Neurocritical Care

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: The Glasgow Coma Scale (GCS) is a universal neurologic severity score in the intensive care unit and is incorporated into APACHE, SOFA, mortality prediction models, ICU benchmarking, and quality metrics. In mechanically ventilated patients, however, the verbal component cannot be assessed. Common conventions, including assigning a normal total GCS of 15 or excluding patients with missing verbal scores, may misclassify the sickest patients as neurologically normal or remove them from analysis. Objective: To quantify non-assessable verbal GCS examinations after acute brain injury and determine how different handling conventions affect severity scoring and mortality-model performance across two independent critical care databases. Materials and Methods: We conducted a retrospective cohort study of adults with acute brain injury during their first ICU stay in MIMIC-IV, with replication in eICU-CRD. A verbal examination was considered non-assessable when documented as No Response-ETT. We measured the burden and determinants of non-assessability, compared the MIMIC-IV derived GCS convention with a component-aware GCS, and evaluated mortality-model handling strategies. Results: Among 14,230 patients, 45.2% had a non-assessable verbal examination, and 47.5% of ventilated patients had no assessable verbal score in the first 24 hours. Non-assessability was strongly associated with mechanical ventilation and mortality. The MIMIC-IV derived GCS assigned a score of 15 to 42.9% of patients and placed 11.6% in the lowest severity category despite eye and motor findings consistent with GCS [≤]9. Complete-case handling excluded 28.5% of patients, who accounted for 50.2% of deaths. Similar distortions were observed in eICU-CRD/APACHE across 171 hospitals. Discussion: Default-to-normal scoring can make severely ill intubated patients appear neurologically normal, while complete-case analysis removes the highest-risk patients. Conclusion: Non-assessable verbal GCS in mechanically ventilated patients should be explicitly flagged and reported in ICU severity scores, risk-adjusted mortality models, and benchmarking systems.

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.

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 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: Stroke remains a leading cause of death and long-term disability worldwide, and a substantial proportion of patients experience incomplete recovery despite modern reperfusion strategies. Minocycline is an inexpensive, widely available agent with anti-inflammatory, anti-apoptotic and matrix metalloproteinase-modulating properties that make it an attractive neuroprotective adjunct in acute ischemic stroke or intracerebral hemorrhage. Despite new evidence for minocycline use, its needed an updated quantitative synthesis focused on clinically meaningful outcomes. Methods: This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of minocycline in adults with AIS and ICH. A total of 1,633 records were screened. A total of 11 studies comprising 2428 patients were included in the review dataset. Outcomes were analyzed including 90-day disability, neurological recovery, recurrent stroke, and composite vascular events (cardiovascular event, non-fatal stroke, and non-fatal MI). Results: Minocycline was associated with better 90-day neurological recovery, with a greater reduction in NIHSS score at 90 days (mean difference [MD] -2.17, 95% CI -2.68 to -1.65, moderate certainty) and lower functional disability at 90 days measured by mean modified Rankin Scale (mRS) score (MD -0.25, 95% CI -0.38 to -0.13, moderate certainty). Categoric functional outcomes also favored minocycline, including mRS 0-1 at 90 days (odds ratio [OR] 1.21, 95% CI 1.02 to 1.45, high certainty), while the effect for mRS 0-2 at 90 days was borderline (OR 1.21, 95% CI 1.00 to 1.47, moderate certainty). No significant difference was observed for stroke recurrence at 90 days (OR 1.13, 95% CI 0.78 to 1.64). Composite vascular events at 90 days also favored minocycline (OR 1.21, 95% CI 1.02 to 1.45). Conclusions: Minocycline appears to be a promising, low-cost adjunctive therapy for acute ischemic stroke and intracerebral hemorrhage with evidence of improved 90-day functional and neurological outcomes. These findings support prioritization of minocycline for confirmatory trials and highlight its relevance in stroke care and clinical practice.

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: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) remains associated with high mortality and severe disability, yet contemporary outcomes may differ substantially from historical estimates. We performed a systematic review and meta-analysis to evaluate long-term outcomes after poor-grade aSAH and assess temporal, geographic, and treatment-related factors associated with prognosis. Methods: PubMed/MEDLINE, Embase, Cochrane Central, Scopus, and Google Scholar were searched from inception through March 2026. Studies enrolling consecutive adults with poor-grade aSAH (World Federation of Neurosurgical Societies grades IV-V, Hunt-Hess grades IV-V, or equivalent) reporting mortality and/or functional outcomes at 3 months were included. To minimize survivorship bias, studies excluding untreated patients or patients dying before aneurysm treatment were excluded. Random-effects meta-analyses of proportions were performed using generalized linear mixed models. Prespecified subgroup analyses and exploratory meta-regression analyses evaluated temporal, geographic, and treatment-related factors associated with outcomes. Results: Forty-two studies including 7,726 patients from 16 countries across 4 continents were included. The pooled favorable functional outcome rate was 27.2% (95% CI, 23.9%-30.8%), whereas pooled overall mortality was 53.3% (95% CI, 49.0%-57.5%). Pre- and post-treatment mortality were 25.9% and 33.9%, respectively. Aneurysm treatment rate was 72.0% (95% CI, 65.6%-77.7%). Favorable outcomes improved over time from 13.5% (95% CI, 7.0%-24.3%) in the 1980s to 33.7% in the 1990s but plateaued thereafter. In exploratory meta-regression analyses, higher aneurysm treatment rates were independently associated with improved favorable functional outcome (0.134 log-odds increase per 10% increase in treatment rate; p = 0.01) and lower mortality (-0.224 log-odds per 10% increase in treatment rate; p < .001). Publication year was associated with lower mortality (p = 0.03) but not favorable outcome. Geographic region, country income group, and the proportion of grade V patients were not independently associated with outcomes. Conclusions: Mortality after poor-grade aSAH remains high, but approximately one-third of patients achieved favorable outcome. Higher aneurysm treatment rates were independently associated with improved functional outcomes and lower mortality.

Abstract: Background: Lacunar stroke is a common and disabling cerebrovascular disease. Small-vessel vasculopathy is thought to be the most common underlying cause, but this has only been identified on histopathology. 7T MRI allows small vessels to be seen in vivo. This study aimed to investigate rates of small vessel vasculopathy in lacunar stroke using 7T MRI. Methods: Patients with lacunar stroke at an Australian tertiary stroke centre were prospectively screened and recruited to the study. Patients underwent 7T MRI with T1, T2, time-of-flight (TOF), diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI) sequences. Images were interpreted by two blinded neuroradiologists. Results: The likely symptomatic perforator could be identified in 16/19 (84%) of cases. Amongst cases where the symptomatic perforator was observed, 14/16 (88%) of the symptomatic perforator vessels had focal stenosis consistent with steno-occlusive vasculopathy. There were 3/19 (16%) of cases with associated large artery vasculopathy. There were 7/16 (44%) cases where an occluded perforator was seen. The majority of patients had at least one vascular risk factor (15/19, 79%) and there were no cases where non-atherosclerotic vasculopathy was suspected. Conclusions: Lacunar stroke is commonly associated with small vessel vasculopathy, likely due to atherosclerosis, which can be identified in vivo with 7T MRI time-of-flight imaging.

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.

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.

Background The ischemic penumbra, a metabolically compromised yet potentially salvageable region surrounding the ischemic core, is a prime target for acute stroke intervention. Yet an objective molecular definition of the penumbra, particularly during the earliest stages of ischemia, remains lacking. Methods and Results We applied principal component analysis (PCA) followed by k-means clustering to high-resolution mass spectrometry imaging data covering multiple metabolic pathways to identify a metabolically defined penumbra in a mouse model of hyperacute stroke (45 min middle cerebral artery occlusion, MCAO). Targeted spatial metabolomic profiling by matrix-assisted laser desorption/ionization (MALDI) and desorption electrospray ionization (DESI) reveals a distinct penumbral metabolic profile, marked by relative preservation of high-energy phosphates, comparable lactate accumulation, and reduced succinate accumulation relative to the core. Spatial transcriptomics revealed selective induction of immediate-early genes, including Npas4, Fos and Junb, within the penumbra. Consistently, imaging mass cytometry shows enrichment of phospho-histone H3 (pHH3) within the penumbra, suggesting a chromatin-associated response potentially linked to immediate-early gene activation. Conclusion Together, these findings provide a multimodal molecular atlas of the hyperacute metabolically defined penumbra and reveal molecular features that facilitates its identification and inform future therapeutic strategies.

Background: Mechanical thrombectomy (MT) is a time-sensitive reperfusion treatment for acute ischemic stroke caused by large-vessel occlusion. Workflow time metrics for MT remain poorly characterized in Indonesia, where stroke burden is substantial. This study describes pre-hospital and in-hospital time-interval metrics for MT across two major tertiary hospitals in Jakarta and evaluates institutional trends over a nine-year period. Methods: We conducted a retrospective descriptive study of consecutive patients undergoing MT at dr. Cipto Mangunkusumo National General Hospital (RSCM) and Prof. Dr. dr. Mahar Mardjono National Brain Center Hospital (RSPON) from 2017 to 2025. Pre-hospital and in-hospital time-interval metrics were reported as median (interquartile range [IQR]) and stratified by institution. Results: Among 330 registered patients, 71 were excluded due to incomplete data, leaving 259 in the final cohort (RSCM n=38; RSPON n=221). The pooled cohort had a mean age of 58.12 {+/-} 11.09 years; 63.71% were male. Hypertension was the most prevalent vascular risk factor (53.67%). Median door-to-CT time was 9 minutes (IQR 18), door-to-decision 101 minutes (IQR 100), and door-to-groin puncture 272 minutes (IQR 152). Total ischemic time (onset-to-groin puncture) was 468 minutes (IQR 294). MT volume increased substantially over the study period, particularly after 2022 at RSPON, which also demonstrated progressive improvement in in-hospital workflow times. RSCM showed increasing delays in later years, consistent with institutional congestion at a general multispecialty center. Conclusions: Early brain imaging was achievable at both centers; however, post-imaging delays particularly in CT-to-groin intervals, represent the dominant in-hospital bottleneck. Future quality-improvement efforts should prioritize decision-making, team mobilization, and pre-hospital coordination to reduce total ischemic time and improve access to reperfusion therapy.

Background: Dizziness is a frequent presenting complaint in the emergency department (ED), prompting extensive diagnostic evaluation. Non-contrast brain computed tomography (CT) is often utilized to rule out serious central pathologies, but its diagnostic yield is debated, leading to concerns about overuse. This study aimed to identify clinical predictors associated with abnormal brain CT findings in patients with acute dizziness to help refine imaging selection criteria. Methods: We conducted a retrospective analysis of 291 consecutive adult patients who presented with new-onset dizziness and underwent a non-contrast brain CT scan at Namazi Hospital, a tertiary referral center, between January 2019 and 2021. Patient data, including demographics, comorbidities, clinical symptoms, and hospital outcomes, were extracted from medical records. Statistical analyses were performed to determine associations between clinical variables and CT findings, with odds ratios (OR) and 95% confidence intervals (CI) calculated. Results: The diagnostic yield of brain CT was low, with a significant majority of scans (72.2%, n=210) revealing no acute pathology. Key clinical factors predicting abnormal CT findings included a history of diabetes mellitus, the presence of ataxic gait, and headache. Conversely, nausea and vomiting were significant predictors of normal findings, being associated with lower odds of central pathology. Conclusion: The diagnostic yield of routine brain CT in patients with acute dizziness is low. However, specific clinical indicators can effectively stratify risk. The presence of focal neurological signs like ataxia, headache, and certain comorbidities such as diabetes should heighten suspicion for central pathology and support the use of neuroimaging. In contrast, isolated vestibular symptoms like nausea and vomiting are associated with a lower probability of abnormal findings. These results could inform the development of clinical decision rules to optimize CT utilization, thereby reducing unnecessary radiation exposure and healthcare costs.

Objective: To quantify the burden, structure, and downstream analytic consequences of "Unable to Assess" (UTA) delirium documentation in the intensive care unit (ICU). Design: Retrospective cross-sectional and repeated-measures study. Setting: A single US academic medical center (Medical Information Mart for Intensive Care IV [MIMIC-IV], 2008-2019). Patients: 72,944 adult ICU stays with at least 1 delirium screen. Interventions: None. Measurements and Main Results: Among 610,632 screens, 130,455 (21.4%; 95% CI, 21.0%-21.8%) were recorded as UTA, exceeding the 119,052 (19.5%) scored positive. The UTA fraction rose from 2.0% at a Richmond Agitation-Sedation Scale (RASS) score of 0 to 97.8% at RASS -4; 22.0% of UTA screens occurred in arousable patients, where UTA was associated with mechanical ventilation (odds ratio [OR], 3.43; 95% CI, 3.17-3.71) and non-English primary language (OR, 3.74; 95% CI, 3.43-4.08). Building the delirium label three ways from the same patients shifted prevalence modestly (32.1% to 30.8%) and prediction (area under the curve, 0.737 to 0.719) but most affected the delirium-mortality association: in a baseline-adjusted model the OR was 4.12 (95% CI, 3.88-4.36) under complete-case handling and fell to 2.16 (95% CI, 2.06-2.27) when UTA was recoded as negative. UTA was recoverable from the observed clinical state (area under the curve, 0.95). Conclusions: In this ICU cohort, Unable to Assess was the most common recorded delirium result other than Negative, exceeding positive screens; recoding it as negative roughly halved the apparent delirium-mortality association by relabeling deeply sedated, high-mortality patients. Delirium datasets should preserve and report UTA, whose concentration among arousable non-English-speaking patients is a measurable equity target.

Background: Net Water Uptake (NWU) is a non-contrast CT (NCCT) biomarker of early cerebral edema in ischemic stroke, calculated from attenuation differences between ischemic and contralateral non-ischemic brain regions. Manual NWU quantification is labor-intensive and prone to inter-operator variability, limiting clinical uptake and research scalability. We developed and internally validated a fully automated NWU evaluation pipeline. Methods: We analyzed 24-hour follow-up NCCT scans from the AcT (Alteplase compared to Tenecteplase) trial. Infarcts were automatically obtained by segmentation framework based on a synchronous image-label diffusion probability model. The images and extracted infarcts were registered to the standard MNI152 space, allowing us to mirror the infarct onto the contralateral hemisphere symmetrically, regardless of size or tilt angle. Subsequently, the mirrored region was inversely transformed to return to its original space. Voxels outside the range of 20-80 Hounsfield Units (HU) were excluded to remove non-parenchymal tissue. Automated NWU was computed as the percentage difference in mean HU between infarct and mirrored contralateral regions. The agreement with manually determined NWU was evaluated using Pearson correlation, mean absolute error (MAE), and Bland-Altman analysis. Results: Of 1,327 patients in the trial, 298 (22.5%) met predefined imaging-quality criteria for the manual validation analysis, including well-aligned raw NCCT scans in the axial plane and clear parenchymal infarct segmentations. Automated 24-hour NWU showed excellent agreement with manual measurements (r = 0.99). Mean absolute error was 0.18% (95% CI: 0.01-0.46). Bland-Altman analysis demonstrated minimal bias (0.09%) and satisfactory limits of agreement (-4.05% to +4.24%). Ninety-nine percent of cases fell within {+/-}5% of the manually determined value. Conclusions: Our automated mirrored segmentation pipeline enables accurate and reproducible NWU quantification from routine 24-hour NCCT scans, matching expert manual measurements with minimal bias.

Background: Remote ischemic perconditioning (RIperC) is a simple, noninvasive neuroprotective strategy based on brief cycles of limb ischemia-reperfusion during cerebral ischemia. REMOTE-CAT suggested a potential functional benefit of prehospital RIperC in acute ischemic stroke. However, its effect on poststroke cognitive outcomes, which may not be fully captured by global disability scales, remains uncertain. Methods: We performed an exploratory cognitive substudy of the multicenter, randomized, double-blind, sham-controlled REMOTE-CAT trial. Patients with suspected acute ischemic stroke within 8 hours, prestroke modified Rankin Scale score <3, and RACE motor score >0 were randomized prehospital to RIperC or sham. RIperC consisted of five 5-minute cuff inflation-deflation cycles during ambulance transfer. At 90 days, patients from one center underwent a standardized neuropsychological battery assessing five cognitive domains. Results: Among 122 patients in the primary analysis, 58 (47.5%) completed neuropsychological assessment: 26 allocated to RIperC and 32 to sham. No statistically significant between-group differences were observed in domain-specific Z scores. Cognitive impairment in at least one domain was numerically less frequent with RIperC than sham (26.9% versus 34.4%). Impairment in more than one domain was also less frequent with RIperC (7.7% versus 21.9%), although the overall distribution of impaired domains did not differ significantly between groups (P=0.244). The largest domain-specific difference was observed for visual memory impairment (3.8% versus 21.9%). Conclusions: In this exploratory substudy, prehospital RIperC did not significantly improve 90-day cognitive outcomes after acute ischemic stroke. Nevertheless, RIperC-treated patients showed numerically favorable trends, particularly in global cognitive burden and visual memory. These hypothesis-generating findings support incorporating standardized cognitive outcomes in future ischemic conditioning trials.

Investigating futile recanalization indicators is very important. Here, we explored plasma endothelial microvesicles (EMVs) as biomarkers for recombinant tissue plasminogen activator (rtPA)-treated acute ischemic stroke. This study prospectively enrolled 195 acute IS patients who underwent rtPA and measured plasma EMVs levels via fluorescence nanoparticle tracking analysis at baseline, 24 h and 90 days. Early futile recanalization was assessed by transcranial Doppler and the National Institutes of Health Stroke Scale. The ROC curves and corresponding areas under the curve (AUC) of the EMVs were analysed. The plasma EMVs levels at baseline and 24 h were positively related to both early and late futile recanalization. In both the late recanalization and futile recanalization groups, the plasma levels of EMVs significantly increased at 24 h but decreased at 90 days. For early futile recanalization, the baseline and 24-h EMVs AUCs were 0.7 and 0.67, respectively. For late futile recanalization, the AUCs for baseline and 24-h EMVs levels were 0.52 and 0.66, respectively. Collectively, the results imply that the plasma level of EMVs could serve as a surrogate indicator of futile recanalization (both early and late) following rtPA administration in acute IS.

Abstract Objective To validate a neonatal seizure detection algorithm that is based on extracted clinical features of the aEEG and CSA on a cohort of cooled neonatal patients with HIE. Methods A seizure detection algorithm was designed using aEEG margin features, CSA features, trained on a public dataset of 79 neonatal EEGs with three supervised machine learning classifiers. It was subsequently tested on an inhouse cohort of 23 neonates with asphyxia whose EEGs were collected during hypothermia therapy. Results The trained Random Forest Classifier, Support Vector Machines and Artificial Neural Network classifiers had an AUC of 0.76, 0.77, and 0.77 and an average accuracy of 0.85, 0.86, and 0.85 respectively. Finally, the average AUC across the 10 seizure patients included was 0.85. Conclusion A neonatal seizure detection algorithm that uses a combination of aEEG and CSA clinical features can capture seizures in HIE patients. Performance across seizure patients is not correlated with seizure duration.

ABSTRACT Objective Delayed cerebral infarction (DCIn) is a severe complication following aneurysmal subarachnoid hemorrhage (aSAH). Previous studies suggest that glycemic variability is associated with DCIn. However, whether diabetes status modifies the relationship between glycemic traits and DCIn remains unknown. Methods Clinical data were collected from aSAH patients admitted to the First Affiliated Hospital of Shantou University Medical College between January 2015 and April 2025. The collected data included demographic characteristics, clinical variables, and glycemic traits. Glycemic traits included mean blood glucose (GLU-M), standard deviation of blood glucose (GLU-SD), coefficient of variation of blood glucose (GLU-CV), variance of blood glucose (GLU-Var), range of blood glucose (GLU-R), average real variability of blood glucose (GLU-ARV), and variability independent of the mean (GLU-VIM). After 1:2 case-control matching, conditional logistic regression models were used to evaluate the associations between glycemic traits and DCIn risk, with stratified analyses performed according to diabetes status. Multiplicative interaction terms were additionally included to assess the potential modifying effect of diabetes status. Results A total of 306 patients with aSAH were included. Among them, 102 developed DCIn cases. For each of these 102 cases, two controls were matched by age ({+/-}5 years), sex and year of admission ({+/-}5 years). In the overall population, higher GLU-M and GLU-ARV were associated with increased DCIn risk, with odds ratios (ORs) per 1-SD increase of 1.62 (95% CI, 1.25-2.11) and 1.63 (95% CI, 1.25-2.11), respectively. Among patients without diabetes (n=266), the associations with DCIn per 1-SD were observed for GLU-M (OR, 2.23; 95% CI, 1.56-3.19), GLU-SD (OR, 1.53; 95% CI, 1.13-2.06), GLU-Var (OR, 1.48; 95% CI, 1.04-2.10), and GLU-ARV (OR, 1.88; 95% CI, 1.38-2.55). No significant associations were observed among patients with diabetes. Significant interactions were observed between diabetes status and GLU-SD and GLU-Var, with P for interaction values of 0.033 and 0.032, respectively. Conclusion Higher mean blood glucose and greater glycemic variability are associated with an increased risk of DCIn in aSAH patients, especially in those without diabetes.