Neurocritical Care

The SAFE MRI ECMO (NCT05469139) study established the safety of ultra-low-field 64mT MRI in patients receiving extracorporeal membrane oxygenation (ECMO) in the setting of intensive care and demonstrated that these images were highly sensitive in detecting acquired brain injuries. This retrospective analysis of prospectively collected observational data sought to expand on these findings in light of the crucial need for neurological monitoring while patients receive ECMO by evaluating the feasibility of volumetric analyses derived from ultra-low-field MR images. T2-weighted scans from thirty patients who received ultra-low-field MRI while undergoing ECMO at Johns Hopkins Hospital were analyzed using a volumetric pipeline to determine whole brain volume and volumes of total grey matter, total white matter, subcortical grey matter, ventricles, left hemisphere, right hemisphere, telencephalon, left and right lateral ventricles, the total intracranial volume, and the cerebellum. Segmented brain volumes in patients undergoing ECMO were comparable to measurements obtained using conventional field and ultra-low-field MRI in the absence of ECMO instrumentation. The subgroup analysis demonstrated subtle volumetric differences between patients supported with venoarterial ECMO and those receiving venovenous ECMO. These data provide the first evidence that ultra-low-field MRI provides volumetric measurements comparable to conventional field-strength MRI, even in the presence of ECMO circuitry, supporting its feasibility for neuroimaging in critically ill patients.

BackgroundHyperglycemia after intracerebral hemorrhage (ICH) may be associated with worse outcomes. In this study, we evaluated the association of early post-ICH glucose trajectories and clinical outcomes. MethodsWe performed a secondary analysis of the ATACH-2 trial dataset. Hyperglycemia was defined as a blood glucose of [&ge;]140 mg/dl. Glucose levels at 0h, 24h, 48h, and 72h were analyzed using a linear mixed effects model, with fixed effects for time and random intercept/slopes. Patient-specific estimates were used to predict glucose values at 0h and 72h, informed by all four timepoints, to classify patients into the following glycemic trajectory groups: (1) early hyperglycemia, (2) late hyperglycemia, (3) persistent hyperglycemia, and (4) persistent normoglycemia. Outcomes were compared using univariate analysis and log-rank test survival analysis. Good outcomes were defined as a modified Rankin Score of 0 to 2. The association between glycemic trajectories and functional outcomes was tested using logistic regression models adjusted for patient demographics and clinical variables. ResultsOf 1000 patients (median age 62 [IQR 52-71]; 38% female) in the study, 81 (8.1%) had early hyperglycemia, 59 (5.9%) late hyperglycemia, 225 (22.5%) persistent hyperglycemia, and 635 (63.5%) persistent normoglycemia. On univariate analysis, 45.8% of patients with persistent normoglycemia had favorable 90-day functional outcomes compared to 30.9% in early, 30.5% in late, and 32.0% in persistent hyperglycemia patients (p<0.001). The late hyperglycemia patients had the highest rate of hematoma expansion (35.3%, p=0.029) and the lowest Kaplan Meier-estimated survival (86%, p=0.015). In adjusted multivariable regression models, early hyperglycemia was significantly associated with a poor functional outcome (OR 2.27, 95% CI 1.10-4.68, p=0.026). ConclusionEarly hyperglycemia was associated with worse functional outcomes, while late and persistent hyperglycemia were associated with worse survival rates. These findings suggest that glycemic trajectories may affect or predict prognosis. This highlights the importance of continuous glucose monitoring and glycemic control strategies after ICH.

Background: The Functional Outcome in Patients with Primary Intracerebral Hemorrhage (FUNC) score was initially validated for prediction of functional independence on the Glasgow Outcome Scale (GOS) 90 days after intracerebral hemorrhage (ICH), but recovery often extends beyond three months. Aims: Our objective was to extend the FUNC score for prediction of 12-month functional independence to strengthen its utility for family counseling and research methodology. Methods: We conducted a single-center prospective cohort study enrolling adult patients with primary ICH between February 2009 and January 2018. We calculated FUNC scores at admission and assessed GOS 12 months after ICH. The primary outcome was 12-month functional independence, defined as a GOS score [&ge;]4. We calculated the area under the receiver operating characteristic curve (AUC) of the FUNC score using logistic regression, handling missing GOS with multiple imputation by chained equations. We evaluated score calibration using a calibration curve and the Brier score, and we assessed clinical utility using decision curve analysis. We explored the statistical efficiency gains of using FUNC-based sliding dichotomy thresholds for favorable outcome definitions by running simulations of a clinical trial with 1:1 randomization. We ran 5000 simulations for each sample size (100 to 1000, in increments of 10) and treatment effect (odds ratio of 1.5, 2.0 and 2.5) combination and calculated efficiency gains for each respective treatment effect as the percentage reduction in sample size required to have 80% power using sliding versus fixed dichotomy thresholds. Results: A total of 535 patients were included (median [IQR] age 68 [54-79], 237 [44%] female, median [IQR] NIHSS 16 [6-25], median [IQR] FUNC 8 [6-9]). Overall, 99 of 445 (22%) patients with known 12-month GOS achieved functional independence. The FUNC score had an AUC of 0.79 (95%-CI: 0.75-0.84) for 12-month functional independence. The calibration plot was reasonable, with modest evidence of overestimation at low predicted probabilities, and the Brier score was 0.15. A net benefit was observed across 5-50% threshold probabilities. Sliding dichotomy had an efficiency gain of 27% for a treatment effect of OR=2.0, and a gain of 22% for a treatment effect of OR=2.5. The efficiency gain for a treatment effect of OR=1.5 could not be calculated because the fixed dichotomy did not reach 80% power despite a sample size of 1000 patients. Conclusions: The FUNC score's predictive performance for 12-month functional independence was comparable to its originally validated 3-month discrimination. Following external validation across centers, the FUNC score may be leveraged to counsel families on global measures of long-term functional independence and to implement sliding dichotomy methodology in ICH research.

BackgroundNeonatal cerebral venous sinus thrombosis (CVST) is associated with intracranial hemorrhage (ICH) and ischemic lesions. There is no scale to characterize the spectrum of brain injury secondary to neonatal CVST. ObjectiveTo develop the Neonatal CVST Hemorrhage Score (NeoCVST Score) to characterize ICH and brain injury in neonates with CVST. MethodsThis was a retrospective cohort study of neonates with CVST diagnosed using brain MRI/MRV. The NeoCVST Score was developed using the study cohort, integrating elements from previous hemorrhage classification systems and expert consensus. Logistic regression examined associations between NeoCVST score and neurodevelopmental outcomes (Pediatric Stroke Outcome Measure). Interrater reliability was assessed with intraclass correlation coefficient. ResultsThe study included 100 neonates (77% term and 23% preterm) with CVST. Thrombosis of multiple venous sinuses was present in 62%. ICH was present in 63%. Supratentorial hemorrhage was present in 57% and included germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) grades 1-2 (22%), GMH-IVH grade 3 (15%), parenchymal (43%) and thalamic (18%) hemorrhage. Infratentorial hemorrhage was present in 19% and included cerebellar (18%) and brainstem (4%) hemorrhage. Extra-axial hemorrhage was present in 32% and included epidural (2%), subdural (26%) and subarachnoid hemorrhage (6%). Ischemic brain injury was present in 67% and included lesions in the medullary vein distribution (13%), white matter (54%), basal ganglia (17%) and thalamus (25%). Neurodevelopmental outcomes included 40% with normal outcomes and 60% with neurodevelopmental impairments. NeoCVST total score (OR=1.1, P=0.02) and subscores for thalamic hemorrhage (OR=1.9, P=0.04), thalamic ischemia (OR=2.2, P=0.005) and bilateral thalamic ischemia (OR=2.8, P=0.01) were predictors of adverse neurodevelopmental outcome. Inter-rater reliability showed moderate-good agreement between reviewers with an intraclass correlation coefficient of 0.71. ConclusionsThe NeoCVST Score is a simple clinical tool to characterize ICH and brain injury secondary to neonatal CVST. Increasing NeoCVST total score and subscores for thalamic hemorrhage and ischemia were associated with worse neurodevelopmental outcomes.

BackgroundNeonatal global hypoxic-ischemic cerebral injury is a leading cause of infant mortality and lifelong disability. Current rodent models do not replicate neonatal global cerebral ischemia (nGCI) and reperfusion injury. Here, we developed and characterized a rodent model of cardiac arrest and cardiopulmonary reperfusion (CA/CPR) to induce nGCI, producing acute systemic ischemia, mild neuronal injury, white matter alterations, and motor and memory deficits. MethodsRat pups underwent CA/CPR or sham procedure on postnatal day 9-11. CA/CPR in rat pups was performed under anesthesia while intubated. Asystole was induced with intravenous (IV) KCl and maintained for 10-14 minutes. Resuscitation included oxygen ventilation, chest compressions, and IV epinephrine. ResultsTwelve minutes of asystole provided an optimal balance between survival and systemic injury. Behavioral testing on postoperative day (POD) 7 revealed memory impairments. Despite the absence of overt neuronal death in the hippocampus or cerebellum, we observed evidence of glial activation and white matter alterations. ConclusionThis novel rodent model of nGCI addresses limitations in existing models while offering clinically relevant features to support future mechanistic and translational research. ImpactO_LIThis study validates cardiac arrest and cardiopulmonary resuscitation (CA/CPR) as a novel model for neonatal global cerebral ischemia (nGCI), complementing existing rodent models of unilateral and permanent injury by enabling investigation of both global ischemia and reperfusion injury. C_LIO_LInGCI results in memory impairment in the absence of overt neuronal cell death. Functional deficits are associated with neuroinflammatory responses in the hippocampus, white matter, and cerebellum. C_LIO_LINeonatal CA/CPR induces global cerebral ischemia which uniquely allows investigation of hindbrain structures, such as cerebellum, which are typically spared in existing rodent models of neonatal hypoxia-ischemia. C_LI

BackgroundIntensive systolic blood pressure (SBP) reduction is routinely employed to limit hematoma expansion in spontaneous intracerebral hemorrhage (ICH). However, the renal consequences of sustained aggressive SBP lowering in real-world clinical practice remain incompletely characterized. MethodsWe conducted a retrospective cohort study of adults admitted to the intensive care unit with spontaneous ICH between 2011 and 2023. Hourly SBP measurements over the first 7 days were standardized and clustered using k-Shape time-series clustering to identify distinct shape-based SBP trajectories. Acute kidney injury (AKI) was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Multivariable logistic regression assessed associations between SBP trajectory cluster and AKI, adjusting for demographics, baseline illness severity, renal function, and nephrotoxic medication exposure. ResultsAmong 233 patients (mean age 61.2{+/-}14.1 years), two distinct SBP trajectories were identified: Cluster 1 (rebound SBP trajectory), a progressive upward SBP trajectory with gradual rebound, and Cluster 2 (rapid-drop SBP trajectory), a lower SBP trajectory characterized by rapid early reduction and sustained levels below 140 mm Hg. Overall, 70.4% developed AKI of any stage. Patients of Cluster 1 (rebound SBP trajectory) had significantly higher odds of AKI compared to those of Cluster 2 (rapid-drop SBP trajectory) (adjusted OR 1.97; 95% CI, 1.03-3.78). Higher maximum nicardipine dose was independently associated with AKI (OR 1.14 per mg/h; 95% CI, 1.03-1.26). SBP trajectory cluster was not significantly associated with hematoma expansion (defined as a binary outcome based on physician-documented expansion vs. no expansion), neurological outcomes, or 1-year mortality. ConclusionsIn ICH patients, rapid early decline in SBP followed by relative stabilization at lower levels (<140 mm Hg) is associated with increased risk of AKI without clear neurological benefit. These findings highlight the importance of balancing cerebral hemorrhage control with renal perfusion and support cautious implementation of intensive BP targets in clinical practice.

BACKGROUNDEarly prognostic stratification of aneurysmal subarachnoid hemorrhage (aSAH) is clinically important. We developed and temporally validated an admission-based prediction model for 90-day outcomes in a cohort of patients with aSAH. METHODSConsecutive treatment-eligible patients with aSAH, managed at a single center between January 2021 and December 2025, were retrospectively analyzed. Patients treated from 2021-2023 and 2024-2025 comprised the development and temporal validation cohorts, respectively. Prediction models were developed using admission variables, including age, pre-morbid modified Rankin Scale (mRS) score, World Federation of Neurosurgical Societies grade, modified Fisher grade, and intracerebral hemorrhage on initial computed tomography. The primary outcome was a 90-day mRS score of 0-3. A sensitivity model was constructed for 90-day mRS scores of 0-2. RESULTSA total of 245 patients were included (development cohort: 160; validation cohort: 85); 107 patients were aged [&ge;] 70 years. For mRS 0-3, the model demonstrated good discrimination in both the development and validation cohorts (area under the curve [AUC]: 0.917 and 0.868), while mRS 0-2 had corresponding AUCs of 0.920 and 0.840, respectively. Among patients aged [&ge;] 70 years, the validation AUCs were 0.842 and 0.768 for mRS scores of 0-3 and 0-2, respectively. Calibration was acceptable overall but less stable in older patients. CONCLUSIONSIn an aSAH cohort with a substantial proportion of older patients, an admission-based five-variable model provided 90-day outcome prediction with good discrimination on temporal validation. This tool may facilitate early risk stratification at admission, pending multicenter external validation. CLINICAL PERSPECTIVEO_ST_ABSWhat is New?C_ST_ABSO_LIWe developed and temporally validated a simple admission-based prediction model for 90-day functional outcomes after aneurysmal subarachnoid hemorrhage in a contemporary, consecutive, single-center cohort comprising a substantial proportion of older patients. C_LIO_LIBased on five readily available admission variables, the model showed good discrimination in both the overall population and the subgroup aged [&ge;] 70 years, with additional support for clinical utility from decision curve analysis and an exploratory external assessment in an independent published cohort. C_LI What are the Clinical Implications?O_LIAdmission-based prediction may support early prognostic estimation, family counseling, and initial risk stratification at admission when treatment-related information is unavailable. C_LIO_LIBecause the cohort comprised treatment-eligible patients who received active aneurysm treatment, the model was intended for prognostic estimation rather than for guiding treatment allocation or withdrawal decisions. C_LI

Background Chronic subdural hematoma (cSDH) recurrence requiring reoperation occurs in 5-33% of cases, representing a substantial clinical and economic burden. The ability to predict recurrence could enable risk-stratified surveillance protocols, potentially reducing imaging burden in low-risk patients while maintaining close monitoring for high-risk individuals. We evaluated whether machine learning algorithms could achieve clinically actionable recurrence prediction using routinely available clinical and radiographic variables. Methods This retrospective single-center study included 564 consecutive patients who underwent surgical evacuation of cSDH between 2015 and 2023. Data were randomly divided into training (75%, n=422) and test (25%, n=142) sets. We developed and compared three machine learning models--regularized logistic regression, Random Forest, and XGBoost--using 31 predictor variables including demographics, comorbidities, medications, laboratory values, hematoma characteristics, and postoperative features. Model development and hyperparameter tuning were performed exclusively on the training set using 10-fold cross-validation. The best-performing model was selected and evaluated on the held-out test set. The primary outcome was postoperative recurrence requiring reoperation. Results Postoperative recurrence occurred in 170 patients (30.1%). Within the training set, XGBoost achieved the highest cross-validated ROC AUC of 0.713 (SE=0.024), outperforming regularized logistic regression (0.686) and matching Random Forest (0.713). Variable importance analysis identified hematoma volume, coagulation parameters (INR, platelets, aPTT), and disease severity markers (ICU admission, GCS) as the most influential predictors, though absolute effect sizes remained modest. On the held-out test set, the final XGBoost model achieved ROC AUC 0.688 (95% CI: 0.590-0.772) with excellent calibration. However, at the clinically relevant 90% sensitivity threshold, test set specificity was only 30.3%, allowing potential imaging reduction in approximately one-third of non-recurrence patients. The consistency between training and test performance confirmed that limitations stem from inherent predictor information content rather than overfitting. Conclusions Machine learning models using routinely available clinical and radiographic variables cannot achieve clinically actionable risk stratification for cSDH recurrence. Despite rigorous methodology and internal validation, discriminative capacity remained insufficient to identify a low-risk patient subgroup suitable for de-escalated surveillance. These findings suggest that recurrence is driven by factors not captured in standard clinical assessment, and support either uniform surveillance protocols or symptom-driven imaging strategies rather than risk-stratified approaches.

Background: Thalamic low-intensity transcranial focused ultrasound (tFUS) has shown promise for increasing behavioral responsiveness in disorders of consciousness (DOC), but no study has examined whether it can causally modulate the well-validated behavioral, electrophysiological, and metabolic biomarkers of DOC impairment. Methods: Sixteen adult patients (44% Female; Age, M=37.81, SD=15.97) with a chronic DOC (Time Since Injury, M=3.39, SD=1.94 years) secondary to severe brain injury (TBI 44%, non-TBI 56%) underwent a 10-day inpatient, longitudinal, single-arm, open-label protocol. tFUS was delivered in a single session targeting the left central thalamus. Well-known behavioral (CRS-R), electrophysiological (EEG {delta}/{beta} ratio), metabolic (18F-FDG PET), and polysomnographic outcomes were assessed at baseline and after sonication. Results: The maximum CRS-R total score increased significantly following tFUS compared to baseline (M=13.27 vs. M=10.33; t(14)=7.407, p<0.001, d=1.913), as did the global EEG {delta}/{beta} ratio (N=14; W=17, p=0.025, r=0.68), with the degree of frontal slowing positively predicting behavioral gains ({tau}b=0.51, p=0.016). Glucose metabolism decreased bilaterally in thalamus and frontal, temporal, and parietal cortices at both post-tFUS timepoints compared to baseline. Finally, N2 sleep increased by 33% following tFUS (N=11; t(10)=2.386, p=0.038, d=0.72), though this did not survive correction. No severe adverse events were observed. Conclusion: Thalamic tFUS can causally modulate well-validated behavioral, electrophysiological, and metabolic biomarkers of DOC. The convergent inhibitory signature across these measures suggests a thalamocortical reset mechanism, complementing existing excitatory neuromodulation approaches and providing the mechanistic foundation for a large, randomized sham-controlled trial.

BackgroundNeurodevelopmental impairment remains common in neonatal hypoxic-ischemic encephalopathy (HIE) despite treatment with the standard of care, therapeutic hypothermia (TH). The complement response activates at reperfusion and is known to exacerbate neuroinflammation and injury, though its full role and interaction with hypothermia are incompletely defined. We hypothesized that modulating the complement response could improve structural and functional outcomes in HIE, and tested a novel complement therapy (CT), consisting of C3a peptides and the C5a-receptor antagonist PMX205, as both a stand-alone treatment and as an adjuvant to TH. MethodsWistar rat pups were randomized to the following treatment groups: Sham (uninjured control), NT (uninjured, normothermia/not treated control), or injured and treated with either TH, CT, or CT+TH. At term-equivalence, mild-moderate hypoxic-ischemic injury was induced by Vannuccis method. To capture the short and long-term effects of the treatments, cohorts were harvested 3 or 66-72 days post-injury, respectively. Cerebral injury was measured by quantifying levels of inflammatory markers and cerebral tissue loss, and functional outcomes were assessed in a series of behavioral tests. The data were stratified to detect sexual dimorphisms. ResultsCT and TH treatments demonstrated test and sex-dependent differences in improvement compared to untreated, injured rats. In male rats, TH treatment worsened long-term hippocampal and thalamic brain injury and functional measures of ataxia and attention. CT-treatment worsened long-term thalamic loss in females. Combining the two treatments (CT+TH) demonstrated additive improvement in both sexes, including short and long-term cortical loss and ataxia. ConclusionsComplement modulation enhances the neuroprotective effects of TH after neonatal hypoxic-ischemic injury, with sex-specific effects on inflammation and behavior. Combining complement modulation with the standard of care often demonstrated synergistic improvement in both sexes, supporting complement-targeted therapy as a promising adjunct to hypothermia in neonatal HIE. Graphical abstract. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/717097v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@1025d1forg.highwire.dtl.DTLVardef@2fa4e5org.highwire.dtl.DTLVardef@1f2c1c4org.highwire.dtl.DTLVardef@8f3410_HPS_FORMAT_FIGEXP M_FIG C_FIG Created with BioRender. Saadat, A. (2026) https://BioRender.com/siwm825.

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.

BackgroundGlobal cerebral anoxia is a leading cause of death and resuscitated patients often remained persistently affected by neurological deficits. While previous studies suggest that brain-heart electrophysiological interactions may predict severity and prognosis after hypoxic brain injury coma, little is known about the brain-heart dynamics at near-death. Gaining insight into these mechanisms is crucial for developing targeted interventions in critical conditions. ResultsUsing a rodent model of reversible systemic anoxia (n=29, male and female rats), we investigated whether brain-heart interactions during the asphyxia onset could predict the return of brain electrical activities after resuscitation. Electrophysiological recordings confirmed that cerebral activity declines following asphyxia, coinciding with increased heart rate variability. Notably, the strong coupling between cardiac parasympathetic activity and high-frequency brain activity in the somatosensory cortex and hippocampus serves as a key predictor of a favorable outcome. ConclusionOur study underscores the involvement of the brain-heart axis mechanisms in the physiology of dying and the potential prognostic significance of these mechanisms, paving the way for translational research into critical care, based on new characterizations of cardiac reflexes and brain-heart interactions.

This research demonstrates that the trans-aqueduct approach is a feasible, minimally invasive access pathway to the third ventricle, offering a potential route to the deep brain for therapeutic technologies. Further pre-clinical investigation is required to thoroughly evaluate physiological tolerance, trauma risk, and the long-term implications of intraventricular implantation. The third ventricle is a high-value site for neuromodulation due to its proximity to deep-brain targets, including the subthalamic nucleus (STN) and globus pallidus internus (GPi). This study defined the anatomical pathway; and evaluated the technical feasibility of retrograde access to the third ventricle via the cerebral aqueduct using minimally invasive interventional techniques. Evaluation was conducted in three phases using human MRI datasets (n=16; mean age 48.4 years) and cadaveric specimens (n=6; mean age 88.2 years). Phase 1 involved morphometric MRI analysis of the aqueduct and ventricles. Phase 2 tested trans-aqueduct access on cadaver specimens via fluoroscopically guided guidewires and catheters. Phase 3 utilized direct anatomical dissections on cadaver specimens (n=3) to morphometrically measure the third ventricular cavity and its relationship to deep-brain nuclei. Measurements across the sample groups showed a mean aqueduct diameter of 1.6 mm (SD=0.14). Third ventricle dimensions averaged 27.6 mm (ventral-dorsal), 19.9 mm (caudal-cranial), and 5.7 mm (lateral). Successful access to the third ventricle was achieved in 83% (5/6) of cadaveric specimens. The optimal technical configuration utilized a 0.018'' angled-tip guidewire and 5-6 Fr catheters; the aqueduct accommodated diameters up to 2.0 mm with minimal resistance. The STN and GPi were localized within 5-20 mm of the ventricular volumetric centroid. The trans-aqueduct approach is a technically feasible, minimally invasive pathway for accessing the third ventricle. This route offers a potential alternative for the delivery of therapeutic neurotechnologies. Further research is required to assess physiological tolerance, trauma risk, and the long-term safety of intraventricular implantation.

Background: Clinical evidence on the contemporary management and functional outcomes of patients with Wernicke encephalopathy remains limited. This study aimed to clarify the nationwide patterns of thiamine administration and functional outcomes at discharge. Methods: Using the Japanese nationwide inpatient Diagnosis Procedure Combination database, we identified patients hospitalized with Wernicke encephalopathy between July 2010 and March 2024. Initial intravenous thiamine doses were categorized as low ([&le;]300 mg/day), medium (301-900 mg/day), or high (>900 mg/day). Outcomes included in-hospital mortality and functional status (Barthel Index) at discharge. Results: We identified 7856 patients with Wernicke encephalopathy. Over the 13-year study period, the proportion of patients receiving initial high-dose thiamine increased markedly from 5.4% to 49.0%, while the frequency of low-dose therapy decreased from 83.0% to 37.9%. Despite prompt intervention [median time to initial administration: 0 days (interquartile range, 0 to 0 days)], 56.1% of patients were discharged with impaired activities of daily living (Barthel Index <90), and the in-hospital mortality rate was 3.8%. Conclusions: High-dose thiamine treatment is increasingly implemented for Wernicke encephalopathy in Japan. Although in-hospital mortality was relatively low, the high prevalence of functional impairment at discharge, despite early treatment initiation, indicates substantial burden of Wernicke encephalopathy. Given the limited clinical evidence, further research investigating the optimal thiamine dose and develop effective primary prevention strategies for Wernicke encephalopathy is needed.

Objective: Neuroendoscopy has emerged as a crucial minimally invasive strategy for the treatment of intracranial hemorrhage (ICH). This bibliometric analysis aims to systematically delineate the global research architecture and evolution of neuroendoscopic ICH research over the past two decades. Methods: Relevant publications were retrieved from the Web of Science Core Collection using a reproducible search strategy. Bibliometric tools were applied to analyze contributions from countries, institutions, authors, publications, keywords and journals, enabling the construction of a comprehensive knowledge map and evolutionary framework of this field. Results: A total of 403 articles were identified, involving 2128 authors from 555 institutions across 43 countries. The publication trajectory exhibited fluctuating growth, reflecting the dynamic interplay between clinical demand and technological maturation. China contributed the highest publications and citation impact, followed by the US, jointly anchoring the global influence of the field. The research keywords have evolved from ?intracerebral hemorrhage? and ?initial conservative treatment? to ?augmented reality.? Thematic evolution analysis revealed a clear progression from early emphasis on operative feasibility, safety, and perioperative outcomes toward more rigorous evidence appraisal and the refinement of context-specific clinical indications, accompanied by continuous technological innovation. Conclusion: These findings collectively position neuroendoscopy as a cornerstone of modern ICH management, reshaping clinical strategies toward precision, minimal invasiveness, and multimodal intervention. Future progress will depend on strengthened international collaboration to generate high-quality evidence that supports patient stratification. The integration of emerging technologies, including advanced endoscopic robotics, is expected to further accelerate the translational and clinical landscape of neuroendoscopic ICH therapy.

Fv-HSP72 is a rapid cell-penetrating human heat shock protein for the treatment of traumatic organ injuries. We have shown this re-engineered protein (HSP72) is capable of crossing the blood brain barrier (BBB) of rats suffering a controlled cortical impact (CCI) and remains in brain tissue for up to 12 hours; long after clearance from the cortex of uninjured rats. Peptide sequences unique to Fv-HSP72 allow for its differential detection from endogenous HSP72. Male Sprague-Dawley rats were divided into 10 groups of n=10 with those animals receiving a CCI subjected to a unilateral cortical contusion simulating a moderate to severe brain injury using an electronically controlled pneumatic impact device. Control groups were either uninjured (Sham), injured (TBI Only), or injured and given buffer (TBI+Vehicle). Rats treated with one of three Fv-HSP72 variants were dosed at 10 or 30mg/kg 15m post-impact, then sacrificed 48 hours later. Cortical tissues were extracted from the ipsilateral and contralateral hemispheres for biomarker analysis. Here we report results of our drug inhibiting neurodegeneration based on five biomarkers (NF-L, pNF-H, pTau [T181, T231, S396]). These results were statistically significant, especially for one of the Fv-HSP72 variants, when comparing differences both between treatment groups and within groups (i.e. when comparing ipsi-vs. contralateral hemispheres). Significant inhibition of oxidative stress (3-NT) and inflammatory (IL-6) biomarkers were also observed (both p<0.0001). With similar results obtained for a blast injury model being published elsewhere, the analyses suggest Fv-HSP72 is neuroprotective following a direct impact brain injury. One sentence summaryThis study describes the effectiveness of a biologic agent, Fv-HSP72, in significantly inhibiting neuronal tissue damage in the brain when administered after a direct cortical impact.

ObjectiveThe JAK2 V617F mutation increases the risk of thrombosis in patients with myeloproliferative neoplasms (MPNs). However, it remains unclear whether individuals who carry the JAK2 V617F mutation without MPN also have an increased risk of stroke. MethodsWe prospectively tested for the JAK2 617F mutation in consecutive patients with acute ischemic stroke or transient ischemic attack (TIA) admitted between January 2020 and September 2024. Patients with overt MPN or abnormal blood counts were excluded. We used allele-specific PCR to detect the mutations. ResultsIn total, 921 patients (median age, 77 years; 557 men (62%); TIA, 32 patients) were enrolled in this study. Among them, 11 patients (1.2%; median age, 72 years; 8 male) tested positive for the JAK2 V617F mutation. There were no significant differences in clinical background, including age, sex, BMI, comorbidities, or history of thrombosis, between the positive and negative groups. The blood count and coagulation parameters did not differ significantly between the two groups. Among the 11 patients in the positive group, 9 had embolic stroke and 2 had thrombotic stroke. Embolic stroke of undetermined source (ESUS) was more frequently observed in the positive group than in the negative group (45 vs. 13%; p=0.002). Stroke severity and outcomes did not differ between the two groups. DiscussionApproximately 1% of patients with acute ischemic stroke or TIA carry the JAK2 V617F mutation despite normal blood counts. Of the 11 mutation-positive patients, nine (82%) exhibited embolic imaging features and five (45%) met the ESUS criteria, whereas other clinical characteristics did not differ significantly from the mutation-negative group.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a severe form of stroke associated with higher morbidity and mortality. Posterior circulation aneurysms are considered to have worse prognosis than anterior circulation aneurysms due to anatomical location, hemorrhage severity, and treatment complexity. We aimed to determine whether aneurysm location independently influences clinical outcomes following aSAH Methods: PubMed, Scopus, Embase, and Web of Science were searched from January 2000 to December 2025 for studies reporting outcomes in anterior or posterior circulation aSAH. The outcome analysis included mortality, functional recovery (modified Rankin Scale [mRS] 0-2 and 3-6 at 6 months and 1 year), hydrocephalus, delayed cerebral ischemia (DCI), and symptomatic cerebral vasospasm. Pooled proportions and subgroup comparisons were performed using random-effects meta-analysis (DerSimonian-Laird method). Publication bias was evaluated using contour-enhanced funnel plots and Egger's test. Results: Nineteen analytic entries from 18 studies (anterior: n = 1,625; posterior: n = 986; total N = 2,611) were included. Pooled mortality was 13% (95% CI: 10%-17%; I2 = 84.6%), with no significant difference between the anterior (14%; 95% CI: 10%-20%) and posterior (11%; 95% CI: 7%-18%) circulation subgroups (p = 0.437). Good functional outcome was 60% at 6 months (95% CI: 51%-67%) and 55% at 1 year (95% CI: 46%-64%), with no location-based differences. Hydrocephalus (35% vs 35%; p = 0.979) and DCI (17% vs 17%; p = 0.939) were comparable between subgroups. Symptomatic cerebral vasospasm was the only outcome differing significantly by location, occurring more frequently in anterior circulation aSAH (24% vs 11%; {chi}2 = 5.59; p = 0.018). Conclusion: Aneurysm location does not independently determine mortality, functional recovery, hydrocephalus, or DCI following aSAH. Symptomatic cerebral vasospasm was the only location-specific outcome. Admission neurological grade (World Federation of Neurosurgical Societies [WFNS]), rather than vascular territory, appears to be the primary determinant of mortality. Aneurysm location alone should not guide prognostic decisions or limit aggressive treatment.

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.

IntroductionDelivering large-bore aspiration catheters through tortuous anatomy remains challenging during mechanical thrombectomy (MT). The Carrier delivery-assist catheter (DAC) was designed to facilitate aspiration catheter navigation, but multicenter data remain limited. We evaluated the efficiency and safety of the Carrier DAC. MethodsWe performed a multicenter retrospective study of prospectively collected data from patients undergoing MT at 15 U.S. Comprehensive Stroke Centers (September 2024-September 2025). Co-primary endpoints were puncture-to-clot engagement time and first-pass effect (FPE; eTICI 2c-3). A pre-specified single-center analysis compared upfront contact aspiration using the Carrier DAC versus standard 0.021'' microcatheter techniques with identical aspiration catheter sizes. ResultsThe multicenter cohort included 211 Carrier-assisted MTs. Median aspiration catheter inner diameter was 0.071'', with super-bore catheters used in 5.7%. Median puncture-to-clot time was 12 minutes, and FPE was achieved in 50.7%. Median puncture-to-reperfusion time was 20 minutes, and mFPE occurred in 74.4%. Parenchymal hematoma and subarachnoid hemorrhage occurred in 11.8% and 6.6%, respectively. Cavernous tortuosity did not affect primary endpoints. The single-center analysis included 242 patients. Carrier use was associated with shorter puncture-to-clot times and numerically higher FPE rates without increased hemorrhagic complications. ConclusionsThe Carrier DAC enables efficient navigation of large-bore aspiration catheters and may reduce procedural time while maintaining procedural safety. Prospective studies are warranted.