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Climate, e.g., air temperature and precipitation, differs strongly between urban and peripheral areas, which causes diverse life conditions for trees. In order to compare tree growth, we sampled in total 252 small-leaved lime trees (Tilia cordata Mill) in the city of Berlin along a gradient from the city center to the surroundings. By means of increment cores, we are able to trace back their growth for the last 50 to 100 years. A general growth trend can be shown by comparing recent basal area growth with estimates from extrapolating a growth function that had been fitted with growth data from earlier years. Estimating a linear model, we show that air temperature and precipitation significantly influence tree growth within the last 20 years. Under consideration of housing density, the results reveal that higher air temperature and less precipitation led to higher growth rates in high-dense areas, but not in low-dense areas. In addition, our data reveal a significantly higher variance of the ring width index in areas with medium housing density compared to low housing density, but no temporal trend. Transferring the results to forest stands, climate change is expected to lead to higher tree growth rates.

Background: Intraoperative navigated ultrasonography has reached clinical acceptance, while published data for the accuracy of some systems are missing. We technically quantified and optimised the accuracy of the integration of an external ultrasonography system into a BrainLab navigation system., Methods: A high-end ultrasonography system (Elegra; Siemens, Erlangen, Germany) was linked to a navigation system (Vector Vision; BrainLab, Munich, Germany). In vitro accuracy and precision was calculated from differences between a real world target (high-precision crosshair phantom) and the ultrasonography image of this target in the navigation coordinate system. The influence of the intrinsic component of the calibration phantom (for ultrasonography probe registration), type of target definition (manual versus automatic) and orientation of the ultrasound probe in relation to the navigation tracking device on accuracy and precision were analysed in different settings (100 measurements for each setting) resembling clinically relevant scenarios in the neurosurgical operating theatre., Results: Line-of-sight angles of 45°, 62° and 90° for the optical tracking of the navigated ultrasonography probe and a distance of 1.8 m revealed best accuracy and precision. Technical accuracy of the integration of ultrasonography into a standard navigation system is high [Euclidean error: median, 0.79 mm; mean, 0.89 ± 0.42 mm for 62° angle; median range: 1.16-1.46 mm; mean range (±SD): 1.22 ± 0.32 mm to 1.46 ± 0.55 mm for grouped analysis of all angles tested]. Software-based automatic target definition improved precision significantly (p < 0.001)., Conclusions: Integration of an external ultrasonography system into the BrainLab navigation is accurate and precise. By modifying registration (and measurement conditions) via software modification, the in vitro accuracy and precision is improved and requirements for a clinical application are fully met.

Multiple trauma (MT) associated with hemorrhagic shock (HS) might lead to cerebral hypoperfusion and brain damage. We investigated cerebral alterations using a new porcine MT/HS model without traumatic brain injury (TBI) and assessed the neuroprotective properties of mild therapeutic hypothermia. Male pigs underwent standardized MT with HS (45% or 50% loss of blood volume) and resuscitation after 90/120 min (T90/T120). In additional groups (TH90/TH120) mild hypothermia (33°C) was induced following resuscitation. Normothermic or hypothermic sham animals served as controls. Intracranial pressure, cerebral perfusion pressure (CPP), and cerebral oxygenation (PtiO2) were recorded up to 48.5 h. Serum protein S-100B and neuron-specific enolase (NSE) were measured by ELISA. Cerebral inflammation was quantified on hematoxylin and eosin -stained brain slices; Iba1, S100, and inducible nitric oxide synthase (iNOS) expression was assessed using immunohistochemistry. Directly after MT/HS, CPP and PtiO2 were significantly lower in T90/T120 groups compared with sham. After resuscitation both parameters showed a gradual recovery. Serum protein S-100B and NSE increased temporarily as a result of MT/HS in T90 and T90/T120 groups, respectively. Cerebral inflammation was found in all groups. Iba1-staining showed significant microgliosis in T90 and T120 animals. iNOS-staining indicated a M1 polarization. Mild hypothermia reduced cerebral inflammation in the TH90 group, but resulted in increased iNOS activation. In this porcine long-term model, we did not find evidence of gross cerebral damage when resuscitation was initiated within 120 min after MT/HS without TBI. However, trauma-related microglia activation and M1 microglia polarization might be a consequence of temporary hypoxia/ischemia and further research is warranted to detail underlying mechanisms. Interestingly, mild hypothermia did not exhibit neuroprotective properties when initiated in a delayed fashion.

Background: Previous studies revealed evidence that induced hypothermia attenuates ischemic organ injuries after severe trauma. In the present study, the effect of hypothermia on liver damage was investigated in a porcine long term model of multi-system injury, consisting of blunt chest trauma, penetrating abdominal trauma, musculoskeletal injury, and hemorrhagic shockMETHODS: In 30 pigs, a standardized polytrauma including blunt chest trauma, penetrating abdominal trauma, musculoskeletal injury, and hemorrhagic shock of 45% of total blood volume was induced. Following trauma, hypothermia of 33∘C was induced for 12 h and intensive care treatment was evaluated for 48 h. As outcome parameters, we assessed liver function and serum transaminase levels as well as a histopathological analysis of tissue samples. A further 10 animals served as controls., Results: Serum transaminase levels were increased at the end of the observation period following hypothermia without reaching statistical significance compared to normothermic groups. Liver function was preserved (p⩽ 0.05) after the rewarming period in hypothermic animals but showed no difference at the end of the observation period. In H&E staining, cell death was slightly increased hypothermic animals and caspase-3 staining displayed tendency towards more apoptosis in hypothermic group as well., Conclusions: Induction of hypothermia could not significantly improve hepatic damage during the first 48 h following major trauma. Further studies focusing on multi-organ failure including a longer observation period are required to illuminate the impact of hypothermia on hepatic function in multiple trauma patients.

Despite the importance of urban trees, their growth reaction to climate change and to the urban heat island effect has not yet been investigated with an international scope. While we are well informed about forest growth under recent conditions, it is unclear if this knowledge can be simply transferred to urban environments. Based on tree ring analyses in ten metropolises worldwide, we show that, in general, urban trees have undergone accelerated growth since the 1960s. In addition, urban trees tend to grow more quickly than their counterparts in the rural surroundings. However, our analysis shows that climate change seems to enhance the growth of rural trees more than that of urban trees. The benefits of growing in an urban environment seem to outweigh known negative effects, however, accelerated growth may also mean more rapid ageing and shortened lifetime. Thus, city planners should adapt to the changed dynamics in order to secure the ecosystem services provided by urban trees.

Background: The basic necessities for surgical procedures are illumination, exposure, and magnification. These have undergone transformation in par with technology. One of the recent developments is the compact magnifying exoscope system. In this report, we describe the application of this system for surgical operations and discuss its advantages and pitfalls., Methods: We used the ViTOM exoscope mounted on the mechanical holding arm. The following surgical procedures were conducted: lumbar and cervical spinal canal decompression (n = 5); laminotomy and removal of lumbar migrated disk herniations (n = 4); anterior cervical diskectomy and fusion (n = 1); removal of intraneural schwannomas (n = 2); removal of an acute cerebellar hemorrhage (n = 1); removal of a parafalcine atypical cerebral hematoma caused by a dural arteriovenous fistula (n = 1); and microsutures and anastomoses of a nerve (n = 1), an artery (n = 1), and veins (n = 2)., Results: The exoscope offered excellent, magnified, and brilliantly illuminated high-definition images of the surgical field. All surgical operations were successfully completed. The main disadvantage was the adjustment and refocusing using the mechanical holding arm. The time required for the surgical operation under the exoscope was slightly longer than the times required for a similar procedure performed using an operating microscope., Conclusions: The magnifying exoscope is an effective and nonbulky tool for surgical procedures. In visualization around the corners, the exoscope has better potential than a microscope. With technical and technologic modifications, the exoscope might become the next generation in illumination, visualization, exposure, and magnification for high-precision surgical procedures., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Quartz crystal microbalance (QCM) is emerging as a versatile tool for studying lipid phase behavior. The technique is attractive for fundamental biophysical studies as well applications because of its simplicity, flexibility, and ability to work with very small amounts of material crucial for biomedical studies. Further progress hinges on the understanding of the mechanism, by which a surface-acoustic technique such as QCM, senses lipid phase changes. Here, we use a custom-built instrument with improved sensitivity to investigate phase behavior in solid-supported lipid systems of different geometries (adsorbed liposomes and bilayers). We show that we can detect a model anesthetic (ethanol) through its effect on the lipid phase behavior. Further, through the analysis of the overtone dependence of the phase transition parameters, we show that hydrodynamic effects are important in the case of adsorbed liposomes, and viscoelasticity is significant in supported bilayers, while layer thickness changes make up the strongest contribution in both systems.

The first example of a bis-hemithioindigo (bis-HTI)-based molecular receptor was realized. Its folding and selective binding affinity for aromatic guest molecules can be precisely controlled by visible light and heat. The thermodynamically stable state of the bis-HTI is the s-shaped planar Z,Z-configuration. After irradiation with 420 nm light only the E,Z-configuration is formed in a highly selective photoisomerization. The E,Z-isomer adopts a helical conformation because of the implementation of repulsive steric interactions. The E,Z-configured helix is able to recognize electron-poor aromatic guests exclusively through polar aromatic interactions and also distinguishes between regioisomers. After heating, the Z,Z-configuration is completely restored and the aromatic guest molecule is efficiently released., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Near-infrared spectroscopy (NIRS) has been shown to aid in the diagnosis of extremity acute compartment syndrome (ACS), offering continuous real-time capability to monitor perfusion in extremities. Porcine models of ACS have been developed to attempt to aid in the understanding of the development of ACS and provide better methods of diagnosing ACS. The objective of the present study was to assess and correlate NIRS, tibial intracompartmental pressure (TICP), tibial intracompartmental perfusion pressure (TIPP), serum markers of inflammation and muscle injury in a balloon compression model of ACS., Methods: Six swine were used. Balloon catheters were inflated below the cranial tibial muscle. Systolic, diastolic, and mean arterial pressures; compartmental pressures; and oximetry were measured before, during, and after balloon inflation/deflation. Cranial tibial muscle was collected for muscle damage scoring. Serum creatine kinase, myoglobin, tumor necrosis factor α, IL-1β, and IL-6 were measured. Data analysis included comparing differences in TICP, NIRS, and TIPP measurements as well as creatine kinase, myoglobin, tumor necrosis factor α, IL-1β, and IL-6 levels between time points. Pearson correlations were calculated for muscle degeneration and edema and NIRS., Results: Increases in TICP and decreases in TIPP were found. Near-infrared spectroscopy detected significant changes in tissue oxygenation at all the same time points. Myoglobin significantly increased from 45.7 ± 13.0 ng/mL (baseline) to 219.5 ± 57.3-ng/mL (balloon deflation) and continued to increase over the duration of the study. Creatine kinase significantly increased 2 hours after balloon deflation. Cranial tibial muscle degeneration, necrosis, and edema scores were higher in the test than the control legs., Conclusions: Near-infrared spectroscopy of the compartment provided a reliable, sensitive measure of both an increase and decrease in TICP and TIPP in this porcine balloon model of ACS. Creatine kinase and myoglobin significantly increased following balloon removal. Significant correlations between muscle degeneration, edema, hemorrhage, and NIRS were found.

Objective: Premature craniosynostosis of the lambdoid suture is rare. The use of differential diagnosis to rule out positional occipital plagiocephaly is crucial. Nevertheless, once diagnosed, lambdoid craniosynostosis requires corrective surgery to prevent intracranial harm and aesthetic stigma by significant dyscrania. Operative correction of the lambdoid fusion is often performed by suturectomy and helmet therapy, total occipital remodeling interventions, transposition of occipital bone flaps, or occipital advancement procedures either with or without distraction osteogenesis. We present a simple surgical maneuver to potentially correct the occipital and suboccipital constriction caused by unilateral lambdoid craniosynostosis., Materials and Methods: Three patients with true unilateral lambdoid synostosis underwent surgery. A straight-line skin incision was created, beginning at the caudal pole of the ipsilateral mastoideal bulge. The incision ran cranially and corresponded to the course of the lambdoid suture up to the posterior fontanel. The periosteum was incised and the contralateral (potent) lambdoid suture was identified at its origin. One burr-hole was created to separate the dura from the intern tabula. Afterwards, a square meander-shaped craniotomy was performed along the assumed course of the lambdoid suture. The squares were then forced apart to form the occipital and suboccipital area into a more rounded shape. The squares were fixed in those positions with resorbable plates or sutures. Pre- and postoperative three-dimensional (3D) photoscans were performed and analyzed with special software to follow the perioperative course of the cranial shape., Results: This new approach minimized the operative time and degree of blood-loss, and rounding of the occipital area was accomplished with only one unilateral intervention. In terms of the available photogrammetric data of two of the patients, the cranial vault asymmetry index, posterior symmetry ratio, and posterior/anterior skull volume ratio were improved but not normalized completely. The measurement outcome, as determined by an automated analysis of the photoscans, however, indicated clear flaws with regard to repeatability., Conclusion: A unilateral approach using a square meander-shaped craniotomy and subsequent inclination may be a suitable surgical method for correcting assorted cases of lambdoid craniosynostosis. Transposition of the occipital bone flaps, subtotal craniectomies of the occipital area, and occipital advancements with or without distraction devices may not be essential in all cases of lambdoid synostosis. However, the reliability of the automated analysis of three-dimensional photoscans must be determined., (Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

The worldwide cardiovascular disease (CVD) epidemic is of grave concern. A major role in the etiology of CVDs is played by the platelets (thrombocytes). Platelets are anuclear cell fragments circulating in the blood. Their primary function is to catalyze clot formation, limiting traumatic blood loss in the case of injury. The same process leads to thrombosis in the case of CVDs, which are commonly managed with antiplatelet therapy. Platelets also have other, nonhemostatic functions in wound healing, inflammation, and tissue regeneration. They play a role in the early stages of atherosclerosis and the spread of cancer through metastases. Much remains to be learned about the regulation of these diverse platelet functions under physiological and pathological conditions. Breakthroughs in this regard are expected to come from single platelet studies and systems approaches. The immobilization of platelets at surfaces is advantageous for developing such approaches, but platelets are activated when they come in contact with foreign surfaces. In this work, we develop and validate a protocol for immobilizing platelets on supported lipid bilayers without activation due to immobilization. Our protocol can therefore be used for studying platelets with a wide variety of surface-sensitive techniques.

Neuroendocrine disturbances are common after traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH), but only a few data exist on long-term anterior pituitary deficiencies after brain injury. We present data from the Structured Data Assessment of Hypopituitarism after TBI and SAH, a multi-center study including 1242 patients. We studied a subgroup of 351 patients, who had sustained a TBI (245) or SAH (106) at least 1 year before endocrine assessment (range 1-55 years) in a separate analysis. The highest prevalence of neuroendocrine disorders was observed 1-2 years post-injury, and it decreased over time only to show another maximum in the long-term phase in patients with brain injury occurring ≥5 years prior to assessment. Gonadotropic and somatotropic insufficiencies were most common. In the subgroup from 1 to 2 years after brain injury (n = 126), gonadotropic insufficiency was the most common hormonal disturbance (19%, 12/63 men) followed by somatotropic insufficiency (11.5%, 7/61), corticotropic insufficiency (9.2%, 11/119), and thyrotropic insufficiency (3.3%, 4/122). In patients observed ≥ 5 years after brain injury, the prevalence of somatotropic insufficiency increased over time to 24.1%, whereas corticotropic and thyrotrophic insufficiency became less frequent (2.5% and 0%, respectively). The prevalence differed regarding the diagnostic criteria (laboratory values vs. physician`s diagnosis vs. stimulation tests). Our data showed that neuroendocrine disturbances are frequent even years after TBI or SAH, in a cohort of patients who are still on medical treatment.

Depression is predicted to be the most common cause of disability in the coming decade. Self-inflicted hammer blow to the cranium is a rare phenomenon seen in patients with a history of attempted suicide. The resulting comminuted depressed skull fracture of the midline vertex is life threatening. Rapid interdisciplinary communication and intervention are essential to reduce morbidity and mortality. We present a case of self-inflicted hammer blows to the head, review the relevant literature on this topic, and discuss neurosurgical and psychiatric implications.

Background: The microsurgical unilateral laminotomy (MUL) technique for bilateral decompression of lumbar spinal stenosis (LSS) is a less destabilizing alternative to laminectomy and leads to good short-term outcomes. However, little is known about the long-term results including predictive factors., Methods: Medical records of patients who underwent MUL for LSS decompression between 2005 and 2010 were reviewed, and a questionnaire was distributed to complement the long-term outcome data. The study population consisted of 176 patients including 17 patients with stable grade I spondylolisthesis. Complications and reoperations were meticulously analyzed. Clinical outcome was measured using a modified Prolo scale and was further dichotomized in good vs. poor outcome. Predictive factors were obtained from uni- and multivariate analyses., Results: The median age of the cohort was 70.0 years and the follow-up 71.7 months. Complications occurred in 5.1 % of the patients. The overall reoperation rate was 17.0 %, including surgery, which was exclusively performed at other levels in 4.0 %. The reoperation rate for fusion was 4.5 %. Good neurogenic claudication outcome faded from 98.3 % at hospital discharge to 47.2 % at 6 years. Multivariate analysis identified previous lumbar operation as a potential independent predictor of a reoperation; potential independent predictors of poor long-term claudication outcome were older age, female gender, higher body mass index (BMI) and tobacco smoking., Conclusions: In our experience, the long-term reoperation rate after MUL for LSS is not negligible and higher in previously operated patients. It seems like the good initial clinical results after MUL may fade over time, and several patient-related predictive factors including potentially modifiable obesity and tobacco smoking seem to play an important role.

Pre-treatment with antiplatelet agents is described to be a risk factor for mortality after spontaneous intracerebral hemorrhage (ICH). However, the impact of antithrombotic agents on mortality in patients who undergo hematoma evacuation compared to conservatively treated patients with ICH remains controversial. This analysis is based on a prospective registry for quality assurance in stroke care in the State of Hesse, Germany. Patients' data were collected between January 2008 and December 2012. Only patients with the diagnosis of spontaneous ICH were included (International Classification of Diseases 10th Revision codes I61.0-I61.9). Predictors of in-hospital mortality were determined by univariate analysis. Predictors with P<0.1 were included in a binary logistic regression model. The binary logistic regression model was adjusted for age, initial Glasgow Coma Score (GCS), the presence of intraventricular hemorrhage (IVH), and pre-ICH disability prior to ictus. In 8,421 patients with spontaneous ICH, pre-treatment with oral anticoagulants or antiplatelet agents was documented in 16.3% and 25.1%, respectively. Overall in-hospital mortality was 23.2%. In-hospital mortality was decreased in operatively treated patients compared to conservatively treated patients (11.6% versus 24.0%; P<0.001). Patients with antiplatelet pre-treatment had a significantly higher risk of death during the hospital stay after hematoma evacuation (odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.24-4.97; P=0.010) compared to patients without antiplatelet pre-treatment treatment (OR: 0.9; 95% CI: 0.79-1.09; P=0.376). In conclusion a higher rate of in-hospital mortality after pre-treatment with antiplatelet agents in combination with hematoma evacuation after spontaneous ICH was observed in the presented cohort., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

High-mobility group AT-hook protein 2 (HMGA 2) is a transcription factor associated with malignancy and poor prognosis in a variety of human cancers. We correlated HMGA 2 expression with clinical parameters, survival, and O-6-methylguanine-DNA methyltransferase methylation status (MGMT) in glioblastoma patients. HMGA 2 expression was determined by performing quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in 44 glioblastoma patients and 5 non-tumorous brain specimens as controls. Gene expression levels of MGMT methylated vs. unmethylated patients, and gene expression levels between patient groups, both for qPCR and IHC data were compared using the Mann-Whitney U test. The relationship between HMGA 2 expression, progression-free survival and overall survival was analyzed using the Kaplan-Meier method and the log-rank test. P-values of <0.05 were considered statistically significant throughout the analyses. The mean age of patients at diagnosis was 57.4 ± 15.7 years, and the median survival was 16 months (SE 2.8; 95% CI, 10.6-21.4). HMGA 2 gene expression was significantly higher in glioblastoma compared to normal brain tissue on qPCR (mean, 0.35; SD, 0.27 vs. 0.03, SD, 0.05) and IHC levels (IRS mean, 17.21; SD, 7.43 vs. 3.20; SD, 1.68) (p=0.001). Survival analysis revealed that HMGA 2 overexpression was associated with a shorter progression-free and overall survival time in patients with methylation (n=24). The present study shows a tendency that HMGA 2 overexpression correlates with a poor prognosis of glioblastoma patients independent of MGMT methylation status. The results suggest that HMGA 2 could play an important role in the treatment of glioblastoma and could have a function in prognosis of this type of cancer.

Objective: Secondary complications (SC) after intracerebral hemorrhage (ICH) can worsen outcome and are associated with early death. The purpose of the present study was to determine in-hospital mortality rates and SC after spontaneous ICH during acute care stay in a population-based cohort in central Europe., Methods: A prospective database of the State of Hesse, Germany, was screened for all patients with the primary diagnosis of spontaneous ICH (International statistical classification-10: I61.0-I61.9) between January 2007 and December 2012., Results: In the examined time period 10,029 patients with spontaneous ICH were identified. The cumulative rate of SC was 39.9% (1, 2, or ≥3 SC were documented in 25.0%, 10.1%, and 4.7%, respectively). The most common SC were pneumonia (15.1%), brain edema (6.5%), cardiac decompensation (5.9%), urogenital infection (5.5%), hydrocephalus (4.6%), epilepsy (3.4%), and rebleeding (3.4%). One, 2, or ≥3 SC were found in 2512 patients (25.0%), 1012 (10.1%), 473 (4.7%) patients, respectively. One SC was only a predictor of in-hospital mortality in conservatively treated patients (odds ratio [OR], 1.3; 95% confidence interval [CI] 1.2-1.5, P< 0.001). With an accumulation of SC to ≥3 the chance of in-hospital death increases for surgically (OR, 3.7, 95% CI 2.3-5.9; P< 0.001) and conservatively (OR, 3.0, 95% CI 2.3-3.9; P< 0.001) treated patients., Conclusions: Surgical treatment of hematomas is associated with an increased rate of SC, but not with higher mortality rates compared with conservatively treated patients. The prevention of an accumulation of SC could lead to a decrease of in-hospital mortality after spontaneous ICH., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: The N-myc down-regulated gene (NDRG) family is a group of genes that have predominantly tumor-suppressive effects. The goal of this study was to investigate the expression of NDRG2 and NDRG4 in surgical specimens of human glioblastoma and in normal brain tissue, and to search for correlations with overall (OS) and progression-free survival (PFS)., Materials and Methods: Samples from 44 patients (31 males, 13 females; mean age±SD=57.4±15.7 years) with primary (n=40) or recurrent glioblastoma (n=4) were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry, with dimensionless semiquantitative immunoreactivity score (IRS), ranging from 0-30] for expression of NDRG2 and NDRG4. Five non-tumorous autopsy brain specimens were used as controls., Results: On the protein level, expression of NDRG2 was significantly down-regulated in glioblastoma (IRS=3.5±3.0 vs. 8.8±3.3; p=0.001), while expression of NDRG4 was significantly up-regulated (IRS=5.4±3.7 vs. 0.75±0.4 vs, p<0.001). There was no statistically significant difference in PFS between a group of 15 patients with glioblastoma with MGMT methylation and enhanced expression of NDRG4 mRNA who were treated with adjuvant radiochemotherapy (temozolomide and 60 Gy) and a group of patients with low expression of NDRG4 mRNA [10 (range=5.5-14.2) months vs. 21 (range=10.7-31.3) months] (p=0.13)., Conclusion: Expression of both NDRG2 and NDRG4 genes is significantly altered in glioblastomas. PFS among the patients with glioblastoma with MGMT methylation treated with radiochemotherapy differed significantly in high-expression groups compared to patients without MGMT methlation and without radiochemotherapy (p<0.05)., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objective: To evaluate the need for postnatal neurosurgical intervention after fetoscopic patch coverage of spina bifida aperta (SBA)., Methods: This was a retrospective analysis of a cohort of 71 fetuses which underwent minimally invasive fetoscopic patch coverage of SBA between 21 + 0 and 29 + 1 weeks of gestation. Postnatal neurosurgical procedures were classified into two types: re-coverage of the SBA within the first 3 months following birth, and shunt placement as treatment of associated hydrocephalus within the first year., Results: Location of the SBA was lumbosacral in 59 cases, lumbar in seven, thoracic in three and sacral in two. In total, 20/71 (28%) patients underwent early postnatal neurosurgical intervention by means of re-coverage of the SBA. This was performed because of cerebrospinal fluid leakage in seven (35%), adhesions with functional deterioration in three (15%), incomplete coverage in five (25%) and skin defect in five (25%) cases. Ventriculoperitoneal shunt placement within 1 year was required in 32 (45%) cases and was preceded by ventriculostomy in two. Three (4%) infants needed Chiari decompression surgery in the first 12 months following birth, because of syringomyelia or gait disturbance., Conclusions: Fetoscopic patch coverage of SBA may require postnatal re-coverage in some cases. In most cases, conservative wound treatment shows good results, without requiring neurosurgical intervention. The low 1-year-shunt rate is comparable to data of the Management of Myelomeningocele Study and lower compared with published data of patients with postnatal only coverage of SBA., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Background: The definition of prolonged length of stay (LOS) during acute care remains unclear among surgically and conservatively treated patients with intracerebral hemorrhage (ICH)., Methods: Using a population-based quality assessment registry, we calculated change points in LOS for surgically and conservatively treated patients with ICH. The influence of comorbidities, baseline characteristics at admission, and in-hospital complications on prolonged LOS was evaluated in a multivariate model., Results: Overall, 13272 patients with ICH were included in the analysis. Surgical therapy of the hematoma was documented in 1405 (10.6%) patients. Change points for LOS were 22 days (CI: 8, 22; CL 98%) for surgically treated patients and 16 days (CI: 16, 16; CL: 99%) for conservatively treated patients. Ventilation therapy was related to prolonged LOS in surgically (OR: 2.2, 95% CI: 1.5-3.1; P < 0.001) and conservatively treated patients (OR: 2.5, 95% CI: 2.2-2.9; P < 0.001). Two or more in-hospital complications in surgical patients (OR: 2.7, 95% CI: 2.1-3.5) and ≥1 in conservative patients (OR: 3.0, 95% CI: 2.7-3.3) were predictors of prolonged LOS., Conclusion: The definition of prolonged LOS after ICH could be useful for several aspects of quality management and research. Preventing in-hospital complications could decrease the number of patients with prolonged LOS.

The first three valence transitions of the two nitromethane conformers (CH3NO2) are two dark n → π* transitions and a very intense π → π* transition. In this work, these transitions in gas-phase and solvated in water of both conformers were investigated theoretically. The polarizable continuum model (PCM), two conductor-like screening (COSMO) models, and the discrete sequential quantum mechanics/molecular mechanics (S-QM/MM) method were used to describe the solvation effect on the electronic spectra. Time dependent density functional theory (TDDFT), configuration interaction including all single substitutions and perturbed double excitations (CIS(D)), the symmetry-adapted-cluster CI (SAC-CI), the multistate complete active space second order perturbation theory (CASPT2), and the algebraic-diagrammatic construction (ADC(2)) electronic structure methods were used. Gas-phase CASPT2, SAC-CI, and ADC(2) results are in very good agreement with published experimental and theoretical spectra. Among the continuum models, PCM combined either with CASPT2, SAC-CI, or B3LYP provided good agreement with available experimental data. COSMO combined with ADC(2) described the overall trends of the transition energy shifts. The effect of increasing the number of explicit water molecules in the S-QM/MM approach was discussed and the formation of hydrogen bonds was clearly established. By including explicitly 24 water molecules corresponding to the complete first solvation shell in the S-QM/MM approach, the ADC(2) method gives more accurate results as compared to the TDDFT approach and with similar computational demands. The ADC(2) with S-QM/MM model is, therefore, the best compromise for accurate solvent calculations in a polar environment., (© 2015 Wiley Periodicals, Inc.)

Background: An animal polytrauma model was developed, including trunk and extremity injuries combined with hemorrhagic shock and a prolonged post-traumatic phase. This could be useful for the assessment of different therapeutic approaches during intensive care therapy., Methods: A standardized polytrauma including lung contusion, liver laceration and lower leg fracture was applied in 25 pigs. They underwent controlled haemorrhage either with a blood volume loss of 45 % and a median arterial pressure (MAP) <30 mmHg/90 min (group L, n = 15) or a 50 % blood loss of and an MAP <25 mmHg/120 min (group H, n = 10). Five non-traumatized pigs served as a control (group C). Subsequently, intensive care treatment was given for an observational period of 48 h., Results: Both trauma groups showed signs of shock and organ injury (heart rate, MAP and lactate). The frequency of cardiopulmonary resuscitation (CPR) and lung injury was directly related to the severity of the haemorrhagic shock (CPR-group L: 4 of 15 pigs, group H: 4 of 10 pigs; Respiratory failure-group L: 3 of 13, group H: 3 of 9. There was no difference in mortality between trauma groups., Conclusion: The present data suggest that our model reflects the mortality and organ failure of polytrauma in humans during shock and the intensive care period. This suggests that the experimental protocol could be useful for the assessment of therapeutic approaches during the post-traumatic period.

Background: Stump neuroma pain in amputees can be quite challenging. Surgical treatment may be largely subdivided into neuromodulative and non-neuromodulative methods. The latter includes neurocapsis, insertion of nerve stump into the bone marrow, centro-central short circuit (CCSC), and coverage with vascularized soft tissue flaps. CCSC was shown to be extremely effective in alleviation of pain. Reports on CCSC for the treatment of stump neuroma pain have disappeared from the literature, with a shift toward neuromodulation for the treatment of pain irrespective of etiology., Methods: We observed 8 lower limb amputees undergoing CCSC of the sciatic nerve during a follow-up of 12 years. All had the same stump neuroma pain rendering them unable to wear their prostheses. The sciatic nerve was explored at the midthigh area, much proximal to the amputation site, and a short circuit was established between the tibial and peroneal parts of the nerve. Assessment was by means of pain quantification as per the quadruple visual analogue scale, medication intake, and ability to use prostheses., Results: The median worst quadruple visual analogue scale before surgery was 8.0. After surgery it decreased to 2.5 (P = 0.00094). Medication intake was reduced from regular intake of a combination of opioids, nonsteroidal anti-inflammatory drugs, tricyclic antidepressants, and pregabalin in all patients to irregular intake of nonsteroidal anti-inflammatory drug alone in 3 of 8 patients. All patients were able to wear their limb prosthesis since surgery., Conclusions: CCSC is a simple, effective, and long-lasting method to treat painful stump neuromas in amputees. It should be strongly considered in deserving cases before resorting to neuromodulative methods., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Forest ecosystems have been exposed to climate change for more than 100 years, whereas the consequences on forest growth remain elusive. Based on the oldest existing experimental forest plots in Central Europe, we show that, currently, the dominant tree species Norway spruce and European beech exhibit significantly faster tree growth (+32 to 77%), stand volume growth (+10 to 30%) and standing stock accumulation (+6 to 7%) than in 1960. Stands still follow similar general allometric rules, but proceed more rapidly through usual trajectories. As forest stands develop faster, tree numbers are currently 17-20% lower than in past same-aged stands. Self-thinning lines remain constant, while growth rates increase indicating the stock of resources have not changed, while growth velocity and turnover have altered. Statistical analyses of the experimental plots, and application of an ecophysiological model, suggest that mainly the rise in temperature and extended growing seasons contribute to increased growth acceleration, particularly on fertile sites.

While previous studies focused on tree growth in pure stands, we reveal that tree resistance and resilience to drought stress can be modified distinctly through species mixing. Our study is based on tree ring measurement on cores from increment boring of 559 trees of Norway spruce (Picea abies [L.] Karst.), European beech (Fagus sylvatica [L.]) and sessile oak (Quercus petraea (Matt.) Liebl.) in South Germany, with half sampled in pure, respectively, mixed stands. Indices for resistance, recovery and resilience were applied for quantifying the tree growth reaction on the episodic drought stress in 1976 and 2003. The following general reaction patterns were found. (i) In pure stands, spruce has the lowest resistance, but the quickest recovery; oak and beech were more resistant, but recover was much slower and they are less resilient. (ii) In mixture, spruce and oak perform as in pure stands, but beech was significantly more resistant and resilient than in monoculture. (iii) Especially when mixed with oak, beech is facilitated. We hypothesise that the revealed water stress release of beech emerges in mixture because of the asynchronous stress reaction pattern of beech and oak and a facilitation of beech by hydraulic lift of water by oak. This facilitation of beech in mixture with oak means a contribution to the frequently reported overyield of beech in mixed versus pure stands. We discuss the far-reaching implications that these differences in stress response under intra- and inter-specific environments have for forest ecosystem dynamics and management under climate change., (© 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.)

Bradykinin is known for its pathophysiological role as mediator of inflammation. Following cerebral ischemia, bradykinin promotes the secondary brain damage through an increase of vascular permeability and brain edema formation, again hallmarks of inflammation. It is not clear, whether bradykinin also activates inflammatory cells and regulates microcirculatory blood flow in the brain. The purpose of the study is to investigate the reaction of bradykinin upon cerebral leukocyte- and thrombocyte-endothelium interactions as well as microvascular perfusion. Intravital fluorescence microscopy of pial blood vessels was performed in gerbils. Intracarotid injection of bradykinin resulted in increased numbers of rolling and adherent leukocytes as well as rolling platelets at the venular endothelium. This was reversed by administration of a bradykinin B2 receptor antagonist. In contrast, after additional administration of a B1 receptor antagonist, microvascular blood-flow and capillary density was decreased. We conclude that bradykinin initiates leukocyte- and platelet-endothelium interactions in the cerebral microcirculation via activation of B2 receptors. Activation of B1 receptors ensures regular cerebral perfusion. Thus, to attenuate secondary brain damage, inhibition of B2 but not B1 receptors might be of therapeutical benefit., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To examine the independent association of gender with injury severity, clinical course, pituitary dysfunction and outcome after traumatic brain injury (TBI)., Design: Prospective cohort, analysis of a data sub-set collected as part of the nation-wide database 'The Structured Data Assessment of Hypopituitarism after TBI and SAH'., Methods and Procedures: Four hundred and twenty-seven patients following TBI were observed from acute care through neurological rehabilitation. Outcome was measured by Glasgow Outcome Scale (GOS), employment status and living situation post-injury. As a secondary outcome measure anterior pituitary function was assessed., Results: There were no differences in injury severity between men and women. Age had a significant effect on the GCS score (p = 0.0295), but gender did not (p = 0.4105). The outcome was equivalent between men and women once corrected for age. Logistic regression revealed that gender had no effect (p = 0.8008), but age (p = 0.0021) and initial injury severity (p = 0.0010) had an effect on the GOS. After correcting for pre-injury living situation and employment only initial injury severity (p = 0.0005) influenced GOS. Pituitary insufficiency was not affected by sex or age., Conclusion: Gender does not seem to influence the course and outcome of TBI. Outcome parameters were affected foremost by initial injury severity and by age, but not by sex.

Canine lymphoma is a common spontaneous tumor with many similarities to human lymphoma, and thus has potential to be an important animal model of lymphomagenesis. This study determined that microRNA (miRNA) expression in canine tumors can be assessed using a commercially available human cancer miRNA qPCR array. miRNA expression in six different canine lymphoid cell lines and in naturally occurring canine B- and T-cell lymphomas was compared using RNA harvested from normal canine peripheral blood mononuclear cells (PBMC) and normal lymph nodes (LN) as controls. We found that false discovery rate (FDR) correction for multiple testing after quantile normalization controlled for variation across arrays and that they were the best methods for normalization and statistical analysis. Increases in miRNAs known to upregulate oncogenes (miR19a+b, miR17-5p) and decreased expression of miRNAs with tumor suppressor functions (miR-203, miR-218, and miR-181a) also seen in human lymphoid malignancies were observed. However, there were few similarities between canine groups. The results of this study indicate that the use of both PBMC and LN cells as controls provides different, but potentially equally important targets for further analysis. Our findings of miRNA dysregulation in canine lymphoid cell lines and clinical cases of lymphoma emphasize the potential of canine lymphoma as an important spontaneous, large animal model of human B- and T-cell lymphomas., (Copyright © 2011 Wiley-Liss, Inc.)

A 15-year-old female red-tailed hawk (Buteo jamaicensis) was evaluated because of dyspnea, anorexia, and coelomic distension. Diagnostic imaging results confirmed severe coelomic effusion and revealed a markedly dilated right ventricle. The diagnosis was right-sided congestive heart failure. Results of measurements of vitamin E, selenium, lead, zinc, and cardiac troponin levels were normal or nondiagnostic. The hawk was treated with furosemide, antifungal and antimicrobial agents, and supplemental fluids and oxygen, but euthanasia was elected because of the poor prognosis and the practical difficulties associated with intensive case management. To our knowledge, this is the first described case of cardiomyopathy and congestive heart failure in a captive red-tailed hawk.

Intraoperative computed tomography (iCT) has gained increasing impact among modern neurosurgical techniques. Multislice CT with a sliding gantry in the OR provides excellent diagnostic image quality in the visualization of vascular lesions as well as bony structures including skull base and spine. Due to short acquisition times and a high spatial and temporal resolution, various modalities such as iCT-angiography, iCT-cerebral perfusion and the integration of intraoperative navigation with automatic re-registration after scanning can be performed. This allows a variety of applications, e.g. intraoperative angiography, intraoperative cerebral perfusion studies, update of cerebral and spinal navigation, stereotactic procedures as well as resection control in tumour surgery. Its versatility promotes its use in a multidisciplinary setting. Radiation exposure is comparable to standard CT systems outside the OR. For neurosurgical purposes, however, new hardware components (e.g. a radiolucent headholder system) had to be developed. Having a different range of applications compared to intraoperative MRI, it is an attractive modality for intraoperative imaging being comparatively easy to install and cost efficient.

STUDY DESIGN.: A prospective interventional case-series study plus a retrospective analysis of historical patients for comparison of data. OBJECTIVE.: To evaluate workflow, feasibility, and clinical outcome of navigated stabilization procedures with data acquisition by intraoperative computed tomography. SUMMARY OF BACKGROUND DATA.: Routine fluoroscopy to assess pedicle screw placement is not consistently reliable. Our hypothesis was that image-guided spinal navigation using an intraoperative CT-scanner can improve the safety and precision of spinal stabilization surgery. METHODS.: CT data of 94 patients (thoracolumbar [n = 66], C1/2 [n = 12], cervicothoracic instability [n = 16]) were acquired after positioning the patient in the final surgical position. A sliding gantry 40-slice CT was used for image acquisition. Data were imported to a frameless infrared-based neuronavigation workstation. Intraoperative CT was obtained to assess the accuracy of instrumentation and, if necessary, the extent of decompression. All patients were clinically evaluated by Odom-criteria after surgery and after 3 months. RESULTS.: Computed accuracy of the navigation system reached <2 mm (0.95 +/- 0.3 mm) in all cases. Additional time necessary for the preoperative image acquisition including data transfer was 14 +/- 5 minutes. The duration of interrupting the surgical process for iCT until resumption of surgery was 9 +/- 2.5 minutes. Control-iCT revealed incorrect screw position >/=2 mm without persistent neurologic or vascular damage in 20/414 screws (4.8%) leading to immediate correction of 10 screws (2.4%). Control-iCT changed the course of surgery in 8 cases (8.5% of all patients). The overall revision rate was 8.5% (4 wound revisions, 2 CSF fistulas, and 2 epidural hematomas). There was no reoperation due to implant malposition. According to Odom-criteria all patients experienced a clinical improvement. A retrospective analysis of 182 patients with navigated thoracolumbar transpedicular stabilizations in the preiCT era revealed an overall revision rate of 10.4% with 4.4% of patients requiring screw revision. CONCLUSION.: Intraoperative CT in combination with neuronavigation provides high accuracy of screw placement and thus safety for patients undergoing spinal stabilization. Reoperations due to implant malpositions could be completely avoided. The system can be installed into a pre-existing operating environment without need for special surgical instruments. The procedure is rapid and easy to perform without restricted access to the patient and-by replacing pre- and postoperative imaging-is not associated with an additional exposure to radiation. Multidisciplinary use increases utilization of the system and thus improves cost-efficiency relation.

The development of a space-occupying hemispheric infarction occurs in a subset of patients with ischaemic cerebrovascular stroke. It is a life-threatening condition with a high mortality rate of up to 80% with medical therapy alone. Previous retrospective and uncontrolled case series have suggested that decompressive hemicraniectomy can significantly reduce mortality to 20-30% compared to conservative treatment. This evidence has now been confirmed by the data of prospective randomised studies. The data also indicate that the reduction of mortality is not accompanied by an increase in the number of completely disabled patients. However, the number of disabled patients depending on the assistance of others increases significantly, and the patients and their caregivers need to be comprehensively informed about the long-term consequences prior to surgery. Furthermore, questions concerning the optimal time point for decompression and the upper age limit at which patients still benefit from surgery remain unanswered. Thus the indication for surgery is to a great extent still dependent on the individual situation of the patient and the experience of the treating physicians. This review covers the indications, the surgical technique, the prognostic factors and the clinical outcome with this procedure based on the data of retrospective series and the results of the recently published prospective randomised trials., (Georg Thieme Verlag KG Stuttgart * New York.)

Background and Purpose: Blood-pool agents are promising in the imaging of small vessels with slow or complex flow. Our aim was to compare blood-pool contrast-enhanced MR angiography (BPCE-MRA) using gadofosveset trisodium (Vasovist) with 3D time-of-flight MRA (TOF-MRA) in the follow-up of intracranial aneurysms after endovascular therapy., Materials and Methods: We included 32 patients with a total of 37 coiled aneurysms. MRAs in the early steady-state phase were performed on a 1.5T scanner within 8 days of digital subtraction angiography (DSA). Two radiologists independently analyzed TOF-MRA and BPCE-MRA images. Consensus was reached by review involving a third neuroradiologist. DSA images were interpreted separately by an interventional radiologist. Findings were assigned to 1 of 3 categories: 1) complete occlusion, 2) residual neck, and 3) residual aneurysm., Results: Follow-up DSA demonstrated 13 complete obliterations (class 1), 13 residual necks (class 2), and 11 residual aneurysms (class 3). Weighted kappa statistics showed substantial concordance of TOF-MRA and DSA (0.664) as well as BPCE-MRA and DSA (0.724) ratings. Comparison between TOF-MRA and BPCE-MRA found excellent agreement (0.818) with only 6 (16.2%) discrepancies. For detecting residual flow, the difference in accuracy of both MRA techniques (83.8% versus 91.9%) was not significant (McNemar, P = 1.000). BPCE-MRA showed a tendency towards higher sensitivity and specificity (91.7% and 92.3%, respectively) compared with TOF-MRA (87.5% and 76.9%)., Conclusions: In classifying the completeness of endovascular cerebral aneurysm therapy, we found that BPCE-MRA and 3D TOF-MRA showed very good agreement. The use of Vasovist did not lead to a significantly increased accuracy of MRA follow-up.

Background: The strongest evidence in medical clinical literature is represented by randomized controlled trials (RCTs). This study was designed to evaluate neurosurgically relevant RCTs published recently by neurosurgeons., Method: A literature search in MEDLINE and EMBASE included all clinical studies published up to 30 June 2006. RCTs with neurosurgical relevance published by at least one author with affiliation to a neurosurgical department were selected. The number and characteristics of individual trials were recorded, and the quality of the trials with regard to study design, quality of reporting, and relevance for clinical practice was assessed by two different investigators using a modification of the Scottish Intercollegiate Guidelines Network methodology checklist. Changes of RCT quality over time as well as factors influencing the quality were analyzed., Findings: From the initial search results (MEDLINE n = 3,860, EMBASE n = 3,113 articles), 159 RCTs published by neurosurgeons were extracted for final evaluation. Of the RCTs, 62% have been published since 1995; 52% came from the USA, UK, and Germany. The median RCT sample size was 78 patients and the median follow-up 35.7 weeks. Fifty-two percent of all RCTs were of good, 37% of moderate, and 11% of bad quality, with an improvement over time. RCTs with financial funding and RCTs with a sample size of >78 patients were of significantly better quality. There were no major differences in the rating of the studies between the two investigators., Conclusions: Only a fraction of neurosurgically relevant literature consists of RCTs, but the quality is satisfying and has significantly improved over the last years. An adequate sample size and sufficient financial support seem to be of substantial importance with regard to the quality of the study. Our data also show that by using a standardized checklist, the quality of trials can be reliably assessed by observers of different experience and educational levels.

Objective: We report our preliminary experience in a prospective series of patients with regard to feasibility, work flow, and image quality using a multislice computed tomographic (CT) scanner combined with a frameless neuronavigation system (NNS)., Methods: A sliding gantry 40-slice CT scanner was installed in a preexisting operating room. The scanner was connected to a frameless infrared-based NNS. Image data was transferred directly from the scanner into the navigation system. This allowed updating of the NNS during surgery by automated image registration based on the position of the gantry. Intraoperative CT angiography was possible. The patient was positioned on a radiolucent operating table that fits within the bore of the gantry. During image acquisition, the gantry moved over the patient. This table allowed all positions and movements like any normal operating table without compromising the positioning of the patient. For cranial surgery, a carbon-made radiolucent head clamp was fixed to the table., Results: Experience with the first 230 patients confirms the feasibility of intraoperative CT scanning (136 patients with intracranial pathology, 94 patients with spinal lesions). After a specific work flow, interruption of surgery for intraoperative scanning can be limited to 10 to 15 minutes in cranial surgery and to 9 minutes in spinal surgery. Intraoperative imaging changed the course of surgery in 16 of the 230 cases either because control CT scans showed suboptimal screw position (17 of 307 screws, with 9 in 7 patients requiring correction) or that tumor resection was insufficient (9 cases). Intraoperative CT angiography has been performed in 7 cases so far with good image quality to determine residual flow in an aneurysm. Image quality was excellent in spinal and cranial base surgery., Conclusion: The system can be installed in a preexisting operating environment without the need for special surgical instruments. It increases the safety of the patient and the surgeon without necessitating a change in the existing surgical protocol and work flow. Imaging and updating of the NNS can be performed at any time during surgery with very limited time and modification of the surgical setup. Multidisciplinary use increases utilization of the system and thus improves the cost-efficiency relationship.

Object: The purpose of this study was to assess the value of myelography using flat-panel detector-based computed tomography (fpCT) in 5 patients in whom the image quality of multislice CT (MSCT) or MR imaging was limited by metal artifacts., Methods: The application of fpCT to myelographic imaging of the lumbar spine and cervicothoracic junction after surgery was feasible. Multiplanar, preferably sagittal, and 3D reconstructions adequately depicted disc space implants and provided high resolution images of osseous structures., Results: The images obtained with fpCT allowed evaluation of anatomical details such as single nerve roots and proved especially valuable in a patient with impaired MR imaging results caused by metal artifacts from an intraoperative abrasion. In a case of recurrent disc herniation, imaging results of myelographic fpCT and MSCT scanning were in good agreement., Conclusions: The novel imaging technique the authors describe yielded adequate results in patients with a history of spinal surgery, may be superior to MSCT scanning in depicting osseous structures and metallic implants, and has the potential to provide multilevel spinal images. Myelographic fpCT scanning may be the preferred modality in patients with expected or known metal artifacts on myelographic MSCT scans and/or MR images.

Nitrous oxide is a widely used anesthetic gas. The aim of this study was to investigate the effect of this agent on inflammatory side effects in the brain. The cerebral microcirculation of Mongolian gerbils was investigated by fluorescent intravital microscopy for up to 7 h after induction of anesthesia. Anesthesia was induced and maintained with isoflurane or halothane alone or in combination with nitrous oxide (70%). The number of leukocytes that were rolling along and firmly adherent to the endothelial wall of cerebral venules was significantly elevated in animals anesthetized with nitrous oxide in combination with isoflurane and halothane compared to isoflurane and halothane alone. A significantly increased number of neutrophil granulocytes invading the brain parenchyma in histological slices from animals treated with the combination of isoflurane or halothane and nitrous oxide compared to controls treated with isoflurane or halothane alone was observed. Our data show that prolonged anesthesia with nitrous oxide induces inflammation of the cerebral microcirculation and brain.

Object: Endoscopic third ventriculostomy is the treatment of choice in patients with obstructive hydrocephalus caused by aqueductal stenosis. The authors examined the clinical course and results of surgical treatment for obstructive hydrocephalus with pre- and postoperative refined constructive interference in steady-state (CISS) MR imaging., Methods: Forty patients with obstructive hydrocephalus underwent pre- and postoperative 3D-CISS imaging and clinical evaluation. Radiological findings were correlated with intraoperative observations of the thickness and transparency of the floor of the third ventricle and the patient's postoperative clinical course., Results: Three-dimensional CISS MR imaging provides precise visualization of the basilar/posterior cerebral artery, its distance to the clivus, the diameter of the foramen of Monro, and the extension of and thickness of the floor of the third ventricle. In 71% of patients a flow void was detectable postoperatively on the ventriculostomy. In this group 81.5% had strong and 14.8% moderate clinical benefit, and 3.7% required secondary shunt placement. In the remaining 29% of the patients without a visible flow void, strong improvement was seen in 54.5%, moderate improvement in 18.2%, and stoma failure occurred in 27.3% (p = 0.094). Radiological measurements of the thickness of the third ventricle floor correlated with intraoperative findings (r = 0.35, p = 0.029). Comparison of outcomes showed a statistically significant tendency for a better outcome in patients with thin and easily perforated third ventricle floors (p = 0.04)., Conclusions: Endoscopic ventriculostomy in patients with obstructive hydrocephalus is safe and mostly successful, and 3D-CISS MR imaging seems to be a valuable diagnostic method for precisely identifying the anatomy of relevant structures. Furthermore, 3D-CISS MR imaging allows judgment of the thickness of the third ventricle floor and display of the ventriculostomy/flow void, which are predictive for intraoperative course and clinical outcome.

Objective: Magnetically guided neuronavigation of flexible instruments is a new tool that can be used in the frameless navigation of deep-seated lesions or shunt placements. Disadvantages of optical systems such as the line-of-sight problem, the necessity of rigid pin fixation of the head, and missing tracking of the tip of flexible instruments should be solved by the new tracking system. Until now, the accuracy of magnetically guided systems was mostly estimated in laboratory setups., Methods: In this study, intraoperative accuracy of the system was tested in 60 patients with either hydrocephalus or cranial base tumors. In daily routine use, different operative setups with a variety of metallic instruments were examined. Accuracy of the neuronavigation system was estimated, comparing microscopically or endoscopically identified anatomic landmarks with neuronavigated data and postoperative computed tomographic scans., Results: The main advantage of the new system is the tracking of a magnetic coil at the tip of a flexible instrument. After an initial learning curve during the developmental phase of the system, the latter showed reliable accuracy values with no operative setups leading to mismatch of more than 2 mm., Conclusion: Tracking of flexible instruments was easily accomplished as the tip of the instrument was followed within the patient's head. There were no major interferences with other metallic instruments within the surgical field.

The angiogenic growth factor Vascular Endothelial Growth Factor-C (VEGF-C) and its receptor VEGFR-3 are also known to be implicated in the development of lymphatic vessels. We assessed the expression of VEGF-C and VEGFR-3, together with blood and lymphatic vessel extents and proliferation index (PI) values, by immunohistochemistry (IHC) in 6 normal human pituitary glands and 53 pituitary adenomas of different tumour grade, on consecutive tissue sections. VEGF-C was detected in around 10% of the endocrine cells in normal pituitary tissue, while this gland was devoid of lymphatic vascularization and showed very few vessels positive for VEGFR-3. Concerning tumour tissue, most of the adenomas showing VEGF-C immunoreactivity (21/47) were positive in 60% of the tumour cells and the ones positive for VEGFR-3 showed a number of immunostained vessels higher than those observed in the normal pituitary. Most of the tumours positive for VEGFR-3 did not show any LYVE-1 positive vessels (18/53), suggesting that at least in these cases, VEGFR-3 is expressed on blood vessels. Nevertheless, we observed a significant association between low expression of VEGFR-3 and low lymphatic vessel number, suggesting that VEGFR-3 might be involved in the starting of DE NOVO lymphangiogenesis in this tumour type. Moreover, tumours bearing lymphatic vessels showed the tendency to shift towards a more aggressive behaviour (high tumour grade and high PI). In conclusion, the VEGF-C/VEGFR-3 system might be involved in controlling tumour angiogenesis in the pituitary adenomas lacking lymphatic vessels, but may also play a role in starting the process of tumour lymphangiogenesis.

Even though being a rare condition in the era of antibiotic treatment, complications of acute frontal sinusitis still pose a potentially life-threatening problem. We present a clinical case series using a combined surgical approach. Within a 7 year period, all patients with a suppurative complication of an acute frontal sinusitis were included into this retrospective study and evaluated concerning histories, diagnostic and therapeutic procedures and achieved outcomes. Twelve patients (11-74 years) were identified; this corresponds to 0.3% of all patients that have undergone paranasal sinus surgery and 15.4% of all patients with infectious complications of sinusitis. The cases could be subdivided as follows: intracranial complications (4/12), osteomyelitis of the frontal bone (4/12), frontal/orbital soft tissue involvement (3/12) and endoluminal empyema (1/12). These were all correctly diagnosed by CT and (especially in the cases of intracranial complications) MRI. The microbiological spectrum comprised mostly non-multiresistant Staphylococci and Streptococci. All patients received aggressive antibiotic and combined surgical treatment. Within a mean follow up period of 32 months, the disease-related mortality and the rate of severe long-term ailment was 0%. If detected and treated early, both long-term morbidity and mortality can be minimised. A close cooperation with the related specialties (neurosurgery, ophthalmology, radiology) is thereby of utmost importance.

Objective: The aim of this study was to measure microvascular perfusion (MVP) on the brain surface in global ischemia and reperfusion by means of intravital fluorescence microscopy., Methods: Global ischemia was induced in gerbils for 15 minutes with 3 hours of reperfusion. The passage of a rhodamine bolus (25 mul intravenously) from an arteriole to a venule was analyzed by intravital fluorescence microscopy through a cranial window. After the changes of fluorescence intensities in an arteriole and venule, the arteriovenous transit time and the MVP were calculated using the integral difference method. Additionally, regional cerebral blood flow was assessed by laser Doppler flowmetry and vessel diameters and blood pressure were recorded., Results: The baseline mean MVP was 2.21 +/- 0.89 sec(-1) in the control group, remaining stable throughout observation in sham operated animals. In ischemic animals, the MVP was 2.11 +/- 0.47 sec(-1) at baseline, showing a significant decrease during ischemia to 0.07 +/- 0.16 sec(-1) (3%; P < 0.01). There was postischemic maximum hyperperfusion of 2.72 +/- 0.40 sec(-1) (134 +/- 11%; P < 0.05) at 15.4 +/- 6.9 minutes and hypoperfusion of 1.63 +/- 0.57 sec(-1) (77 +/- 13%; P = 0.19) at 36.6 +/- 16.4 minutes. There was a strong, significant correlation between MVP and regional cerebral blood flow (R = 0.82; P < 0.0001)., Conclusion: MVP on the brain surface can be calculated from the transit time of a dye bolus from an arteriole to a venule. MVP shows a high correlation to regional cerebral blood flow. The assessment of MVP allows one to easily and repeatedly quantify perfusion changes of the microvascular network on the brain surface.

Vascular abnormalities or dissection of the vertebral artery are rare causes for cervical monoradiculopathy. We present the case of a 44-year-old female patient with a short history of radiculopathy of the right C5 root with radicular pain and a severe motor deficit. CT-imaging showed a hyperdense structure at the C4/C5 level suggesting a herniated disc. Because of the neurological deficit the patient was operated by a dorsal approach. Intraoperatively no herniated disc but only a congested epidural venous plexus was found. Postoperative MRI and angiography showed occlusion of the vertebral artery from C3 to C6 level probably due to dissection. The present case shows that a CT-study suggestive for a herniated disc can be misleading. Enlargement of the vertebral artery secondary to dissection or occlusion may lead to compression of the venous plexus which resembles disc material on CT-scan.

The role of leukocyte-endothelial interactions (LEI) as part of the inflammatory response after global cerebral ischemia (GCI) is hardly understood and may be detrimental as well as beneficial. Objective of the current study was to investigate the cause-effect relationship of activated leukocytes for the development of ischemic brain damage. Mongolian gerbils were subjected to 15 min of global cerebral ischemia. A cranial window was implanted for quantitative analysis of the pial microcirculation focusing on leukocyte-endothelium interactions by intravital fluorescence microscopy up to 3 h of reperfusion. Subsequently the animals were daily screened for neurological deficits and the evolving brain damage was assessed histologically after 4 days. After global cerebral ischemia the number of rolling and adherent leukocytes increased 20- and >23-fold, respectively upon 3 h of reperfusion as compared to controls (P<0.05). Ischemic animals developed neurological deficits and showed a significant loss of neurons in selective vulnerable areas of the brain. The extent of leukocyte activation, i.e. the maximum number of rollers and stickers directly correlated to the number of viable neurons on day 4 in hippocampus, cortex, and striatum. We conclude that there is a relationship between activation of leukocyte-endothelium interactions and the reduction of ischemic brain damage after global cerebral ischemia. Activation of leukocytes may have neuroprotective potential or indicate regenerative processes.

Activation of platelets induces interactions with platelets, endothelial cells, and leukocytes. In vivo observation of these interactions in the cerebral microcirculation is rare. The purpose of the present study was to develop a model enabling the in vivo observation of platelet kinetics in the cerebral microcirculation. Intravital fluorescence microscopy was performed in the Mongolian gerbil. Platelets of a donor were labeled ex vivo with carboxyfluorescein diacetat-succinimidylester (CFDA-SE), providing long-term fluorescence. Platelet function was tested ex vivo by flow cytometric analysis and in vivo by analyzing platelet-endothelium interactions. Labeled platelets stimulated with adenosine diphosphate ADP (200 micromol/L) or thrombin (1000 U/L) showed aggregation in flow cytrometric analysis, whereas unstimulated platelets were not aggregated. Irradiation of the brain surface after intravenous injection of the photosensitizing dye Photosan first induced rolling and firm adherence of platelets on arteriolar and venular endothelium, followed by the formation of a thrombus obstructing the vessel. Quantitative analysis (n x 100 microm(-1) min(-1)) before and after 6 mins of irradiation showed 2.6+/-3.2 versus 29.0+/-28.9 rolling, and 0.0+/-0.0 versus 1.7+/-2.3 firm adherent platelets in arterioles, and 3.9+/-3.3 versus 36.6+/-20.9 rolling and 0.0+/-0.0 versus 13.6+/-8.9 firm adherent platelets in venules. Thus, we conclude that ex vivo labeling of platelets with CFDA-SE does not activate platelets. Platelet aggregation and adhesion was achieved by platelet-specific stimulation such as ADP, thrombin or irradiation. In vivo assessment of physiologic and pathophysiologic mechanisms of platelets in the cerebral microcirculation can be achieved in this model.

Lumbar spinal stenosis is one of the most frequent causes of spinal surgical interventions in over 60-year olds. The exact relationship between degenerative changes and the resulting symptoms is unclear since imaging shows stenotic changes in the spines of many symptom-free patients. The concurrence of imaging findings, the symptoms described and manifestations is crucial for the indication of surgical decompression. Nevertheless, spinal claudication that is refractory to conservative therapy is the most frequent indication for surgery. The success rate two years after OP is approximately 80% in over 75-year olds. Five years after surgical intervention, an improvement in the symptoms is still recognizable in 50% of these patients.

The diagnosis is established through neurological examinations, laboratory and imaging diagnostics. Conservative treatment such as a neck brace, drug and physical therapies could bring relief. Manifest or progressing deficiency symptoms associated with sensory or motoric deficit, bladder, rectal or erectile disorder are indications for early surgery.

As for any solid tumour, pituitary adenoma expansion is dependent on neovascularization through angiogenesis. In this process, vascular endothelial growth factor (VEGF) and its receptors VEGFR-1, VEGFR-2 and neuropilin-1 (NRP-1) may play an outstanding role. The intention of this work was to study the expression/localization and possible function of VEGF receptors in pituitary adenomas. VEGF receptor mRNA and protein expression was studied by in situ hybridization, immunohistochemistry and RT-PCR in 6 normal human pituitaries, 39 human pituitary adenomas and 4 rodent pituitary adenoma cell lines. VEGFR-1 expressing somatotroph MtT-S cells were used as a model to study the role of VEGF on cell proliferation and to elucidate the underlying mechanism of action. In normal pituitaries, VEGFR-1 was detected in endocrine cells, whereas VEGFR-2 and NRP-1 were exclusively expressed in endothelial cells. In pituitary tumours, a heterogeneous VEGFR expression pattern was observed by IHC. VEGFR-1, VEGFR-2 and NRP-1 were detected in 24, 18 and 17 adenomas respectively. In the adenomas, VEGFR-1 was expressed in epithelial tumour cells and VEGFR-2/NRP-1 in vessel endothelial cells. Functional studies in VEGFR-1-positive MtT-S cells showed that the ligands of VEGFR-1 significantly stimulated cell proliferation. This effect was mediated through the phosphatidylinositol-3-kinase-signalling pathway and involves induction of cyclin D1 and Bcl-2. Based on our results, we speculate that the ligands of VEGF receptors, such as VEGF-A and placenta growth factor, not only play a role in angiogenesis in pituitary adenomas, but also affect the growth of pituitary tumour cells through VEGFR-1.