Search

Consensus is currently lacking in the optimal treatment for blunt traumatic cerebral venous sinus thrombosis (tCVST). Anticoagulation (AC) is used for treating spontaneous CVST, but its role in tCVST remains unclear.To investigate the characteristics and outcomes of patients treated with AC compared with patients managed conservatively.We retrospectively reviewed patients who presented to a Level 1 trauma center with acute skull fracture after blunt head trauma who underwent dedicated venous imaging.There were 137 of 424 patients (32.3%) presenting with skull fractures with tCVST on venous imaging. Among them, 82 (60%) were treated with AC while 55 (40%) were managed conservatively. Analysis of baseline characteristics demonstrated no significant difference in age, sex, admission Glasgow Coma Scale, admission Injury Severity Score, rates of associated intracranial hemorrhage, or neurosurgical interventions. New or worsening intracranial hemorrhage was seen in 7 patients treated with AC. Patients on AC had significantly lower mortality than non-AC (1% vs 15%; P = .003). There was no difference in the Glasgow Coma Scale or Glasgow Outcome Scale at last clinical follow-up. On follow-up venous imaging, patients treated with AC were more likely to experience full thrombus recanalization than non-AC (54% vs 32%; P = .012), and subsequent multiple regression analysis revealed that treatment with AC was a significant predictor of full thrombus recanalization (odds ratio, 5.18; CI, 1.60-16.81; P = .006).Treatment with AC for tCVST due to blunt head trauma may promote higher rates of complete thrombus recanalization when compared with conservative management.

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

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. 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. 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

Over the past four decades, there have been progressive changes in the epidemiology of traumatic spinal cord injury (tSCI). We assessed trends in demographic and injury-related variables in traumatic cervical spinal cord injury (tCSCI) patients over an 18-year period at a single Level I trauma center. We included all magnetic resonance imaging-confirmed tCSCI patients ≥15 years of age for years 2001-2018. Among 1420 patients, 78.3% were male with a mean age 51.5 years. Etiology included falls (46.9%), motor vehicle collisions (MVCs; 34.2%), and sports injuries (10.9%). Median American Spinal Injury Association (ASIA) Motor Score (AMS) was 44, complete tCSCI was noted in 29.6% of patients, fracture dislocations were noted in 44.7%, and median intramedullary lesion length (IMLL) was 30.8 mm (complete injuries 56.3 mm and incomplete injuries 27.4 mm). Over the study period, mean age and proportion of falls increased (

Background Patients with traumatic intracranial hemorrhage (ICH) and concomitant pulmonary embolus (PE) have competing care needs and demand a careful balance of anticoagulation (AC) versus potential worsening of their ICH. The goal of this study is to determine the safety of therapeutic AC for PE in patients with ICH. Methods This is a retrospective single-center study of patients older than 16 years with concomitant ICH and PE occurring between June 2013 and December 2017. Early AC was defined as within 7 days of injury or less; late was defined as after 7 days. Primary outcomes included death, interventions for worsening ICH following AC, and pulmonary complications. Multivariate logistic regression was used to evaluate for clinical and demographic factors associated with worsening traumatic brain injury (TBI), and recursive partitioning was used to differentiate risk in groups. Results Fifty patients met criteria. Four did not receive any AC and were excluded. Nineteen (41.3%) received AC early (median, 4.1; interquartile range, 3.1-6) and 27 (58.7%) received AC late (median, 14; interquartile range, 9.7-19.5). There were four deaths in the early group, and none in the late cohort (21.1% vs. 0%, p = 0.01). Two deaths were due to PE and the others were from multi-system organ failure or unrecoverable underlying TBI. Three patients in the early group, and two in the late, had increased ICH on computed tomography (17.6% vs. 7.4%, p = 0.3). None required intervention. Conclusion This retrospective study failed to find instances of clinically significant progression of TBI in 46 patients with computed tomography-proven ICH after undergoing AC for PE. Therapeutic AC is not associated with worse outcomes in patients with TBI, even if initiated early. However, two patients died from PE despite AC, underlining the severity of the disease. Intracranial hemorrhage should not preclude AC treatment for PE, even early after injury. Level of evidence Care management, Level IV.

External ventricular drainage (EVD) is a high-risk medical procedure that involves inserting a catheter inside a patient’s skull, through the brain and into a ventricle, to drain cerebrospinal fluid and thus relieve elevated intracranial pressure. Once the catheter has entered the skull, its tip cannot be seen. The neurosurgeon has to imagine its location inside the cranium and direct it toward the ventricle using only anatomic landmarks. The EVD catheter is thin and thus hard to track using infra-red depth sensors. Traditional optical tracking using fiducial or other markers inevitably changes the shape or weight of the medical instrument. We present an augmented reality system that depicts the catheter for EVD and a new technique to precisely track the catheter inside the skull. Our technique uses a new linear marker detection method that requires minimal changes to the catheter and is well suited for tracking other thin medical devices that require high-precision tracking.

In cervical traumatic spinal cord injury (TSCI), the therapeutic effect of timing of surgery on neurological recovery remains uncertain. Additionally, the relationship between extent of decompression, imaging biomarker evidence of injury severity, and outcome is incompletely understood. We investigated the effect of timing of decompression on long-term neurological outcome in patients with complete spinal cord decompression confirmed on postoperative magnetic resonance imaging (MRI). American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade conversion was determined in 72 AIS grades A, B, and C patients 6 months after confirmed decompression. Thirty-two patients underwent decompressive surgery ultra-early (< 12 h), 25 underwent decompressive surgery early (12–24 h), and 15 underwent decompressive surgery late (> 24–138.5 h) after injury. Age, gender, injury mechanism, intramedullary lesion length (IMLL) on MRI, admission ASIA motor score, and surgical technique were not statistically different among groups. Motor complete patients (p = 0.009) and those with fracture dislocations (p = 0.01) tended to be operated on earlier. Improvement of one grade or more was present in 55.6% of AIS grade A, 60.9% of AIS grade B, and 86.4% of AIS grade C patients. Admission AIS motor score (p = 0.0004) and pre-operative IMLL (p = 0.00001) were the strongest predictors of neurological outcome. AIS grade improvement occurred in 65.6%, 60%, and 80% of patients who underwent decompression ultra-early, early, and late, respectively (p = 0.424). Multiple regression analysis revealed that IMLL was the only significant variable predictive of AIS grade conversion to a better grade (odds ratio, 0.908; confidence interval [CI], 0.862–0.957; p

Introduction: Patients with tIPH (used here to refer to traumatic intraparenchymal hemorrhagic contusion) or intraparenchymal hemorrhage face high rates of mortality and persistent functional deficits. Prior studies have found an association between blood pressure variability (BPV) and neurologic outcomes in patients with spontaneous IPH. Our study investigated the association between BPV and discharge destination (a proxy for functional outcome) in patients with tIPH. Methods: We retrospectively reviewed the charts of patients admitted to a Level I trauma center for ≥ 24 hours with tIPH. We examined variability in hourly BP measurements over the first 24 hours of hospitalization. Our outcome of interest was discharge destination (home vs facility). We performed 1:1 propensity score matching and multivariate regressions to identify demographic and clinical factors predictive of discharge home. Results: We included 354 patients; 91 were discharged home and 263 to a location other than home. The mean age was 56 (SD 21), 260 (73%) were male, 22 (6%) were on anticoagulation, and 54 (15%) on antiplatelet therapy. Our propensity-matched cohorts included 76 patients who were discharged home and 76 who were discharged to a location other than home. One measure of BPV (successive variation in systolic BP) was identified as an independent predictor of discharge location in our propensity-matched cohorts (odds ratio 0.89, 95% confidence interval 0.8-0.98; P = 0.02). Our model demonstrated good goodness of fit (P-value for Hosmer-Lemeshow test = 0.88) and very good discriminatory capability (AUROC = 0.81). High Glasgow Coma Scale score at 24 hours and treatment with fresh frozen plasma were also associated with discharge home. Conclusion: Our study suggests that increased BPV is associated with lower rates of discharge home after initial hospitalization among patients with tIPH. Additional research is needed to evaluate the impact of BP control on patient outcomes.

Blood pressure variability (BPV) has been shown to correlate with intraparenchymal hematoma progression (HP) and worse outcomes in patients with spontaneous intracerebral hemorrhage (sICH). However, this association has not been elucidated in patients with traumatic intraparenchymal hemorrhage or contusion (tIPH). We hypothesized that 24 h-BPV from time of admission is associated with hemorrhagic progression of contusion or intraparenchymal hemorrhage (HPC), and worse outcomes in patients with tIPH.We performed a retrospective observational analysis of adult patients treated at an academic regional Level 1 trauma center between 01/2018-12/2019. We included patients who had tIPH and ≥ 2 computer tomography (CT) scans within 24 h of admission. HP, defined as ≥30% of admission hematoma volume, was calculated by the ABC/2 method. We performed stepwise multivariable logistic regressions for the association between clinical factors and outcomes.We analyzed 354 patients' charts. Mean age (Standard Deviation [SD]) was 56 (SD = 21) years, 260 (73%) were male. Mean admission hematoma volume was 7 (SD =19) cubic centimeters (cmSBP

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.

Objective The AOSpine Subaxial Cervical Spine Injury Classification System was introduced to improve communication, clinical management, and research. Here, the system was studied in relation to injury severity along with admission and long term neurologic follow-up. Methods A retrospective study was performed in subaxial cervical spine injury patients. Morphology was classified using the AOSpine Subaxial Cervical Spine Injury Classification System. Six major morphology subtypes were selected for analysis. The American Spinal Injury Association (ASIA) motor and Abbreviated Injury Severity (AIS) scores were recorded at admission and at follow-up >6 months. Admission intramedullary lesion length (IMLL) on MRI was recorded. Results In all, 82 patients met criteria for analysis. The mean follow-up time was 11 months (range, 6–33 months). The were 36 patients with morphology subtypes A0, 4 with A1/A2, 9 with A3/A4, 8 with B2, 11 with B3, and 14 with C. The A1/2 subtype had the least severe injuries on admission. The C and A3/A4 subtypes had the most severe injuries. The subtype C had the lowest ASIA Motor Score (AMS) and second highest percentage of complete injuries. A3/A4 patients had the highest percentage of complete injuries on admission. At follow-up, A3/A4 patients had the lowest AMS, and 33% of patients continued to have complete injuries. C subtype injuries all converted to AIS incomplete injuries on follow-up (P = 0.04). IMLL was found to be significantly different compared across multiple morphologic subtypes. Surgical management for each morphology subtype was reported. Conclusion The AOSpine Subaxial Cervical Spine Injury Classification System successfully associated injury morphology with IMLL along with admission and long-term neurologic function and recovery.

The therapeutic significance of timing of decompression in acute traumatic central cord syndrome (ATCCS) caused by spinal stenosis remains unsettled. We retrospectively examined a homogenous cohort of patients with ATCCS and magnetic resonance imaging (MRI) evidence of post-treatment spinal cord decompression to determine whether timing of decompression played a significant role in American Spinal Injury Association (ASIA) motor score (AMS) 6 months following trauma. We used the t test, analysis of variance, Pearson correlation coefficient, and multiple regression for statistical analysis. During a 19-year period, 101 patients with ATCCS, admission ASIA Impairment Scale (AIS) grades C and D, and an admission AMS of ≤95 were surgically decompressed. Twenty-four of 101 patients had an AIS grade C injury. Eighty-two patients were males, the mean age of patients was 57.9 years, and 69 patients had had a fall. AMS at admission was 68.3 (standard deviation [SD] 23.4); upper extremities (UE) 28.6 (SD 14.7), and lower extremities (LE) 41.0 (SD 12.7). AMS at the latest follow-up was 93.1 (SD 12.8), UE 45.4 (SD 7.6), and LE 47.9 (SD 6.6). Mean number of stenotic segments was 2.8, mean canal compromise was 38.6% (SD 8.7%), and mean intramedullary lesion length (IMLL) was 23 mm (SD 11). Thirty-six of 101 patients had decompression within 24 h, 38 patients had decompression between 25 and 72 h, and 27 patients had decompression >72 h after injury. Demographics, etiology, AMS, AIS grade, morphometry, lesion length, surgical technique, steroid protocol, and follow-up AMS were not statistically different between groups treated at different times. We analyzed the effect size of timing of decompression categorically and in a continuous fashion. There was no significant effect of the timing of decompression on follow-up AMS. Only AMS at admission determined AMS at follow-up (coefficient = 0.31; 95% confidence interval [CI]:0.21; p = 0.001). We conclude that timing of decompression in ATCCS caused by spinal stenosis has little bearing on ultimate AMS at follow-up.

Background Pedicle subtraction osteotomy (PSO) can improve sagittal alignment but carries risks, including iatrogenic spinal cord and nerve root injury. Critically, during the reduction phase of the technique, medullary kinking or neural element compression can lead to neurologic deficits. Methods We describe 3 cases of thoracic PSO and evaluate the feasibility, findings, and utility of intraoperative ultrasound in this setting. Results Intraoperative ultrasound can provide a visual assessment of spinal cord morphology before and after PSO reduction and influences surgical decision making with regard to the final amount of sagittal plane correction. This modality is particularly useful for confirming ventral decompression of disc–osteophyte complex before reduction and also after reduction maneuvers when there is kinking of the thecal sac but uncertainty about the underlying status of the spinal cord. Intraoperative ultrasound is a reliable modality that fits well into the technical sequence of PSO, adds a minimal amount of operative time, and has few limitations. Conclusions We propose that intraoperative ultrasound is a useful supplement to standard neuromonitoring modalities for ensuring safe PSO reduction and decompression of neural elements.

Cerebral edema occurs in essentially all forms of CNS injury and is frequently encountered in neurosurgical patients. Prompt recognition and appropriate treatment of cerebral edema is critical for adequate neurosurgical care. In this chapter, we discuss the history of cerebral edema and current models of cerebral edema pathophysiology. We discuss the diagnosis of cerebral edema, current methods of treatment, and complications of both edema and of its therapeutics. We anticipate that this chapter will serve as a guide to the neurosurgeon confronted with a patient suffering from cerebral edema and increased intracranial pressure.

Background Research regarding the impact of acute spinal cord injury (aSCI) on energy expenditure is limited. Patients with aSCI are prone to complications of both over- and under-feeding, making appropriate nutrition support pivotal to patient care. The purpose of this study was to describe energy expenditure and assess the performance of predictive equations in mechanically ventilated adults with aSCI. Methods Adult patients admitted to a single trauma center from March 2017 through June 2018 with aSCI and a documented indirect calorimetry (IC) within 6 weeks of injury were included for analysis. Predictive equations evaluated included Penn State 2003b (PS 2003b), the derived Weir equation, 25 kcal/kg and 30 kcal/kg. Sub-set analysis was performed for patients with and without obesity, isolated aSCI, and concomitant traumatic injuries. Results On hundres fifteen IC studies in 51 patients were included for analysis. Median energy expenditure was 1747 kcal/day (interquartile range [IQR], 1492-2099 kcal/day), or 22.7 kcal/kg (IQR, 19.3-25.9 kcal/kg). When stratified by hospital day, energy expenditure ranged from 20 to 25 kcal/kg. PS 2003b and the derived Weir equation had similar correlation coefficients (r = 0.81 and 0.82, respectively). The 25 and 30 kcal/kg performed unacceptably (r = 0.61). PS 2003b predicted within 10% of measured energy expenditure most frequently. All equations were biased towards overfeeding, except for PS 2003b in the obese subset. Conclusion In the absence of IC, PS 2003b or the derived Weir equation may be acceptable predictive equations in this population. However, bedside clinicians should monitor carefully for signs and symptoms of overfeeding.

Objective Hemorrhagic contusion in cervical spinal cord injury (CSCI) is poorly understood. We investigated hemorrhagic expansion in patients with CSCI with an assigned elevated mean arterial pressure (MAP) goal of >85 mm Hg. The change in hemorrhagic area and long-term follow-up data ≥6 months after injury was studied. Methods A retrospective review was performed from 2005 to 2016 to identify patients with motor complete CSCI with 2 cervical magnetic resonance imaging (MRI) scans within 7 days of injury showing evidence of hemorrhagic contusion and assigned a MAP goal of >85 mm Hg for 7 days. T2-weighted MRI was used to calculate the hemorrhagic surface area in the sagittal plane. A calculated MAP was recorded for each blood pressure measure between the initial and follow-up MRI scans. The American Spinal Injury Association impairment scale (AIS) and American Spinal Injury Association motor scores were recorded at the final follow-up examination at ≥6 months. Results A total of 193 patients were identified. The mean change in the hemorrhagic area was 24.0 mm2. Of the 193 patients, the AIS grade was A for 114 and B for 79 patients. Multiple logistic regression analysis demonstrated that the MAP and systolic blood pressure were nonsignificant predictors of hemorrhagic contusion expansion. An increased hemorrhagic contusion area on the follow-up MRI scan was associated with a reduced odds of AIS improvement of ≥1 and ≥2 points (odds ratio, 0.97; 95% confidence interval, 0.87–0.97; P = 0.028; and odds ratio, 0.92; 95% confidence interval, 0.99–1.13; P = 0.008, respectively) at the final ≥6-month follow-up examination. Conclusion The present study investigated the clinical safety of elevated MAP goals for patients with CSCI and hemorrhagic contusion. Elevated MAPs did not significantly increase the risk of hemorrhagic expansion in those with CSCI. We have also reported the use of hemorrhagic contusion size as a potential radiographic biomarker for neurological outcomes.

Introduction: Patients with spontaneous intracranial hemorrhage (sICH) are associated with high mortality and require early neurosurgical interventions. At our academic referral center, the neurocritical care unit (NCCU) receives patients directly from referring facilities. However, when no NCCU bed is immediately available, patients are initially admitted to the critical care resuscitation unit (CCRU). We hypothesized that the CCRU expedites transfer of sICH patients and facilitates timely external ventricular drain (EVD) placement comparable to the NCCU. Methods: This is a pre-post study of adult patients transferred with sICH and EVD placement. Patients admitted between January 2011–July 2013 (2011 Control) were compared with patients admitted either to the CCRU or the NCCU (2013 Control) between August 2013–September 2015. The primary outcome was time interval from arrival at any intensive care units (ICU) to time of EVD placement (ARR-EVD). Secondary outcomes included time interval from emergency department transfer request to arrival, and in-hospital mortality. We assessed clinical association by multivariable logistic regressions. Results: We analyzed 259 sICH patients who received EVDs: 123 (48%) CCRU; 81 (31%) 2011 Control; and 55 (21%) in the 2013 Control. The groups had similar characteristics, age, disease severity, and mortality. Median ARR-EVD time was 170 minutes [106–311] for CCRU patients; 241 minutes [152–490] (p < 0.01) for 2011 Control; and 210 minutes [139–574], p = 0.28) for 2013 Control. Median transfer request-arrival time for CCRU patients was significantly less than both control groups. Multivariable logistic regression showed each minute delay in ARR-EVD was associated with 0.03% increased likelihood of death (odds ratio 1.0003, 95% confidence interval, 1.0001–1.006, p = 0.043). Conclusion: Patients admitted to the CCRU had shorter transfer times when compared to patients admitted directly to other ICUs. Compared to the specialty NCCU, the CCRU had similar time interval from arrival to EVD placement. A resuscitation unit like the CCRU can complement the specialty unit NCCU in caring for patients with sICH who require EVDs.

The incidence of traumatic spinal cord injury (SCI) has not changed much over the years due to an aging population suffering falls, yet advances have been made in quality of life and survival time. In addition to initial medical and surgical stabilization, modern intensive care unit (ICU) care throughout the critical early period following SCI is essential to avoid continued secondary injury to the spinal cord. Cervical SCI patients are particularly prone and sensitive to periods of cardiovascular instability and respiratory failure directly resulting from their injuries. Preclinical and class III clinical data suggest improved outcomes by maintaining the mean arterial pressure > 85 mm Hg and avoiding hypoxemia at least for 7 days following cervical SCI, and this level of monitoring and support should occur in the ICU.

BACKGROUND AND PURPOSE: Hemorrhagic contusions are associated with iodine leakage. We aimed to identify quantitative iodine-based dual-energy CT variables that correlate with the type of intracranial pressure management. MATERIALS AND METHODS: Consecutive patients with contusions from May 2016 through January 2017 were retrospectively analyzed. Radiologists, blinded to the outcomes, evaluated CT variables from unenhanced admission and short-term follow-up head dual-energy CT scans obtained after contrast-enhanced whole-body CT. Treatment intensity of intracranial pressure was broadly divided into 2 groups: those managed medically and those managed surgically. Univariable analysis followed by logistic regression was used to develop a prediction model. RESULTS: The study included 65 patients (50 men; median age, 48 years; Q1 to Q3, 25–65.5 years). Twenty-one patients were managed surgically (14 by CSF drainage, 7 by craniectomy). Iodine-based variables that correlated with surgical management were higher iodine concentration, pseudohematoma volume, iodine quantity in pseudohematoma, and iodine quantity in contusions. The regression model developed after inclusion of clinical variables identified 3 predictor variables: postresuscitation Glasgow Coma Scale (adjusted OR = 0.55; 95% CI, 0.38–0.79; P = .001), age (adjusted OR = 0.9; 95% CI, 0.85–0.97; P = .003), and pseudohematoma volume (adjusted OR = 2.05; 95% CI, 1.1–3.77; P = .02), which yielded an area under the curve of 0.96 in predicting surgical intracranial pressure management. The 2 predictors for craniectomy were age (adjusted OR = 0.89; 95% CI, 0.81–0.99; P = .03) and pseudohematoma volume (adjusted OR = 1.23; 95% CI, 1.03–1.45; P = .02), which yielded an area under the curve of 0.89. CONCLUSIONS: Quantitative iodine-based parameters derived from follow-up dual-energy CT may predict the intensity of intracranial pressure management in patients with hemorrhagic contusions.

BackgroundTraumatic hemorrhagic contusions are associated with iodine leak; however, quantification of leakage and its importance to outcome is unclear.PurposeTo identify iodine-based dual-energy CT variables that correlate with in-hospital mortality and short-term outcomes for contusions at hospital discharge.Materials and MethodsIn this retrospective study, consecutive patients with contusions from May 2016 through January 2017 were analyzed. Two radiologists evaluated CT variables from unenhanced admission head CT and follow-up head dual-energy CT scans obtained after contrast material-enhanced whole-body CT. The outcomes evaluated were in-hospital mortality, Rancho Los Amigos scale (RLAS) score, and disability rating scale (DRS) score. Logistic regression and linear regression were used to develop prediction models for categorical and continuous outcomes, respectively.ResultsThe study included 65 patients (median age, 48 years; interquartile range, 25-65.5 years); 50 were men. Dual-energy CT variables that correlated with mortality, RLAS score, and DRS score were iodine concentration, pseudohematoma volume, iodine quantity in pseudohematoma, and iodine quantity in contusion. The single-energy CT variable that correlated with mortality, RLAS score, and DRS score was hematoma volume at follow-up CT. Multiple logistic regression analysis after inclusion of clinical variables identified two predictors that enabled determination of mortality: postresuscitation Glasgow coma scale (P-GCS) (adjusted odds ratio, 0.42; 95% confidence interval [CI]: 0.2, 0.86; P = 0.01) and iodine quantity in pseudohematoma (adjusted odds ratio, 1.4 per milligram; 95% CI: 1.02 per milligram, 1.9 per milligram; P = 0.03), with a mean area under the receiver operating characteristic curve of 0.96 ± 0.05 (standard error). For RLAS, the predictors were P-GCS (mean coefficient, 0.32 ± 0.06; P < .001) and iodine quantity in contusion (mean coefficient, -0.04 per milligram ± 0.02; P = 0.01). Predictors for DRS were P-GCS (mean coefficient, -1.15 ± 0.27; P < .001), age (mean coefficient, 0.13 per year ± 0.04; P = .002), and iodine quantity in contusion (mean coefficient, 0.19 per milligram ± 0.07; P = .02).ConclusionIodine-based dual-energy CT variables correlate with in-hospital mortality and short-term outcomes for contusions at hospital discharge.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Talbott and Hess in this issue.

Introduction The practice of platelet transfusion to mitigate the deleterious effects of antiplatelet agents on spontaneous intracerebral hemorrhage (ICH) remains common. However, the effect of antiplatelet agents on patients with ICH is still controversial and transfusing platelets is not without risk. We performed a meta-analysis in order to determine the effect of platelet transfusion on antiplatelet agent associated ICH. Methods We queried PubMed, Embase, and Scopus databases to identify cohort studies, case-control studies, and randomized control trials. Study quality was graded by the Newcastle-Ottawa Scale and Cochrane Risk of Bias tool, as appropriate. Outcomes of interest included functional independence as measured by the modified Rankin Scale and mortality. We compared patients with antiplatelet agent associated ICH who received platelet transfusion to those that did not. Results We identified 625 articles. After reviewing 44 full text articles, 5 were deemed appropriate for meta-analysis, including 4 cohort studies and one randomized control trial. Considerable heterogeneity was present among the studies (I2 > 81% for all analyses). We did not find a significant effect of platelet transfusions on functional independence (Odds Ratio [OR] 1.3, 95% CI.0.45–3.9) or mortality (OR 0.58, 95% Confidence Interval [CI] 0.12–2.6). Conclusion We found no evidence for an effect of platelet transfusions on functional independence or mortality following antiplatelet associated ICH. More randomized trials are needed to evaluate platelet transfusion in patients with ICH and proven reduced platelet activity or those requiring neurosurgical intervention.

Data regarding who will require tracheostomy are lacking which may limit investigations into therapeutic effects of early tracheostomy. We performed an observational study of adult traumatic brain injury (TBI) patients requiring intensive care unit (ICU) admission for ≥ 72 h and mechanical ventilation for ≥ 24 h between January 2014 and December 2014 at a level 1 trauma center. Patients who had life-sustaining measures withdrawn were excluded. Multivariable logistic regression analyses were used to assess admission and inpatient factors associated with receiving a tracheostomy and to develop predictive models. Inpatient complications prior to day 7 were used to standardize data collection for patients with and without tracheostomy. Patients who received tracheostomy prior to day 7 were excluded from analysis. In total, 209 patients (78% men, mean 48 years old, median Glasgow Coma Scale score (GCS) 8) met study criteria with tracheostomy performed in 94 (45%). Admission predictors of tracheostomy included GCS, chest tube, Injury Severity Score, and Marshall score. Inpatient factors associated with tracheostomy included the requirement for an external ventricular drain (EVD), number of operations, inpatient dialysis, aspiration, GCS on day 5, and reintubation. Multiple logistic regression analysis demonstrated that the number of operation room trips (adjusted odds ratio [AOR], 1.75; 95% CI, 1.04–2.97; P = 0.036), reintubation (AOR, 8.45; 95% CI, 1.91–37.44; P = .005), and placement of an EVD (AOR, 3.48; 95% CI, 1.27–9.58; P = .016) were independently associated with patients undergoing tracheostomy. Higher GCS on hospital day 5 (AOR, 0.52; 95% CI, 0.40–0.68; P

High-energy monochromatic (190 keV) images may be more reliable than standard 120 kV Images for detecting intracranial hemorrhages. We aimed to retrospectively compare virtual high monochromatic (190 keV) and standard 120 kV images from dual-energy computed tomography (CT; DECT) for the diagnosis of intracranial hemorrhages in traumatic brain injury (TBI). We analyzed admission CT studies in 100 trauma patients. Three radiologists independently reviewed four image sets: 120 kV and 190 keV (thin [1 mm] and thick [5 mm] section) images for the presence of various types of intracranial hemorrhages. The proportions of positive variables were compared and differences calculated by McNemar test and sensitivities determined by contingency tables. Randomly selected hemorrhagic lesions were analyzed for contrast index (CI). Thin-section 190 keV images were superior in the detection of subdural hematomas (SDH) (p 0.0001), supratentorial contusions (p 0.0001), and epidural hematomas (EDH) (p = 0.014), when compared with standard 120 kV images. However, 190 keV images were inferior to standard 120 kV images in diagnosis of subarachnoid hemorrhage (SAH) (thin-sections, p = 0.059; thick-sections, 0.0075). The 190 keV images yielded moderate increase in CI of contusions (Cohen's d 0.53) and a large increase in CI of extra-axial hematomas (Cohen's d 0.86). Our results indicate that virtual high monochromatic (190 keV, thin-section) images combined with standard 120 kV images may provide optimal diagnostic performance for evaluation of patients suspected of TBI.

Although decompressive surgery following traumatic spinal cord injury (TSCI) is recommended, adequate surgical decompression is rarely verified via imaging. We utilized magnetic resonance imaging (MRI) to analyze the rate of spinal cord decompression after surgery. Pre-operative (within 8 h of injury) and post-operative (within 48 h of injury) MRI images of 184 motor complete patients (American Spinal Injury Association Impairment Scale [AIS] grade A = 119, AIS grade B = 65) were reviewed to verify spinal cord decompression. Decompression was defined as the presence of a patent subarachnoid space around a swollen spinal cord. Of the 184 patients, 100 (54.3%) underwent anterior cervical discectomy and fusion (ACDF), and 53 of them also underwent laminectomy. Of the 184 patients, 55 (29.9%) underwent anterior cervical corpectomy and fusion (ACCF), with (26 patients) or without (29 patients) laminectomy. Twenty-nine patients (16%) underwent stand-alone laminectomy. Decompression was verified in 121 patients (66%). The rates of decompression in patients who underwent ACDF and ACCF without laminectomy were 46.8% and 58.6%, respectively. Among these patients, performing a laminectomy increased the rate of decompression (72% and 73.1% of patients, respectively). Twenty-five of 29 (86.2%) patients who underwent a stand-alone laminectomy were found to be successfully decompressed. The rates of decompression among patients who underwent laminectomy at one, two, three, four, or five levels were 58.3%, 68%, 78%, 80%, and 100%, respectively (p

The pathophysiology of acute-on-chronic subdural hematoma (ACSDH) is complex and incompletely understood. Evidence to date indicates that the overall process is initiated by rotational force with movement of the brain inside the skull, which exerts tensile strain and rupture of bridging veins, leading in turn to acute hemorrhage in the subdural potential space. This is followed by the proliferation of mesenchymal elements with angiogenesis and inflammation, which in turn becomes a substrate for repeated hemorrhage and expansion of the lesion. Given the prevalence of traumatic subdural processes in the forensic setting and the importance of proper assessment of timing, etiology, risk factors, and clinicopathological correlation, we studied 47 patients presenting to the University of Maryland Shock Trauma Center, all of whom underwent craniotomy with resection of the outer membrane due to symptomatic ACSDH. The surgically resected tissue was examined for histopathologic features in all cases. Our findings highlight that ACSDH is a condition precipitated by trauma that affects middle-aged and older adults, is relatively indolent, is unilateral or asymmetric, and has a low in-hospital mortality rate. Pathological analysis demonstrates a substantial outer membrane in all cases with varying degrees of inflammation and organization that cannot be precisely dated as a function of clinical presentation. The extrapolation of adult ACSDH to mixed acute and chronic subdural hemorrhage in the pediatric setting is problematic due to substantial differences in clinical presentation, severity of underlying brain injury, gross and microscopic findings, and outcome.

Assessment of neurologic injury and the evolution of severe neurologic injury is limited in comatose or critically ill patients that lack a reliable neurologic examination. For common yet severe pathologies such as the comatose state after cardiac arrest, aneurysmal subarachnoid hemorrhage (aSAH), and severe traumatic brain injury (TBI), critical medical decisions are made on the basis of the neurologic injury. Decisions regarding active intensive care management, need for neurosurgical intervention, and withdrawal of care, depend on a reliable, high-quality assessment of the true state of neurologic injury, and have traditionally relied on limited assessments such as intracranial pressure monitoring and electroencephalogram. However, even within TBI there exists a spectrum of disease that is likely not captured by such limited monitoring and thus a more directed effort towards obtaining a more robust biophysical signature of the individual patient must be undertaken. In this review, multimodal monitoring including the most promising serum markers of neuronal injury, cerebral microdialysis, brain tissue oxygenation, and pressure reactivity index to access brain microenvironment will be discussed with their utility among specific pathologies that may help determine a more complete picture of the neurologic injury state for active intensive care management and long-term outcomes. Goal-directed therapy guided by a multi-modality approach appears to be superior to standard intracranial pressure (ICP) guided therapy and should be explored further across multiple pathologies. Future directions including the application of optogenetics to evaluate brain injury and recovery and even as an adjunct monitoring modality will also be discussed.

The underlying molecular mechanisms of the remodeling after myocardial infarction (MI) remain unclear. The purpose of this study was to investigate the role of a survival pathway (PI3K/Akt) and an apoptosis pathway (calcineurin/BAD) in the remodeling after MI in a large animal model.Ten Dorset hybrid sheep underwent 25% MI in the left ventricle (LV, n=10). Five sheep were used as sham control. The regional strain was calculated from sonomicrometry. Apoptosis and the activation of the PI3K/Akt and calcineurin/BAD pathways were evaluated in the non-ischemic adjacent zone and the remote zone relative to infarct by immunoblotting, immunoprecipitation, and immunofluorescence staining.Dilation and dysfunction of LV were present at 12 weeks after MI. The regional strain in the adjacent zone was significantly higher than in the remote zone at 12 weeks (36.6 ± 4.0% vs 9.5 ± 3.6%, p0.05). Apoptosis was more severe in the adjacent zone than in the remote zone. The PI3K/Akt and calcineurin/BAD pathways were activated in the adjacent zone. Dephosphorylation and translocation of BAD were evident in the adjacent zone. Regional correlation between the strain and the expression of calcineurin/BAD indicated that the activation was strain-related (R(2)=0.46, 0.48, 0.39 for calcineurin, BAD, mitochondrial BAD, respectively, p0.05).The PI3K/Akt survival and calcineurin/BAD apoptotic pathways were concomitantly activated in the non-ischemic adjacent zone after MI. The calcineurin/BAD pathway is strain related and its imbalanced activation may be one of the causes of progressive remodeling after MI.

Object The authors performed a study to determine if lesion expansion occurs in humans during the early hours after spinal cord injury (SCI), as has been established in rodent models of SCI, and to identify factors that might predict lesion expansion. Methods The authors studied 42 patients with acute cervical SCI and admission American Spinal Injury Association Impairment Scale Grades A (35 patients) and B (7 patients) in whom 2 consecutive MRI scans were obtained 3–134 hours after trauma. They recorded demographic data, clinical information, Injury Severity Score (ISS), admission MRI-documented spinal canal and cord characteristics, and management strategies. Results The characteristics of the cohort were as follows: male/female ratio 37:5; mean age, 34.6 years; and cause of injury, motor vehicle collision, falls, and sport injuries in 40 of 42 cases. The first MRI study was performed 6.8 ±2.7 hours (mean ± SD) after injury, and the second was performed 54.5 ± 32.3 hours after injury. The rostrocaudal intramedullary length of the lesion on the first MRI scan was 59.2 ± 16.1 mm, whereas its length on the second was 88.5 ± 31.9 mm. The principal factors associated with lesion length on the first MRI study were the time between injury and imaging (p = 0.05) and the time to decompression (p = 0.03). The lesion's rate of rostrocaudal intramedullary expansion in the interval between the first and second MRI was 0.9 ± 0.8 mm/hour. The principal factors associated with the rate of expansion were the maximum spinal cord compression (p = 0.03) and the mechanism of injury (p = 0.05). Conclusions Spinal cord injury in humans is characterized by lesion expansion during the hours following trauma. Lesion expansion has a positive relationship with spinal cord compression and may be mitigated by early surgical decompression. Lesion expansion may be a novel surrogate measure by which to assess therapeutic effects in surgical or drug trials.

Background Cardiac remodeling has been shown to have deleterious effects at both the global and local levels. The objective of this study is to investigate the role of strain in the initiation of structural and functional changes of myocardial tissue and its relation to alteration of calcium-handling proteins during cardiac remodeling after myocardial infarction. Methods Sixteen sonomicrometry transducers were placed in the left ventricular free wall of 9 sheep to measure the regional strain in the infarct, adjacent, and remote myocardial regions. Hemodynamic, echocardiographic, and sonomicrometry data were collected before myocardial infarction, after infarction, and 2, 6, and 8 weeks after infarction. Regional myocardial tissues were collected for calcium-handling proteins at the end study. Results At time of termination, end-systolic strains in 3 regionally distinct zones (remote, adjacent, and infarct) of myocardium were measured to be −14.65 ± 1.13, −5.11 ± 0.60 ( P ≤ .05), and 0.92 ± 0.56 ( P ≤ .05), respectively. The regional end-systolic strain correlated strongly with the abundance of 2 major calcium-handling proteins: sarcoplasmic reticulum Ca 2+ adenosine triphosphatase subtype 2a ( r 2 = 0.68, P ≤ .05) and phospholamban ( r 2 = 0.50, P ≤ .05). A lesser degree of correlation was observed between the systolic strain and the abundance of sodium/calcium exchanger type 1 protein ( r 2 = 0.17, P ≤ .05). Conclusions Regional strain differences can be defined in the different myocardial regions during postinfarction cardiac remodeling. These differences in regional strain drive regionally distinct alterations in calcium-handling protein expression.

INTRODUCTION:Cerebral venous sinus thrombosis (CVST) is a potentially devastating neurological outcome of closed head trauma. Current guidelines recommend anticoagulation in adults with spontaneous CVST. Although intracranial hemorrhage resulting from a sinus thrombosis is not considered a contraind

Traumatic brain injury (TBI) caused by an explosive blast (blast-TBI) is postulated to result, in part, from transvascular transmission to the brain of a hydrodynamic pulse (a.k.a., volumetric blood surge, ballistic pressure wave, hydrostatic shock, or hydraulic shock) induced in major intrathoracic blood vessels. This mechanism of blast-TBI has not been demonstrated directly. We tested the hypothesis that a blast wave impacting the thorax would induce a hydrodynamic pulse that would cause pathological changes in the brain. We constructed a Thorax-Only Blast Injury Apparatus (TOBIA) and a Jugular-Only Blast Injury Apparatus (JOBIA). TOBIA delivered a collimated blast wave to the right lateral thorax of a rat, precluding direct impact on the cranium. JOBIA delivered a blast wave to the fluid-filled port of an extracorporeal intravenous infusion device whose catheter was inserted retrograde into the jugular vein, precluding lung injury. Long Evans rats were subjected to sublethal injury by TOBIA or JOBIA. Blast injury induced by TOBIA was characterized by apnea and diffuse bilateral hemorrhagic injury to the lungs associated with a transient reduction in pulse oximetry signals. Immunolabeling 24 h after injury by TOBIA showed up-regulation of tumor necrosis factor alpha, ED-1, sulfonylurea receptor 1 (Sur1), and glial fibrillary acidic protein in veins or perivenular tissues and microvessels throughout the brain. The perivenular inflammatory effects induced by TOBIA were prevented by ligating the jugular vein and were reproduced using JOBIA. We conclude that blast injury to the thorax leads to perivenular inflammation, Sur1 up-regulation, and reactive astrocytosis resulting from the induction of a hydrodynamic pulse in the vasculature.

The cellular and molecular basis of growth hormone (GH) actions on the heart remain poorly defined, and it is unclear whether GH effects on the myocardium are direct or mediated at least in part via insulin-like growth factor (IGF-1). Here, we demonstrate that the cultured neonatal cardiomyocyte is not an appropriate model to study the effects of GH because of artifactual loss of GH receptors (GHRs). To circumvent this problem, rat neonatal cardiomyocytes were infected with a recombinant adenovirus expressing the murine GHR. Functional integrity of GHR was suggested by GH-induced activation of the cognate JAK2/STAT5, MAPK, and Akt intracellular pathways in the cells expressing GHR. Although exposure to GH resulted in a significant increase in the size of the cardiomyocyte and increased expression of c-fos, myosin light chain 2, and skeletal alpha-actin mRNAs, there were no significant changes in IGF-1 or atrial natriuretic factor mRNA levels in response to GH stimulation. In this model, GH increased incorporation of leucine, uptake of palmitic acid, and abundance of fatty acid transport protein mRNA. In contrast, GH decreased uptake of 2-deoxy-d-glucose and levels of Glut1 protein. Thus, in isolated rat neonatal cardiomyocytes expressing GHR, GH induces hypertrophy and causes alterations in cellular metabolic profile in the absence of demonstrable changes in IGF-1 mRNA, suggesting that these effects may be independent of IGF-1.

The growth hormone (GH) receptor is essential for the actions of growth hormone on postnatal growth and metabolism. GH receptor transcripts are characterized by the presence of disparate 5'-untranslated exons. Factors regulating the expression of the GC rich L2 transcript of the murine GH receptor gene have hitherto remained unidentified. To characterize the mechanisms regulating expression of the L2 transcript, primer extension and ribonuclease protection assays were used to identify transcription start sites in RNA from liver of adult mice. Transient transfection experiments revealed that 2.0 kilobase pairs of the L2 5'-flanking sequence exhibited promoter activity in BNL CL.2 (mouse liver) cells, CV-1 (monkey kidney) cells, and HRP.1 trophoblasts. Deletional analysis localized a major regulatory region to within 75 base pairs of the 5' transcription start site. Sequence analysis revealed that the region contained consensus binding sites for the Sp family of transcription factors. Standard gel shift and supershift analysis using liver nuclear extracts established that Sp1 and Sp3 bound this regulatory element. Transfection of wild type but not mutant decoy oligonucleotides into BNL CL.2 cells decreased the activity of the L2 promoter. Overexpression of Sp1 and Sp3 protein in Drosophila Schneider cells established that Sp3 is more potent than Sp1 in transactivating the L2 promoter. Co-transfection experiments further established that Sp1 antagonizes the activity of Sp3 to transactivate the L2 promoter. Western blot analysis of liver nuclear extracts revealed that the levels of Sp3 increase significantly after birth, suggesting a role for the Sp family of transcription factors in controlling the fetal to postnatal increase in GH receptor gene expression.

Pituitary growth hormone (GH) is essential for postnatal growth in animals. GH exerts its actions by direct effect on target organs and by stimulating the production of insulin-like growth factor I (IGF-I). At the tissue level, the pleiotropic actions of GH result from the interaction of GH with a specific cell surface receptor, the GH receptor (GHR). The GHR belongs to the hematopoietic receptor superfamily. The human GHR is the product of a single gene located on chromosome 5p13.1-p12 and spans at least 87 kb. Transcripts from this gene are characterized by the presence of disparate 5' untranslated exons. In the liver at least eight different GHR 5' untranslated regions (UTRs) have been described. This heterogeneity in the 5' UTR most likely results from the splicing of the various exon 1 fragments to a common splice site located 11 bp upstream of the initiating ATG. Heterogeneity in the 5' UTR sequences of the GHR transcripts indicates that transcriptional control of the locus is complex. GHR gene expression is minimal to absent in the fetus, with the postnatal increase in expression in the liver being maximal during pregnancy. GHR gene expression is also regulated by factors such as nutritional intake, GH, steroid hormones, and diabetes mellitus. Available information about the molecular mechanisms regulating expression of the GHR gene is discussed. Thus the GHR gene presents a picture of multiple 5' untranslated exons under the control of multiple promoters. The use of alternate promoters for initiation of transcription in conjunction with differential splicing allows for exquisite regulation of gene expression. This schema is appropriate for a protein that is essential to many of the physiological processes that are crucial for the survival and well-being of the organism.

We studied a model of hemorrhagic encephalopathy of prematurity (EP) that closely recapitulates findings in humans with hemorrhagic EP. This model involves tandem insults of 20 min intrauterine ischemia (IUI) plus an episode of elevated venous pressure induced by intraperitoneal glycerol on post-natal day (P) 0. We examined Sur1 expression, which is upregulated after focal ischemia but has not been studied after brief global ischemia including IUI. We found that 20 min IUI resulted in robust upregulation of Sur1 in periventricular microvessels and tissues. We studied tandem insult pups from untreated or vehicle-treated dams (TI-CTR), and tandem insult pups from dams administered a low-dose, non-hypoglycemogenic infusion of the Sur1 blocker, glibenclamide, for 1 week after IUI (TI-GLIB). Compared to pups from the TI-CTR group, pups from the TI-GLIB group had significantly fewer and less severe hemorrhages on P1, performed significantly better on the beam walk and accelerating Rotarod on P35 and in tests of thigmotaxis and rapid learning on P35–49, and had significantly greater body and brain weights at P52. We conclude that low-dose glibenclamide administered to the mother at the end of pregnancy protects pups subjected to IUI from post-natal events of elevated venous pressure and its consequences.

The sulfonylurea receptor 1 (Sur1)-regulated NCCa-ATP channel is a nonselective cation channel that is regulated by intracellular calcium and adenosine triphosphate. The channel is not constitutively expressed, but is transcriptionally upregulated de novo in all cells of the neurovascular unit, in many forms of central nervous system (CNS) injury, including cerebral ischemia, traumatic brain injury (TBI), spinal cord injury (SCI), and subarachnoid hemorrhage (SAH). The channel is linked to microvascular dysfunction that manifests as edema formation and delayed secondary hemorrhage. Also implicated in oncotic cell swelling and oncotic (necrotic) cell death, the channel is a major molecular mechanism of ‘accidental necrotic cell death’ in the CNS. In animal models of SCI, pharmacological inhibition of Sur1 by glibenclamide, as well as gene suppression of Abcc8, prevents delayed capillary fragmentation and tissue necrosis. In models of stroke and TBI, glibenclamide ameliorates edema, secondary hemorrhage, and tissue damage. In a model of SAH, glibenclamide attenuates the inflammatory response due to extravasated blood. Clinical trials of an intravenous formulation of glibenclamide in TBI and stroke underscore the importance of recent advances in understanding the role of the Sur1-regulated NCCa-ATP channel in acute ischemic, traumatic, and inflammatory injury to the CNS.

We developed a forwarding-imaging needle-type OCT probe for avoiding the hemorrhage and guiding neurosurgical interventions. The feasibility of vessel detection and neurosurgical guidance were demonstrated on sheep brain in vivo and human brain ex vivo.