Overlapping Physiologic Signs of Sepsis and Paroxysmal Sympathetic Hyperactivity After Traumatic Brain Injury: Exploring A Clinical Conundrum.

BACKGROUND: Paroxysmal sympathetic hyperactivity (PSH) occurs in a subset of patients with traumatic brain injury (TBI) and is associated with worse outcomes. Sepsis is also associated with worse outcomes after TBI and shares several physiologic features with PSH, potentially creating diagnostic confusion and suboptimal management of each. This is the first study to directly investigate the interaction between PSH and infection using robust diagnostic criteria. METHODS: We performed a retrospective cohort study of patients with TBI admitted to a level I trauma center intensive care unit with hospital length of stay of at least 2 weeks. From January 2016 to July 2018, 77 patients diagnosed with PSH were 1:1 matched by age and Glasgow Coma Scale to 77 patients without PSH. Trauma infectious diseases subspecialists prospectively documented assessments corroborating diagnoses of infection. Extracted data including incidence, timing, classification, and anatomical source of infections were compared according to PSH diagnosis. We also evaluated daily PSH clinical feature severity scores and systemic inflammatory response syndrome (SIRS) criteria and compared values for patients with and without confirmed infection, stratified by PSH diagnosis. RESULTS: During the first 2 weeks of hospitalization, there were no differences in rates of suspected (62%) nor confirmed (48%) infection between patients with PSH and controls. Specific treatments for PSH were initiated on median hospital day 7 and for confirmed infections on median hospital day 8. SIRS criteria could identify infection only in patients who were not diagnosed with PSH. CONCLUSIONS: In the presence of brain injury-induced autonomic nervous system dysregulation, the initiation and continuation of antimicrobial therapy is a challenging clinical decision, as standard physiologic markers of sepsis do not distinguish infected from noninfected patients with PSH, and these entities often present around the same time. Clinicians should be aware that PSH is a potential driver of SIRS, and familiarity with its diagnostic criteria as proposed by the PSH assessment measure is important. Management by a multidisciplinary team attentive to these issues may reduce rates of inappropriate antibiotic usage and misdiagnoses.

Treatment of hyperammonemia using in-line renal replacement and hyperosmolar therapies within an extracorporeal membrane oxygenation circuit.

After orthotopic lung transplantation, hyperammonemia can be a rare complication secondary to infection by organisms that produce urease or inhibit the urea cycle. This can cause neurotoxicity, cerebral edema, and seizures. Ammonia is unique in that it has a large volume of distribution. However, it is also readily dialyzable given its small molecular weight. As such, removal of ammonia requires renal replacement modalities that can both rapidly remove ammonia from the plasma space and allow for continuous removal to prevent rebound accumulation from intracellular stores. Prevention of iatrogenic osmotic lowering in this setting is required to prevent worsening of cerebral edema. Herein, we describe use of sequential in-line renal replacement therapy using both intermittent hemodialysis and continuous venovenous hemofiltration within an extracorporeal membrane oxygenation circuit in conjunction with higher sodium dialysate and 7.5% hypertonic saline to achieve these treatment goals.

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.

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.

Admission Features Associated With Paroxysmal Sympathetic Hyperactivity After Traumatic Brain Injury: A Case-Control Study.

OBJECTIVES: Paroxysmal sympathetic hyperactivity occurs in a subset of critically ill traumatic brain injury patients and has been associated with worse outcomes after traumatic brain injury. The goal of this study was to identify admission risk factors for the development of paroxysmal sympathetic hyperactivity in traumatic brain injury patients. DESIGN: Retrospective case-control study of age- and Glasgow Coma Scale-matched traumatic brain injury patients. SETTING: Neurotrauma ICU at the R. Adams Cowley Shock Trauma Center of the University of Maryland Medical System, January 2016 to July 2018. PATIENTS: Critically ill adult traumatic brain injury patients who underwent inpatient monitoring for at least 14 days were included. Cases were identified based on treatment for paroxysmal sympathetic hyperactivity with institutional first-line therapies and were confirmed by retrospective tabulation of established paroxysmal sympathetic hyperactivity diagnostic and severity criteria. Cases were matched 1:1 by age and Glasgow Coma Scale to nonparoxysmal sympathetic hyperactivity traumatic brain injury controls, yielding 77 patients in each group. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Admission characteristics independently predictive of paroxysmal sympathetic hyperactivity included male sex, higher admission systolic blood pressure, and initial CT evidence of diffuse axonal injury, intraventricular hemorrhage/subarachnoid hemorrhage, complete cisternal effacement, and absence of contusion. Paroxysmal sympathetic hyperactivity cases demonstrated significantly worse neurologic outcomes upon hospital discharge despite being matched for injury severity at admission. CONCLUSIONS: Several anatomical, epidemiologic, and physiologic risk factors for clinically relevant paroxysmal sympathetic hyperactivity can be identified on ICU admission. These features help characterize paroxysmal sympathetic hyperactivity as a clinical-pathophysiologic phenotype associated with worse outcomes after traumatic brain injury.

Pain Trajectories Following Subarachnoid Hemorrhage are Associated with Continued Opioid Use at Outpatient Follow-up.

BACKGROUND: Subarachnoid hemorrhage (SAH) is characterized by the worst headache of life and associated with long-term opioid use. Discrete pain trajectories predict chronic opioid use following other etiologies of acute pain, but it is unknown whether they exist following SAH. If discrete pain trajectories following SAH exist, it is uncertain whether they predict long-term opioid use. We sought to characterize pain trajectories after SAH and determine whether they are associated with persistent opioid use. METHODS: We reviewed pain scores from patients admitted to a single tertiary care center for SAH from November 2015 to September 2019. Group-based trajectory modeling identified discrete pain trajectories during hospitalization. We compared outcomes across trajectory groups using χ2 and Kruskal-Wallis tests. Multivariable regression determined whether trajectory group membership was an independent predictor of long-term opioid use, defined as continued use at outpatient follow-up. RESULTS: We identified five discrete pain trajectories among 305 patients. Group 1 remained pain free. Group 2 reported low scores with intermittent spikes and slight increase over time. Group 3 noted increasing pain severity through day 7 with mild improvement until day 14. Group 4 experienced maximum pain with steady decrement over time. Group 5 reported moderate pain with subtle improvement. In multivariable analysis, trajectory groups 3 (odds ratio [OR] 3.5; 95% confidence interval [CI] 1.5-8.3) and 5 (OR 8.0; 95% CI 3.1-21.1), history of depression (OR 3.6; 95% CI 1.3-10.0) and racial/ethnic minority (OR 2.3; 95% CI 1.3-4.1) were associated with continued opioid use at follow-up (median 62 days following admission, interquartile range 48-96). CONCLUSIONS: Discrete pain trajectories following SAH exist. Recognition of pain trajectories may help identify those at risk for long-term opioid use.

Functional Reorganization of Right Prefrontal Cortex Underlies Sustained Naming Improvements in Chronic Aphasia via Repetitive Transcranial Magnetic Stimulation.

BACKGROUND AND OBJECTIVE: While noninvasive brain stimulation techniques show promise for language recovery after stroke, the underlying mechanisms remain unclear. We applied inhibitory repetitive transcranial magnetic stimulation (rTMS) to regions of interest in the right inferior frontal gyrus of patients with chronic poststroke aphasia and examined changes in picture naming performance and cortical activation. METHODS: Nine patients received 10 days of 1-Hz rTMS (Monday through Friday for 2 weeks). We assessed naming performance before and immediately after stimulation on the first and last days of rTMS therapy, and then again at 2 and 6 months post-rTMS. A subset of six of these patients underwent functional magnetic resonance imaging pre-rTMS (baseline) and at 2 and 6 months post-rTMS. RESULTS: Naming accuracy increased from pre- to post-rTMS on both the first and last days of treatment. We also found naming improvements long after rTMS, with the greatest improvements at 6 months post-rTMS. Long-lasting effects were associated with a posterior shift in the recruitment of the right inferior frontal gyrus: from the more anterior Brodmann area 45 to the more posterior Brodmann areas 6, 44, and 46. The number of left hemispheric regions recruited for naming also increased. CONCLUSIONS: This study found that rTMS to the right hemisphere Broca area homologue confers long-lasting improvements in picture naming performance. The mechanism involves dynamic bilateral neural network changes in language processing, which take place within the right prefrontal cortex and the left hemisphere more generally. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Identifier NCT00608582).

A variable number of tandem repeats in the 3'-untranslated region of the dopamine transporter modulates striatal function during working memory updating across the adult age span.

Dopamine modulation of striatal function is critical for executive functions such as working memory (WM) updating. The dopamine transporter (DAT) regulates striatal dopamine signaling via synaptic reuptake. A variable number of tandem repeats in the 3'-untranslated region of SLC6A3 (DAT1-3'-UTR-VNTR) is associated with DAT expression, such that 9-repeat allele carriers tend to express lower levels (associated with higher extracellular dopamine concentrations) than 10-repeat homozygotes. Aging is also associated with decline of the dopamine system. The goal of the present study was to investigate the effects of aging and DAT1-3'-UTR-VNTR on the neural activity and functional connectivity of the striatum during WM updating. Our results showed both an age-related decrease in striatal activity and an effect of DAT1-3'-UTR-VNTR. Ten-repeat homozygotes showed reduced striatal activity and increased striatal-hippocampal connectivity during WM updating relative to the 9-repeat carriers. There was no age by DAT1-3'-UTR-VNTR interaction. These results suggest that, whereas striatal function during WM updating is modulated by both age and genetically determined DAT levels, the rate of the age-related decline in striatal function is similar across both DAT1-3'-UTR-VNTR genotype groups. They further suggest that, because of the baseline difference in striatal function based on DAT1-3'-UTR-VNTR polymorphism, 10-repeat homozygotes, who have lower levels of striatal function throughout the adult life span, may reach a threshold of decreased striatal function and manifest impairments in cognitive processes mediated by the striatum earlier in life than the 9-repeat carriers. Our data suggest that age and DAT1-3'-UTR-VNTR polymorphism independently modulate striatal function.

Traumatic Brain Injury and Traumatic Spinal Cord Injury.

OBJECTIVE: This article reviews the mechanisms of primary traumatic injury to the brain and spinal cord, with an emphasis on grading severity, identifying surgical indications, anticipating complications, and managing secondary injury. LATEST DEVELOPMENTS: Serum biomarkers have emerged for clinical decision making and prognosis after traumatic injury. Cortical spreading depolarization has been identified as a potentially modifiable mechanism of secondary injury after traumatic brain injury. Innovative methods to detect covert consciousness may inform prognosis and enrich future studies of coma recovery. The time-sensitive nature of spinal decompression is being elucidated. ESSENTIAL POINTS: Proven management strategies for patients with severe neurotrauma in the intensive care unit include surgical decompression when appropriate, the optimization of perfusion, and the anticipation and treatment of complications. Despite validated models, predicting outcomes after traumatic brain injury remains challenging, requiring prognostic humility and a model of shared decision making with surrogate decision makers to establish care goals. Penetrating injuries, especially gunshot wounds, are often devastating and require public health and policy approaches that target prevention.

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.

Venovenous extracorporeal membrane oxygenation in patients with traumatic brain injuries and severe respiratory failure: A single-center retrospective analysis.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV ECMO) can support trauma patients with severe respiratory failure. Use in traumatic brain injury (TBI) may raise concerns of worsening complications from intracranial bleeding. However, VV ECMO can rapidly correct hypoxemia and hypercarbia, possibly preventing secondary brain injury. We hypothesize that adult trauma patients with TBI on VV ECMO have comparable survival with trauma patients without TBI. METHODS: A single-center, retrospective cohort study involving review of electronic medical records of trauma admissions between July 1, 2014, and August 30, 2022, with discharge diagnosis of TBI who were placed on VV ECMO during their hospital course was performed. RESULTS: Seventy-five trauma patients were treated with VV ECMO; 36 (48%) had TBI. Of those with TBI, 19 (53%) had a hemorrhagic component. Survival was similar between patients with and without a TBI (72% vs. 64%, p = 0.45). Traumatic brain injury survivors had a higher admission Glasgow Coma Scale (7 vs. 3, p < 0.001) than nonsurvivors. Evaluation of prognostic scoring systems on initial head computed tomography demonstrated that TBI VV ECMO survivors were more likely to have a Rotterdam score of 2 (62% vs. 20%, p = 0.03) and no survivors had a Marshall score of ≥4. Twenty-nine patients (81%) had a repeat head computed tomography on VV ECMO with one incidence of expanding hematoma and one new focus of bleeding. Neither patient with a new/worsening bleed received anticoagulation. Survivors demonstrated favorable neurologic outcomes at discharge and outpatient follow-up, based on their mean Rancho Los Amigos Scale (6.5; SD, 1.2), median Cerebral Performance Category (2; interquartile range, 1-2), and median Glasgow Outcome Scale-Extended (7.5; interquartile range, 7-8). CONCLUSION: In this series, the majority of TBI patients survived and had good neurologic outcomes despite a low admission Glasgow Coma Scale. Venovenous extracorporeal membrane oxygenation may minimize secondary brain injury and may be considered in select patients with TBI. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

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.

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.

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.

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.

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.

Neurophysiological correlates of age-related changes in working memory updating.

Normal aging is associated with a gradual decline in executive functions such as set-shifting, inhibition, and updating, along with a progressive decline of neurotransmitter systems including the dopamine system. Modulation from the dopamine system is thought to be critical for the gating of information during working memory. Given the known relationships between executive aging, cognition, and dopamine, this study aims to explore the neurobiology underlying age-related changes in working memory updating using fMRI with healthy subjects from across the adult age spectrum. Our results indicate that older age is associated with poorer performance, reduced meso-cortico-striatal activation, and reduced functional coupling between the caudate and the VLPFC during the updating task. Additionally, caudate activation is associated with improved accuracy and VLPFC activation with faster reaction times in the full sample. Thus, older subjects' under-recruitment of and reduced functional coupling between these regions may specifically underlie age-related changes in working memory updating. These results are consistent with computational models of executive cognition and dopamine-mediated age-related cognitive decline.