The effects of cerebral pressure autoregulation status and CPP levels on cerebral metabolism in pediatric traumatic brain injury.

BACKGROUND: Cerebral perfusion pressure (CPP) management in the developing child with traumatic brain injury (TBI) is challenging. The pressure reactivity index (PRx) may serve as marker of cerebral pressure autoregulation (CPA) and optimal CPP (CPPopt) may be assessed by identifying the CPP level with best (lowest) PRx. To evaluate the potential of CPPopt guided management in children with severe TBI, cerebral microdialysis (CMD) monitoring levels of lactate and the lactate/pyruvate ratio (LPR) (indicators of ischemia) were related to actual CPP levels, autoregulatory state (PRx) and deviations from CPPopt (ΔCPPopt). METHODS: Retrospective study of 21 children ≤ 17 years with severe TBI who had both ICP and CMD monitoring were included. CPP, PRx, CPPopt and ΔCPPopt where calculated, dichotomized and compared with CMD lactate and lactate-pyruvate ratio. RESULTS: Median age was 16 years (range 8-17) and median Glasgow coma scale motor score 5 (range 2-5). Both lactate (p = 0.010) and LPR (p = < 0.001) were higher when CPP ≥ 70 mmHg than when CPP < 70. When PRx ≥ 0.1 both lactate and LPR were higher than when PRx < 0.1 (p = < 0.001). LPR was lower (p = 0.012) when CPPopt ≥ 70 mmHg than when CPPopt < 70, but there were no differences in lactate levels. When ΔCPPopt > 10 both lactate (p = 0.026) and LPR (p = 0.002) were higher than when ΔCPPopt < -10. CONCLUSIONS: Increased levels of CMD lactate and LPR in children with severe TBI appears to be related to disturbed CPA (PRx). Increased lactate and LPR also seems to be associated with actual CPP levels ≥ 70 mmHg. However, higher lactate and LPR values were also seen when actual CPP was above CPPopt. Higher CPP appears harmful when CPP is above the upper limit of pressure autoregulation. The findings indicate that CPPopt guided CPP management may have potential in pediatric TBI.

A Transfusion Regimen With Same-donor Packed Red Blood Cells Reduces Exposure to Multiple Blood Donors in Craniosynostosis Surgery.

In major craniosynostosis surgery with moderate to severe blood loss, patients may be exposed to multiple donors. We have previously reported a method for reducing donor exposure using mixed pediatric units including plasma. To further reduce donor exposure, we used plasma-free divided pediatric units. The study aimed to investigate the feasibility of the new strategy for reducing donor exposure. This prospective observational study recruited children younger than 1 year who were scheduled for nonsyndromic craniosynostosis surgery. One adult red blood cell unit was divided into 4 equal units on the day before the operation for use intra- or postoperatively. Number of donor exposures, estimated blood loss, crystalloid, colloid, and blood product volumes, and coagulation parameters were evaluated. Nineteen infants were included. The mean estimated blood loss was 19 (3) mL/kg and the transfusion volume was 17 (7) mL/kg. The median donor exposure per patient was 1 (range, 1-3). During surgery, all infants received at least one DPU. Two infants received transfusions from more than one donor during the intraoperative period. In the first 24 hours postoperatively, 14 infants received transfusion; 10 received only DPUs, whereas 4 received from multiple donors. In all, multiple donor exposure was prevented in 14 of 19 infants. Postoperative Pk-INR was 1.33 (0.16); no plasma or platelets were transfused. The plasma-free DPU transfusion protocol may be useful to reduce donor exposure in open craniosynostosis surgery in infants.

ICP, PRx, CPP, and ∆CPPopt in pediatric traumatic brain injury: the combined effect of insult intensity and duration on outcome.

PURPOSE: The aim was to investigate the combined effect of insult intensity and duration, regarding intracranial pressure (ICP), pressure reactivity index (PRx), cerebral perfusion pressure (CPP), and optimal CPP (CPPopt), on clinical outcome in pediatric traumatic brain injury (TBI). METHOD: This observational study included 61 pediatric patients with severe TBI, treated at the Uppsala University Hospital, between 2007 and 2018, with at least 12 h of ICP data the first 10 days post-injury. ICP, PRx, CPP, and ∆CPPopt (actual CPP-CPPopt) insults were visualized as 2-dimensional plots to illustrate the combined effect of insult intensity and duration on neurological recovery. RESULTS: This cohort was mostly adolescent pediatric TBI patients with a median age at 15 (interquartile range 12-16) years. For ICP, brief episodes (minutes) above 25 mmHg and slightly longer episodes (20 min) of ICP 20-25 mmHg correlated with unfavorable outcome. For PRx, brief episodes above 0.25 as well as slightly lower values (around 0) for longer periods of time (30 min) were associated with unfavorable outcome. For CPP, there was a transition from favorable to unfavorable outcome for CPP below 50 mmHg. There was no association between high CPP and outcome. For ∆CPPopt, there was a transition from favorable to unfavorable outcome when ∆CPPopt went below -10 mmHg. No association was found for positive ∆CPPopt values and outcome. CONCLUSIONS: This visualization method illustrated the combined effect of insult intensity and duration in relation to outcome in severe pediatric TBI, supporting previous notions to avoid high ICP and low CPP for longer episodes of time. In addition, higher PRx for longer episodes of time and CPP below CPPopt more than -10 mmHg were associated with worse outcome, indicating a potential role for autoregulatory-oriented management in pediatric TBI.

Incidence of Non-Syndromic and Syndromic Craniosynostosis in Sweden.

ABSTRACT: Premature craniosynostosis is a rare condition, with a wide range of incidence estimations in the literature. The aim of this study was to establish the current incidence among the Swedish population. Since the surgical care for these children is centralized to the 2 centers of Sahlgrenska University Hospital and Uppsala University Hospital, the 2 craniofacial hospital registries were examined for surgically treated children, all having a computed tomography verified diagnosis. Results show an incidence of 7.7 cases per 10,000 live births, including 0.60/10,000 syndromic craniosynostosis. Due to information programs among health care staff and a system for early diagnosis through rapid communication, these results seem to mirror the true incidence of craniosynostosis in the Swedish population. The updated incidence data will facilitate healthcare planning and make future studies of possible changes in craniosynostosis incidence more accurate.

Temporal effects of barbiturate coma on intracranial pressure and compensatory reserve in children with traumatic brain injury.

BACKGROUND: The aim was to study the effects of barbiturate coma treatment (BCT) on intracranial pressure (ICP) and intracranial compensatory reserve (RAP index) in children (< 17 years of age) with traumatic brain injury (TBI) and refractory intracranial hypertension (RICH). METHODS: High-resolution monitoring data were used to study the effects of BCT on ICP, mean arterial pressure (MAP), cerebral perfusion pressure (CPP), and RAP index. Four half hour long periods were studied: before bolus injection and at 5, 10, and 24 hours thereafter, respectively, and a fifth tapering period with S-thiopental between < 100 and < 30 µmol/L. S-thiopental concentrations and administered doses were registered. RESULTS: Seventeen children treated with BCT 2007-2017 with high-resolution data were included; median age 15 (range 6-17) and median Glasgow coma score 7 (range 3-8). Median time from trauma to start of BCT was 44.5 h (range 2.5-197.5) and from start to stop 99.0 h (range 21.0-329.0). Median ICP was 22 (IQR 20-25) in the half hour period before onset of BCT and 16 (IQR 11-20) in the half hour period 5 h later (p = 0.011). The corresponding figures for CPP were 65 (IQR 62-71) and 63 (57-71) (p > 0.05). The RAP index was in the half hour period before onset of BCT 0.6 (IQR 0.1-0.7), in the half hour period 5 h later 0.3 (IQR 0.1-0.7) (p = 0.331), and in the whole BCT period 0.3 (IQR 0.2-0.4) (p = 0.004). Eighty-two percent (14/17) had favorable outcome (good recovery = 8 patients and moderate disability = 6 patients). CONCLUSION: BCT significantly reduced ICP and RAP index with preserved CPP. BCT should be considered in case of RICH.

Cerebral Perfusion Pressure Variability Between Patients and Between Centres.

INTRODUCTION: The aim of this analysis was to investigate to what extent median cerebral perfusion pressure (CPP) differs between severe traumatic brain injury (TBI) patients and between centres, and whether the 2007 change in CPP threshold in the Brain Trauma Foundation guidelines is reflected in patient data collected at several centres over different time periods. METHODS: Data were collected from the Brain-IT database, a multi-centre project between 2003 and 2005, and from a recent project in four centres between 2009 and 2013. For patients nursed with their head up at 30° and with the blood pressure transducer at atrium level, CPP was corrected by 10 mmHg. Median CPP, interquartile ranges and total CPP ranges over the monitoring time were calculated per patient and per centre. RESULTS: Per-centre medians pre-2007 were situated between 50 and 70 mmHg in 6 out of 16 centres, while 10 centres had medians above 70 mmHg and 4 above 80 mmHg. Post-2007, three out of four centres had medians between 60 and 70 mmHg and one above 80 mmHg. One out of two centres with data pre- and post-2007 shifted from a median CPP of 76 mmHg to 60 mmHg, while the other remained at 68-67 mmHg. CONCLUSIONS: CPP data are characterised by a high inter-individual variability, but the data also suggest differences in CPP policies between centres. The 2007 guideline change may have affected policies towards lower CPP in some centres. Deviations from the guidelines occur in the direction of CPP > 70 mmHg.

Visualizing Cerebrovascular Autoregulation Insults and Their Association with Outcome in Adult and Paediatric Traumatic Brain Injury.

OBJECTIVE: The aim of this study is to assess visually the impact of duration and intensity of cerebrovascular autoregulation insults on 6-month neurological outcome in severe traumatic brain injury. MATERIAL AND METHODS: Retrospective analysis of prospectively collected minute-by-minute intracranial pressure (ICP) and mean arterial blood pressure data of 259 adult and 99 paediatric traumatic brain injury (TBI) patients from multiple European centres. The relationship of the 6-month Glasgow Outcome Scale with cerebrovascular autoregulation insults (defined as the low-frequency autoregulation index above a certain threshold during a certain time) was visualized in a colour-coded plot. The analysis was performed separately for autoregulation insults occurring with cerebral perfusion pressure (CPP) below 50 mmHg, with ICP above 25 mmHg and for the subset of adult patients that did not undergo decompressive craniectomy. RESULTS: The colour-coded plots showed a time-intensity-dependent association with outcome for cerebrovascular autoregulation insults in adult and paediatric TBI patients. Insults with a low-frequency autoregulation index above 0.2 were associated with worse outcomes and below -0.6 with better outcomes, with and approximately exponentially decreasing transition curve between the two intensity thresholds. All insults were associated with worse outcomes when CPP was below 50 mmHg or ICP was above 25 mmHg. CONCLUSIONS: The colour-coded plots indicate that cerebrovascular autoregulation is disturbed in a dynamic manner, such that duration and intensity play a role in the determination of a zone associated with better neurological outcome.

Effect of HHH-Therapy on Regional CBF after Severe Subarachnoid Hemorrhage Studied by Bedside Xenon-Enhanced CT.

BACKGROUND: Management of delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH) is difficult and still carries controversies. In this study, the effect of therapeutic hypervolemia, hemodilution, and hypertension (HHH-therapy) on cerebral blood flow (CBF) was assessed by xenon-enhanced computerized tomography (XeCT) hypothesizing an increase in CBF in poorly perfused regions. METHODS: Bedside XeCT measurements of regional CBF in mechanically ventilated SAH patients were routinely scheduled for day 0-3, 4-7, and 8-12. At clinical suspicion of DCI, patients received 5-day HHH-therapy. For inclusion, XeCT was required at 0-48 h before start of HHH (baseline) and during therapy. Data from corresponding time-windows were also collected for non-DCI patients. RESULTS: Twenty patients who later developed DCI were included, and twenty-eight patients without DCI were identified for comparison. During HHH, there was a slight nonsignificant increase in systolic blood pressure (SBP) and a significant reduction in hematocrit. Median global cortical CBF for the DCI group increased from 29.5 (IQR 24.6-33.9) to 38.4 (IQR 27.0-41.2) ml/100 g/min (P = 0.001). There was a concomitant increase in regional CBF of the worst vascular territories, and the proportion of area with blood flow below 20 ml/100 g/min was significantly reduced. Non-DCI patients showed higher CBF at baseline, and no significant change over time. CONCLUSIONS: HHH-therapy appeared to increase global and regional CBF in DCI patients. The increase in SBP was small, while the decrease in hematocrit was more pronounced, which may suggest that intravascular volume status and rheological effects are of importance. XeCT may be potentially helpful in managing poor-grade SAH patients.

Cerebellar mutism syndrome in children with brain tumours of the posterior fossa.

BACKGROUND: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has been reported in up to 39% of the patients but the exact incidence is uncertain since milder cases may be unrecognized. Recovery is usually incomplete. Reported risk factors are tumour type, midline location and brainstem involvement, but the exact aetiology, surgical and other risk factors, the clinical course and strategies for prevention and treatment are yet to be determined. METHODS: This observational, prospective, multicentre study will include 500 children with posterior fossa tumours. It opened late 2014 with participation from 20 Nordic and Baltic centres. From 2016, five British centres and four Dutch centres will join with a total annual accrual of 130 patients. Three other major European centres are invited to join from 2016/17. Follow-up will run for 12 months after inclusion of the last patient. All patients are treated according to local practice. Clinical data are collected through standardized online registration at pre-determined time points pre- and postoperatively. Neurological status and speech functions are examined pre-operatively and postoperatively at 1-4 weeks, 2 and 12 months. Pre- and postoperative speech samples are recorded and analysed. Imaging will be reviewed centrally. Pathology is classified according to the 2007 WHO system. Germline DNA will be collected from all patients for associations between CMS characteristics and host genome variants including pathway profiles. DISCUSSION: Through prospective and detailed collection of information on 1) differences in incidence and clinical course of CMS for different patient and tumour characteristics, 2) standardized surgical data and their association with CMS, 3) diversities and results of other therapeutic interventions, and 4) the role of host genome variants, we aim to achieve a better understanding of risk factors for and the clinical course of CMS - with the ultimate goal of defining strategies for prevention and treatment of this severely disabling condition. TRIAL REGISTRATION: Clinicaltrials.gov : NCT02300766 , date of registration: November 21, 2014.

An evaluation of the mixed pediatric unit for blood loss replacement in pediatric craniofacial surgery.

BACKGROUND: Surgical correction for craniosynostosis is often associated with significant perioperative hemorrhage. We implemented a transfusion strategy with a strict protocol including transfusion triggers, frequent assessment of coagulation tests, and the use of a novel transfusion unit, the mixed pediatric unit. AIM: The aim of the study was to evaluate if the applied transfusion strategy could reduce total blood loss and number of blood donors. METHODS: Children <1 year old admitted for craniosynostosis surgery were included for the study. On the day before surgery, an adult red blood cell unit was mixed with plasma and split into two mixed pediatric units-one intended for intraoperative use and the other saved for the postoperative period. A series of blood samples were obtained for standard coagulation parameters as well as thromboelastography to evaluate potential coagulopathy. Estimated blood loss, the number of additional standard packed red cell units opened in the first 24 h after surgery, the volume of fluid administered, and the total transfusion volumes were compared to a historical control group with similar age and characteristics. RESULTS: Nineteen infants were included in the study group, and were compared to 21 historical controls. There was a significant reduction of intraoperative transfusion volume. Twelve patients were transfused postoperatively, but in 8 of these additional exposure to packed red cell donor blood was avoided by using the saved mixed pediatric unit. In the historical controls, a total of 10 packed red cell units were used in nine patients postoperatively. No additional transfusions of plasma, platelets, fibrinogen, or tranexamic acid were needed in either group, and the coagulation parameters including thromboelastography remained within their respective normal ranges in the study group. CONCLUSION: For craniofacial surgery in infants, moderate perioperative blood loss and avoidance of coagulopathy is possible when a multifactorial approach is implemented. In this setting, intraoperative, but not total perioperative blood loss was reduced with the studied protocol. The study indicates that there may be a role for mixed pediatric units to reduce exposure to multiple donors although the reduction in total donor exposure was not significant.

Increased risk of critical CBF levels in SAH patients with actual CPP below calculated optimal CPP.

BACKGROUND: Cerebral pressure autoregulation can be quantified with the pressure reactivity index (PRx), based on the correlation between blood pressure and intracranial pressure. Using PRx optimal cerebral perfusion pressure (CPPopt) can be calculated, i.e., the level of CPP where autoregulation functions best. The relation between cerebral blood flow (CBF) and CPPopt has not been examined. The objective was to assess to which extent CPPopt can be calculated in SAH patients and to investigate CPPopt in relation to CBF. METHODS: Retrospective study of prospectively collected data. CBF was measured bedside with Xenon-enhanced CT (Xe-CT). The difference between actual CPP and CPPopt was calculated (CPP∆). Correlations between CPP∆ and CBF parameters were calculated with Spearman's rank order correlation coefficient (rho). Separate calculations were done using all patients (day 0-14 after onset) as well as in two subgroups (day 0-3 and day 4-14). RESULTS: Eighty-two patients with 145 Xe-CT scans were studied. Automated calculation of CPPopt was possible in adjunct to 60% of the Xe-CT scans. Actual CPP < CPPopt was associated with higher numbers of low-flow regions (CBF <10 ml/100 g/min) in both the early phase (day 0-3, n = 39, Spearman's rho = -0.38, p = 0.02) and late acute phase of the disease (day 4-14, n = 35, Spearman's rho = -0.39, p = 0.02). CPP level per se was not associated with CBF. CONCLUSIONS: Calculation of CPPopt is possible in a majority of patients with severe SAH. Actual CPP below CPPopt is associated with low CBF.

Telemetric intracranial pressure monitoring: a noninvasive method to follow up children with complex craniosynostoses. A case report.

INTRODUCTION: There are no reliable noninvasive methods of monitoring ICP. Most assessments are made by indirect measures and are difficult to follow over time. Invasive studies can be used but up until now have required in-hospital transcutaneous measurements. Accurate ICP recordings over longer periods of time can be very valuable in timing different surgical procedures in syndromal cases. This case shows that telemetric ICP monitoring can be used for long-term follow-up in patients that may need repeated surgeries related to their craniosynostosis condition. CASE REPORT: In this report, the telemetric ICP probe (Raumedic Neurovent-P-tel) was implanted before surgery and was used for repeated "noninvasive" ICP recordings pre- and postoperatively in a patient with craniosynostosis. The patient was an eight-year-old girl with pansynostosis with only the right lambdoid suture open. A telemetric ICP probe was implanted the day before cranial vault remodeling and the ICP was monitored pre- and postoperatively. The ICP was above 15 mmHg 72.2 % of the monitoring time before surgery, and the amplitude of the curve was greater than normal suggesting impaired compliance. Direct postoperative ICP was normal, and the amplitude was lower. The ICP was then monitored both in out-patient clinic and in four longer hospital stays. Both the values and the curves were analyzed, and the time with ICP above 15 mmHg decreased over time, and the waveform amplitude of the curves improved. CONCLUSION: This "noninvasive" way of recording ICP is a feasible and helpful tool in decision-making and intervening in patients with craniosynostosis.

Bedside Xenon-CT Shows Lower CBF in SAH Patients with Impaired CBF Pressure Autoregulation as Defined by Pressure Reactivity Index (PRx).

BACKGROUND: Subarachnoid hemorrhage (SAH) is a disease with a high rate of unfavorable outcome, often related to delayed cerebral ischemia (DCI), i.e., ischemic injury that develops days-weeks after onset, with a multifactorial etiology. Disturbances in cerebral pressure autoregulation, the ability to maintain a steady cerebral blood flow (CBF), despite fluctuations in systemic blood pressure, have been suggested to play a role in the development of DCI. Pressure reactivity index (PRx) is a well-established measure of cerebral pressure autoregulation that has been used to study traumatic brain injury, but not extensively in SAH. OBJECTIVE: To study the relation between PRx and CBF in SAH patients, and to examine if PRx can be used to predict DCI. METHODS: Retrospective analysis of prospectively collected data. PRx was calculated as the correlation coefficient between mean arterial blood pressure (MABP) and intracranial pressure (ICP) in a 5 min moving window. CBF was measured using bedside Xenon-CT (Xe-CT). DCI was diagnosed clinically. RESULTS: 47 poor-grade mechanically ventilated patients were studied. Patients with disturbed pressure autoregulation (high PRx values) had lower CBF, as measured by bedside Xe-CT; both in the early (day 0-3) and late (day 4-14) acute phase of the disease. PRx did not differ significantly between patients who developed DCI or not. CONCLUSION: In mechanically ventilated and sedated SAH patients, high PRx (more disturbed CBF pressure autoregulation) is associated with low CBF, both day 0-3 and day 4-14 after onset. The role of PRx as a monitoring tool in SAH patients needs further studying.

Cerebral pressure autoregulation and optimal cerebral perfusion pressure during neurocritical care of children with traumatic brain injury.

OBJECTIVE: The management of cerebral perfusion pressure (CPP) is a challenge in children with traumatic brain injury (TBI) because the normal blood pressure is age dependent and the role of cerebral pressure autoregulation (CPA) is unclear. In this study, the authors aimed to examine the pressure reactivity index (PRx), CPP, optimal CPP (CPPopt), and deviations from CPPopt (ΔCPPopt) in a series of children with TBI generally and regarding age relations, temporal changes, and the influence on outcome. METHODS: Intracranial pressure (ICP) and mean arterial pressure (MAP) monitoring data were collected during neurointensive care in 57 children who sustained a TBI and were ≤ 17 years of age. CPP, PRx, CPPopt, and ΔCPPopt (actual CPP - CPPopt) were calculated. Clinical outcomes at 6 months postinjury were dichotomized into favorable outcomes (Glasgow Outcome Scale [GOS] score 4 or 5) and unfavorable outcomes (GOS scores 1-3). RESULTS: The median patient age was 15 (range 0.5-17) years, and the median Glasgow Coma Scale motor score at admission was 5 (range 2-5). Forty-nine (86%) of the 57 patients had favorable outcomes. For the entire group, lower PRx (better preserved CPA) was associated with a more favorable outcome (p = 0.023, ANCOVA adjusted for age). When the children were divided into age groups, this finding was statistically significant in children ≤ 15 years of age (p = 0.016), but not in children ≥ 16 years (p = 0.528). In children ≤ 15 years, a lower proportion of time with ΔCPPopt < -10% was significantly associated with a favorable outcome (p = 0.038), but not in the older age group. Temporal analysis indicated that PRx was higher (more impaired CPA) from day 4 and CPPopt was higher from day 6 in the unfavorable outcome group compared with the favorable outcome group, although those findings were not significant. CONCLUSIONS: Impaired CPA is related to poor outcome, particularly in children ≤ 15 years of age. In that age group, actual CPP below the CPPopt level contributed significantly to unfavorable outcome, while levels close to or above the CPPopt were unrelated to outcome. CPPopt appears to be higher during the time period when CPA is most impaired.

Decompressive craniectomy as a second/third-tier intervention in traumatic brain injury: A multicenter observational study.

OBJECTIVES: RESCUEicp studied decompressive craniectomy (DC) applied as third-tier option in severe traumatic brain injury (TBI) patients in a randomized controlled setting and demonstrated a decrease in mortality with similar rates of favorable outcome in the DC group compared to the medical management group. In many centers, DC is being used in combination with other second/third-tier therapies. The aim of the present study is to investigate outcomes from DC in a prospective non-RCT context. METHODS: This is a prospective observational study of 2 patient cohorts: one from the University Hospitals Leuven (2008-2016) and one from the Brain-IT study, a European multicenter database (2003-2005). In thirty-seven patients with refractory elevated intracranial pressure who underwent DC as a second/third-tier intervention, patient, injury and management variables including physiological monitoring data and administration of thiopental were analysed, as well as Extended Glasgow Outcome score (GOSE) at 6 months. RESULTS: In the current cohorts, patients were older than in the surgical RESCUEicp cohort (mean 39.6 vs. 32.3; p < 0.001), had higher Glasgow Motor Score on admission (GMS < 3 in 24.3% vs. 53.0%; p = 0.003) and 37.8% received thiopental (vs. 9.4%; p < 0.001). Other variables were not significantly different. GOSE distribution was: death 24.3%; vegetative 2.7%; lower severe disability 10.8%; upper severe disability 13.5%; lower moderate disability 5.4%; upper moderate disability 2.7%, lower good recovery 35.1%; and upper good recovery 5.4%. The outcome was unfavorable in 51.4% and favorable in 48.6%, as opposed to 72.6% and 27.4% respectively in RESCUEicp (p = 0.02). CONCLUSION: Outcomes in DC patients from two prospective cohorts reflecting everyday practice were better than in RESCUEicp surgical patients. Mortality was similar, but fewer patients remained vegetative or severely disabled and more patients had a good recovery. Although patients were older and injury severity was lower, a potential partial explanation may be in the pragmatic use of DC in combination with other second/third-tier therapies in real-life cohorts. The findings underscore that DC maintains an important role in managing severe TBI.

Novel amplifications in pediatric medulloblastoma identified by genome-wide copy number profiling.

Medulloblastoma (MB) is a WHO grade IV, invasive embryonal CNS tumor that mainly affects children. The aggressiveness and response to therapy can vary considerably between cases, and despite treatment, ~30% of patients die within 2 years from diagnosis. Furthermore, the majority of survivors suffer long-term side-effects due to severe management modalities. Several distinct morphological features have been associated with differences in biological behavior, but improved molecular-based criteria that better reflect the underlying tumor biology are in great demand. In this study, we profiled a series of 25 MB with a 32K BAC array covering 99% of the current assembly of the human genome for the identification of genetic copy number alterations possibly important in MB. Previously known aberrations as well as several novel focally amplified loci could be identified. As expected, the most frequently observed alteration was the combination of 17p loss and 17q gain, which was detected in both high- and standard-risk patients. We also defined minimal overlapping regions of aberrations, including 16 regions of gain and 18 regions of loss in various chromosomes. A few noteworthy narrow amplified loci were identified on autosomes 1 (38.89-41.97 and 84.89-90.76 Mb), 3 (27.64-28.20 and 35.80-43.50 Mb), and 8 (119.66-139.79 Mb), aberrations that were verified with an alternative platform (Illumina 610Q chips). Gene expression levels were also established for these samples using Affymetrix U133Plus2.0 arrays. Several interesting genes encompassed within the amplified regions and presenting with transcript upregulation were identified. These data contribute to the characterization of this malignant childhood brain tumor and confirm its genetic heterogeneity.

Central nervous system hemangioblastomas in von Hippel-Lindau disease: Total growth rate and risk of developing new lesions not associated with circulating VEGF levels.

BACKGROUND: Hemangioblastomas of the central nervous system are a prominent feature of von Hippel-Lindau-disease (vHL). Hemangioblastomas are known to secrete vascular endothelial growth factor (VEGF), suggesting a potential role of VEGF as a biomarker for tumor growth. METHODS: Plasma VEGF samples from 24 patients with von Hippel-Lindau disease were analyzed by solid-phase proximity ligation assay (PLA). Levels were monitored over time together with numeric and volumetric CNS tumor burden, and compared to plasma VEGF levels in healthy controls. RESULTS: The mean yearly progression in tumor volume was 65.5%. Yearly risk of developing one or several new CNS tumor(s) was 50%. No significant correlation between tumor burden and levels of VEGF was seen. VEGF levels in patients (31.55-92.04; mean 55.83, median 56.41) as measured by immunodetection in a solid-phase PLA did not differ significantly from controls (37.38-104.56; mean 58.89, median 54.12) (p = 0,266). CONCLUSION: The increase in total CNS tumor volume in vHL occurred in a saltatory manner. The risk of developing a new lesion was 50% per year. We found no evidence for VEGF secretion from CNS hemangioblastomas in vHL in circulating blood. Other potential biomarkers should be explored to assess progression of tumor burden in vHL.

Neurointensive care is justified in elderly patients with severe subarachnoid hemorrhage--an outcome and secondary insults study.

PURPOSE: The aim was to study the outcome and the occurrence of secondary brain insults in elderly patients with severe subarachnoid hemorrhage (SAH) in comparison to younger patients. METHODS: Ninety-nine patients with severe SAH requiring a ventriculostomy and management at the neurointensive care unit with at least 120 h of multimodality monitoring data during the first 240 h following SAH were included. Data were continuously recorded for intracranial pressure (ICP), cerebral perfusion pressure, blood pressure, oxygen saturation, and temperature. Secondary insult levels were defined and quantified as percent of good monitoring time at insult level. Outcome according to the Glasgow Outcome Scale was evaluated at 6 months after the SAH. Age-dependent differences in occurrence of secondary insults and clinical characteristics were analyzed with multiple regression analysis. RESULTS: Good recovery or moderate disability was achieved in 24.1% of the elderly and in 42.9% of the younger patients. The frequency of severe disability was 41.4% in the elderly and 37.1% in the younger patients. The occurrence of ICP insults was lower and the occurrence of hypertensive, hypotensive, and hypoxemic insults were higher in the elderly patients. CONCLUSIONS: An independent outcome was achieved in a substantial proportion of the elderly with severe SAH, and the proportion of severe disability was not greater than among the younger patients, which justifies neurointensive care also in elderly patients. The occurrence of secondary insults was age dependent. Future studies of multimodality monitoring may provide age-specific secondary insult levels necessary for a tailored neurointensive care specific for elderly patients with severe SAH.