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Purpose of review This review illustrates the evolution and progress with standardization of fellowship education in neuroanesthesiology. It provides a structured discussion around the need for curricula and framework which individual training programs in neuroanesthesiology can use to meet defined educational standards thus meeting criteria for accreditation. Recent findings Neuroanesthesiology training has traditionally been heterogenous around the world but international efforts from the community of neuroanesthesiology have culminated in the development of an international council for perioperative training in neuroscience in anesthesiology(ICPNT). This serves not only as an accrediting body but also creates a platform through their neuroanesthesia program relations committee for collaboration and engagement between various training programs internationally, increasing the educational standards of the individual programs and collectively increasing the overall level of standards for neuroanesthesia training. Standardized curriculum and competency-based assessments and milestones would help with narrowing the focus to quality education in neuroanesthesiology. Summary Structured training around the three pillars of neuroanesthesiology with concomitant accreditation is expected to lead to higher education standards with better patient care. The SNACC created milestones for neuroanesthesiology training during residency and the ICPNT can now use this as a foundation for fellowship training. Having a council to accredit and standardize will likely become indispensable in creating a set path for training in neuroanesthesiology. Additionally, the flexibility built in due to the international nature would allow modified and variable pathways depending upon individual capabilities and interests. The path forward will include widespread adoption of standardization supporting the overarching goal of excellent patient outcomes around the world.

Aim We evaluated the association of physiological parameters measured by intracranial multimodality neuromonitoring with neurologic outcome in a consecutive series of patients with hypoxic-ischemic brain injury (HIBI). Methods We retrospectively identified all patients with HIBI who underwent combined invasive intracranial pressure (ICP) and brain tissue oxygen (PbtO2) monitoring over a 3 year period. Cerebrovascular pressure reactivity index (PRx) was calculated continuously as a surrogate of cerebral autoregulation. Favorable outcome was defined as recovery of consciousness (Glasgow Coma Scale motor score = 6). Differences in mean ICP, PRx and PbtO2 for the entire monitoring period across outcomes were measured. Logistic regression and area under receiver operating characteristic (AUROC) curve were used to assess the association of each monitoring parameter with neurologic outcome. Results We analyzed data from 36 patients. Most (89%) had an antecedent sudden cardiac arrest. Favorable outcome occurred in 8 (22%) patients. ICP and PRx were higher in patients with unfavorable outcome (ICP: 26 ± 4.1 mmHg vs 7.5 ± 2 mmHg, p = 0.0002; PRx: 0.51 ± 0.05 vs 0.11 ± 0.05, p 15 mmHg, PRx > 0.2, and PbtO2 Conclusion Cerebrovascular pressure reactivity and intracranial pressure appear to be associated with neurologic outcome in patients with HIBI.

Background The COVID-19 pandemic is an international crisis placing tremendous strain on medical systems around the world. Like other specialties, neuroanesthesiology has been adversely affected and training programs have had to quickly adapt to the constantly changing environment. Methods An email-based survey was used to evaluate the effects of the pandemic on clinical workflow, clinical training, education, and trainee well-being. The impact of the International Council on Perioperative Neuroscience Training (ICPNT) accreditation was also assessed. Results Responses were received from 14 program directors (88% response rate) in 10 countries and from 36 fellows in these programs. Clinical training was adversely affected because of the cancellation of elective neurosurgery and other changes in case workflow, the introduction of modified airway and other protocols, and redeployment of trainees to other sites. To address educational demands, most programs utilized online platforms to organize clinical discussions, journal clubs, and provide safety training modules. Several initiatives were introduced to support trainee well-being during the pandemic. Feelings of isolation and despair among trainees varied from 2 to 8 (on a scale of 1 to 10). Fellows all reported concerns that their clinical training had been adversely affected by the coronavirus disease 2019 (COVID-19) pandemic because of decreased exposure to elective subspecialty cases and limited opportunities to complete workplace-based assessments and training portfolio requirements. Cancellation of examination preparation courses and delayed examinations were cited as common sources of stress. Programs accredited by the ICPNT reported that international networking and collaboration was beneficial to reduce feelings of isolation during the pandemic. Conclusion Neuroanesthesia fellowship training program directors introduced innovative ways to maintain clinical training, educational activity and trainee well-being during the COVID-19 pandemic.

The pandemic of coronavirus disease 2019 (COVID-19) has unique implications for the anesthetic management of endovascular therapy for acute ischemic stroke. The Society for Neuroscience in Anesthesiology and Critical Care appointed a task force to provide timely, consensus-based expert recommendations using available evidence for the safe and effective anesthetic management of endovascular therapy for acute ischemic stroke during the COVID-19 pandemic. The goal of this consensus statement is to provide recommendations for anesthetic management considering the following (and they are): (1) optimal neurological outcomes for patients; (2) minimizing the risk for health care professionals, and (3) facilitating judicious use of resources while accounting for existing variability in care. It provides a framework for selecting the optimal anesthetic technique (general anesthesia or monitored anesthesia care) for a given patient and offers suggestions for best practices for anesthesia care during the pandemic. Institutions and health care providers are encouraged to adapt these recommendations to best suit local needs, considering existing practice standards and resource availability to ensure safety of patients and providers.

Environmental factors contribute to autism spectrum disorder. Fentanyl, one of the most widely used opioid analgesics in anaesthesia, can induce neurotoxicity, but its role in autism remains unknown. We determined whether fentanyl induced autism-like behaviours in young mice and the underlying mechanisms.Young male and female mice received fentanyl at postnatal days 6, 8, and 10, and performed behavioural tests, including three-chamber social preference, elevated plus maze, grooming behaviour, and open-field test, from postnatal days 30-32. Expression of Grin2b, the gene encoding the GluN2B subunit of the N-methyl-d-aspartate receptor, was assessed in the anterior cingulate cortex of male mice using fluorescence in situ hybridisation histochemistry. We used bisulfite target sequencing to determine Grin2b hypermethylation sites after fentanyl treatment. In the specific activation and rescue experiments, we injected the mu opioid receptor agonist [D-Ala,Fentanyl induced autism-like behaviours in both young male and female mice, and downregulated Grin2b expression (0.49-fold [0.08] vs 1.00-fold [0.09]; P0.01) and GluN2B protein amounts (0.38-fold [0.07] vs 1.00-fold [0.12]; P0.01) in the anterior cingulate cortex through hypermethylation of Grin2b. The mu-opioid receptor antagonist naloxone and overexpression of Grin2b in anterior cingulate cortex attenuated the fentanyl-induced effects, whereas DAMGO injection into the anterior cingulate cortex induced autism-like behaviours.These data suggest that fentanyl induces autism-like behaviours in young mice via an epigenetic mechanism. Further research is required to determine possible clinical relevance to autism risk.

Background The physiological and neurochemical changes that accompany brain death are not well described. Materials and methods A retrospective observational study of patients with acute brain injury who underwent intracranial multimodality neuromonitoring between October 2015 and June 2018. Patients were included for analysis either if brain death was diagnosed or refractory intracranial hypertension with persistent equalization of intracranial pressure (ICP) and mean arterial pressure (MAP) developed. Results Of 114 patients who underwent invasive neuromonitoring, 11 cases with MAP/ICP equalization were identified. Of those, 9 were declared brain dead based on accepted national and institutional criteria. An additional 2 cases with MAP/ICP equalization who died after withdrawal of life-sustaining therapies were identified. Of the 11 identified patients, 10 had continuous monitoring data available for analysis. Cerebral microdialysis data were available for 4 patients.In the 10 cases with available continuous data, ICP/MAP equalization was associated with marked reduction of cerebral blood flow and brain tissue oxygen tension to near zero levels as well as a significant decrease in brain temperature compared with body temperature. In the 4 patients with microdialysis monitoring, ICP/MAP equalization resulted in a near complete depletion of cerebral glucose and pyruvate, as well as a marked rise in cerebral glycerol. Finally, ICP/MAP equalization was accompanied by complete loss of cerebrovascular pressure reactivity, decrease in intracranial pulse pressure, and a paradoxical improvement of ICP waveform morphology. Conclusions A characteristic set of changes in cerebrovascular physiology and neurochemistry occurs during brain death. These changes can be identified by intracranial neuromonitoring.

INTRODUCTION: Mechanical thrombectomy is revolutionizing treatment of acute stroke due to large vessel occlusion (LVO). Unfortunately, use of the modified Thrombolysis in Cerebral Infarction score (mTICI) to characterize recanalization of the cerebral vasculature does not address microvascular perfusion of the distal parenchyma, nor provide more than a vascular “snapshot”. Thus, little is known about tissue-level hemodynamic consequences of LVO recanalization. Diffuse correlation spectroscopy (DCS) and diffuse optical spectroscopy (DOS) are promising methods for continuous, non-invasive, contrast-free transcranial monitoring of cerebral microvasculature. METHODS: Here we use a combined DCS/DOS system to monitor frontal lobe hemodynamic changes during endovascular treatment of two patients with ischemic stroke due to cervical internal carotid artery (ICA) occlusions. RESULTS AND DISCUSSION: The monitoring instrument identified a recanalization-induced increase in ipsilateral cerebral blood flow (CBF) with little or no concurrent change in contralateral CBF and extracerebral blood flow. The results suggest that diffuse optical monitoring is sensitive to intracerebral hemodynamics in patients with cervical ICA occlusion and can measure microvascular responses to mechanical thrombectomy.

Monitoring critical closing pressure (CrCP) can be a useful and noninvasive measure of intracranial pressure (ICP), especially in patients with high risk factors for brain injury. We monitored five patients undergoing cardiac ablation procedures using diffuse correlation spectroscopy (DCS). We utilized the prolonged diastolic events that occur during this procedure to validate non-invasive measurements of CrCP with DCS. to estimate the gold standard CrCP during long diastolic events induced during the procedure and compared them to estimations from normal pressure and flow waveforms prior to each event.

Intracranial pressure (ICP) is a critical biomarker measured invasively with the risk of complications. There is a need for non-invasive methods to estimate ICP. Diffuse correlation spectroscopy (DCS) allows the non-invasive measurement of pulsatile, microvascular cerebral blood flow which contains information about ICP. Recently, our proof-of-concept study used machine-learning to deduce ICP from DCS signals to estimate ICP resulting in excellent linearity and a reasonable accuracy (±4 mmHg). Here, we extend to a multi-center (three centers) data set of adults with acute brain injury (N=34). We will present the results from the complete data set as new data flows in.

BACKGROUND Analysis of intracranial multimodality monitoring data is challenging, and quantitative methods may help identify unique physiological signatures that inform therapeutic strategies and outcome prediction. The aim of this study was to test the hypothesis that data-driven approaches can identify distinct physiological states from intracranial multimodality monitoring data. METHODS This was a single-center retrospective observational study of patients with either severe traumatic brain injury or high-grade subarachnoid hemorrhage who underwent invasive multimodality neuromonitoring. We used hierarchical cluster analysis to group hourly values for heart rate, mean arterial pressure, intracranial pressure, brain tissue oxygen, and cerebral microdialysis across all included patients into distinct groups. Average values for measured physiological variables were compared across the identified clusters, and physiological profiles from identified clusters were mapped onto physiological states known to occur after acute brain injury. The distribution of clusters was compared between patients with favorable outcome (discharged to home or acute rehab) and unfavorable outcome (in-hospital death or discharged to chronic nursing facility). RESULTS A total of 1704 observations from 20 patients were included. Even though the difference in mean values for measured variables between patients with favorable and unfavorable outcome were small, we identified four distinct clusters within our data: (1) events with low brain tissue oxygen and high lactate-to-pyruvate ratio-values (consistent with cerebral ischemia), (2) events with higher intracranial pressure values without evidence for ischemia (3) events which appeared to be physiologically "normal," and (4) events with high cerebral lactate without brain hypoxia (consistent with cerebral hyperglycolysis). Patients with a favorable outcome had a greater proportion of cluster 3 (normal) events, whereas patients with an unfavorable outcome had a greater proportion of cluster 1 (ischemia) and cluster 4 (hyperglycolysis) events (p

Intracranial pressure (ICP) monitoring and control is a cornerstone of neuroanesthesia and neurocritical care. However, because elevated ICP can be due to multiple pathophysiological processes, its interpretation is not straightforward. We propose a formal taxonomy of intracranial hypertension, which defines ICP elevations into 3 major pathophysiological subsets: increased cerebral blood volume, masses and edema, and hydrocephalus. (1) Increased cerebral blood volume increases ICP and arises secondary to arterial or venous hypervolemia. Arterial hypervolemia is produced by autoregulated or dysregulated vasodilation, both of which are importantly and disparately affected by systemic blood pressure. Dysregulated vasodilation tends to be worsened by arterial hypertension. In contrast, autoregulated vasodilation contributes to intracranial hypertension during decreases in cerebral perfusion pressure that occur within the normal range of cerebral autoregulation. Venous hypervolemia is produced by Starling resistor outflow obstruction, venous occlusion, and very high extracranial venous pressure. Starling resistor outflow obstruction tends to arise when cerebrospinal fluid pressure causes venous compression to thus increase tissue pressure and worsen tissue edema (and ICP elevation), producing a positive feedback ICP cycle. (2) Masses and edema are conditions that increase brain tissue volume and ICP, causing both vascular compression and decrease in cerebral perfusion pressure leading to oligemia. Brain edema is either vasogenic or cytotoxic, each with disparate causes and often linked to cerebral blood flow or blood volume abnormalities. Masses may arise from hematoma or neoplasia. (3) Hydrocephalus can also increase ICP, and is either communicating or noncommunicating. Further research is warranted to ascertain whether ICP therapy should be tailored to these physiological subsets of intracranial hypertension.

The morbidity and mortality resulting from traumatic brain injury (TBI) stems not only from the primary brain damage caused by the initial impact but also from the secondary insults that follow. Given the delayed presentation, these secondary insults represent an opportunity for clinical intervention. Recognition and treatment of these evolving processes is critical to ensuring optimal outcome following serious brain injury. In this discussion, we outline the evidence for intensive care unit management practices and their impact on patient outcomes following severe TBI.

To the editor In recent years, an acute amnestic syndrome associated with hippocampal damage has emerged in patients with a history of opioid abuse.[1][1] Residual anterograde memory loss for weeks to months or longer in these patients has raised the possibility that opioids may be directly toxic

Inhaled anesthetics have been utilized mostly for general anesthesia in the operating room and oftentimes for sedation and for treatment of refractory status epilepticus and status asthmaticus in the intensive care unit. These contexts in the ICU setting are related to potential for prolonged administration wherein potential organ toxicity is a concern. Over the last decade, several clinical and animal studies of neurotoxicity attributable to inhaled anesthetics have been emerging, particularly in extremes of age. This review overviews potential for and potential mechanisms of neurotoxicity and systemic toxicity of prolonged inhaled anesthesia and clinical scenarios where inhaled anesthesia has been used in order to assess safety of possible prolonged use for sedation. High dose inhaled agents are associated with postoperative cognitive dysfunction (POCD) and other situations. However, thus far no strong indication of problematic neuro or organ toxicity has been demonstrated after prolonged use of low dose volatile anesthesia.

John T Pierce,1 Guy Kositratna,2 Mark A Attiah,1 Michael J Kallan,3 Rebecca Koenigsberg,1 Peter Syre,1 David Wyler,4 Paul J Marcotte,1 W Andrew Kofke,1,2 William C Welch1 1Department of Neurosurgery, 2Department of Anesthesiology and Critical Care, 3Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, 4Department of Anesthesiology and Critical Care, Neurosurgery, Jefferson Hospital of Neuroscience, Thomas Jefferson University, Philadelphia PA, USA Background: Previous studies have shown varying results in selected outcomes when directly comparing spinal anesthesia to general in lumbar surgery. Some studies have shown reduced surgical time, postoperative pain, time in the postanesthesia care unit (PACU), incidence of urinary retention, postoperative nausea, and more favorable cost-effectiveness with spinal anesthesia. Despite these results, the current literature has also shown contradictory results in between-group comparisons. Materials and methods: A retrospective analysis was performed by querying the electronic medical record database for surgeries performed by a single surgeon between 2007 and 2011 using procedural codes 63030 for diskectomy and 63047 for laminectomy: 544 lumbar laminectomy and diskectomy surgeries were identified, with 183 undergoing general anesthesia and 361 undergoing spinal anesthesia (SA). Linear and multivariate regression analyses were performed to identify differences in blood loss, operative time, time from entering the operating room (OR) until incision, time from bandage placement to exiting the OR, total anesthesia time, PACU time, and total hospital stay. Secondary outcomes of interest included incidence of postoperative spinal hematoma and death, incidence of paraparesis, plegia, post-dural puncture headache, and paresthesia, among the SA patients. Results: SA was associated with significantly lower operative time, blood loss, total anesthesia time, time from entering the OR until incision, time from bandage placement until exiting the OR, and total duration of hospital stay, but a longer stay in the PACU. The SA group experienced one spinal hematoma, which was evacuated without any long-term neurological deficits, and neither group experienced a death. The SA group had no episodes of paraparesis or plegia, post-dural puncture headaches, or episodes of persistent postoperative paresthesia or weakness. Conclusion: SA is effective for use in patients undergoing elective lumbar laminectomy and/or diskectomy spinal surgery, and was shown to be the more expedient anesthetic choice in the perioperative setting. Keywords: spinal anesthesia, general anesthesia, efficiency, expedient

Introduction: The optimal cerebral perfusion pressure (CPP) following hypoxic-ischemic brain injury (HIBI) is currently unknown. We retrospectively analyzed intracranial monitoring data from a cohort of patients with HIBI to identify a threshold level for CPP that optimizes cerebrovascular pressure reactivity (a surrogate for CA) while limiting the risk of intracranial hypertension and brain tissue hypoxia. Hypothesis: We hypothesized that higher CPP values would be associated with improved cerebrovascular pressure reactivity. Methods: ICP, brain tissue oxygen (P bt O 2 ), MAP, and CPP (defined as MAP - ICP) were recorded continuously and time synchronized for all patients using a bedside monitor (CNS Monitor, Moberg Research). Pressure Reactivity Index (PRx) was calculated as the time varying correlation between MAP and ICP over 5 min intervals updated every minute. The degree of CA impairment (defined as % time PRx > 0.2) was plotted against MAP and CPP, respectively. The relationships between ICP and P bt O 2 versus CPP, as well as ICP and P bt O 2 versus % time PRx > 0.2, were similarly calculated. Results: We analyzed 37 patients (33 cardiac arrest, 4 prolonged hypoxia) with HIBI who underwent intracranial neuromonitoring over a 3 year period. Lower CPP values were associated with higher degrees of CA impairment. The cumulative burden of elevated PRx was significantly lower for CPP values above a cutoff of 85 mmHg compared to lower CPP values (p < 0.001, Wilcoxon rank sum test). A similar cutoff for MAP could not be identified, although lower MAP values were also associated with greater CA impairment. Intracranial hypertension (ICP > 20 mmHg) and brain hypoxia (P bt O2 < 20 mmHg) were both associated with CA impairment (p < 0.001 and p < 0.001, respectively, Wilcoxon rank sum test). Conclusions: Higher CPP and MAP values appear to be associated with improved CA after HIBI. Given that CA impairment is associated with both intracranial hypertension and brain hypoxia, our work reaffirms the notion that higher blood pressure targets may improve outcome after HIBI. The identification of a distinct CPP cutoff for CA optimization suggests that targeting CPP instead of MAP may be advantageous, although further work is required to clarify this issue.

The purpose of this study was to assess the accuracy of absolute cerebral blood flow (CBF) measurements obtained by dynamic contrast-enhanced (DCE) near-infrared spectroscopy (NIRS) using indocyanine green as a perfusion contrast agent. For validation, CBF was measured independently using the MRI perfusion method arterial spin labeling (ASL). Data were acquired at two sites and under two flow conditions (normocapnia and hypercapnia). Depth sensitivity was enhanced using time-resolved detection, which was demonstrated in a separate set of experiments using a tourniquet to temporally impede scalp blood flow. A strong correlation between CBF measurements from ASL and DCE-NIRS was observed (slope = 0.99 ± 0.08, y-intercept = −1.7 ± 7.4 mL/100 g/min, and R2 = 0.88). Mean difference between the two techniques was 1.9 mL/100 g/min (95% confidence interval ranged from −15 to 19 mL/100g/min and the mean ASL CBF was 75.4 mL/100 g/min). Error analysis showed that structural information and baseline absorption coefficient were needed for optimal CBF reconstruction with DCE-NIRS. This study demonstrated that DCE-NIRS is sensitive to blood flow in the adult brain and can provide accurate CBF measurements with the appropriate modeling techniques.

We present pilot results on the validation of non-invasive assessment of elevated intracranial pressure with optical measurement of critical closing pressure. A strong correlation (r=0.85) between optical measurements of critical closing pressure and invasive measurements of intracranial pressure was observed in 5 infants with hydrocephalus, and 1 adult patient with diffuse hypoxic ischemic brain injury. By facilitating timely detection of intracranial hypertension, this approach has potential to reduce risk of brain damage in hydrocephalus and other vulnerable patient populations.

Rapid detection of ischemic conditions at the bedside can improve treatment of acute brain injury. In this observational study of 11 critically ill brain-injured adults, we employed a monitoring approach that interleaves time-resolved near-infrared spectroscopy (TR-NIRS) measurements of cerebral oxygen saturation and oxygen extraction fraction (OEF) with diffuse correlation spectroscopy (DCS) measurement of cerebral blood flow (CBF). Using this approach, we demonstrate the clinical promise of non-invasive, continuous optical monitoring of changes in CBF and cerebral metabolic rate of oxygen (CMRO2). In addition, the optical CBF and CMRO2 measures were compared to invasive brain tissue oxygen tension (PbtO2), thermal diffusion flowmetry CBF, and cerebral microdialysis measures obtained concurrently. The optical CBF and CMRO2 information successfully distinguished between ischemic, hypermetabolic, and hyperemic conditions that arose spontaneously during patient care. Moreover, CBF monitoring during pressor-induced changes of mean arterial blood pressure enabled assessment of cerebral autoregulation. In total, the findings suggest that this hybrid non-invasive neurometabolic optical monitor (NNOM) can facilitate clinical detection of adverse physiological changes in brain injured patients that are otherwise difficult to measure with conventional bedside monitoring techniques.

Background: Diffuse correlation spectroscopy (DCS) noninvasively permits continuous, quantitative, bedside measurements of cerebral blood flow (CBF). To test whether optical monitoring (OM) can detect decrements in CBF producing cerebral hypoxia, we applied the OM technique continuously to probe brain-injured patients who also had invasive brain tissue oxygen (PbO 2 ) monitors. Methods: Comatose patients with a Glasgow Coma Score (GCS) < 8) were enrolled in an IRB-approved protocol after obtaining informed consent from the legally authorized representative. Patients underwent 6–8 h of daily monitoring. Brain PbO 2 was measured with a Clark electrode. Absolute CBF was monitored with DCS, calibrated by perfusion measurements based on intravenous indocyanine green bolus administration. Variation of optical CBF and mean arterial pressure (MAP) from baseline was measured during periods of brain hypoxia (defined as a drop in PbO 2 below 19 mmHg for more than 6 min from baseline (PbO 2 > 21 mmHg). In a secondary analysis, we compared optical CBF and MAP during randomly selected 12-min periods of “normal” (> 21 mmHg) and “low” (< 19 mmHg) PbO 2 . Receiver operator characteristic (ROC) and logistic regression analysis were employed to assess the utility of optical CBF, MAP, and the two-variable combination, for discrimination of brain hypoxia from normal brain oxygen tension. Results: Seven patients were enrolled and monitored for a total of 17 days. Baseline-normalized MAP and CBF significantly decreased during brain hypoxia events (p < 0.05). Through use of randomly selected, temporally sparse windows of low and high PbO 2 , we observed that both MAP and optical CBF discriminated between periods of brain hypoxia and normal brain oxygen tension (ROC AUC 0.761, 0.762, respectively). Further, combining these variables using logistic regression analysis markedly improved the ability to distinguish low- and high-PbO 2 epochs (AUC 0.876). Conclusions: The data suggest optical techniques may be able to provide continuous individualized CBF measurement to indicate occurrence of brain hypoxia and guide brain-directed therapy.

Supplemental Material for Quantification of cerebral blood flow in adults by contrast-enhanced near-infrared spectroscopy: Validation against MRI by Daniel Milej, Lian He, Androu Abdalmalak, Wesley B Baker, Udunna C Anazodo, Mamadou Diop, Sudipto Dolui, Venkaiah C Kavuri, William Pavlosky, Lin Wang, Ramani Balu, John A Detre, Olivia Amendolia, Francis Quattrone, W Andrew Kofke, Arjun G Yodh and Keith St Lawrence in Journal of Cerebral Blood Flow & Metabolism

Introduction Patients undergoing cardiac surgery are at high risk for postoperative delirium, which is associated with longer hospital and intensive care lengths of stays, increased morbidity and mortality. Because sleep disturbances are common in delirium, melatonin has been an area of interest in the treatment of delirium. The rs10830963 single nucleotide polymorphism of the melatonin receptor 1B gene can cause pathological dysfunction of this receptor and is associated with delayed morning offset of melatonin. We hypothesized patients undergoing aortic cardiac surgery who have the risk genotype of a melatonin receptor 1B polymorphism would have a higher incidence of postoperative delirium. Methods Ninety-eight patients undergoing aortic root or valve surgery underwent analysis for melatonin receptor 1B single nucleotide polymorphism, rs10830963. Using a validated method, CHART-DEL, all charts were retrospectively reviewed and scored for the presence of delirium while blinded to the results of the melatonin receptor 1B gene polymorphism. Results Genotyping for melatonin receptor 1B polymorphism was acceptable in 76 subjects of European descent of which 18 (23.7%) had delirium. Four of seven subjects with the risk genotype had delirium versus only 20.3% of subjects without the risk genotype. This carried an odds ratio of 5.2 (1.0, 26.1), p = 0.050. Conclusion This observation suggests a role of the risk genotype of a melatonin receptor 1B polymorphism in the development of postoperative delirium. These hypotheses generating results warrant further prospective studies in a larger cohort group with delirium, circadian rhythm and melatonin assessments.

© The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License 2017. We investigate a scheme for noninvasive continuous monitoring of absolute cerebral blood flow (CBF) in adult human patients based on a combination of time-resolved dynamic contrast-enhanced near-infrared spectroscopy (DCE-NIRS) and diffuse correlation spectroscopy (DCS) with semi-infinite head model of photon propogation. Continuous CBF is obtained via calibration of the DCS blood flow index (BFI) with absolute CBF obtained by intermittent intravenous injections of the optical contrast agent indocyanine green. A calibration coefficient (?) for the CBF is thus determined, permitting conversion of DCS BFI to absolute blood flow units at all other times. A study of patients with acute brain injury (N 7) is carried out to ascertain the stability of ?. The patientaveraged DCS calibration coefficient across multiple monitoring days and multiple patients was determined, and good agreement between the two calibration coefficients measured at different times during single monitoring days was found. The patient-averaged calibration coefficient of 1.24 × 109 omL/100 g/ min/ocm2/sp was applied to previously measured DCS BFI from similar brain-injured patients; in this case, absolute CBF was underestimated compared with XeCT, an effect we show is primarily due to use of semi-infinite homogeneous models of the head.

Background: Neuroprotection studies are generally unable to demonstrate efficacy in humans. Our specific hypothesis is that multiple pathophysiologic pathways, of variable importance, contribute to ischemic brain damage. As a corollary to this, we discuss the broad hypothesis that a multifaceted approach will improve the probability of efficacious neuroprotection. But to properly test this hypothesis the nature and importance of the multiple contributing pathways needs elucidation. Our aim is to demonstrate, using functional genomics, in human cardiac surgery procedures associated with cerebral ischemia, that the pathogenesis of perioperative human ischemic brain damage involves the function of multiple variably weighted proteins involving several pathways. We then use these data and literature to develop a proposal for rational design of human neuroprotection protocols. Methods: Ninety-four patients undergoing deep hypothermic circulatory arrest (DHCA) and/or aortic valve replacement surgery had brain damage biomarkers, S100β and neurofilament H (NFH), assessed at baseline, 1 and 24 h post-cardiopulmonary bypass (CPB) with analysis for association with 92 single nucleotide polymorphisms (SNPs) (selected by co-author WAK) related to important proteins involved in pathogenesis of cerebral ischemia. Results: At the nominal significance level of 0.05, changes in S100β and in NFH at 1 and 24 h post-CPB were associated with multiple SNPs involving several prospectively determined pathophysiologic pathways, but were not individually significant after multiple comparison adjustments. Variable weights for the several evaluated SNPs are apparent on regression analysis and, notably, are dissimilar related to the two biomarkers and over time post CPB. Based on our step-wise regression model, at 1 h post-CPB, SOD2, SUMO4, and GP6 are related to relative change of NFH while TNF, CAPN10, NPPB, and SERPINE1 are related to the relative change of S100B. At 24 h post-CPB, ADRA2A, SELE, and BAX are related to the relative change of NFH while SLC4A7, HSPA1B, and FGA are related to S100B. Conclusions: In support of the proposed hypothesis, association SNP data suggest function of specific disparate proteins, as reflected by genetic variation, may be more important than others with variation at different post-insult times after human brain ischemia. Such information may support rational design of post-insult time-sensitive multifaceted neuroprotective therapies.

Acute hippocampal injury represents a relatively rare cause of amnesia. Interestingly however, between 2012 and 2017, 18 patients were reported at hospitals in Massachusetts with sudden-onset amnesia in the setting of complete diffusion-weighted hyperintensity of both hippocampi on magnetic resonance imaging. Notably, 17 of the 18 patients tested positive for opioids or had a recorded history of opioid use. This observation suggests an association between opioids and acute hippocampal injury. With particular attention to the Massachusetts cluster and data on fentanyl and its congeners, the epidemiological and pathophysiological evidence that supports this hypothesis is presented, as are potential underlying mechanisms.