Evaluating the glymphatic system via magnetic resonance diffusion tensor imaging along the perivascular spaces in brain tumor patients.

PURPOSE: To investigate glymphatic system function in patients with brain tumors, including both primary and secondary tumors, using diffusion tensor imaging along perivascular spaces (DTI-ALPS). METHODS: We retrospectively analyzed the MR DTI of 24 patients with unilateral brain tumors and compared them with age and sex-matched controls. We compared the DTI-ALPS index of the ipsi- and contralateral brain hemispheres. The region of interest was placed in the periventricular vessels adjacent to the lateral ventricles. Differences between sex, age, and kind of tumor (primary or brain metastasis) were evaluated. Correlations between DTI-ALPS index and age and the tumor's apparent diffusion coefficient (ADC) were also investigated. RESULTS: The DTI-ALPS index was significantly lower (p < 0.05) in the tumor-affected hemisphere (mean = 1.26 ± 0.24) than contralateral (mean = 1.43 ± 0.28). A comparison with healthy controls revealed no significant difference on the matched ipsilateral side. However, the DTI-ALPS index of the contralateral side of the patients was larger than the HC. Additionally, no statistically significant differences were found when analyzing the DTI-ALPS index vs. age, sex, and tumor entity. Additionally, we did not find a correlation between the DTI-ALPS index and patient age or tumor ADC. CONCLUSION: The decreased DTI-ALPS index in the tumor-affected hemisphere may be related to impaired glymphatic system function. However, cancer is often a systemic disease; thus, the DTI-ALPS index from the contralateral brain hemisphere may not generally be considered as a normal control. Nonetheless, the DTI-ALPS index does not only reflect diffusion in the perivascular spaces but it can also be influenced by factors such as axonal degeneration. Therefore, it does not directly reflect brain waste clearance and changes in the index should be interpreted carefully.

Prospective Observational Study of Volatile Sedation with Sevoflurane After Aneurysmal Subarachnoid Hemorrhage Using the Sedaconda Anesthetic Conserving Device.

BACKGROUND: Volatile sedation is still used with caution in patients with acute brain injury because of safety concerns. We analyzed the effects of sevoflurane sedation on systemic and cerebral parameters measured by multimodal neuromonitoring in patients after aneurysmal subarachnoid hemorrhage (aSAH) with normal baseline intracranial pressure (ICP). METHODS: In this prospective observational study, we analyzed a 12-h period before and after the switch from intravenous to volatile sedation with sevoflurane using the Sedaconda Anesthetic Conserving Device with a target Richmond Agitation Sedation Scale score of - 5 to - 4. ICP, cerebral perfusion pressure (CPP), brain tissue oxygenation (PBrO2), metabolic values of cerebral microdialysis, systemic cardiopulmonary parameters, and the administered drugs before and after the sedation switch were analyzed. RESULTS: We included 19 patients with a median age of 61 years (range 46-78 years), 74% of whom presented with World Federation of Neurosurgical Societies grade 4 or 5 aSAH. We observed no significant changes in the mean ICP (9.3 ± 4.2 vs. 9.7 ± 4.2 mm Hg), PBrO2 (31.0 ± 13.2 vs. 32.2 ± 12.4 mm Hg), cerebral lactate (5.0 ± 2.2 vs. 5.0 ± 1.9 mmol/L), pyruvate (136.6 ± 55.9 vs. 134.1 ± 53.6 µmol/L), and lactate/pyruvate ratio (37.4 ± 8.7 vs. 39.8 ± 9.2) after the sedation switch to sevoflurane. We found a significant decrease in mean arterial pressure (MAP) (88.6 ± 7.6 vs. 86.3 ± 5.8 mm Hg) and CPP (78.8 ± 8.5 vs. 76.6 ± 6.6 mm Hg) after the initiation of sevoflurane, but the decrease was still within the physiological range requiring no additional hemodynamic support. CONCLUSIONS: Sevoflurane appears to be a feasible alternative to intravenous sedation in patients with aSAH without intracranial hypertension, as our study did not show negative effects on ICP, cerebral oxygenation, or brain metabolism. Nevertheless, the risk of a decrease of MAP leading to a consecutive CPP decrease should be considered.

Mathematical model calibrated to in vitro data predicts mechanisms of antiviral action of the influenza defective interfering particle "OP7".

Defective interfering particles (DIPs) are regarded as potent broad-spectrum antivirals. We developed a mathematical model that describes intracellular co-infection dynamics of influenza standard virus (STV) and "OP7", a new type of influenza DIP discovered recently. Based on experimental data from in vitro studies to calibrate the model and confirm its predictions, we deduce OP7's mechanisms of interference, which were yet unknown. Simulations suggest that the "superpromoter" on OP7 genomic viral RNA enhances its replication and results in a depletion of viral proteins. This reduces STV genomic RNA replication, which appears to constitute an antiviral effect. Further, a defective viral protein (M1-OP7) likely causes the deficiency of OP7's replication. It appears unable to bind to genomic viral RNAs to facilitate their nuclear export, a critical step in the viral life cycle. An improved understanding of OP7's antiviral mechanism is crucial toward application in humans as a prospective antiviral treatment strategy.

Risks of nimodipine dose reduction during the high-risk period for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Nimodipine dose reduction is recommended in case of high vasopressor demand after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to assess potential adverse effects of nimodipine reduction during the high-risk period for delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) between days 5 and 10 after hemorrhage. Demographic and clinical data as well as daily nimodipine dose of aSAH patients admitted between 2010 and 2019 were retrospectively analyzed. Univariable and multivariable regression analyses were performed to identify factors associated with DCI, angiographic CVS, DCI-related infarction, and unfavorable outcome. A total of 205 patients were included. Nimodipine dose reduction occurred in 108 (53%) patients ('nimodipine reduction group'), while 97 patients (47%) received the full dose ('no nimodipine reduction group'), Patients in the 'nimodipine reduction group' had significant worse WFNS and Fisher grades and developed significantly more often DCI and angiographic CVS. DCI-related infarction and unfavorable outcome were also significantly increased in the 'nimodipine reduction group.' 'Reduced nimodipine dose' was the only independent predictor for the occurrence of DCI and angiographic CVS in multivariable regression analysis. 'Poor WFNS grade' and 'reduced nimodipine dose' were identified as independent risk factors for DCI-related infarction while 'older age,' 'poor WFNS grade,' and 'reduced nimodipine dose' were associated with unfavorable outcome at 3 months after discharge. Nimodipine dose reduction during the high-risk period of DCI and CVS between days 5 and 10 after hemorrhage might abrogate the positive prognostic effects of nimodipine and should be critically evaluated.

Reversible intracranial contrast medium accumulation after embolization of unruptured cerebral aneurysms and its association with transient neurological deficits: A single center experience.

BACKGROUND: Use of iodine-containing contrast medium (CM) is obligatory for endovascular treatment (EVT) of cerebral aneurysms. After EVT, intracranial density increases (DIs) can be detected in cranial computed tomography (CT). Those DI can correspond to subarachnoid hemorrhage (SAH), infarction or reversible CM accumulation (RCMA). The latter can be mistaken for hemorrhage, especially if they are accompanied by neurological deficits. OBJECTIVE: To analyze postinterventional DI after EVT of unruptured cerebral aneurysms and associated clinical symptoms and to identify risk factors for the occurrence of RCMA. METHODS: For differentiation of DI, we compared CT scans following EVT and additionally 24 h ± 5 h later. Diagnosis of RCMA was based on marked regression of DI on follow-up scans. We analyzed continuous variables (age, duration of intervention and anesthesia, aneurysm diameter, amount of CM and renal function) and categorial variables (gender, aneurysm location, devices for EVT, antiplatelet therapy [APT] and associated neurological deficits) to identify risk factors for the occurrence of RCMA. RESULTS: We studied 58 patients (44 female, mean age 59.5 [range 39-81]) who underwent EVT for a total of 68 cerebral aneurysms in 62 therapy sessions over a 3-year period without periprocedural complications. Postinterventional DI occurred after 17 therapy sessions. All 17 DI turned out to be RCMA in the follow-up imaging. Two patients who had no DI on initial postinterventional CT showed new SAH on follow-up CT. Infarctions were not observed. Transient neurological deficits occurred in eight patients (12.9%) and were associated with RCMA (P = 0.010). Postinterventional RCMA was associated with the duration of EVT (P = 0.038) and with APT (acetylsalicylic acid [ASA] + clopidogrel: P =0.040; ASA alone: P =0.011). CONCLUSIONS: RCMA is common after EVT of unruptured cerebral aneurysms and often accompanied by transient neurological deficits. Long procedure duration and APT appear to predispose to the occurrence of RCMA.

Evaluation of DeGIR registry data on endovascular treatment of cerebral vasospasm in Germany 2018-2021: an overview of the current care situation. / Auswertung der DeGIR-Registerdaten zur endovaskulären Therapie von zerebralen Vasospasmen in Deutschland 2018­2021: Ein Überblick über die aktuelle Versorgungssituation.

BACKGROUND: Evaluation of endovascular therapies for cerebral vasospasm (CVS) documented in the DeGIR registry from 2018-2021 to analyse the current clinical care situation in Germany. METHODS: Retrospective analysis of the clinical and procedural data on endovascular spasm therapies (EST) documented anonymously in the DeGIR registry. We analysed: pre-interventional findings of CTP and consciousness; radiation dose applied, interventional-technical parameters (local medication, devices, angiographic result), post-interventional symptoms, complications and mortality. RESULTS: 3584 patients received a total of 7628 EST (median age/patient: 53 [range: 13-100, IQR: 44-60], 68.2 % women) in 91 (2018), 92 (2019), 100 (2020) and 98 (2021) centres; 5388 (70.6 %) anterior circulation and 378 (5 %) posterior circulation (both involved in 1862 cases [24.4 %]). EST was performed once in 2125 cases (27.9 %), with a mean of 2.1 EST/patient. In 7476 times, purely medicated EST were carried out (nimodipine: 6835, papaverine: 401, nitroglycerin: 62, other drug not specified: 239; combinations: 90). Microcatheter infusions were documented in 1132 times (14.8 %). Balloon angioplasty (BA) (additional) was performed in 756 EST (9.9 %), other mechanical recanalisations in 154 cases (2 %) and stenting in 176 of the EST (2.3 %). The median dose area product during ET was 4069 cGycm² (drug: 4002/[+]BA: 8003 [p < 0.001]). At least 1 complication occurred in 95 of all procedures (1.2 %) (drug: 1.1 %/[+]BA: 4.2 % [p < 0.001]). Mortality associated with EST was 0.2 % (n = 18). After EST, overall improvement or elimination of CVS was found in 94.2 % of cases (drug: 93.8 %/[+]BA: 98.1 % [p < 0.001]). In a comparison of the locally applied drugs, papaverine eliminated CVS more frequently than nimodipine (p = 0.001). CONCLUSION: EST have a moderate radiation exposure and can be performed with few complications. Purely medicated EST are predominantly performed, especially with nimodipine. With (additional) BA, radiation exposure, complication rates and angiographic results are higher or better. When considering drug EST alone, there is evidence for an advantage of papaverine over nimodipine, but a different group size has to be taken into account. In the analysis of EST, the DeGIR registry data are suitable for answering more specific questions, especially due to the large number of cases; for this purpose, further subgroupings should be sought in the data documentation. KEY POINTS: · In Germany, there are currently no guidelines for the endovascular treatment of cerebral vasospasm following spontaneous subarachnoid hemorrhage.. · In addition to oral nimodipine administration endovascular therapy is used to treat cerebral vasospasm in most hospitals.. · This is the first systematic evaluation of nationwide registry data on endovascular treatment of cerebral vasopasm in Germany.. · This real-world data shows that endovascular treatment for cerebral vasospasm has a moderate radiation exposure and can be performed with few complications overall. With (additional) balloon angioplasty, radiation exposure, complication rates and angiographic therapy results are higher or better.. CITATION FORMAT: · Neumann A, Weber W, Küchler J et al. Evaluation of DeGIR registry data on endovascular treatment of cerebral vasospasm in Germany 2018-2021: an overview of the current care situation. Fortschr Röntgenstr 2023; 195: 1018 - 1026.

Limitations of prone positioning in patients with aneurysmal subarachnoid hemorrhage and concomitant respiratory failure.

OBJECTIVE: Prone positioning (PP) is an established treatment modality for respiratory failure. After aneurysmal subarachnoid hemorrhage (aSAH), PP is rarely performed considering the risk of intracranial hypertension. The aim of this study was to analyze the effects of PP on intracranial pressure (ICP), cerebral perfusion pressure (CPP) and cerebral oxygenation following aSAH. PATIENTS AND METHODS: Demographic and clinical data of aSAH patients admitted over a 6-year period and treated with PP due to respiratory insufficiency were retrospectively analyzed. ICP, CPP, brain tissue oxygenation (pBrO2), respiratory parameters and ventilator settings were analyzed before and during PP. RESULTS: Thirty patients receiving invasive multimodal neuromonitoring were included. Overall, 97 PP sessions were performed. Mean arterial oxygenation and pBrO2 increased significantly during PP. We found a significant increase in median ICP compared to the baseline level in supine position. No significant changes in CPP were observed. Five PP sessions had to be terminated early due to medically refractory ICP-crisis. The affected patients were younger (p = 0.02) with significantly higher baseline ICP values (p = 0.009). Baseline ICP correlates significantly (p < 0.001) with ICP 1 h (R: 0.57) and 4 h (R: 0.55) after onset of PP. CONCLUSION: PP in aSAH patients with respiratory insufficiency is an effective therapeutic option improving arterial and global cerebral oxygenation without compromising CPP. The significant increase in ICP was moderate in most sessions. However, as some patients experience intolerable ICP crises during PP, continuous ICP-Monitoring is considered mandatory. Patients with elevated baseline ICP and reduced intracranial compliance should not be considered for PP.

Volatile Sedation With Isoflurane in Neurocritical Care Patients After Poor-grade Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Volatile sedation after aneurysmal subarachnoid hemorrhage (aSAH) promises several advantages, but there are still concerns regarding intracranial hypertension due to vasodilatory effects. We prospectively analyzed cerebral parameters during the switch from intravenous to volatile sedation with isoflurane in patients with poor-grade (World Federation of Neurosurgical Societies grade 4-5) aSAH. METHODS: Eleven patients were included in this prospective observational study. Between day 3 and 5 after admission, intravenous sedation was switched to isoflurane using the Sedaconda Anesthetic Conserving Device (Sedana Medical, Danderyd, Sweden). Intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygenation (PBrO2), cerebral mean flow velocities (MFVs; transcranial Doppler ultrasound) and regional cerebral oxygen saturation (rSO2, near-infrared spectroscopy monitoring), as well as cardiopulmonary parameters were assessed before and after the sedation switch (-12 to +12 hours). Additionally, perfusion computed tomography data during intravenous and volatile sedation were analyzed retrospectively for changes in cerebral blood flow. RESULTS: There were no significant changes in mean ICP, CPP, and PBrO2 after the sedation switch to isoflurane. Mean rSO2 showed a non-significant trend towards higher values, and mean MFV in the middle cerebral arteries increased significantly after the initiation of volatile sedation. Isoflurane sedation resulted in a significantly increased norepinephrine administration. Despite an increase in mean inspiratory pressure, we observed a significant increase in mean partial arterial pressure of carbon dioxide. CONCLUSIONS: Isoflurane sedation does not compromise ICP or cerebral oxygenation in poor-grade aSAH patients, but the significant depression of CPP could limit the use of volatiles in case of hemodynamic instability or high vasopressor demand.

Ethanol tolerance of Clostridium thermocellum: the role of chaotropicity, temperature and pathway thermodynamics on growth and fermentative capacity.

BACKGROUND: Clostridium thermocellum is a promising candidate for consolidated bioprocessing of lignocellulosic biomass to ethanol. The low ethanol tolerance of this microorganism is one of the remaining obstacles to industrial implementation. Ethanol inhibition can be caused by end-product inhibition and/or chaotropic-induced stress resulting in increased membrane fluidization and disruption of macromolecules. The highly reversible glycolysis of C. thermocellum might be especially sensitive to end-product inhibition. The chaotropic effect of ethanol is known to increase with temperature. This study explores the relative contributions of these two aspects to investigate and possibly mitigate ethanol-induced stress in growing and non-growing C. thermocellum cultures. RESULTS: To separate chaotropic from thermodynamic effects of ethanol toxicity, a non-ethanol producing strain AVM062 (Pclo1313_2638::ldh* ∆adhE) was constructed by deleting the bifunctional acetaldehyde/alcohol dehydrogenase gene, adhE, in a lactate-overproducing strain. Exogenously added ethanol lowered the growth rate of both wild-type and the non-ethanol producing mutant. The mutant strain grew quicker than the wild-type at 50 and 55 °C for ethanol concentrations ≥ 10 g L-1 and was able to reach higher maximum OD600 at all ethanol concentrations and temperatures. For the wild-type, the maximum OD600 and relative growth rates were higher at 45 and 50 °C, compared to 55 °C, for ethanol concentrations ≥ 15 g L-1. For the mutant strain, no positive effect on growth was observed at lower temperatures. Growth-arrested cells of the wild-type demonstrated improved fermentative capacity over time in the presence of ethanol concentrations up to 40 g L-1 at 45 and 50 °C compared to 55 °C. CONCLUSION: Positive effects of temperature on ethanol tolerance were limited to wild-type C. thermocellum and are likely related to mechanisms involved in the ethanol-formation pathway and redox cofactor balancing. Lowering the cultivation temperature provides an attractive strategy to improve growth and fermentative capacity at high ethanol titres in high-cellulose loading batch cultivations. Finally, non-ethanol producing strains are useful platform strains to study the effects of chaotropicity and thermodynamics related to ethanol toxicity and allow for deeper understanding of growth and/or fermentation cessation under industrially relevant conditions.

Absolute quantification of viral proteins during single-round replication of MDCK suspension cells.

Madin-Darby canine kidney (MDCK) cells are widely used in basic research and for the propagation of influenza A viruses (IAV) for vaccine production. To identify targets for antiviral therapies and to optimize vaccine manufacturing, a detailed understanding of the viral life cycle is important. This includes the characterization of virus entry, the synthesis of the various viral RNAs and proteins, the transfer of viral compounds in the cell and virus budding. In case quantitative information is available, the analysis can be complemented by mathematical modelling approaches. While comprehensive studies focusing on IAV entry as well as viral mRNA, vRNA and cRNA accumulation in the nucleus of cells have been performed, quantitative data regarding IAV protein synthesis and accumulation was mostly lacking. In this study, we present a mass spectrometry (MS)-based method to evaluate whether an absolute quantification of viral proteins is possible for single-round replication in suspension MDCK cells. Using influenza A/PR/8/34 (H1N1, RKI) as a model strain at a multiplicity of infection of ten, defined amounts of isotopically labelled peptides of synthetic origin of four IAV proteins (hemagglutinin, neuraminidase, nucleoprotein, matrix protein 1) were added as an internal standard before tryptic digestion of samples for absolute quantification (AQUA). The first intracellular protein detected was NP at 1 h post infection (hpi). A maximum extracellular concentration of 7.7E+12 copies/mL was achieved. This was followed by hemagglutinin (3 hpi, maximum 4.1E+12 copies/mL at 13 hpi), matrix protein 1 (5 hpi, maximum 2.2E+12 copies/mL at 13 hpi) and neuraminidase (5 hpi, 6.0E+11 copies/mL at 13 hpi). In sum, for the first time absolute IAV protein copy numbers were quantified by a MS-based method for infected MDCK cells providing important insights into viral protein dynamics during single-round virus replication. SIGNIFICANCE: Influenza A virus is a significant human pathogen worldwide. To improve therapies against influenza and overcome bottlenecks in vaccine production in cell culture, it is critical to gain a detailed understanding of the viral life cycle. In addition to qPCR-based models, this study will examine the dynamics of influenza virus proteins during infection of producer cells to gain initial insights into changes in absolute copy numbers.

Radiotherapy with or without Decompressive Surgery for Metastatic Spinal Cord Compression: A Retrospective Matched-Pair Study Including Data from Prospectively Evaluated Patients.

In 2005, a randomized trial showed that addition of surgery to radiotherapy improved outcomes in patients with metastatic spinal cord compression (MSCC). Since then, only a few studies compared radiotherapy plus surgery to radiotherapy alone. We performed a retrospective matched-pair study including data from prospective cohorts treated after 2005. Seventy-nine patients receiving radiotherapy alone were matched to 79 patients assigned to surgery plus radiotherapy (propensity score method) for age, gender, performance score, tumor type, affected vertebrae, other bone or visceral metastases, interval tumor diagnosis to MSCC, time developing motor deficits, and ambulatory status. Improvement of motor function by ≥1 Frankel grade occurred more often after surgery plus radiotherapy (39.2% vs. 21.5%, p = 0.015). No significant differences were found for post-treatment ambulatory rates (59.5% vs. 67.1%, p = 0.32), local progression-free survival (p = 0.47), overall survival (p = 0.51), and freedom from in-field recurrence of MSCC (90.1% vs. 76.2% at 12 months, p = 0.58). Ten patients (12.7%) died within 30 days following radiotherapy alone and 12 patients (15.2%) died within 30 days following surgery (p = 0.65); 36.7% of surgically treated patients did not complete radiotherapy as planned. Surgery led to significant early improvement of motor function and non-significantly better long-term control. Patients scheduled for surgery must be carefully selected considering potential benefits and risk of perioperative complications.

Analysis of Angiographic Treatment Response to Intra-Arterial Nimodipine Bolus Injection in Patients with Medically Refractory Cerebral Vasospasm After Spontaneous Subarachnoid Hemorrhage.

BACKGROUND: Intra-arterial nimodipine (IAN) injections are performed in refractory delayed cerebral ischemia (DCI) related to cerebral vasospasm (CVS) after spontaneous subarachnoid hemorrhage (sSAH), but the clinical benefits are inconclusive and angiographic treatment failure is observed. We analyzed angiographic IAN response in a detailed vessel-specific manner and examined the impact of poor angiographic response on the further clinical course. METHODS: Clinical data were retrospectively assessed in patients with spontaneous subarachnoid hemorrhage with symptomatic CVS receiving IAN bolus treatment. Clinical and angiographic predictors for poor angiographic response, DCI-related infarction, and unfavorable outcome were analyzed. RESULTS: Eighty-nine patients were included and 356 treated vessel segments, mainly located in the anterior circulation (93%), were analyzed. Angiographic response was good in 77% of the treated segments. Older age, poor World Federation of Neurosurgical Societies (WFNS) grade 4-5 and early onset of CVS were independently associated with poor angiographic response. The factors short-segment, distal, and bilateral CVS as well as treatment of multiple vessel segments, WFNS grade 4-5, and early onset of CVS were significantly associated with an increased risk of DCI-related infarction. Clinical outcome was significantly influenced by poor WFNS grade and early onset of CVS, whereas poor angiographic response was not related to DCI-related infarction or unfavorable outcome. CONCLUSIONS: The risk of angiographic treatment failure is significantly increased in older patients and those with poor WFNS grade as in cases of early-onset CVS. Although the extent of angiographic CVS significantly affected the development of DCI-related infarction, poor angiographic response had no impact on cerebral infarction and clinical outcome.

The "Shiny and Thick High Heel Sign" : A novel radiologic sign for detecting intracranial dural arteriovenous fistulas with time-of-flight magnetic resonance angiography.

PURPOSE: Together with the foramen ovale, the middle meningeal artery (MMA) looks like a high heel shoe print on axial time-of-flight magnetic resonance angiography (TOF-MRA) images, with the MMA resembling the heel. Cranial dural arteriovenous fistulas (DAVF) are often fed by the MMA, which can lead to an increase of signal intensity and diameter of this vessel, resulting in a more "shiny" and "thick" high heel print appearance than on the contralateral side. We describe this finding as a novel radiologic sign and provide cut-off values for the ratios of MMA signal intensities and diameters for predicting the presence of a DAVF. METHODS: A total of 84 TOF-MRA examinations of 44 patients with DAVFs (40 with unilateral MMA feeders, 4 with bilateral feeders) and of 40 patients without DAVFs were included. Diameters and signal intensities of both MMAs were measured by two raters and evaluated using receiver operating characteristic analysis. RESULTS: The diameters of feeding and non-feeding MMAs differed significantly, as did the ratios of signal intensities and of diameters of DAVF and control patients (P < 0.0001). Cut-off values were 1.25 for average signal intensity ratio (shiny high heel sign) and 1.21 for diameter ratio (thick high heel sign). The combination of the "shiny" and the "thick" high heel sign resulted in the highest sensitivity (92.5%) and positive predictive value (95%). CONCLUSION: The described sign seems promising for the detection of DAVFs with noncontrast-enhanced MRI. The TOF-MRA source images should be reviewed with special attention to the MMA.

Are radiation-induced cavernomas clinically relevant findings? Results from long-term follow-up with brain magnetic resonance imaging of childhood cancer survivors.

INTRODUCTION: Radiation-induced cavernomas (RIC) after cranial radiotherapy have an unknown risk of hemorrhage. Zabramski magnetic resonance imaging (MRI) classification is touted as being able to indicate non-radiation-induced cavernomas hemorrhage risk. The aim of our study was to assess the hemorrhage risk of RIC during long-term follow-up of childhood cancer survivors based on brain MRI examinations. PATIENTS AND METHODS: We analyzed retrospectively long-term follow-up data of 36 childhood cancer survivors after initial diagnosis with acute leukemia (n = 18) or brain tumor (n = 18), all treated with cranial radiotherapy. Detected RIC in long-term follow-up brain MRI (1.5 or 3 Tesla) were classified following the Zabramski MRI classification and were categorized into "high" (Zabramski type I, II or V) or "low" (type III or IV) risk of hemorrhage. RESULTS: 18 patients (50%) showed RIC with a significant relation to the original tumor entity (p = 0.023) and the cumulative radiation dose to the brain (p = 0.016): all 9 childhood cancer survivors diagnosed with medulloblastoma developed RIC. We classified RIC in only 3/36 childhood cancer survivors (8%) (1 patient with acute lymphoblastic leukemia [Zabramski type II] and 2 patients with medulloblastoma [type I and type II]) as high risk for hemorrhage, the remaining RIC were classified as Zabramski type IV with low risk for hemorrhage. None of the childhood cancer survivors with RIC showed symptomatic hemorrhages. CONCLUSIONS: RIC are common late effects in childhood cancer survivors treated with cranial radiotherapy affecting half of these patients. However, only a few RIC (occurring in 8% of all reviewed childhood cancer survivors) were classified as high risk for hemorrhage and none of the childhood cancer survivors with RIC developed symptomatic hemorrhages. Thus, we conclude that RIC are low-risk findings in brain MRI and the course is mainly benign.

The addition of chloroquine and bevacizumab to standard radiochemotherapy for recurrent glioblastoma multiforme.

INTRODUCTION: Hypoxia-induced autophagy leads to an increase in vasculogenic-mimicry (VM) and the development of resistance of glioblastoma-cells to bevacizumab (BEV). Chloroquine (HCQ) inhibits autophagy, reduces VM and can thus produce a synergistic effect in anti-angiogenic-therapy by delaying the development of resistance to BEV. PURPOSE: We retrospectively compared the combined addition of HCQ+BEV and adjuvant-radiochemotherapy (aRCT) to aRCT alone for recurrent-glioblastoma (rGBM) in regards of overall survival (OS). METHODS: Between 2006 and 2016, 134 patients underwent neurosurgery for rGBM at our institution. Forty-two patients (Karnofsky-Performance-Score>60%) with primary-glioblastoma underwent repeat-surgery and aRCT for recurrence. Four patients (9.5%) received aRCT+HCQ+BEV. Five patients received aRCT+BEV. RESULTS: In rGBM-patients who were treated with aRCT+HCQ+BEV, median OS was 36.57 months and median post-recurrence-survival (PRS) was 23.92 months while median PRS in the control-group was 9.63 months (p=0.022). In patients who received aRCT+BEV, OS and PRS were 26.83 and 12.97 months, respectively. CONCLUSIONS: Although this study was performed on a small number of highly selected patients, it demonstrates a synergistic effect of HCQ+BEV in the treatment of rGBM which previously could be demonstrated based on experimental data. A significant increase of OS in patients who receive aRCT+HCQ+BEV cannot be ruled out and should be further investigated in randomised-controlled-trials.

Effects of post-interventional antiplatelet therapy on angiographic vasospasm, delayed cerebral ischemia, and clinical outcome after aneurysmal subarachnoid hemorrhage: a single-center experience.

Platelet activation has been postulated to be involved in the pathogenesis of delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to investigate potentially beneficial effects of antiplatelet therapy (APT) on angiographic CVS, DCI-related infarction and functional outcome in endovascularly treated aSAH patients. Retrospective single-center analysis of aSAH patients treated by endovascular aneurysm obliteration. Based on the post-interventional medical regime, patients were assigned to either an APT group or a control group not receiving APT. A subgroup analysis separately investigated those APT patients with aspirin monotherapy (MAPT) and those receiving dual treatment (aspirin plus clopidogrel, DAPT). Clinical and radiological characteristics were compared between groups. Possible predictors for angiographic CVS, DCI-related infarction, and an unfavorable functional outcome (modified Rankin scale ≥ 3) were analyzed. Of 160 patients, 85 (53%) had received APT (n = 29 MAPT, n = 56 DAPT). APT was independently associated with a lower incidence of an unfavorable functional outcome (OR 0.40 [0.19-0.87], P = 0.021) after 3 months. APT did not reduce the incidence of angiographic CVS or DCI-related infarction. The pattern of angiographic CVS or DCI-related infarction as well as the rate of intracranial hemorrhage did not differ between groups. However, the lesion volume of DCI-related infarctions was significantly reduced in the DAPT subgroup (P = 0.011). Post-interventional APT in endovascularly treated aSAH patients is associated with better functional outcome at 3 months. The beneficial effect of APT might be mediated by reduction of the size of DCI-related infarctions.

Routine use of perfusion computed tomography for the detection of delayed cerebral ischemia in unconscious patients after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) is difficult to diagnose in unconscious patients, but it is essential for the prognosis. We analyzed the diagnostic value of routinely performed perfusion computed tomography (rPCT) to detect DCI-related hypoperfusion in this subgroup of patients. METHODS: Retrospective analysis of unconscious aSAH patients who underwent rPCT according to a predefined protocol. We exclusively analyzed PCT examinations in patients who were clinically and functionally asymptomatic with regard to transcranial Doppler ultrasound (TCD) and invasive neuromonitoring at the time of the PCT examination. The perfusion maps were quantitatively evaluated to detect DCI-related hypoperfusion. Possible clinical risk factors for the occurrence of DCI-related hypoperfusion in rPCT imaging were analyzed by multivariate analyses. RESULTS: One hundred thirty-six rPCTs were performed in 55 patients. New onset of DCI-related hypoperfusion was observed in 18% of rPCTs. The positive predictive value of rPCT to detect angiographic CVS was 0.80. Between examination days 6 and 10, the rate of DCI-related hypoperfusion was increased significantly (p < 0.05). After rPCT imaging with proof of DCI-related hypoperfusion, short-term follow-up showed secondary cerebral infarction (SCI) in 38%, compared with 5% for patients with normal perfusion on rPCT. The parameters "high risk phase (examination days 6-10)" and "new onset of DCI-related SCI" were significantly associated with the occurrence of DCI-related hypoperfusion in rPCT. CONCLUSIONS: In unconscious and asymptomatic aSAH patients, rPCT identifies DCI-related hypoperfusion in a relevant number of examinations. However, despite timely endovascular rescue therapy, a significant proportion of secondary infarction still occurs in this subgroup.

Non-compliant and compliant balloons for endovascular rescue therapy of cerebral vasospasm after spontaneous subarachnoid haemorrhage: experiences of a single-centre institution with radiological follow-up of the treated vessel segments.

BACKGROUND: For endovascular rescue therapy (ERT) of cerebral vasospasm (CVS) due to spontaneous subarachnoid haemorrhage (sSAH), non-compliant (NCB) and compliant (CB) balloons are used with both balloon types bearing the risk of vessel injury due to specific mechanical properties. Although severe delayed arterial narrowing after transluminal balloon angioplasty (TBA) for CVS has sporadically been described, valid data concerning incidence and relevance are missing. Our aim was to analyse the radiological follow-up (RFU) of differently TBA-treated arteries (CB or NCB). METHODS: Twelve patients with utilisation of either NCB or CB for CVS were retrospectively analysed for clinical characteristics, ERT, functional outcome after 3 months and RFU. Compared with the initial angiogram, we classified delayed arterial narrowing as mild, moderate and severe (<30%, 30%-60%, respectively >60% calibre reduction). RESULTS: Twenty-three arteries were treated with CB, seven with NCB. The median first RFU was 11 months after TBA with CB and 10 after NCB. RFU was performed with catheter angiography in 18 arteries (78%) treated with CB and in five (71%) after NCB; magnetic resonance angiography was acquired in five vessels (22%) treated with CB and in two (29%) after NCB. Mild arterial narrowing was detected in three arteries (13%) after CB and in one (14%) after NCB. Moderate or severe findings were neither detected after use of CB nor NCB. CONCLUSION: We found no relevant delayed arterial narrowing after TBA for CVS after sSAH. Despite previous assumptions that CB provides for more dilatation in segments adjacent to CVS, we observed no disadvantages concerning long-term adverse effects. Our data support TBA as a low-risk treatment option.

Cerebral Vasospasm After Spontaneous Subarachnoid Hemorrhage: Angiographic Pattern and Its Impact on the Clinical Course.

OBJECTIVE: To analyze angiographic characteristics of cerebral vasospasm (CVS) after spontaneous subarachnoid hemorrhage (sSAH) and their potential impact on secondary infarction and functional outcome. METHODS: Demographic, clinical, and imaging data of sSAH patients with angiographic CVS admitted over a 6-year period were retrospectively analyzed. RESULTS: A total of 85 patients were included in the final analysis. A total of 311 arterial territories in 85 angiographies demonstrated angiographic CVS. The anterior cerebral artery (ACA) was the most common site of angiographic CVS (42.1%), followed by the middle cerebral artery (MCA) (26.7%). In 29 angiographies (34%) CVS was found in more than 3 vessels and a bilateral pattern was identified in 53 cases (62%). Older age (OR 3.24 [95% CI 1.30-8.07], P = 0.012) was identified as the only significant risk factor for CVS-related infarction (OR 22.67, P = 0.015). Unfavorable outcome was associated with older age (OR 3.24, P = 0.023) and poor World Federation of Neurosurgical Societies grade (OR 3.64, P = 0.015). Analyses of angiographic characteristics did not reveal any risk factors for unfavorable outcome. We identified distal CVS as a significant risk factor for CVS-related infarction (OR 2.89, P = 0.026). CONCLUSIONS: Angiographic CVS after sSAH shows a specific distribution pattern in favor of ACA and MCA and in most cases 2-3 affected vessels are affected, often bilaterally. Patients exhibiting distal CVS have a higher risk for CVS-related infarction and should be observed closely. Nonetheless, the majority of angiographic characteristics did not allow conclusions about functional outcome nor the occurrence of CVS-related infarction in sSAH patients.