Neurocritical Care

Background: There are currently no therapies proven to accelerate recovery of consciousness for patient with acute severe traumatic brain injury (TBI) in the intensive care unit (ICU). Methods: We performed an open-label, Phase 1 safety and dose-finding study of intravenous methylphenidate (IV MPH) in ICU patients with acute disorders of consciousness (DoC) caused by severe TBI. IV MPH was administered in daily doses of 0.5, 1.0, and 2.0 mg/kg. The primary outcome measure was the number of adverse events (AEs) at each dose. IV MPH pharmacokinetics were measured for 24 hours after each dose. The effect of IV MPH on brain networks was measured using EEG and resting-state functional MRI (rs-fMRI). A pharmacodynamic response was defined by change-point analysis of EEG and rs-fMRI time-series data. Behavioral responses were assessed using the Coma Recovery Scale-Revised (CRS-R). Findings: Between August 24, 2020, and April 1, 2024, we screened 488 ICU patients with TBI and enrolled 9 males (age 23-79 years) with acute traumatic DoC: coma (n=3), vegetative state/unresponsive wakefulness syndrome (n=3), and minimally conscious state (n=3). There were no serious AEs at any dose. Mild-moderate AEs observed at 1.0 mg/kg or 2.0 mg/kg included insomnia, emesis, paroxysmal sympathetic hyperactivity, and transaminitis. Maximum plasma MPH concentration ranged from mean (SD) 312.7 (100.6) ng/mL to 1319.5 (433.8) ng/mL and occurred within a median of 7-14 minutes across doses. Pharmacodynamic responses were observed via EEG in 7/8 participants who received 0.5 mg/kg (1/9 did not undergo EEG), 6/9 who received 1.0 mg/kg, and 4/6 who received 2.0 mg/kg. One of two patients who completed rs-fMRI showed a pharmacodynamic response. CRS-R level of arousal increased within 15 min of the IV MPH bolus for 6/9 participants at 0.5 mg/kg, 5/9 at 1.0 mg/kg, and 0/6 at 2.0 mg/kg. Interpretation: For patients with acute severe TBI, IV MPH may be safe at doses of 0.5-2.0 mg/kg. Pharmacodynamic and behavioral responses suggest that IV MPH promotes recovery of arousal, a prerequisite of consciousness, in the ICU.

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is frequently complicated by delayed cerebral ischaemia (DCI), for which current therapies incompletely target the underlying multifactorial pathophysiology. Transauricular vagus nerve stimulation (taVNS) modulates inflammatory, vasoactive and autonomic pathways and may attenuate secondary brain injury after aSAH. Methods: We conducted a prospective, single-centre, single-blind, randomised, sham-controlled pilot trial in adults within 5 days of aneurysm securing for non-traumatic aSAH. Participants were allocated 1:1 to active taVNS (left tragus) or sham (left earlobe) using a portable device delivered for 45 minutes twice daily over 5 days. Primary outcomes were safety (taVNS-related serious adverse events), acceptability, and compliance; secondary outcomes included inflammatory biomarkers, DCI, in-hospital complications, and functional outcomes to 1 month. Results: Thirty patients were randomised (16 taVNS, 14 sham), with numerically more severe aSAH at baseline in the taVNS arm. No taVNS-related serious adverse events occurred; side effects were generally mild and transient, and over 80% of planned sessions were completed. TaVNS produced greater reductions in serum tumour necrosis factor- and trends towards reductions in interleukin-1{beta} and interleukin-10, with numerically fewer DCI events (6.6% vs 35.7%) and neurological impairments (16.7% vs 53.8%), although functional outcomes were not statistically different at 1 month. Conclusions: Early taVNS after aSAH is safe, acceptable, and feasible in the neurocritical care setting and shows biologically plausible signals warranting evaluation in larger multi-centre trials.

Purpose. Prognostic assessments after acute brain injury are largely narrative, and how prognostic language relates to subsequent care has not been measured at scale. We quantified where it is written and its association with a subsequent code-status limitation. Materials and Methods. Multidatabase observational study of adults with acute brain injury or a related neurologic emergency, using MIMIC-IV (2008-2019; discharge summaries and radiology reports) and a timestamped MIMIC-III cohort (notes and code-status orders). The exposure was documented prognostic language; outcomes were its association with a subsequent full-code-to-limitation transition, note-stream location, and completeness of documented command-following relative to structured Glasgow Coma Scale (GCS) motor scores. Results. Among 31,993 admissions (27,054 patients; median age, 69 years; 54.9% male), prognostic language in the timestamped cohort (MIMIC-III) was associated with a subsequent code-status limitation after multivariable adjustment (adjusted hazard ratio, 4.3; 95% CI, 2.9-6.5; unadjusted 14-day cumulative incidence, 40% vs 8.5%), including the comfort-measures component (3.9), a higher-risk subgroup (4.4), and after acute-physiology adjustment (4.1); the association was concentrated in the first 3 days. Non-prognostic severity language showed no comparable association (hazard ratios, 1.1-1.3). Prognostic language localized almost entirely to the narrative (4.9% of discharge summaries vs 0.015% of radiology reports); command-following was undocumented in 55.7% of summaries, and no final-24-hour GCS motor score was charted in 72.8%. Conclusions. Documented prognostic language after acute brain injury was written in the narrative, not structured fields, and was associated with a subsequent code-status limitation after multivariable adjustment. This observational association cannot establish causation but warrants prospective study.

Introduction: Intracerebral hemorrhage (ICH) carries higher morbidity and mortality than ischemic stroke. Recent studies have demonstrated improved patient outcomes by applying ultra-early bundled interventions including blood pressure management, coagulopathy reversal, and osmotic therapy. Effective strategies to deliver these ultra-early treatment options are currently being explored. On December 19th, 2022, the Mayo Clinic Comprehensive Stroke Center (CSC) launched the "ICH Phases'' communication system to accelerate ICH patient care. Objective: To evaluate adherence to the AHA/ASA guidelines in acute ICH care following the implementation of our novel-tiered paging system. Methods: We retrospectively reviewed patients admitted with spontaneous ICH during 2024 and 2025. We excluded traumatic cases. We extracted clinical data such as time to imaging, documentation of ICH score, blood pressure control, reversal of anticoagulation, venous thrombo-embolism (VTE) prophylaxis and discharge disposition. Results: Among 67 patients, 68.7% underwent CT imaging within 25 minutes. We documented the ICH score within 6 hours in 82.9% of patients. Nearly 94.7% of patients with SBP>140 mm Hg received antihypertensive therapy, yet only 18% reached target BP within 60 minutes. We completed the reversal of anticoagulation within 120 minutes in 75% of patients. VTE prophylaxis was initiated within 24 hours in 91% of patients. Discussion: Our novel system demonstrated adherence to the AHA/ASA guidelines, and time sensitive benchmarks in neuroimaging, reversal of anticoagulation, and VTE prophylaxis. Early BP control remains a challenge, that highlights the discrepancy between guidelines and real-ground implementation. Conclusion: A novel tiered paging system is effective for enhancing early ICH care. Such a holistic system remains critical for sustained improvement in quality of care.

BACKGROUND Children receiving extracorporeal membrane oxygenation (ECMO) are at high risk for focal cerebral injury (FCI). There is emerging evidence that electroencephalography (EEG) may aid FCI detection. The EEG Correlate of Injury to the Nervous System (COIN) index quantifies and displays focal background asymmetries. We evaluated whether COIN is associated with FCI in pediatric ECMO. METHODS Retrospective, cross-sectional study of patients age 28 days to 21 years, on venoarterial ECMO at a tertiary children's hospital, who received EEG monitoring and neuroimaging during ECMO. COIN was calculated from all available EEG data. COIN of 0 implies a symmetric EEG and negative COIN values are observed with FCI. Median COIN values near FCI recognition time were compared to median COIN values from randomly selected control EEG batches using logistic regression. A receiver operator characteristic curve was used to identify multilevel FCI test ranges. Likelihood ratios were calculated to estimate the posttest FCI probability for each COIN range. RESULTS During the 8-year study period (2015-2023), 33 of 142 ECMO runs met study criteria for COIN analysis. Twelve patients (36%) had FCI. The COIN cutoff of -13.3 had 92% sensitivity and 67% specificity for FCI. The COIN cutoff of -27.7 had 67% sensitivity and 90% specificity. Likelihood ratios were 0.13 for COIN (0 to -13.3), 1.1 for COIN (-13.3 to -27.7), and 7.0 for COIN (< -27.7). Posttest probability was 0.02, 0.13, 0.49 in each respective range. CONCLUSION FCI on ECMO is associated with COIN-measured EEG asymmetry. COIN may support FCI risk-stratification during ECMO.

Background Spontaneous intracerebral hemorrhage (ICH) is the most devastating type of stroke but lacks the established time-critical treatment guidelines available for acute ischemic stroke. This study investigated the impact of Code Stroke activation and warfarin use on anticoagulation reversal times to identify opportunities for quality improvement. Methods We retrospectively assessed patients with anticoagulation-associated ICH admitted to our medical center between January 1, 2020, and December 31, 2025. Patients with warfarin- or direct oral anticoagulant (DOAC)-associated ICH were identified from our ICH clinical trial screening log, Vizient, and AHA's Get With The Guidelines-Stroke registry. Code Stroke activation, warfarin or DOAC use, anticoagulation reversal times, causes of delay, and clinical outcomes at hospital discharge were analyzed. Results Of 892 ICH admissions, 50 patients had confirmed anticoagulation-associated ICH. Among those who underwent reversed at our center (n=34), Code Stroke activation (n=24) significantly reduced door-to-CT time (16.5 [12.8-22.0] vs 172.5 [49.0-261.5] minutes, p <0.001), reversal agent order-to-needle time (37.5 [24.7-56.9] vs 57.0 [39.0-85.0] minutes, p <0.001), and door-to-treatment (DTT) time (64 [48-98] vs 277 [159-305] minutes, p <0.001) compared to non-activation (n=10). Conversely, warfarin use was associated with higher international normalized ratios (INR) (2.7 [2.2-3.6] vs 1.3 [1.2-1.9], p =0.003) and significantly longer DTT time (95 [51-108] vs 64 [48-77] minutes, p =0.007). Primary DTT delays stemmed from the absence of a time-critical treatment protocol, weight-based dosing for 4F-PCC, waiting for INR results, and a lack of Code Stroke activation for patients with mild symptoms, trauma or unexplained unresponsiveness. Conclusions Our findings suggest that Code Stroke activation for all suspected cases of ICH, a time-critical emergency department algorithm targeting a DTT time of less than 60 minutes, and immediate anticoagulation reversal with fixed-dose 4F-PCC without waiting for INR results may optimize the acute management of anticoagulation-associated ICH.

Background and Purpose-Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating cerebrovascular event, with delayed cerebral ischemia (DCI) representing its most feared complication. High-altitude environments induce profound cerebrovascular adaptations, yet no study has systematically examined aSAH outcomes in chronically hypoxic populations. We characterized clinical features and identified DCI predictors among aSAH patients on the Tibetan Plateau. Methods-This single-center retrospective cohort included 256 consecutive aSAH patients admitted at a tertiary neurosurgical center in Tibet (altitude 2,330-4,920 m) between 2013 and 2015. The primary outcome was DCI per consensus criteria. Multivariable logistic regression identified independent predictors; receiver operating characteristic analysis evaluated model performance. Altitude and hemoglobin were specifically evaluated as altitude-related risk factors. Results-DCI occurred in 26 patients (10.2%). In-hospital mortality was 1.6%. Most patients presented with good-grade aSAH (Hunt-Hess I-II, 73.0%; Fisher I-II, 73.1%). On multivariable analysis, only Fisher grade independently predicted DCI (odds ratio, 3.63 [95% CI, 1.14-11.52]; P=0.029). Neither altitude (P=0.697) nor hemoglobin concentration (P=0.858) was associated with DCI risk. The predictive model achieved an area under the curve of 0.812. At 1-year follow-up, 77.8% achieved favorable functional outcomes (modified Rankin Scale 0-2). Conclusions-Fisher grade is the sole independent predictor of DCI in high-altitude aSAH patients, while chronic hypoxia and compensatory hemoglobin elevation do not significantly modify DCI risk. Established sea-level prognostic frameworks remain valid in high-altitude settings, supporting their continued use for clinical risk stratification. Keywords: aneurysmal subarachnoid hemorrhage; high altitude; delayed cerebral ischemia; Fisher grade; Tibetan Plateau; prognosis

Background: Unruptured intracranial aneurysms (UIAs) are increasingly identified incidentally, and management balances rupture risk against treatment risk. UIA diagnosis has been linked to psychological distress, but psychotropic medication initiation after UIA discovery has not been compared across the full UIA management spectrum. Methods: We conducted a retrospective cohort study using IBM MarketScan claims (CCAE, MDCD, and MDCR; 2009-2023) among adults with a UIA diagnosis, continuous enrollment for 365 days before and after the index date, and no SAH/rupture on or before the index date. We compared the prevalence of 6 mental-health diagnoses before versus after UIA discovery and used adjusted logistic regression to examine psychotropic medication initiation within 365 days by management strategy (untreated observation as the reference). Results: Among 54,945 patients (untreated, 78.5%; endovascular, 11.3%; clipping, 3.0%; other/uncertain, 7.2%), prevalence of every mental-health diagnosis was higher after UIA discovery, most for depression (+4.6 percentage points) and anxiety (+4.5 points). Medication initiation was most common for benzodiazepines (8.7%). Endovascular treatment was associated with higher adjusted odds of benzodiazepine (aOR, 1.21), SSRI (aOR, 1.20), and sedative-hypnotic (aOR, 1.25) initiation.Surgical clipping demonstrated the broadest association, with higher odds across 5 of 6 classes, including benzodiazepines (aOR, 1.71) and sedative-hypnotics (aOR, 1.86). Benzodiazepines had the lowest 1-year persistence (10.5%) despite being the most commonly initiated class. Findings were consistent across sensitivity analyses, with the exception of the increase in panic disorder, which was no longer observed after applying a 30-day post-index lag. Conclusions: Mental-health diagnoses and psychotropic medication initiation increased after UIA discovery, and medication initiation was most pronounced among patients treated with surgical clipping. These findings support psychological assessment as part of aneurysm management regardless of strategy.

Background: aneurysmal subarachnoid hemorrhage (aSAH) is neurological emergency associated with substantial mortality and disability. Current grading systems such as the modified Fisher Scale (mFS) and World Federation of Neurological Societies (WFNS) score, rely on semiquantitative and examination based assessments. Hence, they demonstrate limited predictive precision. The enhanced subarachnoid hemorrhage (eSAH) score is a simplified quantitative model integrating age, Glasgow Coma Scale (GCS), and cisternal subarachnoid hemorrhage volume (SAHV) to predict clinical outcomes after aSAH. Methods: We performed a retrospective multicenter cohort study that included 1088 patients across three tertiary-care centers the United States. Predictive performance for unfavorable functional outcome, in-hospital mortality and delayed cerebral ischemia (DCI) was evaluated using receiver operating characteristic (ROC) analysis and area under the curve (AUC). Comparative analyses were performed and compared to the WFNS and mFS grading systems. Results: the eSAH score demonstrated excellent discrimination for unfavorable functional outcome at discharge ( AUC 0.89 ) and in-hospital mortality (AUC 0.87). The DCI subscore demonstrated good discriminatory performance for predicting DCI (AUC 0.77). Compared with conventional grading systems, this was superior to both the WFNS (AUC 0.75) and the mFS ( AUC 0.70). increasing eSAH scores were additionally associated with progressively higher rates of mortality and unfavorable functional outcomes. Conclusion: the eSAH score demonstrates strong external validity, reproducibility and superior predictive performance compared with conventional grading systems in a large multicenter cohort. These findings support the clinical utility of quantitative hemorrhage burden integration for early risk stratification in patients with aSAH.

Background: Cerebral vasospasm is a frequent complication after aneurysmal subarachnoid hemorrhage (aSAH) and is associated with delayed cerebral ischemia (DCI) and unfavorable outcome. While CTA-based vasospasm grading is frequently used, its relationship with actual cerebral perfusion remains incompletely understood. This study investigates the association between vasospasm severity and distribution and territorial perfusion deficits. Methods: In this retrospective single-center study, 513 CT examinations (CTA and CT perfusion) from 194 patients with aSAH were analyzed. Vasospasm was graded per vessel segment using the CTA Vasospasm Score, and perfusion deficits were assigned to corresponding vascular territories (left/right anterior circulation, posterior circulation). Vasospasm distribution was further classified by severity and multifocality. Associations between vasospasm score and perfusion deficits were assessed using a generalized linear mixed model with binomial distribution, adjusting for Hunt & Hess grade, modified Fisher score, and days since hemorrhage. Results: Vasospasm was detected in 79.3% of examinations, and a perfusion deficit in at least one territory was present in 62.6%. The proportion of perfusion deficits increased progressively with both vasospasm severity and multifocality, ranging from 21.7-25.0% in the absence of vasospasm to 81.2-82.2% in severe multifocal vasospasm. The CTA Vasospasm Score was significantly associated with perfusion deficits in all territories (OR 1.36-1.50), with stronger associations in the anterior than posterior circulation. Conclusion: Vasospasm severity and distribution are strongly associated with perfusion deficits, supporting a continuum model of ischemic risk. However, the substantial proportion of perfusion deficits occurring independent of vasospasm suggests additional microcirculatory mechanisms not captured by CTA. CT perfusion should be considered complementary to CTA, particularly in clinically deteriorating or non-assessable patients.

Background: Recent AHA guidelines recommend the use of IV Tenecteplase (TNK) in adult stroke patients, but there is minimal safety and dosing data on TNK in pediatric patients. We performed a safety surveillance study aiming to evaluate risk of symptomatic intracranial hemorrhage (ICH) in children who received TNK for suspected acute ischemic stroke (AIS). Methods: This was a prospective observational cohort surveillance study analyzing responses from a monthly email survey sent to members of two large international pediatric stroke and neurocritical care research consortia querying recent use of TNK in children. Limited demographic, clinical, and outcome data were collected. A Bayesian beta-binomial model for risk of symptomatic ICH with IV TNK was fit using a prior distribution based on the risk level in adults. Results: Between February 2023-June 2026, 44 children received TNK for suspected AIS. Most patients (n=37, 84.1%) were adolescents; no children under 5 received TNK. Twelve patients (27.3%) were ultimately diagnosed with a stroke mimic. Symptomatic ICH was not reported in any children who received IV TNK; 3 had asymptomatic ICH on follow-up imaging. One patient received intra-arterial TNK and experienced symptomatic ICH. No other major bleeding events were reported. Conclusions: IV TNK is being administered to pediatric patients with suspected stroke in clinical practice, and may be safe in older children with AIS. Rigorous prospective studies are needed to better assess risk and outcomes in this unique population.

BackgroundGlobal cerebral ischemia initiates a cascade of pathophysiological changes that progressively impair subsequent perfusion of brain tissue. Some authors have proposed that adequate cerebral perfusion becomes impossible after approximately 10-30 minutes of global ischemia. However, the extant evidence base for this threshold and its variation across studies have not yet been systematically examined. ObjectiveTo synthesize the literature on post-ischemic cerebral perfusion success as a function of ischemia duration. MethodsWe searched PubMed (February 11, 2026) for studies of global cerebral ischemia in animal or human models that reported quantitative or categorical measures of perfusion quality. Eligible studies included those assessing perfusion via restoration of blood flow, via external perfusion of non-blood solutions, and/or via tracer injection following reperfusion. Studies of focal ischemia were excluded. Data extracted included species, ischemia duration, temperature during ischemia, ischemia model, perfusate type, and perfusion quality assessment method. The perfusion quality outcome was operationalized as either the average percentage of brain tissue perfused or the percentage of brains in a group that were adequately perfused. Study quality was assessed using a custom domain-specific checklist. The review protocol was preregistered on the Open Science Framework (https://osf.io/2qm3w). ResultsWe included 60 studies with 192 study arms reporting on the perfusion of the brains of rabbits, rats, pigs, dogs, cats, and humans. Studies differed in the model of ischemia, the perfusate, the perfusion parameters, the quality assessment methods, and other factors. Longer ischemia was associated with lower perfusion quality, but the relationship appeared to be a gradual decline rather than a sharp threshold. Additionally, the variability across studies was large, and some studies have found that at least partial perfusion is possible after longer periods. Within-study dose-response curves were more consistent than the pooled cross-study pattern. ConclusionsHow long the brain remains perfusable after circulatory arrest has not yet been definitively established. On average, perfusion quality clearly declines rapidly as the duration of global cerebral ischemia increases. However, some studies, often using interventions such as hypothermia or vasopressors, have reported at least partial perfusion of the brain even after 30 or 60 minutes of ischemia. Moreover, at least partial perfusion has been reported in human brain banking studies after postmortem intervals of several hours or days in some donors. Limitations of this review include substantial heterogeneity in study methods and outcome measures, which precluded formal meta-analysis. Future research may benefit from more thorough and precise measures of perfusion quality.

Background: Serial glial fibrillary acidic protein (GFAP) trajectories have become an important framework for contextualizing evolving secondary-injury pathophysiology after moderate-to-severe traumatic brain injury (msTBI). However, total GFAP pools release and clearance signals that may be less useful for longitudinal bedside decisions than a proteoform-resolved assay. We compared total GFAP with neoGFAP, defined here as calpain-generated GFAP proteoforms intended to index active astroglial proteolysis during the subacute phase. Methods: We analyzed 651 serial serum samples from 95 msTBI patients from a previously described single-site cohort. Total GFAP and neoGFAP were measured on the same MSD platform from 6 to 240 hours after injury. Early (6 to 72 h) and late (96 to 240 h) windows, data-derived tertiles, and serial trajectory summaries were calculated directly from serial samples. Models were benchmarked against age plus admission post-resuscitation Glasgow Coma Scale (GCS) and the admission IMPACT extended risk score using five-fold stratified cross-validation. Outcomes were unfavorable outcome (GOSE 1 to 4), less-than-good recovery (GOSE 1 to 6), Disability Rating Scale (DRS) [&ge;]15, mortality, and neuroimaging worsening at 6 months. Results: The cohort contributed 95 serial biomarker profiles, with 90 participants evaluable for 6-month GOSE and 89 for DRS. Unfavorable outcome occurred in 57/90 (63.3%), and less-than-good recovery in 79/90 (87.8%). For unfavorable outcome, IMPACT plus early neoGFAP reached AUROC 0.85 versus 0.84 for IMPACT plus early total GFAP and 0.81 for IMPACT alone. For less-than-good recovery, IMPACT plus late neoGFAP achieved AUROC 0.90 versus 0.84 for late total GFAP and 0.82 for IMPACT alone. Secondary analyses for DRS, mortality, and neuroimaging worsening showed smaller differences. Conclusions: In this retrospective analysis, neoGFAP provided clearer incremental value than total GFAP for recovery-oriented monitoring, especially when late-window reassessment of patients who remained at risk for less-than-good recovery was required. Results support prospective testing of neoGFAP as a pathophysiology-informed adjunct to serial bedside decision making, repeat-assessment thresholds, and recovery stratification.

Background: Early risk stratification in traumatic brain injury (TBI) is essential for timely triage, resource allocation, and clinical decision-making within the critical first hours of admission. This study aimed to compare the predictive performance of five established clinical scoring systems includes the Glasgow Coma Scale (GCS), Revised Trauma Score (RTS), Mechanism, GCS, Age, and Arterial Pressure (MGAP) score, Modified Early Warning Score (MEWS), and Rapid Emergency Medicine Score (REMS) for early mortality prediction in patients with blunt TBI. Methods: This single-center retrospective observational cohort study evaluated 444 patients aged 18 to 89 years with blunt TBI admitted to the intensive care unit of a tertiary trauma center in Tehran, Iran, between March 2022 and March 2025. The primary outcome was early mortality, defined as death within 24 hours of admission. Discriminative performance was assessed using the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals (CI) derived via bootstrap resampling (1,000 iterations). Pairwise comparisons of AUCs were conducted, and optimal diagnostic cutoffs were identified using the Youden Index. Results: Within 24 hours of hospital admission, early mortality occurred in 97 patients (21.8%), while 347 patients (78.2%) survived. The trauma-specific and neurological scoring systems demonstrated the highest discriminative capacities: RTS achieved the highest accuracy (AUC = 0.676, 95% CI: 0.617-0.737), followed closely by GCS (AUC = 0.669, 95% CI: 0.608-0.727) and MGAP (AUC = 0.657, 95% CI: 0.594-0.724). General physiological scores exhibited lower performance, with MEWS achieving an AUC of 0.651 (95% CI: 0.595-0.707) and REMS demonstrating the lowest discriminative ability (AUC = 0.601, 95% CI: 0.538-0.659). Pairwise analysis confirmed that RTS GCS and MGAP significantly outperformed REMS, though no statistically significant differences were observed among RTS, GCS, and MGAP themselves. All evaluated systems demonstrated only modest overall predictive performance (AUC < 0.70). Conclusion: Trauma-specific and neurologically oriented scoring systems (RTS, GCS, and MGAP) provide superior and comparable prognostic accuracy for 24-hour mortality in blunt TBI compared to general emergency scores like REMS. However, the absolute predictive power of all evaluated models remains modest. Traditional systems relying on static admission variables fail to capture the dynamic, multifactorial nature of secondary brain injury, highlighting the critical need for multidimensional prognostic tools incorporating physiological time-series data or machine learning algorithms.

Objective: Shunt-dependent hydrocephalus is a common and costly complication of aneurysmal subarachnoid hemorrhage (aSAH), affecting up to 28% of survivors. Existing prediction tools, including the Chronic Hydrocephalus Ensuing from SAH Score (CHESS), have limited discriminative accuracy. We developed the CHECKMATE score, a clinically practical tool to improve prediction of ventriculoperitoneal shunt dependency after aSAH. Methods: In this multicenter retrospective cohort of 486 patients with aSAH from Mayo Clinic (January 1, 2006-December 31, 2021), we used multivariable logistic regression and machine learning to identify independent predictors of ventriculoperitoneal shunt placement. The CHECKMATE score was derived from 5 weighted variables: symptomatic hydrocephalus (10 points), intraventricular hemorrhage (5 points), SAH volume greater than 10 mL (3 points), neutrophil-to-lymphocyte ratio greater than 12 (2 points), and 10-year incremental age thresholds starting at older than 60 years (1 point each). Results: Of 486 patients (mean age, 56.3 years; 64.6% female), 137 (28.2%) required ventriculoperitoneal shunt placement. The CHECKMATE score achieved an area under the curve of 0.808 (compared to 0.737 for CHESS), with a sensitivity of 0.85, specificity of 0.67, and negative predictive value of 0.92 at the optimal cutoff of 14 points. Conclusions: The CHECKMATE score outperforms CHESS for predicting ventriculoperitoneal shunt dependency after aSAH and is easily used at the bedside. Its high negative predictive value helps identify low-risk patients who may benefit from earlier external ventricular drain weaning and shorter hospital stays.

Background Machine learning (ML) models for traumatic brain injury (TBI) prediction increasingly demand extensive data, computational resources, and energy consumption, yet simpler models may offer comparable clinical benefit with lower barriers to deployment. This study compares predictive performance, computational efficiency, carbon footprint, and real-world feasibility of resource-efficient ("pauci-parameter") versus data-intensive ("multiparameter") ML models for predicting TBI patient care pathways and outcomes. Methods External validation study in a level 1 trauma center (n=534 adult TBI patients with GCS<9 and/or intracranial injuries). Seven models tested: two pauci-parameter models using only routine prehospital variables (PREHOSP, 15 variables) or CT image analysis (CT-TIQUA), and five multiparameter models integrating clinical and imaging data. Primary outcome: positive likelihood ratio for predicting neurocritical care intensity, mortality (7/30-day, 6-month), and functional outcome (Glasgow Outcome Scale Extended). Secondary outcomes: computation time, carbon footprint, clinical implementability. Results Multiparameter models showed superior performance but did not consistently translate to better clinical utility. PREHOSP (pauci-parameter) showed comparable performance to complex models for most outcomes. The best-performing multiparameter model (MULTI-PRE) required 100-fold longer inference time and 10-fold higher carbon emissions per prediction versus simple models, while net clinical benefit was nearly identical (0.06 vs 0.05). Models using only prehospital data demonstrated greater generalizability and lower deployment barriers. Interpretation Computational complexity and resource intensity should factor equally with predictive performance in clinical AI deployment decisions. For sustainable digital health implementation--especially in resource-limited settings--simpler models with comparable clinical benefit may enable broader access while reducing environmental and financial costs.

Endovascular thrombectomy (EVT) improves outcomes in acute ischemic stroke caused by large vessel occlusion. Despite successful recanalization, early neurological deterioration (END) remains frequent and predicts poor outcomes. Disturbances in cerebral autoregulation may contribute to END, yet reliable bedside predictors are limited. Transcranial Doppler (TCD) provides noninvasive bedside assessment of cerebral blood flow velocities and may identify hemodynamic patterns associated with post-EVT deterioration. PRECISE-TCD is a prospective, single-center observational study enrolling 180-300 patients undergoing EVT for anterior circulation large vessel occlusion at a tertiary academic medical center. TCD examinations will be performed as soon as feasible after EVT, daily through 72 hours, and near END events. Hemodynamic parameters including peak systolic velocity (PSV), end-diastolic velocity (EDV), mean flow velocity (MFV), and pulsatility index (PI) will be measured in bilateral MCA, ACA, PCA, carotid siphon, vertebrobasilar, and ophthalmic artery territories. The primary outcome is the association between TCD-derived parameters and END within 72 hours, defined as an increase of [&ge;]4 points in total NIHSS score, an increase of [&ge;]1 point in NIHSS subcategory 1a, radiologic evidence of intracranial hemorrhage within 72 hours, or any neurological change prompting emergent head CT at clinician discretion. Secondary outcomes include NIHSS at 24 hours and discharge, discharge disposition, and modified Rankin Scale (mRS) at 90 {+/-} 10 days after hospital discharge. Joint models for longitudinal and time-to-event data will determine the association between TCD parameter trajectories and time to END. Unsupervised clustering will identify TCD-based hemodynamic phenotypes using vessel velocities, pulsatility indices, hemispheric asymmetry measures, collateral flow, and temporal trajectory patterns. We hypothesize that abnormal post-EVT hemodynamic phenotypes will correlate with END and hemorrhagic transformation. Identifying such signatures may support development of TCD-guided, individualized blood pressure strategies to reduce secondary injury after reperfusion and inform future interventional trials. The study is registered at ClinicalTrials.gov (NCT07013396).

Background: Evidence regarding delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) remains sparse. We aimed to identify its predictors and occurrence and evaluate its role in ischemic stroke and functional outcome under treatment with interventional rescue therapy (IRT). Methods: This retrospective single-center study included 628 adults with aSAH from 2014?2023. The primary endpoint was occurrence of refractory DCI (= refractory despite induced hypertension) treated with at least one IRT. Multivariable models evaluated refractory DCI, new ischemic stroke, and poor functional outcome (mRS 3?6) at 6?12 months. Results: Among 628 included patients, 61 who died within 3 days were excluded from DCI analysis; 166/567 (29%) developed refractory DCI. Younger age (OR = 0.98; P<0.001), female sex (OR = 0.57; P=0.007), and higher WFNS grade (OR = 1.18; P=0.011) were independently associated with refractory DCI. Earlier first IRT was associated with longer DCI duration (IRR = 0.88; P<0.001) and more required IRTs (IRR = 0.91; P<0.001). IRT was performed later than day 14 in 29/166 patients (17.5%); none was older than 70 years. Refractory DCI was associated with new ischemic stroke (OR = 4.68; P<0.001) and poor functional outcome (OR = 2.37; P<0.001); earlier first IRT was associated with poor outcome within the refractory DCI subgroup (OR = 0.86; P=0.03). Outcomes after 1?2 IRTs did not differ from those without refractory DCI (P=0.4), whereas ?3 IRTs were associated with poor outcome (P=0.04). Conclusions: Refractory DCI affected 29% of aSAH patients, predominantly younger women and patients with poorer initial neurological status, and extended beyond day 14 in nearly 20% of affected patients, none of whom was older than 70 years. Refractory DCI and earlier onset were associated with poorer radiological and functional outcomes. The absence of a detected outcome difference after 1?2 IRTs suggests that favorable outcomes may remain achievable despite refractory DCI.

Objective: Outcome after surgical hematoma evacuation for intracerebral hemorrhage (ICH) depends on hematoma location. As corticospinal tract (CST) integrity affects motor recovery after stroke, we hypothesized that CST integrity drives heterogeneity in surgical outcomes and investigated this in a secondary analysis of MISTIE-III participants. Methods: Risk of CST injury was categorized into four levels, based on the interaction between the CST, the hematoma, and perihematomal edema (PHE) on automatically segmented stability CT: no risk, PHE infiltration, hematoma infiltration, and complete interruption of the CST. Associations with outcome were tested using multivariable linear regression for motor National Institutes of Health Stroke Scale (NIHSS) at day 180 and ordinal regression for modified Rankin Scale (mRS) at day 365, introducing an interaction term between CST risk and treatment group. Results: Day 180 motor NIHSS was significantly lower for 'no risk' ({beta}:-3.77, [95% confidence interval [CI]: -5.8 to -1.70], p=0.0003) and 'PHE infiltration' ({beta}:-2.3, [95%CI: -3.5 to -1.1]; p=0.0002) vs. 'complete interruption'. Surgery was associated with lower Day 180 motor NIHSS in participants with hematoma infiltration ({beta}:-2.07, [95%CI: -3.8 to -0.4], p=0.016). Compared to complete interruption, 'no risk' (adjusted odds ratio [aOR]:0.27, [95%CI: 0.10 to 0.74], p=0.01) and 'PHE infiltration' (aOR:0.41, [95%CI: 0.23 to 0.74]; p=0.003) were associated with lower odds of unfavorable day 365 mRS. Surgery was associated with lower mRS in participants with no risk (aOR:0.23, [95%CI: 0.05 to 0.97, p=0.045). Interpretation: Increasing CST risk is associated with worse motor recovery (day 180) and disability (day 365). CST risk modifies the effect of the MISTIE-III procedure on motor recovery and disability.

Background and Purpose- Prehospital large-vessel occlusion (LVO) scales identify severe stroke syndromes but may not distinguish LVO from intracerebral hemorrhage (ICH). We aimed to prospectively validate the PreICH scale, with the primary diagnostic objective of differentiating ICH from confirmed LVO, and to explore whether additional hemorrhage-oriented variables could refine its performance. Methods- We conducted a prospective observational study of consecutive stroke-code activations evaluated before neuroimaging by a vascular neurologist. PreICH was calculated prospectively. Patients with calculable PreICH and valid final diagnosis were included. The primary diagnostic cohort comprised confirmed LVO and ICH. Secondary cohorts included ischemic stroke versus ICH and the overall stroke-code cohort, including stroke mimics. Multivariable NIHSS-adjusted models identified variables associated with ICH. A modified PreICH score (mPreICH) was derived post hoc and evaluated as exploratory apparent performance. Results- Among 1012 screened activations, 982 patients were analyzed: 597 ischemic strokes, 91 ICH, and 294 stroke mimics. The LVO-versus-ICH cohort included 144 LVO and 91 ICH. NIHSS and RACE were higher in ICH than in ischemic stroke, but did not differ between LVO and ICH (NIHSS, 13 [IQR, 7-20] versus 15 [5-23], P=0.300; RACE, 5 [2-8] versus 6 [2-8], P=0.435). In the LVO-versus-ICH cohort, PreICH showed an AUC of 0.758 (95% CI, 0.696-0.820), whereas RACE did not discriminate LVO from ICH (AUC, 0.530 [95% CI, 0.453-0.607]). The exploratory mPreICH showed apparent AUCs of 0.835 (95% CI, 0.785-0.884) for ischemic stroke versus ICH and 0.798 (95% CI, 0.740-0.856) for LVO versus ICH. Conclusions- In this prospective stroke-code cohort, severity-based scales distinguished ICH from the overall ischemic stroke population but showed limited ability to differentiate LVO from ICH. An exploratory modified PreICH scale incorporating additional hemorrhage-oriented variables improved apparent discriminative performance, including in the LVO-versus-ICH setting. External validation is required before potential implementation in prehospital decision-making.