The Effect of Targeted Hyperoxemia on Brain Immunohistochemistry after Long-Term, Resuscitated Porcine Acute Subdural Hematoma and Hemorrhagic Shock.

Epidemiological data suggest that moderate hyperoxemia may be associated with an improved outcome after traumatic brain injury. In a prospective, randomized investigation of long-term, resuscitated acute subdural hematoma plus hemorrhagic shock (ASDH + HS) in 14 adult, human-sized pigs, targeted hyperoxemia (200 < PaO2 < 250 mmHg vs. normoxemia 80 < PaO2 < 120 mmHg) coincided with improved neurological function. Since brain perfusion, oxygenation and metabolism did not differ, this post hoc study analyzed the available material for the effects of targeted hyperoxemia on cerebral tissue markers of oxidative/nitrosative stress (nitrotyrosine expression), blood-brain barrier integrity (extravascular albumin accumulation) and fluid homeostasis (oxytocin, its receptor and the H2S-producing enzymes cystathionine-ß-synthase and cystathionine-γ-lyase). After 2 h of ASDH + HS (0.1 mL/kgBW autologous blood injected into the subdural space and passive removal of 30% of the blood volume), animals were resuscitated for up to 53 h by re-transfusion of shed blood, noradrenaline infusion to maintain cerebral perfusion pressure at baseline levels and hyper-/normoxemia during the first 24 h. Immediate postmortem, bi-hemispheric (i.e., blood-injected and contra-lateral) prefrontal cortex specimens from the base of the sulci underwent immunohistochemistry (% positive tissue staining) analysis of oxidative/nitrosative stress, blood-brain barrier integrity and fluid homeostasis. None of these tissue markers explained any differences in hyperoxemia-related neurological function. Likewise, hyperoxemia exerted no deleterious effects.

Biological Connection of Psychological Stress and Polytrauma under Intensive Care: The Role of Oxytocin and Hydrogen Sulfide.

This paper explored the potential mediating role of hydrogen sulfide (H2S) and the oxytocin (OT) systems in hemorrhagic shock (HS) and/or traumatic brain injury (TBI). Morbidity and mortality after trauma mainly depend on the presence of HS and/or TBI. Rapid "repayment of the O2 debt" and prevention of brain tissue hypoxia are cornerstones of the management of both HS and TBI. Restoring tissue perfusion, however, generates an ischemia/reperfusion (I/R) injury due to the formation of reactive oxygen (ROS) and nitrogen (RNS) species. Moreover, pre-existing-medical-conditions (PEMC's) can aggravate the occurrence and severity of complications after trauma. In addition to the "classic" chronic diseases (of cardiovascular or metabolic origin), there is growing awareness of psychological PEMC's, e.g., early life stress (ELS) increases the predisposition to develop post-traumatic-stress-disorder (PTSD) and trauma patients with TBI show a significantly higher incidence of PTSD than patients without TBI. In fact, ELS is known to contribute to the developmental origins of cardiovascular disease. The neurotransmitter H2S is not only essential for the neuroendocrine stress response, but is also a promising therapeutic target in the prevention of chronic diseases induced by ELS. The neuroendocrine hormone OT has fundamental importance for brain development and social behavior, and, thus, is implicated in resilience or vulnerability to traumatic events. OT and H2S have been shown to interact in physical and psychological trauma and could, thus, be therapeutic targets to mitigate the acute post-traumatic effects of chronic PEMC's. OT and H2S both share anti-inflammatory, anti-oxidant, and vasoactive properties; through the reperfusion injury salvage kinase (RISK) pathway, where their signaling mechanisms converge, they act via the regulation of nitric oxide (NO).

The evolution of invasive cerebral vasospasm treatment in patients with spontaneous subarachnoid hemorrhage and delayed cerebral ischemia-continuous selective intracarotid nimodipine therapy in awake patients without sedation.

Cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) are major factors that limit good outcome in patients with spontaneous subarachnoid hemorrhage (SAH). Continuous therapy with intra-arterial calcium channel blockers has been introduced as a new step in the invasive treatment cascade of CV and DCI. Sedation is routinely necessary for this procedure. We report about the feasibility to apply this therapy in awake compliant patients without intubation and sedation. Out of 67 patients with invasive endovascular treatment of cerebral vasospasm due to spontaneous SAH, 5 patients underwent continuous superselective intracarotid nimodipine therapy without intubation and sedation. Complications, neurological improvement, and outcome at discharge were summarized. Very good outcome was achieved in all 5 patients. The Barthel scale was 100 and the modified Rankin scale 0-1 in all cases at discharge. We found no severe complications and excellent neurological monitoring was possible in all cases due to patients' alert status. Symptoms of DCI resolved within 24 h in all 5 cases. We could demonstrate the feasibility and safety of selective intracarotid arterial nimodipine treatment in awake, compliant patients with spontaneous SAH and symptomatic CV and DCI. Using this method, an excellent monitoring of neurological function as well as early detection of other complications is possible. It might be an important step in the risk reduction of invasive CV therapy to improve the outcome with CV and DCI after SAH in selected patients.

Sensitivity and specificity of linear array intraoperative ultrasound in glioblastoma surgery: a comparative study with high field intraoperative MRI and conventional sector array ultrasound.

INTRODUCTION: Linear array intraoperative ultrasound (lioUS) is an emerging technology for intracranial use. We evaluated sensitivity and specificity of lioUS to detect residual tumor in patients harboring a glioblastoma. METHODS: After near total resection in 20 patients, residual tumor detection using lioUS, conventional intraoperative ultrasound (cioUS), and gadopentetic-diethylenetriamine penta-acetic acid (Gd-DTPA)-enhanced intraoperative MRI (iMRI) were compared. Sensitivity and specificity were calculated based on 68 navigated biopsies. Receiver operator characteristic (ROC) curves and correlation with histopathological findings of each imaging modality were calculated. Additionally, results were evaluated in the subgroup of recurrent disease (23 biopsies in 8 patients). RESULTS: Sensitivity of lioUS (76 %) was significantly higher compared with iMRI (55 %) and cioUS (24 %). Specificity of lioUS (58 %) was significantly lower than in cioUS (96 %), while there was no significant difference to iMRI (74 %). All imaging modalities correlated significantly with histopathological findings. In the subgroup of recurrent disease, sensitivity and specificity decreased in all modalities. However, cioUS showed significant lower values than iMRI and lioUS. In ROC curves, lioUS showed a higher area und the curve (AUC) in comparison with iMRI and cioUS. We found similar results in the subgroup of recurrent disease. CONCLUSION: Tumor detection using a lioUS is significantly superior to cioUS. Overall test performance in lioUS is comparable with results of iMRI. While, the latter has a higher specificity and a significantly lower sensitivity in comparison with lioUS.

Cognitive performance following spontaneous subarachnoid haemorrhage versus other forms of intracranial haemorrhage.

OBJECTIVE: The exact cause of cognitive deficits following intracranial haemorrhage is unclear. This prospective study examines the abilities after spontaneous subarachnoid haemorrhage (SAH), intracerebral haemorrhage (ICH) and chronic subdural haematoma (SDH) to elucidate the cognitive outcome. PATIENTS AND METHODS: Ninety-nine patients with SAH (N = 60), ICH (N = 25), and SDH (N = 14) were followed up for an average of 6 and 12 months post-haemorrhage. Cognitive tests were used to examine attention, memory, concentration, and executive function. Following were used for analysis: 1. the percentage of patients falling below the 25th percentile per test, 2. the general development from the first to second test point and 3. the incidence of significant changes between the test points. Significance was established as p ≤ 0.05. RESULTS: All three types of haemorrhage resulted in deficits as concerns abstract language (53%-75%). The processing speed was below the normal levels in more than 70% of the patients tested. The cognitive performance of SAH patients was similar to that of patients with SDH and ICH patients after 6 months. The number of patients with outcomes falling below the 25th percentile (to some extent more than 75% in patients post-SAH) is high in all patient groups and mostly decreases over the course. Nevertheless, patients with SAH reveal improvements in many more areas than with ICH and SDH (p ≤ 0.006). CONCLUSIONS: The cognitive impairments following SAH, ICH and SDH deficits appear to develop in a similar way regardless of the type of haemorrhage. Cognitive improvement is most pronounced in patients with SAH.

Brain metastases in gastrointestinal cancers: is there a role for surgery?

About 10% of all cancer patients will develop brain metastases during advanced disease progression. Interestingly, the vast majority of brain metastases occur in only three types of cancer: Melanoma, lung and breast cancer. In this review, we focus on summarizing the prognosis and impact of surgical resection of brain metastases originating from gastrointestinal cancers such as esophageal, gastric, pancreatic and colorectal cancer. The incidence of brain metastases is <1% in pancreatic and gastric cancer and <4% in esophageal and colorectal cancer. Overall, prognosis of these patients is very poor with a median survival in the range of only months. Interestingly, a substantial number of patients who had received surgical resection of brain metastases showed prolonged survival. However, it should be taken into account that all these studies were not randomized and it is likely that patients selected for surgical treatment presented with other important prognostic factors such as solitary brain metastases and exclusion of extra-cranial disease. Nevertheless, other reports have demonstrated long-term survival of patients upon resection of brain metastases originating from gastrointestinal cancers. Thus, it appears to be justified to consider aggressive surgical approaches for these patients.

Outcome after Intracerebral Haemorrhage and Decompressive Craniectomy in Older Adults.

OBJECTIVE: There is a relationship between the incidence of spontaneous intracerebral haemorrhage (ICH) and age. The incidence increases with age. This study aims to facilitate the decision-making process in the treatment of ICH. It therefore investigated the outcome after ICH and decompressive craniectomy (DC) in older adults (>65 years of age). METHODS: Retrospective, multicentre, descriptive observational study including only consecutive patients who received DC as the consequence of ICH. Additive evacuation of ICH was performed after the individual decision of the neurosurgeon. Besides demographic data, clinical outcomes both at discharge and 12 months after surgery were evaluated according to the Glasgow Outcome Scale (GOS). Patients were divided into age groups of ≤65 and >65 years and cohorts with favourable outcome (GOS IV-V) and unfavourable outcome (GOS I to III). RESULTS: 56 patients were treated. Mean age was 53.3 (SD: 16.13) years. There were 41 (73.2%) patients aged ≤65 years and 15 (26.8%) patients aged >65 years. During hospital stay, 10 (24.4%) patients in the group of younger (≤65 years) and 5 (33.3%) in the group of older patients (>65 years) died. Mean time between ictus and surgery was 44.4 (SD: 70.79) hours for younger and 27.9 (SD: 41.71) hours for older patients. A disturbance of the pupillary function on admission occurred in 21 (51.2%) younger and 2 (13.3%) older patients (p = 0.014). Mean arterial pressure was 99.9 (SD: 17.00) mmHg for younger and 112.9 (21.80) mmHg in older patients. After 12 months, there was no significant difference in outcome between younger patients (≤65 years) and older patients (>65 years) after ICH and DC (p = 0.243). Nevertheless, in the group of younger patients (≤65 years), 9% had a very good and 15% had a good outcome. There was no good recovery in the group of older patients (>65 years). CONCLUSION: Patients >65 years of age treated with microsurgical haematoma evacuation and DC after ICH are likely to have a poor outcome. Furthermore, in the long term, only a few older adults have a good functional outcome with independence in daily life activities.

Brain metastasis in pancreatic cancer.

Pancreatic cancer is a fatal disease with a 5-year survival rate below 5%. Most patients are diagnosed at an advanced tumor stage and existence of distant metastases. However, involvement of the central nervous system is rare in pancreatic cancer. We retrospectively analyzed all cases of brain metastases in pancreatic cancer reported to date focusing on patient characteristics, clinical appearance, therapy and survival. Including our own, 12 cases of brain metastases originating from pancreatic cancer were identified. In three patients brain metastases were the first manifestation of pancreatic cancer. All other patients developed brain metastases during their clinical course. In most cases, the disease progressed rapidly and the patients died within weeks or months. However, two patients showed long-term survival. Of note, both patients received resection of the pancreatic cancer as well as curative resection of the metachronous brain metastases. Brain metastases in pancreatic cancer are a rare condition and usually predict a very poor prognosis. However, there is evidence that resection of brain metastases of pancreatic cancer can be immensely beneficial to patient's survival, even with the chance for cure. Therefore, a surgical approach in metastatic pancreatic cancer should be considered in selective cases.

An exploratory study investigating the effect of targeted hyperoxemia in a randomized controlled trial in a long-term resuscitated model of combined acute subdural hematoma and hemorrhagic shock in cardiovascular healthy pigs.

Severe physical injuries and associated traumatic brain injury and/or hemorrhagic shock (HS) remain leading causes of death worldwide, aggravated by accompanying extensive inflammation. Retrospective clinical data indicated an association between mild hyperoxemia and improved survival and outcome. However, corresponding prospective clinical data, including long-term resuscutation, are scarce. Therefore, the present study explored the effect of mild hyperoxemia for 24 hours in a prospective randomized controlled trial in a long-term resuscitated model of combined acute subdural hematoma (ASDH) and HS. ASDH was induced by injecting 0.1 ml × kg-1 autologous blood into the subdural space and HS was triggered by passive removal of blood. After 2 hours, the animals received full resuscitation, including retransfusion of the shed blood and vasopressor support. During the first 24 hours, the animals underwent targeted hyperoxemia (PaO2 = 200 - 250 mmHg) or normoxemia (PaO2 = 80 - 120 mmHg) with a total observation period of 55 hours after the initiation of ASDH and HS. Survival, cardiocirculatory stability, and demand for vasopressor support were comparable between both groups. Likewise, humoral markers of brain injury and systemic inflammation were similar. Multimodal brain monitoring, including microdialysis and partial pressure of O2 in brain tissue, did not show significant differences either, despite a significantly better outcome regarding the modified Glasgow Coma Scale 24 hours after shock that favors hyperoxemia. In summary, the present study reports no deleterious and few beneficial effects of mild targeted hyperoxemia in a clinically relevant model of ASDH and HS with long-term resuscitation in otherwise healthy pigs. Further beneficial effects on neurological function were probably missed due to the high mortality in both experimental groups. The present study remains exploratory due to the unavailability of an a priori power calculation resulting from the lack of necessary data.

13C-Metabolic flux analysis detected a hyperoxemia-induced reduction of tricarboxylic acid cycle metabolism in granulocytes during two models of porcine acute subdural hematoma and hemorrhagic shock.

Introduction: Supplementation with increased inspired oxygen fractions has been suggested to alleviate the harmful effects of tissue hypoxia during hemorrhagic shock (HS) and traumatic brain injury. However, the utility of therapeutic hyperoxia in critical care is disputed to this day as controversial evidence is available regarding its efficacy. Furthermore, in contrast to its hypoxic counterpart, the effect of hyperoxia on the metabolism of circulating immune cells remains ambiguous. Both stimulating and detrimental effects are possible; the former by providing necessary oxygen supply, the latter by generation of excessive amounts of reactive oxygen species (ROS). To uncover the potential impact of increased oxygen fractions on circulating immune cells during intensive care, we have performed a 13C-metabolic flux analysis (MFA) on PBMCs and granulocytes isolated from two long-term, resuscitated models of combined acute subdural hematoma (ASDH) and HS in pigs with and without cardiovascular comorbidity. Methods: Swine underwent resuscitation after 2 h of ASDH and HS up to a maximum of 48 h after HS. Animals received normoxemia (PaO2 = 80 - 120 mmHg) or targeted hyperoxemia (PaO2 = 200 - 250 mmHg for 24 h after treatment initiation, thereafter PaO2 as in the control group). Blood was drawn at time points T1 = after instrumentation, T2 = 24 h post ASDH and HS, and T3 = 48 h post ASDH and HS. PBMCs and granulocytes were isolated from whole blood to perform electron spin resonance spectroscopy, high resolution respirometry and 13C-MFA. For the latter, we utilized a parallel tracer approach with 1,2-13C2 glucose, U-13C glucose, and U-13C glutamine, which covered essential pathways of glucose and glutamine metabolism and supplied redundant data for robust Bayesian estimation. Gas chromatography-mass spectrometry further provided multiple fragments of metabolites which yielded additional labeling information. We obtained precise estimations of the fluxes, their joint credibility intervals, and their relations, and characterized common metabolic patterns with principal component analysis (PCA). Results: 13C-MFA indicated a hyperoxia-mediated reduction in tricarboxylic acid (TCA) cycle activity in circulating granulocytes which encompassed fluxes of glutamine uptake, TCA cycle, and oxaloacetate/aspartate supply for biosynthetic processes. We further detected elevated superoxide levels in the swine strain characterized by a hypercholesterolemic phenotype. PCA revealed cell type-specific behavioral patterns of metabolic adaptation in response to ASDH and HS that acted irrespective of swine strains or treatment group. Conclusion: In a model of resuscitated porcine ASDH and HS, we saw that ventilation with increased inspiratory O2 concentrations (PaO2 = 200 - 250 mmHg for 24 h after treatment initiation) did not impact mitochondrial respiration of PBMCs or granulocytes. However, Bayesian 13C-MFA results indicated a reduction in TCA cycle activity in granulocytes compared to cells exposed to normoxemia in the same time period. This change in metabolism did not seem to affect granulocytes' ability to perform phagocytosis or produce superoxide radicals.

Brain Histology and Immunohistochemistry After Resuscitation From Hemorrhagic Shock in Swine With Pre-Existing Atherosclerosis and Sodium Thiosulfate (Na2S2O3) Treatment.

Background: The hydrogen sulfide (H2S) and the oxytocin/oxytocin receptor (OT/OTR) systems interact in the central nervous and cardiovascular system. As a consequence of osmotic balance stress, H2S stimulates OT release from the paraventricular nuclei (PVN) in the hypothalamic regulation of blood volume and pressure. Hemorrhagic shock (HS) represents one of the most pronounced acute changes in blood volume, which, moreover, may cause at least transient brain tissue hypoxia. Atherosclerosis is associated with reduced vascular expression of the main endogenous H2S producing enzyme cystathionine-γ-lyase (CSE), and, hence, exogenous H2S administration could be beneficial in these patients, in particular after HS. However, so far cerebral effects of systemic H2S administration are poorly understood. Having previously shown lung-protective effects of therapeutic Na2S2O3 administration in a clinically relevant, long-term, porcine model of HS and resuscitation we evaluated if these protective effects were extended to the brain. Methods: In this study, available unanalyzed paraffin embedded brain sections (Na2S2O3 N = 8 or vehicle N = 5) of our recently published HS study were analyzed via neuro-histopathology and immunohistochemistry for the endogenous H2S producing enzymes, OT, OTR, and markers for brain injury and oxidative stress (glial fibrillary acidic protein (GFAP) and nitrotyrosine). Results: Neuro-histopathological analysis revealed uninjured brain tissue with minor white matter edema. Protein quantification in the hypothalamic PVN showed no significant inter-group differences between vehicle or Na2S2O3 treatment. Conclusions: The endogenous H2S enzymes, OT/OTR co-localized in magnocellular neurons in the hypothalamus, which may reflect their interaction in response to HS-induced hypovolemia. The preserved blood brain barrier (BBB) may have resulted in impermeability for Na2S2O3 and no inter-group differences in the PVN. Nonetheless, our results do not preclude that Na2S2O3 could have a therapeutic benefit in the brain in an injury that disrupts the BBB, e.g., traumatic brain injury (TBI) or acute subdural hematoma (ASDH).

Assessing neurodevelopmental outcome in children with hydrocephalus in Malawi. A pilot study.

INTRODUCTION: Congenital and infantile hydrocephalus are assumed to be major contributors to pediatric morbidity, mortality and functional disability in low-income countries. Despite this, epidemiologic data and the overview of neurodevelopmental outcomes in these regions is very limited. We aimed to pilot the use of a wide range of more locally suitable tools to assess neurodevelopment to understand whether they were feasible for use and could provide estimates of developmental delay and poor functioning in a population of children with hydrocephalus in Malawi. METHODS: We conducted a prospective observational cohort study, at the tertiary neurosurgery clinic in Blantyre, Malawi in 2018, recruiting consecutive children with congenital and infantile hydrocephalus who were previously treated with ventriculoperitoneal shunts and endoscopic third ventriculostomy (ETV) in the neurosurgery unit of the hospital. We assessed demographic details, and gained information on children's functioning using the Liverpool Outcome Score (LOS), and the Eating and Drinking Ability Classification System as well as full anthropometric assessment and child development with the Malawi Developmental Assessment Tool (MDAT). RESULTS: All tools were feasible for use, easy to train on, could be used for assessing children with hydrocephalus and were suitable to adapt for our environment. We evaluated 41 children, aged 2-60 months with a mean age of 22.6 months (interquartile range [IQR] = 8.3 months -36.5 months). Functional assessment using the Liverpool Outcome Score showed the majority of children 92.7% (CI 80.1-98.5, n = 38) had severe sequelae from the hydrocephalus and were dependent on their parents or caregivers. Only 27 children (65.9%, CI 49.4, 80.0) had full or expected control of their bowel and bladder and 6 children (14.6%, CI 5.6, 29.2), had a recent history of seizures. About two thirds (63.4% CI 45.0-77.9, n = 26/41) of children were able to eat and to drink safely and efficiently. Over two thirds of the children (70.7%, CI 56.8, 84.6, n = 29) were stunted and almost half of the cohort underweight (43.9%,(CI 28.5, 60.3, n = 18). Almost half 48.8% (CI 32.9, 64.9, n = 20/41) had developmental delay on MDAT with 41.5% (CI 26.4, 56.6, n = 17/41) graded as severely delayed (-<2sd on developmental age z score). We found significant associations between dependence identified by the LOS and developmental delay according to the MDAT (p = 0.014, Pearson's chi-squared test). CONCLUSION: This pilot study demonstrates that the assessment tools we used identified a high proportion of children with hydrocephalus as having functional difficulties, stunted growth and developmental delay, in Malawi. Use of these tools can now be scaled up and will be helpful to support research in understanding what factors contribute to poor functioning, growth and development in these cohorts and help us to investigate what strategies may prevent and support children with hydrocephalus in African settings.

Orbital Tumors-Clinical, Radiologic and Histopathologic Correlation.

Orbital masses include a broad spectrum of benign and malignant entities. Often these masses are asymptomatic or show a slow growth rate, so that emergence of clinical symptoms is prolonged. In this context, cross-sectional imaging plays an elementary role in the characterization of these lesions. Aside from the characterization of the underlying entity, an evaluation of the involved compartments is possible by sufficient imaging, which also facilitates optimal treatment and surgery planning. The purpose of this review is to explore different benign and malignant orbital tumors and their typical appearance in imaging together with histopathologic findings.

The effect of targeted hyperoxemia in a randomized controlled trial employing a long-term resuscitated, model of combined acute subdural hematoma and hemorrhagic shock in swine with coronary artery disease: An exploratory, hypothesis-generating study.

Controversial evidence is available regarding suitable targets for the arterial O2 tension (PaO2) after traumatic brain injury and/or hemorrhagic shock (HS). We previously demonstrated that hyperoxia during resuscitation from hemorrhagic shock attenuated cardiac injury and renal dysfunction in swine with coronary artery disease. Therefore, this study investigated the impact of targeted hyperoxemia in a long-term, resuscitated model of combined acute subdural hematoma (ASDH)-induced brain injury and HS. The prospective randomized, controlled, resuscitated animal investigation consisted of 15 adult pigs. Combined ASDH plus HS was induced by injection of 0.1 ml/kg autologous blood into the subdural space followed by controlled passive removal of blood. Two hours later, resuscitation was initiated comprising re-transfusion of shed blood, fluids, continuous i.v. noradrenaline, and either hyperoxemia (target PaO2 200 - 250 mmHg) or normoxemia (target PaO2 80 - 120 mmHg) during the first 24 h of the total of 54 h of intensive care. Systemic hemodynamics, intracranial and cerebral perfusion pressures, parameters of brain microdialysis and blood biomarkers of brain injury did not significantly differ between the two groups. According to the experimental protocol, PaO2 was significantly higher in the hyperoxemia group at the end of the intervention period, i.e., at 24 h of resuscitation, which coincided with a higher brain tissue PO2. The latter persisted until the end of observation period. While neurological function as assessed using the veterinary Modified Glasgow Coma Score progressively deteriorated in the control group, it remained unaffected in the hyperoxemia animals, however, without significant intergroup difference. Survival times did not significantly differ in the hyperoxemia and control groups either. Despite being associated with higher brain tissue PO2 levels, which were sustained beyond the intervention period, targeted hyperoxemia exerted neither significantly beneficial nor deleterious effects after combined ASDH and HS in swine with pre-existing coronary artery disease. The unavailability of a power calculation and, thus, the limited number of animals included, are the limitations of the study.

Variations of the aortic arch - a study on the most common branching patterns.

BACKGROUND: Anatomical variants of the aortic arch and its branching patterns often appear as an incidental finding during routine computed tomography (CT) scanning. These variations can be of relevance when performing angiography or endovascular interventions and may cause symptoms such as dysphagia. PURPOSE: To analyze common anatomical variations found within the arteries originating from the aortic arch in patients using contrast CT imaging techniques. MATERIAL AND METHODS: A total of 2033 contrast CT scans were analyzed. To obtain a truly representative sample, cases were chosen from different hospital departments without previous knowledge of the patient history. RESULTS: The total percentage of variations within the analyzed patients was 13.3%. In 8.0% a truncus bicaroticus was found. 4.2% of the patients showed a left vertebral artery originating directly from the aortic arch, mostly proximal, and in 1 case distal to the left subclavian artery. In 1.0% we found an aberrant right subclavian artery. We also found a single case of a right descending aortic arch. CONCLUSION: Variations of the aortic arch and its branching are frequently found, mostly as an incidental finding during routine diagnostic scanning. A contrast-enhanced CT scan is a good method with which to study the aortic arch and its associated branching pattern.

Localization of the hydrogen sulfide and oxytocin systems at the depth of the sulci in a porcine model of acute subdural hematoma.

In the porcine model discussed in this review, the acute subdural hematoma was induced by subdural injection of autologous blood over the left parietal cortex, which led to a transient elevation of the intracerebral pressure, measured by bilateral neuromonitoring. The hematoma-induced brain injury was associated with albumin extravasation, oxidative stress, reactive astrogliosis and microglial activation in the ipsilateral hemisphere. Further proteins and injury markers were validated to be used for immunohistochemistry of porcine brain tissue. The cerebral expression patterns of oxytocin, oxytocin receptor, cystathionine-γ-lyase and cystathionine-ß-synthase were particularly interesting: these four proteins all co-localized at the base of the sulci, where pressure-induced brain injury elicits maximum stress. In this context, the pig is a very relevant translational model in contrast to the rodent brain. The structure of the porcine brain is very similar to the human: the presence of gyri and sulci (gyrencephalic brain), white matter to grey matter proportion and tentorium cerebelli. Thus, pressure-induced injury in the porcine brain, unlike in the rodent brain, is reflective of the human pathophysiology.

The value of intraoperative angiography in the time of indocyanine green videoangiography in the treatment of cerebrovascular lesions: Efficacy, workflow, risk-benefit and cost analysis A prospective study.

INTRODUCTION: Intraoperative digital subtraction angiography (ioDSA) allows early treatment evaluation after neurovascular procedures. However, the value and efficiency of this procedure has been discussed controversially. We have evaluated the additional value of hybrid operating room equipped with an Artis Zeego robotic c-arm regarding cost, efficiency and workflow. Furthermore, we have performed a risk-benefit analysis and compared it with indocyanine green (ICG) angiography. METHODS: For 3 consecutive years, we examined all neurovascular patients, treated in the hybrid operating theater in a risk-benefit analysis. After using microdoppler and ICG angiography for best operative result, every patient received an additional ioDSA to look for remnants or unfavorable clip placement which might lead to a change of operating strategy or results. Furthermore, a workflow-analysis reviewing operating steps, staff positioning, costs, technical errors or complications were conducted on randomly selected cases. RESULTS: 54 patients were enrolled in the risk-benefit analysis, 22 in the workflow analysis. The average duration of a cerebrovascular operation was 4 h 58 min 2 min 35 s accounted for ICG angiography, 46 min 4 s for ioDSA. Adverse events occurred during one ioDSA. In risk-benefit analysis, ioDSA was able to detect a perfusion rest in 2 out of 43 cases (4,7%) of aneurysm surgery, which could not have been visualized by ICG angiography before. In arterio-venous-malformation (AVM) surgery, one of 11 examined patients (7,7%) showed a remnant in ioDSA and resulted in additional resection. The average cost of an ioDSA in Ulm University can be estimated with 1928,00€. CONCLUSION: According to our results ioDSA associated complications are low. Relevant findings in ioDSA can potentially avoid additional intervention, however, due to the high costs and lower availability, the main advantage might lie in the treatment of selected patients with complexes neurovascular pathologies since ICG angiography is equally safe but associated with lower costs and better availability.

Adverse Events and Complications in Continuous Intra-arterial Nimodipine Infusion Therapy After Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: To determine the frequency and severity of complications associated with the continuous intra-arterial infusion of nimodipine (CIANI) as a new treatment of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). METHODS: Patients from two centers (n = 718) treated for SAH between 2008 and 2016 were included. Demographic and SAH-related parameters were evaluated, and also the frequency of adverse events (AEs) and complications including their severity (mild, moderate, and severe). Clinical outcome was analyzed using Glasgow Outcome Scale (GOS). The unfavorable outcome was defined as GOS 1 to 3, and favorable outcome as GOS 4 to 5. The Short-Form 36 (SF-36) health-related quality-of-life (QoL) questionnaire served as a QoL measurement. RESULTS: Of 718 patients, 65 (9%) were treated by CIANI and had a higher clinical or imaging grade of bleeding severity. Clinical deterioration while on treatment happened more often in patients who were treated with CIANI than in others. In patients with CIANI, 67% had AEs and/or complications during the treatment. Nimodipine-associated hypotension was seen in 8% (mild). Catheter-associated thrombus occurred in 9% (moderate). New intracerebral hemorrhage was found in 14% (moderate). A total of 6% treated by CIANI died during the treatment period (severe). More than one-third (39%) of patients of CIANI reached at least moderate disability, and 23% showed good recovery. Patients who received CIANI showed reduced QoL, but differences in mental and general health, and also pain were minimal. CONCLUSION: Patients who received CIANI had higher rates of AEs and complications. However, this does not exclude the possibility that the use of CIANI might be helpful in patients with severe and therapy-refractory CV and DCI. Controlled and randomized studies would be helpful to clarify this question but they are methodologically and ethically challenging.

Effects of Acute Subdural Hematoma-Induced Brain Injury On Energy Metabolism in Peripheral Blood Mononuclear Cells.

ABSTRACT: In activated immune cells, differentiation and function are determined by cell type-specific modifications of metabolic patterns. After traumatic brain injury both immune cell activation and suppression were reported. Therefore, we sought to explore immune cell energy metabolism in a long-term, resuscitated porcine model of acute subdural hematoma (ASDH)-induced acute brain injury devoid of impaired systemic hemodynamics and oxygen transport.Before and up to 50 h after induction of ASDH, peripheral blood mononuclear cells (PBMCs) were separated by density gradient centrifugation, and cell metabolism was analyzed using high-resolution respirometry for mitochondrial respiration and electron spin resonance for reactive oxygen species production. After incubation with stable isotope-labeled 1,2-13C2-glucose or 13C5-glutamine, distinct labeling patterns of intermediates of glycolysis or tricarboxylic acid (TCA) cycle and 13CO2 production were measured by gas chromatography-mass spectroscopy. Principal component analysis was followed by a varimax rotation on the covariance across all measured variables and all measured time points.After ASDH induction, average PBMC metabolic activity remained unaffected, possibly because strict adherence to intensive care unit guidelines limited trauma to ASDH induction without any change in parameters of systemic hemodynamics, oxygen transport, and whole-body metabolism. Despite decreased glycolytic activity fueling the TCA cycle, the principal component analysis indicated a cell type-specific activation pattern with biosynthetic and proliferative characteristics.

The use of recombinant activated factor VII in neurosurgery.

BACKGROUND: Bleeding complications in neurosurgery often take alarming proportions without major hemodynamic effect or impairment of coagulation physiology because severe neurologic deficits are to be expected. Any measures used to stabilize or normalize coagulation are therefore of great interest. Administration of packed red cells, fresh frozen plasma, and platelet concentrates is associated with volume loading, which is suspected to multiply the secondary brain damage, for example, by the development of an edema. In this respect, the administration of rFVIIa may develop into a new option associated with low-volume administration. CASE DESCRIPTIONS: We report on 5 neurosurgical patients to whom rFVIIa was given at doses of 51 to 202 microg/kg of body weight for the treatment of severe intraoperative bleeding (n = 3) or as prophylaxis of bleeding (n = 2). The operation was completed successfully in all patients after administration of rFVIIa, with stabilization of the coagulation status. CONCLUSION: Therefore, reported cases constitute an approach in treatment and prophylaxis of bleeding complications in neurosurgery. There are reports of thromboembolic events in use of rFVIIa, particularly in unlabeled use. But according to our findings and current literature, there is no evidence of higher risk of thromboembolic adverse events in treatment with rFVIIa. However, the number of patients presented does not allow any final assessment to be made as to whether the properties of rFVIIa are of particular benefit for neurosurgical patients. Further studies with appropriate study design are required to verify effects observed in this investigation.