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Objective Spreading depolarizations (SD) are characterized by breakdown of transmembrane ion gradients and excitotoxicity. Experimentally, N-methyl-d-aspartate receptor (NMDAR) antagonists block a majority of SDs. In many hospitals, the NMDAR antagonist s-ketamine and the GABAA agonist midazolam represent the current second-line combination treatment to sedate patients with devastating cerebral injuries. A pressing clinical question is whether this option should become first-line in sedation-requiring individuals in whom SDs are detected, yet the s-ketamine dose necessary to adequately inhibit SDs is unknown. Moreover, use-dependent tolerance could be a problem for SD inhibition in the clinic. Methods We performed a retrospective cohort study of 66 patients with aneurysmal subarachnoid hemorrhage (aSAH) from a prospectively collected database. Thirty-three of 66 patients received s-ketamine during electrocorticographic neuromonitoring of SDs in neurointensive care. The decision to give s-ketamine was dependent on the need for stronger sedation, so it was expected that patients receiving s-ketamine would have a worse clinical outcome. Results S-ketamine application started 4.2 ± 3.5 days after aSAH. The mean dose was 2.8 ± 1.4 mg/kg body weight (BW)/h and thus higher than the dose recommended for sedation. First, patients were divided according to whether they received s-ketamine at any time or not. No significant difference in SD counts was found between groups (negative binomial model using the SD count per patient as outcome variable, p = 0.288). This most likely resulted from the fact that 368 SDs had already occurred in the s-ketamine group before s-ketamine was given. However, in patients receiving s-ketamine, we found a significant decrease in SD incidence when s-ketamine was started (Poisson model with a random intercept for patient, coefficient − 1.83 (95% confidence intervals − 2.17; − 1.50), p p p p Conclusions These results provide a foundation for a multicenter, neuromonitoring-guided, proof-of-concept trial of ketamine and midazolam as a first-line sedative regime.

Fatigue resulting from shift work and extended hours can compromise patient care and the safety and health of nurses, as well as increasing nursing turnover and health care costs.This research aimed to identify aspects of nurses' work patterns associated with increased risk of reporting fatigue-related outcomes.A national survey of work patterns and fatigue-related outcomes in 6 practice areas expected to have high fatigue risk (child health including neonatology, cardiac care/intensive care, emergency and trauma, in-patient mental health, medical, and surgical nursing).The 5-page online questionnaire included questions addressing: demographics, usual work patterns, work in the previous two weeks, choice about shifts, and four fatigue-related outcomes - having a sleep problem for at least 6 months, sleepiness (Epworth Sleepiness Scale), recalling a fatigue-related error in clinical practice in the last 6 months, and feeling close to falling asleep at the wheel in the last 12 months. The target population was all registered and enrolled nurses employed to work in public hospitals at least 30 h/week in one of the 6 practice areas. Participation was voluntary and anonymous.Respondents (n = 3133) were 89.8% women and 8% Māori (indigenous New Zealanders), median age 40 years, range 21-71 years (response rate 42.6%). Nurses were more likely than New Zealand adults in general to report chronic sleep problems (37.73% vs 25.09%, p 0.0001) and excessive sleepiness (33.75% vs 14.9%, p 0.0001). Fatigue-related error(s) in the last 6 months were recalled by 30.80% and 64.50% reported having felt sleepy at the wheel in the last 12 months. Logistic regression analyses indicated that fatigue-related outcomes were most consistently associated with shift timing and sleep. Risk increased with more night shifts and decreased with more nights with sleep between 11 p.m. and 7 a.m. and on which nurses had enough sleep to feel fully rested. Risk also increased with roster changes and more shift extensions greater than 30 min and decreased with more choice about shifts. Comparisons between intensive care/cardiac care and in-patient mental health nursing highlight that fatigue has different causes and consequences in different practice areas.Findings confirm the need for a more comprehensive and adaptable approach to managing fatigue. We advocate an approach that integrates safety management and scientific principles with nursing and management expertise. It should be data-driven, risk-focused, adaptable, and resilient in the face of changes in the services required, the resources available, and the overall goals of the healthcare system.

Spreading depolarization (SD) is a fundamental pathophysiological mechanism of both pannecrotic and selective neuronal lesions following deprivation of energy. SD with brain injury has been reported including in one patient during an intracranial operation. However, the incidence of SDs in operative resections is unknown. We performed (a) retrospective analysis of intraoperative AC-recordings of 69 patients and (b) a prospective study using intraoperative near-DC recording. All patients had the diagnosis of pharmaco-resistant epilepsy. Both studies were designed to determine the incidence and characteristics of SDs intraoperatively. In the retrospective analysis, we used intraoperative electrocorticography (iECoG) recordings obtained from AC-recording of 69 patients. In the prospective analysis, we used an Octal Bio Amp and Power Lab ECoG recorder with near-DC range. In the retrospective study, we included 69 patients with a mean of 1 h 3 min of iECoG recordings. In the prospective study, we recruited 20 patients with near DC recordings. A total of 35 h 41 min of iECoG recordings with mean of 2 h 32 min/patient were analyzed. We did not find SD in either study. SDs were not detected during intraoperative recordings of epilepsy surgery using AC- or DC-amplifiers.

The main objective of this study was to generate a hemodynamically stable swine model to detect spreading depolarizations (SDs) using electrocorticography (ECoG) and intrinsic optical signal (IOS) imaging and laser speckle flowmetry (LSF) after a 30-h middle cerebral artery (MCA) occlusion (MCAo) in German Landrace Swine. A total of 21 swine were used. The study comprised a training group (group 1, n = 7), a group that underwent bilateral craniectomy and MCAo (group 2, n = 10) and a group used for 2,3,5-triphenyltetrazolium (TTC) staining (group 3, n = 5). In group 2, nine animals that underwent MCAo survived for 30 h, and one animal survived for 12 h. We detected MCA variants with 2 to 4 vessels. In all cases, all of the MCAs were occluded. The intensity changes exhibited by IOS and LSF after clipping were closely correlated and indicated a lower blood volume and reduced blood flow in the middle cerebral artery territory. Using IOS, we detected a mean of 2.37 ± (STD) 2.35 SDs/h. Using ECoG, we detected a mean of 0.29 ± (STD) 0.53 SDs/h. Infarctions were diagnosed using histological analysis. TTC staining in group 3 confirmed that the MCA territory was compromised and that the anterior and posterior cerebral arteries were preserved. We confirm the reliability of performing live monitoring of cerebral infarctions using our MCAo protocol to detect SDs.

Haemodynamic responses to spreading depolarizations (SDs) have an important role during the development of secondary brain damage. Characterization of the haemodynamic responses in larger brains, however, is difficult due to movement artefacts. Intrinsic optical signal (IOS) imaging, laser speckle flowmetry (LSF) and electrocorticography were performed in different configurations in three groups of in total 18 swine. SDs were elicited by topical application of KCl or occurred spontaneously after middle cerebral artery occlusion. Movement artefacts in IOS were compensated by an elastic registration algorithm during post-processing. Using movement-compensated IOS, we were able to differentiate between four components of optical changes, corresponding closely with haemodynamic variations measured by LSF. Compared with ECoG and LSF, our setup provides higher spatial and temporal resolution, as well as a better signal-to-noise ratio. Using IOS alone, we could identify the different zones of infarction in a large gyrencephalic middle cerebral artery occlusion pig model. We strongly suggest movement-compensated IOS for the investigation of the role of haemodynamic responses to SDs during the development of secondary brain damage and in particular to examine the effect of potential therapeutic interventions in gyrencephalic brains.

Spreading depolarization (SD) generates significant alterations in cerebral haemodynamics, which can have detrimental consequences on brain function and integrity. Ketamine has shown an important capacity to modulate SD; however, its impact on SD haemodynamic response is incompletely understood. We investigated the effect of two therapeutic ketamine dosages, a low-dose of 2 mg/kg/h and a high-dose of 4 mg/kg/h, on the haemodynamic response to SD in the gyrencephalic swine brain. Cerebral blood volume, pial arterial diameter and cerebral blood flow were assessed through intrinsic optical signal imaging and laser-Doppler flowmetry. Our findings indicate that frequent SDs caused a persistent increase in the baseline pial arterial diameter, which can lead to a diminished capacity to further dilate. Ketamine infused at a low-dose reduced the hyperemic/vasodilative response to SD; however, it did not alter the subsequent oligemic/vasoconstrictive response. This low-dose did not prevent the baseline diameter increase and the diminished dilative capacity. Only infusion of ketamine at a high-dose suppressed SD and the coupled haemodynamic response. Therefore, the haemodynamic response to SD can be modulated by continuous infusion of ketamine. However, its use in pathological models needs to be explored to corroborate its possible clinical benefit.

Objective Spreading depolarization (SD) occurs after traumatic brain injury, subarachnoid hemorrhage, malignant hemispheric stroke and intracranial hemorrhage. SD has been associated with secondary brain injury, which can be reduced by ketamine. In this present study frequency bands of electrocorticographic (ECoG) recordings were investigated with regards to SDs. Methods A total of 43 patients after acute brain injury were included in this retrospective and explorative study. Relative delta 0.5–4Hz, theta 4–8Hz, alpha 8–13Hz and beta 13–40Hz bands were analyzed with regards to SD occurrence and analgesic and sedative administration. Higher frequencies, including gamma 40–70Hz, fast gamma 70–100Hz and high frequency oscillations 100–200Hz were analyzed in a subset of patients with a sampling rate of up to 400Hz. Results A close association of relative beta frequency and SD was found. Relative beta frequency was suppressed up to two hours prior to SD when compared to hours with no SD. This finding was partially explained by administration of ketamine. Even after removal of all patient data during administration of ketamine, SDs occurred predominantly during times with low relative beta frequency in a patient-independent analysis. Conclusion Suppression of beta frequency by ketamine or without ketamine is associated with low SD counts. Significance Alteration of beta frequency might help to predict occurrence of SDs in acutely brain injured patients.

BACKGROUND: Disease progression and delayed neurological complications are common after aneurysmal subarachnoid hemorrhage (aSAH). We explored the potential of quantitative blood-brain barrier (BBB) imaging to predict disease progression and neurological outcome. METHODS: Data were collected as part of the Co-Operative Studies of Brain Injury Depolarizations (COSBID). We analyzed retrospectively, blinded and semi-automatically magnetic resonance images from 124 aSAH patients scanned at 4 time points (24–48 h, 6–8 days, 12–15 days and 6–12 months) after the initial hemorrhage. Volume of brain with apparent pathology and/or BBB dysfunction (BBBD), subarachnoid space and lateral ventricles were measured. Neurological status on admission was assessed using the World Federation of Neurosurgical Societies and Rosen-Macdonald scores. Outcome at ≥6 months was assessed using the extended Glasgow outcome scale and disease course (progressive or non-progressive based on imaging-detected loss of normal brain tissue in consecutive scans). Logistic regression was used to define biomarkers that best predict outcomes. Receiver operating characteristic analysis was performed to assess accuracy of outcome prediction models. FINDINGS: In the present cohort, 63% of patients had progressive and 37% non-progressive disease course. Progressive course was associated with worse outcome at ≥6 months (sensitivity of 98% and specificity of 97%). Brain volume with BBBD was significantly larger in patients with progressive course already 24–48 h after admission (2.23 (1.23–3.17) folds, median with 95%CI), and persisted at all time points. The highest probability of a BBB-disrupted voxel to become pathological was found at a distance of ≤1 cm from the brain with apparent pathology (0·284 (0·122–0·594), p

ObjectiveTo investigate whether spreading depolarization (SD)-related variables at 2 different time windows (days 1–4 and 5–8) after aneurysmal subarachnoid hemorrhage (aSAH) correlate with the stereologically determined volume of early focal brain injury on the preinterventional CT scan.MethodsIn this observational multicenter study of 54 patients, volumes of unaffected brain tissue, ventricles, cerebellum, aSAH, intracerebral hemorrhage, and focal parenchymal hypodensity were stereologically estimated. Patients were electrocorticographically monitored using subdural electrodes for 81.8 hours (median) (interquartile range: 70.6–90.5) during days 1–4 (n = 54) and for 75.9 (59.5–88.7) hours during days 5–8 (n = 51). Peak total SD-induced depression duration of a recording day (PTDDD) and peak numbers of (1) SDs, (2) isoelectric SDs, and (3) spreading depressions of a recording day were determined following the recommendations of the Co-Operative Studies on Brain Injury Depolarizations.ResultsThirty-three of 37 patients with early focal brain injury (intracerebral hemorrhage and/or hypodensity) in contrast to 7 of 17 without displayed SDs during days 1–4 (sensitivity: 89% [95% confidence interval, CI: 75%–97%], specificity: 59% [CI: 33%–82%], positive predictive value: 83% [CI: 67%–93%], negative predictive value: 71% [CI: 42%–92%], Fisher exact test, p < 0.001). All 4 SD-related variables during days 1–4 significantly correlated with the volume of early focal brain injury (Spearman rank order correlations). A multiple ordinal regression analysis identified the PTDDD as the most important predictor.ConclusionsOur findings suggest that early focal brain injury after aSAH is associated with early SDs and further support the notion that SDs are a biomarker of focal brain lesions.

Background General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers. Methods We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment. Results The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36–40 mmHg (4.8–5.3 kPa) in case of controlled intracranial pressure (ICP)

OBJECT The pressure reactivity index (PRx) correlates with outcome after traumatic brain injury (TBI) and is used to calculate optimal cerebral perfusion pressure (CPPopt). The PRx is a correlation coefficient between slow, spontaneous changes (0.003–0.05 Hz) in intracranial pressure (ICP) and arterial blood pressure (ABP). A novel index—the so-called long PRx (L-PRx)—that considers ABP and ICP changes (0.0008–0.008 Hz) was proposed. METHODS The authors compared PRx and L-PRx for 6-month outcome prediction and CPPopt calculation in 307 patients with TBI. The PRx- and L-PRx–based CPPopt were determined and the predictive power and discriminant abilities were compared. RESULTS The PRx and L-PRx correlation was good (R = 0.7, p < 0.00001; Spearman test). The PRx, age, CPP, and Glasgow Coma Scale score but not L-PRx were significant fatal outcome predictors (death and persistent vegetative state). There was a significant difference between the areas under the receiver operating characteristic curves calculated for PRx and L-PRx (0.61 ± 0.04 vs 0.51 ± 0.04; z-statistic = −3.26, p = 0.011), which indicates a better ability by PRx than L-PRx to predict fatal outcome. The CPPopt was higher for L-PRx than for PRx, without a statistical difference (median CPPopt for L-PRx: 76.9 mm Hg, interquartile range [IQR] ± 10.1 mm Hg; median CPPopt for PRx: 74.7 mm Hg, IQR ± 8.2 mm Hg). Death was associated with CPP below CPPopt for PRx (χ2 = 30.6, p < 0.00001), and severe disability was associated with CPP above CPPopt for PRx (χ2 = 7.8, p = 0.005). These relationships were not statistically significant for CPPopt for L-PRx. CONCLUSIONS The PRx is superior to the L-PRx for TBI outcome prediction. Individual CPPopt for L-PRx and PRx are not statistically different. Deviations between CPP and CPPopt for PRx are relevant for outcome prediction; those between CPP and CPPopt for L-PRx are not. The PRx uses the entire B-wave spectrum for index calculation, whereas the L-PRX covers only one-third of it. This may explain the performance discrepancy.

Objectives The detection of the hemodynamic and propagation patterns of spreading depolarizations (SDs) in the gyrencephalic brain using intrinsic optical signal imaging (IOS). Methods The convexity of the brain surface was surgically exposed in fourteen male swine. Within the boundaries of this window, brains were immersed and preconditioned with an elevated K+ concentration (7 mmol/l) in the standard Ringer lactate solution for 30–40 min. SDs were triggered using 3–5 μl of 1 mol/l KCl solution. Changes in tissue absorbency or reflection were registered with a CCD camera at a wavelength of 564 nm (14 nm FWHM), which was mounted 25 cm above the exposed cortex. Additional monitoring by electrocorticography and laser-Doppler was used in a subset of animals (n = 7) to validate the detection of SD. Results Of 198 SDs quantified in all of the experiments, 187 SDs appeared as radial waves that developed semi-planar fronts. The morphology was affected by the surface of the gyri, the sulci and the pial vessels. Other SD patterns such as spirals and reverberating waves, which have not been described before in gyrencephalic brains, were also observed. Diffusion gradients created in the cortex surface (i.e., KCl concentrations), sulci, vessels and SD–SD interactions make the gyrencephalic brain prone to the appearance of irregular SD waves. Conclusion The gyrencephalic brain is capable of irregular SD propagation patterns. The irregularities of the gyrencephalic brain cortex may promote the presence of re-entrance waves, such as spirals and reverberating waves.

To evaluate an intraparenchymal probe for intracranial pressure (ICP) and temperature (TEMP) monitoring as well as determination of cerebral hemodynamics using a near-infrared spectroscopy (NIRS) and indocyanine green (ICG) dye dilution method (NIRS-ICP probe).The NIRS-ICP probe was applied after aneurysmal subarachnoid hemorrhage if multimodal monitoring was established due to poor neurological condition. ICP and TEMP values were obtained from ventricular catheters and systemic temperature sensors. Repeated NIRS-ICG measurements (2 injections within 30 min) were performed daily for determination of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time of ICG (mttICG). Secondary neurologic dysfunction was defined as brain tissue oxygen tension20 mmHg and/or lactate/pyruvate ratio35 obtained from cerebral probing.A total of 128 NIRS-ICG measurements were performed in ten patients. The correlation coefficients between ICP and TEMP values obtained with the NIRS-ICP probe and values from routine monitoring were r = 0.72 and r = 0.96, respectively. The mean values were 30.3 ± 13.6 ml/100 g/min for CBF, 3.3 ± 1.2 ml/100 g for CBV, and 6.8 ± 1.6 s for mttICG. The coefficients of variation from repeated NIRS-ICG measurements were 10.9 % for CBF, 11.7 % for CBV, and 3.8 % for mttICG. The sensitivity for detection of secondary neurologic dysfunction was 85 % and the specificity 83 % using a CBF-threshold of 25 ml/100 g/min.Multimodal monitoring using the NIRS-ICP probe is feasible with high reproducibility of measurement values and the ability to detect secondary neurologic dysfunction. No safety concerns exist for the routine clinical use of the NIRS-ICP probe.

Cerebral autoregulation and, consequently, cerebrovascular pressure reactivity, can be disturbed after traumatic brain injury (TBI). Continuous monitoring of autoregulation has shown its clinical importance as an independent predictor of neurological outcome. The cerebral pressure reactivity index (PRx) reflects that changes in seconds of cerebrovascular reactivity have prognostic significance. Using an alternative algorithm similar to PRx, we investigate whether the utilization of lower-frequency changes of the order of minutes of mean arterial blood pressure (MAP) and intracranial pressure (ICP) could have a prognostic value in TBI patients.Head-injured patients requiring continued advanced multimodal monitoring, including hemodynamic, ICP and microdialysis (MD) monitoring, were analyzed retrospectively. A low-frequency sample pressure reactivity index (L-PRx) was calculated, using 20-min averages of MAP and ICP data as a linear Pearson's correlation. The mean values per patient were correlated to outcome at 6 months after injury. Differences of monitoring parameters between non-survivors and survivors were compared.A total of 29 patients (mean age 37.2 years, 26 males) suffering from TBI were monitored for a mean of 109.6 h (16-236 h, SD ± 60.4). Mean L-PRx was found to be of 0.1 (-0.2 to 0.6, SD ± 0.20), six patients presented impaired (0.2) values. The averaged L-PRx correlated significantly with ICP (r = 0.467, p = 0.011) and 6-month outcome (r = -0.556, p = 0.002). Significant statistical differences were found in L-PRx, cerebral perfusion pressure (CPP), lactate, and lactate-pyruvate ratio when comparing patients who died (n = 5) and patients who survived.L-PRx correlates with the 6-month outcome in TBI patients. Very slow changes of MAP and ICP may contain important autoregulation information. L-PRx may be an alternative algorithm for the estimation of cerebral autoregulation and clinical prognosis.

Study Objective Recent experimental evidence identified GABAergic sedation as a possible cause for deprived neuroregeneration and poor outcome after acute brain injury. Patients with aneurysmal subarachnoid hemorrhage are often sedated, and GABAergic sedation, such as midazolam and propofol, is commonly used. Design Retrospective cohort study based on a prospectively established database. Setting Single-center neurointensive care unit. Patients Twenty-nine patients after subarachnoid hemorrhage. Intervention Noninterventional study. Measurements The relationship between mean GABAergic sedative dose during the acute phase and outcome after 6 months according to the Glasgow Outcome Scale, and initial Glasgow Coma Scale was investigated. Main Results Use of GABAergic sedatives was negatively correlated with Glasgow Outcome Scale ( r 2 =0.267; P =.008). Administration of sedatives was independent of the initial Glasgow Coma Scale. GABAergic sedatives flunitrazepam, midazolam, and propofol were used differently during the first 10 days after ictus. Conclusion Administration of GABAergic sedation was associated with an unfavorable outcome after 6 months. To avoid bias (mainly through the indication to use sedation), additional experimental and comparative clinical investigation of, for example, non-GABAergic sedation, and clinical protocols of no sedation is necessary.

BACKGROUND Disturbed brain metabolism is a signature of primary damage and/or precipitates secondary injury processes after severe brain injury. Sedatives and analgesics target electrophysiological functioning and are as such well-known modulators of brain energy metabolism. Still unclear, however, is how sedatives impact glucose metabolism and whether they differentially influence brain metabolism in normally active, healthy brain and critically impaired, injured brain. We therefore examined and compared the effects of anesthetic drugs under both critical ( 1 mmol/L) extracellular brain glucose levels. METHODS We performed an explorative, retrospective analysis of anesthetic drug administration and brain glucose concentrations, obtained by bedside microdialysis, in 19 brain-injured patients. RESULT Our investigations revealed an inverse linear correlation between brain glucose and both the concentration of extracellular glutamate (Pearson r=-0.58, P=0.01) and the lactate/glucose ratio (Pearson r=-0.55, P=0.01). For noncritical brain glucose levels, we observed a positive linear correlation between midazolam dose and brain glucose (P

Spreading depolarization (SD) is a wave of mass neuronal and glial depolarization that propagates across the cerebral cortex and has been implicated in the pathophysiology of brain injury states and migraine with aura. Analgesics and sedatives seem to have a significant effect on SD modulation. Studies have shown that ketamine, an NMDA receptor blocker, has the capacity to influence SD occurrence. The aim of this study was to analyze the dose-dependent effect of ketamine on SD susceptibility through electrocorticography (ECoG) and intrinsic optical signal (IOS) imaging in a gyrencephalic brain. Ketamine in a low-dose infusion (2 mg/kg/h) decreases SD spread and had an effect on the amplitude of SD deflections, as well as on duration, and speed. Moreover, during ketamine infusion at this dose, there was a sustained decrease in the hyperemic response following SD. However, a high-dose infusion (4 mg/kg/h) of ketamine inhibited SD induction and expansion. Furthermore, a high-dose bolus (4 mg/kg), 1 min after stimulation, blocked SD propagation abruptly within 1-2 min, and hindered SD induction and expansion for the following 15-30 min. The results suggest that ketamine may be therapeutically beneficial in preventing SDs. Nonetheless, an adequate dosage and way of administration should be considered and established for human use.

Introduction Current guidelines for spontaneous intracerebral hemorrhage (ICH) recommend maintaining cerebral perfusion pressure (CPP) between 50 and 70 mmHg, depending on the state of autoregulation. We continuously assessed dynamic cerebral autoregulation and the possibility of determination of an optimal CPP (CPPopt) in ICH patients. Associations between autoregulation, CPPopt and functional outcome were explored. Methods Intracranial pressure (ICP), mean arterial pressure (MAP) and CPP were continuously recorded in 55 patients, with 38 patients included in the analysis. The pressure reactivity index (PRx) was calculated as moving correlation between MAP and ICP. CPPopt was defined as the CPP associated with the lowest PRx values. CPPopt was calculated using hourly updated of 4 hour windows. The modified Rankin Scale (mRS) was assessed at 3 months and associations between PRx, CPPopt and outcomes were explored using Pearson correlation and Fisher’s exact test. Multivariate stepwise logistic regression models were calculated including standard outcome predictors along with percentage of time with PRx >0.2 and percentage of time within the CPPopt range. Results An overall PRx indicating impairment of pressure reactivity was found in 47% of patients (n = 18). The mean PRx and the time spent with a PRx > 0.2 significantly correlated with mRS at 3 months (r = 0.50, P = 0.002; r = 0.46, P = 0.004). CPPopt was calculable during 57% of the monitoring time. The median CPP was 78 mmHg, the median CPPopt 83 mmHg. Mortality was lowest in the group of patients with a CPP close to their CPPopt. However, for none of the CPPopt variables a significant association to outcome was found. The percentage of time with impaired autoregulation and hemorrhage volume were independent predictors for acceptable outcome (mRS 1 to 4) at three months. Conclusions Failure of pressure reactivity seems common following severe ICH and is associated with unfavorable outcome. Real-time assessment of CPPopt is feasible in ICH and might provide a tool for an autoregulation-oriented CPP management. A larger trial is needed to explore if a CPPopt management results in better functional outcomes.

The aim of this study was to co-record electrical changes using electrocorticography (ECoG) and blood volume changes using intrinsic optical signal (IOS) imaging during the induction, propagation, and termination of cortical spreading depolarizations (CSDs).Anesthetized male swine were craniotomized and monitored over 16-20 h. A ten-contact electrode strip was placed on the cortex of one hemisphere for ECoG. An optical imaging recording was implemented using a camera with an optical bandpass filter (564 nm, FWHM:15 nm) and a full spectrum light source. CSDs were induced by mechanical and KCl stimulation. Co-occurrences of ECoG baseline shifts and blood volume changes around electrodes were identified.A mean of 3 CSDs per hour were induced, in a total of 4 swine during 80 h of recording. The propagation of the CSDs increased progressively over the monitoring time. IOS enabled us to clearly visualize the induction, propagation, and termination of CSDs with a spatial resolution within the sub-millimeter range. Every CSD recorded using ECoG could also be observed in IOS imaging, although some blood volume changes of CSDs were observed that terminated before reaching any of the ECoG electrodes.IOS imaging enables an in vivo evaluation of CSD dynamics over a large surface of gyrencephalic brain.

Background: The role of decompressive craniectomy (DC) in aneurysmal subarachnoid hemorrhage (aSAH) patients is still controversial. In this study we evaluated the effect of DC for aSAH patients. Methods: A matched-pair analysis was performed to compare the outcomes of patients with DC to those of patients without DC. Among 295 consecutive aSAH patients, 56 required DC. Of the remaining group, 56 matched controls were found. The match was conducted on the basis of epidemiological and potential prognostic factors, such as age, gender, World Federation of Neurosurgical Societies (WFNS) grade, Fisher group and occurrence of vasospasm. Results: Fifty-four of 56 (96.4%) patients with DC were dependent or dead at 1 month, compared with 49 of 56 (87.5%) without DC. There was no significant difference between the groups (p = 0.16). One-year outcomes were available for 108 patients (96.4%). Thirty-nine of 54 (72.2%) patients treated with DC were dependent or dead at 1 year, compared with 30 of 54 (55.6%) patients in the control group. There was no significant difference between the groups (p = 0.11). This result was unaffected by age, sex and WFNS grade. Subgroup analyses whether DC was performed primarily or delayed, and whether DC was performed due to spasm, hematoma or vessel occlusion failed to detect any significant difference. Conclusion: There was no significant advantage for patients treated with DC, but more than 25% achieved a good long-term outcome. While the value of DC is deemed uncertain, it may be effective for a very specific subset of aSAH patients. Further comparative studies are needed to resolve this matter.

Background and Purpose— We studied the dynamics of extracellular brain tissue concentrations of glucose, lactate, pyruvate, and glutamate during the occurrence of spreading depolarizations (SDs) in patients with aneurysmal subarachnoid hemorrhage. Methods— In this prospective observational study, patients with aneurysmal subarachnoid hemorrhage received multimodal cerebral monitoring, including intracranial pressure, cerebral microdialysis, and subdural electrocorticography. Results— Seven of the 17 recruited patients had intracerebral hemorrhage, acute ischemia and severe brain oedema leading to acute ischemic neurological deficits associated with early disturbance of metabolism at the recording site. They displayed a total of 130 SDs. The remaining 10 patients without acute ischemic neurological deficits exhibited 138 single SDs and 68 SDs in clusters. In patients without acute ischemic neurological deficits, clustered SDs were associated with a significant transient decrease in glucose and increase in lactate compared with baseline during the first 140 minutes after SDs. Moreover, the number of clustered SDs correlated with the outcome ( R =−0.659; P Conclusion— SDs can propagate in nonischemic human brain tissue. Clusters of SDs are related to metabolic changes suggestive of ongoing secondary damage in primarily nonischemic brain tissue.

The pathogenesis of delayed cerebral ischemia (DCI) is multifactorial and not completely elucidated. Our objective was to determine if episodes of spreading depolarization (SD) are reflected in compromised levels of extracellular glucose monitored by bedside microdialysis (MD) in aneurysmal subarachnoid hemorrhage (aSAH) patients. Patients with aSAH, prospectively included in the COSBID (CoOperative Study on Brain Injury Depolarisations) protocol (Berlin, Heidelberg), had hourly monitoring of cerebral glucose by MD and in parallel electrocorticographic (ECoG) monitoring for SD detection on day of admission until days 10-14 after aSAH. Cerebral MD probes were placed in the vascular territory at risk for DCI. Twenty-one aSAH patients (53.3 ± 9.1 years; mean ± standard deviation), classified according to the World Federation of Neurosurgical Societies (WFNS) in low (I-III, 11) and high (IV-V, 10) grades, were studied. Of these, 13 patients (62%) presented with DCI. Median glucose was 1.48 (0.00-8.79). Median occurrence of SD was 7 (0-66)/patients. High WFNS grade (WFNS grades IV-V) patients had more SDs (p = 0.027), while the overall glucose level did not differ. In high-grade SAH patients, SDs were more frequent. Individually, the occurrence of SD was not linked to local deviations (neither high nor low) from the LOWESS (locally weighted scatterplot smoothing) trend curve for extracellular glucose concentrations. Rapid-sampling MD techniques and analyses of SD clusters may elucidate more detail of the relationship between SD and brain energy metabolism.

To evaluate whether cortical spreading depolarizations (CSD) occur in the early stage after cortical intracerebral hemorrhage (ICH).Ten anesthetized male swine were examined over 19 h. Two cerebral probes were inserted around the ICH (microdialysis and thermodiffusion cerebral blood flow), ICP was monitored contralaterally and up to two electrocorticographic grid electrodes were positioned over the hemisphere after hemicraniectomy and dural opening. A right frontal autologous, arterial ICH (3.0 mL) was induced in all the animals studied.Using a modified injection technique an 80% success rate in ICH formation could be achieved. Eight animals with cortical ICH could be analyzed finally. After induction of ICH, ICP increased non-significantly. Overall, six out of eight animals had CSDs, of either single type or clusters. In one animal a CSD occurred as early as 2 h after ICH; in all other animals the first CSD did not occur before 5 h after onset.CSD's occur in cortical experimental ICH. As ICP remained stable owing to the hemicraniectomy we cannot argue in favor of ICP-related triggering of CSD. Modifications of the experimental setup avoiding hemicraniectomy may better describe the pathophysiology of CSD related to ICH in future studies.

The infection by Helicobacter pylori affects approximately 50% of the world population, in average, nevertheless the geographical area and the socioeconomic conditions are determining for the infection in earlier ages, not even that, only 20% of these patients will develop gastroduodenal disease. The infection is distributed universally, concerning more to the countries in routes of development, where he appears with major frequency in the infantile and young population. In Mexico the seroprevalence studies founded that 20% of the children of one year old already had developed antibodies Ig G against Helicobacter pylori and 50% of them are positive 10 years after The major prevalence is reached between 25 and 30 years of age. In our community we do not know the prevalence of active infection.The study group became from three different communities: Group A. Formed with children from half-low socioeconomic level, which they come habitually to a school placed in the conurban zone of the city of Puebla, Mexico and that inhabit a marginal area of asistential services of sanitary attention. Group B. Formed with children from the rural zone, of socioeconomic rural way, which habitually they come to a school placed in the surroundings of the City of Puebla, Mexico and that live in a rural zone, with regular services of sanitary attention. Group C. Formed with children from high socioeconomic level, which they come habitually to a private school placed in the city of It Populates, Mexico and that inhabit in zones with all the sanitary services.The group A was formed by 94 children, 23 of them was positive to Hp antigen (24.46%) and negatives 71 (75.54%). The group B was formed by 94 children, 17 of them was positive to Hp antigen (18.08%) and negatives 77 (81.92%). The group C was formed by 94 children, two of them was positive to Hp antigen (2.12%) and 92 negatives (97.88%). Statistically significant differences was found in: The days that eat meat, the drainage in the domicile, in the prevalence of antigen, if they have breakfast every day, the number of persons who live in the room, if there is drinkable water in the domicile, if they have drainage in the domicile, if they present diarrheic stools, if they possess wild animals. And no relation with the age, the kind (genre), the existence of domestic animals and the presence of abdominal pain.It is a question of three different populations in the same territory, the first one located in a conurban zone of regular services of health demonstrates a prevalence of almost 25%. The second from a rural zone, who live and study out of the circle of the city and in this one found 18% of positive results and the third group living in the city but with all the sanitary services that reported 2%. Only the drainage presence intra domiciliary and the fact that they were eating meat a week demonstrated to have statistic importance in three groups. To have drinkable water and the number of persons who coexist in the house demonstrated the sanitary conditions that also prevailed statistically in the group A and B in relation to the control group; The presence of diarrheic stools in the group A statistically significant make us suspect that one hand the sanitary environmental conditions to that these children are submitted are not the bestones.

Different types of scabies have been described based on their clinical outcome, one of which is the Crusted (Norwegian) type. This is an extreme manifestation of scabies that can be observed mainly among immunosupressed patients. A case ofa 42 year-old homosexual man is described. The patient was diagnosed with HIV, presenting pruritic lesions with a 4 month evolution in trunk and extremities. Lesions included xerosis, decapitated papules, badges with erythema, residual hyperchromic stains, multiple abrasions and ungueal pigmentation in both feet. At the beginning it was treated as apsorasiform dermatitis with steroids and antipruritics without success. Through a biopsy the suspected diagnosis of Crusted (Norwegian) scabies was confirmed. The patient was treated with a dose of oral ivermectin and topical benzyl benzoate and showed remission after two days.