CLR (C-Reactive Protein to Lymphocyte Ratio) Served as a Promising Predictive Biomarker for Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage (aSAH): A Retrospective Cohort Study.

Background: Subarachnoid hemorrhage is a devastating disease. Even after state-of-the-art treatment patients suffer from complications, including cerebral vasospasm (CVS), delayed cerebral ischemia (DCI), and chronic hydrocephalus (CH) following aneurysmal subarachnoid hemorrhage (aSAH). The aim of our study is to identify the predictive value of the C-reactive protein to lymphocyte ratio (CLR) for neurological functional outcome and complications after aSAH. Methods: We retrospectively analyzed a total of 166 aSAH patients who met the inclusion criteria enrolled in our study. Multivariate logistic regression analyses were performed to evaluate the independent risk factors. The predictive value of different models was compared by calculating the areas under the receiver operating characteristic (ROC) curve. Results: On-admission levels of CLR in patients with poor outcomes (6 months mRS 3-6), CVS, DCI, and CH were significantly higher than those in patients with good outcomes (6 months mRS 0-2), non-CVS, non-DCI, and non-CH. Multivariate logistic regression analysis revealed that admission CLR was independently associated with CVS (OR [95% CI] 2.116 [1.507-2.971]; p < 0.001), and DCI (OR [95% CI] 1.594 [1.220-2.084]; p = 0.001). In ROC analysis, the area under the curve (AUC) of CLR for poor outcomes (6 months mRS 3-6), CVS, DCI, and CH prediction were (AUC [95% CI] 0.639 [0.555-0.724]; p = 0.002), (AUC [95% CI] 0.834 [0.767-0.901]; p < 0.001), (AUC [95% CI] 0.679 [0.581-0.777]; p < 0.001), and (AUC [95% CI] 0.628 [0.543-0.713]; p = 0.005) revealing that admission CLR had a favorable predictive value for CVS after aSAH. The sensitivity and specificity of admission CLR for CVS prediction were 77.1% and 75.4%. On-admission CLR of 0.757 mg × 10-6 was identified as the best cutoff threshold to discriminate between CVS and non-CVS (CVS: CLR < 0.757 mg × 10-6 11/100 [11.0%] vs. CLR ≥ 0.757 mg × 10-6 37/66 [56.1%]; p < 0.001). Conclusions: High levels of on-admission CLR serve as an independent risk factor for CVS and DCI after aSAH. Admission CLR is an easy-to-quantify laboratory parameter that efficiently predicts the CVS after aSAH, which can provide some guidance for clinicians to evaluate for possible progression and treatment strategies in patients with aSAH.

Trans-lateral ventricular approach for surgical treatment of high-located P2-P3 junction posterior cerebral artery aneurysms: from anatomical research to clinical application.

BACKGROUND: Posterior cerebral artery (PCA) aneurysms, though rare, pose treatment challenges. Endovascular therapy is the preferred option, but microsurgery becomes necessary in certain cases. Various microsurgical approaches have been suggested for PCA aneurysms, particularly those at the P2-P3 junction. This study highlights the trans-lateral ventricular approach (TVA) for addressing these complex aneurysms. This study aims to assess the feasibility and safety of the trans-lateral ventricular approach (TVA) for treating high-located complex PCA aneurysms at the P2-P3 junction. The study evaluates both clinical outcomes and anatomical considerations. METHODS: Two cases of PCA aneurysms at the P2-P3 junction were treated using TVA in 2019. Navigation-guided entry via the interparietal sulcus was planned. Ventriculostomy was performed from the cortex to the lateral ventricle's atrium. Medial atrial floor dissection exposed PCA's P2-P3 segments. Neuronavigation and ultrasound-aided guidance was used. Anatomical studies on fixed and contrast-perfused specimens refined the approach. RESULTS: Both cases saw successful aneurysm clipping. The unruptured aneurysm patient was discharged in 6 days. The poor-grade SAH patient required extended ICU care, moving to rehabilitation with mRS = 4. The unruptured complex aneurysm case exhibited no deficits, returning to work in 3 months. Anatomical dissections validated TVA for high-located P2-P3 junction PCA aneurysms. CONCLUSION: While endovascular therapy remains primary, this study demonstrates the viability of navigation-guided TVA for select high-located P2-P3 junction PCA aneurysms. Successes and challenges underscore the importance of patient selection and anatomical awareness.

Clinical Outcome Prediction of Early Brain Injury in Aneurysmal Subarachnoid Hemorrhage: the SHELTER-Score.

BACKGROUND: Despite intensive research on preventing and treating vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage (aSAH), mortality and morbidity rates remain high. Early brain injury (EBI) has emerged as possibly the major significant factor in aSAH pathophysiology, emphasizing the need to investigate EBI-associated clinical events for improved patient management and decision-making. This study aimed to identify early clinical and radiological events within 72 h after aSAH to develop a conclusive predictive EBI score for clinical practice. METHODS: This retrospective analysis included 561 consecutive patients with aSAH admitted to our neurovascular center between 01/2014 and 09/2022. Fourteen potential predictors occurring within the initial 72 h after hemorrhage were analyzed. The modified Rankin Scale (mRS) score at 6 months, discretized to three levels (0-2, favorable; 3-5, poor; 6, dead), was used as the outcome variable. Univariate ordinal regression ranked predictors by significance, and forward selection with McFadden's pseudo-R2 determined the optimal set of predictors for multivariate proportional odds logistic regression. Collinear parameters were excluded, and fivefold cross-validation was used to avoid overfitting. RESULTS: The analysis resulted in the Subarachnoid Hemorrhage Associated Early Brain Injury Outcome Prediction score (SHELTER-score), comprising seven clinical and radiological events: age (0-4 points), World Federation of Neurosurgical Societies (0-2.5 points), cardiopulmonary resuscitation (CPR) (2 points), mydriasis (1-2 points), midline shift (0.5-1 points), early deterioration (1 point), and early ischemic lesion (2 points). McFadden's pseudo-R2 = 0.339, area under the curve for death or disability 0.899 and 0.877 for death. A SHELTER-score below 5 indicated a favorable outcome (mRS 0-2), 5-6.5 predicted a poor outcome (mRS 3-5), and ≥ 7 correlated with death (mRS 6) at 6 months. CONCLUSIONS: The novel SHELTER-score, incorporating seven clinical and radiological features of EBI, demonstrated strong predictive performance in determining clinical outcomes. This scoring system serves as a valuable tool for neurointensivists to identify patients with poor outcomes and guide treatment decisions, reflecting the great impact of EBI on the overall outcome of patients with aSAH.

Revisiting the WFNS Score: Native Computed Tomography Imaging Improves Identification of Patients With "False Poor Grade" Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND OBJECTIVES: In patients suffering from aneurysmal subarachnoid hemorrhage (aSAH), the optimal time to determine the World Federation of Neurosurgical Societies (WFNS) score remains controversial because of possible confounding factors. Goals of this study were (1) to analyze the most sensitive timepoint to determine the WFNS score in patients with aSAH and (2) to evaluate the impact of initial native computed tomography (CT) imaging on reducing the mismatch of "false poor grade" patients. METHODS: We retrospectively analyzed daily WFNS scores from admission until day 7 in 535 aSAH patients and evaluated their predictive value for the modified Rankin Scale at discharge and 6 months postbleeding. Patients with an initial WFNS score of IV-V who showed improvement to a WFNS score of I-II within the first 7 days (even short-term) were defined as "false poor grade" patients. We tried to identify the "false poor grade" patients using parameters of the initial native CT imaging. RESULTS: Later determination of the WFNS score (day 1 vs 7; pseudo-R 2 = 0.13 vs 0.21) increasingly improved its predictive value for neurological outcome at discharge ( P < .001). We identified 39 "false poor grade" patients who had significantly better outcomes than "real poor grade" patients (N = 220) (modified Rankin Scale-discharge: 0-2, 56% vs 1%, P < .001; 3-5: 41% vs 56%, P = .12; 6: 3% vs 43%, P < .001). "False poor grade" patients differed significantly in initial CT parameters. A predictive model called "initial CT WFNS" ( ICT WFNS) was developed, incorporating SEBES, Hijdra score, and LeRoux score (sensitivity = 0.95, specificity = 0.84, accuracy = 0.859, F1 = 0.673). ICT WFNS scores of ≤4.6 classified patients as "false poor grade." CONCLUSION: The initial WFNS score may misclassify a subgroup of patients with aSAH as poor grade, which can be avoided by later determination of the WFNS score, at days 3-4 losing its usefulness. Alternatively, the initial WFNS score can be improved in its predictive value, especially in poor-grade patients, using criteria from the initial native CT imaging, such as the Hijdra, LeRoux, and Subarachnoid Hemorrhage Early Brain Edema score, combined in the ICT WFNS score with even higher predictive power.

Novel Insights into Pathophysiology of Delayed Cerebral Ischemia: Effects of Current Rescue Therapy on Microvascular Perfusion Heterogeneity.

General microvascular perfusion and its heterogeneity are pathophysiological features of delayed cerebral ischemia (DCI) that are gaining increasing attention. Recently, CT perfusion (CTP) imaging has made it possible to evaluate them radiologically using mean transit time (MTT) and its heterogeneity (measured by cvMTT). This study evaluates the effect of multimodal rescue therapy (intra-arterial nimodipine administration and elevation of blood pressure) on MTT and cvMTT during DCI in aneurysmal subarachnoid haemorrhage (aSAH) patients. A total of seventy-nine aSAH patients who underwent multimodal rescue therapy between May 2012 and December 2019 were retrospectively included in this study. CTP-based perfusion impairment (MTT and cvMTT) on the day of DCI diagnosis was compared with follow-up CTP after initiation of combined multimodal therapy. The mean MTT was significantly reduced in the follow-up CTP compared to the first CTP (3.7 ± 0.7 s vs. 3.3 ± 0.6 s; p < 0.0001). However, no significant reduction of cvMTT was observed (0.16 ± 0.06 vs. 0.15 ± 0.06; p = 0.44). Mean arterial pressure was significantly increased between follow-up and first CTP (98 ± 17 mmHg vs. 104 ± 15 mmHg; p < 0.0001). The combined multimodal rescue therapy was effective in addressing the general microvascular perfusion impairment but did not affect the mechanisms underlying microvascular perfusion heterogeneity. This highlights the need for research into new therapeutic approaches that also target these pathophysiological mechanisms of DCI.

Anterior inferior cerebellar artery (AICA) aneurysms: a radiological study of 15 consecutive patients.

Introduction: The aneurysms of the anterior inferior cerebellar artery (AICA) are rare lesions of the posterior circulation and to treat them is challenging. We aim to present anatomical and morphological characteristics of AICA aneurysms in a series of 15 patients. Method: The DSA and CT angiography images of AICA aneurysms in 15 consecutive patients were analyzed retrospectively. Different anatomical characteristics were quantified, including morphology, location, width, neck width, length, bottleneck factor, and aspect ratio. Results: Eighty percent of the patients were females. The age was 52.4 ± 9.6 (mean ± SD) years. 11 patients were smokers. Ten patients had a saccular aneurysm and five patients had a fusiform aneurysm. Aneurysm in 10 patients were located in the proximal segment, in three patients in the meatal segment, and in two patients in the distal segment. Ten out of 15 patients presented with a ruptured aneurysm. The size of AICA aneurysms was 14.8 ± 18.9 mm (mean ± SD). The aspect ratio was 0.92 ± 0.47 (mean ± SD) and bottleneck factor was 1.66 ± 1.65 (mean ± SD). Conclusion: AICA aneurysms are rare lesions of posterior circulation predominantly found in females, present predominantly with subarachnoid hemorrhage, and are mostly large in size.

Evaluation of MTT Heterogeneity of Perfusion CT Imaging in the Early Brain Injury Phase: An Insight into aSAH Pathopysiology.

The concept of early brain injury (EBI) is based on the assumption of a global reduction in brain perfusion following aneurysmal subarachnoid hemorrhage (aSAH). However, the heterogeneity of computed tomography perfusion (CTP) imaging in EBI has not yet been investigated. In contrast, increased mean transit time (MTT) heterogeneity, a possible marker of microvascular perfusion heterogeneity, in the delayed cerebral ischemia (DCI) phase has recently been associated with a poor neurological outcome after aSAH. Therefore, in this study, we investigated whether the heterogeneity of early CTP imaging in the EBI phase is an independent predictor of the neurological outcome after aSAH. We retrospectively analyzed the heterogeneity of the MTT using the coefficient of variation (cvMTT) in early CTP scans (within 24 h after ictus) of 124 aSAH patients. Both linear and logistic regression were used to model the mRS outcome, which were treated as numerical and dichotomized values, respectively. Linear regression was used to investigate the linear dependency between the variables. No significant difference in cvMTT between the patients with and those without EVD could be observed (p = 0.69). We found no correlation between cvMTT in early CTP imaging and initial modified Fisher (p = 0.07) and WFNS grades (p = 0.23). The cvMTT in early perfusion imaging did not correlate significantly with the 6-month mRS for the entire study population (p = 0.15) or for any of the subgroups (without EVD: p = 0.21; with EVD: p = 0.3). In conclusion, microvascular perfusion heterogeneity, assessed by the heterogeneity of MTT in early CTP imaging, does not appear to be an independent predictor of the neurological outcome 6 months after aSAH.

2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

AIM: The "2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage" replaces the 2012 "Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage." The 2023 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with aneurysmal subarachnoid hemorrhage. METHODS: A comprehensive search for literature published since the 2012 guideline, derived from research principally involving human subjects, published in English, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline, was conducted between March 2022 and June 2022. In addition, the guideline writing group reviewed documents on related subject matter previously published by the American Heart Association. Newer studies published between July 2022 and November 2022 that affected recommendation content, Class of Recommendation, or Level of Evidence were included if appropriate. Structure: Aneurysmal subarachnoid hemorrhage is a significant global public health threat and a severely morbid and often deadly condition. The 2023 aneurysmal subarachnoid hemorrhage guideline provides recommendations based on current evidence for the treatment of these patients. The recommendations present an evidence-based approach to preventing, diagnosing, and managing patients with aneurysmal subarachnoid hemorrhage, with the intent to improve quality of care and align with patients' and their families' and caregivers' interests. Many recommendations from the previous aneurysmal subarachnoid hemorrhage guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Treatment and Outcome of Anterior Inferior Cerebellar Artery (AICA) Aneurysms: Helsinki Series of 15 Consecutive Patients.

Objective Anterior inferior cerebellar artery (AICA) aneurysms are rare posterior circulation lesions that are challenging to treat. This article presents the treatment and clinical outcome of AICA aneurysms in an unselected cohort of patients. Methods A retrospective analysis of patient record files, digital subtraction angiography, and computed tomography angiography images of 15 consecutive patients harboring AICA aneurysms treated between 1968 and 2017. Results Of the 15 AICA aneurysm patients reviewed, 12 (80%) were females. Twenty percent had intracerebral hemorrhage and 40% presented with intraventricular hemorrhage. Eleven out of 15 (73%) patients presented with subarachnoid hemorrhage (SAH); 82% of SAH patients had a good-grade SAH (Hunt and Hess grade 1-3). Eleven patients (73%) were treated surgically, three (20%) were treated conservatively, and one (7%) had coil embolization. In 27% of patients, a subtemporal approach with anterior petrosectomy was performed. A retrosigmoid approach was used in the remaining 73%. In 18% of the patients, a parent vessel occlusion was necessary to occlude the aneurysm. Five out of 11 (47%) of the patients developed postoperative cranial nerve deficits. Twenty-seven percent developed shunt-dependent hydrocephalus. All patients who presented with an unruptured AICA aneurysm had good clinical outcome (modified Rankin scale [mRS] 1-2). In patients with SAH, 82% achieved good clinical outcome and 18% had poor clinical outcome (mRS 3-6) after 1 year. Conclusion Surgical treatment of AICA aneurysms has a high rate of cranial nerve deficits but most of patients have a good long-term clinical outcome.

Clustering of serum biomarkers involved in post-aneurysmal subarachnoid hemorrhage (aSAH) complications.

Post-aSAH sequela is characterized by the onset of life-threatening complications along with the upregulated underlying inflammation. Cerebral vasospasm (CVS) is one of the most frequent complication after aSAH, which contributes majorly to delayed cerebral ischemia and poor clinical outcome. The objective of this study was to identify the clusters of serum biomarkers that are associated with cerebral vasospasm (CVS) after suffering from aneurysmal subarachnoid hemorrhage (aSAH). In this single-center study, serum concentrations of 10 potential biomarkers, together with clinical and demographic parameters, for 66 aSAH patients were recorded within 24 h after aSAH. The dataset was split into a training set (43 patients) and a validation set. Correlation heatmaps for both datasets were computed. Variables with inconsistent correlations on the two subsets were excluded. Clusters of relevant biomarkers were identified on the complete set, separately for patients who developed post-aSAH CVS and those who did not. Two clusters were found to be specific for patients who suffered from CVS: mitochondrial gene fragments (cytochrome B (Cyt-B), cytochrome C oxidase subunit-1 (Cox-1), displacement loop (D-loop), and IL-23, and the other one, containing IL-6, IL-10, age, and Hunt and Hess score. Clusters of serum biomarkers, analyzed within 24 h of the onset of aSAH, days before the CVS development, are expressed differently in patients suffering from post-aSAH CVS, compared to patients without CVS. This suggests that these biomarkers may be involved in the pathophysiological processes leading to CVS and may be used as its early predictors. These interesting findings are potentially highly relevant for the management of CVS and call for validation on a larger sample of patients.

Effects of Dendrimer-microRNA Nanoformulations against Glioblastoma Stem Cells.

Glioblastoma is a rapidly progressing tumor quite resistant to conventional treatment. These features are currently assigned to a self-sustaining population of glioblastoma stem cells. Anti-tumor stem cell therapy calls for a new means of treatment. In particular, microRNA-based treatment is a solution, which in turn requires specific carriers for intracellular delivery of functional oligonucleotides. Herein, we report a preclinical in vitro validation of antitumor activity of nanoformulations containing antitumor microRNA miR-34a and microRNA-21 synthetic inhibitor and polycationic phosphorus and carbosilane dendrimers. The testing was carried out in a panel of glioblastoma and glioma cell lines, glioblastoma stem-like cells and induced pluripotent stem cells. We have shown dendrimer-microRNA nanoformulations to induce cell death in a controllable manner, with cytotoxic effects being more pronounced in tumor cells than in non-tumor stem cells. Furthermore, nanoformulations affected the expression of proteins responsible for interactions between the tumor and its immune microenvironment: surface markers (PD-L1, TIM3, CD47) and IL-10. Our findings evidence the potential of dendrimer-based therapeutic constructions for the anti-tumor stem cell therapy worth further investigation.

Blood Pressure Affects the Early CT Perfusion Imaging in Patients with aSAH Reflecting Early Disturbed Autoregulation.

BACKGROUND: Early computed tomography perfusion (CTP) is frequently used to predict delayed cerebral ischemia following aneurysmatic subarachnoid hemorrhage (aSAH). However, the influence of blood pressure on CTP is currently controversial (HIMALAIA trial), which differs from our clinical observations. Therefore, we aimed to investigate the influence of blood pressure on early CTP imaging in patients with aSAH. METHODS: We retrospectively analyzed the mean transit time (MTT) of early CTP imaging within 24 h after bleeding prior to aneurysm occlusion with respect to blood pressure shortly before or after the examination in 134 patients. We correlated the cerebral blood flow with the cerebral perfusion pressure in the case of patients with intracranial pressure measurement. We performed a subgroup analysis of good-grade (World Federation of Neurosurgical Societies [WFNS] I-III), poor-grade (WFNS IV-V), and solely WFNS grade V aSAH patients. RESULTS: Mean arterial pressure (MAP) significantly correlated inversely with the mean MTT in early CTP imaging (R = - 0.18, 95% confidence interval [CI] - 0.34 to - 0.01, p = 0.042). Lower mean blood pressure was significantly associated with a higher mean MTT. Subgroup analysis revealed an increasing inverse correlation when comparing WFNS I-III (R = - 0.08, 95% CI - 0.31 to 0.16, p = 0.53) patients with WFNS IV-V (R = - 0.2, 95% CI - 0.42 to 0.05, p = 0.12) patients, without reaching statistical significance. However, if only patients with WFNS V are considered, a significant and even stronger correlation between MAP and MTT (R = - 0.4, 95% CI - 0.65 to 0.07, p = 0.02) is observed. In patients with intracranial pressure monitoring, a stronger dependency of cerebral blood flow on cerebral perfusion pressure is observed for poor-grade patients compared with good-grade patients. CONCLUSIONS: The inverse correlation between MAP and MTT in early CTP imaging, increasing with the severity of aSAH, suggests an increasing disturbance of cerebral autoregulation with the severity of early brain injury. Our results emphasize the importance of maintaining physiological blood pressure values in the early phase of aSAH and preventing hypotension, especially in patients with poor-grade aSAH.

Defining activities in neurovascular microsurgery training: entrustable professional activities for vascular neurosurgery.

BACKGROUND: Entrustable professional activities (EPAs) represent an assessment framework with an increased focus on competency-based assessment. Originally developed and adopted for undergraduate medical education, concerns over resident ability to practice effectively after graduation have led to its implementation in residency training but yet not in vascular neurosurgery. Subjective assessment of resident or fellow performance can be problematic, and thus, we aim to define core EPAs for neurosurgical vascular training. METHODS: We used a nominal group technique in a multistep interaction between a team of experienced neurovascular specialists and a medical educator to identify relevant EPAs. Panel members provided feedback on the EPAs until they reached consent. RESULTS: The process produced seven core procedural EPAs for vascular residency and fellowship training, non-complex aneurysm surgery, complex aneurysm surgery, bypass surgery, arteriovenous malformation resection, spinal dural fistula surgery, perioperative management, and clinical decision-making. CONCLUSION: These seven EPAs for vascular neurosurgical training may support and guide the neurosurgical society in the development and implementation of EPAs as an evaluation tool and incorporate entrustment decisions in their training programs.

Microvascular anastomosis of the human lacrimal gland: a concept study towards transplantation of the human lacrimal gland.

INTRODUCTION: Severe aqueous tear deficiency is caused by primary or secondary main lacrimal gland insufficiency. The transplantation of a human lacrimal gland could become a potential treatment option to provide physiological tears with optimal properties. To this end, we performed an ex vivo study to develop a surgical strategy that would ensure a vascular supply for a lacrimal gland transplant using microvascular techniques. MATERIAL AND METHODS: Five cadaver heads were used to perform a lateral orbitotomy in order to identify the vascular pedicle and the lacrimal gland itself. The principal feasibility and the time of the required surgical steps for an intraorbital microvascular re-anastomosis of the human lacrimal gland were documented. Patency and potential leakage of the anastomosis were tested with hematoxylin intraoperatively. Postoperatively, routine histological, as well as scanning electron microscopy (SEM) of the gland and vascular anastomosis, were performed. RESULTS: The vascular pedicle of all five glands could be isolated over a minimum stretch of at least 1 cm, severed, and successfully reanastmosed microsurgically. Time for arterial anatomization (n = 4) was 23 ± 7 min and 22 ± 3 min for the vein (p = 0.62). The total time for the entire microvascular anastomosis was 46 ± 9 min. All anastomosis were patent upon testing. SEM revealed well-aligned edges of the anastomosis with tight sutures in place. CONCLUSION: Our study demonstrates as proof of principle the feasibility of intraorbital microvascular re-anastomosis of a human lacrimal gland within the presumed window of ischemia of this tissue. This should encourage orbital surgeons to attempt lacrimal gland transplantation in humans in vivo.

The impact of preoperative MRI-based apparent diffusion coefficients on local recurrence and outcome in patients with cerebral metastases.

BACKGROUND: Surgery of single cerebral metastases is standard but frequently fails to achieve local tumour control. Reliable predictors for local tumour progression and overall survival are unknown. MRI-based apparent diffusion coefficients (ADC) correlate with tumour cellularity and invasion. The present study analysed a potential relation between the MRI based apparent diffusion coefficients local recurrence and outcome in patients with brain metastases. METHODS: A retrospective analysis was performed for patients with cerebral metastases and complete surgical resection evaluated by an early postoperative MRI < 72h. Minimal ADC and mean ADC were assessed in preoperative 1,5T-MRI scans by placing regions of interests in the tumour and the peritumoural tissue. RESULTS: Analysis of the relation between ADC values, local progression and outcome was performed in 86 patients with a mean age of 59 years (range 33-83 years). Primary site was NSCLC in 37.2% of all cases. Despite complete resection 33.7% of all patients suffered from local in-brain-progression. There were no significant differences in ADC values in groups based on histology. In the present cohort, the mean ADCmin and the mean ADCmean within the metastasis did not differ significantly between patients with and without a later local in-brain progression (634 × 10-6 vs. 661 × 10-6 mm2/s and 1324 × 10-6 vs. 1361 × 10-6 mm2/s; 1100 × 10-6 vs. 1054 × 10-6 mm2/s; each p > 0.05). Mean ADC values did not correlate significantly with PFS and OAS. CONCLUSION: In the present study analysed ADC values had no significant impact on local in brain progression and survival parameters.

Treatment of Unique Bilateral Distal Fusiform Superior Cerebellar Artery Aneurysms with Mini-Flow Diverter Device Implantation: Case Report.

Currently, surgical revascularization procedures using intracranial-intracranial (IC-IC) or extracranial-intracranial (EC-IC) bypass and distal clipping or trapping are the valid and rescue treatment modality for extremely rare unilateral distal fusiform superior cerebellar artery (SCA) aneurysms. Yet, in case of bilateral fusiform SCA aneurysms, surgical therapy reaches its limit. Mini-flow diverter devices (FDDs) have only recently become available for treating fusiform aneurysms of such small vessels. We report the unique case of bilateral distal fusiform SCA aneurysms in a 43-year-old man with subarachnoid hemorrhage (Fisher grade IV and World Federation of Neurosurgical Societies [WFNS] grade II) treated with endovascular implantation of bilateral mini-FDDs with excellent outcome and no radiographic signs of infarction. Yet, occlusion of one of the FDDs was found in the follow-up, which again shows the eminent danger of occlusion in case of an implantation of FDDs in such small-caliber vessels, which leaves the discussion about the optimal therapy method open.

Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases.

Excess alcohol consumption is a potential risk factor for cardiovascular diseases and is linked to accelerated aging. Drug discovery to reduce toxic cellular events of alcohol is required. Here, we investigated the effects of ethanol on human umbilical vein endothelial cells (HUVECs) and explored if doxycycline attenuates ethanol-mediated molecular events in endothelial cells. Initially, a drug screening using a panel of 170 drugs was performed, and doxycycline was selected for further experiments. HUVECs were treated with different concentrations (300 mM and 400 mM) of ethanol with or without doxycycline (10 µg/mL). Telomere length was quantified as telomere to single-copy gene (T/S) ratio. Telomere length and the mRNA expression were quantified by qRT-PCR, and protein level was analyzed by Western blot (WB). Ethanol treatment accelerated cellular aging, and doxycycline treatment recovered telomere length. Pathway analysis showed that doxycycline inhibited mTOR and NFκ-B activation. Doxycycline restored the expression of aging-associated proteins, including lamin b1 and DNA repair proteins KU70 and KU80. Doxycycline reduced senescence and senescence-associated secretory phenotype (SASP) in ethanol-treated HUVECs. In conclusion, we report that ethanol-induced inflammation and aging in HUVECs were ameliorated by doxycycline.

SARS-CoV-2 infection increases risk of intracranial hemorrhage.

Introduction: SARS-CoV-2 virus infection causes a dysbalanced and severe inflammatory response, including hypercytokinemia and immunodepression. Systemic inflammation triggered by a viral infection can potentially cause vascular damage, which may lead to cardiovascular and neurovascular events. Research question: The aim was to investigate whether CNS complications are related to COVID-19. Materials and methods: We examined 21 patients suffering from stroke and intracranial hemorrhage (ICH) and 9 (43%) of them were male. We compared relative frequencies using Fisher's exact test. As we had few observations and many variables, we used principal component analysis (PCA) to reduce data dimensionality. We trained a linear support vector machine (SVM) on the first two PCs of the laboratory data to predict COVID-19. Results: Patients suffering from stroke had either hypertension or SARS-CoV-2 infection, but seldom both (OR = 0.05, p = 0.0075). The presence of SARS-CoV-2 infection was strongly associated with the logarithm of CRP (p = 1.4e-07) and with D-DIMER (p = 1.6e-05) and moderately with PT (p = 0.0024). SARS-CoV-2 infection was not related to any other factor. CRP, D-DIMER, PT, and INR were all related to each other (R 2 ranging from 0.19 to 0.52, p ranging from 0.012 to < 0.0001). The first two PCs covered 96% of the variance in the four variables. Using them, perfect linear discrimination between patients suffering from COVID-19 and other patients could be achieved. Discussion and conclusion: SARS-CoV-2 infection causes systemic inflammation, which is suggested as a predictor of the severe course of ICH. SARS-CoV-2 infection is an additional risk factor for vascular complications.

Meta-review on Perforation Model of Subarachnoid Hemorrhage in Mice: Filament Material as a Possible Moderator of Mortality.

Robust preclinical models are inevitable for researchers to unravel pathomechanisms of subarachnoidal hemorrhage (SAH). For the mouse perforation model of SAH, the goal of this meta-review was the determination of variances in mortality, SAH severity grade, and vasospasm, and their experimental moderators, as many researchers are facing with incomparable results. We searched on the databases PubMed, Embase, and Web of Science for articles describing in vivo experiments using the SAH perforation mouse model and measuring mortality, SAH grade, and/or vasospasm. After screening, 42 articles (total of 1964 mice) were included into systematic review and meta-analysis. Certain model characteristics were insufficiently reported, e.g., perforation location (not reported in six articles), filament (material (n = 15) and tip texture (n = 25)), mouse age (n = 14), and weight (n = 10). Used injective anesthetics and location of perforation showed large variation. In a random-effects meta-analysis, the overall animal mortality following SAH was 21.3% [95% CI: 17.5%, 25.7%] and increased with longer observational periods. Filament material significantly correlated with animal mortality (p = 0.024) after exclusion of hyperacute studies (time after SAH induction < 24 h). Reported mean SAH grade was 10.7 [9.6, 11.7] on the scale of Sugawara (J Neurosci Methods 167:327-34, 2008). Furthermore, mean diameter of large cerebral arteries after SAH was reduced by 27.6% compared to sham-operated non-SAH mice. Uniforming standards of experimental procedures and their reporting are indispensable to increase overall comparability.