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Keywords = cerebrovascular hemorrhage

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20 pages, 1899 KiB  
Case Report
Ruptured Posterior Inferior Cerebellar Artery Aneurysms: Integrating Microsurgical Expertise, Endovascular Challenges, and AI-Driven Risk Assessment
by Matei Șerban, Corneliu Toader and Răzvan-Adrian Covache-Busuioc
J. Clin. Med. 2025, 14(15), 5374; https://doi.org/10.3390/jcm14155374 - 30 Jul 2025
Viewed by 441
Abstract
Background/Objectives: Posterior inferior cerebellar artery (PICA) aneurysms are one of the most difficult cerebrovascular lesions to treat and account for 0.5–3% of all intracranial aneurysms. They have deep anatomical locations, broad-neck configurations, high perforator density, and a close association with the brainstem, which [...] Read more.
Background/Objectives: Posterior inferior cerebellar artery (PICA) aneurysms are one of the most difficult cerebrovascular lesions to treat and account for 0.5–3% of all intracranial aneurysms. They have deep anatomical locations, broad-neck configurations, high perforator density, and a close association with the brainstem, which creates considerable technical challenges for either microsurgical or endovascular treatment. Despite its acceptance as the standard of care for most posterior circulation aneurysms, PICA aneurysms are often associated with flow diversion using a coil or flow diversion due to incomplete occlusions, parent vessel compromise and high rate of recurrence. This case aims to describe the utility of microsurgical clipping as a durable and definitive option demonstrating the value of tailored surgical planning, preservation of anatomy and ancillary technologies for protecting a genuine outcome in ruptured PICA aneurysms. Methods: A 66-year-old male was evaluated for an acute subarachnoid hemorrhage from a ruptured and broad-necked fusiform left PICA aneurysm at the vertebra–PICA junction. Endovascular therapy was not an option due to morphology and the center of the recurrence; therefore, a microsurgical approach was essential. A far-lateral craniotomy with a partial C1 laminectomy was carried out for proximal vascular control, with careful dissection of the perforating arteries and precise clip application for the complete exclusion of the aneurysm whilst preserving distal PICA flow. Results: Post-operative imaging demonstrated the complete obliteration of the aneurysm with unchanged cerebrovascular flow dynamics. The patient had progressive neurological recovery with no new cranial nerve deficits or ischemic complications. Long-term follow-up demonstrated stable aneurysm exclusion and full functional independence emphasizing the sustainability of microsurgical intervention in challenging PICA aneurysms. Conclusions: This case intends to highlight the current and evolving role of microsurgical practice for treating posterior circulation aneurysms, particularly at a time when endovascular alternatives are limited by anatomy and hemodynamics. Advances in artificial intelligence cerebral aneurysm rupture prediction, high-resolution vessel wall imaging, robotic-assisted microsurgery and new generation flow-modifying implants have the potential to revolutionize treatment paradigms by embedding precision medicine principles into aneurysm management. While the discipline of cerebrovascular surgery is expanding, it can be combined together with microsurgery, endovascular technologies and computational knowledge to ensure individualized, durable, and minimally invasive treatment options for high-risk PICA aneurysms. Full article
(This article belongs to the Special Issue Neurovascular Diseases: Clinical Advances and Challenges)
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17 pages, 6355 KiB  
Article
Regulation of Hindbrain Vascular Development by rps20 in Zebrafish
by Xinyu Shen, Zhaozhi Wen, Shunze Deng, Yuxuan Qiu, Weijie Ma, Xinyue Dong, Jie Gong, Yu Zhang, Dong Liu and Bing Xu
Cells 2025, 14(14), 1070; https://doi.org/10.3390/cells14141070 - 13 Jul 2025
Viewed by 503
Abstract
During aging, the brain vasculature undergoes significant deterioration characterized by increased arterial tortuosity, compromised blood–brain barrier integrity, and reduced cerebral blood flow, all of which contribute to various neurological disorders. Thus, understanding the mechanisms underlying aging-related cerebrovascular defects is critical for developing strategies [...] Read more.
During aging, the brain vasculature undergoes significant deterioration characterized by increased arterial tortuosity, compromised blood–brain barrier integrity, and reduced cerebral blood flow, all of which contribute to various neurological disorders. Thus, understanding the mechanisms underlying aging-related cerebrovascular defects is critical for developing strategies to alleviate aging-associated neurological diseases. In this study, we investigated the role of aging-related genes in brain vascular development using zebrafish as an in vivo model. By thoroughly analyzing scRNA-seq datasets of mid- and old-aged brain vascular endothelial cells (human/mouse), we found ribosomal protein S20 (rps20) significantly down-regulated during aging. qPCR analysis and whole-mount in situ hybridization validated a high expression of rps20 during early zebrafish development, which progressively decreased in adult and aged zebrafish brains. Functional studies using the CRISPR/Cas9-mediated knockout of rps20 revealed an impaired growth of central arteries in the hindbrain and a marked increased intracranial hemorrhage incidence. Mechanistically, qPCR analysis demonstrated a significant downregulation of vegfa, cxcl12b, and cxcr4a, key signaling molecules required for hindbrain vascular development, in rps20-deficient embryos. In conclusion, our findings demonstrate that rps20 is essential for proper brain vascular development and the maintenance of vascular homeostasis in zebrafish, revealing a novel mechanism by which aging-related genes regulate brain vascular development. This study provides new insights that may aid in understanding and treating aging-associated vascular malformations and neurological pathologies. Full article
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2 pages, 118 KiB  
Abstract
Developing Gene-Targeted Therapies for COL4A1- and COL4A2-Related Disorders: Opportunities and Challenges
by Patricia L. Musolino
Proceedings 2025, 120(1), 7; https://doi.org/10.3390/proceedings2025120007 - 8 Jul 2025
Viewed by 238
Abstract
Background: COL4A1/2-related disorders are genetically driven multisystem diseases characterized by small vessel cerebrovascular pathology, including fetal and perinatal strokes, intracranial hemorrhage, and progressive white matter damage [...] Full article
(This article belongs to the Proceedings of The 2nd COL4A1-A2 International Conference)
11 pages, 478 KiB  
Systematic Review
The Role of Immature Platelet Fraction and Reticulated Platelets in Stroke Monitoring and Outcome Prognosis: A Systematic Review
by Alexandra Tsankof, Dimitrios A. Tsakiris, Lemonia Skoura, Panagiota Tsiatsiou, Eleftheria Ztriva, Georgios Ntaios, Christos Savopoulos and Georgia Kaiafa
J. Clin. Med. 2025, 14(13), 4760; https://doi.org/10.3390/jcm14134760 - 5 Jul 2025
Viewed by 398
Abstract
Background/Objectives: Immature platelet fraction (IPF) and reticulated platelets (RPs) are biomarkers reflecting the youngest and most metabolically active platelets in circulation. RPs, a subset of immature platelets, contain residual RNA and have been associated with increased thrombotic potential. Elevated IPF levels indicate [...] Read more.
Background/Objectives: Immature platelet fraction (IPF) and reticulated platelets (RPs) are biomarkers reflecting the youngest and most metabolically active platelets in circulation. RPs, a subset of immature platelets, contain residual RNA and have been associated with increased thrombotic potential. Elevated IPF levels indicate enhanced platelet production, commonly observed during elevated platelet turnover, such as in autoimmune reactions, consumption, and thrombotic events. This systematic review aims to evaluate the potential role of IPF and RPs in the context of cerebrovascular events, specifically ischemic and hemorrhagic stroke, as well as transient ischemic attacks (TIAs), and to assess their clinical utility in stroke monitoring and management. Methods: A comprehensive literature search was conducted in PubMed, Scopus, Cochrane Library, and Web of Science for studies published between 2000 and 2024, which focused on IPF and RPs in human subjects with cerebrovascular events. Results: Six studies met the inclusion criteria. Findings suggest that elevated levels of IPF and RP are associated with the acute and chronic phases of ischemic stroke and TIA and may reflect increased platelet turnover and thrombotic activity. Some evidence supports their role in predicting stroke severity, recurrence, and underlying etiology, although results are not yet consistent across all studies. Conclusions: IPF and RPs are emerging biomarkers with potential applications in acute ischemic stroke and risk stratification. While current evidence is promising, further research is needed to standardize measurement techniques and validate their routine use in clinical practice. Full article
(This article belongs to the Section Vascular Medicine)
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18 pages, 1598 KiB  
Article
Trends and Predictors of Venous Thromboembolism and Major Hemorrhagic Events in Hospitalized Leukemia Patients: A Cross-Sectional Analysis of the NIS (2016–2020)
by Daniel Antwi-Amoabeng, Bryce D. Beutler, Vijay Neelam and Mark Ulanja
Clin. Pract. 2025, 15(7), 117; https://doi.org/10.3390/clinpract15070117 - 25 Jun 2025
Viewed by 326
Abstract
Background/Objectives: Venous thromboembolism (VTE) and major hemorrhagic events are significant complications in hospitalized leukemia patients, but contemporary analyses of their epidemiology, predictors, and impact on clinical outcomes remain limited. Methods: We conducted a cross-sectional study using the National Inpatient Sample (NIS) database from [...] Read more.
Background/Objectives: Venous thromboembolism (VTE) and major hemorrhagic events are significant complications in hospitalized leukemia patients, but contemporary analyses of their epidemiology, predictors, and impact on clinical outcomes remain limited. Methods: We conducted a cross-sectional study using the National Inpatient Sample (NIS) database from 2016 to 2020. Hospitalized leukemia patients were identified using ICD-10 codes. Trends in the incidence of venous thromboembolism (VTE) and bleeding were assessed across the years, and multivariable logistic regression models were used to evaluate the predictors of VTE and bleeding. We assessed the influence thromboembolic and hemorrhagic complications on length of stay, cost, and mortality outcomes. Results: Among 430,780 leukemia hospitalizations, the overall incidence of VTE was 5.4% and remained stable throughout the study period (p = 0.09), while hemorrhagic events = 5.6%) showed a significant upward trend (p = 0.01). Cerebrovascular accidents, central venous catheter insertion, and protein calorie malnutrition (PCM) were significant predictors of both VTE and hemorrhage. PCM demonstrated a dose-dependent relationship with both complications. VTE was associated with a 33.5% increase in length of stay (LOS) and a 35% increase in cost of care (COC). Hemorrhage was associated with 23.2% increase in LOS and 32.6% increase in COC. Only hemorrhagic events were independently associated with increased mortality (adjusted OR 2.88, p < 0.001). Conclusions: The incidence of VTE in hospitalized leukemia patients has remained stable while hemorrhagic complications have increased significantly. Nutritional status represents a potentially modifiable risk factor for both VTE and bleeding complications. The competing risk between thrombosis and hemorrhage varies with age and nutritional status, suggesting the need for nuanced thromboprophylaxis strategies in this vulnerable population. Full article
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28 pages, 1969 KiB  
Review
Clinical Management of Cerebral Amyloid Angiopathy
by Aikaterini Theodorou, Stella Fanouraki, Eleni Bakola, Georgia Papagiannopoulou, Lina Palaiodimou, Maria Chondrogianni, Maria-Ioanna Stefanou, Lampis Stavrinou, Athanasia Athanasaki, Klearchos Psychogios, Odysseas Kargiotis, Apostolos Safouris, Georgios Velonakis, Georgios P. Paraskevas and Georgios Tsivgoulis
J. Clin. Med. 2025, 14(12), 4259; https://doi.org/10.3390/jcm14124259 - 15 Jun 2025
Viewed by 4951
Abstract
Background: Cerebral amyloid angiopathy (CAA) represents a progressive cerebrovascular disorder, characterized by aberrant accumulation of beta-amyloid isoforms in cortical and leptomeningeal vessel walls of cerebrum and cerebellum. Methods: We sought to investigate the clinical manifestations, current different diagnostic tools, various therapeutic strategies and [...] Read more.
Background: Cerebral amyloid angiopathy (CAA) represents a progressive cerebrovascular disorder, characterized by aberrant accumulation of beta-amyloid isoforms in cortical and leptomeningeal vessel walls of cerebrum and cerebellum. Methods: We sought to investigate the clinical manifestations, current different diagnostic tools, various therapeutic strategies and most uncommon subtypes of the disease. Results: The vast majority of CAA remains sporadic, with increasing prevalence with age and very frequent coexistence with Alzheimer’s disease. Clinically, CAA can present with spontaneous lobar intracerebral hemorrhage, transient focal neurologic episodes attributed to convexity subarachnoid hemorrhage or cortical superficial siderosis, and progressive cognitive decline leading to dementia. Inflammatory CAA subtype should be recognized early and treated promptly so that better functional outcomes may be achieved. Moreover, genetic and iatrogenic CAA forms are rare, yet increasingly recognized during the last years. Therapeutic management remains challenging for clinicians, especially when markers indicative of higher bleeding risk are present. A targeted therapy does not currently exist. However, various clinical trials are in progress, focusing on offering new promising insights into the disease treatment. Conclusions: This review aims to deepen our understanding of CAA diagnosis and therapeutic approach but also summarizes current evidence on the most uncommon subtypes of this cerebral small-vessel disease. Full article
(This article belongs to the Section Clinical Neurology)
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14 pages, 425 KiB  
Review
Clinical Impact of Vaping
by Francesco Petrella, Paola Faverio, Andrea Cara, Enrico Mario Cassina, Lidia Libretti, Sara Lo Torto, Emanuele Pirondini, Federico Raveglia, Francesca Spinelli, Antonio Tuoro, Elisa Perger and Fabrizio Luppi
Toxics 2025, 13(6), 470; https://doi.org/10.3390/toxics13060470 - 1 Jun 2025
Viewed by 1915
Abstract
The term ‘vaping’ refers to the use of electronic cigarettes or other devices to inhale a variety of heated and aerosolized substances. Vaping has been promoted as a less harmful and potentially oncogenic alternative to nicotine cigarettes, particularly to help heavy smokers quit. [...] Read more.
The term ‘vaping’ refers to the use of electronic cigarettes or other devices to inhale a variety of heated and aerosolized substances. Vaping has been promoted as a less harmful and potentially oncogenic alternative to nicotine cigarettes, particularly to help heavy smokers quit. While vaping products do not produce the same carcinogenic substances—such as polycyclic aromatic hydrocarbons—generated by the combustion of tobacco, and while their fluids lack tobacco-related carcinogens like nitrosamines, it is now well established that they still generate harmful and potentially oncogenic byproducts. Several mechanisms have been proposed to explain the potential oncogenic effects of vaping fluids, including direct chemical action, epithelial–mesenchymal transition induction, redox stress, mitochondrial toxicity, and DNA damage. In addition to cancer risk, there have been reports of adverse effects on cardiovascular health, reproductive function, and non-oncologic lung injuries. These include exogenous lipoid pneumonia, diffuse alveolar hemorrhage with proven alveolar injury, and vaping-associated bronchiolitis obliterans. The aim of this review is to examine vaping devices, their potential role in lung carcinogenesis, vaping-associated lung injury, and other clinical implications, including impacts on cardiovascular, cerebrovascular, and respiratory diseases, and also pregnancy and fetus health. Full article
(This article belongs to the Section Human Toxicology and Epidemiology)
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12 pages, 246 KiB  
Review
Cerebrovascular Management Considerations in Patients on AATs
by Dylan Ryan, Wuwei Feng and Andy J. Liu
J. Clin. Med. 2025, 14(10), 3420; https://doi.org/10.3390/jcm14103420 - 14 May 2025
Viewed by 437
Abstract
The prevalence of Alzheimer’s Disease (AD) is increasing worldwide, with more emergency providers and neurologists expecting to encounter these patients. The paradigm of management of AD is expected to change given the recent approval of anti-amyloid therapies (AATs). The most concerning complication of [...] Read more.
The prevalence of Alzheimer’s Disease (AD) is increasing worldwide, with more emergency providers and neurologists expecting to encounter these patients. The paradigm of management of AD is expected to change given the recent approval of anti-amyloid therapies (AATs). The most concerning complication of these therapies is amyloid-related imaging abnormalities (ARIA), which can lead to an increased risk of cerebrovascular complications. Given a growing population of patients with AD and growing use of AATs, providers must be prepared to manage patients at risk of cerebrovascular disease and those presenting with neurologic deficits. This subpopulation warrants a unique approach given the risk of ischemic stroke and the associated risk of hemorrhage present in the use of AATs. In this narrative review, we present and propose management considerations in the acute stroke setting and patients at risk of cerebrovascular disease, including patients with indications for anticoagulation, to most appropriately manage this special population. Future cross-disciplinary collaboration and use of registry data will be essential to narrow management approaches and develop safety data. Full article
(This article belongs to the Section Vascular Medicine)
14 pages, 533 KiB  
Review
Emerging Advances in the Management of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Narrative Review
by Shinsuke Muraoka, Takashi Izumi, Masahiro Nishihori, Shunsaku Goto, Issei Takeuchi and Ryuta Saito
J. Clin. Med. 2025, 14(10), 3403; https://doi.org/10.3390/jcm14103403 - 13 May 2025
Viewed by 2028
Abstract
Background/Objectives: Aneurysmal subarachnoid hemorrhage (aSAH) remains a life-threatening cerebrovascular event with high rates of mortality and long-term morbidity. Among its complications, delayed cerebral ischemia (DCI) is a major contributor to poor clinical outcomes. Although cerebral vasospasm has traditionally been considered the primary mechanism [...] Read more.
Background/Objectives: Aneurysmal subarachnoid hemorrhage (aSAH) remains a life-threatening cerebrovascular event with high rates of mortality and long-term morbidity. Among its complications, delayed cerebral ischemia (DCI) is a major contributor to poor clinical outcomes. Although cerebral vasospasm has traditionally been considered the primary mechanism underlying DCI, recent studies have revealed the multifactorial nature of this condition. This review aims to provide a comprehensive overview of the pathophysiology, preventive strategies, and current treatment options for DCI following aSAH. Methods: A narrative literature review was conducted using the PubMed database to identify peer-reviewed articles relevant to the prevention and treatment of DCI following aSAH. The search strategy employed the following terms: (“Subarachnoid Hemorrhage” [MeSH]) AND “Delayed Cerebral Ischemia” AND (“Prevention and Control” [Subheading] OR “Secondary Prevention” [MeSH]). This search strategy was designed to capture studies addressing both pharmacological and non-pharmacological preventive measures for DCI. Results: A comprehensive PubMed search identified a total of 113 relevant articles. Among these, 40 publications primarily addressed pharmacological interventions, while 22 focused on neuromonitoring techniques. An additional 20 articles explored the pathophysiological mechanisms underlying DCI, and 15 involved preclinical studies utilizing animal models. The remaining 16 articles encompassed diverse topics, including prophylactic endovascular therapies, newly proposed definitions of DCI, treatment algorithm development, functional outcome analyses, and entries in clinical trial registries. Emerging evidence highlights that vasospasm alone does not account for all cases of DCI. Pharmacological approaches such as nimodipine, clazosentan, and fasudil have shown varying degrees of efficacy. Circulatory management and removal of subarachnoid hematoma via CSF drainage or thrombolytics may reduce DCI risk, although their impact on long-term neurological outcomes remains controversial. Endovascular therapy and adjunctive agents such as cilostazol or anticoagulants have demonstrated potential but require further validation through large-scale trials. Conclusions: Effective DCI prevention and treatment require a multimodal approach targeting diverse pathological mechanisms beyond vasospasm. Improved risk stratification, early detection, and individualized therapy are essential for advancing the management of patients with aSAH. Full article
(This article belongs to the Special Issue Clinical Updates and Perspectives on Subarachnoid Hemorrhage)
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22 pages, 1486 KiB  
Review
Lipoprotein(a) as a Stroke Biomarker: Pathophysiological Pathways and Therapeutic Implications
by Evangelos Panagiotopoulos, Lina Palaiodimou, Aikaterini Theodorou, Georgia Papagiannopoulou, Eleni Bakola, Maria Chondrogianni, Klearchos Psychogios, Odysseas Kargiotis, Apostolos Safouris, Charalambos Vlachopoulos, Sotirios Giannopoulos, Marios Themistocleous, Vaia Lambadiari, Georgios Tsivgoulis and Maria-Ioanna Stefanou
J. Clin. Med. 2025, 14(9), 2990; https://doi.org/10.3390/jcm14092990 - 25 Apr 2025
Viewed by 1266
Abstract
Lipoprotein(a) [Lp(a)] has attracted widespread interest as a potential biomarker for cerebrovascular diseases due to its genetically determined and stable plasma concentration throughout life. Lp(a) exhibits pro-atherogenic and pro-thrombotic properties that contribute to vascular pathology in both extracranial and intracranial vessels. Elevated Lp(a) [...] Read more.
Lipoprotein(a) [Lp(a)] has attracted widespread interest as a potential biomarker for cerebrovascular diseases due to its genetically determined and stable plasma concentration throughout life. Lp(a) exhibits pro-atherogenic and pro-thrombotic properties that contribute to vascular pathology in both extracranial and intracranial vessels. Elevated Lp(a) levels are strongly associated with large-artery atherosclerotic stroke, while data on its role in other ischemic subtypes and hemorrhagic stroke remains limited and inconsistent. Recent advances in Lp(a)-lowering therapies, such as antisense oligonucleotides and RNA-based agents, have demonstrated significant efficacy in reducing plasma Lp(a) levels. These advances have prompted increasing research into their potential application in the prevention and treatment of cerebrovascular diseases, aiming to determine whether Lp(a) reduction may translate into a reduced risk of stroke and large-artery atherosclerosis. This narrative review summarizes the current evidence on the association between Lp(a) and stroke, focusing on its utility in patient risk stratification. It also highlights existing knowledge gaps and outlines directions for future research, particularly in understanding subtype-specific effects and evaluating the clinical benefits of Lp(a)-targeted therapies. Full article
(This article belongs to the Special Issue Biomarkers and Diagnostics in Neurological Diseases)
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19 pages, 7764 KiB  
Systematic Review
Risk of Cerebrovascular Events in Deep Brain Stimulation for Parkinson’s Disease Focused on STN and GPi: Systematic Review and Meta-Analysis
by Cristofer Zarate-Calderon, Carlos Castillo-Rangel, Iraís Viveros-Martínez, Estefanía Castro-Castro, Luis I. García and Gerardo Marín
Brain Sci. 2025, 15(4), 413; https://doi.org/10.3390/brainsci15040413 - 18 Apr 2025
Viewed by 965 | Correction
Abstract
Background/Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder treated with deep brain stimulation (DBS) for advanced stages, targeting the subthalamic nucleus (STN) or the internal globus pallidus (GPi). Despite DBS’s symptomatic benefits, cerebrovascular events (CVEs) remain a concern. This study assessed [...] Read more.
Background/Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder treated with deep brain stimulation (DBS) for advanced stages, targeting the subthalamic nucleus (STN) or the internal globus pallidus (GPi). Despite DBS’s symptomatic benefits, cerebrovascular events (CVEs) remain a concern. This study assessed CVE risk in PD patients undergoing DBS. Methods: We performed a systematic review and meta-analysis following PRISMA 2020 guidelines. Studies published between 2014 and 2024 that reported CVEs in PD patients treated with DBS-STN or DBS-GPi were included. Data on CVEs, DBS targets, perioperative period, and microelectrode recording (MER) use were extracted, and probability proportions were pooled using a random-effects model. Results: Twenty-three studies (4795 patients) were included. The overall CVE probability was 2.71% (95% CI: 2.27–3.18%). Descriptive probabilities were 2.56% (95% CI: 1.94–3.24%) for STN and 0.93% (95% CI: 0.00–3.08%) for GPi. Hemorrhagic events were most common (STN: 2.47%; GPi: 1.98%), while ischemic events were rare (STN: 0.07%; GPi: 1.98%). Note that GPi estimates are based on a considerably smaller population and should be interpreted with caution. Postoperative CVEs (1.74%) were more frequent than intraoperative events (0.17%), and MER use did not significantly alter risk (MER: 2.89% vs. NON-MER: 2.92%). Conclusions: Our results suggest that DBS in PD is associated with a relatively low CVE risk (~2.7%), with hemorrhage being the most frequent type; CVEs remain a potential risk factor. Comprehensive evaluation of patient-specific factors and further prospective studies focusing on CVE outcomes are essential to optimize DBS safety in managing PD. Full article
(This article belongs to the Section Neurodegenerative Diseases)
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25 pages, 1925 KiB  
Review
A Systematic Review of MicroRNAs in Hemorrhagic Neurovascular Disease: Cerebral Cavernous Malformations as a Paradigm
by Roberto J. Alcazar-Felix, Aditya Jhaveri, Javed Iqbal, Abhinav Srinath, Carolyn Bennett, Akash Bindal, Diana Vera Cruz, Sharbel Romanos, Stephanie Hage, Agnieszka Stadnik, Justine Lee, Rhonda Lightle, Robert Shenkar, Janne Koskimäki, Sean P. Polster, Romuald Girard and Issam A. Awad
Int. J. Mol. Sci. 2025, 26(8), 3794; https://doi.org/10.3390/ijms26083794 - 17 Apr 2025
Cited by 1 | Viewed by 684
Abstract
Hemorrhagic neurovascular diseases, with high mortality and poor outcomes, urge novel biomarker discovery and therapeutic targets. Micro-ribonucleic acids (miRNAs) are potent post-transcriptional regulators of gene expression. They have been studied in association with disease states and implicated in mechanistic gene interactions in various [...] Read more.
Hemorrhagic neurovascular diseases, with high mortality and poor outcomes, urge novel biomarker discovery and therapeutic targets. Micro-ribonucleic acids (miRNAs) are potent post-transcriptional regulators of gene expression. They have been studied in association with disease states and implicated in mechanistic gene interactions in various pathologies. Their presence and stability in circulating fluids also suggest a role as biomarkers. This review summarizes the current state of knowledge about miRNAs in the context of cerebral cavernous malformations (CCMs), a disease involving cerebrovascular dysmorphism and hemorrhage, with known genetic underpinnings. We also review common and distinct miRNAs of CCM compared to other diseases with brain vascular dysmorphism and hemorrhage. A systematic search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline, queried all peer-reviewed articles published in English as of January 2025 and reported miRNAs associated with four hemorrhagic neurovascular diseases: CCM, arteriovenous malformations, moyamoya disease, and intracerebral hemorrhage. The PubMed systematic search retrieved 154 articles that met the inclusion criteria, reporting a total of 267 unique miRNAs identified in the literature on these four hemorrhagic neurovascular diseases. Of these 267 miRNAs, 164 were identified in preclinical studies, while 159 were identified in human subjects. Seventeen miRNAs were common to CCM and other hemorrhagic diseases. Common and unique disease-associated miRNAs in this systematic review motivate novel mechanistic hypotheses and have potential applications in diagnostic, predictive, prognostic, and therapeutic contexts of use. Much of current research can be considered hypothesis-generating, reflecting association rather than causation. Future areas of mechanistic investigation are proposed alongside approaches to analytic and clinical validations of contexts of use for biomarkers. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Emerging Therapies in Neurovascular Disease)
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27 pages, 2813 KiB  
Review
Intracranial Aneurysm Biomarkers: A Convergence of Genetics, Inflammation, Oxidative Stress, and the Extracellular Matrix
by Enhao Zhang, Xu Yan, Hangyu Shen, Mingyue Zhao, Xiang Gao and Yi Huang
Int. J. Mol. Sci. 2025, 26(7), 3316; https://doi.org/10.3390/ijms26073316 - 2 Apr 2025
Viewed by 1298
Abstract
Intracranial aneurysm (IA) is a common cerebrovascular disease in which sacral aneurysms occurring in the Wills ring region can lead to devastating subarachnoid hemorrhage. Despite advances in research, the underlying mechanisms of IA formation and rupture remain incompletely understood, hindering early diagnosis and [...] Read more.
Intracranial aneurysm (IA) is a common cerebrovascular disease in which sacral aneurysms occurring in the Wills ring region can lead to devastating subarachnoid hemorrhage. Despite advances in research, the underlying mechanisms of IA formation and rupture remain incompletely understood, hindering early diagnosis and effective treatment. This review comprehensively summarizes the current landscape of IA biomarkers, encompassing genetic markers, DNA, RNA, inflammatory molecules, oxidative stress proteins, and extracellular matrix (ECM) components. Accumulating evidence suggests that various biomarkers are associated with different stages of IA pathogenesis, including initiation, progression, and rupture. Aberrant ECM composition and remodeling have been observed in IA patients, and extracellular matrix-degrading enzymes are implicated in IA growth and rupture. Biomarker research in IA holds great potential for improving clinical outcomes. Future studies should focus on validating the existing biomarkers, identifying novel ones, and investigating their underlying mechanisms to facilitate the development of personalized preventive and therapeutic strategies for IA. Full article
(This article belongs to the Section Molecular Neurobiology)
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16 pages, 4980 KiB  
Case Report
Complex Anatomy, Advanced Techniques: Microsurgical Clipping of a Ruptured Hypophyseal Artery Aneurysm
by Corneliu Toader, Matei Serban, Nicolaie Dobrin, Razvan-Adrian Covache-Busuioc, Mugurel Petrinel Radoi, Alexandru Vlad Ciurea and Octavian Munteanu
J. Clin. Med. 2025, 14(7), 2361; https://doi.org/10.3390/jcm14072361 - 29 Mar 2025
Cited by 1 | Viewed by 820
Abstract
Background: Ruptured intracranial aneurysms remain the subject of debate in their management, but the management of lesions located at high-risk locations, such as the hypophyseal artery, continue to prove to be a challenge in anatomical orientation and proximity to vascular structures. While endovascular [...] Read more.
Background: Ruptured intracranial aneurysms remain the subject of debate in their management, but the management of lesions located at high-risk locations, such as the hypophyseal artery, continue to prove to be a challenge in anatomical orientation and proximity to vascular structures. While endovascular therapies have changed the treatment paradigms, microsurgical clipping is the gold standard for wide-necked aneurysms for which endovascular techniques may be suboptimal. The successful treatment of a ruptured hypophyseal artery aneurysm in an elderly patient is described in this report, which highlights the importance of advanced imaging, careful technique, and new understanding of personalized aneurysm management. Methods: An 82-year-old woman was admitted with a thunderclap headache, alteration of consciousness and meningeal signs, suggestive of subarachnoid hemorrhage (SAH). A non-contrast computed tomography (CT) and digital subtraction angiography (DSA) confirmed a saccular 12 × 10 mm aneurysm with a broad 3.13 mm neck arising from the hypophyseal artery. The location and morphology of the aneurysm required microsurgical clipping, which was performed through a right pterional craniotomy. Results: Correct clip placement, complete exclusion of the aneurysm, and resorption of the subarachnoid blood were both observed on postoperative imaging. The neurological examination was completely normal, with no complications. Follow-up imaging at three months demonstrated stable, marked cerebral atrophy with compensatory ventricular enlargement without evidence of recurrence. Conclusions: This case illustrates the important role of micro-surgical clipping in anatomically complex aneurysms and its sustainable outcome and accuracy in cases where endovascular practices would have limitations. Advanced imaging, like three-dimensional DSA and intraoperative tools, have revolutionized precision surgery, allowing achievement of optimal outcomes, even for more-complicated cases. With an evolving, dynamic field and exciting new technologies coming to the fore—such as artificial intelligence to predict rupture risk and augmented reality navigation—decision-making and treatment of complex aneurysms will be optimized along secure pathways towards tailored, high-resolution treatment in the sense of personalized and yet high-precision care. Full article
(This article belongs to the Special Issue Intracranial Aneurysms: Diagnostics and Current Treatment)
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22 pages, 919 KiB  
Review
Vitamin K Properties in Stroke and Alzheimer’s Disease: A Janus Bifrons in Protection and Prevention
by Lorenzo Grimaldi, Rosaria A. Cavallaro, Domenico De Angelis, Andrea Fuso and Giulia Sancesario
Molecules 2025, 30(5), 1027; https://doi.org/10.3390/molecules30051027 - 24 Feb 2025
Cited by 2 | Viewed by 3871
Abstract
Vitamin K is essential for many physiological processes, including coagulation, bone metabolism, tissue calcification, and antioxidant activity. Vitamin K vitamers are represented by lipophilic compounds with similar chemical structure (i.e., phylloquinone (vitamin K1) and menaquinone (vitamin K2)). Vitamin K deficiency can affect coagulation [...] Read more.
Vitamin K is essential for many physiological processes, including coagulation, bone metabolism, tissue calcification, and antioxidant activity. Vitamin K vitamers are represented by lipophilic compounds with similar chemical structure (i.e., phylloquinone (vitamin K1) and menaquinone (vitamin K2)). Vitamin K deficiency can affect coagulation and vascular calcification, increasing the risk of hemorrhages, atherosclerosis, cerebrovascular diseases, and neurodegeneration. Recently, several studies have hypothesized a possible dual role of vitamin K vitamers in benefiting both vascular and cerebral health, e.g., by sphingolipids biosynthesis or ferroptosis inhibition. The aim of this narrative review is to deepen the understanding of biological activities of vitamin K and its possible dual protective/preventive actions in neurovascular and degenerative conditions, e.g., stroke and dementia. Given the difficulties related to hemorrhagic risk entailed in the prevention of strokes, the function of vitamin K antagonists is also investigated. Finally, we track the development of a clinical concept for a future preventive strategy and innovative use of vitamin K as a supplement to counteract neurovascular and pathological processes, focusing in particular on stroke and dementia. Full article
(This article belongs to the Special Issue The Design, Synthesis, and Biological Activity of New Drug Candidates)
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