Neurological Death Research Articles

Cerebral Air Embolism: Process Change with Unintended Consequences.

During a cerebrovascular procedure, diligent care is made to ensure no air is present in lines and connectors. Should air enter the cerebral vasculature, cerebral air emboli can cause worsening neurological outcome or death. This communication outlines how a process change of refrigerating mixed heparin for storage lead to the presence of unintentional air, or off-gassing of the fluid. The off-gassing phenomenon was noted during procedure. Various hypotheses were considered, including manufacturing defect of lines, tubes and fluid preparation. Further investigation identified a new process in mixing of heparin bags and then refrigerated. The off-gassing was noted during the procedure when cold fluid flowed through tubing draped across a warming blanket. This article utilizes the explanatory research method to describe the cause and effect relationship. The aim is to provide knowledge of this phenomenon to prevent future occurrences. Fluids used for neuro endovascular procedures should be warmed to prevent off-gassing, which can lead to cerebral air embolus. Air formation or out-gassing can occur when cold fluids are warmed. During neuro endovascular procedure, this unintentional air can cause significant morbidity or mortality to the patient. Understanding and recognizing this phenomenon is important to prevent patient harm.

Explainable artificial intelligence for stroke prediction through comparison of deep learning and machine learning models

Failure to predict stroke promptly may lead to delayed treatment, causing severe consequences like permanent neurological damage or death. Early detection using deep learning (DL) and machine learning (ML) models can enhance patient outcomes and mitigate the long-term effects of strokes. The aim of this study is to compare these models, exploring their efficacy in predicting stroke. This study analyzed a dataset comprising 663 records from patients hospitalized at Hazrat Rasool Akram Hospital in Tehran, Iran, including 401 healthy individuals and 262 stroke patients. A total of eight established ML (SVM, XGB, KNN, RF) and DL (DNN, FNN, LSTM, CNN) models were utilized to predict stroke. Techniques such as 10-fold cross-validation and hyperparameter tuning were implemented to prevent overfitting. The study also focused on interpretability through Shapley Additive Explanations (SHAP). The evaluation of model’s performance was based on accuracy, specificity, sensitivity, F1-score, and ROC curve metrics. Among DL models, LSTM showed superior sensitivity at 96.15%, while FNN exhibited better specificity (96.0%), accuracy (96.0%), F1-score (95.0%), and ROC (98.0%) among DL models. For ML models, RF displayed higher sensitivity (99.9%), accuracy (99.0%), specificity (100%), F1-score (99.0%), and ROC (99.9%). Overall, RF outperformed all models, while DL models surpassed ML models in most metrics except for RF. DL models (CNN, LSTM, DNN, FNN) achieved sensitivities from 93.0 to 96.15%, specificities from 80.0 to 96.0%, accuracies from 92.0 to 96.0%, F1-scores from 87.34 to 95.0%, and ROC scores from 95.0 to 98.0%. In contrast, ML models (KNN, XGB, SVM) showed sensitivities between 29.0% and 94.0%, specificities between 89.47% and 96.0%, accuracies between 71.0% and 95.0%, F1-scores between 44.0% and 95.0%, and ROC scores between 64.0% and 95.0%. This study demonstrates the efficacy of DL and ML models in predicting stroke, with the RF models outperforming all others in key metrics. While DL models generally surpassed ML models, RF’s exceptional performance highlights the potential of combining these technologies for early stroke detection, significantly improving patient outcomes by preventing severe consequences like permanent neurological damage or death.

Real-world efficacy of transfusion with liberal or restrictive strategy in traumatic brain injury.

The short-term efficacy of red blood cell (RBC) transfusion among general traumatic brain injury (TBI) patients is unclear. We used the MIMIC database to compare the efficacy of liberal (10 g/dL) versus conservative (7 g/dL) transfusion strategy in TBI patients. The outcomes were neurological progression (decrease of Glasgow coma scale (GCS) of at least 2 points) and death within 28 days of ICU admission. Each eligible individual was cloned and assigned each of the replicates to one of the treatment arm. The imbalance induced by informative censoring was adjusted by inverse probability weighting. The standardized, weighted pooled logistic regression with 500 bootstrap resampling was used to estimate the cumulative risk difference and 95% confidence interval (CI). Of the 1141 eligible individuals, 29.0% received RBC transfusion. Compared with the restrictive group, the liberal strategy reduced early death (3 days: 5%, 95% CI: 2%-7%; 7 days: 6%, 95% CI: 3%-11%); however, no significant difference of mortality risk at 28-day or neurological progression risk at any time points was observed. The risk of coagulopathy at 3 days was increased by 7% (95% CI: 1%-19%) in the liberal group. The subgroup analysis indicated a beneficial effect of liberal transfusion on mortality in hemodynamically unstable patients. Compared with the restrictive strategy, the liberal strategy does not improve the short-term neurological prognosis and death among patients with TBI in a real-world situation. The liberal strategy may be beneficial to survival at very early stage or in hemodynamically unstable subgroup.

The PERFORMANCE II Trial: A Prospective Multicenter Investigation of a Novel Carotid Stent System.

Several randomized clinical trials have shown that the composite endpoint of death, stroke, and myocardial infarction (MI) is equivalent between carotid artery stenting and carotid endarterectomy. However, the risk of minor stroke has been consistently higher with carotid artery stenting. The authors sought to evaluate the safety and effectiveness of a novel carotid stent system comprised of a stent, an adjustable integrated embolic filter and a postdilation balloon, in patients at elevated risk for adverse events from carotid endarterectomy. PERFORMANCE II (Protection against Emboli during caRotid artery stenting using a 3-in-1 delivery system comprised oF a pOst-dilation balloon, integRated eMbolic filter, and A Novel Carotid stEnt II) was a prospective, multicenter, single-arm study. The primary endpoint was the composite of major adverse events defined as death, all stroke, and MI within 30days of the procedure, plus ipsilateral stroke through 12months. 305 patients were enrolled at 32 centers in the United States and Europe. The mean age was 69.6 ± 7.5 years; 65.9% were male, and 20% were symptomatic. The mean lesion length was 19.1 ± 6.7mm, and 34.5% of lesions were severely calcified. At 30days, there were 4minor strokes (1.3%), with no major strokes. There was 1 cardiac death on day 30, resulting in a stroke/death rate of 1.6% and a stroke/death/MI rate of 2.3%. The 12-month primary endpoint occurred in 2.8%; there were no major strokes, clinically driven target lesion revascularizations, stent thromboses, or neurological deaths. The 30-day all stroke plus ipsilateral stroke through 12months rate was 1.8%. The rate of major adverse events was extremely low, demonstrating the study system is a safe, effective, and durable treatment option for high-risk patients. (Protection against Emboli during caRotid artery stenting using a 3-in-1 delivery system comprised oF a pOst-dilation balloon, integRated eMbolic filter, and A Novel Carotid stEnt II [PERFORMANCE II]; NCT04201132).

Intravenous glibenclamide for cerebral oedema after large hemispheric stroke (CHARM): a phase 3, double-blind, placebo-controlled, randomised trial

No treatment is available to prevent brain oedema, which can occur after a large hemispheric infarction. Glibenclamide has previously been shown to improve functional outcome and reduce neurological or oedema-related death in patients younger than 70 years who were at risk of brain oedema after an acute ischaemic stroke. We aimed to assess whether intravenous glibenclamide could improve functional outcome at 90 days in patients with large hemispheric infarction. CHARM was a phase 3, double-blind, placebo-controlled, randomised trial conducted across 143 acute stroke centres in 21 countries. We included patients aged 18-85 years with a large stroke, defined either by an Alberta Stroke Program Early CT Score (ASPECTS) of 1-5 or by an ischaemic core lesion volume of 80-300 mL on CT perfusion or MRI diffusion-weighted imaging. Patients were randomly assigned in a 1:1 ratio to either intravenous glibenclamide (8·6 mg over 72 h) or placebo. The study drug was started within 10 h of stroke onset. The primary efficacy outcome was the shift in the distribution of scores on the modified Rankin Scale at day 90, as a measure of functional outcome. The primary efficacy outcome was analysed in a modified intention-to-treat population, which included all randomly assigned patients aged 18-70 years. The safety population comprised all randomly assigned patients who received a dose. This trial is registered with ClinicalTrials.gov (NCT02864953). The trial was stopped early by the sponsor for strategic and operational reasons (slow enrolment because of COVID-19), before any unblinding or knowledge of the trial results. Between Aug 29, 2018, and May 23, 2023, 535 patients were enrolled and randomly assigned, of whom 518 received a dose (safety population) and 431 were aged 18-70 years and comprised the modified intention-to-treat population (217 were assigned glibenclamide and 214 placebo). The mean age of patients was 58·7 (SD 9·0) years in the placebo group and 58·0 (9·5) years in the glibenclamide group; the median US National Institutes of Health Stroke Scale (NIHSS) score was 19 (IQR 16-23) in the placebo group and 19 (IQR 16-22) in the glibenclamide group; and the mean time from stroke onset to study drug start was 8·9 h (SD 2·1) in the placebo group and 9·2 h (2·1) in the glibenclamide group. Intravenous glibenclamide was not associated with a favourable shift in the modified Rankin scale at 90 days (common odds ratio [OR] 1·17 [95% CI 0·80-1·71], p=0·42). 90-day mortality was 29% (61 of 214) in the placebo group and 32% (70 of 217) in the glibenclamide group (hazard ratio 1·20 [0·85-1·70]; p=0·30). Serious adverse events in the prespecified safety population were consistent with the known safety profile of glibenclamide and included hypoglycaemia in 15 (6%) of 259 patients in the glibenclamide group and in four (2%) of 259 patients in the placebo group, leading to dose interruption or reduction in seven (3%) patients in the glibenclamide group and in one (<1%) in the placebo group. Intravenous glibenclamide did not improve functional outcome in patients aged 18-70 years after large hemispheric infarction, although the trial was underpowered to make definitive conclusions because it was stopped early. Future prospective evaluation could be warranted to identify a possible benefit of intravenous glibenclamide in specific subgroups. Biogen.

Tracheostomy Tube Monitoring Accessory to Detect Accidental Decannulation and Obstruction Emergencies in Ventilator-Independent Pediatric Patients

Introduction: Some of the leading causes of tracheostomy-related complications in pediatric populations are accidental decannulation and obstruction events that result in permanent neurological damage or death if not mitigated quickly enough. Despite the severity of tracheostomy tube emergency events, there is currently no effective medical technology available that can specifically detect accidental decannulation or obstruction in a tracheostomized patient that is not ventilator dependent. Therefore, a pediatric tracheal breathing model system was developed to assist with testing new tracheostomy tube technologies for identifying emergency events. Methods: A custom carbon dioxide monitoring tracheostomy tube attachment was engineered to collect breathing waveform data during emergency events (e.g., improper insertion, accidental decannulation, and mucus obstruction). Anatomically accurate pediatric tracheal models for various age groups (0-3 months, 2-4 years, and 10-12 years old) were developed with modelling software and a 3D printer. A breathing simulator was integrated with the tracheal models to generate age-dependent respiration patterns during simulated tracheostomy tube emergencies. Results: Carbon dioxide readings from the custom tracheostomy tube attachment indicated distinct waveform recordings during simulated tracheostomy tube emergency events for all age groups tested. During incorrect insertion, accidental decannulation, and complete blockage of a tracheostomy tube, exhaled carbon dioxide readings remained static at ambient levels. Partial mucus obstruction of a tracheostomy tube decreased exhaled carbon dioxide waveform amplitude relative to unobstructed conditions. Conclusions: The tracheostomy tube attachment successfully recorded respiration patterns during simulated tracheostomy tube emergencies in pediatric patients of varying age. Breathing waveform data collected from the model system will aid in the development of emergency airway event detection software integrated in the tracheostomy tube sensing accessory.

Current knowledge of vertebral osteomyelitis: a review.

As life expectancy increases worldwide, the elderly population in every country is growing in both the size and proportion. This review aims to provide a comprehensive overview of the microbiology, clinical presentation, diagnostic strategies, and therapeutic approaches to vertebral osteomyelitis, summarizing the latest evidence to guide effective treatment. A comprehensive literature search was conducted using the Medline and Embase databases to identify relevant studies on vertebral osteomyelitis. The search included the following keywords: "vertebral osteomyelitis," "spinal infection," "discitis," "spondylitis," " spondylodiscitis," and "spinal epidural abscess." Both retrospective and prospective studies, case series, and reviews were considered. This condition is commonly caused by bacteria such as Staphylococcus aureus or gram-negative bacilli, but can also be caused by other pathogens like fungi and parasites. The onset of vertebral osteomyelitis is insidious, with low specificity in clinical manifestations, often making early diagnosis difficult. Delayed or inadequate treatment may lead to sepsis, permanent neurological damage, or even death. Treatment strategies emphasize the importance of identifying the causative pathogen to guide effective antimicrobial therapy. Current consensus does not advocate for empirical antibiotic treatment unless patients exhibit signs of neurological impairment or severe sepsis. Severe cases involving neurological paralysis, spinal instability, or sepsis may require surgical intervention. Vertebral osteomyelitis requires prompt diagnosis and treatment for a good prognosis. Delayed diagnosis and treatment can lead to permanent neurological deficits or death. Identifying the causative organism is crucial for guiding appropriate antimicrobial therapy. In addition to conservative and surgical treatments, local drug delivery systems offer new approaches to managing spinal osteomyelitis.

Prognostic value of gray–white matter ratio measured by brain MRI-based CT structures in comatose patients after cardiac arrest

BackgroundPost-cardiac arrest care advancements have improved resuscitation outcomes, but many survivors still face severe neurological deficits or death from brain injury. Herein, we propose a consistent prognosis prediction approach using magnetic resonance imaging (MRI) to analyze anatomical regions represented by the gray and white matter, and subsequently apply it on computed tomography (CT) to calculate the gray–white matter ratio (GWR). We compared this novel method with traditional measures to validate its ability to predict the prognosis of patients resuscitated after cardiac arrest. MethodsConducted retrospectively at two South Korean tertiary university hospitals from January 2018 to December 2022, the study included adult cardiac arrest survivors treated with therapeutic target temperature management. Patients underwent brain CT within 2 h and brain MRI within 3 days of return of spontaneous circulation. The outcome was the neurological status at discharge. Statistical analyses included receiver operating characteristic curve analysis and determining cutoff values to predict poor neurological outcomes. ResultsOverall, 51 of the 421 adult comatose cardiac arrest survivors examined met the inclusion criteria. Among these, 33 and 18 exhibited good and poor neurological outcomes, respectively. Demographic and cardiac arrest characteristics were compared between the two groups, revealing significant differences. Analyses of gray and white matter attenuation and GWR measurements highlighted significant differences between the good and poor outcome groups. ConclusionOur study introduces a novel method for measuring GWR using MRI-based brain CT, demonstrating superior prognostic accuracy in predicting neurological outcomes in patients with post-cardiac arrest syndrome compared to traditional methods.

Experiences of mothers of long-term surviving patients with cerebral adrenoleukodystrophy: a qualitative study

BackgroundAdrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder. Its cerebral form presents as a learning and behavioral disorder that, if untreated, leads to rapid neurological regression, disability, and death within 10 years of diagnosis. Therefore, the disease significantly impacts patients’ quality of life, making quality of life assessment crucial for effective medical treatment and care. However, no disease-specific quality of life scale exists for ALD. Therefore, we conducted qualitative research to determine the experiences of patients and their families as a preliminary step toward developing one.ResultsFour mothers of patients with cerebral ALD were interviewed. Based on classification using the qualitative content analysis method, the verbatim transcripts were grouped into four themes: support needs for patients, support needs for families, the impact of treatment, and challenges within support systems.ConclusionsSupport for patients and family members is required after ALD is diagnosed. In addition to addressing symptoms, daily life support and caregiving burden should be considered. Furthermore, several challenges and opportunities exist for improving treatment and support systems. Therefore, combining appropriate supporters and support systems according to the progressive and hereditary characteristics of ALD is crucial.

LncRNA MSTRG.13,871/miR155-5p/Grip1 network involved in the post-cardiac arrest brain injury

Post-cardiac arrest brain (PCABI) is a severe medical condition characterized by a significant risk of neurological impairment and death. Nevertheless, the specific process and essential molecules responsible for its development are not fully understood. Profiling based on competing endogenous RNAs (ceRNA) has been implicated in the onset and progression of neurological disorders, yet its role in PCABI remains unclear. In this study, we performed RNA transcriptome sequencing analysis to identify differentially expressed genes in the rat model for cardiac arrest and cardiopulmonary resuscitation (CA/CPR). A hub ceRNA regulatory network was constructed using miRWalk 2.0 and Cytohubba plug-in in Cytoscape. Subsequently, real-time quantitative reverse transcription-polymerase chain reaction and dual-luciferase activity assays validated MSTRG.13,871, miR-155-5p, and Grip1 as differentially expressed in CA/CPR group, with MSTRG.13,871 capable of targeting both miR-155-5p and Grip1. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed the ceRNA network enrichment in immunoregulation mechanisms such as mitochondrion, apoptotic process, and negative regulation cell death. Our research highlights the mechanism of PCABI by revealing a critical regulatory axis involving MSTRG.13,871-miR-155-5p-Grip1 in the hippocampus CA1 region after CA/CPR in rats, proposing a feasible controlled mechanism, which may serve as a theoretical basis for designing innovative therapies.

A Method for Compensating Hemoglobin Interference in Total Serum Bilirubin Measurement Using a Simple Two-Wavelength Reflectance Photometer.

Neonatal hyperbilirubinemia (NH) is a common condition in newborns, with elevated bilirubin levels potentially causing neurological damage or death. Accurate and timely measurements of total serum bilirubin are essential to prevent these outcomes. Direct spectrophotometry, a reliable method for measuring bilirubin, is particularly useful in constrained settings due to its potential for portable low-cost instrumentation. However, this method is susceptible to interference from hemoglobin, often present due to hemolysis. Typically, this interference is reduced using complex optical filters, reagents, multiple wavelengths, or combinations thereof, which increase costs and complexity while reducing usability. This study presents a hemoglobin compensation algorithm applied to a simple, portable, two-wavelength (465 and 590 nm) reflectance photometer designed to receive 30 µL of plasma or whole blood samples and perform the measurement without any reagents. Testing across five bilirubin and hemoglobin levels (4.96 to 28 mg/dL and 0.06 to 0.99 g/dL, respectively) demonstrated that the algorithm effectively reduces hemoglobin interference and overestimation errors. The overall root mean square error was reduced from 4.86 to 1.45 mg/dL, while the measurement bias decreased from -4.46 to -0.10 mg/dL. This substantial reduction in overestimation errors supports future clinical trials with neonatal blood samples.

Safety and Efficacy of Carotid Artery Stenting without the Use of Protective Embolic Devices

Abstract Background Stroke is the third most common cause of disability and second most common cause of death worldwide. Extra cranial carotid stenosis accounts for about 15-20% of cerebral ischemic events. Aim of the Work To evaluate the efficacy, and safety of carotid artery stenting without using cerebral protection device in selected patients with symptomatic high risk carotid artery stenosis. Patients and Methods All available patients during the study duration will be included in the study, NIR unit archives of all available carotid artery stenosis cases meeting the inclusion who underwent carotid artery stenting without using embolic protection devices as well as patients who will be referred to NIR Unit with carotid artery stenosis meeting the inclusion and exclusion criteria and candidates for the procedure in the proceeding 6 months. Results In our study of assessing safety and efficacy of unprotected CAS all cases were clinically assessed using the NIHSS as a baseline before CAS. Immediately after the intervention, seventy-eight cases (97.5%) had no change in their initial NIHSS and two cases (2.5%) showed mild deterioration of the NIHSS with no cases showing major disabling strokes nor neurological related deaths peri procedurally and during follow up period. Conclusion Carotid stenting without the use of embolic protection devices performed by skillful experienced hands can achieve satisfactory safety and efficacy outcomes as long as we rely on tailored approach for patient selection especially in settings of low resources.

Evolving Strategies for the Management of Carotid Artery Injuries due to Penetrating Trauma

Penetrating carotid injuries, although less common than other forms of vascular trauma, carry a significant risk of morbidity and mortality, with the potential for severe central neurologic deficits and death rates ranging from 10% to 50%. Penetrating trauma to the carotid arteries occurs in up to 20% of all trauma neck cases and when these injuries are not promptly diagnosed and treated, the consequences can be dire. Penetrating carotid injuries are often the result of violence, such as knife wounds or low-velocity firearm injuries, particularly in urban settings. In contrast, in military or combat environments, high-velocity firearm injuries are more common, and these are typically more severe and life-threatening. The urgency in managing carotid injuries lies in the need to quickly restore and maintain cerebral blood flow, prevent stroke, and manage hemorrhage, all while navigating the complex and delicate structures of the neck and concomitant injuries. In this manuscript, we will explore the anatomic considerations, clinical presentation, and evolving strategies for the surgical and endovascular management of penetrating carotid trauma. The focus will be on how modern diagnostic tools and treatment approaches, particularly the shift from traditional zone-based management to a more flexible "no-zone" approach, have improved outcomes for patients with these potentially fatal injuries.

Evaluation of knowledge of risk factors and warning signs of stroke among paramedical students

Stroke is a medical emergency caused by a blockage or rupture in the blood vessels that supply blood to the brain. This prevents brain tissue from receiving oxygen, leading to the death of brain cells within minutes and causing neurological damage, disability, or death. Aim: The aim of the present study was to assess baseline knowledge regarding stroke risk factors, symptoms, treatment, and information resources. The “golden hour” is a time span of 60 minutes or less after stroke symptoms begin. There are two types of stroke, namely ischemic and hemorrhagic stroke. Ischemic stroke is further divided into thrombotic and embolic stroke. Hemorrhagic stroke is further divided into intracerebral hemorrhage and subarachnoid hemorrhage. Methods: The research method used in the study is a quantitative research approach. Purposive sampling techniques were used and 1050 participants were assessed The questionnaire consists of demographic details such as department, level of education, family history, and knowledge questions based on risk factors and management. Results: This study comprises 1040 patients who fulfill the inclusion criteria. The survey assessed the knowledge of risk factors and warning signs of stroke among future healthcare professionals (pharmacy, nursing, and AHS). The current findings reported that 51.8% of the paramedical students had knowledge about stroke, while the majority of them reported poor knowledge overall. The findings identified that 57.4% of the student population were knowledgeable about risk factors, 69.9% were knowledgeable about warning signs, and 51.8% were knowledgeable about management. These results were similar to many previous studies conducted around the world. Conclusion: Better knowledge about stroke, recognizing the risk factors, and being able to provide immediate management are essential for paramedical students. This is crucial for reducing stroke incidence and improving survival rates of patients by providing better medical help through early detection, rapid intervention, and better long-term health outcomes not only in a medical setup but also in their respective environments.

Stereotactic Radiosurgery for 1-10 Brain Metastases to avoid Whole-Brain Radiotherapy - Results of the CYBER-SPACE Randomized Phase 2 Trial.

Stereotactic Radiosurgery (SRS) is an emerging alternative to whole-brain radiotherapy (WBRT) for treating multiple brain metastases (BM), reducing toxicity and improving tumor control. The CYBER-SPACE trial compared SRS based on either SPACE or MPRAGE MRI sequence for avoiding or delaying WBRT in patients with 1-10 BM. Patients with 1-10 untreated BM were randomized 1:1 to receive SRS of all lesions based on either SPACE or MPRAGE MRI sequences. If subsequently new BM occurred, SRS was repeated. WBRT was indicated upon occurrence of >10 new BM, leptomeningeal disease or exhausted SRS-radiotolerance. The primary outcome was freedom from WBRT indication (WBRTi). Secondary outcomes included overall survival (OS), safety, and quality of life. 202 patients were randomized; SPACE n=99, MPRAGE n=103. 12-month WBRTi-free survival was 77.1% (95%-CI: 69.5%-83.1%) overall, 78.5% (95%-CI: 66.7%-86.5%) for SPACE, and 76.0% (95%-CI: 65.2%-83.9%) for MPRAGE (HR=0.84, 95%-CI: 0.43-1.63, p=0.590). Patients with 5-10 BM had shorter WBRTi-free survival (HR=3.13, 95%-CI: 1.53-6.40, p=0.002). Median OS was 13.1 months overall, 10.5 months for SPACE, and 15.2 months for MPRAGE (HR=1.10, 95%-CI: 0.78-1.56, p=0.585). Neurologic death rate was 10.1%. Predictors for longer OS included Karnofsky Performance Status >80% (HR=0.51, 95%-CI: 0.33-0.77, p=0.002) and concurrent immunotherapy (HR=0.34, 95%-CI: 0.23-0.52, p<0.001). The more sensitive SPACE sequence did not improve outcomes over MPRAGE. SRS with thorough monitoring and immediate re-treatment for new lesions decreases the need for WBRT and achieves low neurologic death rates. SRS should be considered a favorable alternative to WBRT for patients with 1-10 BM.

Etiology and characteristics of non-aneurysmal thunderclap headache presenting to an acute setting

ObjectivesTo describe the characteristics and causes of non-aneurysmal thunderclap headache (TCH) and compare serious from benign underlying causes. MethodsRetrospective cohort study of consecutive adult patients with TCH presenting to a tertiary care academic medical center between 2010 and 2020. Aneurysmal subarachnoid hemorrhage cases were excluded. Cases were categorized into serious or benign; serious TCH was defined as any condition in which delayed diagnosis and treatment could result in neurological disability or death. Risk factors for serious TCH were analyzed. We adhere to standardized guidelines for reporting observational studies. ResultsA total of 932 patients presented with TCH. After exclusion of 393 patients with aneurysmal-type subarachnoid hemorrhage, 539 were included in the analysis. One-half (n = 275, 51.0 %) had a serious cause. Median age was 51 years, 69.0 % were female. Most frequent diagnoses were intracranial hemorrhage (n = 102, 18.9 %), reversible cerebral vasoconstriction syndrome (n = 97, 18.0 %), and idiopathic TCH (n = 102, 38.6 %). A multivariable logistic regression model for prediction of serious TCH included age, hypertension, migraines, recurrent TCH, level of consciousness and other clinical exam findings, and achieved an AUROC of 0.732. This score had a sensitivity of 79.9 % (95 % CI 73.5–83.5 %) for the identification of serious TCH. A 0.5-point increase in the risk score was associated with a 73 % increase in the odds of serious TCH (odds ratio 1.73, 95 % CI 1.53–1.95, p < 0.001). ConclusionOur study describes the relative frequency of presentation and etiologies among patients with TCH This score can aide clinicians in recognising patients with potentially serious cause of TCH, for whom additional imaging and neurological consultation is necessary.

Elucidating the Substrate Envelope of Enterovirus 68-3C Protease: Structural Basis of Specificity and Potential Resistance.

Enterovirus-D68 (EV68) has emerged as a global health concern over the last decade with severe symptomatic infections resulting in long-lasting neurological deficits and death. Unfortunately, there are currently no FDA-approved antiviral drugs for EV68 or any other non-polio enterovirus. One particularly attractive class of potential drugs are small molecules inhibitors, which can target the conserved active site of EV68-3C protease. For other viral proteases, we have demonstrated that the emergence of drug resistance can be minimized by designing inhibitors that leverage the evolutionary constraints of substrate specificity. However, the structural characterization of EV68-3C protease bound to its substrates has been lacking. Here, we have determined the substrate specificity of EV68-3C protease through molecular modeling, molecular dynamics (MD) simulations, and co-crystal structures. Molecular models enabled us to successfully characterize the conserved hydrogen-bond networks between EV68-3C protease and the peptides corresponding to the viral cleavage sites. In addition, co-crystal structures we determined have revealed substrate-induced conformational changes of the protease which involved new interactions, primarily surrounding the S1 pocket. We calculated the substrate envelope, the three-dimensional consensus volume occupied by the substrates within the active site. With the elucidation of the EV68-3C protease substrate envelope, we evaluated how 3C protease inhibitors, AG7088 and SG-85, fit within the active site to predict potential resistance mutations.

Hyperglycemia in a NOD Mice Model of Type-I Diabetes Aggravates Collagenase-Induced Intracerebral Hemorrhagic Injury.

Intracerebral hemorrhage (ICH) is a severe type of stroke with high mortality. Persistent hyperglycemia following ICH is linked to deteriorated neurological functions and death. However, the exacerbating effect of hyperglycemia on ICH injury at the molecular level is still unclear. Therefore, this study explores the impact of diabetes on ICH injury using a non-obese diabetic (NOD) mouse model of type I diabetes mellitus. NOD and non-diabetic (non-obese resistant) mice subjected to ICH by intrastriatal injection of collagenase were sacrificed three days following the ICH. Brains were collected for hematoma volume measurement and immunohistochemistry. Neurobehavioral assays were conducted 24 h before ICH and then repeated at 24, 48 and 72 h following ICH. NOD mice showed increased hematoma volume and impairment in neurological function, as revealed by rotarod and grip strength analyses. Immunohistochemical staining showed reduced glial cell activation, as indicated by decreased GFAP and Iba1 staining. Furthermore, the expression of oxidative/nitrosative stress markers represented by 3-nitrotyrosine and inducible nitric oxide synthase was reduced in the diabetic group. Overall, our findings support the notion that hyperglycemia exacerbates ICH injury and worsens neurological function and that the mechanism of injury varies depending on the type of diabetes model used.

Impact of extracorporeal cardiopulmonary resuscitation on neurological prognosis and survival in adult patients after cardiac arrest: An individual pooled patient data meta-analysis

BackgroundWe aimed to estimate the effect of extracorporeal cardiopulmonary resuscitation (ECPR) on neurological outcome and mortality, when compared to conventional cardiopulmonary resuscitation (CCPR), using an individual patient data meta-analysis (IPDMA). MethodsA systematic literature search was performed up to the 20th of October 2022 in the PubMed, EMBASE and CENTRAL databases. For observational studies with unmatched populations, a propensity score including age, location of arrest and initial rhythm was used to match ECPR and CCPR patients in a 1:1 ratio. The primary and secondary outcomes were unfavorable neurological outcome (Cerebral Performance Category of 3–5) and mortality, respectively, which were both collected at different time-points. ResultsData from 17 studies, including 2064 matched cardiac arrest (CA) patients (1031 ECPR and 1033 CCPR cases) were included. In comparison to CCPR, ECPR was associated with a decreased odds of unfavorable neurological outcome (847, 82.2% vs. 897, 86.8% − OR 0.68 [95%CI 0.53–0.87]; p = 0.002) and death (803, 77.9% vs. 860, 83.3% − OR 0.68 [95%CI 0.54–0.86]; p = 0.001). These results were consistent across most of the prespecified subgroups. Moreover, the odds of both unfavorable neurological outcome and mortality were significantly influenced by initial rhythm, cause of arrest and combinations of lactate levels on admission and duration of resuscitation. ConclusionsThis IPDMA showed that ECPR was associated with significantly lower rates of unfavorable neurological outcome and mortality in refractory CA. The overall effect could be influenced by CA characteristics and the severity of the initial injury.

Long-Term Mortality and Morbidity after Carotid Endarterectomy for Symptomatic and Asymptomatic Carotid Stenosis

To investigate whether the occurrence of ischemic stroke due to carotid stenosis is a marker of the severity of atherosclerotic disease and of an excess risk of cardiovascular morbidity and mortality, and of all-cause mortality, after carotid endarterectomy (CEA). Patients who had undergone a CEA from June 2015 to august 2016 were included. Patients were classified into 2 groups, namely symptomatic and asymptomatic. Neurological event, myocardial infarction, and death during early follow up were monitored. Major adverse cardiovascular events, major limb eventss, and all-cause mortality were compared for patients with a CEA for an asymptomatic carotid stenosis versus those with a symptomatic stenosis. Among the 190 patients included, 86 (51%) had a CEA for an asymptomatic stenosis and 84 (49%) for a symptomatic stenosis. During the first 30days, the rate of all-cause death or ischemic stroke was similar in both groups (1%, P=0.986). After 30days, there were a total of 35 major adverse cardiovascular events (21.3%) and 15 major limb events (9.1%) during mean follow up of 53 (22.6) months. Overall cardiovascular morbidity and mortality was 30.4% and did not differ between groups (P=0.565). New ischemic stroke occurred in 11 patients (9.1%) and was significantly more frequent in the asymptomatic group (9 (14.8%) versus 2 (3.6%) in the symptomatic group, (odds ratio: 4.96; confidence interval 95% [1.04-23.77]; P=0.013)). Overall all-cause mortality was 24% in both groups (P=0.93) CONCLUSIONS: The occurrence of ischemic stroke of carotid origin before revascularization does not appear to be associated with an excess risk of cardiovascular morbidity or mortality or all-cause mortality after surgery.