Serum Neuron-Specific Enolase as a Biomarker of Neonatal Brain Injury-New Perspectives for the Identification of Preterm Neonates at High Risk for Severe Intraventricular Hemorrhage.

Neonatal brain injury (NBI) is a critical condition for preterm neonates with potential long-term adverse neurodevelopmental outcomes. This prospective longitudinal case-control study aimed at investigating the levels and prognostic value of serum neuron-specific enolase (NSE) during the first 3 days of life in preterm neonates (<34 weeks) that later developed brain injury in the form of either periventricular leukomalacia (PVL) or intraventricular hemorrhage (IVH) during their hospitalization. Participants were recruited from one neonatal intensive care unit, and on the basis of birth weight and gestational age, we matched each case (n = 29) with a neonate who had a normal head ultrasound scan (n = 29). We report that serum NSE levels during the first three days of life do not differ significantly between control and preterm neonates with NBI. Nevertheless, subgroup analysis revealed that neonates with IVH had significantly higher concentrations of serum NSE in comparison to controls and neonates with PVL on the third day of life (p = 0.014 and p = 0.033, respectively). The same pattern on the levels of NSE on the third day of life was also observed between (a) neonates with IVH and all other neonates (PVL and control; p = 0.003), (b) neonates with II-IV degree IVH and all other neonates (p = 0.003), and (c) between control and the five (n = 5) neonates that died from the case group (p = 0.023). We conclude that NSE could be an effective and useful biomarker on the third day of life for the identification of preterm neonates at high risk of developing severe forms of IVH.

Neurodevelopmental outcomes in congenital heart disease: Usefulness of biomarkers of brain injury.

INTRODUCTION: At present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. METHODS: Prospective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. RESULTS: the study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. CONCLUSIONS: children with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer follow-ups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD.

Plasma ubiquitin C-terminal hydrolase-L1 (UCH-L1) level as a blood biomarker of neurological damage after allogeneic hematopoietic cell transplantation.

Several biofluid-based biomarkers for traumatic brain injury show promise for use in diagnosis and outcome prediction. In contrast, few studies have investigated biomarkers for non-traumatic brain injury. We focused on ubiquitin C-terminal hydrolase-L1 (UCH-L1), which has been proposed as a screening tool for traumatic brain injury, and investigated whether the plasma UCH-L1 level could also be a useful biomarker in patients with non-traumatic brain injury. We measured UCH-L1 in 25 patients who had experienced neurological complications after allogeneic hematopoietic cell transplantation (HCT) and 22 control patients without any complications or graft-versus-host disease. Although UCH-L1 levels before HCT did not differ significantly (P = 0.053), levels after HCT were higher in patients with neurological complications compared with the control group (P < 0.001). At a UCH-L1 cutoff value of 0.072 ng/ml, sensitivity was 68.0% and specificity was 100%. The statistical power of UCH-L1 for neurological complications seemed to be higher than that of CT and comparable to that of MRI. Thus, increased levels of UCH-L1 might reflect the presence of neurological damage even in patients with non-traumatic brain injury. Further large cohort investigations are warranted.

Serum brain injury biomarkers are gestationally and post-natally regulated in non-brain injured neonates.

BACKGROUND: To determine the association of gestational age (GA) and day of life (DOL) with the circulating serum concentration of six brain injury-associated biomarkers in non-brain injured neonates born between 23 and 41 weeks' GA. METHODS: In a multicenter prospective observational cohort study, serum CNS-insult, inflammatory and trophic proteins concentrations were measured daily in the first 7 DOL. RESULTS: Overall, 3232 serum samples were analyzed from 745 enrollees, median GA 32.3 weeks. BDNF increased 3.7% and IL-8 increased 8.9% each week of gestation. VEGF, IL-6, and IL-10 showed no relationship with GA. VEGF increased 10.8% and IL-8 18.9%, each DOL. IL-6 decreased by 15.8% each DOL. IL-10 decreased by 81.4% each DOL for DOL 0-3. BDNF did not change with DOL. Only 49.67% of samples had detectable GFAP and 33.15% had detectable NRGN. The odds of having detectable GFAP and NRGN increased by 53% and 11%, respectively, each week after 36 weeks' GA. The odds of having detectable GFAP and NRGN decreased by 15% and 8%, respectively, each DOL. CONCLUSIONS: BDNF and IL-8 serum concentrations vary with GA. VEGF and interleukin concentrations are dynamic in the first week of life, suggesting circulating levels should be adjusted for GA and DOL for clinically relevant assessment of brain injury. IMPACT: Normative data of six brain injury-related biomarkers is being proposed. When interpreting serum concentrations of brain injury biomarkers, it is key to adjust for gestational age at birth and day of life during the first week to correctly assess for clinical brain injury in neonates. Variation in levels of some biomarkers may be related to gestational and postnatal age and not necessarily pathology.

Determination of Predictors of Brain Injury in Very Preterm Infants - A Retrospective Cohort Study.

Background: Despite decades of research, there is inadequate evidence on the etiological factors of brain injury in preterm infants. Objective: To study the perinatal risk factors for preterm brain injury and to assess their strength of association. Methods: In this retrospective cohort study, we included infants born at <32 weeks' gestation and had either magnetic resonance imaging (MRI) or cranial ultrasound (CUS) performed at term equivalent age. Significant brain injury was diagnosed based on Kidokoro global brain injury score was ≥4 in MRI or cystic periventricular leukomalacia in CUS. Results: Among the 698 infants, 48 had significant brain injury and 650 were taken as controls. In multiple logistic regression, intraventricular hemorrhage (IVH) grade 3-4 [adjusted odds ratio, 92.892 (19.495-442.619)], culture-positive sepsis [4.162 (1.729-10.021)], prolonged ventilation [3.688 (1.087-12.510)], and small for gestational age (SGA) [2.645 (1.181-5.924] were associated with greater risk of preterm brain injury. Conclusion: Severe IVH, culture-positive sepsis, prolonged ventilation and SGA were significant risk factors for preterm brain injury with severe IVH being the most significant contributing factor.

Relative changes in brain and kidney biomarkers with Exertional Heat Illness during a cool weather marathon.

BACKGROUND: Medical personnel may find it challenging to distinguish severe Exertional Heat Illness (EHI), with attendant risks of organ-injury and longer-term sequalae, from lesser forms of incapacity associated with strenuous physical exertion. Early evidence for injury at point-of-incapacity could aid the development and application of targeted interventions to improve outcomes. We aimed to investigate whether biomarker surrogates for end-organ damage sampled at point-of-care (POC) could discriminate EHI versus successful marathon performance. METHODS: Eight runners diagnosed as EHI cases upon reception to medical treatment facilities and 30 successful finishers of the same cool weather marathon (ambient temperature 8 rising to 12 ºC) were recruited. Emerging clinical markers associated with injury affecting the brain (neuron specific enolase, NSE; S100 calcium-binding protein B, S100ß) and renal system (cystatin C, cysC; kidney-injury molecule-1, KIM-1; neutrophil gelatinase-associated lipocalin, NGAL), plus copeptin as a surrogate for fluid-regulatory stress, were sampled in blood upon marathon collapse/completion, as well as beforehand at rest (successful finishers only). RESULTS: Versus successful finishers, EHI showed significantly higher NSE (10.33 [6.37, 20.00] vs. 3.17 [2.71, 3.92] ug.L-1, P<0.0001), cysC (1.48 [1.10, 1.67] vs. 1.10 [0.95, 1.21] mg.L-1, P = 0.0092) and copeptin (339.4 [77.0, 943] vs. 18.7 [7.1, 67.9] pmol.L-1, P = 0.0050). Discrimination of EHI by ROC (Area-Under-the-Curve) showed performance that was outstanding for NSE (0.97, P<0.0001) and excellent for copeptin (AUC = 0.83, P = 0.0066). CONCLUSIONS: As novel biomarker candidates for EHI outcomes in cool-weather endurance exercise, early elevations in NSE and copeptin provided sufficient discrimination to suggest utility at point-of-incapacity. Further investigation is warranted in patients exposed to greater thermal insult, followed up over a more extended period.

Chronic subdural haematoma: the role of peri-operative medicine in a common form of reversible brain injury.

Epidemiological studies project a significant rise in cases of chronic subdural haematoma over the next 20 years. Patients with this condition are frequently older and medically complex, with baseline characteristics that may increase peri-operative risk. The intra-operative period is only a small portion of a patient's total hospital stay, with a majority of patients in the United Kingdom transferred between institutions for their surgical and rehabilitative care. Definitive management remains surgical, but peri-operative challenges exist which resonate with other surgical cohorts where multidisciplinary working has become the gold standard. These include shared decision-making, medical optimisation, the management of peri-operative anticoagulation and the identification of key points of equipoise for examination in the future trials. In this narrative review, we use a stereotyped patient journey to provide context to the recent literature, highlighting where multidisciplinary expertise may be required to optimise patient care and maximise the benefits of surgical management. We discuss the triage, pre-operative optimisation, intra-operative management and immediate postoperative care of patients undergoing surgery for a chronic subdural haematoma. We also discuss where adjunctive medical management may be indicated. In so doing, we present the current and emerging evidence base for the role of an integrated peri-operative medicine team in the care of patients with a chronic subdural haematoma.

A bioimpedance-based monitor for real-time detection and identification of secondary brain injury.

Secondary brain injury impacts patient prognosis and can lead to long-term morbidity and mortality in cases of trauma. Continuous monitoring of secondary injury in acute clinical settings is primarily limited to intracranial pressure (ICP); however, ICP is unable to identify essential underlying etiologies of injury needed to guide treatment (e.g. immediate surgical intervention vs medical management). Here we show that a novel intracranial bioimpedance monitor (BIM) can detect onset of secondary injury, differentiate focal (e.g. hemorrhage) from global (e.g. edema) events, identify underlying etiology and provide localization of an intracranial mass effect. We found in an in vivo porcine model that the BIM detected changes in intracranial volume down to 0.38 mL, differentiated high impedance (e.g. ischemic) from low impedance (e.g. hemorrhagic) injuries (p < 0.001), separated focal from global events (p < 0.001) and provided coarse 'imaging' through localization of the mass effect. This work presents for the first time the full design, development, characterization and successful implementation of an intracranial bioimpedance monitor. This BIM technology could be further translated to clinical pathologies including but not limited to traumatic brain injury, intracerebral hemorrhage, stroke, hydrocephalus and post-surgical monitoring.

Perinatal blood biomarkers for the identification of brain injury in very low birth weight growth-restricted infants.

OBJECTIVE: To determine if blood biomarkers measured at delivery and shortly after birth can identify growth-restricted infants at risk for developing severe brain injury. STUDY DESIGN: In a cohort of very low birth weight neonates, fetal growth restricted (FGR) (birth weight <10%) were compared to non-FGR neonates, and within the FGR group those with brain injury were compared to those without. Biomarkers were measured in cord blood at delivery, and daily for the 1st 5 days of life. RESULT: FGR was associated with significantly higher levels of interleukin (IL)-6, IL-8, IL-10, and lower levels of vascular endothelial growth factor (VEGF). FGR and brain injury were associated with significantly higher levels of IL-6, IL-8, IL-10, and glial fibrillary acidic protein (GFAP). CONCLUSION: Interleukins may be involved in a common pathway contributing to both the development of growth restriction and brain injury, and GFAP may help identify brain injury within this growth-restricted group.

Broader Insights into Understanding Tumor Necrosis Factor and Neurodegenerative Disease Pathogenesis Infer New Therapeutic Approaches.

Proinflammatory cytokines such as tumor necrosis factor (TNF), with its now appreciated key roles in neurophysiology as well as neuropathophysiology, are sufficiently well-documented to be useful tools for enquiry into the natural history of neurodegenerative diseases. We review the broader literature on TNF to rationalize why abruptly-acquired neurodegenerative states do not exhibit the remorseless clinical progression seen in those states with gradual onsets. We propose that the three typically non-worsening neurodegenerative syndromes, post-stroke, post-traumatic brain injury (TBI), and post cardiac arrest, usually become and remain static because of excess cerebral TNF induced by the initial dramatic peak keeping microglia chronically activated through an autocrine loop of microglial activation through excess cerebral TNF. The existence of this autocrine loop rationalizes post-damage repair with perispinal etanercept and proposes a treatment for cerebral aspects of COVID-19 chronicity. Another insufficiently considered aspect of cerebral proinflammatory cytokines is the fitness of the endogenous cerebral anti-TNF system provided by norepinephrine (NE), generated and distributed throughout the brain from the locus coeruleus (LC). We propose that an intact LC, and therefore an intact NE-mediated endogenous anti-cerebral TNF system, plus the DAMP (damage or danger-associated molecular pattern) input having diminished, is what allows post-stroke, post-TBI, and post cardiac arrest patients a strong long-term survival advantage over Alzheimer's disease and Parkinson's disease sufferers. In contrast, Alzheimer's disease and Parkinson's disease patients remorselessly worsen, being handicapped by sustained, accumulating, DAMP and PAMP (pathogen-associated molecular patterns) input, as well as loss of the LC-origin, NE-mediated, endogenous anti-cerebral TNF system. Adrenergic receptor agonists may counter this.

Association between cerebrospinal fluid biomarkers of neuronal injury or amyloidosis and cognitive decline after major surgery.

BACKGROUND: Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function. METHODS: In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid ß (Aß1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1-2 weeks before surgery, at discharge from the hospital (2-5 days after surgery), and at 3 months after surgery. RESULTS: CSF and blood concentrations of T-tau, neurone-specific enolase, and Aß1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Aß1-42. CONCLUSIONS: The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction.

Serious neonatal morbidities are associated with differences in DNA methylation among very preterm infants.

BACKGROUND: Infants born very preterm are more likely to experience neonatal morbidities compared to their term peers. Variations in DNA methylation (DNAm) associated with these morbidities may yield novel information about the processes impacted by these morbidities. METHODS: This study included 532 infants born < 30 weeks gestation, participating in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants study. We used a neonatal morbidity risk score, which was an additive index of the number of morbidities experienced during the NICU stay, including bronchopulmonary dysplasia (BPD), severe brain injury, serious neonatal infections, and severe retinopathy of prematurity. DNA was collected from buccal cells at discharge from the NICU, and DNAm was measured using the Illumina MethylationEPIC. We tested for differential methylation in association with the neonatal morbidity risk score then tested for differentially methylated regions (DMRs) and overrepresentation of biological pathways. RESULTS: We identified ten differentially methylated CpGs (α Bonferroni-adjusted for 706,278 tests) that were associated with increasing neonatal morbidity risk scores at three intergenic regions and at HPS4, SRRD, FGFR1OP, TNS3, TMEM266, LRRC3B, ZNF780A, and TENM2. These mostly followed dose-response patterns, for 8 CpGs increasing DNAm associated with increased numbers of morbidities, while for 2 CpGs the risk score was associated with decreasing DNAm. BPD was the most substantial contributor to differential methylation. We also identified seven potential DMRs and over-representation of genes involved in Wnt signaling; however, these results were not significant after Bonferroni adjustment for multiple testing. CONCLUSIONS: Neonatal DNAm, within genes involved in fibroblast growth factor activities, cellular invasion and migration, and neuronal signaling and development, are sensitive to the neonatal health complications of prematurity. We hypothesize that these epigenetic features may be representative of an integrated marker of neonatal health and development and are promising candidates to integrate with clinical information for studying developmental impairments in childhood.

[Scalp-recorded cortical spreading depolarizations (CSDs) of EEG with time constant of 2 seconds in a patient with acute traumatic brain injury].

An 82-year-old female suffered from head trauma, and developed acute consciousness disturbance 6 days after the event. Head CT showed the acute subdural hematoma in the left temporooccipital area and the patient underwent emergency hematoma evacuation and decompression. However, her consciousness disturbance became worse after surgery. Intermittent large negative infraslow shifts (lasting longer than 40 seconds) were recorded in the right posterior quadrant by scalp EEG with TC of 2 sec, that was defined as cortical spreading depolarizations (CSDs). Clinically consciousness disturbance sustained poor until 1 month after surgery in spite of treatment by anti-epileptic drugs. CSDs were observed on the right side where head injury most likely occurred. It may explain the sustained consciousness disturbance associated with significant prolonged ischemia. Once scalp EEG could record CSDs in this particular patient, the degree and its prognosis of traumatic head injury were estimated.

Machine-learning based MRI radiomics models for early detection of radiation-induced brain injury in nasopharyngeal carcinoma.

BACKGROUND: Early radiation-induced temporal lobe injury (RTLI) diagnosis in nasopharyngeal carcinoma (NPC) is clinically challenging, and prediction models of RTLI are lacking. Hence, we aimed to develop radiomic models for early detection of RTLI. METHODS: We retrospectively included a total of 242 NPC patients who underwent regular follow-up magnetic resonance imaging (MRI) examinations, including contrast-enhanced T1-weighted and T2-weighted imaging. For each MRI sequence, four non-texture and 10,320 texture features were extracted from medial temporal lobe, gray matter, and white matter, respectively. The relief and 0.632 + bootstrap algorithms were applied for initial and subsequent feature selection, respectively. Random forest method was used to construct the prediction model. Three models, 1, 2 and 3, were developed for predicting the results of the last three follow-up MRI scans at different times before RTLI onset, respectively. The area under the curve (AUC) was used to evaluate the performance of models. RESULTS: Of the 242 patients, 171 (70.7%) were men, and the mean age of all the patients was 48.5 ± 10.4 years. The median follow-up and latency from radiotherapy until RTLI were 46 and 41 months, respectively. In the testing cohort, models 1, 2, and 3, with 20 texture features derived from the medial temporal lobe, yielded mean AUCs of 0.830 (95% CI: 0.823-0.837), 0.773 (95% CI: 0.763-0.782), and 0.716 (95% CI: 0.699-0.733), respectively. CONCLUSION: The three developed radiomic models can dynamically predict RTLI in advance, enabling early detection and allowing clinicians to take preventive measures to stop or slow down the deterioration of RTLI.

Modern Brain Retractors and Surgical Brain Injury: A Review.

Surgical brain injury caused by brain retraction is a well-known consequence of intracranial surgery. Modern retractor designs, particularly since the 1980s, have significantly improved ease of use, improved visibility for surgeons, and minimized retraction-induced injuries, though not yet been entirely eliminated. Today, brain retractors come in a broad range of styles, each with its own pros and cons regarding operational utility and patient safety. Which type is chosen for use depends on the surgical approach, lesion size and depth, cost, and surgeon preference. Traditionally, self-retaining brain retractors with moveable arms and 1 or more attachable blades made from malleable stainless steel or silicone rubber have been the tool of choice; however, recently tubular retraction systems that only require fixation to the head frame and cause less focal pressure damage than older retractors have gained in popularity for some cases. This review aims to address the history of brain retraction and discuss each of the commonly used brain retractor types, as well as some newer and less common varieties especially in terms of the extent of tissue damage typically caused as well as the types of injuries reported by the users.

Purines: From Diagnostic Biomarkers to Therapeutic Agents in Brain Injury.

The purines constitute a family of inter-related compounds that serve a broad range of important intracellular and extracellular biological functions. In particular, adenosine triphosphate (ATP) and its metabolite and precursor, adenosine, regulate a wide variety of cellular and systems-level physiological processes extending from ATP acting as the cellular energy currency, to the adenosine arising from the depletion of cellular ATP and responding to reduce energy demand and hence to preserve ATP during times of metabolic stress. This inter-relationship provides opportunities for both the diagnosis of energy depletion during conditions such as stroke, and the replenishment of ATP after such events. In this review we address these opportunities and the broad potential of purines as diagnostics and restorative agents.

Orbital metastatic neuroblastoma presenting as posttraumatic exophthalmos.

A 2-year-old female patient with a recent history of head trauma was admitted to the Ophthalmology Clinic with left exophthalmos. A differential diagnosis between traumatic and tumoral etiology was made. The orbitocranial MRI and fine needle ganglion biopsy settled the malignant etiology of the exophthalmia. Further investigations at the Pediatric Oncology Clinic decided on the diagnosis of orbital metastatic neuroblastoma. This case report presented an unusual association: orbital metastatic neuroblastoma becoming clinically positive soon after a head trauma.

Onset of brain injury in infants with prenatally diagnosed congenital heart disease.

BACKGROUND: The exact onset of brain injury in infants with congenital heart disease (CHD) is unknown. Our aim was, therefore, to assess the association between prenatal Doppler flow patterns, postnatal cerebral oxygenation and short-term neurological outcome. METHODS: Prenatally, we measured pulsatility indices of the middle cerebral (MCA-PI) and umbilical artery (UA-PI) and calculated cerebroplacental ratio (CPR). After birth, cerebral oxygen saturation (rcSO2) and fractional tissue oxygen extraction (FTOE) were assessed during the first 3 days after birth, and during and for 24 hours after every surgical procedure within the first 3 months after birth. Neurological outcome was determined preoperatively and at 3 months of age by assessing general movements and calculating the Motor Optimality Score (MOS). RESULTS: Thirty-six infants were included. MOS at 3 months was associated with MCA-PI (rho 0.41, P = 0.04), UA-PI (rho -0.39, P = 0.047, and CPR (rho 0.50, P = 0.01). Infants with abnormal MOS had lower MCA-PI (P = 0.02) and CPR (P = 0.01) and higher UA-PI at the last measurement (P = 0.03) before birth. In infants with abnormal MOS, rcSO2 tended to be lower during the first 3 days after birth, and FTOE was significantly higher on the second day after birth (P = 0.04). Intraoperative and postoperative rcSO2 and FTOE were not associated with short-term neurological outcome. CONCLUSION: In infants with prenatally diagnosed CHD, the prenatal period may play an important role in developmental outcome. Additional research is needed to clarify the relationship between preoperative, intra-operative and postoperative cerebral oxygenation and developmental outcome in infants with prenatally diagnosed CHD.

Effects of Isolated Impaired Fasting Glucose on Brain Injury During Cardiac Surgery Under Cardiopulmonary Bypass.

Objective: To evaluate the effects of isolated impaired fasting glucose (IIFG) on brain injury in patients undergoing cardiopulmonary bypass (CPB) surgery. Methods: Patients with rheumatic heart valve disease who underwent elective mitral valve replacement were included and divided into control and IIFG groups. Pre-, intra-, and postoperative blood glucose levels, serum insulin levels, insulin resistance index (HOMA-IR), lactic acid levels, and neuron-specific enolase (NSE) and S100B levels were measured. The cerebral oxygen extraction ratio (OER) was calculated. Cognitive function was assessed via the Mini-Mental State Examination (MMSE). Results: HOMA-IR levels were higher in the IIFG group than the control group 30 min after the beginning of CPB, at the termination of CPB, and 2 h after the termination of CPB. Cerebral OER and lactic acid increased intraoperatively in both groups, especially in the IIFG group. NSE and S100B levels were higher in the IIFG group than in the control group at the termination of CPB, 2 h after the termination of CPB, and at 24 h postoperatively. The MMSE scores did not significantly differ between the two groups. Delirium occurred in two patients in the IIFG group, and one in the control group. No other signs and symptoms of brain injuries were detected in either group. Conclusions: The increased postoperative NSE and S100B levels in the IIFG group compared with controls may be associated with severe insulin resistance and stress hyperglycemia. However, the IIFG group did not have clinical manifestations of brain injuries, including cognitive impairment.