Advanced Research on Cerebrovascular Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 21146

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Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
Interests: bioinformatic analysis; glioma, single-cell; meta-analysis; intracerebral hemorrhage; subarachnoid hemorrhage
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Special Issue Information

Dear Colleagues,

Cerebrovascular disease refers to a group of conditions that affect blood flow and the blood vessels in the brain. Cerebrovascular disease includes stroke, carotid stenosis, vertebral stenosis and intracranial stenosis, aneurysms, and vascular malformations.  A wide variety of conditions, risk factors, and disorders lead to cerebrovascular diseases, although the underlying molecular mechanisms remain enigmatic.

In this Special Issue, we aim to present new data obtained on the molecular mechanisms of cerebrovascular diseases. We also expect the discovery of new biomarkers and novel therapeutical targets. We welcomed the submission of review and original research articles (clinical or basic) regarding pathophysiology, as well as the diagnosis and treatment of cerebrovascular diseases.

Prof. Dr. Zhong Wang
Guest Editor

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Keywords

  • cerebrovascular disease
  • stroke
  • inflammation
  • biomarkers

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Published Papers (10 papers)

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Research

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12 pages, 523 KiB  
Article
The Importance of Increased Serum GFAP and UCH-L1 Levels in Distinguishing Large Vessel from Small Vessel Occlusion in Acute Ischemic Stroke
by Ivan Kraljević, Sara Sablić, Maja Marinović Guić, Danijela Budimir Mršić, Ivana Štula, Krešimir Dolić, Benjamin Benzon, Vana Košta, Krešimir Čaljkušić, Marino Marčić, Daniela Šupe Domić and Sanja Lovrić Kojundžić
Biomedicines 2024, 12(3), 608; https://doi.org/10.3390/biomedicines12030608 - 7 Mar 2024
Viewed by 1408
Abstract
Acute ischemic stroke (AIS) is one of the leading causes of morbidity worldwide, thus, early recognition is essential to accelerate treatment. The only definite way to diagnose AIS is radiological imaging, which is limited to hospitals. However, two serum neuromarkers, glial fibrillary acidic [...] Read more.
Acute ischemic stroke (AIS) is one of the leading causes of morbidity worldwide, thus, early recognition is essential to accelerate treatment. The only definite way to diagnose AIS is radiological imaging, which is limited to hospitals. However, two serum neuromarkers, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1), have been proven as indicators of brain trauma and AIS. We aimed to investigate the potential utility of these markers in distinguishing between large vessel occlusion (LVO) and small vessel occlusion (SVO), considering differences in treatment. Sixty-nine AIS patients were included in our study and divided into LVO and SVO groups based on radiological imaging. Control group consisted of 22 participants without history of neurological disorders. Results showed differences in serum levels of both GFAP and UHC-L1 between all groups; control vs. SVO vs. LVO (GFAP: 30.19 pg/mL vs. 58.6 pg/mL vs. 321.3 pg/mL; UCH-L1: 117.7 pg/mL vs. 251.8 pg/mL vs. 573.1 pg/mL; p < 0.0001), with LVO having the highest values. Other prognostic factors of stroke severity were analyzed and did not correlate with serum biomarkers. In conclusion, a combination of GFAP and UCH-L1 could potentially be a valuable diagnostic tool for differentiating LVO and SVO in AIS patients. Full article
(This article belongs to the Special Issue Advanced Research on Cerebrovascular Diseases)
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13 pages, 267 KiB  
Article
The Interplay of Dyslipidemia, Oxidative Stress, and Clinical Outcomes in Acute Ischemic Stroke Patients with and without Coronary Artery Disease
by Branislav Kollar, Pavel Siarnik, Katarina Konarikova, Stanislav Oravec, Stanislava Klobucka, Katarina Klobucnikova, Michal Poddany, Zofia Radikova, Maria Janubova, Peter Turcani, Livia Gajdosova and Ingrid Zitnanova
Biomedicines 2024, 12(2), 332; https://doi.org/10.3390/biomedicines12020332 - 1 Feb 2024
Cited by 1 | Viewed by 1644
Abstract
We assessed lipid and lipoprotein profiles, along with oxidative stress (OS) parameters, in patients within the crucial 24 h period following an acute ischemic stroke (AIS), comparing those with and without coronary artery disease (CAD). We aimed to correlate these measures with clinical [...] Read more.
We assessed lipid and lipoprotein profiles, along with oxidative stress (OS) parameters, in patients within the crucial 24 h period following an acute ischemic stroke (AIS), comparing those with and without coronary artery disease (CAD). We aimed to correlate these measures with clinical condition scales (NIHSS, mRS) post-AIS. This study included 27 AIS patients without CAD (AIS group) and 37 AIS patients with CAD (CAD-AIS group). Using polyacrylamide gel electrophoresis (Lipoprint system), we determined plasma LDL and HDL subfractions. Spectrophotometric methods were used to assess plasma antioxidant capacity, lipoperoxides, homocysteine (HC) levels, paraoxonase1, and catalase activities. We also measured urine isoprostanes and the activities of antioxidant enzymes (SOD, GPx) with commercial kits. CAD-AIS patients had notably higher HC levels, while there were no significant differences in lipoprotein subfractions and OS parameters between both groups. In the AIS group, mRS scores showed negative correlations with catalase, GPx activities, and total cholesterol. In the CAD-AIS group, atherogenic lipoproteins (IDLC, LDL2, LDL3–7) exhibited a significant positive correlation with mRS. This study underscores the role of dyslipidemia and OS in the development of AIS and CAD. It emphasizes the complex connections between specific biomarkers and post-stroke clinical outcomes. Our results suggest a significant impact of CAD treatment on lipid profile but not on homocysteine levels. The traditional narrative associating high cholesterol as the ultimate risk factor for cardiovascular diseases needs to be challenged, at least with respect to neurological outcomes. These insights may guide more targeted therapeutic approaches. Full article
(This article belongs to the Special Issue Advanced Research on Cerebrovascular Diseases)
11 pages, 276 KiB  
Article
Changes in Cognitive Functions after Carotid Endarterectomy and Carotid Stenting: A Decade-Apart Comparison
by Daniel Václavík, David Pakizer, Tomáš Hrbáč, Martin Roubec, Václav Procházka, Tomáš Jonszta, Roman Herzig and David Školoudík
Biomedicines 2024, 12(1), 13; https://doi.org/10.3390/biomedicines12010013 - 20 Dec 2023
Cited by 1 | Viewed by 1440
Abstract
Background: This study investigates changes in cognitive function in patients with severe carotid stenosis who underwent carotid endarterectomy (CEA) and carotid stenting (CAS) over two decades. Methods: We compared cognitive function within 30 days after the procedure in 267 patients (first 100 each [...] Read more.
Background: This study investigates changes in cognitive function in patients with severe carotid stenosis who underwent carotid endarterectomy (CEA) and carotid stenting (CAS) over two decades. Methods: We compared cognitive function within 30 days after the procedure in 267 patients (first 100 each for CEA and CAS in two periods: 2008–2012 and 2018–2022) in a single institution. Assessments used Adenbrooke’s Cognitive Examination–Revised (ACE-R), the Mini-Mental State Examination (MMSE), Speech Fluency Test (SFT), and Clock Drawing Test (CDT), conducted before and 30 ± 2 days after surgery. Results: Patients (mean age 67.2 years, 70%+ carotid stenosis) exhibited different cognitive changes over periods. In 2008–2012, significant declines in MMSE (CEA, p = 0.049) and CDT (CAS, p = 0.015) were observed among asymptomatic patients. On the contrary, in 2018–2022, improvements were observed in ACE-R and MMSE for symptomatic and asymptomatic patients undergoing CEA and CAS. Conclusion: Over a decade, advances in interventional techniques and patient management have reduced risks of cognitive decline in patients with asymptomatic carotid stenosis and also have improved cognitive functions in both symptomatic and asymptomatic individuals. Full article
(This article belongs to the Special Issue Advanced Research on Cerebrovascular Diseases)
12 pages, 2225 KiB  
Article
Brain Endothelial Cells Activate Neuroinflammatory Pathways in Response to Early Cerebral Small Vessel Disease (CSVD) Patients’ Plasma
by Adriana Cifù, Francesco Janes, Catia Mio, Rossana Domenis, Maria Elena Pessa, Riccardo Garbo, Francesco Curcio, Mariarosaria Valente and Martina Fabris
Biomedicines 2023, 11(11), 3055; https://doi.org/10.3390/biomedicines11113055 - 14 Nov 2023
Cited by 1 | Viewed by 1309
Abstract
The pathogenesis of cerebral small vessel disease (CSVD) is largely unknown. Endothelial disfunction has been suggested as the turning point in CSVD development. In this study, we tested the effect of plasma from CSVD patients on human cerebral microvascular endothelial cells with the [...] Read more.
The pathogenesis of cerebral small vessel disease (CSVD) is largely unknown. Endothelial disfunction has been suggested as the turning point in CSVD development. In this study, we tested the effect of plasma from CSVD patients on human cerebral microvascular endothelial cells with the aim of describing the pattern of endothelial activation. Plasma samples from three groups of young subjects have been tested: PTs (subjects affected by early stage CSVD); CTRLs (control subjects without abnormalities at MRI scanning); BDs (blood donors). Human Brain Endothelial Cells 5i (HBEC5i) were treated with plasma and total RNA was extracted. RNAs were pooled to reduce gene expression-based variability and NGS analysis was performed. Differentially expressed genes were highlighted comparing PTs, CTRLs and BDs with HBEC5i untreated cells. No significantly altered pathway was evaluated in BD-related treatment. Regulation of p38 MAPK cascade (GO:1900744) was the only pathway altered in CTRL-related treatment. Indeed, 36 different biological processes turned out to be deregulated after PT treatment of HBEC5i, i.e., the cytokine-mediated signaling pathway (GO:0019221). Endothelial cells activate inflammatory pathways in response to stimuli from CSVD patients’ plasma, suggesting the pathogenetic role of neuroinflammation from the early asymptomatic phases of cerebrovascular disease. Full article
(This article belongs to the Special Issue Advanced Research on Cerebrovascular Diseases)
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29 pages, 5140 KiB  
Article
Prevalence and Impact of Cerebral Microbleeds on Clinical and Safety Outcomes in Acute Ischaemic Stroke Patients Receiving Reperfusion Therapy: A Systematic Review and Meta-Analysis
by Shraddha Tipirneni, Peter Stanwell, Robert Weissert and Sonu M. M. Bhaskar
Biomedicines 2023, 11(10), 2865; https://doi.org/10.3390/biomedicines11102865 - 23 Oct 2023
Cited by 5 | Viewed by 2234
Abstract
Background: Cerebral microbleeds (CMBs), a notable neuroimaging finding often associated with cerebral microangiopathy, demonstrate a heightened prevalence in patients diagnosed with acute ischemic stroke (AIS), which is in turn linked to less favourable clinical prognoses. Nevertheless, the exact prevalence of CMBs and their [...] Read more.
Background: Cerebral microbleeds (CMBs), a notable neuroimaging finding often associated with cerebral microangiopathy, demonstrate a heightened prevalence in patients diagnosed with acute ischemic stroke (AIS), which is in turn linked to less favourable clinical prognoses. Nevertheless, the exact prevalence of CMBs and their influence on post-reperfusion therapy outcomes remain inadequately elucidated. Materials and Methods: Through systematic searches of PubMed, Embase and Cochrane databases, studies were identified adhering to specific inclusion criteria: (a) AIS patients, (b) age ≥ 18 years, (c) CMBs at baseline, (d) availability of comparative data between CMB-positive and CMB-negative groups, along with relevant post-reperfusion therapy outcomes. The data extracted were analysed using forest plots of odds ratios, and random-effects modelling was applied to investigate the association between CMBs and symptomatic intracerebral haemorrhage (sICH), haemorrhagic transformation (HT), 90-day functional outcomes, and 90-day mortality post-reperfusion therapy. Results: In a total cohort of 9776 AIS patients who underwent reperfusion therapy, 1709 had CMBs, with a pooled prevalence of 19% (ES 0.19; 95% CI: 0.16, 0.23, p < 0.001). CMBs significantly increased the odds of sICH (OR 2.57; 95% CI: 1.72; 3.83; p < 0.0001), HT (OR 1.53; 95% CI: 1.25; 1.88; p < 0.0001), as well as poor functional outcomes at 90 days (OR 1.59; 95% CI: 1.34; 1.89; p < 0.0001) and 90-day mortality (OR 1.65; 95% CI: 1.27; 2.16; p < 0.0001), relative to those without CMBs, in AIS patients undergoing reperfusion therapy (encompassing intravenous thrombolysis [IVT], endovascular thrombectomy [EVT], either IVT or EVT, and bridging therapy). Variations in the level of association can be observed among different subgroups of reperfusion therapy. Conclusions: This meta-analysis underscores a significant association between CMBs and adverse postprocedural safety outcomes encompassing sICH, HT, poor functional outcome, and increased mortality in AIS patients undergoing reperfusion therapy. The notable prevalence of CMBs in both the overall AIS population and those undergoing reperfusion therapy emphasizes their importance in post-stroke prognostication. Full article
(This article belongs to the Special Issue Advanced Research on Cerebrovascular Diseases)
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14 pages, 853 KiB  
Article
Assessing Stroke-Related Sarcopenia in Chronic Stroke: Identification of Clinical Assessment Tools—A Pilot Study
by Anna Arnal-Gómez, Sara Cortés-Amador, Maria-Arantzazu Ruescas-Nicolau, Juan J. Carrasco, Sofía Pérez-Alenda, Ana Santamaría-Balfagón and M. Luz Sánchez-Sánchez
Biomedicines 2023, 11(10), 2601; https://doi.org/10.3390/biomedicines11102601 - 22 Sep 2023
Viewed by 1694
Abstract
Stroke-related sarcopenia has recently been defined as the muscle atrophy consequent to stroke and assessing it following the guidelines with simple clinical tools is crucial in chronic stroke survivors. The aim of this study was to determine the characteristics of patient-friendly instruments sarcopenia [...] Read more.
Stroke-related sarcopenia has recently been defined as the muscle atrophy consequent to stroke and assessing it following the guidelines with simple clinical tools is crucial in chronic stroke survivors. The aim of this study was to determine the characteristics of patient-friendly instruments sarcopenia in a chronic stroke sample (SG) compared to non-stroke counterparts (CG). Each participant underwent a single assessment which consisted of: SARC-F questionnaire, assessment of muscle strength (hand grip and five-times sit-to-stand test, 5STS), the calf circumference (CC) of both legs, the short physical performance battery (SPPB), and the 10 m walk test. A total of 68 participants were included (SG, n = 34 and CG, n = 34). All variables showed statistical differences (p < 0.05) between the SG and the CG, except handgrip although it showed lower values for SG. The values of the 5STS (16.26 s) and the SPPB (7 points) were below to the cutoff values for the SG. The five-times sit-to-stand test, SPPB, and gait speed can lead clinicians to detect stroke-related sarcopenia. Maximum handgrip shows a trend of low values for men and women in the SG, however, CC did not detect sarcopenia in our sample. Full article
(This article belongs to the Special Issue Advanced Research on Cerebrovascular Diseases)
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Review

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26 pages, 780 KiB  
Review
Molecular Mechanisms of Ischemic Stroke: A Review Integrating Clinical Imaging and Therapeutic Perspectives
by Sana Rehman, Arsalan Nadeem, Umar Akram, Abeer Sarwar, Ammara Quraishi, Hina Siddiqui, Muhammad Abdullah Javed Malik, Mehreen Nabi, Ihtisham Ul Haq, Andrew Cho, Ishan Mazumdar, Minsoo Kim, Kevin Chen, Sadra Sepehri, Richard Wang, Aneri B. Balar, Dhairya A. Lakhani and Vivek S. Yedavalli
Biomedicines 2024, 12(4), 812; https://doi.org/10.3390/biomedicines12040812 - 7 Apr 2024
Cited by 3 | Viewed by 4693
Abstract
Ischemic stroke poses a significant global health challenge, necessitating ongoing exploration of its pathophysiology and treatment strategies. This comprehensive review integrates various aspects of ischemic stroke research, emphasizing crucial mechanisms, therapeutic approaches, and the role of clinical imaging in disease management. It discusses [...] Read more.
Ischemic stroke poses a significant global health challenge, necessitating ongoing exploration of its pathophysiology and treatment strategies. This comprehensive review integrates various aspects of ischemic stroke research, emphasizing crucial mechanisms, therapeutic approaches, and the role of clinical imaging in disease management. It discusses the multifaceted role of Netrin-1, highlighting its potential in promoting neurovascular repair and mitigating post-stroke neurological decline. It also examines the impact of blood–brain barrier permeability on stroke outcomes and explores alternative therapeutic targets such as statins and sphingosine-1-phosphate signaling. Neurocardiology investigations underscore the contribution of cardiac factors to post-stroke mortality, emphasizing the importance of understanding the brain–heart axis for targeted interventions. Additionally, the review advocates for early reperfusion and neuroprotective agents to counter-time-dependent excitotoxicity and inflammation, aiming to preserve tissue viability. Advanced imaging techniques, including DWI, PI, and MR angiography, are discussed for their role in evaluating ischemic penumbra evolution and guiding therapeutic decisions. By integrating molecular insights with imaging modalities, this interdisciplinary approach enhances our understanding of ischemic stroke and offers promising avenues for future research and clinical interventions to improve patient outcomes. Full article
(This article belongs to the Special Issue Advanced Research on Cerebrovascular Diseases)
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15 pages, 290 KiB  
Review
Current and Future Applications of Arterial Spin Labeling MRI in Cerebral Arteriovenous Malformations
by Matteo De Simone, Marco Maria Fontanella, Anis Choucha, Karl Schaller, Paolo Machi, Giuseppe Lanzino, Philippe Bijlenga, Felix T. Kurz, Karl-Olof Lövblad and Lucio De Maria
Biomedicines 2024, 12(4), 753; https://doi.org/10.3390/biomedicines12040753 - 28 Mar 2024
Cited by 7 | Viewed by 1648
Abstract
Arterial spin labeling (ASL) has emerged as a promising noninvasive tool for the evaluation of both pediatric and adult arteriovenous malformations (AVMs). This paper reviews the advantages and challenges associated with the use of ASL in AVM assessment. An assessment of the diagnostic [...] Read more.
Arterial spin labeling (ASL) has emerged as a promising noninvasive tool for the evaluation of both pediatric and adult arteriovenous malformations (AVMs). This paper reviews the advantages and challenges associated with the use of ASL in AVM assessment. An assessment of the diagnostic workup of AVMs and their variants in both adult and pediatric populations is proposed. Evaluation after treatments, whether endovascular or microsurgical, was similarly examined. ASL, with its endogenous tracer and favorable safety profile, offers functional assessment and arterial feeder identification. ASL has demonstrated strong performance in identifying feeder arteries and detecting arteriovenous shunting, although some studies report inferior performance compared with digital subtraction angiography (DSA) in delineating venous drainage. Challenges include uncertainties in sensitivity for specific AVM features. Detecting AVMs in challenging locations, such as the apical cranial convexity, is further complicated, demanding careful consideration due to the risk of underestimating total blood flow. Navigating these challenges, ASL provides a noninvasive avenue with undeniable merits, but a balanced approach considering its limitations is crucial. Larger-scale prospective studies are needed to comprehensively evaluate the diagnostic performance of ASL in AVM assessment. Full article
(This article belongs to the Special Issue Advanced Research on Cerebrovascular Diseases)
21 pages, 1760 KiB  
Review
Neuroendovascular Surgery Applications in Craniocervical Trauma
by Michael Kim, Galadu Subah, Jared Cooper, Michael Fortunato, Bridget Nolan, Christian Bowers, Kartik Prabhakaran, Rolla Nuoman, Krishna Amuluru, Sauson Soldozy, Alvin S. Das, Robert W. Regenhardt, Saef Izzy, Chirag Gandhi and Fawaz Al-Mufti
Biomedicines 2023, 11(9), 2409; https://doi.org/10.3390/biomedicines11092409 - 28 Aug 2023
Cited by 3 | Viewed by 1950
Abstract
Cerebrovascular injuries resulting from blunt or penetrating trauma to the head and neck often lead to local hemorrhage and stroke. These injuries present with a wide range of manifestations, including carotid or vertebral artery dissection, pseudoaneurysm, occlusion, transection, arteriovenous fistula, carotid-cavernous fistula, epistaxis, [...] Read more.
Cerebrovascular injuries resulting from blunt or penetrating trauma to the head and neck often lead to local hemorrhage and stroke. These injuries present with a wide range of manifestations, including carotid or vertebral artery dissection, pseudoaneurysm, occlusion, transection, arteriovenous fistula, carotid-cavernous fistula, epistaxis, venous sinus thrombosis, and subdural hematoma. A selective review of the literature from 1989 to 2023 was conducted to explore various neuroendovascular surgical techniques for craniocervical trauma. A PubMed search was performed using these terms: endovascular, trauma, dissection, blunt cerebrovascular injury, pseudoaneurysm, occlusion, transection, vasospasm, carotid-cavernous fistula, arteriovenous fistula, epistaxis, cerebral venous sinus thrombosis, subdural hematoma, and middle meningeal artery embolization. An increasing array of neuroendovascular procedures are currently available to treat these traumatic injuries. Coils, liquid embolics (onyx or n-butyl cyanoacrylate), and polyvinyl alcohol particles can be used to embolize lesions, while stents, mechanical thrombectomy employing stent-retrievers or aspiration catheters, and balloon occlusion tests and super selective angiography offer additional treatment options based on the specific case. Neuroendovascular techniques prove valuable when surgical options are limited, although comparative data with surgical techniques in trauma cases is limited. Further research is needed to assess the efficacy and outcomes associated with these interventions. Full article
(This article belongs to the Special Issue Advanced Research on Cerebrovascular Diseases)
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Other

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8 pages, 4049 KiB  
Case Report
Successful Mechanical Thrombectomy for Basilar Artery Occlusion in a Pediatric Patient: A Case Report
by Agnete Teivāne, Inga Naļivaiko, Kristaps Jurjāns, Jānis Vētra, Andris Veiss, Arina Novaša, Sarmīte Dzelzīte, Dainis Krieviņš and Evija Miglāne
Biomedicines 2023, 11(10), 2774; https://doi.org/10.3390/biomedicines11102774 - 13 Oct 2023
Cited by 1 | Viewed by 1676
Abstract
Studies have shown the benefits of endovascular treatment (EVT) in adult stroke cases, but its application in pediatric stroke remains controversial. Despite evidence of improved outcomes in adults, there are no established recommendations for EVT in children. Conducting individual case reports and case [...] Read more.
Studies have shown the benefits of endovascular treatment (EVT) in adult stroke cases, but its application in pediatric stroke remains controversial. Despite evidence of improved outcomes in adults, there are no established recommendations for EVT in children. Conducting individual case reports and case series is vital to understanding its potential advantages and disadvantages in this context. In this case report, a 9-year-old male initially diagnosed with gastroenteritis developed sudden left-sided weakness 1 day after admission. Comprehensive imaging revealed acute ischemia in the cerebellum, indicating a basilar artery thrombus. Urgent endovascular treatment (EVT) was performed 8.5 h after the onset of neurological symptoms, achieving successful revascularization. The patient underwent rehabilitation and was later discharged with improved neurological status. Despite extensive investigations, the stroke’s origin remained unknown. After six months, the patient exhibited complete neurological recovery, highlighting the patient’s remarkable resilience. Full article
(This article belongs to the Special Issue Advanced Research on Cerebrovascular Diseases)
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