Expression of Zinc-Finger Antiviral Protein in hCMEC/D3 Human Cerebral Microvascular Endothelial Cells: Effect of a Toll-Like Receptor 3 Agonist.

INTRODUCTION: Invasion of viruses into the brain causes viral encephalitis, which can be fatal and causes permanent brain damage. The blood-brain barrier (BBB) protects the brain by excluding harmful substances and microbes. Brain microvascular endothelial cells are important components of the BBB; however, the mechanisms of antiviral reactions in these cells have not been fully elucidated. Zinc-finger antiviral protein (ZAP) is a molecule that restricts the infection of various viruses, and there are 2 major isoforms: ZAPL and ZAPS. Toll-like receptor 3 (TLR3), a pattern-recognition receptor against viral double-stranded RNA, is implicated in antiviral innate immune reactions. The aim of this study was to investigate the expression of ZAP in cultured hCMEC/D3 human brain microvascular endothelial cells treated with an authentic TLR3 agonist polyinosinic-polycytidylic acid (poly IC). METHODS: hCMEC/D3 cells were cultured and treated with poly IC. Expression of ZAPL and ZAPS mRNA was investigated using quantitative reverse transcription-polymerase chain reaction, and protein expression of these molecules was examined using western blotting. The role of nuclear factor-κB (NF-κB) was examined using the NF-κB inhibitor, SN50. The roles of interferon (IFN)-ß, IFN regulatory factor 3 (IRF3), tripartite motif protein 25 (TRIM25), and retinoic acid-inducible gene-I (RIG-I) in poly IC-induced ZAPS expression were examined using RNA interference. Propagation of Japanese encephalitis virus (JEV) was examined using a focus-forming assay. RESULTS: ZAPS mRNA and protein expression was upregulated by poly IC, whereas the change of ZAPL mRNA and protein levels was minimal. Knockdown of IRF3 or TRIM25 decreased the poly IC-induced upregulation of ZAPS, whereas knockdown of IFN-ß or RIG-I did not affect ZAPS upregulation. SN50 did not affect ZAPS expression. Knockdown of ZAP enhanced JEV propagation. CONCLUSION: ZAPL and ZAPS were expressed in hCMEC/D3 cells, and ZAPS expression was upregulated by poly IC. IRF3 and TRIM25 are involved in poly IC-induced upregulation of ZAPS. ZAP may contribute to antiviral reactions in brain microvascular endothelial cells and protect the brain from invading viruses such as JEV.

Description of an Association Between Leukocytosis and Clinical Outcomes in Large Hemispheric Infarctions.

BACKGROUND: Large hemispheric infarctions (LHI) are associated with significant morbidity and mortality. Leukocytosis has been observed to directly correlate with stroke severity but has not been specifically described in the LHI population. We hypothesized that patients with LHI and leukocytosis on admission have worse clinical outcomes. METHODS: Retrospective study of patients admitted to the neurosciences intensive care unit at a tertiary care center with the diagnosis of acute ischemic stroke from Jan 2012 to Dec 2018. Inclusion criteria included admission imaging with stroke size greater than two-thirds of the middle cerebral artery territory, with or without other vascular territory involvement. Patients were excluded if antibiotics were started on admission for presumed infection. White blood cell count was recorded at admission, along with Modified Rankin Scale on admission and discharge, need for mechanical ventilation, tracheostomy, and discharge disposition. Logistic regression was used for association measures. RESULTS: Of the 2,318 patients that were screened, 360 met inclusion criteria. Mean age was 64, median was 63; 51.7% were female. Mean and median NIHSS were 21. Leukocytosis on admission was seen in 139 patients (38.6%), and it was associated with need for mechanical ventilation (p<0.0001, OR 2.54, [1.64-3.95]) and mortality during hospitalization (p<0.0003, OR 2.66, [1.56-4.55]). Results persisted after correction for age and sex in a logistic regression model. CONCLUSIONS: Leukocytosis on admission in patients with LHI significantly correlated with mortality and need for mechanical ventilation. There was a trend towards association with poor outcome at discharge, although not statistically significant. Further research may identify how leukocytosis and other SIRS markers may be used to prognosticate outcomes in this challenging patient population.

Analysis of Changes in Microcirculation Parameters of Symmetrical Areas of the Human Head under Conditions of Hypoxic Influences.

The reactions of microcirculation parameters of symmetrical areas of the human head to hypoxic loads were studied. The study was conducted in 10 healthy male volunteers aged 18-19 years. Short-term hypoxia was modeled using a ReOxy Cardio normobaric device (S. A. Aimediq). Synchronous measurements of microcirculation parameters in symmetrical temporal regions of the head at the basal state and immediately after short-term hypoxic exposure were carried out by the method of laser Doppler flowmetry. We evaluated statistical characteristics of perfusion of both sides, as well as regression characteristics of the relationship between changes in the microcirculation parameters and the initial values of these parameters. It was shown that the reaction of the microcirculation parameters in symmetrical regions of the head to hypoxia depends on the initial microcirculation parameters in ipsi- and contralateral sides. 3D graphs were constructed and regression equations describing these relationships were formulated. A new method of geometric sensing is proposed, which allows predicting the direction of reactions to hypoxic effects. The obtained data illustrate the specificity of regulation of microcirculation of paired organs determined by the presence of functional asymmetry. A new method of geometric zoning is proposed, which allows solving the problems of personalized assessments of the state of the microcirculation system in patients.

Differential vasomotor responses to isocapnic hyperoxia: cerebral versus peripheral circulation.

Isocapnic hyperoxia (IH) evokes cerebral and peripheral hypoperfusion via both disturbance of redox homeostasis and reduction in nitric oxide (NO) bioavailability. However, it is not clear whether the magnitude of the vasomotor responses depends on the vessel network exposed to IH. To test the hypothesis that the magnitude of IH-induced reduction in peripheral blood flow (BF) may differ from the hypoperfusion response observed in the cerebral vascular network under oxygen-enriched conditions, nine healthy men (25 ± 3 yr, mean ± SD) underwent 10 min of IH during either saline or vitamin C (3 g) infusion, separately. Femoral artery (FA), internal carotid artery (ICA), and vertebral artery (VA) BF (Doppler ultrasound), as well as arterial oxidant (8-isoprostane), antioxidant [ascorbic acid (AA)], and NO bioavailability (nitrite) markers were simultaneously measured. IH increased 8-isoprostane levels and reduced nitrite levels; these responses were followed by a reduction in both FA BF and ICA BF, whereas VA BF did not change. Absolute and relative reductions in FA BF were greater than IH-induced changes in ICA and VA perfusion. Vitamin C infusion increased arterial AA levels and abolished the IH-induced increase in 8-isoprostane levels and reduction in nitrite levels. Whereas ICA and VA BF did not change during the vitamin C-IH trial, FA perfusion increased and reached similar levels to those observed during normoxia with saline infusion. Therefore, the magnitude of IH-induced reduction in femoral blood flow is greater than that observed in the vessel network of the brain, which might involve the determinant contribution that NO has in the regulation of peripheral vascular perfusion.

Spectrophotometry of cerebrospinal fluid for xanthochromia is a sensitive and specific test for subarachnoid bleeding but adds little to computed tomography.

Subarachnoid hemorrhage (SAH) is a serious neurological event associated with high morbidity and mortality. Computed tomography of the cerebrum (CTC) is the diagnostic method of choice, but in case of negative CTC but strong suspicion of SAH, lumbar puncture with spectrophotometric analysis of cerebrospinal fluid (CSF) for xanthochromia is performed. We wanted to examine the diagnostic properties of CSF spectrophotometry for xanthochromia testing. We performed a retrospective study of the diagnostic properties of CSF analysis for xanthochromia using spectrophotometry in the diagnosis of SAH. A total of 489 CSF samples were analyzed for xanthochromia, according to international guidelines, from 2009 until 2014 and for 411 of these the patient files were retrieved and examined for final clinical diagnosis and result of CTC. One patient with SAH did not have a positive spectrophotometry report and another patient with SAH had an equivocal report. In four patients did initial CTC not correctly identify SAH. For patients with a negative CTC within six hours of symptom onset spectrophotometry for xanthochromia in the CSF had a diagnostic sensitivity of 100% and a diagnostic specificity of 98.5%. The positive predictive value was 16.7% and the negative predictive value 100%. We conclude that spectrophotometry of CSF for xanthochromia is a sensitive and specific test for diagnosing SAH. However, it seems that an initial CTC identifies almost all patients with SAH. This suggests that in our and similar diagnostic settings, lumbar puncture and testing for xanthochromia might only be relevant in very few cases, if not obsolete.

Dashcam-captured moment of right hemispheric stroke.

A bus driver presented with neurological abnormalities following a driving mishap. He was diagnosed cardioembolic stroke. The bus was equipped with a dashboard camera that recorded the moment when the patient suffered the stroke. We reported the first case dashcam-captured images at the first sign of a right hemispheric stroke.

Effect of Recanalization on Cerebral Edema, Long-Term Outcome, and Quality of Life in Patients with Large Hemispheric Infarctions.

OBJECTIVES: Space-occupying cerebral edema is the main cause of mortality and poor functional outcome in patients with large cerebral artery occlusion (LVO). We aimed to determine whether recanalization of LVO would augment cerebral edema volume and the impact on functional outcome and quality of life (QoL). MATERIALS AND METHODS: Prospectively, 43 patients with large middle cerebral artery territory infarction or NIHSS ≥ 12 on admission were enrolled. The degree of recanalization (partial and complete versus no recanalization) was assessed by computed tomography (CT)-angiography or Duplex ultrasound more than 24 h after symptom onset. Cerebral edema volume was measured on follow up CTs by computer-based planimetry. Mortality, functional outcome (by modified Ranking Scale (mRS) and Barthel Index (BI)) were assessed at discharge and 12 months, and QoL (by SF-36 and EQ-5D-3L) at 12 months. RESULTS: Mean cerebral edema volume was 333±141 ml without recanalization (n=13, group 1) and 276±140 ml with partial or complete recanalization (n=30, group 2, p= 0.23). There were no significant differences in mortality at discharge (38% versus 23%), at 12 months (58% versus 48%), in functional outcome at discharge (mRS 0-3: 0% both; mRS 4-5: 62% versus 77%) and at 12 months (mRS 0-3: 0% versus 11%; mRS 4-5: 42% versus 41%). The BI improved significantly from discharge to 12 months only in group 2 (p=0.001). Mean physical component score in SF-36 was 25.6±6.4, psychological component score was 41.9±14.1. In the EQ-5D-3L, most patients reported problems with activities of daily living, reduced mobility, and selfcare. CONCLUSIONS: Recanalization of a large cerebral artery occlusion in the anterior circulation territories is not associated with amplification of post-ischemic cerebral edema but may be correlated with better long-term functional outcome. QoL was low and mainly dependent on physical disability. The association between recanalization, collateral status and development of cerebral edema after LVO and the effect on functional outcome and quality of life should be explored in a larger patient population.

Bihemisphere Ischemia Due to a Unilateral Lesion: A Case Report.

Bihemispheric ischemic strokes secondary to unilateral vessel disease are uncommon. We present the case of a 70-year-old man with multiple acute/subacute bilateral infarcts. The patient was found to have stenosis of the left internal carotid artery secondary to herpes zoster ophthalmicus vasculopathy, with involvement of the left proximal middle and anterior cerebral arteries. Angiographic studies also revealed A1 segment aplasia of the right anterior cerebral artery (ACA), thus indicating dependence on the left-sided circulation for perfusion of the bilateral ACA vascular territory. This case illustrates how A1 segment aplasia, an anatomic variant of the circle of Willis detected by angiographic studies, can contribute to bilateral infarction in the ACA vascular territory.

Poor Outcomes Related to Anterior Extension of Large Hemispheric Infarction: Topographic Analysis of GAMES-RP Trial MRI Scans.

BACKGROUND: We aimed to assess the correlation of lesion location and clinical outcome in patients with large hemispheric infarction (LHI). METHODS: We analyzed admission MRI data from the GAMES-RP trial, which enrolled patients with anterior circulation infarct volumes of 82-300 cm3 within 10 hours of onset. Infarct lesions were segmented and co-registered onto MNI-152 brain space. Voxel-wise general linear models were applied to assess location-outcome correlations after correction for infarct volume as a co-variate. RESULTS: We included 83 patients with known 3-month modified Rankin scale (mRS). In voxel-wise analysis, there was significant correlation between admission infarct lesions involving the anterior cerebral artery (ACA) territory and its middle cerebral artery (MCA) border zone with both higher 3-month mRS and post-stroke day 3 and 7 National Institutes of Health Stroke Scale (NIHSS) total score and arm/leg subscores. Higher NIHSS total scores from admission through poststroke day 2 correlated with left MCA infarcts. In multivariate analysis, ACA territory infarct volume (P = .001) and admission NIHSS (P = .005) were independent predictors of 3-month mRS. Moreover, in a subgroup of 36 patients with infarct lesions involving right MCA-ACA border zone, intravenous (IV) glibenclamide (BIIB093; glyburide) treatment was the only independent predictor of 3-month mRS in multivariate regression analysis (P = .016). CONCLUSIONS: Anterior extension of LHI with involvement of ACA territory and ACA-MCA border zone is an independent predictor of poor functional outcome, likely due to impairment of arm/leg motor function. If confirmed in larger cohorts, infarct topology may potentially help triage LHI patients who may benefit from IV glibenclamide. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182.

Cerebral blood flow rates in recent great apes are greater than in Australopithecus species that had equal or larger brains.

Brain metabolic rate (MR) is linked mainly to the cost of synaptic activity, so may be a better correlate of cognitive ability than brain size alone. Among primates, the sizes of arterial foramina in recent and fossil skulls can be used to evaluate brain blood flow rate, which is proportional to brain MR. We use this approach to calculate flow rate in the internal carotid arteries (Q˙ICA), which supply most of the primate cerebrum. Q˙ICA is up to two times higher in recent gorillas, chimpanzees and orangutans compared with 3-million-year-old australopithecine human relatives, which had equal or larger brains. The scaling relationships between Q˙ICA and brain volume (Vbr) show exponents of 1.03 across 44 species of living haplorhine primates and 1.41 across 12 species of fossil hominins. Thus, the evolutionary trajectory for brain perfusion is much steeper among ancestral hominins than would be predicted from living primates. Between 4.4-million-year-old Ardipithecus and Homo sapiens, Vbr increased 4.7-fold, but Q˙ICA increased 9.3-fold, indicating an approximate doubling of metabolic intensity of brain tissue. By contrast, Q˙ICA is proportional to Vbr among haplorhine primates, suggesting a constant volume-specific brain MR.

Routine assessment of cerebroplacental ratio at 35-37 weeks' gestation in the prediction of adverse perinatal outcome.

BACKGROUND: Third-trimester studies in selected high-risk pregnancies have reported that low cerebroplacental ratio, due to high pulsatility index in the umbilical artery, and or decreased pulsatility index in the fetal middle cerebral artery, is associated with increased risk of adverse perinatal outcomes. OBJECTIVE: To investigate the predictive performance of screening for adverse perinatal outcome by the cerebroplacental ratio measured routinely at 35-37 weeks' gestation. STUDY DESIGN: This was a prospective observational study in 47,211 women with singleton pregnancies undergoing routine ultrasound examination at 35+6 to 37+6 weeks' gestation, including measurement of umbilical artery-pulsatility index and middle cerebral artery-pulsatility index. The measured umbilical artery-pulsatility index and middle cerebral artery-pulsatility index and their ratio were converted to multiples of the median after adjustment for gestational age. Multivariable logistic regression analysis was used to determine whether umbilical artery-pulsatility index, middle cerebral artery-pulsatility index, and cerebroplacental ratio improved the prediction of adverse perinatal outcome that was provided by maternal characteristics, medical history, and obstetric factors. The following outcome measures were considered: (1) adverse perinatal outcome consisting of stillbirth, neonatal death, or hypoxic-ischemic encephalopathy grades 2 and 3; (2) presence of surrogate markers of perinatal hypoxia consisting of umbilical arterial or venous cord blood pH ≤7 and ≤7.1, respectively, 5-minute Apgar score <7, or admission to the neonatal intensive care unit for >24 hours; (3) cesarean delivery for presumed fetal compromise in labor; and (4) neonatal birthweight less than the third percentile for gestational age. RESULTS: First, the incidence of adverse perinatal outcome, presence of surrogate markers of perinatal hypoxia, and cesarean delivery for presumed fetal compromise in labor was greater in pregnancies with small for gestational age neonates with birthweight <10th percentile compared with appropriate for gestational age neonates; however, 80%-85% of these adverse events occurred in the appropriate for gestational age group. Second, low cerebroplacental ratio <10th percentile was associated with increased risk of adverse perinatal outcome, presence of surrogate markers of perinatal hypoxia, cesarean delivery for presumed fetal compromise in labor, and birth of neonates with birthweight less than third percentile. However, multivariable regression analysis demonstrated that the prediction of these adverse outcomes by maternal demographic characteristics and medical history was only marginally improved by the addition of cerebroplacental ratio. Third, the performance of low cerebroplacental ratio in the prediction of each adverse outcome was poor, with detection rates of 13%-26% and a false-positive rate of about 10%. Fourth, the detection rates of adverse outcomes were greater in small for gestational age than in appropriate for gestational age babies and in pregnancies delivering within 2 weeks rather than at any stage after assessment; however, such increase in detection rates was accompanied by an increase in the false-positive rate. Fifth, in appropriate for gestational age neonates, the predictive accuracy of cerebroplacental ratio was low, with positive and negative likelihood ratios ranging from 1.21 to 1.82, and 0.92 to 0.98, respectively; although the accuracy was better in small for gestational age neonates, this was also low with positive likelihood ratios of 1.31-2.26 and negative likelihood ratios of 0.69-0.92. Similar values were obtained in fetuses classified as small for gestational age and appropriate for gestational age according to the estimated fetal weight. CONCLUSIONS: In pregnancies undergoing routine antenatal assessment at 35-37 weeks' gestation, measurement of cerebroplacental ratio provides poor prediction of adverse perinatal outcome in both small for gestational age and appropriate for gestational age fetuses.

Near-infrared spectroscopy after out-of-hospital cardiac arrest.

BACKGROUND: Cerebral hypoperfusion may aggravate neurological damage after cardiac arrest. Near-infrared spectroscopy (NIRS) provides information on cerebral oxygenation but its relevance during post-resuscitation care is undefined. We investigated whether cerebral oxygen saturation (rSO2) measured with NIRS correlates with the serum concentration of neuron-specific enolase (NSE), a marker of neurological injury, and with clinical outcome in out-of-hospital cardiac arrest (OHCA) patients. METHODS: We performed a post hoc analysis of a randomised clinical trial (COMACARE, NCT02698917) comparing two different levels of carbon dioxide, oxygen and arterial pressure after resuscitation from OHCA with ventricular fibrillation as the initial rhythm. We measured rSO2 in 118 OHCA patients with NIRS during the first 36 h of intensive care. We determined the NSE concentrations from serum samples at 48 h after cardiac arrest and assessed neurological outcome with the Cerebral Performance Category (CPC) scale at 6 months. We evaluated the association between rSO2 and serum NSE concentrations and the association between rSO2 and good (CPC 1-2) and poor (CPC 3-5) neurological outcome. RESULTS: The median (inter-quartile range (IQR)) NSE concentration at 48 h was 17.5 (13.4-25.0) µg/l in patients with good neurological outcome and 35.2 (22.6-95.8) µg/l in those with poor outcome, p < 0.001. We found no significant correlation between median rSO2 and NSE at 48 h, rs = - 0.08, p = 0.392. The median (IQR) rSO2 during the first 36 h of intensive care was 70.0% (63.5-77.0%) in patients with good outcome and 71.8% (63.3-74.0%) in patients with poor outcome, p = 0.943. There was no significant association between rSO2 over time and neurological outcome. In a binary logistic regression model, rSO2 was not a statistically significant predictor of good neurological outcome (odds ratio 0.99, 95% confidence interval 0.94-1.04, p = 0.635). CONCLUSIONS: We found no association between cerebral oxygenation measured with NIRS and NSE concentrations or outcome in patients resuscitated from OHCA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02698917 . Registered on 26 January 2016.

Non-pulsatile blood flow is associated with enhanced cerebrovascular carbon dioxide reactivity and an attenuated relationship between cerebral blood flow and regional brain oxygenation.

BACKGROUND: Systemic blood flow in patients on extracorporeal assist devices is frequently not or only minimally pulsatile. Loss of pulsatile brain perfusion, however, has been implicated in neurological complications. Furthermore, the adverse effects of absent pulsatility on the cerebral microcirculation are modulated similarly as CO2 vasoreactivity in resistance vessels. During support with an extracorporeal assist device swings in arterial carbon dioxide partial pressures (PaCO2) that determine cerebral oxygen delivery are not uncommon-especially when CO2 is eliminated by the respirator as well as via the gas exchanger of an extracorporeal membrane oxygenation machine. We, therefore, investigated whether non-pulsatile flow affects cerebrovascular CO2 reactivity (CVR) and regional brain oxygenation (rSO2). METHODS: In this prospective, single-centre case-control trial, we studied 32 patients undergoing elective cardiac surgery. Blood flow velocity in the middle cerebral artery (MCAv) as well as rSO2 was determined during step changes of PaCO2 between 30, 40, and 50 mmHg. Measurements were conducted on cardiopulmonary bypass during non-pulsatile and postoperatively under pulsatile blood flow at comparable test conditions. Corresponding changes of CVR and concomitant rSO2 alterations were determined for each flow mode. Each patient served as her own control. RESULTS: MCAv was generally lower during hypocapnia than during normocapnia and hypercapnia (p < 0.0001). However, the MCAv/PaCO2 slope during non-pulsatile flow was 14.4 cm/s/mmHg [CI 11.8-16.9] and 10.4 cm/s/mmHg [CI 7.9-13.0] after return of pulsatility (p = 0.03). During hypocapnia, non-pulsatile CVR (4.3 ± 1.7%/mmHg) was higher than pulsatile CVR (3.1 ± 1.3%/mmHg, p = 0.01). Independent of the flow mode, we observed a decline in rSO2 during hypocapnia and a corresponding rise during hypercapnia (p < 0.0001). However, the relationship between ΔrSO2 and ΔMCAv was less pronounced during non-pulsatile flow. CONCLUSIONS: Non-pulsatile perfusion is associated with enhanced cerebrovascular CVR resulting in greater relative decreases of cerebral blood flow during hypocapnia. Heterogenic microvascular perfusion may account for the attenuated ΔrSO2/ΔMCAv slope. Potential hazards related to this altered regulation of cerebral perfusion still need to be assessed. TRIAL REGISTRATION: The study was retrospectively registered on October 30, 2018, with Clinical Trial.gov (NCT03732651).

Regional Cerebral Oxygen Saturation Decreases During Primary Hip Arthroplasty: An Analysis of Perioperative Regional Cerebral Oxygenation (rSO2), S100 Calcium-Binding Protein B (S100B) and Glial Fibrillary Acidic Protein (GFAP) Values. A Pilot Study.

BACKGROUND The incidence of postoperative cognitive dysfunction (POCD) after major joint arthroplasty is high. In the etiology of POCD, many factors have been cited, including thromboembolic complications. The incidence of cerebral embolization after lower extremity arthroplasty may be as high as 40-60%. The potential events of cerebral embolization could lead to a decrease in the regional cerebral oxygenation (rSO2) and increased serum levels of biochemical markers of brain damage. The objective of the study was to test whether there are any changes in the rSO2 values and serum markers of brain damage in patients who underwent total hip arthroplasty. MATERIAL AND METHODS Fifteen patients who underwent primary hip arthroplasty under spinal anesthesia were analyzed. The rSO2 was monitored using infrared spectroscopy. Biochemical analyses of S100 calcium-binding protein B (S100B) protein and fibrillary acidic protein (GFAP) serum concentrations were performed using immunoassay methods. RESULTS The values of rSO2 decreased during the surgery, but this was not related to mean arterial pressure variations or hemoglobin saturation. The concentration of S100B was increased compared to its preoperative values, and there were no changes in GFAP values. The changes in rSO2 readings correlated with the biomarkers' levels just after the surgery. CONCLUSIONS Our results suggest that S100B may be a more specific marker of astroglial damage in patients after primary total hip arthroplasty. The decrease in rSO2 readings may be due to micro-thromboembolic events that occurred during the surgery. However, the results of this study are preliminary, and further studies are needed to establish its clinical efficacy.

Near-infrared spectroscopy monitoring during out-of-hospital cardiac arrest: can the initial cerebral tissue oxygenation index predict ROSC?

STUDY OBJECTIVES: Near-infrared spectroscopy is a modality that can monitor tissue oxygenation index (TOI) and has potential to evaluate return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation (CPR). This study's objectives were to evaluate whether TOI could be associated with ROSC and used to help guide the decision to either terminate CPR or proceed to extracorporeal CPR (ECPR). METHODS: In this observational study, we assessed the patients with out-of-hospital cardiac arrest with non-traumatic cause receiving CPR on arrival at our ED between 2013 and 2016. TOI monitoring was discontinued either on CPR termination after ROSC was reached or on patient death. Patients were classified into two groups: ROSC and non-ROSC group. RESULTS: Out of 141 patients, 24 were excluded and the remaining 117 were classified as follows: ROSC group (n=44) and non-ROSC group (n=73). ROSC group was significantly younger and more likely to have their event witnessed and bystander CPR. ROSC group showed a higher initial TOI than non-ROSC group (60.5%±17.0% vs 37.9%±13.7%: p<0.01). Area under the curve analysis was more accurate with the initial TOI than without it for predicting ROSC (0.88, 95% CI 0.82 to 0.95 vs 0.79, 95% CI 0.70 to 0.87: p<0.01). TOI cut-off value ≥59% appeared to favour survival to hospital discharge whereas TOI ≤24% was associated with non-ROSC. CONCLUSIONS: This study demonstrated an association between higher initial TOI and ROSC. Initial TOI could increase the accuracy of ROSC prognosis and may be a clinical factor in the decision to terminate CPR and select patients who are to proceed to ECPR.

Near Infrared Spectroscopy Based Clinical Algorithm Applicability During Spinal Neurosurgery and Postoperative Cognitive Disturbances.

Background and Objectives: Postoperative cognitive disturbances (POCD) can significantly alter postoperative recovery. Inadequate intraoperative cerebral oxygen supply is one of the inciting causes of POCD. Near-infrared spectroscopy (NIRS) devices monitor cerebral oxygen saturation continuously and can help to guide intraoperative patient management. The aim of the study was to evaluate the applicability of the NIRS-based clinical algorithm during spinal neurosurgery and to find out whether it can influence postoperative cognitive performance. Materials and Methods: Thirty four patients scheduled for spinal neurosurgery were randomized into a study group (n = 23) and a control group (n = 11). We monitored regional cerebral oxygen saturation (rScO2) throughout surgery, using a NIRS device (INVOS 4100). If rScO2 dropped bilaterally or unilaterally by more than 20% from baseline values, or under an absolute value of 50%, the NIRS-based algorithm was initiated in the study group. In the control group, rScO2 was monitored blindly. To evaluate cognitive function, Montreal-Cognitive Assessment (MoCA) scale was used in both groups before and after the surgery. Results: In the study group, rScO2 dropped below the threshold in three patients and the NIRS-based algorithm was activated. Firstly, we verified correct positioning of the head; secondly, we increased mean systemic arterial pressure in the three patients by injecting repeated intravenous bolus doses of Ephedrine, ultimately resulting in an rScO2 increase above the approved threshold level. None of the three patients showed POCD. In the control group, one patient showed a drop in rScO2 of 34% from baseline and presented with a POCD. RScO2 drop occurred with other stable intraoperative measurements. Conclusions: A significant rScO2 drop may occur during spinal surgery in prone position despite other intraoperative measurements remaining stable, allowing it to stay otherwise unrecognized. Use of the NIRS-based clinical algorithm can help to avoid POCD in patients after spinal surgery.

Impaired cerebral autoregulation is associated with brain dysfunction in patients with sepsis.

BACKGROUND: Sepsis-associated brain dysfunction (SABD) is associated with high morbidity and mortality. The pathophysiology of SABD is multifactorial. One hypothesis is that impaired cerebral autoregulation (CAR) may result in brain hypoperfusion and neuronal damage leading to SABD. METHODS: We studied 100 adult patients with sepsis (July 2012-March 2017) (age = 62 [52-71] years; Acute Physiology and Chronic Health Evaluation II score on admission = 21 [15-26]). Exclusion criteria were acute or chronic intracranial disease, arrhythmias, extracorporeal membrane oxygenation, and known intra- or extracranial supra-aortic vessel disease. The site of infection was predominantly abdominal (46%) or pulmonary (28%). Transcranial Doppler was performed, insonating the left middle cerebral artery with a 2-MHz probe. Middle cerebral artery blood flow velocity (FV) and arterial blood pressure (ABP) signals were recorded simultaneously; Pearson's correlation coefficient (mean flow index [Mxa]) between ABP and FV was calculated using MATLAB. Impaired CAR was defined as Mxa > 0.3. RESULTS: Mxa was 0.29 [0.05-0.62]. CAR was impaired in 50 patients (50%). In a multiple linear regression analysis, low mean arterial pressure, history of chronic kidney disease and fungal infection were associated with high Mxa. SABD was diagnosed in 57 patients (57%). In a multivariable analysis, altered cerebral autoregulation, mechanical ventilation and history of vascular disease were independent predictors of SABD. CONCLUSIONS: Cerebral autoregulation was altered in half of the patients with sepsis and was associated with the development of SABD. These findings support the concept that cerebral hypoxia could contribute to the development of SABD.

Exposure to traffic-generated air pollutants mediates alterations in brain microvascular integrity in wildtype mice on a high-fat diet.

Air pollution-exposure is associated with detrimental outcomes in the central nervous system (CNS) such as cerebrovascular disorders, including stroke, and neurodegenerative diseases. While the mechanisms of these CNS-related outcomes involved have not been fully elucidated, exposure to traffic-generated air pollutants has been associated with altered blood brain barrier (BBB) integrity and permeability. The current study investigated whether inhalation exposure to mixed vehicle emissions (MVE) alters cerebral microvascular integrity in healthy 3 mo old C57BL/6 mice, as well as whether exposure-mediated effects were exacerbated by a high-fat (HF) vs. low-fat (LF) diet. Mice on each diet were randomly assigned to be exposed to either filtered air (FA) or MVE [100PM/m3 vehicle emissions mixture: 30µg PM/m3 gasoline engine + 70µg PM/m3 diesel engine emissions; median size ~ 60nm; particle mass size distribution median of ~ 1µm (range: < 0.5-20µm)] for 6h/d, 7d/wk, for 30d. Using sodium fluorescein as a tracer, we observed a significant increase in BBB permeability in both HF + MVE exposed and HF + FA animals, compared to LF + FA controls. Exposure to HF + MVE also led to a significant increase plasma ox-LDL and ox-LDL scavenger receptors (LOX-1 and CD-36) expression in the cerebral vasculature. Histological analysis revealed decreased expression of TJ protein, claudin-5, associated with increased matrix metalloproteinase (MMP)-9 activity and oxidative stress in the cerebral vasculature of HF + MVE mice, compared to LF + MVE. Such findings indicate that inhalation exposure to traffic-generated pollutants, coupled with a HF diet, results in altered BBB integrity and increased ox-LDL signaling in the cerebral vasculature in a wildtype animal model.

Upshaw-Schulman syndrome diagnosed during pregnancy complicated by reversible cerebral vasoconstriction syndrome.

Upshaw-Schulman syndrome (USS) is an inherited type of thrombotic thrombocytopenic purpura (TTP) that is extremely rare, but often diagnosed during pregnancy. Reversible cerebral vasoconstriction syndrome (RCVS) is the transient stenosis of several cerebral arteries that is frequently diagnosed post-partum. We describe a 28-year-old woman with USS complicated by RCVS after delivery that was treated by plasma exchange with a good outcome. She was referred to our hospital with thunderclap headache, anemia and thrombocytopenia that occurred immediately postpartum. She was diagnosed with TTP and multiple cerebral infarctions. Plasma exchange promptly improved her symptoms on hospital day 3. Moreover, multiple stenoses of cerebral arteries indicating RCVS were resolved. Since her sister also had an episode of thrombocytopenia during pregnancy, inherited TTP was suspected and genetic analyses confirmed USS. Pregnancy is a risk for not only TTP, but also RCVS. Endothelial damage might be an underlining cause and vasospasm after delivery is a trigger of RCVS. Plasma exchange was effective against both TTP and RCVS.

Near-infrared spectroscopy is a promising noninvasive technique for monitoring the effects of feeding regimens on the cerebral and splanchnic regions.

AIM: The effects of different milk and, or, administration regimens on cerebro-splanchnic perfusion are still a matter of debate. We investigated the effects of the bolus administration of breast milk or formula on cerebro-splanchnic oximetry, function and perfusion, assessed by near-infrared spectroscopy (NIRS). METHODS: This observational study of 30 infants fed with breast (n = 15) or formula (n = 15) milk, and matched for gestational age and birth weight, was carried out in the neonatal intensive care unit of the C Arrigo Children's Hospital, Alessandria, Italy, a tertiary-level referral centre, from October 2015 to December 2016. NIRS monitoring parameters, such as cerebral and splanchnic oximetry, fraction of tissue oxygen extraction and the cerebral-splanchnic ratio, were recorded before, during and after feeding. RESULTS: Breast milk led to a significant increase in cerebro-splanchnic oximetry and tissue oxygen extraction (p < 0.001) during and after feeding, and the cerebro-splanchnic perfusion ratio was significantly higher (p < 0.001) in the breast than formula group. CONCLUSION: Our study results suggest that breast milk was better tolerated than formula, requiring lower energy expenditure and lower cerebro-splanchnic haemodynamic redistribution. The findings could prompt investigations using NIRS as a promising noninvasive tool for cerebral and splanchnic longitudinal monitoring during neonatal feeding.