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Cerebral blood flow is tightly regulated by cerebrovascular autoregulation (CVA), and intraoperative impairment of CVA has been linked with perioperative neurocognitive disorders. We aim to assess whether impairment of CVA during major oncologic surgery is associated with delayed neurocognitive recovery (DNCR) postoperatively. We performed a secondary analysis of prospectively collected data. Patients were included if they had undergone complete pre- and postoperative neuropsychological assessments, continuous intraoperative measurement of CVA, and major oncologic surgery for visceral, urological, or gynecological cancer. Intraoperative CVA was measured using the time-correlation method based on near-infrared-spectroscopy, and DNCR was assessed with a neuropsychological test battery. A decline in cognitive function before hospital discharge compared with a preoperative baseline assessment was defined as DNCR. One hundred ninety-five patients were included in the analysis. The median age of the study population was 65 years (IQR: 60–68); 11 patients (5.6%) were female. Forty-one patients (21.0%) fulfilled the criteria for DNCR in the early postoperative period. We found a significant association between impaired intraoperative CVA and DNCR before hospital discharge (OR = 1.042 [95% CI: 1.005; 1.080], p = 0.028). The type of surgery (radical prostatectomy vs. other major oncologic surgery; OR = 0.269 [95% CI: 0.099; 0.728], p = 0.010) and premedication with midazolam (OR = 3.360 [95% CI: 1.039; 10.870], p = 0.043) were significantly associated with the occurrence of DNCR in the early postoperative period. Intraoperative impairment of CVA is associated with postoperative neurocognitive function early after oncologic surgery. Therefore, intraoperative monitoring of CVA may be a target for neuroprotective interventions. The initial studies were retrospectively registered with primary clinical trial registries recognized by the World Health Organization (ClinicalTrials.gov Identifiers: DRKS00010014, 21.03.2016 and NCT04101006, 24.07.2019).

BACKGROUND Diastolic dysfunction is a risk factor for postoperative major cardiovascular events. During anesthesia, patients with diastolic dysfunction might experience impaired hemodynamic function and worsening of diastolic function, which in turn, might be associated with a higher incidence of postoperative complications.We aimed to investigate whether patients with diastolic dysfunction require higher doses of norepinephrine during general anesthesia. Furthermore, we aimed to examine the association between the grade of diastolic dysfunction and the E/e' ratio during anesthesia. A high E/e' ratio corresponds to elevated filling pressures and is an important measure of impaired diastolic function. METHODS We conducted a prospective observational cohort study at a German university hospital from February 2017 to September 2018. Patients aged ≥60 years and undergoing general anesthesia (ie, propofol and sevoflurane) for elective noncardiac surgery were enrolled. Exclusion: mitral valve disease, atrial fibrillation, and implanted mechanical device.The primary outcome parameter was the administered dose of norepinephrine within 30 minutes after anesthesia induction (μg·kg-1 30 min-1). The secondary outcome parameter was the change of Doppler echocardiographic E/e' from ECHO1 (baseline) to ECHO2 (anesthesia). Linear models and linear mixed models were used for statistical evaluation. RESULTS A total of 247 patients were enrolled, and 200 patients (75 female) were included in the final analysis. Diastolic dysfunction at baseline was not associated with a higher dose of norepinephrine during anesthesia (P = .6953). The grade of diastolic dysfunction at baseline was associated with a decrease of the E/e' ratio during anesthesia (P < .001). CONCLUSIONS We did not find evidence for an association between diastolic dysfunction and impaired hemodynamic function, as expressed by high vasopressor support during anesthesia. Additionally, our findings suggest that diastolic function, as expressed by the E/e' ratio, does not worsen during anesthesia.

OBJECTIVE To assess the effects of robot-assisted radical prostatectomy in the Trendelenburg position on postoperative neurocognitive outcomes this study compared cognitive function between patients who underwent robot-assisted radical prostatectomy and those who underwent open retropubic radical prostatectomy. METHODS Objective evaluations of pre- and postoperative cognitive function were performed upon admission and before hospital discharge, by using a neuropsychological test battery. We collected self-reported data on cognitive failures at 3 months postoperatively. Binary logistic regression analysis was used to assess the effects of surgical technique on postoperative cognitive performance. RESULTS The pre- and postoperative neuropsychological assessments were completed by 367 patients with a median age of 64 years (range 44-76). The incidence of postoperative cognitive dysfunction was 23.9% after robot-assisted (39/165) and 22.3% after open radical prostatectomy (45/202). There was no significant difference in postoperative cognitive function during the early postoperative period (P = 0.758) and self-reported cognitive failures at 3 months (P = 0.303) between robot-assisted and open surgery. Surgical technique was not associated with early postoperative cognitive dysfunction in multivariable analysis (OR 1.012, 95%CI: 0.608-1.685, P = 0.962). CONCLUSION Compared with open surgery in supine position postoperative neurocognitive disorders do not occur more frequently after robot-assisted radical prostatectomy in the extreme Trendelenburg position. Based on these findings potential adverse effects on cognitive function do not have to be considered in the choice of surgical approach for radical prostatectomy.

About 20% of ICU patients with COVID-19 require renal replacement therapy (RRT). Mid-regional pro-adrenomedullin (MR-proADM) might be used for risk assessment. This study investigates MR-proADM for RRT prediction in ICU patients with COVID-19.We analysed data of consecutive patients with COVID-19, requiring ICU admission at a university hospital in Germany between March and September 2020. Clinical characteristics, details on AKI, and RRT were assessed. MR-proADM was measured on admission.64 patients were included (49 (77%) males). Median age was 62.5y (54-73). 47 (73%) patients were ventilated and 50 (78%) needed vasopressors. 25 (39%) patients had severe ARDS, and 10 patients needed veno-venous extracorporeal membrane oxygenation. 29 (45%) patients required RRT; median time from admission to RRT start was 2 (1-9) days. MR-proADM on admission was higher in the RRT group (2.491 vs. 1.23 nmol/l;AKI requiring RRT is frequent in ICU patients with COVID-19. MR-proADM on admission was able to predict RRT requirement, which may be of interest for risk stratification and management.

Background This RCT investigated the effect of opioid titration by three different nociception monitoring devices or clinical signs during general anaesthesia. Methods Ninety-six patients undergoing radical retropubic prostatectomy with propofol/remifentanil anaesthesia were randomised into one of four groups to receive remifentanil guided by one of three nociception monitoring devices (surgical pleth index [SPI], pupillary pain index [PPI], or nociception level [NOL]) or by clinical judgement (control). Intraoperative remifentanil requirement was the primary endpoint, whereas recovery parameters and stress hormone levels were secondary endpoints. Results The mean [95% confidence interval {CI}] remifentanil administration rate differed between the groups: control 0.34 (0.32–0.37), SPI 0.46 (0.38–0.55), PPI 0.07 (0.06–0.08), and NOL 0.16 (0.12–0.21) μg kg−1 min−1(P Conclusions The nociception monitoring devices and clinical signs reflect the extent of nociception differently, leading to dissimilar doses of remifentanil. Very low remifentanil doses were associated with an increase and higher remifentanil doses were accompanied by a decrease in serum cortisol concentrations. Use of nociception monitoring devices for guiding intra-operative opioid dosing needs further validation. Clinical trial registration NCT03380949.

Neuroprotection through targeted temperature management is currently investigated in patients with severe brain injury in multiple trials. Feedback devices have been shown to precisely reach and maintain target temperature by constantly adjusting cooling activity. We analyzed the association between cooling activity expressed as cool bath temperatures and functional neurological outcome.Data were retrospectively analyzed from a prospective randomized trial on controlled prophylactic normothermia (i.e., 36.5 °C) in patients with severe cerebrovascular disease. Body core temperature of patients who had been randomized to the endovascular group, was controlled using an endovascular cooling device. Cool bath temperature was analyzed over a period of 168 h. Functional neurological outcome was evaluated at 180 days using the modified Rankin Scale.51 of 102 patients included were randomized to the endovascular group. Cool bath temperature data were available from 47/51 patients. Patients with lower cool bath temperatures reflecting high cooling activity had a more favorable neurological outcome at 180 days (mRS 0-2) than patients with low cooling activity (p0.05). We did not find a significant correlation between cool bath temperature and inflammatory markers.High cooling activity of an endovascular feedback device is associated with favorable outcome in patients with severe cerebrovascular disease.

Background Nosocomial infections are common in patients with spontaneous subarachnoid hemorrhage (SAH). The aim of this retrospective cohort study was to determine the incidence of infections during SAH and to evaluate the course of inflammation parameters and its implications for long term outcome. Objective Ninety-nine consecutive coiled SAH patients were included. Laboratory and clinical parameters as well as culture positive infections were followed over the disease course. Long-term outcome was assessed at 6-month by the Glasgow Outcome score (GOS) and dichotomized in favorable (GOSg3) and unfavorable outcome (GOS≤3). Results The most frequent infections were pulmonary (30.3%) urinary tract (25.3%), blood stream infections (20.2%) and ventriculitis (5.1%). The incidence of infections did not significantly differ between outcome groups. In contrast, patients with unfavorable outcome had a higher incidence of sepsis (46.7% versus 24.6%). C-reactive protein (CRP) and leukocytes were significantly higher in patients with unfavorable outcome. A CRP increase of 6 mg/dl or more in the first 3 days after SAH was independently associated with unfavorable outcome (OR 7.19 CI 1.7-30.52; p=0.008). Patients with an early CRP increase were more frequently treated with antimicrobial therapy in the first 3 days after admission which led to a significantly lower incidence of culture positive infections in the later course. Conclusion A sharp CRP-increase in the acute phase of SAH could potentially aid the intensivist in the early identification of patients at high risk for neurological morbidity. Early antimicrobial treatment reduces the rate of patients showing culture positive infections in the course of the disease.

Introduction: Animal data suggest an association between neuroinflammation and secondary brain injury including axonal injury after aneurysmal subarachnoid hemorrhage (aSAH). We sought to study the association between brain extracellular interleukin (IL)-6 and TAU-protein levels as a surrogate marker for neuroinflammation and axonal injury in patients with poor grade aSAH. Methods: Prospectively collected data from 26 consecutive poor-grade aSAH patients with multimodal neuromonitoring including cerebral microdialysis (CMD) were retrospectively analyzed. IL-6 and TAU-protein levels were analyzed using ELISA from a single CMD-sample every 24 hours and correlated with brain metabolic and hemodynamic parameters. Patients were dichotomized to high-grade (N=10) or low-grade (N=16) neuroinflammation according to their median CMD-IL-6 levels. Data were analyzed using generalized estimating equations to account for multiple within-subject measurements. Results: Perilesional probe location (P=0.02) and aSAH related intracerebral hemorrhage (aICH) volume (P=0.003) at admission were associated with high-grade neuroinflammation. Brain extracellular TAU-protein levels (P=0.001), metabolic distress and delayed cerebral infarction (DCI; P=0.001) were linked to high-grade neuroinflammation. Relative or absolute phosphor-TAU levels were not correlated with CMD-IL-6 levels. High-grade neuroinflammation was a predictor for worse outcome three months after ictus, independently from probe location, initial Hunt&Hess grade and age (P=0.01). Conclusions: Neuroinflammation after aSAH is associated with intraparenchymal bleeding, deranged cerebral metabolism and TAU-protein release. The impact of potential anti-inflammatory treatment strategies on secondary brain injury after aSAH has to be investigated in future studies.

Recent evidence suggests axonal injury after aneurysmal subarachnoid haemorrhage (aSAH). The microtubule-associated protein, tau, has been shown to be elevated in the cerebrospinal fluid after aSAH, however, brain extracellular tau levels and their relation to long-term neurological and cognitive outcomes have not been investigated.Serial cerebral microdialysis (CMD) samples were collected from 22 consecutive aSAH patients with multimodal neuromonitoring to determine CMD-total-tau by ELISA. CMD-total-tau was analysed considering other brain metabolic parameters, brain tissue oxygen tension (PbtO2), and functional and neuropsychological outcome at 12 months. All outcome models were analysed using generalised estimating equations with an autoregressive working correlation matrix to account for multiple measurements of brain extracellular proteins per subject.CMD-total-tau levels positively correlated with brain extracellular fluid levels of lactate (r=0.40, p0.001), glutamate (r=0.45, p0.001), pyruvate (r=0.26, p0.001), and the lactate-pyruvate ratio (r=0.26, p0.001), and were higher in episodes of hypoxic (PbtO220 mm Hg) brain extracellular lactate elevation (4 mmol/L) (p0.01). More importantly, high CMD-total-tau levels were associated with poor functional outcome (modified Rankin Scale ≥4) 12 months after aSAH even after adjusting for disease severity and age (p=0.001). A similar association was found with 3/5 neuropsychological tests indicative of impairments in cognition, psychomotor speed, visual conceptualisation and frontal executive functions at 1 year after aSAH (p0.01).These results suggest that CMD-total tau may be an important biomarker for predicting long-term outcome in patients with severe aSAH. The value of axonal injury needs further confirmation in a larger patient cohort, preferably combined with advanced imaging techniques.

Alois J. Schiefecker *, Ronny Beer , Josef Steidl , Florian Sohm, Andrea Griesmacher , Alexander K. Brendel , Iris Unterberger , Marlene Fischer , Anelia Dietmann , Bettina Pfausler , Claudius Thome , Erich Schmutzhard , Raimund Helbok a Division of Neurocritical Care, Department of Neurology, Medical University Innsbruck, Austria Central Institute of Medical and Chemical Laboratory Diagnostics, Medical University Innsbruck, Austria Department of Neurosurgery, Medical University Innsbruck, Austria

Brain derived neurotrophic factor (BDNF) is associated with pain modulation and central sensitization. Recently, a role of BDNF in migraine and cluster headache pathophysiology has been suspected due to its known interaction with calcitonin gene-related peptide. Bi-center prospective study was done enrolling four diagnostic groups: episodic migraine with and without aura, episodic cluster headache, frequent episodic tension-type headache, and healthy individuals. In migraineurs, venous blood samples were collected twice: outside and during migraine attacks prior to pain medication. In cluster headache patients serum samples were collected in and outside cluster bout. Analysis of BDNF was performed using enzyme-linked immunosorbent assay technique. Migraine patients revealed significantly higher BDNF serum levels during migraine attacks (n = 25) compared with headachefree intervals (n = 53, P\0.01), patients with tensiontype headache (n = 6, P\0.05), and healthy controls (n = 22, P\0.001). There was no significant difference between patients with migraine with aura compared with those without aura, neither during migraine attacks nor during headache-free periods. Cluster headache patients showed significantly higher BDNF concentrations inside (n = 42) and outside cluster bouts (n = 24) compared with healthy controls (P\0.01, P\0.05). BDNF is increased during migraine attacks, and in cluster headache, further supporting the involvement of BDNF in the pathophysiology of these primary headaches. © The Author(s) 2012.

Little is known about endothelial activation under the influence of endovascular temperature management. This analysis was designed to measure the endothelial markers Angiopoietin-1 (Ang-1) and -2 (Ang-2) in endovascularly based prophylactic normothermia versus conventional temperature management.In this randomized controlled trial patients with spontaneous subarachnoid or spontaneous intracerebral hemorrhage were prospectively enrolled and randomized in two treatment arms: (a) prophylactic normothermia group with target core temperature 36.5°C using endovascular cooling, (b) active control group with conventional stepwise predefined fever management using antipyretic medication and surface cooling. Blood samples were obtained on days 1, 4, and 7. In a substudy Ang-1 and -2 were measured in 63 patients for whom samples on consecutive days were available.The median total fever burden during the course of treatment was 0.0°C and 5.9°C h in the endovascular and the conventional group, respectively (P 0.0001). Angiopoietin serum levels did not yield a statistical difference when comparing the two treatment arms. Ang-1 was significantly lowered, whereas Ang-2 levels were significantly elevated on day 4 compared to baseline levels irrespective of group allocation (P 0.0001). The application of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with significantly increased Ang-1 (P 0.05) and lower Ang-2 levels on day 7 (P 0.05).Endovascular long-term temperature management did not alter Ang-1 and -2 levels compared to the control group indicating that the endovascular cooling technique itself does not lead to additional endothelial impairment. However, application of NSAIDs led to lower Ang-2 serum concentrations in the endovascular group.

Background and Purpose— We analyzed the impact of long-term endovascularly based prophylactic normothermia versus conventional temperature management on inflammatory parameters in patients with severe cerebrovascular disease. Methods— This was a prospective, randomized, controlled trial comparing the course of inflammatory parameters between the 2 treatment arms: (1) prophylactically endovascular long-term normothermia; and (2) conventional, stepwise fever management with antiinflammatory drugs and surface cooling. Inclusion criteria were (1) spontaneous subarachnoid hemorrhage with Hunt–Hess grade between 3 and 5; (2) spontaneous intracerebral hemorrhage with a Glasgow Coma Scale score of ≤10; or (3) complicated cerebral infarction requiring intensive care unit treatment with a NIH Stroke Scale score of ≥15. Treatment period was 336 hours in subarachnoid hemorrhage patients and 168 hours in patients with complicated stroke or intracerebral hemorrhage patients. Results— A total of 102 patients (56 female) were enrolled during a 3.5-year period. Overall median total fever burden during the course of treatment was 0.0°C hour and 4.3°C hours in the catheter and conventional group, respectively ( P P P Conclusions— The proinflammatory cytokines C-reactive protein and interleukin-6 were significantly elevated in patients receiving prophylactic endovascularly based long-term normothermia. Nonsteroidal antiinflammatory drugs significantly affected the course of proinflammatory parameters; thus, future trials should investigate the role of nonsteroidal antiinflammatory drugs in severe cerebrovascular disease patients and their interaction with temperature management. Clinical Trial Registration— Trial not registered; enrollment began before July 2005.

Background and Purpose— Spontaneous subarachnoid hemorrhage (SAH) still has a high risk for poor outcome that is frequently attributable to symptomatic cerebral vasospasm (CVS). We hypothesize that cellular microparticles (MP) play a role in the pathogenesis of CVS and may serve as biomarkers for CVS. Methods— In 20 consecutive SAH patients, endothelial, leukocyte, platelet, and erythrocyte MP were measured during 15 days after ictus. CVS was detected by transcranial Doppler sonography. Twenty matched volunteers served as healthy controls. Results— Endothelial, leukocyte, and erythrocyte MP were elevated in SAH patients compared to healthy controls. CD105 + and CD62e + endothelial MP were significantly higher in SAH patients with Doppler sonographic CVS. CD105 + endothelial MP were especially increased on the days of Doppler sonographic CVS onset. In patients experiencing cerebral infarction attributable to vasospasm, CD41 + platelet MP were elevated in addition to endothelial MP. CD41 + platelet MP were significantly higher in patients with any level of disability (modified Rankin Scale score ≥1) compared to those who made a full recovery (modified Rankin Scale score=0) on discharge from hospital. Conclusion— Endothelial MP were elevated in patients with SAH. This elevation coincided with the occurrence of Doppler sonographic CVS and therefore could be a novel biomarker for CVS. Platelet MP might be involved in the pathogenesis of cerebral infarction attributable to vasospasm, resulting in neurological morbidity.

Introduction There is a substantial amount of evidence from animal models that early brain injury (EBI) may play an important role for secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Cerebral microdialysis (CMD) allows online measurement of brain metabolites, including the pro-inflammatory cytokine interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9), which is indicative for disruption of the blood-brain barrier. Methods Twenty-six consecutive poor-grade aSAH patients with multimodal neuromonitoring were analyzed for brain hemodynamic and metabolic changes, including CMD-IL-6 and CMD-MMP-9 levels. Statistical analysis was performed by using a generalized estimating equation with an autoregressive function. Results The baseline cerebral metabolic profile revealed brain metabolic distress and an excitatory response which improved over the following 5 days (P P P P = 0.04), whereas admission disease severity and early brain tissue hypoxia were associated with higher CMD-MMP-9 levels (P P ≤0.01). All models were adjusted for probe location, aneurysm securing procedure, and disease severity as appropriate. Conclusions Multimodal neuromonitoring techniques allow insight into pathophysiologic changes in the early phase after aSAH. The results may be used as endpoints for future interventions targeting EBI in poor-grade aSAH patients.

Background Triptans are recommended as first-line therapy in the acute phase of a migraine attack. We describe patterns of triptan use in a tertiary care headache outpatient clinic, particularly addressing factors that are associated with triptan discontinuation. Methods From December 2009 until August 2012, demographic and clinical data of consecutive patients with migraine were collected. The Headache Impact Test (HIT-6) was used to measure the adverse impact of headaches. Factors associated with triptan discontinuation were analyzed using binary logistic regression. Results Of 511 migraine patients included, 73.2% (n = 374) were triptan naive on first consultation. At follow-up, 57.1% of new triptan users (n = 72/126) reported pain-freedom or pain relief after 2 hours, 40.5% (n = 51/126) did not refill their triptan, another 15.1% (n = 19/126) switched to a different type of triptan. Negative response to triptan treatment and substantial or severe headache impact (HIT-6 score ≥56) at first follow-up were associated with triptan discontinuation (OR 0.39 [95% CI 0.20—0.78], P = .007; OR 3.33 [95% CI 1.10–10.03], P = .033). Conclusions Although triptans have been in clinical use for more than two decades, many migraine sufferers in our study population were found to be triptan naive on first consultation. The HIT-6 score may be used as an indicator of triptan adherence and help to identify patients at risk for triptan discontinuation.

Background Numerous studies suggest an increased vascular risk in patients with migraine, in particular in those with aura. A possible link between both conditions might be a dysfunction of the vascular endothelium. This observational study analyzed the endothelial markers angiopoietin-1, angiopoietin-2, Tie-2, sFlt-1 and NT-proBNP for the first time in migraineurs, patients with other primary headache disorders and healthy controls. Methods Patients with episodic migraine with and without aura, episodic cluster headache, tension-type headache and healthy controls were included. Blood samples were obtained during migraine attacks and headache-free periods in migraineurs, in and out of bout in cluster headache and during headache-free periods in tension-type headache and healthy individuals to analyze markers of endothelial function. Results No significant difference in endothelial markers between migraine, other headache disorders and healthy controls was detected. There was no significant difference between migraine attacks and headache-free intervals. Additionally, no distinction could be found between migraine with and without aura. Discussion The endothelial markers analyzed do not display a characteristic pattern in different headache disorders especially migraine compared to healthy controls. The novel findings of our study indicate that factors other than endothelial dysfunction seem to be responsible for the at least statistical association of migraine with vascular disease.

Background: Atrial natriuretic peptide (ANP) is a well-known prognostic marker of outcome and mortality in patients with cardiovascular disease. Midregional proatrial natriuretic peptide (MR-proANP) is a stable fragment of the ANP precursor hormone. As a prognostic marker after ischemic stroke, it reliably predicts poststroke mortality and functional outcome. This study aimed to analyze the prognostic value of MR-proANP in patients with hemorrhagic stroke, i.e. subarachnoid (SAH) and intracerebral hemorrhage (ICH). Methods: MR-proANP was analyzed in patients with spontaneous SAH or spontaneous ICH. All patients were prospectively randomized into two treatment arms: (1) a prophylactic normothermia group with a target core temperature 36.5°C using endovascular cooling, and (2) a control group with conventional stepwise predefined fever management using antipyretic medication and surface cooling. Blood samples were obtained on admission and on days 4 and 7. Measurement of MR-proANP was performed in serum using sandwich immunoassay. The primary endpoint was functional outcome [assessed by the Glasgow Outcome Score (GOS)] and the secondary endpoints were mortality within 180 days after hemorrhagic stroke and influence of temperature on MR-proANP. A favorable outcome was defined as GOS 4-5, and the patients were considered to have a poor outcome with a 180-day GOS score between 1 and 3. Results: Analysis of MR-proANP was performed in 24 patients with spontaneous SAH and 22 patients with spontaneous ICH. MR-proANP was elevated on days 4 and 7 as compared to baseline levels (p < 0.05 and p < 0.001, respectively). High MR-proANP levels (>120 pmol/l) were associated with increased mortality and poor outcome (after 180 days; p < 0.05, respectively). There was no significant difference regarding MR-proANP serum concentrations between the endovascular and the control groups. Conclusions: Increased levels of MR-proANP are independently associated with poor functional outcome and increased mortality after 180 days in patients with hemorrhagic stroke. Endovascular temperature control had no significant influence on MR-proANP levels.

Background Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in vascular remodeling, (neuro)inflammation, blood-brain barrier breakdown and neuronal apoptosis. Proinflammatory mechanisms are suggested to play an important role during early brain injury and cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). This study aimed to analyze MMP-3, MMP-9, TIMP-1 and TIMP-3 in patients with SAH and their respective association with cerebral vasospasm (CVS). Methods Blood samples were collected in 20 SAH patients on days 1 to 7, 9, 11, 13 and 15 and 20 healthy age and gender matched volunteers. Serum MMPs and TIMPs were analyzed using enzyme-linked immunosorbent assay. Doppler sonographic CVS was defined as a mean blood flow velocity above 120 cm/sec in the middle cerebral artery. When discharged from hospital and at 6 month follow-up neurological outcome was evaluated using the Glasgow Outcome Score and the modified Rankin Scale. Results MMP-9 was higher in SAH patients compared to healthy controls (p

Background Angiopoietin-1 (Ang-1) and -2 (Ang-2) are keyplayers in the regulation of endothelial homeostasis and vascular proliferation. Angiopoietins may play an important role in the pathophysiology of cerebral vasospasm (CVS). Ang-1 and Ang-2 have not been investigated in this regard so far. Methods 20 patients with subarachnoid hemorrhage (SAH) and 20 healthy controls (HC) were included in this prospective study. Blood samples were collected from days 1 to 7 and every other day thereafter. Ang-1 and Ang-2 were measured in serum samples using commercially available enzyme-linked immunosorbent assay. Transcranial Doppler sonography was performed to monitor the occurrence of cerebral vasospasm. Results SAH patients showed a significant drop of Ang-1 levels on day 2 and 3 post SAH compared to baseline and HC. Patients, who developed Doppler sonographic CVS, showed significantly lower levels of Ang-1 with a sustained decrease in contrast to patients without Doppler sonographic CVS, whose Ang-1 levels recovered in the later course of the disease. In patients developing cerebral ischemia attributable to vasospasm significantly lower Ang-1 levels have already been observed on the day of admission. Differences of Ang-2 between SAH patients and HC or patients with and without Doppler sonographic CVS were not statistically significant. Conclusions Ang-1, but not Ang-2, is significantly altered in patients suffering from SAH and especially in those experiencing CVS and cerebral ischemia. The loss of vascular integrity, regulated by Ang-1, might be in part responsible for the development of cerebral vasospasm and subsequent cerebral ischemia.

BACKGROUND: As brain temperature is reported to be extensively higher than core body temperature in traumatic brain injury (TBI) patients, posttraumatic hyperthermia is of particular relevance in the injured brain. OBJECTIVE: To study the influence of prophylactic normothermia on brain temperature and the temperature gradient between brain and core body in patients with severe TBI using an intravascular cooling system and to assess the relationship between brain temperature and intracranial pressure (ICP) under endovascular temperature control. METHODS: Prospective case series study conducted in the neurologic intensive care unit of a tertiary care university hospital. Seven patients with severeTBI with a Glasgow Coma Scale score of 8 or less were consecutively enrolled. Prophylactic normothermia, defined as a target temperature of 36.5� C, was maintained using an intravascular cooling system. Simultaneous measurements of brain and urinary bladder temperature and ICP were taken over a 72-hour period. RESULTS: The mean bladder temperature in normothermic patients was 36.3 6 0.4� C, and the mean brain temperature was determined as 36.4 6 0.5� C. The mean temperature difference between brain and bladder was 0.1� C. We found a significant direct correlation between brain and bladder temperature (r = 0.95). In 52.4% of all measurements, brain temperature was higher than core body temperature. The mean ICP was 18 6 8 mm Hg. CONCLUSION: Intravascular temperature management stabilizes both brain and body core temperature; prophylactic normothermia reduces the otherwise extreme increase of intracerebral temperature in patients with severe TBI. The intravascular cooling management proved to be an efficacious and feasible method to control brain temperature and to avoid hyperthermia in the injured brain. We could not find a statistically significant correlation between brain temperature and ICP.

Background and Purpose— We sought to study the effectiveness and safety of endovascular cooling to maintain prophylactic normothermia in comparison with standardized, stepwise, escalating fever management to reduce fever burden in patients with severe cerebrovascular disease. Methods— This study was a prospective, randomized, controlled trial with a blinded neurologic outcome evaluation comparison between prophylactic, catheter-based normothermia (CoolGard; ie, body core temperature 36.5°C) and conventional, stepwise fever management with anti-inflammatory drugs and surface cooling. Patients admitted to 1 of the 2 neurointensive care units were eligible for study inclusion when they had a (1) spontaneous subarachnoid hemorrhage with Hunt & Hess grade between 3 and 5, (2) spontaneous intracerebral hemorrhage with a Glasgow Coma Scale score ≤10, or (3) complicated cerebral infarction requiring intensive care unit treatment with a National Institutes of Health Stroke Scale score ≥15. Results— A total of 102 patients (56 female) were enrolled during a 3.5-year period. Fifty percent had a spontaneous subarachnoid hemorrhage, 40% had a spontaneous intracerebral hemorrhage, and 10% had a complicated cerebral infarction. Overall median total fever burden during the course of treatment was 0.0°C hour and 4.3°C hours in the catheter and conventional groups, respectively ( P Conclusions— Long-term, catheter-based, prophylactic normothermia significantly reduces fever burden in neurointensive care unit patients with severe cerebrovascular disease and is not associated with increased major adverse events.

Introduction Elevated brain potassium levels ([K+]) are associated with neuronal damage in experimental models. The role of brain extracellular [K+] in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) and its association with hemorrhage load, metabolic dysfunction and outcome has not been studied so far. Methods Cerebral microdialysis (CMD) samples from 28 poor grade aSAH patients were analyzed for CMD [K+] for 12 consecutive days after ictus, and time-matched to brain metabolic and hemodynamic parameters as well as corresponding plasma [K+]. Statistical analysis was performed using a generalized estimating equation with an autoregressive function to handle repeated observations of an individual patient. Results CMD [K+] did not correlate with plasma [K+] (Spearman’s ρ = 0.114, P = 0.109). Higher CMD [K+] was associated with the presence of intracerebral hematoma on admission head computed tomography, CMD lactate/pyruvate ratio >40 and CMD lactate >4 mmol/L (P