Background/Objectives: “Ring-like” intracranial aneurysms—historically described as “doughnut-like” or “donut sign”—represent a rare configuration in which a central thrombus coexists with a circumferential mural flow ring. Traditionally considered a radiologic curiosity, this morphology likely reflects a shear-driven hemodynamic state rather than a stable organized thrombus. We aimed to summarize all PubMed-documented cases of ring-like aneurysms, define their morphologic and clinical spectrum, and assess their hemodynamic significance, rupture risk, and treatment outcomes. An additional aim is to formalize the use of the term “ring-like aneurysm” as a distinct morphologic subtype and to clearly differentiate it from the neuroradiologic “donut sign,” which represents an imaging appearance rather than a specific anatomic configuration. Methods: A systematic PubMed search (1996–2024) was conducted using the following combinations of keywords and Boolean operators: (“ring-like aneurysm” OR “donut aneurysm” OR “doughnut aneurysm” OR “ring-shaped aneurysm” OR “circumferential lumen” OR “central thrombus”) AND (“intracranial” OR “cerebral” OR “basilar” OR “aneurysm”). Only English-language, PubMed-indexed reports describing true ring-like (donut-shaped) aneurysms were included. Non-indexed, non-English, and serpentine or fusiform aneurysms mimicking ring-like morphology were excluded. Extracted data included aneurysm location, size, presentation (ruptured, symptomatic, or incidental), treatment strategy, and clinical outcome. Statistical proportions were analyzed using descriptive methods, Wilson 95% confidence intervals, and a binomial test to compare the observed subarachnoid hemorrhage (SAH) rate against the expected conservative rupture proportion. Results: The search identified 16 individual patients reported in 10 publications. All aneurysms were large or giant (14–36 mm) displaying characteristic thrombosed pattern. Ruptured presentation occurred in 6 out of 16 cases (37.5%) and symptomatic unruptured in 10 (62.5%). No incidental cases were reported. Posterior circulation involvement was present in 44%, with a female predominance of 69%. Conclusions: Ring-like aneurysms constitute a distinct, shear-maintained hemodynamic entity combining mural jet flow with central thrombosis. Their frequent symptomatic or ruptured presentation supports the concept that this morphology represents a pre-ruptural configuration rather than a chronic thrombotic residue. Early recognition and targeted endovascular exclusion of the inflow zone are essential to prevent delayed rupture.

We present a rare case of a 16-year-old male who was admitted with bilateral tinnitus and subsequently underwent magnetic resonance imaging (MRI) and digital subtraction angiography (DSA) for further evaluation. The left internal carotid (ICA) artery had a normal caliber but ended as a stump at the C7 segment, with a network of filiform vessels from both the stump and right posterior communicating artery (PComm). The right PComm was hypertrophic and the right posterior cerebral artery (PCA) was mainly supplied by the right ICA. The right ICA’s bifurcation and the initial middle cerebral artery (MCA) segment were absent, while the MCA trunk was hypoplastic. The right PCA and pial branches vascularized the temporal lobe, with collaterals between the PCA and MCA. The left ICA was slightly enlarged with double fenestration at the left A1 segment. The right A1 segment of the anterior cerebral artery had double fenestration and while several diagnoses were considered, no single diagnosis fully explained all clinical findings. A thorough review of the existing literature yielded no comparable cases, highlighting the uniqueness of this presentation. This case emphasizes the complexity of cerebral vascular anomalies and the challenges associated with diagnosing such rare conditions, underscoring the need for careful assessment.

Background/Objectives: This study explores the potential of LB-100 (a protein phosphatase 2A—PP2A inhibitor) combined with adavosertib (a WEE1 kinase inhibitor) and doxorubicin (DOX), to overcome multidrug resistance (MDR) in cancer cells and enhance treatment efficacy. Methods: We evaluated LB-100 combinations with adavosertib and DOX in patient-derived glioblastoma and non-small cell lung carcinoma cells (NSCLCs) using a real-time cell analyzer. Effectiveness was also assessed through immunofluorescence assay, and interactions were analyzed via SynergyFinder+. We also examined P-glycoprotein (P-gp) expression and drug resistance genes’ expression in MDR glioblastoma and NSCLCs after LB-100 treatment, as well as LB-100 sensitizing effect on DOX and DOX accumulation. Results: LB-100 significantly boosts the effectiveness of adavosertib and DOX after multiple applications. It also enhances these drugs’ cytotoxicity in a single application without acting synergistically. Additionally, LB-100 reduces P-gp expression in MDR glioblastoma and NSCLCs, sensitizing them to DOX and increasing its accumulation. Conclusions: LB-100 enhances the effectiveness of drugs against MDR cancer cells, presenting a promising strategy to overcome drug resistance in glioblastoma and NSCLCs through P-gp modulation.

Background and Objectives: Partially thrombosed aneurysms represent a subset primarily found within large and giant aneurysms. The presence of an intraluminal thrombus can cause an aneurysm to present in different shapes upon angiographic examination. We present a series of five cases of “donut-shaped” aneurysms observed over the past decade at the Clinic for Neurosurgery in the University Clinical Centre of Serbia. Materials and Methods: The management of “donut-shaped” aneurysms was accomplished through endovascular interventions, employing techniques such as the deployment of flow-diverting stents or a combination of stent placement and coil embolization. Results: Four out of five patients underwent endovascular treatment, yielding positive outcomes with complete thrombosis of the aneurysms during follow-up. The fifth patient was successfully diagnosed; however, due to their deteriorating condition, treatment was not feasible. Conclusions: Given the potential life-threatening complications associated with this entity, accurate diagnosis and appropriate management are crucial. In our cohort, endovascular interventions demonstrated efficacy in the majority of cases, underscoring the significance of this approach in treating “donut-shaped” aneurysms. Nevertheless, considering the rarity of this condition, further research is justified to refine diagnostic and therapeutic strategies for these complex intracranial vascular anomalies.

Two novel hybrid compounds, CON1 and CON2, have been developed by combining sclareol (SC) and doxorubicin (DOX) into a single molecular entity. These hybrid compounds have a 1:1 molar ratio of covalently linked SC and DOX. They have demonstrated promising anticancer properties, especially in glioblastoma cells, and have also shown potential in treating multidrug-resistant (MDR) cancer cells that express the P-glycoprotein (P-gp) membrane transporter. CON1 and CON2 form nanoparticles, as confirmed by Zetasizer, transmission electron microscopy (TEM), and chemical modeling. TEM also showed that CON1 and CON2 can be found in glioblastoma cells, specifically in the cytoplasm, different organelles, nucleus, and nucleolus. To examine the anticancer properties, the U87 glioblastoma cell line, and its corresponding multidrug-resistant U87-TxR cell line, as well as patient-derived astrocytoma grade 3 cells (ASC), were used, while normal human lung fibroblasts were used to determine the selectivity. CON1 and CON2 exhibited better resistance and selectivity profiles than DOX, showing less cytotoxicity, as evidenced by real-time cell analysis, DNA damage determination, cell death induction, mitochondrial respiration, and mitochondrial membrane depolarization studies. Cell cycle analysis and the β-galactosidase activity assay suggested that glioblastoma cells die by senescence following CON1 treatment. Overall, CON1 and CON2 showed great potential as they have better anticancer features than DOX. They are promising candidates for additional preclinical and clinical studies on glioblastoma.

Introduction. Juvenile nasopharyngeal angiofibroma are benign tumors, with locally aggressive behavior. Preoperative tumor embolization with polyvinyl alcohol particles can reduce intraoperative blood loss and facilitate surgical resection. Case outline. A 16-year-old male was admitted to hospital due to profuse epistaxis and sense of nose fullness. Multidetector computed tomographic angiography examination showed a tumor mass in the right nasal cavity with extension to the right maxillary sinus and ethmoidal cells on the right, and in the left nasal cavity. It rested on the nasal septum, but without bone destruction. After application of contrast agent, described mass became intensely opacified. Preprocedural digital subtraction angiography of external and internal carotid arteries of both sides showed extensive pathological vascularization, which received main contribution from branches of maxillary artery on right and, to a lesser extent, on left side. Due to danger of penetration of a particle embolization agent of smaller diameter into orbital branches and possible retrograde migration into carotid artery, we decided to apply particle embolization agent of larger diameter (500?700 ?m) than prescribed by modern standards. Tumor was completely surgically removed third day after embolization, and patient was discharged without any neurological deficit. Control contrast enhanced multidetector computed tomographic angiographies were performed at third and seventh month after surgery and showed no tumor residue or recurrence. Conclusion. The use of particles of larger diameter gave satisfactory results during operation ? surgical excision of tumor, when dangerous anastomoses do not allow use of particles of smaller diameter and can be safely performed without significant neurological nor systemic complications.

Anaplastic astrocytoma WHO (World Health Organization) grade 3 represents about 7% of all primary brain tumours in the adult population. The standard treatment protocol involves safe surgical resection, chemotherapy and radiotherapy. Advances in therapeutic protocols have been noted over the past few decades, but the prognoses are still poor with a median survival of 31 months. We present a case of a male patient who is alive 25 years after the initial diagnosis and treatment of anaplastic astrocytoma WHO grade 3. The patient was operated and reoperated two times due to local tumour recurrence in the first two years after the initial diagnosis. After the last operation, the patient abandoned medical therapy and started praying. The patient is still alive without any clinical or radiological signs of tumour recurrence.

Introduction Patients with severe spasticity are effectively treated with intrathecal baclofen therapy (ITB), but because of their invalidity, in case of infection, prognosis is poor. Case outline We present three cases (two men and one woman) of patients treated with baclofen intrathecal therapy due to spasticity of all four extremities who underwent SARS-CoV2 virus infection. Two of them have multiple sclerosis, and one has trauma of the cervical segment of the spinal cord. In all three patients, the clinical presentation of COVID-19 infection occurred within six months of implantation of the pump for ITB. They were successfully treated in hospital with same dose of the drug and without exacerbation of neurological status. Barthel index (BI) and modified Rankin score were same before and after COVID-19 infection. In two cases BI was 20, and in one 69; and modified Rankin score (mRS) was 3 in one case, and 5 in two cases. Conclusion Patients with severe spasticity who require intrathecal baclofen therapy can be safely treated regardless of the pandemic.

Introduction. Anomalies of the middle cerebral artery (MCA) are very rare. ?Rete MCA,? ?twig-like MCA? (T-MCA), ?aplastic MCA,? ?unfused MCA,? and others are all synonyms for unilateral embryological anomaly of the M1 segment of the MCA, where, due to an unknown cause, fusion of primordial arteries of the M1 segment did not happen. As a result, the M1 segment of the affected side consists of a mesh of small arteries from which arise normal perforators and cortical branches. Moyamoya disease, moyamoya-like syndrome, atherosclerotic steno-occlusive disease, vasculitis, and dissection of the MCA should be considered in differential diagnosis. Case outline. We present a 60-year-old female patient with twig-like left MCA, incidentally diagnosed due to persistent headaches six days prior to admission. Non-contrast computed tomography head examination was without peculiarities. Computed tomography angiography showed a network of small vessels in place of the left M1 segment, bridging internal carotid artery terminus with branches of the MCA bifurcation and giving rise to lenticulostriate arteries. Fourteen months later, on physical examination, the patient was in good general condition, without a neurological deficit, with occasional episodes of headache no stronger than 3?4/10 on the visual analogue scale. Conclusion. We report a patient with extremely rare variation of the M1 segment of the left MCA, incidentally diagnosed due to headaches.

BACKGROUND:Glioblastoma (GBM) highly expresses Src tyrosine kinase involved in survival, proliferation, angiogenesis and invasiveness of tumor cells. Src activation also reduces reactive oxygen species (ROS) generation, whereas Src inhibitors are able to increase cellular ROS levels.METHODS:Pro-oxidative effects of two pyrazolo[3,4-d]pyrimidine derivatives-Src tyrosine kinase inhibitors, Si306 and its prodrug pro-Si306-were investigated in human GBM cells U87 and patient-derived GBM-6. ROS production and changes in mitochondrial membrane potential were assessed by flow cytometry. The expression levels of superoxide dismutase 1 (SOD1) and 2 (SOD2) were studied by Western blot. DNA damage, cell death induction and senescence were also examined in GBM-6 cells.RESULTS:Si306 and pro-Si306 more prominently triggered ROS production and expression of antioxidant enzymes in primary GBM cells. These effects were followed by mitochondrial membrane potential disruption, double-strand DNA breaks and senescence that eventually led to necrosis.CONCLUSION:Src kinase inhibitors, Si306 and pro-Si306, showed significant pro-oxidative potential in patient-derived GBM cells. This feature contributes to the already demonstrated anti-glioblastoma properties of these compounds in vitro and in vivo and encourages clinical investigations.

Introduction. Intracranial aneurysms with a radiological sign of a donut are a medical priority and have been described in a small number of cases. This radiological sign occurs in aneurysms in which there is partial thrombosis inside aneurismal sac and circular laminar flow between the aneurismal wall and the thrombus in its center. Consequently, there is a central contrast-filling defect of the aneurysm sac observed on different angiographic imaging methods. Case outline. We present a 35-year-old female patient admitted for examination due to frequent headaches, visual disturbances on the left and loss of sight on the right eye. Digital subtraction angiography (DSA) showed an aneurysm on the right internal carotid artery measuring 25.6 ? 25 mm, while neck measured 11 mm and included part of the C6 and C7 segments. Treatment decision was made that placing a flow-diverting stent across the aneurysm neck would be most beneficial in this case. After the procedure, the patient was discharged in the same general condition as she was before admission to the hospital. Seven months after the intervention, she reported for her first DSA control examination. Normal position of the left A1 segment was demonstrated, suggesting shrinkage of the aneurysm sac. An improvement of vision on both eyes was stated. Conclusion. We present a patient with a ?donut? aneurysm on the internal carotid artery, successfully treated with a flow-diverting stent.

Patients with coronary artery disease (CAD) are the primary candidates to receive small-diameter tissue-engineered blood vessels (TEBVs). Peripheral blood derived endothelial progenitor cells (EPCs) from CAD patients (CAD EPCs) represent a minimally invasive source of autologous cells for TEBV endothelialization. We have previously shown that human CAD EPCs are highly proliferative and express many of the hallmarks of mature and healthy endothelial cells; however, their behavior on stromal cells that comprise the media of TEBVs has not yet been evaluated. Primary CAD EPCs or control human aortic endothelial cells (HAECs) were seeded over confluent, quiescent layers of human smooth muscle cells (SMCs) using a direct co-culture model. The percent coverage, adhesion strength, alignment under flow and generation of flow-induced nitric oxide of the seeded CAD EPCs were compared to that of HAECs. The integrin-binding profile of CAD EPCs was also evaluated over a layer of confluent, quiescent SMCs. Direct comparison of our CAD EPC results to analogous co-culture studies with cord blood EPCs show that both types of blood-derived EPCs are viable options for endothelialization of TEBVs.

Glioblastoma (GBM), as the most aggressive brain tumor, displays a high expression of Src tyrosine kinase, which is involved in the survival, migration, and invasiveness of tumor cells. Thus, Src emerged as a potential target for GBM therapy. The effects of Src inhibitors pyrazolo[3,4-d]pyrimidines, Si306 and its prodrug pro-Si306 were investigated in human GBM cell lines (U87 and U87-TxR) and three primary GBM cell cultures. Primary GBM cells were more resistant to Si306 and pro-Si306 according to the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. However, the ability of all GBM cells to degrade the extracellular matrix was considerably compromised after Si306 and pro-Si306 applications. Besides reducing the phosphorylation of Src and its downstream signaling pathway components, both compounds decreased the phosphorylated form of focal adhesion kinase (FAK) and epidermal growth factor receptor (EGFR) expression, showing the potential to suppress the aggressiveness of GBM. In vivo, Si306 and pro-Si306 displayed an anti-invasive effect against U87 xenografts in the zebrafish embryo model. Considering that Si306 and pro-Si306 are able to cross the blood-brain barrier and suppress the spread of GBM cells, we anticipate their clinical testing in the near future. Moreover, the prodrug showed similar efficacy to the drug, implying the rationality of its use in clinical settings.

The patient we report is a 59-year-old male with lumbar radiculopathy due to epidural mass lipoma associated with unilateral posterior facet joint ostheoarthritis unresponsive to conservative treatment. Elective surgical intervention with right laminectomy, facetectomy, and foraminotomy for resection of the mass was performed. An encapsulated lipomatous lesion was excised. Pathohistological findings revealed true lipomatous tissue. Our case report increase suspicion for this rare spinal pathology on patients with lumbar radiculopathy and epidural mass diagnosed by MRI and histopathology. We strongly suggest operative treatment for this kind of symptomatic spinal epidural lesions.

PurposeGlioblastoma is the most common and lethal adult brain tumor. Despite current therapeutic strategies, including surgery, radiation and chemotherapy, the median survival of glioblastoma patients is 15months. The development of this tumor depends on a sub-population of glioblastoma stem cells governing tumor propagation and therapy resistance. SOX3 plays a role in both normal neural development and carcinogenesis. However, little is known about its role in glioblastoma. Thus, the aim of this work was to elucidate the role of SOX3 in glioblastoma.MethodsSOX3 expression was assessed using real-time quantitative PCR (RT-qPCR), Western blotting and immunohistochemistry. MTT, immunocytochemistry and Transwell assays were used to evaluate the effects of exogenous SOX3 overexpression on the viability, proliferation, migration and invasion of glioblastoma cells, respectively. The expression of Hedgehog signaling pathway components and autophagy markers was assessed using RT-qPCR and Western blot analyses, respectively.ResultsHigher levels of SOX3 expression were detected in a subset of primary glioblastoma samples compared to those in non-tumoral brain tissues. Exogenous overexpression of this gene was found to increase the proliferation, viability, migration and invasion of glioblastoma cells. We also found that SOX3 up-regulation was accompanied by an enhanced activity of the Hedgehog signaling pathway and by suppression of autophagy in glioblastoma cells. Additionally, we found that SOX3 expression was elevated in patient-derived glioblastoma stem cells, as well as in oncospheres derived from glioblastoma cell lines, compared to their differentiated counterparts, implying that SOX3 expression is associated with the undifferentiated state of glioblastoma cells.ConclusionFrom our data we conclude that SOX3 can promote the malignant behavior of glioblastoma cells.

Patients with brain arteriovenous malformation (AVM) have a certain risk to bleed, and the goal of this study was to examine the effect of radiological and clinical predictive characteristics of AVM hemorrhage using multidetector computed tomographic (MDCT) angiography. The study included a series of 57 patients, mean age 35.46 years, who were diagnosed during their hospitalization at Clinical Department of Neurosurgery, Clinical Center of Serbia, in the period from January 2008 to March 2016. In all patients, the diagnosis was made using MDCT angiography. Two groups of patients were observed. The first group included patients who did not initially present with hemorrhage, while the second group initially presented with hemorrhage. Both groups were treated with medical therapy or a combination of medical therapy with embolization/surgery/radiotherapy. Deep venous drainage (p<0.05), combined arterial supply from different basins (p<0.05) with a length <60 mm, venous dilatation present in the drainage vein (p<0.01), and the angle of casting sup-ply arteries in the nidus (p<0.01) carry a risk of repeated bleeding. In the group of patients who had initial hemorrhage, the mean value of the casting angle size was 130°, while in the group that did not have initial bleeding the mean value of the measured angle size was 103.81° with standard deviation of 17.21° (p<0.01). In conclusion, AVMs with deep venous drainage from the carotid and vertebrobasilar basin, the length of the feeding arteries <60 mm, the angle of the casting feeding arteries in the nidus ≥130° and dilatation and/or venous aneurysm of drainage vessel are predictive for clinical presenting by hemorrhage.

AIM:Brainstem gliomas (BSG) constitute less than 2% of brain tumors in adults. Therapeutic options are limited and BSG are associated with a high morbidity and mortality.MATERIAL AND METHODS:We reviewed the records of 51 patients with BSG treated at the Institute of Neurosurgery, Clinical Center of Serbia in Belgrade between 1998 and 2012. We recorded demographic and clinical variables as well as radiological findings and survival.RESULTS:Of the 51 patients, 62.7% were male and 37.3% were female. The mean age was 30.6±19.3 years. High grade glioma (Astrocytoma grade III and IV) was most common at the age of 38.2±17.9 years (t=.481, p=0.017) while low grade glioma (Astrocytoma grade I and II) was common in younger age as 25.4±17.4 years (X2=4.013; p=0.045), with localization in the pons (X2=5.299; p=0.021) and exophytic presentation (X2=3.862; p=0.049). Ataxia, as initial symptom, was a predictor of poor outcome (HR:5.546, p=0.012).CONCLUSION:Due to its specific localization, BSG present a major challenge for neurosurgery, because of the necessity of safe approach for radical resection. Histological verification of BSG determines the need for additional therapeutic procedures such as radiotherapy and chemotherapy. Benefit from correct diagnosis is reflected in the avoidance of potentially adverse effects of treatment.

Synchronous occurrence of multiple lung cancers in the same lobe of the lung is very rare. Most of the tumors diagnosed in this way have the same histologic type. With imaging methods it is difficult to determine if the multiple lung lesions present hematogenous spread of lung cancer (or cancer from other origin) or these lesions present the second primary lung cancer. We report a rare and unusual case of synchronous occurrence of primary adenocarcinoma and squamous cell carcinoma in the same lobe of the lung. Our case demonstrates that in case of synchronous occurrence of multiple lung lesions each lesion should be sampled and histologic type of every lesion should be determined so the further treatment can be planned accordingly.

We are reporting the case of a 53-year old woman presenting to our hospital with a hemorrhagic low-grade glioma (LGG). She was admitted to a nearby general hospital where she had presented with aphasia, right hemiplegia and change of mental status. Computer tomography (CT) images showed a left temporo-parietal hemorrhage with mass effect. She was transferred to our hospital neuro-intensive care unit where emergency craniotomy was performed. A tumor with hematoma was removed and further histopathology analysis revealed tumor progression.We reviewed the literature reporting cases of central nervous system tumors hemorrhage and found that these types of events are exquisitely rare in adults with LGG. However these events are possible, suggesting that it should be included in the differential diagnosis of any patient presenting with intracranial hemorrhage. This case raises questions regarding the benefit of early versus late intervention for patients known to have LGG.