Plasma D-dimer levels are independently associated with poor prognosis following aneurysmal subarachnoid hemorrhage (aSAH). However, the underlying mechanisms contributing to early D-dimer elevation remain unclear. This study aimed to evaluate the association between admission D-dimer levels and total bleeding volume (TBV) and to further explore their combined predictive power for functional outcomes using interpretable machine learning approaches. We analyzed data from 473 patients with aSAH enrolled in the retrospective PROSAH-MPC cohort, including clinical, radiological, and laboratory parameters. Patients were stratified by D-dimer quartiles. Multivariable logistic regression was employed to assess associations between D-dimer, TBV, and 12-month modified Rankin scale (mRS) outcomes. Boruta algorithm was applied for feature selection, identifying D-dimer, TBV, age, Hunt–Hess grade, and modified Fisher score (mFS) as top predictors. Subsequently, seven machine learning models were developed for outcome prediction. SHapley Additive exPlanations (SHAP) analysis was used to interpret the contribution of these features. Unfavorable outcomes occurred in 125 patients (26.4
The neurocritical care treatment team frequently interacts with patient surrogates and Organ Procurement Organizations (OPOs) at the end-of-life. A 2025 survey of Neurocritical Care Society (NCS) members assessing experiences and attitudes related to organ donation identified the need to enhance education for the treatment team about organ donation and opportunities for improvement in palliative interventions after withdrawal of life-sustaining therapies for potential donation after cardiac death/death by circulatory-respiratory criteria. Additionally, members noted concerns regarding blurred boundaries between patient care and care directed towards organ donation; a potential lack of transparency, empathy and cultural sensitivity in communication between OPOs and patient surrogates; and the ethics of first-person authorization for organ donation. In response to these concerns, the NCS Ethics Committee developed this statement to provide education and ethical guidance for organ donation at the end-of-life. Members had an opportunity to share feedback on the statement from April 6-19, 2026. This statement provides an informal narrative review of the literature related to organ donation that is pertinent to the care of potential organ donors at the end-of-life and includes practical guidance related to the legal definitions of death and first-person authorization, collaborative communication, and management of potential conflicts.
High-resolution neuromonitoring data with time-stamped clinical annotations offer valuable insights into treatment responses, though reliability is limited by manual documentation. This study aims to develop and demonstrate a three-step methodological framework to evaluate the plausibility of time-stamped clinical annotations using a high-frequency dataset. The framework integrates visual inspection of reference annotations and automated classification based on predefined physiological criteria. Annotated interventions in the High-Resolution Collaborative European Neuro Trauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) dataset were retrospectively analysed. Step 1 included visually inspecting physiotherapy and suctioning annotations to assess the overall plausibility of annotations at the patient level. In Step 2, an intracranial pressure (ICP)-based classification was applied to the period before osmotherapy annotations. Rejected annotations were those without sustained intracranial hypertension (ICP > 20 mm Hg for ≥ 5 min) beforehand. Step 3 classified the accepted annotations as effective (ICP reduction ≥ 10 mm Hg or normalisation) or ineffective on the basis of the post-annotation ICP trend. Across 205 patients, 15,455 annotated interventions were identified. Visual inspection (Step 1) classified 90.2
Despite advances in mechanical thrombectomy (MT), in-hospital mortality remains approximately 10–15
Subarachnoid hemorrhage (SAH) carries high mortality worldwide. Seasonal patterns have been documented in temperate regions, but evidence from tropical and subtropical populations remains limited. We investigated associations between meteorological variables and SAH hospital admissions across diverse climate zones in Brazil. We conducted an ecological time-series analysis linking nationwide SAH hospitalizations [International Classification of Diseases Version 10 (ICD-10; I60.0–I60.9)] from Brazil’s Unified Health System with meteorological data from the National Institute of Meteorology (January 2020–November 2024). Quasi-Poisson generalized linear models were used to estimate relative risks (RR) per 1 °C decrease in mean minimum temperature, overall and stratified by season. Sensitivity analyses excluded the first coronavirus disease 2019 (COVID-19) pandemic year. Among 9903 SAH hospital admissions over 59 months, seasonal variation was observed, with the highest proportion occurring in autumn (27.2
Traumatic brain injury (TBI) trials commonly assess global functional outcome using the Glasgow Outcome Scale (GOS) or Extended Glasgow Outcome Scale (GOSE). Because GOS- and GOSE-based trials are often pooled or compared in evidence synthesis, whether treatment-effect estimates differ systematically by outcome scale remains unresolved. We aim to estimate the between-trial contrast in treatment-effect estimates comparing GOSE-based with GOS-based randomized controlled trials (RCTs) of moderate-to-severe TBI. We conducted a meta-epidemiologic analysis of RCTs comparing acute-phase interventions with a concurrent control in adults with moderate-to-severe TBI and reporting 6-month global functional outcome using GOS or GOSE. Random-effects meta-regression estimated the ratio of odds ratios (ROR) contrasting GOSE- with GOS-based trials, adjusted for publication year, multicenter status, income setting, intervention class, endpoint role, and sample size. Sensitivity, structural, and small-study-effect analyses were prespecified. Eighty-four RCTs (> 20,000 participants) met eligibility criteria. Dichotomous outcomes were available for 78 trials (53 GOS and 26 GOSE observations). The adjusted outcome-scale contrast was ROR 0.880 [95
Delayed cerebral ischemia (DCI) remains a major cause of morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Induced hypertension (IH) is frequently used to improve cerebral perfusion in patients with DCI, with current practice primarily supported by observational evidence with inconsistent guideline recommendations. We conducted a nationwide survey to assess current institutional approaches to IH in the management of DCI after aSAH in Germany. An 11-item web-based questionnaire was distributed via LimeSurvey® between May and October 2025 to neurological and neurosurgical departments in Germany involved in the treatment of aSAH. The survey assessed institutional approaches to IH, monitoring and imaging strategies, and DCI treatment. Overall, 60/132 departments (45
A survey of 44 worldwide clinical experts in continuous monitoring of cerebral autoregulation (CCA) revealed that while half used a CCA index in clinical decision making, only 39
Bolus hypertonic saline (HTS) is a cornerstone for managing intracranial hypertension, yet its transient effect mandates repeated dosing and may induce wide sodium fluctuations. Whether augmenting bolus 7.5
We review the international experience of placing monitoring probes intrathecally at the injury site in patients with acute, severe traumatic spinal cord injuries. The aims are to assess the types of probes used, their placement, signal quality, and safety. We analyzed data from 109 adult patients managed in intensive care units in Aarhus, Leuven, Ljubljana, London, and Madrid. A questionnaire was distributed to all participating sites and data were retrospectively collected from each patient’s medical record. Admission American Spinal Injury Association (AIS) grade was A (58.7
BACKGROUND:Bolus hypertonic saline (HTS) is a cornerstone for managing intracranial hypertension, yet its transient effect mandates repeated dosing and may induce wide sodium fluctuations. Whether augmenting bolus 7.5% HTS with continuous 3% saline infusion to sustain osmotic gradients improves outcomes in neurocritical patients remains unknown. METHODS:We conducted a retrospective cohort study of 993 neurocritical patients treated with 7.5% HTS at a tertiary academic hospital in South Korea. Patients were classified as bolus-alone (n = 851) or combined therapy (7.5% bolus plus 3% continuous infusion; n = 142). The primary analysis focused on patients with severe brain injury (Glasgow Coma Scale [GCS] 3-9; n = 212). Inverse probability of treatment weighting (IPTW) was used to adjust for confounding. Robustness was confirmed through five sensitivity analyses, including multiple imputations and E-value assessment for unmeasured confounding. RESULTS:In the severe brain injury subgroup, combined therapy was associated with markedly lower ICU mortality (16.2% vs. 41.1%; adjusted odds ratio [OR] 0.23, 95% CI 0.08-0.65, p = 0.006) and 28-day mortality (18.9% vs. 45.7%; adjusted OR 0.20, 95% CI 0.07-0.55, p = 0.002). All five sensitivity analyses consistently confirmed these findings. In the overall cohort, trends favored combined therapy but did not reach significance (ICU mortality: OR 0.58, p = 0.121; 28-day mortality: OR 0.59, p = 0.110), although time-to-event analysis showed a significant overall survival benefit (Kaplan-Meier log-rank p = 0.006). Strikingly, despite a greater total sodium load, the combined group achieved lower peak serum sodium yet superior ICP control, suggesting that sustained osmotic gradients-not peak sodium-drive the benefit. CONCLUSIONS:In patients with severe brain injury, combined 7.5% HTS bolus and 3% continuous saline infusion was associated with substantially lower mortality compared with bolus therapy alone. These findings support further prospective investigation of combination osmotic therapy in neurocritical care. These observational findings should be interpreted with caution; despite IPTW adjustment and high E-values, confounding by indication cannot be fully excluded, and prospective validation is required before clinical adoption.
Early risk stratification following aneurysmal subarachnoid hemorrhage (aSAH) is clinically challenging. Beyond the initial hemorrhage severity, chronic metabolic vulnerability may contribute to secondary brain injury. Skin autofluorescence (SAF) is a rapid, noninvasive bedside biomarker that quantifies advanced glycation end product (AGE) accumulation. The prognostic relevance after aSAH has not been characterized previously. In a prospective single-center cohort study, SAF was measured during the index hospital stay in consecutive adult patients with confirmed aSAH. The primary endpoint was poor functional outcome at 90 days, defined as a modified Rankin Scale (mRS) score of 4–6. Secondary endpoints included delayed cerebral ischemia (DCI; defined as delayed neurological deterioration ≥ 1 h and/or new cerebral infarction not attributable to other causes) and radiographic vasospasm. Associations were assessed using logistic regression and receiver operating characteristic (ROC) curve analyses. A total of 50 patients completed 90-day follow-up; 22 (44
Predicting successful extubation in traumatic brain injury (TBI) remains challenging. We examined associations between structural neuroimaging characteristics and extubation failure in TBI, and the ability to enhance prognostic models based on clinical characteristics alone. Retrospective cohort study of patients with moderate-severe TBI [Glasgow Coma Scale (GCS) ≤ 12] who were mechanically ventilated ≥ 24 h and underwent ≥ 1 planned extubation attempt. We fit multivariable logistic regression models (adjusted for age, GCS, and cardiopulmonary disease) to examine associations between validated head computed tomography (CT)-based scores (on both the admission CT and pre-extubation CT) and extubation failure (reintubation ≤ 5 days from extubation). We used DeLong’s test to compare the area under the curve (AUC) for two predictive clinical models (model 1: cough, gag, age; model 2: temperature, hypertension, respiratory rate) with and without neuroimaging characteristics. Of 2044 patients screened, 181 (74
Autonomic nervous system (ANS) dysfunction and reduced signal complexity (SC) appear to occur after traumatic brain injury (TBI) and may reflect impaired physiological adaptability. However, their relationships with cerebral physiology and functional outcome during neurointensive care (NIC) remain incompletely understood. This study explores heart rate variability (HRV), baroreflex sensitivity (BRS) and multiscale entropy-derived SC of systemic and cerebral signals in patients with moderate-to-severe TBI during NIC. This retrospective, single-centre study included 649 TBI patients with intracranial pressure (ICP) monitoring for longer than 24 h, treated in the NIC unit at Uppsala University Hospital, Sweden (2008–2024). HRV, BRS and SC (multiscale entropy complexity index) of heart rate (HR), mean arterial pressure (MAP), ICP, ICP pulse amplitude (AMP) and cerebral perfusion pressure (CPP), respectively, were analysed over the first 10 days of NIC. Associations with demographics, injury severity, NIC physiology (ICP, CPP, pressure reactivity index [PRx]) and 6-month Glasgow Outcome Scale-Extended (GOSE) were assessed using Spearman’s correlations, multivariable ordinal logistic regression and two-variable outcome heatmaps. In multivariable regression (adjusted for age, Glasgow Coma Scale motor score [GCS M], pupillary reactivity, ICP, CPP and PRx) higher HRV and SC of each of HR, ICP, AMP and CPP independently correlated with better functional outcome in separate models. Outcome heatmaps demonstrated that reduced SC combined with high ICP, low CPP or high PRx was particularly associated with poor recovery. Lower admission GCS M, barbiturate use and decompressive craniectomy were generally associated with reduced HRV, BRS and SC. Higher ICP and PRx and lower CPP correlated with reduced systemic and cerebral SC. Reduced SC and HRV are independently associated with worse outcome after TBI, even when adjusted for conventional NIC predictors. Reduced SC may co-occur with higher ICP and PRx and lower CPP in TBI.
Secondary sepsis is a frequent and clinically important complication after spontaneous intracerebral hemorrhage (ICH), but biomarkers linking hemorrhage-related heme stress to subsequent systemic complications remain poorly defined. We investigated cerebrospinal fluid hemopexin (CSF-HPX) as a candidate biomarker associated with hemorrhage burden, secondary sepsis, and in-hospital outcome after ICH. We integrated a 2-hit exploratory animal proteomics model with a retrospective clinical CSF cohort. In rats, autologous blood-induced ICH was followed 6 h later by cecal ligation and puncture (CLP), and soluble brain proteins collected at 24 h were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ)-based liquid chromatography–tandem mass spectrometry (LC–MS/MS). In the clinical cohort, archived CSF samples obtained through routine external ventricular drainage within 24 h after surgery were analyzed in adults with first-ever spontaneous ICH (n = 41). HPX and vitamin D-binding protein(GC/VDBP) were quantified by enzyme-linked immunosorbent assay (ELISA). Secondary sepsis was identified using an operationalized Sepsis-3 framework after excluding infection or sepsis at admission. In the animal model, ICH + CLP was associated with worse early survival than ICH alone (log-rank χ2 = 12.25, p = 0.0005), and HPX was identified as a candidate protein linked to the combined hemorrhage–sepsis condition. In the clinical cohort, CSF-HPX was positively associated with hematoma volume and was higher in patients who subsequently developed secondary sepsis than in those who did not (558.17 [279.48–773.39] ng/mL vs. 305.99 [218.77–354.24] ng/mL, p = 0.006). This association remained significant after adjustment (adjusted odds ratio (OR) 1.016, 95
The risk of vasospasm and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is well characterized. However, the risk of these complications in cases of aneurysmal rupture causing intracerebral hemorrhage is less clear. Here, we characterized the incidence and radiographic features of aneurysmal ICH (aICH) and the associated risk of vasospasm and DCI. This is a retrospective single-center cohort study of 442 patients with aneurysmal hemorrhage from 2014 to 2021. Clinical and radiographic features were compared in those with versus without ICH and presence of ICH was analyzed as an independent risk factor for vasospasm and DCI. Further, the incidence of vasospasm/DCI in those with aneurysmal ICH without SAH was compared to those with ICH and cisternal SAH. Vasospasm and DCI were evaluated only in those surviving at least four days. Overall, 83 of 442 patients (19
There is limited real-world evidence on the diagnosis, treatment, and outcomes of refractory status epilepticus (RSE) in Latin America. This study describes the clinical characteristics, management, and outcomes of RSE in a tertiary neurological intensive care unit (NICU) in Mexico. We conducted a retrospective cohort study of adults (≥ 18 years) with RSE admitted from 2010 to 2022. All patients were initially analyzed as a single cohort; a prespecified secondary analysis stratified patients by preexisting epilepsy and identified those with new-onset RSE (NORSE). Patients were identified via electronic medical records and met the International League Against Epilepsy (ILAE) definition. Clinical, imaging, laboratory, and EEG data were collected. Outcomes included seizure cessation, functional status at NICU discharge (mRS), and prognostic scores (STESS and END-IT). Statistical analysis involved descriptive measures, chi-square/Fisher’s exact tests, t-test or Mann–Whitney U test, and multinomial logistic regression. Significance was set at p < 0.05. We analyzed 102 patients with RSE; 52.9
To identify the clinical timepoint of World Federation of Neurosurgical Societies (WFNS) grading that provides the highest prognostic accuracy for short- and long-term outcomes in aneurysmal subarachnoid hemorrhage (aSAH). In this cohort study of 389 patients, WFNS grades were recorded at first medical contact, hospital admission, immediately pre-occlusion, and 48 h post-occlusion. Functional outcome was assessed using the Glasgow Outcome Scale–Extended (GOSE) and modified Rankin Scale (mRS) at discharge, 1 year, and at least 2 years after ictus. Prognostic performance was evaluated using receiver operating characteristic (ROC) analysis and compared across timepoints with DeLong’s test. Prognostic accuracy varied significantly between assessment timepoints. Across all outcomes, WFNS grading at 48 h post-occlusion demonstrated the highest discriminative power. For functional outcome at discharge, the area under the curve (AUC) reached 0.817 for GOSE and 0.845 for mRS, exceeding all values obtained from earlier assessments. The prognostic accuracy remained superior at the 1 year follow-up (GOSE AUC 0.844, mRS AUC 0.823) and at long-term follow-up after 2 years or more (GOSE AUC 0.819, mRS AUC 0.784). DeLong’s Test confirmed the significantly better predictive performance 48 h post-occlusion compared with all earlier timepoints, whereas no significant differences were observed among the earlier timepoints. The WFNS assessment at 48 h post-occlusion provides a better prediction of both short- and long-term functional outcomes after aSAH compared with earlier evaluations. This timepoint may more accurately reflect a stabilized neurological status and could be used in addition to the WFNS scale obtained at admission.
Aneurysmal subarachnoid hemorrhage (aSAH) remains associated with substantial mortality and functional disability despite advances in neurosurgical and intensive care management. Systemic inflammation and thromboinflammatory activation play key roles in early brain injury and secondary complications. We aimed to evaluate the prognostic value of albumin-anchored inflammatory ratios—C-reactive protein/Albumin ratio (CAR) and D-dimer-to-Albumin Ratio (DAR)—for predicting functional outcome and in-hospital mortality in patients with aSAH. In this retrospective multicenter cohort study, 212 adult patients with radiologically confirmed aSAH were included. Admission laboratory parameters obtained within the first 24 h were analyzed. The primary outcome was poor functional status at discharge (modified Rankin Scale [mRS] ≥ 3); the secondary outcome was in-hospital mortality. Univariable and multivariable logistic regression analyses were performed. Discriminatory performance was evaluated using receiver operating characteristic (ROC) analysis, and incremental prognostic value was assessed through model comparison, calibration analysis, and decision curve analysis. Poor functional outcome occurred in 88 patients (41.5
