Background Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating cerebrovascular condition with significant morbidity and mortality. While inflammation plays a critical role in post-hemorrhagic complications, the specific polarization dynamics of monocyte and T cell subpopulations in this context remain poorly understood. This study aims to investigate these immune cell shifts and their correlation with major complications such as angiographic cerebral vasospasm and delayed cerebral ischemia (DCI). Methods We conducted a prospective, controlled observational single-center cohort study in a neurovascular university center of maximum care in Germany. A total of 75 patients with aSAH and 20 healthy controls were included. Blood samples were collected on days 1, 4, 7, and 11 post-bleeding. Flow cytometry was used to analyze monocyte (M1, intermediate, M2) and T cell (Th1, Th2, Th17, Treg) polarization patterns. Primary outcomes included the incidence of angiographic cerebral vasospasm, clinical DCI and/or cerebral infarction due to DCI, and clinical outcome assessed at 6 months via the modified Rankin Scale (mRS). Results Compared to healthy controls, patients with aSAH exhibited a significant decrease in anti-inflammatory alternatively activated monocytes (6.3% vs. 3.0%; p = 0.04) within 24 h post-bleeding, an increase in pro-inflammatory Th17 T cells (36.3% vs. 6.2%; p < 0.001) and decrease in anti-inflammatory Th2 cells (45.5% vs. 75.2%; p < 0.001). A loss of anti-inflammatory alternatively activated monocytes was observed prior to the onset of angiographic cerebral vasospasm (3.8% vs. 2.7%; p = 0.031) and DCI (4.2% vs. 2.9%; p = 0.006). No significant correlation was found between immune cell subpopulations and long-term clinical outcomes. Conclusions This study demonstrates a shift toward pro-inflammatory immune cell subpopulations following aSAH, with significant losses of alternatively activated monocytes preceding major complications such as vasospasm and DCI. These findings suggest that immune subpopulation profiling may hold potential as a diagnostic and therapeutic tool in the context of aSAH-related complications. Future studies should aim to clarify whether the observed peripheral immune changes reflect analogous intracerebral immune mechanisms and whether modulating these pathways can improve clinical outcomes.

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.

ObjectiveThe increasing prevalence of unruptured intracranial aneurysms, detected through advanced brain imaging, necessitates a cautious approach to surgical intervention, with a focus on minimizing associated risks. This retrospective study explores the safety and better aesthetic outcomes of a Virtual Reality (VR) guided Focused Sylvian Approach (FSA) in comparison to the standard Pterional Surgical Approach (SPA) for the clipping of unruptured small-medium-size (<10 mm) Middle Cerebral Artery (MCA) aneurysms.Methods23 patients with 23 unruptured MCA aneurysms underwent the VR-guided FSA from June 2020 to September 2023, while 22 patients with 23 unruptured MCA aneurysms who underwent SPA were retrospectively recruited from the medical records database from January 2017 to May 2020. The comparative analysis involved surgical duration, postoperative complications, hospital stay, and a three-month follow-up patient's sequela survey.ResultsAll aneurysms were effectively treated. The FSA procedure demonstrated a shorter surgical duration compared to the SPA group (164 ± 48 min vs. 196 ± 133 min, P = 0.2974). Despite a slightly higher median age in the FSA group (59 vs. 56 years), the median hospital stay was shorter in the FSA group (6 days) compared to the SPA group (7 days). The SPA group exhibited a higher incidence of complications (17/23) including cephalalgia, scar irritation, scar numbness, and temporal muscle dysfunction, compared to the FSA group (1/23), with a statistical significance of P < 0.05. Although FSA cannot demonstrate significant surgical efficiency in surgical duration and hospitalization, its superior aesthetics and preservation of temporalis muscle function compared to the SPA group.ConclusionThe VR-guided FSA offers improved aesthetics and preservation of muscle function compared to the SPA. Our retrospective study underscores the potential benefits of VR-guided, personalized, focused Sylvian approaches for managing unruptured small-medium-size MCA aneurysms.

Summary Background Patients diagnosed with low-grade glioma (LGG) must live with constant knowledge of an upcoming malignant tumor transformation which may lead to increased anxiety and reduced quality of life. Here, we (1) analyzed the prevalence and risk factors for distress in LGG patients using (2) different screening tools to subsequently (3) evaluate their need for psychological support. Method Patients with LGG-suspicious findings in MRI studies as well as patients with histopathological confirmed LGG were screened using three established self-assessment instruments (Hospital Anxiety and Depression Scale, Distress Thermometer, EORTC-QLQ-C30-BN20). Screening results were correlated with sociodemographic factors. Results One hundred forty-nine patients (74 men and 75 women) were prospectively included. Patients were further divided into different subgroups regarding the time of screening and diagnosis. An increased level of distress was observed in 20.8% (mean score 1.21, 95% CI 1.15–1.28) of all patients screened by HADS. Significant associated factors were pre-existing psychiatric disorders (p = 0.003) and psychotropic medication (p = 0.029). HRQoL (p = 0.022) and global health item (p = 0.015), as well as future uncertainty (p = 0.047), assessed by the EORTC-QLQ-C30-BN20 were significantly higher in those patients without histopathological diagnosis. Increased distress was significantly correlated with results in chosen sub-items of the HRQoL questionnaire (p < 0.001). Conclusions Our results demonstrate the need for frequent distress screening. If specific tools are not available, HRQoL questionnaires can also be used. Patients with pre-existing psychological stress should be offered additional psychooncological support, irrespectively of the time of screening or tumor diagnosis. Clinical trial registration number: 4087

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.

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.

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.

Abstract 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.

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.

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.

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.

Up to 40% of neuro-oncological patients already deal with high levels of distress under conventional circumstances. Due to COVID-19, pandemic hospital visitor rules have been restricted and patients did not receive the same level of supporting caregiver network as before COVID. The aim of the present study was to analyse the impact of the COVID pandemic on the prevalence of distress, anxiety and depression in neuro-oncological patients. Patients admitted for brain tumour surgery were screened regarding distress, anxiety and depression. Furthermore, aspects of patients' quality of life and clinical data were covered. Retrospectively available data of patients treated pre-pandemic (group A) and throughout the COVID-19 pandemic (group B) were statistically analysed using Chi-square tests and independent-sample t-tests, and regression analysis was performed to support statistical findings. Data from 110 patients were available. In all, 48 patients were included pre-COVID-19 and 62 during the COVID-19 pandemic. The authors found no significant difference between pre-COVID-19 prevalence of distress (p = 0.112), anxiety (p = 0.385) or depression (p = 0.084). Regression analyses additionally did not show any significant influence of COVID-19 on the above analysed parameter. Analyses of our cohort's data could not underline the negative impact of COVID-19 restrictions, shortcuts of professional and remodelled caregiver support on psycho-oncological outcomes.

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- R 2 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- R 2 = 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.

Abstract Background and Purpose – Untreated hypertension can lead to severe posterior reversible encephalopathy syndrome (PRES), that is a reversible intracranial complication. Involvement of posterior fossa structures including brainstem is extremely rare but life-threatening condition if not treated properly and timely. Here we review different clinical aspects of surgically treated cases of PRES with brainstem involvement and present an illustrative case. Methods – We searched the MEDLINE electronic database for studies on PRES with brainstem involvement. Hypertensive crisis as a cause of PRES and surgical treatment of PRES were inclusion criteria. We show a successfully treated case with this constellation. Finally, we summarize the data in current literature to provide treatment recommendation for this rare devastating condition. Results – We found 5 reports with a total of 7 patients of PRES with brainstem involvement which were treated by posterior fossa decompression. Hypertension or malignant hypertension were common at onset of PRES. 85% of all cases were females and one of these cases was a 3-year-old girl. 71% of patients had a mRS ≤ 3 at discharge. Conclusions – A clinically manifest brainstem PRES can be alleviated successfully through posterior fossa decompression so the ischemic and oedematous brain tissue can regenerate without further injury due to mechanical compression.

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.

Subarachnoid hemorrhage (SAH) is a highly morbid and fatal type of hemorrhagic strokes and it accounts for only 5% of all strokes. SAH is characterized by the sentinel extravasation of the arterial blood into the subarachnoid space and sometimes also involves ventricles and brain parenchyma. An important concern regarding this highly fatal and morbid disease is that it affects younger people of working age compared to the ischemic strokes leading to a significant socioeconomic loss. The major cause of SAH is the rupture of intracranial aneurysms (ICAs), which are weakened bulging lesions usually formed at the arterial bifurcation sites due to chronic shear stress and chronic inflammation. Almost, 3–5% of the population harbors ICAs with a slight prevalence in females compared to males. Transcriptomic studies offer the opportunity to elucidate the pathophysiological mechanisms in the formation, growth and rupture of the ICAs. Consequently, several studies have shown the differential expression of genes in the ruptured and unruptured ICAs and also highlight the implication of the associated pathways. Even peripheral blood and immune cells can be used to differentiate between ruptured and unruptured ICAs. These investigations have biomarker potential as well as they can be used for therapeutic modulation of the pathways showing differential expression of the genes among ruptured and unruptured ICAs.

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.

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.