Search Results (150)

Background: Traumatic brain injury (TBI) remains a major cause of neurological morbidity and mortality. Mitochondria, being embedded as one of the key organelles disrupted after injury, play a central role in regulating neuronal metabolism, oxidative balance, and cell survival, hence the growing interest in their role after TBI. Methods: We present a narrative review of the literature on mitochondrial dysfunction after TBI to highlight the potential role in diagnosis, monitoring, prognostication and treatment strategies. Following SANRA guidelines we conducted a synthesis of 159 selected references published between 1997 and 2026, including 70 references published from 2020 onward. Results: Mitochondrial dysfunction underpins bioenergetic failure through the impairment of critical regulatory pathways, including oxidative phosphorylation, dysregulated reactive oxygen species production, and dysregulated calcium handling. These changes trigger downstream processes of oxidative damage, epigenetic and proteomic remodeling, and activation of regulated cell death pathways such as apoptosis, necroptosis, and ferroptosis in the context of an inflammatory milieu. As such, mitochondrial-derived molecules (such as mitochondrial DNA and microRNA) are emerging candidate biomarkers of TBI severity and prognosis. Additionally, therapeutic approaches under investigation include inhibition of the mitochondrial permeability transition pore, mitigation of mitochondrial oxidative stress using targeted antioxidants, restoration of NAD⁺-dependent metabolic pathways, and metabolic support through ketogenic interventions. Conclusions: Mitochondrial biology is advancing our understanding of TBI and offers a promising framework for improving its management. Full article

Objective: Continuous pressure-flow cerebral bio-signals are critical for monitoring cerebrovascular dynamics but are often disrupted by missing data segments caused by artifacts from a variety of sources. These missing segments refer to segments of the signal that do not contain any valid physiological data. Such interruptions fragment the signals, resulting in discontinuities that compromise their overall integrity. Therefore, reconstructing missing values and preserving signal continuity are essential for ensuring the stable computation of signal trajectories and the accuracy of derived cerebrovascular indices. Methods: To address this issue, this systematic scoping review aimed to identify and synthesize existing interpolation and imputation strategies for handling missing segments in continuous pressure-flow cerebral bio-signals. Following the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a comprehensive search of five electronic databases was conducted from their inception to 24 September 2024, and updated on 16 June 2025, using a detailed search string. Results: The initial searches yielded 19,403 results, and 8 studies were filtered and included in the review. All included studies employed interpolation techniques, such as linear and spline interpolation algorithms, to correct distorted signal segments. However, none of the included studies directly utilized interpolation or imputation strategies to reconstruct or completely fill missing data segments. Conclusions: This reveals a critical knowledge gap, as no study has systematically addressed the utilization of interpolation or imputation strategies for missing segments in pressure-flow cerebral bio-signals. Therefore, this systematic review emphasizes the need for specialized methodologies and standardized frameworks to enable reliable recovery of missing data segments in pressure-flow cerebral bio-signals, which is critical for advancing real-time neurocritical care monitoring and experimental neuroscience/psychological research. Significance: This systematic review lays the groundwork for future research into physiologically informed interpolation and imputation strategies for pressure-flow cerebral bio-signals in clinical and research applications. Full article

Electrical impedance tomography (EIT) is a promising imaging tool in critical care. Its capacity to provide noninvasive bedside visualization of regional ventilation and perfusion with high temporal resolution makes it an ideal monitoring modality for patients on ventilation. However, its widespread implementation has been hindered by physical limitations in spatial resolution and a lack of robust evidence linking its use to improved clinical outcomes. In recent years, the commercialization of several bedside devices has led to growing clinical experience, gradually yielding concrete evidence regarding its clinical utility. Furthermore, beyond respiratory monitoring, data are increasingly accumulating in non-pulmonary fields, including perfusion, neuro-critical care and gastroenterology. Therefore, the objective of this review is to synthesize emerging evidence regarding the recent clinical applications of electrical impedance tomography and discuss future perspectives. Full article

Background: Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) central nervous system (CNS) infections represent a major therapeutic challenge in neurosurgical patients. Intraventricular or intrathecal polymyxin B sulfate (PMB) is commonly used as salvage therapy but is limited by substantial neurotoxicity. Ceftazidime–avibactam (CZA) exhibits potent in vitro activity against KPC-Kp; however, prospective clinical and pharmacokinetic evidence supporting its use in CNS infections remains limited. Methods: In this prospective, single-centre observational study, adult neurosurgical patients with culture-confirmed KPC-Kp CNS infections admitted to the neurointensive care unit of Huashan Hospital were enrolled. Patients received either intravenous CZA (CZA group, n = 15) or intrathecal/intraventricular PMB-based therapy (PMB group, n = 10). Primary outcomes included clinical cure, microbiological eradication, 28-day mortality, and safety. Therapeutic drug monitoring was performed to determine steady-state plasma and cerebrospinal fluid (CSF) concentrations of ceftazidime, avibactam, and polymyxin B, enabling assessment of CSF penetration and exposure–toxicity relationships. Results: Overall clinical cure and microbiological eradication rates were 68.0% and 84.0%, respectively, with a 28-day mortality of 20.0%. Compared with PMB, CZA was associated with a significantly higher clinical cure rate (86.7% vs. 40.0%, p = 0.024) and a numerically higher eradication rate (93.3% vs. 70.0%). No neurological adverse events occurred in the CZA group, whereas neurological toxicity was observed in 60.0% of PMB-treated patients (p < 0.001). Functional outcomes favoured the CZA group, with lower modified Rankin Scale scores at discharge and at 6 months. Pharmacokinetic analyses demonstrated that steady-state CSF concentrations of ceftazidime and avibactam exceeded commonly accepted pharmacodynamic targets, while markedly elevated PMB CSF concentrations were observed in patients with neurological toxicity. Conclusions: While intravenous CZA showed potentially favourable efficacy and safety compared with local PMB in this cohort, these preliminary findings should be interpreted as hypothesis-generating given the small sample size and non-randomised design. These results provide a rationale for further validation in larger multicentre, randomised controlled trials. Full article

Background: Subarachnoid hemorrhage (SAH) results from extravasation of blood into the subarachnoid space and is associated with high morbidity and mortality. This study aimed to compare systolic blood pressure variability (SBPV) and intracranial pressure variability (ICPV) in three 8 h intervals during the first 24 h after hospital admission and investigate their associations with discharge disposition and in-hospital mortality. Methods: We retrospectively reviewed charts of adult patients with spontaneous, non-traumatic SAH admitted for at least 24 h from 2016 to 2020. Hourly measurements were recorded for both systolic blood pressure (SBP) and intracranial pressure (ICP), and SBPV and ICPV were measured using successive variation (SV) and standard deviation (SD). Results: A total of 240 patients were included (mean age 57 ± 14.2 years, 64.6% female); 40 (16.7%) died. Univariate analyses showed higher SBP-SV (22.7 ± 13.8) in the first 8 h to be significantly associated with mortality (p = 0.028) and not being discharged home (p = 0.022), compared to those who survived (17.6 ± 7.5) or were discharged home (16.7 ± 5.5). Multivariate logistic regression did not show an association between SBPV and outcomes of interest. Conclusions: Greater early SBPV was associated with mortality in univariate analysis but was not independently predictive after adjustment for clinical severity, suggesting it reflects underlying physiologic instability rather than an independent prognostic factor in SAH. Full article

Healthcare-associated infections (HAIs) are clinically relevant complications in critically ill stroke patients, particularly in neurological intensive care settings, where severe neurological injury, dysphagia, immobilization, invasive device exposure, and prolonged hospitalization increase infection susceptibility. Romanian data focused on deceased stroke patients admitted to neurological intensive care units remain limited. This retrospective descriptive single-center hospital-based study, supported by focused literature contextualization, was conducted in the Neurological Intensive Care Unit of the Brașov County Emergency Clinical Hospital, Romania. Adult stroke patients who died during hospitalization over a six-year observation period were included. Clinical data were extracted from a working hospital database and analyzed descriptively after data cleaning and harmonization. The final cohort comprised 190 deceased stroke patients; ischemic stroke was documented in 69.5% and hemorrhagic stroke in 28.9%. Hypertension (73.7%) and ischemic heart disease and/or previous myocardial infarction (60.0%) were the most frequently recorded comorbidities. Pneumonia was the dominant documented infectious complication, recorded in 52.6% of patients, followed by urinary tract infection (11.6%), pressure sore-related infection (4.7%), and sepsis-related coding (6.8%). The median in-hospital survival interval was 6 days (IQR 3.0–10.75). Because year-by-year stratification was not sufficiently robust, the temporal component was interpreted only in aggregate form. These findings provide a descriptive hospital-based profile of documented infectious complications in a fatal stroke ICU cohort and support the need for more standardized infection documentation and better linkage between clinical and microbiological data in neurocritical care settings. Full article

Background: Subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality despite advances in neurocritical care. Vitamin D plays a role in immune modulation, endothelial function, and neuroprotection; however, its impact on outcomes following SAH remains poorly defined. We evaluated the association between low vitamin D status and clinical outcomes in patients with nontraumatic SAH. Methods: We conducted a retrospective propensity score-matched cohort study using the TriNetX Research Network database. Adult patients with nontraumatic SAH and at least one recorded serum 25-hydroxyvitamin D level obtained within 3 months on or before diagnosis were included. The low vitamin D cohort was defined as 0–20 ng/mL, and the comparator cohort as 20–40 ng/mL. Cohorts were matched 1:1 using propensity scores adjusted for demographic and clinical covariates, including chronic kidney disease, liver disease, osteoporosis, and intestinal malabsorption. The primary outcome was 30-day all-cause mortality. Secondary outcomes included seizures, hydrocephalus, cerebral edema, and external ventricular drain placement. Results: After matching, 2314 patients were included in each cohort. Thirty-day mortality occurred in 9.3% of patients in the low vitamin D cohort and 7.6% of patients in the comparator cohort (hazard ratio [HR] 1.229; 95% CI, 1.006–1.503; p = 0.043). Seizures were more frequent in the low vitamin D cohort (8.6% vs. 6.9%; odds ratio [OR] 1.274; 95% CI, 1.026–1.581; p = 0.028). Hydrocephalus was also more common among patients with low vitamin D (5.1% vs. 3.9%; OR 1.328; 95% CI, 1.003–1.758; p = 0.047). No significant differences were observed in cerebral edema or external ventricular drain placement. Conclusions: Low vitamin D status was associated with increased short-term mortality, seizure incidence, and hydrocephalus following nontraumatic SAH. These findings suggest that vitamin D status may represent a potential prognostic biomarker warranting prospective investigation. Full article

Percutaneous tracheotomy represents a critical airway procedure, yet training opportunities in pediatric patients remain limited due to the low incidence and high risk associated with the procedure. Simulation-based training plays a key role in enabling physicians to develop procedural skills in a safe environment. This study presents the design, fabrication, and validation of a high-fidelity physical simulator for pediatric percutaneous tracheotomy using the Frova screw technique. The simulator reproduces the anatomy of an eight-year-old patient in a hyperextended neck position, allowing rigid bronchoscope insertion, and includes relevant anatomical landmarks. The presence of a blood pocket enhances procedural realism. The modular design, with a reusable base and disposable cartridge, enables rapid reset between sessions while minimizing maintenance costs. Soft tissues were reproduced through silicone molding, while rigid components were fabricated using fused deposition modeling 3D printing. Validation was performed by 39 physicians using a structured five-point Likert scale questionnaire. The simulator achieved a mean score of 4.2/5, with item scores ranging from 3.6 to 4.7, indicating a high level of perceived realism, procedural fidelity, and educational value, as well as highlighting potential areas of improvement. These findings suggest that the proposed simulator is a useful tool for simulation-based education, with the potential to improve operator confidence and patient safety in complex airway emergencies. Full article

Background: Magnesium regulates neuronal excitability, NMDA receptor activity, and cerebrovascular tone. Dysmagnesemia is common in patients with acute brain injury (>65%), yet large randomized trials of magnesium neuroprotection have been neutral despite strong physiological rationale and consistent observational associations with outcomes. A key limitation may be diagnostic misclassification: the total serum magnesium poorly reflects the biologically active ionized fraction and may misclassify magnesium status in 20–85% of ICU patients during critical illness. Purpose: This narrative review synthesizes current evidence on magnesium physiology, measurement limitations, and clinical implications in neurocritical care. Overview: We discuss the mechanisms of magnesium depletion, outline the conceptual “two-hit” model (chronic deficiency plus acute ICU losses), and highlight the potential value of ionized magnesium for improved patient evaluation. Emerging syndrome-specific data suggest that magnesium disturbances are associated with prognostic signals. Improved phenotyping may help explain prior trial neutrality and support stratified approaches to magnesium monitoring and repletion. Future studies should evaluate magnesium-guided strategies and phenotype-driven trials to clarify the therapeutic role of magnesium in neurocritical care. Full article

Aneurysmal subarachnoid hemorrhage (SAH) remains a devastating cerebrovascular disorder with high morbidity and mortality, despite advances in aneurysm securing and neurocritical care. Clinical outcomes are determined by early brain injury (EBI), delayed cerebral ischemia (DCI), hydrocephalus, and long-term cognitive impairment, extending beyond the traditional focus on large-vessel vasospasm alone. Emerging evidence identifies the dysfunction of the glymphatic system and meningeal lymphatic pathway, the brain’s primary clearance pathways, as a central and unifying mechanism linking acute hemorrhagic injury to delayed and chronic neurological sequelae. Following SAH, acute intracranial pressure elevation, subarachnoid blood clot burden, loss of arterial pulsatility, venous congestion, astrocytic aquaporin-4 perivascular depolarization, and neuroinflammation converge to suppress cerebrospinal fluid–interstitial fluid exchange and outflow in glymphatic system and subsequent meningeal lymphatic drainage. Persistent clearance failure promotes the retention of blood breakdown products, inflammatory mediators, and metabolic waste, amplifying microvascular dysfunction, cortical spreading depolarizations, blood–brain barrier disruption, and secondary ischemic injury. Importantly, accumulating data highlight venous pathology and meningeal lymphatic impairment as critical, yet underappreciated, contributors to delayed injury and post-SAH hydrocephalus. In this review, we synthesize the current knowledge of the physiological organization of glymphatic and meningeal lymphatic systems, delineate the mechanistic and molecular drivers of their dysfunction after SAH, and discuss clinical implications for EBI, DCI, hydrocephalus, and long-term cognitive outcomes. We further outline future directions, including translational imaging, biomarker development, and therapeutic strategies targeting clearance pathways, to advance disease-modifying approaches in SAH. Full article

Background/Objectives: Prognostication in traumatic brain injury (TBI) remains challenging. The urine-to-serum osmolality (U/S) ratio may reflect hypothalamic–pituitary axis integrity, a critical but underexplored prognostic domain. We investigated whether the U/S ratio provides early prognostic value and enhances prediction when combined with conventional severity markers. Methods: This retrospective study included 128 adult TBI patients admitted to a neurosurgical intensive care unit (ICU) with simultaneous osmolality measurements within 6 h of admission. The primary outcome was ICU mortality; the secondary outcome was poor neurological outcomes (Glasgow Outcome Scale 1–3). Results: ICU mortality was 14.1% (18/128), and poor neurological outcome occurred in 41.8% (46/110). Non-survivors had significantly lower U/S ratios than survivors (1.09 ± 0.58 vs. 1.70 ± 0.68, p < 0.001). For ICU mortality, U/S ratios (AUC = 0.803) showed similar discriminative ability to GCS (AUC = 0.806). For poor neurological outcomes, the U/S ratio (AUC = 0.768) significantly outperformed both GCS (AUC = 0.641, p = 0.038) and the Acute Physiology and Chronic Health Evaluation (APACHE) II score (AUC = 0.553, p < 0.001). Combining the U/S ratio with GCS improved mortality prediction (AUC = 0.890), as did combinations with the APACHE II score (AUC = 0.847). The U/S ratio remained independently associated with ICU mortality and poor neurological outcomes after adjusting for GCS or APACHE II scores. Quartile analyses revealed a dose–response relationship, with ICU mortality of 34.4% in Q1 versus 3.1% in Q4 (p for trend < 0.001). Prognostic value was preserved in patients receiving osmotic therapy (n = 86). Conclusions: The U/S ratio is a simple, readily available biomarker that independently predicts mortality and poor neurological outcomes in TBI patients. Particularly for neurological outcome predictions, it outperforms GCS or the APACHE II score alone. Combined with established severity scores, it may serve as a practical bedside tool reflecting hypothalamic–pituitary function in neurocritical care. Full article

Background: Effective management of key physiological parameters, such as blood pressure, temperature, blood glucose, and gas exchange, is central to neurocritical care. However, the clinical impact of variability within guideline target ranges after an acute ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage remains unclear. Methods: In this multicenter observational study of nine German neurocritical care units, we analyzed in-range measurements over 96 h. Of 524 screened patients, 281 met the predefined criteria for sufficient in-range data. Variability in systolic blood pressure, mean arterial pressure, body temperature, blood glucose, partial arterial pressure of oxygen and carbon dioxide was quantified using the coefficient of variation. Associations between in-range variability of each physiological parameter and clinical outcomes including duration of mechanical ventilation, NIHSS score at discharge, and in-hospital mortality were evaluated using multivariable regression models. Results: Variability for all parameters peaked in the first 24 h and then remained largely stable; blood glucose showed a secondary rise after ~60 h. Greater in-range blood glucose variability was associated with in-hospital mortality in hemorrhagic stroke (adjusted OR 1.08; 95% CI 1.00–1.17; p = 0.04), while no other parameter’s variability was associated with the evaluated outcomes. Conclusions: Overall, in-range variability had limited short-term prognostic value, supporting current guideline-based management. Full article

The presence of traumatic brain injury (TBI) is a critical determinant of post-traumatic mortality and morbidity. Not only is TBI one of the leading causes of death among severely injured patients, but it also substantially impacts long-term outcomes following severe trauma. Neurocritical care has a profound effect on outcomes following brain injury; nevertheless, its application in preclinical studies remains infrequent. This review therefore discusses strategies to improve the translational relevance of experimental TBI research, including the integration of neurocritical care principles in animal models. The review further addresses the impact of observation periods after injury and the selection of appropriate animal models (large vs. small animal models). In addition, commonly used injury induction methods—including controlled cortical impact (CCI), fluid percussion injury (FPI), weight-drop models, and blast injury paradigms—are discussed in terms of their reproducibility and clinical relevance. Finally, the review explores whether age, comorbidities, and sex influence TBI outcomes—and, if so, how these variables should be incorporated into experimental designs to improve translational fidelity. Full article

Intensive Care Unit (ICU) readmissions following Intracerebral Hemorrhage (ICH) are associated with increased mortality and resource burden. Current prediction models predominantly rely on static admission features, failing to capture the temporal evolution of physiological instability. This study proposes a novel deep learning framework to predict ICU readmission by leveraging high-resolution time-series data from the MIMIC-III and MIMIC-IV databases. We developed a Stacked Gated Recurrent Unit (GRU) Architecture Ensemble, integrated with Time-series Generative Adversarial Networks (TimeGAN) to address the inherent class imbalance of readmission events. Our model achieved a state-of-the-art Area Under the Receiver Operating Characteristic Curve (AUC) of 0.912, significantly outperforming traditional machine learning baselines and static feature models. The sensitivity of 88.1% highlights the model’s efficacy in minimizing unsafe premature discharges. Furthermore, interpretability analysis using SHAP values identified Length of Stay, MELD Score, and Monocytes as critical predictors, revealing that readmission risk is driven by a complex interplay between systemic organ dysfunction and inflammatory response. These findings demonstrate that incorporating temporal dynamics and generative data augmentation significantly enhances risk stratification, offering a robust clinical decision support tool to optimize discharge timing in neurocritical care. Full article

Monitoring intracranial pressure (ICP) dynamics is critical for the management of traumatic brain injury, stroke, other neurosurgical conditions, and cerebral blood flow autoregulation; however, invasive ICP monitoring carries risks such as infection, hemorrhage, and sensor zero drift. Increasing evidence suggests that ICP waveform morphology provides clinically relevant information beyond mean ICP value alone. In this first-in-human prospective comparative clinical study, we evaluated the feasibility and accuracy of a novel, fully passive, non-invasive ICP pulse waveform monitoring system (Archimedes 02) based on the detection of eyeball mechanical movement. Fifteen intensive care unit patients (6 males, 9 females; mean age 57.1 ± 18.8 years) with clinically indicated invasive ICP monitoring or external ventricular drainage were enrolled. Three-minute monitoring sessions were performed to simultaneously acquire non-invasive ICP pulse waveforms, invasive ICP waveforms, and invasive radial artery blood pressure (ABP) waveforms. Averaged waveforms were derived for each patient and compared graphically and using correlation analysis. Non-invasive ICP pulse waves recorded with Archimedes 02 showed a strong correlation with invasive ICP waveforms ($\overline{\mathrm{R}}$ = 0.965). In contrast, correlations between non-invasive ICP and ABP waveforms ($\overline{\mathrm{R}}$ = 0.699), as well as between invasive ICP and ABP waveforms ($\overline{\mathrm{R}}$ = 0.749), were lower. These findings indicate that the non-invasive signal primarily reflects ICP dynamics rather than arterial blood pressure. This novel non-invasive ICP monitoring approach has the potential to enhance neurocritical care, particularly in settings where invasive monitoring is impractical or unavailable. Further validation in larger and more diverse patient populations is warranted. Full article