Pressure Time Dose as a Representation of Intracranial Pressure Burden and Its Dependency on Intracranial Pressure Waveform Morphology at Different Time Intervals.

Intracranial pressure (ICP) burden or pressure time dose (PTD) is a valuable clinical indicator for pending intracranial hypertension, mostly based on threshold exceedance. Pulse frequency and waveform morphology (WFM) of the ICP signal contribute to PTD. The temporal resolution of the ICP signal has a great influence on PTD calculation but has not been systematically studied yet. Hence, the temporal resolution of the ICP signal on PTD calculation is investigated. We retrospectively analysed continuous 48 h ICP recordings with high temporal resolution obtained from 94 patients at the intensive care unit who underwent neurosurgery due to an intracranial haemorrhage and received an intracranial pressure probe (43 females, median age: 72 years, range: 23 to 88 years). The cumulative area under the curve above the threshold of 20 mmHg was compared for different temporal resolutions of the ICP signal (beat-to-beat, 1 s, 300 s, 1800 s, 3600 s). Events with prolonged ICP elevation were compared to those with few isolated threshold exceedances. PTD increased for lower temporal resolutions independent of WFM and frequency of threshold exceedance. PTDbeat-to-beat best reflected the impact of frequency of threshold exceedance and WFM. Events that could be distinguished in PTDbeat-to-beat became magnified more than 7-fold in PTD1s and more than 104 times in PTD1h, indicating an overestimation of PTD. PTD calculation should be standardised, and beat-by-beat PTD could serve as an easy-to-grasp indicator for the impact of frequency and WFM of ICP elevations on ICP burden.

CT and DSA for evaluation of spontaneous intracerebral lobar bleedings.

Purpose: This study retrospectively examined the extent to which computed tomography angiography (CTA) and digital subtraction angiography (DSA) can help identify the cause of lobar intracerebral bleeding. Materials and methods: In the period from 2002 to 2020, data from patients who were >18 years at a university and an academic teaching hospital with lobar intracerebral bleeding were evaluated retrospectively. The CTA DSA data were reviewed separately by two neuroradiologists, and differences in opinion were resolved by consensus after discussion. A positive finding was defined as an underlying vascular etiology of lobar bleeding. Results: The data of 412 patients were retrospectively investigated. DSA detected a macrovascular cause of bleeding in 125/412 patients (33%). In total, sixty patients had AVMs (15%), 30 patients with aneurysms (7%), 12 patients with vasculitis (3%), and 23 patients with dural fistulas (6%). The sensitivity, specificity, positive and negative predictive values, and accuracy of CTA compared with DSA were 93, 97, 100, and 97%. There were false-negative CTA readings for two AVMs and one dural fistula. Conclusion: The DSA is still the gold standard diagnostic modality for detecting macrovascular causes of ICH; however, most patients with lobar ICH can be investigated first with CTA, and the cause of bleeding can be found. Our results showed higher sensitivity and specificity than those of other CTA studies.

No Gender Differences in Pain Perception and Medication after Lumbar Spine Sequestrectomy-A Reanalysis of a Randomized Controlled Clinical Trial.

BACKGROUND: Gender issues have received increasing attention in clinical research of the past years, and biological sex has been introduced as a moderating variable in experimental pain perception. However, in clinical studies of acute pain and gender, there are conflicting results. In particular, there are limited data on the impact of gender differences after spinal sequestrectomy. The aim of this work is to examine gender differences in postoperative pain and pain medication consumption in an inpatient clinical setting. METHODS: Data of a completed double-blind RCT was subdivided by gender and reanalyzed by means of an analysis of variance in repeated measures. Outcomes included pain severity measured on a VAS, affective (SES-A) and sensory pain perception (SES-S) and morphine equivalent doses (MED) of analgesics after spinal sequestrectomy. RESULTS: In total, 42 female (47.73%) and 46 male (52.27%) patients were analyzed. No differences in pain severity (VAS: Gender × Time F = 0.35; (df = 2, 86); p = 0.708), affective and sensory pain perception (SES-A: Gender × Time F = 0.08; (df = 2, 86); p = 0.919; SES-S: Gender × Time F = 0.06; (df = 2, 86); p = 0.939) or post-operative opioid use between men and women (MEDs: Gender × Time F = 1.44; (df = 2, 86); p = 0.227) could be observed. CONCLUSIONS: This reanalysis of an RCT with respect to gender differences is to our knowledge the first attempt to investigate the role of gender in pain perception and medication after lumbar spine sequestrectomy. In contrast to other studies, we were not able to show significant differences between male and female patients in all pain-related outcomes. Apart from well-established pain management, psychological reasons such as gender-specific response biases or the observer effect might explain our results. TRIAL REGISTRATION: The study was registered as a regulatory phase IV study at the German Clinical Trials Register (DRKS), an open-access online register for clinical trials conducted in Germany (Reg-No: DRKS00007913).

Hypericum perforatum to Improve Postoperative Pain Outcome After Monosegmental Spinal Sequestrectomy (HYPOS): Results of a Randomized, Double-Blind, Placebo-Controlled Trial.

Introduction: Patients undergoing lumbar spine surgery often suffer from severe radicular postoperative pain leading to the prescription of high-dose opioids. In Integrative Medicine, Hypericum perforatum is known as a remedy to relieve pain caused by nerve damage. Objectives: This trial investigated whether homeopathic Hypericum leads to a reduction in postoperative pain and a decrease in pain medication compared with placebo. Design: Randomized double blind, monocentric, placebo controlled clinical trial. Settings/Location: Department of Neurosurgery, Community Hospital Herdecke. Subjects: Inpatients undergoing lumbar sequestrectomy surgery. Interventions: Homeopathic treatment versus placebo in addition to usual pain management. Outcomes Measures: Primary endpoint was pain relief measured with a visual analog scale. Secondary endpoints were the reduction of inpatient postoperative analgesic medication and change in sensory and affective pain perception. Results: Baseline characteristics were comparable between the groups. Pain perception between baseline and day 3 did not significantly differ between the study arms. With respect to pain medication, total morphine equivalent doses did not differ significantly. However, a statistical trend and a moderate effect (d = 0.432) in the decrease of pain medication consumption in favor of the Hypericum group was observed. Conclusion: This is the first trial of homeopathy that evaluated the efficacy of Hypericum C200 after lumbar monosegmental spinal sequestrectomy. Although no significant differences between the groups could be shown, we found that patients who took potentiated Hypericum in addition to usual pain management showed lower consumption of analgesics. Further investigations, especially with regard to pain medication, should follow to better classify the described analgesic reduction. Clinical Trial Registration Number: German Clinical Trials Register No: DRKS00007913.

Comparison of Two Algorithms Analysing the Intracranial Pressure Curve in Terms of the Accuracy of Their Start-Point Detection and Resistance to Artefacts.

OBJECTIVES: For further insight into the possibly predictive quality of the intracranial pressure (ICP) waveform morphology a definite and reliable identification of its components is a prerequisite but presents the problem of artefacts in physiological signals. METHODS: ICP and electrocardiogram (ECG) data were recorded to depict not only their numerical value but also their respective waveforms and were analysed by two algorithms, which were then compared for their artefact resistance.The algorithms in question identify the start point of every ICP wave, one (AR[SA]) by scale analysis, the other (AR[ECG]) by analysing the ICP wave linked to the ECG. RESULTS: Start-point identification accuracy in rhythmic patients showed sensitivity of 95.14% for AR[SA] and 99.99% for AR[ECG], with a positive predictive value (ppv) of 98.30% for AR[SA] and 99.76% for AR[ECG].In arrhythmic patients sensitivity was 98.05% for AR[SA] and 99.73% for AR[ECG], with a ppv of 100% for AR[SA] and 99.78% for AR[ECG]. CONCLUSIONS: AR[ECG] has proven to be more resistant to artefacts than AR[SA], even in cases such as cardiac arrhythmia. It facilitates reliable, three-dimensional visualisation of long-term changes in ICP-wave morphology and is thus suited for analysis in cases of more complex or irregular vital parameters.

Hypericum perforatum to improve post-operative Pain Outcome after monosegmental Spinal microdiscectomy (HYPOS): a study protocol for a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Spinal disc herniation is a frequently occurring degenerative disease of the spine. Many patients undergoing surgery suffer from radicular pain, known as memory pain, beginning from the third post-operative day. This results in the prescription of high-dose opioid medications. In homeopathy, Hypericum perforatum is known as a remedy for unbearable, shooting or jabbing pain especially when neural damage is involved. Reduction of pain after application of H. perforatum has been observed in previous studies. This study is aimed to investigate whether homeopathic H. perforatum in a potentisation of C200 leads to the reduction of post-operative pain and a decrease of pain medication compared to placebo. METHODS/DESIGN: This is a monocentric, double-blind, randomised placebo-controlled trial conducted at the Department of Neurosurgery at the Community Hospital Herdecke, Germany. One hundred study participants are being recruited from inpatients undergoing elective, monosegmental, lumbar microdiscectomy surgery. Patients are randomly allocated to receive homeopathic treatment or placebo in addition to usual pain management after surgery. The primary clinical outcome is pain reduction after 3 days of inpatient care as measured by pain reduction of subjective pain on a 100-mm Visual Analogue Scale (VAS) at the third post-operative day. Statistical analysis will be carried out by means of a covariance model with adjustment for baseline values and patient expectation for all randomised patients. DISCUSSION: This study is the first trial of classical homeopathy that will evaluate the efficacy of homeopathic H. perforatum after monosegmental spinal microdiscectomy. We intend to clarify the potential of homoeopathic H. perforatum to reduce surgery-associated pain. TRIAL REGISTRATION: German Clinical Trials Register, ID: DRKS00007913 . Registered on 17 October 2014. EudraCT - Nr: 2013-001383-31. Data sets from the German Clinical Trials Register (DRKS, Deutsches Register Klinischer Studien) are updated every 4 weeks automatically to the International Clinical Trials Registry Platform of World Health Organisation: http://apps.who.int/trialsearch/ . Responsibilities Sponsor: Witten/Herdecke University Alfred-Herrhausen-Straße 50 58,448 Witten Deputy of the sponsor: Dr. Wolfgang Eglmeier (Head of Centre for Clinical Trials Witten/Herdecke) Alfred-Herrhausen-Straße 50 58,448 Witten E-mail: wolfgang.eglmeier@uni-wh.de Principal investigator: Prof. Dr. med. Wolfram Scharbrodt Community Hospital Herdecke Department for Neurosurgery Gerhard-Kienle-Weg 4 58,313 Herdecke w.scharbrodt@gemeinschaftskrankenhaus.de Project coordination: Christa Raak Faculty for Health (Department for Integrative and Anthroposophic Medicine) University Witten/Herdecke gGmbh Gerhard-Kienle-Weg 4 58,313 Herdecke christa.raak@uni-wh.de Project manager/data analysis/biometry: Prof. Dr. Thomas Ostermann Faculty for Health (Department for Psychology and Psychotherapy) University Witten/Herdecke gGmbh Alfred-Herrhausen-Straße 50 58,448 Witten thomas.ostermann@uni-wh.de.

Mean hemoglobin concentration after acute subarachnoid hemorrhage and the relation to outcome, mortality, vasospasm, and brain infarction.

Lower mean hemoglobin (HGB) levels are associated with unfavorable outcome after spontaneous subarachnoid hemorrhage (SAH). Currently, there is no cutoff level for mean HGB levels associated with unfavorable outcome. This study was conducted to evaluate a threshold for mean HGB concentrations after SAH, and to observe the relation to outcome. The medical records of 702 patients with spontaneous SAH were reviewed. Predictors of outcome were proved by univariate analysis. Predictors with p<0.1 were included in a multivariate binary logistic regression model. Cutoff points for mean HGB levels were calculated by receiver operating characteristic curve analysis. Mean HGB was 11.9 g/dl (±standard deviation [SD] 1.7 g/dl) in patients with favorable outcome compared to 10.8 g/dl (±SD 1.1g/dl) in patients with unfavorable outcome (p<0.001). The highest Youden's index value was found for a HGB cutoff at 11.1 g/dl. In a binary logistic regression model, predictors of unfavorable outcome were identified as an initially high Hunt-Hess grade (odds ratio [OR]: 7.7; 95% confidence interval [CI]: 4.4-13.4; p<0.001), cerebral infarction on a CT scan during hospital stay (OR: 3.8; 95% CI: 2.0-7.3; p<0.001), rebleeding during the hospital stay (OR: 3.5; 95% CI: 1.6-8.0; p=0.002), mean HGB concentration <11.1g/dl (OR: 3.3; 95% CI: 2.0-5.3; p<0.001), and hydrocephalus (OR: 2.3; 95% CI: 1.4-3.7; p=0.001). In conclusion, a mean HGB concentration <11.1 g/dl during the hospital stay was associated with unfavorable outcome after acute SAH.

The mechanisms of energy crisis in human astrocytes after subarachnoid hemorrhage.

BACKGROUND: Calcium (Ca2+) is a cofactor of multiple cellular processes. The mechanisms that lead to elevated cytosolic Ca2+ concentration are unclear. OBJECTIVE: To illuminate how bloody cerebrospinal fluid (bCSF) from patients with intraventricular hemorrhage causes cell death of cultured human astrocytes. METHODS: Cultured astrocytes were incubated with bCSF. In control experiments, native CSF was used. Cytosolic Ca2+ concentration was measured by fura-2 fluorescence. Apoptosis and necrosis were evaluated by staining with Hoechst-3342 and propidium iodide. RESULTS: Incubation of astrocytes with bCSF provoked a steep Ca2+ concentration peak that was followed by a slow Ca2+ rise during the observation period of 50 minutes. Necrosis, but not apoptosis, was induced. Blockade of ATP-sensitive P2 receptors with suramin inhibited the bCSF-induced initial Ca2+ peak and necrosis. Blockade of P1 receptors with 8-phenyltheophylline or of N-methyl-D-aspartate receptors with D(-)-2-amino-5-phosphopentanoic acid had no significant effect. Preincubation with xestospongin D, a blocker of inositol 1,4,5-trisphosphate receptors, prevented the initial Ca2+ rise and reduced the rate of necrosis. Preemptying of the endoplasmic reticulum with thapsigargin protected astrocytes from the bCSF-induced Ca2+ peak. Inhibition of mitochondrial permeability transition pores opening with cyclosporin A reduced the rate of astrocytic necrosis significantly, although it did not influence the initial Ca peak. CONCLUSION: bCSF elicits a steep, transient Ca rise when administered to human astrocytes by activation of ATP-sensitive P2 receptors and subsequent inositol 1,4,5-trisphosphate-dependent Ca release from endoplasmic reticulum. This massive Ca overload leads to subsequent mitochondrial permeability transition pores opening and necrosis of the cells.

Cerebrospinal fluid lactate concentration after withdrawal of metabolic suppressive therapy in subarachnoid hemorrhage.

Hyperglycolysis is a known phenomenon after severe subarachnoid hemorrhage (SAH) and after brain injury. It is characterized by decreased oxidative metabolism and relatively increased anaerobic glycolysis. Metabolic suppressive therapy reduces the cerebral metabolic rate of oxygen (CMRO(2)) and the cerebral metabolic rate of glucose (CMRGluc). If CMRO(2) is suppressed after SAH, withdrawal of metabolic suppressive therapy could lead to the accumulation of lactate. In this project, we assessed the relationship between the withdrawal of metabolic suppressive therapy and cerebrospinal fluid (CSF) lactate concentration. A prospective observational database containing 262 patients with SAH was retrospectively analyzed. CSF lactate levels were compared with the daily dose of metabolic suppressive therapy. Outcome was assessed with the Glasgow Outcome Scale (GOS). In 56% of patients an increase in CSF lactate (mean: 3.2 ± 0.9 mmol/L) after withdrawal of metabolic suppressive therapy was observed. Mean Glasgow Outcome Score (GOS) was lower in patients with an increase in CSF lactate concentration (>0.5 mmol/L) after withdrawal of metabolic suppressive therapy (p = 0.095). In 88% of patients who died during the first 30 days after SAH, a CSF lactate elevation of more than 0.5 mmol/L after withdrawal of metabolic suppressive therapy was found (p = 0.071).

Intracerebral hemorrhage in the very old: future demographic trends of an aging population.

BACKGROUND AND PURPOSE: In most European societies and in the United States, the percentage of patients ≥80 years has been rising over the past century. The present study was conducted to observe this demographic change and its impact on patients with intracerebral hemorrhage (ICH). METHODS: We reviewed patients' data with the diagnosis of ICH from January 2007 to December 2009. All data were collected out of a prospective stroke registry covering the entire state of Hesse, Germany. Incidence rates and absolute numbers of patients with ICH for 2009 to 2050 were calculated. RESULTS: Of 3448 patients, 34% had an age ≥80 years. Hospital mortality was 35.9% for patients ≥80 years and 20.0% for patients <80 years. Unfavorable outcome (modified Rankin Scale score >2) was more often found in patients ≥80 years compared with patients <80 years (84.9% versus 74.8%). By the year 2050, the proportion of all patients with ICH ≥80 years will be 2.5-fold higher than in 2009. The total number of ICH cases will increase approximately 35.2% assuming that ICH probability stays the same. The number of patients who die in the hospital will increase approximately 60.2%. The total number of patients with severe disability due to ICH will increase approximately 36.8%. CONCLUSIONS: If current treatment strategies according to age remain unchanged, an increase of in-hospital mortality and a higher proportion of patients who need lifelong care after ICH can be expected in the coming decades.

The prediction of 30-day mortality and functional outcome in spontaneous intracerebral hemorrhage with secondary ventricular hemorrhage: a score comparison.

The original ICH (oICH) score was tested in different populations and showed good accuracy in the prediction of outcome and 30-day mortality after spontaneous ICH. The oICH was developed to stratify patients with all types of spontaneous intracerebral hemorrhage (SICH). Several modifications of the oICH score exist in the literature.In the current study, we tested the oICH score, two modified ICH scores, and the IVH score on a cohort of 171 patients with SICH and mandatory secondary intraventricular hemorrhage (IVH). Receiver-operating characteristic (ROC) curves were plotted, and the areas under the curves (AUC) were calculated for each score.The calculated AUCs for the prediction of 30-day mortality in the cohort were 0.736, 0.816, 0.805, and 0.836 for the original ICH, the mICH-A, the mICH-B, and the new IVH score, respectively. The best AUC for functional outcome was observed for the mICH-B score (0.823). For the mICH-A and the IVH score, an AUC of 0.811 was calculated.The scores that include the quantification of IVH or the grading of hydrocephalus show good accuracy in the prediction of 30-day mortality and functional outcome at 6 months in SICH with secondary IVH.

Clinical and methodological precision of spinal navigation assisted by 3D intraoperative O-arm radiographic imaging.

OBJECT: In recent years, the importance of intraoperative navigation in neurosurgery has been increasing. Multiple studies have proven the advantages and safety of computer-assisted spinal neurosurgery. The use of intraoperative 3D radiographic imaging to acquire image information for navigational purposes has several advantages and should increase the accuracy and safety of screw guidance with navigation. The aim of this study was to evaluate the clinical and methodological precision of navigated spine surgery in combination with the O-arm multidimensional imaging system. METHODS: Thoracic, lumbar, and sacral pedicle screws that were placed with the help of the combination of the O-arm and StealthStation TREON plus navigation systems were analyzed. To evaluate clinical precision, 278 polyaxial pedicle screws in 139 vertebrae were reviewed for medial or caudal perforations on coronal projection. For the evaluation of the methodological accuracy, virtual and intraoperative images were compared, and the angulation of the pedicle screw to the midsagittal line was measured. RESULTS: Pedicle perforations were recorded in 3.2% of pedicle screws. None of the perforated pedicle screws damaged a nerve root. The difference in angulation between the actual and virtual pedicle screws was 2.8° ± 1.9°. CONCLUSIONS: The use of the StealthStation TREON plus navigation system in combination with the O-arm system showed the highest accuracy for spinal navigation compared with other studies that used traditional image acquisition and registration for navigation.

Parenteral and enteral nutrition in the management of neurosurgical patients in the intensive care unit.

The iatrogenic malnutrition of neurosurgical patients in intensive care units (ICU) is an underestimated problem. It may cause a decrease in plasma albumin and oncotic pressure, leading to an increase in the amount of water entering the brain and increased intracranial pressure (ICP). This study was conducted to test the hypothesis that combined high-protein parenteral and enteral nutrition is beneficial for neurosurgical patients in ICU. A total of 202 neurosurgical patients in ICU (mean age+/-standard deviation, 56 years+/-16 years; male:female=1.2:1) were studied. Two consecutive 1-year time periods were compared, during which two different nutritional regimens were followed. In the first time period (Y1) patients were given a low-protein/high-fat formulation parenterally, followed by a standard enteral regimen. In the second time period (Y2) a protein-rich, combined parenteral and enteral diet was prospectively administered. The Glasgow Outcome Score was measured at 3-6 months after discharge. The following clinical parameters were recorded during the first 2 weeks after admission: ICP; albumin; cholinesterase (CHE); daily hours of ICP > 20 mmHg and cerebral perfusion pressure<70 mmHg; and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. It was found that overall albumin (32.4 g/L+/-4.1g/L vs. 27.5 g/L+/-3.6g/L) and CHE was higher during Y2, although the total energy supply, glucose and fat intake was lower. Higher GOS scores were seen when patients had lower APACHE II scores and received the Y2 nutritional regimen. During Y2, the total hours of ICP > 20 mmHg were fewer. With the Y2 nutrition, maintenance of adequate cerebral perfusion required less catecholamine medication and colloidal fluid replacement. Therefore, adequate nutrition is an important parameter in the management of neurosurgical patients in ICU.

The prediction of long-term outcome after subarachnoid hemorrhage as measured by the Short Form-36 Health Survey.

The Glasgow Outcome Scale (GOS) score is widely used to assess outcome after a subarachnoid hemorrhage (SAH). Patients who have recovered fully or with a mild disability (GOS scores 4 and 5) frequently complain about difficulties in conducting their daily activities. The Short Form-36 (SF-36) Health Survey is a questionnaire that assesses outcomes in multiple categories. This study was conducted to compare the quality of outcome assessment between the SF-36 Health Survey and GOS scores. A total of 128 patients with SAH (all data expressed as mean+/-standard deviation) aged 53.1+/-12.1 years, and a mean Hunt and Hess grade on admission of 2+/-1, were retrospectively included in the study. Medical charts were reviewed to assess previous medical history, location of the aneurysm and the presence of vasospasm. The SF-36 and GOS scores were collected in structured interviews approximately 5 years (+/-2 years) after the SAH. The SF-36 data were compared to a historical healthy control cohort of 2,474 individuals. The results showed that 52% of patients experienced a favourable outcome after SAH (GOS scores 4 and 5). Vasospasm was recorded in 25% of patients. However, the average SF-36 results were lower in all tested categories for patients after SAH than the healthy normal controls. None of the SF-36 categories except physical function correlated significantly with the GOS score. Aneurysm location did not have an impact on SF-36 data. Patients after a SAH assessed as GOS score 5 are significantly impaired in social functioning and general health. We conclude that patients continue to suffer neuropsychological deficits years after a SAH. The GOS score is a rough outcome measure that primarily focuses on physical functioning. SF-36 is a useful tool to include in the neuropsychological outcome assessment of patients with SAH.

Cytosolic Ca2+ oscillations in human cerebrovascular endothelial cells after subarachnoid hemorrhage.

Molecular mechanisms of cerebral vasospasm after subarachnoid hemorrhage (SAH) include specific modes of cell signaling like activation of nuclear factor (NF)-kappaB and vascular cell adhesion molecules (VCAM)-1 expression. The study's hypothesis is that cisternal cerebral spinal fluid (CSF) from patients after SAH may cause Ca(2+) oscillations which induce these modes of vascular inflammation in an in vitro model of human cerebral endothelial cells (HCECs). HCECs were incubated with cisternal CSF from 10 SAH patients with confirmed cerebral vasospasm. The CSF was collected on days 5 and 6 after hemorrhage. Cytosolic Ca(2+) concentrations and cell contraction as an indicator of endothelial barrier function were examined by fura-2 microflurometry. Activation of NF-kappaB and VCAM-1 expression were measured by immunocytochemistry. Incubation of HCEC with SAH-CSF provoked cytosolic Ca(2+) oscillations (0.31+/-0.09 per min), cell contraction, NF-kappaB activation, and VCAM-1 expression, whereas exposure to native CSF had no significant effect. When endoplasmic reticulum (ER) Ca(2+)-ATPase and ER inositol trisphosphate (IP3)-sensitive Ca(2+) channels were blocked by thapsigargin or xestospongin, the frequency of the Ca(2+) oscillations was reduced significantly. In analogy to the reduction of Ca(2+) oscillation frequency, the blockers impaired HCEC contraction, NF-kappaB activation, and VCAM-1 expression. Cisternal SAH-CSF induces cytosolic Ca(2+) oscillations in HCEC that results in cellular constriction, NF-kappaB activation, and VCAM-1 expression. The Ca(2+) oscillations depend on the function of ER Ca(2+)-ATPase and IP3-sensitive Ca(2+) channels.

Arteriovenous differences of oxygen and transcranial Doppler sonography in the management of aneurysmatic subarachnoid hemorrhage.

After subarachnoid hemorrhage (SAH) the detection of hemodynamically significant vasospasm is frequently difficult, especially in comatose patients. Most clinicians use transcranial Doppler sonography (TCD) to detect increasing mean blood flow velocities in the basal arteries as markers of cerebral vasospasm, without accounting for the effects of sedation and variations in blood pressure or pCO(2). This study was conducted to test the hypothesis that the arteriovenous difference of oxygen (avDO(2); in terms of % volume) could also be useful for the evaluation of vasospasm. A total of 22 SAH patients (M : F = 1 : 1.75, age 58+/-10 years, median Hunt and Hess grade 4) were prospectively enrolled. All patients were sedated with continuous doses of midazolam/fentanyl and/or propofol. TCD studies and avDO(2) measurements were conducted at the same time or in close succession. The blood flow velocity of the middle cerebral artery was recorded. A cranial CT scan was conducted if the avDO(2) increased by at least 0.8%. Overall, 82 measurements were recorded in 22 patients between days 1 and 13 after SAH. TCD mean flow velocities increased as expected. In contrast, avDO(2) decreased until post-hemorrhage day 4 before it increased again. Overall, after SAH, avDO(2) was significantly lower than in normal individuals. Cerebral infarction occurred primarily in patients with a maximal change of avDO(2) of more than 1%. TCD velocities alone are poor indicators of the severity of vasospasm. In contrast, daily avDO(2) seems to be a more robust parameter. However, collection of additional metabolic information is warranted.

Cerebral energy failure after subarachnoid hemorrhage: the role of relative hyperglycolysis.

After subarachnoid hemorrhage (SAH) cerebral metabolism is significantly impaired. Hyperglycolysis describes the reduction of oxidative metabolism followed by a relative increase of anaerobic glycolysis to maintain energy supply. This phenomenon is known in head injury but has not as yet been shown after SAH. This study was conducted to test the hypothesis that hyperglycolysis is present in SAH patients and is associated with vasospasm. A total of 105 measurements were conducted on 21 SAH patients (age 49+/-15 years, median World Federation of Neurosurgical Societies Grade 4) over the first 5 days following admission. Arteriovenous differences were calculated for oxygen (avDO2) and glucose (avDGlc). Relative hyperglycolysis was defined as metabolic ratio (MR=avDO2[mmol/L]/avDGlc[mmol/L])<3.44. Jugular-venous saturation for oxygen (SjvO2), mean arterial blood pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP) were monitored. Relative hyperglycolyis was recorded in 34% of studies after SAH. In hyperglycolytic studies both jugular-venous lactate and SjvO2 were significantly elevated (jugular-venous lactate 14.9+/-9.9 vs. 11.8+/-5.5 mg/dL, p=0.04; SjvO2: 70.0+/-18% vs. 81.7+/-9%, p=0.002). Relative hyperglycolysis is associated with outcome after SAH. In patients who died after SAH almost 50% of studies showed hyperglycolysis, whereas patients who survived without neurological deficit had no hyperglycolytic events. Relative hyperglycolysis is a common event after SAH. It may be associated with relative hyperemia but most importantly with outcome.