Cerebral Insult Research Articles

Novel Intranasal Drug Delivery: Geraniol Charged Polymeric Mixed Micelles for Targeting Cerebral Insult as a Result of Ischaemia/Reperfusion

Novel Intranasal Drug Delivery: Geraniol Charged Polymeric Mixed Micelles for Targeting Cerebral Insult as a Result of Ischaemia/Reperfusion

Multimodality monitoring in neurocritical care

Monitoring the health of an injured brain is essential to forewarn neurological worsening and to gain insight into the pathophysiology of a complex disorder.Clinical examination remains a cornerstone in monitoring patients with brain injury. The Glasgow coma score (GCS) is widely used but lacks information regarding brain stem functions like pupillary reaction and shows moderate inter-observer reliability. However, despite these shortcomings, GCS remains a robust indicator of the need for surgery and prognosis after cardiac arrest, hypoxic brain injury, and posterior circulation stroke. A new scoring system called Full Outline of Unresponsiveness has been proposed and shows excellent inter-observer reliability and includes points concerning brain stem functions.1 The most commonly used monitoring modality is intracranial pressure (ICP) monitoring. ICP shows threshold physiology where the outcome of the patients changes after a threshold of 20 to 25 mmHg. Refractory ICP is a good predictor of mortality but not of the functional outcome after traumatic brain injury.Brain injury causes varying degrees of disruption to cerebral blood flow and its autoregulation. Studying autoregulation provides a useful strategy for targeting cerebral perfusion pressure close to the autoregulatory range. Transcranial Doppler and ICMplus (Intensive Care Monitoring) are used to study autoregulation. ICMplus is a software-based tool that studies the correlation between slow changes in mean arterial pressure and ICP to evaluate the state of autoregulation throughout the duration of ICP monitoring.2 Brain tissue oxygen measures the partial pressure of oxygen in the extracellular fluid of the neural tissue. Reduction in brain tissue oxygen is a marker of cellular distress. A phase 2 trial on brain tissue oxygen monitoring demonstrated the safety and feasibility of the protocol-based management of brain tissue oxygenation and ICP, and a trend towards lower mortality and improved functional outcome in patients treated with combined oxygen and ICP protocol.3 Microdialysis is a point of care test that monitors substrate delivery and metabolism at the cellular level. The lactate-pyruvate (LP) ratio is an indicator of the redox state of cells and a high LP ratio is associated with an unfavourable outcome.4 The electroencephalogram (EEG) is used in critical care for monitoring sedation and diagnosis of seizure activity. EEG is a complex signal which requires advanced training and skills for interpretation. Novel EEG-based monitors are aimed at simplifying the signal for straightforward interpretation by bedside medical professionals. Cerebral function monitor (CFM) is a compressed single channel amplitude integrated EEG monitor mainly used for the detection of status epilepticus and burst suppression during thiopentone infusion. A novel technique that uses direct electrodes applied on the cortical surface called Electrocorticogram (ECoG) shows spreading depolarisations on the cortical surface that are caused by loss of ionic homeostasis and substrate delivery.5 These depolarisations are a sensitive indicator of impending neuronal death and may serve as a target for novel mechanistically oriented therapies.Detection, prevention, and monitoring of secondary cerebral insults that alter the prognosis from the injury, remains at the centre stage in neurocritical care. In the future, integrated informatics derived from multimodality monitoring will play a pivotal role in clinical decision algorithms.

Outcomes following veno-arterial extracorporeal membrane oxygenation for post-cardiotomy cardiogenic shock in adult cardiac surgical patients with a normal preoperative left ventricular ejection fraction

Introduction Post- cardiotomy cardiogenic shock (PCCS) is a syndrome that occurs following separation from cardiopulmonary bypass or anytime in the immediate postoperative Course(1). The aim of our study was to identify risk factors for mortality and outcomes in patients with normal preoperative left ventricular ejection fraction (LVEF) who received veno- arterial extracorporeal membrane oxygenation (VA ECMO) for PCCS in first 48 h post-cardiac surgery. Methods Retrospective cohort analysis of adult patients, who received VA ECMO for PCCS from 1998-2018. Association between all collected variables and mortality were analyzed, with bivariate and multivariate analysis. Results Of the 62,125 patients who underwent cardiac surgery procedures at our institution during the study period, a total of 173 patients (0.3%) with normal preoperative LVEF required PCCS. The mean age was 65 years (46.8% females) and a logistic Euroscore was 14.7%. 53% of patients were elective. Procedures were isolated coronary artery bypass grafting (CABG) in 24.2%, valve surgery 32.3%, CABG plus valve surgery 15.1%, aortic valve+ascending aorta 22.0%, aortic arch surgery 6.4%. Amongst these, 28.0% of patients were redo procedures, 11.6% had endocarditis, and 2.3% Type A dissection. VA ECMO was instituted in 74.6% patients on the day of surgery (49.6% in operating room, 25.0% after admission to the ICU), 16.8% on first postop day, and 8.7% on the second day. The median duration of ECMO support was 5 days. The reasons for ECMO implantation was: acute coronary insufficiency in 43.4% of patients, arrythmias (8.7 %), pulmonary embolism (1.2%), valvular insufficiency (1.7%), and cardiogenic shock in 46.2%. ECMO complications were bleeding in 40.0%, acute kidney injury (18.0%), stroke (6.4%), gastrointestinal complications (5.2%), sepsis (5.8%), limb thrombosis (3.0%). No complications were noted in 21.4% of patients. The overall in-hospital mortality was 57.8 %. Causes of mortality were therapy refractory shock in 40.0%, LCOS (Low cardiac output syndrome)after ECMO weaning (17.0%) multiorgan dysfunction (33.0%), and cerebral insult (10.0%). Independent risk factors for mortality were female gender (OR 2 (95%CI 1.1-3.7), Diabetes mellitus (DM) (OR 2 (95%CI 1.1-3.9), preoperative peripheral vascular disease (PVD) (OR 2.2 (95%CI 1.1-4.5), prior cardiac surgery (OR 3 (95%CI 1.4-6.3) and postoperative MI (Myocardial infarction) (OR 2.4 (95%CI 1.1-5.4). Non survivors had a median hospital stay of 7 (2-11) days and survivors had a median of hospital stay after ECMO of 19 (11-28) days. Discussion VA-ECMO is associated with high mortality for PCCS in adult cardiac patients with normal preoperative LVEF. In our cohort of patients, female gender, DM, preoperative PVD, prior cardiac surgery and postoperative MI were independent predictors of in-hospital mortality.

Intracranial Hypertension and Cerebral Perfusion Pressure Insults in Adult Hypertensive Intraventricular Hemorrhage: Occurrence and Associations With Outcome.

Elevated intracranial pressure and inadequate cerebral perfusion pressure may contribute to poor outcomes in hypertensive intraventricular hemorrhage. We characterized the occurrence of elevated intracranial pressure and low cerebral perfusion pressure in obstructive intraventricular hemorrhage requiring extraventricular drainage. Prospective observational cohort. ICUs of 73 academic hospitals. Four hundred ninety-nine patients enrolled in the CLEAR III trial, a multicenter, randomized study to determine if extraventricular drainage plus intraventricular alteplase improved outcome versus extraventricular drainage plus saline. Intracranial pressure and cerebral perfusion pressure were recorded every 4 hours, analyzed over a range of thresholds, as single readings or spans (≥ 2) of readings after adjustment for intracerebral hemorrhage severity. Impact on 30- and 180-days modified Rankin Scale scores was assessed, and receiver operating curves were analyzed to identify optimal thresholds. Of 21,954 intracranial pressure readings, median interquartile range 12 mm Hg (8-16), 9.7% were greater than 20 mm Hg and 1.8% were greater than 30 mm Hg. Proportion of intracranial pressure readings from greater than 18 to greater than 30 mm Hg and combined intracranial pressure greater than 20 plus cerebral perfusion pressure less than 70 mm Hg were associated with day-30 mortality and partially mitigated by intraventricular alteplase. Proportion of cerebral perfusion pressure readings from less than 65 to less than 90 mm Hg and intracranial pressure greater than 20 mm Hg in spans were associated with both 30-day mortality and 180-day mortality. Proportion of cerebral perfusion pressure readings from less than 65 to less than 90 mm Hg and combined intracranial pressure greater than 20 plus cerebral perfusion pressure less than 60 mm Hg were associated with poor day-30 modified Rankin Scale, whereas cerebral perfusion pressure less than 65 and less than 75 mm Hg were associated with poor day-180 modified Rankin Scale. Elevated intracranial pressure and inadequate cerebral perfusion pressure are not infrequent during extraventricular drainage for severe intraventricular hemorrhage, and level and duration predict higher short-term mortality and long-term mortality. Burden of low cerebral perfusion pressure was also associated with poor short- and long-term outcomes and may be more significant than intracranial pressure. Adverse consequences of intracranial pressure-time burden and cerebral perfusion pressure-time burden should be tested prospectively as potential thresholds for therapeutic intervention.

Integrative monitoring of systemic hemodynamics and the oxygen-transport status and the choice of the intensive therapy tactics in patients, suffering an ischemic cerebral insult

Objective. To elaborate the intensive therapy tactic in patients, suffering ischemic cerebral insult (ICI) depending on changes in the systemic hemodynamics indices and the oxygen-transportation status.Маterials and methods. In 42 patients, suffering the ICI of middle severity, ageing 45 - 88 years old, the integrative monitoring of the neurological state severity, systemic hemodynamics indices and the oxygen-transportation status on background of targeted intensive therapy was conducted.
 Results. In the patients, suffering initial hypoxemia, a hypokinetic heart index (HI) - (2,0±0,1) l×min-1×m-2 and the lowered systemic delivery of oxygen (DO2) - (356±21) ml×min-1×m-2were revealed. Prophylactic oxygenation is needed if the value of the oxygen content in arterial blood (SаO2) exceeds 95% and DO2 is lesser than 520 ml×min-1×m-2. Aiming the achievement of eukinetic values of the HI, correction of vascular spasm and antihypertensive therapy was conducted, using alpha-adrenoblocking agent (urapydil) up to stabilization of the DO2 indices on the level of 520-600 ml×min-1×m-2. In hyperoxidal state a hyperkinetic HI - (3.6±0.1) l×min-1×m-2 and a raised DO2 - (699±14) ml×min-1×m-2 were revealed. Prophylactic oxygenation is not indicated if the value of the SаO2 index exceeds 95% and DO2 exceeds 600 ml×min-1×m-2. Aiming to achieve eukinetic values of HI it is mandatory to conduct antihypertensive therapy, using therapy with аlpha-beta-аdrenoblocking agent (labetalol).
 Conclusion. Targeted intensive therapy, oriented towards balance with general oxygenation of the organism tissues, normalizes the oxygen-transport homeostasis in shortest terms, what impacts the results of treatment in patients, suffering ICI, immediately.

Vascular Cognitive Impairment: Information from Animal Models on the Pathogenic Mechanisms of Cognitive Deficits.

Vascular cognitive impairment (VCI) is the second most common cause of cognitive deficit after Alzheimer’s disease. Since VCI patients represent an important target population for prevention, an ongoing effort has been made to elucidate the pathogenesis of this disorder. In this review, we summarize the information from animal models on the molecular changes that occur in the brain during a cerebral vascular insult and ultimately lead to cognitive deficits in VCI. Animal models cannot effectively represent the complex clinical picture of VCI in humans. Nonetheless, they allow some understanding of the important molecular mechanisms leading to cognitive deficits. VCI may be caused by various mechanisms and metabolic pathways. The pathological mechanisms, in terms of cognitive deficits, may span from oxidative stress to vascular clearance of toxic waste products (such as amyloid beta) and from neuroinflammation to impaired function of microglia, astrocytes, pericytes, and endothelial cells. Impaired production of elements of the immune response, such as cytokines, and vascular factors, such as insulin-like growth factor 1 (IGF-1), may also affect cognitive functions. No single event could be seen as being the unique cause of cognitive deficits in VCI. These events are interconnected, and may produce cascade effects resulting in cognitive impairment.

LncRNA SNHG12 as a potent autophagy inducer exerts neuroprotective effects against cerebral ischemia/reperfusion injury

Long-non-coding RNA small nucleolar RNA host gene 12(SNHG12) was reported to be highly up-regulated in brain microvascular endothelium after cerebral ischemia. Autophagy has been shown to have protective effects against cerebral ischemic insults. However, molecular mechanisms of SNHG12 in regulating autophagy during cerebral ischemia/reperfusion (I/R) injury remain unclear. Here, we established middle cerebral artery occlusion/reperfusion (MCAO/R) model in mice and adopted oxygen-glucose deprivation and reperfusion (OGD/R) SH-SY5Y cell model to mimic cerebral I/R injury in vitro. Triphenyltetrazolium chloride (TTC) staining was used to measure infarct size. Bederson and Longa score systems were used to evaluate neurological behavioral and defects, respectively. CCK-8, EdU staining, flow cytometry and Hoechst 33258 staining were performed to determine the biological function of SNHG12 on SH-SY5Y cell under OGD/R condition. The autophagy levels were determined by Western blotting and LC3B immunofluorescence. We found the expression of SNHG12 was up-regulated by cerebral I/R in mice andSH-SY5Y cell model after OGD/R. Up-regulated SNHG12 alleviated OGD/R-induced SH-SY5Y cell injury and induced autophagy activation, as indicated by an increased ratio of LC3 II/I and Beclin-1, decreased p62. On the contrary, down-regulation of SNHG12 exacerbated SH-SY5Y cell injury after OGD/R and inhibited autophagy. Furthermore, autophagy activator rapamycin or inhibitor 3-MA partially reversed the down-regulation or up-regulation of SNHG12 effect in OGD/R-inducedSH-SY5Y cell injury, respectively. Taken together, these findings suggest that SNHG12 as an autophagy inducer alleviates cerebral I/R injury, which might be a new therapeutic target of ischemic stroke.

Subgroups of monocytes predict cardiovascular events in patients with coronary heart disease. The PHAMOS trial (Prospective Halle Monocytes Study)

BackgroundMonocytes can be differentiated by the presence of CD14 and CD16 (CD14++CD16-, classical; CD14++CD16+, intermediate and CD14 + CD16++, non-classical monocytes). Recent studies have reported conflicting results regarding an association between subtypes of monocytes as defined by the expression of these two surface markers in atherosclerosis. MethodsWe investigated subtypes of monocytes in n = 994 patients with angiographically documented coronary artery disease (CAD). We compared total numbers of monocyte subgroups stratified by tertiles with the occurrence of the pre-defined combined endpoint (non-fatal myocardial infarction, cardiovascular death and non-haemorrhagic cerebral insult). Patients were followed up for a minimum of 52 weeks. Classical risk factors of coronary heart disease were included in multivariate analysis. ResultsThe primary endpoint occurred 134 times at a median time of 34.5 weeks (IR 10.6/59.6). Intermediate (p = 0.813), non-classical (p = 0.725) and the number of total monocytes (p = 0.626) stratified by tertiles showed no significant association with the combined endpoint. However, a higher absolute number of classical monocytes divided in tertiles was associated with incidence of the combined endpoint {T1 = 8.9% vs T2 = 14.2% vs T3 = 16.0% (p = 0.021)}. When comparing the third with the first tertile of Mo1 population, multivariate analysis showed a hazard ratio of 1.646 (CI: 1.005-2.699, p = 0.048). ConclusionsThe absolute counts of classical monocytes divided in tertiles are predictive of major adverse cardiac events in patients with CAD. A tremendous shift from classical to intermediate monocytes was also confirmed in patients with CAD. These data highlight the importance of CD14++ monocytes in cardiovascular diseases.

Role of automated pupillometry in critically ill patients.

Pupillary examination has fundamental diagnostic and prognostic values in clinical practice. However, pupillary assessment was relied until present on manual, qualitative, examination, using manual flash penlights or lamps. Quantitative examination with the use of automated infrared video-pupillometers allows an objective assessment of several pupillary parameters and may be superior to manual subjective examination. The potential for quantitative pupillometry is multiple in the setting of critical care, for the monitoring and detection of secondary cerebral insults and to assess brainstem dysfunction and early coma outcome prognostication, and in the intra-operative anesthesiology setting, to assess analgesia and opioid requirement. Here, we describe the pupillometry technique and review recent critical care and anesthesiology studies that demonstrate the value and potential clinical utility of quantitative pupillometry as neuromonitoring bedside modality.

Shenmai injection maintains blood-brain barrier integrity following focal cerebral ischemia via modulating the expression and trafficking of occludin in lipid rafts

Ethnopharmacological relevanceShenmai injection (SMI), a traditional Chinese herbal medicine is widely used for the clinical treatment of cerebral infarction in China.Aim of the study: Tight junctions (TJs) are major components of the blood-brain barrier (BBB) that physically restrict the paracellular diffusion of blood-borne substances between endothelial cells into the CNS. TJ proteins are associated with cholesterol-enriched regions of plasma membrane known as lipid rafts, which are critical for the trafficking, positioning and function of TJ proteins. In this study, we investigated the effect of SMI on the expression and trafficking of the key TJ-associated protein, occludin, in lipid rafts. Materials and methodsUsing a neutral pH, rat cerebral microvessels were subjected to detergent-free density-gradient fractionation to isolate lipid rafts containing occludin. Transmission electron microscopy (TEM) was performed to study the effects of drug administration on ultrastructural changes to TJs. Western blotting (WB), immunofluorescence (IF), and co-immunoprecipitation (COIP) were used to observe the localization and function of TJ-associated proteins. ResultsWe successfully isolated cerebral microvessels and separated lipid rafts from plasma membranes. With SMI treatment, extravasation of FITC-albumin decreased around the cerebral vessels by IF, the tight junctions were found to still be intact and the basement membrane appeared to be of uniform thickness in TEM. Compared with the untreated group, the co-expression of flotillin-1 and occludin in microvascular endothelial cells was increased and distributed continuously in SMI treatment as shown in double label IF. SMI significantly increased the translocation of occludin to lipid raft fractions by WB and COIP. ConclusionsSMI helps maintain the proper assembly of the TJ multiprotein complex in lipid rafts, thereby helping to preserve BBB functional integrity during focal cerebral ischemic insult. Our findings enhance our understanding of the mechanisms underlying the neuroprotective effect of SMI in cerebral ischemia.

Spectrum of neurovascular complications from central nervous system infections (viral, bacterial and fungal).

In the following pictorial review, common and uncommon neurovascular complications associated with a spectrum of viral, bacterial and fungal infections involving the central nervous system will be illustrated. These complications include cerebral vascular insult, venous thrombosis, vasculitis and aneurysm formation. They can occur as separate entities but are often inter-related. The imaging features of neurovascular complication related to infections can provide clues and aid diagnosis when considering the potential mode of infectious spread and the type of potential infectious organism involved. The radiological appearances vary from common features that are shared by several types of pathogens to typical characteristics of a type of infectious organism.

Short term outcome and predictors of survival among birth asphyxiated babies at a tertiary academic hospital in Enugu, South East, Nigeria.

Birth asphyxia (BA) is a preventable cause of cerebral insults in newborns. It is associated with high morbidity and mortality. Of the 120 million babies born in third world countries annually, it is estimated that about 3.6 million will develop BA. We aimed to determine the short term outcome and predictors of survival among birth asphyxiated babies using Apgar score. This study was carried out in the Newborn Unit of Enugu State University Teaching Hospital. In-hospital deliveries (Inborn) and those from other centers (Out-born) with one minute Apgar score ≤ 6 were included. Interviewer administered questionnaire was used to collect data from caregivers. Information sought included gestational age (GA), birth weight (BW), Apgar score, place of delivery and outcome. Data was analyzed using SPSS. Bivariate and multivariate logistic regressions were done. Of the 150 neonates, 61.3% survived. Majority of the dead were out-born. The difference was statistically significant (p < 0.001). The inborn were about 1.2 times (AOR = 1.22; 95% CI: 1.06-1.78) more likely to survive BA. Among low birth weights (LBWs), 73.9% died, 23.7% of normal weights and 14.3% of macrosomics died. The difference was statistically significant (p < 0.001). The normal weights were about 2 (AOR = 2.23, 95% CI: 1.76-6.25) and the macrosomics about 5 times more likely to survive BA than LBWs. Regarding GA, 78.8%, 17.2% and 18.2% of the pre-terms, term and post-dates died respectively. The difference was statistically significant (p < 0.001). The term babies were about 11 (AOR = 11.27; 95% CI: 4.02-31-56) and post-dates about 9 (AOR = 8.79; 95% CI: 1.43-54.04) times more likely to survive BA than preterms. Other significant factors were degree of asphyxia (p = 0.003), and parental education (p < 0.001). BW, GA, degree of asphyxia, place of delivery and parental education all predicts survival among birth asphyxiated newborns.

Abstract TMP38: Dysregulated Post-Stroke Immune Response is Associated With Cerebral Volume Loss in the Contralateral Non-Ischemic Hemisphere

Background: There is delicate homeostatic balance between the central nervous system and immune system. Cerebral insults, like ischemia, trigger an immune-depressive state to suppress a potential immune response directed against the neuroglial tissue; however, this supposedly protective reaction inadvertently creates an infection-prone state in the peri-stroke setting. In this study, we assessed the magnitude of cerebral volume loss in the unaffected contralateral hemisphere following stroke, and determined its relationship with the intimate cascades of inflammation, immune-depression and infection. Methods: The change in contralateral hemisphere volume was determined by voxel-based morphometry on admission and follow-up MRI’s in a consecutive series of 50 patients with ischemic stroke involving the MCA territory. Information related to clinical features, infectious complications, and markers of inflammation (erythrocyte sedimentation rate, neutrophil/lymphocyte ratio, C-reactive protein) and immunodepression (plasma high mobility group box 1 protein level; HMGB-1) were prospectively collected. Results: The contralateral hemisphere volume decreased by a median (interquartile range) of 2.80% (0.70-5.64) after a follow-up duration of 101 (63-123) days (p&lt;0.001); the monthly volume reduction was 0.82% (0.18-1.79). Old age, stroke severity, neutrophil/lymphocyte ratio, and development of infections during hospitalization were significantly associated with monthly volume loss (p&lt;0.05). Stroke severity (NIHSS score or infarct volume) and inflammation related parameters (neutrophil/lymphocyte ratio or systemic infections) remained independently and positively associated with monthly volume loss when assessed in multivariate regression models, while plasma HMGB-1 levels were inversely related to this loss. Conclusions: Cerebral tissue damage following stroke is not limited to the ischemic hemisphere. Apart from stroke severity, a pro-inflammatory state and an impaired immune-depressive response contribute to cerebral volume loss in the non-ischemic hemisphere.

Hemşirelik Girişimleri İkincil Beyin Hasarına Neden Olabilir mi?

As a result of increase in intracranial pressure, decrease in cerebral perfusion pressure, hypotension and decrease in cerebral blood flow secondary brain insult may occur. The main focus of treatment and nursing care in neurosurgical patients is to prevent intracranial pressure increase. But some nursing interventions can also cause secondary brain damage. Routine nursing interventions such as endotracheal suction, oral care, body bath, rotationing and repositioning of patients and clusteringof nursing interventions may cause secondary brain insult by increasing cerebral metabolism rate, decreasing cerebral perfusion pressure and affecting cerebral blood flow. This systematic review aims to provide guidance to nurses about the prevention of secondary brain insult by reviewing the nursing interventions that may cause secondary brain insult in neurosurgical patients in the light of current literature

Neuroprotective role of dexmedetomidine in epilepsy surgery: A preliminary study.

Long standing temporal lobe epilepsy (TLE) causes cerebral insult and results in elevated brain injury biomarkers, S100b and neuron specific enolase (NSE). Surgery for TLE, has the potential to cause additional cerebral insult. Dexmedetomidine is postulated to have neuroprotective effects. The aim of this study was to assess the effect of intraoperative dexmedetomidine on S100b and NSE during TLE surgery. 19 consenting adult patients with TLE undergoing anteromedial temporal lobectomy were enrolled and divided into two groups. Patients in Group D (n = 9) received dexmedetomidine whereas patients in Group C (n = 10) received saline as placebo in addition to the standard anaesthesia technique. Blood samples of these patients were drawn, before induction of anaesthesia, at the end of surgery, as well at 24 hours and 48 hours postoperatively, and analysed for serum S100b and NSE. The demographic and clinical profile was comparable in both the groups. The baseline S100b in group C and group D was 66.7 ± 26.5 pg/ml and 34.3 ± 21.7 pg/ml (P = 0.013) respectively. After adjustment for the baseline, the overall value of S100b was 71.0 ± 39.8 pg/ml and 40.5 ± 22.5 pg/ml (P = 0.002) in the control and study group, respectively. The values of S100b (79.3 ± 53.6 pg/ml) [P = 0.017] were highest at 24 hours postoperatively. The mean value of NSE in the control and study group was 32.8 ± 43.4 ng/ml (log 3.0 ± 0.1) and 13.51 ± 9.12 ng/ml (log 2.42 ± 0.60), respectively. The value of NSE in both the groups was comparable at different time points. Lower perioperative values of S100b were observed in patients who received intraoperative dexmedetomidine. Dexmedetomidine may play a role in cerebroprotection during epilepsy surgery.

Influence of stenting with open-cell stents vs close-cell stents on the outcomes of patients with bilateral carotid stenosis.

Carotid artery stenting (CAS) is an effective way to prevent stroke in patients with severe carotid stenosis. However, several studies comparing the outcomes of stenting with open-cell stents (OCS) vs closed-cell stents (CCS) have yielded inconclusive results. This study aimed to compare the outcomes of CAS with OCS vs CCS in the same patients.From year 2000 to 2016, we included 52 patients with severe bilateral carotid stenosis who underwent OCS deployment in one artery and CCS deployment in the contralateral artery. Stents were selected according to arterial anatomy and lesion morphology, and the peri-procedural and long-term outcomes of treatment with OCS vs CCS, were compared in terms of rates of ischemic spot development on early post-procedural diffusion-weighted imaging (ISDWI), in-stent restenosis (ISR), and recurrent stroke.After stenting with OCS vs CCS, the number (rate) of arteries with no lesion, < 5 lesions, and ≥ 5 lesions on DWI was 9 (32%) vs 8 (27%), 8 (29%) vs 17 (57%), and 11 (39%) vs 5 (17%) (p = .10); number (rate) of arteries with 0%, < 50%, and >50% ISR was 34 (65%) vs 34 (65%), 9 (17%) vs 11 (21%), and 9 (17%) vs 7 (13%) (p = .71); number (rate) of recurrent strokes after CAS was 2 (4%) vs 0 (0%).The rates of peri-procedural cerebral ischemic insult, long-term stent patency, and stroke recurrence indicate that no one carotid stent cell design is superior to the other. We suggest both OCS and CCS are reasonable options for the treatment of severe carotid stenosis.

Adenosine deaminase 2 deficiency with a novel variant of CECR1 gene mutation: Responding to tumor necrosis factor antagonist therapy

Deficiency of Adenosine deaminase 2 (DADA2) syndrome is a chronic, systemic, and inflammatory disorder, characterized by early-onset recurrent strokes, fever, livedo reticularis, and immunodeficiency. We report the case of a 4-year-old child, a product of consanguineous marriage, who presented with three episodes of hemiparesis within 1 year. She also manifested skin discoloration in the form of livedo reticularis. Workup with magnetic resonance imaging (MRI) of the brain revealed acute infarction in the right aspect of the cerebral peduncle and chronic lacunars infarct in the right thalamus with diffusion restriction. Repeated MRI after 5 months revealed diffuse loss of brain volume. The blood workup showed high inflammatory markers and significantly low adenosine deaminase 2 (ADA2) level. After being on corticosteroid and anticoagulant treatments, she suffered from a recurrent episode of cerebral infarction, after which she was commenced on tumor necrosis factor (TNF)-antagonist therapy in addition to monthly fresh plasma infusion. Thereafter, there was no cerebral insult reported for >18 months. The genetic study of the child and her parents revealed a homozygous mutation c. 336C>A, p. (His112Gln) in the CECR1 gene, and her parents were heterozygous for the same variant. This variant was not previously reported in literature. We would suggest to link this novel variant c. 336C>A, p. (His112Gln) of CECR1 gene mutation with the clinical picture, along with the positive response to TNF-antagonist therapy in the era of ADA2 deficiency syndrome.

Hyponatremia in Neurosurgical Patients.

Hyponatremia is a frequent occurrence in patients with neurosurgical disorders. Acute onset hyponatremia is particularly common in patients who have any type of cerebral insult, including traumatic brain injury, subarachnoid hemorrhage, and brain tumors. Furthermore, it is a common complication of intracranial procedures. Acute hyponatremia creates an osmotic gradient between the brain and the plasma, which promotes the movement of water from the plasma into brain cells, causing cerebral edema and neurological compromise. It is therefore far more likely to be symptomatic, and to have adverse outcomes, than chronic hyponatremia. Uncorrected acute hyponatremia with consequent cerebral edema may manifest through impaired consciousness level, seizures, elevated intracranial pressure, and, potentially, death due to cerebral herniation. The majority of cases of hyponatremia due to neurosurgical pathology are caused by the syndrome of inappropriate antidiuresis, but acute glucocorticoid insufficiency is increasingly being recognized as an important contributing factor. In this chapter, we summarize the existing literature on the clinical features and differential diagnosis of hyponatremia in the neurosurgical patient, and briefly discuss the management options.

Pretreated fucoidan confers neuroprotection against transient global cerebral ischemic injury in the gerbil hippocampal CA1 area via reducing of glial cell activation and oxidative stress

Fucoidan is a sulfated polysaccharide derived from brown algae and possesses various beneficial activities, including antioxidant property. Previous studies have shown that fucoidan displays protective effect against ischemia-reperfusion injury in some organs. However, few studies have been reported regarding the protective effect of fucoidan against transient cerebral ischemic insults and its related mechanisms. Therefore, in this study, we examined the neuroprotective effect of fucoidan against transient global cerebral ischemia (tGCI), as well as underlying its mechanism using a gerbil model of tGCI which shows a loss of pyramidal neurons in the hippocampal cornu ammonis 1 (CA1) area after 5 min of tGCI. Fucoidan (25 and 50 mg/kg) was intraperitoneally administered once daily for 5 days before tGCI. Pretreatment with 50 mg/kg of fucoidan, not 25 mg/kg of fucoidan, attenuated tGCI-induced hyperactivity and protected CA1 pyramidal neurons from tGCI. In addition, pretreatment with 50 mg/kg of fucoidan inhibited activations of astrocytes and microglia in the ischemic CA1 area. Furthermore, pretreatment with 50 mg/kg of fucoidan significantly reduced the increased 4-hydroxy-2-noneal and superoxide anion radical production in the ischemic CA1 area and significantly increased expressions of SOD1 and SOD2 in the CA1 pyramidal neurons before and after tGCI. Additionally, treatment with diethyldithiocarbamate (an inhibitor of SODs) to the fucoidan-treated gerbils notably abolished the fucoidan-mediated neuroprotection. In brief, our present results indicate that fucoidan can effectively protect neurons from tGCI through attenuation of activated glial cells and reduction of oxidative stress via increase of SODs. Thus, we strongly suggest that fucoidan can be used as a useful preventive agent in cerebral ischemia.

Caffeine attenuates brain injury but increases mortality induced by high-intensity blast wave exposure

Caffeine is a substance that is consumed worldwide, and it may exert neuroprotective effects against various cerebral insults, including neurotrauma, which is the most prevalent injury among military personnel. To investigate the effects of caffeine on high-intensity blast wave-induced severe blast injury in mice, three different paradigms of caffeine were applied to male C57BL/6 mice with severe whole body blast injury (WBBI). The results demonstrated that chronic caffeine treatment alleviated blast-induced traumatic brain injury (bTBI); however, both chronic and acute caffeine treatments exacerbated blast-induced lung injuries and, more importantly, increased both the cumulative and time-segmented mortalities postinjury. Interestingly, withdrawing caffeine intake preinjury resulted in favorable outcomes in mortality and lung injury, similar to the findings in water-treated mice, and had the trend to attenuate brain injury. These findings demonstrated that although drinking coffee or caffeine preparations attenuated blast-induced brain trauma, these beverages may place personnel in the battlefield at high risk of casualties, which will help us re-evaluate the therapeutic strategy of caffeine application, particularly in multiple-organ-trauma settings. Furthermore, these findings provided possible strategies for reducing the risk of casualties with caffeine consumption, which may help to change the coffee-drinking habits of military personnel.