Bacterial Aggregation in Cerebral Spinal Fluid: The Extent it Occurs and the Clinical Ramifications.

Bacteria can form aggregates in synovial fluid that are resistant to antibiotics, but the ability to form aggregates in cerebral spinal fluid (CSF) is poorly defined. Consequently, the aims of this study were to assess the propensity of four bacterial species to form aggregates in CSF under various conditions. To achieve these aims, bacteria were added to CSF in microwell plates and small flasks at static and different dynamic conditions with the aid of an incubating shaker. The aggregates that formed were assessed for antibiotic resistance and the ability of tissue plasminogen activator (TPA) to disrupt these aggregates and reduce the number of bacteria present when used with antibiotics. The results of this study show that under dynamic conditions all four bacteria species formed aggregates that were resistant to high concentrations of antibiotics. Yet with static conditions, no bacteria formed aggregates and when the CSF volume was increased, only Staphylococcus aureus formed aggregates. Interestingly, the aggregates that formed were easily dispersed by TPA and significant (p < 0.005) decreases in colony-forming units were seen when a combination of TPA and antibiotics were compared to antibiotics alone. These findings have clinical significance in that they show bacterial aggregation does not habitually occur in central nervous system infections, but rather occurs under specific conditions. Furthermore, the use of TPA combined with antibiotics may be advantageous in recalcitrant central nervous system infections and this provides a pathophysiological explanation for an unusual finding in the CLEAR III clinical trial.

Behavioral Assessment With the Coma Recovery Scale-Revised Is Safe and Feasible in Critically Ill Patients With Disorders of Consciousness.

OBJECTIVES: Accurate classification of disorders of consciousness (DoC) is key in developing rehabilitation plans after brain injury. The Coma Recovery Scale-Revised (CRS-R) is a sensitive measure of consciousness validated in the rehabilitation phase of care. We tested the feasibility, safety, and impact of CRS-R-guided rehabilitation in the ICU for patients with DoC after acute hemorrhagic stroke. DESIGN: Retrospective cohort study. SETTING: This single-center study was conducted in the neurocritical care unit at the University of Maryland Medical Center. PATIENTS: We analyzed records from consecutive patients with subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH), who underwent serial CRS-R assessments during ICU admission from April 1, 2018, to December 31, 2021, where CRS-R less than 8 is vegetative state/unresponsive wakefulness syndrome (VS/UWS); CRS-R greater than or equal to 8 is a minimally conscious state (MCS). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes included adverse events during CRS-R evaluations and associations between CRS-R and discharge disposition, therapy-based function, and mobility. We examined the utility of CRS-R compared with other therapist clinical assessment tools in predicting discharge disposition. Seventy-six patients (22 SAH, 54 ICH, median age = 59, 50% female) underwent 276 CRS-R sessions without adverse events. Discharge to acute rehabilitation occurred in 4.4% versus 41.9% of patients with a final CRS-R less than 8 and CRS-R greater than or equal to 8, respectively (odds ratio [OR] 13.4; 95% CI, 2.7-66.1; p < 0.001). Patients with MCS on final CRS-R completed more therapy sessions during hospitalization and had improved mobility and functional performance. Compared with other therapy assessment tools, the CRS-R had the best performance in predicting discharge disposition (area under the curve: 0.83; 95% CI, 0.72-0.94; p < 0.0001). CONCLUSIONS: Early neurorehabilitation guided by CRS-R appears to be feasible and safe in the ICU following hemorrhagic stroke complicated by DoC and may enhance access to inpatient rehabilitation, with the potential for lasting benefit on recovery. Further research is needed to assess generalizability and understand the impact on long-term outcomes.

Longitudinal Assessment of Glymphatic Changes Following Mild Traumatic Brain Injury: Insights from PVS burden and DTI-ALPS Imaging.

Traumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery. In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6-12 months (6-12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis. Our key findings include: 1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. 2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. 3) The increase in the ALPS index from acute (14Day) to the chronic (6-12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information, highlighting their distinct roles in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.

Super Refractory Status Epilepticus Improved After Emergency Use of Ganaxolone: Case Report.

We present a case of a 34-year-old man with epilepsy who developed super refractory status epilepticus in the setting of COVID-19 pneumonia in whom aggressive therapy with multiple parenteral, enteral, and non-pharmacologic interventions were utilized without lasting improvement in clinical examination or electroencephalogram (EEG). The patient presented with multiple recurrences of electrographic status epilepticus throughout a prolonged hospital stay. Emergency use authorization was obtained for intravenous ganaxolone, a neuroactive steroid that is a potent modulator of both synaptic and extrasynaptic GABAA receptors. Following administration of intravenous ganaxolone according to a novel dosing paradigm, the patient showed sustained clinical and electrographic improvement.

Utilizing ultra-early continuous physiologic data to develop automated measures of clinical severity in a traumatic brain injury population.

Determination of prognosis in the triage process after traumatic brain injury (TBI) is difficult to achieve. Current severity measures like the Trauma and injury severity score (TRISS) and revised trauma score (RTS) rely on additional information from the Glasgow Coma Scale (GCS) and the Injury Severity Score (ISS) which may be inaccurate or delayed, limiting their usefulness in the rapid triage setting. We hypothesized that machine learning based estimations of GCS and ISS obtained through modeling of continuous vital sign features could be used to rapidly derive an automated RTS and TRISS. We derived variables from electrocardiograms (ECG), photoplethysmography (PPG), and blood pressure using continuous data obtained in the first 15 min of admission to build machine learning models of GCS and ISS (ML-GCS and ML-ISS). We compared the TRISS and RTS using ML-ISS and ML-GCS and its value using the actual ISS and GCS in predicting in-hospital mortality. Models were tested in TBI with systemic injury (head abbreviated injury scale (AIS) ≥ 1), and isolated TBI (head AIS ≥ 1 and other AIS ≤ 1). The area under the receiver operating characteristic curve (AUROC) was used to evaluate model performance. A total of 21,077 cases (2009-2015) were in the training set. 6057 cases from 2016 to 2017 were used for testing, with 472 (7.8%) severe TBI (GCS 3-8), 223 (3.7%) moderate TBI (GCS 9-12), and 5913 (88.5%) mild TBI (GCS 13-15). In the TBI with systemic injury group, ML-TRISS had similar AUROC (0.963) to TRISS (0.965) in predicting mortality. ML-RTS had AUROC (0.823) and RTS had AUROC 0.928. In the isolated TBI group, ML-TRISS had AUROC 0.977, and TRISS had AUROC 0.983. ML-RTS had AUROC 0.790 and RTS had AUROC 0.957. Estimation of ISS and GCS from machine learning based modeling of vital sign features can be utilized to provide accurate assessments of the RTS and TRISS in a population of TBI patients. Automation of these scores could be utilized to enhance triage and resource allocation during the ultra-early phase of resuscitation.

Comparison of induction agents for rapid sequence intubation in refractory status epilepticus: A single-center retrospective analysis.

Endotracheal intubation, frequently required during management of refractory status epilepticus (RSE), can be facilitated by anesthetic medications; however, their effectiveness for RSE control is unknown. We performed a single-center retrospective review of patients admitted to a neurocritical care unit (NCCU) who underwent in-hospital intubation during RSE management. Patients intubated with propofol, ketamine, or benzodiazepines, termed anti-seizure induction (ASI), were compared to patients who received etomidate induction (EI). The primary endpoint was clinical or electrographic seizures within 12 h post-intubation. We estimated the association of ASI on post-intubation seizure using logistic regression. A sub-group of patients undergoing electroencephalography during intubation was identified to evaluate the immediate effect of ASI on RSE. We screened 697 patients admitted to the NCCU for RSE and identified 148 intubated in-hospital (n = 90 ASI, n = 58 EI). There was no difference in post-intubation seizure (26 % (n = 23) ASI, 29 % (n = 17) EI) in the cohort, however, there was increased RSE resolution with ASI in 24 patients with electrographic RSE during intubation (ASI: 61 % (n = 11/18) vs EI: 0 % (n = 0/6), p =.016). While anti-seizure induction did not appear to affect post-intubation seizure occurrence overall, a sub-group of patients undergoing electroencephalography during intubation had a higher incidence of seizure cessation, suggesting potential benefit in an enriched population.

Iodine-based dual-energy CT predicts early neurological decline from cerebral edema after large hemispheric infarction.

Background & Purpose: Ischemia affecting two thirds of the MCA territory predicts development of malignant cerebral edema. However, early infarcts are hard to diagnose on conventional head CT. We hypothesize that high-energy (190keV) virtual monochromatic images (VMI) from dual-energy CT (DECT) imaging enables earlier detection of secondary injury from malignant cerebral edema (MCE). Methods: Consecutive LHI patients with NIHSS ≥ 15 and DECT within 10 hours of reperfusion from May 2020 to March 2022 were included. We excluded patients with parenchymal hematoma-type 2 transformation. Retrospective analysis of clinical and novel variables included VMI Alberta Stroke Program Early CT Score (ASPECTS), total iodine content, and VMI infarct volume. Primary outcome was early neurological decline (END). Secondary outcomes included hemorrhagic transformation, decompressive craniectomy (DC), and medical treatment of MCE. Fisher's exact test and Wilcoxon test were used for univariate analysis. Logistic regression was used to develop prediction models for categorical outcomes. Results: Eighty-four LHI patients with a median age of 67.5 [IQR 57,78] years and NIHSS 22 [IQR 18,25] were included. Twenty-nine patients had END. VMI ASPECTS, total iodine content, and VMI infarct volume were associated with END. VMI ASPECTS, VMI infarct volume, and total iodine content were predictors of END after adjusting for age, sex, initial NIHSS, and tPA administration, with a AUROC of 0.691 [0.572,0.810], 0.877 [0.800, 0.954], and 0.845 [0.750, 0.940]. By including all three predictors, the model achieved AUROC of 0.903 [0.84,0.97] and was cross validated by leave one out method with AUROC of 0.827. Conclusion: DECT with high-energy VMI and iodine quantification is superior to conventional CT ASPECTS and is a novel predictor for early neurological decline due to malignant cerebral edema after large hemispheric infarction.

Natural History, Pathophysiology, and Recent Management Modalities of Intraventricular Hemorrhage.

Intraventricular hemorrhage (IVH) is a clinical challenge observed among 40-45% of intracerebral hemorrhage (ICH) cases. IVH can be classified according to the source of the hemorrhage into primary and secondary IVH. Primary intraventricular hemorrhage (PIVH), unlike secondary IVH, involves only the ventricles with no hemorrhagic parenchymal source. Several risk factors of PIVH were reported which include hypertension, smoking, age, and excessive alcohol consumption. IVH is associated with high mortality and morbidity and several prognostic factors were identified such as IVH volume, number of ventricles with blood, involvement of fourth ventricle, baseline Glasgow Coma Scale score, and hydrocephalus. Prompt management of patients with IVH is required to stabilize the clinical status of patients upon admission. Nevertheless, further advanced management is crucial to reduce the morbidity and mortality associated with intraventricular bleeding. Recent treatments showed promising outcomes in the management of IVH patients such as intraventricular anti-inflammatory drugs, lumbar drainage, and endoscopic evacuation of IVH, however, their safety and efficacy are still in question. This literature review presents the epidemiology, physiopathology, risk factors, and outcomes of IVH in adults with an emphasis on recent treatment options.

Steroids Provide Temporary Improvement of Refractory Pain Following Subarachnoid Hemorrhage.

Introduction: Evidence for optimal analgesia following subarachnoid hemorrhage (SAH) is limited. Steroid therapy for pain refractory to standard regimens is common despite lack of evidence for its efficacy. We sought to determine if steroids reduced pain or utilization of other analgesics when given for refractory headache following SAH. Methods: We performed a retrospective within-subjects cohort study of SAH patients who received steroids for refractory headache. We compared daily pain scores, total daily opioid, and acetaminophen doses before, during, and after steroids. Repeated measures were analyzed with a multivariable general linear model and generalized estimating equations. Results: Included 52 patients treated with dexamethasone following SAH, of whom 11 received a second course, increasing total to 63 treatment epochs. Mean pain score on the first day of therapy was 7.92 (standard error of the mean [SEM] .37) and decreased to 6.68 (SEM .36) on the second day before quickly returning to baseline levels, 7.36 (SEM .33), following completion of treatment. Total daily analgesics mirrored this trend. Mean total opioid and acetaminophen doses on days one and two and two days after treatment were 47.83mg (SEM 6.22) and 1848mg (SEM 170.66), 34.24mg (SEM 5.12) and 1809mg (SEM 150.28), and 46.38mg (SEM 11.64) and 1833mg (SEM 174.23), respectively. Response to therapy was associated with older age, decreasing acetaminophen dosing, and longer duration of steroids. Hyperglycemia and sleep disturbance/delirium effected 28.6% and 55.6% of cases, respectively. Conclusion: Steroid therapy for refractory pain in SAH patients may have modest, transient effects in select patients.

Neurocritical Care Recovery Clinics: An Idea Whose Time Has Come.

PURPOSE OF REVIEW: Purposes were to identify evidence for post-intensive care syndrome (PICS) and post-intensive care syndrome-family (PICS-F), defined as the psychological impact on families from exposure to critical care, in the neurologically injured population and to characterize existing models for neurorecovery clinics and the evidence to support their use. RECENT FINDINGS: There has been an explosion of post-ICU clinics among the general critical care population, with their use largely justified based on the management of PICS and PICS-F, terminology which excludes brain injured patients. In contrast, neurocritical care recovery clinics are not common and not well-described. There is however evidence in the neuro-ICU population supporting the provision of "dyadic" care, whereby the patient and caregiver are treated as one unit. Brain injured populations likely experience many of the same PICS phenomena as medically ill patients but are not represented in this body of literature. These patients deserve the same level of follow-up as other patients who have experienced critical illness. We propose a neuro-ICU transitional care clinic that addresses PICS-like symptoms and is modeled after transitional care provided to other brain injured populations. Future investigations should be targeted toward understanding the sequalae of a neuro-ICU admission, mechanisms for providing dyadic care, and the impact of neurorecovery clinics on long-term outcomes.

Rapid prediction of secondary neurologic decline after traumatic brain injury: a data analytic approach.

Secondary neurologic decline (ND) after traumatic brain injury (TBI) is independently associated with outcome, but robust predictors of ND are lacking. In this retrospective analysis of consecutive isolated TBI admissions to the R. Adams Cowley Shock Trauma Center between November 2015 and June 2018, we aimed to develop a triage decision support tool to quantify risk for early ND. Three machine learning models based on clinical, physiologic, or combined characteristics from the first hour of hospital resuscitation were created. Among 905 TBI cases, 165 (18%) experienced one or more ND events (130 clinical, 51 neurosurgical, and 54 radiographic) within 48 h of presentation. In the prediction of ND, the clinical plus physiologic data model performed similarly to the physiologic only model, with concordance indices of 0.85 (0.824-0.877) and 0.84 (0.812-0.868), respectively. Both outperformed the clinical only model, which had a concordance index of 0.72 (0.688-0.759). This preliminary work suggests that a data-driven approach utilizing physiologic and basic clinical data from the first hour of resuscitation after TBI has the potential to serve as a decision support tool for clinicians seeking to identify patients at high or low risk for ND.

Simulation-based assessment of trainee's performance in post-cardiac arrest resuscitation.

Objectives: To assess trainees' performance in managing a patient with post-cardiac arrest complicated by status epilepticus. Methods: In this prospective, observational, single-center simulation-based study, trainees ranging from sub interns to critical care fellows evaluated and managed a post cardiac arrest patient, complicated by status epilepticus. Critical action items were developed by a modified Delphi approach based on American Heart Association guidelines and the Neurocritical Care Society's Emergency Neurological Life Support protocols. The primary outcome measure was the critical action item sum score. We sought validity evidence to support our findings by including attending neurocritical care physicians and comparing performance across four levels of training. Results: Forty-nine participants completed the simulation. The mean sum of critical actions completed by trainees was 10/21 (49%). Eleven (22%) trainees verbalized a differential diagnosis for the arrest. Thirty-two (65%) reviewed the electrocardiogram, recognized it as abnormal, and consulted cardiology. Forty trainees (81%) independently decided to start temperature management, but only 20 (41%) insisted on it when asked to reconsider. There was an effect of level of training on critical action checklist sum scores (novice mean score [standard deviation (SD)] = 4.8(1.8) vs. intermediate mean score (SD) = 10.4(2.1) vs. advanced mean score (D) = 11.6(3.0) vs. expert mean score (SD) = 14.7(2.2)). Conclusions: High-fidelity manikin-based simulation holds promise as an assessment tool in the performance of post-cardiac arrest care.

Leveraging Continuous Vital Sign Measurements for Real-Time Assessment of Autonomic Nervous System Dysfunction After Brain Injury: A Narrative Review of Current and Future Applications.

Subtle and profound changes in autonomic nervous system (ANS) function affecting sympathetic and parasympathetic homeostasis occur as a result of critical illness. Changes in ANS function are particularly salient in neurocritical illness, when direct structural and functional perturbations to autonomic network pathways occur and may herald impending clinical deterioration or intervenable evolving mechanisms of secondary injury. Sympathetic and parasympathetic balance can be measured quantitatively at the bedside using multiple methods, most readily by extracting data from electrocardiographic or photoplethysmography waveforms. Work from our group and others has demonstrated that data-analytic techniques can identify quantitative physiologic changes that precede clinical detection of meaningful events, and therefore may provide an important window for time-sensitive therapies. Here, we review data-analytic approaches to measuring ANS dysfunction from routine bedside physiologic data streams and integrating this data into multimodal machine learning-based model development to better understand phenotypical expression of pathophysiologic mechanisms and perhaps even serve as early detection signals. Attention will be given to examples from our work in acute traumatic brain injury on detection and monitoring of paroxysmal sympathetic hyperactivity and prediction of neurologic deterioration, and in large hemispheric infarction on prediction of malignant cerebral edema. We also discuss future clinical applications and data-analytic challenges and future directions.

Impact of Enteral Albuterol on Bradycardic Events After Acute Cervical Spinal Cord Injury.

BACKGROUND: Acute cervical spinal cord injury (ACSCI) is commonly complicated by spinal shock, resulting in hemodynamic instability characterized by bradycardia and hypotension that can have fatal consequences. Current guidelines recommend the use of intravenous beta and dopamine agonists, such as norepinephrine and dopamine, respectively. We sought to determine whether enteral albuterol would be a safe and feasible treatment for bradycardia without an increase in the occurrence of known side effects of albuterol in patients with ACSCI. METHODS: A retrospective review of patients with ACSCI admitted to an intensive care unit at a level I trauma center and treated with enteral albuterol was conducted. Patients were excluded for the following reasons: pure beta blocker use prior to injury, concurrent use of pacemaker, age of less than 18 years, or age more than 75 years. As part of the standard of care, all patients underwent mean arterial pressure (MAP) augmentation to reach a goal of greater than 85 mm Hg during the first 7 days post injury. All eligible patient charts were reviewed for demographic characteristics, daily minimum and maximum heart rate and MAP, and concomitant vasoactive medication use. Bradycardia and tachycardia were defined as heart rate less than 60 beats per minute (bpm) and greater than 100 bpm, respectively. Factors found to be associated with bradycardia on univariate analysis were entered into a multivariable generalized estimating equation analysis to determine factors independently associated with bradycardia during the study period. RESULTS: There were 58 patients with cervical ASCI (age 45 ± 18 years, 76% men) admitted between January 1, 2016, and December 31, 2017, that met the study criteria. The mean time to initiation of albuterol was 1.5 ± 1.7 days post injury, with a duration of 9.3 ± 4.5 days and a mean daily dosage of 7.8 ± 4.5 mg. Bradycardia was observed in 136 of 766 patient days (17%). There were a few episodes of hyperglycemia (1%) and tachycardia (3%), but no episodes of hypokalemia. In a multivariable analysis, female sex (P = 0.006) and American Spinal Cord Injury Association grade A, B, or C (P < 0.001) were associated with a higher risk of developing bradycardia, whereas dosage of albuterol (P = 0.009) and norepinephrine use (P = 0.008) were associated with a lower risk of developing bradycardia. CONCLUSIONS: Albuterol administration in ASCI is a safe and feasible treatment for bradycardia, given that no significant side effects, such as hyperglycemia, hypokalemia, or tachycardia, were observed. The administration of enteral albuterol was well tolerated and, in a dose-dependent manner, associated with a lower occurrence of bradycardia. Further prospective trials for the use of enteral albuterol after SCI are warranted.

Neurologic Outcomes After Extracorporeal Cardiopulmonary Resuscitation: Recent Experience at a Single High-Volume Center.

Extracorporeal cardiopulmonary resuscitation (ECPR)-veno-arterial extracorporeal membrane oxygenation (ECMO) for refractory cardiac arrest-has grown rapidly, but its widespread adoption has been limited by frequent neurologic complications. With individual centers developing best practices, utilization may be increasing with an uncertain effect on outcomes. This study describes the recent ECPR experience at the University of Maryland Medical Center from 2016 through 2018, with attention to neurologic outcomes and predictors thereof. The primary outcome was dichotomized Cerebral Performance Category (≤2) at hospital discharge; secondary outcomes included rates of specific neurologic complications. From 429 ECMO runs over 3 years, 57 ECPR patients were identified, representing an increase in ECPR utilization compared with 41 cases over the previous 6 years. Fifty-two (91%) suffered in-hospital cardiac arrest, and 36 (63%) had an initial nonshockable rhythm. Median low-flow time was 31 minutes. Overall, 26 (46%) survived hospitalization and 23 (88% of survivors, 40% overall) had a favorable discharge outcome. Factors independently associated with good neurologic outcome included lower peak lactate, initial shockable rhythm, and higher initial ECMO mean arterial pressure. Neurologic complications occurred in 18 patients (32%), including brain death in 6 (11%), hypoxic-ischemic brain injury in 11 (19%), ischemic stroke in 6 (11%), intracerebral hemorrhage in 1 (2%), and seizure in 4 (7%). We conclude that good neurologic outcomes are possible for well-selected ECPR patients in a high-volume program with increasing utilization and evolving practices. Markers of adequate peri-resuscitation tissue perfusion were associated with better outcomes, suggesting their importance in neuroprognostication.

Verticalization for Refractory Intracranial Hypertension: A Case Series.

BACKGROUND: Severe intracranial hypertension is strongly associated with mortality. Guidelines recommend medical management involving sedation, hyperosmotic agents, barbiturates, hypothermia, and surgical intervention. When these interventions are maximized or are contraindicated, refractory intracranial hypertension poses risk for herniation and death. We describe a novel intervention of verticalization for treating intracranial hypertension refractory to aggressive medical treatment. METHODS: This study was a single-center retrospective review of six cases of refractory intracranial hypertension in a tertiary care center. All patients were treated with a standard-of-care algorithm for lowering intracranial pressure (ICP) yet maintained an ICP greater than 20 mmHg. They were then treated with verticalization for at least 24 h. We compared the median ICP, the number of ICP spikes greater than 20 mmHg, and the percentage of ICP values greater than 20 mmHg in the 24 h before verticalization vs. after verticalization. We assessed the use of hyperosmotic therapies and any changes in the mean arterial pressure and cerebral perfusion pressure related with the intervention. RESULTS: Five patients were admitted with subarachnoid hemorrhage and one with intracerebral hemorrhage. All patients had ICP monitoring by external ventricular drain. The median opening pressure was 30 mmHg (25th-75th interquartile range 22.5-30 mmHg). All patients demonstrated a reduction in ICP after verticalization, with a significant decrease in the median ICP (12 vs. 8 mmHg; p < 0.001), the number of ICP spikes (12 vs. 2; p < 0.01), and the percentage of ICP values greater than 20 mmHg (50% vs. 8.3%; p < 0.01). There was a decrease in total medical interventions after verticalization (79 vs. 41; p = 0.05) and a lower total therapy intensity level score after verticalization. The most common adverse effects included asymptomatic bradycardia (n = 3) and pressure wounds (n = 4). CONCLUSIONS: Verticalization is an effective noninvasive intervention for lowering ICP in intracranial hypertension that is refractory to aggressive standard management and warrants further study.

Simulation-Based Assessment of Graduate Neurology Trainees' Performance Managing Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Multidisciplinary acute stroke teams improve acute ischemic stroke management but may hinder trainees' education, which in turn may contribute to poorer outcomes in community hospitals on graduation. Our goal was to assess graduate neurology trainee performance independently of a multidisciplinary stroke team in the management of acute ischemic stroke, tissue plasminogen activator (tPA)-related hemorrhage, and cerebral herniation syndrome. METHODS: In this prospective, observational, single-center simulation-based study, participants (subinterns to attending physicians) managed a patient with acute ischemic stroke followed by tPA-related hemorrhagic conversion leading to cerebral herniation. Critical actions were developed by a modified Delphi approach based on relevant American Heart Association guidelines and the Neurocritical Care Society's Emergency Neurologic Life Support protocols. The primary outcome measure was graduate neurology trainees' critical action item sum score. We sought validity evidence to support our findings by comparing performance across 4 levels of training. RESULTS: Fifty-three trainees (including 31 graduate neurology trainees) and 5 attending physicians completed the simulation. The mean sum of critical actions completed by graduate neurology trainees was 15 of 22 (68%). Ninety percent of graduate neurology trainees properly administered tPA; 84% immediately stopped tPA infusion after patient deterioration; but only 55% reversed tPA according to guidelines. There was a moderately strong effect of level of training on critical action sum score (level 1 mean [SD] score 7.2 [2.8] vs level 2 mean [SD] score 12.3 [2.6] vs level 3 mean [SD] score 13.3 [2.2] vs level 4 mean [SD] score 16.3 [2.4], p < 0.001, R 2 = 0.54). DISCUSSION: Graduate neurology trainees reassuringly perform well in initial management of acute ischemic stroke but frequently make errors in the treatment of hemorrhagic transformation after thrombolysis, suggesting the need for more education surrounding this low-frequency, high-acuity event. High-fidelity simulation holds promise as an assessment tool for acute stroke management performance.

Cytotoxic Edema Associated with Hemorrhage Predicts Poor Outcome after Traumatic Brain Injury.

Magnetic resonance imaging (MRI) is used rarely in the acute evaluation of traumatic brain injury (TBI) but may identify findings of clinical importance not detected by computed tomography (CT). We aimed to characterize the association of cytotoxic edema and hemorrhage, including traumatic microbleeds, on MRI obtained within hours of acute head trauma and investigated the relationship to clinical outcomes. Patients prospectively enrolled in the Traumatic Head Injury Neuroimaging Classification study (NCT01132937) with evidence of diffusion-related findings or hemorrhage on neuroimaging were included. Blinded interpretation of MRI for diffusion-weighted lesions and hemorrhage was conducted, with subsequent quantification of apparent diffusion coefficient (ADC) values. Of 161 who met criteria, 82 patients had conspicuous hyperintense lesions on diffusion-weighted imaging (DWI) with corresponding regions of hypointense ADC in proximity to hemorrhage. Median time from injury to MRI was 21 (10-30) h. Median ADC values per patient grouped by time from injury to MRI were lowest within 24 h after injury. The ADC values associated with hemorrhagic lesions are lowest early after injury, with an increase in diffusion during the subacute period, suggesting transformation from cytotoxic to vasogenic edema during the subacute post-injury period. Of 118 patients with outcome data, 60 had Glasgow Outcome Scale Extended scores ≤6 at 30/90 days post-injury. Cytotoxic edema on MRI (odds ratio [OR] 2.91 [1.32-6.37], p = 0.008) and TBI severity (OR 2.51 [1.32-4.74], p = 0.005) were independent predictors of outcome. These findings suggest that in patients with TBI who had findings of hemorrhage on CT, patients with DWI/ADC lesions on MRI are more likely to do worse.

Relationship Between Nutrition Intake and Outcome After Subarachnoid Hemorrhage: Results From the International Nutritional Survey.

BACKGROUND: A previous study suggested an association between low caloric intake(CI), negative nitrogen balance, and poor outcome after subarachnoid hemorrhage(SAH). Objective of this multinational, multicenter study was to investigate whether clinical outcomes vary by protein intake(PI) or CI in SAH patients adjusting for the nutritional risk as judged by the modified NUTrition Risk in the Critically Ill (mNUTRIC) score. METHODS: The International Nutrition Survey(INS) 2007-2014 was utilized to describe the characteristics, outcomes and nutrition use. A subgroup of patients from 2013 and 2014(when NUTRIC score was captured) examined the association between CI and PI and time to discharge alive(TTDA) from hospital using Cox regression models, adjusting for nutrition risk classified by the mNUTRIC score as low(0-4) or high(5-9). RESULTS: There were 489 SAH patients(57% female with a mean ± SD age 57.5 ± 13.9 years, BMI of 25.9 ± 5.3 kg/m2 and APACHE-2 score 19.4 ± 7.0. Majority(85%) received enteral nutrition(EN) only, with a time to initiation of EN of 35.4 ± 35.2 hours. 64% had EN interrupted. Patients received a CI of 14.6 ± 7.1 calories/kg/day and PI 0.7 ± 0.3 grams/kg/day corresponding to 59% and 55% of total prescribed CI and PI respectively. In the 2013 and 2014 subgroup there were 226 SAH patients with a mNUTRIC score of 3.4 ± 1.8. Increased CI and PI were associated with faster TTDA among high mNUTRIC patients(HR per 20% of prescription received = 1.34[95% CI,1.03 -1.76] for CI and 1.44[1.07 -1.93] for PI), but not low mNUTRIC patients(CI: HR = 0.95[0.77 -1.16] PI:0.95[0.78 -1.16]). CONCLUSIONS: Results from this multicenter study found that SAH patients received under 60% of their prescribed CI and PI. Further, achieving greater CI and PI in hi risk SAH patients was associated with improved TTDA. mNUTRIC serves to identify SAH patients that benefit most from artificial nutrition and efforts to optimize protein and caloric delivery in this subpopulation should be maximized.