratified by fracture status in a tertiary care center. Adults ([&ge;]18 years) presenting to the ED with MSK injuries of [&le;] 48 hours duration and pain intensity >3/10 were randomized to receive vitamin C 900 mg twice daily for three days or placebo. Participants completed a six-day diary (electronic or paper) and were contacted on day six to document analgesic use, treatment adherence, and pain intensity. ResultsOverall, 147 patients were screened; 63 (42.9%) were excluded, 24 (16.4%) refused, leaving 60 (41.1%) participants, with a consent rate of 13.0/month. Mean age (SD) was 41.8 years (14.23) and 50% were female. Lost to follow-up rate differed between participants with electronic diary (n=7; 16.7%) and participants with paper diary (n=10; 55.6%). Patients compliance with treatment was 97.6%. The least-squares mean difference between group A and group B in the time-weighted sum of pain intensity differences over 72 hours (SPID72) was 348.7 (95% confidence interval [CI]:-698.9 to 1396.4) for the intention-to-treat analysis and 357.6 (95%CI:-709.67 to 1424.82) for the per-protocol analysis. ConclusionThis pilot study supports the feasibility of a larger randomized controlled trial on the analgesic properties of vitamin C for acute MSK injured ED patients. Strategies to reduce the missed patients and lost to follow-up rates are proposed. Trial registration numberNCT06306183, ClinicalTrials.gov

PurposeAqueous humor drains fluid from the eye not only via the conventional pathway through the trabecular meshwork and Schlemms canal, but also within the eye is known to occur via pathways through the posterior chamber and optic nerve to the cerebrospinal fluid (CSF) surrounding the optic nerve. The mechanism is poorly understood, and non-invasive method for evaluation in living humans has not been established. We previously showed that eye drops containing O-17-labeled water (H217O) distribute in the anterior chamber but not the vitreous. This study aimed to evaluate the distribution of H217O in the CSF along the optic nerve. MethodsFive ophthalmologically normal participants (20-31 years, all females) were selected from a previous prospective study based on 1H MR images of the eyes that included the optic nerve. They received eye drops of 10 mol% H217O in their right eye. Dynamic image time series was created by normalizing the signal of each 1H-T2WI by the pre-drop average signal. Region-of-interest analyses were performed for signal changes in the anterior chamber, vitreous, and CSF. ResultsIn the quantitative evaluation, the normalized intensity in the anterior chamber and CSF was significantly lower than that in the pre-drop signal (anterior chamber: 0.78 {+/-} 0.07, p < 0.005; CSF: 0.89 {+/-} 0.07, p < 0.05). No distribution was identified in the vitreous. Qualitatively, the distribution of H217O in the anterior chamber was detected in all five participants and in the CSF of four participants (80%). ConclusionH217O eye drops were distributed in the anterior chamber and CSF, but not in the vitreous. These findings suggest that the visualization of aqueous humor outflow, not via the Schlemms canal, may contribute to ocular fluid homeostasis, including the ocular glymphatic system.

BackgroundIn critically ill patients admitted to the intensive care unit (ICU), rapid skeletal muscle atrophy frequently develops in the acute phase. This ICU-acquired weakness can significantly impair long-term physical function. Although the biceps brachii cross-sectional area (CSA) is commonly used to assess muscle atrophy, its ultrasound imaging can be technically challenging, and the flexor carpi ulnaris may offer a more accessible alternative. Therefore, this study aimed to investigate whether CSA changes of the flexor carpi ulnaris correlate with those of the biceps brachii in critically ill patients admitted to the ICU, as well as whether the flexor carpi ulnaris CSA reflects systemic muscle atrophy in the acute phase of the ICU stay. MethodsTwenty critically ill patients admitted to the ICU underwent serial ultrasound assessment of the biceps brachii and flexor carpi ulnaris CSAs on days 0, 5, 7, and 14 after admission. Longitudinal changes in CSA were analyzed using the Friedman and Wilcoxon signed-rank tests. Correlations between the biceps brachii and flexor carpi ulnaris were examined using Spearmans rank correlation, and structural equation modeling was applied to explore causal relationships between clinical variables and CSA changes. ResultsSignificant CSA reductions were observed in both the flexor carpi ulnaris (-20.6%) and biceps brachii (-16.3%) by day 14, and the relative CSA changes of the biceps brachii and flexor carpi ulnaris showed a moderate positive correlation ({rho} = 0.5489, p = 0.0122). Structural equation modeling analysis revealed that the biceps brachii CSA change had positive effect on that of the flexor carpi ulnaris ({beta} = 0.249, p = 0.0011). Moreover, body mass index was positively associated with the baseline flexor carpi ulnaris CSA ({beta} = 0.042, p = 0.0004). However, the baseline flexor carpi ulnaris CSA was not a significant predictor of subsequent CSA changes. ConclusionUltrasound measurement of the flexor carpi ulnaris CSA offers a practical alternative to that of the biceps brachii for early detection of muscle wasting in ICU patients. Given its anatomical accessibility and high sensitivity to early atrophic changes, it may serve as a feasible screening tool for ICU-acquired weakness and inform timely interventions.

BackgroundLarge middle cerebral artery (MCA) infarctions can result in life-threatening cerebral edema. Quantitative brain atrophy may improve risk stratification for severe edema. We examined whether quantitative brain atrophy is associated with severe midline shift after large ischemic stroke and whether incorporating atrophy improves prediction beyond established clinical and radiographic predictors. MethodsThis was a retrospective observational cohort study of patients with [&ge;][1/2] MCA ischemic infarction, presentation within 24 hours of last known well, and at least one follow-up head CT, admitted to two academic hospitals with comprehensive stroke centers between 2006 and 2024. The study was approved by the institutional review boards of both centers. Brain atrophy was quantified as the inverse of standardized brain volume on admission head CT. The primary outcome was severe radiographic mass effect, defined as midline shift [&ge;]5 mm on follow-up CT. The secondary outcome was in-hospital mortality. Multivariable regression models assessed associations between quantified atrophy and outcomes. Incremental prognostic value was evaluated by comparing models with and without atrophy using measures of goodness of fit, calibration, and discrimination. ResultsAmong 565 patients (mean age 67.5{+/-}15.7 years; 49.9% female), 223 (39.5%) developed severe mass effect. Greater atrophy was associated with lower odds of midline shift [&ge;]5 mm (OR 0.44, 95% CI 0.34-0.58), but not with in-hospital mortality. Incorporation of atrophy significantly improved prediction of severe mass effect compared to the baseline model (likelihood ratio test {chi}{superscript 2} (1) = 41, p <0.001; AIC 703 vs. 741; BIC 733 vs. 767; AUC 0.68 vs. 0.60). ConclusionsQuantified brain atrophy is independently associated with a reduced risk of severe mass effect after large MCA stroke and improved the performance of established predictive models. Incorporation of this imaging biomarker may enhance early risk stratification, monitoring, and intervention planning for patients at risk of life-threatening cerebral edema.

ObjectiveTo compare early cerebrospinal fluid (CSF) cytokine profiles in intracerebral hemorrhage (ICH) versus subarachnoid hemorrhage (SAH), with a focus on angiography-negative SAH (anSAH). MethodsWe conducted a retrospective observational cohort study of adults with spontaneous hemorrhagic stroke (ICH or SAH). For cytokine analyses, we included patients with external ventricular drains (EVDs) and analyzed the first CSF sample obtained within 72 hours of symptom onset. Cytokines were measured using a multiplex bead-based assay and included interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor A (VEGF-A), C-C motif chemokine ligand-2 (CCL2), and granulocyte colony-stimulating factor (G-CSF). Cytokine concentrations were log-transformed due to non-normal distribution. Functional outcomes were assessed using the modified Rankin Scale (mRS) at discharge and 3 months. ResultsCSF cytokine analyses included 120 patients with available CSF samples (43 ICH and 77 SAH), while functional outcome analyses included a broader cohort of 490 patients with ICH or SAH to characterize discharge and 3-month outcomes across hemorrhage subtypes. Compared with SAH, ICH demonstrated higher early CSF log[IL-8] and log[VEGF-A] and had worse functional outcomes at discharge and 3 months. Within SAH, anSAH had higher log[IL-8] and log[VEGF-A] than aSAH, and its cytokine profile more closely aligned with that of primary ICH in hemorrhages without vascular malformations. DiscussionEarly CSF cytokine patterns suggest anSAH shares a more ICH-like inflammatory signature than aneurysmal SAH, supporting anSAH as a potentially biologically distinct SAH phenotype.

ImportancePrognosticating functional independence after an acute stroke is critical for anticipatory guidance and rehabilitation planning. Here we demonstrate that poor brain health at the time of incident stroke is linked to worse functional outcomes for women compared to men. ObjectiveTo determine if brain health at time of stroke presentation has a differential effect on functional outcomes between men and women. DesignRetrospective cross-sectional study. SettingAnalysis conducted in 2025 with multi-center patient data that included participants from two large acute ischemic stroke cohorts; local (GASROS) and multinational (MRI-GENIE) between the years 2003 and 2011. ParticipantsClinical data collected for enrolled study participants included demographic data, medical history of hypertension, diabetes mellitus, hyperlipidemia, smoking status, acute stroke severity as measured by National Institutes of Health Stroke Scale (NIHSS), stroke etiology, and modified Rankin Scale (mRS) score at 90 days post-stroke. Brain health was quantified as effective reserve derived from acute neuroimaging data. Exposure(s)designated sex, retrieved from registration records. Main OutcomeFunctional outcome was measured by mRS scores at 90 days post-stroke, in men and women with poor, moderate, or good brain health at time of stroke injury. ResultsA total of 1039 patients were included in the analysis, 37.8 % women, median age 67 [interquartile range 56-77]. Women with poor brain health (i.e. lowest quartile of effective reserve) had worse functional outcomes at 90 days (55.6% with mRS>2) compared to men with poor brain health (31.2% with mRS>2: p < 0.001). This difference between men and women was not observed in categories of moderate or good brain health. There was no observed significant difference in stroke severity, volume of acute lesion, burden of white matter hyperintensities, or stroke etiology between men and women with poor brain health. Conclusions and RelevanceBrain health at the time of incident stroke has a differential effect on functional outcomes at 90 days between men and women. Women with poor brain health endure disproportionately worse outcomes compared to men. This highlights an important step in understanding sex-specific vulnerability in early recovery post-stroke, and can inform disposition, rehabilitation services, and resource allocation planning.

IntroductionThe ischaemic penumbra is the principal therapeutic target in acute ischaemic stroke (AIS). Although perfusion imaging enables identification of salvageable tissue, its availability is limited and iodinated contrast exposure carries risk. Validated blood-based biomarkers could serve as scalable surrogates for imaging-defined penumbra. ObjectiveWe conducted a systematic review and meta-analysis to assess the association between blood-based biomarkers reported in the literature and the ischaemic penumbra. MethodsWe searched Ovid MEDLINE, Embase (Ovid), PsycINFO (Ovid), and Web of Science until December 3, 2025, for studies involving human subjects with AIS aged over 18 years or animal subjects that reported the presence of infarct and ischaemic penumbra. The primary outcome was the difference in mean biomarker levels in subjects with and without ischaemic penumbrae as defined by the study authors. We used the QUADAS-2 tool to assess risk of bias. We calculated each biomarkers pooled standardized mean difference (SMD) and 95% CI where possible. Protein-protein interaction network (PPI) and pathway analyses were conducted in Cytoscape and the enrichR R package (PROSPERO: CRD42023453175). ResultsWe identified 11 studies (1765 human subjects and 8 nonhuman primates) that assessed 53 candidate blood-based biomarkers. Two studies had a low risk of bias, while nine had a risk of bias. A meta-analysis was conducted for seven biomarkers in humans from four studies. Of these, three biomarkers demonstrated significant association with penumbrae in humans: mid-regional pro-adrenomedullin (MR-proADM; SMD 0.80 [95% CI 0.49 to 1.10]), interleukin-10 (IL-10; SMD 1.94 [0.85 to 3.03]), and neuron-specific enolase (NSE; SMD -0.71 [-1.40 to -0.01]). However, substantial statistical heterogeneity was observed for several pooled biomarkers (I{superscript 2} >90%), limiting confidence in effect size precision. Amongst biomarkers where meta-analysis was not possible, 37 biomarkers showed significant association with presence of a penumbra. Oxygen radical absorbance capacity after perchloric acid treatment (ORACPCA; SMD 0.31 [0.01 to 0.60]) showed significant association with penumbra presence; 34 genes (e.g., STK26 r = 0.58, p = 0.003; MGA r = 0.58, p = 0.004; IL1B r = -0.59, p = 0.003; NUP98 r = -0.71, p < 0.001), circOGDH (r = 0.962, p = 0.002), and NT-proBNP (r = 0.199, p < 0.001) were significantly correlated with penumbra volume. PPI analysis identified IL-1{beta} as the most highly connected node (10 interactions), followed by IL-10 and HDAC1/HCAR2. Cdc42 was reported to be significantly associated with penumbrae in nonhuman primates, but there were insufficient data to calculate SMD. Pathway enrichment revealed positive associations with angiogenesis and IL-12 signalling, and negative associations with leukocyte migration, chemokine signalling, and platelet activation. ConclusionsCurrently reported biomarkers of ischaemic penumbra are not ready for clinical implementation. Although implicated pathways converge on inflammatory regulation, haemostasis, and cerebral perfusion, rigorous prospective validation is required before integration into prehospital or emergency triage workflows.

BackgroundSedentary behavior is highly prevalent following traumatic brain injury (TBI) and compounds existing risks for cardiovascular, neurodegenerative, and affective disorders. The cognitive and behavioral sequelae of TBI, including impaired decision-making, blunted reward processing, and cognitive fatigue, create particular barriers to adopting and maintaining an active lifestyle. Despite this, effective behavior change interventions targeting physical activity in community-dwelling TBI survivors remain scarce. Here, we evaluated the feasibility, compliance, and preliminary efficacy of a 12-week remotely delivered walking intervention combining planning, behavioral reminders, and monetary micro-incentives. MethodsFifty-six adults aged 40-80 years with a mild-to-moderate TBI diagnosed between 3 months and 15 years prior were randomized to either a planning, reminders, and micro-incentives intervention (n=23) or a health advice control condition (n=25). Participants wore a Fitbit Inspire 3 continuously throughout the study. Intervention participants completed weekly phone calls to plan five 30-minute walks for the following week, received daily text message or email reminders on planned walk days, and earned small monetary incentives upon walk completion. Control participants received weekly health education calls. Feasibility was assessed through recruitment, retention, and adverse event rates. Compliance was assessed via phone call completion rates and Fitbit wear time. Efficacy outcomes included weekly walk counts, walking duration, and step counts, modeled using Poisson generalized linear mixed models and linear mixed-effects models over 12 weeks. ResultsForty-eight participants completed the study (retention rate: 84.2%), with high phone call compliance in both groups (intervention: 98.4%; control: 98.1%). Intervention participants completed significantly more walks than controls from week 1 onward (aIRR = 5.33, 95% CI: 2.27-12.5, p < 0.001), with the group difference growing over time (interaction aIRR = 1.09 per week, 95% CI: 1.01-1.17, p = 0.029). Estimated marginal means indicated that intervention participants completed 5.5 times more walks than controls at week 1, increasing to 15.5 times more by week 12. The intervention group also walked significantly longer at week 1 (b = 62.14 min, 95% CI: 1.05-123.23, p = .046), with the advantage growing over time; by week 12, intervention participants walked 5.3 times longer than controls. Similarly, the intervention group accumulated significantly more steps during walks at week 1 (b = 4,779 steps, 95% CI: 45.50-9,513.00, p = .048), accumulating 3.1 times more steps than controls by week 12. ConclusionsA remotely delivered, multicomponent walking intervention targeting planning, behavioral reminders, and micro-incentives was feasible, well-tolerated, and produced meaningful increases in walking activity in community-dwelling adults with TBI. With high retention and compliance, and consistent effects on walk counts, duration, and steps across the intervention period, these findings provide compelling support for a larger, fully powered trial.

BackgroundPropofol dosing guidelines recommend age-based reductions because hypnotic sensitivity increases in older adults. Most real-world evaluations of induction practice, however, have relied on total weight-normalized dose (mg/kg) rather than estimating cerebral exposure using pharmacokinetic models. Because age-related pharmacokinetic changes alter the relationship between administered dose and peak effect-site concentration (Ce,max), mg/kg surrogates may misrepresent true age-dependent exposure during induction. MethodsA retrospective reconstruction of 250,640 adult anesthetic inductions was performed using high-fidelity EHR medication timestamps. Propofol effect-site concentration trajectories were simulated at 1-second resolution using the Eleveld model. Ce,maxwas benchmarked against age-adjusted hypnotic requirements (Ce50) derived from the Eleveld model (standardized to a target Bispectral Index{approx} 47). Age-exposure relationships were estimated using covariate-adjusted natural cubic splines, controlling for BMI, sex, and ASA physical status. ResultsFrom young adulthood (18-24 years) to the oldest cohort (85-89 years), weight-normalized induction doses were reduced by 32% (3.16 to 2.16 mg/kg). However, modeled Ce,max declined by only 17% (3.70 to 3.06 {micro}g/mL), while the estimated physiological requirement declined by 34% (3.37 to 2.21 {micro}g/mL), creating a widening titration offset with age. At age 75, the adjusted probability of exceeding the individual hypnotic requirement was 89.6% (95% CI: 89.3-89.8%). Notably, 54.7% (95% CI: 54.2-55.2%) of 75-year-old patients achieved peak exposures exceeding the aver-age requirement of a healthy 20-year-old, indicating persistent anchoring of exposure to youthful levels. Findings were robust across model specifications and inclusion criteria. ConclusionsIn over a quarter-million inductions, real-world age-based dose re-ductions did not produce proportional reductions in peak propofol brain exposure. Achieved concentrations declined far more slowly than modeled geriatric sensitivity increases, consistent with systematic over-exposure in older adults. These findings suggest that weight-based dosing heuristics inadequately capture age-dependent exposure and support a transition toward exposure-informed and neurophysiologically guided induction titration in geriatric anesthesia.

AbstractsO_ST_ABSBackgroundC_ST_ABSSelf-management is essential for stroke survivors to maintain a healthy lifestyle and reduce recurrence risk. Although theory-based self-management interventions are widely recommended, the theoretical frameworks underpinning them and their comparative effectiveness remain unclear. AimsTo systematically identify the theories, models, and frameworks (TMFs) used in self-management interventions for stroke survivors, to explore how they guide interventions, and evaluate their effectiveness on self-management behaviors and self-efficacy. MethodsPubMed, Embase, Web of Science, ProQuest Health & Medical Collection and the Cochrane Library were searched from inception to July 15, 2025. Randomized controlled trials or quasi-experimental studies evaluating theory-based self-management interventions for stroke survivors were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias (Cochrane RoB 2.0). Meta-analyses were performed using random-effects models. ResultsFrom 11,495 records, 32 studies with 3,212 participants were included. Sixteen distinct TMFs were identified; self-efficacy theory was most frequent (13/32), followed by social cognitive theory (6/32). All TMFs were middle-range theories. Meta-analysis showed TMFs-based interventions significantly improved self-management behaviors (SMD = 4.26, 95%CI: 0.20-8.31, I{superscript 2} = 98.2%) and self-efficacy (SMD = 0.60, 95%CI: 0.32-0.88, I{superscript 2} = 72.8%). However, the effect for behaviors is likely inflated due to extreme heterogeneity and theoretical diversity. Theory-specific analysis of self-efficacy theory (k = 8) confirmed significant effects on self-efficacy (SMD = 0.64, 95%CI: 0.21-1.08). ConclusionsThis review identified 16 distinct theoretical models; self-efficacy theory was most frequently applied, followed by social cognitive theory. Theory-based interventions significantly improved self-management behaviours and self-efficacy.

Background: Platform trials are an efficient trial design which enable testing of multiple interventions simultaneously. They could advance knowledge of treatments for intracerebral haemorrhage (ICH). We aimed to investigate the views of clinicians involved in stroke research on recruitment to a future platform trial for ICH. Methods: Between April and July 2025, we conducted a UK-wide online survey of clinicians actively involved in stroke research using convenience sampling through professional organisations. Participants considered factors related to the consent process and research environment and could provide optional free text responses about additional barriers or facilitators to recruitment. We used descriptive statistics for quantitative data and content analysis for qualitative data. Results: Among 73 respondents, 46 (63%) were female, 36 (50%) were stroke physicians, 24 (34%) nurses, 6 (8%) allied health professionals, and 7 (10%) were in other roles. 36 (49%) had >20 years of clinical experience, 45 (61%) reported spending <10% of their role in research. 66 (91%) thought that a platform trial would be a good option for testing interventions for patients with stroke due to ICH. Across 11 modifiable factors, clinicians most frequently rated perceived importance of the research question as a facilitator of recruitment (94%), while clinician preference for specific treatments was most frequently rated as a barrier (48%). Two themes emerged from free text responses: study design and infrastructure. Regarding study design respondents perceived consent procedures (n=9), study materials (n=8), study procedures (n=8), eligibility assessment (n=6), the research question (n=3) and randomization (n=3) as important for a future platform trial. Regarding infrastructure, emergent factors were staffing (n=17), local research culture and capacity (n=9), research governance and delivery (n=6), and training (n=6). Conclusion: The overwhelming majority of respondents from the UK clinical stroke community supported a platform trial for ICH, although the influence of survey responder bias is unknown.

BackgroundSuccessful recanalisation without functional independence is a frequent phenomenon following endovascular thrombectomy for large vessel occlusion stroke. AimTo demonstrate safety and efficacy of adjunct tirofiban therapy after endovascular thrombectomy in patients with anterior circulation large vessel occlusion stroke achieving successful recanalization defined as modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3. DesignThe study of adjunct tirofiban treatment after successful endovascular thrombectomy recanalisation (ATTRACTION) is a multicenter, prospective, double-blind, randomized trial enrolling 1360 patients in China. Eligible patients will be randomised 1:1 to either the tirofiban or placebo group. OutcomeThe primary efficacy outcomes is assessed as the proportion of participants with a modified Rankin Scale (mRS) score of 0-2 at 90 days, and the primary safety outcome is symptomatic intracranial haemorrhage within 48 hours from randomisation. ConclusionThis study will provide evidence on the efficacy and safety of sequential tirofiban therapy after successful recanalisation in patients with anterior circulation large vessel occlusion stroke. Trial registration numberNCT06265051 WHAT IS ALREADY KNOWN ON THIS TOPICSuccessful recanalization without functional independence is a frequent phenomenon following endovascular thrombectomy and previous small-sample, retrospective studies supported the administration of adjunct tirofiban therapy in patients after endovascular thrombectomy achieving successful recanalization. WHAT THIS STUDY ADDSThe ATTRACTION trial aims to access the efficacy and safety of adjunct tirofiban therapy and the protocol describes the rationale and design of the trial. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYATTRACTION trial will inform whether tirofiban therapy after successful recanalisation by endovascular thrombectomy can improve patient outcomes.

BackgroundDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables non-invasive characterization of carotid atherosclerotic plaque. PurposeTo evaluate the performance and reproducibility of a simplified DCE-MRI quantification method for carotid plaque assessment. MethodsT1-weighted black-blood DCE-MRI of the carotid arteries at 3T was performed at baseline and after six months in patients with mild-to-moderate atherosclerotic lesions in a pilot placebo-controlled randomized trial evaluating the effects of low-dose (0.5mg daily) colchicine therapy on carotid plaque volume. DCE-MRI signal intensity was measured in manually drawn regions of interest in the plaque core, remote non-atherosclerotic vessel wall, and skeletal muscle. Peak signal intensities were normalized to skeletal muscle signal in the same slice. ResultsIn patients (n=28, median [interquartile range] age 72 [64-74] years, 36% female, n=13/15 colchicine/placebo), normalized peak signal intensity was higher in the plaque core than in the remote vessel wall at both baseline (3.5 [2.3-4.1] vs 2.1 [1.7-2.5], p<0.001) and follow-up (3.2 [2.5-4.4] vs 2.0 [1.7-2.5], p<0.001). Measurements did not differ between baseline and follow-up for all patients (0.7{+/-}0.7 for plaque core, 0.6{+/-}0.4 for remote vessel wall, p>0.80 for both) nor between colchicine intervention and placebo control (p>0.35 for either region). ConclusionsNormalised peak signal intensity on DCE-MRI was consistently higher in the carotid plaque core than in the remote vessel wall, showed excellent reproducibility in both regions over six months, and was not altered by colchicine treatment. This simplified, muscle-normalised approach may facilitate future studies exploring DCE-MRI measures potentially related to plaque vulnerability.

Sensory organization at the spinal segment level is commonly inferred from dermatomal maps that assume a fixed correspondence between cutaneous regions and spinal segments. However, based on the complexities of spinal neuroanatomy and neurophysiology, the distribution of sensory signals within the cord may be broader and less segment-specific than dermatomal maps suggest, leaving the segment-level localization of sensory-evoked activity in humans uncertain. Spinal cord functional magnetic resonance imaging (fMRI) is currently the only technique capable of noninvasively mapping sensory activity with high spatial resolution in the human spinal cord. However, its application remains technically challenging and is limited by the uncertainty in segmental localization. In this study, we leveraged recent advancements in spinal cord fMRI, including spinal nerve rootlet-based spatial normalization, to investigate how sensory information is represented and distributed within the human spinal cord during electrocutaneous stimulation of the third digit of the right hand (i.e., C7 dermatome). Forty healthy adults were scanned with electrocutaneous stimulation at four individualized intensities across multiple runs to quantify (i) the rostrocaudal distribution of sensory-evoked activity, (ii) intensity-dependent changes in detectability and localization, and (iii) the effect of normalization strategy on segmental localization. Across participants, stimulation produced activation localized in the lower cervical cord (e.g., C6-C8), with the most consistent segmental localization near C7. Stronger stimulation increased detectability and produced more consistent segmental localization across participants. Importantly, normalization that incorporated nerve rootlet landmarks sharpened localization and improved sensitivity relative to conventional intervertebral disc-based alignment. This highlights the value of functionally relevant anatomical landmarks for group inference in the spinal cord. Responses were strongest in the initial run and attenuated with repetition, suggesting habituation or adaptation that can bias multi-run paradigms if unmodeled. Together, our results define practical acquisition and analysis conditions (e.g., stimulation strength, anatomical alignment strategy, and run structure) under which segment-level spinal sensory responses can be detected, thereby supporting more reliable studies of human spinal cord future basic and translational studies, including pain mechanisms, sensory function, and spinal injury.