Quantitative Electroencephalographic Changes Associated With Brain Tissue Hypoxia After Pediatric Traumatic Brain Injury: A Retrospective Exploratory Analysis.

PURPOSE: Brain tissue hypoxia is associated with poor outcomes after pediatric traumatic brain injury. Although invasive brain oxygenation (PbtO 2 ) monitoring is available, noninvasive methods assessing correlates to brain tissue hypoxia are needed. We investigated EEG characteristics associated with brain tissue hypoxia. METHODS: We performed a retrospective analysis of 19 pediatric traumatic brain injury patients undergoing multimodality neuromonitoring that included PbtO 2 and quantitative electroencephalography(QEEG). Quantitative electroencephalography characteristics were analyzed over electrodes adjacent to PbtO 2 monitoring and over the entire scalp, and included power in alpha and beta frequencies and the alpha-delta power ratio. To investigate relationships of PbtO 2 to quantitative electroencephalography features using time series data, we fit linear mixed effects models with a random intercept for each subject and one fixed effect, and an auto-regressive order of 1 to model between-subject variation and correlation for within-subject observations. Least squares (LS) means were used to investigate for fixed effects of quantitative electroencephalography features to changes in PbtO 2 across thresholds of 10, 15, 20, and 25 mm Hg. RESULTS: Within the region of PbtO 2 monitoring, changes in PbtO 2 < 10 mm Hg were associated with reductions of alpha-delta power ratio (LS mean difference -0.01, 95% confidence interval (CI) [-0.02, -0.00], p = 0.0362). Changes in PbtO 2 < 25 mm Hg were associated with increases in alpha power (LS mean difference 0.04, 95% CI [0.01, 0.07], p = 0.0222). CONCLUSIONS: Alpha-delta power ratio changes are observed across a PbtO 2 threshold of 10 mm Hg within regions of PbtO 2 monitoring, which may reflect an EEG signature of brain tissue hypoxia after pediatric traumatic brain injury.

Hyperbaric oxygen treatment in delayed post-hypoxic encephalopathy following inhalation of liquefied petroleum gas: a case report.

Delayed post-hypoxic encephalopathy can occur after an episode of anoxia or hypoxia. Symptoms include apathy, confusion, and neurological deficits. We describe a 47-year-old male patient who inhaled gas from a kitchen stove liquid petroleum gas cylinder. He was diagnosed with hypoxic ischaemic encephalopathy 12 hours after his emergency department admission. He received six sessions of hyperbaric oxygen treatment (HBOT) and was discharged in a healthy state after six days. Fifteen days later, he experienced weakness, loss of appetite, forgetfulness, depression, balance problems, and inability to perform self-care. One week later, he developed urinary and fecal incontinence and was diagnosed with post-hypoxic encephalopathy. After 45 days from the onset of symptoms, he was referred to the Underwater and Hyperbaric Medicine Department for HBOT. The patient exhibited poor self-care and slow speech rate, as well as ataxic gait and dysdiadochokinesia. Hyperbaric oxygen was administered for twenty-four sessions, which significantly improved the patient's neurological status with only hypoesthesia in the left hand remaining at the end of treatment. Hyperbaric oxygen has been reported as successful in treating some cases of delayed neurological sequelae following CO intoxication. It is possible that HBO therapy may also be effective in delayed post-hypoxic encephalopathy from other causes. This may be achieved through mechanisms such as transfer of functional mitochondria to the injury site, remyelination of damaged neurons, angiogenesis and neurogenesis, production of anti-inflammatory cytokines, and balancing of inflammatory and anti-inflammatory cytokines.

Preterm Infants off Positive Pressure Respiratory Support Have a Higher Incidence of Occult Cerebral Hypoxia.

OBJECTIVE: To use cerebral near-infrared spectroscopy (NIRS) to quantify occult cerebral hypoxia across respiratory support modes in preterm infants. STUDY DESIGN: In this prospective, longitudinal, observational study, infants ≤32 weeks gestation underwent serial pulse oximetry (oxygen saturation [SpO2]) and cerebral NIRS monitoring (4-6 hours per session) following a standardized recording schedule (daily for 2 weeks, every other day for 2 weeks, then weekly until 35 weeks corrected gestational age). Four calculations were made: median cerebral saturation, median cerebral hypoxia burden (proportion of NIRS samples below the hypoxia threshold [<67%]), median systemic saturation, and median systemic hypoxia burden (proportion of SpO2 samples below the desaturation threshold [<85%]). During each recording session, respiratory support mode was noted (room air, low-flow nasal cannula, high-flow nasal cannula, noninvasive positive pressure ventilation, continuous positive airway pressure, and invasive ventilation). RESULTS: There were 1013 recording sessions made from 174 infants with a median length of 6.9 hours. Although the systemic (SpO2) hypoxia burden was significantly greater for infants on the highest respiratory support (invasive and noninvasive positive pressure ventilation), the cerebral hypoxia burden was significantly greater during recording sessions made on the lowest respiratory support (8% for room air; 29% for low-flow nasal cannula). CONCLUSIONS: Premature infants on the highest levels of respiratory support have less cerebral hypoxia than those on lower respiratory support. These results raise concern about unrecognized cerebral hypoxia during lower acuity periods of neonatal intensive care unit hospitalization and adverse outcomes.

Discrepancies in the late auditory potentials of post-anoxic patients: Watch out for focal brain lesions, a pilot retrospective study.

AIMS: Late auditory evoked potentials, and notably mismatch negativity (MMN) and P3 responses, can be used as part of the multimodal prognostic evaluation in post-anoxic disorders of consciousness (DOC). MMN response preferentially stems from the temporal cortex and the arcuate fasciculus. Situations with discrepant evaluations, for example MMN absent but P3 present, are frequent and difficult to interpret. We hypothesize that discrepant MMN-/P3+ results could reflect a higher prevalence of lesions in MMN generating regions. This study presents correlations between neurophysiological and neuroradiological results. METHODS: This retrospective study was conducted on 38 post-anoxic DOC patients. Brain lesions were analyzed on 3T MRI both anatomically and through computation of the local arcuate fasciculus fractional anisotropy values on Diffusion Tensor Imaging sequences. Neurophysiological data and outcome were also analyzed. RESULTS: Our cohort included 8 MMN-/P3+, 7 MMN+/P3+, 21 MMN-/P3- and 2 MMN-/P3+ patients, assessed at a median delay of 20.5 days since cardiac arrest. Our results show that MMN-/P3+ patients tended to have fewer temporal and basal ganglia lesions than MMN-/P3- patients, and more than MMN+/P3+ patients (p-values for trend: p = 0.02 for temporal and p = 0.02 for basal ganglia lesions). There was a statistical difference across groups for mean fractional anisotropy values in the arcuate fasciculus (p = 0.008). The percentage of patients regaining consciousness at three months in MMN-/P3+ patients was higher than in MMN-/P3- patients and lower than in MMN+/P3+ patients. CONCLUSION: This study suggests that discrepancies in late auditory evoked potentials may be linked to focal post-anoxic brain lesions, visible on brain MRI.

Transient central hypoxemia due to intermittent high-degree atrioventricular block in a heart-transplanted patient diagnosed during routine electroencephalography: a case report.

BACKGROUND: Bradycardia frequently occurs in heart-transplanted patients, mainly as a temporally restricted manifestation early after transplantation and often without symptoms. A high-degree atrioventricular block is mostly symptomatic through cerebral hypoxia induced through cerebral hypoperfusion. Only a few published cases show this specific electroencephalography result in this context. The purpose of this case is to bring attention to atypical manifestations of typical cardiac complications after heart transplantation and the importance of perseverance in the diagnostic. CASE PRESENTATION: A Central European man in his 50s with history of heart transplantation 31 years previously was admitted to the internal medicine ward for short-lived recurrent episodes of generalized weakness with multiple falls but without loss of consciousness. During routine electroencephalography, the patient perceived this recurrent sensation. This episode coincided with a transient third-degree atrioventricular block followed 8-10 seconds later by a generalized slowing of the electroencephalography, reflecting cerebral hypoxia due to cerebral hypoperfusion. Holter monitoring confirmed the diagnosis. A pacemaker was implanted, consequently resolving the episodes. CONCLUSION: This case report illustrates the pathophysiological central hypoxemic origin of episodes of generalized weakness caused by a high-degree atrioventricular block in a patient surviving 29 years after heart transplant. It highlights the benefit of electroencephalography as a diagnostic tool in well-selected patients.

"THE MANTLE" bundle for minimizing cerebral hypoxia in severe traumatic brain injury.

To ensure neuronal survival after severe traumatic brain injury, oxygen supply is essential. Cerebral tissue oxygenation represents the balance between oxygen supply and consumption, largely reflecting the adequacy of cerebral perfusion. Multiple physiological parameters determine the oxygen delivered to the brain, including blood pressure, hemoglobin level, systemic oxygenation, microcirculation and many factors are involved in the delivery of oxygen to its final recipient, through the respiratory chain. Brain tissue hypoxia occurs when the supply of oxygen is not adequate or when for some reasons it cannot be used at the cellular level. The causes of hypoxia are variable and can be analyzed pathophysiologically following "the oxygen route." The current trend is precision medicine, individualized and therapeutically directed to the pathophysiology of specific brain damage; however, this requires the availability of multimodal monitoring. For this purpose, we developed the acronym "THE MANTLE," a bundle of therapeutical interventions, which covers and protects the brain, optimizing the components of the oxygen transport system from ambient air to the mitochondria.

NLRP3 inflammasome regulates astrocyte transformation in brain injury induced by chronic intermittent hypoxia.

BACKGROUND: Obstructive sleep apnea (OSA) is mainly characterized by sleep fragmentation and chronic intermittent hypoxia (CIH), the latter one being associated with multiple organ injury. Recently, OSA-induced cognition dysfunction has received extensive attention from scholars. Astrocytes are essential in neurocognitive deficits via A1/A2 phenotypic changes. Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome is considered the most important factor inducing and maintaining neuroinflammation. However, whether the NLRP3 regulates the A1/A2 transformation of astrocytes in CIH-related brain injury remains unclear. METHODS: We constructed an OSA-related CIH animal model and assessed the rats' learning ability in the Morris water maze; the histopathological assessment was performed by HE and Nissl staining. The expression of GFAP (astrocyte marker), C3d (A1-type astrocyte marker), and S100a10 (A2-type astrocyte marker) were detected by immunohistochemistry and immunofluorescence. Western blotting and RT-qPCR were used to evaluate the changes of A1/A2 astrocyte-related protein and NLRP3/Caspase-1/ASC/IL-1ß. RESULTS: The learning ability of rats decreased under CIH. Further pathological examination revealed that the neurocyte in the hippocampus were damaged. The cell nuclei were fragmented and dissolved, and Nissl bodies were reduced. Immunohistochemistry showed that astrocytes were activated, and morphology and number of astrocytes changed. Immunofluorescence, Western blotting and RT-qPCR showed that the expression of C3d was increased while S100a10 was decreased. Also, the expression of the inflammasome (NLRP3/Caspase-1/ASC/IL-1ß) was increased. After treatment of MCC950 (a small molecule inhibitor of NLRP3), the damage of nerve cells was alleviated, the Nissl bodies increased, the activation of astrocytes was reduced, and the expression of A2-type astrocytes was increased. In contrast, A1-type astrocytes decreased, and the expression of inflammasome NLRP3/Caspase-1/ASC/IL-1ß pathway-related proteins decreased. CONCLUSION: The NLRP3 inflammasome could regulate the A1/A2 transformation of astrocytes in brain injury induced by CIH.

Mechanisms of hypoxia in the hippocampal CA3 region in postoperative cognitive dysfunction after cardiopulmonary bypass.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a complication with high morbidity and mortality, commonly observed in the elderly who underwent anesthesia and surgery. The incidence is much higher in cardiac surgery. However, the reason and the mechanism of POCD remains unclear, but cerebral hypoxia is a common neurological complication after cardiac surgery. This study aims to investigate what role cerebral hypoxia plays in the pathogenesis of POCD. METHODS: The POCD model was established using cardiopulmonary bypass (CPB) surgery. Cognitive function was detected using Y maze and Morris water maze. The hypoxia in central nervous system was assessed using HE staining, western blot, and immunofluorescence. Inflammatory factors in hippocampus and plasma were detected by enzyme-linked immunosorbent assay. Evans blue was used to detect destruction of the blood brain barrier (BBB). RESULTS: Cognitive impairment markedly occurred to rats underwent 2-h CPB operation. Cerebral thrombosis and hypoxia occurred in the hippocampal CA3 region of rats after surgery. In addition, microglia in hippocampal was activated and the expression of inflammatory factors such as IL-1ß, IL-6 and TNF-α was upregulated. Moreover, the permeability of BBB increased in rats after CPB. CONCLUSION: Hypoxia in hippocampal CA3 region was involved in the occurrence and the mechanism may be associated with neuroinflammation and the damage of BBB.

A Severe Baclofen Intoxication Mimicking Post-Hypoxic Encephalopathy: Wait and See!

BACKGROUND: A severe baclofen intoxication is a potentially life-threatening condition. It is associated with coma and can cause brainstem reflexes to disappear, simulating a brain death-like condition. When given intensive supportive care and time, patients can recover without residual neurological damage. CASE REPORT: We present a case of a patient with known spastic cerebral palsy who was found unresponsive with no signs of breathing. He was brought to the Emergency Department, intubated, put on the ventilator, and hemodynamically stabilized. Brainstem reflexes were absent and he appeared brain dead. During the secondary survey, an intrathecal baclofen pump was found at his left lower abdomen, with a swelling next to it. A baclofen intoxication was suspected. He was admitted to the Intensive Care Unit, and after 72 h of supportive care complete neurological recovery was achieved. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Systemic baclofen intoxication can simulate a brain death-like condition. There is no reliable correlation between baclofen serum levels and central nervous system depression in case of an intoxication. It is important for emergency physicians to recognize a baclofen intoxication as a possible cause of coma and absent brainstem reflexes. Recuperation is spontaneous and can follow within days without residual damage. Because these patients may be brought in after a period of apnea or cardiopulmonary resuscitation, focus may be on post-hypoxic encephalopathy considerations instead of a possible baclofen intoxication.

Early cerebral hypoxia in extremely preterm infants and neurodevelopmental impairment at 2 year of age: A post hoc analysis of the SafeBoosC II trial.

BACKGROUND: The SafeBoosC II, randomised clinical trial, showed that the burden of cerebral hypoxia was reduced with the combination of near infrared spectroscopy and a treatment guideline in extremely preterm infants during the first 72 hours after birth. We have previously reported that a high burden of cerebral hypoxia was associated with cerebral haemorrhage and EEG suppression towards the end of the 72-hour intervention period, regardless of allocation. In this study we describe the associations between the burden of cerebral hypoxia and the 2-year outcome. METHODS: Cerebral oxygenation was continuously monitored from 3 to 72 hours after birth in 166 extremely preterm infants. At 2 years of age 114 of 133 surviving children participated in the follow-up program: medical examination, Bayley II or III test and the parental Ages and Stages Questionnaire. The infants were classified according to the burden of hypoxia: within the first three quartiles (n = 86, low burden) or within in the 4th quartile (n = 28, high burden). All analyses were conducted post hoc. RESULTS: There were no statistically significant differences between the quantitative assessments of neurodevelopment in the groups of infants with the low burden of cerebral hypoxia versus the group of infants with the high burden of cerebral hypoxia. The infants in the high hypoxia burden group had a higher-though again not statistically significant-rate of cerebral palsy (OR 2.14 (0.33-13.78)) and severe developmental impairment (OR 4.74 (0.74-30.49). CONCLUSIONS: The burden of cerebral hypoxia was not significantly associated with impaired 2-year neurodevelopmental outcome in this post-hoc analysis of a feasibility trial.

Maternal N-Acetyl-Cysteine Prevents Neonatal Hypoxia-Induced Brain Injury in a Rat Model.

Perinatal hypoxia is a major cause of infant brain damage, lifelong neurological disability, and infant mortality. N-Acetyl-Cysteine (NAC) is a powerful antioxidant that acts directly as a scavenger of free radicals. We hypothesized that maternal-antenatal and offspring-postnatal NAC can protect offspring brains from hypoxic brain damage.Sixty six newborn rats were randomized into four study groups. Group 1: Control (CON) received no hypoxic intervention. Group 2: Hypoxia (HYP)-received hypoxia protocol. Group 3: Hypoxia-NAC (HYP-NAC). received hypoxia protocol and treated with NAC following each hypoxia episode. Group 4: NAC Hypoxia (NAC-HYP) treated with NAC during pregnancy, pups subject to hypoxia protocol. Each group was evaluated for: neurological function (Righting reflex), serum proinflammatory IL-6 protein levels (ELISA), brain protein levels: NF-κB p65, neuronal nitric oxide synthase (nNOS), TNF-α, and IL-6 (Western blot) and neuronal apoptosis (histology evaluation with TUNEL stain). Hypoxia significantly increased pups brain protein levels compared to controls. NAC administration to dams or offspring demonstrated lower brain NF-κB p65, nNOS, TNF-α and IL-6 protein levels compared to hypoxia alone. Hypoxia significantly increased brain apoptosis as evidenced by higher grade of brain TUNEL reaction. NAC administration to dams or offspring significantly reduce this effect. Hypoxia induced acute sensorimotor dysfunction. NAC treatment to dams significantly attenuated hypoxia-induced acute sensorimotor dysfunction. Prophylactic NAC treatment of dams during pregnancy confers long-term protection to offspring with hypoxia associated brain injury, measured by several pathways of injury and correlated markers with pathology and behavior. This implies we may consider prophylactic NAC treatment for patients at risk for hypoxia during labor.

Preserved Cerebral Oxygenation with Worsening Global Myocardial Strain during Pediatric Chronic Hemodialysis.

BACKGROUND: Cerebral and myocardial hypoperfusion occur during hemodialysis in adults. Pediatric patients receiving chronic hemodialysis have fewer cardiovascular risk factors, yet cardiovascular morbidity remains prominent. METHODS: We conducted a prospective observational study of pediatric patients receiving chronic hemodialysis to investigate whether intermittent hemodialysis is associated with adverse end organ effects in the heart or with cerebral oxygenation (regional tissue oxyhemoglobin saturation [rSO2]). We assessed intradialytic cardiovascular function and rSO2 using noninvasive echocardiography to determine myocardial strain and continuous noninvasive near-infrared spectroscopy for rSO2. We measured changes in blood volume and measured central venous oxygen saturation (mCVO2) pre-, mid-, and post-hemodialysis. RESULTS: The study included 15 patients (median age, 12 years; median hemodialysis vintage, 13.2 [9-24] months). Patients were asymptomatic. The rSO2 did not change during hemodialysis, whereas mCVO2 decreased significantly, from 73% to 64.8%. Global longitudinal strain of the myocardium worsened significantly by mid-hemodialysis and persisted post-hemodialysis. The ejection fraction remained normal. Lower systolic BP and faster blood volume change were associated with worsening myocardial strain; only blood volume change was significant in multivariate analysis (ß-coefficient, -0.3; 95% confidence interval [CI], -0.38 to -0.21; P<0.001). Blood volume change was also associated with a significant decrease in mCVO2 (ß-coefficient, 0.42; 95% CI, 0.07 to 0.76; P=0.001). Access, age, hemodialysis vintage, and ultrafiltration volume were not associated with worsening strain. CONCLUSIONS: Unchanged rSO2 suggested that cerebral oxygenation was maintained during hemodialysis. However, despite maintained ejection fraction, intradialytic myocardial strain worsened in pediatric hemodialysis and was associated with blood volume change. The effect of hemodialysis on individual organ perfusion in pediatric versus adult patients receiving hemodialysis might differ.

Monitoring and modifying brain oxygenation in patients at risk of hypoxic ischaemic brain injury after cardiac arrest.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .

Severe diabetic ketoacidosis precipitated by COVID-19 in pediatric patients: Two case reports. / Cetoacidosis diabética severa precipitada por COVID-19 en pacientes pediátricos: reporte de dos casos.

INTRODUCTION: The association of COVID-19 with diabetes mellitus is bidirectional. In one direction, diabetes mellitus is associated with an increased risk of severe COVID-19. In the opposite direction, in patients with COVID-19 new-onset diabetes mellitus, severe diabetic ketoacidosis and severe metabolic complications have been described. CLINICAL CASE: This report describes two patients with diabetes mellitus who came to our hospital with ketoacidosis resulting from new-onset diabetes mellitus. We describe the clinical course and the management approach during the COVID-19 pandemic. CONCLUSION: COVID-19 is associated with metabolic complications such as severe diabetic ketoacidosis.

INTRODUCCIÓN: La relación entre la enfermedad por el coronavirus de 2019 (COVID-19) secundaria a SARS-CoV-2 y la diabetes mellitus es bidireccional. Por un lado, la diabetes mellitus se asocia con un mayor riesgo de COVID-19 grave. Por otro lado, en pacientes con COVID-19 se han observado diabetes mellitus de nueva aparición con presentaciones de cetoacidosis diabética y complicaciones metabólicas graves de dicha presentación. CASOS CLÍNICOS: En este informe, describimos a dos pacientes pediátricos con diabetes mellitus que acudieron a nuestro hospital con cetoacidosis diabética, de debut inicial. Describimos la evolución y el manejo clínico y terapéutico durante la pandemia de COVID-19. CONCLUSIÓN: La infección por COVID-19 puede precipitar complicaciones como cetoacidosis diabética severa.

Prehospital, post-ROSC blood pressure and associated neurologic outcome.

OBJECTIVE: To investigate the relationship between hypotension and neurologic outcome in adults with return of spontaneous circulation after out-of-hospital cardiac arrest. METHODS: Blood pressure and medication data were extracted from adult patients who had ROSC after OHCA in Alameda County and matched with neurologic outcome using the CARES database from January 1, 2018 through July 1, 2019. We used univariate logistic regression with p ≤ 0.2 followed by multivariate logistic regression and reported an odds ratio with 95% confidence intervals. RESULTS: Among the 781 adult patients who had ROSC after OHCA, 107 (13.7%) were noted to be hypotensive and 61 (57% of the hypotensive group) received vasopressors. Patients with a final prehospital blood pressure recording of <90 mmHg were more likely to have a poor neurologic outcome (adjusted odds ratio 2.13, adj p = 0.048). About twice as many patients who were not hypotensive had a good neurologic outcome compared to hypotensive patients who had a good neurologic outcome (23% to 10.3%). Additionally, patients who were hypotensive and did not receive vasopressors had a similar neurologic outcome compared to patients who did receive vasopressors. CONCLUSION: Prehospital post-ROSC hypotension was associated with worse neurologic outcome and giving hypotensive patients vasopressors may not improve neurologic outcome in the prehospital setting.

Prediction of encephalopathy in perinatal asphyxia score: reaching the unreached.

OBJECTIVES: Neonates who develop moderate to severe encephalopathy following perinatal asphyxia will benefit from therapeutic hypothermia. Current National Institute of Child Health and Human Development (NICHD) criteria for identifying encephalopathic neonates needing therapeutic hypothermia has high specificity. This results in correctly identifying neonates who have already developed moderate to severe encephalopathy but miss out many potential beneficiaries who progress to develop moderate to severe encephalopathy later. The need is therefore not just to diagnose encephalopathy, but to predict development of encephalopathy and extend the therapeutic benefit for all eligible neonates. The primary objective of the study was to develop and validate the statistical model for prediction of moderate to severe encephalopathy following perinatal asphyxia and compare with current NICHD criteria. METHODS: The study was designed as prospective observational study. It was carried out in a single center Level 3 perinatal unit in India. Neonates>35 weeks of gestation and requiring resuscitation at birth were included. Levels of resuscitation and blood gas lactate were used to determine the pre-test probability, Thompson score between 3 and 5 h of life was used to determine post-test probability of developing encephalopathy. Primary outcome measure: Validation of Prediction of Encephalopathy in Perinatal Asphyxia (PEPA) score by Holdout method. RESULTS: A total of 55 babies were included in the study. The PEPA score was validated by Holdout method where the fitted receiver-operating characteristic (ROC) area for the training and test sample were comparable (p=0.758). The sensitivity and specificity of various PEPA scores for prediction of encephalopathy ranged between 74 and 100% in contrast to NICHD criteria which was 42%. PEPA score of 30 had a best combination of sensitivity and specificity of 95 and 89% respectively. CONCLUSIONS: PEPA score has a higher sensitivity than NICHD criteria for prediction of Encephalopathy in asphyxiated neonates.

Recovery of Hypoxic Regions in a Rat Model of Microembolism.

OBJECTIVES: Endovascular treatment (EVT) has become the standard of care for acute ischemic stroke. Despite successful recanalization, a limited subset of patients benefits from the new treatment. Human MRI studies have shown that during removal of the thrombus, a shower of microclots is released from the initial thrombus, possibly causing new ischemic lesions. The aim of the current study is to quantify tissue damage following microembolism. MATERIALS AND METHODS: In a rat model, microembolism was generated by injection of a mixture of polystyrene fluorescent microspheres (15, 25 and 50 µm in diameter). The animals were killed at three time-points: day 1, 3 or 7. AMIRA and IMARIS software was used for 3D reconstruction of brain structure and damage, respectively. CONCLUSIONS: Microembolism induces ischemia, hypoxia and infarction. Infarcted areas persist, but hypoxic regions recover over time suggesting that repair processes in the brain rescue the regions at risk.

Combined transplantation of neural stem cells and bone marrow mesenchymal stem cells promotes neuronal cell survival to alleviate brain damage after cardiac arrest via microRNA-133b incorporated in extracellular vesicles.

Neural stem cell (NSC) transplantation has prevailed as a promising protective strategy for cardiac arrest (CA)-induced brain damage. Surprisingly, the poor survival of neuronal cells in severe hypoxic condition restricts the utilization of this cell-based therapy. Extracellular vesicles (EVs) transfer microRNAs (miRNAs) between cells are validated as the mode for the release of several therapeutic molecules. The current study reports that the bone marrow mesenchymal stem cells (BMSCs) interact with NSCs via EVs thereby affecting the survival of neuronal cells. Hypoxic injury models of neuronal cells were established using cobalt chloride, followed by co-culture with BMSCs and NSCs alone or in combination. BMSCs combined with NSCs elicited as a superior protocol to stimulate neuronal cell survival. BMSCs-derived EVs could protect neuronal cells against hypoxic injury. Silencing of miR-133b incorporated in BMSCs-derived EVs could decrease the cell viability and the number of NeuN-positive cells and increase the apoptosis in the CA rat model. BMSCs-derived EVs could transfer miR-133b to neuronal cells to activate the AKT-GSK-3ß-WNT-3 signaling pathway by targeting JAK1. Our study demonstrates that NSCs promotes the release of miR-133b from BMSCs-derived EVs to promote neuronal cell survival, representing a potential therapeutic strategy for the treatment of CA-induced brain damage.

Proteus syndrome caused by novel somatic AKT1 duplication.

Proteus syndrome (PS) is a rare overgrowth disorder that presents with asymmetrical growth of the bone and fat tissues following a mosaic pattern mutation. The estimated worldwide incidence is approximately one in one million live births. Proteus syndrome causes disfigurement and psychological impact through its effects on somatic tissue. Due to its rarity and diversity of tissues involved, it represents a significant challenge to caregivers and multidisciplinary medical teams. Here, we report a Saudi girl, with a large left cervical mass discovered antenatally. This mass was identified as a growing cystic hygroma, and she had features of overgrowth and hemangiomas. Whole exome sequencing was negative from the blood lymphocytes and affected tissue sample.  However, deletion duplication analysis from tissue shows a novel mosaic somatic mutation of the AKT1 gene. Somatic mutation remains an obstacle, and the geneticist has an essential role in its management, providing an established genetic diagnosis, prognosis, and family counselling.