Neurological Injury Research Articles

Intensive Interdisciplinary Rehabilitation in the Pediatric Hematology/Oncology Setting: Feasibility and Perceived Benefit of the Acute Neurological Injury Service.

(1) Background: Intensive interdisciplinary rehabilitation services more effectively promote recovery from acquired brain injury than a single discipline approach. However, research literature is lacking regarding the perceived feasibility and utility of an interdisciplinary approach across disciplines for patients within a tertiary care pediatric hematology/oncology setting. (2) Methods: The Acute Neurological Injury (ANI) service applied an acquired brain injury/inpatient rehabilitation interdisciplinary approach to a pediatric hematology/oncology population, with a focus on interdisciplinary communication, shared goal setting, and coordinated transition planning. Caregivers whose children received coordinated ANI program care were interviewed regarding the perceived feasibility and utility of ANI program components. (3) Results: An interdisciplinary approach to a pediatric hematology/oncology population is feasible for caregivers and for providers of rehabilitation and psychosocial services within a tertiary care cancer hospital setting. Parents perceived benefits from aspects of this approach including coordinated interdisciplinary care planning, the implementation of an interdisciplinary goal, parent brain injury education, neuropsychological assessment reports, and weekly cognitive intervention sessions. Parents were interested in both having a peer mentor while managing new cancer diagnoses and later serving in a mentor role for a newly diagnosed family. (4) Conclusions: An interdisciplinary acquired brain injury approach to a pediatric hematology/oncology population is feasible with perceived benefits to families managing new cancer diagnoses.

FACTFINDERS FOR PATIENT SAFETY: Minimizing risks with cervical epidural injections

This series of FactFinders presents a brief summary of the evidence and outlines recommendations to minimize risks associated with cervical epidural injections.Evidence in support of the following facts is presented.Minimizing Risks with Cervical Interlaminar Epidural Steroid Injections – 1) CILESIs should be performed at C6-C7 or below, with C7-T1 as the preferred access point due to the more generous dorsal epidural space at this level compared to the more cephalad interlaminar segments. This reduces the risk of the minor complication of dural puncture and the major complication of spinal cord injury due to inadvertent needle placement. 2) LF gaps are most prevalent in the midline cervical spine. This can result in diminished tactile feedback with loss of resistance (LOR), increasing the risk for inadvertent dural puncture or spinal cord injury. Based on current evidence, needle placement in the paramedian portion of the interlaminar space is safest to avoid LF gaps. 3) An optimal AP trajectory view and the physician's ability to discern engagement in the LF and subsequent LOR are crucial. Confirmation of minimal needle insertion depth relative to the ventral margin of the lamina with either a lateral or contralateral oblique (CLO) safety view is critical to minimize the risk of inadvertently inserting the needle too ventral. 4) There have been closed claims and case reports of patients who have suffered catastrophic neurologic injuries while receiving CILESIs under deep sedation. If sedation is administered, the least amount necessary should be utilized to ensure the patient can provide verbal feedback during the procedure. 5) CILESIs are an elective procedure; therefore, necessity and likelihood of benefit must be foremost considerations. Current guidelines recommend holding ACAP therapy before CILESIs due to the potentially catastrophic complications associated with epidural hematoma (EH) formation. However, there is also a risk of severe systemic complications with ceasing ACAP in specific clinical scenarios. The treating physician is obligated to determine if the procedure is indicated and can ultimately decide to delay the intervention or not perform the procedure if the benefit does not outweigh the risks.Minimizing Risks with Cervical Transforaminal Epidural Steroid Injections – the Role of Preprocedural Review of Advanced Imaging -- Variations in vascular anatomy may warrant a modified approach to CTFESI. Preprocedural review of cross-sectional imaging can provide critical information for safe injection angle planning specific to individual patients and may help to decrease the risk of unintended vascular events with potentially catastrophic outcomes.Safety of Multi-level or Bilateral Fluoroscopically-Guided Cervical Transforaminal Epidural Steroid Injections -- Safe performance of a CTFESI procedure requires the ability to detect inadvertent arterial injection. Contrast medium placed into the epidural space and/or along the exiting spinal nerves during an initial CTFESI may obscure the detection of inadvertent cannulation of a radiculomedullary artery by a subsequent CTFESI. While no available literature directly addresses the potential risk that exists with a multi-level or bilateral CTFESI, caution is still warranted.

High frequency oscillations may improve somatosensory evoked potential detection of good outcomes in disorders of consciousness secondary to acute neurologic injury

BackgroundSomatosensory evoked potentials (SEPs) are highly specific predictors of poor prognosis in hypoxic-ischemic coma when cortical responses (N20s) are absent. However, bilateral N20 presence is nonspecific for good outcomes. High-frequency oscillations (HFOs) in the SEP waveform predict neurologic recovery in animals, but clinical applications are poorly understood. We sought to develop a clinical measure of HFOs to potentially improve detection of good outcomes in coma. Materials and MethodsWe collected SEP waveform data from all comatose inpatients (GCS<=8) who underwent neurologic prognostication from 2020 to 2022 at Johns Hopkins Hospital. We developed a novel measure − HFO evoked to spontaneous ratios (HFO-ESRs) – and applied this to those patients with bilaterally present N20s using both standard univariate classification and cubic kernal vector machine (SVM) models to predict the last documented in-hospital Glasgow Coma Scale (GCS) prior to discharge or death. ResultsOf 58 total patients, 34 (58.6%) had bilaterally present N20s. Of these, 14 had final GCS>=9, and 20 had final GCS<=8. Mean age was 52 (+/− 17) years, 20.1% female. Etiologies of coma were primarily global hypoxic-ischemic brain injury (79.4%), intracranial hemorrhage (11.8%), and traumatic brain injury (2.9%). In univariate classification, the addition of averaged HFO-ESRs to bilaterally present N20s predicted final GCS>=9 with 68% specificity. The SVM model further improved specificity to 85%. ConclusionsIn this pilot investigation, we developed a novel clinical measure of SEP HFOs. Incorporation of this measure may improve the specificity of the SEP to predict in-hospital GCS outcomes in coma, but requires further validation in specific neurologic injuries and with longitudinal outcomes.

Altered Mental Status in the Solid-Organ Transplant Recipient.

Patients undergoing solid-organ transplantation (SOT) face a tumultuous journey. Prior to transplant, their medical course is characterized by organ dysfunction, diminished quality of life, and reliance on organ support, all of which are endured in hopes of reaching the haven of organ transplantation. Peritransplant altered mental status may indicate neurologic insults acquired during transplant and may have long-lasting consequences. Even years after transplant, these patients are at heightened risk for neurologic dysfunction from a myriad of metabolic, toxic, and infectious causes. This review provides a comprehensive examination of causes, diagnostic approaches, neuroimaging findings, and management strategies for altered mental status in SOT recipients. Given their complexity and the numerous etiologies for neurologic dysfunction, liver transplant patients are a chief focus in this review; however, we also review lesser-known contributors to neurological injury across various transplant types. From hepatic encephalopathy to cerebral edema, seizures, and infections, this review highlights the importance of recognizing and managing pre- and posttransplant neurological complications to optimize patient outcomes.

Enhancing Neuroprotection in Cardiac and Aortic Surgeries: A Narrative Review

Background: Neurological injury poses a significant challenge in aortic surgery, encompassing spinal cord injury from thoraco-abdominal aorta intervention or stroke post-surgery on the arch and ascending aorta. Despite ample literature and proposals, a fully effective strategy for preventing or treating neurological injury remains elusive. This narrative review aims to analyze the most common neuroprotective strategies implemented for aortic arch surgery and aortic surgery. Results: Results from the reviewed studies showed that several strategies, including deep hypothermia cardiac induction (DHCA) and cerebral perfusion techniques (retrograde cerebral perfusion, RCP, and selective anterograde cerebral perfusion, SACP) aim to mitigate these risks. Monitoring methods such as electroencephalogram (EEG), somatosensory evoked potential (SEPs), and near-infrared spectroscopy (NIRS) offer valuable insights into cerebral function during surgery, aiding in the management of hypothermia and perfusion. Pharmacological agents and blood gas management (pH stat vs. alpha stat, hematocrit level, glycemic control) are crucial in preventing post-operative complications. Additionally meticulous management of atheromatous debris is essential to minimize embolic risks during surgery. Methods: For this narrative review, PubMed, Scopus, and Medline have been used to search articles about neuroprotection strategies in aortic and aortic arch surgeries. The search was narrowed to articles between 1975 and 2024. A total of 3418 articles were initially identified to be potentially relevant for this review. A total of 66 articles were included and were found to match the inclusion criteria. Conclusions: While an overabundance of neuroprotection strategies exists for cardiac surgery, particularly in procedures involving the aorta and the arch, their efficacy varies, with some well-documented and others still under scrutiny. Further research is imperative to advance our comprehension and refine prevention techniques for cardiac-surgery-related brain injury. This is crucial given its substantial contribution to both mortality and, notably, post-operative morbidity.

What is the Impact of Early Rehabilitation and Rehabilitation Management on Outcome after Polytrauma?

Patients with polytrauma and other severe musculoskeletal injuries often suffer from permanently impaired functionality and quality of life. This results in long-term damage with high costs for the social system. A narrative review will show the impact of targeted coordination in the rehabilitation process from early rehabilitation to long-term case management on patients with severe musculoskeletal injuries. A systematic database search of MEDLINE and the Cochrane Library identified studies of multiple injuries that compared the outcome of early rehabilitation and rehabilitation management with other types of care. Studies of predominantly neurologic injury types, soldiers, and mild injury types with an ISS less than 9 or AIS less than 3 were excluded. Four studies were included and analyzed. They looked at functionality, quality of life, psychological impairment, and costs. While treatment and total costs were higher for early rehabilitation and rehabilitation management, no better results for improved function, psychological condition and quality of life could be demonstrated in the group comparison. An effect estimate is possible due to small group differences and the small number of individual studies included. There are insufficient studies to draw conclusions about the effectiveness of the early interventions. Future studies are needed that take into greater account structures of standard care and national differences in social security systems, as well as the chosen rehabilitation management interventions.

The regulatory role of miR-21 in ferroptosis by targeting FTH1 and the contribution of microglia-derived miR-21 in exosomes to arsenic-induced neuronal ferroptosis

Arsenic is recognized as a hazardous environmental toxicant strongly associated with neurological damage, but the mechanism is ambiguous. Neuronal cell death is one of the mechanisms of arsenic-induced neurological injury. Ferroptosis is involved in the pathophysiological process of many neurological diseases, however, the role and regulatory mechanism of ferroptosis in nerve injury under arsenic exposure remains uncovered. Our findings confirmed the role of ferroptosis in arsenic-induced learning and memory disorder and revealed miR-21 played a regulatory role in neuronal ferroptosis. Further study discovered that miR-21 regulated neuronal ferroptosis by targeting at FTH1, a finding which has not been documented before. We also found an extra increase of ferroptosis in neuronal cells conditionally cultured by medium collected from arsenic-exposed microglial cells when compared with neuronal cells directly exposed to the same dose of arsenic. Moreover, microglia-derived exosomes removal or miR-21 knockdown in microglia inhibited neuronal ferroptosis, suggesting the role of intercellular communication in the promotion of neuronal ferroptosis. In summary, our findings highlighted the regulatory role of miR-21 in ferroptosis and the contribution of microglia-derived miR-21 in exosomes to arsenic-induced neuronal ferroptosis.

Neural mechanisms responsible for vagus nerve stimulation-dependent enhancement of somatosensory recovery

Impairments in somatosensory function are a common and often debilitating consequence of neurological injury, with few effective interventions. Building on success in rehabilitation for motor dysfunction, the delivery of vagus nerve stimulation (VNS) combined with tactile rehabilitation has emerged as a potential approach to enhance recovery of somatosensation. In order to maximize the effectiveness of VNS therapy and promote translation to clinical implementation, we sought to optimize the stimulation paradigm and identify neural mechanisms that underlie VNS-dependent recovery. To do so, we characterized the effect of tactile rehabilitation combined with VNS across a range of stimulation intensities on recovery of somatosensory function in a rat model of chronic sensory loss in the forelimb. Consistent with previous studies in other applications, we find that moderate intensity VNS yields the most effective restoration of somatosensation, and both lower and higher VNS intensities fail to enhance recovery compared to rehabilitation without VNS. We next used the optimized, moderate intensity to evaluate the mechanisms that underlie recovery. We find that moderate intensity VNS enhances transcription of Arc, a canonical mediator of synaptic plasticity, in the cortex, and that transcript levels were correlated with the degree of somatosensory recovery. Moreover, we observe that blocking plasticity by depleting acetylcholine in the cortex prevents the VNS-dependent enhancement of somatosensory recovery. Collectively, these findings identify neural mechanisms that subserve VNS-dependent somatosensation recovery and provide a basis for selecting optimal stimulation parameters in order to facilitate translation of this potential intervention.

Safety of Phenobarbital Versus Benzodiazepines for Alcohol Withdrawal in Critically Ill Patients With Primary Neurologic Injuries.

Alcohol withdrawal syndrome (AWS) is a complication of alcohol use disorder that manifests as a range of symptoms. Symptom-triggered benzodiazepines (BZDs) are often used as first-line treatment of AWS. However, recent literature suggests phenobarbital (PHB) may be safer and more efficacious, but studies are limited by exclusion of patients with neurological injuries. We aimed to evaluate the safety of PHB compared to BZDs for the management of AWS among patients with primary neurologic injuries. Retrospective cohort study of patients with primary neurologic injuries admitted to an ICU who received PHB or symptom-triggered BZD for AWS between December 2013 and February 2020. The primary outcome was incidence of oversedation, defined as Richmond Agitation Sedation Scale (RASS) scores from -5 to -3 within 24 hours of initial PHB or BZD dose. Secondary outcomes included largest decrease in RASS, need for mechanical ventilation, and additional sedative use within 24 hours of initial PHB or BZD dose. A multivariable analysis was performed to evaluate the association of PHB administration with the primary outcome. Among 600 patients treated for AWS, 84 patients were included in our analysis (PHB, n = 56; BZD, n = 28). In the unadjusted analysis, there were no differences between the PHB and BZD groups for the primary outcome of oversedation (21.4 vs. 7.1%, P = 0.13), or secondary outcomes of decrease in RASS (P = 0.34), or new ventilator requirement (P = 0.55). Patients who received PHB had higher rates of additional sedative use (P < 0.01). Multivariable regression revealed an increase in oversedation among intubated patients (P = 0.014), while PHB administration was not independently associated with oversedation (P = 0.516). Phenobarbital did not independently increase the risk of oversedation compared to BZD for AWS in patients with primary neurologic injuries. Future studies should determine optimal dosing of PHB in this population.

End-tidal carbon dioxide and arterial to end-tidal carbon dioxide gradient are associated with mortality in patients with neurological injuries

Pre-hospital end-tidal carbon dioxide (EtCO2) monitoring and arterial to end-tidal carbon dioxide gradient (Pa-EtCO2) have been associated with mortality in patients with traumatic brain injury. Our study aimed to analyze the association between alveolar EtCO2 or Pa-EtCO2 and mortality in patients admitted in intensive care unit (ICU) with neurological injuries. In our retrospective analysis from using large de-identified ICU databases (MIMIC-III and -IV and eICU databases), we included 2872 ICU patients with neurological injuries, identified according to the International Classification of Diseases (ICD-9 and -10), who underwent EtCO2 monitoring. We performed logistic regression and extended Cox regression to assess the association between mortality and candidate covariates, including EtCO2 and Pa-EtCO2. In-hospital mortality was 26% (n = 747). In univariate analysis, both the Pa-EtCO2 gradient and EtCO2 levels during the first 24 h were significantly associated with mortality (for a 1 mmHg increase: OR = 1.03 [CI95 1.016–1.035] and OR = 0.94 [CI95 0.923–0.953]; p < 0.001). The association remained significant in multivariate analysis. The time-varying evolution of EtCO2 was independently associated with mortality (for a 1 mmHg increase: HR = 0.976 [CI95 0.966–0.985]; p < 0.001). The time-varying Pa-EtCO2 gradient was associated with mortality only in univariate analysis. In neurocritical patients, lower EtCO2 levels at admission and throughout the ICU stay were independently associated with mortality and should be avoided.

Mild (34 °C) versus moderate hypothermia (24 °C) in a swine model of extracorporeal cardiopulmonary resuscitation

BackgroundThe role of hypothermia in post-arrest neuroprotection is controversial. Animal studies suggest potential benefits with lower temperatures, but high-fidelity ECPR models evaluating temperatures below 30 °C are lacking. ObjectivesTo determine whether rapid cooling to 24 °C initiated upon reperfusion reduces brain injury compared to 34 °C in a swine model of ECPR. MethodsTwenty-four female pigs had electrically induced VF and mechanical CPR for 30 min. Animals were cannulated for VA-ECMO and cooled to either 34 °C for 4 h (n = 8), 24 °C for 1 h with rewarming to 34 °C over 3 h (n = 7), or 24 °C for 4 h without rewarming (n = 9). Cooling was initiated upon VA-ECMO reperfusion by circulating ice water through the oxygenator. Brain temperature and cerebral and systemic hemodynamics were continuously monitored. After four hours on VA-ECMO, brain tissue was obtained for examination. ResultsTarget brain temperature was achieved within 30 min of reperfusion (p = 0.74). Carotid blood flow was higher in the 24 °C without rewarming group throughout the VA-ECMO period compared to 34 °C and 24 °C with rewarming (p < 0.001). Vasopressin requirement was higher in animals treated with 24 °C without rewarming (p = 0.07). Compared to 34 °C, animals treated with 24 °C with rewarming were less coagulopathic and had less immunohistochemistry-detected neurologic injury. There were no differences in global brain injury score. ConclusionsDespite improvement in carotid blood flow and immunohistochemistry detected neurologic injury, reperfusion at 24 °C with or without rewarming did not reduce early global brain injury compared to 34 °C in a swine model of ECPR.

Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Outcomes and Endpoints.

Clinical management of persons with disorders of consciousness (DoC) is dedicated largely to optimizing recovery. However, selecting a measure to evaluate the extent of recovery is challenging because few measures are designed to precisely assess the full range of potential outcomes, from prolonged DoC to return of preinjury functioning. Measures that are designed specifically to assess persons with DoC are often performance-based and only validated for in-person use. Moreover, there are no published recommendations addressing which outcome measures should be used to evaluate DoC recovery. The resulting inconsistency in the measures selected by individual investigators to assess outcome prevents comparison of results across DoC studies. The National Institute of Neurological Disorders and Stroke (NINDS) common data elements (CDEs) is an amalgamation of standardized variables and tools that are recommended for use in studies of neurologic diseases and injuries. The Neurocritical Care Society Curing Coma Campaign launched an initiative to develop CDEs specifically for DoC and invited our group to recommend CDE outcomes and endpoints for persons with DoCs. The Curing Coma Campaign Outcomes and Endpoints CDE Workgroup, consisting of experts in adult and pediatric neurocritical care, neurology, and neuroscience, used a previously established five-step process to identify and select candidate CDEs: (1) review of existing NINDS CDEs, (2) nomination and systematic vetting of new CDEs, (3) CDE classification, (4) iterative review and approval of panel recommendations, and (5) development of case report forms. Among hundreds of existing NINDS outcome and endpoint CDE measures, we identified 20 for adults and 18 for children that can be used to assess the full range of recovery from coma. We also proposed 14 new outcome and endpointCDE measures for adults and 5 for children. The DoC outcome and endpoint CDEs are a starting point in the broader effort to standardize outcome evaluation of persons with DoC. The ultimate goal is to harmonize DoC studies and allow for more precise assessment of outcomes after severe brain injury or illness. An iterative approach is required to modify and adjust these outcome and endpoint CDEs as new evidence emerges.

Impaired microglial glycolysis promotes inflammatory responses after intracerebral haemorrhage via HK2-dependent mitochondrial dysfunction

IntroductionIntracerebral haemorrhage (ICH) is a devastating disease that leads to severe neurological deficits. Microglia are the first line of defence in the brain and play a crucial role in neurological recovery after ICH, whose activities are primarily driven by glucose metabolism. However, little is known regarding the status of glucose metabolism in microglia and its interactions with inflammatory responses after ICH. ObjectivesThis study investigated microglial glycolysis and its mechanistic effects on microglial inflammation after ICH. MethodsWe explored the status of glucose metabolism in the ipsilateral region and in fluorescence-activated-cell-sorting-isolated (FACS-isolated) microglia via 2-deoxy-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) analyses and gamma emission, respectively. Energy-related targeted metabolomics, along with 13C-glucose isotope tracing, was utilised to analyse glycolytic products in microglia. Mitochondrial membrane potential and mitochondrial reactive oxygen species (MitoROS) accumulation was assessed by flow cytometry. Behavioural, western blotting, gene regulation, and enzymatic activity analyses were conducted with a focus on microglia. ResultsNeurological dysfunction was strongly correlated with decreased FDG-PET signals in the perihaematomal region, where microglial uptake of FDG was reduced. The decreased quantity of glucose-6-phosphate (G-6-P) in microglia was attributed to the downregulation of glucose transporter 1 (GLUT1) and hexokinase 2 (HK2). Enhanced inflammatory responses were driven by HK2 suppression via decreased mitochondrial membrane potential, which could be rescued by MitoROS scavengers. HK inhibitors aggravated neurological injury by suppressing FDG uptake and enhancing microglial inflammation in ICH mice. ConclusionThese findings indicate an unexpected metabolic status in pro-inflammatory microglia after ICH, consisting of glycolysis impairment caused by the downregulation of GLUT1 and HK2. Additionally, HK2 suppression promotes inflammatory responses by disrupting mitochondrial function, providing insight into the mechanisms by which inflammation may be facilitated after ICH and indicating that metabolic enzymes as potential targets for ICH treatment.

Clinical trauma severity of indoor and outdoor injurious falls requiring emergency medical service response

BackgroundInjurious falls represent a significant public health burden. Research and policies have primarily focused on falls occurring indoors despite evidence that outdoor falls account for 47–58% of all falls requiring some medical attention. This study described the clinical trauma severity of indoor versus outdoor injurious falls requiring Emergency Medical Services (EMS) response.MethodsUsing the 2019 National Emergency Medical Services Information System (NEMSIS) dataset, we identified the location of patients injured from falls that required EMS response. We classified injury severity using (1) the Revised Trauma Score for Triage (T-RTS): ≤ 11 indicated the need for transport to a Trauma Center; (2) Glasgow Coma Scale (GCS): ≤ 8 and 9–12 indicated severe and moderate neurologic injury; and (3) patient clinical acuity by EMS: Dead, Critical, Emergent, Low.ResultsOf 1,854,909 encounters for patients with injurious falls, the vast majority occurred indoors (n = 1,596,860) compared to outdoors (n = 152,994). For patients who fell indoors vs outdoors on streets or sidewalks, the proportions were comparable for moderate or severe GCS scores (3.0% vs 3.9%), T-RTS scores indicating need for transport to a Trauma Center (5.2% vs 5.9%) and EMS acuity rated as Emergent or Critical (27.7% vs 27.1%). Injurious falls were more severe among male patients compared to females and males injured by falling on streets or sidewalks had higher percentages for moderate or severe GCS scores (5.2% vs 1.9%) and T-RTS scores indicating the need for transport to a Trauma Center (7.3% vs 3.9%) compared to falling indoors. Young and middle-aged patients who fell on streets or sidewalks had higher proportions for a T-RTS score indicating the need for Trauma Center care compared to those in this subgroup who fell indoors. Yet older patients injured by falling indoors were more likely to have a T-RTS score indicating the need for transport to a Trauma Center than older patients who fell on streets or sidewalks.ConclusionsThere was a similar proportion of patients with severe injurious falls that occurred indoors and outdoors on streets or sidewalks. These findings suggest the need to determine outdoor environmental risks for outdoor falls to support location-specific interventions.

Effect of propofol infusion vs ketamine plus dexmedetomidine infusion on the amplitude of motor evoked potential in pediatric patients undergoing tethered spinal cord surgeries; a randomized, double blind controlled study

Background &amp; objective: The use of intraoperative neurophysiologic monitoring (IOM) has increased over the past two decades for the detection and prevention of iatrogenic neurologic injuries. Motor evoked potentials (MEP) are extremely sensitive to changes in physiological variables and inhalational agents reduce MEPs in a dose dependent manner. So IV anesthetics (propofol or ketamine) and opioids (fentanyl or remifentanil), are frequently used in spinal surgeries under MEPs monitoring. We compared the effects of propofol and fentanyl to those of ketamine, dexmedetomidine, and fentanyl in terms of minimizing their effects on MEP amplitude and hemodynamic stability during surgery Methodology: This double blind, randomized, prospective study was conducted on 46 children, who were randomly allocated into 2 groups Ketamine–dexmedetomidine group: (n = 23) Maintenance throughout the procedure, by infusing Dexmedetomidine (0.4 -0.6 μg/.kg /.hr) ketamine, (1 -2m/.kg/.hr.) and giving bolus of fentanyl, (1-2μg/.kg/ ). Propofol-group:(n = 23) Maintenance throughout the procedure, By infusing propofol (100 ug L/kg/min) and giving bolus of fentanyl, (1-2μg/.kg/ ), with keeping mean arterial blood pressure changes within 25% of the baseline in both groups. Results: Right and left quadriceps muscle measurements were insignificantly different between both groups at base line and were significantly higher in Group KD than Group P at skin incision, surgical manipulation and surgical closure. Right and left adductor hallucis muscle measurements were insignificantly different between both groups at base line and were significantly higher in Group KD than Group P at 5 mins, 10 mins, 15 mins, skin incision, surgical manipulation and surgical closure (P value &lt;0.001). Intraoperative fentanyl consumption was significantly lower in Group KD than Group P. Conclusion: The combination of dexmedetomidine and ketamine infusion is efficacious, safe, and has minimal effect on evoked potentials compared with the propofol-based TIVA group during spine pediatrics surgery. In addition, this combination increases the reliability and accuracy of MEP monitoring with hemodynamic stability and adequate post-operative pain relief. Using dexmedetomidine and ketamine infusions during pediatric spine surgery might successfully replace the typical propofol-based TIVA, although more studies are required . Registration: ClinicalTrials.gov registration number NCT05591001. Keywords: Motor evoked potential, dexmedetomidine, ketamine, propofol. Citation: Saleh AH, Hammad SH, Hassan PF. Effect of propofol infusion vs ketamine plus dexmedetomidine infusion on the amplitude of motor evoked potential in pediatric patients undergoing tethered spinal cord surgeries; a randomized, double blind controlled study. Anaesth. pain intensive care 2024;28(4):692−699; DOI: 10.35975/apic.v28i4.2218 Received: May 08, 2023; Reviewed: February 02, 2024; Accepted: July 03, 2924

Topical application of daphnetin hydrogel for traumatic brain injury.

Traumatic brain injury (TBI) causes neuronal cell damage and dysfunction. According to previous studies, daphnetin (Dap) has a protective effect in neurological injury. However, the in vivo bioavailability of daphnetin is not high. The purpose of this study was to determine whether administering daphnetin directly into the site of injury via a hydrogel drug carrier could improve its therapeutic impact. Tripolycerol monostearates / daphnetin (TM/Dap) hydrogels were prepared and characterised using water bath heating, scanning electron microscopy (SEM) and small animal in vivo imaging techniques. The TBI model was established using the Feeney free fall impact method. Using the Morris water maze test, the mNSS neurological deficit rating scale, haematoxylin-eosin staining, and liver and kidney function tests, the therapeutic benefit of TM/Dap and its toxic side effects were assessed. The therapeutic effects of TM/Dap were further investigated using wet and dry gravimetric methods, Evans blue staining, protein immunoblotting, immunofluorescence staining techniques and ELISA. The efficacy of the TM/Dap hydrogel in gradually releasing daphnetin in the context of traumatic brain damage was shown by both in vitro and in vivo tests. Behavioral experiments showed that the learning and spatial memory abilities of TM/Dap hydrogel treated mice were significantly improved in the water maze experiment. And TM/Dap hydrogel has high biosafety for organisms. The results of the therapeutic mechanism of action showed that TM/Dap hydrogel showed more significant efficacy in reducing the neuroinflammatory response caused by TNF-α, IL-6 and other factors, as well as promoting the recovery of post-traumatic neurological function. The use of hydrogel as a drug carrier for daphnetin showed more significant efficacy in reducing neuroinflammatory response, protecting nerve tissue and promoting post-traumatic neurological recovery compared with traditional drug delivery methods.

Comparative Efficacy of Wound Drainage and Non-Drainage in Posterior Spinal Surgery

Background: The recent trend has been toward recommendation of nondrainage in spinal surgery. However, the use of drains following posterior spinal surgery is still controversial. It has been claimed that wound drainage confers no significant advantages, increases the risk of infection and the need for blood transfusion with the attendant risks of this therapy. Suction drainage is used to minimize infection, prevention of wound swelling, improvement of the local wound environment, prevent hematoma and /or seroma formation. The aim of this study was to determine the incidence of post-operative complications after posterior lumbar instrumentation with and without a subfascial drain. Methods: This is prospective analysis of 32 adult (≥18 years old) spine patients that underwent elective and emergency posterior lumbar instrumentation at Kathmandu Medical College Teaching Hospital, from January to December 2023. There were randomly assigned 16 (50%) patients who had a post-operative drain and 16 (50%) patients who did not have a postoperative drain (No-Drain: n=16; Drain-Use: n=16). Patient demographics, comorbidities, intra- and post-operative complication rates were collected for each patient. The primary outcome investigated in this study was pain, the need for post-operative transfusion, dressing changes, surgery – discharge interval, the rate of post-operative complications, specifically surgical site infections (SSI) and hematoma formation. Data was analyzed using SPSS statistics version 29 (IBM Corp., New York). Results: Our study revealed that no significant differences regarding wound infection (P = 1), hematoma, neurological injury, estimated blood loss (P = 0.3), or dry and moderate dressing drainage between the groups. There were no 30-day hospital readmission or incidence of 30-day wound dehiscence, draining wound or bleeding between both patient groups. Conclusions: There is no obvious advantage of the application of suction drains for spinal surgery. There was no significant difference in the rate of infection or wound healing and no patient developed a postoperative neurologic deficit. However, a decision of wound drainage or wound non-drainage should be individualized for each patient because many factors affect the outcomes.

Iron Accumulation and Metabolic Alterations in Aneurysmal Subarachnoid Hemorrhage

Background Aneurysmal subarachnoid hemorrhage (aSAH) is a severe type of stroke that is associated with poor outcome. A subset of patients with aSAH will develop secondary complications, most notably delayed cerebral ischemia (DCI), which potentiates neurological injury. In this study, we investigate the relationship between cerebrospinal fluid (CSF) iron accumulation, brain metabolism, and neuronal injury in patients with aSAH with or without DCI. Methods We collected longitudinal CSF samples of patients immediately after hospitalization and 5 to 8 days after onset of ictus. CSF was analyzed with electron paramagnetic resonance spectroscopy and metabolomics to determine the presence of redox‐active iron species and metabolic alterations associated with aSAH and DCI. Neuronal pathology induced by iron overload was characterized in neuronal and meningeal cell models. Results Electron paramagnetic resonance spectroscopy identified higher levels of an Fe(III) protoporphyrin IX (hemin)‐like molecule in the CSF of patients who developed DCI compared with patients who did not show secondary ischemic injury after aSAH or controls without neurological disease. Treatment of a human neuronal cell line with Fe(III)‐containing hemin resulted in the disruption of the axonal mitochondrial network and loss of viability. This was cell‐type dependent as a meningeal cell line was resistant to hemin treatment, despite both cell types upregulating the iron ferroxidase ceruloplasmin. Metabolomic profiling of the same CSF samples uncovered significant dysregulation of metabolic pathways associated with energy generation and amino acid utilization, consistent with mitochondrial dysfunction. Using machine learning, we identified a set of metabolites that predicted intensive care unit length of stay. Conclusion aSAH leads to the accumulation of an Fe(III)‐containing heme species in the CSF of a subset of patients who subsequently develop DCI. The accumulation of an Fe(III) protoporphyrin induces axonal mitochondrial dysfunction, leading to cell death. aSAH alters the CSF metabolome involved in mitochondrial function and a subset of these metabolites are predictive of intensive care unit stay. These results identify potential biomarkers for mitochondrial pathology and provide insight into alterations in brain iron metabolism triggered by aSAH.

Application and Development of Cell Membrane Functionalized Biomimetic Nanoparticles in the Treatment of Acute Ischemic Stroke.

Ischemic stroke is a serious neurological disease involving multiple complex physiological processes, including vascular obstruction, brain tissue ischemia, impaired energy metabolism, cell death, impaired ion pump function, and inflammatory response. In recent years, there has been significant interest in cell membrane-functionalized biomimetic nanoparticles as a novel therapeutic approach. This review comprehensively explores the mechanisms and importance of using these nanoparticles to treat acute ischemic stroke with a special emphasis on their potential for actively targeting therapies through cell membranes. We provide an overview of the pathophysiology of ischemic stroke and present advances in the study of biomimetic nanoparticles, emphasizing their potential for drug delivery and precision-targeted therapy. This paper focuses on bio-nanoparticles encapsulated in bionic cell membranes to target ischemic stroke treatment. It highlights the mechanism of action and research progress regarding different types of cell membrane-functionalized bi-onic nanoparticles such as erythrocytes, neutrophils, platelets, exosomes, macrophages, and neural stem cells in treating ischemic stroke while emphasizing their potential to improve brain tissue's ischemic state and attenuate neurological damage and dysfunction. Through an in-depth exploration of the potential benefits provided by cell membrane-functionalized biomimetic nanoparticles to improve brain tissue's ischemic state while reducing neurological injury and dysfunction, this study also provides comprehensive research on neural stem cells' potential along with that of cell membrane-functionalized biomimetic nanoparticles to ameliorate neurological injury and dysfunction. However, it is undeniable that there are still some challenges and limitations in terms of biocompatibility, safety, and practical applications for clinical translation.

MicroRNA-128-3p Affects Neuronal Apoptosis and Neurobehavior in Cerebral Palsy Rats by Targeting E3 Ubiquitin-Linking Enzyme Smurf2 and Regulating YY1 Expression.

This study was dedicated to investigating the effects of microRNA-128-3p (miR-128-3p) on neuronal apoptosis and neurobehavior in cerebral palsy (CP) rats via the Smurf2/YY1 axis.In vivo modeling of hypoxic-ischemic (HI) CP was established in neonatal rats. Neurobehavioral tests (geotaxis reflex, cliff avoidance reaction, and grip test) were measured after HI induction. The HI-induced neurological injury was evaluated by HE staining, Nissl staining, TUNEL staining, immunohistochemical staining, and RT-qPCR. The expression of miR-128-3p, Smurf2, and YY1 was determined by RT-qPCR and western blot techniques. Moreover, primary cortical neurons were used to establish the oxygen and glucose deprivation (OGD) model in vitro, cell viability was detected by CCK-8 assay, neuronal apoptosis was assessed by flow cytometry and western blot, and the underlying mechanism between miR-128-3p, Smurf2 and YY1 was verified by bioinformatics analysis, dual luciferase reporter assay, RIP, Co-IP, ubiquitination assay, western blot, and RT-qPCR.In vivo, miR-128-3p and YY1 expression was elevated, and Smurf2 expression was decreased in brain tissues of hypoxic-ischemic CP rats. Downregulation of miR-128-3p or overexpression of Smurf2 improved neurobehavioral performance, reduced neuronal apoptosis, and elevated Nestin and NGF expression in hypoxic-ischemic CP rats, and downregulation of Smurf2 reversed the effects of downregulation of miR-128-3p on neurobehavioral performance, neuronal apoptosis, and Nestin and NGF expression in hypoxic-ischemic CP rats, while overexpression of YY1 reversed the effects of Smurf2 on neurobehavioral performance, neuronal apoptosis, and Nestin and NGF expression in hypoxic-ischemic CP rats. In vitro, downregulation of miR-128-3p effectively promoted the neuronal survival, reduced the apoptosis rate, and decreased caspase3 protein expression after OGD, and overexpression of YY1 reversed the ameliorative effect of downregulation of miR-128-3p on OGD-induced neuronal injury. miR-128-3p targeted to suppress Smurf2 to lower YY1 ubiquitination degradation and decrease its expression.Inhibition of miR-128-3p improves neuronal apoptosis and neurobehavioral changes in hypoxic-ischemic CP rats by promoting Smurf2 to promote YY1 ubiquitination degradation and reduce YY1 expression.