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Background : Spondylodiscitis is an infectious disease affecting an intervertebral disc and the adjacent vertebral bodies and is often the complication of a distant focus of infection. This study aims to ascertain the regional and hospital-specific disparities in bacterial patterns and resistance profiles in spontaneous and iatrogenic spondylodiscitis and their implications for patient treatment. Methods: We enrolled patients from two German hospitals, specifically comparing a university hospital (UVH) with a peripheral non-university hospital (NUH). We documented patient demographics, laboratory results, and surgical interventions. Microbiological assessments, antibiotic regimens, treatment durations, and resistance profiles were recorded. Results: This study included 135 patients. Upon admission, 92.4% reported pain, with 16.2% also presenting neurological deficits. The primary microbial species identified in both the UVH and NUH cohorts were S. aureus (37.3% vs. 31.3%) and cog. neg. staphylococci (28.8% vs. 34.4%), respectively. Notably, a higher prevalence of resistant bacteria was noted in the UVH group ( p < 0.001). Additionally, concomitant malignancies were significantly more prevalent in the UVH cohort. Conclusion: Significant regional variations exist in bacterial prevalence and resistance profiles. Consequently, treatment protocols need to consider these nuances and undergo regular critical evaluation. Moreover, patients with concurrent malignancies face an elevated risk of spondylodiscitis.

Study Design: Retrospective cohort study., Objective: Cavernous malformations (CMs) and hemangioblastomas (HBs) of the spinal cord exhibit distinct differences in histopathology but similarities in the neurological course. The aim of our study was to analyze the clinical differences between the vascular pathologies and a benign tumor of the spinal cord in a perioperative situation., Methods: We performed a retrospective analysis of patients who had undergone surgery for lesions in the spinal cord between 1984 and 2015. Patients were screened for CMs and HBs as the primary inclusion criteria. General patient information, surgical data, and disease-specific data were collected from the records. Cooper-Epstein scores for clinical symptoms were evaluated preoperatively, at discharge, and at the 6-month follow-up., Results: A total of 112 patients were included, of which 46 had been diagnosed with CMs and 66 with HBs. Patients with CMs often demonstrated more preoperative neurological deterioration compared to those with HBs ( P < .05); accordingly, in took longer to diagnose HBs. Complete resection was possible for 96.8% of all patients with CMs and 90% of those with HBs. At the 6-month follow-up, patients with HBs more often presented with persisting neurologic impairment of the upper extremities compared to the CM patients ( P < .001)., Conclusion: CMs and HBs of the spinal cord have similarities but also exhibit significant differences in neurological presentation and perioperative course. Surgical therapy is the treatment of choice for symptomatic lesions, and complete surgical resection is possible in the majority of cases for both entities. Neurologic outcomes are usually favorable, although patients with HBs retain neurologic deficits more often., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Aneurysmal subarachnoid hemorrhage (SAH) presents occasionally with cardiac arrest (CA). The impact of pre-hospital and emergency room (ER) treatment on outcome remains unclear. Therefore, we investigated the impact of pre-hospital treatment, focusing on lay cardiopulmonary resuscitation (CPR), and ER handling on the outcome of SAH patients with out-of-hospital CA (OHCA)., Methods: In this bi-centric retrospective analysis, we reviewed SAH databases for OHCA and CPR from January 2011 to June 2021. Patients were analyzed for general clinical and epidemiological parameters. CPR data were obtained from ambulance reports and information on ER handling from the medical records. Data were correlated with patient survival at hospital discharge as a predefined outcome parameter., Results: Of 1,120 patients with SAH, 45 (4.0%) were identified with OHCA and CPR, 38 of whom provided all required information and were included in this study. Time to resuscitation was significantly shorter with lay resuscitation (5.3 ± 5.2 min vs. 0.3 ± 1.2 min, p  = 0.003). Nineteen patients were not initially scheduled for cranial computed tomography (CCT), resulting in a significantly longer time interval to first CCT (mean ± SD: 154 ± 217 min vs. 40 ± 23 min; p  < 0.001). Overall survival to discharge was 31.6%. Pre-hospital lay CPR was not associated with higher survival ( p  = 0.632). However, we observed a shorter time to first CCT in surviving patients ( p  = 0.065)., Conclusions: OHCA in SAH patients is not uncommon. Besides high-quality CPR, time to diagnosis of SAH appears to play an important role. We therefore recommend considering CCT diagnostics as part of the diagnostic algorithm in patients with OHCA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Pantel, Neulen, Mader, Kurz, Piffko, Fassl, Westphal, Gempt, Ringel and Czorlich.)

Purpose: To analyze the reliability of the classification of intraoperative adverse events (ClassIntra) to reflect intraoperative complications of neurosurgical procedures and the potential to predict the postoperative outcome including the neurological performance. The ClassIntra classification was recently introduced and found to be reliable for assessing intraoperative adverse events and predicting postoperative complications across different surgical disciplines. Nevertheless, its potential role for neurosurgical procedures remains elusive., Methods: This is a prospective, monocentric cohort study assessing the ClassIntra in 422 adult patients who underwent a neurosurgical procedure and were hospitalized between July 1, 2021, to December 31, 2021. The primary outcome was the occurrence of intraoperative complications graded according to ClassIntra and the association with postoperative outcome reflected by the Clavien-Dindo classification and comprehensive complication index (CCI). The ClassIntra is defined as intraoperative adverse events as any deviation from the ideal course on a grading scale from grade 0 (no deviation) to grade V (intraoperative death) and was set at sign-out in agreement between neurosurgeon and anesthesiologist. Secondary outcomes were the neurological outcome after surgery as defined by Glasgow Coma Scale (GCS), modified Rankin scale (mRS), Neurologic Assessment in Neuro-Oncology (NANO) scale, National Institute Health of Strokes Scale (NIHSS), and Karnofsky Performance Score (KPS), and need for unscheduled brain scan., Results: Of 442 patients (mean [SD] age, 56.1 [16.2]; 235 [55.7%] women and 187 [44.3%] men) who underwent a neurosurgical procedure, 169 (40.0%) patients had an intraoperative adverse event (iAE) classified as ClassIntra I or higher. The NIHSS score at admission (OR, 1.29; 95% CI, 1.03-1.63, female gender (OR, 0.44; 95% CI, 0.23-0.84), extracranial procedures (OR, 0.17; 95% CI, 0.08-0.61), and emergency cases (OR, 2.84; 95% CI, 1.53-3.78) were independent risk factors for a more severe iAE. A ClassIntra ≥ II was associated with increased odds of postoperative complications classified as Clavien-Dindo (p < 0.01), neurological deterioration at discharge (p < 0.01), prolonged hospital (p < 0.01), and ICU stay (p < 0.01). For elective craniotomies, severity of ClassIntra was associated with the CCI (p < 0.01) and need for unscheduled CT or MRI scan (p < 0.01). The proportion of a ClassIntra ≥ II was significantly higher for emergent craniotomies (56.2%) and associated with in-hospital mortality, and an unfavorable neurological outcome (p < 0.01)., Conclusion: Findings of this study suggest that the ClassIntra is sensitive for assessing intraoperative adverse events and sufficient to identify patients with a higher risk for developing postoperative complications after a neurosurgical procedure., (© 2023. The Author(s).)

Traumatic brain injury (TBI) causes the release of danger-associated molecular patterns (DAMP) from damaged or dead cells, which contribute to secondary brain damage after TBI. Cell-free DNA (cfDNA) is a DAMP known to cause disruption of the blood-brain barrier (BBB), promote procoagulant processes, brain edema, and neuroinflammation. This study tested the hypothesis that administration of deoxyribonuclease-I (DNase-I) has a beneficial effect after TBI. Mice (n = 84) were subjected to controlled cortical impact (CCI) and posttraumatic intraperitoneal injections of low dose (LD) or high dose (HD) of DNase-I or vehicle solution at 30 min and 12 h after CCI. LD was most effective to reduce lesion volume (p = 0.003), brain water content (p < 0.0001) and to stabilize BBB integrity (p = 0.019) 1 day post-injury (dpi). At 6 h post injury LD-treated animals showed less cleavage of fibrin (p = 0.0014), and enhanced perfusion as assessed by micro-computer-tomography (p = 0.027). At 5 dpi the number of Iba1-positive cells (p = 0.037) were reduced, but the number of CD45-positive cells, motoric function and brain lesion volume was not different. Posttraumatic-treatment with DNase-I therefore stabilizes the BBB, reduces the formation of brain edema, immune response, and delays secondary brain damage. DNase-I might be a new approach to extend the treatment window after TBI., (© 2023. The Author(s).)

Background:  Exoscopic 3D4K video systems (EX) have recently been introduced as an alternative to conventional operating microscopes (OM). However, experience in handling and setup remains scarce. This study evaluated the practicability of exoscopic surgery in a wide range of procedures., Material and Methods:  All EX operations performed between August 2018 and May 2020 were evaluated and compared with procedures using OM. A standardized questionnaire was used to evaluate surgeons' comfort, image quality (including fluorescence modes), and handling., Results:  In all, 513 EX operations were performed during the investigated period. EX was generally rated as a valuable surgical tool. In particular, the digital 5-aminolevulinic acid (5-ALA) fluorescence and the comfort level of posture during surgery were stated to be superior to OM (100 and 83%, respectively)., Conclusion:  EX has been used for a significant number of neurosurgical procedures. While presuming that the technical methodology as such will not influence outcome of glioma surgery, proof of equipoise between different techniques expands the spectrum of surgical environments giving neurosurgeons a choice to work according to their preferred ergonomics., Competing Interests: J.R. works as a medical consultant for Olympus.F.L.R. performs routine paid lectures on neurosurgical procedures for Olympus., (Thieme. All rights reserved.)

Purpose: Spinal abnormalities frequently occur in patients with mucopolysaccharidosis (MPS) types I, II, IV, and VI. The symptoms are manifold, which sometimes prolongs the diagnostic process and delays therapy. Spinal stenosis (SS) with spinal cord compression due to bone malformations and an accumulation of storage material in soft tissue are serious complications of MPS disease. Data on optimal perioperative therapeutic care of SS is limited., Methods: A retrospective chart analysis of patients with MPS and SS for the time period 01/1998 to 03/2021 was performed. Demographics, clinical data, neurological status, diagnostic evaluations (radiography, MRI, electrophysiology), and treatment modalities were documented. The extent of the SS and spinal canal diameter were analyzed. A Cox regression analysis was performed to identify prognostic factors for neurological outcomes., Results: Out of 209 MPS patients, 15 were included in this study. The most dominant type of MPS was I (-H) (n = 7; 46.7%). Preoperative neurological deterioration was the most frequent indication for further diagnostics (n = 12; 80%). The surgical procedure of choice was dorsal instrumentation with microsurgical decompression (n = 14; 93.3%). A univariate Cox regression analysis showed MPS type I (-H) to be associated with favorable neurological outcomes., Conclusion: Early detection of spinal stenosis is highly relevant in patients with MPS. Detailed neurological assessment during follow-up is crucial for timeous detection of patients at risk. The surgical intervention of choice is dorsal instrumentation with microsurgical decompression and resection of thickened intraspinal tissue. Patients with MPS type I (-H) demonstrated the best neurological course., (© 2022. The Author(s).)

Background: In recent years, 3D4K exoscope systems (EXs) have been introduced to microneurosurgery and reported to be an alternative to conventional operating microscopes (OMs). This study reviews our single-center experience using an 3D4K EX in intracranial aneurysm surgery., Objective: To investigate the applicability of a novel 3D4K EX for intracranial aneurysm surgery., Methods: A retrospective analysis of patients who underwent microsurgical repair of incidentally or ruptured cerebral aneurysms between August 2018 and August 2020 was performed. Patient and aneurysm characteristics and technical features, including 3-dimensional indocyanine green fluorescence, were evaluated. Data on surgery duration were statically assessed for a time trend and comparability with the OM cohort., Results: Overall, we collected 185 aneurysm cases in which the exoscope was used in 44 cases. The mean duration of surgery using the EX was in similar range to those using the OM (165.5 ± 45.8 minutes vs 160.5 ± 39.2 minutes, P > .05). Routine postoperative computed tomography angiography showed comparable rates of complete aneurysm occlusion (95.5% vs 92.2%, P > .05) and postoperative complications (9.1% vs 9.7%, P > .05). There was no necessity to revert to the OM from the EX. Three-dimensional indocyanine green fluorescence was used in all procedures without any malfunction., Conclusion: The 3D4K EX for vascular microsurgical cases proved to be as useful as the OM. Because of the ease of use and comparable surgical results, the EX has the potential to become an accepted and additional visualization tool in vascular microsurgery next to the OM., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Traumatic brain injury (TBI) involves primary mechanical damage and delayed secondary damage caused by vascular dysfunction and neuroinflammation. Intracellular components released into the parenchyma and systemic circulation, termed danger-associated molecular patterns (DAMPs), are major drivers of vascular dysfunction and neuroinflammation. These DAMPs include cell-free RNAs (cfRNAs), which damage the blood-brain barrier (BBB), thereby promoting edema, procoagulatory processes, and infiltration of inflammatory cells. We tested the hypothesis that intraperitoneal injection of Ribonuclease-1 (RNase1, two doses of 20, 60, or 180 µg/kg) at 30 min and 12 h after controlled-cortical-impact (CCI) can reduce secondary lesion expansion compared to vehicle treatment 24 h and 120 h post-CCI. The lowest total dose (40 µg/kg) was most effective at reducing lesion volume (- 31% RNase 40 µg/kg vs. vehicle), brain water accumulation (- 5.5%), and loss of BBB integrity (- 21.6%) at 24 h post-CCI. RNase1 also reduced perilesional leukocyte recruitment (- 53.3%) and microglial activation (- 18.3%) at 120 h post-CCI, but there was no difference in lesion volume at this time and no functional benefit. Treatment with RNase1 in the early phase following TBI stabilizes the BBB and impedes leukocyte immigration, thereby suppressing neuroinflammation. RNase1-treatment may be a novel approach to delay brain injury to extend the window for treatment opportunities after TBI., (© 2022. The Author(s).)

Extracorporeal membrane oxygenation (ECMO) is potentially lifesaving for patients with acute respiratory distress syndrome (ARDS) but may be accompanied by serious adverse events, including intracranial hemorrhage (ICRH). We hypothesized that ICRH occurs more frequently in patients with COVID-19 than in patients with ARDS of other etiologies. We performed a single-center retrospective analysis of adult patients treated with venovenous (vv-) ECMO for ARDS between January 2011 and April 2021. Patients were included if they had received a cranial computed tomography (cCT) scan during vv-ECMO support or within 72 h after ECMO removal. Cox regression analysis was used to identify factors associated with ICRH. During the study period, we identified 204 patients with vv-ECMO for ARDS, for whom a cCT scan was available. We observed ICRH in 35.4% ( n = 17/48) of patients with COVID-19 and in 16.7% ( n = 26/156) of patients with ARDS attributable to factors other than COVID-19. COVID-19 (HR: 2.945; 95%; CI: 1.079-8.038; p = 0.035) and carboxyhemoglobin (HR: 0.330; 95%; CI: 0.135-0.806; p = 0.015) were associated with ICRH during vv-ECMO. In patients receiving vv-ECMO, the incidence of ICRH is doubled in patients with COVID-19 compared to patients suffering from ARDS attributable to other causes. More studies on the association between COVID-19 and ICRH during vv-ECMO are urgently needed to identify risk patterns and targets for potential therapeutic interventions.

Cerebral vasospasm that occurs in the weeks after subarachnoid hemorrhage, a type of hemorrhagic stroke, contributes to delayed cerebral ischemia. A problem encountered in experimental studies using murine models of SAH is that methods for in vivo monitoring of cerebral vasospasm in mice are lacking. Here, we demonstrate the application of high frequency ultrasound to perform transcranial Duplex sonography examinations on mice. Using the method, the internal carotid arteries (ICA) could be identified. The blood flow velocities in the intracranial ICAs were accelerated significantly after induction of SAH, while blood flow velocities in the extracranial ICAs remained low, indicating cerebral vasospasm. In conclusion, the method demonstrated here allows functional, noninvasive in vivo monitoring of cerebral vasospasm in a murine SAH model.

Objective: Intraoperative blood loss in patients undergoing oncological spine surgery poses a major challenge for vulnerable patients. The goal of this study was to assess how the surgical procedure, tumor type, and tumor anatomy, as well as anesthesiological parameters, affect intraoperative blood loss in oncological spine surgery and to use this information to generate a short preoperative checklist for spine surgeons and anesthesiologists to identify patients at risk for increased intraoperative blood loss., Methods: The authors performed a retrospective analysis of 430 oncological patients who underwent spine surgery between 2013 and 2018 at the university medical spine center. Enrolled patients had metastatic tumor of the spine requiring surgical decompression of neural structures and/or stabilization including tumor biopsy using an open, percutaneous, and/or combined dorsoventral approach. Patients requiring vertebro- and kyphoplasty or biopsy only were excluded. Statistical analyses performed included a multiple linear regression analysis., Results: The mean intraoperative blood loss in the study patient cohort was 1176 ± 1209 ml. In total, 33.8% of patients received intraoperative red blood cell transfusions. The statistical analyses showed that tumor histology indicating myeloma, operative procedure length, epidural spinal cord compression (ESCC) score, tumor localization, BMI, and surgical strategy were significantly associated with increased intraoperative blood loss or risk of needing allogeneic blood transfusions. Anesthesiological parameters such as the American Society of Anesthesiologists (ASA) Physical Status classification score were not associated with blood loss. Multiple linear regression analysis demonstrated good predictive value (r = 0.437) for a five-item preoperative checklist to identify patients at risk for high intraoperative blood loss., Conclusions: The analyses performed in this study demonstrated key factors affecting intraoperative blood loss and showed that a simple preoperative checklist including these factors can be used to identify patients undergoing surgery for metastatic spine tumors who are at risk for increased intraoperative blood loss., Abbreviations: ABT = allogeneic blood transfusion; ASA = American Society of Anesthesiologists; ESCC = epidural spinal cord compression; KW = Kruskal-Wallis; MET = metabolic equivalent of task; RBC = red blood cell., Competing Interests: Dr. Dreimann is supported by Stryker, Medtronic, Spineart (speaker), Medtronic (research support), and Spineart (advisory board).

Objective: Unruptured Intracranial Aneurysm (UIA) Treatment Score (UIATS) and PHASES score are used to inform treatment decision making for UIAs (treatment or observation). We assessed the ability of the scoring systems to discriminate between ruptured aneurysms and UIAs in a subarachnoid hemorrhage (SAH) cohort with multiple aneurysms. Methods: We retrospectively applied PHASES and UIATS scoring to the aneurysms of 40 consecutive patients with SAH and multiple intracranial aneurysms. Results: PHASES score discriminated better between ruptured aneurysms and UIAs than UIATS. PHASES scores and the difference between the UIATS subscores were higher for ruptured aneurysms compared with UIAs, which reached significance for the PHASES score. PHASES score estimated a low 5-year rupture risk in a larger proportion of the UIAs (≤0.7% in 62.3%, ≤1.7% in 98.4%) than of the ruptured aneurysms (≤0.7% in 22.5%, ≤1.7% in 82.5%). In the 40 ruptured aneurysms, UIATS provided recommendation for treatment in 11 (27.5%), conservative management in 14 (35.0%), and was inconclusive in 15 cases (37.5%). In the 61 UIAs, UIATS recommended treatment in 16 (26.2%), conservative management in 29 (47.5%), and was inconclusive in 16 (26.2%) cases. Conclusion: Similar to previous SAH cohorts, a significant proportion of the ruptured aneurysms exhibited a low-rupture risk. Nevertheless, PHASES score discriminated between ruptured aneurysms and UIAs in our cohort; the lower discriminatory power of UIATS was due to high weights of aneurysm-independent factors. We recommend careful integration of the scores for individual decision making. Large-scale prospective trials are required to establish score-based treatment strategies for UIAs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Neulen, Pantel, König, Brockmann, Ringel and Kantelhardt.)

Cerebral hypoperfusion is a key factor for determining the outcome after subarachnoid hemorrhage (SAH). A subset of SAH patients develop neurogenic stress cardiomyopathy (NSC), but it is unclear to what extent cerebral hypoperfusion is influenced by cardiac dysfunction after SAH. The aims of this study were to examine the association between cardiac function and cerebral perfusion in a murine model of SAH and to identify electrocardiographic and echocardiographic signs indicative of NSC. We quantified cortical perfusion by laser SPECKLE contrast imaging, and myocardial function by serial high-frequency ultrasound imaging, for up to 7 days after experimental SAH induction in mice by endovascular filament perforation. Cortical perfusion decreased significantly whereas cardiac output and left ventricular ejection fraction increased significantly shortly post-SAH. Transient pathological ECG and echocardiographic abnormalities, indicating NSC (right bundle branch block, reduced left ventricular contractility), were observed up to 3 h post-SAH in a subset of model animals. Cerebral perfusion improved over time after SAH and correlated significantly with left ventricular end-diastolic volume at 3, 24, and 72 h. The murine SAH model is appropriate to experimentally investigate NSC. We conclude that in addition to cerebrovascular dysfunction, cardiac dysfunction may significantly influence cerebral perfusion, with LVEDV presenting a potential parameter for risk stratification.

Background: A considerable number of patients with subarachnoid hemorrhage (SAH) develop vasospasms of the infratentorial arteries. Transcranial Doppler sonography (TCD) is used to screen for vasospasm. In this study, we used a technical modification that combines TCD with an image guidance device that the operator can use to navigate to the ultrasonic window and to predefined intracranial vascular targets. Our aim was to analyze the feasibility, spatial precision, and spatial reproducibility of serial image-guided TCD of infratentorial and-for comparison-supratentorial arteries in the clinical setting of monitoring for vasospasm after SAH., Methods: The study included 10 SAH patients, who each received 5 serial image-guided TCD examinations. Using computed tomography angiography data, trajectories to the infratentorial and supratentorial cerebral arteries were planned and loaded into an image guidance device tracking the Doppler probe. As a measure of spatial precision and spatial reproducibility, we analyzed the distances between the positions of preplanned vascular targets and optimal Doppler signals., Results: The mean distance between preplanned and optimal target points was 4.8 ± 2.1 mm (first exam), indicating high spatial precision. The spatial precision decreased with increasing depth of the vascular target. In all patients, image-guided TCD detected all predefined supratentorial and infratentorial vascular segments. There were no significant changes in spatial precision in serial exams, indicating high reproducibility., Conclusions: Image-guided TCD is feasible for supratentorial and infratentorial arteries. It shows high spatial precision and reproducibility. This study provides a basis for future clinical studies on image-guided TCD for post-SAH vasospasm screening., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Computed tomography angiography (CTA) is frequently used with computed tomography perfusion imaging (CTP) to evaluate whether endovascular vasospasm treatment is indicated for subarachnoid hemorrhage patients with delayed cerebral ischemia. However, objective parameters for CTA evaluation are lacking. In this study, we used an automated, investigator-independent, digital method to detect vasospasm, and we evaluated whether the method could predict the need for subsequent endovascular vasospasm treatment. Methods: We retrospectively reviewed the charts and analyzed imaging data for 40 consecutive patients with subarachnoid hemorrhages. The cerebrovascular trees were digitally reconstructed from CTA data, and vessel volume and the length of the arteries of the circle of Willis and their peripheral branches were determined. Receiver operating characteristic curve analysis based on a comparison with digital subtraction angiographies was used to determine volumetric thresholds that indicated severe vasospasm for each vessel segment. Results: The automated threshold-based volumetric evaluation of CTA data was able to detect severe vasospasm with high sensitivity and negative predictive value for predicting cerebral hypoperfusion on CTP, although the specificity and positive predictive value were low. Combining the automated detection of vasospasm on CTA and cerebral hypoperfusion on CTP was superior to CTP or CTA alone in predicting endovascular vasospasm treatment within 24 h after the examination. Conclusions: This digital volumetric analysis of the cerebrovascular tree allowed the objective, investigator-independent detection and quantification of vasospasms. This method could be used to standardize diagnostics and the selection of subarachnoid hemorrhage patients with delayed cerebral ischemia for endovascular diagnostics and possible interventions., (Copyright © 2020 Neulen, Kunzelmann, Kosterhon, Pantel, Stein, Berres, Ringel, Brockmann, Brockmann and Kantelhardt.)

Aim: Meta-analyses indicate positive effects of both antipsychotic and cognitive-behavioural interventions in subjects clinically at high risk (CHR) for psychosis in terms of a delay or prevention of psychotic disorders. However, these effects have been limited regarding social functioning and the relative efficacy of both types of interventions remains unclear. Furthermore, neuroprotective substances seem to be a promising alternative agent in psychosis-prevention as they are associated with few and weak side-effects., Methods: In this multi-centre randomized controlled trial (RCT), we investigate the effects of two interventions on transition to psychosis and social functioning: (a) an integrated preventive psychological intervention (IPPI) including stress-/symptom-management and social-cognitive remediation; (b) N-acetyl-l-cysteine (NAC) as a pharmacological intervention with glutamatergic, neuroprotective and anti-inflammatory capabilities., Results: This is a double-blind, placebo-controlled RCT with regard to NAC and a single-blind RCT with regard to IPPI using a 2 × 2-factorial design to investigate the individual and combined preventive effects of both interventions. To this aim, a total of 200 CHR subjects will be randomized stratified by site to one of four conditions: (a) IPPI and NAC; (b) IPPI and Placebo; (c) NAC and psychological stress management; (d) Placebo and psychological stress management. Interventions are delivered over 26 weeks with a follow-up period of 12 months., Conclusion: This paper reports on the rationale and protocol of an indicated prevention trial to detect the most effective and tolerable interventions with regard to transition to psychosis as well as improvements in social functioning, and to evaluate the synergistic effects of these interventions., (© 2019 John Wiley & Sons Australia, Ltd.)

Cerebral hypoperfusion in the first hours after subarachnoid haemorrhage (SAH) is a major determinant of poor neurological outcome. However, the underlying pathophysiology is only partly understood. Here we induced neutropenia in C57BL/6N mice by anti-Ly6G antibody injection, induced SAH by endovascular filament perforation, and analysed cerebral cortical perfusion with laser SPECKLE contrast imaging to investigate the role of neutrophils in mediating cerebral hypoperfusion during the first 24 h post-SAH. SAH induction significantly increased the intracranial pressure (ICP), and significantly reduced the cerebral perfusion pressure (CPP). At 3 h after SAH, ICP had returned to baseline and CPP was similar between SAH and sham mice. However, in SAH mice with normal neutrophil counts cortical hypoperfusion persisted. Conversely, despite similar CPP, cortical perfusion was significantly higher at 3 h after SAH in mice with neutropenia. The levels of 8-iso-prostaglandin-F2α in the subarachnoid haematoma increased significantly at 3 h after SAH in animals with normal neutrophil counts indicating oxidative stress, which was not the case in neutropenic SAH animals. These results suggest that neutrophils are important mediators of cortical hypoperfusion and oxidative stress early after SAH. Targeting neutrophil function and neutrophil-induced oxidative stress could be a promising new approach to mitigate cerebral hypoperfusion early after SAH.

Purpose: Together with other diagnostic modalities, computed tomography angiography (CTA) is commonly used to indicate endovascular vasospasm treatment after subarachnoid hemorrhage (SAH), despite the fact that objective, user-independent parameters for evaluation of CTA are lacking. This exploratory study was designed to investigate whether quantification of vasospasm by automated volumetric analysis of the middle cerebral artery M1 segment from CTA data could be used as an objective parameter to indicate endovascular vasospasm treatment., Methods: We retrospectively identified SAH patients who underwent transcranial Doppler sonography (TCD), CTA, and CT perfusion (CTP), with or without subsequent endovascular treatment. We determined vessel volume/vessel length of the M1 segments from CTA data and used receiver operating characteristic curve analysis to determine the optimal threshold of vessel volume to predict vasospasm requiring endovascular treatment. In addition, blinded investigators independently analyzed TCD, CTA, and CTP data., Results: Of 45 CTA examinations with corresponding CTP and TCD examinations (24 SAH patients), nine indicated the need for endovascular vasospasm treatment during examination. In our patients, vessel volume < 5.8 µL/mm was moderately sensitive but fairly specific to detect vasospasm requiring endovascular treatment (sensitivity, 67%; specificity, 78%; negative predictive value (NPV), 89%; positive predictive value (PPV), 46%). For CTA, CTP, and TCD, we found NPVs of 96%, 92%, and 89%, PPVs of 40%, 35%, and 35%, sensitivities of 89%, 78%, and 67%, and specificities of 67%, 64%, and 69%, respectively., Conclusion: Vessel volumes could provide a new objective parameter for the interpretation of CTA data and could thereby improve multimodal assessment of vasospasm in SAH patients.

Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke. Cerebral vasospasm that occurs in the aftermath of the bleeding is an important factor determining patient outcome and is therefore frequently taken as a study endpoint. However, in small animal studies on SAH, quantification of cerebral vasospasm is a major challenge. Here, an ex vivo method is presented that allows quantification of volumes of entire vessel segments, which can be used as an objective measure to quantify cerebral vasospasm. In a first step, endovascular casting of the cerebral vasculature is performed using a radiopaque casting agent. Then, cross-sectional imaging data are acquired by micro computed tomography. The final step involves 3-dimensional reconstruction of the virtual vascular tree, followed by an algorithm to calculate center lines and volumes of the selected vessel segments. The method resulted in a highly accurate virtual reconstruction of the cerebrovascular tree shown by a diameter-based comparison of anatomical samples with their virtual reconstructions. Compared with vessel diameters alone, the vessel volumes highlight the differences between vasospastic and non-vasospastic vessels shown in a series of SAH and sham-operated mice.

Clinical studies on subarachnoid hemorrhage (SAH) have shown discrepancies between large vessel vasospasm, cerebral perfusion, and clinical outcome. We set out to analyze the contribution of large vessel vasospasm to impaired cerebral perfusion and neurological impairment in a murine model of SAH. SAH was induced in C57BL/6 mice by endovascular filament perforation. Vasospasm was analyzed with microcomputed tomography, cortical perfusion by laser SPECKLE contrast imaging, and functional impairment with a quantitative neuroscore. SAH animals developed large vessel vasospasm, as shown by significantly lower vessel volumes of a 2.5-mm segment of the left middle cerebral artery (MCA) (SAH 5.6 ± 0.6 nL, sham 8.3 ± 0.5 nL, p < 0.01). Induction of SAH significantly reduced cerebral perfusion of the corresponding left MCA territory compared to values before SAH, which only recovered partly (SAH vs. sham, 15 min 35.7 ± 3.1 vs. 101.4 ± 10.2%, p < 0.01; 3 h, 85.0 ± 8.6 vs. 121.9 ± 13.4, p < 0.05; 24 h, 75.3 ± 4.6 vs. 110.6 ± 11.4%, p < 0.01; 72 h, 81.8 ± 4.8 vs. 108.5 ± 14.5%, n.s.). MCA vessel volume did not correlate significantly with MCA perfusion after 72 h (r = 0.34, p = 0.25). Perfusion correlated moderately with neuroscore (24 h: r = - 0.58, p < 0.05; 72 h: r = - 0.44, p = 0.14). There was no significant correlation between vessel volume and neuroscore after 72 h (r = - 0.21, p = 0.50). In the murine SAH model, cerebral hypoperfusion occurs independently of large vessel vasospasm. Neurological outcome is associated with cortical hypoperfusion rather than large vessel vasospasm.

Introduction: Quantification of cerebral vasospasm after subarachnoid hemorrhage (SAH) is crucial in animal studies as well as clinical routine. We have developed a method for computer-based volumetric assessment of intracranial blood vessels from cross-sectional imaging data. Here we demonstrate the quantification of vasospasm from micro computed tomography (micro-CT) data in a rodent SAH model and the transferability of the volumetric approach to clinical data., Methods: We obtained rodent data by performing an ex vivo micro-CT of murine brains after sham surgery or SAH by endovascular filament perforation on day 3 post hemorrhage. Clinical CT angiography (CTA) was performed for diagnostic reasons unrelated to this study. We digitally reconstructed and segmented intracranial vascular trees, followed by calculating volumes of defined vessel segments by standardized protocols using Amira® software., Results: SAH animals demonstrated significantly smaller vessel diameters compared with sham (MCA: 134.4±26.9μm vs.165.0±18.7μm, p<0.05). We could highlight this difference by analyzing vessel volumes of a defined MCA-ICA segment (SAH: 0.044±0.017μl vs. sham: 0.07±0.006μl, p<0.001). Analysis of clinical CTA data allowed us to detect and volumetrically quantify vasospasm in a series of 5 SAH patients. Vessel diameters from digital reconstructions correlated well with those measured microscopically (rodent data, correlation coefficient 0.8, p<0.001), or angiographically (clinical data, 0.9, p<0.001)., Conclusions: Our methodological approach provides accurate anatomical reconstructions of intracranial vessels from cross-sectional imaging data. It allows volumetric assessment of entire vessel segments, hereby highlighting vasospasm-induced changes objectively in a murine SAH model. This method could also be a helpful tool for analysis of clinical CTA.